Quantitative and qualitative influences of tapasin on the class I peptide repertoire

Tapasin is critical for efficient loading and surface expression of most HLA class I molecules. The high level surface expression of HLA-B*2705 on tapasin-deficient 721.220 cells allowed the influence of this chaperone on peptide repertoire to be examined. Comparison of peptides bound to HLA-B*2705 expressed on tapasin-deficient and -proficient cells by mass spectrometry revealed an overall reduction in the recovery of B*2705-bound peptides isolated from tapasin-deficient cells despite similar yields of B27 heavy chain and beta (2)-microglobulin. This indicated that a proportion of suboptimal ligands were associated with B27, and they were lost during the purification process. Notwithstanding this failure to recover these suboptimal peptides, there was substantial overlap in the repertoire and biochemical properties of peptides recovered from B27 complexes derived from tapasin-positive and -negative cells. Although many peptides were preferentially or uniquely isolated from B*2705 in tapasin-positive cells, a number of species were preferentially recovered in the absence of tapasin, and some of these peptide ligands have been sequenced. In general, these ligands did not exhibit exceptional binding affinity, and we invoke an argument based on lumenal availability and affinity to explain their tapasin independence. The differential display of peptides in tapasin-negative and -positive cells was also apparent in the reactivity of peptide-sensitive alloreactive CTL raised against tapasin-positive and -negative targets, demonstrating the functional relevance of the biochemical observation of changes in peptide repertoire in the tapasin-deficient APC. Overall, the data reveal that tapasin quantitatively and qualitatively influences ligand selection by class I molecules.

The human temporal cortex: Characterization of neurons expressing nitric oxide synthase, neuropeptides and calcium-binding proteins, and their glutamate receptor subunit profiles

Immunocytochemical techniques were used to examine the distribution of neurons immunoreactive (-ir) for nitric oxide synthase (nNOS), somatostatin (SOM), neuropeptide Y (NPY), parvalbumin (PV), calbindin (CB) and calretinin (CH), in the inferotemporal gyros (Brodmann's area 21) of the human neocortex. Neurons that colocalized either nNOS or SOM with PV, CB or CR were also identified by double-labeling techniques. Furthermore, glutamate receptor subunit profiles (GluR1, GluR2/3, GluR2/4, GluR5/6/7 and NMDAR1) were also determined for these cells. The number and distribution of cells containing nNOS, SOM, NPY, PV, CB or CR differed for each antigen. In addition, distinct subpopulations of neurons displayed different degrees of colocalization of these antigens depending on which antigens were compared. Moreover, cells that contained nNOS, SOM, NPY, PV, GB or CR expressed different receptor subunit profiles. These results show that specific subpopulations of neurochemically identified nonpyramidal cells may be activated via different receptor subtypes. As these different subpopulations of cells project to specific regions of pyramidal calls, facilitation of subsets of these cells via different receptor subunits may activate different inhibitory circuits. Thus, various distinct, but overlapping, inhibitory circuits may act in concert in the modulation of normal cortical function, plasticity and disease.

A field trial of the effect of improved piglet management on smallholder sow productivity in the Philippines

We conducted a randomised, controlled field trial during 1998/1999 to evaluate the hypothesis that improved piglet management would improve the reproductive performance of smallholder sows. Simple changes were introduced into the treatment herds including the construction of a heated piglet-separation pen, vitamin injections, creep feeding and early weaning. The control herds were unchanged. Data were collected from all sows in each enrolled herd over two farrowings. We enrolled 176 sows, including 170 (96 treatment and 74 control) sows that remained throughout the study period. Significant differences in the reproductive performance of treatment and control sows were recorded for interfarrowing interval (median 176 versus 220 days), average number liveborn over 2 litters (11 versus 12), and average preweaning mortality over 2 litters (0 versus 37%). Based on a discount rate of 17%, the benefit-cost ratio of the treatment was 11.1 and 12.1 over 3 and 5 years, respectively. (C) 2001 Elsevier Science B.V. All rights reserved.

(-)-CGP 12177 increases contractile force and hastens relaxation of human myocardial preparations through a propranolol-resistant state of the beta1-adrenoceptor

Two forms of the activated beta(1)-adrenoceptor exist, one that is stabilized by (-)-noradrenaline and is sensitive to blockade by (-)-propranolol and another which is stabilized by partial agonists such as (-)-pindolol and (-)-CGP 12177 but is relatively insensitive to (-)-propranolol. We investigated the effects of stimulation of the propranolol-resistant PI-adrenoceptor in the human heart. Myocardium from non-failing and failing human hearts were set up to contract at 1 Hz. In right atrium from non-ailing hearts in the presence of 200 nM (-)-propranolol, (-)-CGP 12177 caused concentration-dependent increases in contractile force (-logEC(50)[M] 7.3+/-0.1, E-max 23+/-1% relative to maximal (-)-isoprenaline stimulation of beta(1)- and beta(2)-adrenoceptors, n=86 patients), shortening of the time to reach peak force (-logEC(50)[M] 7.4+/-0.1, E-max 37+/-5%, n=61 patients) and shortening of the time to reach 50% relaxation (t(50%), -logEC(50)[M] 7.3+/-0.1, E-max 33+/-2%, n=61 patients). The potency and maxima of the positive inotropic effects were independent of Ser49Gly- and Gly389Arg-beta(1)-adrenoceptor polymorphisms but were potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (-logEC(50)[M] 7.7+/-0.1, E-max 68+/-6%, n=6 patients, P

Parvalbumin-, calbindin-, and calretinin-immunoreactive neurons in the prefrontal cortex of the owl monkey (Aotus trivirgatus): A standardized quantitative comparison with sensory and motor areas

Recent studies have revealed regional variation in the density and distribution of inhibitory neurons in different cortical areas, which are thought to reflect area-specific specializations in cortical circuitry. However, there are as yet few standardized quantitative data regarding how the inhibitory circuitry in prefrontal cortex (PFC), which is thought to be involved in executive functions such as cognition, emotion and decision making, compares to that in other cortical areas. Here we used immunohistochemical techniques to determine the density and distribution of parvalbumin (PV)-, calbindin (CB)-, and calretinin (CR)-immunoreactive (ir) neurons and axon terminals in the dorsolateral and orbital PFC of the owl monkey (Aotus trivirgatus), and compared them directly with data obtained using the same techniques in 11 different visual, somatosensory and motor areas. We found marked differences in the density of PV-ir, CB-ir, and CR-ir interneurons in several cortical areas. One hundred and twenty eight of all 234 possible between-area pairwise comparisons were significantly different. The density of specific subpopulations of these cells also varied among cortical areas, as did the density of axon terminals. Comparison of PFC with other cortical areas revealed that 40 of all 66 possible statistical comparisons of the density of PV-ir, CB-ir, and CR-ir cells were significantly different. We also found evidence for heterogeneity in the pattern of labeling of PV-ir, CB-ir, and CR-ir cells and axon terminals between the dorsolateral and orbital subdivisions of PFC. These data are likely to reflect basic differences in interneuron circuitry, which are likely to influence inhibitory function in the cortex. Copyright (C) 2003 S. Karger AG, Basel.

Exporta F??cil: o servi??o de exporta????o dos Correios

Lan??ado em novembro de 2000, na cidade piauiense de Pedro II ??? escolhida por abrigar uma cooperativa de tecel??s, que exporta tape??aria para a Alemanha, e pelas dificuldades envolvidas no processo exportador ???, o Exporta F??cil foi desenhado para facilitar a exporta????o de produtos de micro, pequenas, m??dias e grandes empresas para mais de 200 pa??ses, nas vendas externas de at?? US$ 10 mil por pacote de at?? 30 kg. As atividades relacionadas ??s exporta????es eram percebidas pelos clientes como extremamente burocr??ticas e de altos custos, pelo governo como caminho para um pa??s mais competitivo internacionalmente e pelos Correios como oportunidade de se tornarem referencial de provedor de servi??os e solu????es para as empresas brasileiras que desejassem vencer no mercado internacional

Sustentabilidade de iniciativas premiadas no concurso inova????o: ind??cios de mudan??a da gest??o no governo federal ?

Com o t??rmino da 11?? edi????o do Concurso Inova????o na Gest??o P??blica Federal, em 2007, A ENAP considerou oportuno incluir em sua programa????o o desenvolvimento de pesquisas que, recuperando a trajet??ria do pr??mio, permitissem identificar como ocorrem as inova????es no governo federal e quais caracter??sticas desses processos podem criar ambientes favor??veis ou desfavor??veis ?? gera????o de inova????o, ?? sua perman??ncia e difus??o. Neste Caderno as pesquisas tiveram como foco a sustentabilidade das iniciativas premiadas e a sua dissemina????o. A an??lise empreendida apontou o car??ter end??geno das inova????es selecionadas e mostrou a import??ncia das equipes n??o s?? na concep????o das iniciativas, mas tamb??m na sua continuidade e relev??ncia pr??tica, oferecendo contribui????es para orientar os incentivos ?? inova????o no setor p??blico, potencializando os impactos do pr??prio Concurso Inova????o na Gest??o P??blica Federal, que completou 15 anos em 2010

Semin??rio: o desafio da implementa????o das pol??ticas p??blicas

Debater sobre os desafios da incorpora????o dos temas transversais, relacionados a p??blicos espec??ficos, nos processos de implementa????o de pol??ticas p??blicas da Administra????o P??blica Federal

Sustentabilidade de iniciativas premiadas no concurso inova????o: ind??cios de mudan??a da gest??o no governo federal?

O prop??sito da pesquisa que trata da sustentabilidade das inova????es premiadas no Concurso Inova????o na Gest??o P??blica Federal, de 1996 a 2006, consistiu em identificar o grau de perman??ncia das inova????es premiadas no per??odo e explorar as condi????es que favoreceram a continuidade. Como resultado mais significativo do estudo, identificou-se elevado ??ndice de sustentabilidade nas pr??ticas: 71,7% das inova????es pesquisadas continuavam ativas quando da realiza????o da entrevista, indicando razo??vel enraizamento no acervo das institui????es federais.A hip??tese ?? a de que a continuidade de inova????es por longos per??odos de tempo, sob distintas administra????es, constitui ind??cio de uma mudan??a mais profunda na gest??o p??blica federal, ultrapassando as altera????es no plano pol??tico e governamental.A an??lise focada nas iniciativas ativas permitiu inferir circunst??ncias que parecem favorecer essa continuidade, tais como a visibilidade dos resultados alcan??ados,o envolvimento dos servidores na inova????o, a exist??ncia de uma lideran??a ativa e de ambiente institucional que promova o acompanhamento e o ajuste das iniciativas a novas circunst??ncias

Sistema de tratamento de parcelamento: tratapar

O sistema de Trata Parcelamentos - TRATAPAR tem como objetivo realizar procedimentos operacionais para constitui????o de processos de parcelamentos para contribuintes com d??vidas na Secretaria da Receita Federal, mediante a integra????o entre os muitos sistemas de cobran??a existentes, possibilitando, de forma autom??tica, o cadastramento dos processos, a recupera????o e a suspens??o dos cr??ditos tribut??rios. A proposta do sistema ?? a redu????o do trabalho necess??rio para a constitui????o dos processos de parcelamentos, de forma automatizada, e como apoio na negocia????o entre os representantes da Secretaria da Receita Federal e os contribuintes interessados em parcelar e solucionar suas d??vidas

Programa gerador de declara????es de imposto de renda pessoa jur??dica em disquete

Visando a simplifica????o do processo de apresenta????o das Declara????es de Rendimento ou Ajuste ?? Secretaria da Receita Federal, a redu????o dos custos e oferecendo uma forma mais amig??vel e segura do contribuinte preencher sua declara????o, desde 1991 a SRF oferece aos contribuintes os Programas Geradores de Declara????o de Imposto de Renda Pessoa Jur??dica. Os programas s??o distribu??dos em disquete pela SRF, gratuitamente. Os mesmos podem ser obtidos nos ??rg??os da SRF ou a partir do ano de 1996, via Internet