2,531 research outputs found
Did Very Massive Stars Pre-enrich and Reionize the Universe?
Recent studies of heavy r-process elements in low [Fe/H] halo stars have
suggested that an initial population of metal-free very massive stars (VMSs)
may be required to provide early Fe enrichment without coproducing heavy r
nuclei. We find similar abundance trends in alpha-elements (which should be
copiously produced by VMSs), but not in other elements such as carbon (which
should not), in agreement with this hypothesis. We then combine the
corresponding level of prompt initial enrichment with models of VMS
nucleosynthetic yields and spectra to estimate the corresponding ionizing
fluxes. The result suggests that there may have been enough VMS activity to
reionize the universe. The unusually hard spectrum of VMSs would imply a
different reionization history from canonical models. HeII could have been
reionized at high redshift, only to recombine as a subsequent generation of
stars formed with a ``normal'' initial mass function.Comment: 4 pages, to appear in ApJ Letter
Mediators of the effects of canagliflozin on kidney protection in patients with type 2 diabetes
Canagliflozin reduced kidney disease progression in participants with type 2 diabetes in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program that explored potential mediators of the effects of canagliflozin on kidney outcomes. The percent mediating effect of 18 biomarkers indicative of disease was determined by comparing the hazard ratios for the effect of randomized treatment from an unadjusted model and from a model adjusting for the average post-randomization level of each biomarker. Multivariable analyses assessed the joint effects of biomarkers that mediated most strongly in univariable analyses. The kidney outcome was defined as a composite of 40% estimated glomerular filtration rate decline, end-stage kidney disease, or death due to kidney disease. Nine biomarkers (systolic blood pressure [8.9% of effect explained], urinary albumin:creatinine ratio [UACR; 23.9%], gamma glutamyltransferase [4.1%], hematocrit [51.1%], hemoglobin [41.3%], serum albumin [19.5%], erythrocytes [56.7%], serum urate [35.4%], and urine pH [7.5%]) individually mediated the effect of canagliflozin on the kidney outcome. In a parsimonious multivariable model, erythrocyte concentration, serum urate, and systolic blood pressure maximized cumulative mediation (115%). Mediating effects of UACR, but not other mediators, were highly dependent upon the baseline level of UACR: UACR mediated 42% and 7% of the effect in those with baseline UACR 30 mg/g or more and under 30 mg/g, respectively. The identified mediators support existing hypothesized mechanisms for the prevention of kidney outcomes with sodium glucose co-transporter 2 inhibitors. Thus, the disparity in mediating effects across baseline UACR subgroups suggests that the mechanism for kidney protection with canagliflozin may vary across patient subgroups
Evolutionary Status of Dwarf ``Transition'' Galaxies
We present deep B, R and Halpha imaging of 3 dwarf galaxies: NGC3377A,
NGC4286, and IC3475. Based on previous broadband imaging and HI studies, these
mixed-morphology galaxies were proposed by Sandage & Hoffman (1991) to be,
respectively, a gas-rich low surface brightness Im dwarf, a nucleated dwarf
that has lost most of its gas and is in transition from Im to dS0,N, and the
prototypical example of a gas-poor ``huge low surface brightness'' early-type
galaxy. From the combination of our broadband and Halpha imaging with the
published information on the neutral gas content of these three galaxies, we
find that (1) NGC3377A is a dwarf spiral; (2) NGC3377A and NGC4286 have
comparable amounts of ongoing star formation, as indicated by their Halpha
emission, while IC3475 has no detected HII regions to a very low limit; (3) the
global star formation rates are at least a factor of 20 below that of 30
Doradus for NGC3377A and NGC4286; (4) while the amount of star formation is
comparable, the distribution of star forming regions is very different between
NGC3377A and NGC4286; (5) given their current star formation rates and gas
contents, both NGC3377A and NGC4286 can continue to form stars for more than a
Hubble time; (6) both NGC3377A and NGC4286 have integrated total B-R colors
that are redder than the integrated total B-R color for IC3475, and thus it is
unlikely that either galaxy will ever evolve into an IC3475 counterpart; and
(7) IC3475 is too blue to be a dE. We thus conclude that we have not identified
potential precursors to galaxies such as IC3475, and unless signifcant changes
occur in the star formation rates, neither NGC3377A nor NGC4286 will evolve
into a dwarf elliptical or dwarf spheroidal within a Hubble time.Comment: 34 pages, 6 jpg figures, 3 postscript figures, and 4 tables, uses
AASTeX, ApJ, in pres
Impact of proteoglycan‐4 and parathyroid hormone on articular cartilage
Proteoglycan‐4 ( Prg4 ) protects synovial joints from arthropathic changes by mechanisms that are incompletely understood. Parathyroid hormone (PTH), known for its anabolic actions in bone, increases Prg4 expression and has been reported to inhibit articular cartilage degeneration in arthropathic joints. To investigate the effect of Prg4 and PTH on articular cartilage, 16‐week‐old Prg4 mutant and wild‐type mice were treated with intermittent PTH (1–34) or vehicle control daily for six weeks. Analyses included histology of the knee joint, micro‐CT of the distal femur, and serum biochemical analysis of type II collagen fragments (CTX‐II). Compared to wild‐type littermates, Prg4 mutant mice had an acellular layer of material lining the surfaces of the articular cartilage and menisci, increased articular cartilage degradation, increased serum CTX‐II concentrations, decreased articular chondrocyte apoptosis, increased synovium SDF‐1 expression, and irregularly contoured subchondral bone. PTH‐treated Prg4 mutant mice developed a secondary deposit overlaying the acellular layer of material lining the joint surfaces, but PTH‐treatment did not alter signs of articular cartilage degeneration in Prg4 mutant mice. The increased joint SDF‐1 levels and irregular subchondral bone found in Prg4 mutant mice introduce novel candidate mechanisms by which Prg4 protects articular cartilage. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 183–190, 2013Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94686/1/22207_ftp.pd
Aberrant Crosstalk between Insulin Signaling and mTOR in Young Down Syndrome Individuals Revealed by Neuronal-Derived Extracellular Vesicles
INTRODUCTION: Intellectual disability, accelerated aging, and early-onset Alzheimer-like neurodegeneration are key brain pathological features of Down syndrome (DS). Although growing research aims at the identification of molecular pathways underlying the aging trajectory of DS population, data on infants and adolescents with DS are missing.
METHODS: Neuronal-derived extracellular vesicles (nEVs) were isolated form healthy donors (HDs, n = 17) and DS children (n = 18) from 2 to 17 years of age and nEV content was interrogated for markers of insulin/mTOR pathways.
RESULTS: nEVs isolated from DS children were characterized by a significant increase in pIRS1Ser636, a marker of insulin resistance, and the hyperactivation of the Akt/mTOR/p70S6K axis downstream from IRS1, likely driven by the higher inhibition of Phosphatase and tensin homolog (PTEN). High levels of pGSK3βSer9 were also found.
CONCLUSIONS: The alteration of the insulin-signaling/mTOR pathways represents an early event in DS brain and likely contributes to the cerebral dysfunction and intellectual disability observed in this unique population
Effects of Canagliflozin in Patients with Baseline eGFR:Subgroup Analysis of the Randomized CREDENCE Trial
BACKGROUND AND OBJECTIVES: The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial demonstrated that the sodium glucose cotransporter 2 (SGLT2) inhibitor canagliflozin reduced the risk of kidney failure and cardiovascular events in participants with type 2 diabetes mellitus and CKD. Little is known about the use of SGLT2 inhibitors in patients with eGFR 300-5000 mg/g, and an eGFR of 30 to 0.20). The estimate for kidney failure in participants with eGFR 0.12). CONCLUSIONS: This post hoc analysis suggests canagliflozin slowed progression of kidney disease, without increasing AKI, even in participants with eGFR <30 ml/min per 1.73 m2
Zyxin Links Fat Signaling to the Hippo Pathway
Using genetic and molecular analyses, the authors identify Zyx as a positive regulator of Hippo signaling and characterize its role within the pathway
Colour reconnection in e+e- -> W+W- at sqrt(s) = 189 - 209 GeV
The effects of the final state interaction phenomenon known as colour
reconnection are investigated at centre-of-mass energies in the range sqrt(s) ~
189-209 GeV using the OPAL detector at LEP. Colour reconnection is expected to
affect observables based on charged particles in hadronic decays of W+W-.
Measurements of inclusive charged particle multiplicities, and of their angular
distribution with respect to the four jet axes of the events, are used to test
models of colour reconnection. The data are found to exclude extreme scenarios
of the Sjostrand-Khoze Type I (SK-I) model and are compatible with other
models, both with and without colour reconnection effects. In the context of
the SK-I model, the best agreement with data is obtained for a reconnection
probability of 37%. Assuming no colour reconnection, the charged particle
multiplicity in hadronically decaying W bosons is measured to be (nqqch) =
19.38+-0.05(stat.)+-0.08 (syst.).Comment: 30 pages, 9 figures, Submitted to Euro. Phys. J.
Search for the Standard Model Higgs Boson with the OPAL Detector at LEP
This paper summarises the search for the Standard Model Higgs boson in e+e-
collisions at centre-of-mass energies up to 209 GeV performed by the OPAL
Collaboration at LEP. The consistency of the data with the background
hypothesis and various Higgs boson mass hypotheses is examined. No indication
of a signal is found in the data and a lower bound of 112.7GeV/C^2 is obtained
on the mass of the Standard Model Higgs boson at the 95% CL.Comment: 51 pages, 21 figure
Search for R-Parity Violating Decays of Scalar Fermions at LEP
A search for pair-produced scalar fermions under the assumption that R-parity
is not conserved has been performed using data collected with the OPAL detector
at LEP. The data samples analysed correspond to an integrated luminosity of
about 610 pb-1 collected at centre-of-mass energies of sqrt(s) 189-209 GeV. An
important consequence of R-parity violation is that the lightest supersymmetric
particle is expected to be unstable. Searches of R-parity violating decays of
charged sleptons, sneutrinos and squarks have been performed under the
assumptions that the lightest supersymmetric particle decays promptly and that
only one of the R-parity violating couplings is dominant for each of the decay
modes considered. Such processes would yield final states consisting of
leptons, jets, or both with or without missing energy. No significant
single-like excess of events has been observed with respect to the Standard
Model expectations. Limits on the production cross- section of scalar fermions
in R-parity violating scenarios are obtained. Constraints on the supersymmetric
particle masses are also presented in an R-parity violating framework analogous
to the Constrained Minimal Supersymmetric Standard Model.Comment: 51 pages, 24 figures, Submitted to Eur. Phys. J.
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