2,507 research outputs found
A Selberg integral for the Lie algebra A_n
A new q-binomial theorem for Macdonald polynomials is employed to prove an
A_n analogue of the celebrated Selberg integral. This confirms the g=A_n case
of a conjecture by Mukhin and Varchenko concerning the existence of a Selberg
integral for every simple Lie algebra g.Comment: 32 page
Single-base substitutions in the CHM promoter as a cause of choroideremia
Although over 150 unique mutations affecting the coding sequence of CHM have been identified in patients with the X-linked chorioretinal disease choroideremia (CHM), no regulatory mutations have been reported, and indeed the promoter has not been defined. Here, we describe two independent families affected by CHM bearing a mutation outside the gene's coding region at position c.-98: C>A and C>T, which segregated with the disease. The male proband of family 1 was found to lack CHM mRNA and its gene product Rab escort protein 1, whereas whole-genome sequencing of an affected male in family 2 excluded the involvement of any other known retinal genes. Both mutations abrogated luciferase activity when inserted into a reporter construct, and by further employing the luciferase reporter system to assay sequences 5′ to the gene, we identified the CHM promoter as the region encompassing nucleotides c.-119 to c.-76. These findings suggest that the CHM promoter region should be examined in patients with CHM who lack coding sequence mutations, and reveals, for the first time, features of the gene's regulation
A Minimal Model of Signaling Network Elucidates Cell-to-Cell Stochastic Variability in Apoptosis
Signaling networks are designed to sense an environmental stimulus and adapt
to it. We propose and study a minimal model of signaling network that can sense
and respond to external stimuli of varying strength in an adaptive manner. The
structure of this minimal network is derived based on some simple assumptions
on its differential response to external stimuli. We employ stochastic
differential equations and probability distributions obtained from stochastic
simulations to characterize differential signaling response in our minimal
network model. We show that the proposed minimal signaling network displays two
distinct types of response as the strength of the stimulus is decreased. The
signaling network has a deterministic part that undergoes rapid activation by a
strong stimulus in which case cell-to-cell fluctuations can be ignored. As the
strength of the stimulus decreases, the stochastic part of the network begins
dominating the signaling response where slow activation is observed with
characteristic large cell-to-cell stochastic variability. Interestingly, this
proposed stochastic signaling network can capture some of the essential
signaling behaviors of a complex apoptotic cell death signaling network that
has been studied through experiments and large-scale computer simulations. Thus
we claim that the proposed signaling network is an appropriate minimal model of
apoptosis signaling. Elucidating the fundamental design principles of complex
cellular signaling pathways such as apoptosis signaling remains a challenging
task. We demonstrate how our proposed minimal model can help elucidate the
effect of a specific apoptotic inhibitor Bcl-2 on apoptotic signaling in a
cell-type independent manner. We also discuss the implications of our study in
elucidating the adaptive strategy of cell death signaling pathways.Comment: 9 pages, 6 figure
Intergenerational change and familial aggregation of body mass index
The relationship between parental BMI and that of their adult offspring, when increased adiposity can become a clinical issue, is unknown. We investigated the intergenerational change in body mass index (BMI) distribution, and examined the sex-specific relationship
between parental and adult offspring BMI. Intergenerational
change in the distribution of adjusted BMI in 1,443
complete families (both parents and at least one offspring)
with 2,286 offspring (1,263 daughters and 1,023 sons) from
the west of Scotland, UK, was investigated using quantile
regression. Familial correlations were estimated from
linear mixed effects regression models. The distribution
of BMI showed little intergenerational change in the normal
range (\25 kg/m2), decreasing overweightness (25–
\30 kg/m2) and increasing obesity (C30 kg/m2). Median
BMI was static across generations in males and decreased
in females by 0.4 (95% CI: 0.0, 0.7) kg/m2; the 95th percentileincreased by 2.2 (1.1, 3.2) kg/m2 in males and 2.7
(1.4, 3.9) kg/m2 in females. Mothers’ BMI was more
strongly associated with daughters’ BMI than was fathers’
(correlation coefficient (95% CI): mothers 0.31 (0.27,
0.36), fathers 0.19 (0.14, 0.25); P = 0.001). Mothers’ and
fathers’ BMI were equally correlated with sons’ BMI
(correlation coefficient: mothers 0.28 (0.22, 0.33), fathers
0.27 (0.22, 0.33). The increase in BMI between generations
was concentrated at the upper end of the distribution. This,
alongside the strong parent-offspring correlation, suggests that the increase in BMI is disproportionally greater among
offspring of heavier parents. Familial influences on BMI among middle-aged women appear significantly stronger from mothers than father
Risk factors for delayed presentation and referral of symptomatic cancer: Evidence for common cancers
Background:It has been suggested that the known poorer survival from cancer in the United Kingdom, compared with other European countries, can be attributed to more advanced cancer stage at presentation. There is, therefore, a need to understand the diagnostic process, and to ascertain the risk factors for increased time to presentation.Methods:We report the results from two worldwide systematic reviews of the literature on patient-mediated and practitioner-mediated delays, identifying the factors that may influence these.Results:Across cancer sites, non-recognition of symptom seriousness is the main patient-mediated factor resulting in increased time to presentation. There is strong evidence of an association between older age and patient delay for breast cancer, between lower socio-economic status and delay for upper gastrointestinal and urological cancers and between lower education level and delay for breast and colorectal cancers. Fear of cancer is a contributor to delayed presentation, while sanctioning of help seeking by others can be a powerful mediator of reduced time to presentation. For practitioner delay, ‘misdiagnosis’ occurring either through treating patients symptomatically or relating symptoms to a health problem other than cancer, was an important theme across cancer sites. For some cancers, this could also be linked to inadequate patient examination, use of inappropriate tests or failing to follow-up negative or inconclusive test results.Conclusion:Having sought help for potential cancer symptoms, it is therefore important that practitioners recognise these symptoms, and examine, investigate and refer appropriately. © 2009 Cancer Research UK All rights reserved
ABCD of Beta Ensembles and Topological Strings
We study beta-ensembles with Bn, Cn, and Dn eigenvalue measure and their
relation with refined topological strings. Our results generalize the familiar
connections between local topological strings and matrix models leading to An
measure, and illustrate that all those classical eigenvalue ensembles, and
their topological string counterparts, are related one to another via various
deformations and specializations, quantum shifts and discrete quotients. We
review the solution of the Gaussian models via Macdonald identities, and
interpret them as conifold theories. The interpolation between the various
models is plainly apparent in this case. For general polynomial potential, we
calculate the partition function in the multi-cut phase in a perturbative
fashion, beyond tree-level in the large-N limit. The relation to refined
topological string orientifolds on the corresponding local geometry is
discussed along the way.Comment: 33 pages, 1 figur
Comparative Evaluation of Light-Trap Catches, Electric Motor Mosquito Catches and Human Biting Catches of Anopheles in the Three Gorges Reservoir
The mosquito sampling efficiency of light-trap catches and electric motor mosquito catches were compared with that of human biting catches in the Three Gorges Reservoir. There was consistency in the sampling efficiency between light-trap catches and human biting catches for Anopheles sinensis (r = 0.82, P<0.01) and light-trap catches were 1.52 (1.35–1.71) times that of human biting catches regardless of mosquito density (r = 0.33, P>0.01), while the correlation between electric motor mosquito catches and human biting catches was found to be not statistically significant (r = 0.43, P>0.01) and its sampling efficiency was below that of human biting catches. It is concluded that light-traps can be used as an alternative to human biting catches of Anopheles sinensis in the study area and is a promising tool for sampling malaria vector populations
Comparison of sapwood invasion by three Phytophthora spp.in different hosts
Many Phytophthora spp. have recently been isolated from native vegetation in Western Australia. As their pathogenicity is often unknown, it is not possible to provide advice to land managers on the impact of site infestation on native plants and how these infestations should be managed. We describe a rapid screening method based on sapwood invasion that has been used to compare the pathogenicity of Phytophthora arenaria, P. cinnamomi and P. multivora. Radial invasion into the xylem of six banksias and three eucalypts was assessed in an excised branch assay in summer and winter. Branches were wound inoculated and invasion was assessed by plating from a strip of tissue cut across the stem at the inoculation point and at 40 mm above and below. A symptomless infection had established in both the bark and sapwood within 6 days. P. arenaria was only isolated from the strip of tissue at the inoculation point. P. cinnamomi was isolated from the sapwood of Banksia attenuata, B. burdettii, B. menziesii and B. speciosa 40 mm above or below the inoculation point in some experiments. P. multivora was isolated from B. speciosa 40 mm below the inoculation point in one experiment. Hyphae of both species were seen in both ray parenchyma cells and xylem vessels. The invasiveness of the Phytophthora spp. was compared on the two groups of hosts using scores for sapwood invasion at the inoculation point. For banksias, P. cinnamomi and P. multivora had significantly higher invasion scores on banksias than P. arenaria but were not significantly different to one another. There was no significant difference between the three Phytophthora spp. on the eucalypt hosts. Assessing sapwood invasion provides a rapid, inexpensive and biologically meaningful way of screening the many Phytophthora spp. that have been isolated from native vegetation
Parental smoking during pregnancy and offspring bone mass at age 10Â years: findings from a prospective birth cohort
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