5,659 research outputs found
Black Hole Thermodynamics and Heavy Fermion Metals
Heavy fermion alloys at critical doping typically exhibit non-Fermi-liquid
behavior at low temperatures, including a logarithmic or power law rise in the
ratio of specific heat to temperature as the temperature is lowered. Anomalous
specific heat of this type is also observed in a simple class of gravitational
dual models that exhibit anisotropic scaling with dynamical critical exponent z
> 1.Comment: 17 pages, 4 figures; v2: added references; v3: matches published
versio
Field-induced quantum fluctuations in the heavy fermion superconductor CeCu2Ge2
Quantum-mechanical fluctuations in strongly correlated electron systems cause
unconventional phenomena such as non-Fermi liquid behavior, and arguably high
temperature superconductivity. Here we report the discovery of a field-tuned
quantum critical phenomenon in stoichiometric CeCu2Ge2, a spin density wave
ordered heavy fermion metal that exhibits unconventional superconductivity
under ~ 10 GPa of applied pressure. Our finding of the associated quantum
critical spin fluctuations of the antiferromagnetic spin density wave order,
dominating the local fluctuations due to single-site Kondo effect, provide new
information about the underlying mechanism that can be important in
understanding superconductivity in this novel compound.Comment: Heavy Fermion, Quantum Critical Phenomeno
Genomic Regions Identified by Overlapping Clusters of Nominally-Positive SNPs from Genome-Wide Studies of Alcohol and Illegal Substance Dependence
Declaring âreplicationâ from results of genome wide association (GWA) studies is straightforward when major gene effects provide genome-wide significance for association of the same allele of the same SNP in each of multiple independent samples. However, such unambiguous replication is unlikely when phenotypes display polygenic genetic architecture, allelic heterogeneity, locus heterogeneity and when different samples display linkage disequilibria with different fine structures. We seek chromosomal regions that are tagged by clustered SNPs that display nominally-significant association in each of several independent samples. This approach provides one ânontemplateâ approach to identifying overall replication of groups of GWA results in the face of difficult genetic architectures. We apply this strategy to 1 M SNP GWA results for dependence on: a) alcohol (including many individuals with dependence on other addictive substances) and b) at least one illegal substance (including many individuals dependent on alcohol). This approach provides high confidence in rejecting the null hypothesis that chance alone accounts for the extent to which clustered, nominally-significant SNPs from samples of the same racial/ethnic background identify the same sets of chromosomal regions. It identifies several genes that are also reported in other independent alcohol-dependence GWA datasets. There is more modest confidence in: a) identification of individual chromosomal regions and genes that are not also identified by data from other independent samples, b) the more modest overlap between results from samples of different racial/ethnic backgrounds and c) the extent to which any gene not identified herein is excluded, since the power of each of these individual samples is modest. Nevertheless, the strong overlap identified among the samples with similar racial/ethnic backgrounds supports contributions to individual differences in vulnerability to addictions that come from newer allelic variants that are common in subsets of current humans
Protein crystals in adenovirus type 5-infected cells: requirements for intranuclear crystallogenesis, structural and functional analysis
Intranuclear crystalline inclusions have been observed in the nucleus of epithelial cells infected with Adenovirus serotype 5 (Ad5) at late steps of the virus life cycle. Using immuno-electron microscopy and confocal microscopy of cells infected with various Ad5 recombinants modified in their penton base or fiber domains, we found that these inclusions represented crystals of penton capsomers, the heteromeric capsid protein formed of penton base and fiber subunits. The occurrence of protein crystals within the nucleus of infected cells required the integrity of the fiber knob and part of the shaft domain. In the knob domain, the region overlapping residues 489â492 in the FG loop was found to be essential for crystal formation. In the shaft, a large deletion of repeats 4 to 16 had no detrimental effect on crystal inclusions, whereas deletion of repeats 8 to 21 abolished crystal formation without altering the level of fiber protein expression. This suggested a crucial role of the five penultimate repeats in the crystallisation process. Chimeric pentons made of Ad5 penton base and fiber domains from different serotypes were analyzed with respect to crystal formation. No crystal was found when fiber consisted of shaft (S) from Ad5 and knob (K) from Ad3 (heterotypic S5-K3 fiber), but occurred with homotypic S3K3 fiber. However, less regular crystals were observed with homotypic S35-K35 fiber. TB5, a monoclonal antibody directed against the Ad5 fiber knob was found by immunofluorescence microscopy to react with high efficiency with the intranuclear protein crystals in situ. Data obtained with Ad fiber mutants indicated that the absence of crystalline inclusions correlated with a lower infectivity and/or lower yields of virus progeny, suggesting that the protein crystals might be involved in virion assembly. Thus, we propose that TB5 staining of Ad-infected 293 cells can be used as a prognostic assay for the viability and productivity of fiber-modified Ad5 vectors
Challenges of Profile Likelihood Evaluation in Multi-Dimensional SUSY Scans
Statistical inference of the fundamental parameters of supersymmetric
theories is a challenging and active endeavor. Several sophisticated algorithms
have been employed to this end. While Markov-Chain Monte Carlo (MCMC) and
nested sampling techniques are geared towards Bayesian inference, they have
also been used to estimate frequentist confidence intervals based on the
profile likelihood ratio. We investigate the performance and appropriate
configuration of MultiNest, a nested sampling based algorithm, when used for
profile likelihood-based analyses both on toy models and on the parameter space
of the Constrained MSSM. We find that while the standard configuration is
appropriate for an accurate reconstruction of the Bayesian posterior, the
profile likelihood is poorly approximated. We identify a more appropriate
MultiNest configuration for profile likelihood analyses, which gives an
excellent exploration of the profile likelihood (albeit at a larger
computational cost), including the identification of the global maximum
likelihood value. We conclude that with the appropriate configuration MultiNest
is a suitable tool for profile likelihood studies, indicating previous claims
to the contrary are not well founded.Comment: 21 pages, 9 figures, 1 table; minor changes following referee report.
Matches version accepted by JHE
Genome wide association for substance dependence: convergent results from epidemiologic and research volunteer samples
<p>Abstract</p> <p>Background</p> <p>Dependences on addictive substances are substantially-heritable complex disorders whose molecular genetic bases have been partially elucidated by studies that have largely focused on research volunteers, including those recruited in Baltimore. Maryland. Subjects recruited from the Baltimore site of the Epidemiological Catchment Area (ECA) study provide a potentially-useful comparison group for possible confounding features that might arise from selecting research volunteer samples of substance dependent and control individuals. We now report novel SNP (single nucleotide polymorphism) genome wide association (GWA) results for vulnerability to substance dependence in ECA participants, who were initially ascertained as members of a probability sample from Baltimore, and compare the results to those from ethnically-matched Baltimore research volunteers.</p> <p>Results</p> <p>We identify substantial overlap between the home address zip codes reported by members of these two samples. We find overlapping clusters of SNPs whose allele frequencies differ with nominal significance between substance dependent <it>vs </it>control individuals in both samples. These overlapping clusters of nominally-positive SNPs identify 172 genes in ways that are never found by chance in Monte Carlo simulation studies. Comparison with data from human expressed sequence tags suggests that these genes are expressed in brain, especially in hippocampus and amygdala, to extents that are greater than chance.</p> <p>Conclusion</p> <p>The convergent results from these probability sample and research volunteer sample datasets support prior genome wide association results. They fail to support the idea that large portions of the molecular genetic results for vulnerability to substance dependence derive from factors that are limited to research volunteers.</p
Signatures of arithmetic simplicity in metabolic network architecture
Metabolic networks perform some of the most fundamental functions in living
cells, including energy transduction and building block biosynthesis. While
these are the best characterized networks in living systems, understanding
their evolutionary history and complex wiring constitutes one of the most
fascinating open questions in biology, intimately related to the enigma of
life's origin itself. Is the evolution of metabolism subject to general
principles, beyond the unpredictable accumulation of multiple historical
accidents? Here we search for such principles by applying to an artificial
chemical universe some of the methodologies developed for the study of genome
scale models of cellular metabolism. In particular, we use metabolic flux
constraint-based models to exhaustively search for artificial chemistry
pathways that can optimally perform an array of elementary metabolic functions.
Despite the simplicity of the model employed, we find that the ensuing pathways
display a surprisingly rich set of properties, including the existence of
autocatalytic cycles and hierarchical modules, the appearance of universally
preferable metabolites and reactions, and a logarithmic trend of pathway length
as a function of input/output molecule size. Some of these properties can be
derived analytically, borrowing methods previously used in cryptography. In
addition, by mapping biochemical networks onto a simplified carbon atom
reaction backbone, we find that several of the properties predicted by the
artificial chemistry model hold for real metabolic networks. These findings
suggest that optimality principles and arithmetic simplicity might lie beneath
some aspects of biochemical complexity
Towards strange metallic holography
We initiate a holographic model building approach to `strange metallic'
phenomenology. Our model couples a neutral Lifshitz-invariant quantum critical
theory, dual to a bulk gravitational background, to a finite density of gapped
probe charge carriers, dually described by D-branes. In the physical regime of
temperature much lower than the charge density and gap, we exhibit anomalous
scalings of the temperature and frequency dependent conductivity. Choosing the
dynamical critical exponent appropriately we can match the non-Fermi liquid
scalings, such as linear resistivity, observed in strange metal regimes. As
part of our investigation we outline three distinct string theory realizations
of Lifshitz geometries: from F theory, from polarised branes, and from a
gravitating charged Fermi gas. We also identify general features of
renormalisation group flow in Lifshitz theories, such as the appearance of
relevant charge-charge interactions when . We outline a program to
extend this model building approach to other anomalous observables of interest
such as the Hall conductivity.Comment: 71 pages, 8 figure
Adar3 is involved in learning and memory in mice
© 2018 Mladenova, Barry, Konen, Pineda, Guennewig, Avesson, Zinn, Schonrock, Bitar, Jonkhout, Crumlish, Kaczorowski, Gong, Pinese, Franco, Walkley, Vissel and Mattick. The amount of regulatory RNA encoded in the genome and the extent of RNA editing by the post-transcriptional deamination of adenosine to inosine (A-I) have increased with developmental complexity and may be an important factor in the cognitive evolution of animals. The newest member of the A-I editing family of ADAR proteins, the vertebrate-specific ADAR3, is highly expressed in the brain, but its functional significance is unknown. In vitro studies have suggested that ADAR3 acts as a negative regulator of A-I RNA editing but the scope and underlying mechanisms are also unknown. Meta-analysis of published data indicates that mouse Adar3 expression is highest in the hippocampus, thalamus, amygdala, and olfactory region. Consistent with this, we show that mice lacking exon 3 of Adar3 (which encodes two double stranded RNA binding domains) have increased levels of anxiety and deficits in hippocampus-dependent short- and long-term memory formation. RNA sequencing revealed a dysregulation of genes involved in synaptic function in the hippocampi of Adar3-deficient mice. We also show that ADAR3 transiently translocates from the cytoplasm to the nucleus upon KCl-mediated activation in SH-SY5Y cells. These results indicate that ADAR3 contributes to cognitive processes in mammals
Heterogeneity within the Asian American community
BACKGROUND: Educational interventions are grounded on scientific data and assumptions about the community to be served. While the Pan Asian community is composed of multiple, ethnic subgroups, it is often treated as a single group for which one health promotion program will be applicable for all of its cultural subgroups. Compounding this stereotypical view of the Pan Asian community, there is sparse data about the cultural subgroups' similarities and dissimilarities. The Asian Grocery Store based cancer education program evaluation data provided an opportunity to compare data collected under identical circumstances from members of six Asian American cultural groups. METHODS: A convenience sample of 1,202 Asian American women evaluated the cultural alignment of a cancer education program, completing baseline and follow-up surveys that included questions about their breast cancer knowledge, attitudes, and screening behaviors. Participants took part in a brief education program that facilitated adherence to recommended screening guidelines. RESULTS: Unique recruitment methods were needed to attract participants from each ethnic group. Impressions gained from the aggregate data revealed different insights than the disaggregate data. Statistically significant variations existed among the subgroups' breast cancer knowledge, attitudes, and screening behaviors that could contribute to health disparities among the subgroups and within the aggregate Pan Asian community. CONCLUSION: Health promotion efforts of providers, educators, and policy makers can be enhanced if cultural differences are identified and taken into account when developing strategies to reduce health disparities and promote health equity
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