Yes sir, Ideas Count! The Value in the University of Chicago • A firm belief in the value of open, rigorous, and intense inquiry • Argumentation rather than deference is the route to clarity • Insistence that arguments stand or fall on their merits, not the background, position, or fame of the proponent • Flexible organization that fosters rigorous and imaginative analysis of complex problems from multiple perspectives A great university would not achieve its educational reputation grandeur and has deep impact to humanity if no great ideas permeate from it. To have great ideas, one must first have ideas, even bad ones! Ideas from a university emerge from what the slide outlines, through open-minded inquisitiveness, debates, and argumentation from everyone within the university. There must be an atmosphere of exuberance and intensity where ideas can flow freely, ubiquitously, wandered aimlessly and debated furiously at every square inch of space within university. It is through “Insistence that arguments stand or fall on their merits, not the background, position, or fame of the proponent.” Hence, University of Chicago was chosen not just because it had great intellects. That it does have, and as we noticed, a large number.
Recently I participated in many partys and met many people. I really enjoy talking to them and they brought a lot of stories to me. 1A genus boy Cyrus is a little boy in Grade 5. After he found I came here frome Beijing,he drew a picture for me. I am so surprised at the precisemap of Terminal Three of Beijing Capital Airport .Cyrus is Lisa'eldstson with a round face and
博主按：据说这是主要靠严格的饮食疗法治愈多发性硬化症的唯一病例。病人自身是美国爱荷华大学医学院的医学博士，一位女士。这应该是宝贵的资料，所以我把她的文章转贴一下。 The Seventy Percent Solution Terry L. Wahls, MD University of Iowa Carver College of Medicine, Iowa City VA Medical Center, Iowa City, IA, USA. KEY WORDS: secondary progressive multiple sclerosis; recovery; nutrition. J Gen Intern Med DOI: 10.1007/s11606-010-1631-3 Society of General Internal Medicine 2011 I loved practicing Tae Kwon Do. The forms are precise, crisp like an elegant dance. But I most especially loved the thrill of sparring. Stepping into the ring, ducking, dodging, kicking, and flying in spinning tornado kicks; I loved the surge of adrenaline that came with the controlled combat of tournaments. I competed nationally, even winning a bronze medal in the trials for the Pan American Games. But that was a long time ago. A lot has happened since then—medical school, an internal medicine residency, a son, a daughter. I became an academic general internist, and I developed a chronic disease. Like many with an autoimmune disease, my troubles had begun two decades before the diagnosis: loss of stamina and strength, problems with balance, bouts of horrific facial pain, dips in visual acuity. When I developed the foot drop, the diagnosis was made: multiple sclerosis (MS). What caused my immune cells to begin their assault on my brain?Mydoctor said that genetics accounted for only 10 to30%of the risk ofMS; the rest was due to some combination of unknown environmental factors.He never toldmewhat I could do to address those unknown factors, only offering interferon and copolymer-1 to reduce the risk of relapse. He said that fewer relapses would mean less disability, a greater chance that I’d still be walking, working, and living my life as I once knew it ten years later. I started the injections right away. Over the next four years I had only one relapse—a transient weakness of the right arm. Still, I grew steadily weaker, losing more and more function and activity tolerance. Jogging left me first. Then, standing for any time became difficult. Ultimately, despite my use of the most current pharmacotherapies, walking and even sitting was tiring, so I needed a tilt-recline wheelchair. It was increasingly apparent that, with time, becoming bedridden due to my illness was inevitable. I was at a crossroads. *** Physician self-experimentation, driven either by passionate belief in our ideas or refusal to go quietly to our demise, has occurred for centuries. I had only two options: accommodation and acceptance of deepening disability despite optimal treatment, or increased involvement in my own health care. Though I had once been a fighter, I was now exhausted. Still, I wanted to walk—even a few steps—as long as I could. I began my own study of the literature, reading article after article on PubMed, knowing that the seeds for today’s clinical care were laid years, sometimes decades earlier in the basic science literature. I hoped to find a magic bullet that would halt my worsening disability. At first, I looked for recent articles testing new MS drugs in animal models. Eventually, realizing I could not access those drugs unless I was in a clinical trial, I turned to articles concerning neurodegeneration of all types—dementia, Parkinson’s disease, Huntington’s, and Lou Gehrig’s disease. Convinced that mitochondrial failure drove much of MS-related disability, I immersed myself in this literature over the next four years, gradually relearning much of what I had forgotten in my basic science years: cellular physiology, biochemistry, and neurophysiology. I found basic science articles testing various nutrients to slow animal models of neurodegeneration, so I translated mouse-sized doses to human ones and began my selfexperimentation with B vitamins, omega-3 fatty acids, alpha lipoic acid, coenzyme Q, and L-carnitine. I slowly added more vitamins and supplements to my list of brain nutrients. The rate of my decline slowed and I was grateful. However, although my decline had slowed, I was still declining. My disease was reclassified as secondary progressive MS, meaning there were no FDA-approved treatments capable of restoring my lost function. Walking became more difficult. Even taking a few steps using two canes exhausted me. Then in the summer of 2007, another metamorphosis began. Reviewing a study protocol for the University of Iowa’s Institutional Review Board, I learned about neuromuscular electrical stimulation and wondered if it might help me. I searched PubMed, finding 212 articles—three involving cerebral palsy, two involving stroke, the rest involving athletes, but nothing involving MS. Still, I wondered whether neuromuscular electrical stimulation might allow me to walk for another year or two. I asked my physical therapist to let me have a test session. He told me that e-stim (as he called it) was not an approved treatment for MS—that it was painful, exhausted most athletes, and that while it could grow muscle, there was no guarantee that my brain could to talk to these new muscles. This potentially dead and useless muscle weight might make the small amount of walking that I could still do even more difficult. But he did let me have a test session. He was right. It did hurt. A lot. But to my surprise, when I was finished, I was not exhausted. In fact, probably because of all of the endorphins released by the e-stim, I felt the best I’d felt in years. My therapist implemented a program of e-stim coupled with daily exercise. At the same time that I began e-stim, I had an important epiphany. What about nutrition? Was I getting all the micronutrients that my brain needed? I returned to the literature. Bourre’s1,2 review on the impact of micronutrients on brain function and structure led me to add sulfur amino acids, kelp (iodine), resveratrol (flavonoids), and vitamin D to my daily regimen. As good as the article was, it did not list all of the building blocks needed for optimal brain health. I decided to think more critically about food. If I ate more foods that contained the vitamins, minerals, and essential fatty acids that I was taking in pill form each day, I might get important building blocks that had not yet been identified. Identifying the food sources for those critical nutrients was not easy. The medical literature didn’t have that information, nor did the registered dieticians with whom I consulted, nor did I see it in the food science literature. I turned eventually to Google, which did help me, nutrient by nutrient, to understand where various micronutrients I was taking by pill each day were located in the food supply. My new diet was nine cups of vegetables and fruit each day, grass-fed meat, and wild fish. Determined to optimize everything I could to help my brain heal, I next looked more deeply at the environmental factors associated with poorly explained neurological and psychological symptoms. Two stood out: food allergies and toxic load. Food allergies can cause a myriad of neurological and psychological symptoms, typically without any abdominal complaints, decades before diagnosis and are very difficult to identify. My best option was to eliminate the most common offenders: gluten, dairy, and eggs. I also learned about toxic load—increased mercury stores in the brains of people with dental fillings, high levels of the herbicide atrazine in private wells in Iowa, the strong association between pesticide exposure and neurodegeneration, the association of single nucleotide polymorphisms involving metabolism of sulfur and or B vitamins, and inefficient clearing of toxins3,4. Having grown up on an Iowa farm—with exposure to plenty of pesticides and herbicides, a mouthful of mercury, and tens of thousands of toxic chemicals registered with the Environmental Protection Agency—I knew there was not one single test to determine which, if any, toxins were being stored in my fat and in my brain. Deciding my best option was to improve my ability to excrete toxins,5,6 I added already-methylated folate and B12, more sulfur amino acids, and fiber to my regimen. *** Physician self-experimentation sometimes does not go as anticipated. I had wanted to only slow my descent; I had no hope of recovery. The unthinkable—the unimaginable—happened, stunning me, my family, and my physicians. Two months after starting my e-stim and intensive nutrition, I could again sit in a standard desk chair without being exhausted—for the first time in years. At three months, I could walk between exam rooms in the clinic. At five months, I could walk to the clinic, and at seven months, I could bicycle around the block. A year after starting e-stim and intensive nutrition, I was able to bicycle 18 miles, and the following year I rode a horse on a trail ride in the Canadian Rockies. As a result, I’ve changed how I practice medicine. Now I focus on teaching my patients how to optimize their nutrition, reduce their toxic load, and reduce their risk of food allergies— often seeing their blood sugars improve, blood pressures fall, and angina resolve. Three years into my healing, I am again experimenting. This time, it is a real experiment, with an IRB-approved protocol. I am testing my interventions in others with secondary progressive MS. So far, our results are promising. In Science in 2002, Willett7 noted that 70 to 90% of the risk for diabetes, heart disease, cancer, and autoimmunity is due to environmental factors. The genes do not drive most chronic diseases. It is the environment. It is time we stop blaming our genes and focus on the 70% under the individual’s control. That is the real solution to the health care crisis. Corresponding Author: Terry L. Wahls, MD; University of Iowa Carver College of Medicine, Iowa City VA Medical Center, 601 Highway 6 West, Iowa City, IA 52246, USA (e-mail: Terry.Wahls@va . gov). REFERENCES 1. Bourre JM. Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 2: macronutrients. J Nutr Health Aging. 2006;10(5):386–99. 2. Bourre JM. Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients. J Nutr Health Aging. 2006;10(5):377–85. 3. McFadden SA. Phenotypic variation in xenobiotic metabolism and adverse environmental response: focus on sulfur-dependent detoxification pathways 3. Toxicology. 1996;111(1–3):43–65. 4. Cummings AM, Kavlock RJ. Gene-environment interactions: a review of effects on reproduction and development. Crit Rev Toxicol. 2004;34 (6):461–85. 5. Eliaz I, Hotchkiss AT, Fishman ML, Rode D. The effect of modified citrus pectin on urinary excretion of toxic elements. Phytother Res. 2006;20 (10):859–64. 6. Zhao ZY, Liang L, Fan X, et al. The role of modified citrus pectin as an effective chelator of lead in children hospitalized with toxic lead levels. Altern Ther Health Med. 2008;14(4):34–8. 7. Willett WC. Balancing life-style and genomics research for disease prevention. Science. 2002;296(5568):695–8
http://docs.par-tec.com/html/psmpi-userguide/rn01re07.html Name psh — run a command on or copy a file to multiple nodes. Synopsis psh ] psh Description psh runs a command on all or a group of nodes. The output of each command is parsed and common parts are only shown once. With the option -s or -sync, one or more file(s) and/or entire directories (including subdirectories) are synchronized (copied) to the selected nodes. Global options -c, -configfile file Define a group and a configuration file to use. The file is looked up in the current directory. -g, -group group Use nodes and other parameters in group group , defined in the configuration file ~/.psh.d/ group . This is short for of -c ~/.psh.d/ group . -n, -node nodelist Add nodes nodelist to the list of nodes. -x, -xnode nodelist Exclude nodes nodelist from the list of nodes. -rcmd command Use command command to start up a remote command. Command could be pssh (default), rsh or ssh . -diff command Use command command to parse and compare the command output. Default is diff -q. -autocd path Change to directory path on each node before running the command or copying the file. Default is ${PWD/${HOME}/~}. Use an empty path ("") to disable changing to a directory first. -v Be verbose. -h Show a help message. Without option -g or option -c, a default file named like the current hostname, the current hostname without trailing numerical characters ( *), or default (in this order) within ~/.psh.d/ is used. If none of this files is found, an empty template file ~/.psh.d/default is created. This file may be modified to fit your needs! Nodelist is a comma separated list of node names. The list can be abbreviated to node- , e.g. node- will be expanded to node-001 , node-003 , node-004 , ..., node-115 . Examples This example shows a configuration file ~/.psh.d/rack1 defining nodes node-01 up to node-16 within rack number 1: ## psh defaults for rack 1 ## uncomment all options you need... ## default nodelist: # node nodename node node- ## default remote command: # rcmd ssh -x ## don't start more than 1 remote shell at the same time? # max 1 ## be always verbose ? # verbose To see the uptime of all nodes in rack 1, execute # psh -g rack1 uptime In order to compare the current date on all nodes, run date on all nodes: # psh date === node- Mon Jul 18 12:45:17 CEST 2005 === node-05 Mon Jul 18 12:45:18 CEST 2005 To calculate and compare the md5sum of all Linux kernels on all but node node-03, execute: # psh -x node-03 md5sum /boot/vmlinux === node- c9c0728c41ca03a9ee9982869e28216e /boot/vmlinuz === node-05 ff62b57a078f1f8244796c5609a053e8 /boot/vmlinuz To copy the file /etc/hosts to all nodes, execute: # psh -sync /etc/hosts Prepare files for distribution: /tmp/pshout.1235 /etc/hosts Continue (y/n)? (Presuming a suitable configuration file within ~/.psh.d is found.) Note The local file /etc/hosts is also replaced by a copy of this file. To copy the file /etc/hosts to all but the local node, execute: # psh -s -x `hostname` /etc/hosts Prepare files for distribution: /tmp/pshout.1236 /etc/hosts Continue (y/n)? Files ~/.psh.d/* Configuration files for different groups. See also pssh (8) and psmstart (8) .
今天看到Nature Methods一篇关于protein-protein interactions(PPIs)的Y2H的Correspondence和Author Reply，个人认为特别对现今众多研究方法的选择和比较有借鉴意义，所以作以记录分享。 2009年Braun,P在Nature Methods发表一项方法学比较研究( Nat Methods. An experimentally derived confidence score for binary protein-pro.pdf )，比较了5种检测PPIs的方法的tool kit —— 1. The Y2H system ；2. MAPPIT；3. The YFP reconstitution of the PCA assay；4. The LUMIER pull-down assay；5. The completely in vitro performed wNAPPA。 5种kit单独检测92种金标准protein pairs的检出率都不超过36%，每个方法平均检出率只有31.3%，联合检测则达到67.4%。由此，Braun希望能对每个方法检测出的每种protein-protein interactions 作出可信度评价，以重新评估相互作用网络中PPIs的真实情况。 2010年Yu-chi Chen在Nature Methods发表了一个相似结论的Correspondence ( Nat Methods. Exhaustive benchmarking of the yeast two-hybrid system.pdf )，方法是采用5种不同的Yeast Two-Hybrid System(Bait-Prey Vectors)——pGBGT7g-pGADCg；pGBGT7g-pGADT7g；pDEST32-pDEST22； pGBKCg-pGADT7g；pGBKCg-pGADCg，目的是展示出相似蛋白的不同亚型，最后得到与Braun相似的数据是92种金标准protein pairs检出率也只有40%，每个方法的平均检出率为25.3%，联合检测也只达到79.3%。 Chen的目的在于想阐明：其实只要采用不同的Y2H载体，即便是单独Y2H系统就能得到和联合其他4种方法相似的数据；也就是因为这些PPIs检测方法原理上显著性差异，所以未来必须结合 multiple protocols ——可以是Braun描述的different methods，也可以是Chen描述的same method的不同变化。即是他赞成系统间验证，也认为系统内验证也是合理可行的！ Braun在同期的Reply里首先对Chen的工作表示欢迎，和部分肯定。也重新表明了自己希望建立“可信度”的观念， 即一个特定方法检测筛选到的任何protein interaction都必须再经过multiple orthogonal validation assays（多重正交确认试验），筛选和验证实验必须相互独立才能尽可能消除系统假阳性的危险.筛选和验证采用同一试验，即使应用不同的构象，也可能引入这样的系统偏差。 Braun reply 原文 Braun et al. reply: We applaud the thorough and revealing study by Chen et al.in this issue of Nature Methods. The work expands our previous findings in thoroughly characterizing different yeast two-hybrid (Y2H) implementations, with respect to overall assay sensitivity, by testing each implementation against a panel of reference protein-protein interactions. The standardized reference sets make the data easily comparable to our previous analyses and clearly demonstrate that different Y2H assays detect different sub-sets of interacting pairs of proteins. Given the proven utility of using several assay configurations, the next question is where and how to deploy them. The high-throughput capabilities of Y2H make it an ideal primary screening assay. Having multiple versions of Y2H that detect different subsets of interactions will be of a great value to generate more comprehensive data sets, which would then need to be validated using a scheme such as the “confidence scoring” scheme that we proposed. A key concept of our confidence scoring method is that any interaction detected by a given screening assay is subsequently confirmed by multiple orthogonal validation assays. The screening and validation assays must be as independent from each other as possible to eliminate the danger of systematic assay dependent artifacts, which could make protein pairs appear as robustly interacting when they may not be. Use of a single type of assay for both screening and validation, even if implemented in different configurations, may introduce such systematic biases. It is therefore critical to obtain orthogonal validation ideally of all interacting pairs identified in an initial screen.
Controls: 1. positive controls: single staining for each of the target proteins using the appropriate label 2. negative controls: omission of one of the primary antibodies but retaining all of the secondary immunoreagents. 3. so for a double staining experiment, there are four control conditions: A. single immunochemical staining for protein A; B. single immunochemical staining for protein B; C. multiple immunochemical staining, omitting anti-protein A primary antibody; D. multiple immunochemical staining, omitting anti-protein B primary antibody. Protein A Protein B Mouse anti- protein A Goat anti-protein B Rabbit anti- protein A Mouse anti- protein A Correct Incorrect
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