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Search Results: 1 - 10 of 322611 matches for " Daryl J Thomas "
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Presymptomatic Risk Assessment for Chronic Non-Communicable Diseases
Badri Padhukasahasram,Eran Halperin,Jennifer Wessel,Daryl J. Thomas,Elana Silver,Heather Trumbower,Michele Cargill,Dietrich A. Stephan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0014338
Abstract: The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies.
Novel pharmacotherapeutic treatments for cocaine addiction
Daryl Shorter, Thomas R Kosten
BMC Medicine , 2011, DOI: 10.1186/1741-7015-9-119
Abstract: Cocaine is a stimulant that leads to the rapid accumulation of catecholamines and serotonin in the brain due to prevention of their re-uptake into the neuron that released the neurotransmitter. Cocaine use disorders are widely accepted as a significant cause of morbidity and mortality. Cocaine use is associated with numerous acute and chronic medical complications, ranging from coronary syndromes, myocardial infarction, and respiratory disease to neurologic and psychiatric consequences such as cerebral hemorrhage, mood disorders, and psychosis [1,2]. Additionally, cocaine use has been associated with increased risk of HIV, hepatitis B and C, and violence [3-6].Development of effective treatments for cocaine dependence is necessary to reduce the impact of this illness upon both the individual and society. These effective treatments need most importantly to reduce cocaine use and to have excellent compliance, which has encouraged depot and other long lasting formulations. Currently, however, there are no US Food and Drug Administration (FDA) approved medications for the treatment of this illness, and behavioral therapies alone have demonstrated limited efficacy [7]. Our growing understanding of cocaine neurobiology has translated into numerous studies of pharmacologic agents for treatment of cocaine dependence in both animal and human models. These models include human laboratory drug administration studies using surrogate endpoints such as craving, subjective effects, and behavioral choices of money versus drug. This article reviews findings from recent cocaine pharmacotherapy clinical trials in humans that target dopamine and gamma-aminobutyric acid (GABA) neurotransmitter systems or uniquely target the cocaine itself through a vaccine preventing cocaine from getting into the brain. Additionally, preclinical studies for a novel medication, levo-tetrahydropalmatine (l-THP) are discussed.The final common pathway for reward and reinforcement associated with substances
Fast-evolving noncoding sequences in the human genome
Christine P Bird, Barbara E Stranger, Maureen Liu, Daryl J Thomas, Catherine E Ingle, Claude Beazley, Webb Miller, Matthew E Hurles, Emmanouil T Dermitzakis
Genome Biology , 2007, DOI: 10.1186/gb-2007-8-6-r118
Abstract: Here we identify 1,356 CNC sequences that appear to have undergone dramatic human-specific changes in selective pressures, at least 15% of which have substitution rates significantly above that expected under neutrality. The 1,356 'accelerated CNC' (ANC) sequences are enriched in recent segmental duplications, suggesting a recent change in selective constraint following duplication. In addition, single nucleotide polymorphisms within ANC sequences have a significant excess of high frequency derived alleles and high FSTvalues relative to controls, indicating that acceleration and positive selection are recent in human populations. Finally, a significant number of single nucleotide polymorphisms within ANC sequences are associated with changes in gene expression. The probability of variation in an ANC sequence being associated with a gene expression phenotype is fivefold higher than variation in a control CNC sequence.Our analysis suggests that ANC sequences have until very recently played a role in human evolution, potentially through lineage-specific changes in gene regulation.The manner in which the expression of genes is regulated defines and determines many of the cellular and developmental processes in an organism. It has been hypothesized that variation in gene regulation is responsible for much of the phenotypic diversity within and between species [1]. In particular, it was proposed a few decades ago that the phenotypic divergence between human and chimpanzees is largely due to changes in gene regulation rather than changes in the protein-coding sequences of genes [2]. Although it has been long recognized that regulatory sequences play an important role in genome function, the fine structure and evolutionary patterns of such sequences are not well understood [3], mainly because such sequences have a much more complex functional code and appear not to be restricted to particular sequence motifs. One of the most powerful approaches with which to identify regula
Antiferromagnetic Domains and Superconductivity in UPt3
Matthias J. Graf,Daryl. W. Hess
Physics , 2000, DOI: 10.1103/PhysRevB.63.134502
Abstract: We explore the response of an unconventional superconductor to spatially inhomogeneous antiferromagnetism (SIAFM). Symmetry allows the superconducting order parameter in the E-representation models for UPt3 to couple directly to the AFM order parameter. The Ginzburg-Landau equations for coupled superconductivity and SIAFM are solved numerically for two possible SIAFM configurations: (I) abutting antiferromagnetic domains of uniform size, and (II) quenched random disorder of `nanodomains' in a uniform AFM background. We discuss the contributions to the free energy, specific heat, and order parameter for these models. Neither model provides a satisfactory account of experiment, but results from the two models differ significantly. Our results demonstrate that the response of an E_{2u} superconductor to SIAFM is strongly dependent on the spatial dependence of AFM order; no conclusion can be drawn regarding the compatibility of E_{2u} superconductivity with UPt3 that is independent of assumptions on the spatial dependence of AFM
Ultrafast tilting of the dispersion of a photonic crystal and adiabatic spectral compression of light pulses
Daryl M. Beggs,Thomas F. Krauss,L. Kuipers,Tobias Kampfrath
Physics , 2012, DOI: 10.1103/PhysRevLett.108.033902
Abstract: We demonstrate, by theory and experiment, the ultrafast tilting of the dispersion curve of a photonic-crystal waveguide following the absorption of a femtosecond pump pulse. By shaping the pump-beam cross section with a nanometric shadow mask, different waveguide eigenmodes acquire different spatial overlap with the perturbing pump, leading to a local flattening of the dispersion by up to 11 %. We find that such partial mode perturbation can be used to adiabatically compress the spectrum of a light pulse traveling through the waveguide.
On the Temperature Dependent Excitation and Reflection Spectra of Ln3Al5O12:Ce3+ Ceramics (Ln = Y, Lu) for White LEDs  [PDF]
Thomas Jansen, Thomas Jüstel
Materials Sciences and Applications (MSA) , 2014, DOI: 10.4236/msa.2014.514110
Abstract: Yttrium aluminum garnet (YAG) and Lutetium aluminum garnet (LuAG) doped with Ce3+ are widely applied phosphor powders or ceramics for the conversion of blue into green to yellow light in the rapidly expanding market of white light emitting high power LEDs. Surprisingly, the temperature dependent reflection and excitation spectra of these well-established materials have not been investigated until today. In this work, we report the temperature dependence of the reflection and excitation spectra of Ce3+ doped YAG and LuAG in the temperature range from 300 to 800 K.
Kre?imir Dvojkovi?,Zlatko ?atovi?,Georg Drezner,Daryl J. Somers
Poljoprivreda (Osijek) , 2010,
Abstract: The plant height of wheat is an important quantitative trait, controlled by severalgenes with strong effect. However, in worldwide wheat breeding, only several ofthose genes have been used. Rht8 (Reduced Height Gene) is especially importantin agro-climatic conditions of South-East Europe. Because of its close linkage withdwarfing gene Rht8, microsatellite marker gwm261 has been accepted as the diagnosticmolecular marker for gene Rht8. In this study, allelic variability at the locusXgwm261 for 122 Croatian and foreign wheat cultivars by means of microsatellitemarker gwm261 was determined. A 192 base pairs allele at the locus Xgwm261was found for 84 Croatian cultivars. The genetic heritage of Croatian cultivars at thelocus Xgwm261 is the consequence of new parental components usage, carriers ofshort plant and early maturity attributes and the consequent selection of progenywith these traits during breeding process. The results of this research will be helpfulin characterization of domestic wheat cultivars, as well as in more accurateselection of parents for hybridization purposes.
Salinity Preference in Hatchery-Reared Juvenile Red Drum
Daryl C. Parkyn,Debra J. Murie,Edward T. Sherwood
The Scientific World Journal , 2002, DOI: 10.1100/tsw.2002.347
BRAVO for many-server QED systems with finite buffers
Daryl J. Daley,Johan S. H. van Leeuwaarden,Yoni Nazarathy
Mathematics , 2013,
Abstract: This paper demonstrates the occurrence of the feature called BRAVO (Balancing Reduces Asymptotic Variance of Output) for the departure process of a finite-buffer Markovian many-server system in the QED (Quality and Efficiency-Driven) heavy-traffic regime. The results are based on evaluating the limit of a formula for the asymptotic variance of death counts in finite birth--death processes.
Measuring the spatial extent of individual localized photonic states
Marko Spasenovic,Daryl M. Beggs,Philippe Lalanne,Thomas F. Krauss,L.,Kuipers
Physics , 2011, DOI: 10.1103/PhysRevB.86.155153
Abstract: We measure the spatial extent of individual localized photonic states in a slow-light photonic crystal waveguide. The size of the states is measured by perturbing each state individually through a local electromagnetic interaction with a near-field probe. We find localized states which are not observed in transmission and show that these states are shorter than the waveguide. We also directly obtain near-field measurements of the participation ratio, from which the size of the states can be derived, in quantitative agreement with the size measured with the perturbation method.
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