White matter integrity as an intermed
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Unit 1Reading A The Human complex— A Never –failing Source of Wonderment(人类的复杂性——一个永远不会失去惊叹的话题)“ In my view, ” wrote Thomas Jefferson in 1814 , “no knowledge can be more satisfactory to a man that of his own frame, its parts, their functions and action s. ” Distinguished thinkers before and since Jefferson have held this belief, but curiously, it is not one that the average person wholeheartedly shares.Man’s attitude toward his own body—his single most precious possession—is decidedly ambivalent. At one and the same time he is fascinated by it and fearful of it, partly in echo of ancient taboos, partly in the conviction that the body is too complicated to understand.( “在我看来,”托马斯杰佛逊于1814年写道:“对人来说,没有什么知识会比了解自身的架构、部件、功能和作用更能使他满足。
”包括杰佛逊在内的杰出思想家均持有这个观点,但有趣的是,这个观点并不为普罗大众所由衷地接受。
人们对自己的身体,这个对他自身来说最为宝贵的财富,态度其实是充满矛盾的。
AmazoniteThe Meaning of AmazoniteAmazonite soothes all chakras and is particularly rejuvenating to the heart center and throat chakra. It enhances communications concerning love. It can be used in the treatment in disorders of the nervous system and to dissipate energy blockages which could propagate the improper flow of neural impulsesAmethystBirth Month: FebruaryThe Meaning of Amethyst:Amethyst is the stone of spirituality and contentment. Its color ranges from pale lilac to deep purple. Amethyst bestows stability, strength, invigoration, and peace, the peace being the perfect peace which was present prior to birth. It is "warm and cuddly" as well as regal and ruling. It has been used to encourage and support sobriety. It is an excellent stone for one who is attempting to find freedom from addictive personalities (oneself or another). Calming, strong, protective qualities, healing, divine love and inspiration. Enhances one's psychic and creative abilities. Also believed to give courage, bring victories to soldiers in battle, and attract favors from those in high places. Other attributes that have been associated with the stone are it's ability to soothe the nerves in times of stress, make the wear become calm and gentle, repress evil and make people successful in business. Good for Spiritual Upliftment.Amethyst has historically been a favorite stone for royalty and has been seen as a symbol for peace and tranquility. The stone is mined in Africa and South America and is available in an array of sizes and shapesBLUE the giver of Love, devotion and harmony. Its stone is the Amethyst, the super-sacred of the seven jewels. Pale blue in the aura represents devotion, while dark blue shows fanaticism. One can either be "true blue or have a fit of the "blues", according to one's outlook. Blue is the color of the element of Water. It symbolizes the ocean, sleep, the sky, and twilight. Pacifying, refreshing and calming. Healing, peace, psychism, patience, happiness.Wear Amethyst Jewelry for tranquility.Aqua QuartzSynthetic - Crafted from the special gem-quality glass known as aqua quartz. Aqua Quartz has a transparent shade of an aquamarine hue.Aventurine (Green)The Meaning of Green Aventurine:Green Aventurine reinforces ones decisiveness, amplifies ones leadership qualities, and is a willing participant in instinctive action. Emotional tranquility, positive attitudes towards life, brings one into alignment with their center. Independence, health and well being , heals the heart chakra. You should never buy a lottery ticket without an aventurine in your left pocket. Lady Luck will be in your left pocket. This is the stone of opportunity. Aventurine is known as the stone of chance or luck. If you gamble or play the lotto, keep this stone in your left pocket. It is used to aid nearsightedness. It is said to increase perception and creative insight.GREEN It is the meeting ground between the thermal or heating and expanding colors of red, orange and yellow and the electrical contracting colors of blue, indigo and violet. Green gives stability, endurance and quietude. We are allowed much of it to look at in nature and to partake of as nourishment. Its action is to cool the blood and animate the nerves If the green is dark and crude it tells that its owner , so concerned with the affairs of others , has become"green with envy." Green gives us a serene feeling.Green is the color that represents money, prosperity, employment, fertility, healing, growth. It is the color of the element of the earth and symbolic of the planet's fertility and life. Green is pacifying, refreshing and calming. Pale and medium greens connect with nature.Wear Green Aventurine Jewelry for LuckMatching Stones: Green Aventurine, New JadeCandy JadeDyed - Candy Jade is made from top quality white jade and put through a complex heating and color enhancing process and penetrated from surface to center with vibrant colors.CarnelianThe Meaning of Carnelian:Carnelian originates as a dull brown, translucent banded agate. It is heat-treated to achieve a bright, burnt orange color. Carnelian protects against fear, envy, and rage, and helps to banish sorrow from the emotional structure. The message of carnelian is that since one "is" love, there is nothing to do but to offer the love - each offering of love bringing an exponential increase in the quantity of love returned. Carnelian stimulates inquisitiveness and subsequent initiative. It can assist one in drama and pursuits related to theatrical presentations. Keep a carnelian with you and feel the energy flow to you. Known to give energy to the user. Carnelian gives energy and protects from bad vibrations. It is said to guard against poverty. Carnelian also helps give a sense of humor.Carnelian, is found in Brazil, India and Uruguay. The ancient technique of laying carnelian in the sun to deepen its color is still used today in India.ORANGE is a color associated with the Sun, and has also a warming and invigorating effect. But whereas red is stimulating to the body and the blood, orange is stimulating to the emotions. It is alsoconsidered the color of the brave. General attraction and energy.Wear Carnelian Jewelry for Inner StrengthCrystal (Rock)The Meaning of Rock Crystal:Rock crystal was once believed to be able to foretell the future. When squeezed this stone becomes electrically charged. Synthetic quartz crystals are used to regulate watch movements and the electronic frequency of radios because they vibrate at a single constant frequency when an electric current is run through them.GarnetBirth Month: JanuaryThe Meaning of Garnet:Known as the "stone of health" - ridding the body of negative energies and transmuting them to a beneficial state. Also know in the past as a "stone of commitment" - to purpose, to others, to oneself. The loving power of garnet tends to reflect the attributes of devotion, bringing the love of others to expressions of warmth and understanding. It both monitors and adjusts the flow of energy, providing for a balanced energy field around the physical body and aligning the emotional and intellectual bodies with the perfection of "All that is". Garnet represents friendship. According to legend, if you wear garnets they will improve your personal relationships and protect you from harm. This benefit supposedly doubles if your birthday is in January. They were often used as good luck charms by the bourgeoisie in the 18th and 19th centuries in Europe. Also thought to assure the wearer of love, devotion from loved ones, health, faithfulness, energy, and to keep a person from having bad dreams during sleep. When worn on the body, it is thought to prevent skin diseases and protect against infection of wounds.Garnet is found in abundance and in a variety of colors such as dark brown-red, rosy-red, orange-red and green. In fact the garnet actually represents seven different stone species. Both versatile and affordable, garnet is the gem of faith.There is folklore that if a garnet is put under a pillow it will cure depression.Garnets can be used to make a person popular and have self-esteem when worn as jewelry. It helps protect one on trips. Garnets bring constancy to friendships.Garnets are also known for stimulating success in business.Wear Garnet Jewelry for HealthHematiteThe Meaning of Hematite:Slightly grounding, reduces stress, enhances personal magnetism, optimism, will, courage. "Stone for the mind" it helps one to realize that the only limitations which exist are self-limiting concepts within the mind. Stimulates attainment of peace, self-control, and inner happiness. Balances yin-yang energies. Assists in the focusing of energy and emotions for balance between the body, mind, and spirit. Helps transform negativity to the purity of the universal light of love.If you need your personal relationship to be better, have a hematite with you always. Hematite is known as the blood stone. It helps improve relationships.Hematite is a metallic gray color. It is a heavy stone. The name comes from the Greek wo rd for blood. Hematite is found in United States, Canada Venezuela and Brazil.It has been used as an amulet against bleeding, therefore, known as the "blood stone". Hematite is used to improve relations. It has been used in mourning jewelryBLACK absorbs them all and is warm, although neutralizedMatching Stone: black Onyx, HematiteWear Hematite Jewelry for help in Love and Relationships.IoliteThe Meaning of Iolite:Also known as Cordierite and "water sapphire" is usually a blue to violet colored gemstone. Metaphysical properties include: stimulation of the third eye, enhancement of your inner knowing; helps one to eliminate debt by accepting responsibility which leads to successful management of money; has been a stone worn by Shamans in the past to insure accuracy of visions; also can aid the elimination of disharmony in relationships.INDIGO: It is, like green, a meeting-ground for all the colors. It In the aura it shows dignity and high aspirations.Wear Iolite Jewelry to aid financial situations.JadeThe Meaning of Jade:Jade facilitates peace within the physical, emotional, and intellectual structures, as well as within the materialistic world. It was said to bring accord the environment, to transmute negativity and to instill resourcefulness. A very lucky stone, Jade has been used as early as 3000 BC for ornaments. It is said jade will help keep one young and also help to stimulate occult wisdom and universal attunement. In business it is said that if you hold a jade in the right hand, the correct decision will be made.Jade amulets have been found in tombs in Egypt, China and Mexico.Wear New Jade Jewelry for Luck.Jasper - RedThe 'protection' stone. Can clear negativity and assists in grounding. Represents the elemental nature of humanity and our connection with the components of physical reality. Clears toxins, soothes the nerves and balances the mineral ratio for the body. Helps the body to stabilize itself during dietary changes and improves the assimilations of trace minerals. Helps one to stabilize emotions, eliminate contradiction and create a sense of connection between all worlds during travel out of body.LaboraditePossibly treats disorders of the brain, aids in digestion, reduces anxiety and stress, stimulates mental sharpness. Helps to advance without constraint. Provides clarity of purpose and insight into ones direction according to the preconceived plans of your higher self.MoonstoneThe meaning of Moonstone:The energy of moonstone is balancing, introspective, reflective, and lunar. It is capable of helping one with the changing structures of ones life on the physical, emotional, mental, and spiritual levels. Once called the "travelers stone" it is used for protection against the perils of travel. Moonstone is a lso a talisman of GOOD FORTUNE. It is also said to both arouse tenderness within the self and to bring happiness to the environment in which it resides.In India a very long time ago, people once thought moonstone was actually moonlight that had solidifie d. Supposedly, it could bring you good fortune and help you foretell the events of the future. It has also been reported by some to attract good luck, protect a person on land and/or while at sea, be able to give you mental inspiration, bring success in love and good fortune in business. People believe that if you want moonstone to bring you good luck, you should keep it wrapped up in a yellow cloth and carry it in your pocket. Moonstone has also been taunted by some as a talisman against cancer, kidney dis ease, anddropsy.The moonstone is the stone of the goddess Diana. The most powerful time to use the moonstone is in a full moon. It has been worn as an amulet to bring good emotions to the wearer, while protecting those of a sensitive nature. It can reunite lovers who have quarreled. Moonstone is considered a good luck stone.Wear Moonstone Jewelry if you travel.GRAY is neutral and used as a partner to other colors.Matching Stone: Grey MoonstoneMother of PearlThe Meaning of Mother of Pearl:It signifies faith, charity, and innocence, enhances personal integrity, and helps to provide focus to ones attention. The pearl has been known as a "stone of sincerity", bring truth to situations and loyalty to a "cause". It has been used to inhibit boisterous behavior, and to provide a reflection of the self such that one may see the manner in which one appears to others.Protection; Know mother's love. This stone is a great protective stone.WHITE absorbs all the rays and is therefore cooling and restful.Matching Stones, Fresh Water Pearl, Crystal and Rock QuartzWear Mother of Pearl for ProtectionOnyxThe Meaning of Onyx:For initiating the modes of centering and alignment of the total person with the higher powers. Can be used to banish grief, to enhance self-control, to stimulate the power of wise decision making, and to encourage happiness and good fortune". It is grounding and can be used to deflect or absorb the negativity of others.BLACK absorbs them all and is warm, although neutralizedMatching Stone: HematiteWear Black Onyx Jewelry for Self Control.Opalescent QuartzSynthetic - A clear milky color when looked at from direct light, Opalescent Quartz has an iridescence that give it its namesake. When placed on black or dark material, it really shines, especially on a necklace with darker colored beads and pendants. These extraordinary pieces are specially made to possess the lovely, pale white opalescence one sees in the natural gemstone known as the opal. Each glass bead is transparent, with slight overtones of creamy white that shift to a startling shade of translucent cyan as the eye moves from one angle to another. Truly magnificent, eye-catching piecesPaua ShellThe Meaning Of Paua ShellThe Paua Shell used at is in completely natural condition. The pieces have been polished in water without chemicals to highlight the beauty of this unique sea shell.Paua (pronounced PAH-WAH), a molusc found exclusively in New Zealand waters has a shell of brilliant rainbow hues. Paua, which belongs to the same family as abalone was a prize food of the pre-European Maori (the native people of New Zealand) and today is still actively sought after as a delicacy for both local consumption and for export.Paua is harvested by skin divers from its habitat below low tide level off rocky exposed coasts around southern New Zealand. The shells were crushed and tumbled to remove the outer layers of lime and marine growth.Colors of Paua: green, blue, purplePearl - Fresh WaterBirth Month: JuneThe Meaning of Fresh Water Pearls:Enables one to accept love. See the good parts of oneself so you can love yourself and others.WHITE absorbs all the rays and is therefore cooling and restful.Matching Stones, Mother of Pearl, Fresh Water Pearl, Crystal and Rock QuartzPearl is a favorite gem for weddings. It has been a favorite for people of many cultures. An old Arab legend tells that pearls were created when dew drops filled with moonlight fell into the ocean and were swallowed by oysters. When Spanish explorers reached the New World, they found rich pearl fisheries run by Native Americans. They used the pearls, along with their shells, which were found in the Tennessee, Ohio and Mississippi River Basins, as well as in the Atlantic Ocean. At one point so manypearls made it to Europe from the New World that it was called the "Land of Pearls."Wear Pearl Jewelry for Love.Pearls - AkoyaAkoya pearls are the specialty of Japanese pearl farms. These were the first pearls to be cultured early in the 1920s, they have a white color with a slight rosé overtone. Akoya pearls are a high-quality pearl, they are well matched for size, shape, and color.Akoya looks very similar to the Freshwater pearl. When compared side-by-side, the difference is a more rounder shape than a natural Freshwater Pearl and a very slight pinkish hue. Akoya pearls are more expensive than a Freshwater Pearl and are on average larger, smoother, rounder, and more lustrous than Freshwater pearls.PeridotBirth Month: AugustThe Meaning of Peridot:This gemstone emits a warm friendly energy; works on both the heart and solar plexus chakras; acts to provide a shield of protection around the body; to help prevent outside influences from affecting alignment and balance. Helps one to find happiness within and over come anger and jealousy.Peridot was the legendary favorite of Cleopatra. The Romans called peridot "evening emerald" since its green color did not darken at night but was still visible by lamplight. Large peridots, more than 200 carats in size adorn the shrine of the three magi at the Cologne Cathedral. Gem quality peridot comes from the Red Sea, Burma and Arizona.Wear Peridot Jewelry for Happiness.Quartz - CrystalThe Meaning of Crystal QuartzQuartz Crystal can bring the energy of the stars into the soul. Traditionally, the natural quartz crystal was said to both harmonize and align human energies, thoughts, consciousness, emotions - with the energies of the universe and to make these greater energies available to humanity. The natural tendency of quartz is for harmony, and is recognized as a "Stone of Power". Stimulates brain function & power, aids clarity of mind. Dispels negativity in ones energy field and environment, aligns all chakras, a very powerful healer.Quartz is the symbol or patience, perseverance and the infinity of space.Quartz crystal is considered the "healing stone" of all spiritual matters.WHITE absorbs all the rays and is therefore cooling and restful.Matching Stones, Mother of Pearl, Fresh Water Pearl, Crystal and Rock QuartzWear Quartz Crystal Jewelry for Clarity.Quartz - coloredPineapple Quartz, Pink Quartz, Aqua Quartz and Turquoise Quartz are all synthetic stones.Quartz- RoseThe Meaning of Rose Quartz:Emits a calming, cooling energy which can work on all chakras to gently remove negativity and to reinstate the loving, gentle forces of self love. Good to wear in a chaotic or crisis situation. It is "the stone of gentle love" bringing peace and calm to relationships. It can be used for spiritual attunement to the energy of love. It is a rejuvenating agent for both physical body and the emotions. It is an excellent energy for healing emotional "wounds". An excellent stone to give to express friendship.Your marriage can have more sparkle and fire when you keep a rose quartz under your pillow.Rose quartz is known as the love stone. It helps the user feel a strong sense of self-worth, therefore being worth love. Rose quartz is the stone of universal love. It is also the stone of love in marriage. When worn in jewelry the wearer feels a sense of self-worth.Wear Rose Quartz Jewelry for Love.Quartz - SmokyThe Meaning of Smoky Quartz:It can be used to gently dissolve negative energies and emotional blockages. It can be used to initiate a powerful force field which will absorb many forms of negativity, both from within ones self and from other forces. It promotes personal pride and joy in living. Smoky quartz has been used to regulate creativity in business, and to encourage astute-ness in purchasing. It works to diffuse communication deficiencies and to dissolve mental and emotional blockages which limit perception and learning.BROWN is the color of the soil and fertility.Wear Brown Quartz Jewelry to absorb Negativity.Rainbow ObsidianMesmerizing rainbow obsidian beads are sparkling smooth with a rich, polished finish. The dark black color of Rainbow Obsidian is mixed with hues of greens and grays that enhance the overall image.RhodochrositeCleanses the subconscious and allows access to higher thoughts. This stone is also known to be useful in treating the thyroid gland. Helps the body to cleanse and remove toxins. Creates emotional balance and assists one in increasing feelings of self-worth and self-esteem. Useful in situations of emotional and physical abuse, it allows the victim to get in touch with feeling deserving of honor and respect.SodaliteSometimes referred to as the stone of endurance, this stone helps you to be grounded and focused before beginning any task. It assists one in following through to completion of tasks and goals with ease. Known to sometimes strengthen the thyroid glands and assists the body in efficient metabolism. It has been used to treat a nervous stomach. Can also assist in allowing clear communication. It opens one to support and self-esteem building situations while promoting a sense of openness and self confidence in one’s choices.related words: birtstoneshttp://www.e-jewel.co.il/en/Site_Page_number.aspx?PageID=232。
revolve(v.) to go to a circle around a central point 旋转,环绕,转动nimble(adv.) able to move quickly and easily with light neat movements 敏捷的,灵活的protest(v.) to state very firmly that sth. is true,especially when other people do not believe you (尤指当别人不相信自己时)力言,声言,申明注:这里有insist的意思disdainful(adj.) showing that you do not respect sb or sth. and think that they are unimportant 鄙视的,轻视的,藐视的,不屑的somber(adj.) dark and without any bright colors 昏暗的,阴沉的,暗淡的overwhelm(v.) cover(sth./sb.) completely by flowing over or pouring down on it/him, submerge suddenly (以浇或灌的方式)淹没(某物或某人),使突然没入或浸入注:这里有受...影响的意思pungent(adj.) a strong and sharp taste or smell (味道、气味)强烈的,刺激性的,刺鼻的stately(adj.) impressive in style and size 堂皇的,雄伟的,高贵的arresting(adj.) catching the attention 引人注意的,显著的,有趣的profusion(n.) a supply or amount that is almost too large 大量,丰富,充沛fade away: 逐渐凋谢,慢慢减弱deprive...of: 剥夺,使丧失make a point of: 把...视为,说成必要的,认为某事重要(+doing) 重视做...,特别注意要...beat sth. down: to persuade sb. to reduce a price 使(某人)压低价钱,杀价rub shoulders with: meet and mix with(people) 与(人们)联系,交往Unit2spectacle(n.) a very impressive show or scene 奇观,壮观(壮丽)的景象agony(n.) very great mental or physical pain (精神上或肉体上的)极度痛苦preoccupation(n.) a matter which takes up an one's attention 令人全神贯注的事物gratitude(n.) the feeling of being grateful 感激(之情)victim(n.) sb. who has been attacked,robbed,or murdered 受害者,牺牲者moor(v.) hold(a ship,etc.)in place by cables or chains to the shore,or by anchors,etc. 系泊,锚泊facade(n.) the front of a building,part of a building facing a street,courtyard,etc. (房屋)正面,门面grin(v.) to smile widely 露着牙齿笑,咧着嘴笑martyred(adj.) a martyred look or expression is an unhappy one,as if you want to make other people feel sorry for you (好像为博取他人同情而显现的神色或表情)痛苦的,伤心的inhibited(adj.) not confident or relaxed enough to do or say what you want to 拘谨的,束手束脚的flash by: move very quickly in the specified direction 急速向某方向运动a good catch: ???linger on: ①(人)苟延残喘②(习俗)历久犹存sank in: ①(of liquids)go down into another substance,be absorbed (指液体)渗入,被吸收②(of words,etc.)be fully absorbed or understood,penetrate esp. gradually (指话语等)完全理解hang over: ①挂在...上,笼罩,突出于,俯临,盘旋于②逼近,威胁着③延期,搁置起来④(hang over from...)从...延续(遗留)下来注:这里应该是挂在....上underlying(adj.) the reason,cause etc. that is the most important,although it is not easily noticed 根本的理由/原因/目标accessible(adj.) that can be approached or entered,easy to approach or enter 能够接近的,能够进去的,易接近的inexorable(adj.) that can't be altered,checked,etc. 不可变的,不可抗拒的,无情的collide(v.) come into violent contact;strike violently against each other;crash 碰撞,猛撞,互撞controversial(adj.) of,subject to,or stirring up controversy;disbatable 争论的,引起争论的swarm(v.) to move in a large uncontrolled crowd 蜂拥,成群地移动(n.)a moving mass.crowd,or throng (移动的)大群,大堆condense(v.) if gas condenses or is condensed,it becomes a liquid as it becomes cooler (使)凝结,(使)冷凝contaminate(v.) to make a place or substance dirty and dangerous by adding sth. to it,for example chemicals or poison 把...弄脏,污染to influence sth. in a way that has a bad effect 毒害,使...变坏disrupt(v.) interrupt the orderly course of 扰乱,破坏assumption(n.) sth. that you think is true although you have no proof 假定,假设tear away: to suddenly start moving very quickly (突然迅速地)离开blot out: 把...遮住,遮盖,涂去,隐藏at stake: to be won or lost;being risked 在胜败关头,冒风险in turn: 反过来,挨个,依次,轮流的注:这里应该是“反过来”pick up: 捡起,拾起,中途搭(人),中途捎带(货物),获得,学会,好转,改进,增加(速度)注:这里应该是“增加(速度)”Unit4homely(adj.) unattractive or ugly people pr faces 相貌平平的,丑陋的totter(v.) be unsteady on one's feet,stagger 蹒跚而行overall(n.) 罩衫,工作服embrace(v.) to put your arms around sb. and hold them in a loving way (拥抱)某人underneath(prep.) directly under or below another object,used especially when one thing is covering or hiding another 在...下面,在...底下envelop(v.) to wrap sth. up or cover it completely 包住,覆盖soothe(v.) to make sb. feel calmer and less anxious,upset,or angry 抚慰,安慰,使平息to make a pain less severe 减轻,缓解(痛苦)trembling(n.) 发抖,战栗,震颤clutch(v.) to hold sth. or sb. tightly,especially because you are frightened,in pain,or don't want to lose sth. 紧握,紧抓portion(n.) a part of sth. larger,especially a part that is different from the other parts 一部分,一份(尤指与其他部分不同)sb's portion sth. that happens in your life that you can't avoid 某人的命运hang back: to be unwilling to speak or do sth. because you are shy 退缩,踌躇不前recompose oneself: restore to composure oneself 使自己恢复镇静fight off: 击退,竭力摆脱,克服run over: 跑过来,溢出,扼要复述,浏览,碾过注:这里应该是“跑过去”bring up: 养育,提起...,谈到steadfast(adj.) faithful and very loyal 忠实的,忠诚的divergence(n.) departure from a particular viewpoint,practice,etc. 偏离,背离,背驰slacken(v.) to gradually become slower,weaker,less active etc. or to make sth. do this (使)减慢,(使)迟缓,(使)减弱enlist(v.) to persuade sb. to help you 请求某人的帮助consult(v.) to ask for information or advice from sb. because it is their job to know about it (向专业人员)咨询,请教outrage(n.) a very cruel,violent,and shocking action or event 残忍的行径,暴行,令人震惊的事情brutish(adj.) showing no human intelligence or feeling 畜生似的,兽性的,没有人性的appetite(n.) a desire or liking for a particular activity 欲望,喜爱intervene(v.) come or be in between as sth. unnecessary or irrelevant;interpose 干涉,干预count on: rely on sb. or sth. with confidence 依靠,依赖,指望注:这里应该是“指望”be devoid of: 缺乏,完全没有strike down: 击倒,杀死,去除in vain: 徒然,枉然appeal to: 向...呼吁,恳求,诉诸,求助于... 注:这里应该是“向...呼吁”Unit6imperious(adj.) overbearing,arrogant,masteful,domineering 傲慢的,专横的,盛气凌人的complication(n.) a problem or situation that makes sth. more difficult to understand or deal with 使复杂化的情况(问题)incriminate(v.) to make sb. seem guilty of a crime 使(某人)显得有罪,连累,牵连concede(v.) to admit that sth. is true or correct although you wish it was not true (勉强地)承认)poise(n.) a calm,confident way of behaving,combined with an ability to control your feelings or reactions in difficult situations 镇定,自信,坦然自若,沉着wrathful(adj.) filled with wrath 愤怒的,激怒的inbred(adj.) innate or deeply instilled 天生的,生来的,先天的twig(v.) to suddenly realize sth. about a situation 突然明白incongruous(adj.) lacking harmony or agreement;incompatible 不和谐的,不调和不相容的,自相矛盾的encompass(v.) shut in all around;surround;encircle 围绕,环绕on the errand: 为了办一件差事get around to: to finally do sh. that you have been intending to do for some time 终于去做(一直打算做的事)adept at: 善于spring to one's feet: 跳起来,飞快的行动turn out: ①最后结果是,最终成为②关上(灯等)③驱逐,赶走Unit7hulking(adj.) large,heavy,and often unwieldly or clumsy 巨大的,庞大的,笨重的correspondent(n.) 报纸或电视台等的)通讯员,记者capricious(adj.)subject to caprices;tending to change abruptly and without apparent reason;inconstant 多变的,变幻莫测的intimidating(adj.) making you feel worried and less confident 令人紧张不安的ubiquitous(adj.) present,or seeming to be present,everywhere at the same time;omnipresent (似乎)同时普遍存在的,似乎无处不在的saunter(v.) walk about idly;stroll 闲逛,漫步portable(adj.) light and able to be carried or moved easily 手提式的,便携式的accrue(v.) come as a natural growth,advantage,or right (to) (常与to连用)(利益等)及到(某人);(权利等)归于(某人)propel(v.) push,drive,or impel onward,forward,or ahead 推动,推进,鼓励soporific(adj.) causing or tending to cause sleep;of or characterized by sleep or sleepiness 催眠的,致睡的,困倦的,酣睡的go astray: 走错路,误入歧途注:老师给出的意思中有“被偷或丢失”,“计划出错”take over: 接管,接手,接任in place: ???beyond the ken: 超出...视野之外Unit8levy???abuse???envision(v.) 想象,预见,展望negotiate(v.) to succeed in getting past or over a difficult place on a path,road,etc. 顺利通过unfulfilled(adj.) a wish,desire,hope,etc. that is unfulfilled has not been achieved 未实现的,未达到的proclaim(v.) to say publicly that sth. important is true or exists 宣布,声明tout(v.) to praise sth. or sb. in order to persuade people that they are important or worth a lot 赞扬,吹捧convergence(n.) 会聚,聚合,辐合clog???conceive(v.) to think of a new idea.plan, etc. and develop it in your mind 构想出,设想,想出beam sth. out: ???nail down: ①nail sth. down 将某物用钉子钉牢,确定某物②nail sb. down 使某人明确说出某人相信的事或要做的事keep tabs on: 记某人的账,监视某人(某物)bet on: 打赌cater to: 满足某种需要和要求。
托福阅读真题第309篇Transcendentalism(答案文章最后)TranscendentalismBeginning in the 1820s, a new intellectual movement known as transcendentalism began to grow in the Northeast. In this context, to transcend means to go beyond the ordinary sensory world to grasp personal insights and gain an appreciation of a deeper reality, and transcendentalists believed that all people could attain an understanding of the world that goes past rational, sensory experience. Transcendentalists were critical of mainstream American culture. They reacted against the age they lived in where people were encouraged to act the same as others and argued for greater individualism against conformity. European romanticism, a movement in literature and art that stressed emotion over cold, calculating reason, also influenced transcendentalists in the United States, especially the transcendentalists’ celebration of the uniqueness of individual feelings.Ralph Waldo Emerson emerged as the leading figure of this movement. Born in Boston in 1803, Emerson came from a religious family. His father served as a minister, and after graduating from Harvard Divinity School in the 1820s, Emerson followed in his father’s footsteps. However, afte r his wife died in 1831, he left the clergy. On a trip to Europe in 1832, he met leading figures of romanticism who rejected the cold, strict rationalism of popular 18th century Enlightenment thought, emphasizing emotion instead.When Emerson returned home the following year, he began giving lectures on his romanticism-influenced ideas. In 1836, hepublished “Nature,” an essay arguing that humans can find their true spirituality in nature, not in the everyday bustling working world of cities and industrial factories. In 1841, Emerson published his essay "Self-Reliance,” which urged readers to think for themselves and reject the mass conformity he believed had taken root in American life. Emerson expressed concern that a powerful majority could overpower the will of individuals.Emerson’s ideas struck a chord with a class of literate adults who also were dissatisfied with mainstream American life and searching for greater spiritual meaning. Many writers were drawn to transcendentalism, and they started to express its ideas through new stories, poems, essays, and articles. The ideas of transcendentalism were able to permeate American thought and culture through magazines, journals, and newspapers that were widely read.Among those attracted to Emerson’s ideas wa s his friend, Henry David Thoreau, whom he encouraged to write about his own ideas. Thoreau placed a special emphasis on the role of nature as a gateway to the transcendentalist goal of greater individualism. In 1848, Thoreau gave a lecture in which he argued that individuals must stand up to governmental injustice, a topic he chose because of his disgust over the Mexican-American War and slavery. In 1849, he published his lecture, “Civil Disobedience,” and urged readers to refuse to support a government that was immoral.Margaret Fuller also came to prominence as a leading transcendentalist and advocate for women’s equality. Fuller was a friend of Emerson and Thoreau, and other intellectuals of her day. Because she was a woman, she could not attend Harvard, as it was a male-only institution for undergraduate students until1973. However, she was later granted the use of the library there because of her towering intellect. In 1840, she beacame the editor of The Dial, a transcendentalist journal, and she later found employment as a book reviewer for the New York Tribune newspaper. Tragically, in 1850, she died at the age of forty in a shipwreck off Fire Island, New York.Some critics took issue with transcendentalism’s emphasis on individualism by pointing out the destructive consequences of compulsive human behavior. Herman Melville’s novel, Moby Dick, emphasized the problems with individual obsession by telling the tale of Captain Ahab’s single-minded quest to kill a white whale, Moby Dick, which had destroyed Ahab’s original ship and caused him to lose one of his legs. Edgar Allan Poe, a popular author, critic, and poet, decried “the so-called poetry of the so-called transcendentalists. ” These American writers who questioned transcendentalism illustrate the underlying tension between individualism and conformity in American life.Source: Corbett, S.P., Janssen, V., Lund, J.M., Pfannestiel, T., Waskiewicz, S., & Vickery, P. (2014).Reading Paragraph 1Beginning in the 1820s, a new intellectual movement known as transcendentalism began to grow in the Northeast. In this context, to transcend means to go beyond the ordinary sensory world to grasp personal insights and gain an appreciation of a deeper reality, and transcendentalists believed that all people could attain an understanding of the world that goes past rational, sensory experience. Transcendentalists were critical of mainstream American culture. They reacted against the age they lived in where people were encouraged to act the same as others and argued for greater individualism against conformity.European romanticism, a movement in literature and art that stressed emotion over cold, calculating reason, also influenced transcendentalists in the United States, especially the transcendentalists’ celebratio n of the uniqueness of individual feelings.1. According to paragraph 1, what did transcendentalists do?a. They overreacted towards those who acted the same as everyone elseb. They protested the government for greater nonconformityc. They celebrated individualism and nonconformityd. They wrote articles in favor of a more rational cultureReading Paragraph 2Ralph Waldo Emerson emerged as the leading figure of this movement. Born in Boston in 1803, Emerson came from a religious family. His father served as a minister, and after graduating from Harvard Divinity School in the 1820s, Emerson followed in his father’s footsteps. However, after his wife died in 1831, he left the clergy. On a trip to Europe in 1832, he met leading figures of romanticism who rejected the cold, strict rationalism of popular 18th century Enlightenment thought, emphasizing emotion instead.2. Which of the following is NOT true about Ralph Waldo Emerson?a. He was one of the leaders of the transcendentalism movementb. Like his father, he served as a ministerc. He went to Europe after his wife had passed awayd. He met critics of romanticism while visiting EuropeReading Paragraph 3When Emerson returned home the following year, he begangiving lectures on his romanticism-influenced ideas. In 1836, he published “Nature,” an essay arguing that humans can find their true spirituality in nature, not in the everyday bustling working world of cities and industrial factories. In 1841, Emerson published his essay, “Self-Reliance,” which urged readers to think for themselves and reject the mass conformity he believed had taken rootin American life. Emerson expressed concern thata powerful majority could overpower the will of individuals.3. Why does the author say “his romanticism-influencedi deas”?a. To show that his ideas were romantic in natureb. To explain why he published his essays “Nature” and “Self-Reliance”c. To show that his beliefs were inspired by the romanticists he metd. To prove that his ideas came from other sources4. The phrase taken root in paragraph 3 is closest in meaning toa. Become abandonedb. Been establishedc. Been examinedd. Been discoveredReading Paragraph 5Among those attracted to Emerson’s ideas was his friend, Henry David Thoreau, whom he encouraged to write about his own ideas. Thoreau placed a special emphasis on the role of nature as a gateway to the transcendentalist goal of greater individualism. In 1848, Thoreau gave a lecture in which he argued that individuals must stand up to governmental injustice, a topic he chose because of his disgust over the Mexican-American Warand slavery. In 1849, he published his lecture, “Civil Disobedience,” and urged readers to refuse to support a government that was immoral.5. Which of the following is true, according to paragraph five?a. Henry David Thoreau believed that nature could help people achieve more individualismb. Henry David Thoreau was Emerson’s closest friend and had similar ideasc. Emerson suggested that Henry David Thoreau should start giving lecturesd. Thoreau organized groups that protested the injustices of governmentsReading Paragraph 6Margaret Fuller also came to prominence as a leading transcendentalist and advocate for women’s equality. Fuller was a friend of Emerson and Thoreau, and other intellectuals of her day. Because she was a woman, she could not attend Harvard, as it was a male-only institution for undergraduate students until 1973. However, she was later granted the use of the library there because of her towering intellect. In 1840, she became the editor of The Dial, a transcendentalist journal, and she later found employment as a book reviewer for the New York Tribune newspaper. Tragically, in 1850, she died at the age of forty in a shipwreck off Fire Island, New York.6. All of the following are true EXCEPTa. Margaret Fuller did research in the library at Harvardb. Harvard University remained an all-male school until the 20th-centuryc. Margaret Fuller was a transcendentalist and supported the equality of womend. Margaret Fuller met Emerson and Thoreau while studying at HarvardReading Paragraph 6Margaret Fuller also came to prominence as a leading transcendentalist and advocate for women’s equality. Fuller was a friend of Emerson and Thoreau, and other intellectuals of her day. Because she was a woman, she could not attend Harvard, as it was a male-only institution for undergraduate students until 1973. However, she was later granted the use of the library there because of her towering intellect. In 1840, she became the editor of The Dial, a transcendentalist journal, and she later found employment as a book reviewer for the New York Tribune newspaper. Tragically, in 1850, she died at the age of forty in a shipwreck off Fire Island, New York.7. What can be inferred about Margaret Fuller from the information in paragraph six? a. She was the most famous transcendentalist of her timeb. She attended Harvard University even though women were not allowed at that timec. She held positions that most women did not in her timed. She only reviewed books that were of interest to her while at the New York TribuneReading Paragraph 7Some critics took issue with transcendentalism’s emphasis on individualism by pointing out the destructive consequences of compulsive human behavior. Herman Mel ville’s novel, Moby Dick, emphasized the problems with individual obsession by telling the tale of Captain Ahab’s single-minded quest to kill a white whale, Moby Dick, which had destroyed Ahab’s original ship and caused him to lose one of his legs. Edgar Allan Poe, apopular author, critic, and poet, decried “the so-called poetry of the so-called transcendentalists". These American writers who questioned transcendentalism illustrate the underlying tension between individualism and conformity in American life.8. Which of the following best expresses the essential information in the highlighted sentence in paragraph 7? Incorrect choices change the meaning in important ways or leave out essential information.a. Herman Melville wrote a novel called Moby Dick and the main character is Captain Ahabb. The story of Captain Ahab’s quest to kill a white whale is titled Moby Dickc. After learning about transcendentalism, Herman Melville decided to write a book criticizing itd. Herman Melville’s book, Moby Dick, was inspired by the issues surrounding the obsession with individualism9. Look at the four squares (A, B, C, D) that indicate where the following sentence could be added to the passage.However, as with all major movements, transcendentalists faced criticism for their beliefs. Where would the sentence best fit?A Some critics took issue with transcendentalism’s emphasis on individualism by pointing out the destructive consequences of compulsive human behavior.B Herman Melville’s novel, Moby Dick, emphasized the problems with individual obsession by telling the tale of Captain Ahab’s single-minded quest to kill a white whale, Moby Dick, which had destroyed Ahab’s original ship and caused him to lose one of his legs.C Edgar Allan Poe, a popular author, critic, and poet, decried “the so-called poetry of the so-calledtranscendentalists". D These American writers who questioned transcendentalism illustrate the underlying tension between individualism and conformity in American life.10. DIRECTIONS: An introductory sentence for a brief summary of the passage is provided below. Complete the summary by selecting the THREE answer choices that express the most important ideas in the passage. Some sentences do not belong in the summary because they express ideas that are not presented in the passage or are minor ideas in the passage. This question is worth 2 points.Transcendentalism was an intellectual movement in which prominent thinkers sought greater levels of individualism and spirituality.a. Ralph Waldo Emerson encouraged members of society to be more individualisticb. Herman Melville’s book, Moby Dick, subtly criticizes the transcendentalist beliefsc. Emerson was friends with other transcendentalists like Henry David Thoreau and Margaret Fullerd. Margaret Fuller could not attend Harvard because she was a womane. Some transcendentalist subscribers warned of the problems with mass conformityf. American transcendentalist ideas were influenced by European romanticism。
染整专业英语第二版课文翻译第二单元Hi, my name is Marry Fielding and I guess you could say that I am "one ina million". In other words, there are not many people like me. You see, I have a muscle disease which makes me very weak, so I can't run or climb stairs as quickly as other people. In addition, sometimes I am very clumsy and dropthings or bump into furniture. Unfortunately, the doctors don't know how to make me better, but I am very outgoing and have learned to adapt to my disability. My motto is: live One day at a time.Until I was ten years old I was the same as everyone else. I used to climb trees, swim and play football. In fact, I used to dream about playing professional football and possibly representing my country in the World Cup. Then I started to get weaker and weaker, until I could only enjoy footballfrom a bench at the stadium. In the end I went into hospital for medical tests.I stayed there for nearly three months. I think I had at least a billion tests, including one in which they cut out a piece of muscle from my leg and lookedat it under a microscope. Even after all that, no one could give my disease a name and it is difficult to know what the future holds.One problem is that I don't look any different from other people. So sometimes some children in my primary school would laugh, when I got out of breath after running a short way or had to stop and rest halfway up the stairs. Sometimes, too, I was too weak to go to school so my education suffered. Every time I returned after an absence, I felt stupid because I was behind the others.My life is a lot easier at high school because my fellow students have accepted me. The few who cannot see the real person inside my body do not make me annoyed, and I just ignore them. All in all I have a good life. I am happyto have found many things I can do, like writing and computer programming. My ambition is to work for a firm that develops computer software when I grow up. Last year invented a computer football game and a big company has decided to buy it from me. I have a very busy life with no time to sit around feelingsorry for myself. As well as going to the movies and football matches with my friends, I spend a lot of time with my pets. I have two rabbits, a parrot, a tank full of fish and a tortoise. To look after my pets properly takes a lotof time but I find it worthwhile. I also have to do a lot of work, especiallyif I have been away for a while.In many ways my disability has helped me grow stronger psychologically and become more independent. I have to work hard to live a normal life but it has been worth it. If I had a chance to say one thing to healthy children, it would be this: having a disability does not mean your life is not satisfying. So don't feel sorry for the disabled or make fun of them, and don't ignore them either. Just accept them for who they are, and give them encouragement to live as rich and full a life as you do.Thank you for reading my story.Unit 1马丁的故事嗨,我的名字就是马丁。
Unite 3 Doctor’s Dilemma: Treat or Let Die?Abigail Trafford1. Medical advances in wonder drugs, daring surgical procedures, radiation therapies, and intensive-care units have brought new life to thousands of people. Yet to many of them, modern medicine has become a double-edged sword.2. Doctor’s power to treat with an array of space-age techniques has outstripped the body’s capacity to heal. More medical problems can be treated, but for many patients, there is little hope of recovery. Even the fundamental distinction between life and death has been blurred.3. Many Americans are caught in medical limbo, as was the South Korean boxer Duk Koo Kim, who was kept alive by artificial means after he had been knocked unconscious in a fight and his brain ceased to function. With the permission of his family, doctors in Las Vegas disconnected the life-support machines and death quickly followed.4. In the wake of technology’s advances in medicine, a heated debate is taking place in hospitals and nursing homes across the country --- over whether survival or quality of life is the paramount goal of medicine.5. “It gets down to what medicine is all about, ” says Daniel Callahan, director of the Institute of Society, Ethics, and the Life Sciences in Hastings-on-Hudson, New York. “Is it really to save a life? Or is the larger goal the welfare of the patient?”6. Doctors, patients, relatives, and often the courts are being forced to make hard choices in medicine. Most often it is at the two extremes of life that these difficultyethical questions arise --- at the beginning for the very sick newborn and at the end for the dying patient.7. The dilemma posed by modern medical technology has created the growing new discipline or bioethics. Many of the country’s 127 medical s chools now offer courses in medical ethics, a field virtually ignored only a decade ago. Many hospitals have chaplains, philosophers, psychiatrists, and social workers on the staff to help patients make crucial decisions, and one in twenty institutions has a special ethics committee to resolve difficult cases.Death and Dying8. Of all the patients in intensive-care units who are at risk of dying, some 20 percent present difficult ethical choices --- whether to keep trying to save the life or to pull back and let the patient die. In many units, decisions regarding life-sustaining care are made about three times a week.9. Even the definition of death has been changed. Now that the heart-lung machine can take over the functions of breathing and pumping blood, death no longer always comes with the patient’s “last gasp” or when the heart stops beating. Thirty-one states and the District of Columbia have passed brain-death statutes that identify death as when the whole brain ceases to function.10. More than a do zen states recognize “living wills” in which the patients leave instructions to doctors not to prolong life by feeding them intravenously or by other methods if their illness becomes hopeless. A survey of California doctors showed that 20 to 30 percent were following instructions of such wills. Meanwhile, the hospicemovement, which its emphasis on providing comfort --- not cure --- to the dying patient, has gained momentum in many areas.11. Despite progress in society’s understanding of death and dying, t heory issues remain. Example: A woman, 87, afflicted by the nervous-system disorder of Parkinson’s disease, has a massive stroke and is found unconscious by her family. Their choices are to put her in a nursing home until she dies or to send her to a medical center for diagnosis and possible treatment. The family opts for a teaching hospital in New York city. Tests show the woman’s stroke resulted from a blood clot that is curable with surgery. After the operation, she says to her family: “Why did you bring me back to this agony?” Her health continues to worsen, and two years later she dies.12. On the other hand, doctors say prognosis is often uncertain and that patients, just because they are old and disabled, should not be denied life-saving therapy. Ethicists also fear that under the guise of medical decision not to treat certain patients, death may become too easy, pushing the country toward the acceptance of euthanasia.13. For some people, the agony of watching high-technology dying is too great. Earlier this year, Woodrow Wilson Collums, a retired dairyman from Poteet, Texas, was put on probation for the mercy killing of his older brother Jim, who lay hopeless in his bed at a nursing home, a victim of severe senility resul ting from Alzheimer’s disease. After the killing, the victim’s widow said: “I think God, Jim’s out of his misery. I hate to think it had to be done the way it was done, but I understand it. ”Crisis in Newborn Care14. At the other end of the life span, technology has so revolutionized newborn carethat it is no longer clear when human life is viable outside the womb. Newborn care has got huge progress, so it is absolutely clear that human being can survive independently outside the womb. Twenty-five years ago, infants weighting less than three and one-half pounds rarely survived. The current survival rate is 70 percent, and doctors are “salvaging” some babies that weigh only one and one-half pounds. Tremendous progress has been made in treating birth deformities such as spina bifida. Just ten years ago, only 5 percent of infants with transposition of the great arteries --- the congenital heart defect most commonly found in newborns --- survived. Today, 50 percent live.15. Yet, for many infants who owe their lives to new medical advances, survival has come at a price. A significant number emerge with permanent physical and mental handicaps.16. “The question of treatment and nontreatment of seriously ill newborns is not a single one,”says Thomas Murray of the Hastings Center. “But I feel strongly that retardation or the fact that someone is going to be less than perfect is not good grounds for allowing an infant to die.”17. For many parents, however, the experience of having a sick newborn becomes a lingering nightmare. Two years ago, an Atlanta mother gave birth to a baby suffering from Down’s Syndrome, a form of mental retardation; the child also had blocked intestines. The doctors rejected the parents’ plea not to operate, and today the child, severely retarded, still suffers intestinal problems.18. “Every time Melanie has a bowel movement, she cries,” explains her mother.“She’s not able to take care of herself, and we won’t live forever. I wanted to save her from sorrow, pain, and suffering. I don’t understand the emphasis on life at all costs, and I’m very angry at the doctors and the hospital. Who will take care of Melanie after we’re gone? Where will you doctors be then?”Changing Standards19. The choices posed by modern technology have profoundly changed the practice of medicine. Until now, most doctors have been activists, trained to use all the tools in their medical arsenals to treat disease. The current trend is toward nontreatment as doctors grapple with questions not just of who should get care but when to take therapy away.20. Always in the background is the threat of legal action. In August, two California doctors were charged with murdering a comatose patient by allegedly disconnecting the respirator and cutting off food and water. In 1981, a Massachusetts nurse was charged with murdering a cancer patient with massive doses of morphine but was subsequently acquitted.21. Between lawsuits, government regulations, and patients’ rights, many doctors feel they are under siege. Modern technology actually has limited their ability to make choices. More recently, these actions are resolved by committees.Public Policy22. In recent years, the debate on medical ethics has moved to the level of national policy. “It’s just beginning to hit us that we don’t have unlimited resources,” says Washington Hospital Center’s Dr. Lynch. “You can’t talk about ethics without talkingethics without talking about money.”23. Since 1972. Americans have enjoyed unlimited access to a taxpayer-supported, kidney dialysis program that offers life-prolonging therapy to all patients with kidney failure. To a number of police analysts, the program has grown out of control --- to a $1.4billion operation supporting 61,000 patients. The majority are over 50, and about a quarter have other illness, such as cancer or heart disease, conditions that could exclude them from dialysis in other countries.24. Some hospitals are pulling back from certain lifesaving treatment. Massachusetts General Hospital, for example, has decided not perform heart transplants on the ground that the high costs of providing such surgery help too few patients. Burn units --- through extremely effective --- also provide very expensive therapy for very few patients.25. As medical scientists push back the frontiers of therapy, the moral dilemma will continue to grow for doctors and patients alike, making the choice of to treat the basic question in modern medicine.1. 在特效药、风险性手术进程、放疗法以及特护病房方面的医学进展已为数千人带来新生。
A BAR AT THE FOLIES女神游乐场的酒吧间(Un bar auxfolies)A One of the most critically renowned paintings of the19th-century modernist movement is the French painter Edouard Manet's masterwork,A Bar at the Folies.Originally belonging to the composer Emmanuel Chabrier, it is now in the possession of The Courtauld Gallery in London,where it has also become a favourite with the crowds.《女神游乐场的酒吧间》是法国画家爱德华·马奈极为重要,最具声誉的作品之一,创作于19世纪现代主义运动期间。
原本被作曲家埃马纽埃尔·夏布里埃所收藏,如今馆藏于伦敦考陶尔德画廊,深受参观者的喜爱。
B The painting is set late at night in a nineteenth-century Parisian nightclub.A barmaid stands alone behind her bar,fitted out in a black bodice that has a frilly white neckline,and with a spray of flowers sitting across her décolletage.She rests her hands on the bar and gazes out forlornly at a point just below the viewer,not quite making eye contact.Also on the bar are some bottles of liquor and a bowl of oranges, but much of the activity in the room takes place in the reflection of a mirror behind the barmaid.Through this mirror we see an auditorium, bustling with blurred figures and faces:men in top hats,a woman examining the scene below her through binoculars,another in long gloves,even the feet of a trapeze artist demonstrating acrobatic feats above his adoring crowd.In the foreground of the reflection a man with a thick moustache is talking with the barmaid.画中的场景发生在19世纪巴黎的一间酒吧里。
whitelie英文作文Title: The Nuances of White Lies。
White lies, those innocuous fibs we tell to spare feelings or avoid awkwardness, are often viewed as harmless. Yet, delving deeper reveals complexities that challengetheir seemingly benign nature. In this essay, we will explore the intricacies of white lies, examining their implications on relationships, ethics, and societal norms.Firstly, let us dissect the fabric of relationships woven with white lies. At the outset, they may seem like small acts of kindness, smoothing interactions and maintaining harmony. However, beneath this facade lies a potential erosion of trust. When honesty takes a backseatto convenience, the foundation of trust weakens, leaving relationships vulnerable to cracks of suspicion and resentment. Furthermore, reliance on white lies to navigate interpersonal dynamics can hinder genuine communication, stifling authenticity and intimacy. In essence, while whitelies may offer temporary reprieve, they pose a long-term threat to the integrity of relationships.Ethically, the terrain of white lies is fraught with moral ambiguity. Advocates argue that they serve a greater good, shielding individuals from unnecessary pain or embarrassment. Yet, this utilitarian approach raises pertinent questions about the slippery slope of moral relativism. Where do we draw the line between benevolent deception and manipulation? Is it justifiable to sacrifice truth on the altar of expediency? These ethical quandaries underscore the need for a nuanced approach to navigating the moral maze of white lies. Perhaps, a balance between empathy and integrity can offer a guiding compass in determining when, if ever, white lies are ethically permissible.Moreover, white lies are not merely confined to interpersonal interactions but extend their reach into the fabric of societal norms. From the polite "I'm fine" in response to "How are you?" to embellished resumes in pursuit of professional success, society often sanctionswhite lies as social lubricants. Yet, this normalization perpetuates a culture of deceit, where authenticity becomes a casualty of conformity. As individuals, we must interrogate the underlying assumptions that underpin the prevalence of white lies in our social tapestry. Are we sacrificing honesty at the altar of social acceptance? And at what cost?In conclusion, the landscape of white lies is far from monochromatic; rather, it is painted with shades of moral ambiguity and relational intricacies. While they may offer temporary solace, their long-term implications on trust, ethics, and societal norms cannot be overlooked. As we navigate the labyrinth of human interactions, let us tread cautiously, mindful of the delicate balance between kindness and honesty, for therein lies the true essence of integrity.。
White matter integrity as an intermediate phenotype:Exploratorygenome-wide association analysis in individuals at high risk ofbipolar disorderEmma Sprooten a,n,Kathryn M.Fleming a,Pippa A.Thomson b,Mark E.Bastin c,Heather C.Whalley a, Jeremy Hall a,Jess E.Sussmann a,James McKirdy a,Douglas Blackwood a,b,Stephen wrie a, Andrew M.McIntosh aa Division of Psychiatry,University of Edinburgh,Kennedy Tower,Royal Edinburgh Hospital,Morningside Park,Edinburgh EH105HF,UKb Molecular Medicine Centre,University of Edinburgh,Edinburgh,UKc Brain Research Imaging Centre,University of Edinburgh,Edinburgh,UKa r t i c l e i n f oArticle history:Received6April2012Received in revised form14August2012Accepted1November2012Keywords:EndophenotypeQuantitative phenotypePsychiatric geneticsDiffusion tensor imagingFractional anisotropyPathway analysisa b s t r a c tWhite matter integrity,as measured using diffusion tensor imaging(DTI),is reduced in individuals withbipolar disorder(BD),their unaffected relatives and carriers of specific risk-alleles.Fractionalanisotropy(FA),an index of white matter integrity,is highly heritable but the genetic architecture ofthis trait has received little investigation.In this study we performed a genome-wide association studywith FA as quantitative phenotype,in unaffected relatives of patients with BD(N¼70)and a matchedcontrol group(N¼80).Amongst our top results were SNPs located in genes involved in cell adhesion,white matter development and neuronal plasticity.Pathway analysis of the top associated polymorph-isms and genes confirmed the enrichment of processes relevant to BD and white matter development,including axon guidance,ErbB-signalling neurotrophin signalling,phosphatidylinositol signalling,andcell adhesion.The majority of genes implicated in these pathways were differentially associated withFA in individuals at high familial risk,suggesting interactions with genetic background or environ-mental factors secondary to familial risk for BD.Although the presentfindings require independentreplication,the results encourage the use of global FA as a quantitative phenotype in future large-scalestudies which may help to identify the biological processes underlying reduced FA in BD and otherpsychiatric disorders.&2012Elsevier Ireland Ltd.All rights reserved.1.IntroductionThe heritability of bipolar disorder(BD)has been estimated atapproximately80%(Gershon et al.,1982;McGuffin et al.,2003),and genetic linkage and association studies,including genome-wide association studies(GWAS),have now identified a few well-replicated risk-variants(Craddock and Sklar,2009;O’Donovanet al.,2009;Sklar et al.,2011).However,the substantial clinicaland genetic heterogeneity and lack of biological markers of BDhave led to slower progress than in other complex disorders inwhich the underlying disease biology is better understood(Manolio et al.,2008;Cichon et al.,2009).Endophenotypes aremarkers of genetic vulnerability to a disorder and have a geneticarchitecture that is in theory less complex than the clinicalsyndrome.As constructs that lie biologically intermediatebetween gene function and the clinical phenotype,endopheno-types can provide clues to disease pathology,and may aid in thediscovery of new genetic risk variants(Gottesman and Gould,2003;Glahn et al.,2007).The integrity of the brain’s white matter can be measuredin vivo using diffusion tensor imaging(DTI),an MRI techniquesensitive to the magnitude and directionality of water moleculedisplacement in human tissue.Fractional anisotropy(FA)is ascalar metric derived from the diffusion tensor with valuesbetween0and1that quantifies the degree to which waterdiffusion is anisotropic.In healthy white matter,water moleculesdiffuse preferentially along rather than across the mainfibredirection,resulting in anisotropic diffusion and evaluated valuesof FA.Conversely,in less healthy white matter with fewer intactcellular boundaries,water molecules diffuse more equally in alldirections,and FA falls in value.As such,FA reflects a combinationof axonal density,fibre packing and organisation,and myelinthickness,and is therefore assumed to be an approximation ofwhite matter integrity in general(Budde et al.,2007;CercignaniContents lists available at SciVerse ScienceDirectjournal homepage:/locate/psychresPsychiatry Research0165-1781/$-see front matter&2012Elsevier Ireland Ltd.All rights reserved./10.1016/j.psychres.2012.11.002n Corresponding author.Tel.:þ441315376502;fax:þ441315376531.E-mail address:e.sprooten@(E.Sprooten).Psychiatry Research](]]]])]]]–]]]et al.,2001;Gouw et al.,2008;MacDonald et al.,2007;Schmierer et al.,2007;Underwood et al.,2011).FA is reduced in patients with BD(Heng et al.,2010;Mahon et al.,2010;McIntosh et al.,2008b;Sexton et al.,2009;Sussmann et al.,2009)and these reductions are found independently of present mood state in euthymic,manic and depressed patients (Adler et al.,2006;Benedetti et al.,2011;Wang et al.,2008a, 2008b).Importantly,the heritability of FA is estimated between 50%and85%,depending on the brain region,with higher estimates for young people(Chiang et al.,2009,2011;Kochunov et al.,2010).Recently,we have also found subtle,but widespread, FA reductions in unaffected relatives of patients with BD.These reductions were inversely correlated with temperamental mood fluctuations previously associated with disease liability(Sprooten et al.,2011a).The abovefindings support white matter integrity, as measured by FA,as an endophenotype for BD according to the criteria of Gottesman and Gould(2003).In line with this endophenotypic quality,several risk variants in BD candidate genes have been associated with white matter integrity in healthy individuals(Konrad et al.,2009;McIntosh et al.2008a;Sprooten et al.,2009,2011b;Winterer et al.,2008; Zuliani et al.,2011).However,such a candidate gene approach is inherently biased because gene selection is generally inferred from prior biological knowledge or linkage studies.In contrast, GWAS allow for the unbiased investigation of the whole genome in association with a clinical phenotype or a quantitative heritable trait.Previous studies have successfully used hippocampal volume(Stein et al.,2012)or dorsolateral prefrontal brain activation(Potkin et al.,2009a,2009b)as quantitative traits, thereby discovering novel candidate risk-genes for psychiatric disorders.Recently,a genome-wide analysis of a global measure of FA was performed in the Lothian Birth Cohort1936,a large sample of ageing people(mean age¼73years),and two sugges-tive single-nucleotide polymorphisms(SNPs)including one in an ADAM-family gene,were identified(Lopez et al.,2012).In most GWAS,conservative genome-wide significance thresh-olds are applied in order to compensate for type-I error inflation resulting from simultaneously testing of hundreds of thousands of associations.However,significance levels of around10À7inevi-tably give rise to a large number of false negatives,especially if the phenotype has a polygenic origin.In BD,two recent studies have found that a multitude of risk-alleles with small effect size, at extremely liberal p-values(p o0.5,contribute substantially to the accuracy at which genetic variation can predict affection status of BD,whilst a model including only alleles of reasonably high significance(p o10À4)performed only at chance level (Evans et al.,2009;Purcell et al.,2009).Complimentary to considering markers at genome-wide significance levels,in path-way analysis less significant genetic variation is retained,and a large set of top SNPs are clustered according to their biological and molecular functions.This then allows the statistical testing of whether any relevant pathways are significantly over-represented (‘‘enriched’’)in the top-associated SNPs.This approach appears to more accurately capture the polygenic architecture of BD,while at the same time providing important information on the biological functions is likely affected by the associated genes.Furthermore, individuals with different clinical presentations can carry differ-ent risk-alleles to a disease,yet their downstream effects can converge onto the same molecular pathway and/or be measurable in the same endophenotype.Thus,the use of both pathways and endophenotypes in GWAS are likely to capture some of the genetic and clinical heterogeneity of complex disorders that can be missed when looking at individual alleles and behavioural phenotypes alone.Pathway analysis has previously been applied to case-control GWAS(Askland et al.,2009;O’Dushlaine et al., 2011;Torkamani et al.,2008),and more recently to cognitive (Luciano et al.,2011)and brain imaging phenotypes(Lopez et al., 2012;Meda et al.,2012).Here we performed a genome-wide association study using a global measure of white matter integrity as quantitative pheno-type,followed by pathway analyses of the top SNPs and genes. The phenotype,average FA across the centres of the brain’s white matter,was one we previously found to be significantly reduced in unaffected relatives of patients with BD(Sprooten et al., 2011a),while Kochunov et al.(2010)showed it is also highly heritable.We performed this analysis in a sample of healthy individuals,including participants at high genetic risk of BD.This design allowed us to test for main(i.e.additive)effects of SNPs on FA,as well as for SNP-by-risk interaction effects on FA.Main effects would be expected to identify genetic variants and molecular pathways involved in white matter development, plasticity and maintenance,while interaction effects,akin to a gene-by-diagnosis interaction as previously modelled in Potkin et al.(2009a),can identify SNPs whose associations to FA are modulated by familial risk and/or vulnerable genetic background.2.Methods2.1.SampleParticipants were recruited as part of the Bipolar Family Study, a sample of young individuals at high genetic risk(HR)for BD and demographically matched healthy controls(HC).Individuals were considered at HR if they had at least onefirst-degree,or two second degree,family members with bipolar I disorder.Partici-pants were excluded if they fulfilled SCID criteria for an axis-I mood or psychotic disorder,had a major neurological disorder, history of head injury,history of learning disability or metallic implants or other contraindications to MRI examination.For more details of participant recruitment and screening and demo-graphics,see Sprooten et al.(2011a)and Whalley et al.(2011). In this sample,a subset of150unrelated participants provided high quality DTI data and DNA for the generation of whole-genome data,including70HR(34male;mean age¼21.6years) and80HC(37male;mean age¼21.3years)subjects,all between the ages of16and26years at the time of recruitment.2.2.Scan acquisition and DTI processingDTI data were acquired and processed as previously described in Sprooten et al.(2011a).MRI data were collected on a GE Signa Horizon HDX1.5T clinical scanner equipped with a self-shielding gradient set(22mT/m maximum gradient strength)and manufacturer-supplied‘birdcage’quadrature head coil.Whole brain DTI data were acquired for each subject using a single-shot pulsed gradient spin-echo echo-planar imaging(EPI)sequence with diffusion gradients(b¼1000s/mm2)applied in64non-collinear directions,and seven T2-weighted EPI baseline(b¼0s/mm2)scans. Fifty-three2.5mm contiguous axial slices were acquired with a field-of-view of240Â240mm2,and an acquisition matrix of 96Â96(zero-filled to128Â128),giving an acquisition isotropic voxel size of 2.5mm.In addition,a T1-weighted volume was acquired with afield-of-view of240Â240mm2,an acquisition matrix of192Â192,and1801.2mm thick slices,giving a voxel dimension of1.25Â1.25Â1.20mm3.The sequence had an inver-sion time of500ms,an echo time of4ms,and aflip angle of81.The DTI data were converted to4D NIfTI volumes and pre-processed using standard tools available from FSL(http://www. /fsl).This included the following processes:correc-tion for eddy current induced distortions and bulk subject motion in the scanner by registering the diffusion weighed EPI volumes toE.Sprooten et al./Psychiatry Research](]]]])]]]–]]] 2thefirst T2-weighted EPI volume within each subject;brain extraction;and calculation of diffusion tensor characteristics including principal eigenvectors and FA values using DTIFIT.Tract-based spatial statistics(TBSS)was carried out according to standard FSL procedures(Smith et al.,2006;http://www.fmrib. /fsl).First,all subject’s FA volumes were linearly and non-linearly registered to a standard FA template available in the FSL package(‘‘FMRIB58_FA’’).Second,a mean of all registered FA volumes was calculated and a white matter‘‘skeleton’’was created.This was achieved by searching for the maximum FA values in directions perpendicular to the local tract direction in the mean FA map.A threshold of FA40.25was applied to the FA skeleton to exclude predominantly non-white matter voxels. Third,for each subject’s FA volume,at each point on the skeleton the maximum voxel perpendicular to the local skeleton direction was projected onto the skeleton.This results in one FA skeleton map per subject,assumed to contain anatomically corresponding centres of white matter structure.For each individual,the mean FA was extracted from the voxels within the skeleton.All the following analyses were performed using this skeleton-wide FA average as a quantitative phenotype for genome-wide regressions.2.3.Genotyping and genome-wide association of SNPsDNA was extracted from whole-blood samples and genotyped using the Human OmniExpress Illumina Array(http://www.illu /applications/gwas.ilmn),containing$730K tagging SNPs.Afterfiltering for call rate(495%),minor allele frequency (40.05)and deviation from Hardy–Weinberg equilibrium (40.001),565404SNPs remained to be included in the associa-tion analysis.There were no subjects who had more than5% missing genotypes.Genome-wide association analysis was per-formed using two quantitative linear models in PLINK(Purcell et al.,2007;/purcell/plink):(1)a ‘‘main model’’to test for main effect of SNPs on FA,but covarying for group effects;and(2)an‘‘interaction model’’,to test for group-by-SNP interaction effects on FA.Sex,age and thefirst four components resulting from multidimensional scaling(MDS)ana-lysis in PLINK,were also modelled in both regression analyses. Considering group-status and SNPs may be partly explaining overlapping variance in FA,a third exploratory regression(‘‘sim-ple model’’)was performed without group as a co-variate.2.4.Genome-wide association of genes(VEGAS)By chance alone,larger genes are more likely to contain SNPs with lower P-values.For this reason,gene-based p-values were calculated using Versatile Gene-based Association Study(VEGAS; .au/VEGAS;Liu et al.,2010).First,SNPs are allocated to genes according to the UCSC hg18database,750kb ().Second,gene-wide statistics were cal-culated by summing up all w2values within a gene(w2values are derived from the raw p-values).These observed gene-wide statistics were then compared to an empirical null-distribution obtained using simulations from the multivariate distribution. Importantly,the simulated null-distribution calculated by VEGAS not only accounts for gene size but also for the underlying linkage disequilibrium(LD)structure.Of note,the gene-corrected p-values were not genome-wide corrected,and were mainly calculated in order to correct for gene-size,which can otherwise significantly bias pathway analysis towards brain-related pro-cesses(Raychaudhuri et al.,2010).2.5.KEGG pathway analysisThe top1%SNPs(equivalent to5400SNPs,all p o0.01for both models)were tested for enrichment of the molecular pathways of the Kyoto Encyclopaedia of Genes and Genomes(KEGG)using WebGestalt(/webgestalt).This freely available programme compares the selected SNPs against the whole genome with a Hypergeometric test to assess the like-lihood that the observed number of SNPs would be involved in a KEGG pathway by mere chance.One statistic is calculated for each pathway,and all reported p-values are adjusted for the number of pathways tested using false discovery rate correction (Benjamini and Hochberg,1995).The minimum number of genes per process was set at2.KEGG pathway enrichment analyses were performed for each top SNP set resulting from the two PLINK association analyses.The top1%SNPs for each model mapped to approximately 1000genes.The SNP-enrichment results were thus cross-validated with gene-enrichment results,entering the top1000 genes resulting from VEGAS(all p o0.057)into WebGestalt,using the same parameters as in the SNP-based pathway analysis.3.Results3.1.Top SNP resultsQ–Q plots of the SNP p-values for each model showed that the results followed a normal distribution,with a tendency for smaller than expected p-values in the upper tail(Fig.1).Genomic inflation factors were equal to or close to1(l main¼1.0; l interation¼1.02;prior to MDS-component correction),indicating Fig.1.QQ-plots of results for main(SNP)and interaction(SNPÂGroup)models.E.Sprooten et al./Psychiatry Research](]]]])]]]–]]]3the absence of population stratification and other systematic biases to significance inflation.No markers reached the current genome-wide significance threshold at p o 5Â10À8.The top 10SNP results for each model are listed in Tables 1and 2.With respect to the main model,several top markers in association with FA were located in introns in ADAM 7,EPS 15L 1,AK 127888,and CRBN .Two SNPs in the main model’s top 10were intergenic but within 10kb of genes SAP 30L ,HAND 1,TMEM 239,and C 20orf 141.As shown in Table 1,most top markers in the main model were associated with FA in both HR and HC subjects separately,except for the SNPs in AK 127888(all in almost perfect LD).Indeed,these SNPs in AK 127888were also marginally sig-nificant for the group-by-SNP interaction (p o 0.02),and their effect in the main model was clearly driven by the HR participants.Results for the ‘‘simple model’’without group as a covariate did not increase statistical power,with very similar p -values (Supplemen-tary Fig.1)and eight out of the 10top SNPs being identical between the two models.In the interaction model,all top SNPs were significantly asso-ciated with FA within each group,but in opposite directions of effect.Several of the top SNPs were located in or near genes with functions related to cell-adhesion,namely LPP,HEPACAM,HEPN 1,and ROBO 4.In addition,two SNPs mapped to an intron in a gene encoding a calcium/calmodulin protein kinase (CAMK 2D),and another was located near the highly brain-expressed transcription regulator,WDR 5.3.2.Pathway analysisTable 3shows a selection of relevant significant KEGG categories resulting from the top 1%SNP and the top 1000genes analyses in WebGestalt.The top enriched pathway for the main model was arrhythmogenic right ventricular cardiomyopathy (p ¼8.55Â10À9),followed by axon guidance (p ¼4.73Â10À8).For the interaction model,the MAPK signalling pathway was most significantly enriched (p ¼3.05Â10À10).Almost all relevant KEGG categories significantly enriched in the main model were more significant in the interaction model,including axon guidance,cell adhesion molecules (CAMs),focal adhesion,calcium signalling,tight junction,long-term potentiation,the phosphatidylinositol (PI)system,and Wnt signalling.ErbB signalling was significantly enriched for the interaction model only.All of these pathways,apart from calcium signalling,replicated in the gene-based analysis,indicating that their enrichment was not merely driven by gene-size or LD structure.Neurotrophin signalling was the only pathway that seemed more powerful in the gene-based than in the SNP-based analysis,indicat-ing that different independent SNPs within genes were responsible for this signal.For a complete list of significant pathways (p o 0.05)along with the genes contributing to their enrichment,see Supple-mentary Tables 2and 3.The results of pathway analysis for top SNPs in the ‘‘simple model’’were very similar to the results of the main model,and all pathways in Table 3remained similarly significant when not co-varying for group.Table 1Top markers resulting from the main model.Location SNP Gene aSNP function MAF P ALLP HCP HR8p21rs11781622ADAM7Intron 0.14 3.48E-0060.00480.003119p13rs875622EPS15L1Intron 0.19 4.06E-006 6.60E-0040.00997p22rs6977940CARD11,GNA12Intergenic 0.11 4.54E-0060.0277 2.88E-00418q12b rs4800279AK127888Intron 0.06 5.42E-0060.3154 6.00E-0063p26rs1669338CRBN Intron 0.17 5.98E-006 1.43E-0050.00382p25rs2598592450kbIntergenic 0.39 6.85E-0069.18E-0040.001520p13rs7360412TMEM239,C20orf141Intergenic 0.067.49E-0060.0404c5q33rs17116175SAP30L,HAND1Intergenic 0.10 1.08E-0050.0286 4.21E-0045p15rs11133604Fam173B Intron 0.49 1.09E-0050.00230.003716q23rs11647294VAT1LIntron0.331.10E-0050.00950.0012Top markers resulting from the main model,and annotated genes (within 10kb).MAF =minor allele frequency;P HC and P HR :P -values in controls and high-risk samples separately.a Genes are annotated if SNP lies within 50kb of the gene.b Multiple loci in perfect LD:includes rs1940989and rs8085344at same p -values.cSNP failed frequency criterion in this sample.Table 2Top markers resulting from the interaction model.Location SNP Gene aSNP function MAF P ALLP HCP HRb HC3q13rs488628450kbIntergenic 0.21 6.33E-0070.0249 1.28E-005þ3p14rs1036797MIR548A2,ADAMTS9-AS2Intron 0.26 2.09E-0060.0091 4.32E-004þ4q26rs1880529CAMK2D Intron 0.43 3.86E-0060.00120.0020À3q28rs1975991LPPIntron 0.32 6.40E-0060.0127 2.45E-004À2p25rs17491951AK095310Intron 0.38 6.78E-006 3.40E-0040.0022þ1p21rs6689305AGL,FRRS1Intergenic 0.198.56E-0060.00160.0011þ9q34rs4292757WDR5Intergenic 0.06 1.18E-0050.0133bþ11q24rs12222810CCDC15,HEPACAM,HEPN1,ROBO4Intergenic 0.12 1.55E-005 2.38E-0040.0327À4q21rs7659891LOC339966Intergenic 0.08 1.67E-0050.0887bþ4p15rs12503381450kbIntergenic0.071.70E-0050.00490.0066þTop markers resulting from the main model,and annotated genes (within 10kb).MAF =minor allele frequency;P HC and P HR :P -values in controls and high-risk samples separately.The sign of the standardised b in HC is listed in the last column,which was invariably opposite to the b in HR.a Genes are annotated if SNP lies within 50kb of the gene.bSNP failed frequency criterion in this sample.E.Sprooten et al./Psychiatry Research ](]]]])]]]–]]]4The calcium pathway did not replicate in the gene-based analysis in either of the models.This pathway contains a high proportion of large genes,with a mean number of SNPs per gene around60,compared to about nine for the whole genome in our un-imputed dataset.Naturally,the top SNP results are biased towards larger genes,whereas if there is any bias in the top gene analysis it would be greater statistical penalty to SNPs in larger genes.In our dataset,genes with VEGAS gene-wide p values o0.01were significantly smaller than non-significant genes (Mann–Whitney U¼1,491,964,p¼0.009).Using raw SNP p-values biases the results in the other direction,since genes containing a SNP with a p-value o0.005were on average nearly twice as large as those not containing a p-value below0.005(U¼16,942,397, p o10À16).4.DiscussionWhite matter integrity is highly heritable(Chiang et al.,2009, 2011;Kochunov et al.,2010),reduced in BD patients and their unaffected relatives(Chaddock et al.,2009;McIntosh et al.,2008b; Mun˜oz Maniega et al.,2008;Sussmann et al.,2009;Sprooten et al., 2011a),and associated with several risk-genes for BD(Konrad et al., 2009;McIntosh et al.,2008a;Sprooten et al.,2009,2011b;Winterer et al.,2008;Zuliani et al.,2011).Together,thesefindings indicate that white matter integrity,as measured by DTI,could be a potent endophenotype of BD.Here,we implemented this knowledge, by using average FA across the TBSS skeleton as a quantitative phenotype in a genome-wide association analysis in unaffected relatives of BD and a matched control sample.4.1.Single SNPsCell adhesion,cell growth and calcium signalling were com-mon functions of genes containing the top SNPs from both main and interaction models.One top SNP in the main model was located in EPS15L1,an EPS15homologue which is involved in epidermal growth factor receptor signalling.Although EPS15L1 function in the brain specifically is poorly characterised,it is highly brain expressed,and its calcium-binding property suggests it contributes to activity dependent neuronal growth and survival. ADAM7,also supported by the main model,encodes an ADAM-family member,a group of proteins that interact with epidermal growth factors(Seals and Courtneidge,2003),although they are better known as cell adhesion proteins(Reiss and Saftig,2009). Of note,the one other GWAS conducted on a global measure of FA in the elderly also reported a suggestive association with a SNP in an ADAM-family gene,namely ADAMTS18(Lopez et al.,2012). Thefinding that ADAM-family genes appeared in the top‘‘hits’’in association with FA in two demographically different(but Scottish) samples is quite remarkable and supports cell adhesion as a path-way of interest in the genetics of white matter integrity.Also related to cell-adhesion is LPP,which encodes a shuttle protein,and plays a role in cell proliferation,differentiation and migration,presumably through its interactions with the Wnt signalling pathway (Grunewald et al.,2009).Better known for its role in white matter, however,is HEPACAM,a gene encoding the adhesion protein GlialCAM,which is predominantly located in axons and myelin, and mutations in this gene have been associated with macroence-phaly,autism and mental retardation(Lo´pez-Herna´ndez et al., 2011).Equally relevant to white matter is ROBO4,which,as a ROBO-family member,is critical for axon guidance and angiogenesis during embryonic development(Couch and Condron,2002).Two genes in the top-SNP results are closely involved with calcium signalling in the brain:CRBN and CAMK2D.CRBN,or cereblon,controls the density and number of calcium-dependent potassium channels on the neuronal surface,thereby influencing the excitability of neurons(Chang and Stewart,2011).CRBN mutations in humans are linked to mental retardation,and CRBN knock-out mice exhibit selective memory impairment (Rajadhyaksha et al.,2012).CAMK2D encodes a multifunctional calcium/calmodulin-dependent protein kinase,which are essen-tial mediators of long-term potentiation and are thus important in neuronal plasiticity and learning.Although all genes in our top results are brain-expressed to some extent,some of their functions are poorly characterised or too general to warrant more in depth interpretation in this context.In general,these top SNP results are presented as an illustration of what was obtained with the current genome-wide association method,but of course in the absence of independent replication and genome-wide significance,they should be inter-preted with extreme caution.Nevertheless,as explained above,a few of these genes are consistent with prominent roles in brain development and plasticity,including at least two(HEPACAM and ROBO4)with particular relevance to white matter.4.2.PathwaysSimple SNP associations resulting from GWAS require very con-servative significance thresholds in order to accommodate the type-I error resulting from testing hundreds of thousands of SNPs at the same time.Pathway analysis provides a complimentary approach to address the contribution of many,modestly associated SNPs acrossTable3Relevant pathways significantly enriched for top SNP and top gene results.KEGG pathway P-value(BH adj)for SNP enrichment P-value(BH adj)for gene enrichmentAxon guidanceMain 4.73E-080.0216Interaction7.60E-080.0405MAPK signalling pathwayMain 3.87E-060.006Interaction 3.05E-100.0003Calcium signalling pathwayMain 4.00E-06ÀInteraction 2.09E-08ÀRegulation of actin cytoskeletonMain 1.36E-050.004Interaction 1.92E-060.0014Cell adhesion molecules(CAMs)Main 2.71E-05ÀInteraction 1.32E-050.0459Tight junctionMain9.76E-05ÀInteraction 1.27E-070.0009Focal adhesionMain 2.00E-040.0307Interaction8.78E-090.005Long-term potentiationMain 2.58E-02ÀInteraction 6.86E-050.0348Phosphatidylinositol signalling systemMain 3.39E-020.0466Interaction 4.19E-060.0047Wnt signalling pathwayMain 3.87E-020.0386Interaction 1.63E-02ÀErbB signalling pathwayMainÀÀInteraction7.98E-050.0026Neurotrophin signalling pathwayMainÀ0.0391Interaction 1.90E-030.0017E.Sprooten et al./Psychiatry Research](]]]])]]]–]]]5。