基于体外阻抗测量的恶性胶质瘤介电特性

目的研究脑胶质瘤生物电阻抗特性,探索出恶性胶质瘤组织与正常脑组织的特征性电参数,为区分恶性胶质瘤与正常脑组织提供依据。方法基于四电极法阻抗测量设计了一种体外阻抗测量传感器,利用普林斯顿阻抗分析仪Versa STAT3对10例裸鼠脑胶质瘤和脑组织进行阻抗测量,并对20Hz~250 k Hz范围内阻抗频谱特性曲线进行定量分析;结合生物阻抗谱理论,建立体外脑胶质瘤等效电路模型,并利用ZSimp Win对等效阻抗电路进行拟合仿真,以探讨脑胶质瘤在阻抗电路中的特性。结果胶质瘤的阻抗模值在20 Hz~250 k Hz范围内随频率的增大而减小,幅值曲线在200 Hz和50 k Hz附近各存在一个斜坡,这两个斜坡的斜度都小于对应的正常鼠脑组织的斜度。10组裸鼠体外实验中,胶质瘤和脑组织的虚部-实部图中有两个时间环节,可以用两个时间常数的等效电路代替,并且电路元件中的参数R1对于胶质瘤和脑组织差异明显。结论体外鼠脑胶质瘤与正常脑组织可以用阻抗特性曲线的斜坡值进行定量区别。此外,等效电路电参数中的R1也可以作为一个区分胶质瘤和脑组织的指标,这为临床检测和区分胶质瘤组织开拓了新的研究思路。     

基于核磁共振扩散张量成像技术的脑组织3D分割算法研究

无论在临床诊断上还是在脑电/脑磁研究中,脑组织的准确分割都具有重要的作用.由于DT-MRI比传统MRI能够提供更多的关于脑组织生理结构特性的物理信息,所以基于DT-MRI的分割将更加准确有效.基于扩散张量核磁共振成像技术,提出把脑内部分割成灰质、白质、脑脊液3种组织的新方法,对脑脊液采用扩散张量特征值阈值法进行分割,对白质与灰质采用3D不变参数均值聚类算法进行分割.在Matlab 7.1环境下,采用该方法对病人DT-MRI数据进行实际计算验证,得到较好的结果.对DT-MRI张量空间的准确分割,需要高效率算法与不同脑组织生理结构特性先验知识的有机结合.     

由水分子扩散张量计算脑组织电导率张量的新方法

脑组织电导率在脑电/磁研究中是一个重要参数.为了获取脑组织电导率,本研究利用扩散张量成像(DTI)技术,从电化学角度出发,提出了基于Stokes-Einstein与Nernst-Einstein方程的计算脑组织电导率的一种新方法,以三个正交方向上的电导率作为不同脑组织的电导率张量特征值.在人体头部DTI数据上进行计算,并与不同脑组织(白质、灰质、脑脊液)的经验电脑率值进行了对比,发现扩散各向异性越严重的组织,其电导率张量特征值偏离经验值越远,进一步证明了在脑电,磁计算中要考虑脑组织电导率各向异性的必要性.所提出的方法,基于扩散张量,考虑脑液体中各种离子浓度等因素,为获取脑组织各向异性电导率分布提供了一种新的有效途径.     

生物组织光学层析成像技术的理论研究

本文发展了一种能实现生物组织光学层析成像的理论。文中建立了光在生物组织中的散射模型，并利用格林函数法分析了问题的数学基本解的形式，得到了问题的初始值的解析表达式。利用偏微分方程特征线传播的方法，可以把问题的边界值（即测量值）传递给每层的初始值。然后结合初始值的解析形式，构造出一个目标函数，即可把逐层重构组织光学特性参数的问题转化为逐层控制参数使目标函数具有极小值的优化问题，从而逐层地重构出生物组织的光学特性参数。利用组织光学特性参数重构的结果，借助于计算机的图象处理技术，就可进一步得到组织内部的光学层析结构图象。本文最后给出了一个计算机数值仿真解。     

基于ANSYS/LS-DYNA的神经电极植入脑组织过程数值仿真

目的建立神经电极-脑组织数值仿真模型,研究神经电极在植入过程中对脑组织产生的植入损伤。方法采用超黏弹性模型描述脑组织材料,基于单元删除法和最大主应变失效准则模拟组织破坏与分离,并通过平均等效应变量化组织植入损伤,考察神经电极楔形角、植入速度以及电极刚度对脑组织急性损伤的影响规律。结果150°楔角所产生应变值较90°增加37.1%;100μm/s慢速植入时电极植入路径上组织应变值较大(57%),500μm/s较高速植入时植入路径上组织应变明显变小(25%);而电极刚度对组织损伤影响不明显,电极刚度从165 GPa下降至5 k Pa时,组织应变仅增加1%~2%。结论数值仿真模型可为神经电极与植入参数设计提供参考,从而减少组织植入损伤,提高电极工作寿命,满足长期临床应用。     

上海脑库脑组织样本的质量控制分析

目的 通过对脑脊液pH值、脑组织RNA完整值（RIN）、转录组和蛋白质组检测以及形态学观察,评估上海脑库收集的脑组织用于后续生物学研究的可行性。方法 使用pH试纸检测新鲜脑脊液pH值;使用安捷伦RNA 6000 Nano芯片和2100生物分析仪对低温冻存的脑组织RNA进行完整性检测;使用BGIseq-500测序仪对低温冻存的颞上回（STG）或尾状核（CN）进行转录组测序;使用Q Exactive HF质谱仪对低温冻存脑组织进行蛋白质组分析;使用HE染色观察STG的形态学。结果 捐献脑组织样本的脑脊液pH值在6.5左右;65%以上的低温冻存脑组织的RIN>6,RNA质量较好;转录组测序过滤后clean reads比值>20或30的碱基数占总碱基数比例基本达到80%以上,表明文库质量较高;质谱分析得到超过4000个蛋白质组,3万多个肽段,说明蛋白数据质量较好;脑组织形态学较为正常,能清晰观察到神经元形态。结论 上海脑库脑组织样本的RNA和蛋白质质量能用于开展分子生物学相关研究,并可用于形态学观察。     

高散射组织中光传播的门德卡诺模型—Ⅰ:模型预测与扩散理论的比较

随着医用光学仪器的发展迫切要求建立有关人体组织的光学摸型,如组织对光的吸收与散射系数。该模型是建立在可测量的参数的基础上包括表面辐射与扩散反射系数。在光动力学理论中要求了解光在组织间传播的特性,然而要想在多点对光     

患有明显边界线肿瘤的生物组织中光输运的蒙特卡罗法模拟

用蒙特卡罗（ＭＯＮＴＥＣＡＲＬＯ）方法模拟了患有肿瘤的正常生物组织中的光输运过程。为了计算的方便，假设肿瘤具有明确的边界线和简单的几何形态。利用模拟计算的结果，本文研究了生物组织在一定光入射情况下的表面漫反射光分布和组织内部光分布的特点。光分布的情况依赖于组织内部光学特性参数的分布，因而直接与组织的内部结构有关。表面漫反射光分布和组织内部光分布的特点反映了组织几何结构的有关情况     

基于ANSYS/LS-DYNA的神经电极植入脑组织过程数值仿真

目的 建立神经电极-脑组织数值仿真模型,研究神经电极在植入过程中对脑组织产生的植入损伤。方法 采用超黏弹性模型描述脑组织材料,基于单元删除法和最大主应变失效准则模拟组织破坏与分离,并通过平均等效应变量化组织植入损伤,考察神经电极楔形角、植入速度以及电极刚度对脑组织急性损伤的影响规律。结果 150°楔角所产生应变值较90°增加37.1%;100 μm/s慢速植入时电极植入路径上组织应变值较大（>57%）,500 μm/s较高速植入时植入路径上组织应变明显变小（<25%）;而电极刚度对组织损伤影响不明显,电极刚度从165 GPa下降至5 kPa时,组织应变仅增加1%~2%。结论 数值仿真模型可为神经电极与植入参数设计提供参考,从而减少组织植入损伤,提高电极工作寿命,满足长期临床应用。     

基于漫射光子密度波的硬质仿体光学参数的测量

本研究制作了与组织光学参数相近的硬质仿体作为研究对象,使用漫射光子密度波(diffuse photon density waves,DPDW)技术,设计了一个基于DPDW的硬质仿体光学参数测量系统。由网络分析仪在300 KHz~1 MHz频率范围内对激光器进行交流调制,在与光源间隔1 cm处接收漫射光子,经过解调获得幅值与相位的数据。利用光辐射方程对获取的数据进行曲线拟合,进而得到硬质仿体的吸收系数和约化散射系数。实验结果表明,对3种不同吸收系数的硬质仿体的检测中,μa和μ's的检测最大误差分别为0.282、0.003 cm-1,平均相对误差分别为19.8%、23.7%,吸收系数检测结果的相关系数为0.999。测量精度满足常规生物组织光学特性测量要求,本系统将在硬质仿体的检测以及生物组织检测等领域发挥重要作用。     

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.