66 research outputs found
Modeling of Photoionized Plasmas
In this paper I review the motivation and current status of modeling of
plasmas exposed to strong radiation fields, as it applies to the study of
cosmic X-ray sources. This includes some of the astrophysical issues which can
be addressed, the ingredients for the models, the current computational tools,
the limitations imposed by currently available atomic data, and the validity of
some of the standard assumptions. I will also discuss ideas for the future:
challenges associated with future missions, opportunities presented by improved
computers, and goals for atomic data collection.Comment: 17 pages, 8 figures, to appear in the proceedings of Xray2010,
Utrecht, the Netherlands, March 15-17 201
Force unfolding kinetics of RNA using optical tweezers. II. Modeling experiments
By exerting mechanical force it is possible to unfold/refold RNA molecules
one at a time. In a small range of forces, an RNA molecule can hop between the
folded and the unfolded state with force-dependent kinetic rates. Here, we
introduce a mesoscopic model to analyze the hopping kinetics of RNA hairpins in
an optical tweezers setup. The model includes different elements of the
experimental setup (beads, handles and RNA sequence) and limitations of the
instrument (time lag of the force-feedback mechanism and finite bandwidth of
data acquisition). We investigated the influence of the instrument on the
measured hopping rates. Results from the model are in good agreement with the
experiments reported in the companion article (1). The comparison between
theory and experiments allowed us to infer the values of the intrinsic
molecular rates of the RNA hairpin alone and to search for the optimal
experimental conditions to do the measurements. We conclude that long handles
and soft laser traps represent the best conditions to extract rate estimates
that are closest to the intrinsic molecular rates. The methodology and
rationale presented here can be applied to other experimental setups and other
molecules.Comment: PDF file, 32 pages including 9 figures plus supplementary materia
Disappearing Dark Matter in Brane World Cosmology: New Limits on Noncompact Extra Dimensions
We explore cosmological implications of dark matter as massive particles
trapped on a brane embedded in a Randall-Sundrum noncompact higher dimension
space. It is an unavoidable consequence of this cosmology that massive
particles are metastable and can disappear into the bulk dimension. Here, we
show that a massive dark matter particle (e.g. the lightest supersymmetric
particle) is likely to have the shortest lifetime for disappearing into the
bulk. We examine cosmological constraints on this new paradigm and show that
disappearing dark matter is consistent (at the 95% confidence level) with all
cosmological constraints, i.e. present observations of Type Ia supernovae at
the highest redshift, trends in the mass-to-light ratios of galaxy clusters
with redshift, the fraction of X-ray emitting gas in rich clusters, and the
spectrum of power fluctuations in the cosmic microwave background. A best concordance region is identified corresponding to a mean lifetime for
dark matter disappearance of Gyr. The implication
of these results for brane-world physics is discussed.Comment: 7 pages, 7 figures, new cosmological constraints added, accepted for
publication in PR
Dynamic Evolution Model of Isothermal Voids and Shocks
We explore self-similar hydrodynamic evolution of central voids embedded in
an isothermal gas of spherical symmetry under the self-gravity. More
specifically, we study voids expanding at constant radial speeds in an
isothermal gas and construct all types of possible void solutions without or
with shocks in surrounding envelopes. We examine properties of void boundaries
and outer envelopes. Voids without shocks are all bounded by overdense shells
and either inflows or outflows in the outer envelope may occur. These
solutions, referred to as type void solutions, are further
divided into subtypes and
according to their characteristic behaviours across the sonic critical line
(SCL). Void solutions with shocks in envelopes are referred to as type
voids and can have both dense and quasi-smooth edges.
Asymptotically, outflows, breezes, inflows, accretions and static outer
envelopes may all surround such type voids. Both cases of
constant and varying temperatures across isothermal shock fronts are analyzed;
they are referred to as types and
void shock solutions. We apply the `phase net matching procedure' to construct
various self-similar void solutions. We also present analysis on void
generation mechanisms and describe several astrophysical applications. By
including self-gravity, gas pressure and shocks, our isothermal self-similar
void (ISSV) model is adaptable to various astrophysical systems such as
planetary nebulae, hot bubbles and superbubbles in the interstellar medium as
well as supernova remnants.Comment: 24 pages, 13 figuers, accepted by ApS
Large Extra Dimensions and Decaying KK Recurrences
We suggest the possibility that in ADD type brane-world scenarios, the higher
KK excitations of the graviton may decay to lower ones owing to a breakdown of
the conservation of extra dimensional ``momenta'' and study its implications
for astrophysics and cosmology. We give an explicit realization of this idea
with a bulk scalar field , whose nonzero KK modes acquire vacuum
expectation values. This scenario helps to avoid constraints on large extra
dimensions that come from gamma ray flux bounds in the direction of nearby
supernovae as well as those coming from diffuse cosmological gamma ray
background. It also relaxes the very stringent limits on reheat temperature of
the universe in ADD models.Comment: 16 pages, late
The composition of the protosolar disk and the formation conditions for comets
Conditions in the protosolar nebula have left their mark in the composition
of cometary volatiles, thought to be some of the most pristine material in the
solar system. Cometary compositions represent the end point of processing that
began in the parent molecular cloud core and continued through the collapse of
that core to form the protosun and the solar nebula, and finally during the
evolution of the solar nebula itself as the cometary bodies were accreting.
Disentangling the effects of the various epochs on the final composition of a
comet is complicated. But comets are not the only source of information about
the solar nebula. Protostellar disks around young stars similar to the protosun
provide a way of investigating the evolution of disks similar to the solar
nebula while they are in the process of evolving to form their own solar
systems. In this way we can learn about the physical and chemical conditions
under which comets formed, and about the types of dynamical processing that
shaped the solar system we see today.
This paper summarizes some recent contributions to our understanding of both
cometary volatiles and the composition, structure and evolution of protostellar
disks.Comment: To appear in Space Science Reviews. The final publication is
available at Springer via http://dx.doi.org/10.1007/s11214-015-0167-
CD4/CD8 Ratio and Cancer Risk among Adults with HIV
Background: Independent of CD4 cell count, a low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the United States and Canada. Methods: We examined all cancer-free PWH with 1 or more CD4/CD8 values from North American AIDS Cohort Collaboration on Research and Design observational cohorts with validated cancer diagnoses between 1998 and 2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines. Models were adjusted for age, sex, race and ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness. Results: Among 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. The overall median 6-month lagged CD4/CD8 ratio was 0.52 (interquartile range = 0.30-0.82). Compared with a 6-month lagged CD4/CD8 of 0.80, a CD4/CD8 of 0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval = 1.14 to 1.35]). The CD4/CD8 ratio was also inversely associated with non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all 2-sided P <. 05). Results were similar using 12-, 18-, and 24-month lagged CD4/CD8 values. Conclusions: A low CD4/CD8 ratio up to 24 months before cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker
The path to a better biomarker: Application of a risk management framework for the implementation of PD-L1 and TILs as immuno-oncology biomarkers in breast cancer clinical trials and daily practice
Immune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying 651% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-reader reproducibility have been raised. High tumor-infiltrating lymphocytes (TILs) have also been associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin\u2013stained slides and have shown reliable inter-reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD-L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD-L1 and TIL analyses as a more comprehensive immuno-oncological biomarker for patient selection for PD-1/PD-L1 inhibition-based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk-management framework that may help mitigate the risks of suboptimal patient selection for immuno-therapeutic approaches in clinical trials and daily practice based on combined TILs/PD-L1 assessment in BC. \ua9 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
Secular Trends in Breast Cancer Risk Among Women With HIV Initiating ART in North America
Background: Studies suggest lower risk of breast cancer in women with HIV versus without HIV. These estimates may be biased by lower life expectancy and younger age distribution of women with HIV. Our analysis evaluated this bias and characterized secular trends in breast cancer among women with HIV initiating antiretroviral therapy. We hypothesized breast cancer risk would increase over time as mortality decreased. Setting: Women with HIV prescribed antiretroviral therapy in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) from 1997 through 2016. Methods: We estimated breast cancer hazard (cause-specific hazard ratios) and cumulative incidence accounting for competing risks (subdistribution hazard ratios) to assess changes in breast cancer risk over time. This was assessed overall (1997-2016) and within/across calendar periods. Analyses were adjusted for race/ethnicity and inverse probability weighted for cohort. Cumulative incidence was graphically assessed by calendar period and race/ethnicity. Results: We observed 11,587 women during 1997-2016, contributing 63 incident breast cancer diagnoses and 1,353 deaths [73,445 person-years (median followup = 4.5 years)]. Breast cancer cumulative incidence was 3.2% for 1997-2016. We observed no secular trends in breast cancer hazard or cumulative incidence. There were annual declines in the hazard and cumulative incidence of death (cause-specific hazard ratios and subdistribution hazard ratios: 0.89, 95% confidence interval: 0.87 to 0.91) which remained within and across calendar periods. Conclusions: These findings contradict the hypothesis of increasing breast cancer risk with declining mortality over time among women with HIV, suggesting limited impact of changing mortality on breast cancer risk. Additional inquiry is merited as survival improves among women with HIV
Associations between drug and alcohol use, smoking, and frailty among people with HIV across the United States in the current era of antiretroviral treatment
Objective: To examine associations between frailty and drug, alcohol, and tobacco use among a large diverse cohort of people with HIV (PWH) in clinical care in the current era. Methods: PWH at 7 sites across the United States completed clinical assessments of patient-reported measures and outcomes between 2016 and 2019 as part of routine care including drug and alcohol use, smoking, and other domains. Frailty was assessed using 4 of the 5 components of the Fried frailty phenotype and PWH were categorized as not frail, pre-frail, or frail. Associations of substance use with frailty were assessed with multivariate Poisson regression. Results: Among 9336 PWH, 43% were not frail, 44% were prefrail, and 13% were frail. Frailty was more prevalent among women, older PWH, and those reporting current use of drugs or cigarettes. Current methamphetamine use (1.26: 95% CI 1.07–1.48), current (1.65: 95% CI 1.39–1.97) and former (1.21:95% CI 1.06–1.36) illicit opioid use, and former cocaine/crack use (1.17: 95% CI 1.01–1.35) were associated with greater risk of being frail in adjusted analyses. Current smoking was associated with a 61% higher risk of being frail vs. not frail (1.61: 95% CI 1.41–1.85) in adjusted analyses. Conclusions: We found a high prevalence of prefrailty and frailty among a nationally distributed cohort of PWH in care. This study identified distinct risk factors that may be associated with frailty among PWH, many of which, such as cigarette smoking and drug use, are potentially modifiable
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