170 research outputs found
Current-voltage characteristics of diluted Josephson-junction arrays: scaling behavior at current and percolation threshold
Dynamical simulations and scaling arguments are used to study the
current-voltage (IV) characteristics of a two-dimensional model of resistively
shunted Josephson-junction arrays in presence of percolative disorder, at zero
external field. Two different limits of the Josephson-coupling concentration
are considered, where is the percolation threshold. For
and zero temperature, the IV curves show power-law behavior above a disorder
dependent critical current. The power-law behavior and critical exponents are
consistent with a simple scaling analysis. At and finite temperature ,
the results show the scaling behavior of a T=0 superconducting transition. The
resistance is linear but vanishes for decreasing with an apparent
exponential behavior. Crossover to non-linearity appears at currents
proportional to , with a thermal-correlation length exponent
consistent with the corresponding value for the diluted XY model at
.Comment: Revtex, 9 postscript pages, to appear in Phys. Rev.
Transport on percolation clusters with power-law distributed bond strengths: when do blobs matter?
The simplest transport problem, namely maxflow, is investigated on critical
percolation clusters in two and three dimensions, using a combination of
extremal statistics arguments and exact numerical computations, for power-law
distributed bond strengths of the type .
Assuming that only cutting bonds determine the flow, the maxflow critical
exponent \ve is found to be \ve(\alpha)=(d-1) \nu + 1/(1-\alpha). This
prediction is confirmed with excellent accuracy using large-scale numerical
simulation in two and three dimensions. However, in the region of anomalous
bond capacity distributions () we demonstrate that, due to
cluster-structure fluctuations, it is not the cutting bonds but the blobs that
set the transport properties of the backbone. This ``blob-dominance'' avoids a
cross-over to a regime where structural details, the distribution of the number
of red or cutting bonds, would set the scaling. The restored scaling exponents
however still follow the simplistic red bond estimate. This is argued to be due
to the existence of a hierarchy of so-called minimum cut-configurations, for
which cutting bonds form the lowest level, and whose transport properties scale
all in the same way. We point out the relevance of our findings to other scalar
transport problems (i.e. conductivity).Comment: 9 pages + Postscript figures. Revtex4+psfig. Submitted to PR
Orientational pinning and transverse voltage: Simulations and experiments in square Josephson junction arrays
We study the dependence of the transport properties of square Josephson
Junctions arrays with the direction of the applied dc current, both
experimentally and numerically. We present computational simulations of
current-voltage curves at finite temperatures for a single vortex in the array
(), and experimental measurements in
arrays under a low magnetic field corresponding to . We find that
the transverse voltage vanishes only in the directions of maximum symmetry of
the square lattice: the [10] and [01] direction (parallel bias) and the [11]
direction (diagonal bias). For orientations different than the symmetry
directions, we find a finite transverse voltage which depends strongly on the
angle of the current. We find that vortex motion is pinned in the [10]
direction (), meaning that the voltage response is insensitive to small
changes in the orientation of the current near . We call this
phenomenon orientational pinning. This leads to a finite transverse critical
current for a bias at and to a transverse voltage for a bias at
. On the other hand, for diagonal bias in the [11] direction the
behavior is highly unstable against small variations of , leading to a
rapid change from zero transverse voltage to a large transverse voltage within
a few degrees. This last behavior is in good agreement with our measurements in
arrays with a quasi-diagonal current drive.Comment: 9 pages, 9 figure
Fallout radionuclide-based techniques for assessing the impact of soil conservation measures on erosion control and soil quality: An overview of the main lessons learnt under an FAO/IAEA Coordinated Research Project
This paper summarizes key findings and identifies the main lessons learnt from a 5-year (2002-2008) coordinated research project (CRP) on "Assessing the effectiveness of soil conservation measures for sustainable watershed management and crop production using fallout radionuclides" (D1.50.08), organized and funded by the International Atomic Energy Agency through the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture. The project brought together nineteen participants, from Australia, Austria, Brazil, Canada, Chile, China, Japan, Morocco, Pakistan, Poland, Romania, Russian Federation, Turkey, United Kingdom, United States of America and Vietnam, involved in the use of nuclear techniques and, more particularly, fallout radionuclides (FRN) to assess the relative impacts of different soil conservation measures on soil erosion and land productivity. The overall objective of the CRP was to develop improved land use and management strategies for sustainable watershed management through effective soil erosion control practices, by the use of 137Cs (half-life of 30.2 years), 210Pb ex (half-life of 22.3 years) and 7Be (half-life of 53.4 days) for measuring soil erosion over several spatial and temporal scales. The environmental conditions under which the different research teams applied the tools based on the use of fallout radionuclides varied considerably - a variety of climates, soils, topographies and land uses. Nevertheless, the achievements of the CRP, as reflected in this overview paper, demonstrate that fallout radionuclide-based techniques are powerful tools to assess soil erosion/deposition at several spatial and temporal scales in a wide range of environments, and offer potential to monitor soil quality. The success of the CRP has stimulated an interest in many IAEA Member States in the use of these methodologies to identify factors and practices that can enhance sustainable agriculture and minimize land degradation. © 2012 Elsevier Ltd
The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM (-/-) patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors
The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors
AD51B in Familial Breast Cancer
Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk
AI is a viable alternative to high throughput screening: a 318-target study
: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
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