2,476 research outputs found
Genetic landscape of autism spectrum disorder in Vietnamese children
Autism spectrum disorder (ASD) is a complex disorder with an unclear aetiology and an estimated global prevalence of 1%. However, studies of ASD in the Vietnamese population are limited. Here, we first conducted whole exome sequencing (WES) of 100 children with ASD and their unaffected parents. Our stringent analysis pipeline was able to detect 18 unique variants (8 de novo and 10 ×-linked, all validated), including 12 newly discovered variants. Interestingly, a notable number of X-linked variants were detected (56%), and all of them were found in affected males but not in affected females. We uncovered 17 genes from our ASD cohort in which CHD8, DYRK1A, GRIN2B, SCN2A, OFD1 and MDB5 have been previously identified as ASD risk genes, suggesting the universal aetiology of ASD for these genes. In addition, we identified six genes that have not been previously reported in any autism database: CHM, ENPP1, IGF1, LAS1L, SYP and TBX22. Gene ontology and phenotype-genotype analysis suggested that variants in IGF1, SYP and LAS1L could plausibly confer risk for ASD. Taken together, this study adds to the genetic heterogeneity of ASD and is the first report elucidating the genetic landscape of ASD in Vietnamese children
Machine learning reveals mesenchymal breast carcinoma cell adaptation in response to matrix stiffness.
Epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition (MET), are believed to play key roles in facilitating the metastatic cascade. Metastatic lesions often exhibit a similar epithelial-like state to that of the primary tumour, in particular, by forming carcinoma cell clusters via E-cadherin-mediated junctional complexes. However, the factors enabling mesenchymal-like micrometastatic cells to resume growth and reacquire an epithelial phenotype in the target organ microenvironment remain elusive. In this study, we developed a workflow using image-based cell profiling and machine learning to examine morphological, contextual and molecular states of individual breast carcinoma cells (MDA-MB-231). MDA-MB-231 heterogeneous response to the host organ microenvironment was modelled by substrates with controllable stiffness varying from 0.2kPa (soft tissues) to 64kPa (bone tissues). We identified 3 distinct morphological cell types (morphs) varying from compact round-shaped to flattened irregular-shaped cells with lamellipodia, predominantly populating 2-kPa and >16kPa substrates, respectively. These observations were accompanied by significant changes in E-cadherin and vimentin expression. Furthermore, we demonstrate that the bone-mimicking substrate (64kPa) induced multicellular cluster formation accompanied by E-cadherin cell surface localisation. MDA-MB-231 cells responded to different substrate stiffness by morphological adaptation, changes in proliferation rate and cytoskeleton markers, and cluster formation on bone-mimicking substrate. Our results suggest that the stiffest microenvironment can induce MET
The Genetics of Adaptation for Eight Microvirid Bacteriophages
Theories of adaptive molecular evolution have recently experienced significant expansion, and their predictions and assumptions have begun to be subjected to rigorous empirical testing. However, these theories focus largely on predicting the first event in adaptive evolution, the fixation of a single beneficial mutation. To address long-term adaptation it is necessary to include new assumptions, but empirical data are needed for guidance. To empirically characterize the general properties of adaptive walks, eight recently isolated relatives of the single-stranded DNA (ssDNA) bacteriophage φX174 (family Microviridae) were adapted to identical selective conditions. Three of the eight genotypes were adapted in replicate, for a total of 11 adaptive walks. We measured fitness improvement and identified the genetic changes underlying the observed adaptation. Nearly all phages were evolvable; nine of the 11 lineages showed a significant increase in fitness. However, fitness plateaued quickly, and adaptation was achieved through only three substitutions on average. Parallel evolution was rampant, both across replicates of the same genotype as well as across different genotypes, yet adaptation of replicates never proceeded through the exact same set of mutations. Despite this, final fitnesses did not vary significantly among replicates. Final fitnesses did vary significantly across genotypes but not across phylogenetic groupings of genotypes. A positive correlation was found between the number of substitutions in an adaptive walk and the magnitude of fitness improvement, but no correlation was found between starting and ending fitness. These results provide an empirical framework for future adaptation theory
Neutron Stars in Teleparallel Gravity
In this paper we deal with neutron stars, which are described by a perfect
fluid model, in the context of the teleparallel equivalent of general
relativity. We use numerical simulations to find the relationship between the
angular momentum of the field and the angular momentum of the source. Such a
relation was established for each stable star reached by the numerical
simulation once the code is fed with an equation of state, the central energy
density and the ratio between polar and equatorial radii. We also find a regime
where linear relation between gravitational angular momentum and moment of
inertia (as well as angular velocity of the fluid) is valid. We give the
spatial distribution of the gravitational energy and show that it has a linear
dependence with the squared angular velocity of the source.Comment: 19 pages, 14 figures. arXiv admin note: text overlap with
arXiv:1206.331
Nekrasov Functions and Exact Bohr-Sommerfeld Integrals
In the case of SU(2), associated by the AGT relation to the 2d Liouville
theory, the Seiberg-Witten prepotential is constructed from the Bohr-Sommerfeld
periods of 1d sine-Gordon model. If the same construction is literally applied
to monodromies of exact wave functions, the prepotential turns into the
one-parametric Nekrasov prepotential F(a,\epsilon_1) with the other epsilon
parameter vanishing, \epsilon_2=0, and \epsilon_1 playing the role of the
Planck constant in the sine-Gordon Shroedinger equation, \hbar=\epsilon_1. This
seems to be in accordance with the recent claim in arXiv:0908.4052 and poses a
problem of describing the full Nekrasov function as a seemingly straightforward
double-parametric quantization of sine-Gordon model. This also provides a new
link between the Liouville and sine-Gordon theories.Comment: 10 page
Can vitamin D supplementation improve grip strength in elderly nursing home residents? A double-blinded controlled trial
Indicators for the Data Usage Index (DUI): an incentive for publishing primary biodiversity data through global information infrastructure
<p>Abstract</p> <p>Background</p> <p>A professional recognition mechanism is required to encourage expedited publishing of an adequate volume of 'fit-for-use' biodiversity data. As a component of such a recognition mechanism, we propose the development of the Data Usage Index (DUI) to demonstrate to data publishers that their efforts of creating biodiversity datasets have impact by being accessed and used by a wide spectrum of user communities.</p> <p>Discussion</p> <p>We propose and give examples of a range of 14 absolute and normalized biodiversity dataset usage indicators for the development of a DUI based on search events and dataset download instances. The DUI is proposed to include relative as well as species profile weighted comparative indicators.</p> <p>Conclusions</p> <p>We believe that in addition to the recognition to the data publisher and all players involved in the data life cycle, a DUI will also provide much needed yet novel insight into how users use primary biodiversity data. A DUI consisting of a range of usage indicators obtained from the GBIF network and other relevant access points is within reach. The usage of biodiversity datasets leads to the development of a family of indicators in line with well known citation-based measurements of recognition.</p
Ultrasonic intensification as a tool for enhanced microbial biofuel yields
peer-reviewedUltrasonication has recently received attention as a novel bioprocessing tool for process intensification in many areas
of downstream processing. Ultrasonic intensification (periodic ultrasonic treatment during the fermentation process)
can result in a more effective homogenization of biomass and faster energy and mass transfer to biomass over short
time periods which can result in enhanced microbial growth. Ultrasonic intensification can allow the rapid selective
extraction of specific biomass components and can enhance product yields which can be of economic benefit. This
review focuses on the role of ultrasonication in the extraction and yield enhancement of compounds from various
microbial sources, specifically algal and cyanobacterial biomass with a focus on the production of biofuels. The
operating principles associated with the process of ultrasonication and the influence of various operating conditions
including ultrasonic frequency, power intensity, ultrasonic duration, reactor designs and kinetics applied for ultrasonic
intensification are also described
Sialic acid changes in Dalton's lymphoma-bearing mice after cyclophosphamide and cisplatin treatment
Continuation for thin film hydrodynamics and related scalar problems
This chapter illustrates how to apply continuation techniques in the analysis
of a particular class of nonlinear kinetic equations that describe the time
evolution through transport equations for a single scalar field like a
densities or interface profiles of various types. We first systematically
introduce these equations as gradient dynamics combining mass-conserving and
nonmass-conserving fluxes followed by a discussion of nonvariational amendmends
and a brief introduction to their analysis by numerical continuation. The
approach is first applied to a number of common examples of variational
equations, namely, Allen-Cahn- and Cahn-Hilliard-type equations including
certain thin-film equations for partially wetting liquids on homogeneous and
heterogeneous substrates as well as Swift-Hohenberg and Phase-Field-Crystal
equations. Second we consider nonvariational examples as the
Kuramoto-Sivashinsky equation, convective Allen-Cahn and Cahn-Hilliard
equations and thin-film equations describing stationary sliding drops and a
transversal front instability in a dip-coating. Through the different examples
we illustrate how to employ the numerical tools provided by the packages
auto07p and pde2path to determine steady, stationary and time-periodic
solutions in one and two dimensions and the resulting bifurcation diagrams. The
incorporation of boundary conditions and integral side conditions is also
discussed as well as problem-specific implementation issues
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