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Search Results: 1 - 10 of 96565 matches for " Matthew W. Craig "
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The Structure of Dark Matter Halos in an Annihilating Dark Matter Model
Matthew W. Craig,Marc Davis
Physics , 2001, DOI: 10.1016/S1384-1076(01)00072-0
Abstract: The inability of standard non-interacting cold dark matter (CDM) to account for the small scale structure of individual galaxies has led to the suggestion that the dark matter may undergo elastic and/or inelastic scattering. We simulate the evolution of an isolated dark matter halo which undergoes both scattering and annihilation. Annihilations produce a core that grows with time due to adiabatic expansion of the core as the relativistic annihilation products flow out of the core, lessening the binding energy. An effective annihilation cross section per unit mass equal to $>.03 cm^2 g^{-1} (100 km s^{-1}/v$) with a scattering cross section per unit mass of .6 cm g$^{-1}$ produces a 3 kpc core in a 10$^{10}$ M$_{\sun}$ halo that persists for 100 dynamical times. The same cross section leads to a core of only 120 pc in a rich cluster. In addition to creating to cores, annihilation should erase structure on scales below $\sim 3\times10^8$ M$_{\sun}$. Annihilating dark matter provides a mechanism for solving some of the problems of non-interacting CDM, at the expense of introducing a contrived particle physics model.
Mechanism of Selective VEGF-A Binding by Neuropilin-1 Reveals a Basis for Specific Ligand Inhibition
Matthew W. Parker, Ping Xu, Hou-Fu Guo, Craig W. Vander Kooi
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0049177
Abstract: Neuropilin (Nrp) receptors function as essential cell surface receptors for the Vascular Endothelial Growth Factor (VEGF) family of proangiogenic cytokines and the semaphorin 3 (Sema3) family of axon guidance molecules. There are two Nrp homologues, Nrp1 and Nrp2, which bind to both overlapping and distinct members of the VEGF and Sema3 family of molecules. Nrp1 specifically binds the VEGF-A164/5 isoform, which is essential for developmental angiogenesis. We demonstrate that VEGF-A specific binding is governed by Nrp1 residues in the b1 coagulation factor domain surrounding the invariant Nrp C-terminal arginine binding pocket. Further, we show that Sema3F does not display the Nrp-specific binding to the b1 domain seen with VEGF-A. Engineered soluble Nrp receptor fragments that selectively sequester ligands from the active signaling complex are an attractive modality for selectively blocking the angiogenic and chemorepulsive functions of Nrp ligands. Utilizing the information on Nrp ligand binding specificity, we demonstrate Nrp constructs that specifically sequester Sema3 in the presence of VEGF-A. This establishes that unique mechanisms are used by Nrp receptors to mediate specific ligand binding and that these differences can be exploited to engineer soluble Nrp receptors with specificity for Sema3.
Oxidative Stress and Longevity in Okinawa: An Investigation of Blood Lipid Peroxidation and Tocopherol in Okinawan Centenarians
Makoto Suzuki,D. Craig Willcox,Matthew W. Rosenbaum,Bradley J. Willcox
Current Gerontology and Geriatrics Research , 2010, DOI: 10.1155/2010/380460
Abstract: Background. The Free Radical Theory of Aging mechanistically links oxidative stress to aging. Okinawa has among the world's longest-lived populations but oxidative stress in this population has not been well characterized. Methods. We compared plasma lipid peroxide (LPO) and vitamin E—plasma and intracellular tocopherol levels (total α, β, and γ), in centenarians with younger controls. Results. Both LPO and vitamin E tocopherols were lower in centenarians, with the exception of intracellular β-tocopherol, which was significantly higher in centenarians versus younger controls. There were no significant differences between age groups for tocopherol: cholesterol and tocopherol: LPO ratios. Correlations were found between α-Tocopherol and LPO in septuagenarians but not in centenarians. Conclusions. The low plasma level of LPO in Okinawan centenarians, compared to younger controls, argues for protection against oxidative stress in the centenarian population and is consistent with the predictions of the Free Radical Theory of Aging. However, the present work does not strongly support a role for vitamin E in this phenomenon. The role of intracellular β-tocopherol deserves additional study. More research is needed on the contribution of oxidative stress and antioxidants to human longevity. 1. Introduction Human longevity is a complex phenotype that is determined by environment, genetics, and chance [1]. Understanding the mechanisms by which aging leads to longevity, particularly healthy longevity would be of enormous benefit to our aging population. Unfortunately, most research on human aging has focused on phenomenological description of age-related diseases, and much less is known about the mechanisms of aging itself [2]. Among the most promising theories about how and why we age is the Free Radical Theory, initially proposed by Denham Harman in 1956 [3]. Harman proposed that oxygen radicals produced during aerobic respiration induce oxidative damage in DNA, cells, tissues, and organisms that lead to aging and death. Studies in Harman [3] hypothesized, based on observations of enzymatic redox chemistry, that oxygen radical generation occurs in vivo and that mechanisms exist to protect against such damage. Mitochondria were later found to be a principal source of these oxygen radicals [4]. The enzyme superoxide dismutase (SOD) provided early evidence for endogenous antioxidant defenses against such radical damage [5]. Exogenous antioxidant defenders have also been discovered in food sources, among the most studied being vitamin E [6, 7]. Vitamin E consists of
Phylogeography of the Pacific Blueline Surgeonfish, Acanthurus nigroris, Reveals High Genetic Connectivity and a Cryptic Endemic Species in the Hawaiian Archipelago
Joseph D. DiBattista,Christie Wilcox,Matthew T. Craig,Luiz A. Rocha,Brian W. Bowen
Journal of Marine Biology , 2011, DOI: 10.1155/2011/839134
Abstract: Understanding genetic connectivity is fundamental to the design of marine protected areas in the service of ecosystem-scale management. Here we evaluate such trends for a Pacific surgeonfish (Acanthurus nigroris; ) at two spatial scales: (1) within the Hawaiian archipelago, and (2) across the entire species range from the central to southwest Pacific. The mtDNA cytochrome b data reveal genetic divergence ( ) between Hawaii and the rest of the Pacific range indicating a cryptic species pair, with one taxon endemic to Hawaii. Johnston Atoll, 1400?km SW of Hawaii, also has the Hawaiian species but is distinct from most Hawaiian locations in population genetic comparisons, indicating the limits of gene flow for this widespread reef species. No consistent population genetic differences were observed among Hawaiian sites or among the other Pacific island sites. We also detected a modest bias in gene flow from the southeast towards the northwest islands of the Hawaiian Archipelago, indicating that the Papahānaumokuākea Marine National Monument may be a recipient, rather than a source of propagules to replenish reef resources. 1. Introduction Reef fishes have been subject to a number of genetic studies in the interest of understanding the dynamics of population connectivity and phylogeography [1–3]. Early molecular studies indicated that many fishes are genetically homogeneous across wide geographic scales owing to their potential for dispersal over substantial distances during the pelagic larval stages [4–7]. This traditional view has begun to shift, however, with increased genetic surveys and the advent of novel techniques (e.g., [8, 9]). Recent research has shown population genetic structure in marine fishes on the scale of tens to a few hundred kilometers (see [10–13]), challenging the prediction of vast panmictic populations based on potential dispersal during planktonic development [14–16]. Although it is clear that larval dispersal ability remains a predictor of population structure in some cases (e.g., [17]), mounting empirical evidence suggests that other factors such as biogeographic barriers [18], contemporary oceanographic patterns [19], larval behavior [12, 20], local adaptation [21], and the ecological requirements of each species [16, 22] may all play greater roles in shaping population connectivity (for review, see [23]). Contemporary population genetic structure can also be reflective of historical episodes of isolation rather than recent patterns of connectivity. Factors such as population fragmentation, extinction and recolonization, and
Not All Larvae Stay Close to Home: Insights into Marine Population Connectivity with a Focus on the Brown Surgeonfish (Acanthurus nigrofuscus)
Jeff A. Eble,Luiz A. Rocha,Matthew T. Craig,Brian W. Bowen
Journal of Marine Biology , 2011, DOI: 10.1155/2011/518516
Abstract: Recent reports of localized larval recruitment in predominately small-range fishes are countered by studies that show high genetic connectivity across large oceanic distances. This discrepancy may result from the different timescales over which genetic and demographic processes operate or rather may indicate regular long-distance dispersal in some species. Here, we contribute an analysis of mtDNA cytochrome b diversity in the widely distributed Brown Surgeonfish (Acanthurus nigrofuscus; ), which revealed significant genetic structure only at the extremes of the range ( ; ). Collections from Hawaii to the Eastern Indian Ocean comprise one large, undifferentiated population. This pattern of limited genetic subdivision across reefs of the central Indo-Pacific has been observed in a number of large-range reef fishes. Conversely, small-range fishes are often deeply structured over the same area. These findings demonstrate population connectivity differences among species at biogeographic and evolutionary timescales, which likely translates into differences in dispersal ability at ecological and demographic timescales. While interspecific differences in population connectivity complicate the design of management strategies, the integration of multiscale connectivity patterns into marine resource planning will help ensure long-term ecosystem stability by preserving functionally diverse communities. 1. Introduction The recent dramatic decline of marine ecosystems [1–3] has led to an increased interest in the use of spatially explicit management strategies, such as no-take marine reserves, to promote ecosystem stability [4–9]. Yet designing marine reserves that can support a community’s ability to absorb and recover from recurrent ecosystem disturbances requires an understanding of the scale and magnitude of population connectivity for a wide range of species and environments [9–13]. While there have been a number of recent, remarkable insights into larval dispersal distances for some taxonomic groups (e.g., Damselfishes [13, 14]), the lack of data for the majority of species continues to limit the integration of dispersal dynamics into reserve planning and design. Most near-shore marine species exhibit an early pelagic larval phase (reviewed in [15, 16]) and larval duration has been repeatedly explored as a surrogate for species dispersal ability [17–20]. However, a comprehensive review found average pelagic larval duration (PLD) to be a poor predictor of genetic structure, and by extension dispersal ability, with previously reported correlations driven by
Synthesis of Indole Derived Protease-Activated Receptor 4 Antagonists and Characterization in Human Platelets
Summer E. Young, Matthew T. Duvernay, Michael L. Schulte, Craig W. Lindsley, Heidi E. Hamm
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0065528
Abstract: Protease activated receptor-4 (PAR4) is one of the thrombin receptors on human platelets and is a potential target for the management of thrombotic disorders. We sought to develop potent, selective, and novel PAR4 antagonists to test the role of PAR4 in thrombosis and hemostasis. Development of an expedient three-step synthetic route to access a novel series of indole-based PAR4 antagonists also necessitated the development of a platelet based high-throughput screening assay. Screening and subsequent structure activity relationship analysis yielded several selective PAR4 antagonists as well as possible new scaffolds for future antagonist development.
Radial position of single-site gamma-ray interactions from a parametric pulse shape analysis of germanium detector signals
John L. Orrell,Craig E. Aalseth,Matthew W. Cooper,Jeremy D. Kephart,Carolyn E. Seifert
Physics , 2007,
Abstract: Pulse shape analysis of germanium gamma-ray spectrometer signals can yield information on the radial position of individual gamma-ray interactions within the germanium crystal. A parametric pulse shape analysis based on calculation of moments of the reconstructed current pulses from a closed-ended coaxial germanium detector is used to preferentially select single-site gamma-ray interactions. The double escape peak events from the 2614.5 keV gamma-ray of 208-Tl are used as a training set to optimize the single-site event selection region in the pulse shape parameter space. A collimated source of 320.1 keV gamma-rays from 51-Cr is used to scan different radial positions of the same semi-coaxial germanium detector. The previously trained single-site selection region is used to preferentially identify the single-site photoelectric absorption events from the 320.1 keV full-energy peak. From the identified events, a comparison of the pulse shape parameter space distributions between different scan positions allows radial interaction location information to be collected.
ForOpenCL: Transformations Exploiting Array Syntax in Fortran for Accelerator Programming
Matthew J. Sottile,Craig E Rasmussen,Wayne N. Weseloh,Robert W. Robey,Daniel Quinlan,Jeffrey Overbey
Computer Science , 2011,
Abstract: Emerging GPU architectures for high performance computing are well suited to a data-parallel programming model. This paper presents preliminary work examining a programming methodology that provides Fortran programmers with access to these emerging systems. We use array constructs in Fortran to show how this infrequently exploited, standardized language feature is easily transformed to lower-level accelerator code. The transformations in ForOpenCL are based on a simple mapping from Fortran to OpenCL. We demonstrate, using a stencil code solving the shallow-water fluid equations, that the performance of the ForOpenCL compiler-generated transformations is comparable with that of hand-optimized OpenCL code.
Single Cell Analysis Reveals the Stochastic Phase of Reprogramming to Pluripotency Is an Ordered Probabilistic Process
Kyung-Min Chung, Frederick W. Kolling IV, Matthew D. Gajdosik, Steven Burger, Alexander C. Russell, Craig E. Nelson
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095304
Abstract: Despite years of research, the reprogramming of human somatic cells to pluripotency remains a slow, inefficient process, and a detailed mechanistic understanding of reprogramming remains elusive. Current models suggest reprogramming to pluripotency occurs in two-phases: a prolonged stochastic phase followed by a rapid deterministic phase. In this paradigm, the early stochastic phase is marked by the random and gradual expression of pluripotency genes and is thought to be a major rate-limiting step in the successful generation of induced Pluripotent Stem Cells (iPSCs). Recent evidence suggests that the epigenetic landscape of the somatic cell is gradually reset during a period known as the stochastic phase, but it is known neither how this occurs nor what rate-limiting steps control progress through the stochastic phase. A precise understanding of gene expression dynamics in the stochastic phase is required in order to answer these questions. Moreover, a precise model of this complex process will enable the measurement and mechanistic dissection of treatments that enhance the rate or efficiency of reprogramming to pluripotency. Here we use single-cell transcript profiling, FACS and mathematical modeling to show that the stochastic phase is an ordered probabilistic process with independent gene-specific dynamics. We also show that partially reprogrammed cells infected with OSKM follow two trajectories: a productive trajectory toward increasingly ESC-like expression profiles or an alternative trajectory leading away from both the fibroblast and ESC state. These two pathways are distinguished by the coordinated expression of a small group of chromatin modifiers in the productive trajectory, supporting the notion that chromatin remodeling is essential for successful reprogramming. These are the first results to show that the stochastic phase of reprogramming in human fibroblasts is an ordered, probabilistic process with gene-specific dynamics and to provide a precise mathematical framework describing the dynamics of pluripotency gene expression during reprogramming by OSKM.
Bias of the Random Forest Out-of-Bag (OOB) Error for Certain Input Parameters  [PDF]
Matthew W. Mitchell
Open Journal of Statistics (OJS) , 2011, DOI: 10.4236/ojs.2011.13024
Abstract: Random Forest is an excellent classification tool, especially in the –omics sciences such as metabolomics, where the number of variables is much greater than the number of subjects, i.e., “n << p.” However, the choices for the arguments for the random forest implementation are very important. Simulation studies are performed to compare the effect of the input parameters on the predictive ability of the random forest. The number of variables sampled, m-try, has the largest impact on the true prediction error. It is often claimed that the out-of-bag error (OOB) is an unbiased estimate of the true prediction error. However, for the case where n << p, with the default arguments, the out-of-bag (OOB) error overestimates the true error, i.e., the random forest actually performs better than indicated by the OOB error. This bias is greatly reduced by subsampling without replacement and choosing the same number of observations from each group. However, even after these adjustments, there is a low amount of bias. The remaining bias occurs because when there are trees with equal predictive ability, the one that performs better on the in-bag samples will perform worse on the out-of-bag samples. Cross-validation can be performed to reduce the remaining bias.
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