479 research outputs found
Composite Fermion Metals from Dyon Black Holes and S-Duality
We propose that string theory in the background of dyon black holes in
four-dimensional anti-de Sitter spacetime is holographic dual to conformally
invariant composite Dirac fermion metal. By utilizing S-duality map, we show
that thermodynamic and transport properties of the black hole match with those
of composite fermion metal, exhibiting Fermi liquid-like. Built upon
Dirac-Schwinger-Zwanziger quantization condition, we argue that turning on
magnetic charges to electric black hole along the orbit of Gamma(2) subgroup of
SL(2,Z) is equivalent to attaching even unit of statistical flux quanta to
constituent fermions. Being at metallic point, the statistical magnetic flux is
interlocked to the background magnetic field. We find supporting evidences for
proposed holographic duality from study of internal energy of black hole and
probe bulk fermion motion in black hole background. They show good agreement
with ground-state energy of composite fermion metal in Thomas-Fermi
approximation and cyclotron motion of a constituent or composite fermion
excitation near Fermi-point.Comment: 30 pages, v2. 1 figure added, minor typos corrected; v3. revised
version to be published in JHE
The role of scatterometry in ocean model forcing
VI Expanding Ocean Frontiers Conference, 5-7 July 2021, Barcelona, Spain.-- 25 page
Pleural Mesothelioma in New Caledonia: Associations with Environmental Risk Factors
International audienceBackground: High incidences of malignant mesothelioma (MM) have been observed in New Caledonia. Previous work has shown an association between MM and soil containing serpentinite. Objectives: We studied the spatial and temporal variation of MM and its association with environmental factors. Methods: We investigated the 109 MM cases recorded in the Cancer Registry of New Caledonia between 1984 and 2008 and performed spatial, temporal, and space-time cluster analyses. We conducted an ecological analysis involving 100 tribes over a large area including those with the highest incidence rates. Associations with environmental factors were assessed using logistic and Poisson regression analyses. Results: The highest incidence was observed in the HouaĂŻlou area with a world age-standardized rate of 128.7 per 100,000 person-years [95% confidence interval (CI), 70.41-137.84]. A significant spatial cluster grouped 18 tribes (31 observed cases vs. 8 expected cases; p = 0.001), but no significant temporal clusters were identified. The ecological analyses identified serpentinite on roads as the greatest environmental risk factor (odds ratio = 495.0; 95% CI, 46.2-4679.7; multivariate incidence rate ratio = 13.0; 95% CI, 10.2-16.6). The risk increased with serpentinite surface, proximity to serpentinite quarries and distance to the peridotite massif. The association with serpentines was stronger than with amphiboles. Living on a slope and close to dense vegetation appeared protective. The use of whitewash, previously suggested to be a risk factor, was not associated with MM incidence. Conclusions: Presence of serpentinite on roads is a major environmental risk factor for mesothelioma in New Caledonia
A prospective study of hearing changes after beginning zidovudine or didanosine in HIV-1 treatment-naĂŻve people
BACKGROUND: While hearing loss in HIV-infected people after beginning nucleoside reverse transcriptase inhibitors (NRTIs) has been reported, there have been no prospective studies that measured hearing changes longitudinally in treatment-naĂŻve HIV-infected subjects following initiation of regimens containing NRTIs. The goal of this study was to conduct a prospective assessment of the contribution of zidovudine (ZDV) and didanosine (ddI) to hearing loss METHODS/DESIGN: A prospective observational pilot study to determine whether ZDV or ddI, alone or in combination, are associated with sensorineural hearing loss in HIV-infected persons. Changes in hearing levels at all frequencies and in low and high frequency pure tone averages were measured at baseline, 16, and 32 weeks after initiating antiretroviral therapy. DISCUSSION: Treatment with ZDV and ddI did not result in loss of hearing, even after taking into account noise exposure, immune status and age. The results of this prospective pilot study do not support the notion that treatment with nucleoside antiretrovirals damages hearing
Metabolic oscillations on the circadian time scale in Drosophila cells lacking clock genes
Circadian rhythms are cellâautonomous biological oscillations with a period of about 24Â h. Current models propose that transcriptional feedback loops are the primary mechanism for the generation of circadian oscillations. Within this framework, Drosophila S2 cells are regarded as ânonârhythmicâ cells, as they do not express several canonical circadian components. Using an unbiased multiâomics approach, we made the surprising discovery that Drosophila S2 cells do in fact display widespread daily rhythms. Transcriptomics and proteomics analyses revealed that hundreds of genes and their products, and in particular metabolic enzymes, are rhythmically expressed in a 24âh cycle. Metabolomics analyses extended these findings and demonstrate that central carbon metabolism and amino acid metabolism are core metabolic pathways driven by protein rhythms. We thus demonstrate that 24âh metabolic oscillations, coupled to gene and protein cycles, take place in nucleated cells without the contribution of any known circadian regulators. These results therefore suggest a reconsideration of existing models of the clockwork in Drosophila and other eukaryotic systems.Mol Syst Biol. (2018) 14: e837
Alcohol affects neuronal substrates of response inhibition but not of perceptual processing of stimuli signalling a stop response
Alcohol impairs inhibitory control, including the ability to terminate an initiated action. While there is increasing knowledge about neural mechanisms involved in response inhibition, the level at which alcohol impairs such mechanisms remains poorly understood. Thirty-nine healthy social drinkers received either 0.4g/kg or 0.8g/kg of alcohol, or placebo, and performed two variants of a Visual Stop-signal task during acquisition of functional magnetic resonance imaging (fMRI) data. The two task variants differed only in their instructions: in the classic variant (VSST), participants inhibited their response to a âGo-stimulusâ when it was followed by a âStop-stimulusâ. In the control variant (VSST_C), participants responded to the âGo-stimulusâ even if it was followed by a âStop-stimulusâ. Comparison of successful Stop-trials (Sstop)>Go, and unsuccessful Stop-trials (Ustop)>Sstop between the three beverage groups enabled the identification of alcohol effects on functional neural circuits supporting inhibitory behaviour and error processing. Alcohol impaired inhibitory control as measured by the Stop-signal reaction time, but did not affect other aspects of VSST performance, nor performance on the VSST_C. The low alcohol dose evoked changes in neural activity within prefrontal, temporal, occipital and motor cortices. The high alcohol dose evoked changes in activity in areas affected by the low dose but importantly induced changes in activity within subcortical centres including the globus pallidus and thalamus. Alcohol did not affect neural correlates of perceptual processing of infrequent cues, as revealed by conjunction analyses of VSST and VSST_C tasks. Alcohol ingestion compromises the inhibitory control of action by modulating cortical regions supporting attentional, sensorimotor and action-planning processes. At higher doses the impact of alcohol also extends to affect subcortical nodes of fronto-basal ganglia- thalamo-cortical motor circuits. In contrast, alcohol appears to have little impact on the early visual processing of infrequent perceptual cues. These observations clarify clinically-important effects of alcohol on behaviour
Long-Read Sequencing to Unravel Complex Structural Variants of CEP78 Leading to Cone-Rod Dystrophy and Hearing Loss
Inactivating variants as well as a missense variant in the centrosomal CEP78 gene
have been identified in autosomal recessive cone-rod dystrophy with hearing loss
(CRDHL), a rare syndromic inherited retinal disease distinct from Usher syndrome.
Apart from this, a complex structural variant (SV) implicating CEP78 has been reported
in CRDHL. Here we aimed to expand the genetic architecture of typical CRDHL
by the identification of complex SVs of the CEP78 region and characterization of
their underlying mechanisms. Approaches used for the identification of the SVs are
shallow whole-genome sequencing (sWGS) combined with quantitative polymerase
chain reaction (PCR) and long-range PCR, or ExomeDepth analysis on whole-exome
sequencing (WES) data. Targeted or whole-genome nanopore long-read sequencing
(LRS) was used to delineate breakpoint junctions at the nucleotide level. For all SVs
cases, the effect of the SVs on CEP78 expression was assessed using quantitative
PCR on patient-derived RNA. Apart from two novel canonical CEP78 splice variants
and a frameshifting single-nucleotide variant (SNV), two SVs affecting CEP78 were
identified in three unrelated individuals with CRDHL: a heterozygous total gene deletion
of 235 kb and a partial gene deletion of 15 kb in a heterozygous and homozygous
state, respectively. Assessment of the molecular consequences of the SVs on patientâs
materials displayed a loss-of-function effect. Delineation and characterization of the 15-kb deletion using targeted LRS revealed the previously described complex CEP78
SV, suggestive of a recurrent genomic rearrangement. A founder haplotype was
demonstrated for the latter SV in cases of Belgian and British origin, respectively. The
novel 235-kb deletion was delineated using whole-genome LRS. Breakpoint analysis
showed microhomology and pointed to a replication-based underlying mechanism.
Moreover, data mining of bulk and single-cell human and mouse transcriptional datasets,
together with CEP78 immunostaining on human retina, linked the CEP78 expression
domain with its phenotypic manifestations. Overall, this study supports that the CEP78
locus is prone to distinct SVs and that SV analysis should be considered in a genetic
workup of CRDHL. Finally, it demonstrated the power of sWGS and both targeted
and whole-genome LRS in identifying and characterizing complex SVs in patients with
ocular diseases
Time scales and exponential trends to equilibrium: Gaussian model problems
We review results on the exponential convergence of multi- dimensional Ornstein-Uhlenbeck processes and discuss related notions of characteristic timescales with concrete model systems. We focus, on the one hand, on exit time distributions and provide ecplicit expressions for the exponential rate of the distribution in the small noise limit. On the other hand, we consider relaxation timescales of the process to its equi- librium measured in terms of relative entropy and discuss the connection with exit probabilities. Along these lines, we study examples which il- lustrate specific properties of the relaxation and discuss the possibility of deriving a simulation-based, empirical definition of slow and fast de- grees of freedom which builds upon a partitioning of the relative entropy functional in conjuction with the observed relaxation behaviour
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