692 research outputs found

    Theory and simulation of short-range models of globular protein solutions

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    We report theoretical and simulation studies of phase coexistence in model globular protein solutions, based on short-range, central, pair potential representations of the interaction among macro-particles. After reviewing our previous investigations of hard-core Yukawa and generalised Lennard-Jones potentials, we report more recent results obtained within a DLVO-like description of lysozyme solutions in water and added salt. We show that a one-parameter fit of this model based on Static Light Scattering and Self-Interaction Chromatography data in the dilute protein regime, yields demixing and crystallization curves in good agreement with experimental protein-rich/protein-poor and solubility envelopes. The dependence of cloud and solubility points temperature of the model on the ionic strength is also investigated. Our findings highlight the minimal assumptions on the properties of the microscopic interaction sufficient for a satisfactory reproduction of the phase diagram topology of globular protein solutions.Comment: 17 pages, 8 figures, Proc. of Conference "Structural Arrest Transitions in Colloidal Systems with Short-Range Attractions", Messina (ITALY) 17-20 December 200

    Theoretical description of phase coexistence in model C60

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    We have investigated the phase diagram of the Girifalco model of C60 fullerene in the framework provided by the MHNC and the SCOZA liquid state theories, and by a Perturbation Theory (PT), for the free energy of the solid phase. We present an extended assessment of such theories as set against a recent Monte Carlo study of the same model [D. Costa et al, J. Chem. Phys. 118:304 (2003)]. We have compared the theoretical predictions with the corresponding simulation results for several thermodynamic properties. Then we have determined the phase diagram of the model, by using either the SCOZA, or the MHNC, or the PT predictions for one of the coexisting phases, and the simulation data for the other phase, in order to separately ascertain the accuracy of each theory. It turns out that the overall appearance of the phase portrait is reproduced fairly well by all theories, with remarkable accuracy as for the melting line and the solid-vapor equilibrium. The MHNC and SCOZA results for the liquid-vapor coexistence, as well as for the corresponding critical points, are quite accurate. All results are discussed in terms of the basic assumptions underlying each theory. We have selected the MHNC for the fluid and the first-order PT for the solid phase, as the most accurate tools to investigate the phase behavior of the model in terms of purely theoretical approaches. The overall results appear as a robust benchmark for further theoretical investigations on higher order C(n>60) fullerenes, as well as on other fullerene-related materials, whose description can be based on a modelization similar to that adopted in this work.Comment: RevTeX4, 15 pages, 7 figures; submitted to Phys. Rev.

    Mycobacterium tuberculosis Drives Expansion of Low-Density Neutrophils Equipped With Regulatory Activities

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    In human tuberculosis (TB) neutrophils represent the most commonly infected phagocyte but their role in protection and pathology is highly contradictory. Moreover, a subset of low-density neutrophils (LDNs) has been identified in TB, but their functions remain unclear. Here, we have analyzed total neutrophils and their low-density and normal-density (NDNs) subsets in patients with active TB disease, in terms of frequency, phenotype, functional features, and gene expression signature. Full-blood counts from Healthy Donors (H.D.), Latent TB infected, active TB, and cured TB patients were performed. Frequency, phenotype, burst activity, and suppressor T cell activity of the two different subsets were assessed by flow cytometry while NETosis and phagocytosis were evaluated by confocal microscopy. Expression analysis was performed by using the semi-quantitative RT-PCR array technology. Elevated numbers of total neutrophils and a high neutrophil/lymphocyte ratio distinguished patients with active TB from all the other groups. PBMCs of patients with active TB disease contained elevated percentages of LDNs compared with those of H.D., with an increased expression of CD66b, CD33, CD15, and CD16 compared to NDNs. Transcriptomic analysis of LDNs and NDNs purified from the peripheral blood of TB patients identified 12 genes differentially expressed: CCL5, CCR5, CD4, IL10, LYZ, and STAT4 were upregulated, while CXCL8, IFNAR1, NFKB1A, STAT1, TICAM1, and TNF were downregulated in LDNs, as compared to NDNs. Differently than NDNs, LDNs failed to phagocyte live Mycobacterium tuberculosis (M. tuberculosis) bacilli, to make oxidative burst and NETosis, but caused significant suppression of antigen-specific and polyclonal T cell proliferation which was partially mediated by IL-10. These insights add a little dowel of knowledge in understanding the pathogenesis of human TB

    Ab initio study of the vapour-liquid critical point of a symmetrical binary fluid mixture

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    A microscopic approach to the investigation of the behaviour of a symmetrical binary fluid mixture in the vicinity of the vapour-liquid critical point is proposed. It is shown that the problem can be reduced to the calculation of the partition function of a 3D Ising model in an external field. For a square-well symmetrical binary mixture we calculate the parameters of the critical point as functions of the microscopic parameter r measuring the relative strength of interactions between the particles of dissimilar and similar species. The calculations are performed at intermediate (λ=1.5\lambda=1.5) and moderately long (λ=2.0\lambda=2.0) intermolecular potential ranges. The obtained results agree well with the ones of computer simulations.Comment: 14 pages, Latex2e, 5 eps-figures included, submitted to J.Phys:Cond.Ma

    Indoor Fast Neutron Generator for Biophysical and Electronic Applications

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    This study focuses the attention on an indoor fast neutron generator for biophysical and electronic applications. More specifically, the findings obtained by several simulations with the MCNP Monte Carlo code, necessary for the realization of a shield for indoor measurements, are presented. Furthermore, an evaluation of the neutron spectrum modification caused by the shielding is reported. Fast neutron generators are a valid and interesting available source of neutrons, increasingly employed in a wide range of research fields, such as science and engineering. The employed portable pulsed neutron source is a MP320 Thermo Scientific neutron generator, able to generate 2.5 MeV neutrons with a neutron yield of 2.0 x 106 n/s, a pulse rate of 250 Hz to 20 KHz and a duty factor varying from 5% to 100%. The neutron generator, based on Deuterium-Deuterium nuclear fusion reactions, is employed in conjunction with a solid-state photon detector, made of n-type high-purity germanium (PINS-GMX by ORTEC) and it is mainly addressed to biophysical and electronic studies. The present study showed a proposal for the realization of a shield necessary for indoor applications for MP320 neutron generator, with a particular analysis of the transport of neutrons simulated with Monte Carlo code and described the two main lines of research in which the source will be used

    Vasospastic angina and scombroid syndrome: a case report

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    Scombroid syndrome is a fish poisoning characterised by the onset of symptoms compatible with a pseudoallergic reaction; it is rarely also responsible of signs and symptoms of acute coronary syndromes, as demonstrated in this case repor

    Minimally invasive aortic valve surgery

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    Aortic valve disease is a prevalent disorder that affects approximately 2% of the general adult population. Surgical aortic valve replacement is the gold standard treatment for symptomatic patients. This treatment has demonstrably proven to be both safe and effective. Over the last few decades, in an attempt to reduce surgical trauma, different minimally invasive approaches for aortic valve replacement have been developed and are now being increasingly utilized. A narrative review of the literature was carried out to describe the surgical techniques for minimally invasive aortic valve surgery and report the results from different experienced centers. Minimally invasive aortic valve replacement is associated with low perioperative morbidity, mortality and a low conversion rate to full sternotomy. Long-term survival appears to be at least comparable to that reported for conventional full sternotomy. Minimally invasive aortic valve surgery, either with a partial upper sternotomy or a right anterior minithoracotomy provides early- and long-term benefits. Given these benefits, it may be considered the standard of care for isolated aortic valve disease

    Clusterin, a haploinsufficient tumor suppressor gene in neuroblastomas

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    This article is available open access through the publisher’s website. Copyright @ 2009 The Authors.Background - Clusterin expression in various types of human cancers may be higher or lower than in normal tissue, and clusterin may promote or inhibit apoptosis, cell motility, and inflammation. We investigated the role of clusterin in tumor development in mouse models of neuroblastoma. Methods - We assessed expression of microRNAs in the miR-17-92 cluster by real-time reverse transcription–polymerase chain reaction in MYCN-transfected SH-SY5Y and SH-EP cells and inhibited expression by transfection with microRNA antisense oligonucleotides. Tumor development was studied in mice (n = 66) that were heterozygous or homozygous for the MYCN transgene and/or for the clusterin gene; these mice were from a cross between MYCN-transgenic mice, which develop neuroblastoma, and clusterin-knockout mice. Tumor growth and metastasis were studied in immunodeficient mice that were injected with human neuroblastoma cells that had enhanced (by clusterin transfection, four mice per group) or reduced (by clusterin short hairpin RNA [shRNA] transfection, eight mice per group) clusterin expression. All statistical tests were two-sided. Results - Clusterin expression increased when expression of MYCN-induced miR-17-92 microRNA cluster in SH-SY5Y neuroblastoma cells was inhibited by transfection with antisense oligonucleotides compared with scrambled oligonucleotides. Statistically significantly more neuroblastoma-bearing MYCN-transgenic mice were found in groups with zero or one clusterin allele than in those with two clusterin alleles (eg, 12 tumor-bearing mice in the zero-allele group vs three in the two-allele group, n = 22 mice per group; relative risk for neuroblastoma development = 4.85, 95% confidence interval [CI] = 1.69 to 14.00; P = .005). Five weeks after injection, fewer clusterin-overexpressing LA-N-5 human neuroblastoma cells than control cells were found in mouse liver or bone marrow, but statistically significantly more clusterin shRNA-transfected HTLA230 cells (3.27%, with decreased clusterin expression) than control-transfected cells (1.53%) were found in the bone marrow (difference = 1.74%, 95% CI = 0.24% to 3.24%, P = .026). Conclusions - We report, to our knowledge, the first genetic evidence that clusterin is a tumor and metastasis suppressor gene.Sport Aiding Medical Research for Kids (SPARKS), Great Ormond Street Hospital/National Health Service, the National Cancer Institute and University of Parma
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