15,419 research outputs found
Harmful and Beneficial Role of ROS
Reactive oxygen species (ROS) are an unavoidable byproduct of oxygen metabolism and their cellular concentrations are determined by the balance between their rates of production and their rates of clearance by various antioxidant compounds and enzymes. For a long time ROS were thought to cause exclusively toxic effects which were associated with various pathologies, including carcinogenesis, neurodegeneration, atherosclerosis, diabetes, and aging. However, to date, it is known that while prolonged exposure to high ROS concentrations may lead to various disorders, low ROS concentrations exert beneficial effects regulating cell signaling cascades
Hadron Correlators and the Structure of the Quark Propagator
The structure of the quark propagator of in a confining background is
not known. We make an Ansatz for it, as hinted by a particular mechanism for
confinement, and analyze its implications in the meson and baryon correlators.
We connect the various terms in the K\"allen-Lehmann representation of the
quark propagator with appropriate combinations of hadron correlators, which may
ultimately be calculated in lattice . Furthermore, using the positivity of
the path integral measure for vector like theories, we reanalyze some mass
inequalities in our formalism. A curiosity of the analysis is that, the exotic
components of the propagator (axial and tensor), produce terms in the hadron
correlators which, if not vanishing in the gauge field integration, lead to
violations of fundamental symmetries. The non observation of these violations
implies restrictions in the space-time structure of the contributing gauge
field configurations. In this way, lattice can help us analyze the
microscopic structure of the mechanisms for confinement.Comment: 12 pp in LaTeX, preprint Univ. of Valencia, FTUV/94-16, IFIC/94-15.
To appear in Z.Phys.
Parameterized Model-Checking for Timed-Systems with Conjunctive Guards (Extended Version)
In this work we extend the Emerson and Kahlon's cutoff theorems for process
skeletons with conjunctive guards to Parameterized Networks of Timed Automata,
i.e. systems obtained by an \emph{apriori} unknown number of Timed Automata
instantiated from a finite set of Timed Automata templates.
In this way we aim at giving a tool to universally verify software systems
where an unknown number of software components (i.e. processes) interact with
continuous time temporal constraints. It is often the case, indeed, that
distributed algorithms show an heterogeneous nature, combining dynamic aspects
with real-time aspects. In the paper we will also show how to model check a
protocol that uses special variables storing identifiers of the participating
processes (i.e. PIDs) in Timed Automata with conjunctive guards. This is
non-trivial, since solutions to the parameterized verification problem often
relies on the processes to be symmetric, i.e. indistinguishable. On the other
side, many popular distributed algorithms make use of PIDs and thus cannot
directly apply those solutions
The sparticle spectrum in Minimal gaugino-Gauge Mediation
We compute the sparticle mass spectrum in the minimal four-dimensional
construction that interpolates between gaugino mediation and ordinary gauge
mediation.Comment: 21 pages, 9 figures; V2: refs. added; V3: some typos correcte
Flat bands as a route to high-temperature superconductivity in graphite
Superconductivity is traditionally viewed as a low-temperature phenomenon.
Within the BCS theory this is understood to result from the fact that the
pairing of electrons takes place only close to the usually two-dimensional
Fermi surface residing at a finite chemical potential. Because of this, the
critical temperature is exponentially suppressed compared to the microscopic
energy scales. On the other hand, pairing electrons around a dispersionless
(flat) energy band leads to very strong superconductivity, with a mean-field
critical temperature linearly proportional to the microscopic coupling
constant. The prize to be paid is that flat bands can generally be generated
only on surfaces and interfaces, where high-temperature superconductivity would
show up. The flat-band character and the low dimensionality also mean that
despite the high critical temperature such a superconducting state would be
subject to strong fluctuations. Here we discuss the topological and
non-topological flat bands discussed in different systems, and show that
graphite is a good candidate for showing high-temperature flat-band interface
superconductivity.Comment: Submitted as a chapter to the book on "Basic Physics of
functionalized Graphite", 21 pages, 12 figure
Supersymmetry enhancement by monopole operators
We describe a method which allows one to study hidden symmetries in a large
class of strongly coupled supersymmetric gauge theories in three dimensions. We
apply this method to the ABJM theory and to the infrared limit of N=4 SQCD with
adjoint and fundamental matter. We show that the U(N) ABJM model with
Chern-Simons level k=1 or k=2 has hidden N=8 supersymmetry. Hidden
supersymmetry is also shown to occur in N=4 d=3 SQCD with one fundamental and
one adjoint hypermultiplet. The latter theory, as well as the U(N) ABJM theory
at k=1, are shown to have a decoupled free sector. This provides evidence that
both models are dual to the infrared limit of N=8 U(N) super-Yang-Mills theory.Comment: 29 pages, late
Pressure-dependent EPANET extension
In water distribution systems (WDSs), the available flow at a demand node is dependent on the pressure at that node. When a network is lacking in pressure, not all consumer demands will be met in full. In this context, the assumption that all demands are fully satisfied regardless of the pressure in the system becomes unreasonable and represents the main limitation of the conventional demand driven analysis (DDA) approach to WDS modelling. A realistic depiction of the network performance can only be attained by considering demands to be pressure dependent. This paper presents an extension of the renowned DDA based hydraulic simulator EPANET 2 to incorporate pressure-dependent demands. This extension is termed âEPANET-PDXâ (pressure-dependent extension) herein. The utilization of a continuous nodal pressure-flow function coupled with a line search and backtracking procedure greatly enhance the algorithmâs convergence rate and robustness. Simulations of real life networks consisting of multiple sources, pipes, valves and pumps were successfully executed and results are presented herein. Excellent modelling performance was achieved for analysing both normal and pressure deficient conditions of the WDSs. Detailed computational efficiency results of EPANET-PDX with reference to EPANET 2 are included as well
A Clinical and Epidemiological Investigation of the First Reported Human Infection With the Zoonotic Parasite Trypanosoma evansi in Southeast Asia
Background.âTrypanosoma is a genus of unicellular parasitic flagellate protozoa. Trypanosoma brucei species and Trypanosoma cruzi are the major agents of human trypanosomiasis; other Trypanosoma species can cause human disease, but are rare. In March 2015, a 38-year-old woman presented to a healthcare facility in southern Vietnam with fever, headache, and arthralgia. Microscopic examination of blood revealed infection with Trypanosoma. Methods.âMicroscopic observation, polymerase chain reaction (PCR) amplification of blood samples, and serological testing were performed to identify the infecting species. The patient's blood was screened for the trypanocidal protein apolipoprotein L1 (APOL1), and a field investigation was performed to identify the zoonotic source. Results.âPCR amplification and serological testing identified the infecting species as Trypanosoma evansi. Despite relapsing 6 weeks after completing amphotericin B therapy, the patient made a complete recovery after 5 weeks of suramin. The patient was found to have 2 wild-type APOL1 alleles and a normal serum APOL1 concentration. After responsive animal sampling in the presumed location of exposure, cattle and/or buffalo were determined to be the most likely source of the infection, with 14 of 30 (47%) animal blood samples testing PCR positive for T. evansi. Conclusions.âWe report the first laboratory-confirmed case of T. evansi in a previously healthy individual without APOL1 deficiency, potentially contracted via a wound while butchering raw beef, and successfully treated with suramin. A linked epidemiological investigation revealed widespread and previously unidentified burden of T. evansi in local cattle, highlighting the need for surveillance of this infection in animals and the possibility of further human cases
Human Neutrophil Elastase Proteolytic Activity in Ulcerative Colitis Favors the Loss of Function of Therapeutic Monoclonal Antibodies
Purpose: Proteases play an essential role in the pathophysiology of inflammatory bowel disease (IBD), contributing to the intestinal mucosal lesions through the degradation of the extracellular matrix and alteration of the barrier function. Ulcerative colitis (UC) is characterized by an extensive infiltrate of neutrophils into the mucosa and hence, increased proteolytic activity. Human neutrophil elastase (HNE) is a serine protease that has been reported to be increased in UC patientsâ intestinal mucosa. Based on our previous studies, we hypothesized that HNE might induce proteolytic degradation and loss of function of therapeutic monoclonal antibodies in IBD patients.
Patients and Methods: Elastase expression and elastinolytic activity were determined in mucosal explants from ulcerative colitis patients (n=6) and cultured ex vivo in the presence or absence of recombinant elafin. Enzymatic digestions of therapeutic monoclonal antibodies were performed using recombinant HNE and elafin. The integrity of the therapeutic antibodies was evaluated by immunoblotting and protein G binding assay, whereas their TNFneutralizing activity was assessed with a reporter cell line.
Results: We found that HNE and its elastinolytic activity were increased in the gut mucosa of UC patients. We also demonstrated that HNE cleaved biological drugs, impairing the TNF-α neutralizing capacity of anti-TNF monoclonal antibodies. This proteolytic degradation was inhibited by the addition of the specific inhibitor, elafin.
Conclusion: Our results suggest that the high level of proteolytic degradation by mucosal neutrophil elastase, along with a potential imbalance with elafin, contributes to the loss of function of biologic agents, which are currently used in patients with IBD. These findings might explain the non-responsiveness of UC patients to therapeutic monoclonal antibodies and suggest the potential beneficial concomitant use of elafin in this treatment.Facultad de Ciencias ExactasInstituto de Estudios InmunolĂłgicos y FisiopatolĂłgico
Use-case scenarios for an anti-Cryptosporidium therapeutic.
Cryptosporidium is a widely distributed enteric parasite that has an increasingly appreciated pathogenic role, particularly in pediatric diarrhea. While cryptosporidiosis has likely affected humanity for millennia, its recent "emergence" is largely the result of discoveries made through major epidemiologic studies in the past decade. There is no vaccine, and the only approved medicine, nitazoxanide, has been shown to have efficacy limitations in several patient groups known to be at elevated risk of disease. In order to help frontline health workers, policymakers, and other stakeholders translate our current understanding of cryptosporidiosis into actionable guidance to address the disease, we sought to assess salient issues relating to clinical management of cryptosporidiosis drawing from a review of the literature and our own field-based practice. This exercise is meant to help inform health system strategies for improving access to current treatments, to highlight recent achievements and outstanding knowledge and clinical practice gaps, and to help guide research activities for new anti-Cryptosporidium therapies
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