Showing papers by "Stanford University published in 1998"

Cluster analysis and display of genome-wide expression patterns

Abstract: A system of cluster analysis for genome-wide expression data from DNA microarray hybridization is de- scribed that uses standard statistical algorithms to arrange genes according to similarity in pattern of gene expression. The output is displayed graphically, conveying the clustering and the underlying expression data simultaneously in a form intuitive for biologists. We have found in the budding yeast Saccharomyces cerevisiae that clustering gene expression data groups together efficiently genes of known similar function, and we find a similar tendency in human data. Thus patterns seen in genome-wide expression experiments can be inter- preted as indications of the status of cellular processes. Also, coexpression of genes of known function with poorly charac- terized or novel genes may provide a simple means of gaining leads to the functions of many genes for which information is not available currently.

The anatomy of a large-scale hypertextual Web search engine

Abstract: In this paper, we present Google, a prototype of a large-scale search engine which makes heavy use of the structure present in hypertext. Google is designed to crawl and index the Web efficiently and produce much more satisfying search results than existing systems. The prototype with a full text and hyperlink database of at least 24 million pages is available at http://google.stanford.edu/. To engineer a search engine is a challenging task. Search engines index tens to hundreds of millions of web pages involving a comparable number of distinct terms. They answer tens of millions of queries every day. Despite the importance of large-scale search engines on the web, very little academic research has been done on them. Furthermore, due to rapid advance in technology and web proliferation, creating a web search engine today is very different from three years ago. This paper provides an in-depth description of our large-scale web search engine -- the first such detailed public description we know of to date. Apart from the problems of scaling traditional search techniques to data of this magnitude, there are new technical challenges involved with using the additional information present in hypertext to produce better search results. This paper addresses this question of how to build a practical large-scale system which can exploit the additional information present in hypertext. Also we look at the problem of how to effectively deal with uncontrolled hypertext collections where anyone can publish anything they want.

Atomic Decomposition by Basis Pursuit

Abstract: The time-frequency and time-scale communities have recently developed a large number of overcomplete waveform dictionaries --- stationary wavelets, wavelet packets, cosine packets, chirplets, and warplets, to name a few. Decomposition into overcomplete systems is not unique, and several methods for decomposition have been proposed, including the method of frames (MOF), Matching pursuit (MP), and, for special dictionaries, the best orthogonal basis (BOB). Basis Pursuit (BP) is a principle for decomposing a signal into an "optimal" superposition of dictionary elements, where optimal means having the smallest l1 norm of coefficients among all such decompositions. We give examples exhibiting several advantages over MOF, MP, and BOB, including better sparsity and superresolution. BP has interesting relations to ideas in areas as diverse as ill-posed problems, in abstract harmonic analysis, total variation denoising, and multiscale edge denoising. BP in highly overcomplete dictionaries leads to large-scale optimization problems. With signals of length 8192 and a wavelet packet dictionary, one gets an equivalent linear program of size 8192 by 212,992. Such problems can be attacked successfully only because of recent advances in linear programming by interior-point methods. We obtain reasonable success with a primal-dual logarithmic barrier method and conjugate-gradient solver.

Bilateral filtering for gray and color images

Abstract: Bilateral filtering smooths images while preserving edges, by means of a nonlinear combination of nearby image values. The method is noniterative, local, and simple. It combines gray levels or colors based on both their geometric closeness and their photometric similarity, and prefers near values to distant values in both domain and range. In contrast with filters that operate on the three bands of a color image separately, a bilateral filter can enforce the perceptual metric underlying the CIE-Lab color space, and smooth colors and preserve edges in a way that is tuned to human perception. Also, in contrast with standard filtering, bilateral filtering produces no phantom colors along edges in color images, and reduces phantom colors where they appear in the original image.

Why Do Some Countries Produce so Much More Output Per Worker than Others

Abstract: Output per worker varies enormously across countries. Why? On an accounting basis, our analysis shows that differences in physical capital and educational attainment can only partially explain the variation in output per worker--we find a large amount of variation in the level of the Solow residual across countries. At a deeper level, we document that the differences in capital accumulation, productivity, and therefore output per worker are driven by differences in institutions and government policies, which we call social infrastructure. We treat social infrastructure as endogenous, determined historically by location and other factors captured in part by language.

The emerging field of emotion regulation: An integrative review.

Abstract: The emerging field of emotion regulation studies how individuals influence which emotions they have, when they have them, and how they experience and express them. This review takes an evolutionary perspective and characterizes emotion in terms of response tendencies. Emotion regulation is denned and distinguished from coping, mood regulation, defense, and affect regulation. In the increasingly specialized discipline of psychology, the field of emotion regulation cuts across traditional boundaries and provides common ground. According to a process model of emotion regulation, emotion may be regulated at five points in the emotion generative process: (a) selection of the situation, (b) modification of the situation, (c) deployment of attention, (d) change of cognitions, and (e) modulation of responses. The field of emotion regulation promises new insights into age-old questions about how people manage their emotions.

Comprehensive Identification of Cell Cycle–regulated Genes of the Yeast Saccharomyces cerevisiae by Microarray Hybridization

Abstract: We sought to create a comprehensive catalog of yeast genes whose transcript levels vary periodically within the cell cycle. To this end, we used DNA microarrays and samples from yeast cultures sync...

Approximate nearest neighbors: towards removing the curse of dimensionality

Abstract: We present two algorithms for the approximate nearest neighbor problem in high-dimensional spaces. For data sets of size n living in R d , the algorithms require space that is only polynomial in n and d, while achieving query times that are sub-linear in n and polynomial in d. We also show applications to other high-dimensional geometric problems, such as the approximate minimum spanning tree. The article is based on the material from the authors' STOC'98 and FOCS'01 papers. It unifies, generalizes and simplifies the results from those papers.

Teachers, Schools, and Academic Achievement

Abstract: Considerable controversy surrounds the impact of schools and teachers on the achievement of students. This paper disentangles the separate factors influencing achievement with special attention given to the role of teacher differences and other aspects of schools. Unique matched panel data from the Harvard/UTD Texas Schools Project permit distinguishing between total effects and the impact of specific, measured components of teachers and schools. While schools are seen to have powerful effects on achievement differences, these effects appear to derive most importantly from variations in teacher quality. A lower bound suggests that variations in teacher quality account for at least 7« percent of the total variation in student achievement, and there are reasons to believe that the true percentage is considerably larger. The subsequent analysis estimates educational production functions based on models of achievement growth with individual fixed effects. It identifies a few systematic factors a negative impact of initial years of teaching and a positive effect of smaller class sizes for low income children in earlier grades but these effects are very small relative to the effects of overall teacher quality differences.

Evidence for oscillation of atmospheric neutrinos

Abstract: We present an analysis of atmospheric neutrino data from a 33.0 kton yr (535-day) exposure of the Super-Kamiokande detector. The data exhibit a zenith angle dependent deficit of muon neutrinos which is inconsistent with expectations based on calculations of the atmospheric neutrino flux. Experimental biases and uncertainties in the prediction of neutrino fluxes and cross sections are unable to explain our observation. The data are consistent, however, with two-flavor ${\ensuremath{ u}}_{\ensuremath{\mu}}\ensuremath{\leftrightarrow}{\ensuremath{ u}}_{\ensuremath{\tau}}$ oscillations with ${sin}^{2}2\ensuremath{\theta}g0.82$ and $5\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}4}l\ensuremath{\Delta}{m}^{2}l6\ifmmode\times\else\texttimes\fi{}1{0}^{\ensuremath{-}3}\mathrm{eV}{}^{2}$ at 90% confidence level.

Antecedent- and response-focused emotion regulation: Divergent consequences for experience, expression, and physiology.

Abstract: Using a process model of emotion, a distinction between antecedent-focused and response-focused emotion regulation is proposed. To test this distinction, 120 participants were shown a disgusting film while their experiential, behavioral, and physiological responses were recorded. Participants were told to either (a) think about the film in such a way that they would feel nothing (reappraisal, a form of antecedent-focused emotion regulation), (b) behave in such a way that someone watching them would not know they were feeling anything (suppression, a form of response-focused emotion regulation), or (c) watch the film (a control condition). Compared with the control condition, both reappraisal and suppression were effective in reducing emotion-expressive behavior. However, reappraisal decreased disgust experience, whereas suppression increased sympathetic activation. These results suggest that these 2 emotion regulatory processes may have different adaptive consequences.

Indentation size effects in crystalline materials: A law for strain gradient plasticity

Abstract: We show that the indentation size effect for crystalline materials can be accurately modeled using the concept of geometrically necessary dislocations. The model leads to the following characteristic form for the depth dependence of the hardness: H H 0 1+ h ∗ h where H is the hardness for a given depth of indentation, h, H0 is the hardness in the limit of infinite depth and h ∗ is a characteristic length that depends on the shape of the indenter, the shear modulus and H0. Indentation experiments on annealed (111) copper single crystals and cold worked polycrystalline copper show that this relation is well-obeyed. We also show that this relation describes the indentation size effect observed for single crystals of silver. We use this model to derive the following law for strain gradient plasticity: ( σ σ 0 ) 2 = 1 + l χ , where σ is the effective flow stress in the presence of a gradient, σ0 is the flow stress in the absence of a gradient, χ is the effective strain gradient and l a characteristic material length scale, which is, in turn, related to the flow stress of the material in the absence of a strain gradient, l ≈ b( μ σ 0 ) 2 . For materials characterized by the power law σ 0 = σ ref e 1 n , the above law can be recast in a form with a strain-independent material length scale l. ( builtσ σ ref ) 2 = e 2 n + l χ l = b( μ σ ref ) 2 = l ( σ 0 σ ref ) 2 . This law resembles the phenomenological law developed by Fleck and Hutchinson, with their phenomenological length scale interpreted in terms of measurable material parametersbl].

Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal Systems

Abstract: The novel neuropeptides called hypocretins (orexins) have recently been identified as being localized exclusively in cell bodies in a subregion of the tuberal part of the hypothalamus. The structure of the hypocretins, their accumulation in vesicles of axon terminals, and their excitatory effect on cultured hypothalamic neurons suggest that the hypocretins function in intercellular communication. To characterize these peptides further and to help understand what physiological functions they may serve, we undertook an immunohistochemical study to examine the distribution of preprohypocretin-immunoreactive neurons and fibers in the rat brain. Preprohypocretin-positive neurons were found in the perifornical nucleus and in the dorsal and lateral hypothalamic areas. These cells were distinct from those that express melanin-concentrating hormone. Although they represent a restricted group of cells, their projections were widely distributed in the brain. We observed labeled fibers throughout the hypothalamus. The densest extrahypothalamic projection was found in the locus coeruleus. Fibers were also seen in the septal nuclei, the bed nucleus of the stria terminalis, the paraventricular and reuniens nuclei of the thalamus, the zona incerta, the subthalamic nucleus, the central gray, the substantia nigra, the raphe nuclei, the parabrachial area, the medullary reticular formation, and the nucleus of the solitary tract. Less prominent projections were found in cortical regions, central and anterior amygdaloid nuclei, and the olfactory bulb. These results suggest that hypocretins are likely to have a role in physiological functions in addition to food intake such as regulation of blood pressure, the neuroendocrine system, body temperature, and the sleep–waking cycle.

Health promotion from the perspective of social cognitive theory

Abstract: This article examines health promotion and disease prevention from the perspective of social cognitive theory. The areas of overlap with some of the most widely applied psychosocial models of health are identified. The models of health promotion and disease prevention have undergone several generational changes. We have shifted from trying to scare people into health, to rewarding them into health, to equipping them with self-regulatory skills to manage their health habits, to shoring up their habit changes with dependable social supports. These transformations have evolved a multifaceted approach that addresses the reciprocal interplay between self-regulatory and environmental determinants of health behavior. Social cognitive theory addresses the socio structural determinants of health as well as the personal determinants. A comprehensive approach to health promotion requires changing the practices of social systems that have widespread detrimental effects on health rather than solely changing t...

Why patients use alternative medicine : results of a national study

Abstract: Context.—Research both in the United States and abroad suggests that significant numbers of people are involved with various forms of alternative medicine. However, the reasons for such use are, at present, poorly understood.Objective.—To investigate possible predictors of alternative health care use.Methods.—Three primary hypotheses were tested. People seek out these alternatives because (1) they are dissatisfied in some way with conventional treatment; (2) they see alternative treatments as offering more personal autonomy and control over health care decisions; and (3) the alternatives are seen as more compatible with the patients' values, worldview, or beliefs regarding the nature and meaning of health and illness. Additional predictor variables explored included demographics and health status.Design.—A written survey examining use of alternative health care, health status, values, and attitudes toward conventional medicine. Multiple logistic regression analyses were used in an effort to identify predictors of alternative health care use.Setting and Participants.—A total of 1035 individuals randomly selected from a panel who had agreed to participate in mail surveys and who live throughout the United States.Main Outcome Measure.—Use of alternative medicine within the previous year.Results.—The response rate was 69%.The following variables emerged as predictors of alternative health care use: more education (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.1-1.3); poorer health status (OR, 1.3; 95% CI, 1.1-1.5); a holistic orientation to health (OR, 1.4; 95% CI, 1.1-1.9); having had a transformational experience that changed the person's worldview (OR, 1.8; 95% CI, 1.3-2.5); any of the following health problems: anxiety (OR, 3.1; 95% CI, 1.6-6.0); back problems (OR, 2.3; 95% CI, 1.7-3.2); chronic pain (OR, 2.0; 95% CI, 1.1-3.5); urinary tract problems (OR, 2.2; 95% CI, 1.3-3.5); and classification in a cultural group identifiable by their commitment to environmentalism, commitment to feminism, and interest in spirituality and personal growth psychology (OR, 2.0; 95% CI, 1.4-2.7). Dissatisfaction with conventional medicine did not predict use of alternative medicine. Only 4.4% of those surveyed reported relying primarily on alternative therapies.Conclusion.—Along with being more educated and reporting poorer health status, the majority of alternative medicine users appear to be doing so not so much as a result of being dissatisfied with conventional medicine but largely because they find these health care alternatives to be more congruent with their own values, beliefs, and philosophical orientations toward health and life.

CURE: an efficient clustering algorithm for large databases

Abstract: Clustering, in data mining, is useful for discovering groups and identifying interesting distributions in the underlying data. Traditional clustering algorithms either favor clusters with spherical shapes and similar sizes, or are very fragile in the presence of outliers. We propose a new clustering algorithm called CURE that is more robust to outliers, and identifies clusters having non-spherical shapes and wide variances in size. CURE achieves this by representing each cluster by a certain fixed number of points that are generated by selecting well scattered points from the cluster and then shrinking them toward the center of the cluster by a specified fraction. Having more than one representative point per cluster allows CURE to adjust well to the geometry of non-spherical shapes and the shrinking helps to dampen the effects of outliers. To handle large databases, CURE employs a combination of random sampling and partitioning. A random sample drawn from the data set is first partitioned and each partition is partially clustered. The partial clusters are then clustered in a second pass to yield the desired clusters. Our experimental results confirm that the quality of clusters produced by CURE is much better than those found by existing algorithms. Furthermore, they demonstrate that random sampling and partitioning enable CURE to not only outperform existing algorithms but also to scale well for large databases without sacrificing clustering quality.

A general theory of phase noise in electrical oscillators

Abstract: A general model is introduced which is capable of making accurate, quantitative predictions about the phase noise of different types of electrical oscillators by acknowledging the true periodically time-varying nature of all oscillators. This new approach also elucidates several previously unknown design criteria for reducing close-in phase noise by identifying the mechanisms by which intrinsic device noise and external noise sources contribute to the total phase noise. In particular, it explains the details of how 1/f noise in a device upconverts into close-in phase noise and identifies methods to suppress this upconversion. The theory also naturally accommodates cyclostationary noise sources, leading to additional important design insights. The model reduces to previously available phase noise models as special cases. Excellent agreement among theory, simulations, and measurements is observed.

The variable discharge of cortical neurons: implications for connectivity, computation, and information coding

Abstract: Cortical neurons exhibit tremendous variability in the number and temporal distribution of spikes in their discharge patterns. Furthermore, this variability appears to be conserved over large regions of the cerebral cortex, suggesting that it is neither reduced nor expanded from stage to stage within a processing pathway. To investigate the principles underlying such statistical homogeneity, we have analyzed a model of synaptic integration incorporating a highly simplified integrate and fire mechanism with decay. We analyzed a “high-input regime” in which neurons receive hundreds of excitatory synaptic inputs during each interspike interval. To produce a graded response in this regime, the neuron must balance excitation with inhibition. We find that a simple integrate and fire mechanism with balanced excitation and inhibition produces a highly variable interspike interval, consistent with experimental data. Detailed information about the temporal pattern of synaptic inputs cannot be recovered from the pattern of output spikes, and we infer that cortical neurons are unlikely to transmit information in the temporal pattern of spike discharge. Rather, we suggest that quantities are represented as rate codes in ensembles of 50‐ 100 neurons. These column-like ensembles tolerate large fractions of common synaptic input and yet covary only weakly in their spike discharge. We find that an ensemble of 100 neurons provides a reliable estimate of rate in just one interspike interval (10‐50 msec). Finally, we derived an expression for the variance of the neural spike count that leads to a stable propagation of signal and noise in networks of neurons—that is, conditions that do not impose an accumulation or diminution of noise. The solution implies that single neurons perform simple algebra resembling averaging, and that more sophisticated computations arise by virtue of the anatomical convergence of novel combinations of inputs to the cortical column from external sources.

Aggresomes: A Cellular Response to Misfolded Proteins

Abstract: Intracellular deposition of misfolded protein aggregates into ubiquitin-rich cytoplasmic inclusions is linked to the pathogenesis of many diseases. Why these aggregates form despite the existence of cellular machinery to recognize and degrade misfolded protein and how they are delivered to cytoplasmic inclusions are not known. We have investigated the intracellular fate of cystic fibrosis transmembrane conductance regulator (CFTR), an inefficiently folded integral membrane protein which is degraded by the cytoplasmic ubiquitin-proteasome pathway. Overexpression or inhibition of proteasome activity in transfected human embryonic kidney or Chinese hamster ovary cells led to the accumulation of stable, high molecular weight, detergent-insoluble, multiubiquitinated forms of CFTR. Using immunofluorescence and transmission electron microscopy with immunogold labeling, we demonstrate that undegraded CFTR molecules accumulate at a distinct pericentriolar structure which we have termed the aggresome. Aggresome formation is accompanied by redistribution of the intermediate filament protein vimentin to form a cage surrounding a pericentriolar core of aggregated, ubiquitinated protein. Disruption of microtubules blocks the formation of aggresomes. Similarly, inhibition of proteasome function also prevented the degradation of unassembled presenilin-1 molecules leading to their aggregation and deposition in aggresomes. These data lead us to propose that aggresome formation is a general response of cells which occurs when the capacity of the proteasome is exceeded by the production of aggregation-prone misfolded proteins.

Activation of the ATM Kinase by Ionizing Radiation and Phosphorylation of p53

Abstract: The p53 tumor suppressor protein is activated and phosphorylated on serine-15 in response to various DNA damaging agents. The gene product mutated in ataxia telangiectasia, ATM, acts upstream of p53 in a signal transduction pathway initiated by ionizing radiation. Immunoprecipitated ATM had intrinsic protein kinase activity and phosphorylated p53 on serine-15 in a manganese-dependent manner. Ionizing radiation, but not ultraviolet radiation, rapidly enhanced this p53-directed kinase activity of endogenous ATM. These observations, along with the fact that phosphorylation of p53 on serine-15 in response to ionizing radiation is reduced in ataxia telangiectasia cells, suggest that ATM is a protein kinase that phosphorylates p53 in vivo.

Bad News Travels Slowly: Size, Analyst Coverage and the Profitability of Momentum Strategies

Abstract: A number of theories have been proposed to explain the medium-term momentum in stock returns identified by Jegadeesh and Titman (1993). We test one such theory--based on the gradual-information-diffusion model of Hong and Stein (1997)--and establish three key results. First, once one moves past the very smallest stocks (where thin market-making capacity appears to be an issue) the profitability of momentum strategies declines sharply with firm size. Second, holding size fixed, momentum strategies work particularly well among stocks which have low analyst coverage. Finally, there is a strong asymmetry: the effect of analyst coverage is much more pronounced for stocks that are past losers than for stocks that are past winners. These findings are consistent with the hypothesis that firm-specific information only gradually across the investing public.

Mechanisms of wnt signaling in development

Abstract: Wnt genes encode a large family of secreted, cysteine-rich proteins that play key roles as intercellular signaling molecules in development. Genetic studies in Drosophila and Caenorhabditis elegans, ectopic gene expression in Xenopus, and gene knockouts in the mouse have demonstrated the involvement of Wnts in processes as diverse as segmentation, CNS patterning, and control of asymmetric cell divisions. The transduction of Wnt signals between cells proceeds in a complex series of events including post-translational modification and secretion of Wnts, binding to transmembrane receptors, activation of cytoplasmic effectors, and, finally, transcriptional regulation of target genes. Over the past two years our understanding of Wnt signaling has been substantially improved by the identification of Frizzled proteins as cell surface receptors for Wnts and by the finding that beta-catenin, a component downstream of the receptor, can translocate to the nucleus and function as a transcriptional activator. Here we review recent data that have started to unravel the mechanisms of Wnt signaling.

The Transcriptional Program of Sporulation in Budding Yeast

Abstract: Diploid cells of budding yeast produce haploid cells through the developmental program of sporulation, which consists of meiosis and spore morphogenesis DNA microarrays containing nearly every yeast gene were used to assay changes in gene expression during sporulation At least seven distinct temporal patterns of induction were observed The transcription factor Ndt80 appeared to be important for induction of a large group of genes at the end of meiotic prophase Consensus sequences known or proposed to be responsible for temporal regulation could be identified solely from analysis of sequences of coordinately expressed genes The temporal expression pattern provided clues to potential functions of hundreds of previously uncharacterized genes, some of which have vertebrate homologs that may function during gametogenesis

Calcium oscillations increase the efficiency and specificity of gene expression

Abstract: Cytosolic calcium ([Ca2+]i) oscillations are a nearly universal mode of signalling in excitable and non-excitable cells. Although Ca2+ is known to mediate a diverse array of cell functions, it is not known whether oscillations contribute to the efficiency or specificity of signalling or are merely an inevitable consequence of the feedback control of [Ca2+]i. We have developed a Ca2+ clamp technique to investigate the roles of oscillation amplitude and frequency in regulating gene expression driven by the proinflammatory transcription factors NF-AT, Oct/OAP and NF-kappaB. Here we report that oscillations reduce the effective Ca2+ threshold for activating transcription factors, thereby increasing signal detection at low levels of stimulation. In addition, specificity is encoded by the oscillation frequency: rapid oscillations stimulate all three transcription factors, whereas infrequent oscillations activate only NF-kappaB. The genes encoding the cytokines interleukin (IL)-2 and IL-8 are also frequency-sensitive in a way that reflects their degree of dependence on NF-AT versus NF-kappaB. Our results provide direct evidence that [Ca2+]i oscillations increase both the efficacy and the information content of Ca2+ signals that lead to gene expression and cell differentiation.