114 research outputs found

    Electron-electron Bound States in Parity-Preserving QED3

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    By considering the Higgs mechanism in the framework of a parity-preserving Planar Quantum Electrodynamics, one shows that an attractive electron-electron interaction may come out. The e-e interaction potential emerges as the non-relativistic limit of the Moller scattering amplitude and it may result attractive with a suitable choice of parameters. Numerical values of the e-e binding energy are obtained by solving the two-dimensional Schrodinger equation. The existence of bound states is to be viewed as an indicative that this model may be adopted to address the pairing mechanism in some systems endowed with parity-preservation.Comment: 6 pages, 1 table, style revte

    Computed Tomography Measurement of Rib Cage Morphometry in Emphysema

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    Background: Factors determining the shape of the human rib cage are not completely understood. We aimed to quantify the contribution of anthropometric and COPD-related changes to rib cage variability in adult cigarette smokers. Methods: Rib cage diameters and areas (calculated from the inner surface of the rib cage) in 816 smokers with or without COPD, were evaluated at three anatomical levels using computed tomography (CT). CTs were analyzed with software, which allows quantification of total emphysema (emphysema%). The relationship between rib cage measurements and anthropometric factors, lung function indices, and %emphysema were tested using linear regression models. Results: A model that included gender, age, BMI, emphysema%, forced expiratory volume in one second (FEV1)%, and forced vital capacity (FVC)% fit best with the rib cage measurements (R2  = 64% for the rib cage area variation at the lower anatomical level). Gender had the biggest impact on rib cage diameter and area (105.3 cm2; 95% CI: 111.7 to 98.8 for male lower area). Emphysema% was responsible for an increase in size of upper and middle CT areas (up to 5.4 cm2; 95% CI: 3.0 to 7.8 for an emphysema increase of 5%). Lower rib cage areas decreased as FVC% decreased (5.1 cm2; 95% CI: 2.5 to 7.6 for 10 percentage points of FVC variation). Conclusions: This study demonstrates that simple CT measurements can predict rib cage morphometric variability and also highlight relationships between rib cage morphometry and emphysema

    Macrophage Replication Screen Identifies a Novel Francisella Hydroperoxide Resistance Protein Involved in Virulence

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    Francisella tularensis is a Gram-negative facultative intracellular pathogen and the causative agent of tularemia. Recently, genome-wide screens have identified Francisella genes required for virulence in mice. However, the mechanisms by which most of the corresponding proteins contribute to pathogenesis are still largely unknown. To further elucidate the roles of these virulence determinants in Francisella pathogenesis, we tested whether each gene was required for replication of the model pathogen F. novicida within macrophages, an important virulence trait. Fifty-three of the 224 genes tested were involved in intracellular replication, including many of those within the Francisella pathogenicity island (FPI), validating our results. Interestingly, over one third of the genes identified are annotated as hypothetical, indicating that F. novicida likely utilizes novel virulence factors for intracellular replication. To further characterize these virulence determinants, we selected two hypothetical genes to study in more detail. As predicted by our screen, deletion mutants of FTN_0096 and FTN_1133 were attenuated for replication in macrophages. The mutants displayed differing levels of attenuation in vivo, with the FTN_1133 mutant being the most attenuated. FTN_1133 has sequence similarity to the organic hydroperoxide resistance protein Ohr, an enzyme involved in the bacterial response to oxidative stress. We show that FTN_1133 is required for F. novicida resistance to, and degradation of, organic hydroperoxides as well as resistance to the action of the NADPH oxidase both in macrophages and mice. Furthermore, we demonstrate that F. holarctica LVS, a strain derived from a highly virulent human pathogenic species of Francisella, also requires this protein for organic hydroperoxide resistance as well as replication in macrophages and mice. This study expands our knowledge of Francisella's largely uncharacterized intracellular lifecycle and demonstrates that FTN_1133 is an important novel mediator of oxidative stress resistance

    The relationship between organisational characteristics and the effects of clinical guidelines on medical performance in hospitals, a meta-analysis

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    We are grateful to our colleagues involved in the systematic review of guideline dissemination and implementation strategies across all settings especially Cynthia Fraser, Graeme MacLennan, Craig Ramsay, Paula Whitty, Martin Eccles, Lloyd Matowe, Liz Shirran. The systematic review of guideline dissemination and implementation strategies across all settings was funded by the UK NHS Health Technology Assessment Program. Dr Ruth Thomas is funded by a Wellcome Training Fellowship in Health Services Research. (Grant number GR063790MA). The Health Services Research Unit is funded by the Chief Scientists Office of the Scottish Executive Department of Health. Dr Jeremy Grimshaw holds a Canada Research Chair in Health Knowledge Transfer and Uptake. However the views expressed are those of the authors and not necessarily the funders.Peer reviewedPublisher PD

    Novel Photosensitizers Trigger Rapid Death of Malignant Human Cells and Rodent Tumor Transplants via Lipid Photodamage and Membrane Permeabilization

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    BACKGROUND: Apoptotic cascades may frequently be impaired in tumor cells; therefore, the approaches to circumvent these obstacles emerge as important therapeutic modalities. METHODOLOGY/PRINCIPAL FINDINGS: Our novel derivatives of chlorin e(6), that is, its amide (compound 2) and boronated amide (compound 5) evoked no dark toxicity and demonstrated a significantly higher photosensitizing efficacy than chlorin e(6) against transplanted aggressive tumors such as B16 melanoma and M-1 sarcoma. Compound 5 showed superior therapeutic potency. Illumination with red light of mammalian tumor cells loaded with 0.1 µM of 5 caused rapid (within the initial minutes) necrosis as determined by propidium iodide staining. The laser confocal microscopy-assisted analysis of cell death revealed the following order of events: prior to illumination, 5 accumulated in Golgi cysternae, endoplasmic reticulum and in some (but not all) lysosomes. In response to light, the reactive oxygen species burst was concomitant with the drop of mitochondrial transmembrane electric potential, the dramatic changes of mitochondrial shape and the loss of integrity of mitochondria and lysosomes. Within 3-4 min post illumination, the plasma membrane became permeable for propidium iodide. Compounds 2 and 5 were one order of magnitude more potent than chlorin e(6) in photodamage of artificial liposomes monitored in a dye release assay. The latter effect depended on the content of non-saturated lipids; in liposomes consisting of saturated lipids no photodamage was detectable. The increased therapeutic efficacy of 5 compared with 2 was attributed to a striking difference in the ability of these photosensitizers to permeate through hydrophobic membrane interior as evidenced by measurements of voltage jump-induced relaxation of transmembrane current on planar lipid bilayers. CONCLUSIONS/SIGNIFICANCE: The multimembrane photodestruction and cell necrosis induced by photoactivation of 2 and 5 are directly associated with membrane permeabilization caused by lipid photodamage

    UVA/UVA1 phototherapy and PUVA photochemotherapy in connective tissue diseases and related disorders: a research based review

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    BACKGROUND: Broad-band UVA, long-wave UVA1 and PUVA treatment have been described as an alternative/adjunct therapeutic option in a number of inflammatory and malignant skin diseases. Nevertheless, controlled studies investigating the efficacy of UVA irradiation in connective tissue diseases and related disorders are rare. METHODS: Searching the PubMed database the current article systematically reviews established and innovative therapeutic approaches of broad-band UVA irradiation, UVA1 phototherapy and PUVA photochemotherapy in a variety of different connective tissue disorders. RESULTS: Potential pathways include immunomodulation of inflammation, induction of collagenases and initiation of apoptosis. Even though holding the risk of carcinogenesis, photoaging or UV-induced exacerbation, UVA phototherapy seems to exhibit a tolerable risk/benefit ratio at least in systemic sclerosis, localized scleroderma, extragenital lichen sclerosus et atrophicus, sclerodermoid graft-versus-host disease, lupus erythematosus and a number of sclerotic rarities. CONCLUSIONS: Based on the data retrieved from the literature, therapeutic UVA exposure seems to be effective in connective tissue diseases and related disorders. However, more controlled investigations are needed in order to establish a clear-cut catalogue of indications

    The role of ascorbate in antioxidant protection of biomembranes: Interaction with vitamin E and coenzyme Q

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    One of the vital roles of ascorbic acid (vitamin C) is to act as an antioxidant to protect cellular components from free radical damage. Ascorbic acid has been shown to scavenge free radicals directly in the aqueous phases of cells and the circulatory system. Ascorbic acid has also been proven to protect membrane and other hydrophobic compartments from such damage by regenerating the antioxidant form of vitamin E. In addition, reduced coenzyme Q, also a resident of hydrophobic compartments, interacts with vitamin E to regenerate its antioxidant form. The mechanism of vitamin C antioxidant function, the myriad of pathologies resulting from its clinical deficiency, and the many health benefits it provides, are reviewed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44796/1/10863_2004_Article_BF00762775.pd

    Interrogating open issues in cancer precision medicine with patient-derived xenografts

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    Survival of Freeze-dried Leuconostoc mesenteroides and Lactobacillus plantarum Related to Their Cellular Fatty Acids Composition during Storage

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    Lactic acid bacteria strains Lactobacillus plantarum CWBI-B534 and Leuconostoc ssp. mesenteroïdes (L. mesenteroïdes) Kenya MRog2 were produced in bioreactor, concentrated, with or without cryoprotectants. In general, viable population did not change significantly after freeze-drying (p>0.05). In most cases, viable population for cells added with cryoprotectants was significantly lower than those without (p<0.05). Cellular fatty acids (CFAs) from the two strains in this study were analyzed before and after freeze-drying. Six CFAs were identified, namely, palmitic (C16:0), palmitoleic (C16:1), stearic (C18:0), oleic (C18:1), linoleic (C18:2), and linolenic (C18:3) acids were identified. Four of them, C16:0, C16:1, C18:0, and C18:1, make up more than 94% or 93% of the fatty acids in L. mesenteroides and L. plantarum, respectively, with another one, namely, C18:3, making a smaller (on average 5–6%, respectively) contribution. The C18:2 contributed very small percentages (on average≤1%) to the total in each strain. C16:0 had the highest proportion at most points relative to other fatty acids. Moisture content and water activity (a w) increased significantly during the storage period. It was observed that C16:1/C16:0, C18:0/C16:0 and C18:1/C16:0 ratios for freeze-dried L. mesenteroides or L. plantarum, with or without cryoprotectants, did not change significantly during the storage period. According to the packaging mode and storage temperatures, C18:2/C16:0 and C18:3/C16:0 ratios for freeze-dried L. mesenteroides and L. plantarum with or without cryoprotectants decreased as the storage time increased. However, a higher C18:2/C16:0 or C18:3/C16:0 ratio for L. mesenteroides and L. plantarum was noted in the freeze-dried powder held at 4 °C or under vacuum and in dark than at 20 °C or in the presence of oxygen and ligh
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