3,722 research outputs found

    Quantum instanton calculation of rate constants for the C(2)H(6) + H -> C(2)H(5) + H(2) reaction: anharmonicity and kinetic isotope effects

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    Thermal rate constants and kinetic isotope effects for the title reaction are calculated by using the quantum instanton approximation within the full dimensional Cartesian coordinates. The obtained results are in good agreement with experimental measurements at high temperatures. The detailed investigation reveals that the anharmonicity of the hindered internal rotation motion does not influence the rate too much compared to its harmonic oscillator approximation. However, the motion of the nonreactive methyl group in C(2)H(6) significantly enhances the rates compared to its rigid case, which makes conventional reduced-dimensionality calculations a challenge. In addition, the temperature dependence of kinetic isotope effects is also revealed.Scientific Research Foundation of Northwest AF University[Z109021103]; National Science Foundation of China[20833004, 21073146]; Northwest AF Universit

    The phases of deuterium at extreme densities

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    We consider deuterium compressed to higher than atomic, but lower than nuclear densities. At such densities deuterium is a superconducting quantum liquid. Generically, two superconducting phases compete, a "ferromagnetic" and a "nematic" one. We provide a power counting argument suggesting that the dominant interactions in the deuteron liquid are perturbative (but screened) Coulomb interactions. At very high densities the ground state is determined by very small nuclear interaction effects that probably favor the ferromagnetic phase. At lower densities the symmetry of the theory is effectively enhanced to SU(3), and the quantum liquid enters a novel phase, neither ferromagnetic nor nematic. Our results can serve as a starting point for investigations of the phase dynamics of deuteron liquids, as well as exploration of the stability and dynamics of the rich variety of topological objects that may occur in phases of the deuteron quantum liquid, which range from Alice strings to spin skyrmions to Z_2 vortices.Comment: 9 pages, 6 figures; v2: fixed typo

    Oxygen-regulated transcription factors and their role in pulmonary disease

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    The transcription factors nuclear factor interleukin-6 (NF-IL6), early growth response-1 (EGR-1) and hypoxia-inducible factor-1 (HIF-1) have important roles in the molecular pathophysiology of hypoxia-associated pulmonary disease. NF-IL6 controls the production of interleukin (IL)-6 in vascular endothelial cells, which may have anti-inflammatory activity by counteracting effects of IL-1 and IL-8. EGR-1 controls the production of tissue factor by macrophages, which triggers fibrin deposition in the pulmonary vasculature. HIF-1 activates the expression of the vasoconstrictor endothelin-1 in vascular endothelial cells. Angiotensin II induces HIF-1 expression and hypertrophy of pulmonary arterial smooth muscle cells. HIF-1 might therefore have multiple roles in the pathogenesis of pulmonary vascular remodeling

    Carbon Nanotubes Enhance Cytotoxicity Mediated by Human Lymphocytes In Vitro

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    With the expansion of the potential applications of carbon nanotubes (CNT) in biomedical fields, the toxicity and biocompatibility of CNT have become issues of growing concern. Since the immune system often mediates tissue damage during pathogenesis, it is important to explore whether CNT can trigger cytotoxicity through affecting the immune functions. In the current study, we evaluated the influence of CNT on the cytotoxicity mediated by human lymphocytes in vitro. The results showed that while CNT at low concentrations (0.001 to 0.1 µg/ml) did not cause obvious cell death or apoptosis directly, it enhanced lymphocyte-mediated cytotoxicity against multiple human cell lines. In addition, CNT increased the secretion of IFN-γ and TNF-α by the lymphocytes. CNT also upregulated the NF-κB expression in lymphocytes, and the blockage of the NF-κB pathway reduced the lymphocyte-mediated cytotoxicity triggered by CNT. These results suggest that CNT at lower concentrations may prospectively initiate an indirect cytotoxicity through affecting the function of lymphocytes

    Dry weather induces outbreaks of human West Nile virus infections

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    <p>Abstract</p> <p>Background</p> <p>Since its first occurrence in the New York City area during 1999, West Nile virus (WNV) has spread rapidly across North America and has become a major public health concern in North America. By 2002, WNV was reported in 40 states and the District of Columbia with 4,156 human and 14,539 equine cases of infection. Mississippi had the highest human incidence rate of WNV during the 2002 epidemic in the United States. Epidemics of WNV can impose enormous impacts on local economies. Therefore, it is advantageous to predict human WNV risks for cost-effective controls of the disease and optimal allocations of limited resources. Understanding relationships between precipitation and WNV transmission is crucial for predicting the risk of the human WNV disease outbreaks under predicted global climate change scenarios.</p> <p>Methods</p> <p>We analyzed data on the human WNV incidences in the 82 counties of Mississippi in 2002, using standard morbidity ratio (SMR) and Bayesian hierarchical models, to determine relationships between precipitation and human WNV risks. We also entertained spatial autocorrelations of human WNV risks with conditional autocorrelative (CAR) models, implemented in WinBUGS 1.4.3.</p> <p>Results</p> <p>We observed an inverse relationship between county-level human WNV incidence risk and total annual rainfall during the previous year. Parameters representing spatial heterogeneity in the risk of human exposure to WNV improved model fit. Annual precipitation of the previous year was a predictor of spatial variation of WNV risk.</p> <p>Conclusions</p> <p>Our results have broad implications for risk assessment of WNV and forecasting WNV outbreaks. Assessing risk of vector-born infectious diseases will require understanding of complex ecological relationships. Based on the climatologically characteristic drought occurrence in the past and on climate model predictions for climate change and potentially greater drought occurrence in the future, we suggest that the frequency and relative risk of WNV outbreaks could increase.</p

    An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

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    Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

    Variational Methods for Biomolecular Modeling

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    Structure, function and dynamics of many biomolecular systems can be characterized by the energetic variational principle and the corresponding systems of partial differential equations (PDEs). This principle allows us to focus on the identification of essential energetic components, the optimal parametrization of energies, and the efficient computational implementation of energy variation or minimization. Given the fact that complex biomolecular systems are structurally non-uniform and their interactions occur through contact interfaces, their free energies are associated with various interfaces as well, such as solute-solvent interface, molecular binding interface, lipid domain interface, and membrane surfaces. This fact motivates the inclusion of interface geometry, particular its curvatures, to the parametrization of free energies. Applications of such interface geometry based energetic variational principles are illustrated through three concrete topics: the multiscale modeling of biomolecular electrostatics and solvation that includes the curvature energy of the molecular surface, the formation of microdomains on lipid membrane due to the geometric and molecular mechanics at the lipid interface, and the mean curvature driven protein localization on membrane surfaces. By further implicitly representing the interface using a phase field function over the entire domain, one can simulate the dynamics of the interface and the corresponding energy variation by evolving the phase field function, achieving significant reduction of the number of degrees of freedom and computational complexity. Strategies for improving the efficiency of computational implementations and for extending applications to coarse-graining or multiscale molecular simulations are outlined.Comment: 36 page

    Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth

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    Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations
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