74 research outputs found
The solute transport and binding profile of a novel nucleobase cation symporter 2 from the honeybee pathogen Paenibacillus larvae
Here, we report that a novel nucleobase cation symporter 2 encoded in the genome of the honeybee bacterial pathogen Paenibacillus larvae reveals high levels of amino acid sequence similarity to the Escherichia coli and Bacillus subtilis uric acid and xanthine transporters. This transporter is named P. larvae uric acid permease-like protein (PlUacP). Even though PlUacP displays overall amino acid sequence similarities, has common secondary structures, and shares functional motifs and functionally important amino acids with E. coli xanthine and uric acid transporters, these commonalities are insufficient to assign transport function to PlUacP. The solute transport and binding profile of PlUacP was determined by radiolabeled uptake experiments via heterologous expression in nucleobase transporter-deficient Saccharomyces cerevisiae strains. PlUacP transports the purines adenine and guanine and the pyrimidine uracil. Hypoxanthine, xanthine, and cytosine are not transported by PlUacP, but, along with uric acid, bind in a competitive manner. PlUacP has strong affinity for adenine Km 7.04 ± 0.18 Όm, and as with other bacterial and plant NCS2 proteins, PlUacP function is inhibited by the proton disruptor carbonyl cyanide m-chlorophenylhydrazone. The solute transport and binding profile identifies PlUacP as a novel nucleobase transporter
Propagating modes of non-Abelian tensor gauge field of second rank
In the recently proposed extension of the YM theory, non-Abelian tensor gauge
field of the second rank is represented by a general tensor whose symmetric
part describes the propagation of charged gauge boson of helicity two and its
antisymmetric part - the helicity zero charged gauge boson. On the
non-interacting level these polarizations are similar to the polarizations of
the graviton and of the Abelian antisymmetric B field, but the interaction of
these gauge bosons carrying non-commutative internal charges cannot be directly
identified with the interaction of gravitons or B field. Our intention here is
to illustrate this result from different perspectives which would include
Bianchi identity for the corresponding field strength tensor and the analysis
of the second-order partial differential equation which describes in this
theory the propagation of non-Abelian tensor gauge field of the second rank.Comment: 22 pages, Latex fil
Vetting of 384 TESS Objects of Interest with TRICERATOPS and Statistical Validation of 12 Planet Candidates
We present TRICERATOPS, a new Bayesian tool that can be used to vet and
validate TESS Objects of Interest (TOIs). We test the tool on 68 TOIs that have
been previously confirmed as planets or rejected as astrophysical false
positives. By looking in the false positive probability (FPP) -- nearby false
positive probability (NFPP) plane, we define criteria that TOIs must meet to be
classified as validated planets (FPP < 0.015 and NFPP < 10^-3), likely planets
(FPP 10^-1).
We apply this procedure on 384 unclassified TOIs and statistically validate 12,
classify 125 as likely planets, and classify 52 as likely nearby false
positives. Of the 12 statistically validated planets, 9 are newly validated.
TRICERATOPS is currently the only TESS vetting and validation tool that models
transits from nearby contaminant stars in addition to the target star. We
therefore encourage use of this tool to prioritize follow-up observations that
confirm bona fide planets and identify false positives originating from nearby
stars.Comment: Accepted to A
Initial Assessment, Surveillance, and Management of Blood Pressure in Patients Receiving Vascular Endothelial Growth Factor Signaling Pathway Inhibitors
Hypertension is a mechanism-based toxic effect of drugs that inhibit the vascular endothelial growth factor signaling pathway (VSP). Substantial evidence exists for managing hypertension as a chronic condition, but there are few prospectively collected data on managing acute hypertension caused by VSP inhibitors. The Investigational Drug Steering Committee of the National Cancer Institute convened an interdisciplinary cardiovascular toxicities expert panel to evaluate this problem, to make recommendations to the Cancer Therapy Evaluation Program on further study, and to structure an approach for safe management by treating physicians. The panel reviewed: the published literature on blood pressure (BP), hypertension, and specific VSP inhibitors; abstracts from major meetings; shared experience with the development of VSP inhibitors; and established principles of hypertension care. The panel generated a consensus report including the recommendations on clinical concerns summarized here. To support the greatest possible number of patients to receive VSP inhibitors safely and effectively, the panel had four recommendations: 1) conduct and document a formal risk assessment for potential cardiovascular complications, 2) recognize that preexisting hypertension will be common in cancer patients and should be identified and addressed before initiation of VSP inhibitor therapy, 3) actively monitor BP throughout treatment with more frequent assessments during the first cycle of treatment, and 4) manage BP with a goal of less than 140/90 mmHg for most patients (and to lower, prespecified goals in patients with specific preexisting cardiovascular risk factors). Proper agent selection, dosing, and scheduling of follow-up should enable maintaining VSP inhibition while avoiding the complications associated with excessive or prolonged elevation in BP
The TESS Grand Unified Hot Jupiter Survey. II. Twenty New Giant Planets
NASA's Transiting Exoplanet Survey Satellite (TESS) mission promises to
improve our understanding of hot Jupiters by providing an all-sky,
magnitude-limited sample of transiting hot Jupiters suitable for population
studies. Assembling such a sample requires confirming hundreds of planet
candidates with additional follow-up observations. Here, we present twenty hot
Jupiters that were detected using TESS data and confirmed to be planets through
photometric, spectroscopic, and imaging observations coordinated by the TESS
Follow-up Observing Program (TFOP). These twenty planets have orbital periods
shorter than 7 days and orbit relatively bright FGK stars ().
Most of the planets are comparable in mass to Jupiter, although there are four
planets with masses less than that of Saturn. TOI-3976 b, the longest period
planet in our sample ( days), may be on a moderately eccentric orbit
(), while observations of the other targets are consistent
with them being on circular orbits. We measured the projected stellar obliquity
of TOI-1937A b, a hot Jupiter on a 22.4 hour orbit with the Rossiter-McLaughlin
effect, finding the planet's orbit to be well-aligned with the stellar spin
axis (). We also investigated the possibility that
TOI-1937 is a member of the NGC 2516 open cluster, but ultimately found the
evidence for cluster membership to be ambiguous. These objects are part of a
larger effort to build a complete sample of hot Jupiters to be used for future
demographic and detailed characterization work.Comment: 67 pages, 11 tables, 13 figures, 2 figure sets. Resubmitted to ApJS
after revision
Measuring proliferation in breast cancer: practicalities and applications
Various methods are available for the measurement of proliferation rates in tumours, including mitotic counts, estimation of the fraction of cells in S-phase of the cell cycle and immunohistochemistry of proliferation-associated antigens. The evidence, advantages and disadvantages for each of these methods along with other novel approaches is reviewed in relation to breast cancer. The potential clinical applications of proliferative indices are discussed, including their use as prognostic indicators and predictors of response to systemic therapy
Another Shipment of Six Short-Period Giant Planets from TESS
We present the discovery and characterization of six short-period, transiting
giant planets from NASA's Transiting Exoplanet Survey Satellite (TESS) --
TOI-1811 (TIC 376524552), TOI-2025 (TIC 394050135), TOI-2145 (TIC 88992642),
TOI-2152 (TIC 395393265), TOI-2154 (TIC 428787891), & TOI-2497 (TIC 97568467).
All six planets orbit bright host stars (8.9 <G< 11.8, 7.7 <K< 10.1). Using a
combination of time-series photometric and spectroscopic follow-up observations
from the TESS Follow-up Observing Program (TFOP) Working Group, we have
determined that the planets are Jovian-sized (R = 1.00-1.45 R),
have masses ranging from 0.92 to 5.35 M, and orbit F, G, and K stars
(4753 T 7360 K). We detect a significant orbital eccentricity
for the three longest-period systems in our sample: TOI-2025 b (P = 8.872 days,
= ), TOI-2145 b (P = 10.261 days, =
), and TOI-2497 b (P = 10.656 days, =
). TOI-2145 b and TOI-2497 b both orbit subgiant host
stars (3.8 g 4.0), but these planets show no sign of inflation
despite very high levels of irradiation. The lack of inflation may be explained
by the high mass of the planets; M (TOI-2145
b) and M (TOI-2497 b). These six new discoveries
contribute to the larger community effort to use {\it TESS} to create a
magnitude-complete, self-consistent sample of giant planets with
well-determined parameters for future detailed studies.Comment: 20 Pages, 6 Figures, 8 Tables, Accepted by MNRA
Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic
This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic
Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study
Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update ofâand expansion onâthe 2014 analysis, which reported 80 million (95% CI 64â103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11â342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8â1·1) in 2015, corresponding to 71·1 million (62·5â79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe
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