223 research outputs found

    A COMPARISON BETWEEN THE VALUES OBTAINED FROM ACTIVE DRAG ANALYSIS COMPARED TO FORCES PRODUCED IN TETHERED SWIMMING

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    The purpose of this study was to identify in a maximum swim effort by elite freestyle swimmers, if the mean force produced in tethered swimming over a set number of whole strokes could reliably be utilised as an alternative measure for mean propulsive force over the same number of whole strokes. Tethered force can be measured relatively easily. Although mean propulsive force at a maximum swim velocity may be derived, the process of doing so is not direct, is time consuming and requires an extensive setup. Stepwise regression analysis indicated that mean tethered force was not an acceptable alternative for mean propulsive force. Therefore the use of mean propulsive power to monitor training would require the measurement of mean propulsive force rather than simply measuring the mean tethered force in a maximum swim effort

    Polymer composite Belleville springs for an automotive application

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    This paper investigates mathematical modelling and manufacturing of polymer composite Belleville springs, and their potential application. The original expression for load carrying capacity developed for metal springs is refined by considering the variation of elastic modulus and Poisson’s ratio of laminates in polar coordinates. A novel series spring stacking arrangement is proposed to achieve complex stiffness variation by progressive action. The experimental results show consistent effect of number of plies on the spring rate and compare well with the theoretical predictions. Although handmade, the variations in load carrying capacity is very small (~10%) confirming manufacturing viability. It is shown that a smooth, variable spring rate curve can be produced by reducing slip-stick frictional forces with the use of spacers within the spring stacks. In one application, the composite springs are shown to offer significant vehicle dynamic performance improvement through reduction of the tyre contact patch force variation and vehicle body acceleration

    Disease causing mutations in inverted formin 2 regulate its binding to G-actin, F-actin capping protein (CapZ α-1) and profilin 2

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    Focal segmental glomerulosclerosis (FSGS) is a devastating form of nephrotic syndrome which ultimately leads to end stage renal failure (ESRF). Mutations in inverted formin 2 (INF2), a member of the formin family of actin-regulating proteins, have recently been associated with a familial cause of nephrotic syndrome characterized by FSGS. INF2 is a unique formin that can both polymerize and depolymerize actin filaments. How mutations in INF2 lead to disease is unknown. In the present study, we show that three mutations associated with FSGS, E184K, S186P and R218Q, reduce INF2 auto-inhibition and increase association with monomeric actin. Furthermore using a combination of GFP–INF2 expression in human podocytes and GFP-Trap purification coupled with MS we demonstrate that INF2 interacts with profilin 2 and the F-actin capping protein, CapZ α-1. These interactions are increased by the presence of the disease causing mutations. Since both these proteins are involved in the dynamic turnover and restructuring of the actin cytoskeleton these changes strengthen the evidence that aberrant regulation of actin dynamics underlies the pathogenesis of disease

    Counterparts: Clothing, value and the sites of otherness in Panapompom ethnographic encounters

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    This is an Author's Accepted Manuscript of an article published in Anthropological Forum, 18(1), 17-35, 2008 [copyright Taylor & Francis], available online at: http://www.tandfonline.com/10.1080/00664670701858927.Panapompom people living in the western Louisiade Archipelago of Milne Bay Province, Papua New Guinea, see their clothes as indices of their perceived poverty. ‘Development’ as a valued form of social life appears as images that attach only loosely to the people employing them. They nevertheless hold Panapompom people to account as subjects to a voice and gaze that is located in the imagery they strive to present: their clothes. This predicament strains anthropological approaches to the study of Melanesia that subsist on strict alterity, because native self‐judgments are located ‘at home’ for the ethnographer. In this article, I develop the notion of the counterpart as a means to explore these forms of postcolonial oppression and their implications for the ethnographic encounter

    Reproductive Safety of Trazodone After Maternal Exposure in Early Pregnancy: A Comparative ENTIS Cohort Study.

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    Trazodone is indicated for the treatment of major depressive disorder, but more frequently prescribed off-label at lower doses for insomnia in women of childbearing age. The aim of this study was to assess the risks linked to trazodone exposure during pregnancy for which limited safety data are available. This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to trazodone in early pregnancy against those in a reference group of women exposed to a selective serotonin reuptake inhibitors (SSRIs) between 1996 and 2021. The sample included 221 trazodone and 869 SSRI-exposed pregnancies. Exposure to trazodone in the first trimester was not associated with a significant difference in the risk of major congenital anomalies (trazodone [1/169, 0.6%]; SSRI [19/730, 2.6%]; adjusted odds ratio, 0.2; 95% confidence interval, 0.03-1.77). The cumulative incidences of live birth were 61% and 73% in the trazodone and reference group, respectively (25% vs 18% for pregnancy loss and 14% vs 10% for pregnancy termination). Trazodone exposure was not associated with a significantly increased risk of pregnancy termination and pregnancy loss. The rate of small for gestational age infants did not differ between the groups. This study did not reveal a significant difference in the risk of major congenital anomalies after first trimester exposure to trazodone, compared with SSRI exposure. Although this study is the largest so far, these results call for confirmation through further studies

    A study of the dissociative recombination of CaO + with electrons: Implications for Ca chemistry in the upper atmosphere

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    The dissociative recombination of CaO+ ions with electrons has been studied in a flowing afterglow reactor. CaO+ was generated by the pulsed laser ablation of a Ca target, followed by entrainment in an Ar+ ion/electron plasma. A kinetic model describing the gas-phase chemistry and diffusion to the reactor walls was fitted to the experimental data, yielding a rate coefficient of (3.0 ± 1.0) × 10¯⁷ cm³ molecule¯¹ s¯¹ at 295 K. This result has two atmospheric implications. First, the surprising observation that the Ca+/Fe+ ratio is ~8 times larger than Ca/Fe between 90 and 100 km in the atmosphere can now be explained quantitatively by the known ion-molecule chemistry of these two metals. Second, the rate of neutralization of Ca+ ions in a descending sporadic E layer is fast enough to explain the often explosive growth of sporadic neutral Ca layers

    The RING-CH ligase K5 antagonizes restriction of KSHV and HIV-1 particle release by mediating ubiquitin-dependent endosomal degradation of tetherin

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    Tetherin (CD317/BST2) is an interferon-induced membrane protein that inhibits the release of diverse enveloped viral particles. Several mammalian viruses have evolved countermeasures that inactivate tetherin, with the prototype being the HIV-1 Vpu protein. Here we show that the human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is sensitive to tetherin restriction and its activity is counteracted by the KSHV encoded RING-CH E3 ubiquitin ligase K5. Tetherin expression in KSHV-infected cells inhibits viral particle release, as does depletion of K5 protein using RNA interference. K5 induces a species-specific downregulation of human tetherin from the cell surface followed by its endosomal degradation. We show that K5 targets a single lysine (K18) in the cytoplasmic tail of tetherin for ubiquitination, leading to relocalization of tetherin to CD63-positive endosomal compartments. Tetherin degradation is dependent on ESCRT-mediated endosomal sorting, but does not require a tyrosine-based sorting signal in the tetherin cytoplasmic tail. Importantly, we also show that the ability of K5 to substitute for Vpu in HIV-1 release is entirely dependent on K18 and the RING-CH domain of K5. By contrast, while Vpu induces ubiquitination of tetherin cytoplasmic tail lysine residues, mutation of these positions has no effect on its antagonism of tetherin function, and residual tetherin is associated with the trans-Golgi network (TGN) in Vpu-expressing cells. Taken together our results demonstrate that K5 is a mechanistically distinct viral countermeasure to tetherin-mediated restriction, and that herpesvirus particle release is sensitive to this mode of antiviral inhibition

    Tetherin Restricts Productive HIV-1 Cell-to-Cell Transmission

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    The IFN-inducible antiviral protein tetherin (or BST-2/CD317/HM1.24) impairs release of mature HIV-1 particles from infected cells. HIV-1 Vpu antagonizes the effect of tetherin. The fate of virions trapped at the cell surface remains poorly understood. Here, we asked whether tetherin impairs HIV cell-to-cell transmission, a major means of viral spread. Tetherin-positive or -negative cells, infected with wild-type or ΔVpu HIV, were used as donor cells and cocultivated with target lymphocytes. We show that tetherin inhibits productive cell-to-cell transmission of ΔVpu to targets and impairs that of WT HIV. Tetherin accumulates with Gag at the contact zone between infected and target cells, but does not prevent the formation of virological synapses. In the presence of tetherin, viruses are then mostly transferred to targets as abnormally large patches. These viral aggregates do not efficiently promote infection after transfer, because they accumulate at the surface of target cells and are impaired in their fusion capacities. Tetherin, by imprinting virions in donor cells, is the first example of a surface restriction factor limiting viral cell-to-cell spread
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