99 research outputs found
Prospects for asteroseismology
The observational basis for asteroseismology is being dramatically
strengthened, through more than two years of data from the CoRoT satellite, the
flood of data coming from the Kepler mission and, in the slightly longer term,
from dedicated ground-based facilities. Our ability to utilize these data
depends on further development of techniques for basic data analysis, as well
as on an improved understanding of the relation between the observed
frequencies and the underlying properties of the stars. Also, stellar modelling
must be further developed, to match the increasing diagnostic potential of the
data. Here we discuss some aspects of data interpretation and modelling,
focussing on the important case of stars with solar-like oscillations.Comment: Proc. HELAS Workshop on 'Synergies between solar and stellar
modelling', eds M. Marconi, D. Cardini & M. P. Di Mauro, Astrophys. Space
Sci., in the press Revision: correcting abscissa labels on Figs 1 and
Limits on the gravity wave contribution to microwave anisotropies
We present limits on the fraction of large angle microwave anisotropies which
could come from tensor perturbations. We use the COBE results as well as
smaller scale CMB observations, measurements of galaxy correlations, abundances
of galaxy clusters, and Lyman alpha absorption cloud statistics. Our aim is to
provide conservative limits on the tensor-to-scalar ratio for standard
inflationary models. For power-law inflation, for example, we find T/S<0.52 at
95% confidence, with a similar constraint for phi^p potentials. However, for
models with tensor amplitude unrelated to the scalar spectral index it is still
currently possible to have T/S>1.Comment: 23 pages, 7 figures, accepted for publication in Phys. Rev. D.
Calculations extended to blue spectral index, Fig. 6 added, discussion of
results expande
Arrhythmogenic mechanisms in the isolated perfused hypokalaemic murine heart
AIM: Hypokalaemia is associated with a lethal form of ventricular tachycardia (VT), torsade de pointes, through pathophysiological mechanisms requiring clarification. METHODS: Left ventricular endocardial and epicardial monophasic action potentials were compared in isolated mouse hearts paced from the right ventricular epicardium perfused with hypokalaemic (3 and 4 mm [K(+)](o)) solutions. Corresponding K(+) currents were compared in whole-cell patch-clamped epicardial and endocardial myocytes. RESULTS: Hypokalaemia prolonged epicardial action potential durations (APD) from mean APD(90)s of 37.2 ± 1.7 ms (n = 7) to 58.4 ± 4.1 ms (n =7) and 66.7 ± 2.1 ms (n = 11) at 5.2, 4 and 3 mm [K(+)](o) respectively. Endocardial APD(90)s correspondingly increased from 51.6 ± 1.9 ms (n = 7) to 62.8 ± 2.8 ms (n = 7) and 62.9 ± 5.9 ms (n = 11) giving reductions in endocardial–epicardial differences, ΔAPD(90), from 14.4 ± 2.6 to 4.4 ± 5.0 and −3.4 ± 6.0 ms respectively. Early afterdepolarizations (EADs) occurred in epicardia in three of seven spontaneously beating hearts at 4 mm [K(+)](o) with triggered beats followed by episodes of non-sustained VT in nine of 11 preparations at 3 mm. Programmed electrical stimulation never induced arrhythmic events in preparations perfused with normokalemic solutions yet induced VT in two of seven and nine of 11 preparations at 4 and 3 mm [K(+)](o) respectively. Early outward K(+) current correspondingly fell from 73.46 ± 8.45 to 61.16±6.14 pA/pF in isolated epicardial but not endocardial myocytes (n = 9) (3 mm [K(+)](o)). CONCLUSIONS: Hypokalaemic mouse hearts recapitulate the clinical arrhythmogenic phenotype, demonstrating EADs and triggered beats that might initiate VT on the one hand and reduced transmural dispersion of repolarization reflected in ΔAPD(90) suggesting arrhythmogenic substrate on the other
Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy
We review HB stars in a broad astrophysical context, including both variable
and non-variable stars. A reassessment of the Oosterhoff dichotomy is
presented, which provides unprecedented detail regarding its origin and
systematics. We show that the Oosterhoff dichotomy and the distribution of
globular clusters (GCs) in the HB morphology-metallicity plane both exclude,
with high statistical significance, the possibility that the Galactic halo may
have formed from the accretion of dwarf galaxies resembling present-day Milky
Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the
second-parameter problem is presented. A technique is proposed to estimate the
HB types of extragalactic GCs on the basis of integrated far-UV photometry. The
relationship between the absolute V magnitude of the HB at the RR Lyrae level
and metallicity, as obtained on the basis of trigonometric parallax
measurements for the star RR Lyrae, is also revisited, giving a distance
modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are
studied. Finally, the conductive opacities used in evolutionary calculations of
low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and
Space Scienc
An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics
For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types
Adipose tissue concentrations of non-persistent environmental phenols and local redox balance in adults from Southern Spain
The aim was to evaluate the associations of environmental phenol and paraben concentrations with the oxidative
microenvironment in adipose tissue. This study was conducted in a subsample (n=144) of the GraMo cohort
(Southern Spain). Concentrations of 9 phenols and 7 parabens, and levels of oxidative stress biomarkers were
quantified in adipose tissue. Associations were estimated using multivariable linear regression analyses adjusted
for potential confounders.
Benzophenone-3 (BP-3) concentration was borderline associated with enhanced glutathione peroxidase (GPx)
activity [exp(β)=1.20, p=0.060] and decreased levels of reduced glutathione (GSH) [exp(β)=0.55,
p=0.070]. Concentrations of bisphenol A (BPA) and methylparaben (MeP) were associated to lower glutathione
reductase (GRd) activity [exp(β)=0.83, exp(β)=0.72, respectively], and BPA was borderline associated
to increased levels of oxidized glutathione (GSSG) [exp(β)=1.73, p-value=0.062]. MeP was inversely
associated to both hemeoxygenase-1 (HO-1) and superoxide dismustase (SOD) activity, as well as to the levels of
thiobarbituric acid reactive substances (TBARS) [0.75 < exp(β) < 0.79].
Our results suggest that some specific non-persistent pollutants may be associated with a disruption of the
activity of relevant antioxidant enzymes, in addition to the depletion of the glutathione stock. They might act as
a tissue-specific source of free radicals, contributing to the oxidative microenvironment in the adipose tissue.This research was supported
in part by research grants from the European Union Commission
(H2020-EJP-HBM4EU and SOE1/P1/F0082), Biomedical Research
Networking Center-CIBER de Epidemiología y Salud Pública
(CIBERESP), from the Institute of Health Carlos III, supported by
European Regional Development Fund/FEDER (FIS-PI13/02406, FISPI14/
00067, FIS-PI16/01820, FIS-PI16/01812, FIS-PI16/01858 and
FIS-PI17/01743), and from the Consejería de Salud, Junta de Andalucía
(PS-0506-2016). Funding for the equipment used was provided by
Velux Fonden, Augustinus Fonden and Svend Andersen Fonden. The
authors thank Kirsten og Freddy Johansens Fond and the International
Centre for Research and Research Training in Endocrine Disruption of
Male Reproduction and Child Health (EDMaRC, Rigshospitalet,
Copenhagen University) for economic support. Dr. Juan Pedro Arrebola
is under contract within Ramón y Cajal Program (Ministerio de
Economía, Industria y Competitividad de España, RYC-2016-20155)
Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.
Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy
Remoção de fármacos e desreguladores endócrinos em estações de tratamento de esgoto: revisão da literatura
Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics
The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrate our insights into cancer through synthesis of the findings of the TCGA PanCancer Atlas project on three facets of oncogenesis: (1) somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; (2) the influence of the tumor genome and epigenome on transcriptome and proteome; and (3) the relationship between tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies. These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing
Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer
We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, and miRNA expression levels and reverse-phase protein arrays, of which all, except for aneuploidy, revealed clustering primarily organized by histology, tissue type, or anatomic origin. The influence of cell type was evident in DNA-methylation-based clustering, even after excluding sites with known preexisting tissue-type-specific methylation. Integrative clustering further emphasized the dominant role of cell-of-origin patterns. Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which in turn may inform strategies for future therapeutic development. Comprehensive, integrated molecular analysis identifies molecular relationships across a large diverse set of human cancers, suggesting future directions for exploring clinical actionability in cancer treatment
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