Showing papers by "Stanford University published in 2000"

Gene Ontology: tool for the unification of biology

Abstract: Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.

Meta-analysis of observational studies in epidemiology - A proposal for reporting

Abstract: ObjectiveBecause of the pressure for timely, informed decisions in public health and clinical practice and the explosion of information in the scientific literature, research results must be synthesized. Meta-analyses are increasingly used to address this problem, and they often evaluate observational studies. A workshop was held in Atlanta, Ga, in April 1997, to examine the reporting of meta-analyses of observational studies and to make recommendations to aid authors, reviewers, editors, and readers.ParticipantsTwenty-seven participants were selected by a steering committee, based on expertise in clinical practice, trials, statistics, epidemiology, social sciences, and biomedical editing. Deliberations of the workshop were open to other interested scientists. Funding for this activity was provided by the Centers for Disease Control and Prevention.EvidenceWe conducted a systematic review of the published literature on the conduct and reporting of meta-analyses in observational studies using MEDLINE, Educational Research Information Center (ERIC), PsycLIT, and the Current Index to Statistics. We also examined reference lists of the 32 studies retrieved and contacted experts in the field. Participants were assigned to small-group discussions on the subjects of bias, searching and abstracting, heterogeneity, study categorization, and statistical methods.Consensus ProcessFrom the material presented at the workshop, the authors developed a checklist summarizing recommendations for reporting meta-analyses of observational studies. The checklist and supporting evidence were circulated to all conference attendees and additional experts. All suggestions for revisions were addressed.ConclusionsThe proposed checklist contains specifications for reporting of meta-analyses of observational studies in epidemiology, including background, search strategy, methods, results, discussion, and conclusion. Use of the checklist should improve the usefulness of meta-analyses for authors, reviewers, editors, readers, and decision makers. An evaluation plan is suggested and research areas are explored.

Molecular portraits of human breast tumours

Abstract: Human breast tumours are diverse in their natural history and in their responsiveness to treatments. Variation in transcriptional programs accounts for much of the biological diversity of human cells and tumours. In each cell, signal transduction and regulatory systems transduce information from the cell's identity to its environmental status, thereby controlling the level of expression of every gene in the genome. Here we have characterized variation in gene expression patterns in a set of 65 surgical specimens of human breast tumours from 42 different individuals, using complementary DNA microarrays representing 8,102 human genes. These patterns provided a distinctive molecular portrait of each tumour. Twenty of the tumours were sampled twice, before and after a 16-week course of doxorubicin chemotherapy, and two tumours were paired with a lymph node metastasis from the same patient. Gene expression patterns in two tumour samples from the same individual were almost always more similar to each other than either was to any other sample. Sets of co-expressed genes were identified for which variation in messenger RNA levels could be related to specific features of physiological variation. The tumours could be classified into subtypes distinguished by pervasive differences in their gene expression patterns.

A global geometric framework for nonlinear dimensionality reduction.

Abstract: Scientists working with large volumes of high-dimensional data, such as global climate patterns, stellar spectra, or human gene distributions, regularly confront the problem of dimensionality reduction: finding meaningful low-dimensional structures hidden in their high-dimensional observations. The human brain confronts the same problem in everyday perception, extracting from its high-dimensional sensory inputs-30,000 auditory nerve fibers or 10(6) optic nerve fibers-a manageably small number of perceptually relevant features. Here we describe an approach to solving dimensionality reduction problems that uses easily measured local metric information to learn the underlying global geometry of a data set. Unlike classical techniques such as principal component analysis (PCA) and multidimensional scaling (MDS), our approach is capable of discovering the nonlinear degrees of freedom that underlie complex natural observations, such as human handwriting or images of a face under different viewing conditions. In contrast to previous algorithms for nonlinear dimensionality reduction, ours efficiently computes a globally optimal solution, and, for an important class of data manifolds, is guaranteed to converge asymptotically to the true structure.

Dynamic capabilities, what are they?

Abstract: This paper focuses on dynamic capabilities and, more generally, the resource-based view of the firm. We argue that dynamic capabilities are a set of specific and identifiable processes such as product development, strategic decision making, and alliancing. They are neither vague nor tautological. Although dynamic capabilities are idiosyncratic in their details and path dependent in their emergence, they have significant commonalities across firms (popularly termed ‘best practice’). This suggests that they are more homogeneous, fungible, equifinal, and substitutable than is usually assumed. In moderately dynamic markets, dynamic capabilities resemble the traditional conception of routines. They are detailed, analytic, stable processes with predictable outcomes. In contrast, in high-velocity markets, they are simple, highly experiential and fragile processes with unpredictable outcomes. Finally, well-known learning mechanisms guide the evolution of dynamic capabilities. In moderately dynamic markets, the evolutionary emphasis is on variation. In high-velocity markets, it is on selection. At the level of RBV, we conclude that traditional RBV misidentifies the locus of long-term competitive advantage in dynamic markets, overemphasizes the strategic logic of leverage, and reaches a boundary condition in high-velocity markets. Copyright © 2000 John Wiley & Sons, Ltd.

Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling

Abstract: 12 Pathology and Microbiology, and 13 Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumours. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells ('germinal centre B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer.

Global biodiversity scenarios for the year 2100.

Abstract: Scenarios of changes in biodiversity for the year 2100 can now be developed based on scenarios of changes in atmospheric carbon dioxide, climate, vegetation, and land use and the known sensitivity of biodiversity to these changes. This study identified a ranking of the importance of drivers of change, a ranking of the biomes with respect to expected changes, and the major sources of uncertainties. For terrestrial ecosystems, land-use change probably will have the largest effect, followed by climate change, nitrogen deposition, biotic exchange, and elevated carbon dioxide concentration. For freshwater ecosystems, biotic exchange is much more important. Mediterranean climate and grassland ecosystems likely will experience the greatest proportional change in biodiversity because of the substantial influence of all drivers of biodiversity change. Northern temperate ecosystems are estimated to experience the least biodiversity change because major land-use change has already occurred. Plausible changes in biodiversity in other biomes depend on interactions among the causes of biodiversity change. These interactions represent one of the largest uncertainties in projections of future biodiversity change.

How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.

Abstract: The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55‐ 89, 2000)

The genome sequence of Drosophila melanogaster

Abstract: The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

Nanotube molecular wires as chemical sensors

Abstract: Chemical sensors based on individual single-walled carbon nanotubes (SWNTs) are demonstrated. Upon exposure to gaseous molecules such as NO 2 or NH 3 , the electrical resistance of a semiconducting SWNT is found to dramatically increase or decrease. This serves as the basis for nanotube molecular sensors. The nanotube sensors exhibit a fast response and a substantially higher sensitivity than that of existing solid-state sensors at room temperature. Sensor reversibility is achieved by slow recovery under ambient conditions or by heating to high temperatures. The interactions between molecular species and SWNTs and the mechanisms of molecular sensing with nanotube molecular wires are investigated.

Genomic expression programs in the response of yeast cells to environmental changes.

Abstract: We explored genomic expression patterns in the yeast Saccharomyces cerevisiae responding to diverse environmental transitions. DNA microarrays were used to measure changes in transcript levels over time for almost every yeast gene, as cells responded to temperature shocks, hydrogen peroxide, the superoxide-generating drug menadione, the sulfhydryl-oxidizing agent diamide, the disulfide-reducing agent dithiothreitol, hyper- and hypo-osmotic shock, amino acid starvation, nitrogen source depletion, and progression into stationary phase. A large set of genes (approximately 900) showed a similar drastic response to almost all of these environmental changes. Additional features of the genomic responses were specialized for specific conditions. Promoter analysis and subsequent characterization of the responses of mutant strains implicated the transcription factors Yap1p, as well as Msn2p and Msn4p, in mediating specific features of the transcriptional response, while the identification of novel sequence elements provided clues to novel regulators. Physiological themes in the genomic responses to specific environmental stresses provided insights into the effects of those stresses on the cell.

The Earth Mover's Distance as a Metric for Image Retrieval

Abstract: We investigate the properties of a metric between two distributions, the Earth Mover's Distance (EMD), for content-based image retrieval. The EMD is based on the minimal cost that must be paid to transform one distribution into the other, in a precise sense, and was first proposed for certain vision problems by Peleg, Werman, and Rom. For image retrieval, we combine this idea with a representation scheme for distributions that is based on vector quantization. This combination leads to an image comparison framework that often accounts for perceptual similarity better than other previously proposed methods. The EMD is based on a solution to the transportation problem from linear optimization, for which efficient algorithms are available, and also allows naturally for partial matching. It is more robust than histogram matching techniques, in that it can operate on variable-length representations of the distributions that avoid quantization and other binning problems typical of histograms. When used to compare distributions with the same overall mass, the EMD is a true metric. In this paper we focus on applications to color and texture, and we compare the retrieval performance of the EMD with that of other distances.

Consequences of changing biodiversity

Abstract: Human alteration of the global environment has triggered the sixth major extinction event in the history of life and caused widespread changes in the global distribution of organisms. These changes in biodiversity alter ecosystem processes and change the resilience of ecosystems to environmental change. This has profound consequences for services that humans derive from ecosystems. The large ecological and societal consequences of changing biodiversity should be minimized to preserve options for future solutions to global environmental problems.

Mitigating routing misbehavior in mobile ad hoc networks

Abstract: This paper describes two techniques that improve throughput in an ad hoc network in the presence of nodes that agree to forward packets but fail to do so. To mitigate this problem, we propose categorizing nodes based upon their dynamically measured behavior. We use a watchdog that identifies misbehaving nodes and a pathrater that helps routing protocols avoid these nodes. Through simulation we evaluate watchdog and pathrater using packet throughput, percentage of overhead (routing) transmissions, and the accuracy of misbehaving node detection. When used together in a network with moderate mobility, the two techniques increase throughput by 17% in the presence of 40% misbehaving nodes, while increasing the percentage of overhead transmissions from the standard routing protocol's 9% to 17%. During extreme mobility, watchdog and pathrater can increase network throughput by 27%, while increasing the overhead transmissions from the standard routing protocol's 12% to 24%.

RRT-connect: An efficient approach to single-query path planning

Abstract: A simple and efficient randomized algorithm is presented for solving single-query path planning problems in high-dimensional configuration spaces. The method works by incrementally building two rapidly-exploring random trees (RRTs) rooted at the start and the goal configurations. The trees each explore space around them and also advance towards each other through, the use of a simple greedy heuristic. Although originally designed to plan motions for a human arm (modeled as a 7-DOF kinematic chain) for the automatic graphic animation of collision-free grasping and manipulation tasks, the algorithm has been successfully applied to a variety of path planning problems. Computed examples include generating collision-free motions for rigid objects in 2D and 3D, and collision-free manipulation motions for a 6-DOF PUMA arm in a 3D workspace. Some basic theoretical analysis is also presented.

Effect of aquaculture on world fish supplies

Abstract: Global production of farmed fish and shellfish has more than doubled in the past 15 years. Many people believe that such growth relieves pressure on ocean fisheries, but the opposite is true for some types of aquaculture. Farming carnivorous species requires large inputs of wild fish for feed. Some aquaculture systems also reduce wild fish supplies through habitat modification, wild seedstock collection and other ecological impacts. On balance, global aquaculture production still adds to world fish supplies; however, if the growing aquaculture industry is to sustain its contribution to world fish supplies, it must reduce wild fish inputs in feed and adopt more ecologically sound management practices.

A clonogenic common myeloid progenitor that gives rise to all myeloid lineages

Abstract: Haematopoietic stem cells give rise to progeny that progressively lose self-renewal capacity and become restricted to one lineage. The points at which haematopoietic stem cell-derived progenitors commit to each of the various lineages remain mostly unknown. We have identified a clonogenic common lymphoid progenitor that can differentiate into T, B and natural killer cells but not myeloid cells. Here we report the prospective identification, purification and characterization, using cell-surface markers and flow cytometry, of a complementary clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Common myeloid progenitors give rise to either megakaryocyte/erythrocyte or granulocyte/macrophage progenitors. Purified progenitors were used to provide a first-pass expression profile of various haematopoiesis-related genes. We propose that the common lymphoid progenitor and common myeloid progenitor populations reflect the earliest branch points between the lymphoid and myeloid lineages, and that the commitment of common myeloid progenitors to either the megakaryocyte/erythrocyte or the granulocyte/macrophage lineages are mutually exclusive events.

When choice is demotivating: Can one desire too much of a good thing?

Abstract: Current psychological theory and research affirm the positive affective and motivational consequences of having personal choice. These findings have led to the popular notion that the more choice, the better--that the human ability to manage, and the human desire for, choice is unlimited. Findings from 3 experimental studies starkly challenge this implicit assumption that having more choices is necessarily more intrinsically motivating than having fewer. These experiments, which were conducted in both field and laboratory settings, show that people are more likely to purchase gourmet jams or chocolates or to undertake optional class essay assignments when offered a limited array of 6 choices rather than a more extensive array of 24 or 30 choices. Moreover, participants actually reported greater subsequent satisfaction with their selections and wrote better essays when their original set of options had been limited. Implications for future research are discussed.

Purified hematopoietic stem cells can differentiate into hepatocytes in vivo

Abstract: The characterization of hepatic progenitor cells is of great scientific and clinical interest. Here we report that intravenous injection of adult bone marrow cells in the FAH(-/-) mouse, an animal model of tyrosinemia type I, rescued the mouse and restored the biochemical function of its liver. Moreover, within bone marrow, only rigorously purified hematopoietic stem cells gave rise to donor-derived hematopoietic and hepatic regeneration. This result seems to contradict the conventional assumptions of the germ layer origins of tissues such as the liver, and raises the question of whether the cells of the hematopoietic stem cell phenotype are pluripotent hematopoietic cells that retain the ability to transdifferentiate, or whether they are more primitive multipotent cells.

Exercise of Human Agency Through Collective Efficacy

Abstract: Social c ognitive t heory adopts an agentic perspective in which individuals are producers of experiences and shapers of events. Among the mechanisms of human agency, none is more focal or pervading than the belief of personal efficacy. This core belief is the foundation of human agency. Unless people believe that they can produce desired effects and forestall undesired ones by their actions, they have little incentive to act. The growing interdependence of human functioning is placing a premium on the exercise of collective agency through shared beliefs in the power to produce effects by collective action. The present article analyzes the nature of perceived collective efficacy and its centrality in how people live their lives. Perceived collective efficacy fosters groups’ motivational commitment to their missions, resilience to adversity, and performance a ccomplishments.

Adhesive force of a single gecko foot-hair

Abstract: Geckos are exceptional in their ability to climb rapidly up smooth vertical surfaces1,2,3. Microscopy has shown that a gecko's foot has nearly five hundred thousand keratinous hairs or setae. Each 30–130 µm long seta is only one-tenth the diameter of a human hair and contains hundreds of projections terminating in 0.2–0.5 µm spatula-shaped structures2,4. After nearly a century of anatomical description2,4,5,6, here we report the first direct measurements of single setal force by using a two-dimensional micro-electro-mechanical systems force sensor7 and a wire as a force gauge. Measurements revealed that a seta is ten times more effective at adhesion than predicted from maximal estimates on whole animals. Adhesive force values support the hypothesis that individual seta operate by van der Waals forces8,9. The gecko's peculiar behaviour of toe uncurling and peeling2 led us to discover two aspects of setal function which increase their effectiveness. A unique macroscopic orientation and preloading of the seta increased attachment force 600-fold above that of frictional measurements of the material. Suitably orientated setae reduced the forces necessary to peel the toe by simply detaching above a critical angle with the substratum.

Systematic variation in gene expression patterns in human cancer cell lines.

Abstract: We used cDNA microarrays to explore the variation in expression of approximately 8,000 unique genes among the 60 cell lines used in the National Cancer Institute's screen for anti-cancer drugs. Classification of the cell lines based solely on the observed patterns of gene expression revealed a correspondence to the ostensible origins of the tumours from which the cell lines were derived. The consistent relationship between the gene expression patterns and the tissue of origin allowed us to recognize outliers whose previous classification appeared incorrect. Specific features of the gene expression patterns appeared to be related to physiological properties of the cell lines, such as their doubling time in culture, drug metabolism or the interferon response. Comparison of gene expression patterns in the cell lines to those observed in normal breast tissue or in breast tumour specimens revealed features of the expression patterns in the tumours that had recognizable counterparts in specific cell lines, reflecting the tumour, stromal and inflammatory components of the tumour tissue. These results provided a novel molecular characterization of this important group of human cell lines and their relationships to tumours in vivo.

Machines and Mindlessness: Social Responses to Computers

Abstract: Following Langer (1992), this article reviews a series of experimental studiesthat demonstrate that individuals mindlessly apply social rules and expecta-tions to computers. The first set of studies illustrates how individuals overusehuman social categories, applying gender stereotypes to computers and ethnicallyidentifying with computer agents. The second set demonstrates that people exhibitoverlearned social behaviors such as politeness and reciprocity toward comput-ers.Inthethirdsetofstudies,prematurecognitivecommitmentsaredemonstrated:Aspecialisttelevisionsetisperceivedasprovidingbettercontentthanageneralisttelevision set. A final series of studies demonstrates the depth of social responseswith respect to computer “personality.” Alternative explanations for these find -ings, such as anthropomorphism and intentional social responses, cannot explainthe results. We conclude with an agenda for future research.Computer users approach the personal computer in many different ways.Experienced word processors move smoothly from keyboard to mouse to menu,mixing prose and commands to the computer automatically; the distinctionbetween the hand and the tool blurs (Heidegger, 1977; Winograd & Flores, 1987).Novices cautiously strike each key, fearing that one false move will initiate anuncontrollable series of unwanted events. Game players view computers as

The Value of Information Sharing in a Two-Level Supply Chain

Abstract: Many companies have embarked on initiatives that enable more demand information sharing between retailers and their upstream suppliers. While the literature on such initiatives in the business press is proliferating, it is not clear how one can quantify the benefits of these initiatives and how one can identify the drivers of the magnitudes of these benefits. Using analytical models, this paper aims at addressing these questions for a simple two-level supply chain with nonstationary end demands. Our analysis suggests that the value of demand information sharing can be quite high, especially when demands are significantly correlated over time.

Transform analysis and asset pricing for affine jump-diffusions

Abstract: In the setting of ‘‘affine’’ jump-diffusion state processes, this paper provides an analytical treatment of a class of transforms, including various Laplace and Fourier transforms as special cases, that allow an analytical treatment of a range of valuation and econometric problems. Example applications include fixed-income pricing models, with a role for intensity-based models of default, as well as a wide range of option-pricing applications. An illustrative example examines the implications of stochastic volatility and jumps for option valuation. This example highlights the impact on option ‘smirks’ of the joint distribution of jumps in volatility and jumps in the underlying asset price, through both jump amplitude as well as jump timing.

Schooling, Labor-Force Quality, and the Growth of Nations

Abstract: Direct measures of labor-force quality from international mathematics and science test scores are strongly related to growth. Indirect specification tests are generally consistent with a causal link: direct spending on schools is unrelated to student performance differences; the estimated growth effects of improved labor-force quality hold when East Asian countries are excluded; and, finally, home-country quality differences of immigrants are directly related to U.S. earnings if the immigrants are educated in their own country but not in the United States. The last estimates of micro productivity effects, however, introduce uncertainty about the magnitude of the growth effects.

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

Abstract: Various theories have been proposed to explain momentum in stock returns. We test the gradual-information-diffusion model of Hong and Stein ~1999! and establish three key results. First, once one moves past the very smallest stocks, the profitability of momentum strategies declines sharply with firm size. Second, holding size fixed, momentum strategies work better among stocks with low analyst coverage. Finally, the effect of analyst coverage is greater for stocks that are past losers than for past winners. These findings are consistent with the hypothesis that firm-specific information, especially negative information, diffuses only gradually across the investing public.

Searching for genetic determinants in the new millennium

Abstract: Human genetics is now at a critical juncture. The molecular methods used successfully to identify the genes underlying rare mendelian syndromes are failing to find the numerous genes causing more common, familial, non-mendelian diseases. With the human genome sequence nearing completion, new opportunities are being presented for unravelling the complex genetic basis of non-mendelian disorders based on large-scale genome-wide studies. Considerable debate has arisen regarding the best approach to take. In this review I discuss these issues, together with suggestions for optimal post-genome strategies.