878 research outputs found
Global Optimization by Energy Landscape Paving
We introduce a novel heuristic global optimization method, energy landscape
paving (ELP), which combines core ideas from energy surface deformation and
tabu search. In appropriate limits, ELP reduces to existing techniques. The
approach is very general and flexible and is illustrated here on two protein
folding problems. For these examples, the technique gives faster convergence to
the global minimum than previous approaches.Comment: to appear in Phys. Rev. Lett. (2002
Factors Associated with Mutations: Their Matching Rates to Cardiovascular and Neurological Diseases
Monogenic hypertension is rare and caused by genetic mutations, but whether factors associated with mutations are disease-specific remains uncertain. Given two factors associated with high mutation rates, we tested how many previously known genes match with (i) proximity to telomeres or (ii) high adenine and thymine content in cardiovascular diseases (CVDs) related to vascular stiffening. We extracted genomic information using a genome data viewer. In human chromosomes, 64 of 79 genetic loci involving \u3e25 rare mutations and single nucleotide polymorphisms satisfied (i) or (ii), resulting in an 81% matching rate. However, this high matching rate was no longer observed as we checked the two factors in genes associated with essential hypertension (EH), thoracic aortic aneurysm (TAA), and congenital heart disease (CHD), resulting in matching rates of 53%, 70%, and 75%, respectively. A matching of telomere proximity or high adenine and thymine content projects the list of loci involving rare mutations of monogenic hypertension better than those of other CVDs, likely due to adoption of rigorous criteria for true-positive signals. Our data suggest that the factorâdisease matching rate is an accurate tool that can explain deleterious mutations of monogenic hypertension at a \u3e80% matchâunlike the relatively lower matching rates found in human genes of EH, TAA, CHD, and familial Parkinsonâs disease
Constraints on a second planet in the WASP-3 system
There have been previous hints that the transiting planet WASP-3 b is
accompanied by a second planet in a nearby orbit, based on small deviations
from strict periodicity of the observed transits. Here we present 17 precise
radial velocity measurements and 32 transit light curves that were acquired
between 2009 and 2011. These data were used to refine the parameters of the
host star and transiting planet. This has resulted in reduced uncertainties for
the radii and masses of the star and planet. The radial-velocity data and the
transit times show no evidence for an additional planet in the system.
Therefore, we have determined the upper limit on the mass of any hypothetical
second planet, as a function of its orbital period.Comment: Accepted for publication in The Astronomical Journa
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Wivesâ part-time employment and marital stability in Great Britain, West Germany and the United States
Many hail wivesâ part-time employment as a workâfamily balance strategy, but theories offer competing predictions as to the effects of wivesâ employment on relationship stability. We use panel data to test these competing hypotheses among recent cohorts of first-married couples in Great Britain, West Germany 1 and the United States. We find effects of wivesâ employment on marital stability var y across the countries. In West Germany with its high-quality part-time employment, couples where the wife works part time are significantly more stable. In the more liberal British and US labour markets, neither wivesâ part- nor full-time employment significantly alters divorce risk. In the United States, however, mothers working part time have significantly lower divorce risk. West German and British husbandsâ unemployment proves more detrimental to marital stability than wivesâ employment. These results highlight the importance of the socioeconomic context in structuring the optimal employment participation of both partners
Association Analysis of Canonical Wnt Signalling Genes in Diabetic Nephropathy
Several studies have provided compelling evidence implicating the Wnt signalling pathway in the pathogenesis of diabetic nephropathy. Gene expression profiles associated with renal fibrosis have been attenuated through Wnt pathway modulation in model systems implicating Wnt pathway members as potential therapeutic targets for the treatment of diabetic nephropathy. We assessed tag and potentially functional single nucleotide polymorphisms (SNPs; nâ=â31) in four key Wnt pathway genes (CTNNB1, AXIN2, LRP5 and LRP6) for association with diabetic nephropathy using a case-control design.SNPs were genotyped using Sequenom or Taqman technologies in 1351 individuals with type 1 diabetes (651 cases with nephropathy and 700 controls without nephropathy). Cases and controls were white and recruited from the UK and Ireland. Association analyses were performed using PLINK, to compare allele and haplotype frequencies in cases and controls. Adjustment for multiple testing was performed by permutation testing.Following logistic regression analysis adjusted by collection centre, duration of T1D, and average HbA1c as covariates, a single SNP in LRP6 (rs1337791) was significantly associated with DN (ORâ=â0.74; CI: 0.57-0.97; Pâ=â0.028), although this was not maintained following correction for multiple testing. Three additional SNPs (rs2075241 in LRP6; rs3736228 and rs491347 both in LRP5) were marginally associated with diabetic nephropathy, but none of the associations were replicated in an independent dataset. Haplotype and subgroup analysis (according to duration of diabetes, and end-stage renal disease) also failed to reveal an association with diabetic nephropathy.Our results suggest that analysed common variants in CTNNB1, AXIN2, LRP5 and LRP6 are not strongly associated with diabetic nephropathy in type 1 diabetes among white individuals. Our findings, however, cannot entirely exclude these genes or other members of the Wnt pathway, from involvement in the pathogenesis of diabetic nephropathy as our study had limited power to detect variants with small effect size
Testing the role of predicted gene knockouts in human anthropometric trait variation
National Heart, Lung, and Blood Institute (NHLBI)
S.L. is funded by a Canadian Institutes of Health Research
Banting doctoral scholarship. G.L. is funded by Genome Canada
and Génome Québec; the Canada Research Chairs program; and
the Montreal Heart Institute Foundation. C.M.L. is supported by
Wellcome Trust (grant numbers 086596/Z/08/Z, 086596/Z/08/A);
and the Li Ka Shing Foundation. N.S. is funded by National Institutes
of Health (grant numbers HL088456, HL111089, HL116747).
The Mount Sinai BioMe Biobank Program is supported by the Andrea
and Charles Bronfman Philanthropies. GO ESP is supported
by NHLBI (RC2 HL-103010 to HeartGO, RC2 HL-102923 to LungGO,
RC2 HL-102924 to WHISP). The ESP exome sequencing was
performed through NHLBI (RC2 HL-102925 to BroadGO, RC2 HL-
102926 to SeattleGO). EGCUT work was supported through the
Estonian Genome Center of University of Tartu by the Targeted
Financing from the Estonian Ministry of Science and Education
(grant number SF0180142s08); the Development Fund of the University
of Tartu (grant number SP1GVARENG); the European Regional
Development Fund to the Centre of Excellence in
Genomics (EXCEGEN) [grant number 3.2.0304.11-0312]; and
through FP7 (grant number 313010). EGCUT were further supported
by the US National Institute of Health (grant number
R01DK075787). A.K.M. was supported by an American Diabetes
Association Mentor-Based Postdoctoral Fellowship (#7-12-MN-
02). The BioVU dataset used in the analyses described were obtained
from Vanderbilt University Medical Centers BioVU which
is supported by institutional funding and by the Vanderbilt CTSA
grant ULTR000445 from NCATS/NIH. Genome-wide genotyping
was funded by NIH grants RC2GM092618 from NIGMS/OD and
U01HG004603 from NHGRI/NIGMS. Funding to pay the Open Access
publication charges for this article was provided by a block
grant from Research Councils UK to the University of Cambridge
Testing the role of predicted gene knockouts in human anthropometric trait variation
National Heart, Lung, and Blood Institute (NHLBI)
S.L. is funded by a Canadian Institutes of Health Research
Banting doctoral scholarship. G.L. is funded by Genome Canada
and Génome Québec; the Canada Research Chairs program; and
the Montreal Heart Institute Foundation. C.M.L. is supported by
Wellcome Trust (grant numbers 086596/Z/08/Z, 086596/Z/08/A);
and the Li Ka Shing Foundation. N.S. is funded by National Institutes
of Health (grant numbers HL088456, HL111089, HL116747).
The Mount Sinai BioMe Biobank Program is supported by the Andrea
and Charles Bronfman Philanthropies. GO ESP is supported
by NHLBI (RC2 HL-103010 to HeartGO, RC2 HL-102923 to LungGO,
RC2 HL-102924 to WHISP). The ESP exome sequencing was
performed through NHLBI (RC2 HL-102925 to BroadGO, RC2 HL-
102926 to SeattleGO). EGCUT work was supported through the
Estonian Genome Center of University of Tartu by the Targeted
Financing from the Estonian Ministry of Science and Education
(grant number SF0180142s08); the Development Fund of the University
of Tartu (grant number SP1GVARENG); the European Regional
Development Fund to the Centre of Excellence in
Genomics (EXCEGEN) [grant number 3.2.0304.11-0312]; and
through FP7 (grant number 313010). EGCUT were further supported
by the US National Institute of Health (grant number
R01DK075787). A.K.M. was supported by an American Diabetes
Association Mentor-Based Postdoctoral Fellowship (#7-12-MN-
02). The BioVU dataset used in the analyses described were obtained
from Vanderbilt University Medical Centers BioVU which
is supported by institutional funding and by the Vanderbilt CTSA
grant ULTR000445 from NCATS/NIH. Genome-wide genotyping
was funded by NIH grants RC2GM092618 from NIGMS/OD and
U01HG004603 from NHGRI/NIGMS. Funding to pay the Open Access
publication charges for this article was provided by a block
grant from Research Councils UK to the University of Cambridge
Testing the role of predicted gene knockouts in human anthropometric trait variation
National Heart, Lung, and Blood Institute (NHLBI)
S.L. is funded by a Canadian Institutes of Health Research
Banting doctoral scholarship. G.L. is funded by Genome Canada
and Génome Québec; the Canada Research Chairs program; and
the Montreal Heart Institute Foundation. C.M.L. is supported by
Wellcome Trust (grant numbers 086596/Z/08/Z, 086596/Z/08/A);
and the Li Ka Shing Foundation. N.S. is funded by National Institutes
of Health (grant numbers HL088456, HL111089, HL116747).
The Mount Sinai BioMe Biobank Program is supported by the Andrea
and Charles Bronfman Philanthropies. GO ESP is supported
by NHLBI (RC2 HL-103010 to HeartGO, RC2 HL-102923 to LungGO,
RC2 HL-102924 to WHISP). The ESP exome sequencing was
performed through NHLBI (RC2 HL-102925 to BroadGO, RC2 HL-
102926 to SeattleGO). EGCUT work was supported through the
Estonian Genome Center of University of Tartu by the Targeted
Financing from the Estonian Ministry of Science and Education
(grant number SF0180142s08); the Development Fund of the University
of Tartu (grant number SP1GVARENG); the European Regional
Development Fund to the Centre of Excellence in
Genomics (EXCEGEN) [grant number 3.2.0304.11-0312]; and
through FP7 (grant number 313010). EGCUT were further supported
by the US National Institute of Health (grant number
R01DK075787). A.K.M. was supported by an American Diabetes
Association Mentor-Based Postdoctoral Fellowship (#7-12-MN-
02). The BioVU dataset used in the analyses described were obtained
from Vanderbilt University Medical Centers BioVU which
is supported by institutional funding and by the Vanderbilt CTSA
grant ULTR000445 from NCATS/NIH. Genome-wide genotyping
was funded by NIH grants RC2GM092618 from NIGMS/OD and
U01HG004603 from NHGRI/NIGMS. Funding to pay the Open Access
publication charges for this article was provided by a block
grant from Research Councils UK to the University of Cambridge
Intergenerational family support for âGeneration Rentâ:The family home for socially disengaged young people
This paper critically discusses the concept of intergenerational family support in housing for young people. Recognizing increased difficulties faced by the younger generation in the housing market, this paper highlights that support from older family members is increasingly important. Nonetheless, it is critiqued that the role of the family home has been largely ignored in the current âgeneration rentâ discourse. By drawing on recent youth studies debates, this paper argues living in the family home could be an important form of support in housing, especially for marginalized youth. This paper presents insights from qualitative studies in Hong Kong and Scotland and analyses interview accounts of socially disengaged young people. It reflects how remaining at the family home could be interpreted as intergenerational support, and further elicits complexities in expectations, negotiations and emotions involved. This analysis offers new evidence and a more nuanced perspective of intergenerational family support in housing research
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