Showing papers by "University of Massachusetts Amherst published in 1995"

Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein.

Abstract: Alzheimer's disease (AD) is the most common cause of progressive intellectual failure in aged humans. AD brains contain numerous amyloid plaques surrounded by dystrophic neurites, and show profound synaptic loss, neurofibrillary tangle formation and gliosis. The amyloid plaques are composed of amyloid beta-peptide (A beta), a 40-42-amino-acid fragment of the beta-amyloid precursor protein (APP). A primary pathogenic role for APP/A beta is suggested by missense mutations in APP that are tightly linked to autosomal dominant forms of AD. A major obstacle to elucidating and treating AD has been the lack of an animal model. Animals transgenic for APP have previously failed to show extensive AD-type neuropathology, but we now report the production of transgenic mice that express high levels of human mutant APP (with valine at residue 717 substituted by phenylalanine) and which progressively develop many of the pathological hallmarks of AD, including numerous extracellular thioflavin S-positive A beta deposits, neuritic plaques, synaptic loss, astrocytosis and microgliosis. These mice support a primary role for APP/A beta in the genesis of AD and could provide a preclinical model for testing therapeutic drugs.

Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer.

Abstract: Background Metastatic prostate cancer is a leading cause of cancer-related death in men. The rate of response to androgen ablation is high, but most patients relapse as a result of the outgrowth of androgen-independent tumor cells. The androgen receptor, which binds testosterone and stimulates the transcription of androgen-responsive genes, regulates the growth of prostate cells. We analyzed the androgen-receptor genes from samples of metastatic androgen-independent prostate cancers to determine whether mutations in the gene have a role in androgen independence. Methods Complementary DNA was synthesized from metastatic prostate cancers in 10 patients with androgen-independent prostate cancer, and the expression of the androgen-receptor gene was estimated by amplification with the polymerase chain reaction. Exons B through H of the gene were cloned, and mutations were identified by DNA sequencing. The functional effects of the mutations were assessed in cells transfected with mutant genes. Results All andr...

Generalization in Reinforcement Learning: Successful Examples Using Sparse Coarse Coding

Abstract: On large problems, reinforcement learning systems must use parameterized function approximators such as neural networks in order to generalize between similar situations and actions. In these cases there are no strong theoretical results on the accuracy of convergence, and computational results have been mixed. In particular, Boyan and Moore reported at last year's meeting a series of negative results in attempting to apply dynamic programming together with function approximation to simple control problems with continuous state spaces. In this paper, we present positive results for all the control tasks they attempted, and for one that is significantly larger. The most important differences are that we used sparse-coarse-coded function approximators (CMACs) whereas they used mostly global function approximators, and that we learned online whereas they learned offline. Boyan and Moore and others have suggested that the problems they encountered could be solved by using actual outcomes ("rollouts"), as in classical Monte Carlo methods, and as in the TD(λ) algorithm when λ = 1. However, in our experiments this always resulted in substantially poorer performance. We conclude that reinforcement learning can work robustly in conjunction with function approximators, and that there is little justification at present for avoiding the case of general λ.

Reconstruction of solar irradiance since 1610: Implications for climate change

Abstract: Solar total and ultraviolet (UV) irradiances are reconstructed annually from 1610 to the present. This epoch includes the Maunder Minimum of anomalously low solar activity (circa 1645-1715) and the subsequent increase to the high levels of the present Modern Maximum. In this reconstruction, the Schwabe (11-year) irradiance cycle and a longer term variability component are determined separately, based on contemporary solar and stellar monitoring. The correlation of reconstructed solar irradiance and Northern Hemisphere (NH) surface temperature is 0.86 in the pre-industrial period from 1610 to 1800, implying a predominant solar influence. Extending this correlation to the present suggests that solar forcing may have contributed about half of the observed 0.55°C surface warming since 1860 and one third of the warming since 1970.

Chapter 19 DNA Transformation

Abstract: Publisher Summary This chapter discusses DNA transformation. DNA transformation assays in a whole organism provide experimental links between molecular structure and phenotype. Experiments with transgenic Caenorhabditis elegans start in general with the injection of DNA into the adult gonad. Effects on phenotype or gene expression patterns can be analyzed either in F1 progeny derived from the injected animals or in derived transgenic lines. Germ-line transformation has been achieved by microinjection of DNA directly into oocyte nuclei or by microinjection of DNA into the cytoplasm of the hermaphrodite syncytial gonad. Three forms of heritable DNA transformation have been observed in C. elegans are: (1) extra chromosomal transformation; (2) non-homologous integration; and (3) homologous integration. Setting up microinjection in a laboratory already equipped for C. elegans genetics and molecular biology requires a modest investment in space and money. A separate easily scoreable marker gene to identify transformed animals can be extremely useful in a variety of injection experiments. The propensity for injected DNA molecules to recombine with each other generally allows one to coinject the selectable marker with a DNA segment to be tested for activity.

Universe reheating after inflation

Abstract: We study the problem of scalar particle production after inflation by an inflaton field which is oscillating rapidly relative to the expansion of the universe. We use the framework of the chaotic inflation scenario with quartic and quadratic inflaton potentials. Particles produced are described by a quantum scalar field \ensuremath{\chi}, which is coupled to the inflaton via linear and quadratic couplings. The particle production effect is studied using the standard technique of Bogolyubov transformations. Particular attention is paid to parametric resonance phenomena which take place in the presence of the quickly oscillating inflaton field. We have found that in the region of applicability of perturbation theory the effects of parametric resonance are crucial, and estimates based on first-order Born approximation often underestimate the particle production. In the case of the quartic inflaton potential V(cphi)=\ensuremath{\lambda}${\mathit{cphi}}^{4}$, the particle production process is very efficient for either type of coupling between the inflaton field and the scalar field \ensuremath{\chi} even for small values of coupling constants. The energy density of the universe after the decay of the inflaton oscillations is in this case a factor [\ensuremath{\lambda} ln(1/\ensuremath{\lambda})${]}^{\mathrm{\ensuremath{-}}1}$ times larger than the corresponding estimates based on first-order Born approximation. In the case of the quadratic inflaton potential the reheating process depends crucially on the type of coupling between the inflaton and the scalar field \ensuremath{\chi} and on the magnitudes of the coupling constants. If the inflaton coupling to fermions and its linear (in inflaton field) coupling to scalar fields are suppressed, then, as previously discussed by Kofman, Linde, and Starobinsky, the inflaton field will eventually decouple from the rest of the matter, and the residual inflaton oscillations may provide the (cold) dark matter of the universe. In the case of the quadratic inflaton potential we obtain the lowest and the highest possible bounds on the effective energy density of the inflaton field when it freezes out.

Empirical Methods for Artificial Intelligence

Abstract: Empirical research exploratory data analysis basic issues in experiment design hypothesis testing and estimation computer-intensive statistical methods performance assessment explaining performance - interactions and dependencies modelling tactics for generalization.

Strategic alliances: A synthesis of conceptual foundations

Abstract: Strategic alliances, a manifestation of interorganizational cooperative strategies, entails the pooling of specific resources and skills by the cooperating organizations in order to achieve common goals, as well as goals specific to the individual partners. Gaining access to new markets; accelerating the pace of entry into new markets; sharing of research and development, manufacturing, and/or marketing costs; broadening the product line/filling product line gaps; and learning new skills are among the motives underlying the entry of firms into strategic alliances. During the last decade, an increasing number of firms have entered into alliances with other firms within the same industry, as well as within other industries. Some firms have progressed well beyond forming isolated alliances to establishing a web of intra- and interindustry, and intra-and international strategic alliances. Against this backdrop, we provide a synthesis of the conceptual foundations of strategic alliances and explore the role of marketing in strategic alliances.

Searching distributed collections with inference networks

Abstract: The use of information retrieval systems in networked environments raises a new set of issues that have received little attention. These issues include ranking document collections for relevance to a query, selecting the best set of collections from a ranked list, and merging the document rankings that are returned from a set of collections. This paper describes methods of addressing each issue in the inference network model, discusses their implementation in the INQUERY system, and presents experimental results demonstrating their effectiveness.

Foci of trinucleotide repeat transcripts in nuclei of myotonic dystrophy cells and tissues.

Abstract: We have analyzed the intracellular localization of transcripts from the myotonin protein kinase (Mt-PK) gene in fibroblasts and muscle biopsies from myotonic dystrophy patients and normal controls. In affected individuals, a trinucleotide expansion in the gene results in the phenotype, the severity of which is proportional to the repeat length. A fluorochrome-conjugated probe (10 repeats of CAG) hybridized specifically to this expanded repeat. Mt-PK transcripts containing CTG repeat expansions were detected in the nucleus as bright foci in DM patient fibroblasts and muscle biopsies, but not from normal individuals. These foci represented transcripts from the Mt-PK gene since they simultaneously hybridized to fluorochrome-conjugated probes to the 5'-end of the Mt-PK mRNA. A single oligonucleotide probe to the repeat and the sense strand each conjugated to different fluorochromes revealed the gene and the transcripts simultaneously, and indicated that these focal concentrations (up to 13 per nucleus) represented predominately posttranscriptional RNA since only a single focus contained both the DNA and the RNA. This concentration of nuclear transcripts was diagnostic of the affected state, and may represent aberrant processing of the RNA.

Alcohol, Height, and Adiposity in Relation to Estrogen and Prolactin Levels in Postmenopausal Women

Abstract: Background : Alcohol use, height, and postmenopausal adiposity have each been positively associated with postmenopausal breast cancer risk in most epidemiologic studies. The mechanism underlying these associations is unclear, although an effect of these factors on hormone levels has been hypothesized. Few previous studies have evaluated the relationship of either alcohol consumption or height with plasma hormone levels. A positive association between adiposity and plasma estrogen levels in postmenopausal women has been reported consistently. Purpose : Using archived frozen plasma samples and corresponding data from participants in the Nurses' Health Study, we determined plasma hormone levels and assessed these levels in relation to alcohol consumption, height, and adiposity among postmenopausal women. Methods : Blood samples were collected from a subset of participants in the Nurses' Health Study in 1989 and 1990, then stored in liquid nitrogen. Hormone concentrations in 217 archived plasma samples (from healthy postmenopausal women) were analyzed in 1993. Spearman correlation coefficients were calculated to assess the linear association between alcohol consumption during the previous year (mean daily intake in grams per day ascertained from semiquantitative food-frequency questionnaires completed in 1990 or 1991), height, and adiposity (as measured by body mass index [BMI] in kg/m 2 , with weight reported at time of blood collection), and plasma hormone levels. Two-sided P values were also calculated. Results : After controlling for age, height, smoking status, and BMI, alcohol consumption was positively associated with estrone sulfate concentrations (r =.17 ; P =.02) ; no statistically significant association was noted for the other plasma hormones measured. Mean plasma estrone sulfate levels were 159 pg/mL in women who reported no alcohol use versus 211 pg/mL in women consuming 30 g or more of alcohol per day. After adjusting for the other covariates, we observed a strong positive correlation between BMI and plasma estrogens (r ranging from.37 for estrone and estrone sulfate to.63 for bioavailable estradiol, with all P values ≤.01 ; prolactin was the only hormone unassociated with BMI, r = -.01). Height was unrelated to either plasma estrogens or prolactin. Conclusions : BMI and alcohol use were positively associated with postmenopausal plasma estrogen and estrone sulfate levels, respectively. Implications : The association of alcohol consumption and postmenopausal obesity with subsequent breast cancer risk might be mediated, at least in part, through an influence on postmenopausal plasma estrogen levels. Additional studies are needed to further quantify the relationship between alcohol consumption and plasma hormone levels and to elucidate the physiologic basis for this association.

Improving Elevator Performance Using Reinforcement Learning

Abstract: This paper describes the application of reinforcement learning (RL) to the difficult real world problem of elevator dispatching. The elevator domain poses a combination of challenges not seen in most RL research to date. Elevator systems operate in continuous state spaces and in continuous time as discrete event dynamic systems. Their states are not fully observable and they are nonstationary due to changing passenger arrival rates. In addition, we use a team of RL agents, each of which is responsible for controlling one elevator car. The team receives a global reinforcement signal which appears noisy to each agent due to the effects of the actions of the other agents, the random nature of the arrivals and the incomplete observation of the state. In spite of these complications, we show results that in simulation surpass the best of the heuristic elevator control algorithms of which we are aware. These results demonstrate the power of RL on a very large scale stochastic dynamic optimization problem of practical utility.

Advances in the application of ultrasound in food analysis and processing

Abstract: Ultrasonic techniques are finding increasing use in the food industry for both the analysis and modification of foods. Low-intensity ultrasound is a non-destructive technique that provides information about physicochemical properties, such as composition, structure, physical state and flow rate. High-intensity ultrasound is used to alter, either physically or chemically, the properties of foods, for example to generate emulsions, disrupt cells, promote chemical reactions, inhibit enzymes, tenderize meat and modify crystallization processes.

Cellulose Degradation in Anaerobic Environments

Abstract: In anaerobic environments rich in decaying plant material, the decomposition of cellulose is brought about by complex communities of interacting microorganisms. Because the substrate, cellulose, is insoluble, bacterial and fungal degradation occurs exocellularly, either in association with the outer cell envelope layer or extracellularly. Products of cellulose hydrolysis are available as carbon and energy sources for other microbes that inhabit environments in which cellulose is biodegraded, and this availability forms the basis of many microbial interactions that occur in these environments. This review discusses interactions among members of cellulose-decomposing microbial communities in various environments. It considers cellulose decomposing communities in soils, sediments, and aquatic environments, as well as those that degrade cellulose in association with animals. These microbial communities contribute significantly to the cycling of carbon on a global scale.

Validity of the Computer Science and Applications, Inc. (CSA) activity monitor.

Abstract: The validity of the Computer Science and Applications, Inc. (CSA) accelerometer in assessing physical activity was assessed during treadmill walking and running at three different grades. Energy expenditure (EE) served as the criterion measure. CSA data were compared to data collected with the Caltrac accelerometer. Both accelerometers were sensitive to changes in treadmill speed, but neither discriminated changes in treadmill grade. Caltrac and CSA activity counts were significantly and similarly correlated with EE (r = 0.66-0.82), relative VO2 (r = 0.77-0.89), heart rate (r = 0.66-0.80), treadmill speed (r = 0.82-0.92), and with each other (r = 0.77-0.82). CSA data were used to develop models to predict EE (kcal.min-1). Cross-validation resulted in a mean difference between actual and predicted EE of 0.02 kcal.min-1 (SEE = 0.85 kcal.min-1). The range of individual differences in the validation group was large for both the CSA model (-2.86 to +3.86 kcal.min-1) and Caltrac (-4.17 to +2.04 kcal.min-1). It is concluded that the CSA and Caltrac accelerometers have similar validity and that either instrument can be used to estimate EE of groups.

Tile size selection using cache organization and data layout

Abstract: When dense matrix computations are too large to fit in cache, previous research proposes tiling to reduce or eliminate capacity misses. This paper presents a new algorithm for choosing problem-size dependent tile sizes based on the cache size and cache line size for a direct-mapped cache. The algorithm eliminates both capacity and self-interference misses and reduces cross-interference misses. We measured simulated miss rates and execution times for our algorithm and two others on a variety of problem sizes and cache organizations. At higher set associativity, our algorithm does not always achieve the best performance. However on direct-mapped caches, our algorithm improves simulated miss rates and measured execution times when compared with previous work.

Parasitoid foraging and learning.

Abstract: The diminutive size of most parasitoids undoubtedly has limited their choice as subjects for behavioral study, despite their great diversity in lifestyles and reproductive strategies The present chapter addresses their foraging behavior as influenced by learning Most of their adult life female parasitoids search for host insects which, in turn, are under selection to avoid being found and devoured This scenario sets the stage for the evolution of diverse hide-and-seek games played by parasitoids and their victims, most often herbivores That parasitoids are successful in their quest for hosts is evidenced by the vast number of parasitoid species and their importance in insect management

Conjugacy classes in semisimple algebraic groups

Abstract: Review of semisimple groups Basic facts about classes and centralizers Centralizers of semisimple elements The adjoint quotient Regular elements Parabolic subgroups and unipotent classes The unipotent variety and the flag variety Nilpotent orbits and unipotent classes Finite groups of Lie type Springer's Weyl group representations Complements References Index.

Effect of maternal cigarette smoking on pregnancy complications and sudden infant death syndrome.

Abstract: Background The purpose of this study was to estimate the annual morbidity and mortality among fetuses and infants that can be attributed to the use of tobacco products by pregnant women. Methods Published research reports identified by literature review were combined in a series of meta-analyses to compute pooled risk ratios, which, in turn, were used to determine the population attributable risk. Results Each year, use of tobacco products is responsible for an estimated 19,000 to 141,000 tobacco-induced abortions, 32,000 to 61,000 infants born with low birthweight, and 14,000 to 26,000 infants who require admission to neonatal intensive care units. Tobacco use is also annually responsible for an estimated 1900 to 4800 infant deaths resulting from perinatal disorders, and 1200 to 2200 deaths from sudden infant death syndrome (SIDS). Conclusions Tobacco use is an important preventable cause of abortions, low birthweight, and deaths from perinatal disorders and SIDS. All pregnant women should be advised that smoking places their unborn children in danger. The low success rate of smoking cessation among pregnant women suggests that efforts to reduce the complications of pregnancy attributable to tobacco use by pregnant women should focus on preventing nicotine addiction among teenaged girls.

Nonlinear Analysis Catastrophe Theory Modeling and Cobb's Cusp Surface Analysis Program

Abstract: Numerous nonlinear phenomena that exhibit discontinuous jumps in behavior have been modeled with catastrophe theory. Cobb's Cusp Surface Analysis Program (CUSP) provides a way to empirically estima...

A mutation in CSE4, an essential gene encoding a novel chromatin-associated protein in yeast, causes chromosome nondisjunction and cell cycle arrest at mitosis.

Abstract: The centromere, a differentiated region of the eukaryotic chromosome, mediates the segregation of sister chromatids at mitosis. In this study, a Saccharomyces cerevisiae chromosome mis-segregation mutant, cse4-1, has been isolated and shown to increase the nondisjunction frequency of a chromosome bearing a mutant centromere DNA sequence. In addition, at elevated temperatures the cse4-1 allele causes a mitosis-specific arrest with a predominance of large budded cells containing single G2 nuclei and short bipolar mitotic spindles. The wild-type gene, CSE4, is essential for cell division and encodes a protein containing a domain that is 64% identical to the highly conserved chromatin protein, histone H3. Biochemical experiments demonstrate that CSE4p has similar DNA-binding characteristics as those of histone H3 and might form a specialized nucleosome structure in vivo. Interestingly, the human centromere protein, CENP-A, also contains this H3-like domain. Data presented here indicate that CSE4p is required for proper kinetochore function in yeast and may represent an evolutionarily conserved protein necessary for assembly of the unique chromatin structure associated with the eukaryotic centromere.

Development and initial validation of a scale to measure self-efficacy beliefs in patients with chronic pain.

Abstract: The present study describes the development of the Chronic Pain Self-Efficacy Scale (CPSS), a 22-item questionnaire designed to measure chronic pain patients' perceived self-efficacy to cope with the consequences of chronic pain. The CPSS and other measures of psychosocial functioning were administered to 141 consecutive patients who were referred to an outpatient multidisciplinary pain treatment program. An exploratory factor analysis of the CPSS responses identified 3 factors: self-efficacy for pain management (PSE), self-efficacy for coping with symptoms (CSE), and self-efficacy for physical function (FSE). The CPSS then was administered to a replication sample of 136 chronic pain patients. Factor analysis confirmed the 3-factor structure of the CPSS. The subscale scores derived from the factor analysis were significantly correlated with measures of depression, hopelessness, somatic preoccupation, and adaptation to the chronic pain experience. Multiple regression analyses provided further support for the concurrent and construct validity of the CPSS. The scale may aid in the evaluation of the self-efficacy beliefs of chronic pain patients.