Two Methods for Identifying Wiener Cascades Having Noninvertible Static Nonlinearities

Two methods are proposed for identifying the component elements of a Wiener cascade that is comprised of a dynamic linear element (L) followed by a static nonlinearity (N). Both methods avoid potential problems of instability in a procedure presented by Paulin [M. G. Paulin, Biol. Cybern. 69: 67–76, 1993], which itself is a modification of a method described earlier by Hunter and Korenberg [I. W. Hunter and M. J. Korenberg, Biol. Cybern. 55: 135–144, 1996]. The latter method is a rapidly convergent iterative procedure that produces accurate estimates of the L and N elements from short data records, provided that the static nonlinearity N is invertible. Subsequently, Paulin introduced a modification that removed this limitation and enabled identification of Wiener cascades with nonmonotonic static nonlinearities. However, Paulin presented his modification employing an autoregressive moving average (ARMA) model representation for the dynamic linear element. To remove the possibility that the estimated ARMA model could be unstable, we recast the procedure by utilizing instead a rapid method for finding an impulse response representation for the dynamic linear element. However, in this form the procedure did not have good convergence properties, so we introduced two key ideas, both of which provide effective alternatives for identifying Wiener cascades whether or not the static nonlinearities therein are invertible. The new procedures are illustrated on challenging examples involving high-degree polynomial static nonlinearities, of odd or even symmetry, a high-pass linear element, and output noise corruption of 50%. © 1999 Biomedical Engineering Society. PAC99: 8710+e, 0210Nj, 0250-r     

The Heritability of Depression Symptoms in Elderly Danish Twins: Occasion-Specific Versus General Effects

Depression symptomatology was assessed up to four times at 2-year intervals on a sample of 2100 Danish twins initially aged 70 years and older. Data were analyzed using the biometric growth model approach proposed by Neale and McArdle (2000). Results show that occasion-specific depression is moderately and equally heritable in men and women (occasion-specific estimates of heritability ranged from 22% to 37%). Estimates of phenotypic variance, genetic variance, and heritability did not vary systematically across waves. In the best-fitting growth model, depression symptomatology was accounted for by two factors: (1) a level (i.e., average) effect that was highly heritable (estimate of 69% in women and 64% in men) and reflected overall vulnerability, and (2) a residual effect that was nonheritable and reflected occasion-specific circumstances that could either exacerbate or moderate inherited vulnerability. Attempts to identify specific genetic contributions to depression might profitably focus on average levels across multiple assessments, while attempts to identify specific environmental effects might profitably focus on deviations about this average.     

小鼠巨细胞病毒模型的建立

目的为了探讨巨细胞病毒的致病机理。方法４周龄Ｂａｌｂ／Ｃ小鼠腹腔内接种小鼠巨细胞病毒（ＭＣＭＶ）。结果导致小鼠急性感染期体重下降，生长迟缓，唾液腺肿胀以至于死亡。唾液腺中检出高滴度感染性病毒（２．０×１０５ＰＦＵ／ｍｌ）。在小鼠３Ｔ３／Ｓｗｉｓａｌｂｉｎｏ细胞单层上形成的空斑清晰，易判断计数、镜检组织切片可见脑神经原细胞胞浆内包涵体。结论小鼠巨细胞病毒模型的建立为抗－ＣＭＶ有效药物的筛选以及对ＣＭＶ感染的预防、治疗提供了资料。     

人行走时骨盆上下运动参数的模型分析

为了研究正常人行走过程中骨盆在垂直方向的运动特征,提出了一种以测量数据为基础建立骨盆运动参数数学模型的新思想。介绍了基于跑步机的骨盆运动轨迹测量系统,并对30名健康男性青年进行了获取骨盆运动参数的实验研究。实验结果得到了不同受试者分别以不同速度行走时的骨盆在垂直方向的多组运动轨迹,以及运动幅值、周期、初始相位等与行走速度和受试者身高的关系曲线。通过对曲线拟合,建立了各参数及骨盆运动轨迹的数学模型。通过对该模型进一步完善,可使其对康复评定、类人机器人等领域具有一定的应用价值。     

Development and testing of a simple algorithm for a glucose clamp

The glucose clamp technique is widely used in clinical research studies to maintain a constant blood glucose (BG) level during metabolic perturbation. An algorithm is used to set the rate of an intravenous glucose infusion according to measured BG concentrations. Currently used clamp algorithms are unnecessarily complex. This paper describes the development and use of a new algorithm which is simpler to implement. The algorithm employs proportional and differential feedback control. Discrete BG sampling with a sampling period of 5 min is used. Computer simulation with a two-compartment model of glucose dynamics was used to refine the algorithm. A Monte Carlo approach was adopted to examine the effects of random variations in measured BG concentrations and the elapsed time between blood sampling and adjustment of the glucose infusion rate. A coefficient of variation in BG concentration of less than 4 per cent was predicted for a euglycemic clamp. This was confirmed when the algorithm was applied in clinical research studies. This degree of BG control compares well with other published algorithms.     

Afferent axons and their relations with neurons in the nucleus lateralis of the cerebellum: A light microscopic study

Summary The axons of Purkinje cells are the sole corticonuclear afferents to the lateral nucleus. The terminal arborizations of these axons consist of many (30–50) varicose branchlets, which issue from a thick, myelinated parent axon. Each terminal plexus fills a conical field which penetrates the lateral nucleus radially encompassing the cell bodies and parts of the dendritic trees of approximately 40 neurons. The fields of neighboring Purkinje axons overlap considerably. The non-cortical axons are simple, usally unbranched varicose fibers of three sizes: (1) thick, with large varicosities, (2) medium sized with smaller varicosities, or (3) fine, delicate threads with beadlike varicosities. These axons cross the dendritic trees of successive neurons as they penetrate into the nucleus in a radial fashion.The configuration of the dendritic trees of neurons in the various parts of the nucleus—the multipolar neurons and the columnar neurons—can be related to the conical shape of the Purkinje axonal plexus. It is suggested that the organization of converging Purkinje cell axonal fields determines the pattern of input to the cells of the lateral nucleus, rather than the topographical arrangement of Purkinje cells in the cortex. The terminal arborizations of Purkinje cell axons adjacent to one another in the lateral nucleus need not necessarily arise from neighboring Purkinje cells in the cerebellar cortex.The relationships between neurons in the central columnar zone and in the swirled zones of the lateral nucleus with the two classes of afferents are discussed. It is suggested that by virtue of their slender profiles, each of the large columnar neurons falls into the field of one Purkinje cell axonal cone whereas elsewhere, the multipolar neurons tend to share their well spread dendrites with neighboring Purkinje axonal fields. The small neurons that span columns in the central zone are oriented to sample larger numbers of axonal inputs than are adjacent columnar neurons.Supported in part by U.S. Public Health Service Research Grants NS10536, NS03659, Training Grant NS 05591 from the National Institute of Neurological Diseases and Stroke, and a William F. Milton Fund Award from Harvard University.     

The immunology of primary biliary cirrhosis: the end of the beginning?

The chronic liver disease primary biliary cirrhosis (PBC) is characterised by autoreactive B‐cell and T‐cell responses directed against mitochondrial antigens. In recent years these responses have been extensively characterised and the principal PBC associated autoantigen identified as pyruvate dehydrogenase complex (PDC). The identification of anti‐PDC responses (present in over 95% of PDC patients) has given rise to important questions pertinent to our understanding of the pathogenesis of PBC. What specific role to anti‐PDC responses play in target cell damage? How and why does immune tolerance break down to as highly conserved and ubiquitously expressed self‐antigen as PDC? Why does breakdown in tolerance to an antigen present in all nucleated cells result in damage restricted to the intra‐hepatic bile ducts? In attempting to answer these key questions we have, in this review, proposed a unifying hypothesis for the pathogenesis of PBC.     

Effect of resistive discontinuities on waveshape and velocity in a single cardiac fibre

A computer model of a one-dimensional cardiac fibre of resistively coupled cells is used to investigate the influence of the junction resistance on the nature of conduction. The results of the simulations are presented and indicate that the effect of the junction on both intracellular and extracellular waveshape and on the velocity of propagation depends on the size and frequency of the coupling resistance and the kinetics of the active membrane. Significant changes in these factors are not observed without the generation of prepotentials in the action potential upstroke. The absence of this ‘signature’ in microelectrode recordings of activity in ventricular muscle suggests that under normal conditions cardiac tissue behaves as a functional syncytium.     

Lack of Autoimmune Serological Reactions in Rodent Models of Insulin Dependent Diabetes Mellitus

Spontaneous insulitis with insulin-dependent diabetes mellitus (IDDM) in rodent models, the BB rat and NOD mouse, has clarified the pathogenesis of and guided decisions on interventional therapy for human IDDM. However, the occurrence in such models of a standard marker of human IDDM, autoantibodies to β islet cell constituents, has been controversial. Hence we assessed diabetes-prone rodents for the frequencies of raised levels of auto-antibodies to glutamic acid decarboxylase GAD (anti-GAD), insulin and heat shock protein 65 (HSP-65) in relation to levels in non-diabetes-prone animals and levels in human diabetic sera. Assays were performed sequentially at various ages of life. The immunoassays used for anti-GAD and anti-insulin were those validated for sensitivity and specificity for detection of the corresponding autoantibodies in human IDDM sera at international workshops. Positive controls included human IDDM sera with reactivity with GAD or insulin and, for mouse anti-GAD, the highly reactive monoclonal antibody, GAD-6. The results were that levels of autoantibodies in diabetes-prone BB rats or NOD mice to the ‘IDDM-relevant’ autoantigens in our panel did not exceed levels in control rats or mice, and were much lower than levels in humans with IDDM. We conclude that the BB rat and NOD mouse represent a model, but not a facsimile, of human IDDM and that therapeutic successes in such models should be interpreted with caution in relation to interventional therapy for human IDDM.     

Turning point in the design of linkage studies of schizophrenia

Despite extensive genomic scans, linkage studies of multiplex pedigrees have been unable to produce replicable evidence of genes predisposing to schizophrenia. This indicates that it is unlikely that a single gene accounts for a majority of cases of schizophrenia, even in multiplex pedigrees. It is most likely that schizophrenia is caused by the nonlinear interaction of multiple genetic and environmental factors influencing brain development and function. This conclusion has strong implications for the design of linkage and association studies. Recently designed linkage studies involve several improvements to deal with extensive locus heterogeneity and multiplicative interaction. These improvements include much larger samples of pedigrees, systematic ascertainment and sequential extension rules, and standardized procedures at multiple sites to facilitate collaboration and replication. Future improvements are likely to require advances in the assessment of clinical and neurobiological variability in multiplex pedigrees, more systematic environmental assessment, and advances in analytic methods to deal with multiplicative interaction. Rather than focusing only on schizophrenia as one or more discrete disorders, future linkage efforts should also consider the etiology of individual clinical syndromes or dimensional components of risk that interact to cause the complex pattern of syndromal comorbidity observed within schizophrenics and their families. © 1994 Wiley-Liss, Inc.