Showing papers by "University of California, San Diego published in 2004"

Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.

Abstract: There is no consensus definition of acute renal failure (ARF) in critically ill patients. More than 30 different definitions have been used in the literature, creating much confusion and making comparisons difficult. Similarly, strong debate exists on the validity and clinical relevance of animal models of ARF; on choices of fluid management and of end-points for trials of new interventions in this field; and on how information technology can be used to assist this process. Accordingly, we sought to review the available evidence, make recommendations and delineate key questions for future studies. We undertook a systematic review of the literature using Medline and PubMed searches. We determined a list of key questions and convened a 2-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated recommendations and/or directions for future research. We found sufficient consensus on 47 questions to allow the development of recommendations. Importantly, we were able to develop a consensus definition for ARF. In some cases it was also possible to issue useful consensus recommendations for future investigations. We present a summary of the findings. (Full versions of the six workgroups' findings are available on the internet at http://www.ADQI.net ) Despite limited data, broad areas of consensus exist for the physiological and clinical principles needed to guide the development of consensus recommendations for defining ARF, selection of animal models, methods of monitoring fluid therapy, choice of physiological and clinical end-points for trials, and the possible role of information technology.

Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein.

Abstract: Fluorescent proteins are genetically encoded, easily imaged reporters crucial in biology and biotechnology. When a protein is tagged by fusion to a fluorescent protein, interactions between fluorescent proteins can undesirably disturb targeting or function. Unfortunately, all wild-type yellow-to-red fluorescent proteins reported so far are obligately tetrameric and often toxic or disruptive. The first true monomer was mRFP1, derived from the Discosoma sp. fluorescent protein "DsRed" by directed evolution first to increase the speed of maturation, then to break each subunit interface while restoring fluorescence, which cumulatively required 33 substitutions. Although mRFP1 has already proven widely useful, several properties could bear improvement and more colors would be welcome. We report the next generation of monomers. The latest red version matures more completely, is more tolerant of N-terminal fusions and is over tenfold more photostable than mRFP1. Three monomers with distinguishable hues from yellow-orange to red-orange have higher quantum efficiencies.

Comparing Media Systems: three models of media and politics

Abstract: This book proposes a framework for comparative analysis of the relation between the media and the political system Building on a survey of media institutions in eighteen West European and North American democracies, Hallin and Mancini identify the principal dimensions of variation in media systems and the political variables that have shaped their evolution They go on to identify three major models of media system development, the Polarized Pluralist, Democratic Corporatist, and Liberal models; to explain why the media have played a different role in politics in each of these systems; and to explore the force of change that are currently transforming them It provides a key theoretical statement about the relation between media and political systems, a key statement about the methodology of comparative analysis in political communication, and a clear overview of the variety of media institutions that have developed in the West, understood within their political and historical context

Metamaterials and negative refractive index.

Abstract: Recently, artificially constructed metamaterials have become of considerable interest, because these materials can exhibit electromagnetic characteristics unlike those of any conventional materials. Artificial magnetism and negative refractive index are two specific types of behavior that have been demonstrated over the past few years, illustrating the new physics and new applications possible when we expand our view as to what constitutes a material. In this review, we describe recent advances in metamaterials research and discuss the potential that these materials may hold for realizing new and seemingly exotic electromagnetic phenomena.

Probing the Cytotoxicity Of Semiconductor Quantum Dots.

Abstract: With their bright, photostable fluorescence, semiconductor quantum dots (QDs) show promise as alternatives to organic dyes for biological labeling. Questions about their potential cytotoxicity, however, remain unanswered. While cytotoxicity of bulk cadmium selenide (CdSe) is well documented, a number of groups have suggested that CdSe QDs are cytocompatible, at least with some immortalized cell lines. Using primary hepatocytes as a liver model, we found that CdSe-core QDs were indeed acutely toxic under certain conditions. Specifically, we found that the cytotoxicity of QDs was modulated by processing parameters during synthesis, exposure to ultraviolet light, and surface coatings. Our data further suggest that cytotoxicity correlates with the liberation of free Cd2+ ions due to deterioration of the CdSe lattice. When appropriately coated, CdSe-core QDs can be rendered nontoxic and used to track cell migration and reorganization in vitro. Our results provide information for design criteria for the use of ...

A Survey Method for Characterizing Daily Life Experience: The Day Reconstruction Method

Abstract: The Day Reconstruction Method (DRM) assesses how people spend their time and how they experience the various activities and settings of their lives, combining features of time-budget measurement and experience sampling. Participants systematically reconstruct their activities and experiences of the preceding day with procedures designed to reduce recall biases. The DRM's utility is shown by documenting close correspondences between the DRM reports of 909 employed women and established results from experience sampling. An analysis of the hedonic treadmill shows the DRM's potential for well-being research.

Molecular determinants of resistance to antiandrogen therapy

Abstract: Using microarray-based profiling of isogenic prostate cancer xenograft models, we found that a modest increase in androgen receptor mRNA was the only change consistently associated with the development of resistance to antiandrogen therapy. This increase in androgen receptor mRNA and protein was both necessary and sufficient to convert prostate cancer growth from a hormone-sensitive to a hormone-refractory stage, and was dependent on a functional ligand-binding domain. Androgen receptor antagonists showed agonistic activity in cells with increased androgen receptor levels; this antagonist-agonist conversion was associated with alterations in the recruitment of coactivators and corepressors to the promoters of androgen receptor target genes. Increased levels of androgen receptor confer resistance to antiandrogens by amplifying signal output from low levels of residual ligand, and by altering the normal response to antagonists. These findings provide insight toward the design of new antiandrogens.

The ENCODE (ENCyclopedia of DNA elements) Project

Abstract: The ENCyclopedia Of DNA Elements (ENCODE) Project aims to identify all functional elements in the human genome sequence. The pilot phase of the Project is focused on a specified 30 megabases (∼1%) of the human genome sequence and is organized as an international consortium of computational and laboratory-based scientists working to develop and apply high-throughput approaches for detecting all sequence elements that confer biological function. The results of this pilot phase will guide future efforts to analyze the entire human genome.

Effect of Intensive Compared With Moderate Lipid-Lowering Therapy on Progression of Coronary Atherosclerosis A Randomized Controlled Trial

Abstract: ContextStatin drugs reduce both atherogenic lipoproteins and cardiovascular morbidity and mortality. However, the optimal strategy and target level for lipid reduction remain uncertain.ObjectiveTo compare the effect of regimens designed to produce intensive lipid lowering or moderate lipid lowering on coronary artery atheroma burden and progression.Design, Setting, and PatientsDouble-blind, randomized active control multicenter trial (Reversal of Atherosclerosis with Aggressive Lipid Lowering [REVERSAL]) performed at 34 community and tertiary care centers in the United States comparing the effects of 2 different statins administered for 18 months. Intravascular ultrasound was used to measure progression of atherosclerosis. Between June 1999 and September 2001, 654 patients were randomized and received study drug; 502 had evaluable intravascular ultrasound examinations at baseline and after 18 months of treatment.InterventionsPatients were randomly assigned to receive a moderate lipid-lowering regimen consisting of 40 mg of pravastatin or an intensive lipid-lowering regimen consisting of 80 mg of atorvastatin.Main Outcome MeasuresThe primary efficacy parameter was the percentage change in atheroma volume (follow-up minus baseline).ResultsBaseline low-density lipoprotein cholesterol level (mean, 150.2 mg/dL [3.89 mmol/L] in both treatment groups) was reduced to 110 mg/dL (2.85 mmol/L) in the pravastatin group and to 79 mg/dL (2.05 mmol/L) in the atorvastatin group (P<.001). C-reactive protein decreased 5.2% with pravastatin and 36.4% with atorvastatin (P<.001). The primary end point (percentage change in atheroma volume) showed a significantly lower progression rate in the atorvastatin (intensive) group (P = .02). Similar differences between groups were observed for secondary efficacy parameters, including change in total atheroma volume (P = .02), change in percentage atheroma volume (P<.001), and change in atheroma volume in the most severely diseased 10-mm vessel subsegment (P<.01). For the primary end point, progression of coronary atherosclerosis occurred in the pravastatin group (2.7%; 95% confidence interval [CI], 0.2% to 4.7%; P = .001) compared with baseline. Progression did not occur in the atorvastatin group (−0.4%; CI −2.4% to 1.5%; P = .98) compared with baseline.ConclusionsFor patients with coronary heart disease, intensive lipid-lowering treatment with atorvastatin reduced progression of coronary atherosclerosis compared with pravastatin. Compared with baseline values, patients treated with atorvastatin had no change in atheroma burden, whereas patients treated with pravastatin showed progression of coronary atherosclerosis. These differences may be related to the greater reduction in atherogenic lipoproteins and C- reactive protein in patients treated with atorvastatin.

Selective Differentiation of Neural Progenitor Cells by High-Epitope Density Nanofibers

Abstract: Neural progenitor cells were encapsulated in vitro within a three-dimensional network of nanofibers formed by self-assembly of peptide amphiphile molecules. The self-assembly is triggered by mixing cell suspensions in media with dilute aqueous solutions of the molecules, and cells survive the growth of the nanofibers around them. These nanofibers were designed to present to cells the neurite-promoting laminin epitope IKVAV at nearly van der Waals density. Relative to laminin or soluble peptide, the artificial nanofiber scaffold induced very rapid differentiation of cells into neurons, while discouraging the development of astrocytes. This rapid selective differentiation is linked to the amplification of bioactive epitope presentation to cells by the nanofibers.

Processing Fluency and Aesthetic Pleasure: Is Beauty in the Perceiver's Processing Experience?

Abstract: We propose that aesthetic pleasure is a function of the perceiver’s processing dynamics: The more fluently perceivers can process an object, the more positive their aesthetic response. We review variables known to influence aesthetic judgments, such as figural goodness, figure–ground contrast, stimulus repetition, symmetry, and prototypicality, and trace their effects to changes in processing fluency. Other variables that influence processing fluency, like visual or semantic priming, similarly increase judgments of aesthetic pleasure. Our proposal provides an integrative framework for the study of aesthetic pleasure and sheds light on the interplay between early preferences versus cultural influences on taste, preferences for both prototypical and abstracted forms, and the relation between beauty and truth. In contrast to theories that trace aesthetic pleasure to objective stimulus features per se, we propose that beauty is grounded in the processing experiences of the perceiver, which are in part a function of stimulus properties.

Genome sequence of the Brown Norway rat yields insights into mammalian evolution

Abstract: The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.

The Genome of the Diatom Thalassiosira Pseudonana: Ecology, Evolution, and Metabolism

Abstract: Diatoms are unicellular algae with plastids acquired by secondary endosymbiosis. They are responsible for approximately 20% of global carbon fixation. We report the 34 million-base pair draft nuclear genome of the marine diatom Thalassiosira pseudonana and its 129 thousand-base pair plastid and 44 thousand-base pair mitochondrial genomes. Sequence and optical restriction mapping revealed 24 diploid nuclear chromosomes. We identified novel genes for silicic acid transport and formation of silica-based cell walls, high-affinity iron uptake, biosynthetic enzymes for several types of polyunsaturated fatty acids, use of a range of nitrogenous compounds, and a complete urea cycle, all attributes that allow diatoms to prosper in aquatic environments.

Bayesian Phylogenetic Analysis of Combined Data

Abstract: The recent development of Bayesian phylogenetic inference using Markov chain Monte Carlo (MCMC) techniques has facilitated the exploration of parameter-rich evolutionary models. At the same time, stochastic models have become more realistic (and complex) and have been extended to new types of data, such as morphology. Based on this foundation, we developed a Bayesian MCMC approach to the analysis of combined data sets and explored its utility in inferring relationships among gall wasps based on data from morphology and four genes (nuclear and mitochondrial, ribosomal and protein coding). Examined models range in complexity from those recognizing only a morphological and a molecular partition to those having complex substitution models with independent parameters for each gene. Bayesian MCMC analysis deals efficiently with complex models: convergence occurs faster and more predictably for complex models, mixing is adequate for all parameters even under very complex models, and the parameter update cycle is virtually unaffected by model partitioning across sites. Morphology contributed only 5% of the characters in the data set but nevertheless influenced the combined-data tree, supporting the utility of morphological data in multigene analyses. We used Bayesian criteria (Bayes factors) to show that process heterogeneity across data partitions is a significant model component, although not as important as among-site rate variation. More complex evolutionary models are associated with more topological uncertainty and less conflict between morphology and molecules. Bayes factors sometimes favor simpler models over considerably more parameter-rich models, but the best model overall is also the most complex and Bayes factors do not support exclusion of apparently weak parameters from this model. Thus, Bayes factors appear to be useful for selecting among complex models, but it is still unclear whether their use strikes a reasonable balance between model complexity and error in parameter estimates.

Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis.

Abstract: The TAT protein transduction domain (PTD) has been used to deliver a wide variety of biologically active cargo for the treatment of multiple preclinical disease models, including cancer and stroke. However, the mechanism of transduction remains unknown. Because of the TAT PTD's strong cell-surface binding, early assumptions regarding cellular uptake suggested a direct penetration mechanism across the lipid bilayer by a temperature- and energy-independent process. Here we show, using a transducible TAT-Cre recombinase reporter assay on live cells, that after an initial ionic cell-surface interaction, TAT-fusion proteins are rapidly internalized by lipid raft-dependent macropinocytosis. Transduction was independent of interleukin-2 receptor/raft-, caveolar- and clathrin-mediated endocytosis and phagocytosis. Using this information, we developed a transducible, pH-sensitive, fusogenic dTAT-HA2 peptide that markedly enhanced TAT-Cre escape from macropinosomes. Taken together, these observations provide a scientific basis for the development of new, biologically active, transducible therapeutic molecules.

Optimality principles in sensorimotor control

Abstract: The sensorimotor system is a product of evolution, development, learning and adaptation-which work on different time scales to improve behavioral performance. Consequently, many theories of motor function are based on 'optimal performance': they quantify task goals as cost functions, and apply the sophisticated tools of optimal control theory to obtain detailed behavioral predictions. The resulting models, although not without limitations, have explained more empirical phenomena than any other class. Traditional emphasis has been on optimizing desired movement trajectories while ignoring sensory feedback. Recent work has redefined optimality in terms of feedback control laws, and focused on the mechanisms that generate behavior online. This approach has allowed researchers to fit previously unrelated concepts and observations into what may become a unified theoretical framework for interpreting motor function. At the heart of the framework is the relationship between high-level goals, and the real-time sensorimotor control strategies most suitable for accomplishing those goals.

Terahertz magnetic response from artificial materials.

Abstract: We show that magnetic response at terahertz frequencies can be achieved in a planar structure composed of nonmagnetic conductive resonant elements. The effect is realized over a large bandwidth and can be tuned throughout the terahertz frequency regime by scaling the dimensions of the structure. We suggest that artificial magnetic structures, or hybrid structures that combine natural and artificial magnetic materials, can play a key role in terahertz devices.

Spectral grouping using the Nystrom method

Abstract: Spectral graph theoretic methods have recently shown great promise for the problem of image segmentation. However, due to the computational demands of these approaches, applications to large problems such as spatiotemporal data and high resolution imagery have been slow to appear. The contribution of this paper is a method that substantially reduces the computational requirements of grouping algorithms based on spectral partitioning making it feasible to apply them to very large grouping problems. Our approach is based on a technique for the numerical solution of eigenfunction problems known as the Nystrom method. This method allows one to extrapolate the complete grouping solution using only a small number of samples. In doing so, we leverage the fact that there are far fewer coherent groups in a scene than pixels.

The Scientific Consensus on Climate Change

Abstract: Policy-makers and the public who are not members of the relevant research community have had to form opinions about the reality of global climate change on the basis of often conflicting descriptions provided by the media regarding the level of scientific certainty attached to studies of climate. In this Essay, Oreskes analyzes the existing scientific literature to show that there is a robust consensus that anthropogenic global climate change is occurring. Thus, despite claims sometimes made by some groups that there is not good evidence that Earth9s climate is being affected by human activities, the scientific community is in overwhelming agreement that such evidence is clear and persuasive.

MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias

Abstract: Little is known about the expression levels or function of micro-RNAs (miRNAs) in normal and neoplastic cells, although it is becoming clear that miRNAs play important roles in the regulation of gene expression during development [Ambros, V. (2003) Cell 113, 673–676; McManus, M. T. (2003) Semin. Cancer Biol. 13, 253–258]. We now report the genomewide expression profiling of miRNAs in human B cell chronic lymphocytic leukemia (CLL) by using a microarray containing hundreds of human precursor and mature miRNA oligonucleotide probes. This approach allowed us to identify significant differences in miRNome expression between CLL samples and normal CD5+ B cells; data were confirmed by Northern blot analyses and real-time RT-PCR. At least two distinct clusters of CLL samples can be identified that were associated with the presence or absence of Zap-70 expression, a predictor of early disease progression. Two miRNA signatures were associated with the presence or absence of mutations in the expressed Ig variableregion genes or with deletions at 13q14, respectively. These data suggest that miRNA expression patterns have relevance to the biological and clinical behavior of this leukemia.