497 research outputs found

    Electric-field-induced displacement of a charged spherical colloid embedded in an elastic Brinkman medium

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    When an electric field is applied to an electrolyte-saturated polymer gel embedded with charged colloidal particles, the force that must be exerted by the hydrogel on each particle reflects a delicate balance of electrical, hydrodynamic and elastic stresses. This paper examines the displacement of a single charged spherical inclusion embedded in an uncharged hydrogel. We present numerically exact solutions of coupled electrokinetic transport and elastic-deformation equations, where the gel is treated as an incompressible, elastic Brinkman medium. This model problem demonstrates how the displacement depends on the particle size and charge, the electrolyte ionic strength, and Young's modulus of the polymer skeleton. The numerics are verified, in part, with an analytical (boundary-layer) theory valid when the Debye length is much smaller than the particle radius. Further, we identify a close connection between the displacement when a colloid is immobilized in a gel and its velocity when dispersed in a Newtonian electrolyte. Finally, we describe an experiment where nanometer-scale displacements might be accurately measured using back-focal-plane interferometry. The purpose of such an experiment is to probe physicochemical and rheological characteristics of hydrogel composites, possibly during gelation

    A Geophysical Atlas for Interpretation of Satellite-derived Data

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    A compilation of maps of global geophysical and geological data plotted on a common scale and projection is presented. The maps include satellite gravity, magnetic, seismic, volcanic, tectonic activity, and mantle velocity anomaly data. The Bibliographic references for all maps are included

    Molecular determinants of a competent bovine corpus luteum: first vs final wave dominant follicles

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    Reproductive management in cattle requires the synchrony of follicle development and oestrus before insemination. However, ovulation of follicles that have not undergone normal physiological maturation can lead to suboptimal luteal function. Here, we investigated the expression of a targeted set of 47 genes in (a) a first-wave vs final-wave dominant follicle (DF; the latter destined to ovulate spontaneously) and (b) 6-day-old corpora lutea (CLs) following either spontaneous ovulation or induced ovulation of a first-wave DF to ascertain their functional significance for competent CL development. Both the mass and progesterone-synthesising capacity of a CL formed following induced ovulation of a first-wave DF were impaired. These impaired CLs had reduced expression of steroidogenic enzymes (e.g. STAR and HSD3B1), luteotrophic receptors (LHCGR) and angiogenic regulators (e.g. VEGFA) and increased expression of BMP2 (linked to luteolysis). Relative to final-wave DFs, characteristic features of first-wave DFs included reduced oestradiol concentrations and a reduced oestradiol:progesterone ratio in the face of increased expression of key steroidogenic enzymes (i.e. CYP11A1, HSD3B1 and CYP19A1) in granulosa cells and reduced expression of the HDL receptor SCARB1 in thecal cells. Transcripts for further components of the TGF and IGF systems (e.g. INHA, INHBA, IGF2R and IGFBP2) varied between the first- and final-wave DFs. These results highlight the importance of hormones such as progesterone interacting with local components of both the TGF and IGF systems to affect the maturation of the ovulatory follicle and functional competency of the subsequent CL

    Diverging Mechanisms of Activation of Chemokine Receptors Revealed by Novel Chemokine Agonists

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    CXCL8/interleukin-8 is a pro-inflammatory chemokine that triggers pleiotropic responses, including inflammation, angiogenesis, wound healing and tumorigenesis. We engineered the first selective CXCR1 agonists on the basis of residue substitutions in the conserved ELR triad and CXC motif of CXCL8. Our data reveal that the molecular mechanisms of activation of CXCR1 and CXCR2 are distinct: the N-loop of CXCL8 is the major determinant for CXCR1 activation, whereas the N-terminus of CXCL8 (ELR and CXC) is essential for CXCR2 activation. We also found that activation of CXCR1 cross-desensitized CXCR2 responses in human neutrophils co-expressing both receptors, indicating that these novel CXCR1 agonists represent a new class of anti-inflammatory agents. Further, these selective CXCR1 agonists will aid at elucidating the functional significance of CXCR1 in vivo under pathophysiological conditions

    Use of Quantitative Pharmacology in the Development of HAE1, a High-Affinity Anti-IgE Monoclonal Antibody

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    HAE1, a high-affinity anti-IgE monoclonal antibody, is discussed here as a case study in the use of quantitative pharmacology in the development of a second-generation molecule. In vitro, preclinical, and clinical data from the first-generation molecule, omalizumab, were heavily leveraged in the HAE1 program. A preliminary mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model for HAE1 was developed using an existing model for omalizumab, together with in vitro binding data for HAE1 and omalizumab. When phase I data were available, the model was refined by simultaneously modeling PK/PD data from omalizumab studies with the available HAE1 phase I data. The HAE1 clinical program was based on knowledge of the quantitative relationship between a pharmacodynamic biomarker, suppression of free IgE, and clinical response (e.g., lower exacerbation rates) obtained in pivotal studies with omalizumab. A clinical trial simulation platform was developed to predict free IgE levels and clinical responses following attainment of a target free IgE level (≤10 IU/ml). The simulation platform enabled selection of four doses for the phase II dose-ranging trial by two independent methods: dose-response non-linear fitting and linear mixed modeling. Agreement between the two methods provided confidence in the doses selected. Modeling and simulation played a large role in supporting acceleration of the HAE1 program by enabling data-driven decision-making, often based on confirmation of projections and/or learning from incoming new data

    Prevalence and risk factors for mesh erosion after laparoscopic-assisted sacrocolpopexy

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    The purpose of this study is to identify risk factors for mesh erosion in women undergoing minimally invasive sacrocolpopexy (MISC). We hypothesize that erosion is higher in subjects undergoing concomitant hysterectomy. This is a retrospective cohort study of women who underwent MISC between November 2004 and January 2009. Demographics, operative techniques, and outcomes were abstracted from medical records. Multivariable regression identified odds of erosion. Of 188 MISC procedures 19(10%) had erosions. Erosion was higher in those with total vaginal hysterectomy (TVH) compared to both post-hysterectomy (23% vs. 5%, p = 0.003) and supracervical hysterectomy (SCH) (23% vs. 5%, p = 0.109) groups. In multivariable regression, the odds of erosion for TVH was 5.67 (95% CI: 1.88–17.10) compared to post-hysterectomy. Smoking, the use of collagen-coated mesh, transvaginal dissection, and mesh attachment transvaginally were no longer significant in the multivariable regression model. Based on this study, surgeons should consider supracervical hysterectomy over total vaginal hysterectomy as the procedure of choice in association with MISC unless removal of the cervix is otherwise indicated

    A farm-level study of risk factors associated with the colonization of broiler flocks with Campylobacter spp. in Iceland, 2001 – 2004

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    <p>Abstract</p> <p>Background</p> <p>Following increased rates of human campylobacteriosis in the late 1990's, and their apparent association with increased consumption of fresh chicken meat, a longitudinal study was conducted in Iceland to identify the means to decrease the frequency of broiler flock colonization with <it>Campylobacter</it>. Our objective in this study was to identify risk factors for flock colonization acting at the broiler farm level.</p> <p>Methods</p> <p>Between May 2001 and September 2004, pooled caecal samples were obtained from 1,425 flocks at slaughter and cultured for <it>Campylobacter</it>. Due to the strong seasonal variation in flock prevalence, analyses were restricted to a subset of 792 flocks raised during the four summer seasons. Flock results were collapsed to the farm level, such that the number of positive flocks and the total number of flocks raised were summed for each farm. Logistic regression models were fitted to the data using automated and manual selection methods. Variables of interest included manure management, water source and treatment, other poultry/livestock on farm, and farm size and management.</p> <p>Results</p> <p>The 792 flocks raised during the summer seasons originated from 83 houses on 33 farms, and of these, 217 (27.4%) tested positive. The median number of flocks per farm was 14, and the median number of positive flocks per farm was three. Three farms did not have any positive flocks. In general, factors associated with an increased risk of <it>Campylobacter </it>were increasing median flock size on the farm (p ≤ 0.001), spreading manure on the farm (p = 0.004 to 0.035), and increasing the number of broiler houses on the farm (p = 0.008 to 0.038). Protective factors included the use of official (municipal) (p = 0.004 to 0.051) or official treated (p = 0.006 to 0.032) water compared to the use of non-official untreated water, storing manure on the farm (p = 0.025 to 0.029), and the presence of other domestic livestock on the farm (p = 0.004 to 0.028).</p> <p>Conclusion</p> <p>Limiting the average flock size, and limiting the number of houses built on new farms, are interventions that require investigation. Water may play a role in the transmission of <it>Campylobacter</it>, therefore the use of official water, and potentially, treating non-official water may reduce the risk of colonization. Manure management practices deserve further attention.</p
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