Showing papers by "University of California, Irvine published in 1995"

Bayesian Data Analysis

Abstract: FUNDAMENTALS OF BAYESIAN INFERENCE Probability and Inference Single-Parameter Models Introduction to Multiparameter Models Asymptotics and Connections to Non-Bayesian Approaches Hierarchical Models FUNDAMENTALS OF BAYESIAN DATA ANALYSIS Model Checking Evaluating, Comparing, and Expanding Models Modeling Accounting for Data Collection Decision Analysis ADVANCED COMPUTATION Introduction to Bayesian Computation Basics of Markov Chain Simulation Computationally Efficient Markov Chain Simulation Modal and Distributional Approximations REGRESSION MODELS Introduction to Regression Models Hierarchical Linear Models Generalized Linear Models Models for Robust Inference Models for Missing Data NONLINEAR AND NONPARAMETRIC MODELS Parametric Nonlinear Models Basic Function Models Gaussian Process Models Finite Mixture Models Dirichlet Process Models APPENDICES A: Standard Probability Distributions B: Outline of Proofs of Asymptotic Theorems C: Computation in R and Stan Bibliographic Notes and Exercises appear at the end of each chapter.

Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics.

Abstract: Background: Up-regulation of γ-aminobutyric acid A (GABA A ) receptors and decreased GABA uptake in the cerebral cortex of schizophrenics suggest altered GABAergic transmission, which could be caused by primary disturbance of GABA synapses or by decreased production of the transmitter. Decreased production could be due to a shutdown in GABA production or to loss of GABA neurons caused by cell death or their failure to migrate to the cortex during brain development. Methods: To discriminate between these possibilities, we quantified levels of messenger RNA (mRNA) for the 67-kd isoform of glutamic acid decarboxylase (GAD), the key enzyme in GABA synthesis, and the number and laminar distribution of GAD mRNA-expressing neurons in the dorsolateral prefrontal cortex (DLPFC) of schizophrenics and matched controls, using in situ hybridization-histochemistry, densitometry, and cell-counting methods. These data were compared with the total number of neurons, the number of small, round or ovoid neurons 8 to 15 µm in diameter, and overall frontal lobe volume. As a control, mRNA levels for type II calciumcalmodulin-dependent protein kinase (CamIIK) were quantified. Results: Schizophrenics showed a pronounced decrease in GAD mRNA levels in neurons of layer I (40%) and layer II (48%) and an overall 30% decrease in layers III to VI. There were also strong overall reductions in GAD mRNA levels. The CamIIK mRNA levels showed no significant differences between samples. No differences were found in the total number of neurons nor in small, round or ovoid neurons, which should include a majority of the GABA cells. Prefrontal gray and white matter volume did not differ significantly between controls and schizophrenics. The prefrontal cortex of schizophrenics shows reduced expression for GAD in the absence of significant cell loss. This may be brought about by an activitydependent down-regulation associated with the functional hypoactivity of the DLPFC. The lack of significant alterations in cell numbers in the DLPFC and frontal lobe volume in schizophrenics also implies that overall cortical neuronal migration had not been compromised in development. Previous reports of altered neuronal distribution in the subcortical white matter of schizophrenic brains in comparison with that of controls may indicate disturbances of migration or programmed cell death in the cortical subplate, leading to altered connection formation in the overlying cortex of schizophrenics and activity-dependent down-regulation of neurotransmitter-related gene expression. Conclusions: The prefrontal cortex of schizophrenics shows reduced expression for GAD in the absence of significant cell loss. This may be brought about by an activity dependent down-regulation associated with the functional hypoactivity of the DLPFC. The lack of significant alterations in cell numbers in the DLPFC and frontal lobe volume in schizophrenics also implies that overall cortical neuronal migration had not been compromised in development. Previous reports of altered neuronal distribution in the subcortical white matter of schizophrenic brains in comparison with that of controls may indicate disturbances of migration or programmed cell death in the cortical subplate, leading to altered connection formation in the overlying cortex of schizophrenics and activity-dependent down-regulation of neurotrans mitter-related gene expression.

Studying context: a comparison of activity theory, situated action models, and distributed cognition

Abstract: It has been recognized that system design will benefit from explicit study of the context in which users work. The unaided individual divorced from a social group and from supporting artifacts is no longer the model user. But with this realization about the importance of context come many difficult questions. What exactly is context? If the individual is no longer central, what is the correct unit of analysis? What are the relations between artifacts, individuals, and the social groups to which they belong? This chapter compares three approaches to the study of context: activity theory, situated action models, and distributed cognition. I consider the basic concepts each approach promulgates and evaluate the usefulness of each for the design of technology. (http://www.ics.uci.edu/~corps/phaseii/nardi-ch4.pdf)

Bridged polysilsesquioxanes. highly porous hybrid organic-inorganic materials

Abstract: This contribution reviews a new family of inorganic-organic hybrid materials that are assembled by sol-gel polymerization of polyfunctional molecular building blocks. These bridged polysilsesquioxanes are three-dimensional network materials that are distinguished by incorporation of an organic fragment as an integral component of the network. The intimate association of the organic and inorganic phase, a true molecular composite, coupled with the variability of the organic component, permits engineering of both chemical and physical properties of the material. The paper reviews bridged polysilsesquioxanes, arylene-bridged polysilsesquioxanes, alkylene-bridged polysilsesquioxanes; and their applications.

The Drosophila Tumor Suppressor Gene Warts Encodes a Homolog of Human Myotonic Dystrophy Kinase and Is Required for the Control of Cell Shape and Proliferation

Abstract: Homozygous loss of the warts (wts) gene of Drosophila, caused by mitotic recombination in somatic cells, leads to the formation of cell clones that are fragmented, rounded, and greatly overgrown compared with normal controls. Therefore, the gene is required for the control of the amount and direction of cell proliferation as well as for normal morphogenesis. The absence of wts function also results in apical hypertrophy of imaginal disc epithelial cells. Secretion of cuticle over and between the domed apical surfaces of these cells leads to a honeycomb-like structure and gives the superficial wart-like phenotype of mitotic clones on the adult. One wts allele allows survival of homozygotes to the late larval stage, and these larvae show extensive imaginal disc overgrowth. Because of the excess growth and abnormalities of differentiation that follow homozygous loss, we consider wts to be a tumor suppressor gene. The wts gene is defined by the breakpoints of overlapping deficiencies in the right telomeric region of chromosome 3, region 100A, and by lethal P-element insertions and excisions. It encodes a protein kinase that is most similar to human myotonic dystrophy kinase, the Neurospora cot-1 protein kinase, two cell-cycle regulated kinases of yeast, and several putative kinases from plants. These proteins define a new subfamily of protein kinases that are closely related to but distinct from the cyclic AMP-dependent kinases. Although myotonic dystrophy is defined by a neuromuscular disorder, it is sometimes associated with multiple pilomatrixomas, which are otherwise rare epithelial tumors, and with other tumors including neurofibromas and parathyroid adenomas. Our results raise the possibility that homozygous loss of the myotonic dystrophy kinase may contribute to the development of these tumors.

A resource‐based approach to the multibusiness firm: Empirical analysis of portfolio interrelationships and corporate financial performance

Abstract: The resource-based view of the firm has provided important new insights into corporate strategy (Barney, 1991; Peteraf, 1993); however, there has been only limited empirical research linked to the theory (e.g., Farjoun, 1994). Although a great deal of work has been done on Corporate diversification, the measures and data typically have a weak connection to resource-based theory. Empirical research on resource-based corporate strategy has been particularly dificult because key concepts such as tacit knowledge or capabilities resist direct measurement. This study is an effort to narrow the gap between theory and empirical research on the multibusiness firm. It develops a resource-based approach to modeling interrelationships among businesses and applies it to the analysis of corporate economic performance. This approach proves to be significant in explaining the financial performance of large manufacturing firms, and it promises to be an important source of insight into corporate strategy.

Clostridium difficile-associated diarrhea and colitis

Abstract: Objectives To review and summarize the status of diagnosis, epidemiology, infection control, and treatment of Clostridium difficile-associated disease (CDAD). Diagnosis A case definition of CDAD should include the presence of symptoms (usually diarrhea) and at least one of the following positive tests: endoscopy revealing pseudomembranes, stool cytotoxicity test for toxin B, stool enzyme immunoassay for toxin A or B, or stool culture for C difficile (preferably with confirmation of organism toxicity if a direct stool toxin test is negative or not done). Testing of asymptomatic patients, including those who are asymptomatic after treatment, is not recommended other than for epidemiologic purposes. Lower gastrointestinal endoscopy is the only diagnostic test for pseudomembranous colitis, but it is expensive, invasive, and insensitive (51% to 55%) for the diagnosis of CDAD. Stool culture is the most sensitive laboratory test currently in clinical use, but it is not as specific as the cell cytotoxicity assay. Epidemiology C difficile is the most frequently identified cause of nosocomial diarrhea. The majority of C difficile infections are acquired nosocomially, and most patients remain asymptomatic following acquisition. Antimicrobial exposure is the greatest risk factor for patients, especially clindamycin, cephalosporins, and penicillins, although virtually every antimicrobial has been implicated. Cases of CDAD unassociated with prior antimicrobial or antineoplastic use are very rare. Hands of personnel, as well as a variety of environmental sites within institutions, have been found to be contaminated with C difficile, which can persist as spores for many months. Contaminated commodes, bathing tubs, and electronic thermometers have been implicated as sources of C difficile. Symptomatic and asymptomatic infected patients are the major reservoirs and sources for environmental contamination. Both genotypic and phenotypic typing systems for C difficile are available and have enhanced epidemiologic investigation greatly. Infection control Successful infection control measures designed to prevent horizontal transmission include the use of gloves in handling body substances and replacement of electronic thermometers with disposable devices. Isolation, cohorting, handwashing, environmental disinfection, and treatment of asymptomatic carriers are recommended practices for which convincing data of efficacy are not available. The most successful control measure directed at reduction in symptomatic disease has been antimicrobial restriction. Treatment Treatment of symptomatic (but not asymptomatic) patients with metronidazole or vancomycin for 10 days is effective; metronidazole may be preferred to reduce risk of vancomycin resistance among other organisms in hospitals. Recurrence of symptoms occurs in 7% to 20% of patients and is due to both relapse and reinfection. Over 90% of first recurrences can be treated successfully in the same manner as initial cases. Combination treatment with vancomycin plus rifampin or the addition orally of the yeast Saccharomyces boulardii to vancomycin or metronidazole treatment has been shown to prevent subsequent diarrhea in patients with recurrent disease.

Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3

Abstract: Thanatophoric dysplasia (TD), the most common neonatal lethal skeletal dysplasia, affects one out of 20,000 live births. Affected individuals display features similar to those seen in homozygous achondroplasia. Mutations causing achondroplasia are in FGFR3, suggesting that mutations in this gene may cause TD. A sporadic mutation causing a Lys650Glu change in the tyrosine kinase domain of FGFR3 was found in 16 of 16 individuals with one type of TD. Of 39 individuals with a second type of TD, 22 had a mutation causing an Arg248Cys change and one had a Ser371Cys substitution, both in the extracellular region of the protein. None of these mutations were found in 50 controls showing that mutations affecting different functional domains of FGFR3 cause different forms of this lethal disorder.

Cost models for future software life cycle processes: COCOMO 2.0

Abstract: Current software cost estimation models, such as the 1981 Constructive Cost Model (COCOMO) for software cost estimation and its 1987 Ada COCOMO update, have been experiencing increasing difficulties in estimating the costs of software developed to new life cycle processes and capabilities. These include non-sequential and rapid-development process models; reuse-driven approaches involving commercial off-the-shelf (COTS) packages, re-engineering, applications composition, and applications generation capabilities; object-oriented approaches supported by distributed middleware; and software process maturity initiatives. This paper summarizes research in deriving a baseline COCOMO 2.0 model tailored to these new forms of software development, including rationale for the model decisions. The major new modeling capabilities of COCOMO 2.0 are a tailorable family of software sizing models, involving Object Points, Function Points, and Source Lines of Code; nonlinear models for software reuse and re-engineering; an exponentdriver approach for modeling relative software diseconomies of scale; and several additions, deletions and updates to previous COCOMO effort-multiplier cost drivers. This model is serving as a framework for an extensive current data collection and analysis effort to further refine and calibrate the model's estimation capabilities.

A component- and message-based architectural style for GUI software

Abstract: While a large fraction of application code is devoted to graphical user interface (GUI) functions, support for reuse in this domain has largely been confined to the creation of GUI toolkits ("widgets"). We present a novel architectural style directed at supporting larger grain reuse and flexible system composition. Moreover, the style supports design of distributed, concurrent applications. Asynchronous notification messages and asynchronous request messages are the sole basis for intercomponent communication. A key aspect of the style is that components are not built with any dependencies on what typically would be considered lower-level components, such as user interface toolkits. Indeed, all components are oblivious to the existence of any components to which notification messages are sent. While our focus has been on applications involving graphical user interfaces, the style has the potential for broader applicability. Several trial applications using the style are described.

Sex Discrimination in Restaurant Hiring: An Audit Study

Abstract: This paper reports on a small-scale audit study that investigates sex discrimination in restaurant hiring. Comparably matched pairs of men and women applied for jobs as waiters and waitresses at 65 restaurants in Philadelphia. The 130 applications led to 54 interviews and 39 job offers. The results provide statistically significant evidence of sex discrimination against women in high-price restaurants. In high-price restaurants, job applications from women had an estimated probability of receiving a job offer that was lower by about .5, and an estimated probability of receiving an interview that was lower by about .4. These hiring patterns appear to have implications for sex differences in earnings, as informal survey evidence indicates that earnings are higher in high-price restaurants.

Markov random field models for unsupervised segmentation of textured color images

Abstract: We present an unsupervised segmentation algorithm which uses Markov random field models for color textures. These models characterize a texture in terms of spatial interaction within each color plane and interaction between different color planes. The models are used by a segmentation algorithm based on agglomerative hierarchical clustering. At the heart of agglomerative clustering is a stepwise optimal merging process that at each iteration maximizes a global performance functional based on the conditional pseudolikelihood of the image. A test for stopping the clustering is applied based on rapid changes in the pseudolikelihood. We provide experimental results that illustrate the advantages of using color texture models and that demonstrate the performance of the segmentation algorithm on color images of natural scenes. Most of the processing during segmentation is local making the algorithm amenable to high performance parallel implementation. >

Experimental tests of the roles of adaptation, chance, and history in evolution

Abstract: The contributions of adaptation, chance, and history to the evolution of fitness and cell size were measured in two separate experiments using bacteria. In both experiments, populations propagated in identical environments achieved similar fitnesses, regardless of prior history or subsequent chance events. In contrast, the evolution of cell size, a trait weakly correlated with fitness, was more strongly influenced by history and chance.

Motivation and Mathematics Achievement: A Comparative Study of Asian-American, Caucasian-American, and East Asian High School Students

Abstract: This study examined the motivation and mathematics achievement of Asian-American, Caucasian-American, and East Asian students. Subjects were 304 Asian-American, 1,958 Caucasian-American, 1,475 Chinese (Taiwan), and 1,120 Japanese eleventh graders (mean age = 17.6 years). Students were given a curriculum-based mathematics test and a questionnaire. Mathematics scores of the Asian-American students were higher than those of Caucasian-American students but lower than those of Chinese and Japanese students. Factors associated with the achievement of Asian-American and East Asian students included having parents and peers who hold high standards, believing that the road to success is through effort, having positive attitudes about achievement, studying diligently, and facing less interference with their schoolwork from jobs and informal peer interactions. Contrary to the popular belief that Asian-American students' high achievement necessarily takes a psychological toll,they were found not to report a greater frequency of maladjustive symptoms than Caucasian-American students.

Subgraph isomorphism in planar graphs and related problems

Abstract: We solve the subgraph isomorphism problem in planar graphs in linear time, for any pattern of constant size. Our results are based on a technique of partitioning the planar graph into pieces of small tree-width, and applying dynamic programming within each piece. The same methods can be used to solve other planar graph problems including connectivity, diameter, girth, induced subgraph isomorphism, and shortest paths.

Deleterious background selection with recombination.

Abstract: An analytic expression for the expected nucleotide diversity is obtained for a neutral locus in a region with deleterious mutation and recombination. Our analytic results are used to predict levels of variation for the entire third chromosome of Drosophila melanogaster. The predictions are consistent with the low levels of variation that have been observed at loci near the centromeres of the third chromosome of D. melanogaster. However, the low levels of variation observed near the tips of this chromosome are not predicted using currently available estimates of the deleterious mutation rate and of selection coefficients. If considerably smaller selection coefficients are assumed, the low observed levels of variation at the tips of the third chromosome are consistent with the background selection model.

Origins of the avian neural crest: the role of neural plate-epidermal interactions.

Abstract: We have investigated the lineage and tissue interactions that result in avian neural crest cell formation from the ectoderm. Presumptive neural plate was grafted adjacent to non-neural ectoderm in whole embryo culture to examine the role of tissue interactions in ontogeny of the neural crest. Our results show that juxtaposition of non-neural ectoderm and presumptive neural plate induces the formation of neural crest cells. Quail/chick recombinations demonstrate that both the prospective neural plate and the prospective epidermis can contribute to the neural crest. When similar neural plate/epidermal confrontations are performed in tissue culture to look at the formation of neural crest derivatives, juxtaposition of epidermis with either early (stages 4–5) or later (stages 6–10) neural plate results in the generation of both melanocytes and sympathoadrenal cells. Interestingly, neural plates isolated from early stages form no neural crest cells, whereas those isolated later give rise to melanocytes but not crest-derived sympathoadrenal cells. Single cell lineage analysis was performed to determine the time at which the neural crest lineage diverges from the epidermal lineage and to elucidate the timing of neural plate/epidermis interactions during normal development. Our results from stage 8 to 10+ embryos show that the neural plate/neural crest lineage segregates from the epidermis around the time of neural tube closure, suggesting that neural induction is still underway at open neural plate stages.

A potential role for apoptosis in neurodegeneration and Alzheimer's disease

Abstract: Previous studies have shown that β-amyloid (Aβ) peptides are neurotoxic. Recent data suggest that neurons undergoing Aβ-induced cell death exhibit characteristics that correspond to the classical features of apoptosis, suggesting that these cells may initiate a program of cell death. This chapter explores the criteria and precautions that must be applied to evaluate mechanisms of cell death in vitro and in vivo, discusses the evidence supporting an apoptotic mechanism of cell death in response to Aβ in cultured neurons, and describes potential correlations for these findings in the Alzheimer's disease brain. In addition, cellular signaling pathways that may be associated with apoptosis in response to Aβ are examined, and support for apoptosis as a mechanism of cell death for other neurodegeneration-inducing stimuli (e.g., oxidative injury) is described. The connection of multiple stimuli that induce neuronal cell death to an apoptotic mechanism suggests that apoptosis could play a central role in neurodegeneration in the brain.

Mutual policing and repression of competition in the evolution of cooperative groups

Abstract: EVOLUTIONARY theory has not explained how competition among lower level units is suppressed in the formation of higher-level evolutionary units1,2. For example, the key problem of early evolution is how small, individual replicators formed cooperative groups of sufficient complexity to allow accurate copying of the genetic material3. The puzzle is why parasites did not subvert the formation of cells by obtaining benetics benefits from the group without contributing to shared traits that enhance reproduction4. These parasites would outcompete other replicators within the cell, disrupting reproductive fairness among subunits and destroying the functional coherence of the group. A similar problem arose at a later evolutionary stage with the orderly mendelian segregation of subunits (chromosomes) within cells, and reproductive fairness continued to be a problem in the evolution of insect5 and human societies6. Here I present a simple model to show how reproductive fairness evolves among subunits to create functional coherence and higher-level units. Self-restraint, which evolves according to the kin-selection coefficient of relatedness, is not sufficient: mutual policing and enforcement of reproductive fairness are also required for the evolution of increasing social complexity.

Intracellular correlates of hippocampal theta rhythm in identified pyramidal cells, granule cells, and basket cells

Abstract: The cellular-synaptic generation of rhythmic slow activity (RSA or theta) in the hippocampus has been investigated by intracellular recording from principal cells and basket cells in anesthetized rats. In addition, the voltage-, coherence-, and phase versus depth profiles were examined by simultaneously recording field activity at 16 sites in the intact rat, during urethane anesthesia, and after bilateral entorhinal cortex lesion. In the extracellular experiments the large peak of theta at the hippocampal fissure was attenuated by urethane anesthesia and abolished by entorhinal cortex lesion. The phase versus depth profiles were similar during urethane anesthesia and following entorhinal cortex lesion but distinctly different in the intact, awake rat. These observations suggest that dendritic currents underlying theta in the awake rat may not be revealed under urethane anesthesia. The frequency of theta-related membrane potential oscillation was voltage-independent in pyramidal neurons, granule cells, and basket cells. On the other hand, the phase and amplitude of intracellular theta were voltage-dependent in all three cell types with an almost complete phase reversal at chloride equilibrium potential in pyramidal cells and basket cells. At strong depolarization levels (less than 30 mV) pyramidal cells emitted calcium spike oscillations, phase-locked to theta. Basket cells possessed the most regular membrane oscillations of the three cell types. All neurons of this study were verified by intracellular injection of biocytin. The observations provide direct evidence that theta-related rhythmic hyper-polarization of principal cells is brought about by the rhythmically discharging basket neurons.(ABSTRACT TRUNCATED AT 250 WORDS)