Oxidation and reduction reactions of hemerythrin and [mu]-sulfidohemerythrin: mechanism of reduction and implications for electron transfer

The reduction of Phascolopsis gouldii methemerythrin Fe(III),Fe(III) to deoxyhemerythrin (Fe(II),Fe(II) consists of three stages, when monitored by UV-visible absorption. The first stage is dependent upon the concentration and nature of the reductant while the second and third stages are not. Rate constants, k(,2) and k(,3), for the latter stages have values of (TURN)2 x 10(\u27-3)s(\u27-1) and (TURN)2 x 10(\u27-4)s(\u27-1), respectively. The reduction of Themiste zostericola methemerythrin gives similar results. The time courses of UV-visible, EPR and Mossbauer spectra are used to support a new mechanism for the reduction of hemerythrin, which accounts for differences observed between hemerythrins isolated from the two species of sipunculid worms;The rates of reduction of Fe(III),Fe(III) (mu)-S(\u272-)methemerythrin (E(DEGREES)\u27 = (TURN)298 mV) and methemerythrin (E(DEGREES)\u27 = 110 mV versus NHE) to the Fe(II)Fe(III) semi-met level by two heme proteins and several inorganic reagents have been measured. Rates of oxidations of the corresponding semi-met forms have also been measured. When using an apparent physiological reducing agent, cytochrome b(,5) from Phascolopsis gouldii, the respective second order rate constants for reduction of (mu)-S(\u272-)methemerythrin and methemerythrin are 8900 M(\u27-1)s(\u27-1) and 160 M(\u27-1)s(\u27-1) at pH 7.5, 0.15 M Na(,2)SO(,4) and 25(DEGREES)C. When using the nonphysiological reducing agent deoxymyoglobin, the respective second order rate constants for reduction of (mu)-S(\u272-)methemerythrin and methemerythrin are 38 M(\u27-1)s(\u27-1) and 1.22 M(\u27-1)s(\u27-1) at pH 6.3, 0.15 M Na(,2)SO(,4) and 25(DEGREES)C. In all cases (excepting oxidation by Co(phen)(,3)(\u273+)) the relative rates for hemerythrin versus (mu)-S(\u272-)hemerythrin are shown to obey the Marcus relation. The rates of oxidation of cytochrome b(,5) by either (mu)-S(\u272-)met- or methemerythrin are 150-400 times faster than those of deoxymyoglobin. Factors contributing to the higher rates with cytochrome b(,5) are discussed;The carcinogen, chromate, slowly oxidizes deoxyhemerythrin to the semi-met level, k(,obs) = 3 ((+OR-)1) x 10(\u27-5)s(\u27-1), at pH 6.0, and stabilizes the conformation labelled (semi-met)(,O) for up to (TURN)60 hours. The value of k(,obs) is independent of chromate and protein concentrations and a reaction mechanism is proposed

How primary schools really work: Architecture, use, and perspectives

Redacted version only, full version is under permanent embargo.Schools are an important class of architecture. This is for many reasons, not least because primary schools are the first public buildings that most children inhabit for a significant amount of their waking hours and are, thus, their first experience of what should be quality built environment design. To ensure this quality, occupied building evaluation should be an important endeavour in architectural practice. Recent school building performance evaluations have been undertaken from the perspective of facilities management, or building-science, using 'expert' judgement to assess the used built environment. This presents two concerns. First, these techno-economic positions assume that behaviour of users is predictable and logical over the life of the school building, and omits the variety of users, activities, and experience of the 'Architecture'. Second, by using so-called professional 'experts', building performance often omits the voice of users (staff and students) who are expert in their own environment. The primary objective of this inquiry was to, first, establish architectural research methods suitable for including primary school users in building performance evaluation and, second, apply it to investigate the context and user perspective of their school built environment. Five primary schools, located in the Adelaide, South Australia, were selected for recognised heritage, architectural, and educational facility values, and recruited to participate in a mixed-method case study inquiry, as critical cases. Because school architecture and school occupants form a building-occupant system, this inquiry needed a range of data collection methods to capture the system. Architectural assessment, physical (environmental monitoring) and social science (surveys, visual ethnography) data collection methods were integrated to create rich case study interpretations of the schools, at school and classroom units of analysis. It was observed that the building fabric, regardless of age or design intentions, was modified to introduce contemporary permanent technological and sustainability innovations, and also for transitory occupational needs. Data triangulation found that user perspectives of the primary school architecture differed between staff and students, and this difference was aligned with each cohort’s active use of different school facilities. Exploratory Principal Axis Factoring using student participant responses resulted in five factors loaded on variables grouped around wellbeing, smell, acoustics, vision, and satisfaction, in order of their contribution to variance. This suggests that their environment quality is particularly important to primary school students. This finding was confirmed when triangulated against the qualitative data collected. Given this, and the emergent findings from the triangulated staff perspectives with other methods, it was deduced that user perspectives could be grouped into four themes: Place/Architecture, Functionality, Wellbeing, and Environment. These are proposed as a new quality framework and used to as a lens to review the success of recent school technological and sustainability innovations. This research suggests that omitting user voices from building performance evaluation omits important sources of knowledge and design learning since, even with the best intentions, non-occupants, expert or not, cannot speak on behalf of primary school users. This flexible, technosocio paradigm also offers a framework for interdisciplinary research that integrates the knowledge of other disciplines into future architectural inquiries.Thesis (Ph.D.) -- University of Adelaide, School of Architecture and Built Environment, 201

Kentucky’s Primary Care Workforce Shortages 2016 - 2025 and Recommendations for Increasing the Production of Primary Care Physicians for Kentucky

An excerpt from the executive summary: Kentucky and the nation face severe shortages of primary care (PC) physicians. PC physicians are essential to cost-effective healthcare. Kentucky ranks 40th among the United States in its PC physician workforce per 100,000 people, with 2,696 practicing PC physicians statewide. The purposes of this white paper are to: Present up-to-date data and information about the primary care workforce in Kentucky Describe current trainee pipelines that supply new primary care physicians to Kentucky Recommend strategies and tactics for improving the primary care physician workforc

Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition

BACKGROUND: The role of both microglial activation and alpha-synuclein deposition in Parkinson's disease remain unclear. We have tested the hypothesis that if microglia play a primary role in Parkinson's disease pathogenesis, the microglial "activated" phenotype should be associated with histopathological and/or clinical features of the disease. METHODS: We have examined microglial MHC class II expression, a widely used marker of microglial activation, the occurrence of CD68-positive phagocytes and alpha-synuclein immunoreactivity in post-mortem human substantia nigra affected by idiopathic Parkinson's disease (PD). Using semi-quantitative severity ratings, we have examined the relationship between microglial activation, alpha-synuclein deposition, classical neuropathological criteria for PD, subtype of the disease and clinical course. RESULTS: While we did not observe an association between microglial MHC class II expression and clinical parameters, we did find a correlation between disease duration and the macrophage marker CD68 which is expressed by phagocytic microglia. In addition, we observed a significant correlation between the degree of MHC class II expression and alpha-synuclein deposition in the substantia nigra in PD. CONCLUSION: While microglia appeared to respond to alpha-synuclein deposition, MHC class II antigen expression by microglia in the substantia nigra cannot be used as an indicator of clinical PD severity or disease progression. In addition, a contributory or even causative role for microglia in the neuronal loss associated with PD as suggested by some authors seems unlikely. Our data further suggest that an assessment of microglial activation in the aged brain on the basis of immunohistochemistry for MHC class II antigens alone should be done with caution

Use of the Airway Questionnaire 20 to detect changes in quality of life in asthmatic patients and its association with the St George's Respiratory Questionnaire and clinical parameters.

BACKGROUND AND OBJECTIVES: The usefulness of the Airway Questionnaire 20 (AQ20) -- a short version of the St George's Respiratory Questionnaire (SGRQ) -- to evaluate quality of life (QOL) in asthmatic patients following a hospital admission was assessed. METHODS: At baseline and at six months following the index admission, 135 asthmatic patients were asked to complete the AQ20 and the SGRQ. The patient's peak flow, number of subsequent asthma exacerbations and number of repeat hospital admissions were also recorded. RESULTS: The AQ20 scores ranged from 0 to 20, with a high score indicating poor QOL. The AQ20 had good coverage, with no obvious ceiling or floor effects. In multiple regression analysis, all three SGRQ components were important in predicting AQ20 scores (R(2) values were 61.9% and 73.1% for baseline and six-month scores, respectively). The AQ20 was closely correlated with the SGRQ, but not redundant when used together. Bias was low when the retest reliability of the AQ20 was evaluated using the Bland-Altman method, but variation was high (-0.64). Patients with subsequent exacerbations (n=52) had higher AQ20 scores at six-month follow-up (P=0.002). In logistic regression, the AQ20 score was closely associated with the incidence of exacerbations (OR 1.15, 95% CI 1.05 to 1.25), with a similar magnitude of association between the AQ20 and the SGRQ. The AQ20 score did not correlate with peak flow at baseline (r=-0.05; P=0.573) or at six months (r=-0.31; P=0.006), and was not responsive to changes in peak flow (r=-0.06; P=0.583). CONCLUSION: The AQ20 can be substituted for the more complicated SGRQ in the assessment of QOL in patients following a hospital admission for an asthma exacerbation.Peer Reviewe

Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism

SummaryIn cytotoxic T cells (CTL), Akt, also known as protein kinase B, is activated by the T cell antigen receptor (TCR) and the cytokine interleukin 2 (IL-2). Akt can control cell metabolism in many cell types but whether this role is important for CTL function has not been determined. Here we have shown that Akt does not mediate IL-2- or TCR-induced cell metabolic responses; rather, this role is assumed by other Akt-related kinases. There is, however, a nonredundant role for sustained and strong activation of Akt in CTL to coordinate the TCR- and IL-2-induced transcriptional programs that control expression of key cytolytic effector molecules, adhesion molecules, and cytokine and chemokine receptors that distinguish effector versus memory and naive T cells. Akt is thus dispensable for metabolism, but the strength and duration of Akt activity dictates the CTL transcriptional program and determines CTL fate

Valuing labour

The British construction labour process rests on casual, self-employment, output-based pay, rigid trade divisions, low levels of training and a sharp divide between operative and professional/technical skills. Skill shortages beset the industry and their solution focuses not on employment regulation and a comprehensive industry-wide training scheme but on importing the necessary skilled labour. The paper shows how qualitatively differently construction labour is valued in Britain compared with other leading European countries. These rely on higher skill levels, based on knowledge gained through the training process and on a more stable and collectively negotiated structure of training provision and employment. In Britain, in contrast, labour is not valued according to the knowledge it incorporate but according to an individual's ability to fulfil the task in hand, Training is geared to meeting individual employers' immediate needs, qualifications are not a prerequisite for entry, and labour is rewarded for its product not for its potential. The paper pinpoints the key features if the British system that give rise to concern and concludes by outlining the ways in which the British system needs to change for any sustainable development of the construction process

A core outcome set for localised prostate cancer effectiveness trials

Objective: To develop a core outcome set (COS) applicable for effectiveness trials of all interventions for localised prostate cancer. Background: Many treatments exist for localised prostate cancer, although it is unclear which offers the optimal therapeutic ratio. This is confounded by inconsistencies in the selection, definition, measurement and reporting of outcomes in clinical trials. Subjects and methods: A list of 79 outcomes was derived from a systematic review of published localised prostate cancer effectiveness studies and semi-structured interviews with 15 prostate cancer patients. A two-stage consensus process involving 118 patients and 56 international healthcare professionals (HCPs) (cancer specialist nurses, urological surgeons and oncologists) was undertaken, consisting of a three-round Delphi survey followed by a face-to-face consensus panel meeting of 13 HCPs and 8 patients. Results: The final COS included 19 outcomes. Twelve apply to all interventions: death from prostate cancer, death from any cause, local disease recurrence, distant disease recurrence/metastases, disease progression, need for salvage therapy, overall quality of life, stress urinary incontinence, urinary function, bowel function, faecal incontinence, sexual function. Seven were intervention-specific: perioperative deaths (surgery), positive surgical margin (surgery), thromboembolic disease (surgery), bothersome or symptomatic urethral or anastomotic stricture (surgery), need for curative treatment (active surveillance), treatment failure (ablative therapy), and side effects of hormonal therapy (hormone therapy). The UK-centric participants may limit the generalisability to other countries, but trialists should reason why the COS would not be applicable. The default position should not be that a COS developed in one country will automatically not be applicable elsewhere. Conclusion: We have established a COS for trials of effectiveness in localised prostate cancer, applicable across all interventions which should be measured in all localised prostate cancer effectiveness trials