Isoth erma l Titration Calorime try in the student lab

The International Journal of Biochemistry&Cell Biology39(2007)1489–1499ReviewThe thalidomide sagaMagda Melchert a,∗,Alan List ba Moffitt Cancer Center and Research Institute,12902Magnolia Drive,SRB-4,Tampa,FL33612,USAb12902Magnolia Drive,SRB-4,Tampa,FL33612,USAAvailable online30January2007AbstractOver the past50years,thalidomide has been a target of active investigation in both malignant and inflammatory conditions. Although initially developed for its sedative properties,decades of investigation have identified a multitude of biological effects that led to its classification as an immunomodulatory drug(IMiD).In addition to suppression of tumor necrosis factor-alpha(TNF-␣), thalidomide effects the generation and elaboration of a cascade of pro-inflammatory cytokines that activate cytotoxic T-cells even in the absence of co-stimulatory signals.Furthermore,vascular endothelial growth factor(VEGF)and betafibroblast growth factor (bFGF)secretion and cellular response are suppressed by thalidomide,thus antagonizing neoangiogenesis and altering the bone marrow stromal microenvironment in hematologic malignancies.The thalidomide analogs,lenalidomide(CC-5013;Revlimid)and CC-4047(Actimid),have enhanced potency as inhibitors of TNF-␣and other inflammatory cytokines,as well as greater capacity to promote T-cell activation and suppress angiogenesis.Both thalidomide and lenalidomide are effective in the treatment of multiple myeloma and myelodysplastic syndromes for which the Food and Drug Administration granted recent approval.Nonetheless,each of these IMiDs remains the subject of active investigation in solid tumors,hematologic malignancies,and other inflammatory conditions.This review will explore the pharmacokinetic and biologic effects of thalidomide and its progeny compounds.©2007Elsevier Ltd.All rights reserved.Keywords:Thalidomide;Immunomodulatory agent;Angiogenesis;Lenalidomide;CC-4047Contents1.Introduction (1490)2.Pharmacokinetic properties (1490)3.Pharmacodynamic effects (1491)3.1.Immunomodulation (1491)3.2.T-cell activation (1492)3.3.Angiogenesis (1492)3.4.Bone marrow microenvironment (1493)3.5.Anti-tumor and apoptotic mechanisms (1493)4.Role of IMiDs in cancer therapy (1493)4.1.Multiple myeloma (1493)4.2.Myelodysplastic syndromes (1493)5.Conclusion (1496)References (1496)∗Corresponding author.Tel.:+18137453163;fax:+18137453071.E-mail addresses:Melcheme@moffi(M.Melchert),ListAF@moffi(A.List).1357-2725/$–see front matter©2007Elsevier Ltd.All rights reserved.doi:10.1016/j.biocel.2007.01.0221490M.Melchert,A.List/The International Journal of Biochemistry&Cell Biology39(2007)1489–14991.IntroductionThalidomide(Thalomid TM,Celgene Corp,Warren, NJ)is a synthetic glutamic acid derivative which was ini-tially developed in the early1950s as an anticonvulsant for the treatment of epilepsy.Following a lack of suffi-cient efficacy as an anti-epileptic,it was eventually mar-keted as a sleep aid and was also widely used as an anti-emetic during pregnancy(Randall,1990).Prior to its use in gravid women,the teratogenic effects of thalidomide in animals or humans were unknown.However,by1962, two published reports by William McBride in Australia and Widukind Lenz in Germany emerged describing limb and bowel malformations in children born to moth-ers who were exposed to thalidomide during pregnancy (Lenz,1962;McBride,1961).Use of this agent dur-ing thefirst trimester of gestation led to alarming rates of phocomelia,defects in long bones,absence of auri-cles,cleft lip,and cardiac and gastrointestinal anomalies. While thalidomide had not received approval by the Food and Drug Administration(FDA)in the United States (US)at this time due to concerns of neurotoxicity,the widespread international use of this drug as a sedative was eventually halted during the early1960s.The pharmacological effects of thalidomide extended beyond its neurosedative effects,and for that reason, it was subsequently investigated in a number of der-matologic,rheumatologic,and malignant diseases.In 1965,thefirst report of clinical activity in erythema nodosum leprosum(ENL)was serendipitously discov-ered by a dermatologist from Israel,Jacob Sheskin (Sheskin,1965).Thalidomide was found to be effec-tive in reducing fevers,night sweats,and improving skin lesions in a patient with ENL.However,it was not until1998that thalidomidefirst received approval by the FDA for the treatment of ENL(Pearson&Vedagiri, 1969;Sheskin,1965;Waters,1971).More recently, thalidomide was approved for the treatment of multi-ple myeloma in May2006,and has reported efficacy in a wide spectrum of malignant and non-malignant dis-eases.Access to this agent in the US is restricted,and requires participation in the System for Thalidomide Education and Prescription Safety(STEPS)program to prevent adverse outcomes related to teratogenicity (Zeldis,Williams,Thomas,&Elsaved,1999).Thalidomide and its analogs are immunomodula-tory drugs(IMiDs)that exhibit a multitude of biologic effects on cytokine and cell-mediated responses.These effects are largely responsible for the clinical efficacy seen in conditions such as lupus erythematosis,apt-hous ulcers that occur in human immunodeficiency virus and Behcet’s disease,ENL,graft versus host dis-ease,and cancer(Hamuryudan et al.,1998;Jacobson et al.,1997;Kumar,Witzig,&Rajkumar,2004;Parker et al.,1995;Pearson&Vedagiri,1969).Thalidomide is the most widely studied of the IMiDs;however, the newer structural analogs,CC-5013(lenalidomide, Revlimid TM,Celgene Corp.,Warren,NJ)and CC-4047 (Actimid TM),promise even greater activity for clinical development.These two analogs of thalidomide were developed in the mid-1990s with enhanced potency and a relatively favorable toxicity profile.This review will summarize the pharmacokinetic and biologic properties of thalidomide and its derivatives.2.Pharmacokinetic propertiesThalidomide(␣[N=Phthalimido]glutarimide)con-tains a glutarimide moiety with a single chiral center and is formulated as a racemic mixture of two active enantiomers,S(−)and R(+)(see Fig.1).Initially,the S(−)isoform was thought to be the enantiomer pri-marily responsible for the teratogenic effects and the R(−)isoform for the sedative properties.Purification of the R(−)enantiomer was attempted in order to optimize its clinical application,but was eventually not found to be technically feasible secondary to the rapid interconversion of isomers under physiologic con-ditions.Furthermore,both forms were found to be teratogenic in the New Zealand rabbit model,and thus it remains a racemic mixture(Eriksson,Bjorkman,Roth,& Fig.1.Adapted with permission from Macmillan Publishers Ltd:Nature Reviews Cancer,2004(Bartlett et al.,2004);(a)the chemical structure of thalidomide;(b)alteration of the structure of thalidomideby adding an amino(NH2−)group at the4position of the phthaloyl ring to generate the IMiDs CC-5013and CC-4047.For CC-5013,one of the carbonyls(C O)of the4-amino-substituted phthaloyl ring has been removed.M.Melchert,A.List/The International Journal of Biochemistry&Cell Biology39(2007)1489–14991491Hoglund,2000;Fabro,Smith,&Williams,1967).Poor water solubility led to the development of thalidomide exclusively as an oral agent,with peak plasma con-centrations of the drug detected at3–6h(Chen et al., 1989).Upon ingestion,thalidomide undergoes sponta-neous non-enzymatic hydrolytic cleavage into more than 12different metabolites.Thalidomide and its metabo-lites are quickly eliminated in the urine,with a mean elimination half-life of approximately5h.The pharma-cokinetic properties of thalidomide in the presence of renal or hepatic dysfunction are largely unknown.Dos-ing with thalidomide is disease-dependent,with daily oral schedules of50–800mg,demonstrating efficacy in a variety of disease processes.Over the last decade,second-generation IMiD com-pounds have been developed by chemical modification of the structural backbone of thalidomide in order to enhance immunomodulatory potency and minimize the dose-limiting neurotoxic effects.Both lenalidomide and CC-4047are4-amino-gultaramide derivatives of thalidomide in which an amino group was added to the fourth carbon of the phthaloyl ring of the parent com-pound(see Fig.1)(Bartlett,Dredge,&Dalgleish,2004; Teo et al.,2003).Both agents also exist as a racemic mixture of the active S(−)and R(+)forms.Like thalido-mide,they are both administered in daily oral dosing every21–28days of monthly cycles.Renal elimination predominates,and caution is recommended in dosing of patients with impaired creatinine clearance.The ter-minal half-life of lenalidomide and CC-4047after oral administration are reported as3and7h,respectively (Bartlett et al.,2004;Schey et al.,2004).In contrast to thalidomide in which somnolence,constipation,and peripheral neuropathy are common dose-limiting toxic-ities,both lenalidomide and CC-4047lack significant neurosedative toxicity.Dose-limiting neutropenia and thrombocytopenia are the most common toxic sequelae, while venous thromboembolism has been reported with use of all three agents.3.Pharmacodynamic effects3.1.ImmunomodulationThalidomide and its derivatives are potent immunomodulators with biologic effects on both cytokine stimulation and cell-mediated immunity(see Fig.2).One of the key mediators responsible for the anti-inflammatory responses seen with the use of IMiD agents is tumor necrosis factor-alpha(TNF-␣). Thalidomide enhances degradation of TNF-␣mRNA, thus suppressing this pro-inflammatory cytokinerelease Fig.2.Reproduced with permission from Journal of Clinical Oncol-ogy,2004(Kumar et al.,2004).Proposed mechanism of action of thalidomide in cancer illustrated using myeloma as an example. Thalidomide inhibits angiogenesis,enhances effects of the immune system,inhibits binding of tumor cells to stroma,and inhibits various cytokines.Thaliomide may also have direct effects on the tumor.NK: natural killer;TNF:tumor necrosis factor;IL-6:interleukin-6;VEGF: vascular endothelial growth factor;NF-kB:nuclear factor kappa B. from endotoxin-stimulated monocytes and macrophages (Moreira et al.,1993).The effect on TNF-␣is felt to be largely responsible for the clinical benefit seen in patients with inflammatory conditions such as ENL,who have high endogenous TNF-␣production that is suppressed following thalidomide treatment (Sampaio et al.,1993).In addition,both lenalidomide and CC-4047have up to a50,000-fold higher potency than thalidomide as inhibitors of cytokine generation, including suppression of endotoxin-induced TNF-␣secretion(Bartlett et al.,2004;Corral et al.,1999a). Activation of the transcription factor nuclear factor kappa B(NF-kB),a key regulator of TNF-␣and inter-leukin(IL)-8production,is blocked after thalidomide exposure through inhibition of the inhibitor of kappa B (IkB)kinase(Keifer,Guttridge,Ashburner,&Baldwin, 2001).However,the cellular response to IMiD agents is quite complex and lineage and ligand specific,with evidence that TNF-␣generation is actually enhanced in the setting of T-cell activation.This is demonstrable in1492M.Melchert,A.List/The International Journal of Biochemistry&Cell Biology39(2007)1489–1499vitro with upregulation of TNF-␣production by CD4+ and CD8+T-lymphocytes stimulated by anti-CD3 (Marriott et al.,2002).Furthermore,an increase in TNF-␣serum concentration has been reported upon exposure to IMiD agents in early-phase trials involving solid tumors and inflammatory dermatologic diseases such as toxic epidermal necrolysis(Bartlett et al.,2004; Wolkenstein et al.,1998).While the biologic effects of TNF-␣modulation by the IMiD agents may be central to the therapeutic bene-fits seen in a variety of inflammatory conditions,there are several other cytokines that are similarly affected by this class of agents that may play a significant role in immune modulation.Generation of pro-inflammatory enzymes and cytokines,such as cyclooxygenase-2(COX-2), interleukin-1beta(IL-1␤),transforming growth fac-tor(TGF)-␤,and IL-6are suppressed upon exposure to IMiDs,and contribute to the activation of the T-cell receptor(TCR),particularly in the T H1subset (Bartlett et al.,2004;Corral et al.,1999a;Musto,2004). Analogous to TNF-␣modulation,IL-12secretion is sup-pressed by IMiDs when monocytes are stimulated by lipopolysaccharide and is enhanced in the setting of T-cell stimulation(Corral et al.,1999a,1999b).Expansion of both T-cells and NK-cells is promoted by IL-12secre-tion and thus IMiD agents have the potential to be useful adjuncts in the development of cancer vaccines and other immunotherapuetic approaches(Trinchieri,1998).Fur-thermore,IL-12stimulates interferon-␥(IFN-␥)produc-tion and both cytokines have demonstrable anti-tumor activity and anti-angiogenic-activity(Beatty&Paterson, 2001;Qin&Blankenstein,2000;Trinchieri,1998). 3.2.T-cell activationThe immune response to foreign antigens is a highly regulated process requiring the presentation of major histocompatability(MHC)-bound peptides on antigen presenting cells(APCs)to the TCR.Acces-sory molecules,such as B7on APC and CD28on the T-cell surface,provide secondary signals that are vital to the promotion of T-cell responsiveness.These interactions lead to the subsequent activation and pro-liferation of T-cells followed by a cascade of cytokine and cellular responses.Thalidomide and its deriva-tives are able to enhance the CD8+T-cell response in the absence of these secondary co-stimulatory sig-nals(Haslett,Corral,Albert,&Kaplan,1998;Mueller, Jenkins,&Schwartz,1989).In vitro data of primary human T-cells suggest that thalidomide enhances IL-2 mediated T-cell proliferation and IFN-␥production via the TCR complex.The effect of thalidomide on T-cell expansion is dose-dependent and occurs even at low lev-els of CD3stimulation.Furthermore,thalidomide affects the balance between T-helper(Th)-1and-2subsets at least in part through cytokine modulation of IL-4,IL-5,and IFN-␥(McHugh et al.,1995).In the presence of thalidomide,mitogen-and antigen-stimulated human peripheral blood mononuclear cells preferentially induce the Th-2subtype,which corresponds with maximum enhancement of IL-4production.Thalidomide derivatives are also potent co-stimulators of T-cells that enhance activation of CD8+ T-cells in vitro(Stirling,2001).Upon exposure to CMV and influenza virus matrix proteins,both CC-5013and thalidomide were shown to enhance CD8+cytokine production and cytotoxic activity(Haslett,Hanekom, Muller,&Kaplan,2003).CC-4047has demonstrated durable,tumor-specific Th-1type immunity in mice tumor xenograft models(Dredge,Marriott,Todryk et al.,2002).These preclinical investigations have suggested a potential role for the use of IMiD agents in the development of tumor vaccine adjuncts and as modulators of immune response in the setting of defective CD4+mediated immunity such as HIV and graft versus host disease.3.3.AngiogenesisIn the early1990s,thalidomide wasfirst reported to exhibit potent anti-angiogenic properties that were thought to contribute to the teratogenic effects of limb bud malformations observed in offspring of thalidomide exposed gravid mothers(D’Amato,Loughnan,Flynn, &Folkman,1994).Eventually,the effect of IMiDs on vasculogenesis was recognized as a mechanism of poten-tial clinical benefit in the treatment of malignancies in which neoangiogenesis is a conserved feature of the malignant phenotype.Vascular endothelial growth fac-tor(VEGF)and betafibroblast growth factor(bFGF)are potent stromal mitogens that are produced in excess in a variety of malignancies,including multiple myeloma and myeloid disorders.Paracrine and autocrine secre-tion of VEGF causes proliferation of multiple myeloma cell lines and has also been shown to promote self-renewal of leukemia progenitors(Bellamy et al.,2001; Gupta et al.,2001).Secretion of both VEGF and bFGF from tumor and bone marrow stromal cells is sup-pressed upon exposure to IMiDs,resulting in reduced endothelial cell migration and adhesion(D’Amato et al.,1994;Dredge,Marriott,Macdonald et al.,2002; Lentzsch et al.,2003).Both thalidomide and CC-4047 have been shown to suppress the induction of VEGF in co-cultures of multiple myeloma cell lines and boneM.Melchert,A.List/The International Journal of Biochemistry&Cell Biology39(2007)1489–14991493marrow stromal cells(Gupta et al.,2001).Additionally, thalidomide inhibits bFGF-induced angiogenesis in vivo using a rabbit cornea micropocket assay(D’Amato et al.,1994).In murine lymphoma and rectal carcinoma cell line xenografts,IMiDs decrease tumor microvessel formation(Dredge,Marriott,Macdonald et al.,2002; Lentzsch et al.,2003).The latter anti-angiogenic effect is independent of TNF-␣suppression or endothelial cell proliferation,and appears to be dose-or concentration-dependent.Furthermore,lenalidomide has been shown to attenuate AKT-dependent phosphorylation,resulting in a reduction of bFGF-induced endothelial cell migra-tion(Dredge,Marriott,Macdonald et al.,2002;Dredge et al.,2005).3.4.Bone marrow microenvironmentThe pro-inflammatory responses within the bone marrow microenvironment are thought to play a sup-portive or tumor nurturing role in many hematologic diseases,including multiple myeloma and myeloid dis-orders.TNF-␣induces expression of IL-6secretion by bone marrow stromal cells and is markedly upregulated upon adhesion of multiple myeloma cells to bone mar-row stromal cells(Gupta et al.,2001;Witzig,1999). The adhesion molecules,ICAM-1,LFA-1,and VCAM-1,are similarly affected in the bone marrow milieu (Miyamoto et al.,1995).IL-6promotes the prolifera-tion of multiple myeloma cell lines and inhibits Fas-and dexamethasone-induced apoptosis in vitro.Both thalidomide and CC-4047decrease upregulation of IL-6in co-cultures of bone marrow stromal and multiple myeloma cells,suggesting an additional mechanism of therapeutic benefit in multiple myeloma.Lenalido-mide induces activation of cell adhesion molecules and increases␤1integrin-mediated adhesion to extracel-lular matrix proteinfibronectin(Dredge et al.,2005; Miyamoto et al.,1995).3.5.Anti-tumor and apoptotic mechanismsIndependent of the immune-modulating activities, IMiDs have direct anti-proliferative activity in hema-tologic malignancies.The IMiDs,as a class,induce concentration-dependent inhibition of proliferation in multiple myeloma cell lines and primary myeloma cells that are resistant to standard chemotherapy(Lentzsch et al.,2003).Effects on apoptosis are evident at multiple levels of death receptor signaling,including potentia-tion of TNF-related apoptosis-inducing ligand(TRAIL), inhibition of apoptosis protein-2,increased sensitivity to Fas induction,and upregulation of caspase-8activa-tion(Keifer et al.,2001;Mitsiades et al.,2002).G0/G1 cell cycle arrest or apoptosis in leukemia cell lines and other hematologic malignancies occurs with lenalido-mide exposure and is mediated,at least in part,by A-dependent mechanisms(Dredge et al.,2005).Further-more,lenalidomide has preferential anti-proliferative activity against a5q mutant cell line(MUTZ-1)with corresponding induction of expression of genes encoded at the5q locus(Gandhi et al.,2004).These preclinical findings have been confirmed in clinical trials involving patients with myelodysplastic syndromes(MDS).4.Role of IMiDs in cancer therapyThalidomide and its analogs have therapeutic potential in a wide spectrum of diseases given their multifaceted pharmacologic effects.The known immunomodulatory and anti-angiogenic properties of IMiDs provided the impetus to investigate these agents in the treatment of both hematologic malignancies and in solid tumors.Numerous early-phase trials in solid tumors have shown activity in prostate cancer,breast cancer,Kaposi’s sarcoma,renal cell cancer,melanoma, neuroendocrine tumors,hepatocellular carcinoma,lung cancer,and gliomas(Kumar et al.,2004).Response rates have been promising in some;however,further studies are needed to elucidate the true magnitude of thera-peutic benefit in solid tumors.In addition,the IMiDs are attractive agents for the treatment of both myeloid and lymphoid malignancies with reported activity in non-Hodgkin’s lymphoma,acute myeloid leukemia,and myelofibrosis with myeloid metaplasia(Kumar et al., 2004).However,the earliest focus of clinical investiga-tions involved multiple myeloma and MDS and thus will be discussed in further detail.4.1.Multiple myelomaThe use of IMiDs in the treatment of multiple myeloma has recently emerged as the standard of care following multiple reports of efficacy in both front-line therapy and in relapsed or refractory dis-ease(Glasmacher et al.,2006;Rajkumar,Blood,Vesole, Fonseca,&Greipp,2006;Singhal et al.,1999;Tosi, Zamagni,&Cellini,2004).In May2006,thalidomide was approved by the US FDA for the treatment of newly diagnosed multiple myeloma in combination with dex-amethasone.The approval was based on a phase III multicenter trial performed by the Eastern Coopera-tive Oncology Group(ECOG)in which patients were randomized to four cycles of dexamethasone40mg on days1–4,9–12,17–20of28-day cycles either1494M.Melchert,A.List/The International Journal of Biochemistry&Cell Biology39(2007)1489–1499Table1Summary of MM-009and MM-010,phase III trials of CC-5013in multiple myelomaMM-009MM-010North American trial International trialCC-5013+Dex Dex alone CC-5013+Dex Dex alone TTP(weeks)60.120.753.420.6 Overall RR(%)61.222.85821.7CR(%)26.5 4.113.6 4.0 Dex:dexamethasone;TTP:time to progression;RR:response rate;CR:complete response.alone or with200mg daily of thalidomide(Table1) (Rajkumar et al.,2006).Paraprotein responses in serum and urine monoclonal protein levels were observed in63%of patients treated on the combination arm compared to41%of patient receiving dexamethasone alone(p=.0017).Toxicities were significant,with17% of patients developing deep venous thrombosis which prompted the recommendation for anticoagulation dur-ing combination therapy.Other adverse events included rash,bradycardia,and neuropathy.As a consequence,the thalidomide/dexamethasone combination is a common induction regimen for use as initial therapy in multiple myeloma and prior to autologous transplant.Thalidomide has also enjoyed success in the salvage setting,with multiple phase I and II trials demon-strating efficacy either alone with response rates of 25–35%,or in combination with dexamethasone with response rates of50–60%(Glasmacher et al.,2006; Tosi et al.,2004).Combination chemotherapy trials with thalidomide have yielded variable rates of suc-cess in relapsed and refractory disease when applied in conjunction with dexamethasone,cisplatin,adriam-cyin,cyclophosphamide,etoposide,clarithramycin,and melphalan(Coleman et al.,2002;Kyriakou et al.,2005; Lee et al.,2003;Srkalovic,Elson,Trebisky,Karam, &Hussein,2002).Finally,thalidomide has also shown benefit in the maintenance setting.The Intergroupe Fran-cophone du Myelome(IFM)recently reported the results of trial involving597patients who were randomized after autologous stem cell transplantation to three of the treatment strategies,i.e.,either(A)no maintenance, (B)pamidronate maintenance,or(C)thalidomide and pamidronate maintenance treatment until disease pro-gression(Attal et al.,2006).A complete or very good partial response was achieved in55%of patients in arm A,57%in arm B,and67%in arm C(p=0.03).The 3-year post-randomization probability of event-free sur-vival was improved with the thalidomide combination maintenance with36%of patients in arm A,37%in arm B,and52%in arm C remaining without evidence of disease progression(p<.009).The4-year probabil-ity of survival from the date of diagnosis was improved in the thalidomide/pamidronate maintenance arm(77% versus74%versus87%;p<.04).The initial dose of thalidomide was400mg daily,with39%of patients dis-continuing treatment secondary to adverse effects at a median of8months.Thus,while toxicities remain sub-stantial,thalidomide is an effective agent in the treatment of myeloma in all stages of the disease.Of particular importance,maintenance therapy with thalidomide in this trial did not increase the risk of thromboembolic complications,suggesting that thrombogenic potential may be highest when thalidomide is administered dur-ing induction therapy when tumor burden is high or when combined with agents that have intrinsic thrombogenic potential.Lenalidomide was subsequently approved by the FDA in June2006for combination treatment with dex-amethasone for relapsed or refractory multiple myeloma. Based on encouraging data from several phase I and II trials,two phase III randomized,multicenter trials (MM-009,US and MM-010,Europe)were initiated comparing lenalidomide and dexamethasone combi-nation treatment with dexamethasone and placebo in patients with multiple myeloma who had received at least one prior therapy(Weber et al.,2006).Interim results were reported at the American Society of Clinical Oncology Meeting in2006.Lenalidomide was adminis-tered in a daily25mg dose for21days in combination with dexamethasone pulse dose treatment of40mg on days1–4,9–12,and17–20in a28-day cycle.Major reductions in serum paraprotein concentration were reported in51–53%of the lenalidomide/dexamethasone group and were statistically superior to those seen in patients receiving dexamethasone alone(OR 5.5 [3.9,9.1];p<.0001).The median time to progression (TTP)in MM-009compared favorably:37weeks in the lenalidomide/dexamethasone arm versus19.9weeks for dexamethasone alone(HR=0.356[0.257,0.494]; p>.0001).Toxicities were manageable;however,grade 3/4neutropenia and thrombocytopenia were experienced in27%and17%of patients,respectively,with a7.8% incidence of deep vein thrombosis.Importantly,the adverse events commonly seen with thalidomide,such asM.Melchert,A.List/The International Journal of Biochemistry&Cell Biology39(2007)1489–14991495neuropathy,constipation,and sedation,were infrequent in these trials.Other toxicities include included rash, gastrointestinal symptoms,myalgias,and pulmonary embolism.Among patients receiving the lenalidomide combination in the MM-009study,thrombo-embolic events were reported in20of87patients(23%)who received concomitant recombinant erythropoietin ther-apy and in4of83patients who did not receive erythropoietin(5%)(Knight,DeLap,&Zeldis,2006). In the group that received placebo and dexametha-sone,thrombosis occurred in5of67patients(7%) who received concomitant erythropoietin and in1of 103patients(1%)who did not receive erythropoietin. Multivariate analysis of both studies combined showed an independent correlation between the development thrombotic events and treatment with the combination of lenalidomide and high-dose dexamethasone or treatment with concomitant erythropoietin.Of particular interest, thrombotic events were not reported among23patients who received aspirin or salicylates during thefirst month of treatment,as compared with52of668patients who did not receive aspirin or salicylates.A recent study showed a reduction in the thrombosis rate with the administration of aspirin in myeloma patients receiving a combination of thalidomide and anthracycline,sug-gesting that thrombotic risk with the IMiDs may be reduced when used in combination therapy by avoid-ance of recombinant erythropoietins that have inherent thrombotic potential,or prophylaxis with aspirin or alter-nate strategies(Baz et al.,2005).The latter approach is a subject of current investigation in an ECOG study.Dis-tribution of lenalidomide,like its parent compound,is also highly regulated given concerns for possible ter-atogenic effects.All patients prescribed this drug must participate in the Rev-Assist program prior to receiving medication.A phase I,dose-escalation study of CC-4047in multiple myeloma has also been reported with demon-strated safety and efficacy(Schey et al.,2004).The drug was well tolerated,with the main dose-limiting toxic-ities being neutropenia and venous thrombosis with a maximum tolerated dose of2mg/day.A25%or more reduction in paraprotein was seen in67%of patients,and 54%achieved greater than a50%reduction.In support of T-cell activation as possible mechanistic role,increased serum IL-2receptor and IL-12levels were detected in patients receiving CC-4047.4.2.Myelodysplastic syndromesIMiDs were initially targeted as potential agents for the treatment of MDS based on their immunomodula-tory and anti-angiogenic features.Thefirst report of the use of thalidomide in MDS involved a trial of83 patients and included biologic correlates designed to assess angiogenic and inflammatory responses(Raza et al.,2001).Thalidomide was initiated at100mg daily and titrated upwards to a dose of400mg daily as tolerated. At12weeks of treatment,only61%of patients were able to complete the planned course of treatment sec-ondary to dose-limiting toxicities.Only13%of patients experienced a major erythroid response,and platelet or neutrophil improvements were uncommon.How-ever,erythroid responses were durable,with a median duration of306days.Thalidomide has since been inves-tigated in multiple trials at doses of200–1000mg daily in the treatment of both low-and high-risk MDS,with either hematologic improvement or partial responses reported in approximately20–60%of patients(Bouscary et al.,2005;Moreno-Aspitia et al.,2006;Zorat et al.,2001).At these doses,tolerance of thalidomide is discouraging,with a high frequency of dose-limiting fatigue,constipation,neuropathy,and sedation.For this reason,enthusiasm for development of thalidomide in the treatment of MDS has been tempered.In contrast,lenalidomide has shown remarkable activ-ity in the treatment of MDS with toxicities that compare favorably to thalidomide.The initial report on the safety and efficacy of lenalidomide in MDS included 43patients with symptomatic anemia who had either failed treatment with erythropoietin(EPO)or were poor candidates for benefit from EPO therapy(frequent transfusions(>2per month)and/or high endogenous ery-thropoietin serum concentration(>500mU/ml))(List et al.,2005).Patients were randomized to one of three dos-ing schedules:25mg daily,10mg daily,or10mg/day for21of ing the International Work-ing Group(IWG)criteria,56%of patients experienced durable erythroid responses and20of32patients who previously required RBC support became transfusion independent.Furthermore,10of12patients with an isolated interstitial deletion of chromosome5(5q31.1) experienced an erythroid response compared to57%of patients with a normal karyotype or12%of patients with other chromosomal abnormalities.Patients with 5q31.1had particular benefit with a longer duration of transfusion independence.Both cytogenetic responses and decreased medullary myeloblast percentage were noted in patients responding to lenalidomide,and were more pronounced in patients with chromosome5q31.1 deletion.The dose-limiting toxicities were related to myelosuppression,with grade3or greater neutrope-nia(58%)and thrombocytopenia(50%)necessitating dose reductions or treatment interruption in47–77%of。

・96・中国实用医药2019年10月第14卷第28期China Prac Med.Oct2019,Vol.14,No.28•临床案例•李铁教授经方治疗阿狄森氏病1例经验总结汪莉李铁周正国【摘要】阿狄森氏病在中医历代医家未见系统论述，但结合本病临床表现，李铁教授认为,其与“黑疸”、“女劳疸”、“虚劳”等有类似之处。

患者在发病后期可出现全身性黑色素沉着，尤以脸部出现最为明显。

虽然本病的病因病机可以从外感六淫，邪气久积而向元阳不足、命门火衰转化，从肾论治为治疗本病之大法。

临床以和缓为主，以经方八珍汤加减，辅助以益气养阴、化湿解毒等法。

以调和阴阳，改善患者免疫。

在众多交杂的病证中先理胃气，养胃阴，收到了较好的临床效果。

【关键词】阿狄森氏病；女劳疸；黑疸D0I:10.14163/ki.11-5547/r.2019.2&053Professor Li Tie's experience in the treatment of Adison's disease WANG Li,LI Tie,ZHOU Zheng-guo.Dalian Integrated Traditional Chinese and Western Medicine Hospital,Dalian116011,China[Abstract]Adison's disease has not bfcen systematically discussed by physicians in the past dynastiesof traditional Chinese medicine,but according to its clinical manifestations,Professor Li Tie believes that it hassimilarities with"black jaundice","coital jaundice"and"consumptive disease".Patients may have systemicmelanin deposition in the later stage of the disease,especially in the face.Although the etiology and pathogenesisof this disease can be transformed from six exogenous pathogenic factors,chronic accumulation of evil Qi tokidney-yang insufficiency and life-gate fire deficiency,and the treatment of this disease from kidney is the mainmethod.Palliation is the main method in clinic,with the addition and subtraction of the classical prescriptionBazhen Decoction,supplemented by the methods of invigorating Qi and nourishing yin,removing dampness anddetoxification,in order to regulate Yin and Yang and improve the immunity of patients.In many mixed diseasesand syndromes,first regulating stomach qi and nourishing stomach yin have received good clinical effect.[Key words】Adison's disease;Coital jaundice;Black jaundice辽宁省名医李铁教授善治杂症，作者自2014年至今，已经侍诊其左右5载。

Title: My Love for the Versatile Herb, RosemaryAmong the myriad of aromatic plants that grace our gardens and kitchens, one stands out to me as a true favorite – rosemary (Rosmarinus officinalis). This resilient herb, with its needle-like leaves and enchanting fragrance, has woven itself into the fabric of my life, becoming not just a culinary staple but also a symbol of health, resilience, and memories.The Enchanting AromaAt first glance, rosemary may seem unassuming, with its dark green, almost-black leaves and spiky appearance. But it is when you brush past its foliage or inhale deeply near a bush that its true magic is revealed. The fragrance of rosemary is pungent yet refreshing, with hints of pine and citrus that evoke feelings of warmth and comfort. This scent has the power to transport me to Mediterranean shores, where the herb grows wild and abundant.Culinary DelightsOne of the primary reasons I adore rosemary is its versatility in the kitchen. Its robust flavor pairs beautifully with a wide range of dishes, from hearty roasts and stews to delicate salads and breads. Adding a sprig or two of fresh rosemary to a potof simmering soup or braising meat can transform an ordinary meal into a culinary masterpiece. Its pungent essence infuses food with a depth of flavor that is both savory and aromatic, making it a staple in my culinary repertoire.Health BenefitsBeyond its culinary uses, rosemary is also renowned for its numerous health benefits. Traditionally, it has been used to aid digestion, boost memory, and even ease respiratory issues. The herb is rich in antioxidants, which help protect cells from damage and promote overall wellness. Whether consumed as a tea, infused in oil for topical use, or simply enjoyed as a culinary herb, rosemary is a valuable addition to any health-conscious lifestyle.Symbolic SignificanceMoreover, rosemary holds significant symbolic meaning across cultures. In ancient times, it was believed to enhance memory and stimulate the mind, leading to its association with wisdom and longevity. In modern times, it is often given as a token of friendship and loyalty, symbolizing remembrance and the bonds that connect us. This symbolism adds an extra layer ofmeaning to my love for the herb, reminding me of the cherished relationships in my life.Ease of CultivationPerhaps one of the most appealing aspects of rosemary for me is its ease of cultivation. This hardy herb thrives inwell-drained soil and prefers full sun, making it an ideal addition to any garden or indoor herb garden. It is relatively drought-tolerant and requires minimal care, making it alow-maintenance plant that even novice gardeners can enjoy. ConclusionIn conclusion, my love for rosemary stems from its enchanting aroma, culinary versatility, health benefits, symbolic significance, and ease of cultivation. This versatile herb has become an integral part of my life, bringing joy to my kitchen, promoting wellness, and reminding me of the beauty and complexity of nature. As I continue to nurture my rosemary plants and incorporate them into my daily life, I am grateful for the many ways this remarkable herb enriches my world.。

As a high school student with a keen interest in culinary arts, I have always been fascinated by the diversity of flavors that the world has to offer. Exploring different cuisines has been a passion of mine, and today, Id like to share my experience with some unique dishes that have left an indelible mark on my palate.One of the most memorable meals Ive had was when I tried authentic Thai cuisine. The dish that stood out was Som Tam, a spicy green papaya salad. It was a delightful explosion of flavorssweet, sour, salty, and spicy, all at once. The freshness of the ingredients, combined with the heat from the chili peppers, created a symphony of tastes that danced on my tongue. The dish was not only a feast for the taste buds but also a visual treat with its vibrant colors of green papaya, tomatoes, and beansprouts.Another culinary adventure took me to the heart of Mexico, where I discovered Tacos Al Pastor. These tacos are a fusion of Mexican and Lebanese flavors, featuring marinated pork cooked on a vertical spit, similar to shawarma. The meat is then thinly sliced and served in a warm corn tortilla with pineapple chunks, onions, and cilantro. The sweetness of the pineapple perfectly balances the savory marinade, making it a dish that is as satisfying as it is flavorful.My journey through the worlds kitchens also led me to the rich and aromatic dishes of Indian cuisine. Butter Chicken, or Murgh Makhani, was a dish that I couldnt get enough of. The tender chicken pieces are cooked in a creamy tomatobased sauce infused with aromatic spices like cardamom, cinnamon, and ginger. The dish is typically served with fragrant basmatirice or naan bread, making it a complete meal that is both comforting and delectable.Venturing into the Mediterranean, I was introduced to Baklava, a dessert that is as beautiful as it is delicious. Layers of thin phyllo pastry are filled with chopped nuts and sweetened with honey or syrup. The result is a crispy yet flaky texture that melts in your mouth, leaving a lingering sweetness that is hard to resist.In the realm of Japanese cuisine, I found Ramen, a dish that has gained popularity worldwide. A steaming bowl of ramen is a comforting experience, with its rich broth, chewy noodles, and toppings like sliced pork, green onions, and softboiled eggs. The depth of flavor in the broth, which can range from soybased shoyu to the rich miso, is what makes ramen a dish that is both satisfying and soulwarming.Lastly, I must mention the Pavlova, a meringuebased dessert named after the Russian ballerina Anna Pavlova. It is a crisp crust on the outside, hiding a soft, marshmallowlike interior, often topped with whipped cream and fresh fruits. The contrast between the crispness and the softness, along with the burst of fruit flavors, makes this dessert a delightful end to any meal.These dishes are just a glimpse into the vast array of culinary delights that the world has to offer. Each one tells a story of its culture, history, and the passion of its people. As I continue to explore and learn, I am reminded of the power of food to bring people together, to evoke memories, and tocreate new ones. Whether its the fiery kick of a Thai salad, the comforting warmth of a Japanese ramen, or the sweet indulgence of a Mediterranean dessert, each dish is a testament to the diversity and richness of our global culinary heritage.。

千层酥英语作文300字Mille-feuille: A Culinary Masterpiece.Amidst the vast culinary tapestry of the world, where flavors dance and textures intertwine, lies a pastry that has captivated hearts and palates for centuries—the mille-feuille. This exquisite creation, also known as a Napoleon or custard slice, is a testament to the boundless artistry of pastry chefs and the timeless allure of culinary ingenuity.Origins and Etymology.The mille-feuille traces its roots back to the early19th century, emerging in France as a beloved delicacy. Its name, which translates to "a thousand leaves," aptly describes the pastry's most striking characteristic—the multitude of wafer-thin layers that form its delicate structure. Each layer is crafted with precision, creating an ethereal lightness that belies the richness of the dish.Ingredients and Assembly.At its core, the mille-feuille consists of three principal elements: puff pastry, pastry cream, and a decadent glaze.The puff pastry is the foundation upon which this masterpiece is built. It is a labor-intensive dough, demanding patience and skill to create its signature flaky texture. The dough is rolled and folded numerous times, creating countless layers that, when baked, expand into a symphony of crispy, buttery goodness.The pastry cream, al so known as crème pâtissière, provides a velvety smoothness to complement the crunchy pastry. It is typically flavored with vanilla, but variations can incorporate other spices or extracts to cater to different palates.Finally, the mille-feuille is crowned with a shimmering glaze, often made from a combination of sugar, water, andlemon juice. This glaze seals the pastry, protecting itfrom moisture while adding a touch of sweetness and shine.Flavor and Texture.The mille-feuille is an orchestra of flavors andtextures that harmoniously combine to create anunforgettable culinary experience.The crispy, flaky layers of puff pastry provide a delightful crunch, while the smooth, creamy pastry cream melts in the mouth. The combination of these textures creates a playful contrast that keeps the taste buds engaged.The flavors of the mille-feuille are equally captivating. The buttery richness of the puff pastry balances the sweetness of the pastry cream, while thesubtle tang of the glaze adds a finishing touch of elegance.Variations and Adaptations.Over the years, the classic mille-feuille has inspired countless variations and adaptations. Some popular variations include:Mille-feuille au Chocolat: This variation incorporates chocolate into the pastry cream, creating a decadent treat for chocolate lovers.Mille-feuille aux Fruits: This variation features fresh fruit, such as raspberries or strawberries, layered between the pastry and cream. The fruit adds a refreshing burst of flavor and color.Mille-feuille Salé: This savory variation uses a different dough and filling, such as cheese or vegetables, to create a delicious appetizer or main course.Presentation and Appeal.The mille-feuille is not only a culinary delight but also a feast for the eyes. Its towering layers and delicate glaze are visually striking, making it a centerpiece of anydessert table.Traditionally, the mille-feuille is served in individual portions, cut into rectangular or triangular shapes. However, some pastry chefs create larger versions, showcasing their artistry and creativity.Legacy and Enduring Popularity.The mille-feuille has stood the test of time, captivating taste buds and inspiring pastry chefs for generations. Its timeless appeal lies in its perfect balance of texture, flavor, and visual beauty.Today, the mille-feuille remains a beloved dessert enjoyed worldwide. Whether savored as a simple afternoon treat or as the grand finale of a special occasion, this culinary masterpiece continues to enchant and delight all who encounter it.。

小学上册英语第2单元真题试卷英语试题一、综合题(本题有100小题，每小题1分，共100分.每小题不选、错误，均不给分)1.________ was the first female British Prime Minister.2.________ (植物生态监测) provides critical data.3.ers bloom only _____ (晚上). Some flo4. A ______ (植物的分类) helps scientists communicate.5. A chemical reaction can release heat and light in an ______ reaction.6.My ________ (玩具) encourages curiosity.7. A _______ is a series of processes that occur during a chemical reaction.8.I _____ (walks/walk) to school every day.9.I drink _____ (coffee/juice) in the morning.10. A chemical reaction can release energy in the form of _____.11.All acids contain ______ ions.12.In the evening, my family has ________ (晚餐) together. We talk about our day and share our ________ (经历).13.The __________ (历史的交互影响) shape our experiences.14.Galaxies can collide and form larger ______.15.My ______ (哥哥) is learning to ride a bicycle. He is getting better every ______ (天).16.What do we call the study of the classification of living organisms?A. TaxonomyB. EcologyC. BiologyD. Genetics17.Vinegar is an example of an __________.18.What is the opposite of ‘happy’?A. GladB. JoyfulC. SadD. Cheerful19.I have a __________ in my class. (朋友)20.The ________ loves to play.21.The ______ (青蛙) can leap great distances with its strong legs.22.What do we call the scientific study of the earth and its features?A. BiologyB. ChemistryC. GeographyD. HistoryC23.I like to ride my __________ when the weather is nice. (自行车)24.The park is ______ (close) to my house.25.What do you call the process of cooking food in water?A. BoilingB. BakingC. FryingD. Grilling26.The __________ (历史的反思) helps societies grow.27.I see a _____ (cat/dog) in the garden.28.I like _____ (吃) pizza.29._____ (小草) can grow in cracks in the pavement.30.The capital city of Haiti is __________.31.The ________ was a time of great artistic and scientific advancement in Europe.32.The __________ of an animal can vary greatly between species.33.I enjoy _______ (体验) different cultures.34.How many hearts does an octopus have?A. OneB. TwoC. ThreeD. FourC35.We are having ______ for lunch today. (pizza)36.smart growth) focuses on sustainable urban development. The ____37.What do you call the sweet food made from nuts and sugar?A. NougatB. CandyC. PralineD. FudgeB38.The chemical symbol for aluminum is __________.39.The __________ can reveal the historical context of geological formations.40.The _______ helps nourish the soil.41.I like to ______ after school.42. A _____ (植物文化交流) fosters appreciation for diversity.43.Which fruit is yellow and curved?A. AppleB. BananaC. CherryD. Grape44.The process of separating a solid from a liquid is called _______. (过滤)45.The Sun is primarily made of hydrogen and ______.46. ________ (画画) after school. She love47.The __________ (历史的探索) encourages curiosity.48.Asteroids can be found in the ______ belt.49.__________ (化学反应物) must be carefully measured for successful experiments.50.What is the opposite of "fast"?A. QuickB. SlowC. SpeedyD. RapidB51.The first successful airplane flight was achieved by the ______ (莱特兄弟).52.The _____ (金鱼) swims in its bowl.53.What do we call the process of water turning into vapor?A. EvaporationB. CondensationC. PrecipitationD. Filtration54.We have a ______ (丰富的) schedule for school events.55.My teacher’s name is _______ (李老师), and she is very _______ (友好).56.I eat ______ (水果) every day.57.My brother collects ____ (coins) from around the world.58.What is 20 ÷ 4?A. 4B. 5C. 6D. 759.The chemical symbol for selenium is ______.60.What is the largest continent?A. AfricaB. AsiaC. North AmericaD. South America61.What do you call a young vulture?A. ChickB. EagletC. CubD. Hatchling62.What is the main ingredient in a fruit salad?A. VegetablesB. FruitC. NutsD. Grain63.Objects that are far away appear ______ (smaller).64.The grapes are ___ (purple).65.The ______ (植物的利用方式) is diverse and impactful.66.I love to ______ (在阳光下) play outside.67.The garden has many _______ that blossom beautifully all year round.68.The __________ (历史的变化) is a constant theme.69.What do we call a person who studies plants?A. BiologistB. BotanistC. ZoologistD. EcologistB70.I like to ___ (play) outside.71.My pet rabbit loves to hide in ______ (草丛).72.What is the capital of Mozambique?A. MaputoB. BeiraC. NampulaD. TeteA73.We can _______ together to finish the project.74.I built a spaceship with my ________ (玩具名称).75.The ________ (invitation) is for a party.76.Who wrote "Romeo and Juliet"?A. Mark TwainB. Charles DickensC. William ShakespeareD. J.K. RowlingC77. A ____(community needs assessment) identifies gaps in services.78. A whale is a __________ (大型) marine animal.79. A _______ is a chemical reaction where two or more substances combine to form a new substance.80.I love to explore nature trails and observe ________ (野生动物) in their natural habitat.81.What do you call the study of the universe?A. BiologyB. GeographyC. AstronomyD. Chemistry82.My favorite thing to do on a rainy day is __________.83.What do we call the place where we go to see movies?A. TheaterB. MuseumC. GalleryD. LibraryA84.What do we call the feeling of being afraid?A. HappinessB. FearC. ExcitementD. AngerB85.Which sport is played with a ball and a net?A. SoccerB. BasketballC. TennisD. All of the aboveD86.The _____ (马) gallops across the field.87.I like to watch the ______ (云彩) change shapes.88.What do we call the process of creating a new species through evolution?A. SpeciationB. AdaptationC. MutationD. NaturalselectionA Speciation89.I collect _______ from nature (我从大自然中收集_______).90.What do we use to write?A. BrushB. PencilC. HammerD. SpoonB91.I want to create a ________ to celebrate friendship.92.We have _____ (很多) toys to play with.93.The capital city of Iceland is _____.94.The chemical reaction of metals with oxygen produces __________.95.The first successful powered flight lasted _______ seconds. (12)96.I enjoy watching the ______ in the sky.97.I have a toy _______ that spins and plays music when you press a button.98.What is the name of the famous detective created by Arthur Conan Doyle?A. Sherlock HolmesB. Hercule PoirotC. Miss MarpleD. Sam SpadeA99.My favorite season is ________ (秋天) because of the leaves.100.What do you use to write on paper?A. BrushB. PencilC. SpoonD. ForkB。

麻烦麻里英语作文In the vast ocean of language, English composition stands as a fascinating and often challenging endeavor. It is a skill that requires not only a grasp of grammar and vocabulary but also an understanding of the subtle nuances that make written English engaging and effective.The Art of Crafting Sentences:The backbone of any English composition is the sentence. A well-crafted sentence can convey a wealth of information, emotion, and persuasion. It is important to vary sentence length and structure to keep the reader engaged. Short sentences can be used for emphasis, while longer sentences can provide detailed explanations or paint a vivid picture.Building a Coherent Structure:A successful composition is not just a collection of sentences; it is a well-organized structure that guides the reader through a clear narrative or argument. An effective essay will have a clear introduction, body paragraphs that develop the main ideas, and a conclusion that summarizes the points made.The Power of Vocabulary:The richness of English vocabulary is a tool that can elevate the quality of writing. Using a wide range of words not only makes the composition more interesting but also allows for more precise expression of thoughts and ideas. Synonyms andantonyms can be used to avoid repetition and to add depth to the writing.The Role of Grammar:While it is true that grammar is not the most exciting aspect of English composition, it is crucial for clarity and correctness. Proper use of tenses, articles, and prepositions ensures that the reader can follow the writer's train of thought without confusion.The Importance of Proofreading:No composition is complete without a thorough proofreading process. This final step is where the writer can catch and correct any grammatical errors, awkward phrasings, or inconsistencies in the argument. It is also an opportunity to refine the language and ensure that the composition reads smoothly.Overcoming Writer's Block:Sometimes, the blank page can be daunting. To overcomewriter's block, one can start by brainstorming ideas, creating an outline, or even writing a rough draft without worrying about perfection. The key is to get the ideas flowing and then refine them in subsequent drafts.The Joy of Revision:Finally, the process of revision is not a chore but an opportunity to improve the composition. Each draft can bring new insights and improvements, making the final product a reflection of the writer's best efforts.In conclusion, English composition is a multifaceted skill that requires practice, patience, and a keen eye for detail. It is through the careful crafting of sentences, the thoughtful organization of ideas, and the diligent proofreading that a writer can create a composition that is both compelling and correct.。

DIRECTIVE NUMBER: CPL 02-00-150 EFFECTIVE DATE: April 22, 2011 SUBJECT: Field Operations Manual (FOM)ABSTRACTPurpose: This instruction cancels and replaces OSHA Instruction CPL 02-00-148,Field Operations Manual (FOM), issued November 9, 2009, whichreplaced the September 26, 1994 Instruction that implemented the FieldInspection Reference Manual (FIRM). The FOM is a revision of OSHA’senforcement policies and procedures manual that provides the field officesa reference document for identifying the responsibilities associated withthe majority of their inspection duties. This Instruction also cancels OSHAInstruction FAP 01-00-003 Federal Agency Safety and Health Programs,May 17, 1996 and Chapter 13 of OSHA Instruction CPL 02-00-045,Revised Field Operations Manual, June 15, 1989.Scope: OSHA-wide.References: Title 29 Code of Federal Regulations §1903.6, Advance Notice ofInspections; 29 Code of Federal Regulations §1903.14, Policy RegardingEmployee Rescue Activities; 29 Code of Federal Regulations §1903.19,Abatement Verification; 29 Code of Federal Regulations §1904.39,Reporting Fatalities and Multiple Hospitalizations to OSHA; and Housingfor Agricultural Workers: Final Rule, Federal Register, March 4, 1980 (45FR 14180).Cancellations: OSHA Instruction CPL 02-00-148, Field Operations Manual, November9, 2009.OSHA Instruction FAP 01-00-003, Federal Agency Safety and HealthPrograms, May 17, 1996.Chapter 13 of OSHA Instruction CPL 02-00-045, Revised FieldOperations Manual, June 15, 1989.State Impact: Notice of Intent and Adoption required. See paragraph VI.Action Offices: National, Regional, and Area OfficesOriginating Office: Directorate of Enforcement Programs Contact: Directorate of Enforcement ProgramsOffice of General Industry Enforcement200 Constitution Avenue, NW, N3 119Washington, DC 20210202-693-1850By and Under the Authority ofDavid Michaels, PhD, MPHAssistant SecretaryExecutive SummaryThis instruction cancels and replaces OSHA Instruction CPL 02-00-148, Field Operations Manual (FOM), issued November 9, 2009. The one remaining part of the prior Field Operations Manual, the chapter on Disclosure, will be added at a later date. This Instruction also cancels OSHA Instruction FAP 01-00-003 Federal Agency Safety and Health Programs, May 17, 1996 and Chapter 13 of OSHA Instruction CPL 02-00-045, Revised Field Operations Manual, June 15, 1989. This Instruction constitutes OSHA’s general enforcement policies and procedures manual for use by the field offices in conducting inspections, issuing citations and proposing penalties.Significant Changes∙A new Table of Contents for the entire FOM is added.∙ A new References section for the entire FOM is added∙ A new Cancellations section for the entire FOM is added.∙Adds a Maritime Industry Sector to Section III of Chapter 10, Industry Sectors.∙Revises sections referring to the Enhanced Enforcement Program (EEP) replacing the information with the Severe Violator Enforcement Program (SVEP).∙Adds Chapter 13, Federal Agency Field Activities.∙Cancels OSHA Instruction FAP 01-00-003, Federal Agency Safety and Health Programs, May 17, 1996.DisclaimerThis manual is intended to provide instruction regarding some of the internal operations of the Occupational Safety and Health Administration (OSHA), and is solely for the benefit of the Government. No duties, rights, or benefits, substantive or procedural, are created or implied by this manual. The contents of this manual are not enforceable by any person or entity against the Department of Labor or the United States. Statements which reflect current Occupational Safety and Health Review Commission or court precedents do not necessarily indicate acquiescence with those precedents.Table of ContentsCHAPTER 1INTRODUCTIONI.PURPOSE. ........................................................................................................... 1-1 II.SCOPE. ................................................................................................................ 1-1 III.REFERENCES .................................................................................................... 1-1 IV.CANCELLATIONS............................................................................................. 1-8 V. ACTION INFORMATION ................................................................................. 1-8A.R ESPONSIBLE O FFICE.......................................................................................................................................... 1-8B.A CTION O FFICES. .................................................................................................................... 1-8C. I NFORMATION O FFICES............................................................................................................ 1-8 VI. STATE IMPACT. ................................................................................................ 1-8 VII.SIGNIFICANT CHANGES. ............................................................................... 1-9 VIII.BACKGROUND. ................................................................................................. 1-9 IX. DEFINITIONS AND TERMINOLOGY. ........................................................ 1-10A.T HE A CT................................................................................................................................................................. 1-10B. C OMPLIANCE S AFETY AND H EALTH O FFICER (CSHO). ...........................................................1-10B.H E/S HE AND H IS/H ERS ..................................................................................................................................... 1-10C.P ROFESSIONAL J UDGMENT............................................................................................................................... 1-10E. W ORKPLACE AND W ORKSITE ......................................................................................................................... 1-10CHAPTER 2PROGRAM PLANNINGI.INTRODUCTION ............................................................................................... 2-1 II.AREA OFFICE RESPONSIBILITIES. .............................................................. 2-1A.P ROVIDING A SSISTANCE TO S MALL E MPLOYERS. ...................................................................................... 2-1B.A REA O FFICE O UTREACH P ROGRAM. ............................................................................................................. 2-1C. R ESPONDING TO R EQUESTS FOR A SSISTANCE. ............................................................................................ 2-2 III. OSHA COOPERATIVE PROGRAMS OVERVIEW. ...................................... 2-2A.V OLUNTARY P ROTECTION P ROGRAM (VPP). ........................................................................... 2-2B.O NSITE C ONSULTATION P ROGRAM. ................................................................................................................ 2-2C.S TRATEGIC P ARTNERSHIPS................................................................................................................................. 2-3D.A LLIANCE P ROGRAM ........................................................................................................................................... 2-3 IV. ENFORCEMENT PROGRAM SCHEDULING. ................................................ 2-4A.G ENERAL ................................................................................................................................................................. 2-4B.I NSPECTION P RIORITY C RITERIA. ..................................................................................................................... 2-4C.E FFECT OF C ONTEST ............................................................................................................................................ 2-5D.E NFORCEMENT E XEMPTIONS AND L IMITATIONS. ....................................................................................... 2-6E.P REEMPTION BY A NOTHER F EDERAL A GENCY ........................................................................................... 2-6F.U NITED S TATES P OSTAL S ERVICE. .................................................................................................................. 2-7G.H OME-B ASED W ORKSITES. ................................................................................................................................ 2-8H.I NSPECTION/I NVESTIGATION T YPES. ............................................................................................................... 2-8 V.UNPROGRAMMED ACTIVITY – HAZARD EVALUATION AND INSPECTION SCHEDULING ............................................................................ 2-9 VI.PROGRAMMED INSPECTIONS. ................................................................... 2-10A.S ITE-S PECIFIC T ARGETING (SST) P ROGRAM. ............................................................................................. 2-10B.S CHEDULING FOR C ONSTRUCTION I NSPECTIONS. ..................................................................................... 2-10C.S CHEDULING FOR M ARITIME I NSPECTIONS. ............................................................................. 2-11D.S PECIAL E MPHASIS P ROGRAMS (SEP S). ................................................................................... 2-12E.N ATIONAL E MPHASIS P ROGRAMS (NEP S) ............................................................................... 2-13F.L OCAL E MPHASIS P ROGRAMS (LEP S) AND R EGIONAL E MPHASIS P ROGRAMS (REP S) ............ 2-13G.O THER S PECIAL P ROGRAMS. ............................................................................................................................ 2-13H.I NSPECTION S CHEDULING AND I NTERFACE WITH C OOPERATIVE P ROGRAM P ARTICIPANTS ....... 2-13CHAPTER 3INSPECTION PROCEDURESI.INSPECTION PREPARATION. .......................................................................... 3-1 II.INSPECTION PLANNING. .................................................................................. 3-1A.R EVIEW OF I NSPECTION H ISTORY .................................................................................................................... 3-1B.R EVIEW OF C OOPERATIVE P ROGRAM P ARTICIPATION .............................................................................. 3-1C.OSHA D ATA I NITIATIVE (ODI) D ATA R EVIEW .......................................................................................... 3-2D.S AFETY AND H EALTH I SSUES R ELATING TO CSHO S.................................................................. 3-2E.A DVANCE N OTICE. ................................................................................................................................................ 3-3F.P RE-I NSPECTION C OMPULSORY P ROCESS ...................................................................................................... 3-5G.P ERSONAL S ECURITY C LEARANCE. ................................................................................................................. 3-5H.E XPERT A SSISTANCE. ........................................................................................................................................... 3-5 III. INSPECTION SCOPE. ......................................................................................... 3-6A.C OMPREHENSIVE ................................................................................................................................................... 3-6B.P ARTIAL. ................................................................................................................................................................... 3-6 IV. CONDUCT OF INSPECTION .............................................................................. 3-6A.T IME OF I NSPECTION............................................................................................................................................. 3-6B.P RESENTING C REDENTIALS. ............................................................................................................................... 3-6C.R EFUSAL TO P ERMIT I NSPECTION AND I NTERFERENCE ............................................................................. 3-7D.E MPLOYEE P ARTICIPATION. ............................................................................................................................... 3-9E.R ELEASE FOR E NTRY ............................................................................................................................................ 3-9F.B ANKRUPT OR O UT OF B USINESS. .................................................................................................................... 3-9G.E MPLOYEE R ESPONSIBILITIES. ................................................................................................. 3-10H.S TRIKE OR L ABOR D ISPUTE ............................................................................................................................. 3-10I. V ARIANCES. .......................................................................................................................................................... 3-11 V. OPENING CONFERENCE. ................................................................................ 3-11A.G ENERAL ................................................................................................................................................................ 3-11B.R EVIEW OF A PPROPRIATION A CT E XEMPTIONS AND L IMITATION. ..................................................... 3-13C.R EVIEW S CREENING FOR P ROCESS S AFETY M ANAGEMENT (PSM) C OVERAGE............................. 3-13D.R EVIEW OF V OLUNTARY C OMPLIANCE P ROGRAMS. ................................................................................ 3-14E.D ISRUPTIVE C ONDUCT. ...................................................................................................................................... 3-15F.C LASSIFIED A REAS ............................................................................................................................................. 3-16VI. REVIEW OF RECORDS. ................................................................................... 3-16A.I NJURY AND I LLNESS R ECORDS...................................................................................................................... 3-16B.R ECORDING C RITERIA. ...................................................................................................................................... 3-18C. R ECORDKEEPING D EFICIENCIES. .................................................................................................................. 3-18 VII. WALKAROUND INSPECTION. ....................................................................... 3-19A.W ALKAROUND R EPRESENTATIVES ............................................................................................................... 3-19B.E VALUATION OF S AFETY AND H EALTH M ANAGEMENT S YSTEM. ....................................................... 3-20C.R ECORD A LL F ACTS P ERTINENT TO A V IOLATION. ................................................................................. 3-20D.T ESTIFYING IN H EARINGS ................................................................................................................................ 3-21E.T RADE S ECRETS. ................................................................................................................................................. 3-21F.C OLLECTING S AMPLES. ..................................................................................................................................... 3-22G.P HOTOGRAPHS AND V IDEOTAPES.................................................................................................................. 3-22H.V IOLATIONS OF O THER L AWS. ....................................................................................................................... 3-23I.I NTERVIEWS OF N ON-M ANAGERIAL E MPLOYEES .................................................................................... 3-23J.M ULTI-E MPLOYER W ORKSITES ..................................................................................................................... 3-27 K.A DMINISTRATIVE S UBPOENA.......................................................................................................................... 3-27 L.E MPLOYER A BATEMENT A SSISTANCE. ........................................................................................................ 3-27 VIII. CLOSING CONFERENCE. .............................................................................. 3-28A.P ARTICIPANTS. ..................................................................................................................................................... 3-28B.D ISCUSSION I TEMS. ............................................................................................................................................ 3-28C.A DVICE TO A TTENDEES .................................................................................................................................... 3-29D.P ENALTIES............................................................................................................................................................. 3-30E.F EASIBLE A DMINISTRATIVE, W ORK P RACTICE AND E NGINEERING C ONTROLS. ............................ 3-30F.R EDUCING E MPLOYEE E XPOSURE. ................................................................................................................ 3-32G.A BATEMENT V ERIFICATION. ........................................................................................................................... 3-32H.E MPLOYEE D ISCRIMINATION .......................................................................................................................... 3-33 IX. SPECIAL INSPECTION PROCEDURES. ...................................................... 3-33A.F OLLOW-UP AND M ONITORING I NSPECTIONS............................................................................................ 3-33B.C ONSTRUCTION I NSPECTIONS ......................................................................................................................... 3-34C. F EDERAL A GENCY I NSPECTIONS. ................................................................................................................. 3-35CHAPTER 4VIOLATIONSI. BASIS OF VIOLATIONS ..................................................................................... 4-1A.S TANDARDS AND R EGULATIONS. .................................................................................................................... 4-1B.E MPLOYEE E XPOSURE. ........................................................................................................................................ 4-3C.R EGULATORY R EQUIREMENTS. ........................................................................................................................ 4-6D.H AZARD C OMMUNICATION. .............................................................................................................................. 4-6E. E MPLOYER/E MPLOYEE R ESPONSIBILITIES ................................................................................................... 4-6 II. SERIOUS VIOLATIONS. .................................................................................... 4-8A.S ECTION 17(K). ......................................................................................................................... 4-8B.E STABLISHING S ERIOUS V IOLATIONS ............................................................................................................ 4-8C. F OUR S TEPS TO BE D OCUMENTED. ................................................................................................................... 4-8 III. GENERAL DUTY REQUIREMENTS ............................................................. 4-14A.E VALUATION OF G ENERAL D UTY R EQUIREMENTS ................................................................................. 4-14B.E LEMENTS OF A G ENERAL D UTY R EQUIREMENT V IOLATION.............................................................. 4-14C. U SE OF THE G ENERAL D UTY C LAUSE ........................................................................................................ 4-23D.L IMITATIONS OF U SE OF THE G ENERAL D UTY C LAUSE. ..............................................................E.C LASSIFICATION OF V IOLATIONS C ITED U NDER THE G ENERAL D UTY C LAUSE. ..................F. P ROCEDURES FOR I MPLEMENTATION OF S ECTION 5(A)(1) E NFORCEMENT ............................ 4-25 4-27 4-27IV.OTHER-THAN-SERIOUS VIOLATIONS ............................................... 4-28 V.WILLFUL VIOLATIONS. ......................................................................... 4-28A.I NTENTIONAL D ISREGARD V IOLATIONS. ..........................................................................................4-28B.P LAIN I NDIFFERENCE V IOLATIONS. ...................................................................................................4-29 VI. CRIMINAL/WILLFUL VIOLATIONS. ................................................... 4-30A.A REA D IRECTOR C OORDINATION ....................................................................................................... 4-31B.C RITERIA FOR I NVESTIGATING P OSSIBLE C RIMINAL/W ILLFUL V IOLATIONS ........................ 4-31C. W ILLFUL V IOLATIONS R ELATED TO A F ATALITY .......................................................................... 4-32 VII. REPEATED VIOLATIONS. ...................................................................... 4-32A.F EDERAL AND S TATE P LAN V IOLATIONS. ........................................................................................4-32B.I DENTICAL S TANDARDS. .......................................................................................................................4-32C.D IFFERENT S TANDARDS. .......................................................................................................................4-33D.O BTAINING I NSPECTION H ISTORY. .....................................................................................................4-33E.T IME L IMITATIONS..................................................................................................................................4-34F.R EPEATED V. F AILURE TO A BATE....................................................................................................... 4-34G. A REA D IRECTOR R ESPONSIBILITIES. .............................................................................. 4-35 VIII. DE MINIMIS CONDITIONS. ................................................................... 4-36A.C RITERIA ................................................................................................................................................... 4-36B.P ROFESSIONAL J UDGMENT. ..................................................................................................................4-37C. A REA D IRECTOR R ESPONSIBILITIES. .............................................................................. 4-37 IX. CITING IN THE ALTERNATIVE ............................................................ 4-37 X. COMBINING AND GROUPING VIOLATIONS. ................................... 4-37A.C OMBINING. ..............................................................................................................................................4-37B.G ROUPING. ................................................................................................................................................4-38C. W HEN N OT TO G ROUP OR C OMBINE. ................................................................................................4-38 XI. HEALTH STANDARD VIOLATIONS ....................................................... 4-39A.C ITATION OF V ENTILATION S TANDARDS ......................................................................................... 4-39B.V IOLATIONS OF THE N OISE S TANDARD. ...........................................................................................4-40 XII. VIOLATIONS OF THE RESPIRATORY PROTECTION STANDARD(§1910.134). ....................................................................................................... XIII. VIOLATIONS OF AIR CONTAMINANT STANDARDS (§1910.1000) ... 4-43 4-43A.R EQUIREMENTS UNDER THE STANDARD: .................................................................................................. 4-43B.C LASSIFICATION OF V IOLATIONS OF A IR C ONTAMINANT S TANDARDS. ......................................... 4-43 XIV. CITING IMPROPER PERSONAL HYGIENE PRACTICES. ................... 4-45A.I NGESTION H AZARDS. .................................................................................................................................... 4-45B.A BSORPTION H AZARDS. ................................................................................................................................ 4-46C.W IPE S AMPLING. ............................................................................................................................................. 4-46D.C ITATION P OLICY ............................................................................................................................................ 4-46 XV. BIOLOGICAL MONITORING. ...................................................................... 4-47CHAPTER 5CASE FILE PREPARATION AND DOCUMENTATIONI.INTRODUCTION ............................................................................................... 5-1 II.INSPECTION CONDUCTED, CITATIONS BEING ISSUED. .................... 5-1A.OSHA-1 ................................................................................................................................... 5-1B.OSHA-1A. ............................................................................................................................... 5-1C. OSHA-1B. ................................................................................................................................ 5-2 III.INSPECTION CONDUCTED BUT NO CITATIONS ISSUED .................... 5-5 IV.NO INSPECTION ............................................................................................... 5-5 V. HEALTH INSPECTIONS. ................................................................................. 5-6A.D OCUMENT P OTENTIAL E XPOSURE. ............................................................................................................... 5-6B.E MPLOYER’S O CCUPATIONAL S AFETY AND H EALTH S YSTEM. ............................................................. 5-6 VI. AFFIRMATIVE DEFENSES............................................................................. 5-8A.B URDEN OF P ROOF. .............................................................................................................................................. 5-8B.E XPLANATIONS. ..................................................................................................................................................... 5-8 VII. INTERVIEW STATEMENTS. ........................................................................ 5-10A.G ENERALLY. ......................................................................................................................................................... 5-10B.CSHO S SHALL OBTAIN WRITTEN STATEMENTS WHEN: .......................................................................... 5-10C.L ANGUAGE AND W ORDING OF S TATEMENT. ............................................................................................. 5-11D.R EFUSAL TO S IGN S TATEMENT ...................................................................................................................... 5-11E.V IDEO AND A UDIOTAPED S TATEMENTS. ..................................................................................................... 5-11F.A DMINISTRATIVE D EPOSITIONS. .............................................................................................5-11 VIII. PAPERWORK AND WRITTEN PROGRAM REQUIREMENTS. .......... 5-12 IX.GUIDELINES FOR CASE FILE DOCUMENTATION FOR USE WITH VIDEOTAPES AND AUDIOTAPES .............................................................. 5-12 X.CASE FILE ACTIVITY DIARY SHEET. ..................................................... 5-12 XI. CITATIONS. ..................................................................................................... 5-12A.S TATUTE OF L IMITATIONS. .............................................................................................................................. 5-13B.I SSUING C ITATIONS. ........................................................................................................................................... 5-13C.A MENDING/W ITHDRAWING C ITATIONS AND N OTIFICATION OF P ENALTIES. .................................. 5-13D.P ROCEDURES FOR A MENDING OR W ITHDRAWING C ITATIONS ............................................................ 5-14 XII. INSPECTION RECORDS. ............................................................................... 5-15A.G ENERALLY. ......................................................................................................................................................... 5-15B.R ELEASE OF I NSPECTION I NFORMATION ..................................................................................................... 5-15C. C LASSIFIED AND T RADE S ECRET I NFORMATION ...................................................................................... 5-16。

最钦佩的科学家英语作文屠呦呦200字全文共6篇示例，供读者参考篇1The Scientist I Admire Most - Tu YouyouHave you ever heard of Tu Youyou? She's a famous Chinese scientist who discovered a treatment for malaria, a deadly disease. I really admire her because she saved millions of lives with her amazing work!Tu Youyou was born in 1930 in China. When she was young, she loved nature and science. She studied at a medical college and later joined a special research team. Their mission? Find a cure for malaria!For years, Tu and her team searched ancient texts for clues about malaria remedies. They tested hundreds of traditional herb recipes. Finally, in 1972, Tu discovered that an herb called qinghao could treat malaria effectively when prepared a certain way.Thanks to Tu's discovery, a life-saving malaria medicine was produced. It helped many people, especially in Africa wheremalaria was widespread. Tu's work was so important that in 2015, she won the Nobel Prize in Physiology or Medicine!I admire Tu because she never gave up, even when the research was difficult. Her curiosity, persistence, and intelligence led to an amazing breakthrough. Tu Youyou is a true hero who made the world healthier and safer. She is my favorite scientist!篇2The Scientist I Admire Most: Tu YouyouHave you ever heard of Tu Youyou? She's a really amazing scientist from China who made an incredible discovery that has saved millions of lives around the world! I think she's the scientist I admire the most.Tu Youyou was born in 1930 in a small town called Ningbo. When she was young, she loved studying plants and traditional Chinese medicine. She was really smart and hardworking in school. In 1969, there was a big problem - malaria was making lots of people very sick, especially in Africa. Malaria is a deadly disease caused by tiny parasites that get inside your blood. At the time, the malaria parasites were becoming resistant to the medicines used to treat it, so the medicines weren't working anymore.The Chinese government asked scientists to find a new way to cure malaria. Tu Youyou and her team took on this huge challenge. They looked at over 2,000 ancient Chinese medicine recipes to try to find herbs that could kill the malaria parasite. Can you imagine reading through 2,000 really old books trying to find a cure? That's dedication!After years of tireless work, Tu finally made an amazing breakthrough in 1972. She discovered that an extract from the sweet wormwood plant was incredibly effective at destroying the malaria parasite. This plant had been used in traditional Chinese medicine for centuries, but no one had properly tested it as a malaria treatment before. Tu's discovery paved the way for the development of artemisinin, one of the most powerfulanti-malarial drugs ever found.Artemisinin has saved millions upon millions of lives, especially in developing countries where malaria is most deadly. The World Health Organization says it's one of the most important medicinal discoveries of the 20th century. Isn't that incredible? One scientist's curiosity, hard work, and belief in the wisdom of traditional medicine led to this life-saving breakthrough.What I admire most about Tu Youyou is her persistence, creativity, and humble nature. She didn't give up when the research seemed impossible. She thought outside the box by looking to ancient Chinese texts. And even after her monumental achievement, she remained humble and dedicated to helping others. She kept a low profile and didn't seek fame or fortune. Her only goal was to keep developing better malaria treatments.In 2015, at age 84, Tu was finally awarded the Nobel Prize in Medicine for her revolutionary work. She was the first Chinese scientist ever to win a Nobel in science. When she won, she said "The award is a tribute to the performance of the entire team, rather than that of any individual." See, so humble!Tu Youyou is a true hero and role model. Her story inspires me to work hard, think creatively, have courage in my convictions, and use my talents to help make the world a better place. I hope to be as dedicated, brilliant and humble as her one day. The world needs more scientists like Tu Youyou!篇3The Scientist I Admire Most: Tu YouyouMy favorite scientist is Tu Youyou. She is a Chinese woman who won the Nobel Prize in 2015 for her amazing work inmedicine. Tu Youyou discovered a way to treat malaria, a very serious disease that kills lots of people.When Tu Youyou was young, malaria was a huge problem, especially for people in poor countries. Many scientists tried for a long time to find a cure, but they couldn't. Tu wasn't going to give up though! She studied ancient books about traditional Chinese medicine to see if she could find any clues.After many years of hard work, Tu and her team finally discovered a special compound from a plant that could fight malaria. They tested it on themselves first to make sure it was safe! The new malaria medicine they created helped save millions of lives.I really admire Tu Youyou because she never gave up, even when the work was difficult. She used her intelligence and creativity to think of new solutions. Tu showed that women can be brilliant scientists too. Her discovery made the world a much better place. Tu Youyou is my biggest hero!篇4The Scientist I Admire Most: Tu YouyouHi there! My name is Emma and I'm going to tell you about the scientist I admire the most. Her name is Tu Youyou and she's a Chinese scientist who made an amazing discovery that has saved millions of lives!Tu Youyou is a pharmaceutical chemist, which means she studies medicines and how to make them. She was born in 1930 in China. When she was young, she loved studying plants and traditional Chinese medicine. This turned out to be really important later on!In the 1960s, malaria was a huge problem, especially for soldiers fighting in the jungles of Vietnam. Malaria is a terrible disease caused by tiny parasites that get inside your blood and make you very sick with fevers, chills, and flu-like symptoms. If not treated, it can even kill you. The malaria parasites had become resistant to the medicines used to treat them, so new drugs were desperately needed.The Chinese government formed a secret research project called Project 523 to try to find a new treatment for malaria. Tu Youyou was chosen to lead the research team. She was an expert on traditional Chinese herbal medicines, which had been used in China for thousands of years to treat fevers and other illnesses.For years, Tu and her team searched ancient texts and folk remedies, testing over 200 different herbs to see if any could cure malaria. It was incredibly hard work, but Tu never gave up. She had to drink a terrible-tasting muddy mixture made from one of the herbs to see if it would work. It made her so sick, but she kept going because she knew millions of lives were at stake.Finally, in 1972, Tu made an amazing breakthrough. She discovered that a compound derived from a type of wormwood plant could kill the malaria parasites with incredibly powerful results. This new drug, which she called Artemisinin, was tested on herself and her colleagues first to make sure it was safe. It worked! Artemisinin cured malaria with very few side effects.Tu's discovery quickly spread across the world, saving countless lives, especially in developing countries where malaria is most deadly. In 2015, she was awarded the Nobel Prize in Medicine, becoming the first Chinese Nobel laureate in physiology or medicine. Tu said receiving the Nobel Prize was "an honor for China" and she hoped it would inspire more young people to study science.What I admire most about Tu Youyou is her persistence, curiosity, and care for others. She never gave up, even when the work was difficult and discouraging. She used her knowledge oftraditional Chinese medicine in an innovative way. And she did it all to try to save lives and help people suffering from malaria. Tu worked tirelessly for the good of humanity.Tu Youyou shows that with hard work, intelligence, and a never-give-up spirit, one person can change the world for the better. She inspires me to always be curious, study hard, and use my skills and knowledge to help make the world a healthier, happier place. I want to be like Tu Youyou when I grow up - a scientist who makes amazing discoveries that improve people's lives everywhere. She's my hero!篇5The Scientist I Admire Most: Tu YouyouHave you ever heard of Tu Youyou? She's a really amazing scientist from China who won the Nobel Prize in 2015 for her discovery of a treatment for malaria. Malaria is a horrible disease spread by mosquitoes that makes people really sick with fevers, chills, and can even kill them if left untreated. Millions of people around the world, especially in hot regions of Africa and Asia, suffer from malaria every year.Tu Youyou is my biggest hero because her scientific work has saved countless lives and helped so many people avoid thesuffering of malaria. She's living proof that with hard work, intelligence, and perseverance, one person can change the world in incredible ways.Tu was born in 1930 in a town called Ningbo, near Shanghai in eastern China. When she was young, China was going through a very difficult period with wars and famines happening all around her. Despite these challenges from an early age, Tu was a brilliant student who loved reading and learning new things.After finishing university, Tu went to work as a researcher at the Academy of Chinese Traditional Medicine in Beijing in 1955. Back then, malaria was a huge problem in China too, infecting over 30 million people across the country's southern regions. The Chinese leader at the time ordered scientists to find a cure by studying traditional herbal medicines used in ancient Chinese medical texts and folk remedies.Tu took this task extremely seriously. For the next few years, she and her colleagues collected over 2,000 candidate recipes and extracts from traditional Chinese medicine books. They tested 380 different herb extracts on mice, looking for any that could clear the malaria parasites from the rodents' blood.One very old recipe from a mining handbook written 1,600 years earlier caught Tu's attention. It contained an extract fromthe sweet wormwood plant that seemed to hold some promise against malaria. The problem was the extract was so low-yielding and difficult to extract that it was impossible to get enough to run clinical trials on humans.Tu refused to give up. She kept experimenting tirelessly for years, trying different solvents and techniques. Finally, in 1972, she developed an incredibly efficient way to extract the key anti-malarial compound, which she named "artemisinin", from the wormwood plant.When artemisinin was given to malaria patients, the results were miraculous. The drug cleared the malaria parasite from their bodies faster and more thoroughly than any Western medicine available at the time. Tu's breakthrough quickly turned into a highly effective malaria therapy that has saved millions of lives around the globe.Despite her historic accomplishment, Tu remained incredibly humble, gracious, and dedicated to helping others. After winning the Nobel Prize at age 84, all the famous scientist said was "The award...belonged to the entire team's work." She donated her entire prize money to help train younger scientists in China.To me, Tu Youyou is the definition of a true hero. She overcame poverty, war, and long odds through pure intelligence,hard work, and an unwavering sense of purpose. Her scientific tenacity turned an ancient herbal recipe into a modern cure that has relieved incalculable human suffering across the planet.Whenever I feel overwhelmed or think about giving up on something, I remember Tu Youyou's perseverance in the face of challenges. She's living proof that one person's efforts and breakthroughs really can change the world. Her life story inspires me to work hard, never quit, and find ways to use science to make our world a better place, just like Tu did.If we all followed Tu's example of brilliance, resilience, and humility in using knowledge to help our fellow human beings, imagine how many other diseases could be cured and how much more progress we could make. Tu Youyou is the scientist I admire most because her dedication and breakthrough exemplify the limitless potential of the human mind and spirit.篇6The Scientist I Admire the Most: Tu YouyouI really admire the scientist Tu Youyou. She is a Chinese pharmaceutical chemist who helped discover a treatment for malaria. Malaria is a deadly disease spread by mosquitoes thatused to kill over a million people every year, especially in tropical countries.In the 1960s, Tu Youyou was tasked with finding a better malaria treatment by the Chinese government. She looked in ancient medical texts for clues, even though her colleagues laughed at using traditional medicine. After lots of hard work, she discovered that an extract from sweet wormwood plants could cure malaria with few side effects. This new malaria drug saved millions of lives!What I admire most about Tu Youyou is her persistence. Even when others doubted her methods using traditional medicine, she kept researching until she succeeded. Her curiosity, diligence, and creative thinking really paid off. She showed that you should never give up on your goals.In 2015, Tu Youyou was awarded the Nobel Prize in Physiology or Medicine for her malaria research. At age 84, she became the first Chinese Nobel laureate in science. Tu Youyou is a true hero who helped eliminate a major global health threat through her incredible scientific work. I hope to have her drive and passion when I grow up.。

外刊每日精读 | solidarity snips文章脉络【1】人们对农业怀有美好且不切实际的幻想。

【2】对于要求改变现有饮食习惯的提议会遭到愤怒的反抗，但那些保守者却又没有付出合理的行动。

【3】对农业和食物生产问题展开坦率的对话正在受到阻碍。

【4】人们对于Regenesis这本书的态度是愤怒和不满，因为它挑战了“根隐喻”。

【5】查尔斯三世国王钟爱于特兰西瓦尼亚，喜欢那里质朴原始的田园生活方式。

【6】特兰西瓦尼亚的农业看起来十分美好。

【7】特兰西瓦尼亚的农业和食物生产同现代残忍的工业机器完全不同。

【8】现在对农业和食物的讨论中，被推崇喜爱的方式就是这种安逸快乐的农场。

【9】但是这些“浪漫主义者”没有考虑到实际问题，因为这种生产方式无法规模化，只是世外桃源般的幻想。

【10】故事书里的农业从未像浪漫主义者所说的那样发挥作用。

【11】如果不承认美好故事中的农业方式，就会被当成对身份的攻击。

【12】但全球粮食危机真正有效的解决办法既不美好也不舒心。

【13】解决粮食危机的办法不是开垦更多土地，而是改造现有的食物工厂。

【14】解决全球粮食危机存在两个挑战，一是要解决残忍、污染和自我毁灭的主流农业模式，二是要对抗不切实际的美好遐想。

经济学人原文Our infantile view of farming won’t solve the global food crisisThe answer is not more fields, which destroy wild ecosystems, but partly compact, cruelty-free factories that don’t pollute【1】No issue is more important, and none so shrouded in myth and wishful thinking. The way we feed ourselves is the key determinant of whether we survive this century, as no other sector is as damaging . Yet we can scarcely begin to discuss it objectively, thanks to the power of comforting illusions.【2】Food has the extraordinary property of turning even themost progressive people into reactionaries. People who might accept any number of social and political changes can respond with fury if you propose our diets should shift. Stranger still, there’s a gulf between ultraconservative beliefs about how we should eat and the behaviour of people who hold such beliefs.【3】Something is blocking us, a deep repression that stands in the way ofhonest conversation. It pushes food writers, celebrity chefs andsome environmentalists to propose answers to the planetary crisis that are evenmore damaging than the problems they claim to address. Their solutions, suchas pasture-fed meat, with its massive land demand , are impossible to scale without destroying remaining wild ecosystems: there is simply not enough planet. What is this inhibition and how does it arise?【4】It’s now a year since I published Regenesis , a book that has incited levelsof fury shocking even to me. I’ve spent much of this time trying to work out what makes people so angry. I think it’s because the book challenges whatthe cognitive historian Jeremy Lent calls a “root metaphor” : an idea sodeeply embedded in our minds that it affects our preferences withoutour conscious knowledge.【5】The root metaphor in this case is exemplified by King Charles III’slove affair with Transylvania. What he found there “was a perfectly bottled model of life before modernity”. “It’s the timelessness which i s so important,” the king is reported to have said. “The landscape is almost out of some of those stories you used to read as a child.”【6】farming in Transylvania looks (or did until recently) just as it “ought” to look: tiny villages where cows with their calves, ducks with their ducklings and cats with their kittens share the dirt road with ruddy-cheeked farmers driving horses and carts; alpine pastures where sheep graze and people scythe the grass and build conical haystacks. In other words, as the king remarked, it looks like a children’s book.【7】A remarkable number of books for young children are about livestock farms. The farms they imagine look nothing like the industries that produce themeat, dairy and eggs we eat, which are generally places of horror. The stories they tell are a version of an ancient idyll of herders with their animals .Livestock farming here is a place of safety, harmony and comfort, into whichwe subconsciously burrow at times of unease.【8】Much of the discussion of food and farming in public life looks like an effort to recreate that happy place. As a result, many of the proposed solutions to the global food crisis seek, in effect, to revive medieval production systems – to feed a 21st-century population.【9】A scene that reminds us of our place of safety at the dawningof consciousness is used as the model for how we should be fed, regardless of whether it can scale. Bucolic romanticism might seem harmless. But it leads,if enacted, to hunger, ecological destruction or both, on a vast scale.Our arcadian fantasies devour the planet.【10】Storybook farming never worked as the romantics claim. Widespread meat eating in the 19th century became possible only through the colonisationand clearance of Australia and the Americas, and the creation, largely by theBritish empire, of a global system sucking meat into rich nations.【11】The cattle and sheep ranching that supplied our supposedly traditional diet drove the dispossession of Indigenous peoples and destruction of ecosystems ona massive scale, a process that continues to this day. When you challenge the story that masks these grim realities, it’s perceived as an attack on our very identity.【12】Real solutions to our global food crises are neither beautiful nor comforting. They inevitably involve factories, and we all hate factories, don’t we? In reality, almost everything we eat has passed through at least one factory on its way to our plates. We are in deep denial about this, which is why, in the US, where 95% of the population eats meat , a survey found that 47% wanted to ban slaughterhouses . 【13】The answer is not more fields, which means destroying even morewild ecosystems. It is partly better, more compact, cruelty-free and pollution-free factories. Among the best options, horror of horrors, is a shiftfrom farming multicellular organisms (plants and animals)to farming unicellularcreatures (microbes), which allows us to do far more with far less .【14】King Charles would doubtless hate this. But there are 8 billion people to feed and a planet to restore, and neither can be achieved with retentive fantasies. I’ve found myself contesting a cruel, polluting and self-destructive mainstream farming model on one hand and, on the other,an idyllic reverie that would lead us to the twin disaster of agricultural sprawl and world hunger. It’s hard to decide which is worse.。

六年级下册第二单元点餐的场景英语作文Title: An Engaging Encounter: Ordering in a Restaurant SceneIntroduction:Imagine yourself in the lively atmosphere of a bustling restaurant, filled with aromatic scents and excited chatter. In this piece, we will explore the experience of ordering food in a restaurant setting, focusing on a specific scenario from the second unit of Grade 6 textbook.Setting the Scene:As Grade 6 students, we have recently been introduced to various conversations and phrases related to dining out. This particular scene is set in a popular restaurant during lunchtime. The air is filled with anticipation as we navigate our way through ordering meals from the menu.Engaging with the Menu:The extensive menu presents an array of appetizing options that leave us spoilt for choice. Excitement mounts as weadapt our newly acquired English vocabulary and phrases to communicate our preferences to the server.Greeting the Server:Upon arriving at our chosen table, we are greeted by a friendly server who promptly hands us menus with warm smiles. The polite exchange begins as we embark on this culinary adventure. Instead of rushing into taking orders immediately, it's helpful to engage in small talk about the restaurant or express appreciation for its ambiance.Ordering Drinks:Thirst-quenching beverages top our list as we study the drinks section of the menu attentively. Aware that basic conversation skills include expressing preferences and making polite requests, we apply our knowledge when communicating with the server:"I would like a glass of freshly squeezed orange juice, please.""Could I please have a cup of hot tea?""May I ask for some water with lemon?"Exploring Appetizers:Now it's time to delve into appetizers. We peruse through descriptions accompanied by mouth-watering illustrations while trying not to let our rumbling stomachs distract us."I'll start with a classic Caesar salad to whet my appetite.""The mini bruschetta looks delicious - I'd love to trythat!""A plate of crispy calamari rings, please. They're my absolute favorite!"Selecting Main Courses:As we proceed to choose main courses, we take into account our individual tastes and preferences. After all, everyone has different favorites! Engaging in English conversations to express our choices demonstrates our proficiency in the language:"I'm in the mood for a juicy steak with a side of garlic mashed potatoes.""Could I have the grilled salmon with steamed vegetables, please?""I'll go for the vegetarian pasta primavera."Adding Side Dishes and Condiments:To further personalize our meals, we carefully consider additional side dishes and condiments that complement our main courses. Polite requests and clear communicationskills are essential:"May I request a serving of French fries as a side dish?" "Can I have some extra ketchup on the side?""Do you have any chili flakes to add a little spice to my meal?"Wrapping It Up:The dining experience nears its end as desserts are served. Indulging in sweets provides the perfect opportunity to appreciate not only delicious food but also the newfound expertise in ordering meals entirely in English.Conclusion:Through this imaginative exploration of a restaurant scenario from Unit 2 of Grade 6, we've witnessed how students can effectively engage with menu options and confidently communicate their preferences using English phrases. Mastering these skills not only enhances language proficiency but also makes dining out an enjoyable and immersive experience. So let's embark on this flavorful journey armed with vocabulary and phrases - bon appétit!。

食虫植物英语作文Carnivorous Plants: The Fascinating World of Flesh-Eating FloraAmidst the lush verdant landscapes, a captivating and peculiar group of plants thrives, defying the conventional notion of vegetation. These are the carnivorous plants, a remarkable adaptation that has evolved to survive in nutrient-poor environments. These botanical marvels have captured the imagination of scientists, naturalists, and the general public alike, for their unique ability to attract, trap, and digest unsuspecting prey.The term "carnivorous plants" encompasses a diverse array of species, each with its own unique strategy for trapping and consuming its prey. From the iconic Venus flytrap to the delicate sundews, these plants have developed intricate mechanisms to lure, capture, and digest a wide range of small animals, including insects, spiders, and even small vertebrates. This remarkable adaptation has allowed them to thrive in environments where traditional photosynthesis alone would not be sufficient to sustain their growth and development.One of the most well-known carnivorous plants is the Venus flytrap(Dionaea muscipula), native to the bogs and wetlands of the southeastern United States. This plant's leaves are divided into two distinct parts: the trap and the trigger hairs. When an unsuspecting insect or small animal brushes against the trigger hairs, the trap snaps shut, trapping the prey inside. The plant then secretes digestive enzymes, breaking down the captured organism and absorbing the nutrients it provides.Another fascinating example of carnivorous plants is the sundew (Drosera species), found across the globe. These plants have leaves covered in sticky, glandular tentacles that secrete a sticky, sugary substance to lure and trap their prey. When an insect lands on the leaf, the tentacles curl around it, trapping it in the sticky secretions. The plant then releases digestive enzymes to break down the prey, absorbing the nutrients it provides.Beyond the well-known Venus flytrap and sundew, the carnivorous plant family boasts a diverse array of species, each with its own unique adaptations. The pitcher plant (Nepenthes species), found primarily in Southeast Asia, has evolved specialized leaves that form a deep, pitcher-like structure filled with digestive fluids. Unsuspecting insects and small animals are lured into the pitcher, where they become trapped and ultimately digested.The bladderwort (Utricularia species) is another fascinatingcarnivorous plant, found in aquatic and semi-aquatic environments around the world. These plants have tiny, underwater bladder-like structures that are triggered by the movement of small aquatic organisms. When the trigger hairs are touched, the bladder quickly opens, sucking in the prey and trapping it inside.The adaptations of carnivorous plants are not limited to their trapping mechanisms. Many species have also evolved intricate strategies to attract their prey, using a combination of visual, olfactory, and even thermal cues. Some plants produce nectar-like secretions or colorful, fragrant flowers to lure insects, while others utilize heat signatures to attract warm-blooded animals.The ecological significance of carnivorous plants cannot be overstated. In nutrient-poor environments, these plants play a crucial role in the ecosystem, providing a valuable source of nutrients that would otherwise be scarce. By capturing and digesting small animals, they are able to obtain the essential nutrients they need to thrive, effectively filling a niche that other plants cannot.Moreover, the study of carnivorous plants has led to numerous scientific discoveries and advancements. Researchers have investigated the intricate mechanisms behind the plants' trapping and digestive processes, leading to a better understanding of plant physiology and adaptations. Additionally, the unique properties ofcarnivorous plants have inspired the development of biomimetic technologies, such as self-cleaning surfaces and micro-scale fluid control devices.In conclusion, the world of carnivorous plants is a captivating and truly remarkable aspect of the natural world. These botanical wonders have evolved intricate strategies to not only survive, but thrive in challenging environments, showcasing the incredible adaptability and diversity of life on our planet. As we continue to explore and study these fascinating plants, we uncover new insights into the natural world and the incredible ingenuity of evolution.。

让脂肪到适合的地方的英文全文共四篇示例，供读者参考第一篇示例：Make Fat Go to the Right Places1. Exercise2. Balanced Diet3. Hydration4. Stress ManagementChronic stress can contribute to fat storage in the body, particularly in the abdominal region. Finding effective ways to manage stress, such as practicing mindfulness meditation, yoga, or deep breathing exercises, can help reduce cortisol levels and prevent fat accumulation in the wrong places. Getting an adequate amount of sleep and taking time for self-care activities can also help promote fat redistribution and overall well-being.5. Hormonal Balance第二篇示例：我们常常听到“让脂肪到适合的地方”的说法，这意味着将身体上的脂肪集中到我们想要塑造的部位，如翘臀、纤腰等。

在现代社会中，对身材的要求越来越高，因此很多人都在寻找方法来让脂肪到适合的地方。

以下是一些方法可以帮助你达到这个目标。

要实现让脂肪到适合的地方的目标，首要的是要控制饮食。

要注意饮食的平衡，保证摄入蛋白质、碳水化合物、脂肪、维生素和矿物质的量。

避免食用高糖、高脂肪的食物，尽量选择新鲜、天然的食材。

控制饮食的量，避免过度进食。

适量的运动也是让脂肪到适合的地方的重要因素。

Isothermal Titration Calorimetric Studies on Interactions of Ionic Surfactant and Poly(oxypropylene)-Poly(oxyethylene)-Poly(oxypropylene)Triblock Copolymers in Aqueous SolutionsS.Dai,K.C.Tam,*and L.LiSchool of Mechanical and Production Engineering,Nanyang Technological University,Nanyang Avenue,Singapore639798,Republic of SingaporeReceived February23,2001;Revised Manuscript Received June6,2001ABSTRACT:Isothermal titration calorimetry was used to investigate the binding characteristics of sodium dodecyl sulfate(SDS)and PEP-type[P and E represent poly(oxypropylene)and poly(oxyethylene), respectively]triblock copolymers in aqueous solution.Beyond the critical aggregation concentration(CAC), PEP/SDS aggregation complexes are formed through the polymer-induced micellization process.SDS monomers first bind to the PPO segments followed by binding to the PEO segments.The polymer chains are dehydrated and solubilized in the hydrophobic core of SDS micelles containing an aggregation number smaller than that of free SDS micelles in water.From the contribution to the Gibbs energy,it is found that the formation of polymer/SDS aggregation complex is an entropic-driven process.The CAC is independent of the molecular weight of polymer,is weakly dependent on the polymer concentrations, and is strongly dependent on polymer composition.An increase in the length of PPO segments results in the reduction in the CAC.At the saturation concentration C2,the polymer chains are saturated with SDS micelles,where the polymer chains are bound to the surface of SDS micelles through ion-dipole associations.C2is sensitive to polymer concentration and shifts to higher values with increasing polymer concentrations.A physical model describing the interactions between SDS and the copolymers is proposed.IntroductionWater-soluble triblock copolymers of poly(oxypropy-lene)and poly(oxyethylene)are widely used in various industrial applications such as emulsifying,wetting, thickening,coating,solubilizing,stabilizing,dispersing, lubricating,and foaming agents.1These polymers ex-hibit interesting structural and phase behaviors in solution.Numerous studies have been carried out on aqueous solutions of these copolymers.At present,two types of poly(oxypropylene)(or PPO)and poly(oxyeth-ylene)(or PEO)triblock copolymers are available for commercial applications,which are termed as the EPE-type[E and P represent poly(oxypropylene)and poly-(oxyethylene),respectively]or Pluronic copolymers and the PEP-type or Pluronic-R copolymers.These polymers are commonly abbreviated as(EO)m(PO)n(EO)m and (PO)m(EO)n(PO)m,where m and n represent the number of repeat units.In the past several years,the EPE-type copolymers were systematically studied by various techniques such as laser light scattering,2-7dye solu-bilization,8surface tension and gel filtration.9The polymers associate into micellar aggregates in the forms of spherical to rodlike structure,depending on the temperature and concentration.However,relatively few studies were reported for the PEP-type copolymers.10-12 For these polymers in aqueous medium,random net-work or micelles could be formed by varying the chemi-cal composition and concentration as well as tempera-ture.For the PEP copolymers,PPO segments associate with each other,bridged by PEO segments.The ag-gregation number of PEP copolymers is much smaller than that for the EPE system.The details of the association behaviors of these polymers can be found in the monographs by Chu.1,13Polymer/surfactant systems are commercially impor-tant in a number of applications.The interaction between surfactants and polymers can be described by two critical concentrations.The first concentration, critical aggregation concentration(CAC),corresponds to the surfactant concentration when binding interac-tion between surfactants and polymer molecules first occurs,which represents the onset for the formation of polymer/surfactant aggregation complex.In some lit-erature,the notation of T1was used instead of CAC.14 The second critical concentration,C2or T2,is more obscure.It is commonly used to represent the surfactant concentration when the polymer becomes saturated with surfactant aggregates in polymer/surfactant aggregation complexes.In addition,another critical concentration C m,representing the formation of free surfactant mi-celles in the polymer solution,was previously reported in the literature.15-21For some of polymer/surfactant systems,free surfactant micelles start to form after the saturation concentration,C2.Under this condition,C m is analogous to C2.However,for other polymer/surfac-tant systems,the formation of free surfactant micelles precedes C2or C m is less than C2.In this case,there is a competition between the formation of free surfactant micelles and that of polymer/surfactants aggregation complexes at surfactant concentrations between C m and C2.Bloor and co-workers have made substantial con-tributions to the determination of CAC,C m and C2using both surfactant ion selective electrodes and microcalo-rimetry techniques.17-21Numerous studies on the interactions between sur-factants and polymers have been reported in the lit-erature.22-25A detailed review on this topic can be found in the monographs by Goddard26and Kwak.27However, relatively few studies on the interactions between ionic surfactants and water-soluble triblock copolymers of PEO and PPO have been reported in the literature.28,29*To whom correspondence should be addressed.Fax:(65)791-1859.E-mail:mkctam@.sg.7049Macromolecules2001,34,7049-705510.1021/ma010329k CCC:$20.00©2001American Chemical SocietyPublished on Web08/29/2001Recently,Bloor and co-workers 30,31reported on the binding behavior of the EPE system (Pluronic F127)and SDS,where the aggregation process was examined by electromotive force,light scattering and microcalorim-etry.However,the exact mechanism on how SDS binds to Pluronic-R copolymers is still unclear.In this study,the interaction of Pluronic-R copolymers and sodium dodecyl sulfate (SDS)was investigated using an isothermal titration calorimetry (ITC)tech-nique.The effects of concentrations,polymer molecular weights,and copolymer compositions were examined.The present system was compared with the interactions between SDS and PEO at the similar molecular weight.The driving force for the polymer/surfactant interactions was analyzed based on the thermodynamic parameters obtained from the ITC measurements.Experimental SectionMaterials.Three triblock Pluronic-R copolymers of 10R5,17R4,and 25R4were donated by BASF (Mount Olive,NJ).10R5has a composition of (PO)8(EO)22(PO)8with a nominal molar mass of 1950Da.17R4represents (PO)14(EO)24(PO)14with a nominal molar mass of 2650Da,while 25R4refers to (PO)19(EO)33(PO)19with a nominal molar mass of 3600Da.The poly(ethylene glycol)or poly(ethylene oxide),PEG75,with the molar mass of 3350Da was supplied by Union Carbide (Danbury,CT).Similar to the studies by Chu et al.and Brown et al.,10,11these polymers were used as received with no further purification.Sodium dodecyl sulfate (SDS)was purchased from BDH Laboratory Supplies (Poole,U.K.).The deionized water used was from a Millipore Alpha-Q water purifying system.Then 0.2M SDS aqueous solution and 0.5wt %tri-block copolymer solutions were prepared and used as stock solutions.Solutions with lower concentrations were prepared by diluting the stock solution with deionized water.Isothermal Titration Calorimetry (ITC).The microcalo-rimeter used in this study is the Microcal ITC system (Northampton,MA).A detailed description of this power compensated system could be found in Wiseman et al.32The microcalorimeter consists of a reference cell and a sample cell of 1.35mL,with both cells insulated by an adiabatic shield.The titration was carried out by step-by-step injections of a concentrated titrant solution from a 250µL injection syringe into the sample cell filled with a dilute titrate solution.The syringe is tailor-made such that the tip acts as a blade-type stirrer to ensure continuous mixing efficiency at ing the interactive software,an injection schedule was automatically carried out after setting up the number of injections,volume of each injection and time between each injection.In ITC experiments,one measures the enthalpy changes associated with the processes occurring at a constant temperature.The measurements of critical micelle concentra-tion (cmc),CAC,the ∆H of micellization,and the ∆H associ-ated with polymer -surfactant interactions were performed at a constant temperature of 25.0(0.02°C.Results and DiscussionDilution Behaviors of SDS and 25R4in Water.By titrating a micellar surfactant solution into water,the demicellization behavior could be determined from the ITC experiment.Figure 1shows the dilution curve of 0.2M SDS into water (open circles),where ∆H mic is -2.20(0.04kJ/mol and the cmc is 8.30mM.These values are similar to those reported in the literature.33,34Using the expressions given by eqs 1and 2,∆G mic )-21.95(0.03kJ/mol and T ∆S mic )19.75(0.04kJ/mol.The factor of (1+K )accounts for the electrostatic interactions observed for ionic surfactants,where K (micellar charge fraction)equals 0.85for SDS.15,16The dilution curve of 0.5wt %(∼1.4mM)25R4into water is shown in Figure 2(open circles).Negligible heat changes were detected,which implies that demicelliza-tion of micelles does not occur,confirming that 25R4chains are in the form of unimers.This agrees with the published data for 17R4(with very similar composition to 25R4),where the cmc at 40°C was reported to be approximately 10wt %.11Binding Behaviors of SDS and 25R4in Aqueous Solutions.The ∆H profile for the titration of 0.2M SDS into 0.053wt %25R4as a function of SDS concentration (C SDS )is shown in Figure 1(filled circles).It is evident that the titration thermogram of SDS into 25R4is different from that for titration into water.The curve comprises of an endothermic peak followed by a broad exothermic peak,which then merges with the pure SDS micelle dilution curve.The difference between the titration of SDS into 25R4and into water is attributed to the interactions between SDS and 25R4.The CAC and C 2are common nomenclatures used to describe the critical features of the polymer/surfactant interaction.In this paper,the CAC was determined from the peak in the difference enthalpy plot i.e.,[∆H (k )-∆H (k -1)]/∆m vs C SDS ,which corresponds totheFigure 1.Calorimetric titration curves for the addition of 200mM SDS into water (O )and into 0.053wt %25R4aqueous solution (b )at 298K.The inset is the difference curves of the ITC titrationcurves.Figure 2.Calorimetric titration curves for the addition of 0.5wt %25R4into water (O )and into 100mM SDS solutions (b )at 298K.∆G mic )(1+K )RT ln(cmc)(1)∆G mic )∆H mic -T ∆S mic(2)7050Dai et al.Macromolecules,Vol.34,No.20,2001concentration of the inflection point in the leading edge of the endothermic peak.C2is defined when the differ-ence enthalpies becomes zero where C m is analogue to C2for this system.The curve of the difference enthalpy changes and C SDS for titrating0.2M SDS into0.053wt %25R4is shown as the inset in Figure1.It is found that the CAC is1.36mM and C2is16.26mM,which are marked in the figure.From thermodynamics consideration,the enthalpy change at CAC can be expressed by the equation below:35Since the enthalpy changes for the SDS dilution and the demicellization of SDS micelles are small compared to the binding∆H interaction between SDS monomers and polymer chains,the measured enthalpy change is mainly attributed to the enthalpy change for the forma-tion of polymer/SDS aggregation complexes,∆H agg. Using the thermodynamic equations derived from the phase separation and the mass-action model,36,37the Gibbs energy for the formation of polymer/SDS ag-gregates(∆G agg)can be determined from eq4where K is the micellar charge fraction with a value of 0.85for SDS.All the thermodynamic parameters are summarized in Table1.Since∆H agg is positive,the contribution to the Gibbs energy is dictated by the magnitude of T∆S.Hence,the aggregation process at CAC is an entropic-driven process.With respect to the titration thermogram of SDS into 25R4solution,similar ITC curves were observed for interactions between SDS and various water-soluble polymers.17,18,23,38-40At C SDS<CAC,the∆H for the SDS/polymer system is slightly larger than the SDS/ water system.The presence of25R4alters the solvent environment,which affects the demicellization behavior of SDS micelles.At C SDS>CAC,the∆H becomes more endothermic,approaching a maxinum at C SDS of∼1.80 mM.Beyond this,∆H decreases and crossover with the SDS dilution curve at∼4.71mM.After that,it becomes exothermic and decreases to a minimum at C SDS∼11.16mM and then merges with the dilution curve of SDS in water at C2of16.26mM.On the basis of the interpretation of the ITC data for SDS/PEO system,23,39the endothermic and exothermic peaks observed for the SDS/25R4system could be interpreted as follows.At C SDS)CAC,SDS monomers cooperatively bind to the25R4segments to form aggregation com-plexes,which yield a sharp increase in the∆H.Binding of SDS to PPO segments occurs first,followed by binding to PEO segments.The interpretation for the exothermic peak was first proposed by Wang et al.39for SDS/EHEC system based on their previous studies on SDS/pen-tanol-1system.41It was subsequently extended to the PEO/SDS system.42The proportion of SDS molecules participating in the polymer/SDS complex increases with each titration,as reflected by the increasing∆H.A consequence of this is that the electrostatic repulsion between the SDS headgroups increases,and this im-pedes the binding of additional SDS molecules to the polymer/SDS complex.Beyond a C SDS at maximum∆H, the percentage of SDS participating in the polymer/SDS complex decreases,leading to a lower∆H.Further increase in C SDS causes the polymer/SDS complex to reorganize where the25R4segments in the hydrophobic core of SDS micelles rehydrate into the water phase due to their amphiphilic property.The exothermic∆H is related to the rehydration and the subsequent binding of25R4segments to the hydrophilic surface of SDS micelles via ion-dipole association.Close to C2,the micellar core consists mainly of dodecyl chains and the polymer chains reside on the outer region of the charged SDS headgroups,which shield the electrostatic repul-sions between these charged groups.This also mini-mizes the contacts between the hydrophobic segments of the surfactant molecules and water phase.Both effects give rise to the further increase in the SDS aggregation number.It is reported that the aggregation number of the SDS aggregates is about30at CAC and increases to∼60-80at C2for the SDS/PEO system from fluorescence decay measurements.24,43At C2,the ag-gregation number is slightly smaller than the aggrega-tion number of free SDS micelles in water.26The details of the association mechanism for SDS/PEP system will be discussed later.SDS in the polymer/SDS mixed solutions can exist in three forms,i.e.,free SDS monomers,free SDS micelles, and polymer/SDS aggregation complexes.The total concentration of SDS in the solution can be expressed by the following equation26Table1.The Critical Aggregation Concentrations(CAC),the Saturation Concentration(C2),and the Thermodynamic Parameters for SDS in the Presence of PEP-Type Copolymer at298Kpolymer name polymerconcnSDS concn(mM)CAC a(mM)∆H agg b(kJ/mol)C at∆H max a(mM)∆H max b(kJ/mol)C2a(mM)∆G agg(kJ/mol)T∆S agg(kJ/mol)25R40.49wt%2000.9718.7 1.6326.8-31.850.5 25R40.49wt%1000.9718.7 1.7026.4-31.850.5 25R40.49wt%500.9417.9 1.6424.3-32.049.9 25R40.49wt%200.9318.5 1.5023.5-32.050.5 25R40.49wt%2000.9718.7 1.6326.8-31.850.5 25R40.40wt%2000.9717.3 1.6325.4-31.849.1 25R40.30wt%2000.9914.5 1.6222.2-31.746.2 25R40.20wt%200 1.0612.1 1.7218.833.58-31.443.5 25R40.10wt%200 1.209.7 1.8113.123.72-30.840.5 25R40.053wt%200 1.36 6.7 1.808.816.26-30.337.0 25R40.15mM200 1.36 6.7 1.808.816.26-30.337.0 17R40.15mM200 1.62 5.3 2.25 6.716.25-29.534.8 10R50.15mM200 2.55 2.1 4.02 3.616.25-27.429.5 PEG750.29mM200 4.81 2.2 6.90 4.123.57-24.526.7 a Estimated error(0.05mM.b Estimated error(0.1kJ/mol.∆H)∆H(dilution of SDS micelles and monomers)+∆H(demicellization of SDS micelles)+∆H(binding of SDS monomers topolymer chains)(3)∆Gagg )(1+K)RT ln(CAC)(4)Macromolecules,Vol.34,No.20,2001Isothermal Titration Calorimetric Studies7051where X t is the total SDS concentration,X u is the SDS monomer concentration,X p is the total concentration of polymer in solution,N f is the aggregation number of SDS in free micelles,N b is the aggregation number of SDS in the polymer/SDS aggregation complex,K f is the intrinsic equilibrium constant for the formation of free SDS micelles,K b is the intrinsic equilibrium constant for the formation of polymer/SDS aggregation complex, and nX p is the effective mass concentration,which is independent of polymer molecular weight.If K f>K b, and N f=N b,the formation of free micelles is preferred rather than the formation of the aggregation complexes. If K f<K b,and N f=N b,the formation of aggregation complexes occurs first,and upon saturating the polymer chains by SDS molecules,free micelles begin to form. If K f<K b,and N f.N b,the formation of aggregation complexes occurs first,but free micelles begin to form in solution before the saturation of the polymer.For the SDS/PEO system,K f<K b and N f is slightly larger than N b.26Because the thermogram of SDS/25R4is similar to the thermogram of SDS/PEO system,it can be concluded that the equilibrium constant(K b)of SDS/ 25R4aggregation complexes is larger than that of SDS micelles(K f)and N b is slightly smaller than N f.From previous discussions on the titration of micellar SDS solution to25R4,it was observed that SDS concentration affects the binding characteristics.At low C SDS,SDS monomers cooperatively bind to the polymer backbone,producing aggregation complexes containing polymer segments that are solubilized in the hydropho-bic core of SDS micelles.At large C SDS,the polymer chains bind to the surface of SDS micelles.To verify this, we titrated0.5wt%(∼1.4mM)25R4solution into0.1M SDS solution(SDS micelles are in abundance)and the thermogram is shown in Figure2(filled circles).The ∆H for titrating25R4into the SDS solution(filled circles)is much larger than that for titrating25R4into water(open circles).This difference can be ascribed to the interaction of SDS micelles and25R4.In addition, it is evident that the thermogram is different from the result on titrating micellar SDS solution into25R4, thereby confirming that different binding mechanism must be in operation.From Figure2,∆H for the25R4/ SDS system is∼78(0.5kJ/mol,which corresponds to the apparent enthalpy change for the binding of25R4 chains to the surface of SDS micelles via ion-dipole association since only SDS micelles are present in abundance.Effect of Surfactant Concentrations.Figure3 shows the thermograms for titrating20to200mM SDS solutions into0.5wt%25R4solution,where the CAC and∆H agg are independent of C SDS.The computed thermodynamic parameters are summarized in Table 1.The Gibbs energies,enthalpy changes and entropy changes for the formation of polymer/SDS aggregation complexes are not sensitive to the initial concentration of SDS titrant solutions.Effect of Polymer Concentrations.Figure4sum-marizes the thermograms for the titration of0.2M SDS into different concentrations of25R4.The CAC(evident from the insert plot)is mildly dependent on polymer concentrations,where it decreases from1.36to0.97mM when the polymer concentration is increased from0.053 to0.49wt%.The surfactant concentrations correspond-ing to the maximum value of the endothermic peak are also insensitive to the polymer concentration,but the enthalpy changes increase with increasing polymer concentration.However,the exothermic peak and C2 shift to higher SDS concentrations when the polymer concentration is increased.The strong dependence of C2 on polymer concentrations is related to larger amounts of SDS molecules needed to saturate the polymer chains, which is in agreement with previous studies.15,16,23,26,34 The concentration dependence of CAC and C2reveals that the span between CAC and C2increases with polymer concentrations.This can be described by the phase diagram for PEO/SDS system reported by Cabane and Duplessix.26The values of C2-CAC can be used to estimate the amount of bound SDS at a fixed polymer concentration.The values of CAC,C2,and thermody-namic parameters are summarized in Table 1.By comparing the values of∆G agg,polymer concentration does not significantly affect the formation of polymer/ SDS aggregation complexes at CAC.The contribution from the entropy changes increase with polymer con-centrations due to the increase in∆H.Figure5shows the dependence of∆H agg on polymer concentration,where∆H agg increases linearly with polymer concentration.When extrapolated to zero con-centration,the value of∆H agg is6.6kJ/mol,which is three times larger than the∆H mic of SDS(2.2kJ/mol). This confirms that the formation of polymer/SDS ag-gregation complexes is a different cooperative process from the formation of free SDS micelles in aqueous solu-X t )Xu+Nf(KfXu)N f+NbnXp((K b X u)N b1+(KbXu)N b)(5)Figure3.Calorimetric titration curves for titrating differentconcentrations of SDS into0.5wt%25R4at298K.Figure4.Calorimetric titration curves for titrating0.2MSDS into different concentrations of25R4at298K.7052Dai et al.Macromolecules,Vol.34,No.20,2001tion.With increasing polymer concentration,larger pro-portions of the 25R4segments are dehydrated and solu-bilized in the hydrophobic core of SDS mixed micelles resulting in the corresponding increase in ∆H agg .Comparison of SDS Titrations into PEP Copoly-mer and into PEO.To understand the binding behav-ior between SDS and PEP copolymer,the titration of SDS into PEO at similar molecular weight was com-pared.Figure 6reveals the titration curves of 0.2M SDS into 0.29mM PEG75and 0.28mM 25R4.Since both polymers have similar molar masses and molar concen-trations,the numbers of polymer chains and the chain lengths are therefore identical.Although the general trends of the thermograms are similar and both C 2values are identical,the exothermic peak for SDS/PEP system is much broader than that for SDS/PEO system.The CAC of SDS/PEP system is much smaller than SDS/PEO system and the endothermic ∆H is more than double that of PEO/SDS system.Because of the fact that PO contains an additional methyl group,it is more hydrophobic than PEO;hence,polymer/SDS aggregation complexes are produced at lower CAC.Thus,we con-clude that binding of SDS onto PPO occurs first followed by binding to the PEO segments.The value of C 2-CAC can be use to estimate the amount of SDS bound to the polymer chains.For both PEG75and 25R4systems,the molar ratios of (C 2-CAC)/[polymer]are about 65and 80,respectively.These numbers indicate that 25R4can bind more SDS monomers at saturation concentrationC 2,but both are smaller than the aggregation number of free SDS micelles in water.Effect of Polymer Molecular Weights.For PEO/SDS system,cooperative binding of SDS monomers to PEO will occur when the MW exceeds 900Da.However,the formation of ion -dipole associated complex (PEO chains wrapping SDS micelles)required a MW greater than 3350Da.44At MW less than 3350Da,a negligible or very weak exothermic peak is observed in the ITC thermogram.A weak exothermic peak was also observed for PPO/SDS system of MW less than 1000Da.42,45For the PEP polymer with PO and EO segments,the exothermic peak is due to the rehydration of the EO and PO segments into the water phase,and these rehy-drated segments could form an ion -dipole association with the hydrophilic headgroups of SDS micelles.Figure 7shows the thermograms for titrating 0.2M SDS into 0.15mM 17R4and 25R4aqueous solutions,respectively.The 17R4and 25R4have similar molar ratio of PO/EO (∼1.15),but the MW of 25R4is 3600while that of 17R4is parison of the titration curves between 17R4and 25R4provides information on the effect of molecular weights on the interaction between SDS and the PEP copolymers.Both exhibit a distinct endothermic and an exothermic peak.The endothermic peak corresponds to the formation of polymer/SDS aggregation complex induced by hydro-phobic interactions.The exothermic peak describes the formation of the polymer/SDS aggregation complex induced by ion -dipole association.From the figure,it is evident that molecular weights do not significantly affect CAC and C 2,which is in agreement with pub-lished results for SDS/PEO system.26Since CAC is a critical concentration for the onset of hydrophobic binding between SDS and dehydrated polymer seg-ments,it is only sensitive to the character of the solubilized segments and SDS monomer concentrations but independent of the molecular weights.However,both the ∆H agg at CAC and the ∆H of the endothermic peak for 17R4are smaller compared to 25R4system.Since both polymers have the same molar concentration,the numbers of polymer chains in the solution are identical.The higher molecular weight 25R4system possesses a longer backbone,which gives rise to a larger ∆H agg as the enthalpy change at CAC is directly proportional to the concentration of solubilized segments.When the values of (∆H agg /MW)are com-pared,negligible difference is observed.AlthoughtheFigure 5.Relationship of ∆H agg and polymer concentrations for a SDS/25R4system at 298K.Figure parison of the titration curves of 0.2M SDS into 0.28mM 25R4and 0.29mM PEG75at 298K.The open circles represent the dilution curve of 0.2M SDS in water at 298K.Figure 7.Calorimetric titration curves of 0.2M SDS into 0.15mM 25R4and 17R4solutions at 298K.The open circles represent the dilution curve of 0.2M SDS in water at 298K.Macromolecules,Vol.34,No.20,2001Isothermal Titration Calorimetric Studies 7053contribution to the negative Gibbs energy for the forma-tion of polymer/SDS aggregation complex is mainly dictated by ∆S ,the entropy contribution for 17R4is slightly smaller than 25R4due to the different binding enthalpy changes.At C 2,the ion -dipole associated polymer/SDS com-plexes are present and we observed that the molecular weight does not affect C 2.From Figure 7,two exother-mic peaks for 17R4and one broad exothermic peak for 25R4are evident.The origin of these two peaks is still not clear,but it may be caused by the different rehy-dration properties of PPO and PEO segments.It is expected that PEO segments rehydrate first since it is less hydrophobic.The combination of these two pro-cesses yields the trends observed in the thermograms.When the PPO segments are longer,such as 25R4,rehy-dration process is dominated by the rehydration of PPO segments.The contribution from the rehydration of PEO is smaller;hence,only a broad exothermic peak domi-nated by the rehydration of PPO segments is observed.For shorter PPO segments,such as 17R4,both the PEO and PPO segments have equal contribution to the rehydration process,yielding two distinct exothermic peaks.When the length of PO is shorter than EO such as 10R5(PO/EO )0.72),the total rehydration process will be dominated by the rehydration process of PEO segments.This is reflected by a distinct exothermic peak caused by the rehydration of PEO segments and a broad shallow second peak attributed to the rehydration of PPO segments as shown in Figure 9.A schematic description of the binding interactions between SDS and PEP copolymers is shown in Figure 8(concentration regions A -D are marked in Figure 7).SDS micelles are formed on PEP backbones after CAC,PPO segments dehydrate from the water phase first (region A)followed by the dehydration PEO segment to form a SDS/PEP complex (region B).Because of the increase in the aggregation number of SDS,the PEO segments will first rehydrate with the PEO segments binding to the SDS headgroups (region C).In region D,PPO segments rehydrate into the water phase and bind to the SDS headgroups to optimize the aggregation number of SDS micelles.Effect of the Length of PPO.The PPO is more hydrophobic compared to PEO and changing the length of PPO should affect the binding behavior between SDS and PEP copolymers.The titration curves of 0.2M SDS into 0.15mM 17R4and 10R5shown in Figure 9are compared to highlight the effects of length of PPO segment.The molar ratio of PO/EO is 0.72and 1.15for 10R5and 17R4respectively,and both copolymers have similar EO,but different PO length.It is evident that 10R5has a higher CAC,but smaller ∆H agg .The Gibbs energy of 17R4is more negative than 10R5(see Table 1),which suggests that the interactions between SDS and 17R4are more favorable than those between SDS and 10R5.Since 17R4possesses longer and more hydrophobic PPO segments,the polymer interacts more strongly with SDS.The increase in the hydrophobicity of the polymer chains leads to the decrease in the critical aggregation concentration.The onset for binding is strongly dependent on the polymer composition,and the hydrophobicity of telechelic ends.It is evident from Figure 9that the C 2values of the two polymers are fairly similar.This indicates that C 2is not sensitive to the polymer composition for PEP copolymers but is only dependent on the polymer molar concentration.The ratio of (CAC -C 2)/[PEP]corre-sponds to the number of SDS molecules absorbed on one PEP chain.It is estimated that about 94SDS molecules are absorbed on each 17R4and 10R5polymer chain,which implies that either one 10R5or one 17R4chain can bind one SDS micelle at the saturation condition.ConclusionsThe binding interactions of three Pluronic-R triblock copolymers and SDS were studied by isothermal titra-tion calorimetry.The CAC and C 2were determined from the titration curves.Beyond CAC,a significant endot-hermic peak is observed,followed by a broad exothermic peak,and the titration curve finally merges with the dilution curve of SDS micelles in water at C 2.The Gibbs energies at CAC confirmed that the onset for the formation of SDS/PEP aggregation complex is an en-tropic-driven process.The lower value of CAC,compared to cmc,is due to the polymer-induced micellization effect.After CAC,SDS/PEP aggregation complex ap-pears in solution.Binding of PPO and SDS occurs first followed by PEO and SDS.The CACs are independent of polymer molecular weights,weakly dependentonFigure 8.Schematic diagram for the binding process of SDS and PEP copolymers.Regions A -D are marked in Figure 7.A and B represent the polymer-induced micellization process at low SDS concentrations where PPO segments dehydrate from the water phase first followed by PEO segments.C and D indicate the reorganization of SDS/PEP aggregation complex to form ion -dipole association complex,where PEO segments first rehydrate into water phase followed by PPOsegments.Figure 9.Calorimetric titration curves of 0.2M SDS into 0.15mM 10R5and 17R4solutions at 298K.The open circle is the dilution curve of 0.2M SDS in water at 298K.7054Dai et al.Macromolecules,Vol.34,No.20,2001。

迷迭香英语作文秋天50字Rosemary: The Fragrant Herb of Autumn.As the summer days wane and the nights grow cooler, the herb rosemary emerges as a culinary and aromatic star of the autumn season. Its pungent fragrance and earthy flavor add depth and warmth to a wide range of dishes, from savory meats to sweet desserts.Rosemary, a member of the mint family, is native to the Mediterranean region. Its name, derived from the Latin words "ros marinus," translates to "dew of the sea," a testament to its proximity to coastal areas. The plant is characterized by its evergreen leaves, which are narrow, needle-like, and a deep shade of green. Rosemary blooms in late summer through autumn, producing small, pale blue flowers that attract pollinators.Rosemary has been prized for its culinary and medicinal properties for centuries. The ancient Greeks and Romansused rosemary to improve memory and digestion, and it was also believed to have antibacterial and antiviral effects. Today, rosemary is widely used in traditional herbal remedies for a variety of ailments, including headaches, fatigue, and muscle pain.In the kitchen, rosemary is a versatile herb that canbe used fresh, dried, or powdered. Its leaves can be addedto marinades, rubs, and sauces for meats, poultry, and fish. Rosemary also complements vegetables, especially roasted potatoes, carrots, and brussels sprouts. For a touch of sweetness, rosemary can be added to desserts such as cakes, cookies, and pies.One of the most distinctive culinary uses of rosemaryis in the preparation of roasted lamb. The herb's pungent aroma and earthy flavor pair perfectly with the richness of the meat, creating a succulent and flavorful dish. Rosemary can also be used to make a fragrant rosemary oil, which can be drizzled over salads, grilled meats, or vegetables foran extra burst of flavor.Beyond its culinary applications, rosemary is also a popular ingredient in aromatherapy and personal care products. Its essential oil is often used in diffusers or burners to create a calming and relaxing atmosphere. Rosemary extract is also found in soaps, shampoos, and conditioners, where its antibacterial and antifungal properties help to cleanse and revitalize the skin and hair.In the garden, rosemary is a relatively easy plant to grow. It prefers well-drained soil and full sun, althoughit can also tolerate partial shade. Rosemary is drought-tolerant and requires minimal watering once established.The plant can be grown in containers or in the ground, andit is a low-maintenance addition to any herb garden.Harvesting rosemary is a simple process. Simply snipoff the desired amount of leaves or stems with sharp scissors. Fresh rosemary can be stored in the refrigerator for up to a week, or it can be dried and stored in anairtight container for several months.As autumn unfolds, rosemary becomes a ubiquitous herb,adding its distinctive flavor and aroma to countless culinary creations and home remedies. Whether used fresh, dried, or powdered, rosemary is a versatile and fragrant herb that can elevate any dish or space. From savory stews to fragrant potpourris, rosemary is the quintessential herb of autumn.。