425 research outputs found

    Antikaon Production in Proton-Nucleus Reactions and the KK^- properties in nuclear matter

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    We calculate the momentum-dependent potentials for K+K^+ and KK^- mesons in a dispersion approach at nuclear density ρ0\rho_0 using the information from the vacuum K+NK^+ N and KNK^- N scattering amplitudes, however, leaving out the resonance contributions for the in-medium analysis. Whereas the K+K^+ potential is found to be repulsive (\approx + 30 MeV) and to show only a moderate momentum dependence, the KK^- selfenergy at normal nuclear matter density turns out to be \approx - 200 MeV at zero momentum in line with kaon atomic data, however, decreases rapidly in magnitude for higher momenta. The antikaon production in p + A reactions is calculated within a coupled transport approach and compared to the data at KEK including different assumptions for the antikaon potentials. Furthermore, detailed predictions are made for p+12Cp + ^{12}C and p+207Pbp + ^{207}Pb reactions at 2.5 GeV in order to determine the momentum dependent antikaon potential experimentally.Comment: 27 pages, LaTeX, including 14 ps-figures, UGI-98-1

    Selective Uncoupling of Individual Mitochondria within a Cell Using a Mitochondria-Targeted Photoactivated Protonophore

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    Depolarization of an individual mitochondrion or small clusters of mitochondria within cells has been achieved using a photoactivatable probe. The probe is targeted to the matrix of the mitochondrion by an alkyltriphenylphosphonium lipophilic cation and releases the protonophore 2,4-dinitrophenol locally in predetermined regions in response to directed irradiation with UV light via a local photolysis system. This also provides a proof of principle for the general temporally and spatially controlled release of bioactive molecules, pharmacophores, or toxins to mitochondria with tissue, cell, or mitochondrion specificity

    Geriatric Cardiology: Coming of Age

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    Older adults with cardiovascular disease (CVD) contend with deficits across multiple domains of health due to age-related physiological changes and the impact of CVD. Multimorbidity, polypharmacy, cognitive changes, and diminished functional capacity, along with changes in the social environment, result in complexity that makes provision of CVD care to older adults challenging. In this review, we first describe the history of geriatric cardiology, an orientation that acknowledges the unique needs of older adults with CVD. Then, we introduce 5 essential principles for meeting the needs of older adults with CVD: 1) recognize and consider the potential impact of multicomplexity; 2) evaluate and integrate constructs of cognition into decision-making; 3) evaluate and integrate physical function into decision-making; 4) incorporate social environmental factors into management decisions; and 5) elicit patient priorities and health goals and align with care plan. Finally, we review future steps to maximize care provision to this growing population

    Detection of interstellar oxidaniumyl: abundant H2O+ towards the star-forming regions DR21, Sgr B2, and NGC6334

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    We identify a prominent absorption feature at 1115 GHz, detected in first HIFI spectra towards high-mass star-forming regions, and interpret its astrophysical origin. The characteristic hyperfine pattern of the H2O+ ground-state rotational transition, and the lack of other known low-energy transitions in this frequency range, identifies the feature as H2O+ absorption against the dust continuum background and allows us to derive the velocity profile of the absorbing gas. By comparing this velocity profile with velocity profiles of other tracers in the DR21 star-forming region, we constrain the frequency of the transition and the conditions for its formation. In DR21, the velocity distribution of H2O+ matches that of the [CII] line at 158\mu\m and of OH cm-wave absorption, both stemming from the hot and dense clump surfaces facing the HII-region and dynamically affected by the blister outflow. Diffuse foreground gas dominates the absorption towards Sgr B2. The integrated intensity of the absorption line allows us to derive lower limits to the H2O+ column density of 7.2e12 cm^-2 in NGC 6334, 2.3e13 cm^-2 in DR21, and 1.1e15 cm^-2 in Sgr B2.Comment: Accepted for publication in A&

    Antiretroviral therapy partially improves the abnormalities of dendritic cells and lymphoid and myeloid regulatory populations in recently infected HIV patients

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    This study aimed to evaluate the effects of antiretroviral therapy on plasmacytoid (pDC) and myeloid (mDC) dendritic cells as well as regulatory T (Treg) and myeloid-derived suppressor (MDSC) cells in HIVinfected patients. Forty-five HIV-infected patients (20 of them with detectable HIV load −10 recently infected and 10 chronically infected patients-, at baseline and after antiretroviral therapy, and 25 with undetectable viral loads) and 20 healthy controls were studied. The influence of HIV load, bacterial translocation (measured by 16S rDNA and lipopolysaccharide-binding protein) and immune activation markers (interleukin –IL- 6, soluble CD14, activated T cells) was analyzed. The absolute numbers and percentages of pDC and mDC were significantly increased in patients. Patients with detectable viral load exhibited increased intracellular expression of IL-12 by mDCs and interferon -IFN- α by pDCs. Activated population markers were elevated, and the proportion of Tregs was significantly higher in HIV-infected patients. The MDSC percentage was similar in patients and controls, but the intracellular expression of IL-10 was significantly higher in patients. The achievement of undetectable HIV load after therapy did not modify bacterial translocation parameters, but induce an increase in pDCs, mDCs and MDSCs only in recently infected patients. Our data support the importance of early antiretroviral therapy to preserve dendritic and regulatory cell function in HIV-infected individuals

    Predicting the Potential Worldwide Distribution of the Red Palm Weevil Rhynchophorus ferrugineus (Olivier) (Coleoptera: Curculionidae) using Ecological Niche Modeling

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    This is the publisher's version, also available electronically from http://www.bioone.org/doi/abs/10.1653/024.095.0317.The red palm weevil (RPW), Rhynchophorus ferrugineus (Olivier) (Coleoptera: Curculionidae), ranks among the most important pests of various palm species. The pest originates from South and Southeast Asia, but has expanded its range dramatically since the 1980s. We used ecological niche modeling (ENM) approaches to explore its likely geographic potential. Two techniques, the Genetic Algorithm for Rule-set Prediction (GARP) and a maximum entropy approach (MaxEnt), were used. However, MaxEnt provided more significant results, with all 5 random replicate subsamples having P < 0.002 while GARP models failed to achieve statistical significance in 3 of 5 cases, in which predictions achieved probabilities of 0.07 < P < 0.10. The MaxEnt models predicted successfully the known distribution, including the single North American occurrence point of Laguna Beach, California, and various areas where the pest has been reported in North Africa, southern Europe, Middle East and South and Southeastern Asia. In addition, areas where the pest has not been yet reported were found to be suitable for invasion by RPW in sub-Saharan Africa, southern, central and northern America, Asia, Europe, and Oceania. Highly suitable areas in the United States of America were limited mostly to coastal California and southern Florida, while all Caribbean islands were found highly suitable for establishment and spread of the pest

    Effector Memory Th1 CD4 T Cells Are Maintained in a Mouse Model of Chronic Malaria

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    Protection against malaria often decays in the absence of infection, suggesting that protective immunological memory depends on stimulation. Here we have used CD4+ T cells from a transgenic mouse carrying a T cell receptor specific for a malaria protein, Merozoite Surface Protein-1, to investigate memory in a Plasmodium chabaudi infection. CD4+ memory T cells (CD44hiIL-7Rα+) developed during the chronic infection, and were readily distinguishable from effector (CD62LloIL-7Rα−) cells in acute infection. On the basis of cell surface phenotype, we classified memory CD4+ T cells into three subsets: central memory, and early and late effector memory cells, and found that early effector memory cells (CD62LloCD27+) dominated the chronic infection. We demonstrate a linear pathway of differentiation from central memory to early and then late effector memory cells. In adoptive transfer, CD44hi memory cells from chronically infected mice were more effective at delaying and reducing parasitemia and pathology than memory cells from drug-treated mice without chronic infection, and contained a greater proportion of effector cells producing IFN-γ and TNFα, which may have contributed to the enhanced protection. These findings may explain the observation that in humans with chronic malaria, activated effector memory cells are best maintained in conditions of repeated exposure

    TNF autovaccination induces self anti-TNF antibodies and inhibits metastasis in a murine melanoma model

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    TNF is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory diseases, but also in metastasis in certain types of cancer. In terms of therapy, TNF is targeted by anti-TNF neutralising monoclonal antibodies or soluble TNF receptors. Recently, a novel strategy based on the generation of self anti-TNF antibodies (TNF autovaccination) has been developed. We have previously shown that TNF autovaccination successfully generates high anti-TNF antibody titres, blocks TNF and ameliorates collagen-induced arthritis in DBA/1 mice. In this study, we examined the ability of TNF autovaccination to generate anti-TNF antibody titres and block metastasis in the murine B16F10 melanoma model. We found that immunisation of C57BL/6 mice with TNF autovaccine produces a 100-fold antibody response to TNF compared to immunisation with phosphate-buffered saline vehicle control and significantly reduces both the number (P&lt;0.01) and size of metastases (P&lt;0.01) of B16F10 melanoma cells. This effect is also observed when an anti-TNF neutralising monoclonal antibody is administered, confirming the essential role TNF plays in metastasis in this model. This study suggests that TNF autovaccination is a cheaper and highly efficient alternative that can block TNF and reduce metastasis in vivo and trials with TNF autovaccination are already underway in patients with metastatic cancer

    Nasopharyngeal Colonization and Invasive Disease Are Enhanced by the Cell Wall Hydrolases LytB and LytC of Streptococcus pneumoniae

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    Background: Streptococcus pneumoniae is a common colonizer of the human nasopharynx and one of the major pathogens causing invasive disease worldwide. Dissection of the molecular pathways responsible for colonization, invasion, and evasion of the immune system will provide new targets for antimicrobial or vaccine therapies for this common pathogen. Methodology/Principal Findings: We have constructed mutants lacking the pneumococcal cell wall hydrolases (CWHs) LytB and LytC to investigate the role of these proteins in different phases of the pneumococcal pathogenesis. Our results show that LytB and LytC are involved in the attachment of S. pneumoniae to human nasopharyngeal cells both in vitro and in vivo. The interaction of both proteins with phagocytic cells demonstrated that LytB and LytC act in concert avoiding pneumococcal phagocytosis mediated by neutrophils and alveolar macrophages. Furthermore, C3b deposition was increased on the lytC mutant confirming that LytC is involved in complement evasion. As a result, the lytC mutant showed a reduced ability to successfully cause pneumococcal pneumonia and sepsis. Bacterial mutants lacking both LytB and LytC showed a dramatically impaired attachment to nasopharyngeal cells as well as a marked degree of attenuation in a mouse model of colonization. In addition, C3b deposition and phagocytosis was more efficient for the double lytB lytC mutant and its virulence was greatly impaired in both systemic and pulmonary models of infection. Conclusions/Significance: This study confirms that the CWHs LytB and LytC of S. pneumoniae are essential virulence factor
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