269 research outputs found
Modelling radiation-induced cell cycle delays
Ionizing radiation is known to delay the cell cycle progression. In
particular after particle exposure significant delays have been observed and it
has been shown that the extent of delay affects the expression of damage such
as chromosome aberrations. Thus, to predict how cells respond to ionizing
radiation and to derive reliable estimates of radiation risks, information
about radiation-induced cell cycle perturbations is required. In the present
study we describe and apply a method for retrieval of information about the
time-course of all cell cycle phases from experimental data on the mitotic
index only. We study the progression of mammalian cells through the cell cycle
after exposure. The analysis reveals a prolonged block of damaged cells in the
G2 phase. Furthermore, by performing an error analysis on simulated data
valuable information for the design of experimental studies has been obtained.
The analysis showed that the number of cells analyzed in an experimental sample
should be at least 100 to obtain a relative error less than 20%.Comment: 19 pages, 11 figures, accepted for publication in Radiation and
Environmental Biophysic
Health Economic Impact of a Multicenter Quality-of-Care Initiative for Reducing Unplanned Healthcare Utilization Among Patients With Inflammatory Bowel Disease
Evidence-Based Assessment of Child Obsessive Compulsive Disorder: Recommendations for Clinical Practice and Treatment Research
Obsessive-compulsive disorder (OCD) presents heterogeneously and can be difficult to assess in youth. This review focuses on research-supported assessment approaches for OCD in childhood. Content areas include pre-visit screening, diagnostic establishment, differential diagnosis, assessment of comorbid psychiatric conditions, tracking symptom severity, determining psychosocial functioning, and evaluating clinical improvement. Throughout this review, similarities and differences between assessment approaches geared towards clinical and research settings are discussed
Comparing composite likelihood methods based on pairs for spatial Gaussian random fields
In the last years there has been a growing interest in proposing methods for estimating covariance functions for geostatistical data. Among these, maximum likelihood estimators have nice features when we deal with a Gaussian model. However maximum likelihood becomes impractical when the number of observations is very large. In this work we review some solutions and we contrast them in terms of loss of statistical efficiency and computational burden. Specifically we focus on three types of weighted composite likelihood functions based on pairs and we compare them with the method of covariance tapering. Asymptotic properties of the three estimation methods are derived. We illustrate the effectiveness of the methods through theoretical examples, simulation experiments and by analyzing a data set on yearly total precipitation anomalies at weather stations in the United States.In the last years there has been a growing interest in proposing methods for estimating covariance functions for geostatistical data. Among these, maximum likelihood estimators have nice features when we deal with a Gaussian model. However maximum likelihood becomes impractical when the number of observations is very large. In this work we review some solutions and we contrast them in terms of loss of statistical efficiency and computational burden. Specifically we focus on three types of weighted composite likelihood functions based on pairs and we compare them with the method of covariance tapering. Asymptotic properties of the three estimation methods are derived. We illustrate the effectiveness of the methods through theoretical examples, simulation experiments and by analyzing a data set on yearly total precipitation anomalies at weather stations in the United States
Correlates of comorbid anxiety and externalizing disorders in childhood obsessive compulsive disorder
The present study examines the influence of diagnostic comorbidity on the demographic, psychiatric, and functional status of youth with a primary diagnosis of obsessive compulsive disorder (OCD). Two hundred and fifteen children (ages 5â17) referred to a university-based OCD specialty clinic were compared based on DSM-IV diagnostic profile: OCD without comorbid anxiety or externalizing disorder, OCD plus anxiety disorder, and OCD plus externalizing disorder. No age or gender differences were found across groups. Higher OCD severity was found for the OCDÂ +Â ANX group, while the OCDÂ +Â EXT group reported greater functional impairment than the other two groups. Lower family cohesion was reported by the OCDÂ +Â EXT group compared to the OCD group and the OCDÂ +Â ANX group reported higher family conflict compared to the OCDÂ +Â EXT group. The OCDÂ +Â ANX group had significantly lower rates of tic disorders while rates of depressive disorders did not differ among the three groups. The presence of comorbid anxiety and externalizing psychopathology are associated with greater symptom severity and functional and family impairment and underscores the importance of a better understanding of the relationship of OCD characteristics and associated disorders. Results and clinical implications are further discussed
Characterization of MHC-I in the blue tit (Cyanistes caeruleus) reveals low levels of genetic diversity and trans-population evolution across European populations
The major histcompatibility complex (MHC) is a vital component of the adaptive immune system in all vertebrates. This study is the first to characterize MHC class I (MHC-I) in blue tits (Cyanistes caeruleus), and we use MHC-I exon 3 sequence data from individuals originating from three locations across Europe: Spain, the Netherlands to Sweden. Our phylogeny of the 17 blue tit MHC-I alleles contains one allele cluster with low nucleotide diversity compared to the remaining more diverse alleles. We found a significant evidence for balancing selection in the peptide-binding region in the diverse allele group only. No separation according to geographic location was found in the phylogeny of alleles. Although the number of MHC-I loci of the blue tit is comparable to that of other passerine species, the nucleotide diversity of MHC-I appears to be much lower than that of other passerine species, including the closely related great tit (Parus major) and the severely inbred Seychelles warbler (Acrocephalus sechellensis). We believe that this initial MHC-I characterization in blue tits provides an important step towards understanding the mechanisms shaping MHC-I diversity in natural populations
siRNA Silencing of Proteasome Maturation Protein (POMP) Activates the Unfolded Protein Response and Constitutes a Model for KLICK Genodermatosis
Keratosis linearis with ichthyosis congenita and keratoderma (KLICK) is an autosomal recessive skin disorder associated with a single-nucleotide deletion in the 5âČuntranslated region of the proteasome maturation protein (POMP) gene. The deletion causes a relative switch in transcription start sites for POMP, predicted to decrease levels of POMP protein in terminally differentiated keratinocytes. To investigate the pathophysiology behind KLICK we created an in vitro model of the disease using siRNA silencing of POMP in epidermal air-liquid cultures. Immunohistochemical analysis of the tissue constructs revealed aberrant staining of POMP, proteasome subunits and the skin differentiation marker filaggrin when compared to control tissue constructs. The staining patterns of POMP siRNA tissue constructs showed strong resemblance to those observed in skin biopsies from KLICK patients. Western blot analysis of lysates from the organotypic tissue constructs revealed an aberrant processing of profilaggrin to filaggrin in samples transfected with siRNA against POMP. Knock-down of POMP expression in regular cell cultures resulted in decreased amounts of proteasome subunits. Prolonged silencing of POMP in cultured cells induced C/EBP homologous protein (CHOP) expression consistent with an activation of the unfolded protein response and increased endoplasmic reticulum (ER) stress. The combined results indicate that KLICK is caused by reduced levels of POMP, leading to proteasome insufficiency in differentiating keratinocytes. Proteasome insufficiency disturbs terminal epidermal differentiation, presumably by increased ER stress, and leads to perturbed processing of profilaggrin. Our findings underline a critical role for the proteasome in human epidermal differentiation
Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay
We reconstruct the rare decays , , and in a data sample
corresponding to collected in collisions at
by the CDF II detector at the Fermilab Tevatron
Collider. Using and decays we report the branching ratios. In addition, we report
the measurement of the differential branching ratio and the muon
forward-backward asymmetry in the and decay modes, and the
longitudinal polarization in the decay mode with respect to the squared
dimuon mass. These are consistent with the theoretical prediction from the
standard model, and most recent determinations from other experiments and of
comparable accuracy. We also report the first observation of the {\mathcal{B}}(B^0_s \to
\phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}27 \pm 6B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let
Measurements of the properties of Lambda_c(2595), Lambda_c(2625), Sigma_c(2455), and Sigma_c(2520) baryons
We report measurements of the resonance properties of Lambda_c(2595)+ and
Lambda_c(2625)+ baryons in their decays to Lambda_c+ pi+ pi- as well as
Sigma_c(2455)++,0 and Sigma_c(2520)++,0 baryons in their decays to Lambda_c+
pi+/- final states. These measurements are performed using data corresponding
to 5.2/fb of integrated luminosity from ppbar collisions at sqrt(s) = 1.96 TeV,
collected with the CDF II detector at the Fermilab Tevatron. Exploiting the
largest available charmed baryon sample, we measure masses and decay widths
with uncertainties comparable to the world averages for Sigma_c states, and
significantly smaller uncertainties than the world averages for excited
Lambda_c+ states.Comment: added one reference and one table, changed order of figures, 17
pages, 15 figure
Search for a New Heavy Gauge Boson Wprime with Electron + missing ET Event Signature in ppbar collisions at sqrt(s)=1.96 TeV
We present a search for a new heavy charged vector boson decaying
to an electron-neutrino pair in collisions at a center-of-mass
energy of 1.96\unit{TeV}. The data were collected with the CDF II detector
and correspond to an integrated luminosity of 5.3\unit{fb}^{-1}. No
significant excess above the standard model expectation is observed and we set
upper limits on . Assuming standard
model couplings to fermions and the neutrino from the boson decay to
be light, we exclude a boson with mass less than
1.12\unit{TeV/}c^2 at the 95\unit{%} confidence level.Comment: 7 pages, 2 figures Submitted to PR
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