713 research outputs found
Fractoluminescence characterization of the energy dissipated during fast fracture of glass
Fractoluminescence experiments are performed on two kinds of silicate
glasses. All the light spectra collected during dynamic fracture reveal a black
body radiator behaviour, which is interpreted as a crack velocity-dependent
temperature rise close to the crack tip. Crack velocities are estimated to be
of the order of 1300 m.s and fracture process zones are shown to extend
over a few nanometers.Comment: Accepted for publication in Europhysics Letters; 5 pages; 4 figure
The New (Old) Genetics, Version 1.0
The field of Genetics started flourishing after the rediscovery of the Mendelian laws of inheritance at the beginning of the 20th century. These laws are based on a discrete classification of phenotypes and their causative genes. Such a Mendelian way of thinking forms the foundation of modern molecular biology, with its experimental paradigm that a gene function is inferred from the knock-out of the gene. However, most phenotypes are not discrete. Human height, for example, is a continuous phenotype and height measures approximate a Gaussian distribution. The statistical foundation for the genetics of human height was worked out by GALTON at the end of the 19th century. He established the basis of quantitative genetics, a field that has driven the agricultural and breeding programs in the past century. It is not until very recently that the technical developments behind the human genome project have paved the way to reconcile the two contrasting ways of genetic thinking – Mendelian genetics and statistical genetics – through genome-wide analyses. It has now become clear that most phenotypes are rarely determined by single Mendelian genes, but instead, many genes contribute to their determination and variation. It has even been suggested in the omnigenic model that all genes that are expressed at the appropriate time contribute to any given phenotype. These insights are stimulating a major rethinking of how the linear genetic information laid down in the deoxyribonucleic acid (DNA) is converted into the threedimensional structure of an individual. The new conceptual and experimental paradigms have already revolutionized animal and plant breeding. In the field of human genetics, the realization that common diseases also have a polygenic basis is raising new challenges for treatment. And finally, in basic sciences like molecular and evolutionary biology, researchers are starting to revisit traditional, but oversimplified concepts on how genes act and how evolutionary adaptation works
Use of a natural hybrid zone for genome-wide association mapping of craniofacial traits in the house mouse
The identification of the genes involved in morphological variation in nature is still a major challenge. Here we explore a new approach: we combine 178 samples from a natural hybrid zone between two subspecies of the house mouse (Mus musculus domesticus and Mus musculus musculus), and high coverage of the genome (~145K SNPs) to identify loci underlying craniofacial shape variation. Due to the long history of recombination in the hybrid zone, high mapping resolution is anticipated. The combination of genomes from subspecies allows the mapping of both, variation within subspecies and intersubspecific differences, thereby increasing the overall amount of causal genetic variation than can be detected. Skull and mandible shape were measured using 3D landmarks and geometric morphometrics. Using principle component axes as phenotypes, and a linear mixed model accounting for genetic relatedness in the mapping populations, we identified 9 genomic regions associated with skull and 10 with mandible shape. High mapping resolution (median size of significant regions = 148 kb) enabled identification of single or few candidate genes in most cases. Some of the genes act as regulators or modifiers of signaling pathways relevant for morphological development and bone formation, including several with known craniofacial phenotypes in mice and humans. The significant associations combined explain 13% and 7% of the skull and mandible shape variation. In addition, a positive correlation was found between chromosomal length and proportion of variation explained. Our results suggest a complex genetic architecture for shape traits, and support a polygenic model
Tolcapone, a potent aggregation inhibitor for the treatment of familial leptomeningeal amyloidosis
Hereditary transthyretin amyloidosis (ATTR) is a disease characterized by the extracellular deposition of transthyretin (TTR) amyloid fibrils. Highly destabilizing TTR mutations cause leptomeningeal amyloidosis, a rare, but fatal, disorder in which TTR aggregates in the brain. The disease remains intractable, since liver transplantation, the reference therapy for systemic ATTR, does not stop mutant TTR production in the brain. In addition, despite current pharmacological strategies have shown to be effective against in vivo TTR aggregation by stabilizing the tetramer native structure and precluding its dissociation, they display low brain permeability. Recently, we have repurposed tolcapone as a molecule to treat systemic ATTR. Crystal structures and biophysical analysis converge to demonstrate that tolcapone binds with high affinity and specificity to three unstable leptomeningeal TTR variants, stabilizing them and, consequently, inhibiting their aggregation. Because tolcapone is an FDA-approved drug that crosses the blood-brain barrier, our results suggest that it can translate into a first disease-modifying therapy for leptomeningeal amyloidosis. Databases PDB codes for A25T-TTR, V30G-TTR, and Y114C-TTR bound to tolcapone are 6TXV, 6TXW, and 6XTK, respectively
An evaluation of management strategies for Atlantic tuna stocks
International agreements for the International Commission for the Conservation of Atlantic Tunas (ICCAT) convention area imply that Atlantic tuna stocks should be managed by strategies based on maximum sustainable yield (MSY); however, there is concern whether this will actually ensure sustainability with sufficiently high probability consistent with the principals of the precautionary approach. Therefore, the performance of MSY management strategies based on current assessment procedures was evaluated using a computer simulation framework. The framework includes the data collection, assessment, prediction, and management processes, as well as the implementation of management regulations. It therefore provides an integrated way to evaluate the relative importance of and the interactions between each component of the system with regard to the overall success of the management strategy. The study elucidates guidelines about assessment and management that are general enough to be applied to all tunas in the Atlantic Ocean. It does so by comparing different hypotheses about management and assessment for three stocks (North Atlantic albacore, Atlantic bigeye and East Atlantic skipjack), which are representative of the variety encountered (i.e. from data rich to poor and tropical to temperate waters) in ICCAT stocks. Management performance was especially sensitive to the carrying capacity of the stock. The type of proxy used for MSY was more important to the success of the procedure than the frequency of assessment or the number of indices used in the assessment. Whilst the procedure was successful at achieving the management objectives for albacore, it was only partially successful for bigeye and was too conservative for skipjack.No disponibl
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General method for prediction of thermal conductivity for well-characterized hydrocarbon mixtures and fuels up to extreme conditions using entropy scaling
A general and efficient technique is developed to predict the thermal conductivity of well-characterized hydrocarbon mixtures, rocket propellant (RP) fuels, and jet fuels up to high temperatures and high pressures (HTHP). The technique is based upon entropy scaling using the group contribution method coupled with the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) equation of state. The mixture number averaged molecular weight and hydrogen to carbon ratio are used to define a single pseudo-component to represent the compounds in a well-characterized hydrocarbon mixture or fuel. With these two input parameters, thermal conductivity predictions are less accurate when the mixture contains significant amounts of iso-alkanes, but the predictions improve when a single thermal conductivity data point at a reference condition is used to fit one model parameter. For eleven binary mixtures and three ternary mixtures at conditions from 288 to 360 K and up to 4,500 bar, thermal conductivities are predicted with mean absolute percent deviations (MAPDs) of 16.0 and 3.0% using the two-parameter and three-parameter models, respectively. Thermal conductivities are predicted for three RP fuels and three jet fuels at conditions from 293 to 598 K and up to 700 bar with MAPDs of 14.3 and 2.0% using the two-parameter and three-parameter models, respectively
Fermion scattering off electroweak phase transition kink walls with hypermagnetic fields
We study the scattering of fermions off a finite width kink wall during the
electroweak phase transition in the presence of a background hypermagnetic
field. We derive and solve the Dirac equation for such fermions and compute the
reflection and transmission coefficients for the case when the fermions move
from the symmetric to the broken symmetry phase. We show that the chiral nature
of the fermion coupling with the background field in the symmetric phase
generates an axial asymmetry in the scattering processes. We discuss possible
implications of such axial charge segregation for baryon number generation.Comment: 9 pages, 3 Postscript figures, uses RevTeX4. Expanded discussion,
published versio
Microcrystalline silicon thin film transistors obtained by Hot-Wire CVD
Polysilicon thin film transistors (TFT) are of great interest in the field of large area microelectronics, especially because of their application as active elements in flat panel displays. Different deposition techniques are in tough competition with the objective to obtain device-quality polysilicon thin films at low temperature. In this paper we present the preliminary results obtained with the fabrication of TFT deposited by hot-wire chemical vapor deposition (HWCVD). Some results concerned with the structural characterization of the material and electrical performance of the device are presented
Analysing the concept of diagnostic inertia in hypertension: a cross-sectional study
Aims
The aim of this study was to quantify diagnostic inertia (DI) when the physician fails to diagnose hypertension and determine its associated factors.
Methods
This cross-sectional, observational study involved all patients without a diagnosis of hypertension who had their blood pressure (BP) measured at least three times during the second half of 2010 (N = 48,605). Patients with altered mean BP figures (≥ 140/90 mmHg) were considered to experience DI. Secondary variables: gender, atrial fibrillation, diabetes mellitus, dyslipidemia, cardiovascular disease, age and the physician having attended a cardiovascular training course (ESCARVAL). Associated factors were assessed by multivariate logistic regression analysis.
Results
Diagnostic inertia was present in 6450 patients (13.3%, 95% CI: 13.0–13.6%). Factors significantly associated with DI were: male gender (OR = 1.46, 95% CI: 1.37–1.55, p < 0.001), atrial fibrillation (OR = 0.73, 95% CI: 0.58–0.92, p = 0.007), the ESCARVAL cardiovascular course (OR = 0.88, 95% CI: 0.81–0.96, p = 0.005), diabetes mellitus (OR = 0.93, 95% CI: 0.87–0.99, p = 0.016), cardiovascular disease (OR = 0.77, 95% CI: 0.67–0.88, p < 0.001) and older age (years) (18–44[RIGHTWARDS ARROW]OR = 1; 45–59[RIGHTWARDS ARROW]OR = 12.45, 95% CI: 11.11–13.94; 60–74[RIGHTWARDS ARROW]OR = 18.11, 95% CI: 16.30–20.12; ≥ 75[RIGHTWARDS ARROW]OR = 20.43, 95% CI: 18.34–22.75; p < 0.001). The multivariate model had an area under the ROC curve of 0.81 (95% CI: 0.80–0.81, p < 0.001).
Conclusions
This study will help clinical researchers differentiate between the two forms of DI (interpretation of a positive screening test and interpretation of positive diagnostic criteria). The results found here in patients with hypertension suggest that this problem is prevalent, and that a set of associated factors can explain the outcome well (AUC>0.80)
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