6,084 research outputs found
Cytoprotective Activated Protein C Averts Nlrp3 Inflammasome–Induced Ischemia-Reperfusion Injury Via Mtorc1 Inhibition
Cytoprotection by activated protein C (aPC) after ischemia-reperfusion injury (IRI) is associated with apoptosis inhibition. However, IRI is hallmarked by inflammation, and hence, cell-death forms disjunct from immunologically silent apoptosis are, in theory, more likely to be relevant. Because pyroptosis (ie, cell death resulting from inflammasome activation) is typically observed in IRI, we speculated that aPC ameliorates IRI by inhibiting inflammasome activation. Here we analyzed the impact of aPC on inflammasome activity in myocardial and renal IRIs. aPC treatment before or after myocardial IRI reduced infarct size and Nlrp3 inflammasome activation in mice. Kinetic in vivo analyses revealed that Nlrp3 inflammasome activation preceded myocardial injury and apoptosis, corroborating a pathogenic role of the Nlrp3 inflammasome. The constitutively active Nlrp3A350V mutation abolished the protective effect of aPC, demonstrating that Nlrp3 suppression is required for aPC-mediated protection from IRI. In vitro aPC inhibited inflammasome activation in macrophages, cardiomyocytes, and cardiac fibroblasts via proteinase-activated receptor 1 (PAR-1) and mammalian target of rapamycin complex 1 (mTORC1) signaling. Accordingly, inhibiting PAR-1 signaling, but not the anticoagulant properties of aPC, abolished the ability of aPC to restrict Nlrp3 inflammasome activity and tissue damage in myocardial IRI. Targeting biased PAR-1 signaling via parmodulin-2 restricted mTORC1 and Nlrp3 inflammasome activation and limited myocardial IRI as efficiently as aPC. The relevance of aPC-mediated Nlrp3 inflammasome suppression after IRI was corroborated in renal IRI, where the tissue protective effect of aPC was likewise dependent on Nlrp3 inflammasome suppression. These studies reveal that aPC protects from IRI by restricting mTORC1-dependent inflammasome activation and that mimicking biased aPC PAR-1 signaling using parmodulins may be a feasible therapeutic approach to combat IRI
Quantum tunneling from scalar fields in rotating black strings
Using the Hamilton-Jacobi method of quantum tunneling and complex path
integration, we study Hawking radiation of scalar particles from rotating black
strings. We discuss tunneling of both charged and uncharged scalar particles
from the event horizons. For this purpose, we use the Klein-Gordon equation and
find the tunneling probability of outging scalar particles. The procedure gives
Hawking temperature for rotating charged black strings as well.Comment: Corrections and change
Phenomenology of Light Sneutrino Dark Matter in cMSSM/mSUGRA with Inverse Seesaw
We study the possibility of a light Dark Matter (DM) within a constrained
Minimal Supersymmetric Standard Model (cMSSM) framework augmented by a SM
singlet-pair sector to account for the non-zero neutrino masses by inverse
seesaw mechanism. Working within a 'hybrid' scenario with the MSSM sector fixed
at high scale and the singlet neutrino sector at low scale, we find that,
contrary to the case of the usual cMSSM where the neutralino DM cannot be very
light, we can have a light sneutrino DM with mass below 100 GeV satisfying all
the current experimental constraints from cosmology, collider as well as
low-energy experiments. We also note that the supersymmetric inverse seesaw
mechanism with sneutrino as the lightest supersymmetric partner can have
enhanced same-sign dilepton final states with large missing transverse energy
(mET) coming from the gluino- and squark-pair as well as the squark-gluino
associated productions and their cascade decay through charginos. We present a
collider study for the same-sign dilepton+jets+mET signal in this scenario and
propose some distinctions with the usual cMSSM. We also comment on the
implications of such a light DM scenario on the invisible decay width of an 125
GeV Higgs boson.Comment: 24 pages, 4 figures, 7 tables; matches published versio
Practical computational toolkits for dendrimers and dendrons structure design
Dendrimers and dendrons offer an excellent platform for developing novel drug delivery systems and medicines. The rational design and further development of these repetitively branched systems are restricted by difficulties in scalable synthesis and structural determination, which can be overcome by judicious use of molecular modelling and molecular simulations. A major difficulty to utilise in silico studies to design dendrimers lies in the laborious generation of their structures. Current modelling tools utilise automated assembly of simpler dendrimers or the inefficient manual assembly of monomer precursors to generate more complicated dendrimer structures. Herein we describe two novel graphical user interface (GUI) toolkits written in Python that provide an improved degree of automation for rapid assembly of dendrimers and generation of their 2D and 3D structures. Our first toolkit uses the RDkit library, SMILES nomenclature of monomers and SMARTS reaction nomenclature to generate SMILES and mol files of dendrimers without 3D coordinates. These files are used for simple graphical representations and storing their structures in databases. The second toolkit assembles complex topology dendrimers from monomers to construct 3D dendrimer structures to be used as starting points for simulation using existing and widely available software and force fields. Both tools were validated for ease-of-use to prototype dendrimer structure and the second toolkit was especially relevant for dendrimers of high complexity and size.Peer reviewe
Physics Potential of the ICAL detector at the India-based Neutrino Observatory (INO)
The upcoming 50 kt magnetized iron calorimeter (ICAL) detector at the
India-based Neutrino Observatory (INO) is designed to study the atmospheric
neutrinos and antineutrinos separately over a wide range of energies and path
lengths. The primary focus of this experiment is to explore the Earth matter
effects by observing the energy and zenith angle dependence of the atmospheric
neutrinos in the multi-GeV range. This study will be crucial to address some of
the outstanding issues in neutrino oscillation physics, including the
fundamental issue of neutrino mass hierarchy. In this document, we present the
physics potential of the detector as obtained from realistic detector
simulations. We describe the simulation framework, the neutrino interactions in
the detector, and the expected response of the detector to particles traversing
it. The ICAL detector can determine the energy and direction of the muons to a
high precision, and in addition, its sensitivity to multi-GeV hadrons increases
its physics reach substantially. Its charge identification capability, and
hence its ability to distinguish neutrinos from antineutrinos, makes it an
efficient detector for determining the neutrino mass hierarchy. In this report,
we outline the analyses carried out for the determination of neutrino mass
hierarchy and precision measurements of atmospheric neutrino mixing parameters
at ICAL, and give the expected physics reach of the detector with 10 years of
runtime. We also explore the potential of ICAL for probing new physics
scenarios like CPT violation and the presence of magnetic monopoles.Comment: 139 pages, Physics White Paper of the ICAL (INO) Collaboration,
Contents identical with the version published in Pramana - J. Physic
Prevalence and factors associated with intestinal parasites among food handlers of food and drinking establishments in Aksum Town, Northern Ethiopia
Trends and clinico-epidemiological features of human rabies cases in Bangladesh 2006–2018
Vaccinating dogs against rabies is an effective means of reducing human rabies. We subjected 1327 clinically diagnosed human rabies death and mass dog vaccination (MDV) data during 2006–2018 to quantify the impacts of MDV on human rabies incidence in Bangladesh and a subset of rabies death data (422) for clinico-epidemiological analysis. A positive and increasing trend of MDV (p = 0.01 and tau = 0.71) and a negative and declining trend (p < 0.001 and tau = −0.88) of human rabies cases (Correlation coefficient: −0.82) have been observed. Among 422 deaths, the majority (78%) of the victims sought treatment from traditional healers, and 12% received post-exposure prophylaxis (PEP). The mean incubation period of rabies in cases with exposure sites on the head & neck (35 days) was shorter than the upper limb (mean = 64 days, p = 0.02) and lower limb (mean = 89 days, p < 0.01). MDV has been found to be effective for reducing human rabies cases in Bangladesh. Creating awareness among the animal bite victims to stop reliance on traditional healers rather seeking PEP, addressing the role of traditional healers through awareness education programme with respect to the treatment of dog bites, ensuring availability of PEP, and continuing to scale up MDV may help to prevent human rabies deaths
Effects of quantum gravity on the inflationary parameters and thermodynamics of the early universe
The effects of generalized uncertainty principle (GUP) on the inflationary
dynamics and the thermodynamics of the early universe are studied. Using the
GUP approach, the tensorial and scalar density fluctuations in the inflation
era are evaluated and compared with the standard case. We find a good agreement
with the Wilkinson Microwave Anisotropy Probe data. Assuming that a quantum gas
of scalar particles is confined within a thin layer near the apparent horizon
of the Friedmann-Lemaitre-Robertson-Walker universe which satisfies the
boundary condition, the number and entropy densities and the free energy
arising form the quantum states are calculated using the GUP approach. A
qualitative estimation for effects of the quantum gravity on all these
thermodynamic quantities is introduced.Comment: 15 graghes, 7 figures with 17 eps graph
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