1,861 research outputs found
Hybrid Curvatons from Broken Symmetry
We present a new general mechanism for generating curvature perturbations
after inflation. Our model is based on the simple assumption that a field that
starts to oscillate after inflation has a potential characterized by an
underlying global symmetry that is slightly or badly broken. Inhomogeneous
preheating occurs due to the oscillation with the broken symmetry. Unlike the
traditional curvaton model, we will not identify the curvaton with the
oscillating field. The curvaton is identified with the preheat field that could
be either a scalar, vector, or fermionic field. We introduce an explicit mass
term for the curvaton, which is important for later evolution and the decay.
Our present model represents the simplest example of the hybrid of the
curvatons and inhomogeneous preheating.Comment: 21pages, 5 figures, accepted for publication in JHE
Klf6 protects β-cells against insulin resistance-induced dedifferentiation.
In the pathogenesis of type 2 diabetes, development of insulin resistance triggers an increase in pancreatic β-cell insulin secretion capacity and β-cell number. Failure of this compensatory mechanism is caused by a dedifferentiation of β-cells, which leads to insufficient insulin secretion and diabetic hyperglycemia. The β-cell factors that normally protect against dedifferentiation remain poorly defined. Here, through a systems biology approach, we identify the transcription factor Klf6 as a regulator of β-cell adaptation to metabolic stress.
We used a β-cell specific Klf6 knockout mouse model to investigate whether Klf6 may be a potential regulator of β-cell adaptation to a metabolic stress.
We show that inactivation of Klf6 in β-cells blunts their proliferation induced by the insulin resistance of pregnancy, high-fat high-sucrose feeding, and insulin receptor antagonism. Transcriptomic analysis showed that Klf6 controls the expression of β-cell proliferation genes and, in the presence of insulin resistance, it prevents the down-expression of genes controlling mature β-cell identity and the induction of disallowed genes that impair insulin secretion. Its expression also limits the transdifferentiation of β-cells into α-cells.
Our study identifies a new transcription factor that protects β-cells against dedifferentiation, and which may be targeted to prevent diabetes development
A simple example of "Quantum Darwinism": Redundant information storage in many-spin environments
As quantum information science approaches the goal of constructing quantum
computers, understanding loss of information through decoherence becomes
increasingly important. The information about a system that can be obtained
from its environment can facilitate quantum control and error correction.
Moreover, observers gain most of their information indirectly, by monitoring
(primarily photon) environments of the "objects of interest." Exactly how this
information is inscribed in the environment is essential for the emergence of
"the classical" from the quantum substrate. In this paper, we examine how
many-qubit (or many-spin) environments can store information about a single
system. The information lost to the environment can be stored redundantly, or
it can be encoded in entangled modes of the environment. We go on to show that
randomly chosen states of the environment almost always encode the information
so that an observer must capture a majority of the environment to deduce the
system's state. Conversely, in the states produced by a typical decoherence
process, information about a particular observable of the system is stored
redundantly. This selective proliferation of "the fittest information" (known
as Quantum Darwinism) plays a key role in choosing the preferred, effectively
classical observables of macroscopic systems. The developing appreciation that
the environment functions not just as a garbage dump, but as a communication
channel, is extending our understanding of the environment's role in the
quantum-classical transition beyond the traditional paradigm of decoherence.Comment: 21 pages, 6 figures, RevTex 4. Submitted to Foundations of Physics
(Asher Peres Festschrift
Electrical properties of bismuth ferrites:Bi2Fe4O9 and Bi25FeO39
Bi2Fe4O9 was prepared by solid-state reaction and the electrical properties measured by impedance spectroscopy. After annealing in O2 at 900 °C, Bi2Fe4O9 is an electrically-homogeneous insulator. Its high frequency permittivity is constant (∼14.1) over the temperature range 300–400 °C and shows no evidence of incipient ferroelectricity at lower temperatures. On annealing in N2 at 900 °C, the pellets gradually decompose.
Bi25FeO39 was prepared by both solid-state reaction and mechanosynthesis. It showed a modest amount of mixed conduction of both oxide ions and holes. Impedance analysis showed a complex response that best fitted an equivalent circuit consisting of a parallel combination of long-range conduction and short range dielectric relaxation elements.
The electrical conductivity of both Bi2Fe4O9 and Bi25FeO39 is less than that of BiFeO3 prepared by solid-state reaction, which indicates that any leakage conductivity of BiFeO3 is not due to the possible presence of small amounts of these secondary phases
Seroprevalence of Antibodies against Seal Influenza A(H10N7) Virus in Harbor Seals and Gray Seals from the Netherlands
In the spring and summer 2014, an outbreak of seal influenza A(H10N7) virus infection occurred among harbor seals (Phoca vitulina) off the coasts of Sweden and Denmark. This virus subsequently spread to harbor seals off the coasts of Germany and the Netherlands. While thousands of seals were reported dead in Sweden, Denmark and Germany, only a limited number of seals were found dead in the Netherlands. To determine the extent of exposure of seals in the Netherlands to influenza A/H10N7 virus, we measured specific antibody titers in serum samples from live-captured seals and seals admitted for rehabilitation in the Netherlands by use of a hemagglutination inhibition assay and an ELISA. In harbor seals in 2015, antibodies against seal influenza A(H10N7) virus were detected in 41% (32 out of 78) pups, 10% (5 out of 52) weaners, and 58% (7 out of 12) subadults or adults. In gray seals (Halichoerus grypus) in 2015, specific antibodies were not found i
Application of Bayesian statistics to estimate nitrous oxide emission factors of the nitrogen fertilisers in UK grasslands
Trapezoidal integration by linear interpolation of data points is by far the most commonly used method of
cumulative flux calculations of nitrous oxide (N2O) in studies that use flux chambers; however, this method is
incapable of providing accurate uncertainty estimates. A Bayesian approach was used to calculate N2O emission
factors (EFs) and their associated uncertainties from flux chamber measurements made after the application of
nitrogen fertilisers, in the form of ammonium nitrate (AN), urea (Ur) and urea treated with Agrotain® urease
inhibitor (UI) at four grassland sites in the UK. The comparison between the cumulative fluxes estimated using
the Bayesian and linear interpolation methods were broadly similar (R2=0.79); however, the Bayesian method
was capable of providing realistic uncertainties when a limited number of data points is available. The study
reports mean EF values (and 95% confidence intervals) of 0.60 ± 0.63, 0.29 ± 0.22 and 0.26 ± 0.17% of
applied N emitted as N2O for the AN, Ur and UI treatments, respectively. There was no significant difference
between N2O emissions from the Ur and UI treatments. In the case of the automatic chamber data collected at
one site in this study, the data did not fit the log-normal model, implying that more complex models may be
needed, particularly for measurement data with high temporal resolutioninfo:eu-repo/semantics/publishedVersio
Nucleation of Al3Zr and Al3Sc in aluminum alloys: from kinetic Monte Carlo simulations to classical theory
Zr and Sc precipitate in aluminum alloys to form the compounds Al3Zr and
Al3Sc which for low supersaturations of the solid solution have the L12
structure. The aim of the present study is to model at an atomic scale this
kinetics of precipitation and to build a mesoscopic model based on classical
nucleation theory so as to extend the field of supersaturations and annealing
times that can be simulated. We use some ab-initio calculations and
experimental data to fit an Ising model describing thermodynamics of the Al-Zr
and Al-Sc systems. Kinetic behavior is described by means of an atom-vacancy
exchange mechanism. This allows us to simulate with a kinetic Monte Carlo
algorithm kinetics of precipitation of Al3Zr and Al3Sc. These kinetics are then
used to test the classical nucleation theory. In this purpose, we deduce from
our atomic model an isotropic interface free energy which is consistent with
the one deduced from experimental kinetics and a nucleation free energy. We
test di erent mean-field approximations (Bragg-Williams approximation as well
as Cluster Variation Method) for these parameters. The classical nucleation
theory is coherent with the kinetic Monte Carlo simulations only when CVM is
used: it manages to reproduce the cluster size distribution in the metastable
solid solution and its evolution as well as the steady-state nucleation rate.
We also find that the capillary approximation used in the classical nucleation
theory works surprisingly well when compared to a direct calculation of the
free energy of formation for small L12 clusters.Comment: submitted to Physical Review B (2004
Deletion of the protein tyrosine phosphatase PTPN22 for adoptive T cell therapy facilitates CTL effector function but promotes T cell exhaustion
Background: Adoptive cell therapy (ACT) is a promising strategy for treating cancer, yet it faces several challenges such as lack of long-term protection due to T cell exhaustion induced by chronic TCR stimulation in the tumor microenvironment. One benefit of ACT, however, is that it allows for cellular manipulations, such as deletion of the phosphotyrosine phosphatase non-receptor type 22 (PTPN22), which improves CD8+ T cell antitumor efficacy in ACT. We tested whether Ptpn22KO cytolytic T cells (CTLs) were also more effective than Ptpn22WT CTL in controlling tumors in scenarios that favor T cell exhaustion.
Methods: Tumor control by Ptpn22WT and Ptpn22KO CTL was assessed following adoptive transfer of low numbers of CTL to mice with subcutaneously implanted MC38 tumors. Tumor infiltrating lymphocytes were isolated for analysis of effector functions. An in vitro assay was established to compare CTL function in response to acute and chronic restimulation with antigen-pulsed tumor cells. The expression of effector and exhaustion-associated proteins by Ptpn22WT and Ptpn22KO T cells was followed over time in vitro and in vivo using the ID8 tumor model. Finally, the effect of PD-1 and TIM-3 blockade on Ptpn22KO CTL tumor control was assessed using monoclonal antibodies and CRISPR/Cas9-mediated knockout.
Results: Despite having improved effector function at the time of transfer, Ptpn22KO CTL became more exhausted than Ptpn22WT CTL, characterized by more rapid loss of effector functions, and earlier and higher expression of inhibitory receptors (IRs), particularly the terminal exhaustion marker TIM-3. TIM-3 expression, under the control of the transcription factor NFIL3, was induced by IL-2 signaling which was enhanced in Ptpn22KO cells. Antitumor responses of Ptpn22KO CTL were improved following PD-1 blockade in vivo, yet knockout or antibody-mediated blockade of TIM-3 did not improve but further impaired tumor control, indicating TIM-3 signaling itself did not drive the diminished function seen in Ptpn22KO CTL.
Conclusions: This study questions whether TIM-3 plays a role as an IR and highlights that genetic manipulation of T cells for ACT needs to balance short-term augmented effector function against the risk of T cell exhaustion in order to achieve longer-term protection
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