Adapting the overlap-add method to the synthesis of noise

银饰制作工艺作文英语Title: The Craftsmanship of Silver Jewelry Making。

Silver jewelry making is an art form that has been practiced for centuries, blending tradition with innovation to create timeless pieces of adornment. From ancient civilizations to modern artisans, the craft of shaping silver into intricate designs has captivated the imagination and delighted the senses. In this essay, we delve into the fascinating world of silver jewelry making, exploring its techniques, history, and significance.First and foremost, the craftsmanship of silver jewelry making requires skill, patience, and precision. Artisans employ various techniques to manipulate silver into desired shapes and forms. One of the primary methods is casting, where molten silver is poured into molds to createintricate patterns and designs. This process allows for the production of multiple identical pieces with intricate details.Another commonly used technique is fabrication, which involves shaping silver using tools such as hammers, files, and saws. This method allows artisans to create unique,one-of-a-kind pieces that showcase their creativity and craftsmanship. Additionally, techniques like soldering and engraving are often employed to add embellishments and personalization to the jewelry.Beyond technical proficiency, silver jewelry making is steeped in history and cultural significance. Throughout the ages, silver has been prized for its lustrous beauty and versatility. In many cultures, silver jewelry holds symbolic meaning, representing wealth, status, or spiritual beliefs. For example, in ancient Egypt, silver was associated with the moon and believed to possess protective powers. Similarly, in Hindu culture, silver jewelry is often worn during religious ceremonies and celebrations.Furthermore, silver jewelry making has evolved over time, adapting to changes in fashion, technology, and societal norms. While traditional craftsmanship techniquesare still valued and practiced, contemporary artisans are also exploring innovative methods such as 3D printing and computer-aided design (CAD). These advancements have expanded the possibilities of silver jewelry design, allowing artisans to push the boundaries of creativity and expression.In addition to its aesthetic appeal, silver jewelry holds practical value as well. Silver is a durable and hypoallergenic metal, making it suitable for everyday wear. Unlike other metals, such as nickel or brass, silver is less likely to cause skin irritation or allergic reactions, making it an ideal choice for people with sensitive skin.Moreover, silver jewelry making plays a significantrole in the global economy, providing employment opportunities for artisans and supporting local economies. In regions where silver mining is prevalent, such as Mexico and Peru, jewelry making serves as a vital source of income for communities. Artisanal silver jewelry is also highly sought after in the international market, contributing to the growth of the global jewelry industry.In conclusion, silver jewelry making is a time-honored craft that combines technical skill with artistic expression. From ancient civilizations to modern-day artisans, the allure of silver jewelry continues to captivate people around the world. Whether through traditional techniques or innovative methods, the craftsmanship of silver jewelry making reflects the rich tapestry of human creativity and cultural heritage.。

自考英语二的单词和考研英语二的单词重复-回复全文共3篇示例，供读者参考篇1Overlapping Vocabulary: The Shared Lexical Terrain ofSelf-Study and Grad School English ExamsAs a diligent student striving to conquer the linguistic frontiers that await, I find myself traversing a rugged lexical landscape fraught with challenges – one where the paths of self-study and graduate school admissions exams intertwine in an intricate dance of overlapping vocabulary. This phenomenon, a linguistic Venn diagram of sorts, is a subject worthy of closer examination, for it holds the potential to streamline one's journey through the vast expanse of the English language.At the core of this exploration lies the realization that the self-taught English Test Level 2 (henceforth referred to as SET-2) and the Graduate School English Test Level 2 (hereafter abbreviated as GSET-2) share a significant portion of their respective word lists. This intersection, a lexical common ground, presents both opportunities and challenges for the intrepid learner.On the one hand, the existence of this shared vocabulary can be seen as a boon, a literal gift from the linguistic gods. By mastering the words that grace both examinations, one effectively kills two birds with one stone, so to speak. The time and effort invested in committing these terms to memory yield dividends in the form of enhanced performance on not just one, but two pivotal assessments. It is akin to embarking on a hike and discovering that a single trail leads to multiple breathtaking vistas.However, this linguistic overlap also presents a potential pitfall, a treacherous crevasse that must be navigated with care. The risk lies in the false assumption that familiarity with a word in one context automatically translates to mastery in another. Words, much like chameleons, can take on subtle shades of meaning depending on the context in which they are employed.A term that may seem innocuous in the realm of self-study could harbor nuanced complexities when encountered in the crucible of graduate-level discourse.It is therefore imperative that the diligent student approach this shared lexical territory with a discerning eye and an open mind. One must be willing to peel back the layers of each word, to explore its various connotations and applications, lest theyfind themselves ensnared in a web of linguistic misunderstanding.To illustrate this point, let us consider the seemingly innocuous term "hypothesis." In the context of the SET-2, this word may be presented as a simple proposition or educated guess, a stepping stone on the path to scientific inquiry. However, in the rarefied air of graduate-level academia, the notion of a hypothesis takes on a far more nuanced and sophisticated form. It becomes a carefully constructed theoretical framework, a lens through which entire bodies of research are viewed and interpreted. Failing to grasp this subtle distinction could lead to a fundamental misunderstanding of the very foundations upon which academic discourse is built.Thus, the wise student must approach the shared vocabulary of these two examinations with a balanced perspective. On one hand, they should embrace the efficiency and convenience afforded by this lexical overlap, recognizing the opportunity to streamline their studies and make the most of their efforts. On the other, they must remain vigilant, ever mindful of the potential for linguistic nuance and the need to adapt their understanding of words to the specific context in which they are encountered.In this regard, the journey through the shared lexical terrain of the SET-2 and GSET-2 becomes a metaphorical trek through a dense linguistic forest. The path may be well-trodden, but it is far from straightforward. It is a journey that demands patience, perseverance, and a willingness to delve deeper into the rich tapestry of language that surrounds us.As one navigates this intricate lexical landscape, it is essential to cultivate a spirit of curiosity and a thirst for knowledge. Each new word encountered should be treated not merely as a hurdle to be surmounted, but as an opportunity for intellectual growth and linguistic enrichment. By embracing this mindset, the diligent student transforms their studies from a mere exercise in memorization into a voyage of discovery, where the true depths and nuances of language are gradually unveiled.Moreover, it is imperative to recognize that language is a living, breathing entity, ever-evolving and adapting to the changing currents of human thought and expression. The words that grace the pages of today's examinations may take on new meanings or fall into disuse by the time tomorrow's assessments are conceived. As such, the journey through the shared lexical terrain must be viewed not as a finite destination, but as a continuous process of exploration and adaptation.In this light, the overlapping vocabulary of the SET-2 and GSET-2 becomes more than just a practical consideration; it becomes a microcosm of the broader linguistic landscape, a microcosmic representation of the rich tapestry that is the English language. By navigating this terrain with care and dedication, the diligent student not only prepares themselves for success on these specific examinations, but also cultivates the linguistic dexterity and adaptability that will serve them well in countless future endeavors.As I reflect upon this lexical odyssey, I am reminded of the words of the great linguist and philosopher Ludwig Wittgenstein, who once stated, "The limits of my language mean the limits of my world." In embracing the shared vocabulary of the SET-2 and GSET-2, we transcend those limits, expanding our linguistic horizons and opening ourselves to a world of possibilities that lie beyond the confines of any single examination.So, let us forge ahead, my fellow linguistic explorers, with a sense of wonder and a thirst for knowledge that knows no bounds. Let us navigate the shared lexical terrain with equal parts diligence and curiosity, ever mindful of the nuances that lurk beneath the surface of each word we encounter. For in doing so, we not only increase our chances of success on these pivotalassessments, but we also embark on a journey of personal growth and linguistic enrichment that will serve us well long after the echoes of these examinations have faded into the annals of memory.篇2The Road Less Traveled: Navigating the Vocabulary LabyrinthAs students, we often find ourselves knee-deep in anever-ending sea of academic challenges, each one more daunting than the last. Among these trials, the conquest of English vocabulary stands as a formidable foe, its tentacles reaching far and wide across various realms of study. For those of us treading the path of self-taught English proficiency and aspiring to conquer the hallowed grounds of graduate school, the overlap between these two domains can be both a blessing and a curse.The notion of overlapping vocabulary might initially seem like a godsend, a lifeline amidst the chaos of memorization and comprehension. After all, what could be more reassuring than recognizing familiar words across multiple contexts? It's akin tostumbling upon an oasis in the desert, a momentary respite from the relentless pursuit of linguistic mastery.However, as with most things in academia, the reality is far more nuanced. While the shared lexicon between self-taught English and the graduate school entrance exam may appear to be a shortcut, it is a path riddled with pitfalls and potential misunderstandings. It's a treacherous maze where a single misstep can lead to disastrous consequences, akin to a hapless adventurer stumbling into a labyrinth without a trusty ball of thread.The crux of the matter lies in the subtle variations that words can take on in different contexts. A word that holds a particular meaning in the realm of self-taught English might undergo a metamorphosis, donning a new guise when encountered in the rarefied atmosphere of graduate-level examinations. It's a linguistic shapeshifter, a chameleon that adapts to its surroundings, leaving unsuspecting students bewildered and disoriented.Take, for instance, the unassuming word "critical." In the realm of self-taught English, it might evoke notions of importance, significance, or even a dire situation. However, in the hallowed halls of graduate-level discourse, "critical" takes on adifferent hue, often implying a more analytical or evaluative stance. A student who fails to grasp this subtle distinction might find themselves adrift, their comprehension hindered by the very words they thought they knew.The perils don't end there, for the overlap between vocabularies can breed a false sense of security, a dangerous complacency that lulls students into a state of overconfidence. It's akin to a hiker believing they've mastered the trail, only to find themselves lost in the wilderness, their map rendered useless by unexpected detours and treacherous terrain.Yet, despite these obstacles, there is a glimmer of hope, a beacon that guides us through the linguistic labyrinth. It lies in the cultivation of a critical mindset, a willingness to question assumptions and embrace the nuances that words can harbor. By approaching each word with a healthy dose of skepticism and an eagerness to unravel its multifaceted nature, we can navigate the treacherous waters of vocabulary overlap with greater ease.It is a journey of constant learning, a perpetual odyssey where every word is a potential ally or adversary, depending on our ability to wield it with precision. We must become linguistic chameleons ourselves, adapting our understanding to theever-changing landscape of academic discourse, shedding preconceptions like a snake sheds its skin.In this odyssey, collaboration becomes our compass, our guiding light. By engaging in discourse with peers, mentors, and scholars, we can illuminate the nuances that words conceal, uncovering their hidden depths and complexities. It is a collective endeavor, a symphony of perspectives that harmonize to create a richer, more nuanced understanding of the vocabulary we wield.Moreover, we must embrace the power of context, for words are not mere vessels of meaning; they are living, breathing entities that draw sustenance fromtheir surroundings. A word's true essence can only be understood when viewed through the lens of its context, be it academic, cultural, or historical. To neglect this vital aspect is to risk misinterpreting the very language we seek to master.As we navigate the labyrinth of overlapping vocabularies, it is imperative that we cultivate a growth mindset, an unwavering belief in our ability to adapt and evolve. For just as words can shape-shift, so too must we, shedding our preconceptions and embracing the ever-changing landscape of language with open arms.The road ahead is arduous, fraught with challenges and pitfalls that would test the mettle of even the most seasoned linguist. Yet, it is a journey worth undertaking, for within the tangled web of words lies a treasure trove of knowledge, a gateway to intellectual enlightenment and personal growth.So, let us embrace the challenge, fellow travelers. Let us don our linguistic armor and venture forth into the unknown, armed with a critical mind, a collaborative spirit, and an unwavering determination to conquer the vocabulary labyrinth. For in doing so, we not only unlock the doors to academic excellence but also forge a path towards a deeper understanding of ourselves and the world around us.篇3Sure, here's an essay of around 2000 words, written from a student's perspective, discussing the overlap between vocabulary words in self-taught English Level 2 exams and postgraduate English Level 2 exams, in English:English Level 2: Navigating the Vocabulary OverlapAs a diligent student striving to conquer the realms of higher education, I've found myself entangled in the intricate web of English language proficiency examinations. Specifically, I've beengrappling with the daunting task of mastering the vocabulary required for both the self-taught English Level 2 and the postgraduate English Level 2 exams. While these two assessments may seem worlds apart, a closer inspection reveals a surprising overlap in their respective word lists.The journey began with my preparation for the self-taught English Level 2 exam, a rite of passage for those seeking academic advancement through unconventional routes. As I delved into the vast repository of vocabulary, I encountered words that seemed to transcend the boundaries of mere lexical knowledge. Words like "candid," "empirical," and "pragmatic" not only adorned the pages of my study materials but also resonated with the very essence of academic discourse.Little did I know that this initial foray into the depths of English vocabulary would pave the way for my subsequent encounter with the postgraduate English Level 2 exam. As I embarked on this new endeavor, the familiarity of certain words struck me like a comforting embrace amidst the sea of unfamiliar terms. Words like "paradigm," "dichotomy," and "ubiquitous" appeared to be old friends, their meanings etched into my memory from previous encounters.This realization ignited a newfound sense of confidence within me, as I recognized the value of the foundational knowledge I had acquired. It became evident that the mastery of these shared words not only facilitated a smoother transition between the two exams but also fostered a deeper understanding of the nuances that permeate academic discourse.However, the overlap extended beyond mere word recognition; it also encompassed the intricate web of relationships that words weave with one another. Phrases like "inextricably linked," "juxtaposed against," and "paradigm shift" revealed themselves as recurring patterns, stitching together the fabrics of both examinations. This realization underscored the importance of not merely memorizing isolated words but also grasping their contextual usage and interrelationships.As I navigated through the intricacies of these shared vocabularies, I couldn't help but marvel at the profound impact they had on my intellectual growth. Words like "epistemology," "seminal," and "discourse" introduced me to the realms of philosophy, academia, and critical thinking, broadening my horizons and challenging me to think beyond the confines of mere definitions.Moreover, the overlap in vocabulary served as a testament to the universality of academic discourse. It became evident that certain words and phrases transcended disciplinary boundaries, functioning as linguistic threads that wove together the tapestry of knowledge. Words like "dialectic," "synthesis," and "discourse analysis" found their way into diverse fields, from literature to sociology, from psychology to political science.This realization instilled in me a deeper appreciation for the interconnectedness of knowledge and the power of language to bridge divides. It reinforced the notion that true mastery of a subject extends beyond its narrow confines and necessitates an understanding of the broader intellectual landscape.As I continue to navigate the labyrinth of academic pursuits, the overlap between the vocabulary of the self-taught English Level 2 and the postgraduate English Level 2 exams serves as a reminder of the incremental nature of learning. Each word, each phrase, builds upon the foundations laid by previous encounters, creating a tapestry of knowledge that grows richer and more intricate with every new experience.In retrospect, the journey through these shared vocabularies has been nothing short of transformative. It has instilled in me a heightened sense of resilience, enabling me to approach newchallenges with the confidence born of familiarity. It has fostered a deeper appreciation for the interconnectivity of knowledge and the power of language to bridge intellectual divides.As I look ahead, I carry with me the invaluable lessons gleaned from this experience, ready to embrace the next phase of my academic odyssey. For within the confines of these shared words lies a world of possibilities, a gateway to unprecedented intellectual growth and a testament to the enduring power of language to shape our understanding of the world around us.。

诱导契合变构调节英文回答：Inducing rapport and adjusting to the conversation partner's speech style are two important aspects of effective communication. When it comes to inducing rapport, it means creating a sense of connection and harmony with the other person. This can be achieved through various means such as mirroring body language, using similar vocabulary and tone of voice, and showing genuine interest in the other person's thoughts and feelings.For example, if I am speaking to someone who speaks in a more formal and polite manner, I would adjust my speech style to match theirs. I would use formal language, avoid slang or informal expressions, and maintain a respectful tone. This helps to establish a sense of mutual understanding and respect between us.On the other hand, if I am speaking to someone who ismore casual and uses a lot of slang, I would adapt my speech style accordingly. I might use more informal language, incorporate some slang expressions, and adopt a more relaxed tone. This helps to create a sense of camaraderie and makes the conversation more enjoyable for both parties.In addition to inducing rapport, adjusting to the conversation partner's speech style is also important. This means adapting one's language and communication style to match the other person's preferences. For example, if I am speaking to someone who speaks English as a second language and may struggle with complex vocabulary or grammar, I would try to simplify my language and use more common words and phrases. This helps to ensure that the other person can understand and follow the conversation more easily.Similarly, if I am speaking to someone who is very knowledgeable in a specific field, I would adjust my language to include more technical terms and jargon that they are familiar with. This shows that I respect their expertise and helps to establish a sense of credibility andtrust.Overall, inducing rapport and adjusting to the conversation partner's speech style are essential skillsfor effective communication. By creating a sense of connection and adapting to the other person's preferences, we can enhance understanding, build relationships, and make the conversation more enjoyable for everyone involved.中文回答：诱导契合和变构调节是有效沟通的两个重要方面。

(This is a sample cover image for this issue.The actual cover is not yet available at this time.)This article appeared in a journal published by Elsevier.The attached copy is furnished to the author for internal non-commercial research and education use,including for instruction at the authors institutionand sharing with colleagues.Other uses,including reproduction and distribution,or selling or licensing copies,or posting to personal,institutional or third partywebsites are prohibited.In most cases authors are permitted to post their version of thearticle(e.g.in Word or Tex form)to their personal website orinstitutional repository.Authors requiring further informationregarding Elsevier’s archiving and manuscript policies areencouraged to visit:/copyrightReviewSatellite-derived land surface temperature:Current status and perspectivesZhao-Liang Li a ,b ,⁎,Bo-Hui Tang a ,Hua Wu a ,Huazhong Ren c ,Guangjian Yan c ,Zhengming Wan d ,Isabel F.Trigo e ,f ,JoséA.Sobrino gaState Key Laboratory of Resources and Environmental Information System,Institute of Geographic Sciences and Natural Resources Research,Beijing 100101,China bLSIIT,UdS,CNRS,Boulevard Sebastien Brant,BP10413,67412Illkirch,France cState Key Laboratory of Remote Sensing Sciences,School of Geography,Beijing Normal University,Beijing 100875,China dERI,University of California,Santa Barbara,CA 93106,USA eInstituto Português do Mar e da Atmosfera,Lisbon,Portugal fInstituto Dom Luiz,University of Lisbon,Portugal gImage Processing Laboratory,University of Valencia,Valencia 46071,Spaina b s t r a c ta r t i c l e i n f o Article history:Received 24May 2012Received in revised form 19October 2012Accepted 11December 2012Available online xxxx Keywords:Land surface temperature Land surface emissivity RetrievalThermal infraredLand surface temperature (LST)is one of the key parameters in the physics of land surface processes from local through global scales.The importance of LST is being increasingly recognized and there is a strong interest in de-veloping methodologies to measure LST from space.However,retrieving LST is still a challenging task since the LST retrieval problem is ill-posed.This paper reviews the current status of selected remote sensing algorithms for estimating LST from thermal infrared (TIR)data.A brief theoretical background of the subject is presented along with a survey of the algorithms employed for obtaining LST from space-based TIR measurements.The discussion focuses on TIR data acquired from polar-orbiting satellites because of their widespread use,global applicability and higher spatial resolution compared to geostationary satellites.The theoretical framework and methodolo-gies used to derive the LST from the data are reviewed followed by the methodologies for validating satellite-derived LST.Directions for future research to improve the accuracy of satellite-derived LST are then suggested.©2012Elsevier Inc.All rights reserved.Contents 1.Introduction ...............................................................152.Basic theoretical background .......................................................152.1.Radiative transfer equation .....................................................162.2.Dif ficulties and problems in the retrieval of LST from space measurements ..............................173.Estimation of LST from space .......................................................183.1.LST retrieval with known LSEs ...................................................183.1.1.Single-channel method ..................................................183.1.2.Multi-channel method ..................................................193.1.3.Multi-angle method ....................................................213.2.LST retrieval with unknown LSEs ..................................................223.2.1.Stepwise retrieval methods ................................................223.2.2.Simultaneous LST and LSE retrieval methods with known atmospheric information ......................233.2.3.Simultaneous retrieval of LST,LSEs,and atmospheric pro files ..........parison and analysis of different methods ............................................264.Validation of satellite derived LST .....................................................294.1.Temperature-based method (T-based)...............................................294.2.Radiance-based method (R-based).................................................294.3.Cross validation method ................................ (30)Remote Sensing of Environment 131(2013)14–37⁎Corresponding author at:LSIIT,UdS,CNRS,Boulevard Sebastien Brant,BP10413,67412Illkirch,France.Tel.:+33368854516.E-mail address:lizl@ (Z.-L.Li).0034-4257/$–see front matter ©2012Elsevier Inc.All rights reserved./10.1016/j.rse.2012.12.008Contents lists available at SciVerse ScienceDirectRemote Sensing of Environmentj o u r n a l h om e p a g e :ww w.e l s e v i e r.c o m /l o c a t e /r s e5.Future development and perspectives (30)5.1.Methodology to simultaneously derive LST,LSE,and atmospheric profiles(atmospheric quantities)from hyperspectral TIR data (30)5.2.Methodology to simultaneously derive LST and LSE from the new generation of geostationary satellites with multispectral andmulti-temporal data (31)5.3.Refinement of LST retrieval algorithms with the consideration of aerosol and cirrus effects (31)5.4.Retrieval of component temperatures in heterogeneous pixels (31)5.5.Methodology for retrieving LST from passive microwave data and for combining LSTs retrieved from TIR and passive microwave data..315.6.Methodology for angular normalization of LST (32)5.7.Methodology for temporal(time)normalization of LST (32)5.8.Concerns on the newly developed Hyperspectral Infrared Imager (32)5.9.Physical meaning of satellite-derived LST and its applications (33)5.10.Validation of satellite-derived LST (33)Acknowledgments (33)References (33)1.IntroductionAs the direct driving force in the exchange of long-wave radiation and turbulent heatfluxes at the surface–atmosphere interface,land sur-face temperature(LST)is one of the most important parameters in the physical processes of surface energy and water balance at local through global scales(Anderson et al.,2008;Brunsell&Gillies,2003;Karnieli et al.,2010;Kustas&Anderson,2009;Zhang et al.,2008).Knowledge of the LST provides information on the temporal and spatial variations of the surface equilibrium state and is of fundamental importance in many applications(Kerr et al.,2000).As such,the LST is widely used in a variety offields including evapotranspiration,climate change,hy-drological cycle,vegetation monitoring,urban climate and environ-mental studies,among others(Arnfield,2003;Bastiaanssen et al., 1998;Hansen et al.,2010;Kalma et al.,2008;Kogan,2001;Su,2002; Voogt&Oke,2003;Weng,2009;Weng et al.,2004)and has been recog-nized as one of the high-priority parameters of the International Geosphere and Biosphere Program(IGBP)(Townshend et al.,1994). Due to the strong heterogeneity of land surface characteristics such as vegetation,topography,and soil(Liu et al.,2006;Neteler,2010),LST changes rapidly in space as well as in time(Prata et al.,1995;Vauclin et al.,1982)and an adequate characterization of LST distribution and its temporal evolution,therefore,requires measurements with detailed spatial and temporal sampling.Given the complexity of surface temper-ature over land,ground measurements cannot practically provide values over wide areas.With the development of remote sensing from space,satellite data offer the only possibility for measuring LST over the entire globe with sufficiently high temporal resolution and with complete spatially averaged rather than point values.Satellite-based thermal infrared(TIR)data is directly linked to the LST through the radiative transfer equation.The retrieval of the LST from remotely sensed TIR data has attracted much attention,and its his-tory dates back to the1970s(McMillin,1975).To better understand the Earth system at the regional scale and to get the evapotranspiration with an accuracy better than10%,LST must be retrieved at an accuracy of1K or better(Kustas&Norman,1996;Moran&Jackson,1991;Wan& Dozier,1996).However,direct estimation of LST from the radiation emitted in the TIR spectral region is difficult to perform with that accuracy,since the radiances measured by the radiometers onboard sat-ellites depend not only on surface parameters(temperature and emis-sivity)but also on atmospheric effects(Li&Becker,1993;Ottlé& Stoll,1993;Prata et al.,1995).Therefore,besides radiometric calibration and cloud screening,the determination of LSTs from space-based TIR measurements requires both emissivity and atmospheric corrections (Li&Becker,1993;Vidal,1991).Many studies have been carried out, and different approaches have been proposed to derive LSTs from satel-lite TIR data,using a variety of methods to deal with the emissivity and atmospheric effects(Becker&Li,1990b;Gillespie et al.,1998; Hook et al.,1992;Jiménez-Muñoz&Sobrino,2003;Kealy&Hook,1993;Kerr et al.,1992;Pozo Vazquez et al.,1997;Price,1983,1984; Qin et al.,2001;Susskind et al.,1984;Tonooka,2001;Wan&Dozier, 1996;Wan&Li,1997).Consequently,there have been quite a large number of publications on LST retrieval algorithms and methods.It is important to present an overview of the state of the art in LST retrieval algorithms and to direct future research into improving the accuracy of satellite-derived LST.Although there have been earlier reviews on LST retrieval from space,presented by Prata et al.(1995)and Dash et al. (2002),since then there have been several new developments in LST re-trieval algorithms and this review is intended to supplement those re-views with latest approaches.The objective of this paper is to review the progress in estimation of LST from TIR data primarily taken using sensors onboard polar-orbit satellites which have been acquiring data since the mid-eighties and to suggest directions for future research on the subject.Section2provides the theoretical basis for retrieving the LST from satellite TIR data and briefly discusses some major difficulties in LST retrieval from space measurements,including:(i)the coupling of the LST,the land surface emissivity(LSE)and the atmosphere;(ii)the physical meaning of satellite-derived LST;and(iii)validation problems related to satellite-derived LST.Section3presents an overview of a variety of methods and algorithms for estimating the LST.For each method or algorithm,the main theoretical basis and assumptions in-volved in the development of the model will be outlined,and the method's advantages,drawbacks and potential will be highlighted. Section4reviews methods of validating satellite-derived LST.Finally, Section5suggests future developments and provides perspectives on retrieving LST from remotely sensed data.2.Basic theoretical backgroundAll objects with temperatures greater than absolute zero emit radia-tion,and the amount of radiation from a black body in thermal equilib-rium at wavelengthλand temperature T is described by Planck's law: BλTðÞ¼C1λ5exp C2λT−1h i;ð1Þwhere Bλ(T)is the spectral radiance(W m−2μm−1sr−1)of a black body at temperature T(K)and wavelengthλ(μm);C1and C2are physical constants(C1=1.191×108Wμm4sr−1m−2,C2=1.439×104μm·K). Because most natural objects are non-black bodies,the emissivityε, which is defined as the ratio between the radiance of an object and that of a black body at the same temperature,must be taken into account. The spectral radiance of a non-black body is given by the spectral emis-sivity multiplied by Planck's law as shown in Eq.(1).Obviously,if the atmosphere exerts no influence on the measured radiance,LST(i.e.T) can be retrieved by making temperature as the subject of Eq.(1)once the emitted radiance and emissivity are known.The wavelengthλmax15Z.-L.Li et al./Remote Sensing of Environment131(2013)14–37of the peak monochromatic radiance at a given temperature (T)is given by Wien's displacement law:T λmax ¼2897:9K μm :ð2ÞAccording to this equation,the wavelength λmax at which maxi-mum emission occurs varies roughly from 11.6μm to 8.8μm if the LST ranges from 250K to 330K with the average temperature of the Earth being approximately 288K.The wavelength region be-tween 8and 13μm coincides within a clear window in the atmo-sphere which is most transparent to TIR radiation.In cases where the temperature of the surface exceeds 330K,the wavelength peak moves to shorter and shorter wavelengths,for example for a wild fire (about 800K),the maximum emission is around 3.6μm in the mid-infrared (MIR)region (3–5μm)which also coincides with a clear window in the atmosphere.2.1.Radiative transfer equationAn infrared sensor onboard a satellite viewing the Earth's surface measures the radiation from the Earth and its atmosphere along the line of ing the radiative transfer equation (RTE)and assum-ing a cloud-free atmosphere under local thermodynamic equilibrium,as illustrated in Fig.1,the channel infrared radiance I i received by a sensor at the top of the atmosphere (TOA)can be written as I i θ;φðÞ¼R i θ;φðÞτi θ;φðÞ|fflfflfflfflfflfflfflfflfflfflfflffl{zfflfflfflfflfflfflfflfflfflfflfflffl}Surf ace outgoing radiation term attenuated by the atmosphereþR at i ↑θ;φðÞ|fflfflfflfflfflfflffl{zfflfflfflfflfflfflffl}Atmospheric emission termþR sl i ↑θ;φðÞ|fflfflfflfflfflfflffl{zfflfflfflfflfflfflffl}Atmospheric scattering term;ð3Þwith R i being the channel radiance observed in channel i at ground level given byR i θ;φðÞ¼εi θ;φðÞB i T s ðÞ|fflfflfflfflfflfflfflfflfflffl{zfflfflfflfflfflfflfflfflfflffl}Surf ace emission termþ1−εi θ;φðÞ½ R at i ↓|fflfflfflfflfflfflfflfflfflfflfflfflfflffl{zfflfflfflfflfflfflfflfflfflfflfflfflfflffl}Surf ace ref lected downwelling atmospheric emissiontermþ1−εi θ;φðÞ½ R sl i ↓|fflfflfflfflfflfflfflfflfflfflfflfflffl{zfflfflfflfflfflfflfflfflfflfflfflfflffl}Surf ace ref lected downwelling atmospheric scattering termþρb i θ;φ;θs ;φs ðÞE i cos θs ðÞτi θs ;φs ðÞ|fflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflffl{zfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflfflffl}Surf ace ref lected downwelling solar beam term;ð4Þin which θand φrepresent the zenithal and azimuthal viewing angles.For simplicity,the zenithal and azimuthal viewing angles are ignored in the following expressions.τi is the effective transmittance of the atmosphere in channel i .R i τi is the radiance observed at ground level attenuated by the atmosphere (path ①in Fig.1).R ati ↑is the upward at-mospheric thermal radiance (path ②in Fig.1).R sli ↑is the upward solar diffusion radiance resulting from atmospheric scattering of the solar ra-diance (path ③in Fig.1).εi and T s are the effective surface emissivity and surface temperature in channel i .εi B i (T s )represents the radiance emitted directly by surface (path ④in Fig.1).R ati ↓is the downward atmospheric thermal radiance.R sli ↓is the downward solar diffusion ra-diance.(1-εi )R ati ↓and (1-εi )R sli ↓represent the downward atmospheric thermal radiance and solar diffusion radiance re flected by the surface (paths ⑤and ⑥in Fig.1).ρbi is the bi-directional re flectivity of the sur-face,E i is the solar irradiance at the TOA,θs and φs are the solar zenithal and azimuthal angles.ρbi E i cos(θs )τi (θs ,φs )is the direct solar radiance re flected by the surface (path ⑦in Fig.1).Because the contribution of solar radiation at the TOA is negligible in the 8–14μm window during both day and night and in the 3–5μm window at night,theFig.1.Illustration of radiative transfer equation in infrared regions (see the text for the de finitions of symbols).Here,I i is the radiance measured by channel i at the top of atmo-sphere.Path ①represents the radiance observed at ground level attenuated by the atmosphere.Paths ②and ③represent the upward atmospheric thermal radiance and the up-ward solar diffusion radiance,respectively.Path ④represents the radiance emitted directly by the surface.Paths ⑤and ⑥represent the downward atmospheric thermal radianceand solar diffusion radiance re flected by the surface,respectively.Path ⑦represents the direct solar radiance re flected by the surface.16Z.-L.Li et al./Remote Sensing of Environment 131(2013)14–37solar-related items (paths ③,⑥and ⑦in Fig.1)in Eqs.(3)and (4)can be neglected without loss of accuracy.For convenience and mathematical shorthand,the radiances I i and R i measured at the TOA and at ground level are generally expressed in terms of the brightness temperatures where the emissivity is fixed at 1.0.The TOA and ground level brightness temperatures T i and T gi are de fined respectively by B i T i ðÞ¼I iand B i T gi¼R ið5ÞIt is worth noting that all variables/parameters in Eqs.(3)–(5),ex-cept for the angles (θ,φ,θs and φs ),are channel-effective values.Most satellite sensors measure the outgoing radiation with a finite spectral-bandwidth,and the channel-effective quantities of interest are therefore a weighted average expressed by:X i ¼∫λ2λ1g i λðÞX λd λ∫λ2λ1g iλðÞd λ;ð6Þwhere g i (λ)is the spectral response function in channel i ;λ1and λ2are the lower and upper boundaries of the wavelength in channel i ;and X stands for B (T ),I ,R ,R at ↑,R sl ↑,R at ↓,R sl ↓,E ,ε,τ,or ρb .Eqs.(3)and (4)are actually approximations to the theoretical RTE in which monochromatic quantities are replaced with channel-effective values,but these approximations or simpli fications require several important preconditions:•The integral of a product is assumed to be equal to the product of the integrals.This assumption is true only if the variables are con-stant within the integration limits,which is rarely the case.Fortu-nately,the bandwidth of the channel is generally narrow,and the various spectral quantities X λinvolved in Eq.(6)should not feature rapid variations.Therefore,the use of the weighted averages de-fined by Eq.(6)in Eqs.(3)and (4)is a good approximation to the RTE with monochromatic quantities.•Either the surface is assumed to be Lambertian or the downward at-mospheric and solar diffuse radiation are assumed to be isotropic in the calculation of the downward radiations re flected by the surface (paths ⑤and ⑥in Fig.1).In practice,these conditions are never ful filled.However,because the surface-re flected downward atmo-spheric thermal radiation term is much smaller than the surface thermal emission,and the surface-re flected diffuse solar radiation term is much smaller than the surface-re flected direct solar term,this simpli fication of Eqs.(3)and (4)is reasonable and does not in-troduce signi ficant errors.2.2.Dif ficulties and problems in the retrieval of LST from space measurementsAs seen from Eqs.(3)and (4),estimating the LST from the radi-ance measured at the TOA requires corrections for both atmospheric and emissivity effects.Applying these corrections is not a simple task,and some key dif ficulties and problems involved in the retrieval of the LST must be overcome and resolved.These key dif ficulties and problems are the following:(1)The retrieval of the LST from space is mathematicallyunderdetermined and unsolvable (Hook et al.,1992;Kealy &Hook,1993).The RTE described in Eqs.(3)and (4)shows that,if the radiance is measured in N channels,there will always be N +1unknowns,corresponding to N emissivities in each channel and an unknown LST for N equations,even if quantities other than the emissivities and LST are known a priori.Such an ill-posed problem makes the solution of the RTE sets underdetermined at ground level even if the atmospheric quantities involved in Eqs.(3)and (4)are accurately estimated.To make LSTdeterministic,one or more of the LSEs must be known,or the LST and LSEs have to be simultaneously solved with the aid of some assumptions or constraints on the LSEs (Dash et al.,2002;Gillespie et al.,1996;Hook et al.,1992;Kealy &Hook,1993).(2)Measurements in the TIR region are highly correlated,implying that instrumental noise and errors in the atmospheric corrections exert strong in fluences on the accuracy of the LST retrieval.This correlation represents a problem even if the LST is made solvable either by reducing the number of unknowns or by increasing the number of equations through reasonable assumptions or con-straints on the LSEs (Gillespie et al.,1996;Li et al.,2013).These highly correlated measurements make LST retrieval unsta-ble and have hampered the methodological development of LST retrieval.(3)It is dif ficult to decouple the LST,the LSEs,and the downward at-mospheric radiance in the measured radiances.As seen from Eq.(4),the downward atmospheric radiance and the surface emitted radiance are coupled together through LSEs.The non-unity LSE of a natural surface reduces the surface-emitted radiance while increasing the re flection of the down-ward atmospheric radiance back to the atmosphere,which com-pensates partly for the reduction in the surface-emitted radiance.This process can reduce or increase the total surface-leaving radi-ance depending on the atmospheric and surface conditions.This coupling of the re flected downwelling and surface-emitted radi-ation can be used to retrieve LST with the online/of fline method but requires high spatial resolution data.However in passively observed multispectral TIR data,it is impossible to separate,on a physical basis,the contributions of the LST from the contribu-tions of the LSEs and the atmosphere in the observed radiance.For this reason,determining LST from space requires not only the atmospheric corrections but also the knowledge of the LSEs and vice versa.(4)The atmospheric corrections are dif ficult to implement.The pres-ence of the atmosphere between the surface and the sensors af-fects the radiances measured by a radiometer at the TOA.These radiances result primarily from emission/re flection at the surface modulated by the effects of the attenuation,and emission of the atmosphere.The atmospheric corrections thus consist of correcting the radiance measured by the sensors for the effects of atmospheric attenuation,emission and emission-re flection.Correcting for the atmospheric effects requires accurate knowl-edge of the vertical pro files of atmospheric water vapor and tem-perature both of which are highly variable (Perry &Moran,1994).(5)During the daytime,the re flected solar radiation is dif ficult to re-move in the MIR measurements.As mentioned earlier,the highly correlated TIR measurements make LST retrieval unstable even if the solution of the RTE sets becomes deterministic through some assumptions and constraints on the LSEs.In the MIR since the di-rect solar irradiation re flected by the surface is on the same order of magnitude as the radiance directly emitted by the surface,if the surface albedo is about 0.1,the introduction of the MIR chan-nels in LST retrieval signi ficantly reduces the correlation of the RTE sets and greatly improves the accuracy of the estimated LST (Li et al.,2013).Additionally,MIR channels are less sensitiv-ity to the water vapor in the atmosphere compared with TIR channels,and the LST retrieval from the MIR is only half as sensi-tive to errors in emissivity as that from the TIR (Mushkin et al.,2005).Therefore,LST retrieval with the MIR instead of the TIR sounds more appropriate.However,solar effects are dif ficult to eliminate in the MIR during the daytime because the separation of solar irradiation from the total energy measured in the MIR re-quires not only the accurate atmospheric information but also the knowledge of the bidirectional re flectivity of the surface.This information is typically unknown and affected by several factors (Adams et al.,1989;Mushkin et al.,2005),resulting in17Z.-L.Li et al./Remote Sensing of Environment 131(2013)14–37large uncertainties that can lead to an even larger error on the LST retrieved from MIR measurements.Therefore,while the in-troduction of the MIR channels may benefit the retrieval of the LST in certain cases,it can also introduce even larger uncer-tainties in others.(6)How to physically interpret the results of the LST measurementremains a crucial question.As noted by Prata et al.(1995),the def-inition of the surface temperature may depend strongly on the type of application and the method of measurement.Because the surface temperature T s in Eq.(4)is defined using the radiance emitted by a surface,this temperature is called the radiometric temperature(or the skin temperature)that corresponds to the ra-diation emitted from depths less than the penetration depth of a given wavelength(Becker&Li,1995;Norman&Becker,1995).The penetration depth is usually within a few millimeters in the TIR region(Wan,1999).This radiometric temperature physically differs from other definition of temperatures,such as the thermo-dynamic temperature defined for a medium in thermal equilibri-um and measured by a thermometer.For homogeneous and isothermal surfaces,the radiometric and thermodynamic temper-atures are reported to be equivalent.As the thermodynamic tem-perature is actually hard to measure in reality,even for water,the radiometric temperature is often the only practical measure for the homogeneous and isothermal surface.However,most surfaces are not in equilibrium and for heterogeneous and non-isothermal surfaces,these two temperatures are different.Considering that the spatial resolution of the current onboard sys-tems varies approximately from10−2to10km2,there may be several surface types with different temperatures and emissivities within one pixel,which complicates the physical understanding of the LST values retrieved from space and the relation of the ra-diometric temperature at large scales to other temperatures used in different applications.To date,no consensus has been reached on the definition of the LST for heterogeneous and non-isothermal surfaces,but the definition by Becker and Li (1995),which depends on the distributions of the LST and the LSE within a pixel,is measurable from space and is thus recommended for LST retrieval from space.(7)Validation of LST retrieved from spaceborne measurements atthe scale of the sensor's pixels is also challenging.Validation is problematic due to the difficulty of conducting in situ LST mea-surements,and in obtaining representative LST data at the scale of a single pixel.Generally,temperatures over the land surfaces vary strongly in space and time(Prata et al.,1995),and it is not unusual for the LST to vary by more than10K over just a few centimeters of distance or by more than1K in less than a minute over certain cover types.Appropriately scaling the satellite-derived LSTs to those measured at ground level,especially at large scale is also difficult.The strong spatial heterogeneity and temporal variation of the LST limits ground-based validation to several relatively homogeneous land surfaces,such as lakes,de-serts,and densely vegetated land using direct comparisons of in situ temperature measurements with temperatures retrieved from the satellite data(e.g.Hook et al.,2005,2003,2007).A com-plementary approach is to use sites which are homogenous in terms of emissivity using the radiance based validation approach (Hulley et al.,2009).Sand dunes can be one example of this type of sites which are referred to as pseudo-invariant sites(Hulley et al.,2009).Furthermore,how to perform a representative mea-surement of the LST of a complex heterogeneous surface is alsoa critical question.Scaling methods should be developed to relatethe measurements at different scales and help validate the re-trieved LST(Liu et al.,2006;Wu&Li,2009).Besides the difficulties mentioned above in the retrieval of LST from space,the accuracy of the LST data also depends on the performance of the cloud mask used to isolate clear sky data and on the quality of the TIR data,i.e.,the stability of the spectral response function g i(λ),the SNR and the accuracy of the radiometric calibration.3.Estimation of LST from spaceOver the past several decades,LST estimation from satellite TIR mea-surements has significantly improved.Many algorithms have been pro-posed to treat the characteristics of various sensors onboard different satellites and utilizing different assumptions and approximations for the RTE and LSEs.These algorithms can be roughly grouped into three categories:single-channel methods,multi-channel methods,and multi-angle methods,provided that the LSEs are known a priori.If the LSEs are not known,then the algorithms can be categorized into three types:stepwise retrieval method,simultaneous retrieval of LSEs and LST with known atmospheric information,and simultaneous retrieval with unknown atmospheric information.3.1.LST retrieval with known LSEs3.1.1.Single-channel methodThe single TIR channel method,also called the model emissivity method(Hook et al.,1992),uses the radiance measured by the satellite sensor in a single channel,chosen within an atmospheric window,and corrects the radiance for residual atmospheric attenuation and emission using atmospheric transmittance/radiance code that requires input data on the atmospheric profiles.LST is then retrieved from the radiance measured in this channel by inverting the RTE given in Eqs.(3)and(4), provided that the LSE is well known or estimated in advance(Chédin et al.,1985;Hook et al.,1992;Li et al.,2004a;Mushkin et al.,2005;Ottlé& Vidal-Madjar,1992;Price,1983;Susskind et al.,1984).Accurate deter-mination of the LST using this method requires high-quality atmospher-ic transmittance/radiance code to estimate the atmospheric quantities involved in Eqs.(3)and(4),good knowledge of the channel LSE,an ac-curate atmospheric profile,and a correct consideration of the topo-graphic effects(Sobrino et al.,2004b).Generally,the accuracy of atmospheric transmittance/radiance code is primarily limited by the radiative transfer model(RTM)used in the code and by the uncertainties in atmospheric molecular absorption co-efficients and aerosol absorption/scattering coefficients(Wan,1999). The most popular atmospheric RTMs,such as the series of MODTRAN (Berk et al.,2003)and4A/OP(Chaumat et al.,2009),have been widely used to perform atmospheric corrections and/or to simulate satellite TIR data.A few studies have shown that the accuracy of the different RTMs ranges from0.5%to2%within known atmospheric windows,such as 3.4–4.1μm and8–13μm,leading to uncertainties in the retrieved LST of0.4K to1.5K(Wan,1999).It is worth noting that the incomplete characterizations of atmospheric profiles used in compensation for at-mospheric absorption and path radiance constitute a serious problem even if the RTM itself is completely error-free(Gillespie et al.,2011). Studies have also demonstrated that an error of1%in the LSE can give rise to an error in the LST ranging from0.3K for a hot and humid atmo-sphere to0.7K for a cold and dry atmosphere(Dash et al.,2002).As the single channel is usually chosen around10μm where the LSE for most land surfaces can be known within a few percent,the uncertainty in LSE may lead to an error of1K to2K in LST if the single-channel meth-od is used.However,if the LSE is known at a wavelength within the TIR atmospheric window,then any error will be solely due to incorrect re-moval of the atmospheric contribution.Atmospheric profiles are gener-ally obtained either from ground-based atmospheric radiosoundings, from satellite vertical sounders or from meteorological forecasting models.Due to the high spatial and temporal variability of the atmo-spheric water vapor,the use of ground-based radiosoundings far from the area of interest and/or far from the time of satellite overpass may re-sult in large errors in the LST(Cooper&Asrar,1989).On top of these, radiosoundings reported measurement errors are of the order of0.5K18Z.-L.Li et al./Remote Sensing of Environment131(2013)14–37。

法律道德英语作文英文回答：In the intricate tapestry of human existence, where the threads of law and morality intertwine, I stand as an observer, contemplating the profound relationship that binds these two essential elements of our collective experience. Both law and morality, though distinct in their nature, share an inextricable connection, influencing and shaping each other in myriad ways.Law, in its essence, is a system of rules and regulations established by a governing authority to regulate the conduct of individuals within a society. It provides a framework for social order, defines acceptable behavior, and prescribes consequences for transgressions. Morality, on the other hand, encompasses a set of values, principles, and ethical beliefs that guide individual actions and shape our understanding of right and wrong.While law and morality may occasionally overlap, they are not synonymous. Laws are often codified and enforced through external sanctions, while morality relies on internalized values and the dictates of conscience. For example, a law may prohibit murder, but it cannot preventan individual from harboring murderous thoughts. Conversely, morality may condemn certain actions, such as lying or stealing, even though they may not be explicitly forbidden by law.The relationship between law and morality is a dynamic one, constantly evolving and adapting to changing societal norms and values. Laws may be enacted or repealed toreflect shifts in moral sensibilities, while moralprinciples can influence the interpretation and enforcement of laws. For instance, the abolition of slavery in many countries was driven by growing moral outrage against this inhumane practice.In some instances, law and morality may come into conflict, presenting individuals with ethical dilemmas. A law may require a person to do something that they believeis morally wrong, or it may prohibit an action that they believe is morally justified. In such cases, individuals must navigate the tension between legal obligations and moral convictions, often making difficult decisions that test their integrity.The interplay between law and morality is evident in countless aspects of our lives. Consider the legal duty to report crimes, which stems from a moral obligation to protect society from harm. Or, the ethical considerations that guide the medical profession, balancing legal requirements with the moral imperative to preserve patient autonomy and well-being.In conclusion, the relationship between law and morality is a complex and multifaceted one. While distinct in their nature, they are interconnected and mutually influential. Law provides a foundation for social order, while morality shapes our individual actions and ethical choices. By understanding the interplay between these two essential elements, we can navigate the complexities of human behavior and strive to live in a just and virtuoussociety.中文回答：法律与道德，这两大要素在人类存在的复杂图景中交织在一起，构成了社会秩序的经纬线。

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在大学遇到的问题,怎样解决的英语作文全文共3篇示例，供读者参考篇1The Trials and Triumphs of University LifeWhen I arrived at university, I was filled with a heady mix of excitement and trepidation. Having grown up in a small town, the big city campus felt like an alien world - crowded, chaotic, and more than a little intimidating. I knew university would be challenging, but I had no idea just how many hurdles lay ahead. Looking back now after four years, I can't help but feel immense pride at how far I've come and the obstacles I've overcome.My first major problem hit me like a ton of bricks just a few weeks into my first semester - I completely bombed my first round of midterm exams. Maybe it was overconfidence from breezing through high school or just poor time management skills, but I did not take my studying seriously enough. When I saw those abysmal grades, I felt like the wind had been knocked out of me. I started questioning whether I had what it took to make it in university. Calling my parents in tears, I remember my dad giving me some tough love: "This is a wake-up call, but it'snot the end of the world. You can turn this around, but it'll take hard work."And hard work it was. I drastically overhauled my entire study process - I started meticulously planning out my days, formed study groups with classmates, and spent endless hours poring over textbooks and notes in the library. Bit by bit, I felt myself steadily improving. By the time final exams rolled around, I was getting A's and B's. That feeling of accomplishment was unbeatable. I had learned studying wasn't just about brute force grinding, but developing strategies and habits tailored for my learning style. More importantly, I gained confidence that I could overcome even my biggest academic shortcomings.My second year brought fresh challenges in the form of managing my social life. It's easy to get swept up in the party culture of university, and I'll admit I probably went a bit overboard at times with nights out. I struggled to find that balance between having fun and staying on top of my studies. There were too many mornings waking up hungover and dreading my 8am lectures. By the end of first semester, my grades had slipped and I felt like I was losing my way a bit.This time, thankfully, I was able to self-correct before things went totally off the rails. I reconnected with my priorities andscaled back on going out as much. I deleted some time-wasting apps off my phone. And I surrounded myself with positive friendships with people who were focused on their goals. Having a solid support system made such a difference in keeping me grounded and motivated. I'm grateful I was able to turn that around before throwing away all the hard work I had put in.One of the biggest tests of my time in university, however, wasn't directly academic at all. Towards the end of my third year, my mom was diagnosed with breast cancer. It was a scary, uncertain time, and I considered taking a leave of absence to go home and be with my family. Thankfully, my professors were incredibly understanding and accommodating, allowing me to keep up with my coursework remotely when I could. But there were still many emotional ups and downs that took a toll on my state of mind and made focusing difficult.Counseling services on campus were a huge help in getting me through this challenging period. Having an outlet to process what I was going through, manage my stress and anxiety, and develop healthy coping mechanisms was vital. I also made sure to prioritize self-care, whether that was exercise, reading for pleasure, or just getting away from it all for a bit. Dealing with this kind of seismic life event while juggling a full academic loadpushed me to my limits in some ways. But I'm proud that I was able to persevere and make it through one of the toughest times in my life so far.Now, as I prepare to graduate and take that nerve-wracking step into the "real world", I feel a tremendous sense of growth and maturity compared to the bright-eyed but slightly naive teenager who first stepped onto campus. The academics have been grueling at times, but it's battling all the other unexpected adversities that has given me invaluable perspective, resilience, and self-awareness. I've gained priceless problem-solving abilities from overcoming setbacks in my studies, social life, mental health, and personal life.More than anything, university has taught me that no matter how daunting the challenge, there is always a way forward if you stay determined and ask for help when needed. I've learned the importance of work-life balance, self-care, and having a strong support network. Perhaps most importantly, I've developed unshakable belief in my capabilities to adapt and overcome even the most trying of circumstances.The path has been winding with many bumps along the way, but that's ultimately what has made this journey so rewarding. I may be leaving this campus with a degree, but the real prize isthe perseverance, grit, and perspective that no classroom could teach. While I'll forever cherish the incredible experiences of university life, I'm also excited to take these hard-earned lessons into whatever new challenges lie ahead. Bring it on, world - thanks to these last four years, I've got this.篇2Problems at University and How I Overcame ThemWhen I started university, I was incredibly excited but also quite nervous. I had heard so many stories about the challenges of being a student - the heavy workload, the difficulty in managing your time, finding a balance between academics and social life. Little did I know just how many obstacles I would face during those pivotal years. However, I'm proud to say that through determination and resourcefulness, I was able to overcome many of the problems that initially seemed insurmountable. Here are some of the key issues I grappled with and the strategies I used to resolve them.The Transition from High SchoolOne of the very first hurdles I ran into was simply adjusting to the vastly different environment and expectations of university compared to high school. In high school, the classeswere smaller, the teachers handheld you through assignments, and the overall workload was much lighter. All of a sudden at university, I was one student among hundreds in huge lecture halls. The professors trained you through a fire hose of information and you were expected to be an independent,self-motivated learner.It took me quite a while to adapt to this new academic culture. At first, I was completely overwhelmed trying to take verbatim notes on every single thing the professors said. I soon realized this approach was inefficient and caused me to lose focus during lectures. Through trial and error, I developed the skill of summarizing key concepts in my own words as the lecturer spoke. I also got into the habit of reviewing material soon after class so it would solidify in my memory.Developing better study habits such as this was crucial, but I also had to mentally prepare myself that university required a much higher level of self-discipline than high school. There was no one keeping tabs on whether I was getting assignments done or not. If I didn't hold myself accountable, my grades would quickly suffer. It was a harsh wake-up call, but slowly ingraining habits like time blocking, prioritization of tasks, and working ahead of deadlines allowed me to stay on top of my coursework.Managing My FinancesBesides adapting academically, another major challenge I faced was handling my finances independently for the first time. My parents gave me a modest monthly allowance, but It was up to me to budget for expenses like groceries, transportation, textbooks, and entertainment. This was made even trickier with a constantly fluctuating class and work schedule each semester.Early on, I definitely made some mistakes with spending beyond my means, wasting money on frivolous things, and not tracking my purchases diligently. However, I knew I needed to get a handle on my finances before I dug myself into debt. I started by analyzing all my fixed costs like rent and estimating variable expenses like food and going out. Then I set a weekly allowance for discretionary spending that I stuck to rigidly.I became addicted to finding student discounts and looking for deals wherever possible. Instead of buying costly new textbooks, I would rent them or buy used copies online. Rather than constantly getting food delivered, I learned to meal prep at home for the week. Finding a part-time job on campus for some income was also a big help for making ends meet.It took discipline but I slowly optimized where I was spending my money versus where I could be saving. Creating abudget and monitoring every expense with financial apps was a major turning point in taking control of my spending habits.Maintaining a Social LifeAlong with the financial strain, another difficulty I wrestled with was preserving a social life amidst the demands of academics. In high school, you naturally saw your friends every day so maintaining those relationships was relatively frictionless. At university however, people had vastly different schedules of classes, jobs, clubs and so on. If you didn't be proactive about it, it was easy to become isolated.At the start of each semester, I would map out all my friend's schedules and find the small pockets of overlap where we could connect. Coordinating everyone's availability was like a game of Tetris, but I made sure to block off those times as sacred. Even if it was just for a meal together or to sit and chat between classes, it was so important for staying sane.I also consciously built out my social circles through joining clubs and intramural sports teams related to my interests. This allowed me to meet new people with common passions outside of just my classes. I can't emphasize enough how crucial it was to have both a solid friend group as well as some non-academic outlets for alleviating stress.Believe it or not, forming study groups for certain courses also turned out to be a lifeline socially and academically. It provided built-in time to be around colleagues while keeping each other accountable towards shared goals.At first I was apprehensive about studying with others, but it quickly became some of my most productive sessions.Impostor Syndrome and Self-DoubtDespite my best efforts, there were still many moments when I felt in over my head and started to question my capabilities. Impostor syndrome - that feeling of being a fraud who didn't truly belong - weighed heavily on me at times. In university, you're surrounded by brilliant classmates and faculty who can make you feel very small.Whenever I received a poor test score or negative feedback, I would become consumed with doubt about whether I had what it took. My self-confidence would plummet and I would enter a spiral of negative thoughts. It took me a long time to develop strategies for safeguarding my belief in myself.One of the most powerful revelations was that everyone doubts themselves from time to time - even the most accomplished students and professors. Normalizing those feelings of insecurity and separating them from my intrinsicself-worth was huge. It allowed me to still feel those doubts, but not be dragged down into paralysis by them.Building a positive self-talk loop was also transformative. Whenever I caught myself slipping into harsh, self-critical thoughts, I would counter them with affirmations about my strengths and capabilities based on evidence of past achievements. Positive mantras like "You've got this" or "Trust the process" became grounding forces.I also had to learn to contextualize failures as part of the learning journey rather than defining my entire self-worth in that moment. If I didn't perform well on an assignment, I would dispassionately analyze what I could improve on without judgement. Then I would make a concrete plan for applying those lessons on the next opportunity. Bottomline, I learned to be kinder and more compassionate with myself through those bouts of self-doubt.Overall, university presented me with a crash course on prioritizing, problem-solving, and believing in my abilities to overcome obstacles. The challenges I described were some of the most formidable, but there were countless other speed bumps along the way too. What I can say is that each issue I was able to resolve made me more resilient and confident.By the time I walked across that stage at graduation, earning my degree was one of my proudest moments. However, the true accomplishment was the perseverance, ingenuity, and growth that I demonstrated in facing down every single challenge head-on. Those skills of learning how to adapt, grind through adversity, and maintain balance will be invaluable to me no matter what other curveballs life throws my way. For that invaluable education outside the classroom, I'll be forever grateful for my university experience.篇3Problems Encountered at University and How to Overcome ThemCollege life is often romanticized as the best years of one's life – a time of intellectual awakening, personal growth, and forging lifelong friendships. While this can certainly be true, the reality is that university also brings with it a unique set of challenges that many students struggle to overcome. From time management issues to mental health concerns and financial difficulties, the obstacles faced during these formative years can feel overwhelming. However, with the right mindset and coping strategies, it is possible to navigate these hurdles and emerge stronger on the other side.One of the most common problems faced by students is the struggle to balance academic demands with personal responsibilities and social activities. The transition from high school to university often comes with a newfound sense of freedom, which can be both exhilarating and overwhelming. Suddenly, students are responsible for managing their own schedules, attending classes, completing assignments, and studying for exams – all while trying to maintain a social life and potentially juggling a part-time job.Time management is key to striking this delicate balance. Creating a structured routine and prioritizing tasks can help prevent procrastination and ensure that academic obligations are met without sacrificing self-care or leisure time. Utilizing tools like calendars, to-do lists, and productivity apps can also aid in staying organized and on track.Additionally, it's important to recognize when one is struggling and seek help when needed. Many universities offer academic advising services, tutoring programs, and writing centers to assist students in overcoming academic challenges. Building a support network of peers, mentors, and professors can also provide invaluable guidance and encouragement.Another significant challenge faced by many students is the impact of university life on mental health. The pressures of academic performance, social dynamics, and newfound independence can take a toll on emotional well-being. Feelings of anxiety, depression, and loneliness are not uncommon, particularly during the first year of college.Prioritizing self-care is crucial in maintaining good mental health. This can include practices such as regular exercise, mindfulness or meditation, getting enough sleep, and engaging in hobbies or activities that bring joy and relaxation. It's also essential to cultivate a strong support system, whether it's through joining student organizations, attending campus events, or seeking counseling services offered by the university.Financial difficulties can also pose a significant challenge for many students. The rising costs of tuition, housing, textbooks, and living expenses can create substantial financial strain, leading to stress and potentially impacting academic performance.To alleviate financial burdens, students may need to explore various options, such as applying for scholarships, grants, or student loans. Additionally, seeking part-time employment or work-study programs can help offset expenses while gainingvaluable work experience. Careful budgeting and financial literacy are also essential skills to develop during this time.Despite these challenges, the university experience can be incredibly rewarding and provide opportunities for personal and intellectual growth that shape the rest of one's life. By developing effective coping strategies, seeking support when needed, and maintaining a balanced perspective, students can not only overcome the obstacles they face but also emerge as more resilient and well-rounded individuals.One invaluable lesson that university teaches is the importance of adaptability and perseverance in the face of adversity. The ability to problem-solve, think critically, and navigate complex situations are skills that will serve students well beyond their academic careers. Embracing challenges as opportunities for growth and learning can transform what may initially seem like insurmountable obstacles into stepping stones towards success.Furthermore, the university experience fosters independence and self-discovery. Away from the familiar comforts of home, students are forced to confront their own values, beliefs, and aspirations, ultimately shaping their sense of identity and purpose. This process of self-exploration can be bothexhilarating and daunting, but it is an essential step towards becoming a well-rounded, self-aware individual.Ultimately, the challenges faced during university years are not unique to any one student; rather, they are shared experiences that bind together the broader community of learners. By embracing a spirit of resilience, seeking support when needed, and maintaining a balanced perspective, students can not only overcome the obstacles they face but also emerge as more resilient and well-rounded individuals, equipped with the skills and knowledge to navigate the complexities of life beyond the campus gates.。

保护伊犁鼠兔的英语作文The Yili pika, also known as the Ili pika or the magic rabbit, is a small mammal that is native to the Tianshan mountain range in the Xinjiang region of China. This adorable creature has captured the hearts of many due to its round body, short limbs, and big ears. However, the Yili pika is currently facing the threat of extinction, with only a few hundred individuals left in the wild. Inthis essay, I will discuss the importance of protecting the Yili pika, the factors contributing to its decline, and the potential solutions to ensure the survival of this precious species. First and foremost, it is crucial to recognize the significance of protecting the Yili pika. As a unique and endemic species to the Tianshan mountain range, the Yili pika plays a vital role in maintaining the ecological balance of its habitat. As a herbivorous animal, the Yili pika helps to control vegetation growth and serves as a food source for predators such as foxes and birds of prey. Furthermore, the presence of the Yili pika indicates the health of the ecosystem, making it an important indicator species for conservation efforts. Therefore, the protection of the Yili pika is not only essential for the survival of the species itself but also for the overall well-being of the Tianshan mountain range. Several factors have contributed to the decline of the Yili pika population. One of the primary threats is habitat loss and fragmentation due to human activities such as mining, agriculture, and infrastructure development. As human populations continue to expand, the natural habitat of the Yili pika is increasingly encroached upon, leading to a loss of suitable living space and isolation of populations. Additionally, climate change has also impacted the Yili pika's habitat, causing shifts in vegetation patterns and altering theavailability of food sources. These environmental changes have further exacerbated the challenges faced by the Yili pika, making it more vulnerable to extinction. In addition to habitat loss, the Yili pika is also threatened by predation, competition, and disease. Predators such as foxes and birds of prey pose a significant threat to the Yili pika population, especially in areas where their natural habitats overlap. Furthermore, the introduction of non-native species, such as domestic livestock, has led to increased competition for resources and the spread of diseases that can affect the Yili pika. These combined factors haveplaced immense pressure on the survival of the Yili pika, pushing the species to the brink of extinction. Despite the challenges faced by the Yili pika, there are potential solutions that can be implemented to ensure the protection and conservation of this precious species. One approach is the establishment of protected areas and wildlife reserves specifically designed to safeguard thenatural habitat of the Yili pika. By designating these areas as conservation zones, it will help to mitigate the impacts of habitat loss and fragmentation, providinga safe haven for the Yili pika to thrive. Additionally, conservation efforts can also focus on restoring degraded habitats and creating wildlife corridors to connect isolated populations, promoting genetic diversity and resilience. Furthermore, community-based conservation initiatives can play a crucial role in raising awareness and garnering support for the protection of the Yili pika. Engaging local communities and stakeholders in conservation efforts can lead tothe development of sustainable practices that minimize human impacts on the Yili pika's habitat. Through education and outreach programs, individuals can learn about the importance of coexisting with wildlife and the value of preserving biodiversity for future generations. By fostering a sense of stewardship and responsibility, communities can become active participants in the conservation of the Yili pika and its habitat. Another important aspect of protecting the Yili pika is the implementation of research and monitoring programs to better understand the species' ecology and behavior. By studying the population dynamics, reproductive biology, and dietary preferences of the Yili pika, conservationists can gather valuable information that can inform targeted conservation strategies. Additionally, ongoing monitoring efforts can track changes in population size and distribution, identify emerging threats, and assess the effectiveness of conservation measures. This scientific knowledge is essential for making informed decisions and adapting conservation efforts to address the evolving needs of the Yili pika. In conclusion, the protection of the Yili pika is of utmost importance to ensure the preservation of this unique and charismatic species. By addressing the factors contributing to its decline and implementing proactive conservation measures, we can work towards securing a future for the Yili pika in its natural habitat. Through collaborative efforts involving government agencies, conservationorganizations, local communities, and scientific research, we can strive toprotect the Yili pika and uphold the ecological integrity of the Tianshan mountain range. It is our collective responsibility to safeguard the Yili pika and to cherish the magic rabbit for generations to come.。

The Essence of a Meaningful LifeIn the tapestry of life, each thread represents a moment, a choice, an experience. To lead a meaningful life is to weave these threads into a harmonious pattern that resonates with one's core values and aspirations. For me, the essence of a meaningful life lies in three interconnected principles: growth, connection, and contribution.Growth is the continuous effort to expand one's horizons, both internally and externally. It involves a relentless pursuit of knowledge, skills, and understanding, as well as a willingness to embrace change and embrace new challenges. Growth, for me, is not just about acquiring new things, but also about shedding old ideas and beliefs that no longer serve me. It is about becoming a better version of myself, constantly evolving and adapting to the world around me.Connection is the thread that binds me to others and to the world. It is about building meaningful relationships, both personal and professional, that enrich my life and the lives of those I touch. Connection is about understandingthat we are all part of a larger web of existence and that our actions, even the smallest ones, have ripple effects that extend far beyond ourselves. It is about finding common ground and shared values with others, and working together to create positive change in the world.Contribution is the final strand in the tapestry of a meaningful life. It is about giving back to society, to the community, and to those who have come before us. It is about using our talents, skills, and resources to make the world a better place, even in the smallest ways. Contribution is about leaving the world a little better than we found it, leaving a legacy that inspires and encourages others to do the same.Taken together, these three principles form the foundation of a meaningful life for me. They are not separate entities, but are interconnected and overlap, creating a rich and fulfilling existence. Growth allows me to constantly improve and evolve, connection keeps me grounded and engaged with the world, and contribution gives me a sense of purpose and fulfillment.In conclusion, a meaningful life is not one that is free from challenges and difficulties, but one that isfilled with growth, connection, and contribution. It is a life that is lived with intention and purpose, a life that is constantly seeking to improve and contribute, a lifethat is deeply connected to the world and the people around us. It is a life that is lived with passion, courage, and compassion, and one that leaves a lasting impact on the world.**有意义的生活之精髓**在生活的织锦中，每一根线都代表了一个时刻、一个选择、一个经历。

CHAPTER18FFT ConvolutionThis chapter presents two important DSP techniques, the overlap-add method, and FFT convolution. The overlap-add method is used to break long signals into smaller segments for easier processing. FFT convolution uses the overlap-add method together with the Fast Fourier Transform, allowing signals to be convolved by multiplying their frequency spectra. For filter kernels longer than about 64 points, FFT convolution is faster than standard convolution, while producing exactly the same result.The Overlap-Add MethodThere are many DSP applications where a long signal must be filtered insegments. For instance, high fidelity digital audio requires a data rate ofabout 5 Mbytes/min, while digital video requires about 500 Mbytes/min. Withdata rates this high, it is common for computers to have insufficient memory tosimultaneously hold the entire signal to be processed. There are also systemsthat process segment-by-segment because they operate in real time. Forexample, telephone signals cannot be delayed by more than a few hundredmilliseconds, limiting the amount of data that are available for processing atany one instant. In still other applications, the processing may require that thesignal be segmented. An example is FFT convolution, the main topic of thischapter.The overlap-add method is based on the fundamental technique in DSP: (1)decompose the signal into simple components, (2) process each of thecomponents in some useful way, and (3) recombine the processed componentsinto the final signal. Figure 18-1 shows an example of how this is done forthe overlap-add method. Figure (a) is the signal to be filtered, while (b) showsthe filter kernel to be used, a windowed-sinc low-pass filter. Jumping to thebottom of the figure, (i) shows the filtered signal, a smoothed version of (a).The key to this method is how the lengths of these signals are affected by theconvolution. When an N sample signal is convolved with an M sample311312The Scientist and Engineer's Guide to Digital Signal Processingfilter kernel, the output signal is samples long. For instance, the inputN%M&1signal, (a), is 300 samples (running from 0 to 299), the filter kernel, (b), is 101samples (running from 0 to 100), and the output signal, (i), is 400 samples(running from 0 to 399).In other words, when an N sample signal is filtered, it will be expanded bypoints to the right. (This is assuming that the filter kernel runs from M&1index 0 to M. If negative indexes are used in the filter kernel, the expansionwill also be to the left). In (a), zeros have been added to the signal betweensample 300 and 399 to illustrate where this expansion will occur. Don't beconfused by the small values at the ends of the output signal, (i). This issimply a result of the windowed-sinc filter kernel having small values near itsends. All 400 samples in (i) are nonzero, even though some of them are toosmall to be seen in the graph.Figures (c), (d) and (e) show the decomposition used in the overlap-addmethod. The signal is broken into segments, with each segment having 100samples from the original signal. In addition, 100 zeros are added to the rightof each segment. In the next step, each segment is individually filtered byconvolving it with the filter kernel. This produces the output segments shownin (f), (g), and (h). Since each input segment is 100 samples long, and thefilter kernel is 101 samples long, each output segment will be 200 sampleslong. The important point to understand is that the 100 zeros were added toeach input segment to allow for the expansion during the convolution.Notice that the expansion results in the output segments overlapping eachother. These overlapping output segments are added to give the outputsignal, (i). For instance, samples 200 to 299 in (i) are found by adding thecorresponding samples in (g) and (h). The overlap-add method producesexactly the same output signal as direct convolution. The disadvantage isa much greater program complexity to keep track of the overlappingsamples.FFT ConvolutionFFT convolution uses the principle that multiplication in the frequencydomain corresponds to convolution in the time domain. The input signal istransformed into the frequency domain using the DFT, multiplied by thefrequency response of the filter, and then transformed back into the timedomain using the Inverse DFT. This basic technique was known since thedays of Fourier; however, no one really cared. This is because the timerequired to calculate the DFT was longer than the time to directly calculatethe convolution. This changed in 1965 with the development of the FastFourier Transform (FFT). By using the FFT algorithm to calculate theDFT, convolution via the frequency domain can be faster than directlyconvolving the time domain signals. The final result is the same; only thenumber of calculations has been changed by a more efficient algorithm. Forthis reason, FFT convolution is also called high-speed convolution.Chapter 18- FFT Convolution313Sample number -4-224Sample numberSample number 0100200300400-424Sample numberSample numberSample number314The Scientist and Engineer's Guide to Digital Signal ProcessingFFT convolution uses the overlap-add method shown in Fig. 18-1; only the waythat the input segments are converted into the output segments is changed.Figure 18-2 shows an example of how an input segment is converted into anoutput segment by FFT convolution. To start, the frequency response of thefilter is found by taking the DFT of the filter kernel, using the FFT. Forinstance, (a) shows an example filter kernel, a windowed-sinc band-pass filter.The FFT converts this into the real and imaginary parts of the frequencyresponse, shown in (b) & (c). These frequency domain signals may not looklike a band-pass filter because they are in rectangular form. Remember, polarform is usually best for humans to understand the frequency domain, whilerectangular form is normally best for mathematical calculations. These realand imaginary parts are stored in the computer for use when each segment isbeing calculated.Figure (d) shows the input segment to being processed. The FFT is used to findits frequency spectrum, shown in (e) & (f). The frequency spectrum of theoutput segment, (h) & (i) is then found by multiplying the filter's frequencyresponse, (b) & (c), by the spectrum of the input segment, (e) & (f). Sincethese spectra consist of real and imaginary parts, they are multiplied accordingto Eq. 9-1 in Chapter 9. The Inverse FFT is then used to find the outputsegment, (g), from its frequency spectrum, (h) & (i). It is important torecognize that this output segment is exactly the same as would be obtained bythe direct convolution of the input segment, (d), and the filter kernel, (a).The FFTs must be long enough that circular convolution does not take place(also described in Chapter 9). This means that the FFT should be the samelength as the output segment, (g). For instance, in the example of Fig. 18-2,the filter kernel contains 129 points and each segment contains 128 points,making output segment 256 points long. This calls for 256 point FFTs to beused. This means that the filter kernel, (a), must be padded with 127 zeros tobring it to a total length of 256 points. Likewise, each of the input segments,(d), must be padded with 128 zeros. As another example, imagine you needto convolve a very long signal with a filter kernel having 600 samples. Onealternative would be to use segments of 425 points, and 1024 point FFTs.Another alternative would be to use segments of 1449 points, and 2048 pointFFTs.Table 18-1 shows an example program to carry out FFT convolution. Thisprogram filters a 10 million point signal by convolving it with a 400 point filterkernel. This is done by breaking the input signal into 16000 segments, witheach segment having 625 points. When each of these segments is convolvedwith the filter kernel, an output segment of points is625%400&1'1024produced. Thus, 1024 point FFTs are used. After defining and initializing allthe arrays (lines 130 to 230), the first step is to calculate and store thefrequency response of the filter (lines 250 to 310). Line 260 calls amythical subroutine that loads the filter kernel into XX[0] throughXX[399], and sets XX[400] through XX[1023] to a value of zero. Thesubroutine in line 270 is the FFT, transforming the 1024 samples held inXX[ ] into the 513 samples held in REX[ ] & IMX[ ], the real andChapter 18- FFT Convolution315Sample number 064128192256-6.0-4.0-2.00.02.04.06.0Sample number -2.0-1.00.01.02.0Frequency 064128-100-50050100Frequency 064128-100-50050100FrequencyThe Scientist and Engineer's Guide to Digital Signal Processing316The FOR-NEXT loop between lines 340 and 580 controls how the 16000segments are processed. In line 360, a subroutine loads the next segment to beprocessed into XX[0] through XX[624], and sets XX[625] through XX[1023]to a value of zero. In line 370, the FFT subroutine is used to find thissegment's frequency spectrum, with the real part being placed in the 513 pointsof REX[ ], and the imaginary part being placed in the 513 points of IMX[ ].Lines 390 to 430 show the multiplication of the segment's frequency spectrum,held in REX[ ] & IMX[ ], by the filter's frequency response, held in REFR[ ]and IMFR[ ]. The result of the multiplication is stored in REX[ ] & IMX[ ],overwriting the data previously there. Since this is now the frequency spectrumof the output segment, the IFFT can be used to find the output segment. This isdone by the mythical IFFT subroutine in line 450, which transforms the 513points held in REX[ ] & IMX[ ] into the 1024 points held in XX[ ], the outputsegment.Lines 470 to 550 handle the overlapping of the segments. Each output segmentis divided into two sections. The first 625 points (0 to 624) need to becombined with the overlap from the previous output segment, and then writtento the output signal. The last 399 points (625 to 1023) need to be saved so thatthey can overlap with the next output segment.To understand this, look back at Fig 18-1. Samples 100 to 199 in (g) need tobe combined with the overlap from the previous output segment, (f), and canthen be moved to the output signal (i). In comparison, samples 200 to 299 in(g) need to be saved so that they can be combined with the next outputsegment, (h).Now back to the program. The array OLAP[ ] is used to hold the 399 samplesthat overlap from one segment to the next. In lines 470 to 490 the 399 valuesin this array (from the previous output segment) are added to the outputsegment currently being worked on, held in XX[ ]. The mythical subroutine inline 550 then outputs the 625 samples in XX[0] to XX[624] to the file holdingthe output signal. The 399 samples of the current output segment that need tobe held over to the next output segment are then stored in OLAP[ ] in lines 510to 530.After all 0 to 15999 segments have been processed, the array, OLAP[ ], willcontain the 399 samples from segment 15999 that should overlap segment16000. Since segment 16000 doesn't exist (or can be viewed as containing allzeros), the 399 samples are written to the output signal in line 600. Thismakes the length of the output signal points.16000×625%399'10,000,399This matches the length of input signal, plus the length of the filter kernel,minus 1.Speed ImprovementsWhen is FFT convolution faster than standard convolution? The answerdepends on the length of the filter kernel, as shown in Fig. 18-3. The timeChapter 18- FFT Convolution317 100 'FFT CONVOLUTION110 'This program convolves a 10 million point signal with a 400 point filter kernel. The input120 'signal is broken into 16000 segments, each with 625 points. 1024 point FFTs are used.130 '130 ''INITIALIZE THE ARRAYS140 DIM XX[1023] 'the time domain signal (for the FFT)150 DIM REX[512] 'real part of the frequency domain (for the FFT)160 DIM IMX[512] 'imaginary part of the frequency domain (for the FFT)170 DIM REFR[512] 'real part of the filter's frequency response180 DIM IMFR[512] 'imaginary part of the filter's frequency response190 DIM OLAP[398] 'holds the overlapping samples from segment to segment200 '210 FOR I% = 0 TO 398'zero the array holding the overlapping samples220 OLAP[I%] = 0230 NEXT I%240 '250 ' 'FIND & STORE THE FILTER'S FREQUENCY RESPONSE260 GOSUB XXXX 'Mythical subroutine to load the filter kernel into XX[ ]270 GOSUB XXXX 'Mythical FFT subroutine: XX[ ] --> REX[ ] & IMX[ ]280 FOR F% = 0 TO 512 'Save the frequency response in REFR[ ] & IMFR[ ]290 REFR[F%] = REX[F%]300 IMFR[F%] = IMX[F%]310 NEXT F%320 '330 ' 'PROCESS EACH OF THE 16000 SEGMENTS340 FOR SEGMENT% = 0 TO 15999350 '360 GOSUB XXXX 'Mythical subroutine to load the next input segment into XX[ ]370 GOSUB XXXX 'Mythical FFT subroutine: XX[ ] --> REX[ ] & IMX[ ]380 '390 FOR F% = 0 TO 512'Multiply the frequency spectrum by the frequency response400 TEMP = REX[F%]*REFR[F%] - IMX[F%]*IMFR[F%]410 IMX[F%]= REX[F%]*IMFR[F%] + IMX[F%]*REFR[F%]420 REX[F%]= TEMP430 NEXT F%440 '450 GOSUB XXXX'Mythical IFFT subroutine: REX[ ] & IMX[ ] --> XX[ ]460 '470 FOR I% = 0 TO 398'Add the last segment's overlap to this segment480 XX[I%] = XX[I%] + OLAP[I%]490 NEXT I%500 '510 FOR I% = 625 TO 1023'Save the samples that will overlap the next segment520 OLAP[I%-625] = XX[I%]530 NEXT I%540 '550 GOSUB XXXX 'Mythical subroutine to output the 625 samples stored560 ''in XX[0] to XX[624]570 '580 NEXT SEGMENT%590 '600 GOSUB XXXX 'Mythical subroutine to output all 399 samples in OLAP[ ]610 ENDTABLE 18-1for standard convolution is directly proportional to the number of points inthe filter kernel. In comparison, the time required for FFT convolutionincreases very slowly, only as the logarithm of the number of points in the318The Scientist and Engineer's Guide to Digital Signal ProcessingImpulse Response Length。

有关开学的英语日记【十篇】1.有关开学的英语日记The new semester began again. Facing the first ray of sunshine in the morning, we returned to the beautiful campus and began the campus life of the new semester.In the past journey, whether you have laughter or sunshine, it has become an eternal memory. Add a lock to close it! Before us. Everything is new, you see? New life is breaking through the ground. Due to the cruelty of reality, we will incarnate into knights, erase the trauma on our chest, take our weapons and get ready to go. Are you sure about the goal of the new semester?Maybe your goal is to enter your ideal high school. Maybe your goal is to catch up with a classmate. Your goal can be different, but it must not be absent. More importantly, after having a goal, we must take action and go all out. There is no need to wipe a large amount of paper, but you must have a goal in your mind. This road will not be plain sailing. It will always make you cry, but it will always be sunny after cloudy days, because you are a knight, have chivalry, brave knight,and will not be knocked down by any difficulties!We need to make a step-by-step study, treat the school rules and class rules seriously, and resolutely not do anything detrimental to the identity of students. We will be full of passion and embark on the journey. The future is ours! I choose! I like it!We are about to embark on a journey full of passion. The future is for me. This week is the first week of school. After the tense and busy military training, we have ushered in a new high school life, a new environment, new classmates, a new beginning and a new self. New proud and healthy figures are jumping on the basketball court. Turn, break, stop and shoot, a series of actions are completed at one go. The ball is in! The audience cheered and sparkled with new style.Now we are moving towards a new goal at a new starting point!2.有关开学的英语日记I walked into the new classroom for the first week, full of anxiety. My head teacher, Mr. Zhao, is a very strict teacher. When I returned to school for the firsttime, I still didn’t adapt to such strict management, but I was a person with strong adaptability. Therefore, after returning to school for the second time, I gradually adapted to the teacher’s management style.As the saying goes, a good beginning is half success. The first class I had was geography. The teacher gavea lively and colorful lecture, and I also heard it. A45 minute class passed in a blink of an eye. The subsequent classes were also very interesting, which made me find it a very happy thing to listen to the class.When I was in junior high school, I imagined my high school life more than once. I longed for it to be full of fun and laughter, but at the same time I worried that it was boring and full of pressure. But through the first day of study, I found that high school life is a combination of the two, full of fun and pressure. I think the difference between learning in senior high school and learning in junior high school is that senior high school is mainly autonomous learning, while junior high school is more teachers’ hand-in-hand teaching. In addition, the speed of teachers’ lectures is also significantly faster than that of junior middle school.Therefore, I believe that adapting to the autonomous learning style of high school and the speed of teachers’ lectures as soon as possible is the key to improve learning efficiency.When I was just promoted from junior high school to senior high school and just integrated into a new group, I was not very familiar with my classmates and teachers. Therefore, I will often miss our original class and the original classmates. However, only after this week, I found that the original unfamiliar faces became more and more familiar and talked with my classmates more and more, I believe that my new class is no inferior to my original class.I believe that under the leadership of the head teacher, all teachers and the concerted efforts of the students, our class will make greater progress in the future!3.有关开学的英语日记I entered high school and experienced everything new. At the beginning, I was not used to this strange campus, but after several classes of experience life, I have slowly begun to accept this very strange campusToday is the first day of our school. We have stepped into a new campus, got familiar with new students, contacted new teachers, experienced a new life and entered a new environment. In a word, everything in this school is strange in my eyes, but it is even more novel. This also means that we have stepped into the door of youth.By the afternoon, I was familiar with everything about the school. But when I was communicating with my classmates, the school informed us to weed the playground.So I went to the playground with my classmates with a trace of excitement. Unfortunately, I didn’t bring any tools, so I had to pull them down one by one by hand. When one third of the grass was removed, my hand had been soaked in the water. At this time, I thought, “when all the grass was removed, my hand will break.”so I thought of a good idea, Take the loose soil to one side by hand, and plant a winter grass gently with a sharp stone to pull it down smoothly. This method is cumbersome, but for me, who has no ability to bind chickens, this is already a method. By analogy, I alwaysfollow this method. In the end, the grass is not only pulled out, I didn’t hurt my hand either. I thought to myself, “isn’t this a matter of killing two birds with one stone?”How time flies! This weeding activity is over. But at the same time, I am also pleased that I have pulled down so much grass.Yes, life lies in sports, life lies in learning, life lies in curiosity about new things, and believe that you are the best. Learning is important, but there should also be some appropriate work. You can share some hard work for your parents at home. As long as you study hard, you will see a new yourself! Let yourself be as brilliant as a blooming bud in the time of youth! Just as beautiful!4.有关开学的英语日记As time goes by, today we are no longer children who have played in the grass; Today, we are no longer primary school students who read aloud “the bright moon in front of bed”; Today, we have bid farewell to childhood and moved towards youth. With a vision for the future, we came to the high school attached to the National People’s Congress and entered the life of senior one.It’s been a month since the beginning of school and I have a certain understanding of the new environment. There are also many feelings in the face of senior one life. When I was a freshman in senior high school, the first feeling was fresh. The campus is so clean and tidy with trees; The teacher’s lecture is so energetic and fascinating; The students get along so well and happily; The modern library, audio-visual education center, network center and laboratory make me linger. All this is very different from primary school, which makes me feel very fresh and interesting.In the first year of senior high school, the second feeling is the longing for the future. At the opening ceremony, we were excited to tie our good wishes to the balloon and fly to the blue sky. There are all kinds of wishes. Some hope to be a musician and promote Chinese traditional music to the world; Some hope to be a reporter and let all mankind marvel at China’s rapid development today; Some hope to be a writer and let people hear the weak voice in the corner of society. The ideal can only be realized through action. In the three years of junior high school, we will lay a solid foundation for the future and move forward towards thegoal step by step.When I was a freshman in senior high school, I felt nervous again. In middle schools, especially excellent middle schools, the competition for learning is quite fierce, so there will be some pressure. If you don’t pay attention, your grades will fall behind the team, so you can’t relax at all. You should always be in a state of learning. We must adapt to this tense learning atmosphere in order to make achievements in three years of study.As a freshman in senior high school, I was excited, looking forward to and nervous. But in any case, start bit by bit and integrate into the new life. Let’s face the freshman life in high spirits.5.有关开学的英语日记On the first day of school, I was very excited and returned to the friendly campus. We began to dress up the campus, clean up, self-study and so on. This semester, I hope I can continue to make progress Because it’s the first day, I’m inevitably a little excited.When I arrived at school early in the morning, I still had a sense of intimacy, although I once felt that the school was so depressed and a sad place. Because my life may be destined to have some sadness.Sweeping the floor, self-study, aerobics, class... It’s the same as before, but the curriculum has changed, and the study of senior three will be monotonous and complicated. Take turns bombing in addition to the number of words. I sent a lot of review materials in the afternoon. You can imagine the amount of problems. Come on! Although my expectation is just a piece of paper! Anyway, because I’m lucky to be in school.This semester is 23 weeks long and the longest one in my life. The math class in the morning is a new teacher. Like the situation at the time of the third day of junior high school, the first and second day of junior high school were older female teachers. Later, they were replaced by male teachers. They were middle-level cadres of the school and had a lot of teaching experience. But my math grade was very bad in the third year of junior high school. Now think aboutit, there is some pain. But at that time, I admired Mr. Chai very much.I hope I can make a little progress in math this year. I’m sorry for myself. The requirements are not very strict.The Chinese teacher is also specially transferred from Henan. It’s too disgraceful for our class. We already have four Chinese teachers in high school. Now the Chinese teacher is also our head teacher. This is the third.6.有关开学的英语日记On the first day of school, the red flag fluttered in the campus, and the brilliant sunshine brought us a good mood and a good omen. The diary also indicates that our school will continue to develop healthily, stably and orderly.However, unfortunately, there are still some phenomena inconsistent with our school in our campus and some students. For example: some students have conflicts, not running for mutual care and coordination, but looking for someone to retaliate, and then for serious fights. At the beginning of the new term, Iwould like to remind every student to re-examine themselves.Students, if you want to get good grades, you have to study. At first, it was a crawling caterpillar. In order to fly, it first made a cocoon, confined itself, turned into a pupa and completely deformed. After hard work, it will break free from the cocoon and fly freely in the air.Students, let’s learn from butterfly. We accept all this calmly, accept the warmth, richness and enrichment of high school life, and make it carry forward and unforgettable all our lives.7.有关开学的英语日记The time of vacation is always fleeting, and the opening day of school is absolutely sudden.Now, I have been sitting in the classroom of class 3, senior one. There are several old classmates I know, but we just say hello and smile. Time is a thief. When we find it, time has stolen our endless words.Everything in the new class is new, the students are new, the teachers are new, and I have also beenupdated. In the past, I read novels in class, slept in class, picked up the teacher’s words, found trouble for the teacher, didn’t go home after school, and went to fight and sing with my “brothers”. At that time, I was a jerk, but I realized that there was no end and no way out. I gradually realized that learning, going to high school and college were the due goals of a student! So I changed. On the day of school, I changed with time.Now I’m in the classroom of senior one. The students don’t know and the teachers are not familiar with it. It doesn’t matter. Time will tell those who want to know the answer they want!8.有关开学的英语日记Unconsciously, I have been studying in high school for a week. I feel that time passes too fast.Although I am already a high school student, I still don’t believe it. Think about how eager I was to enter high school in Junior 3. It is precisely because of the goal of high school that I studied harder. Now, I am a little afraid when I am admitted here.I had expected that there were many top studentsin high school, but I was afraid when I really came here to study. Take the first Chinese lesson for example! As soon as the teacher arranged it, I was at a loss.I couldn’t write prose and poetry at all. Later, I racked my brains to write it, but it was very poor. The students in the class wrote very well. After looking at their poetry, I couldn’t compare with them. In fact, my language and literature achievements had been good in the past, but when I came here, I felt that there were hermits and people outside the mountain, Chinese is better than I can’t count. The pressure is really great, but I’ve been in mourning all day and I’m constantly reflecting.It is often said that pressure is the driving force. Right? But there’s a lot of pressure here. I’ve been bad in science. When I came here, even my only good Chinese and English have changed. I’m at a loss! I feel very distressed and uncomfortable.But I insist on this sentence: “even if I fall 100 times, I will stand up for the 101st time.” There may be many days like this in the future. You can’t be unhappy every day, can you? may not. I really know thatI should be strong and face everything bravely.Before I came to high school, I asked my mother, “what if I was the last in the class?” But my mother said to me, “there’s no way to be the last one. You just have to study hard now. Don’t think so much about the number one!”Reprimand ~ I have long been prepared to be the last one, but even in the end, I will not give up. I will study with all my strength and make my own efforts. Because I said, “even if you are the last, you should be the last with a clear conscience.”It’s not easy to give up. I’ll do my best if I’m competitive!9.有关开学的英语日记Unconsciously, the happy winter vacation life has really ended. Accordingly, we ushered in the beginning of a new season.That morning, I woke up early from my sleep. Instead of using the alarm clock, I opened my eyes before the alarm clock rang, as if I had realized the beginning of school in my deep sleep.It seems that I immediately kept up with the pace of the beginning of school. I quickly completed my “daily tasks” and set off for school. On the way, I recalled my holiday life. Although I didn’t make rational use of the whole holiday, I successfully completed the holiday learning task, at least I won’t bring the regret of the holiday at the beginning of school.After arriving at the school, I came to my own class. The scene in front of me has not appeared in my vision for a long time: the students are quietly carrying out their own learning tasks in their own positions, while the teacher arranged class representatives on the podium to check the students’ holiday homework. This harmonious and quiet environment is like idealization. The students really matured after the holiday.I also took my seat and started my study plan today. Under the influence of the learning atmosphere in our class, I seem to adapt to the beginning of school very quickly.In the evening, I meditated alone before going tobed: originally, I have started school. This is my new semester, and my efforts should surpass that of last semester. Facing the new semester, I can’t spare my sweat. I want to create a “leader” to pave the way for future study.10.有关开学的英语日记Today is the first day of school. I am very happy. The new semester is coming. Although I want to leave my former teachers and classmates, I also welcome new teachers and classmates. I must study hard this semester and make a good impression on my teachers. In any case, I must do well in the exam this semester.I also want to know more about my classmates, and I specially prepared my homework for this new semester.I also finished practicing the calligraphy. I also wrote all the new words in units 1 to 8. The words are also previewed. I hope I can make a good impression on the teacher this semester, because I seem to be a little lazy in the first few semesters. Since it is a new semester, I will never be lazy again. I want to be in this semester. Getting better and better.The first day of school passed very quickly for me. It didn’t take long for the day to pass. However, itis said that the school will not arrange courses this week. But I’m more looking forward to whether I can learn when there are courses. If I can’t learn it, I think I may ask the teacher. In a word, in a word, this semester I must change my laziness and become better and better.有关开学的英语日记【十篇】。

Guidance for Industry and Reviewers Estimating the Safe Starting Dose in Clinical Trials for Therapeutics in Adult Healthy VolunteersDRAFT GUIDANCEThis guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit comments to Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register.For questions regarding this draft document contact (CDER) Robert Osterberg, 301-594-5476 or (CBER) Martin Green 301-827-5349.U.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)Center for Biologics Evaluation and Research (CBER)December 2002Pharmacology and ToxicologyGuidance for Industry and Reviewers Estimating the Safe Starting Dose in Clinical Trials for Therapeutics in Adult Healthy VolunteersAdditional copies are available from:Office of Training and CommunicationsDivision of Drug Information, HFD-240Center for Drug Evaluation and ResearchFood and Drug Administration5600 Fishers LaneRockville, MD 20857(Tel) 301-827-4573/cder/guidance/index.htmorOffice of Communication, Training andManufacturers Assistance (HFM-40)Center for Biologics Evaluation and ResearchFood and Drug Administration1401 Rockville PikeRockville, MD 20852-1448(Internet) /cber/guidelines.htmMail: The Voice Information System at 800-835-4709 or 301-827-1800U.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)Center for Biologics Evaluation and Research (CBER)December 2002Pharmacology and ToxicologyTable of ContentsI.INTRODUCTION (1)II.SCOPE (1)III.OVERVIEW OF THE ALGORITHM (3)IV.STEP 1: NO OBSERVED ADVERSE EFFECT LEVEL (NOAEL)DETERMINATION (4)V.STEP 2: HUMAN EQUIVALENT DOSE (HED) CALCULATION (5)A.Conversion Based on Body Surface Area (5)B.Basis for Using Mg/Kg Conversions (7)C.Other Exceptions to Mg/M2 Scaling Between Species (8)VI.STEP 3: MOST APPROPRIATE SPECIES SELECTION (8)VII.STEP 4: APPLICATION OF SAFETY FACTOR (9)A.Increasing the Safety Factor (10)B.Decreasing the Safety Factor (11)VIII.STEP 5: CONSIDERATION OF THE PHARMACOLOGICALLY ACTIVE DOSE (PAD) (11)IX.SUMMARY (12)REFERENCES (13)APPENDIX A (15)APPENDIX B (17)APPENDIX C (22)APPENDIX D (23)APPENDIX E (25)GLOSSARY (26)1Guidance for Industry and Reviewers 1234Estimating the Safe Starting Dose in Clinical Trials 5for Therapeutics in Adult Healthy Volunteers6789This draft guidance, when finalized, will represent the Food and Drug Administration's (FDA's) current 10thinking on this topic. It does not create or confer any rights for or on any person and does not operate to 11bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements 12of the applicable statutes and regulations.13141516I.INTRODUCTION1718This guidance outlines a process (algorithm) and vocabulary for deriving the maximum19recommended starting dose (MRSD) for "first in human" clinical trials of new molecular entities 20in adult healthy volunteers and recommends a standardized process by which the MRSD can be 21selected. The purpose of this process is to ensure the safety of the human volunteers.2223The goals of this guidance are to (1) establish a consistent terminology for discussing the starting 24dose, (2) provide common conversion factors for deriving a human equivalent dose, and (3)25delineate a strategy for selecting the MRSD for adult healthy volunteers, regardless of the26projected clinical use. This process is diagrammed with a flow chart that presents the decisions 27and calculations used to generate the MRSD from animal data. 282930II.SCOPE3132The process identified in this document pertains to determining the MRSD for adult healthy 33subjects when beginning a clinical investigation of any new drug or biological therapeutic that 34has been studied in animals. This document is not pertinent to prophylactic vaccines or35endogenous proteins (i.e., recombinant clotting factors) used at physiologic concentrations. The 36process outlined in this document does not address dose escalation or maximum allowable doses 37in clinical trials.38391This guidance has been prepared by the Office of New Drugs in the Center for Drug Evaluation and Research (CDER) in cooperation with the Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration.Although the process outlined in this document uses observed toxicities, administered doses, and 4041an algorithmic approach to calculate the MRSD, an alternative approach could be proposed that 42places primary emphasis on animal pharmacokinetics and modeling rather than dose. In a43limited number of cases, animal pharmacokinetic data may be useful in determining initial44clinical doses.2 However, in the majority of new INDs, animal data are not available in45sufficient detail to construct a scientifically valid, pharmacokinetic model whose aim is to46accurately project an MRSD.4748Toxicity should be avoided at the initial dose. However, doses should be chosen that allowreasonably rapid attainment of the phase 1 trial objectives (e.g., assessment of the therapeutic's 4950tolerability, pharmacodynamic or pharmacokinetic profile). All of the relevant preclinical data, 51including information on the pharmacologically active dose, the full toxicologic profile of the 52compound, and the pharmacokinetics (absorption, distribution, metabolism, and excretion) of the 53therapeutic, should be considered when determining the MRSD. Starting with doses lower than 54the MRSD is always a possible option and may be particularly appropriate to meet some clinical trial objectives.555657The remainder of this document will focus on the recommended algorithmic process for starting 58dose extrapolation from animals to humans based on administered doses, since this method will 59likely be useful for the majority of new INDs seeking to investigate new drugs in healthyvolunteers. Some classes of drugs (e.g., many cytotoxic or biological agents) are commonly6061introduced into initial clinical trials in patient volunteers rather than healthy volunteers.62Typically, this occurs when a drug is suspected or known to be unavoidably toxic. Although this 63document does not specifically address starting doses in patients, many principles and some64approaches recommended here may be applicable to designing such trials.2If the parent drug is measured in the plasma at multiple times and fits the range of toxic dose for two or moreanimal species, it may be possible to develop a pharmacokinetic model predicting human doses and concentrations and draw inferences about human safe plasma levels in the absence of prior human data. While quantitativemodeling for this purpose may be straightforward, the following points suggest this approach may present a number of difficulties when evaluating estimates of a safe starting dose. Generally, at the time of IND initiation, there are a number of unknowns regarding animal toxicity and comparability of human and animal pharmacokinetics andmetabolism: (1) human bioavailability and metabolism may differ significantly from that of animals; (2)mechanisms of toxicity may not be known (i.e., toxic accumulation in a peripheral compartment; and/or (3) toxicity may be due to an unidentified metabolite, not parent drug. Thus, to rely on pharmacokinetic models (based onparent drug in plasma) to gauge starting doses would require multiple untested assumptions. Modeling may be used with greatest validity to estimate human starting doses in special cases where few underlying assumptions would be necessary. Such cases are exemplified by large molecular weight proteins (like humanized monoclonal antibodies), which are intravenously administered, are removed from circulation by endocytosis rather than metabolizism, have immediate and detectable effects on blood cells, and have a volume of distribution limited to the plasma volume.Here, allometric, pharmacokinetic, and pharmacodynamic models have been useful in identifying the human mg/kg dose that would be predicted to correlate with safe drug plasma levels in nonhuman primates. Even in these cases, uncertainties (such as differences between human and chimpanzee receptor sensitivity or density) have been shown to affect human pharmacologic or toxicologic outcomes, and the use of safety factors as described in this document is still warranted.6566III.OVERVIEW OF THE ALGORITHM67The process for selecting the MRSD is presented in Figure 1 and described in this section. The 6869major elements C the determination of the no observed adverse effect levels (NOAELs) in the70tested species, conversion of NOAELs to human equivalent dose (HED), selection of the most 71appropriate species, and application of a safety factor C are all discussed in greater detail in72subsequent sections. Situations are also discussed in which the algorithm should be modified.73The algorithm is intended to be used for systemically administered therapeutics. Topical,intranasal, intra-tissue, and compartmental administration routes and depot formulations may7475have additional considerations, but similar principles should apply.76The process of calculating the MRSD should begin after the toxicity data have been analyzed. 7778Although only the NOAEL should be used directly in the algorithm for calculating a MRSD,79other data (exposure/toxicity relationships, pharmacologic data, or prior clinical experience withrelated drugs) can affect the choice of most appropriate species, scaling, and safety factors.808182The NOAEL for each species tested should be identified, then each should be converted to thehuman equivalent dose (HED) using appropriate scaling factors. For most systemically8384administered therapeutics, this conversion should be based on the normalization of doses to body85surface area. Although body surface area conversion is the usual way to approximate equivalentexposure if no further information is available, in some cases, extrapolating doses based on other 8687parameters may be more appropriate. This decision should be based on the data available for the88individual case. The body surface area normalization and the extrapolation of the animal dose to89human dose should be done in one step by dividing the NOAEL in each of the animal species90studied by the appropriate body surface area conversion factor (BSA-CF). This is a unitless91number that converts mg/kg dose for each animal species to the mg/kg dose in humans, which is92equivalent to the animal’s NOAEL on a mg/m2 basis. The resulting figure is called a human93equivalent dose (HED). The species that generates the lowest HED is called the most sensitive94species.95When information indicates that a particular species is most relevant for assessing human risk 9697(and deemed the most appropriate species), the HED for that species should be used in98subsequent calculations, regardless of whether this species was the most sensitive. This case iscommon for biologic therapies, many of which have high selectivity for binding to human target 99100proteins, and limited reactivity in species commonly used for toxicity testing. In such cases, in101vitro binding and activity studies should be done to select appropriate, relevant species beforetoxicity studies are designed (please refer to the ICH3 guidance for industry S6 Preclinical Safety 102103Evaluation of Biotechnology-Derived Pharmaceuticals for more details). Additionally, a species104might be considered an inappropriate toxicity model for a given drug if a dose-limiting toxicity105in that species was concluded to be of limited value for human risk assessment (based onhistorical comparisons of toxicities in species to those in humans across a therapeutic class). In 1063 International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals forHuman Use (ICH).this case, data from that species should not be used to derive the HED. Without any additional 107108information to guide the choice of the most appropriate species for assessing human risk, the109most sensitive species is designated the most appropriate, because using the lowest HED wouldgenerate the most conservative starting dose.110111112A safety factor should then be applied to the HED to increase assurance that the first dose inhumans will not cause adverse effects. The use of the safety factor should be based on the113114possibility that humans may be more sensitive to the toxic effects of a therapeutic agent than115predicted by the animal models, that bioavailability may vary across species, and that the modelstested do not evaluate all possible human toxicities. For example, ocular disturbances or pain 116117(such as severe headaches) in humans can be significant dose-limiting toxicities that may go118undetected in animal studies.119120In general, a safety factor of 10 is recommended. The MRSD should be obtained by dividing the121HED by the safety factor. Safety concerns or design shortcomings noted in animal studies may122increase the safety factor, and thus reduce the MRSD further. Alternatively, information about123the pharmacologic class (well-characterized classes of therapeutics with extensive human clinical124and preclinical experience) may allay concerns and form the basis of reducing the magnitude of125the default safety factor and increasing the MRSD. Although a dose lower than the MRSD can126be used as the actual starting dose, the process described here will derive the maximum127recommended starting dose. This algorithm generates a MRSD in units of mg/kg, a common128method of dosing used in phase 1 trials, but the equations and conversion factors provided in this129document (Table one, second column) can be used to generate final dosing units in the mg/m2 130form if desired.131132As previously stated, for purposes of initial clinical trials in adult healthy volunteers, the HED133should ordinarily be calculated from the animal NOAEL. If the HED is based on an alternative134index of effect, such as the pharmacologically active dose (PAD), this exception should be135prominently stipulated in descriptions of starting dose calculations.136137The remainder of this document provides a description of the individual steps in the138recommended process and the reasoning behind each step. The method is supported by a general139review and analysis by CDER and CBER examining the results from a number of therapeutics140entered into development.141142143IV.STEP 1: NO OBSERVED ADVERSE EFFECT LEVEL (NOAEL)DETERMINATION144145146The first step in determining the MRSD is to review and evaluate the available animal data sothat a NOAEL can be determined for each study. Several differing definitions of NOAEL exist, 147148but for selecting a starting dose, the following is used here: the highest dose level that does not149produce a significant increase in adverse effects. In this context, adverse effects that arestatistically significant and adverse effects that may be clinically significant (even if they are not 150151statistically significant) should be considered in the determination of the NOAEL. The NOAELis a generally accepted benchmark for safety when derived from appropriate animal studies and 152153can serve as the starting point for determining a reasonably safe starting dose of a new154therapeutic in healthy (or asymptomatic) human volunteers.155156The NOAEL is not the same as the no observed effect level (NOEL), which refers to any effect, 157not just adverse ones, although in some cases the two might be identical. The definition of the NOAEL, in contrast to that of the NOEL, reflects the view that some effects observed in the 158159animal may be acceptable pharmacodynamic actions of the therapeutic and may not raise a safety 160concern. The NOAEL should not be confused with lowest observed adverse effect level(LOAEL) or maximum tolerated dose (MTD). Both of the latter concepts are based on findings 161162of adverse effects and are not generally used as benchmarks for establishing safe starting doses in adult healthy volunteers. The term level refers to dose or dosage, generally expressed as163164mg/kg or mg/kg/day.165Initial IND submissions for first in human studies by definition lack human data or formal166167allometric comparison of pharmacokinetics. Measurements of systemic levels or exposure (i.e., 168AUC or Cmax) cannot be employed for setting a safe starting dose in humans, and it is critical to 169rely on dose and observed toxic response data from adequate and well-conducted toxicology 170studies. However, there are cases where data on bioavailability, metabolite profile, and plasma 171drug levels associated with toxicity may influence the choice of the NOAEL. One such case 172would be when saturation of drug absorption occurs at a dose that produces no toxicity. In this 173case, the lowest saturating dose, not the highest (non-toxic) dose, should be used for calculating 174the HED.175176There are essentially three types of findings in nonclinical toxicology studies that can be used to 177determine the NOAEL: (1) overt toxicity (e.g., clinical signs, macro- and microscopic lesions); 178(2) surrogate markers of toxicity (e.g., serum liver enzyme levels); and (3) exaggerated179pharmacodynamic effects. Although the nature and extent of adverse effects can vary greatlywith different types of therapeutics and it is anticipated that in many instances experts will180181disagree on the characterization of effects as being adverse or not, the use of NOAEL as a182benchmark for dose-setting in healthy volunteers should be acceptable to all responsibleinvestigators. As a general rule, an adverse effect observed in nonclinical toxicology studies 183184used to define a NOAEL for the purpose of dose-setting should be based on an effect that would be unacceptable if produced by the initial dose of a therapeutic in a phase 1 clinical trial185186conducted in adult healthy volunteers.187188189V.STEP 2: HUMAN EQUIVALENT DOSE (HED) CALCULATION190191A.Conversion Based on Body Surface Area192193After the NOAELs in the relevant animal studies have been determined, they are converted to 194human equivalent doses (HEDs). A decision should be made regarding the most appropriate 195method for extrapolating the animal dose to the equivalent human dose. Toxic endpoints fortherapeutics administered systemically to animals, such as the MTD or NOAEL, are usually 196assumed to scale well between species when doses are normalized to body surface area (i.e .,197mg/m 2). The basis for this assumption lies primarily with the work of Freireich et al. (1996) and 198Schein et al. (1970). These investigators reported that, for antineoplastic drugs, doses lethal to 19910 percent of rodents (LD 10s) and MTDs in non-rodents both correlated with the human MTD 200when the doses were normalized to the same administration schedule and expressed as mg/m 2.201Despite the subsequent analyses showing that the MTDs for this set of drugs scale best between 202species when doses are normalized to W 0.75 rather than W 0.67 (inherent in body surface area 203normalization), normalization to body surface area has remained a widespread practice for 204estimating an HED based on an animal dose.205206An analysis of the impact of the allometric exponent on the conversion of an animal dose to the 207HED was conducted (see Appendix A). Based on this analysis and on the fact that correcting for 208body surface area increases clinical trial safety by resulting in a more conservative starting dose 209estimate, it was concluded that the approach of converting NOAEL doses to an HED based on 210body surface area correction factors (i.e ., W 0.67) should be maintained for selecting starting doses 211for initial studies in adult healthy volunteers. Nonetheless, use of a different dose normalization 212approach, such as directly equating the human dose to the NOAEL in mg/kg, may be appropriate 213in some circumstances. Deviations from the surface area approach should be justified. The basis 214for justifying direct mg/kg conversion and examples in which other normalization methods are 215appropriate are described in the following subsection.216217Although normalization to body surface area is an appropriate method for extrapolating doses 218between species, consistent factors for converting doses from mg/kg to mg/m 2 have not always 219been used. Given that body surface area normalization provides a reasonable approach for 220estimating an HED, the factors used for converting doses from each species should be 221standardized. Since surface area varies with W 0.67, the conversion factors are therefore222dependent on the weight of the animals in the studies. However, analyses conducted to address 223the effect of body weight on the actual BSA-CF (body surface area - conversion factor)224demonstrated that a standard factor provides a reasonable estimate of the HED over a broad 225range of human and animal weights (see Appendix B). The conversion factors and divisors 226shown in Table 1, below, are therefore recommended as the standard values to be used for 227interspecies dose conversions for NOAELs in CDER and CBER. These factors may also be 228applied when comparing safety margins for other toxicity endpoints (e.g., reproductive toxicity 229and carcinogenicity) when other data for comparison, (i.e ., AUCs) are unavailable or are 230otherwise inappropriate for comparison.231232233Table 1: Conversion of Animal Doses to Human Equivalent Doses(HED) Based on Body Surface AreaTo convert animal dose in mg/kg to HED a in mg/kg, either:SpeciesTo convert animal dose in mg/kg to dose in mg/m²,multiply by km below:Divide animal dose by:Multiply Animal dose by:Human37------Child (20 kg)b 25------Mouse 312.30.08Hamster 57.40.13Rat 6 6.20.16Ferret7 5.30.19Guinea pig 8 4.60.22Rabbit 12 3.10.32Dog20 1.80.54Primates:Monkeys c 12 3.10.32Marmoset6 6.20.16Squirrel monkey7 5.30.19Baboon 20 1.80.54Micro-pig 27 1.40.73Mini-pig351.10.95aAssumes 60 kg human. For species not listed or for weights outside the standard ranges, human 234equivalent dose can be calculated from the formula:235HED = animal dose in mg/kg x (animal weight in kg/human weight in kg)0.33.236bThis km is provided for reference only since healthy children will rarely be volunteers for phase 1 trials.237cFor example, cynomolgus, rhesus, stumptail.238239 B.Basis for Using Mg/Kg Conversions240241The factors in Table 1 for scaling animal NOAEL to HEDs are based on the assumption that 242doses scale 1:1 between species when normalized to body surface area. However, there are 243occasions for which scaling based on body weight (i.e., setting the HED (mg/kg) = NOAEL 244(mg/kg)) may be more appropriate. To consider mg/kg scaling for a therapeutic, the available 245data should show that the NOAEL occurs at a similar mg/kg dose across species. The factors 246below should be satisfied before extrapolating to the HED on a mg/kg basis rather than using the 247mg/m 2 approach. Note that mg/kg scaling will give a 12-, 6-, and 2- fold higher HED than the 248default mg/m 2 approach for mice, rats, and dogs, respectively. If these factors cannot be met, the 249mg/m 2 scaling approach for determining the HED should be followed as it will lead to a safer 250MRSD.251252 1.NOAELs occur at a similar mg/kg dose across test species (for the studies with a 253given dosing regimen relevant to the proposed initial clinical trial).254255 2.If only two NOAELs from toxicology studies in separate species are available,256one of the following criteria should also be true:257258• The therapeutic is administered orally and the dose is limited by local259toxicities. Gastrointestinal (GI) compartment weight scales by W 0.94 . GI260volume determines the concentration of the therapeutic in the GI tract. It is 261262thus reasonable that the toxicity of the therapeutic would scale by mg/kg263(W1.0).264265•The toxicity in humans (for a particular class) is dependent on an exposure 266parameter that is highly correlated across species with dose on a mg/kg basis. 267For example, complement activation by systemically administered antisense 268oligonucleotides in humans is believed to be dependent upon Cmax (Geary et 269al., 1997). For some antisense drugs, the Cmax correlates across nonclinical 270species with mg/kg dose and in such instances mg/kg scaling would be271justified.272273•Other pharmacologic and toxicologic endpoints also scale between species by 274mg/kg for the therapeutic. Examples of such endpoints include the MTD,lowest lethal dose, and the pharmacologically active dose.275276277C.Other Exceptions to Mg/M2 Scaling Between Species2782791.Therapeutics administered by alternative routes (e.g., topical, intranasal,280subcutaneous, intramuscular) for which the dose is limited by local toxicities. 281Such therapeutics should be normalized to concentration (mg/area of application, 282for instance) or amount of drug (mg) at the application site.2832.Therapeutics administered into anatomical compartments that have little284subsequent distribution outside of the compartment. Examples are intrathecal, 285intravesical, intraocular, intrapleural, and intraperitoneal administration. Such 286therapeutics should be normalized between species according to the287compartmental volumes and concentrations of the therapeutic.2883.Biological products administered intravascularly with M r > 100,000 daltons. Such 289therapeutics should be normalized to mg/kg.290291292VI.STEP 3: MOST APPROPRIATE SPECIES SELECTION293294After the HEDs have been determined from the NOAELs from all toxicology studies relevant to 295the proposed human trial, the next step is to pick one HED for subsequent derivation of theMRSD. This HED should be chosen from the most appropriate species. In the absence of data 296297on species relevance, a default position is that the most appropriate species for deriving the298MRSD for a trial in adult healthy volunteers is the most sensitive species (i.e., the species in 299which the lowest HED can be identified).300301Factors that could influence the choice of the most appropriate species rather than the default to 302the most sensitive species include: (1) differences in the absorption, distribution, metabolism and 303elimination (ADME) of the therapeutic between the species; (2)class experience that may304indicate a particular model is predictive of human toxicity; or (3) limited biological cross-species pharmacologic reactivity of the therapeutic. This latter point is especially important for305。

如何把个人目标和国家目标结合起来英语作文全文共3篇示例，供读者参考篇1How to Combine Personal Goals with National GoalsIntroductionIn today's fast-paced world, it is essential for individuals to have personal goals to achieve growth and success. However, it is equally important to align these personal goals with the broader national goals to contribute to the development and advancement of one's country. This essay will explore the ways in which individuals can integrate their personal goals with national goals for the betterment of society.Understanding National GoalsBefore delving into how to combine personal and national goals, it is essential to understand what national goals entail. National goals are the collective objectives set by a country to achieve prosperity, stability, and progress. These goals encompass various areas such as economic growth, social harmony, environmental sustainability, and technological advancement. By aligning personal goals with national goals,individuals can play an active role in driving the country towards these objectives.Identifying Personal GoalsTo align personal goals with national goals, individuals must first identify their own aspirations, passions, and ambitions. Personal goals can vary greatly from one individual to another and may include career advancement, educational attainment, entrepreneurial success, personal development, and community service. By setting clear and specific personal goals, individuals can work towards achieving their dreams while also contributing to national development.Finding Common GroundOnce personal goals have been established, individuals should seek to find common ground between their aspirations and national goals. This can be done by identifying areas of overlap or synergy between personal and national objectives. For example, if an individual's personal goal is to become a successful entrepreneur, they can contribute to the country's economic growth by creating job opportunities, supporting local businesses, and driving innovation. By aligning personal and national goals in this way, individuals can create a win-winsituation where they achieve personal success while also benefiting society at large.Taking ActionAligning personal goals with national goals is not just about setting intentions; it requires taking concrete actions to bring about positive change. Individuals can actively contribute to national goals by volunteering for community projects, supporting sustainable practices, engaging in civic activities, and advocating for social causes. By taking proactive steps to align personal and national goals, individuals can make a meaningful impact on their country's development and progress.Measuring ProgressTo ensure that personal goals are effectively aligned with national goals, individuals should regularly assess their progress and impact. This can be done by tracking key performance indicators, soliciting feedback from peers and mentors, and reflecting on the outcomes of their actions. By measuring progress towards both personal and national goals, individuals can identify areas for improvement, celebrate successes, and stay motivated to continue their efforts.Conclusionway for individuals to contribute to the well-being and advancement of their country. By understanding national objectives, identifying personal aspirations, finding common ground, taking action, and measuring progress, individuals can make a meaningful impact on society while pursuing their own dreams. Through this alignment of goals, individuals can become agents of positive change and help shape a better future for themselves and their nation.篇2How to Combine Personal Goals with National GoalsIntroductionBoth personal goals and national goals play a crucial role in shaping society and individuals. Personal goals refer to aspirations that individuals set for themselves, which guide their actions and decisions. On the other hand, national goals are goals and objectives set by a country or government to achieve a specific outcome or vision. To create a balanced and harmonious society, it is essential for individuals to align their personal goals with national goals. This essay will explore the importance ofpractical strategies to achieve this alignment.Importance of Aligning Personal Goals with National Goals1. Contribution to the Greater GoodBy aligning personal goals with national goals, individuals are able to contribute to the greater good of society. When personal goals are in line with national goals, individuals work towards achieving outcomes that benefit not only themselves but also their community and country. This alignment fosters a sense of unity and cooperation among individuals, leading to a more prosperous and harmonious society.2. Enhance National DevelopmentWhen individuals align their personal goals with national goals, they contribute to the overall development and progress of their country. By working towards common goals and objectives, individuals can help address key challenges facing the nation, such as economic growth, social cohesion, and environmental sustainability. This alignment ensures that individual efforts are in line with the priorities and needs of the nation, leading to sustainable development and prosperity for all.3. Foster a Sense of Purpose and IdentityBy aligning personal goals with national goals, individuals can develop a sense of purpose and identity. When individuals work towards goals that are aligned with the values and aspirations of their country, they feel a sense of belonging and pride in their contributions to the nation. This alignment also helps individuals connect with their cultural heritage and national identity, fostering a strong sense of unity and solidarity among citizens.Strategies for Aligning Personal Goals with National Goals1. Understand National Priorities and ObjectivesTo align personal goals with national goals, individuals need to have a clear understanding of the priorities and objectives set by their country. This requires staying informed about national policies, programs, and initiatives, as well as engaging with government officials and community leaders to learn more about the nation's goals and challenges. By understanding national priorities, individuals can align their personal goals with the broader objectives of their country.2. Identify Common GroundTo align personal goals with national goals, individuals should identify common ground between their aspirations and the goals of their country. This involves reflecting on personal values, skills, and interests, and determining how these align with the priorities of the nation. By finding areas of overlap, individuals can tailor their personal goals to contribute to national objectives, such as promoting innovation, enhancing education, or supporting sustainable development.3. Seek Collaborative OpportunitiesAligning personal goals with national goals often requires collaboration and cooperation with others. Individuals can seek out opportunities to work with organizations, communities, or government agencies that are aligned with national goals and initiatives. By participating in collective efforts, individuals can leverage their skills and resources to contribute to larger-scale projects and initiatives that benefit the nation. Collaboration ensures that individual actions are aligned with broader national objectives, leading to greater impact and success.4. Evaluate Progress and AdaptAligning personal goals with national goals is an ongoing process that requires regular evaluation and adaptation. Individuals should regularly assess their progress towardsachieving personal and national goals, identifying areas of success and areas for improvement. By monitoring progress and adapting their strategies as needed, individuals can ensure that their actions remain aligned with the evolving priorities of their country. This flexibility and adaptability are essential for achieving long-term alignment between personal and national goals.ConclusionAligning personal goals with national goals is essential for creating a cohesive and prosperous society. By contributing to the greater good, enhancing national development, and fostering a sense of purpose and identity, individuals can make a meaningful impact on their country. By understanding national priorities, identifying common ground, seeking collaborative opportunities, and evaluating progress, individuals can effectively align their personal goals with the goals of their nation. Through this alignment, individuals can contribute to a more inclusive, sustainable, and prosperous future for all.篇3How to Combine Personal Goals with National GoalsIntroductionIn a society where globalization and individualism are on the rise, it can be challenging to find a balance between personal aspirations and the larger goals of the nation. However, it is essential to understand that personal success and national development are not mutually exclusive but rather intertwined. In this essay, we will explore how individuals can align their personal goals with the broader objectives of their country to contribute to overall progress and well-being.Understanding Personal GoalsPersonal goals are unique to each individual and are often driven by one's values, passions, and aspirations. These goals could range from achieving financial stability, pursuing a fulfilling career, to making a positive impact on society. It is essential for individuals to reflect on their values and priorities to determine what they truly want to achieve in life.Aligning Personal Goals with National GoalsWhile personal goals are important, it is equally crucial to consider how these goals can contribute to the development and progress of the nation. One way to align personal goals with national goals is to focus on areas that are in line with the country's priorities and needs. For example, if the nation is focusing on promoting sustainable development, individuals canset goals that contribute to environmental conservation or social equity.Another way to align personal goals with national goals is to be aware of the bigger picture and how one's actions can impact the broader society. By thinking beyond oneself and considering how personal achievements can benefit the community or country as a whole, individuals can find ways to make a meaningful contribution to national development.Taking ActionOnce individuals have identified how their personal goals can align with national goals, it is important to take action and implement strategies to achieve these objectives. This could involve seeking opportunities to contribute to national initiatives, participating in community projects, or advocating for policies that support national development.Furthermore, individuals can also leverage their skills, knowledge, and resources to make a positive impact on society. Whether through volunteering, mentoring, or supporting social causes, individuals can find ways to contribute to the well-being of their country while pursuing their personal goals.ConclusionIn conclusion, finding a balance between personal goals and national goals is a challenging yet rewarding endeavor. By aligning personal aspirations with the larger objectives of the nation, individuals can contribute to national development while pursuing their own success and fulfillment. It is essential for individuals to reflect on their values, prioritize areas of impact, and take concrete actions to make a positive difference in society. Ultimately, by working towards common goals, individuals can help build a more prosperous, equitable, and sustainable future for themselves and their country.。

思考建筑The hard core of beauty美之核心Two weeks ago I happened to hear a radio program on the American poet William Carlos Williams. The program was entitled The Hard Core of Beauty. This phrase caught my attention. I like the idea that beauty has a bard core, and when I think of architecture this association of beauty and a hard core has a certain familiarity. "The machine is a thing that has no superfluous parts," Williams is supposed to have said. And I immediately think I know what he meant. It's a thought that Peter Handke alludes to, I feel, when he says that beauty lies in natural, grown things that do not carry any signs or messages, and when he adds that he is upset when he cannot discover the meaning of things for himself.两周前，我碰巧在广播上听到一个关于美国诗人威廉·卡洛斯·威廉姆斯（William Carlos Williams）①的节目。

家中往返工作地点英文作文样本One of the most significant changes in recent years has been the increasingly blurred line between home and work. With the rise of remote work and flexible working arrangements, more and more people find themselvesshuttling back and forth between their home and workplace. This shift has brought about a range of challenges and opportunities that have sparked debates on how we define and balance our personal and professional lives.One major advantage of working from home is the elimination of commute time. No longer do workers have to navigate rush hour traffic or squeeze into packed public transportation, allowing for more time to focus on tasks at hand or relax with family members. Additionally, remote work offers greater flexibility in terms of scheduling, enabling individuals to tailor their work hours around personal obligations or preferences. This increased autonomy can lead to higher job satisfaction and productivity as employees feel more empowered to manage their own time effectively.On the other hand, the blending of home and work environments can also present challenges. For some individuals, the lack of clear boundaries between professional responsibilities and personal life can lead to feelings of burnout or a constant sense of being "on call." It may become difficult to switch off from work mode when there is no physical distance separating one's living space from one's office space. Furthermore, without the regular social interactions that come with working in a traditional office setting, remote workers may experience feelings of isolation or disconnect from their colleagues.In response to these challenges, companies are adapting by implementing new policies and technologies aimed at supporting employees who shuttle between home and workplace. Virtual collaboration tools facilitate communication among team members regardless of physical location, whilewellness initiatives promote mental health and work-life balance for remote workers. Some organizations are even reconsidering the need for a centralized office altogether, opting instead for satellite spaces or co-workingarrangements that accommodate the shifting needs of modern workers.As we navigate this changing landscape where the boundaries between home and work continue to blur, it becomes increasingly important for individuals to establish routines that support both their professional goals and personal well-being. Whether it be setting aside designated workspace within one's home or establishing boundaries around work hours, finding ways to create structure in an environment where roles overlap is crucial for long-term success.In conclusion, the trend towards shuttling back and forth between one's home and workplace reflects a broader shiftin how we approach our careers in an era defined by technological advancements and evolving societal norms. By acknowledging both the benefits and challenges inherent in this new way of working, individuals can strive to strike a balance that allows them to thrive professionally while prioritizing their overall well-being.。

a r X i v :h e p -l a t /9210041v 1 30 O c t 19921The Interface Tension in Quenched QCD at the Critical Temperature ∗B.Grossmann a ,ursen a ,T.Trappenberg ab †and U.J.Wiese c‡a HLRZ,c/o Kfa Juelich,P.O.Box 1913,D-5170J¨u lich,GermanybInstitute for Theoretical Physics E,RWTH Aachen,Sommerfeldstr.,D-5100Aachen,GermanycUniversit¨a t Bern,Sidlerstr.5,3012Bern,SwitzerlandWe present results for the confinement-deconfinement interface tension αcd of quenched QCD.They were obtained by applying Binder’s histogram method to lattices of size L 2×L z ×L t for L t =2and L =8,10,12and 14with L z =30for L =8and L z =3L otherwise.The use of a multicanonical algorithm and cylindrical geometries have turned out to be crucial for the numerical studies.1.IntroductionAt high temperature a phase transition oc-curs in QCD.In the quenched approximation (i.e.without any light quarks)this transition is of first order and separates a low temperature confined phase from a high temperature deconfined phase.The dynamics of a system which crosses the tran-sition temperature T c (as e.g.in the early uni-verse or in heavy ion collisions)depends on the free energy F cd =αcd A(1)of an interface of area A between regions of confined and deconfined matter.The interface tension αcd =σcd T c was investigated before in Monte Carlo simulations of lattice systems with L t =2using various approaches (see [1–4]).Lately these results have been questioned based on an application of Binder’s histogram method to cubic spatial volumes L 3with L =6,8,10,and 12(see [5,6]).However,these re-sults might have been plagued by interfacial in-teractions.Therefore,we present results using the same method but on asymmetric volumes (L z >L x =L y )thereby reducing these inter-actions.2Figure1.Schematic probability distribution for the order parameter.The dotted line indicates the multicanonical distribution.as depicted in the second part of Fig.2.Since the interface area of the two planar interfaces is independent ofρthe probability P L is constant in the region where their contributions dominate, i.e.aroundρ(min).Because of the C−periodic boundary conditions these interfaces always sep-arate a region in the confined phase from one in the deconfined phase that has Im(ΩL)=0.Thus the corresponding configurations will be exponen-tially suppressed by the interfacial free energy of two confined-deconfined interfaces.Taking into account the capillary wavefluctuations of the in-terfaces as well as their translational degrees of freedom leads to additional power law corrections [8,9]givingP minL∝L2z·L d−3·exp −2σcd L d−1 .(5)for d−dimensional spatial volumes.This relation will be used to determineσcd from the distribu-tions obtained onfinite lattices.In order to calculate the probability distribu-tion P L(ρ),one has to simulate the SU(3)pure gauge theory at the deconfinement phase transi-tion.But because of eq.5any standard local up-dating algorithm will have autocorrelation times τL which increase exponentially with L2(”super-critical slowing down”).The use of the multi-canonical algorithm reduces this effect consider-Figure2.Typical cuts through the lattice in the y−z−plane at valuesρ(1)(first picture)and ρ(min)(second picture)of the order parameter. The two phases are represented by white resp. shaded areas.ably.3.The Multicanonical AlgorithmIn order to overcome the supercritical slowing down,the multicanonical algorithm[10,11]does not sample the configurations with the canonical Boltzmann weightP can L(S)∝exp(βS),(6) where S=1/3 2tr U2is the Wilson action in four dimensions,but rather with a modified weightP mc L(S)∝exp(βL(S)S+αL(S)).(7) The coefficientsαL andβL are chosen such that the probability P L(not to be confused with the Boltzmann weights)is increased for all values of the action corresponding to the region between ρ(1)andρ(2),as shown schematically in Fig.1. Details are described in[6]where the efficiency of the multicanonical algorithm for SU(3)pure gauge theory has been demonstrated.We apply the algorithm to the determination of the inter-facial free energy.4.Numerical ResultsWe have determined the probability distribu-tions for L t=2and the spatial volumes L2×L z3Figure3.ReΩL(z)for a142×42×2lattice.Thedotted lines indicate the bulk expectation valuesof the two phases.with L=8,10,12,and14and L z=30for L=8and L z=3L otherwise.Fig.3shows the real part ofΩL(z)≡1/L2 x,yΩL(x,y,z)for a typi-cal configuration close toρ(min)on a142×42×2 lattice.As expected from section2,one can iden-tify two interfaces between the confined phase and the deconfined phase.The imaginary part ofΩL is always zero.In Fig.4the resulting probability distributions are shown.In contrast to the dis-tributions for cubic volumes(L values as before) they all have a region of constant probability in between the two peaks.This supports the sce-nario developped in section2.In order to extract the interface tension we evaluate the quantitiesF(1) L≡1P L max4ln L z2ln L2L2ln P minL+ln L zP L max≡1P L(max)∝√T3c=0.10(1).(10)It agrees within errors with the value obtained byreplacing the Polyakov line by the action density.The agreement with[1–3]is good while[4]quotesa slightly higher value.Still the discrepency be-tween these results and[5,6]which used Binder’shistogram method for cubic volumes is reducedconsiderably and can thus be attributed mainlyto interfacial interactions.REFERENCES1.K.Kajantie,L.K¨a rkk¨a inen,andK.Rummukainen,Nucl.Phys.B357(1991)693.2.S.Huang,J.Potvin,C.Rebbi,andS.Sanielevici,Phys.Rev.D42(1990)2864.3.R.Brower,S.Huang,J.Potvin,andC.Rebbi,The surface tension of nucleating4Figure5.Results for F(1)L and F(2)L.hadrons using the free energy of an isolated quark,preprint BUHEP-92-3,1992.4. B.Grossmann,ursen,T.Trap-penberg,and U.-J.Wiese,The confine-ment interface tension,wetting,and the spec-trum of the transfer matrix,in Nucl.Phys.B (Proc.Suppl.)(Proceedings of“Lattice92”, Amsterdam),1992.5.W.Janke,B.A.Berg,and M.Katoot,preprint FSU-SCRI-92-40,1992.6. B.Grossmann,ursen,T.Trap-penberg,and U.-J.Wiese,A multicanon-ical algorithm for SU(3)pure gauge theory, Phys.Lett.B(1992).7. A.S.Kronfeld and U.-J.Wiese,Nucl.Phys.B357(1991)521.8. B.Bunk,A note on interfaces with periodicboundaries,in Workshop on the dynamics of first order phase transitions,H.J.Herrmann, W.Janke,and F.Karsch,eds.,HLRZ,1992.9.U.J.Wiese,Capillary waves in Binder’sapproach to the interface tension,preprint BUTP-92/37,1992.10.B. A.Berg and T.Neuhaus,Phys.Lett.B267(1991)249-253,and Phys.Rev.Lett.68(1992)9.11.G.P.E.Marinari,preprint ROMF-92-06,1992.1/LF (i )。

长短期计划的英语单词English Answer:Long-term and short-term planning are two distinct approaches to developing a course of action for achieving specific goals. The primary difference between the two lies in the timeframe they encompass. Long-term planning focuses on objectives that require a longer duration, usually beyond a year, while short-term planning addresses goals that can be accomplished within a shorter time frame, typically less than a year.Long-term planning is crucial for establishing a clear direction and overall strategy for achieving ambitious goals. It involves setting long-term objectives,identifying milestones, and developing strategies to address potential challenges. The process often requires extensive research, analysis, and consultation with stakeholders. Long-term plans provide a roadmap for future decision-making and resource allocation, ensuring thatactions are aligned with the overall vision and mission of the organization.Short-term planning, on the other hand, focuses on immediate and actionable goals. It involves breaking down long-term objectives into smaller, manageable steps. Short-term plans typically cover a period of less than a year, such as a quarter or a fiscal year. They provide specific targets, timelines, and responsibilities, enabling organizations to track progress and make necessary adjustments along the way. Short-term plans are essential for maintaining momentum, staying on track, and meeting immediate business objectives.Both long-term and short-term planning are essentialfor effective goal achievement. Long-term planning provides the overarching framework and direction, while short-term planning ensures timely action and accountability. By aligning short-term goals with long-term objectives, organizations can maintain a consistent focus on their strategic priorities while adapting to changing circumstances.In practice, long-term and short-term planning often overlap and complement each other. Long-term plans inform and guide the development of short-term plans, ensuringthat immediate actions are aligned with the overall strategy. Conversely, short-term plans provide feedback and insights that can inform adjustments to long-term plans, ensuring that they remain relevant and responsive to emerging opportunities and challenges.中文回答：长期规划和短期规划是两种截然不同的方法，用来制定实现特定目标的行动计划。

C hapter 4H LA Typing Using Bead-Based MethodsD aniel T rajanoski and S amantha J.F idlerA bstractT he LABType ®SSO (One Lambda, Inc) and Gen-Probe LIFECODES HLA-SSO HLA Typing tests are rapid and ef fic ient assays for determining human leukocyte antigens (HLAs). The principle of these assays involves the hybridization of reverse sequence-speci fic oligonucleotide probes each attached to a unique colour coded microsphere to identify HLA class I and class II alleles. Target DNA is polymerase chain reaction (PCR) ampli fie d using group-speci fic primers and then biotinylated which allows it to be detected using R-Phycoerythrin-conjugated Streptavidin. The PCR product is then denatured and allowed to hybridise to complementary DNA probes conjugated to flu orescently code microsperes. The Luminex ®Flow Analyser achieves detection by determining the flu orescent intensity of PE on each microsphere. The assignment of HLA alleles is based on the reaction pattern of the various beads compared to patterns with known HLA alleles.K ey words:L ABType ®SSO ,L uminex ®,D enaturation ,G en-Probe LIFECODES HLA-SSO ,H ybridisation ,R-Phycoerythrin-conjugated streptavidin ,P olymerase chain reaction ,H uman leuko-cyte antigen ,M icrosphere1.I ntroductionO ver the past few decades, human leukocyte antigen (HLA) typingmethods have utilized advances in technology to provide assayswith higher resolution whilst reducing cost and time. Historically,HLA typing was fir st performed by serological typing of HLA anti-gens using antisera with de fin ed speci fic ities (1, 2), but this proce-dure has largely been replaced by DNA typing methods. Thepolymerase chain reaction (PCR) assay developed by Saiki et al. in1985 (3)was a major breakthrough technology for HLA genotyp-ing, and methods using PCR-ampli fie d DNA are now widely usedby HLA laboratories throughout the world. Currently there arenumerous DNA-based methods available that can detect HLAalleles from PCR-ampli fie d DNA, such as restriction fragment Frank T. Christiansen and Brian D. Tait (eds.), Immunogenetics: Methods and Applications in Clinical Practice,Methods in Molecular Biology, vol. 882, DOI 10.1007/978-1-61779-842-9_4, © Springer Science+Business Media New York 20124748 D. Trajanoski and S.J. Fidlerlength polymorphism (RFLPs) ( 4 ) , direct sequencing ( 5 ) , sequence-speci fi c primers (SSPs) ( 6) , and many others. Several of these are described elsewhere in this volume. However, all these methodshave their limitations in one way or another in terms of speed, lackof resolution, low throughput of sample number, and high cost.A novel method has been developed by combining PCR-ampli fi e d DNA and sequence-speci fi c oligonucleotide probe (SSO)protocols with the Luminex ® xMAP® technology.T he LABType ® SSO (One Lambda, Inc) and Gen-Probe LIFECODES SSO HLA Typing Assays use SSOs bound tofl u orescently coded microspheres to identify alleles encoded by thesample DNA. The principle involves adapting Luminex® xMAP ® tech-nology to the reverse SSO DNA typing method. Initially targetgenomic DNA is PCR ampli fi e d using a group-speci fi c primer. ThePCR product is biotinylated, which allows it to be detected usingR-Phycoerythrin-conjugated Streptavidin (SAPE). The PCR productis denatured and allowed to rehybridise to complementary DNAprobes conjugated to fl u orescently coded microspheres. After wash-ing the beads, bound ampli fi e d DNA from the test sample is taggedwith SAPE. Using the Luminex® Flow Analyser, the amount of PE on each speci fi c ally identi fi e d microsphere is detected. The assignment ofthe HLA typing is based on the pattern of reactivity of each beadcompared to patterns associated with published gene sequences.1. L uminex ® 100 or 200 Flow Analyser.2. L uminex ® XY Platform.3. C entrifuge M ikro 22 Hettich Zentrifugen or equivalent for 1.5-mL–microtube.S igma Laboratory Centrifuge 4–15 or equivalent for–96-well microplate.4. V ortex mixer with adjustable speed.5. T hermal cycler—ABI 9700 or Equivalent (see Note 1).6. E lectrophoresis apparatus.7. U V transiluminator with photographic image software.8. F reezer (−20 to −80°C).9. R efrigerator (4–8°C).1. G enomic DNA—patient samples and controls (see Note 2).2. D eionised water.3. 70% Ethanol.2.M aterials2.1.L ABType SSO (OneLambda)2.1.1.I nstrumentRequirements 2.1.2.M aterials andReagent Requirements4 HLA Typing Using Bead-Based Methods494. 20% Chlorine Bleach solution or equivalent.5. L uminex Sheath Fluid.6. L uminex Calibrator beads.7. L uminex Control beads.8. A mpliTaq polymerase 1,000 U, 5 U/ μL (ABI Part# N808-0101) (see Note 3).9. I sorack (Eppendorf).10. C rushed Ice bath.11. 1.5-mL Microtube (Eppendorf or equivalent).12. 5-, 20-, and 50-mL Disposable tubes (for making dilutions).13. D isposable pipette tips (10, 20, 100, 200, 1,000 μL).14. P CR pad.15. T imers.16. 10-, 20-, 100-, 200-, and 1,000- μL pipette–Gilson or equivalent.17. P CR 96-well microplates.18. 96-well, 250- μL V-bottom, white polystryene microplates.19. A luminium foil.20. A dhesive Tray seal (OLI Cat# SSPSEA300) or equivalent.21. P CR plate cap strips.22. W ash Troughs/Trays.23. 1% Seakem ME agarose.24. E lectrophoresis loading Dye—6× DNA loading dye (Fermentas)or equivalent.25. D NA lambda ladder—Generuler 100 bp DNA Ladder(Fermentas) or equivalent (see Note 4).26. 1× TBE buffer.27. 5 mg/mL Ethidium Bromide.28. S APE (One Lambda, Inc).29. O ne Lambda SSO Genotyping Kit (see Note 5) containing–®SSO Bead Mixture (Pre-optimised and tested L ABTypemixture of microspheres with covalently attached probes).L ABType–®SSO Hybridisation Buffer.–®SSO Wash buffer.L ABTypeL ABType–®SSO Denaturation Buffer.–®SSO Neutralisation Buffer.L ABType–®SSO Primer Set (Pre-optimised HLA loci-speci fic L ABTypeprimer mix).–®SSO D-Mix.L ABType–®SAPE Buffer.L ABType50 D. Trajanoski and S.J. FidlerR efer to Subheading 2.1.1 . T he same as Subheading 2.1.2 except replace One Lambda SSO Genotyping kit with:G en-Probe ●LIFECODES HLA-SSO Typing Kit (see Note 6) containingL ifeCodes HLA master mix.– L ifeCodes Probe Mix.– D ilution Solution.– S APE.–The methods in this chapter have been written according to cur-rent manufacturer’s protocols. Any changes to these methods suchas volumes of reagents and thermal cycler conditions can be foundin the kit insert and the appropriate websites (h ttp:// andh ttp:// ). These should also be checked following any lot change.1. C reate a LABType ® PCR program on your thermal cycler as shown in Table1 . 2.2.G en-ProbeLIFECODES SSO2.2.1.I nstrumentRequirements2.2.2.M aterials and Reagent Requirements3.M ethods 3.1.L ABType ®SSOHLA Typing Method3.1.1.D NA Ampli fic ation T able 1L ABType ® SSO polymerase chain reaction (PCR) programS tep T emperature and incubation time N umber of cycles514 HLA Typing Using Bead-Based Methods 2. T urn on thermal cycler to keep heated lid warm.3.S elect the appropriate HLA typing kit (locus and resolution) and thaw out ampli fi c ation primers and D -mix (see Note 7).Make sure to keep on ice until ready to use (see Note 8).4. V ortex D-mix and ampli fi c ation primer for at least 15 s andperform a quick centrifuge (5 s) to spin down any liquid trappedunder lid.5. C reate the ampli fi c ation mixture by adding correct volumes ofD-mix and ampli fi c ation primers in a 1.5-mL Eppendorf tubeaccording to Table2 (see Note 9). 6. P ipette 2 μ L of each DNA template (see Note 10) into a96-well PCR microplate.7.A dd the correct amount of AmpliTaq Polymerase (see Table 2 ) to the ampli fi c ation mixture and vortex for 5s (see Note 11).8. A liquot 18 μ L of ampli fi c ation mixture into each well contain-ing DNA (see Note 12).9.C ap or seal the plate and give a quick vortex to mix contents in plate.10.P lace PCR plate in thermal cycler and start the “LABType ® PCR program” shown in Table1 . 11. A fter the “LABType ® PCR program” is fi n ished, remove PCRplate and store in a 4°C fridge.12.P our agarose in a gel tray with the correct numbers of combs needed to electrophorese all the PCR products. (It is recom-T able 2L ABType ®ampli fic ation mixtureN umber of reactions D -mix ( m L )a A mpli fic ation primer ( m L )a A mpliTaq polymerase ( m L )aA s provided in the One Lambda SSO genotyping kit52 D. Trajanoski and S.J. Fidlermended you electrophorese all samples to con fi r m anampli fi c ation product band is present.)13.O nce the agarose gel is set, place gel tray in electrophoresis tank and pour 1× TBE buffer until agarose is fully immersed inthe 1× TBE buffer.14. M ix 5 μ L of DNA lambda ladder and 5 μ L of loading dyeand pipette into fi r st well of each row of the agarose gel (seeNote 13).15. I n a separate clean PCR plate, mix 5 μ L of PCR product and5 μ L of loading dye and pipette into remaining empty wells.Repeat this for all the samples.16.P lace the cover on the electrophoresis tank and run at 150 V for 20 min.17.T ake out gel and place on UV transilluminator to inspect PCR products. Save photo and check all samples have correctlyampli fi e d (see Note 14).1. T urn on thermal cycler and run program to 60°C hold. Make sure lid is heated to optimum temperature before use.2.R emove reagents listed in Tables 3 and 4 and supplied in the SSO genotyping kit from −80°C freezer to room temperatureto thaw and then prepare all reagent volumes in an appropri-3.1.2.D enaturation/Neutralisation T able 3L ABType ®reagent volumesN umber of tests a D enaturation buffer ( m L )b N eutralisation buffer ( m L )b H ybridisation buffer ( m L )b W ash buffer ( m L )b B ead mixture ( m L )b a N umber of tests includes all samples to be tested including appropriate controls and extra volume (see Notes 2 and 9 for comments)b A s provided in the One Lambda SSO genotyping kit534 HLA Typing Using Bead-Based Methods ately sized disposable tube as necessary according to Tables 3 and 4 (see Notes 8 and 15). 3. R eturn any unused reagents to 2–8°C (do not re-freeze bead mixture after thawing). 4. P repare a crushed ice bath. 5. T ransfer 5 μ L of each ampli fi e d DNA sample into the corre-sponding well of a clean 96-well PCR plate (see Note 16). 6. A dd 2.5 μ L Denaturation Buffer to each well of the PCR plate and mix thoroughly by pipetting up and down. Incubate at room temperature (20–24°C) for 10 min. 7. A dd 5 μ L Neutralisation Buffer with pipette to each well of the PCR plate and mix thoroughly (see Note 17). 8. P lace PCR plate on ice bath or 96-well ice rack. 1. P repare Hybridisation Mixture by combining appropriate vol-umes of Bead Mixture and Hybridisation buffer according toTable 3 (see Note 18).2. A dd 38 μ L hybridisation mixture to each well.3. C over with tray seal and give the PCR plate a quick mix usingthe vortex (see Note 19).4. P lace PCR plate into the pre-heated (60°C) thermal cycler,cover with PCR pad, and close and tighten lid. Incubate for15 min.5. R emove the PCR plate seal and quickly add 100 μ L wash buf-fer to each well (see Note 20).6. C over PCR plate with plate seal and centrifuge plate for 5 minat 1,000–1,300 × g . 3.1.3.H ybridisation T able 4L ABType ® R-Phycoerythrin-conjugated Streptavidin (SAPE) and SAPE buffer volumesN umber of tests S APE stock volume ( m L ) S APE buffer volume ( m L )a a A s provided in the One Lambda SSO genotyping kit54 D. Trajanoski and S.J. Fidler7. R emove the tray seal, then remove the wash buffer by dumping/ fl i cking plate upside down (see Note 21). Gently pat on absorbant paper three times to remove any residual liquid. 8. R epeat steps 4– 6 two more times for a total of three wash steps. 9. P repare the 1× SAPE solution at the third centrifugation stage according to Table 4 . 1. A dd 50 μ L of 1× SAPE solution to each well of the PCR plate. 2. C over plate with seal and vortex thoroughly at low speed. 3. P lace PCR plate into the pre-heated (60°C) thermal cycler, cover with PCR pad, and close lid. Incubate for 5 min. 4. R emove the PCR plate seal and quickly add 100 μ L wash buf-fer to each well (see Note 20). 5. C over PCR plate with plate seal and centrifuge plate for 5 min at 1,000–1,300 × g . 6. R emove wash buffer by dumping/ fl i cking plate upside down (see Note 12). 7. A dd 70 μ L wash buffer to each well and gently mix by pipetting. 8. T ransfer contents of each well to a 96-well V-bottom microplate (reading plate) using an 8-channel pipette. To avoid contami-nation use fresh pipette tips each time. 9. C over reading plate with seal and aluminium foil. Keep in dark and at 4°C until ready to read using LABScan™ Flow Analyser (see Note 22). 1. T urn on the system and set up the Luminex ® Flow Analyser for sample acquisition and calibration. (Further details of how to use the Luminex ® F low Analyser can be found in the Luminex ®u ser’s manual.)2. V erify the levels of sheath fl u id and waste fl u id (see Note 23).3. P erform Warm up by selecting “Warm Up” button in theLuminex opening system. The warm up requires no plate orsolution.4. P rime the instrument by selecting “Prime”. Again this steprequires no plate or solution.5. P erform a 70% alcohol fl u sh, followed by four washes withsheath fl u id.6. A calibration should be performed every time the instrumentis turned on or if the temperature of the instrument hasincreased or decreased by more than 3°C from the time ofcalibration.3.1.4.L abelling3.1.5.S ample Acquisitionon Luminex ®FlowAnalyser554 HLA Typing Using Bead-Based Methods 7. T o calibrate instrument, vortex calibration (CAL1 and 2) and control (CON1 and 2) beads thoroughly (see Note 24). 8. P lace four drops of the bead solutions in each of four wells (e.g. A1, B1, C1, and D1) in the following order: CAL1, CAL2, CON1, and CON2. 9. I n the acquisition software, select “CAL1” indicating the location of the bead solution. The instrument will then perform the calibration for CAL1. If the calibration is successful, this will be indicated in the “diagnostic” tab. 10. R epeat steps 8 and 9 for CAL2, CON1, and CON2 (see Note 25). 11. O nce calibration has been performed, perform four washes. 12. S elect the correct template according to the product catalogue and lot number being used (see Note 26). 13. C reate a fi l ename for the samples to be run, for example DATE_LOCUS_USERINITIALS. 14. C heck all template settings are correct (see Note 27). 15. L oad the 96-well reading plate from Subheading 3.1.4 step 9 into instrument and select “Start”. 16. O nce run is fi n ished, wash three times with sheath fl u id, sani-tise once with 20% bleach, wash three times with distilled water and soak with distilled water twice. 17. S hut down Luminex ® instrument. 1. D ata analysis for the HLA Class I and II assays are performed with the software package HLA Fusion™. The LABType ®analysis feature of the program analyses Luminex .csv outputfi l es and is based on catalogue speci fi c ations provided with thesoftware. Import the data fi l es as speci fi e d by the manufacturer(see Note 28).2. T he analysis software establishes the HLA type by fi r stly cate-gorising each of the beads via its internal fl u orescence, thendetermining whether a probe is bound or not by the strength ofexternal fl u orescence on that bead produced by the SAPE. For aparticular sample, the bead/probe fl u orescence for each of thebeads bearing a particular probe is visualised in the lower left-hand quadrant of the software (Fig. 1 ) as a bar chart. Any probecan be selected from this bar chart for further scrutiny. Theupper left quadrant shows the manufacturer’s QC panel reactiv-ity with the selected probe. In this example, the QC for probeA107 (Bead 512) is shown (see Note 29). The upper rightquadrant shows the probe reactivity for all samples in the runbeing analysed (see Note 30). The lower right quadrant showsthe software analysis derived HLA type of the sample based onthe positive and negative probe reactions (see Note 31).3.1.6.D ata Analysis:OneLambda HLA Fusion™56 D. Trajanoski and S.J. Fidler3.T he reporting function in the Fusion™ software allows result-ing via a printed hard-copy report, or export of results via a .csv fi l e (see Note 32).1. S elect the appropriate SSO kit for the HLA locus to be typed.2. A llow the master mix (containing ampli fi c ation primers) to thaw to room temperature (see Note 8).3.U sing Table 5 , prepare the components for ampli fi c ation forn + 2 reactions using the indicated amount of each component per reaction (except for DNA) (see Note 33). 3.2.G en-ProbeLIFECODES HLA-SSOTyping Method3.2.1.D NA Ampli fic ation T able 5G en-Probe LIFECODES components for ampli fic ation mixC omponent V olume per PCR sample reaction aA s provided in the Gen-Probe SSO genotyping kitF ig.1.H LA-Fusion ® analysis software. Quadrant 1 shows the bead/probe fl u orescence for each of the beads bearing a particular probe. Any probe can be selected from this bar chart for further scrutiny. Quadrant 2 shows the manufacturer’s QC panel reactivity with the selected probe (see Note 29). Quadrant 3 shows the probe reactivity for all samples in the run being analysed (see Note 30). Quadrant 4 shows the software analysis derived HLA type of the sample based on the p ositive and negative probe reactions (see Note 31). Courtesy of One Lambda, Inc. Used with permission.T able6G en-Probe LIFECODES thermal cycler conditionsfor amplific ationS tep T emperature and incubation time N umber of cycles4. B ring to a fin al volume of 50 μL (minus the volume of DNAtemplate) per reaction with nuclease free water. Gently vortex, spin down, and place on ice (see Note 9).5. P ipette the appropriate amount of DNA template into thePCR tubes (see Note 34).6. A liquot the ampli fic ation mix into the PCR tubes containingthe DNA. (The total volume of ampli fic ation mix and DNA template should equal 50 μL for each sample reaction.)7. C ap or seal wells tightly to prevent evaporation during PCR.8. P lace samples in the thermal cycler and run program (seeTable 6).9. A fter the program is fin ished, remove PCR plate and store in a4-C fridge.10. P our agarose in a gel tray with the correct number of combsneeded to electrophorese all the PCR products. (It is recom-mended you electrophorese all samples to con fir m ampli fic ation product band is present).11. O nce the agarose gel is set, place gel tray in electrophoresistank and pour 1× TBE buffer until agarose is fully immersed in the 1× TBE buffer.12. M ix 5 μL of DNA lambda ladder and 5 μL of loading dyeand pipette into fir st well of each row of the agarose gel (see Note 12).13. I n a clean PCR plate, mix 5 μL of PCR product and 5 μL ofloading dye and pipette into the remaining empty wells of the agarose gel. Repeat this for all the samples.14. P lace the cover on the electrophoresis tank and run at 150 Vfor 20 min. Take out gel and place on UV transilluminator toinspect PCR products. Save photo and check all samples havecorrectly ampli fie d (see Note 35).1. W arm probe mix in a 55–60°C heat block for at least 5–10 min 3.2.2.H ybridisationto thoroughly solubilise components in probe mixture.2. V ortex brie fly for about 15 s to thoroughly suspend the beads(see Note 18).3. A liquot 5 μL of locus-speci fic PCR product from Subheading3.2.1step 7 into a 96-well PCR plate (see Note 12).4. A liquot 15 μL of corresponding probe mix for the locus-speci fic product into each well. When aliquoting probe mix tomore than 10 wells, gently vortex probe mix after each set often. Seal plate with fil m.5. H ybridize samples under the incubation conditions indicatedin Table 7.6. W hile the samples are hybridizing, prepare a 1:200 DilutionSolution/SAPE mixture. Combine 170 μL Dilution Solution(DS) and 0.85 μL 1 mg/mL SAPE per sample (follow Table 8and see Notes 15, 36, and 37).T able7G en-Probe LIFECODES thermal cycler conditions |forhybridizationS tep T emperature and incubation time N umber of cyclesT able8G en-Probe LIFECODES SAPE and dilution solution volumesN umber of samples D ilution solution (DS) m L a S APE stock volume ( m L)ba A s provided in the Gen-Probe SSO genotyping kit7. A t the 56°C hold step (i.e. step 4, Table 7 ), while the tray is on the thermal cycler, dilute each sample with 170 μ L of the p repared DS/SAPE mixture. It is critical to dilute all samples within 5 min (following the 10 min 56°C step i.e. step 3, Table 7 ) (see Note 15). 8. T ransfer contents of each well to a 96-well V-bottom microplate (reading plate) using an 8-channel pipette. To avoid contami-nation use fresh pipette tips each time. N OTE: The Gen-Probe LIFECODES HLA-SSO assay requires no centrifugation or wash steps. 9. C over reading plate with seal and aluminium foil. Keep in dark and at 4°C until ready to read using LABScan™ 100 Flow Analyser (see Note 22). T he procedure for sample acquisition for the Gen-Probe LIFECODES SSO method is the same as that for the ONE LAMBDA method. Follow Subheading 3.1.5 steps 1– 17 . 1. D ata analysis for the HLA Class I and II assay is performed with the software package LifeMatch™. The Quick-Type™ analysis feature of the program analyses Luminex .csv outputfi l es and is based on catalogue speci fi c ations provided with thesoftware. Import the data fi l es as speci fi e d by the manufacturer(see Note 38).2. T he analysis software establishes the HLA type by fi r stly cate-gorising each of the beads via its internal fl u orescence, thendetermining whether a probe is bound or not by the strengthof external fl u orescence on that bead produced by the SAPE.The probe reactivity thresholds and probe assignments for anindividual sample are shown in the table in section A (Fig. 2 ).In the example shown in Fig. 2 , for probe 331 the positive andnegative thresholds are 0.624 and 0.511, respectively. For thesample tested, for probe 331 the fl u orescence observed is 0.992which is greater than the positive threshold. This is scoredp ositive. An assignment can be changed from positive to nega-tive or vice versa in this table (see Notes 30 and 39). The drop-down in section B allows selection of an individual probe. Inthis section, the probe reactivity for all samples in the run underanalysis can be viewed. In the example in Fig. 2 , probe 202 gavea fl u orescence above the positive threshold for three of the sam-ples displayed. Section C shows the selected probe reactivity forall historical samples. These local data can be used to allow theuser to modify the cut-offs as required. The fi n al HLA type isdisplayed in section D, including any results from other analysesof the same sample. In this example, the fi n al HLA type is A*01,A*02. The suggested allelic combination for an individual s ampleis shown in section E. In this example, possible combinations3.2.3.S ample Acquisitionon Luminex ®FlowAnalyser3.2.4.D ata Analysis-Gen-Probe LifeMatch Quick-Type™F ig.2.L IFECODES ® Quick-Type™ analysis software. Section A shows the probe reactivity thresholds and probe assignments for an individual sample. An assignment can be changed from positive to negative or vice versa in this table (see Notes 30 and 39). The drop-down in section B allows selection of an individual probe. In this section, the probe reactivity for all samples in the run under analysis can be viewed. Section C shows the selected probe reactivity for all historical samples. The fi n al HLA type is displayed in section D, including any results from other analyses of the same sample. The suggested allelic combination for an individual sample is shown in section E. Courtesy of Gen-Probe,ed with permission.are A*01:01:01:01, A*02:01:01:01 or A*01:01:01:01, A*02:01:01:02L or A*01:01:01:01, A*02:01:02, etc.3.T he reporting function in the LIFECODES™ software allows resulting via a printed hard-copy report or export of results viaa .csv fi l e (see Note 23).1.R amping speed is critical for this PCR reaction. If an ABI 9700 thermal cycler is not available, a detailed work-up of the assaymay be required adjusting ramping speed as appropriate.2.A t least one control DNA of well-established HLA type should be included in each typing run. This control can be used as anampli fi c ation control, hybridisation control, and as a run con-trol (sample order control). The concentration of DNArequired is de fi n ed by the manufacturer in the kit insert.4.N otes3. A mpliTaq is recommended by the manufacturer. If an alternativeis used, it will need careful QC to ensure appropriate ampli fic ation of DNA occurs.4. A DNA ladder from 100 to 1,000 bp is suf fic ient to size anyproduct from the LABType SSO range.5. T he LABType SSO range includes HLA typing kits speci fic forHLA-A, -B, -C, -DRB1, -DRB3,4,5, -DQB1, -DQA1, -DPB1.Intermediate resolution kits are available for all loci and high resolution kits are available for some. For the full range refer toh ttp:// .6. T he LifeCodes SSO range includes HLA typing kits speci fic forHLA-A, -B, -C, -DRB1,-DRB3,4,5, -DQB1, -DQA1, -DPB1.Intermediate resolution kits are available for all loci. For the full range refer to h ttp:// .7. D-mix is generic and may be used with any HLA typing kit.However, the ampli fic ation primers are speci fic for each kit and lot speci fic and therefore must not be interchanged.8. O nce the reagents are thawed at room temperature, vortex thevials at medium speed for 20 s followed by a quick centrifuge spin. This is done to spin down any liquid present in the lid.After centrifuging, place them in a cold isorack or crushed ice to keep cool.9. W hen making up the ampli fic ation mixture always make extravolume for the required number of tests needed. The extra volume may be needed depending on pipetting techniques and calibration status of equipment.10. O NE LAMBDA recommend DNA at 20 ng/ μL concentrationwith A260/A280 ratio 1.65:1.8. DNA should not be resus-pended in EDTA. Where DNA concentration is less than20 ng/ μL, the assay may be modi fie d by adding a greater volumeof DNA, and reducing the volume of D-mix as appropriate. 11. W hen adding Taq polymerase, gently mix using vortex on lowspeed or by fli cking tube with fin gers. Excessive fast mixing may denature the Taq polymerase resulting in poor PCR ampli fic ation of the template DNA.12. T ake care not to crosscontaminate samples with one another.Either use a fresh tip each time or if you are multidispensing, place the tip on the top left side of each well and dispense. This should not cause contamination as the tip touches a clean part of the well each time.13. M ake sure to use an 8-channel pipette as this will reducepipetting time, and always use fresh clean tips for each dis-pense. Never re-use tips, as this will cause contamination. 14. T he size of the PCR ampli fic ation product differs according tothe HLA typing kit used. The expected product size can be found。

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