512 research outputs found

    The encapsulation and controlled release of proteins from ā€œmeltableā€ chemically cross-linked hydrogels

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    \ua9 2024 The Authors. Journal of Applied Polymer Science published by Wiley Periodicals LLC.Chemically crosslinked hydrogels can be used for the controlled delivery of therapeutic proteins, however, cargo loading can be challenging. A common approach involves performing the hydrogel crosslinking step in the presence of the cargo proteins, however, this can require the utilization of selective chemistries to ensure the cargos do not chemically react with the forming hydrogel network. We demonstrate that chemically crosslinked hydrogels based upon the protein polymer Capsular antigen fragment 1 (Caf1) can be used to encapsulate proteins within a chemically crosslinked hydrogel network. This encapsulation exploits the ā€œmeltableā€ feature of Caf1 hydrogels, where upon heating the Caf1 protein unfolds with concomitant depolymerization of the hydrogel network. Protein cargos can be loaded into the ā€œmoltenā€ form of the hydrogel which cools with protein refolding and concomitant reformation of the hydrogel network to entrap the cargos, ensuring a more homogenous dispersion of the cargo. Analysis of release profiles indicated lower burst release in comparison to release from identical hydrogels loaded by an absorption method. This work is significant because it suggest that the ā€œmeltableā€ feature of Caf1 hydrogels may present an improved method of loading protein cargos into crosslinked hydrogel networks whilst avoiding the need for crosslinking chemistries

    Hepatic effects of tartrazine (E 102) after systemic exposure are independent of oestrogen receptor interactions in the mouse

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    Tartrazine is a food colour that activates the transcriptional function of the human oestrogen receptor alpha in an in vitro cell model. Since oestrogens are cholestatic, we hypothesised tartrazine will cause periportal injury to the liver in vivo. To test this hypothesis, tartrazine was initially administered systemically to mice resulting in a periportal recruitment of inflammatory cells, increased serum alkaline phosphatase activity and mild periportal fibrosis. To determine whether an oestrogenic effect may be a key event in this response, tartrazine, sulphonated metabolites and a food additive contaminant were screened for their ability to interact with murine oestrogen receptors. In all cases, there were no interactions as agonists or antagonists and further, no oestrogenicity was observed with tartrazine in an in vivo uterine growth assay. To examine the relevance of the hepatic effects of tartrazine to its use as a food additive, tartrazine was orally administered to transgenic NF-ĪŗB-Luc mice. Pre- and concurrent oral treatment with alcohol was incorporated given its potential to promote gut permeability and hepatic inflammation. Tartrazine alone induced NF- ĪŗB activities in the colon and liver but there was no periportal recruitment of inflammatory cells or fibrosis. Tartrazine, its sulphonated metabolites and the contaminant inhibited sulphotransferase activities in murine hepatic S9 extracts. Given the role of sulfotransferases in bile acid excretion, the initiating event giving rise to periportal inflammation and subsequent hepatic pathology through systemic tartrazine exposure is therefore potentially associated an inhibition of bile acid sulphation and excretion and not on oestrogen receptor-mediated transcriptional function. However, these effects were restricted to systemic exposures to tartrazine and did not occur to any significant effect after oral exposure

    Multi-model mapping of phonemic fluency

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    The voluntary generation of non-overlearned responses is usually assessed with phonemic fluency. Like most frontal tasks, it draws upon different complex processes and systems whose precise nature is still incompletely understood. Many claimed aspects regarding the pattern of phonemic fluency performance and its underlying anatomy remain controversial. Major limitations of past investigations include small sample size, scant analysis of phonemic output and methodologically insufficient lesion analysis approaches. We investigated a large number of patients with focal unilateral right or left frontal (n = 110) or posterior (n = 100) or subcortical (n = 65) lesions imaged with magnetic resonance or computed tomography and compared their performance on the number of overall responses, words produced over time, extremely infrequent/unknown words and inappropriate words generated. We also employed, for the first time parcelā€based lesion-symptom mapping, tract-wise statistical analysis as well as Bayesian multi-variate analysis based on meta-analytically defined functional region of interest, including their interactions. We found that left frontal damage was associated with greater impairment than right frontal or posterior damage on overall fluency performance, suggesting that phonemic fluency shows specificity to frontal lesions. We also found that subcorticals, similar to frontals, performed significantly worse than posteriors on overall performance suggesting that subcortical regions are also involved. However, only frontal effects were found for words produced over time, extremely infrequent/unknown and inappropriate words. Parcelā€based lesion-symptom mapping analysis found that worse fluency performance was associated with damage to the posterior segment of the left frontal middle and superior gyrus, the left dorsal anterior cingulate gyrus and caudate nucleus. Tract-wise statistical analysis revealed that disconnections of left frontal tracts are critical. Bayesian multi-variate models of lesions and disconnectome maps implicated left middle and inferior frontal and left dorsomedial frontal regions. Our study suggests that a set of well localized left frontal areas together with subcortical regions and several left frontal tracts are critical for word generation. We speculate that a left lateralized network exists. It involves medial, frontal regions supporting the process of ā€˜energizationā€™, which sustains activation for the duration of the task and middle and inferior frontal regions concerned with ā€˜selectionā€™, required due to the competition produced by associated stored words, respectively. The methodology adopted represents a promising and empirically robust approach in furthering our understanding of the neurocognitive architecture underpinning executive processes

    INFX GUIDE: DEPARTMENT OF ENERGY BILATERAL AGREEMENTS FOR COOPERATION IN THE FIELD OF RADIOACTIVE WASTE MANAGEMENT (INFX: INTERNATIONAL INFORMATION EXCHANGE)

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    As the U. S. Department of Energy (DOE) and DOE contractors have increased the magnitude and scope of their cooperative activities with other nations in the nuclear fuel cycle and waste management field, a need has developed for ready sources of information concerning foreign waste management programs, DOE technology exchange policies, bilateral fuel cycle and waste management agreements and plans and activities to implement those agreements. The INFX (International InLormation E~change) Guide is one of a series of documents that have been prepared to provide that information. The INFX Guide has been compiled under the charter of PNL's International Support Office (IPSO) to maintain for DOE a center to collect, organize, evaluate and disseminate information on foreign and international radioactive waste management programs. Because the information in this document is constantly subject to change, the document is assembled in loose-leaf form to accommodate frequent updates

    The effects of perceived and received support on objective performance outcome.

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    This is a postprint of an article published in European Journal of Sport Science, 2008, Vol. 8, Issue 6, pp. 359 ā€“ 368 Ā© 2008 copyright Taylor & Francis. European Journal of Sport Science is available online at: http://www.tandfonline.com/loi/tejs20In this study, we examined the main and stress-buffering effects of perceived and received support upon objective performance outcome. The sample consisted of 123 male British high performance golfers, mean age 25.3 years (SD = 5.4). Participants completed measures of perceived support, stressors, stress, and received support before competitions. After the competitions, performance outcome (number of shots) was recorded. When both types of support were considered separately, there were significant main effects for perceived (Ī”R2 = .08, b = -.81, p < .01) and received support (Ī”R2 = .05, b = -.68, p < .01) on performance. There were also significant stress-buffering effects for perceived (Ī”R2 = .03, b = -.48, p = .02) and received support (Ī”R2 = .06, b = -.61, p < .01). When both types of support were considered simultaneously, the significant main effect (DR2 = .09, p < .01) was primarily attributable to perceived support (b = -.63, p = .02). The significant stress-buffering effect (DR2 = .06, p = .01) was primarily attributable to received support (b = -.56, p = .04). These results demonstrate the beneficial influence of social support on performance. The findings highlight the need to recognise the distinction between perceived and received support, both in terms of theory and the design of social support interventions with athletes

    Methodology to Estimate Natural- and Vaccine-induced antibodies to Sars-Cov-2 in a Large Geographic Region

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    Accurate estimates of natural and/or vaccine-induced antibodies to SARS-CoV-2 are difficult to obtain. Although model-based estimates of seroprevalence have been proposed, they require inputting unknown parameters including viral reproduction number, longevity of immune response, and other dynamic factors. In contrast to a model-based approach, the current study presents a data-driven detailed statistical procedure for estimating total seroprevalence (defined as antibodies from natural infection or from full vaccination) in a region using prospectively collected serological data and state-level vaccination data. Specifically, we conducted a longitudinal statewide serological survey with 88,605 participants 5 years or older with 3 prospective blood draws beginning September 30, 2020. Along with state vaccination data, as of October 31, 2021, the estimated percentage of those 5 years or older with naturally occurring antibodies to SARS-CoV-2 in Texas is 35.0% (95% CI = (33.1%, 36.9%)). This is 3Ɨ higher than, state-confirmed COVID-19 cases (11.83%) for all ages. The percentage with naturally occurring or vaccine-induced antibodies (total seroprevalence) is 77.42%. This methodology is integral to pandemic preparedness as accurate estimates of seroprevalence can inform policy-making decisions relevant to SARS-CoV-2

    How Does Perceived Support Lead to Better Performance? An Examination of Potential Mechanisms

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    This is a postprint of an article published in Journal of Applied Sport Psychology, 2009, Vol. 21, pp. 421 ā€“ 429 Ā© 2009 copyright Taylor & Francis. Journal of Applied Sport Psychology is available online at: http://www.tandfonline.com/toc/uasp20/currentUsing a high-performance sample of 118 golfers, we examined the relationship between perceived support and performance. Observed variable path analysis revealed that the beneficial effects of perceived support were primarily attributable to esteem support. High levels of esteem support were associated with appraising a competition as less of a threat. Esteem support was also positively associated with situational control, which was positively associated with challenge appraisals and negatively associated with threat appraisals. Challenge appraisals were associated with better performance and threat appraisals with poorer performance. These results highlight possible mechanisms underlying the relationship between esteem support and performance

    Antibody Duration after infection From Sars-Cov-2 in the Texas Coronavirus antibody Response Survey

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    Understanding the duration of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that causes COVID-19 is important to controlling the current pandemic. Participants from the Texas Coronavirus Antibody Response Survey (Texas CARES) with at least 1 nucleocapsid protein antibody test were selected for a longitudinal analysis of antibody duration. A linear mixed model was fit to data from participants (n = 4553) with 1 to 3 antibody tests over 11 months (1 October 2020 to 16 September 2021), and models fit showed that expected antibody response after COVID-19 infection robustly increases for 100 days postinfection, and predicts individuals may remain antibody positive from natural infection beyond 500 days depending on age, body mass index, smoking or vaping use, and disease severity (hospitalized or not; symptomatic or not)

    Job searching with a history of drugs and crime

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    This article explores the experiences and aspirations of offenders with histories of substance misuse in job searching. The analysis is based upon qualitative data from a localised study of 27 men and two women who were undertaking community-based court orders in Scotland. Their perspectives on job searching, job-readiness and aspirations for sustained employment including the role of self-employment are presented. The article concludes that with adequate support, greater tolerance and flexibility by employers and job searchers could contribute to reducing the vicious cycle of suspicion and dishonesty. Policy action needs to be sustained and possibly augmented to include enterprise training

    Measuring the quality and quantity of professional intrapartum support: Testing a computerised systematic observation tool in the clinical setting

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    Background: Continuous support in labour has a significant impact on a range of clinical outcomes, though whether the quality and quantity of support behaviours affects the strength of this impact has not yet been established. To identify the quality and quantity of support, a reliable means of measurement is needed. To this end, a new computerised systematic observation tool, the &lsquo;SMILI' (Supportive Midwifery in Labour Instrument) was developed. The aim of the study was to test the validity and usability of the &lsquo;Supportive Midwifery in Labour Instrument' (SMILI) and to test the feasibility and acceptability of the systematic observation approach in the clinical intrapartum setting. Methods: Systematic observation was combined with a postnatal questionnaire and the collection of data about clinical processes and outcomes for each observed labour. The setting for the study was four National Health Service maternity units in Scotland, UK. Participants in this study were forty five midwives and forty four women. The SMILI was used by trained midwife observers to record labour care provided by midwives. Observations were undertaken for an average of two hours and seventeen minutes during the active first stage of labour and, in 18 cases, the observation included the second stage of labour. Content validity of the instrument was tested by the observers, noting the extent to which the SMILI facilitated the recording of all key aspects of labour care and interactions. Construct validity was tested through exploration of correlations between the data recorded and women's feelings about the support they received. Feasibility and usability data were recorded following each observation by the observer. Internal reliability and construct validity were tested through statistical analysis of the data. Results: One hundred and four hours of labour care were observed and recorded using the SMILI during forty nine labour episodes. Conclusion: The SMILI was found to be a valid and reliable instrument in the intrapartum setting in which it was tested. The study identified that the SMILI could be used to test correlations between the quantity and quality of support and outcomes. The systematic observational approach was found to be an acceptable and feasible method of enquiry
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