Showing papers by "University of California, Irvine published in 2005"
TL;DR: The development, current features, and some directions for future development of the Amber package of computer programs, which contains a group of programs embodying a number of powerful tools of modern computational chemistry, focused on molecular dynamics and free energy calculations of proteins, nucleic acids, and carbohydrates.
Abstract: We describe the development, current features, and some directions for future development of the Amber package of computer programs. This package evolved from a program that was constructed in the late 1970s to do Assisted Model Building with Energy Refinement, and now contains a group of programs embodying a number of powerful tools of modern computational chemistry, focused on molecular dynamics and free energy calculations of proteins, nucleic acids, and carbohydrates.
7,672 citations
TL;DR: The position that the concept of sensemaking fills important gaps in organizational theory is taken, by pinpointing central features of sense making that have been assumed but not made explicit, some of which have changed in significance over time, and some ofWhich have been missing all along or have gone awry.
Abstract: Sensemaking involves turning circumstances into a situation that is comprehended explicitly in words and that serves as a springboard into action. In this paper we take the position that the concept of sensemaking fills important gaps in organizational theory. The seemingly transient nature of sensemaking belies its central role in the determination of human behavior, whether people are acting in formal organizations or elsewhere. Sensemaking is central because it is the primary site where meanings materialize that inform and constrain identity and action. The purpose of this paper is to take stock of the concept of sensemaking. We do so by pinpointing central features of sensemaking, some of which have been explicated but neglected, some of which have been assumed but not made explicit, some of which have changed in significance over time, and some of which have been missing all along or have gone awry. We sense joint enthusiasm to restate sensemaking in ways that make it more future oriented, more action oriented, more macro, more closely tied to organizing, meshed more boldly with identity, more visible, more behaviorally defined, less sedentary and backward looking, more infused with emotion and with issues of sensegiving and persuasion. These key enhancements provide a foundation upon which to build future studies that can strengthen the sensemaking perspective.
4,894 citations
TL;DR: The mitochondria provide a direct link between the authors' environment and their genes and the mtDNA variants that permitted their forbears to energetically adapt to their ancestral homes are influencing their health today.
Abstract: Life is the interplay between structure and energy, yet the role of energy deficiency in human disease has been poorly explored by modern medicine. Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive oxygen species (ROS) as a toxic by-product, I hypothesize that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer. Because mitochondrial DNA (mtDNA) is present in thousands of copies per cell and encodes essential genes for energy production, I propose that the delayed-onset and progressive course of the agerelated diseases results from the accumulation of somatic mutations in the mtDNAs of post-mitotic tissues. The tissue-specific manifestations of these diseases may result from the varying energetic roles and needs of the different tissues. The variation in the individual and regional predisposition to degenerative diseases and cancer may result from the interaction of modern dietary caloric intake and ancient mitochondrial genetic polymorphisms. Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbears to energetically adapt to their ancestral homes are influencing our health today.
3,016 citations
TL;DR: A surface plasmon polariton (SPP) is an electromagnetic excitation existing on the surface of a good metal, whose electromagnetic field decays exponentially with distance from the surface.
2,211 citations
TL;DR: The molecular relationships and physiological functions of these calcium channel proteins are presented and comprehensive information on their molecular, genetic, physiological, and pharmacological properties is provided.
Abstract: The family of voltage-gated sodium channels initiates action potentials in all types of excitable cells. Nine members of the voltage-gated sodium channel family have been characterized in mammals, and a 10th member has been recognized as a related protein. These distinct sodium channels have similar structural and functional properties, but they initiate action potentials in different cell types and have distinct regulatory and pharmacological properties. This article presents the molecular relationships and physiological roles of these sodium channel proteins and provides comprehensive information on their molecular, genetic, physiological, and pharmacological properties.
2,199 citations
TL;DR: It is suggested that low dose curcumin effectively disaggregates Aβ as well as prevents fibril and oligomer formation, supporting the rationale forCurcumin use in clinical trials preventing or treating AD.
2,140 citations
TL;DR: In this article, a recursive analysis of network and institutional evolution is offered to account for the decentralized structure of the commercial field of the life sciences, and four alternative logics of attachment are tested to explain the structure and dynamics of interorganizational collaboration in biotechnology using multiple novel methods.
Abstract: A recursive analysis of network and institutional evolution is offered to account for the decentralized structure of the commercial field of the life sciences Four alternative logics of attachment—accumulative advantage, homophily, follow‐the‐trend, and multiconnectivity—are tested to explain the structure and dynamics of interorganizational collaboration in biotechnology Using multiple novel methods, the authors demonstrate how different rules for affiliation shape network evolution Commercialization strategies pursued by early corporate entrants are supplanted by universities, research institutes, venture capital, and small firms As organizations increase their collaborative activities and diversify their ties to others, cohesive subnetworks form, characterized by multiple, independent pathways These structural components, in turn, condition the choices and opportunities available to members of a field, thereby reinforcing an attachment logic based on differential connections to diverse partners
1,873 citations
TL;DR: This work reorganized probes on more than a dozen popular GeneChips into gene-, transcript- and exon-specific probe sets in light of up-to-date genome, cDNA/EST clustering and single nucleotide polymorphism information, and demonstrates that the original Affymetrix probe set definitions are inaccurate.
Abstract: Genome-wide expression profiling is a powerful tool for implicating novel gene ensembles in cellular mechanisms of health and disease The most popular platform for genome-wide expression profiling is the Affymetrix GeneChip However, its selection of probes relied on earlier genome and transcriptome annotation which is significantly different from current knowledge The resultant informatics problems have a profound impact on analysis and interpretation the data Here, we address these critical issues and offer a solution We identified several classes of problems at the individual probe level in the existing annotation, under the assumption that current genome and transcriptome databases are more accurate than those used for GeneChip design We then reorganized probes on more than a dozen popular GeneChips into gene-, transcript- and exon-specific probe sets in light of up-to-date genome, cDNA/EST clustering and single nucleotide polymorphism information Comparing analysis results between the original and the redefined probe sets reveals ∼30–50% discrepancy in the genes previously identified as differentially expressed, regardless of analysis method Our results demonstrate that the original Affymetrix probe set definitions are inaccurate, and many conclusions derived from past GeneChip analyses may be significantly flawed It will be beneficial to re-analyze existing GeneChip data with updated probe set definitions
1,849 citations
TL;DR: It is proposed that STIM1, a ubiquitously expressed protein that is conserved from Drosophila to mammalian cells, plays an essential role in SOC influx and may be a common component of SOC and CRAC channels.
Abstract: Store-operated Ca2+ (SOC) channels regulate many cellular processes, but the underlying molecular components are not well defined. Using an RNA interference (RNAi)-based screen to identify genes that alter thapsigargin (TG)-dependent Ca2+ entry, we discovered a required and conserved role of Stim in SOC influx. RNAi-mediated knockdown of Stim in Drosophila S2 cells significantly reduced TG-dependent Ca2+ entry. Patch-clamp recording revealed nearly complete suppression of the Drosophila Ca2+ release-activated Ca2+ (CRAC) current that has biophysical characteristics similar to CRAC current in human T cells. Similarly, knockdown of the human homologue STIM1 significantly reduced CRAC channel activity in Jurkat T cells. RNAi-mediated knockdown of STIM1 inhibited TG- or agonist-dependent Ca2+ entry in HEK293 or SH-SY5Y cells. Conversely, overexpression of STIM1 in HEK293 cells modestly enhanced TG-induced Ca2+ entry. We propose that STIM1, a ubiquitously expressed protein that is conserved from Drosophila to mammalian cells, plays an essential role in SOC influx and may be a common component of SOC and CRAC channels.
1,751 citations
TL;DR: This article examined the microprocesses in the social networks of those involved in organizational innovation and their strategic behavioral orientation toward connecting people in their social network by either introducing disconnected individuals or facilitating new coordination between connected individuals.
Abstract: This study examines the microprocesses in the social networks of those involved in organizational innovation and their strategic behavioral orientation toward connecting people in their social network by either introducing disconnected individuals or facilitating new coordination between connected individuals. This tertius iungens (or “third who joins”) strategic orientation, contrasts with the tertius gaudens orientation emphasized in structural holes theory, which concerns the advantage of a broker who can play people off against one another for his or her own benefit. Results of a multimethod study of networks and innovation in an engineering division of an automotive manufacturer show that a tertius iungens orientation, dense social networks, and diverse social knowledge predict involvement in innovation. Implications of the study for innovation and social networks, as well as for social skill and agency within firms are presented.
1,632 citations
TL;DR: Transgenic mice that overexpress human catalase localized to the peroxisome, the nucleus, or mitochondria were generated and the importance of mitochondria as a source of radicals was reinforced.
Abstract: To determine the role of reactive oxygen species in mammalian longevity, we generated transgenic mice that overexpress human catalase localized to the peroxisome, the nucleus, or mitochondria (MCAT). Median and maximum life spans were maximally increased (averages of 5 months and 5.5 months, respectively) in MCAT animals. Cardiac pathology and cataract development were delayed, oxidative damage was reduced, H2O2 production and H2O2-induced aconitase inactivation were attenuated, and the development of mitochondrial deletions was reduced. These results support the free radical theory of aging and reinforce the importance of mitochondria as a source of these radicals.
TL;DR: The study finds that technology competence, firm size, financial commitment, competitive pressure, and regulatory support are important antecedents of e-business use and that, while both front-end and back-end capabilities contribute to e- business value, back- end integration has a much stronger impact.
Abstract: Grounded in the innovation diffusion literature and the resource-based theory, this paper develops an integrative research model for assessing the diffusion and consequence of e-business at the firm level. Unlike the typical focus on adoption as found in the literature, we focus on postadoption stages, that is, actual usage and value creation. The model thus moves beyond dichotomous "adoption versus nonadoption" and accounts for the "missing link"--actual usage--as a critical stage of value creation. The model links technological, organizational, and environmental factors to e-business use and value, based on which a series of hypotheses are developed. The theoretical model is tested by using structural equation modeling on a dataset of 624 firms across 10 countries in the retail industry. To probe deeper into whether e-business use and value are influenced by economic environments, two subsamples from developed and developing countries are compared. The study finds that technology competence, firm size, financial commitment, competitive pressure, and regulatory support are important antecedents of e-business use. In addition, the study finds that, while both front-end and back-end capabilities contribute to e-business value, back-end integration has a much stronger impact. While front-end functionalities are becoming commodities, e-businesses are more differentiated by back-end integration. This is consistent with the resource-based theory because back-end integration possesses the value-creating characteristics of resources (e.g., firm specific, difficult to imitate), which are strengthened by the Internet-enabled connectivity. Our study also adds an international dimension to the innovation diffusion literature, showing that careful attention must be paid to the economic and regulatory factors that may affect technology diffusion across different countries.
TL;DR: These functional CB2 receptors in the brainstem were activated by a CB2 receptor agonist, 2-arachidonoylglycerol, and by elevated endogenous levels of endocannabinoids, which also act at CB1 receptors.
Abstract: The presence and function of CB2 receptors in central nervous system (CNS) neurons are controversial. We report the expression of CB2 receptor messenger RNA and protein localization on brainstem neurons. These functional CB2 receptors in the brainstem were activated by a CB2 receptor agonist, 2-arachidonoylglycerol, and by elevated endogenous levels of endocannabinoids, which also act at CB1 receptors. CB2 receptors represent an alternative site of action of endocannabinoids that opens the possibility of nonpsychotropic therapeutic interventions using enhanced endocannabinoid levels in localized brain areas.
University of California, San Diego1, Vanderbilt University Medical Center2, Georgia Institute of Technology3, Anschutz Medical Campus4, Duke University5, University of Texas Southwestern Medical Center6, Ochanomizu University7, University of Tokyo8, University of Graz9, Utrecht University10, University of California, Irvine11
TL;DR: A comprehensive classification of lipids with a common platform that is compatible with informatics requirements has been developed to deal with the massive amounts of data that will be generated by the lipid community.
TL;DR: It is proposed that STIM1 functions as the missing link between Ca2+ store depletion and SOC influx, serving as aCa2+ sensor that translocates upon store depletion to the plasma membrane to activate CRAC channels.
Abstract: As the sole Ca2+ entry mechanism in a variety of non-excitable cells, store-operated calcium (SOC) influx is important in Ca2+ signalling and many other cellular processes1,2,3. A calcium-release-activated calcium (CRAC) channel in T lymphocytes is the best-characterized SOC influx channel4,5,6 and is essential to the immune response, sustained activity of CRAC channels being required for gene expression and proliferation7,8,9,10. The molecular identity and the gating mechanism of SOC and CRAC channels have remained elusive. Previously we identified Stim and the mammalian homologue STIM1 as essential components of CRAC channel activation in Drosophila S2 cells and human T lymphocytes11. Here we show that the expression of EF-hand mutants of Stim or STIM1 activates CRAC channels constitutively without changing Ca2+ store content. By immunofluorescence, EM localization and surface biotinylation we show that STIM1 migrates from endoplasmic-reticulum-like sites to the plasma membrane upon depletion of the Ca2+ store. We propose that STIM1 functions as the missing link between Ca2+ store depletion and SOC influx, serving as a Ca2+ sensor that translocates upon store depletion to the plasma membrane to activate CRAC channels.
TL;DR: It is shown that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function.
Abstract: Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin-forming cells. Here, we show that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.
TL;DR: A simple model for semantic growth is described, in which each new word or concept is connected to an existing network by differentiating the connectivity pattern of an existing node, which generates appropriate small-world statistics and power-law connectivity distributions.
TL;DR: This study strongly implicates intraneuronal Abeta in the onset of cognitive dysfunction in the 3xTg-AD mice, and rescues the early cognitive deficits on a hippocampal-dependent task.
TL;DR: This review focuses on the biological functions of three structural subgroups of mammalian defensins and the evidence for their involvement as effectors of antimicrobial innate immunity.
Abstract: Defensins are peptidic components of the innate immune system of plants and animals. In mammals, defensins have evolved to have a central function in the host defense properties of granulocytic leukocytes, mucosal surfaces, skin and other epithelia. This review focuses on the biological functions of three structural subgroups of mammalian defensins and the evidence for their involvement as effectors of antimicrobial innate immunity.
TL;DR: A review of several innovative advances in culture and international business to stimulate new avenues for future research is provided in this paper, where the issues surrounding cultural convergence and divergence, and the processes underlying cultural changes are discussed.
Abstract: The paper provides a state-of-the-art review of several innovative advances in culture and international business (IB) to stimulate new avenues for future research. We first review the issues surrounding cultural convergence and divergence, and the processes underlying cultural changes. We then examine novel constructs for characterizing cultures, and how to enhance the precision of cultural models by pinpointing when cultural effects are important. Finally, we examine the usefulness of experimental methods, which are rarely used by IB researchers. Implications of these path-breaking approaches for future research on culture and IB are discussed.
TL;DR: A microfluidic culture platform that polarizes the growth of CNS axons into a fluidically isolated environment without the use of targeting neurotrophins is described and the first evidence that presynaptic but not postsynaptic mRNA is localized to developing rat cortical and hippocampal axons is reported.
Abstract: Investigation of axonal biology in the central nervous system (CNS) is hindered by a lack of an appropriate in vitro method to probe axons independently from cell bodies. Here we describe a microfluidic culture platform that polarizes the growth of CNS axons into a fluidically isolated environment without the use of targeting neurotrophins. In addition to its compatibility with live cell imaging, the platform can be used to (i) isolate CNS axons without somata or dendrites, facilitating biochemical analyses of pure axonal fractions and (ii) localize physical and chemical treatments to axons or somata. We report the first evidence that presynaptic (Syp) but not postsynaptic (Camk2a) mRNA is localized to developing rat cortical and hippocampal axons. The platform also serves as a straightforward, reproducible method to model CNS axonal injury and regeneration. The results presented here demonstrate several experimental paradigms using the microfluidic platform, which can greatly facilitate future studies in axonal biology.
TL;DR: In this paper, the authors used a hybrid semianalytic plus N-body approach to distinguish between the evolution of light and dark matter in accreted satellites, which is essential to produce a realistic stellar halo, with mass and density profile much like that of our own Galaxy, and a surviving satellite population that matches the observed number counts and structural parameter distributions of the satellite galaxies of the Milky Way.
Abstract: If the favored hierarchical cosmological model is correct, then the Milky Way system should have accreted � 100– 200 luminous satellite galaxies in the past � 12 Gyr. We model this process using a hybrid semianalytic plus N-body approach that distinguishes explicitly between the evolution of light and dark matter in accreted satellites. This distinction is essential to our ability to produce a realistic stellar halo, with mass and density profile much like that of our own Galaxy, and a surviving satellite population that matches the observed number counts and structural parameter distributions of the satellite galaxies of the Milky Way. Our accreted stellar halos have density profiles that typically drop off with radius faster than the dark matter and follow power laws at rk30 kpc with � / r � � , � ’ 3 4. They are well fit by Hernquist profiles over the full radial range. We find that stellar halos are assembled from the inside out, with the majority of mass (� 80%) coming from the � 15 most massive accretion events. The satellites that contributetothestellarhalohavemedianaccretiontimes of � 9Gyrinthepast,whilesurvivingsatellitesystems have median accretion times of � 5 Gyr in the past. This implies that stars associated with the inner halo should be quite differentchemicallyfromstarsinsurvivingsatellitesandalsofromstarsintheouterhaloorthoseliberatedinrecent disruptionevents.Webrieflydiscusstheexpectedspatialstructureandphase-spacestructureforhalosformedinthismanner. Searches for this type of structure offer a direct test of whether cosmology is indeed hierarchical on small scales. Subject headingg dark matter — galaxies: dwarf — galaxies: evolution — galaxies: formation — galaxies: halos — galaxies: kinematics and dynamics — Galaxy: evolution — Galaxy: formation — Galaxy: halo — Galaxy: kinematics and dynamics — Local Group
TL;DR: This review of the field ends with a brief discussion of the newer work involving misinformation that has explored the processes by which people come to believe falsely that they experienced rich complex events that never, in fact, occurred.
Abstract: The misinformation effect refers to the impairment in memory for the past that arises after exposure to misleading information. The phenomenon has been investigated for at least 30 years, as investigators have addressed a number of issues. These include the conditions under which people are especially susceptible to the negative impact of misinformation, and conversely when are they resistant. Warnings about the potential for misinformation sometimes work to inhibit its damaging effects, but only under limited circumstances. The misinformation effect has been observed in a variety of human and nonhuman species. And some groups of individuals are more susceptible than others. At a more theoretical level, investigators have explored the fate of the original memory traces after exposure to misinformation appears to have made them inaccessible. This review of the field ends with a brief discussion of the newer work involving misinformation that has explored the processes by which people come to believe falsely that they experienced rich complex events that never, in fact, occurred.
TL;DR: The results indicate that direct protein–lipid interactions are critical during translocon-mediated membrane insertion, and the basic features of this code are determined, including a ‘biological’ hydrophobicity scale.
Abstract: Membrane proteins depend on complex translocation machineries for insertion into target membranes. Although it has long been known that an abundance of nonpolar residues in transmembrane helices is the principal criterion for membrane insertion, the specific sequence-coding for transmembrane helices has not been identified. By challenging the endoplasmic reticulum Sec61 translocon with an extensive set of designed polypeptide segments, we have determined the basic features of this code, including a 'biological' hydrophobicity scale. We find that membrane insertion depends strongly on the position of polar residues within transmembrane segments, adding a new dimension to the problem of predicting transmembrane helices from amino acid sequences. Our results indicate that direct protein-lipid interactions are critical during translocon-mediated membrane insertion.
TL;DR: Observations that Aβ42 and other oligomers caused rapid cellular leakage of anionic fluorescent dyes point to a generalized increase in membrane permeability, which may provide a common mechanism for oligomer-mediated toxicity in many amyloidogenic diseases.
TL;DR: A phase 1 trial of ex vivo NGF gene delivery in eight individuals with mild Alzheimer disease, implanting autologous fibroblasts genetically modified to express human NGF into the forebrain found no long-term adverse effects and brain autopsy from one subject suggested robust growth responses to NGF.
Abstract: Cholinergic neuron loss is a cardinal feature of Alzheimer disease. Nerve growth factor (NGF) stimulates cholinergic function, improves memory and prevents cholinergic degeneration in animal models of injury, amyloid overexpression and aging. We performed a phase 1 trial of ex vivo NGF gene delivery in eight individuals with mild Alzheimer disease, implanting autologous fibroblasts genetically modified to express human NGF into the forebrain. After mean follow-up of 22 months in six subjects, no long-term adverse effects of NGF occurred. Evaluation of the Mini-Mental Status Examination and Alzheimer Disease Assessment Scale-Cognitive subcomponent suggested improvement in the rate of cognitive decline. Serial PET scans showed significant (P < 0.05) increases in cortical 18-fluorodeoxyglucose after treatment. Brain autopsy from one subject suggested robust growth responses to NGF. Additional clinical trials of NGF for Alzheimer disease are warranted.
TL;DR: The first cloned potassium channel gene was the Drosophila voltage-gated shaker channel, and this was rapidly followed by the identification of other potassium channel genes.
Abstract: Potassium-selective channels are the largest and most diverse group of ion channels, represented by some 70 known loci in the mammalian genome. The first cloned potassium channel gene was the Drosophila voltage-gated shaker channel, and this was rapidly followed by the identification of other
TL;DR: SCRATCH is a server for predicting protein tertiary structure and structural features and includes predictors for secondary structure, relative solvent accessibility, disordered regions, domains, disulfide bridges, single mutation stability, residue contacts versus average, individual residue contacts and tertiaries structure.
Abstract: SCRATCH is a server for predicting protein tertiary structure and structural features. The SCRATCH software suite includes predictors for secondary structure, relative solvent accessibility, disordered regions, domains, disulfide bridges, single mutation stability, residue contacts versus average, individual residue contacts and tertiary structure. The user simply provides an amino acid sequence and selects the desired predictions, then submits to the server. Results are emailed to the user. The server is available at http://www.igb.uci.edu/servers/psss.html.
TL;DR: It is shown that both trait-neutral and trait-based mechanisms operate simultaneously to influence diversity loss as production increases, and management that focuses on locally susceptible functional groups and generally susceptible rare species will be essential to maintain biodiversity.
Abstract: Human activities have increased N availability dramatically in terrestrial and aquatic ecosystems. Extensive research demonstrates that local plant species diversity generally declines in response to nutrient enrichment, yet the mechanisms for this decline remain unclear. Based on an analysis of >900 species responses from 34 N-fertilization experiments across nine terrestrial ecosystems in North America, we show that both trait-neutral and trait-based mechanisms operate simultaneously to influence diversity loss as production increases. Rare species were often lost because of soil fertilization, randomly with respect to traits. The risk of species loss due to fertilization ranged from >60% for the rarest species to 10% for the most abundant species. Perennials, species with N-fixing symbionts, and those of native origin also experienced increased risk of local extinction after fertilization, regardless of their initial abundance. Whereas abundance was consistently important across all systems, functional mechanisms were often system-dependent. As N availability continues to increase globally, management that focuses on locally susceptible functional groups and generally susceptible rare species will be essential to maintain biodiversity.
Book•
01 Jan 2005TL;DR: This book covers the fundamental principles of space-time coding for wireless communications over multiple-input multiple-output (MIMO) channels, and sets out practical coding methods for achieving the performance improvements predicted by the theory.
Abstract: This book covers the fundamental principles of space-time coding for wireless communications over multiple-input multiple-output (MIMO) channels, and sets out practical coding methods for achieving the performance improvements predicted by the theory. The theory and practice sections can be used independently of each other. Written by one of the inventors of space-time block coding, this volume is ideal for a graduate student familiar with the basics of digital communications, and for engineers implementing the theory in real systems.