892 research outputs found
High-density SNP association study of the 17q21 chromosomal region linked to autism identifies CACNA1G as a novel candidate gene.
Chromosome 17q11-q21 is a region of the genome likely to harbor susceptibility to autism (MIM(209850)) based on earlier evidence of linkage to the disorder. This linkage is specific to multiplex pedigrees containing only male probands (MO) within the Autism Genetic Resource Exchange (AGRE). Earlier, Stone et al.(1) completed a high-density single nucleotide polymorphism association study of 13.7âMb within this interval, but common variant association was not sufficient to account for the linkage signal. Here, we extend this single nucleotide polymorphism-based association study to complete the coverage of the two-LOD support interval around the chromosome 17q linkage peak by testing the majority of common alleles in 284 MO trios. Markers within an interval containing the gene, CACNA1G, were found to be associated with Autism Spectrum Disorder at a locally significant level (P=1.9 Ă 10(-5)). While establishing CACNA1G as a novel candidate gene for autism, these alleles do not contribute a sufficient genetic effect to explain the observed linkage, indicating that there is substantial genetic heterogeneity despite the clear linkage signal. The region thus likely harbors a combination of multiple common and rare alleles contributing to the genetic risk. These data, along with earlier studies of chromosomes 5 and 7q3, suggest few if any major common risk alleles account for Autism Spectrum Disorder risk under major linkage peaks in the AGRE sample. This provides important evidence for strategies to identify Autism Spectrum Disorder genes, suggesting that they should focus on identifying rare variants and common variants of small effect
Uniqueness and Non-uniqueness in the Einstein Constraints
The conformal thin sandwich (CTS) equations are a set of four of the Einstein
equations, which generalize the Laplace-Poisson equation of Newton's theory. We
examine numerically solutions of the CTS equations describing perturbed
Minkowski space, and find only one solution. However, we find {\em two}
distinct solutions, one even containing a black hole, when the lapse is
determined by a fifth elliptic equation through specification of the mean
curvature. While the relationship of the two systems and their solutions is a
fundamental property of general relativity, this fairly simple example of an
elliptic system with non-unique solutions is also of broader interest.Comment: 4 pages, 4 figures; abstract and introduction rewritte
Interaction paths promote module integration and network-level robustness of spliceosome to cascading effects
CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTĂFICO E TECNOLĂGICO - CNPQFUNDAĂĂO DE AMPARO Ă PESQUISA DO ESTADO DE SĂO PAULO - FAPESPThe functionality of distinct types of protein networks depends on the patterns of protein-protein interactions. A problem to solve is understanding the fragility of protein networks to predict system malfunctioning due to mutations and other errors. Spec8111CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTĂFICO E TECNOLĂGICO - CNPQFUNDAĂĂO DE AMPARO Ă PESQUISA DO ESTADO DE SĂO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTĂFICO E TECNOLĂGICO - CNPQFUNDAĂĂO DE AMPARO Ă PESQUISA DO ESTADO DE SĂO PAULO - FAPESPsem informação2017/08406-7, 2017/06994-9We thank Ana Paula Assis, PĂąmela C. Santana and Leandro Giacobelli for helpful comments. PRG was supported by CNPq and FAPESP (2017/08406-7). PPC was supported by FAPESP (2017/06994-9). MC was supported by a PMP/BS postdoctoral fellowship (UFPR/UNIVALI 4
The Einstein constraints: uniqueness and non-uniqueness in the conformal thin sandwich approach
We study the appearance of multiple solutions to certain decompositions of
Einstein's constraint equations. Pfeiffer and York recently reported the
existence of two branches of solutions for identical background data in the
extended conformal thin-sandwich decomposition. We show that the Hamiltonian
constraint alone, when expressed in a certain way, admits two branches of
solutions with properties very similar to those found by Pfeiffer and York. We
construct these two branches analytically for a constant-density star in
spherical symmetry, but argue that this behavior is more general. In the case
of the Hamiltonian constraint this non-uniqueness is well known to be related
to the sign of one particular term, and we argue that the extended conformal
thin-sandwich equations contain a similar term that causes the breakdown of
uniqueness.Comment: 9 pages, 1 figur
3+1 Approach to the Long Wavelength Iteration Scheme
Large-scale inhomogeneities and anisotropies are modeled using the Long
Wavelength Iteration Scheme. In this scheme solutions are obtained as
expansions in spatial gradients, which are taken to be small. It is shown that
the choice of foliation for spacetime can make the iteration scheme more
effective in two respects: (i) the shift vector can be chosen so as to dilute
the effect of anisotropy on the late-time value of the extrinsic curvature of
the spacelike hypersurfaces of the foliation; and (ii) pure gauge solutions
present in a similar calculation using the synchronous gauge vanish when the
spacelike hypersurfaces have extrinsic curvature with constant trace. We
furthermore verify the main conclusion of the synchronous gauge calculation
which is large-scale inhomogeneity decays if the matter--considered to be that
of a perfect-fluid with a barotropic equation of state--violates the
strong-energy condition. Finally, we obtain the solution for the lapse function
and discuss its late-time behaviour. It is found that the lapse function is
well-behaved when the matter violates the strong energy condition.Comment: 21 pages, TeX file, already publishe
Initial data for fluid bodies in general relativity
We show that there exist asymptotically flat almost-smooth initial data for
Einstein-perfect fluid's equation that represent an isolated liquid-type body.
By liquid-type body we mean that the fluid energy density has compact support
and takes a strictly positive constant value at its boundary. By almost-smooth
we mean that all initial data fields are smooth everywhere on the initial
hypersurface except at the body boundary, where tangential derivatives of any
order are continuous at that boundary.
PACS: 04.20.Ex, 04.40.Nr, 02.30.JrComment: 38 pages, LaTeX 2e, no figures. Accepted for publication in Phys.
Rev.
Atmosphere Assessment for MARS Science Laboratory Entry, Descent and Landing Operations
On August 6, 2012, the Mars Science Laboratory rover, Curiosity, successfully landed on the surface of Mars. The Entry, Descent and Landing (EDL) sequence was designed using atmospheric conditions estimated from mesoscale numerical models. The models, developed by two independent organizations (Oregon State University and the Southwest Research Institute), were validated against observations at Mars from three prior years. In the weeks and days before entry, the MSL "Council of Atmospheres" (CoA), a group of atmospheric scientists and modelers, instrument experts and EDL simulation engineers, evaluated the latest Mars data from orbiting assets including the Mars Reconnaissance Orbiter's Mars Color Imager (MARCI) and Mars Climate Sounder (MCS), as well as Mars Odyssey's Thermal Emission Imaging System (THEMIS). The observations were compared to the mesoscale models developed for EDL performance simulation to determine if a spacecraft parameter update was necessary prior to entry. This paper summarizes the daily atmosphere observations and comparison to the performance simulation atmosphere models. Options to modify the atmosphere model in the simulation to compensate for atmosphere effects are also presented. Finally, a summary of the CoA decisions and recommendations to the MSL project in the days leading up to EDL is provided
The diagonalization method in quantum recursion theory
As quantum parallelism allows the effective co-representation of classical
mutually exclusive states, the diagonalization method of classical recursion
theory has to be modified. Quantum diagonalization involves unitary operators
whose eigenvalues are different from one.Comment: 15 pages, completely rewritte
FANCJ/BACH1 Acetylation at Lysine 1249 Regulates the DNA Damage Response
BRCA1 promotes DNA repair through interactions with multiple proteins, including CtIP and FANCJ (also known as BRIP1/BACH1). While CtIP facilitates DNA end resection when de-acetylated, the function of FANCJ in repair processing is less well defined. Here, we report that FANCJ is also acetylated. Preventing FANCJ acetylation at lysine 1249 does not interfere with the ability of cells to survive DNA interstrand crosslinks (ICLs). However, resistance is achieved with reduced reliance on recombination. Mechanistically, FANCJ acetylation facilitates DNA end processing required for repair and checkpoint signaling. This conclusion was based on the finding that FANCJ and its acetylation were required for robust RPA foci formation, RPA phosphorylation, and Rad51 foci formation in response to camptothecin (CPT). Furthermore, both preventing and mimicking FANCJ acetylation at lysine 1249 disrupts FANCJ function in checkpoint maintenance. Thus, we propose that the dynamic regulation of FANCJ acetylation is critical for robust DNA damage response, recombination-based processing, and ultimately checkpoint maintenance
Phase transitions in biological membranes
Native membranes of biological cells display melting transitions of their
lipids at a temperature of 10-20 degrees below body temperature. Such
transitions can be observed in various bacterial cells, in nerves, in cancer
cells, but also in lung surfactant. It seems as if the presence of transitions
slightly below physiological temperature is a generic property of most cells.
They are important because they influence many physical properties of the
membranes. At the transition temperature, membranes display a larger
permeability that is accompanied by ion-channel-like phenomena even in the
complete absence of proteins. Membranes are softer, which implies that
phenomena such as endocytosis and exocytosis are facilitated. Mechanical signal
propagation phenomena related to nerve pulses are strongly enhanced. The
position of transitions can be affected by changes in temperature, pressure, pH
and salt concentration or by the presence of anesthetics. Thus, even at
physiological temperature, these transitions are of relevance. There position
and thereby the physical properties of the membrane can be controlled by
changes in the intensive thermodynamic variables. Here, we review some of the
experimental findings and the thermodynamics that describes the control of the
membrane function.Comment: 23 pages, 15 figure
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