模糊聚类分析在脑功能磁共振图像处理中的应用

模糊聚类分析作为模式识别中的一种重要的分类器，近年来在脑功能磁共振图像的处理与分析领域引起了极大的关注。在脑功能磁共振图像的处理与分析中应用模糊聚类技术需要解决的一个关键问题就是找出适合于脑功能磁共振图像处理的参数，如模糊指数、距离参数和聚类数等。如何寻找合适的参数，从而使得利用模糊聚类技术处理和分析脑功能磁共振图像得到最佳的聚类结果，成了目前模糊聚类技术研究的焦点问题。近年来模糊聚类分析在脑功能磁共振图像处理的应用中如何选择合适的参数问题进行了综述和讨论。     

激素性股骨头坏死中m6A相关基因差异性的鉴定

背景：已知m6A参与了多种疾病的发生与发展，研究推测其也参与了激素性股骨头坏死的病理改变，但m6A甲基化修饰在激素性股骨头坏死中的研究比较匮乏。目的：通过生物信息学的方法寻找m6A相关基因在激素性股骨头坏死中的差异性表达，并预测与其相关的miRNA，以进一步阐明m6A甲基化在激素性股骨头坏死中所发挥的作用和机制。方法：从GSE123568基因表达谱中分析激素性股骨头坏死与对照组差异基因的表达，通过R语言‘limma’包进行差异基因鉴定，并对差异基因进行功能富集分析。用R语言的‘ggstatsplot’包对相关基因进行差异性分析。通过GSE74089数据集对差异基因进行交叉验证。构建mRNA-miRNA调控网络。采用共表达分析对共表达模块进行聚类并对模块基因进行富集分析。采用ssGSEA方法对激素性股骨头坏死与对照组之间免疫细胞浸润的差异进行量化分析。结果与结论：(1)通过相关性分析发现13个m6A相关基因，进行PPI网络识别和受试者操作特征曲线进一步分析发现YTHDF2有望成为早期生物标志物的核心差异基因；(2)富集分析发现差异基因主要参与炎症反应和免疫应答，并与破骨细胞关系密切；(3...     

基于摄动思想的中医处方模糊聚类分析

基于信息技术的中医方剂自动分析,对中医经验的挖掘和传承具有重要意义.本文采用基于摄动思想的模糊聚类方法,对中医方剂进行了聚类分析研究.其中首先对方剂各味药的性味归经毒性进行模糊化处理,然后将基于传递闭包的摄动思想应用到方剂药群的聚类分析.然后以小柴胡汤的聚类分析为例,将此方法与传统的传递闭包矩阵聚类方法进行了比较.实验结果表明,与传统的传递闭包矩阵的模糊聚类方法相比,基于摄动思想模糊的聚类方法效果更好,可以更加客观地反映中医处方组方原则,对于方剂分析具有较好的指导意义.     

利用转录因子结合位点的基因调控区序列比较

利用DNA中转录因子结合位点分布的序列比较方法对DNA序列进行聚类,并分析基因之间的联系.运用Matlab工具结合TRANSFAC数据库中的数据,对一组基因芯片共调控基因的上游序列进行比较和聚类,获得能够反映基因关系的树状聚类结果,从中确定出具有共同功能特征的基因,揭示了在大骨节病相关的诸多基因中,基因CIDEA、CYP4V2、RHBDD3、ENC1的调控区域有共同序列特征,表达模式和调控机理最为相似.这为更深层次的基因功能分析提供了依据.     

主要过敏原的物种分布及逐步聚类分析

目的 综合分析数据库中过敏原的总体状况，在剖析重组过敏原研究领域的共性问题后，对主要过敏原进行聚类分析，为重组过敏原的深入研究指明方向。方法 以国际免疫学联合会过敏原命名分会公布的正式过敏原名录表为原始数据，对过敏原的物种分布特点进行分析，并采用Kolmogorov-Smironov检验对过敏原类型分布与相应的物种分布的一致性进行检验；针对氨基酸序列数据，采用ClustalW 1．83及MEGA2等生物信息学软件，辅之以手动缩减，对来自公共数据库中的主要过敏原进行逐步聚类分析，以获得代表性过敏原。结果 过敏原物种分布分析显示，510个过敏原归属于9大类共179个物种，不同类型过敏原所涉及的物种数及过敏原例数产生的两类分布相同；用关键词在蛋白质数据库中搜索得到的60条主要过敏原序列，聚类成有着明显差异的7个簇后，逐步聚类缩减到21个氨基酸序列无任何相关的代表性过敏原。结论 过敏原的研究是依所涉及的物种不同而逐步平行地展开，没有明显的物种或过敏原的侧重点；依据氨基酸序列的相似性，可以将不同物种来源的主要过敏原缩减到少数代表性过敏原上，从而减少重组过敏原的工作量。     

吉兰-巴雷综合征相关空肠弯曲菌WLAX基因序列分析

目的了解吉兰-巴雷综合征(GBS)相关空肠弯曲菌的WLAX基因序列特征,为进一步研究GBS相关空肠弯曲菌的分子致病机制打下基础。方法通过PCR方法对该基因进行扩增,将PCR产物克隆到质粒载体上,然后进行测序,将测序结果通过DNAstar软件进行比较和聚类分析。结果与非GBS相关空肠弯曲菌比较,GBS相关空肠弯曲菌的WLAX核苷酸序列发生变异的频率增大;菌株的核苷酸序列与全基因测序空肠弯曲菌NCTC11168比较存在差异;聚类关系反映了空肠弯曲菌具有一定的区域特征。结论GBS相关空肠弯曲菌中WLAX基因发生突变的概率明显增大,这些突变与GBS致病性的关系有待于进一步确定。     

点对称距离模糊C均值聚类算法在脑部MRI图像分割中的应用

背景：在传统的图像分割方法中,模糊C均值聚类算法应用十分广泛。 目的：将改进的模糊C均值聚类算法应用到MRI图像的分割中,提高MRI图像分割的准确度。 方法：针对传统的基于Minkowski距离的模糊C均值聚类算法,提出了基于点对称距离的模糊C均值聚类算法,并将其运用到了脑部MRI图像分割中。 结果与结论：实验结果表明,与模糊C均值聚类算法相比,点对称距离的模糊C均值聚类算法有明显的优势。     

基于流形学习的聚类方法在基因芯片表达谱分析中的应用

对基因芯片表达谱的聚类分析有助于发现共表达的基因,而共表达的特性往往是共调控基因所拥有的性质。因此,对基因表达谱的准确聚类将有利于更加准确地发现基因之间的调控关系。本研究使用机器学习中的等度规映射、局部线性嵌入、拉普拉斯特征根映射等流形学习方法处理基因表达谱数据,得到非线性降维后的数据。在此基础上应用K均值聚类、模糊聚类、自组织映射神经网络等聚类方法,根据给定的阈值,从酵母基因表达数据的382个聚类结果中得到了117个共表达基因对,而从人类血清组织细胞的基因表达数据的132个聚类结果中得到了89个共表达基因对。使用的判别准则表明,基于流形学习的聚类方法与以往的方法相当,且能够被用以发现高维基因芯片表达数据中的低维的流形结构。     

单次事件相关电位聚类分析

本文用模糊神经网络对意境欠事件相关电位进行聚类分析，并提出应用奇异值分解确定最佳聚类数的通用新方法，结果显示它们构成了提取和压缩ＳＥＲＰ动态信息的有效方法 。     

SACNet:一种癌症网络合成与分析系统

目的针对目前癌症的疾病网络构造的片面性和不精确性,提出一个基于集成多种数据源的癌症网络构造分析辅助工具系统。方法基于KEGG数据库的癌症生物通路和DisGeNET数据库的基因疾病关系等数据源,利用生物通路差异分析方法结合癌症基因表达数据获取差异通路集合,集成网络可视化工具生成癌症网络,结合网络聚类分析方法给出聚类分析结果,并对聚类分析结果进行基因功能聚类,分析癌症聚类子网络在癌症中的生物学功能。结果该工具系统生成的癌症网络以及聚类得到的网络分析结果能较准确反映出癌症和致病基因之间的联系。结论该系统界面友好,人机交互性好,可以有效辅助科研人员工作,对探寻癌症内部致病机制具有价值和意义。     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

Hypo- und Hypermagnesämie aus kardiologischer Sicht

Zusammenfassung Eine Reihe pathologischer Zustände bedingen Magnesiummangel. Zustände mit Hypermagnesämie sind ebenfalls bekannt, doch wesentlich seltener. Für den Kardiologen beachtenswert ist, daß unter Therapie mit bestimmten Diuretica bei Herzinsuffizienz, bei Herzinfarkt, Kardiomyopathie, Digitalisintoxikation und bestimmten Herzrhythmusstörungen Hypomagnesämie beobachtet wurde. Leider kann in der klinischen Routine nur ein extracelluläres Magnesiumdefizit durch Serumbestimmungen gemessen werden; über Magnesiummangel einzelner Organe kann nichts ausgesagt werden. Hinweise für Magnesiummangel geben aber neben der Messung des Serumspiegels Anamnese, klinischer Befund, bestimmte EKG-Veränderungen wie auch evtl. Hypokalämie, ein Zustand, bei dem sich oft — besonders bei Aldosteronismus — parallele Veränderungen zeigten.Tierexperimente deuten darauf hin, daß infarktähnliche Läsionen unter Magnesiummangel entstehen, doch ob Herzinfarkt beim Menschen durch Magnesiummangel ausgelöst werden kann, ist noch ungeklärt. In Leichenherzen zeigte sich im Infarktgebiet neben Calciumakkumulation signifikanter Magnesiumverlust, wobei unklar blieb, ob sich Ursache oder Folge des Infarktes widerspiegelten. Falls ein ursächlicher Zusammenhang besteht, ist er im Myokardstoffwechsel selbst zu suchen, wie bei der Alkoholkardiomyopathie, wo myokardialer Magnesiummangel zumindest als pathogenetischer Teilfaktor anerkannt wird. Andererseits versucht man aber auch Beziehungen zwischen Atherosklerose, Blutgerinnung und Hypomagnesämie herzustellen, in der Meinung, daß Magnesiummangel auch über den coronaren Pathomechanismus des Herzinfarktes wirken könnte. Sicher scheint, daß gewisse EKG-Veränderungen und Herzrhythmusstörungen durch einen irritierten Magnesiumhaushalt bedingt sein können, da sie bei Gabe bzw. Entzug von Magnesium verschwinden. Daß Magnesiummangel die Glykosidtoleranz verringert, wird tierexperimentell bestätigt. Unter Hypomagnesämie bewirkt Acetylstrophanthidin eher und länger Rhythmusstörungen als ohne, außerdem lassen diese sich durch Magnesiumgaben eliminieren. Da in gewissen Fällen spontane und digitalisinduzierte Herzrythmusstörungen durch Magnesiuminjektionen beseitigt wurden, scheint Magnesium als Therapeuticum angebracht. Einsatz verschiedener Magnesiumsalze bei Angina pectoris, degenerativen Herzerkrankungen und Herzinsuffizienz ohne geprüften und offensichtlich gestörten Magnesiumhaushalt ist fragwürdig, weil keine eindeutigen klinischen Erfolgsbeweise vorliegen. Immerhin mag es aber larvierte, durch Serumbestimmungen nicht erfaßbare Mangelzustände geben. Allgemein erscheint es aus kardiologischer Sicht ratsam, den Magnesiumhaushalt zu überwachen und in entsprechenden Fällen auszugleichen, um möglichen Myokardläsionen oder fatalen Herzrhythmusstörungen entgegenzuwirken.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.