1,054 research outputs found

    Compressibility of titanosilicate melts

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    The effect of composition on the relaxed adiabatic bulk modulus (K0) of a range of alkali- and alkaline earth-titanosilicate [X 2 n/n+ TiSiO5 (X=Li, Na, K, Rb, Cs, Ca, Sr, Ba)] melts has been investigated. The relaxed bulk moduli of these melts have been measured using ultrasonic interferometric methods at frequencies of 3, 5 and 7 MHz in the temperature range of 950 to 1600°C (0.02 Pa s < s < 5 Pa s). The bulk moduli of these melts decrease with increasing cation size from Li to Cs and Ca to Ba, and with increasing temperature. The bulk moduli of the Li-, Na-, Ca- and Ba-bearing metasilicate melts decrease with the addition of both TiO2 and SiO2 whereas those of the K-, Rb- and Cs-bearing melts increase. Linear fits to the bulk modulus versus volume fraction of TiO2 do not converge to a common compressibility of the TiO2 component, indicating that the structural role of TiO2 in these melts is dependent on the identity of the cation. This proposition is supported by a number of other property data for these and related melt compositions including heat capacity and density, as well as structural inferences from X-ray absorption spectroscopy (XANES). The compositional dependence of the compressibility of the TiO2 component in these melts explains the difficulty incurred in previous attempts to incorporate TiO2 in calculation schemes for melt compressibility. The empirical relationship KV-4/3 for isostructural materials has been used to evaluate the compressibility-related structural changes occurring in these melts. The alkali metasilicate and disilicate melts are isostructural, independent of the cation. The addition of Ti to the metasilicate composition (i.e. X2TiSiO5), however, results in a series of melts which are not isostructural. The alkaline-earth metasilicate and disilicate compositions are not isostructural, but the addition of Ti to the metasilicate compositions (i.e. XTiSiO5) would appear, on the basis of modulus-volume systematics, to result in the melts becoming isostructural with respect to compressibility

    Identification and Dynamics of a Heparin-Binding Site in Hepatocyte Growth Factor †

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    Hepatocyte growth factor (HGF) is a heparin-binding, multipotent growth factor that transduces a wide range of biological signals, including mitogenesis, motogenesis, and morphogenesis. Heparin or closely related heparan sulfate has profound effects on HGF signaling. A heparin-binding site in the N-terminal (N) domain of HGF was proposed on the basis of the clustering of surface positive charges [Zhou, H., Mazzulla, M. J., Kaufman, J. D., Stahl, S. J., Wingfield, P. T., Rubin, J. S., Bottaro, D. P., and Byrd, R. A. (1998) Structure 6, 109-116]. In the present study, we confirmed this binding site in a heparin titration experiment monitored by nuclear magnetic resonance spectroscopy, and we estimated the apparent dissociation constant (K(d)) of the heparin-protein complex by NMR and fluorescence techniques. The primary heparin-binding site is composed of Lys60, Lys62, and Arg73, with additional contributions from the adjacent Arg76, Lys78, and N-terminal basic residues. The K(d) of binding is in the micromolar range. A heparin disaccharide analogue, sucrose octasulfate, binds with similar affinity to the N domain and to a naturally occurring HGF isoform, NK1, at nearly the same region as in heparin binding. (15)N relaxation data indicate structural flexibility on a microsecond-to-millisecond time scale around the primary binding site in the N domain. This flexibility appears to be dramatically reduced by ligand binding. On the basis of the NK1 crystal structure, we propose a model in which heparin binds to the two primary binding sites and the N-terminal regions of the N domains and stabilizes an NK1 dimer

    Fibronectin matrix-mediated cohesion suppresses invasion of prostate cancer cells

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    <p>Abstract</p> <p>Background</p> <p>Invasion is an important early step in the metastatic cascade and is the primary cause of death of prostate cancer patients. In order to invade, cells must detach from the primary tumor. Cell-cell and cell-ECM interactions are important regulators of cohesion - a property previously demonstrated to mediate cell detachment and invasion. The studies reported here propose a novel role for α5β1 integrin - the principle mediator of fibronectin matrix assembly (FNMA) - as an invasion suppressor of prostate cancer cells.</p> <p>Methods</p> <p>Using a combination of biophysical and cell biological methods, and well-characterized prostate cancer cell lines of varying invasiveness, we explore the relationship between cohesion, invasiveness, and FNMA.</p> <p>Results</p> <p>We show that cohesion is inversely proportional to invasive capacity. We also show that more invasive cells express lower levels of α5β1 integrin and lack the capacity for FNMA. Cells were generated to over-express either wild-type α5 integrin or an integrin in which the cytoplasmic domain of α5 was replaced with that of α2. The α2 construct does not promote FNMA. We show that only wild-type α5 integrin promotes aggregate compaction, increases cohesion, and reduces invasion of the more aggressive cells, and that these effects can be blocked by the 70-kDa fibronectin fragment.</p> <p>Conclusions</p> <p>We propose that restoring capacity for FNMA in deficient cells can increase tumor intercellular cohesion to a point that significantly reduces cell detachment and subsequent invasion. In prostate cancer, this could be of therapeutic benefit by blocking an early key step in the metastatic cascade.</p

    Cognitive behaviour therapy versus counselling intervention for anxiety in young people with high-functioning autism spectrum disorders: a pilot randomised controlled trial

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    The use of cognitive-behavioural therapy (CBT) as a treatment for children and adolescents with autism spectrum disorder (ASD) has been explored in a number of trials. Whilst CBT appears superior to no treatment or treatment as usual, few studies have assessed CBT against a control group receiving an alternative therapy. Our randomised controlled trial compared use of CBT against person-centred counselling for anxiety in 36 young people with ASD, ages 12–18. Outcome measures included parent- teacher- and self-reports of anxiety and social disability. Whilst each therapy produced improvements inparticipants, neither therapy was superior to the other to a significant degree on any measure. This is consistent with findings for adults

    Winter Bird Assemblages in Rural and Urban Environments: A National Survey

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    Urban development has a marked effect on the ecological and behavioural traits of many living organisms, including birds. In this paper, we analysed differences in the numbers of wintering birds between rural and urban areas in Poland. We also analysed species richness and abundance in relation to longitude, latitude, human population size, and landscape structure. All these parameters were analysed using modern statistical techniques incorporating species detectability. We counted birds in 156 squares (0.25 km2 each) in December 2012 and again in January 2013 in locations in and around 26 urban areas across Poland (in each urban area we surveyed 3 squares and 3 squares in nearby rural areas). The influence of twelve potential environmental variables on species abundance and richness was assessed with Generalized Linear Mixed Models, Principal Components and Detrended Correspondence Analyses. Totals of 72 bird species and 89,710 individual birds were recorded in this study. On average (±SE) 13.3 ± 0.3 species and 288 ± 14 individuals were recorded in each square in each survey. A formal comparison of rural and urban areas revealed that 27 species had a significant preference; 17 to rural areas and 10 to urban areas. Moreover, overall abundance in urban areas was more than double that of rural areas. There was almost a complete separation of rural and urban bird communities. Significantly more birds and more bird species were recorded in January compared to December. We conclude that differences between rural and urban areas in terms of winter conditions and the availability of resources are reflected in different bird communities in the two environments

    Seroprevalence following the second wave of pandemic 2009 H1N1 influenza in Pittsburgh, PA, USA

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    Background: In April 2009, a new pandemic strain of influenza infected thousands of persons in Mexico and the United States and spread rapidly worldwide. During the ensuing summer months, cases ebbed in the Northern Hemisphere while the Southern Hemisphere experienced a typical influenza season dominated by the novel strain. In the fall, a second wave of pandemic H1N1 swept through the United States, peaking in most parts of the country by mid October and returning to baseline levels by early December. The objective was to determine the seroprevalence of antibodies against the pandemic 2009 H1N1 influenza strain by decade of birth among Pittsburgh-area residents. Methods and Findings: Anonymous blood samples were obtained from clinical laboratories and categorized by decade of birth from 1920-2009. Using hemagglutination-inhibition assays, approximately 100 samples per decade (n = 846) were tested from blood samples drawn on hospital and clinic patients in mid-November and early December 2009. Age specific seroprevalences against pandemic H1N1 (A/California/7/2009) were measured and compared to seroprevalences against H1N1 strains that had previously circulated in the population in 2007, 1957, and 1918. (A/Brisbane/59/2007, A/Denver/1/ 1957, and A/South Carolina/1/1918). Stored serum samples from healthy, young adults from 2008 were used as a control group (n = 100). Seroprevalences against pandemic 2009 H1N1 influenza varied by age group, with children age 10-19 years having the highest seroprevalence (45%), and persons age 70-79 years having the lowest (5%). The baseline seroprevalence among control samples from 18-24 year-olds was 6%. Overall seroprevalence against pandemic H1N1 across all age groups was approximately 21%. Conclusions: After the peak of the second wave of 2009 H1N1, HAI seroprevalence results suggest that 21% of persons in the Pittsburgh area had become infected and developed immunity. Extrapolating to the entire US population, we estimate that at least 63 million persons became infected in 2009. As was observed among clinical cases, this sero-epidemiological study revealed highest infection rates among school-age children. © 2010 Zimmer et al

    Gene silencing in tick cell lines using small interfering or long double-stranded RNA

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    Gene silencing by RNA interference (RNAi) is an important research tool in many areas of biology. To effectively harness the power of this technique in order to explore tick functional genomics and tick-microorganism interactions, optimised parameters for RNAi-mediated gene silencing in tick cells need to be established. Ten cell lines from four economically important ixodid tick genera (Amblyomma, Hyalomma, Ixodes and Rhipicephalus including the sub-species Boophilus) were used to examine key parameters including small interfering RNA (siRNA), double stranded RNA (dsRNA), transfection reagent and incubation time for silencing virus reporter and endogenous tick genes. Transfection reagents were essential for the uptake of siRNA whereas long dsRNA alone was taken up by most tick cell lines. Significant virus reporter protein knockdown was achieved using either siRNA or dsRNA in all the cell lines tested. Optimum conditions varied according to the cell line. Consistency between replicates and duration of incubation with dsRNA were addressed for two Ixodes scapularis cell lines; IDE8 supported more consistent and effective silencing of the endogenous gene subolesin than ISE6, and highly significant knockdown of the endogenous gene 2I1F6 in IDE8 cells was achieved within 48 h incubation with dsRNA. In summary, this study shows that gene silencing by RNAi in tick cell lines is generally more efficient with dsRNA than with siRNA but results vary between cell lines and optimal parameters need to be determined for each experimental system

    An Innovative Database for Epidemiological Field Studies of Neglected Tropical Diseases

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    The neglected tropical diseases (NTDs) are of major public health importance, accounting for 56.6 million disability-adjusted life years (DALYs), which places them sixth out of the ten leading causes of life years lost to disability and premature death [1]. These diseases are prominent in the developing world where there is low income, poor hygiene, and inadequate sanitation [1],[2]. Recent targeting of these diseases for large-scale control programs by the World Health Organization [3] is likely to increase the number of epidemiological field studies requiring valid and reliable data, in order to determine the most appropriate strategies for control. In order to ensure a control strategy is effective and appropriate, the data need to be of a high standard, and as a result, epidemiological field studies require a rigorous and systematic approach to data management. Recent publications by Ali et al. [4] and Roberts et al. [5] stress that the importance of data management is often underestimated in such studies, with greater emphasis instead placed on the study design, data collection, and data analysis [4],[5]. This can result in an ad hoc approach to data management that ultimately affects the reliability and validity of the data collected and increases the workload involved in data cleaning. There are additional difficulties in developing countries in the collection, entry, management, and analysis of high-quality data, mainly due to limited infrastructure and capacity [4]-[7], which can exacerbate the problems associated with ensuring effective and reliable data management. We undertook an epidemiological study of the transmission dynamics of Schistosoma japonicum in China [8] that necessitated a rigorous approach to the collection and management of an extensive dataset. Some technical and conceptual constraints were encountered as the data management protocols in place were designed for the monitoring and control of schistosomiasis, rather than for the evaluation of a complex epidemiological study, requiring expertise in the principles and practice of data management. Language barriers provided additional challenges in implementing an efficient data management system. Accordingly, we present details of the innovative database we developed, which allowed us to produce data that were protected against data entry errors and therefore more likely to be of high quality and reliability. Furthermore, it also provided us with evidence of protection. This database can also serve as a template for other epidemiological studies of NTDs in the future.Full Tex
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