332 research outputs found

    Classical Effective Field Theory for Weak Ultra Relativistic Scattering

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    Inspired by the problem of Planckian scattering we describe a classical effective field theory for weak ultra relativistic scattering in which field propagation is instantaneous and transverse and the particles' equations of motion localize to the instant of passing. An analogy with the non-relativistic (post-Newtonian) approximation is stressed. The small parameter is identified and power counting rules are established. The theory is applied to reproduce the leading scattering angle for either a scalar interaction field or electro-magnetic or gravitational; to compute some subleading corrections, including the interaction duration; and to allow for non-zero masses. For the gravitational case we present an appropriate decomposition of the gravitational field onto the transverse plane together with its whole non-linear action. On the way we touch upon the relation with the eikonal approximation, some evidence for censorship of quantum gravity, and an algebraic ring structure on 2d Minkowski spacetime.Comment: 29 pages, 2 figures. v4: Duration of interaction is determined in Sec 4 and detailed in App C. Version accepted for publication in JHE

    Spin and quadrupole contributions to the motion of astrophysical binaries

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    Compact objects in general relativity approximately move along geodesics of spacetime. It is shown that the corrections to geodesic motion due to spin (dipole), quadrupole, and higher multipoles can be modeled by an extension of the point mass action. The quadrupole contributions are discussed in detail for astrophysical objects like neutron stars or black holes. Implications for binaries are analyzed for a small mass ratio situation. There quadrupole effects can encode information about the internal structure of the compact object, e.g., in principle they allow a distinction between black holes and neutron stars, and also different equations of state for the latter. Furthermore, a connection between the relativistic oscillation modes of the object and a dynamical quadrupole evolution is established.Comment: 43 pages. Proceedings of the 524. WE-Heraeus-Seminar "Equations of Motion in Relativistic Gravity". v2: fixed reference. v3: corrected typos in eqs. (1), (57), (85

    Computational analysis suggests that virulence of Chromobacterium violaceum might be linked to biofilm formation and poly-NAG biosynthesis

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    Groups of genes that produce exopolysaccharide with a N-acetyl-D-glucosamine monomer are in the genome of several pathogenic bacteria. Chromobacterium violaceum, an opportunistic pathogen, has the operon hmsHFR-CV2940, whose proteins can synthesize such polysaccharide. In this work, multiple alignments among proteins from bacteria that synthesize such polysaccharide were used to verify the existence of amino acids that might be critical for pathogen activity. Three-dimensional models were generated for spatial visualization of these amino acid residues. The analysis carried out showed that the protein HmsR preserves the amino acids D135, D228, Q264 and R267, considered critical for the formation of biofilms and, furthermore, that these amino acids are close to each other. The protein HmsF of C. violaceum preserves the residues D86, D87, H156 and W115. It was also shown that these residues are also close to each other in their spatial arrangement. For the proteins HmsH and CV2940 there is evidence of conservation of the residues R104 and W94, respectively. Conservation and favorable spatial location of those critical amino acids that constitute the proteins of the operon indicates that they preserve the same enzymatic function in biofilm synthesis. This is an indicator that the operon hmsHFR-CV2940 is a possible target in C. violaceum pathogenicity

    Effect of different intravenous iron preparations on lymphocyte intracellular reactive oxygen species generation and subpopulation survival

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    <p>Abstract</p> <p>Background</p> <p>Infections in hemodialysis (HD) patients lead to high morbidity and mortality rates and are associated with early cardiovascular mortality, possibly related to chronic inflammation. Intravenous (IV) iron is widely administered to HD patients and has been associated with increased oxidative stress and dysfunctional cellular immunity. The purpose of this study was to examine the effect of three commercially available IV iron preparations on intracellular reactive oxygen species generation and lymphocyte subpopulation survival.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells (PBMC) were isolated from healthy donor buffy coat. PBMC were cultured and incubated with 100 μg/mL of sodium ferric gluconate (SFG), iron sucrose (IS) or iron dextran (ID) for 24 hours. Cells were then probed for reactive oxygen species (ROS) with dichlorofluorescein-diacetate. In separate studies, isolated PBMCs were incubated with the 25, 50 or 100 μg/mL iron concentrations for 72 hours and then stained with fluorescein conjugated monoclonal antibodies for lymphocyte subpopulation identification. Untreated PBMCs at 24 hours and 72 hours served as controls for each experiment.</p> <p>Results</p> <p>All three IV iron preparations induced time dependent increases in intracellular ROS with SFG and IS having a greater maximal effect than ID. The CD4+ lymphocytes were most affected by IV iron exposure, with statistically significant reduction in survival after incubation with all three doses (10, 25 and 100 μg/mL) of SFG, IS and ID.</p> <p>Conclusion</p> <p>These data indicate IV iron products induce differential deleterious effects on CD4+ and CD16+ human lymphocytes cell populations that may be mediated by intracellular reactive oxygen species generation. Further studies are warranted to determine the potential clinical relevance of these findings.</p

    Anatomical Network Comparison of Human Upper and Lower, Newborn and Adult, and Normal and Abnormal Limbs, with Notes on Development, Pathology and Limb Serial Homology vs. Homoplasy

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    How do the various anatomical parts (modules) of the animal body evolve into very different integrated forms (integration) yet still function properly without decreasing the individual's survival? This long-standing question remains unanswered for multiple reasons, including lack of consensus about conceptual definitions and approaches, as well as a reasonable bias toward the study of hard tissues over soft tissues. A major difficulty concerns the non-trivial technical hurdles of addressing this problem, specifically the lack of quantitative tools to quantify and compare variation across multiple disparate anatomical parts and tissue types. In this paper we apply for the first time a powerful new quantitative tool, Anatomical Network Analysis (AnNA), to examine and compare in detail the musculoskeletal modularity and integration of normal and abnormal human upper and lower limbs. In contrast to other morphological methods, the strength of AnNA is that it allows efficient and direct empirical comparisons among body parts with even vastly different architectures (e.g. upper and lower limbs) and diverse or complex tissue composition (e.g. bones, cartilages and muscles), by quantifying the spatial organization of these parts-their topological patterns relative to each other-using tools borrowed from network theory. Our results reveal similarities between the skeletal networks of the normal newborn/adult upper limb vs. lower limb, with exception to the shoulder vs. pelvis. However, when muscles are included, the overall musculoskeletal network organization of the upper limb is strikingly different from that of the lower limb, particularly that of the more proximal structures of each limb. Importantly, the obtained data provide further evidence to be added to the vast amount of paleontological, gross anatomical, developmental, molecular and embryological data recently obtained that contradicts the long-standing dogma that the upper and lower limbs are serial homologues. In addition, the AnNA of the limbs of a trisomy 18 human fetus strongly supports Pere Alberch's ill-named "logic of monsters" hypothesis, and contradicts the commonly accepted idea that birth defects often lead to lower integration (i.e. more parcellation) of anatomical structures

    Total blood lymphocyte counts in hemochromatosis probands with HFE C282Y homozygosity: relationship to severity of iron overload and HLA-A and -B alleles and haplotypes

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    BACKGROUND: It has been reported that some persons with hemochromatosis have low total blood lymphocyte counts, but the reason for this is unknown. METHODS: We measured total blood lymphocyte counts using an automated blood cell counter in 146 hemochromatosis probands (88 men, 58 women) with HFE C282Y homozygosity who were diagnosed in medical care. Univariate and multivariate analyses of total blood lymphocyte counts were evaluated using these variables: sex; age, transferrin saturation, and serum ferritin concentration at diagnosis; units of blood removed by phlebotomy to achieve iron depletion; and human leukocyte antigen (HLA)-A and -B alleles and haplotypes. RESULTS: The mean age at diagnosis was 49 ± 14 years (range 18 – 80 years) in men and 50 ± 13 years (range 22 – 88 years) in women. The correlations of total blood lymphocyte counts with sex, age, transferrin saturation, and serum ferritin concentration at diagnosis, and units of blood removed by phlebotomy to achieve iron depletion were not significant at the 0.05 level. Univariate analyses revealed significant associations between total blood lymphocyte counts and presence of the HLA-A*01, -B*08, and -B*14 alleles, and the A*01-B*08 haplotype. Presence of the A*01 allele, B*08 allele, or A*01-B*08 haplotype were associated with a lower total blood lymphocyte count, whereas presence of the B*14 allele was associated with a greater total blood lymphocyte count. There was an inverse association of total blood lymphocyte count with units of phlebotomy to achieve iron depletion, serum ferritin concentration, and with presence of the A*01-B*08 haplotype. CONCLUSION: We conclude that there is a significant inverse relationship of total blood lymphocyte counts and severity of iron overload in hemochromatosis probands with HFE C282Y homozygosity. The presence of the HLA-A*01 allele or the -B*08 allele was also associated with significantly lower total blood lymphocyte counts, whereas presence of the -B*14 allele was associated with significantly higher total blood lymphocyte counts. In univariate and multivariate analyses, total blood lymphocyte counts were significantly lower in probands with the HLA-A*01-B*08 haplotype than in probands without this haplotype

    Bayesian Approach to Model CD137 Signaling in Human M.tuberculosis in vitro Responses

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    Abstract Immune responses are qualitatively and quantitatively influenced by a complex network of receptor-ligand interactions. Among them, the CD137:CD137L pathway is known to modulate innate and adaptive human responses against Mycobacterium tuberculosis. However, the underlying mechanisms of this regulation remain unclear. In this work, we developed a Bayesian Computational Model (BCM) of in vitro CD137 signaling, devised to fit previously gathered experimental data. The BCM is fed with the data and the prior distribution of the model parameters and it returns theirposterior distribution and the model evidence, which allows comparing alternative signaling mechanisms. The BCM uses a coupled system of non-linear differential equations to describe the dynamics of Antigen Presenting Cells, Natural Killer and T Cells together with the interpheron (IFN)-c and tumor necrosis factor (TNF)-a levels in the media culture. Fast and complete mixing of the media is assumed. The prior distribution of the parameters that describe the dynamics of the immunological response was obtained from the literature and theoretical considerations Our BCM applies successively the Levenberg-Marquardt algorithm to find the maximum a posteriori likelihood (MAP); the Metropolis Markov Chain Monte Carlo method to approximate the posterior distribution of the parameters and Thermodynamic Integration to calculate the evidence of alternative hypothesis. Bayes factors provided decisive evidence favoring direct CD137 signaling on T cells. Moreover, the posterior distribution of the parameters that describe the CD137 signaling showed that the regulation of IFNc levels is based more on T cells survival than on direct induction. Furthermore, the mechanisms that account for the effect of CD137 signaling on TNF-a production were based on a decrease of TNF-a production by APC and, perhaps, on the increase in APC apoptosis. BCM proved to be a useful tool to gain insight on the mechanisms of CD137 signaling during human response against Mycobacterium tuberculosis.Fil: Darío A Fernández Do Porto. UNIV.DE BUENOS AIRES. FAC.DE CS.EXACTAS Y NATURALES. UNIV.DE BUENOS AIRES. FAC.DE CS.EXACTAS Y NATURALES. INST QUIM FISICA D/L/MATERIALES MED AMB Y ENERG.Fil: Jerónimo Auzmendi. UNIV.DE BUENOS AIRES. FAC.DE CS.EXACTAS Y NATURALES. INST QUIM FISICA D/L/MATERIALES MED AMB Y ENERG.Fil: Delfina Peña. UNIV.DE BUENOS AIRES. FAC.DE CS.EXACTAS Y NATURALES. CONSEJO NAC.DE INVEST.CIENTIF.Y TECNICAS. OFICINA DE COORDINACION ADMINISTRATIVA CIUDAD UNIVERSITARIA. INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES. UNIV.DE BUENOS AIRES. FAC.DE CS.EXACTAS Y NATURALES. DTO.DE QUIMICA BIOLOGICA.Fil: Veronica E Garcia. CONSEJO NAC.DE INVEST.CIENTIF.Y TECNICAS. OFICINA DE COORDINACION ADMINISTRATIVA CIUDAD UNIVERSITARIA. INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES.Fil: Luciano Moffatt. UNIV.DE BUENOS AIRES. FAC.DE CS.EXACTAS Y NATURALES. INST QUIM FISICA D/L/MATERIALES MED AMB Y ENERG
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