Showing papers by "University of California, Irvine published in 2003"

International Union of Pharmacology: Approaches to the Nomenclature of Voltage-Gated Ion Channels

Abstract: This issue of Pharmacological Reviews includes a new venture in the collaboration between the International Union of Pharmacology (IUPHAR) and the American Society for Pharmacology and Experimental Therapeutics (ASPET), in that a new classification of voltage-gated ion channels is outlined in this

Common Structure of Soluble Amyloid Oligomers Implies Common Mechanism of Pathogenesis

Abstract: Soluble oligomers are common to most amyloids and may represent the primary toxic species of amyloids, like the Aβ peptide in Alzheimer's disease (AD). Here we show that all of the soluble oligomers tested display a common conformation-dependent structure that is unique to soluble oligomers regardless of sequence. The in vitro toxicity of soluble oligomers is inhibited by oligomer-specific antibody. Soluble oligomers have a unique distribution in human AD brain that is distinct from fibrillar amyloid. These results indicate that different types of soluble amyloid oligomers have a common structure and suggest they share a common mechanism of toxicity.

A Framework to Quantitatively Assess and Enhance the Seismic Resilience of Communities

Abstract: This paper presents a conceptual framework to define seismic resilience of communities and quantitative measures of resilience that can be useful for a coordinated research effort focusing on enhancing this resilience. This framework relies on the complementary measures of resilience: ‘‘Reduced failure probabilities,’’ ‘‘Reduced consequences from failures,’’ and ‘‘Reduced time to recovery.’’ The framework also includes quantitative measures of the ‘‘ends’’ of robustness and rapidity, and the ‘‘means’’ of resourcefulness and redundancy, and integrates those measures into the four dimensions of community resilience—technical, organizational, social, and economic—all of which can be used to quantify measures of resilience for various types of physical and organizational systems. Systems diagrams then establish the tasks required to achieve these objectives. This framework can be useful in future research to determine the resiliency of different units of analysis and systems, and to develop resiliency targets and detailed analytical procedures to generate these values. [DOI: 10.1193/1.1623497]

Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies

Abstract: Germline mutations in BRCA1 and BRCA2 confer high risks of breast and ovarian cancer, but the average magnitude of these risks is uncertain and may depend on the context. Estimates based on multiple-case families may be enriched for mutations of higher risk and/or other familial risk factors, whereas risk estimates from studies based on cases unselected for family history have been imprecise. We pooled pedigree data from 22 studies involving 8,139 index case patients unselected for family history with female (86%) or male (2%) breast cancer or epithelial ovarian cancer (12%), 500 of whom had been found to carry a germline mutation in BRCA1 or BRCA2. Breast and ovarian cancer incidence rates for mutation carriers were estimated using a modified segregation analysis, based on the occurrence of these cancers in the relatives of mutation-carrying index case patients. The average cumulative risks in BRCA1-mutation carriers by age 70 years were 65% (95% confidence interval 44%-78%) for breast cancer and 39% (18%-54%) for ovarian cancer. The corresponding estimates for BRCA2 were 45% (31%-56%) and 11% (2.4%-19%). Relative risks of breast cancer declined significantly with age for BRCA1-mutation carriers (P trend.0012) but not for BRCA2-mutation carriers. Risks in carriers were higher when based on index breast cancer cases diagnosed at <35 years of age. We found some evidence for a reduction in risk in women from earlier birth cohorts and for variation in risk by mutation position for both genes. The pattern of cancer risks was similar to those found in multiple-case families, but their absolute magnitudes were lower, particularly for BRCA2. The variation in risk by age at diagnosis of index case is consistent with the effects of other genes modifying cancer risk in carriers.

Reconceptualizing Organizational Routines as a Source of Flexibility and Change

Abstract: In this paper, we challenge the traditional understanding of organizational routines as creating inertia in organizations. We adapt Latour's distinction between ostensive and performative to build a theory that explains why routines are a source of change as well as stability. The ostensive aspect of a routine embodies what we typically think of as the structure. The performative aspect embodies the specific actions, by specific people, at specific times and places, that bring the routine to life. We argue that the ostensive aspect enables people to guide, account for, and refer to specific performances of a routine, and the performative aspect creates, maintains, and modifies the ostensive aspect of the routine. We argue that the relationship between ostensive and performative aspects of routines creates an on-going opportunity for variation, selection, and retention of new practices and patterns of action within routines and allows routines to generate a wide range of outcomes, from apparent stability t...

The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models.

Abstract: Motivation: Molecular biotechnology now makes it possible to build elaborate systems models, but the systems biology community needs information standards if models are to be shared, evaluated and developed cooperatively. Results: We summarize the Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks. SBML is a software-independent language for describing models common to research in many areas of computational biology, including cell signaling pathways, metabolic pathways, gene regulation, and others. ∗ To whom correspondence should be addressed. Availability: The specification of SBML Level 1 is freely available from http://www.sbml.org/.

Energy, water, and broad-scale geographic patterns of species richness

Abstract: It is often claimed that we do not understand the forces driving the global diversity gradient. However, an extensive literature suggests that contemporary climate constrains terrestrial taxonomic richness over broad geographic extents. Here, we review the empirical literature to examine the nature and form of the relationship between climate and richness. Our goals were to document the support for the climatically based energy hypothesis, and within the constraints imposed by correlative analyses, to evaluate two versions of the hypothesis: the productivity and ambient energy hypotheses. Focusing on studies extending over 800 km, we found that measures of energy, water, or water-energy balance explain spatial variation in richness better than other climatic and non-climatic variables in 82 of 85 cases. Even when considered individually and in isolation, water/ energy variables explain on average over 60% of the variation in the richness of a wide range of plant and animal groups. Further, water variables usually represent the strongest predictors in the tropics, subtropics, and warm temperate zones, whereas energy variables (for animals) or water-energy variables (for plants) dominate in high latitudes. We conclude that the interaction between water and energy, either directly or indirectly (via plant productivity), provides a strong explanation for globally extensive plant and animal diversity gradients, but for animals there also is a latitudinal shift in the relative importance of ambient energy vs. water moving from the poles to the equator. Although contemporary climate is not the only factor influencing species richness and may not explain the diversity pattern for all taxonomic groups, it is clear that understanding water-energy dynamics is critical to future biodiversity research. Analyses that do not include water-energy variables are missing a key component for explaining broad-scale patterns of diversity.

Estrogen plus progestin and the risk of coronary heart disease

Abstract: Background Recent randomized clinical trials have suggested that estrogen plus progestin does not confer cardiac protection and may increase the risk of coronary heart disease (CHD). In this report, we provide the final results with regard to estrogen plus progestin and CHD from the Women's Health Initiative (WHI). Methods The WHI included a randomized primary-prevention trial of estrogen plus progestin in 16,608 postmenopausal women who were 50 to 79 years of age at base line. Participants were randomly assigned to receive conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo. The primary efficacy outcome of the trial was CHD (nonfatal myocardial infarction or death due to CHD). Results After a mean follow-up of 5.2 years (planned duration, 8.5 years), the data and safety monitoring board recommended terminating the estrogen-plus-progestin trial because the overall risks exceeded the benefits. Combined hormone therapy was associated with a hazard ratio for CHD of 1.24 (nominal 95 percent confidence interval, 1.00 to 1.54; 95 percent confidence interval after adjustment for sequential monitoring, 0.97 to 1.60). The elevation in risk was most apparent at one year (hazard ratio, 1.81 [95 percent confidence interval, 1.09 to 3.01]). Although higher base-line levels of low-density lipoprotein cholesterol were associated with an excess risk of CHD among women who received hormone therapy, higher base-line levels of C-reactive protein, other biomarkers, and other clinical characteristics did not significantly modify the treatment-related risk of CHD. Conclusions Estrogen plus progestin does not confer cardiac protection and may increase the risk of CHD among generally healthy postmenopausal women, especially during the first year after the initiation of hormone use. This treatment should not be prescribed for the prevention of cardiovascular disease.

Mechanisms of pulsed laser ablation of biological tissues.

Abstract: Author(s): Vogel, Alfred; Venugopalan, Vasan | Abstract: The mechanisms of pulsed laser ablation of biological tissues were studied. The transiently empty space created between the fiber tip and the tissue surface improved the optical transmission to the target and thus increased the ablation efficiency. It was found that the structure and morphology also affect the energy transport among tissue constituents.

The molecular logic of endocannabinoid signalling

Abstract: The endocannabinoids are a family of lipid messengers that engage the cell surface receptors that are targeted by Δ9-tetrahydrocannabinol, the active principle in marijuana (Cannabis). They are made on demand through cleavage of membrane precursors and are involved in various short-range signalling processes. In the brain, they combine with CB1 cannabinoid receptors on axon terminals to regulate ion channel activity and neurotransmitter release. Their ability to modulate synaptic efficacy has a wide range of functional consequences and provides unique therapeutic possibilities.

Limited Attention, Information Disclosure, and Financial Reporting

Abstract: This paper models firms' choices between alternative means of presenting information, and the effects of different presentations on market prices when investors have limited attention and processing power. In a market equilibrium with partially attentive investors, we examine the effects of alternative: levels of discretion in pro forma earnings disclosure, methods of accounting for employee option compensation, and degrees of aggregation in reporting. We derive empirical implications relating pro forma adjustments, option compensation, the growth, persistence, and informativeness of earnings, short-run managerial incentives, and other firm characteristics to stock price reactions, misvaluation, long-run abnormal returns, and corporate decisions.

Genome Scan Meta-Analysis of Schizophrenia and Bipolar Disorder, Part II: Schizophrenia

Abstract: Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.

Protest and Political Opportunities

Abstract: I review the development of the political opportunity or political process perspective, which has animated a great deal of research on social movements. The essential insight—that the context in which a movement emerges influences its development and potential impact—provides a fruitful analytic orientation for addressing numerous questions about social movements. Reviewing the development of the literature, however, I note that conceptualizations of political opportunity vary greatly, and scholars disagree on basic theories of how political opportunities affect movements. The relatively small number of studies testing political opportunity hypotheses against other explanations have generated mixed results, owing in part to the articulation of the theory and the specifications of variables employed. I examine conflicting specifications of the theory by considering the range of outcomes scholars address. By disaggregating outcomes and actors, I argue, we can reconcile some of the apparent contradictions an...

Structural cohesion and embeddedness: A hierarchical concept of social groups

Abstract: Although questions about social cohesion lie at the core of our discipline, definitions are often vague and difficult to operationalize. Here, research on social cohesion and social embeddedness is linked by developing a concept of structural cohesion based on network node connectivity. Structural cohesion is defined as the minimum number of actors who, if removed from a group, would disconnect the group. A structural dimension of embeddedness can then be defined through the hierarchical nesting of these cohesive structures. The empirical applicability of nestedness is demonstrated in two dramatically different substantive settings, and additional theoretical implications with reference to a wide array of substantive fields are discussed.

Mineral Dust Entrainment and Deposition (DEAD) model: Description and 1990s dust climatology

Abstract: 17 ± 2 Tg; and optical depth at 0.63 mm, 0.030 ± 0.004. This emission, burden, and optical depth are significantly lower than some recent estimates. The model underestimates transport and deposition of East Asian and Australian dust to some regions of the Pacific Ocean. An underestimate of long-range transport of particles larger than 3 mm contributes to this bias. Our experiments support the hypothesis that dust emission ‘‘hot spots’’ exist in regions where alluvial sediments have accumulated and may be disturbed. INDEX TERMS: 0305 Atmospheric Composition and Structure: Aerosols and particles (0345, 4801); 0322 Atmospheric Composition and Structure: Constituent sources and sinks; 4801 Oceanography: Biological and Chemical: Aerosols (0305); 5415 Planetology: Solid Surface Planets: Erosion and weathering; KEYWORDS: mineral dust aerosol, aerosol climatology, mineral deposition, aerosol scavenging, saltation sandblasting, ecosystem fertilization

Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-α

Abstract: Oleylethanolamide (OEA) is a naturally occurring lipid that regulates satiety and body weight. Although structurally related to the endogenous cannabinoid anandamide, OEA does not bind to cannabinoid receptors and its molecular targets have not been defined. Here we show that OEA binds with high affinity to the peroxisome-proliferator-activated receptor-alpha (PPAR-alpha), a nuclear receptor that regulates several aspects of lipid metabolism. Administration of OEA produces satiety and reduces body weight gain in wild-type mice, but not in mice deficient in PPAR-alpha. Two distinct PPAR-alpha agonists have similar effects that are also contingent on PPAR-alpha expression, whereas potent and selective agonists for PPAR-gamma and PPAR-beta/delta are ineffective. In the small intestine of wild-type but not PPAR-alpha-null mice, OEA regulates the expression of several PPAR-alpha target genes: it initiates the transcription of proteins involved in lipid metabolism and represses inducible nitric oxide synthase, an enzyme that may contribute to feeding stimulation. Our results, which show that OEA induces satiety by activating PPAR-alpha, identify an unexpected role for this nuclear receptor in regulating behaviour, and raise possibilities for the treatment of eating disorders.

Information technology and economic performance: A critical review of the empirical evidence

Abstract: For many years, there has been considerable debate about whether the IT revolution was paying off in higher productivity. Studies in the 1980s found no connection between IT investment and productivity in the U.S. economy, a situation referred to as the productivity paradox. Since then, a decade of studies at the firm and country level has consistently shown that the impact of IT investment on labor productivity and economic growth is significant and positive. This article critically reviews the published research, more than 50 articles, on computers and productivity. It develops a general framework for classifying the research, which facilitates identifying what we know, how well we know it, and what we do not know. The framework enables us to systematically organize, synthesize, and evaluate the empirical evidence and to identify both limitations in existing research and data and substantive areas for future research.The review concludes that the productivity paradox as first formulated has been effectively refuted. At both the firm and the country level, greater investment in IT is associated with greater productivity growth. At the firm level, the review further concludes that the wide range of performance of IT investments among different organizations can be explained by complementary investments in organizational capital such as decentralized decision-making systems, job training, and business process redesign. IT is not simply a tool for automating existing processes, but is more importantly an enabler of organizational changes that can lead to additional productivity gains.In mid-2000, IT capital investment began to fall sharply due to slowing economic growth, the collapse of many Internet-related firms, and reductions in IT spending by other firms facing fewer competitive pressures from Internet firms. This reduction in IT investment has had devastating effects on the IT-producing sector, and may lead to slower economic and productivity growth in the U.S. economy. While the turmoil in the technology sector has been unsettling to investors and executives alike, this review shows that it should not overshadow the fundamental changes that have occurred as a result of firms' investments in IT. Notwithstanding the demise of many Internet-related companies, the returns to IT investment are real, and innovative companies continue to lead the way.

Electronic business adoption by European firms: a cross-country assessment of the facilitators and inhibitors

Abstract: In this study, we developed a conceptual model for studying the adoption of electronic business (e-business or EB) at the firm level, incorporating six adoption facilitators and inhibitors, based on the technology-organization-environment theoretical framework. Survey data from 3100 businesses and 7500 consumers in eight European countries were used to test the proposed adoption model. We conducted confirmatory factor analysis to assess the reliability and validity of constructs. To examine whether adoption patterns differ across different e-business environments, we divided the full sample into high EB-intensity and low EB-intensity countries. After controlling for variations of industry and country effects, the fitted Iogit models demonstrated four findings: (1) Technology competence, firm scope and size, consumer readiness, and competitive pressure are significant adoption drivers, while lack of trading partner readiness is a significant adoption inhibitor. (2) As EB-intensity increases, two environmental factors - consumer readiness and lack of trading partner readiness - become less important, while competitive pressure remains significant. (3) In high EB-intensity countries, e-business is no longer a phenomenon dominated by large firms; as more and more firms engage in e-business, network effect works to the advantage of small firms. (4) Firms are more cautious in adopting e-business in high EB-intensity countries - it seems to suggest that the more informed firms are less aggressive in adopting e-business, a somehow surprising result. Explanations and implications are offered.

Unpacking "privacy" for a networked world

Abstract: Although privacy is broadly recognized as a dominant concern for the development of novel interactive technologies, our ability to reason analytically about privacy in real settings is limited. A lack of conceptual interpretive frameworks makes it difficult to unpack interrelated privacy issues in settings where information technology is also present. Building on theory developed by social psychologist Irwin Altman, we outline a model of privacy as a dynamic, dialectic process. We discuss three tensions that govern interpersonal privacy management in everyday life, and use these to explore select technology case studies drawn from the research literature. These suggest new ways for thinking about privacy in socio-technical environments as a practical matter.

Spatial autocorrelation and red herrings in geographical ecology

Abstract: Aim Spatial autocorrelation in ecological data can inflate Type I errors in statistical analyses. There has also been a recent claim that spatial autocorrelation generates 'red herrings', such that virtually all past analyses are flawed. We consider the origins of this phenomenon, the implications of spatial autocorrelation for macro-scale patterns of species diversity and set out a clarification of the statistical problems generated by its presence. Location To illustrate the issues involved, we analyse the species richness of the birds of western/central Europe, north Africa and the Middle East. Methods Spatial correlograms for richness and five environmental variables were generated using Moran's I coefficients. Multiple regression, using both ordinary least-squares (OLS) and generalized least squares (GLS) assuming a spatial structure in the residuals, were used to identify the strongest predictors of richness. Autocorrelation analyses of the residuals obtained after stepwise OLS regression were undertaken, and the ranks of variables in the full OLS and GLS models were compared. Results Bird richness is characterized by a quadratic north-south gradient. Spatial correlograms usually had positive autocorrelation up to c. 1600 km. Including the environmental variables successively in the OLS model reduced spatial autocorrelation in the residuals to non-detectable levels, indicating that the variables explained all spatial structure in the data. In principle, if residuals are not autocorrelated then OLS is a special case of GLS. However, our comparison between OLS and GLS models including all environmental variables revealed that GLS de-emphasized predictors with strong autocorrelation and long-distance clinal structures, giving more importance to variables acting at smaller geographical scales. Conclusion Although spatial autocorrelation should always be investigated, it does not necessarily generate bias. Rather, it can be a useful tool to investigate mechanisms operating on richness at different spatial scales. Claims that analyses that do not take into account spatial autocorrelation are flawed are without foundation.

Natural selection shaped regional mtDNA variation in humans

Abstract: Human mtDNA shows striking regional variation, traditionally attributed to genetic drift. However, it is not easy to account for the fact that only two mtDNA lineages (M and N) left Africa to colonize Eurasia and that lineages A, C, D, and G show a 5-fold enrichment from central Asia to Siberia. As an alternative to drift, natural selection might have enriched for certain mtDNA lineages as people migrated north into colder climates. To test this hypothesis we analyzed 104 complete mtDNA sequences from all global regions and lineages. African mtDNA variation did not significantly deviate from the standard neutral model, but European, Asian, and Siberian plus Native American variations did. Analysis of amino acid substitution mutations (nonsynonymous, Ka) versus neutral mutations (synonymous, Ks) (ka/ks) for all 13 mtDNA protein-coding genes revealed that the ATP6 gene had the highest amino acid sequence variation of any human mtDNA gene, even though ATP6 is one of the more conserved mtDNA proteins. Comparison of the ka/ks ratios for each mtDNA gene from the tropical, temperate, and arctic zones revealed that ATP6 was highly variable in the mtDNAs from the arctic zone, cytochrome b was particularly variable in the temperate zone, and cytochrome oxidase I was notably more variable in the tropics. Moreover, multiple amino acid changes found in ATP6, cytochrome b, and cytochrome oxidase I appeared to be functionally significant. From these analyses we conclude that selection may have played a role in shaping human regional mtDNA variation and that one of the selective influences was climate.

Structural equation modeling for travel behavior research

Abstract: Structural equation modeling (SEM) is an extremely flexible linear-in-parameters multivariate statistical modeling technique. It has been used in modeling travel behavior and values since about 1980, and its use is rapidly accelerating, partially due to the availability of improved software. The number of published studies, now known to be more than 50, has approximately doubled in the past three years. This review of SEM is intended to provide an introduction to the field for those who have not used the method, and a compendium of applications for those who wish to compare experiences and avoid the pitfall of reinventing previous research.

Search for neutrino oscillations on a long base-line at the CHOOZ nuclear power station

Abstract: This final article about the CHOOZ experiment presents a complete description of the $\bar{ u}_e$ source and detector, the calibration methods and stability checks, the event reconstruction procedures and the Monte Carlo simulation. The data analysis, systematic effects and the methods used to reach our conclusions are fully discussed. Some new remarks are presented on the deduction of the confidence limits and on the correct treatment of systematic errors.

Global patterns of the isotopic composition of soil and plant nitrogen

Abstract: [1] We compiled new and published data on the natural abundance N isotope composition (δ15N values) of soil and plant organic matter from around the world. Across a broad range of climate and ecosystem types, we found that soil and plant δ15N values systematically decreased with increasing mean annual precipitation (MAP) and decreasing mean annual temperature (MAT). Because most undisturbed soils are near N steady state, the observations suggest that an increasing fraction of ecosystem N losses are 15N-depleted forms (NO3, N2O, etc.) with decreasing MAP and increasing MAT. Wetter and colder ecosystems appear to be more efficient in conserving and recycling mineral N. Globally, plant δ15N values are more negative than soils, but the difference (δ15Nplant-δ15Nsoil) increases with decreasing MAT (and secondarily increasing MAP), suggesting a systematic change in the source of plant-available N (organic/NH4+ versus NO3−) with climate. Nitrogen isotopes reflect time integrated measures of the controls on N storage that are critical for predictions of how these ecosystems will respond to human-mediated disturbances of the global N cycle.