1Barcoding With the MS-3

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水体中硝酸盐对纳米铁降解五氯酚的影响

ISSN 100020054CN 1122223/N 清华大学学报(自然科学版)J Tsinghua Univ (Sci &Tech ),2010年第50卷第6期2010,Vol.50,No.617/368772880水体中硝酸盐对纳米铁降解五氯酚的影响程　荣1,　戚道铎2,　董伟娜2,　王建龙1(1.清华大学核能与新能源技术研究院,北京100084;2.北京工业大学环境与能源工程学院,北京100124)收稿日期:2009205231基金项目:国家自然科学基金资助项目(50325824)作者简介:程荣(1981—),女(汉),湖北,博士后。

E 2mail :chengrong99@mails.t 通讯作者:王建龙,教授,E 2mail :wangjl @t 摘　要:五氯酚是一种需要优先控制的高毒性污染物。

该文以自制的纳米铁为原料,考察了硝酸盐对纳米铁降解五氯酚的影响。

采用化学还原法制备了纳米铁,测定了不同浓度硝酸盐存在时五氯酚及氯离子的浓度变化情况,分析了五氯酚的降解产物及纳米铁的转化产物。

结果表明:当五氯酚初始浓度为0.1mmol/L 时,硝酸盐浓度低于1mmol/L 时无明显影响;硝酸盐浓度达到2mmol/L 时,五氯酚的降解受到明显抑制;硝酸盐浓度≥3mmol/L 时,五氯酚的降解几乎被停止。

硝酸盐影响五氯酚的脱氯过程,硝酸盐存在时五氯酚更易产生氧化产物。

但有无硝酸盐存在时,纳米铁均转化为Fe 2O 3/Fe 3O 4和FeOO H 。

关键词:纳米铁;五氯酚;硝酸盐;脱氯;降解中图分类号:X 703.1文献标识码:A文章编号:100020054(2010)0620877204E ffect of nitrate on degradation of pentachlorophenol in w ater with ironnanoparticlesCHE NG Rong 1,QI Daoduo 2,DONG Weina 2,WANG Jianlong 1(1.Institute of Nuclear and N e w E nergy T echnology ,Tsinghu a U niversity ,B eijing 100084,China ;2.College of E nvironmental and E nergy E ngineering ,B eijing U niversity of T echnology ,B eijing 100124,China)Abstract :Pentachlorophenol (PCP )is a highly toxic pollutant.The effect of nitrate on t he degradation of PCP by iron nanoparticles synt hesized was investigated using t he chemical reductive met hod.The concentrations of PCP and chloride in solutions wit h different concentrations of nitrate were measured during t he treat ment process.The intermediate and final product s from t he PCP and iron nanoparticles were also analyzed.The result s show t hat when t heinitial concentration of PCP is 0.1mmol ・L -1,NO -3at ≤1mmol ・L -1does not affect t he degradation of PCP.NO -3at 2mmol ・L -1slows t he PCP dechlorination and NO -3at ≥3mmol ・L -1stops t hePCP dechlorination.The oxidized intermediates were more likely wit hNO -3.The iron nanoparticles are transformed toFe 2O 3/Fe 3O 4and FeOO H wit h and not wit h NO -3.K ey w ords :iron nanoparticles ;pentachlorophenol (PCP );nitrate ;dechlorination ;degradation五氯酚(pentachlorop henol ,PCP )是一种难降解有机物,其大量使用,造成了世界范围内的水体和土壤污染[1]。

DNA Barcoding

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What is barcoding? Take the mitochondrial cytochrome c oxidase subunit I (COI，细胞色素c氧化酶亚基1) for example：
Usually 648 base pairs long Conserved regions——usual basis for design of conserved PCR (polymerase chain reaction) primers Marked divergence(明显不同) between genetic distance within marine species
Likelihood-ratio test (LRT) Markov Chain Monte Carlo (MCMC) methods
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How does barcoding work?
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Methodology—present and future High-Throughput Sequencing and Environmental Barcoding
DNA Barcoding & Marine Biodiversity
What is barcoding?
DNA barcoding(条形码) is the derivation of short DNA sequence(s) that enables species identiﬁcation, recognition, and discovery in a particular domain of life.
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Why DNA Barcoding?
DNA barcodes are useful tools to accelerate species-level analysis of marine biodiversity and to facilitate conservation efforts:

年全国医学博士英语统考真题及参考答案

年全国医学博⼠英语统考真题及参考答案2010年全国医学博⼠外语统⼀考试英语试卷答题须知1.请考⽣⾸先将⾃⼰的姓名、所在考点、准考证号在标准答题卡上认真填写清楚，并按“考场指令”要求，在标准答题卡上，将准考证号相应的位置涂好。

2.试卷⼀（paper one）和试卷⼆（paper two）答案都做在标准答题卡上，书⾯表达⼀定要⽤⿊⾊签字笔或钢笔写在标准答题卡上指定区域，不要做在试卷上。

3.试卷⼀答题答题时必须使⽤2B铅笔，将所选答案按要求在相应位置涂⿊；如要更正，先⽤橡⽪擦⼲净。

4.标准答题卡不可折叠，同时必须保持平整⼲净，以利评分。

5.听⼒考试只放⼀遍录⾳，每道题后有15秒左右的答题时间。

Paper OnePart I Listening comprehension(30%)Section ADirections: In this section you will hear fifteen short conversions between two speakers. At the end of each conversion, you will hear a question about what is said. The question willbe read only once. After you hear the question, read the four possible answers markedA, B, C and D. Choose the best answer and mark the letter of your choice on theANSWER SHEET.Listen to the following example.You will hear:Woman: I feel faint.Man: No wonder. You haven’t had a bite all day.Question: What’s the matter with the womanYou will read:A. She is sick.B. She was bitten by an ant.C. She is hungry.D. She spilled her paint.Here C is the right answer.Sample AnswerADNow let’s begin with question Number 1.1. A. She’s looking for a gift.B. She needs a new purse.C. She’s going to give a birthday party.D. She wants to go shopping with her mom.2. A. She hears noises in her ears day and night.B. She has been overworking for a long time.C. Her right ear, hurt in an accident, is troubling her.D. Her ear rings are giving her trouble day and night.3. A. He’ll go to see Mr. White at 10:30 tomorrow.B. He’d like to make an earlier appointment.C. He’d like to cancel the appointment.D. He’d like to see another dentist.4. A. 8:00 B. 8:15 C. 8:40 D. 8:455. A. In a hotel. B. At a fast food bar.C. In the supermarket.D. In the department store.6. A. To resign right away.B.To work one more day as chairman.C.To think twice before he make the decision.D.To receive further training upon his resignation.7. A. She didn’t do anything in particular.B.She send a wounded person to the ER.C.She had to work in the ER.D.She went skiing.8. A. A customs officer. B. The man’s mother.C. A school headmaster.D. An immigration officer.9. A. It feels as if the room is going around.B.It feels like a kind of unsteadiness.C.It feels as if she is falling down.D.It feels as if she is going around.10. A. John has hidden something in the tree.B.John himself should be blamed.C.John has a dog that barks a lot.D.John is unlucky.11. A. The chemistry homework is difficult.B.The chemistry homework is fun.C.The math homework is difficult.D.The math homework is fun.12. A. His backache. B. His broken leg.C. His skin problem.D. His eye condition.13. A. Whooping cough, smallpox and measles.B.Whooping cough, chickenpox and measles.C.Whooping cough, smallpox and German measles.D.Whooping cough, chickenpox and German measles.14. A. Saturday morning. B. Saturday night.C. Saturday afternoon.D. Next weekend.15. A. He’s lost his notebook.B.His handwriting is messy.C.He’ll miss class latter this week.D.He cannot make it for his appointment.Section BDirections: In this section you will hear one conversion and two passages, after each of which, you will hear five questions. After each question, read the four possible answers marked A,B, C and D. Choose the best answer and mark the letter of your choice on theANSWER SHEET.Conversation16. A. He is having a physical checkup.B.He has just undergone an operation.C.He has just recovered from an illness.D.He will be discharged from the hospital this afternoon.17. A. He got an infection in the lungs.B.He had his gallbladder inflamed.C.He was suffering from influenza.D.He had developed a big kidney tone.18. A. A lot better. B. Terribly awful.C. Couldn’t be better.D. Okay, but a bit weak.19. A. To be confined to a wheelchair.B.To stay indoors for a complete recovery.C.To stay in bed and drink a lot of water.D.To move about and enjoy the sunshine.20. A. From 4 pm to 6 pm. B. From 5 pm to 7 pm.C. From 6 pm to 8 pm.D. From 7 pm to 9 pm.Passage One21. A. The link between weight loss and sleep deprivation.B.The link between weight gain and sleep deprivation.C.The link between weight loss and physical exercise.D.The link between weight gain and physical exercise.22. A. More than 68,000. B. More than 60,800.C. More than 60,080.D. More than 60,008.23. A. Sever-hour sleepers gained more weight over time than 5-hour ones.B.Five-hour sleepers gained more weight over time than 7-hour ones.C.Short-sleepers were 15% more likely to become obese.D.Short-sleepers consumed fewer calories than long sleepers.24. A. Overeating among the sleep-deprived.B.Little exercise among the sleep-deprived.C.Lower metabolic rate resulting from less sleep.D.Higher metabolic rate resulting from less sleep.25. A. Exercise every day. B. Take diet pills.C. Go on a diet.D. Sleep more.Passage Two26. A. She is too hard on me.B.She asks too many questions.C.She is always considerate of my feelings.D.She is the meanest mother in the neighborhood.27. A. A university instructor. B. A teaching assistant.C. A phD student.D. A psychiatrist.28. A. They usually say no.B.They usually say yes.C.They usually wait and see.D.They usually refuse to say anything.29. A. They are overconfident.B.Their brains grow too fast.C.They are psychologically dependent.D.Their brains are still immature in some areas.30. A. Be easy on your teen.B.Try to be mean to your teen.C.Say no to your teen when necessary.D.Don’t care about your teen’s feelings.Part II Vocabulary (10%)Section ADirections: In this section all the statements are incomplete, beneath each of which are four words or phrases marked A, B, C and D. Choose the word or phrase that can bestcomplete the statement and mark the letter of your choice on the ANSWERSHEET.31. A number of black youths have complained of being by the police.A. harassedB. distractedC. sentencedD. released32. He rapidly became with his own power in the team.A. irrigatedB. irradiatedC. streetlightD. torchlight33. Throughout his political career he has always been in the .A. twilightB. spotlightC. streetlightD. torchlight34. We that diet is related to most types of cancer but we don’t have definite proof.A. suspendB. superveneC. superviseD. suspect35. A patient who is dying of incurable cancer of the throat is in terrible pain, which can nolonger be satisfactorily .A. alleviatedB. abolishedC. demolishedD. diminished36. The television station is supported by from foundations and other sources.A. donationsB. pensionsC. advertisementsD. accounts37. More legislation is needed to protect the property rights of the patent.A. integrativeB. intellectualC. intelligent38. Officials are supposed to themselves to the welfare and health of the generalpublic.A. adaptB. confineC. commitD. assess39. You should stop your condition and do something about it.A. drawing onB. touching onC. leaning onD. dwelling on40. The author of the book has shown his remarkably keen into human nature.A. perspectiveB. dimensionC. insightD. reflectionSection BDirections: In this section each of the following sentences has a word or phrase underlined, beneath which are four words or phrase. Choose the word or phrase which canbest keep the meaning of the original sentence if it is substituted for theunderlined part. Then mark the letter of your choice on the ANSWER SHEET.41.The chemical was found to be detrimental to human health.A. toxicB. immuneC. sensitiveD. allergic42.It will be a devastating blow for the patient, if the clinic closes.A. permanentB. desperateC. destructiveD. sudden43.He kept telling us about his operation in the most graphic detail.A. verifiableB. explicitC. preciseD. ambiguous44.The difficult case tested the ingenuity of even the most skillful physician.A. credibilityB. commitmentC. honestyD. talent45.He left immediately on the pretext that he had to catch a train.A. claimB. clueC. excuseD. talent46.The nurse was filled with remorse of not believing her .A. anguishB. regretC. apologyD. grief47.The doctor tried to find a tactful way of telling her the truth.A. delicateB. communicativeC. skillfulD. considerate48.Whether a person likes a routine office job or not depends largely on temperament.A. dispositionB. qualificationC. temptationD. endorsement49.The doctor ruled out Friday’s surgery for the patient’s unexpected complications.A. confirmedB. facilitatedC. postponedD. cancelled50.It is not easy to remain tranquil when events suddenly change your life.A. cautiousB. motionlessC. calmD. alertPart III Cloze(10%)Directions: In this section there is a passage with ten numbered blanks. For each blank, there are four choice marked A, B, C and D listed on the right side. Choose the best answer andmark the letter of your choice on the ANSWER SHEET.Experts say about 1% of young women in the United States are almost starving themselves today. They are suffering from a sickness called anorexia.These young women have an abnormal fear of getting fat. They 51 starve themselves so they weigh at 15% less than their normal weight.The National Institute of Mental Health says one 52 ten cases of anorexia leads to serious medical problems. These patients can die from heart failure or the disease can lead young women to 53 themselves. For example, former gymnast Christy Henrich died at age 22. She weighed only61 pounds.A person with anorexia first develops joint and muscle problems. There is a lack of iron in the blood. 54 the sickness progresses, a young woman’s breathing, heartbeat, and blood pressure rates slow down. The important substance calcium is 55 from the bones, something causing bones to break. Sometimes the brain gets smaller, causing changes in 56 a person thinks and acts. Scientists say many patients have further mental and emotional problems. They have 57 opinions about themselves. They feel helpless. Their attempts to become extremely thin may 58 efforts to take control of their lives. They may become dependent on illegal drugs. Some people also feel the need to continually repeat a(n) 59 . For example, they may repeatedly wash their hands although their hands are clean.Anorexia is a serious eating 60 .If it is not treated on time, it can be fatal.51. A. specifically B. purposely C. particularly D. passionately52. A. from B. of C. at D. in53. A. kill B. starve C. abuse D. worsen54. A. When B. While C. As D. Since55. A. lost B. derived C. generated D. synthesized56. A. what B. why C. how D. which57. A. good B. high C. lower D. poor58. A. represent B. make C. present D. exert59. A. medication B. illusion C. motion D. action60. A. habit B. behavior C. disorder D. patternPart IV Reading Comprehension(30%)Direction:In this part there are six passages, each of which is followed by five questions. For each question there are four possible answers marked A, B, C and D. Choose the bestanswer and mark the letter of your choice on the ANSWER SHEET.Passage OneChildren should avoid using mobile phones for all but essential calls because of possible health effects on young brains. This is one of the expected conclusions of an official government report to be published this week. The report is expected to call for the mobile phone industry to refrain from promoting phone use by children, and to start labeling phones with data on the amount of radiation they emit.The Independent Expert Group on Mobile Phones, chaired by former government chief scientist William Stewart, has spent eight months reviewing existing scientific evidence on all aspects of the health effects of using mobile phones. Its report is believed to conclude that because we don’t fully understand the nonthermal effects of radiation on human tissue, the government should adopt a precautionary approach, particularly in relation to children.There is currently no evidence that mobile phones harm users or people living near transmitter masts. But some studies show that cell-phones operating at radiation levels within current safety limits do have some sort of biological effect on the brain.John Tattersall, a researcher on the health effects of radiation at the Defense Evaluation and Research Agency’s site at Porton Down, agrees that it might be wise to limit phone use by children. “If you have a developing nervous system, it’s known to be more susceptible to environmental insults,” he says,“So if phones did prove to be hazardous——which they haven’t yet ——it would be sensible.”In 1998, Tattersall showed that radiation levels similar to those emitted by mobile phones could alter signals from brain cells in slices of rat brain, “What we’ve found is an effect, but we don’t know if it’s hazardous,” he says.Alan Preece of the University of Bristol, who found last year that microwaves increase reaction times in test subjects, agreed that children’s exposure would be greater. “There’s a lot less tissue in the way, and the skill is thinner, so children’s heads are considerably closer,” he says.Stewart’s report is likely to recommend that the current British safety standards on energy emissions from cell-phones should be cut to the level recommended by the International Commission on Non-Ionizing Radiation Protection, which is one-fifth of the current British limit. “The extra safety factor of five is somewhat arbitrary,” says Michael Clark of th e National Radiological Protection Board. “But we accept that it’s difficult for the UK to have different standards from an international body.”61. Just because it has not been confirmed yet whether mobile phone emissions can harm humantissue, according to the government report, does not mean that .A. the government should prohibit children from using cell-phonesB. we should put down the phone for the sake of safetyC. the industry can have a right to promote phone useD. children are safe using cell-phones62. Tattersall argues that it is wise to refrain mobile phone use by children in termsof .A. their neural developmentB. their ill-designed cell-phonesC. the frequency of their irrational useD. their ignorance of its possible health effects63. On the issue in question, Preece .A. does not agree with TattersallB. tries to remove the obstacles in the wayC. asks for further investigationD. would stand by Stewart64. What is worrisome at present is that the UK .A. is going to turn deaf ears to the voice of Stesart’s planB. finds it difficult to cut the current safety standards on phone useC. maintains different standards on safety limit from the international onesD. does not even impose safety limit on the mobile phones’ energy emissions65．Which of the following can bi the best candidate for the title of the passageA . Brain Wave B. For Adults OnlyC. Catch Them YoungD. The Answer in the AirPassage TwoAdvances in cosmetic dentistry and plastic surgery have made it possible to correct facial birth defects, repair damaged teeth and tissue, and prevent or greatly delay the onset of tooth decay and gum disease. As a result, more people smile more often and more openly today than ever in the past, and we can expect more smiles in the future.Evidence of the smile’s ascent may be seen in famous paintings in museums and galleries throughout the world. The vast majority of prosperous bigwigs(要⼈),voluptuous nudes, ormiddle-class family members in formal portraits and domestic scenes appear to have their mouths firmly closed. Soldiers in battle, children at play, beggars, old people, and especially villains may have their mouths open; but their smiles are seldom attractive, and more often suggest strain or violence than joy.Smiles convey a wide range of meanings in different eras and cultures, says art historian Angus Trumble, currently curator(馆长)of Yale University’s Center for British Art, in his book A Brief History of the Smile. Compare, for instance, the varying impressions made by the shy dimples(酒窝)of Leonardo’s Mona Lisa; the rosy-cheeked, mustachioed Laughing Cavalier of Frans Hals; and the”Smiley Face”logo perfected(though not invented)in 1963 by American graphic artist Harvey .In some non-Western cultures, Trumble notes, even a warm, open smile does not necessarily indicate pleasure or agreement. It can simply be a polite mask to cover emotions considered too rude or shocking to bi openly displayed.Subtle differences in muscle movement can convey enormous differences in emotion, from the tranquility of bronze Buddhas, to the erotic bliss of couples entwined in stone on Hindu temples, to the fierce smirk(假笑)of a guardian demon at the entrance to a Chinese tomb.Trumble expects the impact of Western medicine and mass media to further increase the pressure on people to grin broadly and laugh openly in public.”Faint smiles are increasingly thought of in scientific and psychological circles as something that falls short of the true smile ,”and therefore suggest insincerity or lack of enthusiasm, he says.With tattooing, boby piercing, and permanent cosmetics already well established as fashion trends, one can imagine tomorrow’s beauty shops adding plastic surgeons and dentists to their staffs. These comer-store cosmeticians would offer style makeovers to reshape our lips, teeth, and jawlines to mimic the signature smile of one’s favorite celebrity.What can you say to that except” Have a nice day”66. Had it not been for cosmetic advances, as inferred from the passage, .A . people would not have been as happy as they are todayB. the rate of facial birth defect would not have declinedC . there would not have been many more open smilesD. we would not have seen smiling faces in public67. According to the passage, it seems that whether there is a smile or not in the portraits orpictures is decided by .A. one’s internal sense of the external worldB . one’s identity or social positionC . one’s times of existenceD . All of the above68. Trumble’s study on smiles shows that .A. an open smile can serve as a cover-upB . the famous portraits radiate varying smilesC. even the human muscles can arouse varying emotionsD. smiles can represent misinterpretations of different eras and cultures69. What Trumble expects to see is .A. the increasing tendency of broad grins and open smiles in publicB . further impact of Western medicine upon non-Western culturesC. a wider range of meanings to be conveyed by smilesD. more of sincerity and enthusiasm in public70 . At the end of the passage, the author implicates .A. a fortune to come with cosmetic advancesB . an identical smile for everybobyC . future changes in life styleD . the future of smilesPassage ThreeAdolf Hitler survived an assassination attempt in 1944 with the lamp of penicillin made by the Allies, a microbiologist in the UK claims. If the Nazi leader had died from bacterial infection of his many wounds, the Second World War might have been over a year earlier, saving millions of lives, says Milton Wainwright of the University of Sheffield, a noted historian of microbiology.In a paper to be published soon in Perspectives in Biology and Medicine, Wainwright reveals first-hand evidence that Hitler was treated with penicillin by his personal doctor, Theo Morrell, following an assassination attempt in which a bomb in a suitcase exploded next to Hitler’s desk. Hitler was badly hurt, fleeing the scene with his hair and trousers on fire, a badly bleeding arm and countless wooden splinter wounds from the oak table that probably saved his life.Wainwright found confirmation that Morrell gave Hitler antibiotics as a precaution in a recent translation of Morrell’s own diary. “I happened to be reading it for interest when the word penicillin jumped out at me,” he says. He then set about trying to establish where Morrell might have got the drug.At the time, penicillin was available only to the Allies. German and Czechoslovakian teams had tried without much success to make it, Wainwright says, but the small quantities that were available were weak and impure. “It’s g enerally accepted that it was no good,” says Wainwright.He reasons that Morrell would only have risked giving Hitler penicillin to prevent infections if he were confident that the antibiotic would cure, not kill the German premier. “My research shows that Morrell, in a very dodgy(危险的) position as Hitler’s doctor, would only have used pure stuff.” And the only reliable penicillin was that made by the Allies. So where did Morrell get itWainwright’s investigations revealed that Allied airmen carried penicillin, so the Germans may have confiscated some from prisoners of war. The other more likely source is from neutral countries such Spain, which received penicillin from Allied countries for humanitarian purposes, perhaps for treating sick children.“I have proof the Allies were sending it to these countries,” says Wainwright. “I’m saying this would have got through in diplomatic bags, reaching Hitler’s doctor and the higher echelons(阶层)of the Nazi party. So this was almost certainly pure, Allied penicillin.”“We can never be certain it saved Hitler’s life,” says Wainwright. But he notes that one of Hitler’s henchmen(死党)，Reinhard Heydrich, died from blood poisoning after surviving acar-bomb assassination attempt. “Hair from his seat went into his wounds and gave him septicemia,” says Wainwright. Morrell may have been anxious to ensure that Hitler avoided the same fate.71. According to Wainwright, Adolf Hitler .A. might have used biological weapons in the warB. could not have committed suicide as confirmedC. could have died of bacterial infectionD. might have survived a bacterial plague72. Following his assassination in 1944, Adolf Hitler .A. began to exercise precautions against his personal attacksB. was anxious to have penicillin developed in his countryC. received an jinjection of penicillin for blood poisoningD. was suspected of being likely to get infected73. As Wainwright reasons, H itler’s personal doctor .A. cannot have dared to prescribe German-made penicillin to himB. need not have used pure antibiotic for his suspect infectionC. would have had every reason to assassinate himD. must have tried to produce penicillin74. Wainwright implies that the Third Reich .A. met the fate of collapse as expectedB. butchered millions of lives on the earthC. was severely struck by bacterial plaguesD. did have channels to obtain pure penicillin75.Which of the following can be the best title for the passageA.How Hitler Manage to Survive Assassination AttemptsB.Morrell Loyal to His German PrimierC.Hitler Saved by Allied DrugsD.Penicillin Abused in GermanPassage FourGet ready for a new kind of machine at your local gym: one that doesn’t involve huffing and puffing as you burn off calories. Instead, all you have to do is stand still for 30 seconds while the machine measures your body fat. It could then tell you exactly where you could do with losing a few pounds and even advise you on exercises for your problem areas. If the body fat scanner turns out to be accurate enough, its makers hope it could one day help doctors spot disease.The scanner works by simultaneously building up an accurate 3D image of the body, while measuring the body’s effect on an electromagnetic field. Combining the two measurements allows the researchers to work out the distribution of fat and water within. Neither method is new on itsown, says Henri Tapp, at the Institute of Food Research in Norwich in the UK. “The smart thing is that we’ve put them in one machine.”And it’s not just for gym users. The body fat scanner could be used to study fat deposition as children develop, while patients recover from injury, or during pregnancy. And since it uses radio waves rather than X-rays, Tapp’s device is safe to use repeatedly.Body shape is known to be a risk indicator for heart disease and diabetes. So accurately quantifying fat distribution could help doctors suggest preventive measures to patients before problems arise. At the moment, doctors estimate fat content from knowing body volume and water content. To a good approximation, says Tapp, anything that isn’t fat is water. The amount of water in the body is often measured by giving the subject a drink of water that contains a radioactive tracer. The level of tracer in the patient's urine after three hours reveals the total water volume.To find out a body’s volume, subjects are weighed while totally submerged in water, and this is subtracted from their normal weight to give the weight of water displaced, and hence the subject’s volume. But it is scarcely practical for seriously ill people.There are other ways to directly measure body fat, such as passing a minuscule current between the wrists and feet. The overall fat content can then be estimated from the body’s resistance. But this method doesn’t take body shape into account ——so a subject with particularly skinny legs might register a higher fat content than the true value. That’s because skinny legs—with a lower cross-sectional area——will present higher resistance to current. So the machine thinks the water content of the body is lower——rating the subject as fatter. Also, the system can only give an overall measurement of fat.Tapp’s method uses similar calculations, but is more sophisticated because it tells you where you are piling on the pounds.76. The new machine is designed .A. to picture the body’s hidden fatB. to identify those at risk for obesityC. to help clinically treat specific casesD. to measure accurately risky obesity-related effects77. The beauty of the device, according to Tapp, is that .A. it performs a dual functionB. it is of great accuracy in measurementC. it has significant implications in clinical practiceD. it contributes to the evolution of human anatomy78.Which of the following, according to the passage, does the machine have the potential tospareA. A minuscule current.B. A radioactive tracer.C. A water tank.D. All of the above.79.In comparison with the techniques mentioned in the passage, the body fat scanner .A. quickens the pace of the patient’s rehabilitationB. is highly appreciated for its safetyC. features its measuring precisionD. is easy to operate in the clinic80.For scanning, all the subject has to do is .A. take up a form of workout in the gymB. turn round the body fat scannerC. lie on the electromagnetic fieldD. sand in the systemPassage FiveThere is currently abroad a new wave of appreciation for breadth of knowledge. Curricula at universalities and colleges and programs in federal agencies extol(赞扬) the virtues of a broad education. For scientists who work in specialized jobs, it is a pleasure to escape in our spare time to read broadly in fields distant from our own. Some of us have made interdisciplinary study our occupation, which is no surprise, because much of the intellectual action in our society today lies at the interfaces between traditional disciplines. Environmental science is a good example, because it frequently requires us to be conversant in several different sciences and even some unscientific fields.Experiencing this breadth of knowledge is stimulating, but so is delving deeply into a subject. Both are wonderful experiences that are complementary practical and aesthetic(美学的)ways. They are like viewing the marvelous sculpture of knowledge in two different ways. Look at the sculpture from one perspective and you see the piece in its entirety, how its components connect to give it form, balance, and symmetry. From another viewpoint you see its detail, depth, and mass. There is no need to choose between these two perspectives in art. To do so would subtract from the totality of the figure.So it is with science. Sometimes we gaze through a subject and are reluctant to stop for too much detail. As chemists, we are fascinated by computer sciences or molecular genetics, but not enough to become an expert. Or we may be interested in an analytical technique but not enough to stay at its cutting edge. At other times, we become immersed in the detail of a subject and see its beauty in an entirely different way than when we browse. It is as if we penetrate the surface of the sculpture and pass through the crystal structure to the molecular level where the code for the entire structure is revealed. Unfortunately, in our zeal for breadth or depth, we often feel that it is necessary to diminish the value of the other. Specialists are sometimes ridiculed with names such as “nerd”or “technocrats”, generalists are often criticized for being too “soft” or knowing too little about any one thing. Both are ludicrous(可笑的) accusations that deny a part of the reality of environmental science. Let us not be divided by our passion for depth or breadth. The beauty that awaits us on either route is too precious to stifle, too wonderful to diminish by bickering(争吵).81. From a broad education to interdisciplinary study, we can see .A. the integration of theory with practiceB. the enthusiasm for breadth of knowledgeC. the rapid division of traditional disciplinesD. the confrontation between specialists and generalists82. The commentator would say that the totality of the sculpture of knowledge .A. is mainly composed of two elementsB. presents two different points of viewC. cannot be perceived from one perspective。

生物医学英语试题及答案

生物医学英语试题及答案一、选择题（每题2分，共20分）1. Which of the following is the most common type of cancer in the world?A. Lung cancerB. Breast cancerC. Prostate cancerD. Colorectal cancer答案：A2. The term "pathogen" refers to:A. A substance that causes diseaseB. A person who has a diseaseC. An organism that causes diseaseD. A symptom of a disease答案：C3. What is the primary function of red blood cells?A. To carry oxygenB. To fight infectionsC. To clot bloodD. To regulate body temperature答案：A4. The nervous system is divided into two main parts: thecentral nervous system and the:A. Peripheral nervous systemB. Autonomic nervous systemC. Sympathetic nervous systemD. Parasympathetic nervous system答案：A5. Which of the following is a characteristic of a viral infection?A. Presence of bacteria in the bloodB. Inflammation of the heartC. Infection by a virusD. Infection by a fungus答案：C6. The hormone responsible for the regulation of blood sugar levels is:A. InsulinB. Thyroid hormoneC. CortisolD. Adrenaline答案：A7. What is the term for the process by which the body maintains a stable internal environment?A. HomeostasisB. MetabolismC. Circadian rhythmD. Immunity答案：A8. The largest organ in the human body is:A. The brainB. The liverC. The skinD. The heart答案：C9. Which of the following is a type of connective tissue?A. Muscle tissueB. Nervous tissueC. Epithelial tissueD. Cartilage答案：D10. The process of cell division that results in two identical cells is called:A. MitosisB. MeiosisC. ApoptosisD. Cytokinesis答案：A二、填空题（每空1分，共20分）1. The study of the structure of organisms is called__________.答案：anatomy2. The process by which cells extract energy from nutrients is known as __________.答案：metabolism3. The basic unit of heredity is the __________.答案：gene4. The medical specialty that deals with the diagnosis and treatment of diseases of the heart and blood vessels is called __________.答案：cardiology5. The hormone that stimulates the growth and development of bones and muscles is __________.答案：growth hormone6. The study of the causes and effects of diseases is called __________.答案：pathology7. The body's response to injury or infection is known as__________.答案：inflammation8. The process by which the body gets rid of waste products is called __________.答案：excretion9. The largest gland in the human body is the __________.答案：liver10. The study of the nervous system is called __________.答案：neurology三、简答题（每题10分，共20分）1. Explain the role of the immune system in defending the body against infections.答案：The immune system plays a crucial role in defending the body against infections by recognizing and eliminating harmful pathogens such as bacteria, viruses, and otherforeign substances. It consists of various cells, tissues, and organs that work together to protect the body. When a pathogen enters the body, the immune system responds by activating white blood cells and producing antibodies that target and neutralize the invaders. This response helps to prevent the spread of infection and promotes healing and recovery.2. Describe the process of respiration in humans.答案：Respiration in humans is a process that involves the exchange of gases, primarily oxygen and carbon dioxide, between the body and the environment. It consists of two main stages: inhalation and exhalation. During inhalation, air containing oxygen is drawn into the lungs through the nose or mouth, then travels down the trachea and into the bronchi, which branch into smaller tubes called bronchioles. The bronchioles end in tiny air sacs called alveoli, where the exchange of gases occurs. Oxygen from the air diffuses across the thin walls of the alveoli into the bloodstream, where itbinds to hemoglobin in red blood cells. At the same time, carbon dioxide, a waste product of cellular respiration, diffuses from the blood into the alveoli. During exhalation, the diaphragm and intercostal muscles relax, causing the chest cavity to decrease in size and forcing the carbon dioxide-rich air out of the lungs. This cycle of inhal。

某油田不同来源采出水回注处理工艺技术研究与优化

卢宪辉：某油田不同来源采出水回注处理工艺技术研究与优化第13卷第11期（2023-11）某油田不同来源采出水回注处理工艺技术研究与优化卢宪辉（中海油石化工程有限公司）摘要：针对某油田采出水处理设备和注水管道中存在的结垢严重问题，为提高回注水质达标率，满足国家安全环保的相关要求。

利用Scale Chem 结垢预测软件对不同来源采出水中的成垢离子进行调和，定量测算结垢类型和结垢量，结合室内实验和现场验证对阻垢剂、絮凝剂进行工艺优化，最后进行水质评价。

结果表明，混合水样结垢量随注水井筒深度的增加而减少，在近井口地带的结垢量最大；混合水样在水处理设备中的结垢类型为CaCO 3、BaSO 4、SrCO 3，温度超过40℃时，CaCO 3的结垢量快速上升至672mg/L；复配阻垢剂（ATMP∶TPA=2∶1）总浓度为40mg/L 时，阻垢效果最好；PAC 为90mg/L、PAM 为1mg/L，搅拌时间6min、加药间隔30s 时，絮凝效果最好；处理工艺优化后水质得到较大改善，满足SY/T 5329—2016中关于二级回注水质指标的要求。

研究结果可为同类水处理工艺的优化提供实际参考。

关键词：采出水；处理工艺；结垢量；结垢类型；阻垢剂；絮凝剂DOI :10.3969/j.issn.2095-1493.2023.11.004Research and optimization of re-injection treatment technology of produced water from different sources in an oilfield LU XianhuiPetrochemical Engineering Co ．，Ltd ．，CNOOCAbstract：In view of the serious scaling problems existing in the produced water treatment equipment and injection pipeline of an oilfield，in order to improve the water quality standard rate and to meet the relevant requirements of national safety and environmental protection，the Scale Chem scaling predic-tion software is used to reconcile the scale ions in the produced water from different sources，and the scaling types and amounts are quantitatively measured．What's more，the scale inhibitors and flocculat-ing agent are optimized by combining laboratory experiments and field verification，and the water qual-ity is evaluated at last．The results show that the scaling amount of mixed water samples is decreased with the increasing depth of injection wellbore．In particularly，the scaling amount is the largest near the wellhead．The scaling types of mixed water samples in water treatment equipment are CaCO 3，BaSO 4and SrCO 3．When the temperature exceeds 40℃，the scaling amount of CaCO 3will be rapid-ly increased to 672mg/L．When ATMP∶TPA=2∶1and the total concentration is 40mg/L，the scale inhibition effect is the best．When PAC is 90mg/L，PAM is 1mg/L，stirring time is 6min and dosing interval is 30seconds，the flocculation effect is the best．After the optimization of the treatment process，the water quality has been greatly improved and met the requirements of SY/T 5329—2016on the water quality index of secondary re-injection．Most importantly，the research results can be provided practical reference for the optimization of similar water treatment process ．Keywords：produced water；treatment technology；scaling amount；scaling type；scale inhibitor；flocculating agent作者简介：卢宪辉，工程师，2014年毕业于中国石油大学（华东）（环境科学与工程专业），从事石化行业给排水、消防设计工作，197号中海油石化工程有限公司，266101。

电气安全名词术语GB

标准名称：电气安全名词术语GB 4776-84标准编号：GB 4776-84标准正文：国家标准1984-11-30发布1988-07-01实施1基本概念1.1保安性fail-safe为防止产品本身的危险故障而设计的性能。

1.2正常状态nromal condition所有用于防止危险的设施均无损坏的状态。

1.3电气事故electric accident由电流、电磁场、雷电、静电和某些电路故障等直接或间接造成建筑设施、电气设备毁坏、人、动物伤亡，以及引起火灾和爆炸等后果的事件。

1.4触电电击electric shock电流通过人体或动物体而引起的病理、生理效应。

1.5电磁场伤害injury due to electromagnetic field人体在电磁场作用下吸收能量受到的伤害。

1.6破坏性放电介质击穿disruptive discharge dielectric breakdown固体、液体、气体介质及其组合介质在高电压作用下，介质强度丧失的现象。

破坏性放电时，电极间的电压迅速下降到零或接近于零。

1.7短路short circuit通过比较小的电阻或阻抗，偶然地或有意地对一个电路中在正常情况下处于不同电压下的两点或几点之间进行的连接。

1.8绝缘故障insulation fault绝缘电阻的不正常下降。

1.9接地故障earth fault由于导体与地连接或对地绝缘电阻变得小于规定值而引起的故障。

1.10过电流overcurrent超过额定电流的电流。

1.11过电压overvoltage超过额定电压的电压。

1.12过负载overload超过额定负载的负载。

1.13导电部分conductive part能导电，但不一定承载工作电流的部分。

1.14带电部分live part正常使用时被通电的导体或导电部分，它包括中性导体，但按惯例，不包括保护中性导体(PEN导体)。

注：此术语不一定意味着触电危险。

1.15外露导电部分exposed conductive part电气设备能被触及的导电部分。

T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects

DOI: 10.1126/scitranslmed.3002842, 95ra73 (2011);3 Sci Transl Med , et al.Michael Kalos and Can Establish Memory in Patients with Advanced Leukemia T Cells with Chimeric Antigen Receptors Have Potent Antitumor EffectsEditor's Summarythe potential for CAR-modified T cells to bring cancer therapy up to speed.treatment had complete remission of their leukemia. Although this is early in the clinical study, these results highlight scale with a second exposure to CLL cells. Indeed, two of the three CLL patients who underwent the CAR T cell CAR T cells persisted with a memory phenotype, which would allow them to respond more quickly and on a larger these CAR T cells expanded >1000-fold, persisted for more than 6 months, and eradicated CLL cells. Some of these allowing for much broader cellular targeting than is obtained with normal T cells. After transfer into three CLL patients,receptor could activate T cells in response to CD19 in the absence of major histocompatibility complex restriction, specific intracellular signaling domain. The resulting chimeric −specific costimulatory domain and a T cell −both a T cell bind in a restricted manner to the CD19 protein (which is found solely on normal B cells and plasma cells) attached to The CAR T cells used in this study expressed an antigen receptor that consists of antibody binding domains that as reflected by decreased numbers of B cells and plasma cells and the development of hypogammaglobulinemia.tumor cells after transfer into patients; they also mediated cancer remission. Innocent bystanders were also targeted, chronic lymphocytic leukemia (CLL) (a B cell cancer). The designer T cells not only expanded, persisted, and attacked modified T cells to express a chimeric antigen receptor (CAR) to yield so-called CAR T cells that specifically target . have genetically et al cells to the tumor and maintaining these cells in patients remains challenging. Now, Kalos harness the power of the immune system to fight cancers such as leukemia; however, targeting functional immune T to healthy tissues, such as infection or cancer, and then try to deter dangerous activity. Researchers have long sought As members of the body's police force, cells of the immune system vigilantly pursue bad actors that harmGo CAR-Ts in the Fast Lane/content/3/95/95ra73.full.html can be found at:and other services, including high-resolution figures,A complete electronic version of this article /content/suppl/2011/08/08/3.95.95ra73.DC1.htmlcan be found in the online version of this article at: Supplementary Material/about/permissions.dtl in whole or in part can be found at:article permission to reproduce this of this article or about obtaining reprints Information about obtaining last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue (print ISSN 1946-6234; online ISSN 1946-6242) is published weekly, except the Science Translational Medicine o n F e b r u a r y 20, 2012s t m .s c i e n c e m a g .o r g D o w n l o a d e d f r o mL E U K E M I AT Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced LeukemiaMichael Kalos,1,2*Bruce L.Levine,1,2*David L.Porter,1,3Sharyn Katz,4Stephan A.Grupp,5,6 Adam Bagg,1,2Carl H.June1,2†Tumor immunotherapy with T lymphocytes,which can recognize and destroy malignant cells,has been limited by the ability to isolate and expand T cells restricted to tumor-associated antigens.Chimeric antigen receptors(CARs) composed of antibody binding domains connected to domains that activate T cells could overcome tolerance by allowing T cells to respond to cell surface antigens;however,to date,lymphocytes engineered to express CARs have demonstrated minimal in vivo expansion and antitumor effects in clinical trials.We report that CAR T cells that target CD19and contain a costimulatory domain from CD137and the T cell receptor z chain have potent non–cross-resistant clinical activity after infusion in three of three patients treated with advanced chronic lymphocytic leukemia(CLL).The engineered T cells expanded>1000-fold in vivo,trafficked to bone marrow,and continued to express functional CARs at high levels for at least6months.Evidence for on-target toxicity included B cell aplasia as well as decreased numbers of plasma cells and hypogammaglobulinemia.On average,each infused CAR-expressing T cell was calculated to eradicate at least1000CLL cells.Furthermore,a CD19-specific immune re-sponse was demonstrated in the blood and bone marrow,accompanied by complete remission,in two of three patients.Moreover,a portion of these cells persisted as memory CAR+T cells and retained anti-CD19effector functionality,indicating the potential of this major histocompatibility complex–independent approach for the ef-fective treatment of B cell malignancies.INTRODUCTIONUsing gene transfer technologies,T cells can be genetically modified to stably express antibody binding domains on their surface that con-fer novel antigen specificities that are major histocompatibility com-plex(MHC)–independent.Chimeric antigen receptors(CARs)are an application of this approach that combines an antigen recognition domain of a specific antibody with an intracellular domain of the CD3-z chain or Fc g RI protein into a single chimeric protein(1,2). Trials testing CARs are presently under way at a number of academic medical centers(3,4).In most cancers,tumor-specific antigens are not yet well defined,but in B cell malignancies,CD19is an attractive tumor target.Expression of CD19is restricted to normal and malig-nant B cells(5),and CD19is a widely accepted target to safely test CARs.Although CARs can trigger T cell activation in a manner sim-ilar to an endogenous T cell receptor,a major impediment to the clin-ical application of this technology to date has been the limited in vivo expansion of CAR+T cells,rapid disappearance of the cells after in-fusion,and disappointing clinical activity(4,6).CAR-mediated T cell responses may be further enhanced with ad-dition of costimulatory domains.In a preclinical model,we found that inclusion of the CD137(4-1BB)signaling domain significantly increased antitumor activity and in vivo persistence of CARs com-pared to inclusion of the CD3-z chain alone(7,8).To evaluate the safety and feasibility for adoptive transfer of T cells gene-modified to express such CARs,we initiated a pilot clinical trial using autologous T cells expressing an anti-CD19CAR including both CD3-z and the 4-1BB costimulatory domain(CART19cells)to target CD19+malig-nancies.To date,we have treated three patients under this protocol. Some of the findings from one of these patients are described in(9), which reports that this treatment results in tumor regression,CART19 cell persistence,and the unexpected occurrence of delayed tumor lysis syndrome.Here,we show that the CART19cells mediated potent clinical antitumor effects in all three patients treated.On average,each infused CAR T cell and/or their progeny eliminated more than 1000leukemia cells in vivo in patients with advanced chemotherapy-resistant chronic lymphocytic leukemia(CLL).CART19cells underwent robust in vivo T cell expansion,persisted at high levels for at least6 months in blood and bone marrow(BM),continued to express func-tional receptors on cells with a memory phenotype,and maintained anti-CD19effector function in vivo.RESULTSClinical protocolThree patients with advanced,chemotherapy-resistant CLL were enrolled in a pilot clinical trial for CART19cell therapy.Figure1presents a summary of the manufacturing process for the gene-modified T cells (A)and the clinical protocol design(B).All patients were extensively pretreated with various chemotherapy and biologic regimens(Table1). Two of the patients had p53-deficient CLL,a deletion that portends poor response to conventional therapy and rapid progression(10). Each of the patients had a large tumor burden after the preparative1Abramson Cancer Center,University of Pennsylvania,Philadelphia,PA19104,USA.2De-partment of Pathology and Laboratory Medicine,University of Pennsylvania,Philadelphia, PA19104,USA.3Department of Medicine,University of Pennsylvania,Philadelphia,PA 19104,USA.4Department of Radiology,University of Pennsylvania,Philadelphia,PA19104, USA.5Department of Pediatrics,University of Pennsylvania,Philadelphia,PA19104,USA. 6Division of Oncology,Children’s Hospital of Philadelphia,Philadelphia,PA19104,USA.*These authors contributed equally to this work.†To whom correspondence should be addressed.E-mail:cjune@ o n F e b r u a r y 2 0 , 2 0 1 2 s t m . s c i e n c e m a g . o r g D o w n l o a d e d f r o mchemotherapy,including extensive BM infiltration(40to95%)and lymphadenopathy;UPN02also had peripheral lymphocytosis.There was a low abundance of T cells in the apheresis products(2.29to4.46%) (table S1)as well as likely impaired T cell activation,as has been shown previously in CLL patients(11).Additional details of the cell manufac-turing and product characterization for the CART19cell preparation for each patient are shown in table S1.All patients were pretreated1to 4days before CART19cell infusions with lymphodepleting chemo-therapy(Table1).A split-dose cell infusion schedule was used to address potential safety concerns related to the evaluation of a previously untested CAR that incorporated the4-1BB costimulatory signaling domain. In vivo expansion,persistence,and BM trafficking of CART19cellsOur preclinical data in two animal models,including mice bearing xenografts of primary human precursor-B acute lymphoblastic leuke-mia(7,8),indicated that CAR+T cells that express a4-1BB signaling domain expanded after stimulation with anti-CD3/anti-CD28mono-clonal antibody–coated beads(12)and had improved persistence com-pared to CAR+T cells lacking4-1BB.We developed a quantitative polymerase chain reaction(qPCR)assay to enable quantitative tracking of CART19cells in blood and BM.CART19cells expanded and persisted in the blood of all patients for at least6months(Fig.2, A and B).Moreover,CART19cells expanded1000-to10,000-fold in the blood of patients UPN01and03during the first month after infusion,reaching peak frequencies of10to>95%of circulating white blood cells in UPN01and03(Fig.2C).The peak expansion levels coincided with onset of the clinical symptoms after infusion in UPN01 (day15)and UPN03(day23).Furthermore,after an initial decay,which can be modeled with first-order kinetics,the CART19cell numbers stabilized in all three patients from days90to180after infusion (Fig.2B).The CART19cells also trafficked to the BM in all patients, albeit in5-to10-fold fewer numbers than observed in blood(Fig.2D). CART19cells had a log-linear decay in the BM in UPN01and03, with a disappearance half-life of~35days.Induction of specific immune responses in the peripheral blood and BM compartments after CART19infusion Peripheral blood(PB)and BM serum samples from all patients were collected and batch-analyzed to quantitatively determine cytokine levels.A panel of30cytokines,chemokines,and other soluble factors were assessed for potential toxicities and to provide evidence of CART19cell function.The full data set for all of the cytokines measured in each of the three patients through the date of thisapheresisSeed in gas-permeable bags.Transduction w/αCD19-41BBζvectorVector washout.Culture in gas-permeable bagsCulture in WAV EbioreactorHarvest, wash, concentrateCryopreserve final product ininfusible cryomediaCD3/28-positive selection ofT cells with anti-CD3/anti-CD28 mAb-coated magneticbeadsDay 0Day 0-1Day 3Day 5Harvest day(10 ±2)ABManufacture/cryopreservationFig.1.Schematic representation of the gene transfer vector and trans-gene,gene-modified T cell manufacturing,and clinical protocol design.(A)T cell manufacturing.Autologous cells were obtained via leukapher-esis,and T cells were enriched by mononuclear cell elutriation,washed, and expanded by addition of anti-CD3/CD28–coated paramagnetic beads for positive selection and activation of T cells.Residual leukemic cells were depleted.The lentiviral vector was added at the time of cell activation and was washed out on day3after culture initiation.Cells were expanded on a rocking platform device(WAVE Bioreactor System) for8to12days.On the final day of culture,the beads were removed by passage over a magnetic field and the CART19cells were harvested and cryopreserved in infusible medium.mAb,monoclonal antibody.(B)Clin-ical protocol design.Patients were given lymphodepleting chemo-therapy as described,followed by CART19infusion#1by intravenous gravity flow drip over a period of15to20min.The infusion was given using a split-dose approach over3days(10,30,and60%)beginning1to5days after completion of chemotherapy.Endpoint assays were conducted on study week4.At the conclusion of active monitoring, subjects were transferred to a destination protocol for long-term follow-up as per FDA guidance.onFebruary2,212stm.sciencemag.orgmpublication is presented in tables S2to S5.Of the analytes tested, 11had a threefold or more change from baseline,including four cytokines[interleukin-6(IL-6),interferon-g(IFN-g),IL-8,and IL-10], five chemokines[macrophage inflammatory protein–1a(MIP-1a), MIP-1b,monocyte chemotactic peptide–1(MCP-1),CXC chemokine ligand9(CXCL9),and CXCL10],and the soluble receptors IL-1R a and IL-2R a;IFN-g had the largest relative change from baseline (Fig.3).The peak time of cytokine elevation in UPN01and03 correlated temporally with both the previously described clinical symptoms and the peak levels of CART19cells detected in the blood for each patient.Notably,cytokine modulations were transient,and levels reverted to baseline relatively rapidly despite continued func-Table1.Patient demographics and response.CR,complete response;PR,partial response;N/A,not available.Subject UPNAge/sexkaryotypePrevious therapiesCLL tumor burden at baselineTotaldoseof CART19(cells/kg)Response day+30(duration)BM(study day)‡Blood(studyday)‡Nodes/spleen(study day)‡0165/Mnormal Fludarabine×four cycles(2002)Hypercellular70%CLL N/A 6.2×1011to1.0×1012CLL cells(day−37)1.1×109(1.6×107/kg)CR(11+months)Rituximab/fludarabine×four cycles(2005)2.4×1012CLL cells(day−14)Alemtuzumab×12weeks(2006)1.7×1012CLL cells(day−1)Rituximab(two courses,2008to2009)R-CVP×two cycles(2009)Lenalidomide(2009)PCR×two cycles(5/18/2010to6/18/2010)Bendamustine×one cycle(7/31/10to8/1/10)pre-CART190277/M del(17)(p13)*Alemtuzumab×16weeks(6/2007)Hypercellular>95%CLL2.75×1011CLL cells(day−1)1.2×1012to2.0×1012CLL cells(day−24)5.8×108(1.0×107/kg)PR(7months)Alemtuzumab×18weeks(3/2009)3.2×1012CLL cells(day−47)Bendamustine/rituximab:7/1/2010(cycle1)7/28/2010(cycle2)8/26/2010(cycle3)pre-CART190364/M del(17)(p13)†R-Fludarabine×twocycles(2002)Hypercellular40%CLLN/A 3.3×1011to5.5×1011CLL cells(day−10)1.4×107(1.46×105/kg)CR(10+months)R-Fludarabine×four cycles(10/06to1/07)8.8×1011CLL cells(day−1)R-Bendamustine×one cycle(2/09)Bendamustine×three cycles(3/09to5/09)Alemtuzumab×11weeks(12/09to3/10)Pentostatin/cyclophosphamide(9/10/10)pre-CART19*UPN02karyotype[International System for Human Cytogenetic Nomenclature(ISCN)]:45,XY,del(1)(q25),+del(1)(p13),t(2;20)(p13;q11.2),t(3;5)(p13;q35),add(9)(p22),?del(13)(q14q34),-14,del(17) (p13)[cp24].†UPN03karyotype(ISCN):46,XY,del(17)(p12)[18]/44~46,idem,der(17)t(17;21)(p11.2;q11.2)[cp4]/40~45,XY,-17[cp3].‡See the Supplementary Material for methods of tumor burden determination.o n F e b r u a r y 2 0 , 2 0 1 2 s t m . s c i e n c e m a g . o r g D o w n l o a d e d f r o mtional persistence of CART19cells.Only modest changes in cytokine levels were noted in UPN 02,possibly as a result of corticosteroid treatment.We also noted a robust induction of cytokine secretion in the supernatants from BM aspirates of UPN 03(Fig.3D and table S5).Although a pretreatment marrow sample was not available,compared to the late time point (+176),we also observed elevated levels for a number of factors in the +28marrow sample for UPN 01including IL-6,IL-8,IL-2R,and CXCL9;in contrast,compared to the pretreatment marrow sample,no elevation in cytokines was de-tected in the +31day sample for UPN 02(table S5).One of the preclinical rationales for developing CAR +T cells with 4-1BB signaling domains was a projected reduced propensity to trigger IL-2and tumor necrosis factor –a (TNF-a )secretion compared to CAR +T cells with CD28signaling domains (7);indeed,elevated amounts of soluble IL-2and TNF-a were not detected in the serum of the patients.Lower levels of these cytokines may be related to sustained clinical ac-tivity:Previous studies have shown that CAR +T cells are potentially suppressed by regulatory T cells (13),which can be elicited by either CARs that secrete substantial amounts of IL-2or by the provision of exogenous IL-2after infusion.Moreover,the TNF-a is complicit in cy-tokine storm –related effects in patients,which are absent here.Prolonged receptor expression and establishment of a population of memory CART19cells in bloodA central question in CAR-mediated cancer immunotherapy is whether optimized cell manufacturing and costimulation domains will enhance the persistence of genetically modified T cells and permit the establishment of CAR +memory T cells in patients.Previous studies have not demonstrated robust expansion,prolonged persist-ence,or functional expression of CARs on T cells after infusion (14–17).The high persistence of CART19cells that we observed at late time points for UPN 03facilitated a more detailed phenotypic analysis ofpersisting cells.Flow cytometric analysis of samples from both blood and BM 169days after infusion revealed the presence of CAR19-expressing cells in UPN 03as well as an absence of B cells (fig.S1,Aand B).These CAR +cells persisted in allthree patients beyond 4months,as shown by qPCR (Fig.2).The in vivo frequency of CAR +cells by flow cytometry closely matched the values obtained from the PCR assay for the CAR19transgene.CAR expression was also detected on the surface of 5.7and 1.7%of T cells in the blood of patient UPN 01on days 71and286after infusion (fig.S2).We next used polychromatic flow cy-tometry to perform detailed studies and further characterize the expression,phe-notype,and function of CART19cells in UPN 03using an anti-CAR idiotype anti-body (MDA-647)and the gating strategy shown in fig.S3.We observed differencesin the expression of memory and activa-tion markers in both CD4+and CD8+T cells based on CAR19expression.In the CD4+compartment,at day 56,CART19cells were characterized by auniform lack of CCR7,a predominance of CD27+/CD28+/PD-1+cells distributed within both CD57+and CD57−compart-ments,and an essential absence of CD25and CD127expression,the latter two markers defining regulatory CD4+T cells (18)(Fig.4A).In contrast,CAR −cells at this time point were heterogeneous in CCR7,CD27,and PD-1expression;expressed CD127;and also contained a substantialCD25+/CD127−population.By day 169,although CD28expression remained uni-formly positive in all CART19CD4+cells,a fraction of the CART19CD4+cells had acquired a central memory phenotype,withA CB Day (after infusion)110100100010000100000Day (after infusion)T o t a l c e l l s i n c i r c u l a t i o nDay (after infusion)110100100010000D C o p i e s /µg g D N A% W B CDay (after infusion)C o p i e s /µg gD N AWBC and CART 19: Blood CART 19: Marrow 10101010101010Fig.2.Sustained in vivo expansion and persistence in blood and marrow of CART19cells.(A to D )qPCRanalysis was performed on DNA isolated from whole blood (A to C)or bone marrow (BM)(D)samples obtained from UPN 01,UPN 02,and UPN 03to detect and quantify CAR19sequences.The frequency of CART19cells is shown as average transgene copies (A),total calculated CART19cells in circulation (B),or as a fraction of circulating white blood cells (WBCs)(C).(A)Copies CAR19/microgram DNA is calculated as de-scribed in Materials and Methods.(B)The total number of lymphocytes (total normal and CLL cells)versus total CART19+cells in circulation is plotted for all three subjects using the absolute lymphocyte count from complete blood count values and assuming a 5.0-liter volume of peripheral blood.(C)%WBC is calculated as described in Materials and Methods.(D)Bulk qPCR analysis of marrow to quantify CART19sequences.The data from patient UPN 03in (A,C,and D)has been published in (9)and is reprinted here with permission.Each data point represents the average of triplicate measurements on 100to 200ng of genomic DNA,withmaximal percent coefficient of variation (CV)less than 1.56%.Pass/fail parameters for the assay included preestablished ranges for slope and efficiency of amplification,and amplification of a reference sample.The lower limit of quantification for the assay established by the standard curve range was two copies of transgene per microgram of genomic DNA;sample values below that number are considered estimates and presented if at least two of three replicates generated a C t value with percent CV for the values 15%.CART19cells were infused at days 0,1,and 2for UPN 01and 03and at days 0,1,2,and 11for UPN 02. o n F e b r u a r y 20, 2012s t m .s c i e n c e m a g .o r g D o w n l o a d e d f r o mCCR7expression,a higher percentage of CD27−cells,the appearance of a PD-1−subset,and acquisition of CD127expression.At day 169,CAR −cells remained reasonably consistent with their day 56counterparts,with the exception of a reduction in CD27expression and a decrease in the percentage of CD25+/CD127−cells.In the CD8+compartment,at day 56,CART19CD8+cells displayed primarily an effector memory phenotype (CCR7−,CD27−,CD28−),con-sistent with prolonged and robust exposure to antigen (Fig.4B).In con-trast,CAR −CD8+T cells consisted of mixtures of effector and central memory cells,with CCR7expression in a subset of cells,and substantial numbers of cells in the CD27+/CD28−and CD27+/CD28+fractions.Al-though a large percentage of both CART19and CAR −cell populations expressed CD57,a marker associated with memory T cells with high cytolytic potential (19),this molecule was uniformly coexpressed with PD-1in the CART19cells,a possible reflection of the extensive replicative history of these cells.In contrast to the CAR −cell population,the entirety of the CART19CD8+population lacked expression of both CD25and CD127,markers associated with T cell activation and the development of functional memory cells (20).By day 169,although the phenotype of the CAR −cell population remained similar to the day 56cells,the CART19population had evolved to contain a population with features of central memory cells,notably expression of CCR7and higher levels of CD27and CD28,as well as cells that were PD-1−,CD57−,and CD127+.Effector function of CART19cells after 6months in blood In addition to a lack of long-term persistence,a limitation of previous trials with CAR +T cells has been the rapid loss of functional activity of the infused T cells in vivo.The high level of CART19cell persist-ence and surface expression of the CAR19molecule in UPN 03provided the opportunity to directly test anti-CD19–specific effector functions in cells recovered from cryopreserved PB samples.Pe-ripheral blood mononuclear cells (PBMCs)from UPN 03were cultured with target cells that either did or did not express CD19(Fig.4C and fig.S3).Robust CD19-specific effector function of CART19cells was observed by the specific degranulation of CART19cells against CD19+but not CD19−target cells,as assessed by surface CD107a expression.Notably,exposure of the CART19population to CD19+targets induced a rapid internalization of surface CAR19(see fig.S3for constitutive surface expression of CAR19in the same ef-fector cells in standard flow cytometric staining).The presence of costimulatory molecules on target cells was not required for trigger-ing CART19cell degranulation because the NALM-6line,which was used as a target in these studies,does not express CD80or CD86(21).Effector function was evident at day 56after infusion and was re-tained at day 169(Fig.4C).Robust effector function of CAR +and CAR −T cells could also be demonstrated by pharmacologic stimula-tion with phorbol 12-myristate 13-acetate (PMA)and ionomycin.ADay (after infusion)S e r u m c y t o k i n e (f o l d c h a n g e f r o m b a s e l i n e )(f o l d c h a n g e f r o m b a s e l i n e )S e r u m c y t o k i n e (f o l d c h a n g e f r o m b a s e l i n e )BCDay (after infusion)D Day (after infusion)C o n c e n t r a t i o n (p g /m l )αIL-6 IFN-γCXCL10MIP-1βMCP-1CXCL9IL-2R αIL-8 IL-10MIP-1αFig.3.Serum and BM cytokines before and afterCART19cell infusion.(A to C )Longitudinal measure-ments of changes in serum cytokines,chemokines,and receptors in UPN 01(A),UPN 02(B),and UPN 03(C)on the in-dicated day after CART19cell infusion.(D )Serial assessments of the same analytes in the BM from UPN 03.Analytes with agreater than or equal to threefold change are indicated and plotted as relative change from baseline (A to C)or as absolute values (D).In (C)and (D),a subset of the cytokine data (IFN-g ,CXCL10,CXCL9,IL-2R a ,and IL-6)from UPN 03have been pub-lished in (9)and are reprinted here with permission.Absolutevalues for each analyte at each time point were derived from a recombinant protein-based standard curve over a threefold eight-point dilution series,with upper and lower limits of quantification determined by the 80to 120%observed/expected cutoff valuesfor the standard curves.Each sample was evaluated in duplicate with average values calculated and percent CV in most cases less than 10%.To accommodate consolidated data presentation in the context of the wide range for the absolute values,data are presented as fold change over the baseline value for each analyte.In cases where baseline values were not detectable,half of the lowest standard curve value was used as the baseline value.Standard curve ranges for analytes and baseline (day 0)values (listed in parentheses sequentially for UPN 01,02,and 03),all in pg/ml:IL-1R a :35.5to 29,318(689,301,and 287);IL-6:2.7to 4572(7,10.1,and 8.7);IFN-g :11.2to 23,972(2.8,not detected,and 4.2);CXCL10:2.1to 5319(481,115,and 287);MIP-1b :3.3to 7233(99.7,371,and 174);MCP-1:4.8to 3600(403,560,and 828);CXCL9:48.2to 3700(1412,126,and 177);IL-2R a :13.4to 34,210(4319,9477,and 610);IL-8:2.4to 5278(15.3,14.5,and 14.6);IL-10:6.7to 13,874(8.5,5.4,and 0.7);MIP-1a :7.1to 13,778(57.6,57.3,and 48.1).o n F e b r u a r y 20, 2012s t m .s c i e n c e m a g .o r g D o w n l o a d e d f r o mProfound antitumor clinical activity of CART19cellsThere were no significant toxicities observed during the4days after the infusion in any patient other than transient febrile reactions. However,all patients subsequently developed significant clinical and laboratory toxicities between days7and21after the first infusion. With the exception of B cell aplasia,these toxicities were short-term and reversible.Of the three patients treated to date,there are two complete responses and one partial response lasting greater than8months after CART19infusion according to standard criteria(22).Details of past medical history and response to therapy are described in Table1. The clinical course of UPN03has been described in detail(9).In brief,patient UPN02was treated with two cycles of bendamus-tine with rituximab,resulting in stable disease;he received a third dose of bendamustine as lymphodepleting chemotherapy before CART19 cell infusion.After CART19infusion,and coincident with the onset of high fevers,he had rapid clearance of the p53-deficient CLL cells from his PB(Fig.5A)and a partial reduction of adenopathy.He de-veloped fevers to40°C,rigors,and dyspnea requiring a24-hour hos-pitalization on day11after the first infusion and on the day of his second CART19cell boost.Fevers and constitutional symptoms per-sisted,and on day15,he had transient cardiac dysfunction;all symp-toms resolved after corticosteroid therapy was initiated on day18.His BM showed persistent extensive infiltration of CLL1month after therapy despite marked PB cytoreduction.He remained asymptomatic at the time of publication.Patient UPN01developed a febrile syndrome,with rigors and transient hypotension beginning10days after infusion.The fevers persisted for about2weeks and resolved;he has had no further consti-tutional symptoms.He achieved a rapid and complete response(Fig.5, B and C).Between1and6months after infusion,no circulating CLL cells were detected in the blood by deep sequencing(Table2).His BM at1,3,and6months after CART19cell infusions showed sustainedA1.40.67.890.223.58.02939.5CCR7CD28CD127CCR7CD28CD127C0.999.187.97.10.34.65.165.726.72.60.746.551.71.265.814.34.1715.71.81236.949.49.317.644.129CD4Day 169CCR7CD28CD127CCR7CD28CD127CD45RACD27CD25CD45RACD27CD25CD45RACD27CD25CD45RACD2744.017.34.234.4CD57CD5731.932.111.424.648.218.55.128.2CD57CD57PD-1PD-1PD-1PD-150.111.01127.927.841.716.613.874.719.81.73.8CD57CD57CD57CD5735.933.610.220.352.738.94.63.936.09.814.239.974.9230.61.5CD57CD57CD57CD57CD27CD28CD27CD28CD27CD28CD27CD28CD2565.00.60.433.719.959.411.39.231.551.66.610.030.147.910.811.12.459.635.42.639.59.28.842.5CCR7CD28CD127CD57CD57CD5779.516.70.90.36.833.234.925.110.928.041.319.82542.926.16.014.244.524.516.93.7 2.025.468.875.623.70.20.56.040.339.314.316.328.831.922.937.242.318.12.414.338.222.225.36.0 4.530.359.296.6 3.414.67.41464.15.115.760.418.89.411.464.614.60.60.12.596.818.473.03.05.697.10.70.062.111.2 3.111.873.95.58.052.833.77.8 6.454.231.635.559.21.33.927.264.316.779.20.200.898.97.500.891.73.60.10.395.97.60.40.191.90.10.213.885.90.20.312.387.2C00.284.715.100.969.329.80.10.21188.60.20.56.692.74.00.21.194.73.396.6Fig.4.Prolonged surface CAR19expressionand establishment of functional memoryCART19cells in vivo.(A and B)T cell immuno-phenotyping of CD4+(A)and CD8+(B)T cellsubsets.Frozen peripheral blood(PB)samplesfrom UPN03obtained at days56and169afterT cell infusion were subjected to multipara-metric immunophenotyping for expression ofmarkers of T cell memory,activation,and ex-haustion;data are displayed after biexponentialtransformation for objective visualization ofevents.(C)Functional competence of persistingCAR cells.Frozen PB samples from UPN03ob-tained at days56and169after T cell infusion were evaluated directly ex vivo for the ability to recognize CD19-expressing target cells using CD107 degranulation assays.Presented data are for the CD8+gated population.The gating strategies for these figures are presented in fig.S2.onFebruary2,212stm.sciencemag.orgDownloadedfrom。

C反应蛋白检测与临床诊断思路

(a) Negatively stained electron micrograph showing the typical pentameric disc-like structure face-on and side-on (arrows).
(b) Ribbon diagram of the crystal structure, showing the lectin fold and the two calcium atoms (spheres) in the ligand-binding site of each protomer .
CRP--急性时相反应的一个极灵敏的指标
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CRP变化的临床思路
9.良恶性胸腔积液的鉴别诊断
炎性胸腔积液CRP水平＞结核性胸腔积液 CRP水平＞恶性胸腔积液CRP水平
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10.免疫性疾病的判断

Optimization and control of perfusion cultures using a viable cell probe and specific perfusion rate

Cytotechnology42:35–45,2003.©2003Kluwer Academic Publishers.Printed in the Netherlands.35Optimization and control of perfusion cultures using a viable cell probe and cell speciﬁc perfusion ratesJason E.Dowd1,2,3,Anthea Jubb1,2,K.Ezra Kwok2&James M.Piret1,2∗1Biotechnology Laboratory,University of British Columbia,Vancouver,BC,Canada;2Department of Chemical and Biological Engineering,University of British Columbia,Vancouver,BC,Canada;3∗Present address,Process Development&Manufacturing,INEX Pharmaceuticals Corporation,Burnaby,BC,Canada(∗Author for correspondence;E-mail:jpiret@chml.ubc.ca;Fax:(604)8222114)Received23January2003;accepted in revised form5March2003Key words:Cell speciﬁc perfusion feed rates,CHO,Control,Optimization,t-PA,Viable cell probeAbstractConsistent perfusion culture production requires reliable cell retention and control of feed rates.An on-line cell probe based on capacitance was used to assay viable biomass concentrations.A constant cell speciﬁc perfusion rate controlled medium feed rates with a bioreactor cell concentration of∼5×106cells mL−1.Perfusion feeding was automatically adjusted based on the cell concentration signal from the on-line biomass sensor.Cell speciﬁc perfusion rates were varied over a range of0.05to0.4nL cell−1day−1.Pseudo-steady-state bioreactor indices (concentrations,cellular rates and yields)were correlated to cell speciﬁc perfusion rates investigated to maximize recombinant protein production from a Chinese hamster ovary cell line.The tissue-type plasminogen activator concentration was maximized(∼40mg L−1)at0.2nL cell−1day−1.The volumetric protein productivity(∼60mg L−1day−1)was maximized above0.3nL cell−1day−1.The use of cell speciﬁc perfusion rates provided a straightforward basis for controlling,modeling and optimizing perfusion cultures.IntroductionWith increasing biopharmaceutical industry demand for monoclonal antibodies and other complex recom-binant proteins,it is increasingly important to max-imize mammalian cell bioreactor productivity.Con-version of bioreactors from fed-batch to perfusion can increase volumetric productivities over ten-fold.How-ever,perfusion culture production requires reliable cell retention and proper feed rate speciﬁcation.A ma-jor objective of perfusion culture control is to balance the medium feed and cellular uptake rates to maintain pseudo-steady-state conditions.Control of perfusion bioreactors can be espe-cially challenging due to high andﬂuctuating cell concentrations(Vits and Hu,1992)that can rap-idly change environmental conditions.With infrequent daily sampling,the control system can have too little information on which to base an appropriate decision to manipulate the process.In Kurkela et al.(1993),daily feed rate step changes by an operator were inac-curate and process deviations resulted.Recently,more advanced predictive modeling based on daily gluc-ose analysis by Dowd et al.(1999)improved feed rate speciﬁcation and bioreactor control by up to7-fold compared to operator speciﬁcation.Alternatively, the process information can be improved by increas-ing sampling frequency with automatedﬂow injection analysis.Such control systems(Van der Pol et al., 1995;Konstantinov et al.,1996;Ozturk et al.,1997) resulted in<1mM substrate concentrations variations.Robust,automatic feed rate speciﬁcation requires careful design of the three components of a control system:process information,controller logic and a decision to manipulate the process.A control sys-tem based on a constant cell speciﬁc perfusion often depends on manual daily samples and trypan blue ex-clusion hemocytometer cell counting(Heidemann et al.,2000).36Figure1.Schematic of perfusion bioreactor with the viable cell monitor(VCM)and acousticﬁlter.The VCM signal was sent to the computer, which was running BioXpert.In the control algorithm,a cell speciﬁc perfusion rate was speciﬁed and the biomass density signal was averaged and converted to a perfusionﬂow rate.The acousticﬁlter was used to retain cells in the bioreactor,with an automated back-ﬂush of clariﬁed harvest.Design of the controller logic is often overlooked, although it impacts the overall control system per-formance,especially in automatic systems.Kon-stantinov et al.(1996)described controller logic,ma-nipulating the process at the same high frequency it was sampled,such that process noise caused oscil-latory control.Van der Pol et al.(1995)sampled the process at similar high frequencies,but averaged information and manipulated the process at lower fre-quencies,improving the basis upon which to manipu-late the process.Alternatively in Dowd et al.(1999), the control performance was designed a priori and, using predictive models so that from daily sampling, up to8manipulations of the processﬂow rate were performed per day.Process information from on-line systems,such as mass spectrometers or probes can be used to calculate carbon dioxide evolution(Pelletier et al.,1994)and oxygen uptake rates(Kyung et al.,1994)to provide re-latively noisy estimates of the cell density.Direct pro-cess information of the cell density has been obtained by a microscopic imaging analysis system developed by Maruhashi et al.(1994)to determine cell size and viability without sampling or staining.The dead cell concentrations,and corresponding viability,were cor-related to the number of small,cell debris particles. Merten et al.(1985)described an infrared sensor for the determination of cell number,but the range of cell densities tested and the length of operation were ser turbidity probes have been used in batch cultures,with Zhou and Hu(1994)demonstrating a linear relationship up to3×106cells mL−1and Kon-stantinov et al.(1992)calculating the speciﬁc growth rate(after signal noiseﬁltering).Several light-based sensors were tested over a wide range of cell densities up to25×106cells mL−1and up to50days in perfu-sion culture(Wu et al.,1995).Decreases in sensitivity at high cell densities with probes with longer detection37 Figure2.Model prediction of steady-states in perfusion cultures controlled with cell speciﬁc perfusion rates.In(A)cell speciﬁc glucose uptake rates for a batch culture were correlated to reactor glucose concentration.The relationship was used in(B)to predict changing glucose concentrations from a steady-state condition at5.6mM glucose(0.18nL cell−1day−1to9.1mM glucose(0.28nL cell−1day−1).Conﬁdence regions are the uptake-concentration correlation limits.path lengths were observed.In general,probe per-formance was acceptable for high viability cultures. Once calibrated,a cell speciﬁc perfusion rate was spe-ciﬁed and the feed rates were based on the cell probe output(Wu et al.,1995).However,the light-based probes did not distinguish between viable and nonvi-able cells.During process upsets,all the optical probe measures deviated from the cell densities measured by trypan blue exclusion.With dielectric spectroscopy,the capacitance probe output is proportional to the membrane enclosed volume fraction(Harris et al.,1987).Since only intact membranes should store charge,viable biomass is se-lectively measured.This method has been applied to microbial,animal and plant cells(Markx et al.,1991; Fehrenbach,1992;Cerckel et al.,1993;Konstantinov et al.,1994)with reliable readings at minimum mam-malian cell concentrations of∼0.5×106cells mL−1 (Degouys et al.,1993).A particular advantage of dielectric spectroscopy is that it can measure viable cell concentrations in packed bed and porous micro-carrier systems(Guan et al.,1998;Guan and Kemp, 1998;Ducommun et al.,2001,2002).38Figure3.Viable cell concentrations and culture viabilities as a function of cell speciﬁc perfusion rate.In(A),the viable cell probe output and hemocytometer values are compared,while in(B),the culture viability obtained from a hemocytometer are plot ted as a function of cell speciﬁc perfusion rate.The errors bars represent95%conﬁdence region around the average.In this work,automatic perfusion feed rate control was based on estimation of the viable cell concen-tration using on-line dielectric spectroscopy.The cell density was captured and averaged for use in a con-trol algorithm based on cell speciﬁc perfusion rates. Cell speciﬁc perfusion rates were maintained and the quality of the pseudo-steady-states analyzed.The de-pendencies of the substrate,metabolite and protein concentrations,along with uptake and production rates were analyzed as a function of cell speciﬁc perfusion rates.Cell speciﬁc rates that maximized the recombin-ant protein concentrations or volumetric productivity were deﬁned.Materials and methodsCell cultureA DUKX-B11derived CHO cell line(C5.23SFM1, Fann et al.,2000)was cultured in a serum-and methotrexate-free medium(SFM2,Cangene Corp., Winnipeg,MB).Thawed inoculum cultures were grown in T-ﬂasks for7or8days(37◦C,5%CO2), before2subcultures in250mL spinners(Bellco,Vine-land,NJ).Cell counts used trypan blue dye exclusion in a hemocytometer for both reactor and perfusion ef-ﬂuent.Approximately108cells were used to inoculate a0.8L working volume(3L overall)perfusion biore-39actor(Applikon,Foster City,CA)and run for3days in batch mode until perfusion feeding was initiated.An acousticﬁlter(BioSep10L,Applikon)retained cells in the perfusion reactor.The cell bleed rate was controlled by decreasing the acousticﬁlter duty(on :off ratio)to increase net cell bleed rates,between 45on:6off and15on:45off(sec).At high on-off ratios,>99%cell retention was observe,vs.∼85% at the low on-off ratios.The acousticﬁlter was oper-ated with a25mL medium back-ﬂush every15min to avoid pumping cells through a circulation line(Mer-ten,1999).Temperature,pH and dissolved oxygen were maintained at37±0.2◦C,7.2–7.3and60±15% of air saturation,respectively,by a digital control-ler(Applikon BioController1040).An Aber Instru-ments Viable Cell Monitor(Applikon),along with probes for temperature,pH and dissolved oxygen were data logged(BioXpert).A conductance level sensor triggered an outﬂow pump to maintain a constant re-actor working volume.In theﬁrst culture,perfusion rates were0.3,0.25and0.2nL cell−1day−1,while, in the second,0.4,0.3,0.15,0.1and0.05nL cell−1 day−1perfusion rates were investigated.The feed medium contained30mM glucose,except for the preliminary batch and perfusion cultures,performed with25-mM glucose.In the initial perfusion culture, samples were taken from the reactor outﬂow using a refrigerated fraction collector.These samples were used for steady-state characterization.Medium analysisManual samples were analyzed daily for glucose,lact-ate and ammonium concentrations using a Stat10 Blood/Gas Analyzer(NOV A Biomedical,Waltham, MA).The enzymatic activity of t-PA was analyzed by a colorimetric assay(Fann et al.,2000).A conver-sion factor of580000U mg−1(WHO standard speciﬁc activity)was used to convert activity units to concen-trations.The amino acid concentrations were determ-ined by the Pico-Tag method(Cohen and Strydom, 1988;Hagen et al.,1993)followed by separation on a Waters C-18reverse-phase column(Milford,MA) using a Shimadzu(Columbia,MD)HPLC system. Amino acid standards at0.08,0.2and0.8mM were used,with an internal standard of50µM orleucine. Speciﬁcation of perfusion feed ratesThe viable cell monitor(VCM)output was connected to the BioXpert software in a custom setup(Figure1).Every30min,the VCM output was sent to the BioX-pert software,where a control algorithm automatically calculated the requiredﬂow rates,using a computer calibrated and controlled pump.In perfusion cultures, theﬂow rate was based on viable cell concentrations using:F=X v·V·p sp·10−9,(1) where F was theﬂow rate(L day−1),X v the VCM measured viable cell concentration(cells L−1),V the reactor working volume(L)and p sp the cell speciﬁc perfusion rate(nL cell−1day−1).The volume of me-dium corresponding to the calculatedﬂow rate was automatically added hourly,using the average of two VCM readings.Statistical methods and analysisIn the analysis of pseudo-steady states,all data were linearly regressed versus time from24h after the change.The regressed line slope was compared to zero with a95%conﬁdence limit using the standard error for that slope estimate.It was assumed that if the slope was not signiﬁcantly different from zero,and non-linear dynamics were not observed,then a steady-state condition had been achieved.All the data had an expected analysis measurement error.For calculated data(for example,cell speciﬁc glucose uptake rates are based on glucose and cell density measurements), an ANOV A analysis was performed to estimate the expected error for these calculations.Results and discussionTime to steady statePerfusion cultures usually approach steady-state more rapidly than chemostat cultures without cell retention (Miller et al.,1988;Hiller et al.,1993),mainly be-cause of much higher perfusion dilution rates due to greater cell concentrations.Figure2B shows an ex-ample(6.3×106cells mL−1)of a step from0.18to 0.28nL cell−1day−1,where perfusion steady-state glucose concentrations were attained within12–24h of changing the cell speciﬁc perfusion rate.This was conﬁrmed by mass balance based simulations using:d Cd t=FV·(C in−C)−q·X v·10−9V,(2)40Table parison of analysis errors to range ofexperimental dataAnalysis error Range ofexperimental dataGlucose<0.5mM7.0–20mMLactate<0.4mM9.0–22mMAmmonium<0.2mM 1.6–3.3mMt-PA<1.7mM L−122–45mg L−1where C and C in are the reactor and inlet glucose concentrations(mM),q the cell speciﬁc glucose up-take rate(pmol cell−1day−1).Theﬂow rate,F, was speciﬁed in Equation(1).From batch culture data with medium that contained25mM glucose,the cell speciﬁc glucose uptake rate was correlated with the reactor glucose concentration(Figure2A),and represented as:q=0.52·C−0.91,(3) assuming no delay in the cellular response.Pelletier et al.(1994)has shown that batch kinetics can predict glucose concentrations in perfusion culture.The sim-ulated and measured glucose concentrations changed quickly and attained95%of the steady-state con-centration within12h.The limits on the simulation correspond to the95%conﬁdence limits on the correl-ation(Equation(3)).Thus,in perfusion culture,where cell concentrations are controlled,pseudo-steady-state substrate and cell concentrations are possible within 12–24h.Analysis of steady states in perfusion cultures using viable cell monitorIn the perfusion cultures using the viable cell monitor,ﬁxed cell speciﬁc perfusion rates were generally main-tained for a minimum of5days each.All cell culture data(11concentrations,cell speciﬁc rates and yields for the8perfusion cultures)were tested for statist-ical consistency with steady-state conditions.Overall, 73%of the88data sets tested for steady-state exhib-ited slopes not signiﬁcantly different from zero.Of the remaining24data sets,22had standard deviations less than the error in analysis(Table1).Therefore, analysis error was believed often responsible for ap-parent non-steady-state conditions.The2remaining data sets with signiﬁcant slopes were t-PA concentra-tions and cell speciﬁc productivity at0.05nL cell−1day−1,when culture viability was lowest at approxim-ately64%(Figure3).Thus,overall good steady states were achieved.Over the whole tested range of cell speciﬁc per-fusion rates,the average ratio of t-PA production to glucose uptake was1.9g t-PA mol−1glucose.At lower than0.15nL cell−1day−1perfusion rates,the ratio of t-PA production to glucose uptake was more variable(±0.9g t-PA mol−1glucose),while above 0.2nL cell−1day−1,the ratio was more constant (±0.04g t-PA/mol glucose).The increase in t-PA vari-ability at low cell speciﬁc perfusion rates was similar to previous work(Dowd et al.,2001),where,with the same cell clone and medium,a3-fold higher t-PA concentration variability was observed at low glucose concentrations.Cell concentration for a range of perfusion rates Initial calibration of the viable cell probe was per-formed in a batch culture with greater than90%vi-ability.Above a cell speciﬁc perfusion rate of0.2nL cell−1day−1,the average cell concentration was ap-proximately5×106cells mL−1with a culture viabil-ity of approximately90%(Figure3).Hemocytometer counts in this range of perfusion rates were close to the VCM readings.However,below0.2nL cell−1day−1, the viability of the culture declined,the VCM readings underestimated hemocytometer counts by approxim-ately35%,though this may be due to decreasing cell volumes under low viability conditions(Sonderhoff et al.,1992;Ducommun et al.,2002).These results contrast with Wu et al.(1995)who reported that sev-eral optical probe outputs overestimated viable cell concentrations(since nonviable cells scatter light).In straightforward mass balance simulations with a stable protein,constant cell concentration and spe-ciﬁc production rate,protein concentrations would increase with the reciprocal of perfusion rate.How-ever,although lower perfusion rates allowed for higher protein concentrations,t-PA concentrations were lim-ited due to increased extra cellular protein degradation and the inability to prevent cell death at low perfusion rates.t-PA production in perfusion cultures with viable cell monitorThe cell speciﬁc t-PA productivity increased with in-creasing cell speciﬁc perfusion rate and approached a maximum around0.2nL cell−1day−1(Figure4B). The highest t-PA titers were observed between0.1and41 Figure4.Steady-state recombinant protein production as a function of cell speciﬁc perfusion rates.In(A),the t-PA concentrations,in(B),the cell speciﬁc productivity and in(C),volumetric productivity.0.3nL cell−1day−1(Figure4A).The downward trend in concentration at cell speciﬁc perfusion rates greater than0.2nL cell−1day−1was due to the increased ﬂow ratesﬂushing t-PA from the reactor,indicating that the maximal cell speciﬁc production rate had been obtained.The lower t-PA concentrations at low cell speciﬁc perfusion rates corresponded to lower culture viabilities of60to80%.At lower culture viabilities,3-fold higher extra-cellular t-PA degradation rates have been observed with this medium and cell clone(Dowd et al.,2000).V olumetric productivity was a function of both t-PA concentration and perfusionﬂow rate(Fig-ure4C).The low volumetric productivity observed at low cell speciﬁc perfusion rates,reﬂected the lower culture viability and the lowﬂow rate.Reactor environment control using viable cell monitor With increasing cell speciﬁc perfusion rates,nutrient and metabolite concentrations either changed linearly (increasing/decreasing)or exhibited a broad max-imum.Glucose,glutamine and most other amino acids (data not shown)exhibited linear increasing concen-trations(Figures5and6).Lactate,ammonium and glycine(data not shown)exhibited linear decreasing concentrations with increasing cell speciﬁc perfusion42Figure5.Steady-state glucose,lactate and ammonium concentrations and cell speciﬁc rates as a function of cell speciﬁc perfusion rates.rate.Finally,serine,like t-PA,exhibited a broad max-imum between0.1to0.25nL cell−1mL−1.At low cell speciﬁc perfusion rates,along with a drop in viab-ility,there may have been some limitation or inhibition in the culture conditions that reduced production and concentrations.For cell speciﬁc rates,the relationships were gen-erally of a saturation-type,with the changeable com-ponent being the inﬂection point for saturation.For glucose uptake and t-PA production,the inﬂection point was at approximately0.2nL cell−1day−1.The majority of the measured components exhibited inﬂec-tion points at approximately0.3nL cell−1day−1.In contrast,maximal cell speciﬁc ammonium production and glutamate uptake did not appear to be attained over the tested range of cell speciﬁc perfusion rates.The yields of metabolites from substrates were generally constant over the range of cell speciﬁc per-fusion rates(data not shown),which may be expec-ted,as limiting conditions for substrates were not approached.The yield of lactate from glucose was typical in this respect(constant at0.7±0.2).The ratio of glucose to glutamine was also constant(6.9±0.9), with no trends observed.The yields of ammonium and glutamate from glutamine increased slightly above 0.3nL cell−1day−1cell speciﬁc perfusion rates.43 Figure6.Steady-state glutamine,glutamate and serine concentrations and cell speciﬁc rates as a function of cell speciﬁc perfusion rates.Comparison of glucose and viable cell monitor based feed rate controlSpecifying the cell speciﬁc perfusion rate to control the reactor environment resulted in greater glucose concentration variability of up to1.4mM.Dowd et al.(2001)used predictive control protocols based on daily samples to reduce glucose variation to±0.3mM levels(±S.D.).However controlling the reactor based on glucose concentrations requires some form of sampling and subsequent specifying pumpﬂow rates as a result of assayed values.ConclusionsUse of a viable cell probe and cell speciﬁc perfusion rates is a simple and relatively sample free control method for perfusion cultures.Steady states were rap-idly achieved in the reactor after switching cell speciﬁc perfusion rates.The perfusion process feed rate was explored by manipulating the cell speciﬁc perfusion rate and observing the impact on bioreactor perform-ance.The t-PA concentration peaked at approximately 0.2nL cell−1day−1as protein wasﬂushed from the reactor at higher cell speciﬁc perfusion rates.Cell spe-ciﬁc glucose uptake and t-PA production rates reached a maximum above0.2nL cell−1day−1.V olumetric t-PA productivity increased with increasing cell speciﬁc44perfusion rates up to0.3nL cell−1day−1.Estimation of the viable cell concentration with a viable cell probe readily allowed cell speciﬁc perfusion rate selection for optimal process operation. AcknowledgementsFunding from Cangene Corp.(Winnipeg,MB),the Natural Sciences and Engineering Research Council of Canada(NSERC)and the loan of a VCM device by Applikon are gratefully acknowledged.An NSERC Postgraduate Scholarship supported J.E.Dowd. ReferencesCerckel I,Garcia A,Degouys V,Dubois D,Fabry L.and Miller AOA(1993)‘Dielectric spectroscopy of mammalian cells1.Evaluation of the biomass of HeLa-and CHO cells in suspension by low-frequency dielectric spectroscopy’,Cytotechnology13: 185–193.Cohen SA and Strydom DJ(1988)‘Amino acid analysis using phenylisothiocyanate derivatives’,Anal Biochem174:1–16. 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Ducommun P,Bolzonella I,Rhiel M,Pugeaud P,V on Stockar U and Marison IW(2001)‘On-line determination of animal cell concentration’,Biotechnol Bioeng72:515–522.Ducommun P,Kadouri A,V on Stockar U and Marison IW(2002)‘On-line determination of animal cell concentration in two indus-trial high-density culture processes by dielectric spectroscopy’, Biotechnol Bioeng77:316–323.Fann CH,Guirgis F,Chen G,Lao MS and Piret JM(2000)‘Lim-itations to the ampliﬁcation and stability of human tissue-type plasminogen activator expression by Chinese Hamster Ovary cells’,Biotechnol Bioeng69:204–212.Fehrenbach R,Comberbach M and Pêtre JO(1992)‘On-line bio-mass monitoring by capacitance measurement’,J Biotech23: 303–314.Guan Y,Evans PM and Kemp RB(1998)‘Speciﬁc heatﬂow rate: An on-line monitor and potential control variable of speciﬁc metabolic rate in animal cell culture that combines microcalor-imetry with dielectric spectroscopy’,Biotechnol Bioeng58: 87–94.Guan YH and Kemp RB(1998)‘On-line heatﬂux measurements improve the culture medium for the growth and productiv-ity of genetically engineered CHO cells’,Cytotechnology30: 107–120.Hagen SR,Augustin J,Grings E and Tassinari P(1993)‘Precolumn phenylisothiocyanate derivatization and liquid chromatography of free amino acids in biological samples’,Food Chem46:319–323.Harris CM,Todd RW,Bungard SJ,Lovitt RW,Morris JG and Kell DB(1987)‘The dielectric permittivity of microbial suspensions at radio frequencies;A novel method for the real-time estimation of microbial biomass’,Enzyme Microb Technol9:181–186. Heidemann R,Zhang C,Qi H,Rule,JL,Rozales C,Sinyoung P,Chuppa S,Ray M,Michaels J,Konstantinov K and Naveh D(2000)‘The use of peptones as medium additives for the production of a recombinant therapeutic protein in high dens-ity perfusion cultures of mammalian cells’,Cytotechnology32: 157–167.Hiller G,Clark D and Blanch H(1993)‘Cell retention chemo-stat studies of hybridoma cells.Analysis of hybridoma growth and metabolism in continuous suspension culture on serum free medium’,Biotechnol Bioeng42:185–195.Konstantinov K,Chuppa S,Sajan E,Tsai Y,Yoon S and Golini F (1994)‘Real-time biomass-concentration monitoring in animal-cell cultures’,Trends Biotech12:324–333.Konstantinov KB,Pambayun R,Matanguihan R,Yoshida T,Per-usich CM and Hu W-S(1992)‘On-line monitoring of hybridoma cell growth using a laser turbidity sensor’,Biotechnol Bioeng40: 1337–1342.Konstantinov KB,Tsai Y-S,Moles D and Matanguihan R(1996)‘Control of long-term perfusion Chinese Hamster Ovary cell culture by glucose auxostat’,Biotechnol Prog12:102–109. Kurkela R,Fraune E and Vihko P(1993)‘Pilot-scale production of murine monoclonal antibodies in agitated,ceramic-matrix or hollow-ﬁber cell culture systems’,BioTechniques15:674–683. Kyung Y-S,Peshwa MV,Gryte DM and Hu W-S(1994)‘High density culture of mammalian cells with dynamic perfusion based on on-line uptake rate measurements’,Cytotechnology14: 183–190.Markx GH,Davey CL,Kell DB and Morris P(1991)‘The dielec-tric permittivity at radio frequencies and the Bruggeman probe: Novel techniques for the on-line determination of biomass con-centrations in plant cell cultures’,J Biotech20:279–290. Maruhashi F,Murakami S and Baba K(1994)‘Automated monit-oring of cell concentration and viability using an image analysis system’,Cytotechnology15:281–289.Merten OW(2000)Constructive improvement of the ultrasonic sep-aration device ADI1015.16th ESACT,Lugano,Switzerland, Cytotechnology24:175–179.Merten OW,PalﬁGE,Staheli J and Steiner J(1985)‘Invasive infrared sensor for the determination of the cell number in a continuous fermentation of hybridomas’,Devel Biol Stand66: 357–360.Miller WM,Blanch HW and Wilke CR(1988)‘A kinetic analysis of hybridoma growth and metabolism in batch and continuous suspension culture:Effect of nutrient concentration,dilution rate and pH’,Biotechnol Bioeng32:947–965.Ozturk S,Thrift J,Blackie J and Naveh D(1997)‘Real time monitoring and control of glucose and lactate concentrations in a mammalian cell perfusion reactor’,Biotechnol Bioeng53: 372–378.Pelletier F,Fonteix C,De Silva AL,Marc A and Engasser J-M(1994)‘Software sensors for the monitoring of perfusion cultures:Evaluation of the hybridoma density and the me-45dium composition from glucose concentration measurements’, Cytotechnology15:291–299.Sonderhoff SA,Kilburn DG and Piret JM(1992)‘Analysis of mam-malian viable cell biomass based on cellular ATP’,Biotechnol Bioeng39:859–864.Van der Pol JJ,Joksch B,Gätgens J,Biselli M,De Gooijer CD, Tramper J and Wandrey C(1995)‘On-line control of an im-mobilized hybridoma culture with multi-channelﬂow injection analysis’,J Biotechnol43:229–242.Vits H and Hu W-S(1992)‘Fluctuations in continuous mammalian cell bioreactors with retention’,Biotechnol Prog8:397–403. 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医学英语试题及答案

医学英语试题及答案一、选择题（每题1分，共10分）1. Which of the following is a common symptom of the common cold?A. FeverB. DiarrheaC. HeadacheD. All of the above2. The abbreviation "MRI" stands for:A. Magnetic Resonance ImagingB. Medical Research InstituteC. Multiple Risk IndicatorsD. Major Risk Index3. What does the term "anemia" refer to?A. A condition characterized by low blood pressureB. A condition characterized by low red blood cell count or low hemoglobinC. A condition characterized by high blood sugar levelsD. A condition characterized by high cholesterol levels4. The prefix "cardio-" is commonly associated with:A. The heartB. The lungsC. The kidneysD. The brain5. Which of the following is a type of cancer?A. HypertensionB. DiabetesC. MelanomaD. Asthma6. The term "pneumonia" refers to an inflammation of:A. The heartB. The lungsC. The liverD. The kidneys7. In medical terms, "hyperglycemia" is a condition where:A. Blood sugar levels are below normalB. Blood sugar levels are normalC. Blood sugar levels are above normalD. Blood sugar levels are unstable8. The suffix "-itis" generally indicates:A. A condition of deficiencyB. A condition of excessC. An inflammationD. A tumor9. The abbreviation "HIV" stands for:A. Human Immunodeficiency VirusB. High Intensity VirusC. Hepatitis Infection VirusD. Hormone Infection Virus10. Which of the following is a sign of dehydration?A. Frequent urinationB. Dry mouthC. Increased appetiteD. Rapid heartbeat二、填空题（每空1分，共10分）11. The medical term for a break in the skin is a/an _______.12. A person with a fear of heights is said to have _______.13. The process of identifying a disease is called _______.14. The study of the structure of the body is known as_______.15. A medical condition characterized by excessive thirst and urination is _______.16. The abbreviation "CT" stands for _______.17. The term "dermatitis" refers to an inflammation of the_______.18. A person who specializes in treating diseases of the heart is called a _______.19. The medical term for the removal of a kidney stone is_______.20. The abbreviation "BP" stands for _______.三、简答题（每题5分，共20分）21. Explain the difference between "chronic" and "acute" in medical terms.22. What is the function of the thyroid gland in the human body?23. Describe the purpose of a biopsy in medical diagnosis.24. What are the main symptoms of influenza?四、翻译题（每题5分，共10分）25. 将“高血压”翻译成英文。

医学三级英语考试

一、选择题1.Which of the following is the primary function of the heart?A.To filter bloodB.To pump blood throughout the body（答案）C.To store oxygenD.To produce red blood cells2.What is the term used to describe the abnormal growth of cells that can invade andspread to other parts of the body?A.InfectionB.InflammationC.Cancer（答案）D.Allergy3.Which vitamin is essential for bone health and is primarily obtained from sunlight?A.Vitamin AB.Vitamin CC.Vitamin D（答案）D.Vitamin E4.The process of breaking down food into smaller, absorbable molecules is known as:A.Digestion（答案）B.MetabolismC.RespirationD.Circulation5.Which hormone is responsible for regulating blood sugar levels in the body?A.Insulin（答案）B.ThyroxineC.AdrenalineD.Estradiol6.The term used to describe the condition where the body's immune system attacks itsown tissues is:A.Autoimmune disease（答案）B.Allergic reactionC.Infectious diseaseD.Genetic disorder7.Which part of the brain is responsible for coordinating and controlling musclemovements?A.CerebrumB.Cerebellum（答案）C.Medulla oblongataD.Pons8.The process by which the kidneys filter blood, remove waste products, and produceurine is called:A.DialysisB.FiltrationC.UrinationD.Renal function（答案）。

L-阿拉伯糖复配糖对小鼠血糖的影响

陈鑫，王晨，王黎明，等. L-阿拉伯糖复配糖对小鼠血糖的影响[J]. 食品工业科技，2023，44（17）：392−398. doi: 10.13386/j.issn1002-0306.2022100180CHEN Xin, WANG Chen, WANG Liming, et al. Study on the Effect of L-arabinose Compound Sugar on Blood Glucose in Mice[J].Science and Technology of Food Industry, 2023, 44(17): 392−398. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2022100180· 营养与保健 ·L-阿拉伯糖复配糖对小鼠血糖的影响陈　鑫1，王　晨1，王黎明1，赵抒娜1,2, *，赵　芸1,2，刘孟涛1,2，孟庆佳1,*（1.中粮营养健康研究院有限公司，营养健康与食品安全北京市重点实验室，老年营养食品研究北京市工程实验室，北京 102209；2.中粮糖业控股股份有限公司，农业部糖料与番茄质量安全控制重点实验室，新疆昌吉 831100）摘　要：目的：探究食糖与L-阿拉伯糖复配后对C57BL/6N 小鼠血糖的影响，为开发低血糖生成指数食物提供理论参考。

方法：通过灌胃方式给予小鼠复配糖糖水，并以葡萄糖为参考食物，以二甲双胍为阳性对照品分别灌胃，在给糖（药）后的0、15、30、60、120 min 时测量小鼠血糖值，通过曲线下面积增幅（Increamental area under the curve ，IAUC ）、血糖峰值、血糖生成指数（Glycemic index ，GI ）等指标评价复配糖对小鼠血糖的影响。

结果：与葡萄糖组相比，白砂糖或红糖与L-阿拉伯糖复配后均可显著降低IAUC 值（P <0.05）、血糖峰值（P <0.05），在相同可利用碳水化合物的水平下，由于红糖中脂肪、蛋白质、水分、灰分、钾、镁、锌、铬、磷、碘以及总多酚、总黄酮等含量均显著高于白砂糖（P <0.05），白砂糖复配糖在C57BL/6N 小鼠中的GI 值为52，红糖复配糖在C57BL/6N 小鼠中的GI 值为42。

小学上册第9次英语第2单元测验卷(有答案)

小学上册英语第2单元测验卷(有答案)英语试题一、综合题(本题有50小题，每小题1分，共100分.每小题不选、错误，均不给分)1 The clock shows ______ (three) o'clock.2 The ancient Greeks made advancements in ________ and mathematics.3 The rabbit hops around the _______ (花园).4 The ability to convert energy from one form to another is known as _____.5 How many bones are in the adult human body?A. 206B. 205C. 201D. 210答案:A. 2066 What do we call the area of land that is rich in biodiversity?A. Biodiversity hotspotB. Conservation areaC. National parkD. Wildlife reserve答案: A. Biodiversity hotspot7 Gardeners often use ______ (肥料) to help plants grow.8 What is the name of the famous American president known for the Emancipation Proclamation?A. George WashingtonB. Abraham LincolnC. FranklinD. RooseveltD. Thomas Jefferson答案: B9 The _______ can be found in many colors.10 A __________ is formed by the accumulation of organic matter.11 What is the process of taking in oxygen and expelling carbon dioxide?A. PhotosynthesisB. RespirationC. DigestionD. Circulation答案: B12 We have a ______ (运动) day at school.13 The _____ (ball/box) is round.14 The chemical formula for potassium nitrate is ______.15 We will go to the _____ (zoo/museum) on Saturday.16 The ________ was a famous historical figure in India.17 A ladybug has ______ spots.18 A rock that is formed by the accumulation of minerals from water is called a ______ rock.19 My sister is a _____ (演员) who participates in community theater.20 What do you call a person who studies the environment?A. EcologistB. Environmental scientistC. ConservationistD. All of the above答案:D21 What is the capital of the Netherlands?A. AmsterdamB. RotterdamC. The HagueD. Utrecht答案: A22 The ______ is a layer of rock that lies directly beneath the Earth's surface.23 I have a special talent for ______ (唱歌). I love performing in front of my family and friends.24 Metals conduct __________ well.25 I saw a _______ (蝴蝶) land on a flower.26 How many fingers do you have on one hand?A. FourB. FiveC. SixD. Seven27 The garden is ______ (full) of butterflies.28 I love to watch ________ (电视剧).29 The __________ (历史的回响) resonates with our experience.30 Many plants have ______ (药用价值).31 The ______ (绿色建筑) incorporates plants for sustainability.32 What is the main purpose of a computer?A. To play gamesB. To browse the internetC. To process informationD. To print documents答案: C33 What is the freezing point of water in Fahrenheit?A. 0B. 32C. 100D. 212答案:B34 I wear a _____ (围巾) in winter.35 A __________ is a substance that helps speed up a reaction.36 What is the capital of Colombia?A. BogotáB. MedellínC. CaliD. Cartagena37 The chemical symbol for mercury is __________.38 The _____ (袋鼠) jumps high.39 Which shape has three sides?A. SquareB. TriangleC. CircleD. Rectangle40 What do we call the study of the body's systems and structures?A. BiologyB. AnatomyC. PhysiologyD. Medicine答案: B41 My ________ (玩具名称) is a colorful addition to my collection.42 What is 2 + 2?A. 3B. 4C. 5D. 643 A __________ is a substance that speeds up a chemical reaction.44 The ______ (果实) of a plant develops from its flowers.45 What do you call a young otter?A. PupB. KitC. CalfD. Cub46 What is the name of the famous artist known for his "The Girl with a Pearl Earring"?A. Johannes VermeerB. RembrandtC. Vincent van GoghD. Claude Monet47 What do we call a baby kangaroo?A. JoeyB. CalfC. KitD. Cub答案:A48 The element with atomic number is __________.49 The scientist conducts _____ (实验) in the lab.50 What do we call the study of the human mind and behavior?A. SociologyB. PsychologyC. AnthropologyD. Philosophy答案: B51 Chemical reactions can be classified as ________ or endothermic.52 The zebra has black and ________________ (白条纹).53 Which insect makes honey?A. AntB. ButterflyC. BeeD. Fly答案:C54 What is 10 4?A. 5B. 6C. 7D. 8答案:B55 I can see _______ (很多星星) tonight.56 A black hole is formed when a large star _____.57 The __________ is the part of the plant that releases oxygen.58 I like to _____ (参加) community service.59 The __________ (历史的见证者) recount significant moments.60 What is 3 x 4?A. 10B. 11C. 12D. 1361 What is the capital of Mongolia?A. UlaanbaatarB. HohhotC. ErdenetD. Darkhan答案:A. Ulaanbaatar62 What is the name of the famous scientist known for his work on radioactivity?A. Marie CurieB. Albert EinsteinC. Louis PasteurD. Isaac Newton答案: A63 The walrus uses its tusks to _______ (打斗).64 The ______ enjoys hiking and nature.65 A ______ is a geographical area characterized by specific features.66 What is the name of the story about a girl in a red hood?A. CinderellaB. Little Red Riding HoodC. Snow WhiteD. Sleeping Beauty答案: B67 The chemical formula for selenium dioxide is _____.68 The ________ (种子发芽) process is fascinating.69 The chemical formula for calcium sulfate is __________.70 Which of these is a renewable resource?A. CoalB. OilC. Solar EnergyD. Natural Gas答案:C71 His favorite game is ________.72 What is the name of the famous bear in the children's book series by A. A. Milne?A. PaddingtonB. Winnie the PoohC. Yogi BearD. Baloo73 What is the name of the planet known as the "Red Planet"?A. VenusB. MarsC. JupiterD. Saturn答案:B74 What do you call the process of water falling from the sky?A. PrecipitationB. EvaporationC. CondensationD. Sublimation75 The _______ (The Age of Enlightenment) emphasized reason and individual rights.76 The room is very ___. (clean)77 The ________ (繁茂) of a garden is a joy to see.78 I have _____ (many) questions.79 What do we call the person who works on a farm?A. FarmerB. GardenerC. RancherD. Forester答案:A80 The _____ (peony) is a favorite among gardeners.81 What is the capital of Italy?A. RomeB. ParisC. MadridD. Berlin82 Which is the tallest mountain in the world?A. K2B. KilimanjaroC. EverestD. Fuji答案:C83 My grandma shares her __________ (生活经验) with us.84 My teacher is ______ (善良). She always helps us with our ______ (功课).85 The _____ (山羊) grazes in the field.86 My dad is a _______ (司机).87 A __________ is a small-scale representation of the earth's features.88 Which country is known for sushi?A. ChinaB. JapanC. ThailandD. India答案: B89 What is the name of the famous clock tower in London?A. Big BenB. Tower BridgeC. London EyeD. Buckingham Palace90 A ____ is a small creature that enjoys eating fruit.91 What do we call the holiday on October 31st?A. ChristmasB. EasterC. HalloweenD. Thanksgiving92 What is the term for a young zebra?A. CalfB. FoalC. CubD. Kid答案:B93 The __________ was a war fought between the North and South in America.94 What is the term for the movement of the Earth around the sun?A. RotationB. RevolutionC. OrbitD. Spin答案:B95 The number of electrons in a neutral atom equals the number of ______.96 The main function of hemoglobin is to transport ______.97 What do we call a large flat area of land?A. MountainB. HillC. PlainD. Plateau答案: C98 The ______ (小鸟) chirps while perched on a branch.99 The __________ (历史的声音) resonates through time. 100 What do we use to write on paper?A. PaintB. PencilC. BrushD. Marker答案:B。

高三英语生物结构单选题50题

高三英语生物结构单选题50题1.The nucleus of a plant cell is responsible for_____.A.storing waterB.controlling cell activitiesC.producing energyD.breaking down waste答案：B。

本题考查植物细胞中细胞核的功能。

选项A，储存水是液泡的功能；选项C，产生能量主要是线粒体的功能；选项D，分解废物不是细胞核的主要功能。

而细胞核控制细胞的活动。

2.In animal cells, the organelle that is involved in packaging and transporting proteins is_____.A.lysosomeB.endoplasmic reticulumC.Golgi apparatusD.mitochondrion答案：C。

动物细胞中，高尔基体负责包装和运输蛋白质。

选项A，溶酶体主要是分解废物；选项B，内质网参与蛋白质的合成等；选项D，线粒体产生能量。

3.Which of the following is NOT a part of the cell membrane structure?A.PhospholipidsB.ProteinsC.CarbohydratesD.Nucleic acids答案：D。

细胞膜的结构主要由磷脂、蛋白质和少量的糖类组成。

核酸不是细胞膜的组成部分。

4.The cell wall of a plant cell is mainly made up of_____.A.celluloseB.proteinC.lipidD.starch答案：A。

植物细胞的细胞壁主要由纤维素组成。

选项B，蛋白质不是细胞壁的主要成分；选项C，脂质不是细胞壁的成分；选项D，淀粉主要存在于细胞内储存能量。

5.The organelle that is known as the “powerhouse” of the cell is_____.A.nucleusB.chloroplastC.mitochondrionD.endoplasmic reticulum答案：C。

全国职称英语考试理工试题过关训练

你若盛开，蝴蝶自来。

全国职称英语考试理工试题过关训练全国职称英语考试理工试题过关训练Constant dropping wears the stone..以下是我为大家搜寻整理的全国职称英语考试理工试题过关训练，期望能给大家带来帮忙!更多精彩内容请准时关注我们应届毕业生考试网!What Is CancerCancer is actually a group of many related diseases that all have to do with cells.Cells are the very small units that make up all______(1)things，including the human body.There are billions of cells______(2)each persons body.Cancer happens when cells that are not normal grow______(3)spread very fast.Normal body cells grow and divide and know when to stop growing.Over time，they also die.______(4)these normal cells，cancer cells just continue to grow and divide out of control and dont die.Cancer cells usually group together to form tumors(肿瘤).A growing tumor becomes a lump of cancer cells______(5)can destroy the normal cells around the______(6)and damage the bodys healthy tissues.This can make someone very______(7).Sometimes cancer cells break away from the original tumor and travel to other areas of the______(8)，where they keep growing and can go on to form new tumors.This is howcancer______ (9).The spread of a tumor to a new place in the body is______(10)metastasis(转移).第1页/共3页千里之行，始于足下。

小剂量沙库巴曲缬沙坦用于治疗心力衰竭合并慢性肾脏病1～3期患者的研究

天津医药2022年9月第50卷第9期小剂量沙库巴曲缬沙坦用于治疗心力衰竭合并慢性肾脏病1~3期患者的研究黄芃菲，卢成志△摘要：目的分析小剂量沙库巴曲缬沙坦治疗心力衰竭合并慢性肾脏病1~3期患者的疗效和安全性。

方法将72例心力衰竭合并慢性肾脏病1~3期患者随机分为2组，在常规抗心力衰竭治疗的基础上，加用沙库巴曲缬沙坦50mg ，2次/d 治疗，1~2周后其中1组增加剂量至100mg ，2次/d 。

部分患者因无法耐受目标剂量而减量，最终根据实际维持剂量将其分为增量组（100mg ，2次/d ）25例，维持组（50mg ，2次/d ）35例和减量组（25mg ，2次/d ）12例。

比较治疗前后各组患者左心室射血分数（LVEF ）、N 末端B 型利钠肽原（NT-proBNP ）、NYHA 心功能分级、血肌酐（Scr ）、肾小球滤过率估算值（eGFR ）、收缩压（SBP ）、舒张压（DBP ）和不良心血管事件发生情况。

结果与治疗前比较，治疗后3组患者LVEF 升高，NT-proBNP 降低；增量组LVEF 高于减量组和维持组（P ＜0.05）。

3组患者间NT-proBNP 和NYHA 心功能分级改善情况差异无统计学意义（P ＞0.05）。

与治疗前比较，增量组和维持组治疗后Scr 水平降低，eGFR 水平升高（P ＜0.05）；减量组Scr 、eGFR 水平与治疗前差异无统计学意义（P ＞0.05）。

与治疗前比较，3组患者治疗后SBP 、DBP 均降低；维持组DBP 高于减量组和增量组（P ＜0.05）。

患者均未出现低血压、重度肾功能损害、高钾血症、血管性水肿等情况，无死亡发生。

结论小剂量沙库巴曲缬沙坦治疗心力衰竭合并慢性肾脏病1~3期患者安全有效。

关键词：心力衰竭；慢性肾脏病；沙库巴曲缬沙坦；治疗结果；小剂量中图分类号：R541.6文献标志码：ADOI ：10.11958/20212073Efficacy and safety of low-dose sacubitril/valsartan in patients with heart failure andstage 1-3chronic kidney diseaseHUANG Pengfei,LU Chengzhi △Department of Cardiology,the First Central Hospital of Tianjin,Tianjin 300192,China△Corresponding Author E-mail:Abstract:Objective To analyze the efficacy and safety of low-dose sacubitril/valsartan in the treatment of patientswith heart failure complicated with stage 1-3chronic kidney disease.MethodsA total of 72patients with heart failure andstage 1-3chronic kidney disease were randomly divided into the two groups.On the basis of conventional anti-heart failuretherapy,patients were treated with sacubitril/valsartan 50mg twice a day.After 1to 2weeks,the dosage of the one group was increased to 100mg twice a day.According to the actual maintenance dose,patients were finally divided into the three groups:the incremental group (100mg twice a day,25cases),the dose maintenance group (50mg twice a day,35cases)and the dose reduction group (25mg twice a day,12cases).The left ventricular ejection fraction (LVEF),N-terminal pro-B-type natriuretic peptide (NT-proBNP),NYHA heart function classification,serum creatinine (Scr),estimated glomerular filtration rate (eGFR),systolic blood pressure (SBP),diastolic blood pressure (DBP)and adverse cardiovascular events were compared before and after treatment between the three groups.ResultsCompared with before treatment,LVEF increased and NT-proBNP decreased after treatment in the 3groups (P ＜0.05).LVEF was higher in the increment group than that in thedecrement group and the maintenance group (P ＜0.05).There were no significant differences in the improvement of NT-proBNP and NYHA cardiac function grading between the 3groups (P ＞0.05).Compared with before treatment,the Scr level decreased and eGFR level increased after treatment in the increment group and the maintenance group (P ＜0.05).There were no significant differences in Scr and eGFR levels before treatment in the decrement group (P ＞0.05).Compared with before treatment,SBP and DBP decreased after treatment in the 3groups.DBP was higher in the maintenance group thanthat in the decrement group and the increment group (P ＜0.05).None of the patients presented hypotension,severe renal基金项目：天津市医学重点学科（专科）建设项目资助（TJYXZDXK-054B ）作者单位：天津市第一中心医院心内科（邮编300192）作者简介：黄芃菲（1991），女，住院医师，主要从事心血管内科临床方面研究。

南充2024年小学第15次英语第三单元真题(含答案)

南充2024年小学英语第三单元真题(含答案)考试时间：90分钟（总分:120）A卷考试人：_________题号一二三四五总分得分一、综合题(共计100题)1、What is the term for a group of lions?A. PackB. PrideC. FlockD. Herd答案:B2、听力题：Hydraulic systems use fluids to transmit ______.3、What is 6 x 3?A. 15B. 16C. 17D. 184、听力题：She has _____ (two/three) pets at home.5、听力题：The city of Kabul is the capital of _______.6、听力题：The chemical symbol for bismuth is _______.7、填空题：A _____ is a large area covered with trees.8、听力题：A crystalline solid has a regular _______ structure.9、听力题：The process of oxidation involves the loss of ______.10、What is the name of the planet we live on?A. MarsB. EarthC. VenusD. Jupiter11、听力题：The __________ is a large area of rolling grassland.12、填空题：The turtle can hide in its _______ (壳).13、听力题：The first woman to fly in space was _______ Ride.14、听力题：The boy likes ________.15、听力题：The main product of photosynthesis is _____.16、What is the term for a young shark?a. Pupb. Kitc. Calfd. Chick答案:a17、What is the time of day when the sun rises?A. DawnB. DuskC. MidnightD. Noon18、听力题：The chemical name for water is __________.19、填空题：The _____ (jasmine) flower smells sweet at night.20、What is the sound a cow makes?A. BarkB. MeowC. MooD. Roar21、填空题：A _____ (植物) may have medicinal properties.22、What is the capital of Liberia?a. Monroviab. Gbarngac. Buchanand. Robertsport答案:a23、填空题：The chef, ______ (厨师), teaches cooking classes.24、填空题：The __________ (历史的相关性) impacts present-day issues.25、What is the name of the large body of freshwater that is smaller than an ocean?A. LakeB. PondC. RiverD. Stream答案: A26、What do you call a young crocodile?A. HatchlingB. CalfC. PupD. Kit答案:A27、听力题：A ______ can be very protective of its territory.28、填空题：This ________ (玩具) creates a sense of wonder.29、听力题：The __________ is a famous area known for its training grounds.30、听力题：I want to ________ a new bike.31、听力题：A sound that is too high or too low may not be ______.32、What color is a ripe strawberry?A. BlueB. GreenC. RedD. Yellow答案:C33、听力题：I have a _______ (goal) to achieve this year.34、填空题：The __________ (探险) led us to new places.35、What do you call a baby horse?A. CalfB. FoalC. KidD. Lamb36、听力题：The _____ (book/magazine) is interesting.37、填空题：Gardening can provide a wonderful opportunity for ______ and discovery. (园艺可以为学习和探索提供极好的机会。

Daikin VRV Air Conditioner Installation and Operat

● Always be sure to use a properly insulated tool to operate the short-circuit pin on the circuit board. (Do not use your finger.) ● Never switch the power supply ON until the installation has completed. ● Supply electrical current through all indoor units and check the voltage. ● Supply electrical current through all the outdoor units and check each inter-phase voltage. ● Before the test run, ensure to check that the 3-way valve is open. Operating while the valve is closed causes the compressor to
Content check
Power supply cable
● Is the wire set up and connected as described in the instructions? Check for any phase
Indoor/outdoor connection wire
sequence. ● Are the wire connection’s screws loose?
● Short-circuit RUN pin on the outdoor main PCB for one second or longer. Factory setting is cooling operation mode and cooling operation test run starts. If heating operation starts, short-circuit both right side and centre of the MODE pin (centre and COOL) for one second or longer.