882 research outputs found

    Structure and Dynamics of amorphous Silica Surfaces

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    We use molecular dynamics computer simulations to study the equilibrium properties of the surface of amorphous silica. Two types of geometries are investigated: i) clusters with different diameters (13.5\AA, 19\AA, and 26.5\AA) and ii) a thin film with thickness 29\AA. We find that the shape of the clusters is independent of temperature and that it becomes more spherical with increasing size. The surface energy is in qualitative agreement with the experimental value for the surface tension. The density distribution function shows a small peak just below the surface, the origin of which is traced back to a local chemical ordering at the surface. Close to the surface the partial radial distribution functions as well as the distributions of the bond-bond angles show features which are not observed in the interior of the systems. By calculating the distribution of the length of the Si-O rings we can show that these additional features are related to the presence of two-membered rings at the surface. The surface density of these structures is around 0.6/nm^2 in good agreement with experimental estimates. From the behavior of the mean-squared displacement at low temperatures we conclude that at the surface the cage of the particles is larger than the one in the bulk. Close to the surface the diffusion constant is somewhat larger than the one in the bulk and with decreasing temperature the relative difference grows. The total vibrational density of states at the surface is similar to the one in the bulk. However, if only the one for the silicon atoms is considered, significant differences are found.Comment: 30 pages of Latex, 16 figure

    cAMP controls cytosolic Ca(2+ )levels in Dictyostelium discoideum

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    BACKGROUND: Differentiating Dictyostelium discoideum amoebae respond upon cAMP-stimulation with an increase in the cytosolic free Ca(2+ )concentration ([Ca(2+)](i)) that is composed of liberation of stored Ca(2+ )and extracellular Ca(2+)-influx. In this study we investigated whether intracellular cAMP is involved in the control of [Ca(2+)](i). RESULTS: We analyzed Ca(2+)-fluxes in a mutant that is devoid of the main cAMP-phosphodiesterase (PDE) RegA and displays an altered cAMP metabolism. In suspensions of developing cells cAMP-activated influx of extracellular Ca(2+ )was reduced as compared to wild type. Yet, single cell [Ca(2+)](i)-imaging of regA(- )amoebae revealed a cAMP-induced [Ca(2+)](i )increase even in the absence of extracellular Ca(2+). The cytosolic presence of the cAMP PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) induced elevated basal [Ca(2+)](i )in both, mutant and wild type cells. Under this condition wild type cells displayed cAMP-activated [Ca(2+)](i)-transients also in nominally Ca(2+)-free medium. In the mutant strain the amplitude of light scattering oscillations and of accompanying cAMP oscillations were strongly reduced to almost basal levels. In addition, chemotactic performance during challenge with a cAMP-filled glass capillary was altered by EGTA-incubation. Cells were more sensitive to EGTA treatment than wild type: already at 2 mM EGTA only small pseudopods were extended and chemotactic speed was reduced. CONCLUSION: We conclude that there is a link between the second messengers cAMP and Ca(2+). cAMP-dependent protein kinase (PKA) could provide for this link as a membrane-permeable PKA-activator also increased basal [Ca(2+)](i )of regA(- )cells. Intracellular cAMP levels control [Ca(2+)](i )by regulating Ca(2+)-fluxes of stores which in turn affect Ca(2+)-influx, light scattering oscillations and chemotactic performance

    Colorectal cancer screening and subsequent incidence of colorectal cancer: Results from the 45 and Up Study

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    Objective: To investigate the association of colorectal cancer (CRC) screening history and subsequent incidence of CRC in New South Wales, Australia. Design, setting and participants: A total of 196 464 people from NSW recruited to the 45 and Up Study,

    Serum proteomic test in advanced non-squamous non-small cell lung cancer treated in first line with standard chemotherapy

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    Background:VeriStrat is a blood-based proteomic test with predictive and prognostic significance in second-line treatments for non-small cell lung cancer (NSCLC). This trial was designed to investigate the role of VeriStrat in first-line treatment of advanced NSCLC with standard chemotherapy. Here we present the results for 76 non-squamous patients treated with a combination of carboplatin or cisplatin with pemetrexed.Methods:The test-assigned classifications of VeriStrat Good or VeriStrat Poor to samples collected at baseline. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and objective response. Exploratory analyses of end points separately in carboplatin/pemetrexed and cisplatin/pemetrexed subgroups were also conducted.Results:Patients classified as VeriStrat Good had longer PFS and OS than VeriStrat Poor: 6.5 vs 1.6 months and 10.8 vs 3.4 months, respectively; the corresponding hazard ratios (HRs) were 0.36 (P<0.0001) and 0.26 (P<0.0001); they were also more likely to achieve objective response. Prognostic significance of VeriStrat was confirmed in multivariate analysis. Significant differences in OS and PFS between Veristrat classifications were also found when treatment subgroups were analysed separately.Conclusions:The trial demonstrated clinical utility of VeriStrat as a prognostic test for standard first-line chemotherapy of non-squamous advanced NSCLC

    Ca(2+ )regulation in the absence of the iplA gene product in Dictyostelium discoideum

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    BACKGROUND: Stimulation of Dictyostelium discoideum with cAMP evokes an elevation of the cytosolic free Ca(2+ )concentration ([Ca(2+)](i)). The [Ca(2+)](i)-change is composed of liberation of stored Ca(2+ )and extracellular Ca(2+)-entry. The significance of the [Ca(2+)](i)-transient for chemotaxis is under debate. Abolition of chemotactic orientation and migration by Ca(2+)-buffers in the cytosol indicates that a [Ca(2+)](i)-increase is required for chemotaxis. Yet, the iplA(- )mutant disrupted in a gene bearing similarity to IP(3)-receptors of higher eukaryotes aggregates despite the absence of a cAMP-induced [Ca(2+)](i)-transient which favours the view that [Ca(2+)](i)-changes are insignificant for chemotaxis. RESULTS: We investigated Ca(2+)-fluxes and the effect of their disturbance on chemotaxis and development of iplA(- )cells. Differentiation was altered as compared to wild type amoebae and sensitive towards manipulation of the level of stored Ca(2+). Chemotaxis was impaired when [Ca(2+)](i)-transients were suppressed by the presence of a Ca(2+)-chelator in the cytosol of the cells. Analysis of ion fluxes revealed that capacitative Ca(2+)-entry was fully operative in the mutant. In suspensions of intact and permeabilized cells cAMP elicited extracellular Ca(2+)-influx and liberation of stored Ca(2+), respectively, yet to a lesser extent than in wild type. In suspensions of partially purified storage vesicles ATP-induced Ca(2+)-uptake and Ca(2+)-release activated by fatty acids or Ca(2+)-ATPase inhibitors were similar to wild type. Mn(2+)-quenching of fura2 fluorescence allows to study Ca(2+)-influx indirectly and revealed that the responsiveness of mutant cells was shifted to higher concentrations: roughly 100 times more Mn(2+ )was necessary to observe agonist-induced Mn(2+)-influx. cAMP evoked a [Ca(2+)](i)-elevation when stores were strongly loaded with Ca(2+), again with a similar shift in sensitivity in the mutant. In addition, basal [Ca(2+)](i )was significantly lower in iplA(- )than in wild type amoebae. CONCLUSION: These results support the view that [Ca(2+)](i)-transients are essential for chemotaxis and differentiation. Moreover, capacitative and agonist-activated ion fluxes are regulated by separate pathways that are mediated either by two types of channels in the plasma membrane or by distinct mechanisms coupling Ca(2+)-release from stores to Ca(2+)-entry in Dictyostelium. The iplA(- )strain retains the capacitative Ca(2+)-entry pathway and an impaired agonist-activated pathway that operates with reduced efficiency or at higher ionic pressure

    Healthcare-use for Major Infectious Disease Syndromes in an Informal Settlement in Nairobi, Kenya

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    A healthcare-use survey was conducted in the Kibera informal settlement in Nairobi, Kenya, in July 2005 to inform subsequent surveillance in the site for infectious diseases. Sets of standardized questionnaires were administered to 1,542 caretakers and heads of households with one or more child(ren) aged less than five years. The average household-size was 5.1 (range 1-15) persons. Most (90%) resided in a single room with monthly rents of US$ 4.50-7.00. Within the previous two weeks, 49% of children (n=1,378) aged less than five years (under-five children) and 18% of persons (n=1,139) aged ≥5 years experienced febrile, diarrhoeal or respiratory illnesses. The large majority (>75%) of illnesses were associated with healthcare-seeking. While licensed clinics were the most-frequently visited settings, kiosks, unlicensed care providers, and traditional healers were also frequently visited. Expense was cited most often (50%) as the reason for not seeking healthcare. Of those who sought healthcare, 34-44% of the first and/or the only visits were made with non-licensed care providers, potentially delaying opportunities for early optimal intervention. The proportions of patients accessing healthcare facilities were higher with diarrhoeal disease and fever (but not for respiratory diseases in under-five children) than those reported from a contemporaneous study conducted in a rural area in Kenya. The findings support community-based rather than facility-based surveillance in this setting to achieve objectives for comprehensive assessment of the burden of disease

    A robot trace maker: modeling the fossil evidence of early invertebrate behavior.

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    The study of trace fossils, the fossilized remains of animal behavior, reveals interesting parallels with recent research in behavior-based robotics. This article reports robot simulations of the meandering foraging trails left by early invertebrates that demonstrate that such trails can be generated by mechanisms similar to those used for robot wall-following. We conclude with the suggestion that the capacity for intelligent behavior shown by many behavior-based robots is similar to that of animals of the late Precambrian and early Cambrian periods approximately 530 to 565 million years ago
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