921 research outputs found
Local political leadership and the modernisation of local government
Political leadership has been a key element of central government’s attempts to ‘modernise’ local government over the past decade, within a discourse that emphasised ‘strong’ and ‘visible’ leadership and the role of leaders and leadership in driving change within local authorities. In the context of such an approach, and also taking account of academic discourse, this article draws upon interviews with nearly thirty individuals in leadership positions in local authorities in England, Scotland and Wales to assess their experiences of leadership and their views of some aspects of the role and work of councils. It suggests that whilst there is broad convergence between the aspirations of government and the narratives that emerge from these leaders on some aspects of local political leadership, there are also differences, perhaps most notably over the relationship between changes to decision making structures and the loci of political power
Antigenic expression in human choroid plexus carcinoma : report of two cases
Neoplasias provenientes do epitélio de revestimento do plexo coróide são inco-muns, tendo sido descritos 6 padrões morfológicos. O padrão anaplásico, também denominado carcinoma do plexo coróide, é o de menor freqüência e pode dar metastases fora do SNC. A distinção histológica desses tumores, particularmente da variedade anaplásica, com outras neoplasias primárias e metastáticas no SNC pode ser difÃcil. O uso de técnicas imunocitoquimicas em parafina tem-se mostrado útil no esclarecimento das linhagens tumorais. Os papilomas do plexo coróide têm, no entanto, sido objeto de controvérsia, por sua complexa expressão antigênica. Usando a técnica de imunoperoxidase (sistema avidina-biotina-peroxidase) pesquisaram-se, em dois casos da variedade anaplásica, os seguintes marcadores: proteÃna glial fibrilar ácida (GFAP) com anticorpo monoclonal e policlonal; ceratinas de 40-50kDa, ceratinas de 60-70kDa (callus ceratina), enolase neuronal especÃfica (NSE) e proteÃna S-100, com anticorpos monoclonais. Os dois tumores mostraram positividade para NSE, proteÃna S-100 e ceratina de 40-50kDa; uma das duas neoplasias mostrou diferenciação glial, revelando positividade para GFAP tanto com anticorpo monoclonal quanto policlonal.Primary neoplasms of choroid plexus are rare. Six morphological variants have been described: papillary, cystic, acinar, mucus-secreting, oncocytic, and anaplastic. The anaplastic variant, the so-called choroid plexus carcinoma, is the rarest of all and can metastasize. The differential diagnosis of the anaplastic variant of choroid plexus neoplasms with adenocarcinomas, melanomas and indifferentiated neoplasms can be troublesome chiefly in adults. The now large use of immunocytochemical techniques in tissue section has become a powerful tool in the analysis of cell lineages, tumoral and non-tumoral. Nevertheless, the choroid plexus neoplasms have shown a complex and a somewhat confusing pattern of antigenic expression. In two choroid plexus carcinomas (one localized in the right lateral ventricle from a boy of 1 year and 9 months old, and the other localized in the left lateral ventricle from a girl of 3 years old) the following antigens were searched (using the avidin-biotin-peroxydase complex): glial fibrillary acidic protein (GFAP) with monoclonal and polyclonal antibodies; cytokeratins of 40-50kDa, cytokeratins of 60-70kDA (callus cytokeratin), neuronal specific enolase (NSE) and S-100 protein with monoclonal antibodies. The two neoplasms showed immunoreactivity against NSE, S-100 protein and cytokeratin of 40-50kDA The neoplasm of the boy exhibited glial differentiation having immunoreactivity against GFAP with monoclonal and polyclonal antibodies
Mathematical modelling of polyamine metabolism in bloodstream-form trypanosoma brucei: An application to drug target identification
© 2013 Gu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThis article has been made available through the Brunel Open Access Publishing Fund.We present the first computational kinetic model of polyamine metabolism in bloodstream-form Trypanosoma brucei, the causative agent of human African trypanosomiasis. We systematically extracted the polyamine pathway from the complete metabolic network while still maintaining the predictive capability of the pathway. The kinetic model is constructed on the basis of information gleaned from the experimental biology literature and defined as a set of ordinary differential equations. We applied Michaelis-Menten kinetics featuring regulatory factors to describe enzymatic activities that are well defined. Uncharacterised enzyme kinetics were approximated and justified with available physiological properties of the system. Optimisation-based dynamic simulations were performed to train the model with experimental data and inconsistent predictions prompted an iterative procedure of model refinement. Good agreement between simulation results and measured data reported in various experimental conditions shows that the model has good applicability in spite of there being gaps in the required data. With this kinetic model, the relative importance of the individual pathway enzymes was assessed. We observed that, at low-to-moderate levels of inhibition, enzymes catalysing reactions of de novo AdoMet (MAT) and ornithine production (OrnPt) have more efficient inhibitory effect on total trypanothione content in comparison to other enzymes in the pathway. In our model, prozyme and TSHSyn (the production catalyst of total trypanothione) were also found to exhibit potent control on total trypanothione content but only when they were strongly inhibited. Different chemotherapeutic strategies against T. brucei were investigated using this model and interruption of polyamine synthesis via joint inhibition of MAT or OrnPt together with other polyamine enzymes was identified as an optimal therapeutic strategy.The work was carried out under a PhD programme partly funded by Prof. Ray Welland, School of Computing Science, University of Glasgo
Pediatric lymphomas in Brazil
OBJECTIVE: This study provides the clinical pathological characteristics of 1301 cases of pediatric/adolescent lymphomas in patients from different geographic regions of Brazil. METHODS: A retrospective analyses of diagnosed pediatric lymphoma cases in a 10-year period was performed. We believe that it represents the largest series of pediatric lymphomas presented from Brazil. RESULTS: Non-Hodgkin lymphomas represented 68% of the cases, including those of precursor (36%) and mature (64%) cell origin. Mature cell lymphomas comprised 81% of the B-cell phenotype and 19% of the T-cell phenotype. Hodgkin lymphomas represented 32% of all cases, including 87% of the classical type and 13% of nodular lymphocyte predominant type. The geographic distribution showed 38.4% of the cases in the Southeast region, 28.7% in the Northeast, 16.1% in the South, 8.8% in the North, and 8% in the Central-west region. The distribution by age groups was 15-18 years old, 33%; 11-14 years old, 26%; 6-10 years old, 24%; and 6 years old or younger, 17%. Among mature B-cell lymphomas, most of the cases were Burkitt lymphomas (65%), followed by diffuse large B-cell lymphomas (24%). In the mature T-cell group, anaplastic large cell lymphoma, ALK-positive was the most prevalent (57%), followed by peripheral T-cell lymphoma, then not otherwise specified (25%). In the group of classic Hodgkin lymphomas, the main histological subtype was nodular sclerosis (76%). Nodular lymphocyte predominance occurred more frequently than in other series. CONCLUSION: Some of the results found in this study may reflect the heterogeneous socioeconomical status and environmental factors of the Brazilian population in different regions
Politics versus Policies: Fourth Wave Feminist Critiques of Higher Education’s Response to Sexual Violence
This article uses the lens of fourth wave feminism to examine media accounts of institutional and student responses in two cases of sexual violence at institutions of higher education. Competing discourses reveal a disconnect between what institutions say they do and students’ actual experiences of the institutional handling of sexual violence cases. When policies, actions, and values are not fully aligned, institutions of higher education are unable to respond to societal and institutional injustices. Hence, recommendations for better alignment between institutional values and actions are proposed
TMEM16A is associated with voltage-gated calcium channels in mouse retina and its function is disrupted upon mutation of the auxiliary α2δ4 subunit
Photoreceptors rely upon highly specialized synapses to efficiently transmit signals to
multiple postsynaptic targets. Calcium influx in the presynaptic terminal is mediated by
voltage-gated calcium channels (VGCC). This event triggers neurotransmitter release,
but also gates calcium-activated chloride channels (TMEM), which in turn regulate VGCC
activity. In order to investigate the relationship between VGCC and TMEM channels,
we analyzed the retina of wild type (WT) and Cacna2d4 mutant mice, in which the
VGCC auxiliary a2d4 subunit carries a nonsense mutation, disrupting the normal channel
function. Synaptic terminals of mutant photoreceptors are disarranged and synaptic
proteins as well as TMEM16A channels lose their characteristic localization. In parallel,
calcium-activated chloride currents are impaired in rods, despite unaltered TMEM16A
protein levels. Co-immunoprecipitation revealed the interaction between VGCC and
TMEM16A channels in the retina. Heterologous expression of these channels in tsA-201
cells showed that TMEM16A associates with the CaV1.4 subunit, and the association
persists upon expression of the mutant a2d4 subunit. Collectively, our experiments
show association between TMEM16A and the a1 subunit of VGCC. Close proximity
of these channels allows optimal function of the photoreceptor synaptic terminal under
physiological conditions, but also makes TMEM16A channels susceptible to changes
occurring to calcium channels
Avaliação de genótipos de leguminosas forrageiras para utilização na renovação de talhões de cana-de-açúcar com solo compactado.
Comparar, à campo, o desempenho de linhagens selecionadas de guandu (Cajanus cajan), em comparação à cultivares de girassol (Helianthus annuus) e crotalária (Crotalaria juncea), em talhões de cana com problema de compactação de solo
The CMS Monte Carlo Production System: Development and Design
The CMS production system has undergone a major architectural upgrade from its predecessor, with the goal of reducing the operational manpower needed and preparing for the large scale production required by the CMS physics plan. The new production system is a tiered architecture that facilitates robust and distributed production request processing and takes advantage of the multiple Grid and farm resources available to the CMS experiment
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