Tumour necrosis factor alpha induces rapid reduction in AMPA receptor-mediated calcium entry in motor neurones by increasing cell surface expression of the GluR2 subunit: relevance to neurodegeneration

The AMPA receptor (AMPAR) subunit GluR2, which regulates excitotoxicity and the inflammatory cytokine tumour necrosis factor alpha (TNF alpha) have both been implicated in motor neurone vulnerability in Amyotrophic Lateral Sclerosis/Motor Neurone Disease. TNF alpha has been reported to increase cell surface expression of AMPAR subunits to increase synaptic strength and enhance excitotoxicity, but whether this mechanism occurs in motor neurones is unknown. We used primary cultures of mouse motor neurones and cortical neurones to examine the interaction between TNF alpha receptor activation, GluR2 availability, AMPAR-mediated calcium entry and susceptibility to excitotoxicity. Short exposure to a physiologically relevant concentration of TNFalpha (10 ng/ml, 15 min) caused a marked redistribution of both GluR1 and GluR2 to the cell surface as determined by cell surface biotinylation and immunofluorescence. Using Fura-2 AM microfluorimetry we showed that exposure to TNFalpha caused a rapid reduction in the peak amplitude of AMPA-mediated calcium entry in a PI3-kinase and p38 kinase-dependent manner, consistent with increased insertion of GluR2-containing AMPAR into the plasma membrane. This resulted in a protection of motor neurones against kainate-induced cell death. Our data therefore, suggests that TNF alpha acts primarily as a physiological regulator of synaptic activity in motor neurones rather than a pathological drive in ALS

AtTRB1, a telomeric DNA-binding protein from Arabidopsis, is concentrated in the nucleolus and shows highly dynamic association with chromatin

AtTRB1, 2 and 3 are members of the SMH (single Myb histone) protein family, which comprises double-stranded DNA-binding proteins that are specific to higher plants. They are structurally conserved, containing a Myb domain at the N-terminus, a central H1/H5-like domain and a C-terminally located coiled-coil domain. AtTRB1, 2 and 3 interact through their Myb domain specifically with telomeric double-stranded DNA in vitro, while the central H1/H5-like domain interacts non-specifically with DNA sequences and mediates protein–protein interactions. Here we show that AtTRB1, 2 and 3 preferentially localize to the nucleus and nucleolus during interphase. Both the central H1/H5-like domain and the Myb domain from AtTRB1 can direct a GFP fusion protein to the nucleus and nucleolus. AtTRB1–GFP localization is cell cycle-regulated, as the level of nuclear-associated GFP diminishes during mitotic entry and GFP progressively re-associates with chromatin during anaphase/telophase. Using fluorescence recovery after photobleaching and fluorescence loss in photobleaching, we determined the dynamics of AtTRB1 interactions in vivo. The results reveal that AtTRB1 interaction with chromatin is regulated at two levels at least, one of which is coupled with cell-cycle progression, with the other involving rapid exchange.

Provider diversity in the NHS: impact on quality and innovation

The overall objective of the research project has been to assess the impact of provider diversity on quality and innovation in the NHS. The specific research aims were to identify the differences in performance between non-profit Third Sector organisations, for-profit private enterprises, and incumbent public sector institutions within the NHS as providers of health care services, as well as the factors that affect the entry and growth of new private and Third Sector providers. The study used both qualitative and quantitative methods based on case studies of four Local Health Economies (LHEs). Qualitative methods included documentary analysis and interviews with key informants and managers of both commissioning and provider organisations. To provide a focus to the study, two tracer conditions were followed: orthopaedic surgery and home health care for frail older people. In the case of hospital inpatient care, data on patient characteristics were also collected from the HES database. The analysis of this data provided preliminary estimates of the effects of provider type on quality, controlling for client characteristics and case mix. In addition, a survey of patient experience in diverse provider organisations was analysed to compare the different dimensions of quality of provision of acute services between incumbent NHS organisations and new independent sector treatment centres. The research has shown that, in respect of inpatient hospital services, diverse providers supply health services of at least as good quality as traditional NHS providers, and that there is ample opportunity to expand their scale and scope as providers of services commissioned by the NHS. The research used patient experience survey data to investigate whether hospital ownership affects the quality of services reported by NHS patients in areas other than clinical quality. The raw survey data appear to show that private hospitals provide higher quality services than the public hospitals. However, further empirical analysis leads to a more nuanced understanding of the performance differences. Firstly, the analysis shows that each sector offers greater quality in certain specialties. Secondly, the analysis shows that differences in the quality of patients’ reported experience are mainly attributable to patient characteristics, the selection of patients into each type of hospital, and the characteristics of individual hospitals, rather than to hospital ownership as such. Controlling for such differences, NHS patients are on average likely to experience a similar quality of care in a public or privately-run hospital. Nevertheless, for specific groups of patients and for specific types of treatments, especially the more straightforward ones, the private sector provides an improved patient experience compared to the public sector. Elsewhere, the NHS continues to provide a high quality service and outperforms the private sector in a range of services and for a range of clients.

Improving promiscuous mammalian cell entry by the baculovirus AcMNPV

The insect baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) enters many mammalian cell lines, prompting its application as a general eukaryotic gene delivery agent, but the basis of entry is poorly understood. For adherent mammalian cells we show that entry is favoured by low pH and increasing the available cell surface area through transient release from the substratum. Low pH also stimulated baculovirus entry into mammalian cells grown in suspension which, optimally, could reach 90% of the transduced population. The basic loop, residues 268-281, of the viral surface glycoprotein gp64 was required for entry and a tetra mutant with increasing basicity increased entry into a range of mammalian cells. The same mutant failed to plaque in Sf9 cells, instead showing individual cell entry and minimal cell to cell spread, consistent with an altered fusion phenotype. Viruses grown in different insect cells showed different mammalian cell entry efficiencies suggesting additional factors also govern entry.

Identified consumers: an experiment on the informativeness of cross-demand price effects

Often, firms have no information on the specification of the true demand model they are faced with. It is, however, a well established fact that trial-and-error algorithms may be used by them in order to learn how to make optimal decisions. Using experimental methods, we identify a property of the information on past actions which helps the seller of two asymmetric demand substitutes to reach the optimal prices more precisely and faster. The property concerns the possibility of disaggregating changes in each product’s demand into client exit/entry and shift from one product to the other.

Inferring conduct under the threat of entry : the case of Brazilian cement industry

This paper demonstrates that when an industry faces potential entry and this threat of entry constrains pre-entry prices, cost and conduct are not identified from the comparative statics of equilibrium. In such a setting, the identifying assumption behind the well-established technique of relying on exogenous demand perturbations to empirically distinguish between alternative hypotheses of conduct is shown to fail. The Brazilian cement industry, where the threat of imports restrains market outcomes, provides an empirical illustration. In particular, pricecost margins estimated using this established technique are considerably biased downward, underestimating the degree of market power. A test of conduct is proposed, adapted to this constrained setting, which suggests that outcomes in the industry are collusive and characterised by market division.

Motivação no trabalho voluntário: expectativas e motivos na Pastoral da Criança

The present study has proposed a structural model to identify the reasons why individuals become voluntary, keep and exit this type of work. The empirical space was the Pastoral da Criança - social action agency of the National Conference of Bishops of Brazil (CNBB) - community-based institution that has its work based on solidarity and the sharing of knowledge. The theoretical framework has the context in which are volunteering studies in Brazilian and world level. Then discuss the various concepts of volunteering and presented the theoretical models of volunteer motivation. Studies of Mostyn (1983) and studies conducted by the BEPEGE-Base for Studies and Research in Management Policies and Strategies - in their line of research GERQUAL - Human Resource Management and Organizational Quality - of the Federal University of Rio Grande do Norte as Carvalho e Souza(2006), Souza, Medeiros e Fernandes (2006), Souza et al (2009, 2010), Cavalcante et al (2011a, 2011b, 2011c, 2011d) were the main theoretical references for the construction of the model that was tested. Data collection was done through a survey with 71 indicators, in 2 visits to cities from the Diocese of Pesqueira, Pernambuco. The first data collection occurred in the period between May 30 and June 3, 2011, in Buique/PE and the second collection happened in Pesqueira/PE, in St. Joseph Seminary, in the period between July 6-8, 2011. 720 questionnaires were collected. The sample was divided into two parts. Exploratory Factor Analysis was applied in first part and Confirmatory Factor Analysis - structural equation modeling - in the second half. The examination of the results achieved by the expectations, reasons for entry, reasons for staying and exit reasons showed that all hypotheses were accepted. So the motivation of voluntary Pastoral da Criança can be explained by a set of interactions between these five constructs: Altruistic, Affectionate, Amiable, Adjusted and Astute

Structural characteristics and forage mass of Tifton 85 pastures managed under three post-grazing residual leaf areas

The experiment was carried out on Cynodon spp cv. Tifton 85 pastures grazed by sheep under rotational stocking, with the objective of evaluating the structural characteristics as well as the forage mass of the pastures subjected to three grazing intensities in successive cycles. Treatments were composed of three residual leaf area indices (rLAI; 2.4; 1.6 and 0.8), allocated in completely randomized blocks with seven replications, totaling 21 experimental units. Tiller population density, pasture height, leaf area index, forage morphological composition and pasture forage mass were evaluated. The rLAI modified the tiller population density, which increased linearly with decrease in the rLAI of the pastures. Dry masses of leaf blade, stem and dead material were inferior when the rLAI imposed were lower, which resulted in differentiated forage production among the treatments. Tifton 85 pastures grazed by sheep in rotational stocking under tropical conditions with different rLAI show a modified sward structure over successive grazing cycles, mainly by alteration in the height and LAI of the plants at pre-grazing and by light interception post-grazing, which change the tiller population density. The residual leaf area index of 1.6 is the most suitable for pasture management for being equivalent to the heights of entrance and exit of animals on and from paddocks of 33 and 19 cm, respectively, which avoid great accumulation of dead material and excessive stem elongation, in addition to ensuring tillering in the sward.

Effects of temperament and acclimation to handling on feedlot performance of Bos taurus feeder cattle originated from a rangeland-based cow-calf system

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Niobium filtration of conventional and high-frequency x-ray generator beams for intraoral radiography. Effects on absorbed doses, image density and contrast, and photon spectra

We have studied the effects of niobium beam filtration on absorbed doses, on image density and contrast, and on photon spectra with conventional and high-frequency dental x-ray generators. Added niobium reduced entry and superficial absorbed doses in periapical radiography by 9% to 40% with film and digital image receptors, decreased the radiation necessary to produce a given image density on E-speed film and reduced image contrast on D- and E-speed films. As shown by increased half-value layers for aluminum, titanium, and copper and by pulse-height analyses of beam spectra, niobium increased average beam energy by 6% to 19%. Despite the benefits of adding niobium on patient dose reduction and on narrowing the beams' energy spectra, the beam can be overhardened. Adding niobium, therefore, strikes the best balance between radiation dose reduction and beam attenuation, with its risks of increased exposure times, motion blur, and diminished image contrast, when it is used at modest thicknesses (30 μm) and at lower kVp (70) settings. © 1995 Mosby-Year Book, Inc.

The Caribbean countries and the Free Trade Area of the Americas

Includes bibliography

Occluded Tunneled Venous Catheter in Hemodialysis Patients: Risk Factors and Efficacy of Alteplase

Thrombosis of tunneled central venous catheters (CVC) in hemodialysis (HD) patients is common and it can lead to the elimination of vascular sites. This study aimed to evaluate the incidence of thrombotic obstruction of tunneled CVC in HD patients and the efficacy of occlusion treatment with alteplase use, and identify factors associated with thrombotic occlusion. It was a prospective cohort study performed in two centers which evaluated the diagnosis and treatment of thrombotic occlusion of CVC in HD patients for 24 consecutive months. The catheter occlusion was defined as the difficulty infusing or withdrawing fluid from their paths. Alteplase dose was infused to fill the lumen of the occluded catheter and remained for 50 min. As there was no obstruction of the catheter, the procedure was repeated. Three hundred and thirty-nine CVC in 247 patients were evaluated and followed, totalling 67 244 CVC-days. One hundred fifty-seven patients had only one CVC, 88 patients had two CVC during the study, and two patients had three CVC. The median age was 58 (47–66) years, patients were predominantly men (54%), with diabetic nephropathy as the main cause of chronic kidney disease (44%), the internal jugular vein as the main site of implantation (82%), and duration of dialysis before CVC implantation of 119 (41.5 to 585.5) days. Eight hundred and fifteen occlusion episodes were diagnosed (12 episodes/1000 CVC-days), with primary success with alteplase in 596 episodes (77%) and secondary in 81 cases (10%). In 99 episodes (13%), success was not achieved after the second dose of alteplase. Two hundred and thirty CVC were removed during the study and the removal causes were arteriovenous fistula use in 88 patients (38.3%), infectious and mechanical complications in 89 (38.7%) and 21 (9.1%), respectively, and others (transplantation, transfer, or death) in 32 patients (13.9%). Adverse effects were also not observed. In the multivariate analysis, we identified the greatest number of days with CVC (OR = 1.02, CI = 1.01–1.04, P = 0.004), the presence of diabetes (OR = 1.560, CI = 1.351–1.894, P = 0.015), and exit site infection (ESI) (OR = 1.567 CI = 1347–1926, P = 0.023) as factors associated with obstruction. Thrombotic occlusion showed frequent mechanical complication in CVC of HD patients. We observed 12 episodes of obstruction per 1000 CVC-days, with a high success rate after alteplase use (87%). In the multivariate analysis, the time with CVC, the presence of diabetes, and ESI were identified as variables associated with thrombotic obstruction.

Educational Investment, Family Context, and Children’s Math and Reading Growth from Kindergarten through the Third Grade

Drawing on longitudinal data from the Early Childhood Longitudinal Study, Kindergarten Class of 1998–1999, this study used IRT modeling to operationalize a measure of parental educational investments based on Lareau’s notion of concerted cultivation. It used multilevel piecewise growth models regressing children’s math and reading achievement from entry into kindergarten through the third grade on concerted cultivation and family context variables. The results indicate that educational investments are an important mediator of socioeconomic and racial/ethnic disparities, completely explaining the black-white reading gap at kindergarten entry and consistently explaining 20 percent to 60 percent and 30 percent to 50 percent of the black-white and Hispanic-white disparities in the growth parameters, respectively, and approximately 20 percent of the socioeconomic gradients. Notably, concerted cultivation played a more significant role in explaining racial/ethnic gaps in achievement than expected from Lareau’s discussion, which suggests that after socioeconomic background is controlled, concerted cultivation should not be implicated in racial/ethnic disparities in learning.

Accurate ab initio potential energy surfaces for the (3)A '' and (3)A ' electronic states of the O(P-3) plus HBr system

In this work, we report the construction of potential energy surfaces for the (3)A '' and (3)A' states of the system O(P-3) + HBr. These surfaces are based on extensive ab initio calculations employing the MRCI+Q/CBS+SO level of theory. The complete basis set energies were estimated from extrapolation of MRCI+Q/aug-cc-VnZ(-PP) (n = Q, 5) results and corrections due to spin-orbit effects obtained at the CASSCF/aug-cc-pVTZ(-PP) level of theory. These energies, calculated over a region of the configuration space relevant to the study of the reaction O(P-3) + HBr -> OH + Br, were used to generate functions based on the many-body expansion. The three-body potentials were interpolated using the reproducing kernel Hilbert space method. The resulting surface for the (3)A '' electronic state contains van der Waals minima on the entrance and exit channels and a transition state 6.55 kcal/mol higher than the reactants. This barrier height was then scaled to reproduce the value of 5.01 kcal/mol, which was estimated from coupled cluster benchmark calculations performed to include high-order and core-valence correlation, as well as scalar relativistic effects. The (3)A' surface was also scaled, based on the fact that in the collinear saddle point geometry these two electronic states are degenerate. The vibrationally adiabatic barrier heights are 3.44 kcal/mol for the (3)A '' and 4.16 kcal/mol for the (3)A' state. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4705428]

Stochastic foundations of dynamic trade and labor market models

This dissertation consists of three self-contained papers that are related to two main topics. In particular, the first and third studies focus on labor market modeling, whereas the second essay presents a dynamic international trade setup.rnrnIn Chapter "Expenses on Labor Market Reforms during Transitional Dynamics", we investigate the arising costs of a potential labor market reform from a government point of view. To analyze various effects of unemployment benefits system changes, this chapter develops a dynamic model with heterogeneous employed and unemployed workers.rn rnIn Chapter "Endogenous Markup Distributions", we study how markup distributions adjust when a closed economy opens up. In order to perform this analysis, we first present a closed-economy general-equilibrium industry dynamics model, where firms enter and exit markets, and then extend our analysis to the open-economy case.rn rnIn Chapter "Unemployment in the OECD - Pure Chance or Institutions?", we examine effects of aggregate shocks on the distribution of the unemployment rates in OECD member countries.rn rnIn all three chapters we model systems that behave randomly and operate on stochastic processes. We therefore exploit stochastic calculus that establishes clear methodological links between the chapters.