1,244 research outputs found

    Simulation of Surface Runoff and Channel Flows Using a 2D Numerical Model

    Get PDF
    Numerical simulation of surface runoff is used to understand and predict watershed sediment transport and water quality and improve management of agricultural watersheds. However, models currently available are either simplified or parameterized for efficiency. In this chapter, CCHE2D, a physically based hydrodynamic model for general free surface flow hydrodynamics, was applied to study watershed surface runoff and channel flows. Multiple analytical solutions and experimental data were used to verify and validate this finite element model systematically with good results. A numerical scheme for correcting the bilinear interpolation of the water surface elevation solutions from the cell centers to the computational nodes was developed to improve the model. The correction was found necessary and effective for the sheet runoff simulations over the irregular bed topography. The modified numerical model was then used to simulate storms in a low-relief agricultural watershed in the Mississippi River alluvial plain. This physically based model identified the channel networks, watershed boundary automatically, and helped to develop rating curves at the gage station of this complex watershed. The numerical simulations resolved detailed runoff and turbulent channel flows, which can be used for soil erosion and gully development analyses

    Structural basis of human kinesin-8 function and inhibition

    Get PDF
    Kinesin motors play diverse roles in mitosis and are targets for anti-mitotic drugs. The clinical significance of these motors emphasizes the importance of understanding the molecular basis of their function. Equally, investigations into the modes of inhibition of these motors provide crucial information about their molecular mechanisms. Kif18A regulates spindle microtubules through its dual functionality – microtubule-based stepping and regulation of microtubule dynamics. We investigated the mechanism of Kif18A and its inhibition by the small molecule BTB-1. The Kif18A motor domain drives ATP-dependent plus-end microtubule gliding, and undergoes conformational changes consistent with canonical mechanisms of plus-end directed motility. The Kif18A motor domain also depolymerises microtubule plus and minus ends. BTB-1 inhibits both microtubule-based Kif18A activities. A reconstruction of BTB-1-bound, microtubule-bound Kif18A, in combination with computational modelling, identified an allosteric BTB-1 binding site near loop5, where it blocks the ATP-dependent conformational changes we characterised. Strikingly, BTB-1 binding is close to that of well-characterised Kif11 inhibitors that block tight microtubule binding, whereas BTB-1 traps Kif18A on the microtubule. Our work highlights a general mechanism of kinesin inhibition in which small molecule binding near loop5 prevents a range of conformational changes, blocking motor function

    Teachers as writers: a systematic review

    Get PDF
    This paper is a critical literature review of empirical work from 1990-2015 on teachers as writers. It interrogates the evidence on teachers’ attitudes to writing, their sense of themselves as writers and the potential impact of teacher writing on pedagogy or student outcomes in writing. The methodology was carried out in four stages. Firstly, educational databases keyword searches located 438 papers. Secondly, initial screening identified 159 for further scrutiny, 43 of which were found to specifically address teachers’ writing identities and practices. Thirdly, these sources were screened further using inclusion/exclusion criteria. Fourthly, the 22 papers judged to satisfy the criteria were subject to in-depth analysis and synthesis. The findings reveal that the evidence base in relation to teachers as writers is not strong, particularly with regard to the impact of teachers’ writing on student outcomes. The review indicates that teachers have narrow conceptions of what counts as writing and being a writer and that multiple tensions exist, relating to low self-confidence, negative writing histories, and the challenge of composing and enacting teacher and writer positions in school. However, initial training and professional development programmes do appear to afford opportunities for reformulation of attitudes and sense of self as writer

    Workplace Health Promotion and Mental Health: Three-Year Findings from Partnering Healthy@Work

    Get PDF
    This study aimed to investigate the association between mental health and comprehensive workplace health promotion (WHP) delivered to an entire state public service workforce (~28,000 employees) over a three-year period. Government departments in a state public service were supported to design and deliver a comprehensive, multi-component health promotion program, Healthy@Work, which targeted modifiable health risks including unhealthy lifestyles and stress. Repeated cross-sectional surveys compared self-reported psychological distress (Kessler-10; K10) at commencement (N = 3406) and after 3 years (N = 3228). WHP availability and participation over time was assessed, and associations between the K10 and exposure to programs estimated. Analyses were repeated for a cohort subgroup (N = 580). Data were weighted for non-response. Participation in any mental health and lifestyle programs approximately doubled after 3 years. Both male and female employees with poorer mental health participated more often over time. Women's psychological distress decreased over time but this change was only partially attributable to participation in WHP, and only to lifestyle interventions. Average psychological distress did not change over time for men. Unexpectedly, program components directly targeting mental health were not associated with distress for either men or women. Cohort results corroborated findings. Healthy@Work was successful in increasing participation across a range of program types, including for men and women with poorer mental health. A small positive association of participation in lifestyle programs with mental health was observed for women but not men. The lack of association of mental health programs may have reflected program quality, its universality of application or other contextual factors

    Assessing the Long Term Impact of Phosphorus Fertilization on Phosphorus Loadings Using AnnAGNPS

    Get PDF
    High phosphorus (P) loss from agricultural fields has been an environmental concern because of potential water quality problems in streams and lakes. To better understand the process of P loss and evaluate the effects of different phosphorus fertilization rates on phosphorus losses, the USDA Annualized AGricultural Non-Point Source (AnnAGNPS) pollutant loading model was applied to the Ohio Upper Auglaize watershed, located in the southern portion of the Maumee River Basin. In this study, the AnnAGNPS model was calibrated using USGS monitored data; and then the effects of different phosphorus fertilization rates on phosphorus loadings were assessed. It was found that P loadings increase as fertilization rate increases, and long term higher P application would lead to much higher P loadings to the watershed outlet. The P loadings to the watershed outlet have a dramatic change after some time with higher P application rate. This dramatic change of P loading to the watershed outlet indicates that a “critical point” may exist in the soil at which soil P loss to water changes dramatically. Simulations with different initial soil P contents showed that the higher the initial soil P content is, the less time it takes to reach the “critical point” where P loadings to the watershed outlet increases dramatically. More research needs to be done to understand the processes involved in the transfer of P between the various stable, active and labile states in the soil to ensure that the model simulations are accurate. This finding may be useful in setting up future P application and management guidelines

    Competitive Performance Effects of Psychological Skill Training for Youth Swimmers

    Get PDF
    This study assessed the effect of two different psychological methods of skills training-self-talk and goal setting-on the swimming performance of youth swimmers. We allocated a convenience sample of club and county level youth swimmers ( N  = 49; M age  = 10.8, SD  = 1.25) to one of the three groups: self-talk, goal setting, or a control group engaged in no systematic psychological method of skills training. The groups were balanced in terms of competitive performance ability, age, and gender. Participants in the experimental conditions (self-talk and goal setting) completed a 5-week psychological skills intervention program and were measured on pre- and post-200-m swimming time in competition. After controlling for level of engagement in the program, analysis of covariance revealed a significant omnibus effect ( p  = .006, η p 2  = .20) with post hoc pairwise comparisons using magnitude-based statistics demonstrating that goal setting had a small positive effect compared with self-talk ( η 2 = .40; ± 0.45). Both self-talk ( η 2 = .50; ±0.48) and goal setting ( η 2 = .71; ±0.4) showed a small and moderate positive effect, respectively, relative to the control group. A social validation check confirmed that the swimmers found the intervention to be relevant, beneficial, and meaningful for improving performance. Psychological skills training may be effective in improving youth swimming performance; specific mechanisms underlying these benefits need further exploration

    Biased agonists of the kappa opioid receptor suppress pain and itch without causing sedation or dysphoria

    Get PDF
    Agonists targeting the kappa opioid receptor (KOR) have been promising therapeutic candidates because of their efficacy for treating intractable itch and relieving pain. Unlike typical opioid narcotics, KOR agonists do not produce euphoria or lead to respiratory suppression or overdose. However, they do produce dysphoria and sedation, side effects that have precluded their clinical development as therapeutics. KOR signaling can be fine-tuned to preferentially activate certain pathways over others, such that agonists can bias signaling so that the receptor signals through G proteins rather than other effectors such as βarrestin2. We evaluated a newly developed G protein signaling–biased KOR agonist in preclinical models of pain, pruritis, sedation, dopamine regulation, and dysphoria. We found that triazole 1.1 retained the antinociceptive and antipruritic efficacies of a conventional KOR agonist, yet it did not induce sedation or reductions in dopamine release in mice, nor did it produce dysphoria as determined by intracranial self-stimulation in rats. These data demonstrated that biased agonists may be used to segregate physiological responses downstream of the receptor. Moreover, the findings suggest that biased KOR agonists may present a means to treat pain and intractable itch without the side effects of dysphoria and sedation and with reduced abuse potential

    Detection of enterovirus RNA in peripheral blood mononuclear cells correlates with the presence of the predisposing allele of the type 1 diabetes risk gene IFIH1 and with disease stage

    Get PDF
    Aims/hypothesis Enteroviral infection has been implicated consistently as a key environmental factor correlating with the appearance of autoimmunity and/or the presence of overt type 1 diabetes, in which pancreatic insulin-producing beta cells are destroyed by an autoimmune response. Genetic predisposition through variation in the type 1 diabetes risk gene IFIH1 (interferon induced with helicase C domain 1), which encodes the viral pattern-recognition receptor melanoma differentiation-associated protein 5 (MDA5), supports a potential link between enterovirus infection and type 1 diabetes. Methods We used molecular techniques to detect enterovirus RNA in peripheral blood samples (in separated cellular compartments or plasma) from two cohorts comprising 79 children or 72 adults that include individuals with and without type 1 diabetes who had multiple autoantibodies. We also used immunohistochemistry to detect the enteroviral protein VP1 in the pancreatic islets of post-mortem donors (n=43) with type 1 diabetes. Results We observed enhanced detection sensitivity when sampling the cellular compartment compared with the non-cellular compartment of peripheral blood (OR 21.69; 95% CI 3.64, 229.20; p Conclusions/interpretation Our data indicate that, in peripheral blood, antigen-presenting cells are the predominant source of enterovirus infection, and that infection is correlated with disease stage and genetic predisposition, thereby supporting a role for enterovirus infection prior to disease onset.Peer reviewe

    A multicenter, prospective study of a new fully covered expandable metal biliary stent for the palliative treatment of malignant bile duct obstruction

    Get PDF
    Background and Study Aims. Endoscopic placement of self-expanding metal stents (SEMSs) is indicated for palliation of inoperable malignant biliary obstruction. A fully covered biliary SEMS (WallFlex Biliary RX Boston Scientific, Natick, USA) was assessed for palliation of extrahepatic malignant biliary obstruction. Patients and Methods. 58 patients were included in this prospective, multicenter series conducted under an FDA-approved IDE. Main outcome measurements included (1) absence of stent occlusion within six months or until death, whichever occurred first and (2) technical success, need for reintervention, bilirubin levels, stent patency, time to stent occlusion, and adverse events. Results. Technical success was achieved in 98% (57/58), with demonstrated acute removability in two patients. Adequate clinical palliation until completion of followup was achievedin 98% (54/55) of evaluable patients, with 1 reintervention due to stent obstruction after 142 days. Mean total bilirubin decreased from 8.9 mg/dL to 1.2 mg/dL at 1 month. Device-related adverse events were limited and included 2 cases of cholecystitis. One stent migrated following radiation therapy. Conclusions. The WallFlex Biliary fully covered stent yielded technically successful placement with uncomplicated acute removal where required, appropriate reduction in bilirubin levels, and low rates of stent migration and occlusion. This SEMS allows successful palliation of malignant extrahepatic biliary obstruction
    corecore