465 research outputs found
Effect of Soil Chemistry on Microbial Biodiversity and Functionality in Grassland and Tilled Soils
Microorganisms are excellent indicators of soil health, because of their rapid response to environmental change. Traditional microbiology is ineffective for the study of soil, as \u3c 1% of microorganisms are currently culturable (Torsvik et al., 1996). Nucleic acid based methods, however, allow rapid detection of organisms, or particular genes, directly from soil samples. This work investigated, using polymerase chain reaction (PCR)-based approaches, the relationship between key chemical properties and bacterial biodiversity in grassland and tilled soils, with particular emphasis on the abundance and diversity of ammonium oxidisers
NCI-MATCH Arms N & P: Phase II study of PI3K beta inhibitor GSK2636771 in patients (pts) with cancers (ca) with PTEN mutation/deletion (mut/del) or PTEN protein loss
Background: The NCI-MATCH trial is the largest national study (1173 sites) for ptswith relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns tar-geted therapies based on individual tumor molecular alterations detected using theadapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC).We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and Pmay benefit from treatment with the PI3K beta-selective inhibitor GSK2636771.
Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PSâ
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1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete loss of cytoplasmic and nuclear PTEN staining on IHC (Arm P), and no other aberrations activating the PI3K/MTOR and MAPK pathways (mut in PIK3CA, PIK3R1, BRAF, KRAS, AKT1, TSC1/2, mTOR, RHEB, NF2, NRAS, HRAS). Pts received GSK2636771 400mg/day (28-days cycles). RECIST 1.1 overall response rate (ORR) was the primary endpoint.
Results: Of 59 enrolled pts, 56 were eligible and received treatment. Of 22 pts with PTEN mut/del (Arm N: 6 uterine, 2 breast, 2 prostate, 2 head/neck ca, 10 other), all are off treatment as of analysis (14 disease progression, 4 for adverse events [AEs], 4 other). One pt (4.5%) with prostate ca (PTEN deletion, MPRSS2-ERG fusion) attained a partial response (-42%). Of 7 (32%) pts with stable disease (SD), 2 had SDâ
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6 months (uterine leiomyosarcoma; endometrial carcinoma). Of 34 pts with loss of PTEN protein by IHC (Arm P: 7 prostate, 6 breast, 3 squamous anal ca, 2 cholangiocarcinoma, 16 other), all are off treatment as of analysis (26 disease progression, 4 for AE, 4 other). Of 9 (37.5%) pts with SD, 3 had SDâ
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6 months (prostate cancer; squamous bladder cancer, squamous anal cancer). Median progression-free survival was 1.8 months for both arms. Grâ
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3 treatment-related (tr) reversible toxicities were experienced by 30% (7) and 20% (7) of pts in arms N and P, respectively. No tr Gr 5 toxicities were observed in either arm.
Conclusions: Single agent GSK2636771 has very modest activity in ca with PTEN gene mutation/deletion and/or PTEN protein loss
Probing the centre of the large circumstellar disc in M17
We investigated the nature of the hitherto unresolved elliptical infrared
emission in the centre of the ~20000 AU disc silhouette in M 17. We combined
high-resolution JHKsL'M' band imaging carried out with NAOS/CONICA at the VLT
with [Fe II] narrow band imaging using SOFI at the NTT. The analysis is
supported by Spitzer/GLIMPSE archival data and by already published SINFONI/VLT
Integral Field Spectroscopy data. For the first time, we resolve the elongated
central infrared emission into a point-source and a jet-like feature that
extends to the northeast in the opposite direction of the recently discovered
collimated H2 jet. They are both orientated almost perpendicular to the disc
plane. In addition, our images reveal a curved southwestern emission nebula
whose morphology resembles that of the previously detected northeastern one.
Both nebulae are located at a distance of 1500 AU from the disc centre. We
describe the infrared point-source in terms of a protostar that is embedded in
circumstellar material producing a visual extinction of 60 <= Av <= 82. The
observed Ks band magnitude is equivalent to a stellar mass range of 2.8 Msun <=
Mstar <= 8 Msun adopting conversions for a main-sequence star. Altogether, we
suggest that the large M 17 accretion disc is forming an intermediate to
high-mass protostar. Part of the accreted material is expelled through a
symmetric bipolar jet/outflow.Comment: 6 pages, 3 figures, accepted by MNRAS (16 May 2008
Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials
Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatologyâa non-profit international organisation dedicated to consensus methodology in identification of outcome measuresâconducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field
Circumstellar discs: What will be next?
This prospective chapter gives our view on the evolution of the study of
circumstellar discs within the next 20 years from both observational and
theoretical sides. We first present the expected improvements in our knowledge
of protoplanetary discs as for their masses, sizes, chemistry, the presence of
planets as well as the evolutionary processes shaping these discs. We then
explore the older debris disc stage and explain what will be learnt concerning
their birth, the intrinsic links between these discs and planets, the hot dust
and the gas detected around main sequence stars as well as discs around white
dwarfs.Comment: invited review; comments welcome (32 pages
Young and Intermediate-age Distance Indicators
Distance measurements beyond geometrical and semi-geometrical methods, rely
mainly on standard candles. As the name suggests, these objects have known
luminosities by virtue of their intrinsic proprieties and play a major role in
our understanding of modern cosmology. The main caveats associated with
standard candles are their absolute calibration, contamination of the sample
from other sources and systematic uncertainties. The absolute calibration
mainly depends on their chemical composition and age. To understand the impact
of these effects on the distance scale, it is essential to develop methods
based on different sample of standard candles. Here we review the fundamental
properties of young and intermediate-age distance indicators such as Cepheids,
Mira variables and Red Clump stars and the recent developments in their
application as distance indicators.Comment: Review article, 63 pages (28 figures), Accepted for publication in
Space Science Reviews (Chapter 3 of a special collection resulting from the
May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space
Age
Active Brownian Particles. From Individual to Collective Stochastic Dynamics
We review theoretical models of individual motility as well as collective
dynamics and pattern formation of active particles. We focus on simple models
of active dynamics with a particular emphasis on nonlinear and stochastic
dynamics of such self-propelled entities in the framework of statistical
mechanics. Examples of such active units in complex physico-chemical and
biological systems are chemically powered nano-rods, localized patterns in
reaction-diffusion system, motile cells or macroscopic animals. Based on the
description of individual motion of point-like active particles by stochastic
differential equations, we discuss different velocity-dependent friction
functions, the impact of various types of fluctuations and calculate
characteristic observables such as stationary velocity distributions or
diffusion coefficients. Finally, we consider not only the free and confined
individual active dynamics but also different types of interaction between
active particles. The resulting collective dynamical behavior of large
assemblies and aggregates of active units is discussed and an overview over
some recent results on spatiotemporal pattern formation in such systems is
given.Comment: 161 pages, Review, Eur Phys J Special-Topics, accepte
Home-range use patterns and movements of the Siberian flying squirrel in urban forests: Effects of habitat composition and connectivity
Peer reviewe
ERK2 phosphorylation of serine 77 regulates Bmf pro-apoptotic activity
B-cell lymphoma 2 (Bcl-2) homology 3 (BH3)-only proteins represent a class of pro-apoptotic factors that neutralize pro-survival Bcl-2 proteins, and, in some cases, directly activate Bax. The mechanisms of control and the role of BH3-only proteins, such as Bcl-2 like protein 11 extra large and Bad are well studied. By contrast, relatively little is known about the regulation and role of Bcl-2 modifying factor (Bmf). The B-RAF oncogene is mutated in âŒ8% of human tumors. We have previously shown that Bmf is upregulated at the transcript level and is required for apoptosis induced by targeting B-RAF signaling in tumor cells harboring mutant B-RAF. In this study, we show that Bmf is regulated at the post-translational level by mutant B-RAF-MEK-ERK2 signaling. Extracellular signal-regulated kinase (ERK2) directly phosphorylates Bmf on serine 74 and serine 77 residues with serine 77 being the predominant site. In addition, serine 77 phosphorylation reduces Bmf pro-apoptotic activity likely through a mechanism independent of altering Bmf localization to the mitochondria and/or interactions with dynein light chain 2 and the pro-survival proteins, B-cell lymphoma extra large, Bcl-2 and Mcl-1. These data identify a novel mode of regulation in Bmf that modulates its pro-apoptotic activity in mutant B-RAF tumor cells
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