Synthesis of novel sugar derived aziridines, as starting materials giving access to sugar amino acid derivatives

d-Erythrosyl aziridines were obtained from d-erythrosyl triazoles either by photolysis or through diazirine intermediates. These were found to undergo rich, high yielding chemistry by reaction with protic acids (HCl, BiI3/H2O and trifluoroacetic acid) leading to two types of furanoid sugar α-amino acids, and polyhydroxylprolines. Based on experimental evidence, reaction mechanisms have been proposed for the syntheses.We thank FCT for project funding PTDC/QEQ-MED/1671/2012; the NMR Portuguese network (PTNMR, Bruker Avance III 400-Univ. Minho), and FCT and FEDER (European Fund for Regional Development)-COMPETE-QREN-EU for fnancial support to CQ/UM. This study was funded by Fundação para a Ciência e a Tecnologia (SFRH/BD/87292/2012)

Concise synthesis of (S)-7-Hydroxy-5-aza-8a- epi - D -swainsonine from a d -erythrose derivative

A five-step synthesis of (S)-7-hydroxy-5-aza-8a-epi-D-swainsonine [(3S,4S,4aS,5S,6R)-octahydropyrrolo[1,2-b]pyridazine-3,4,5,6- tetraol] was accessed in good overall yield from readily available D-erythrosyl benzylidene acetal buta-1,3-diene. The key step of the reaction sequence is a full stereoselective Diels Alder cycloaddition between the diene and dienophile: diethyl azodicarboxylate (DEAD) or di-tert-butyl azodicarboxylate (DBAD). The cycloadducts were further transformed into the title 5-aza-indolizidine. Optimized procedures were obtained for the synthesis of intermediates and products.We thank Fundacao para a Ciencia e a Tecnologia (FCT) for project funding (PTDC/QEQ-MED/1671/2012 and SFRH/BD/87292/2012) and Fundacao para a Ciencia e a Tecnologia and European Fund for Regional Development FEDER-COMPETE-QREN-EU for financial support to C.Q./U.M

Sequential application of steady and pulsatile medium perfusion enhanced the formation of engineered bone

In native bone, cells experience fluctuating shear forces that are induced by pulsatile interstitial flow associated with habitual loading. We hypothesized that the formation of engineered bone can be augmented by replicating such physiologic stimuli to osteogenic cells cultured in porous scaffolds using bioreactors with medium perfusion. To test this hypothesis, we investigated the effect of fluid flow regime on in vitro bone-like tissue development by human adipose stem cells (hASC) cultivated on porous three-dimensional silk fibroin scaffolds. To this end, we varied the sequential relative durations of steady flow (SF) and pulsatile flow (PF) of culture medium applied over a period of 5 weeks, and evaluated their effect on early stages of bone formation. Porous silk fibroin scaffolds (400-600 μm pore size) were seeded with hASC (30×10(6) cells/mL) and cultured in osteogenic medium under four distinct fluid flow regimes: (1) PF for 5 weeks; (2) SF for 1 week, PF for 4 weeks; (3) SF for 2 weeks, PF for 3 weeks; (4) SF for 5 weeks. The PF was applied in 12 h intervals, with the interstitial velocity fluctuating between 400 and 1200 μm/s at a 0.5 Hz frequency for 2 h, followed by 10 h of SF. In all groups, SF was applied at 400 μm/s. The best osteogenic outcomes were achieved for the sequence of 2 weeks of SF and 3 weeks of PF, as evidenced by gene expression (including the PGE2 mechanotransduction marker), construct compositions, histomorphologies, and biomechanical properties. We thus propose that osteogenesis in hASC and the subsequent early stage bone development involve a mechanism, which detects and responds to the level and duration of hydrodynamic shear forces.We gratefully acknowledge funding support of this work by the NIH (DE161525, AR061988 and EB02520 to G.V.-N.), and the FCT PhD grant (SFRH/BD/42316/2007 to C.C.). The authors thank Dr. Darja Marolt and Supansa Yodmuang for their help with the experiments, Professor David L. Kaplan (Tufts University) for providing silk scaffolds, and Professor Jeffrey M. Gimble (Louisiana State University) for providing adipose stem cells used in this study

Anti-staphylococcal effectiveness of nisaplin in refrigerated pizza doughs

This study evaluated the effectiveness of nisaplin, commercial product having nisin as active component, in decreasing the staphylococcal population in refrigerated pizza doughs. The refrigerated pizza dough pieces randomly chosen were dipped in the solutions with nisaplin concentrations of 1.0 x 10-3 g and 1.0 x 10-2 g nisaplin/mL named for the treatment A and B and kept under refrigeration (7 °C ± 1 °C). On times 0, 15 and 30 days post treatment the Staphylococcus spp. count was carried out. The results showed that both nisaplin treatments were able to reduce the Staphylococcus spp. count (CFU/g) in the refrigerated pizza doughs. However, only treatment B showed statistically significant reducer effect (p < 0.05) on the count providing a decrease of 1.0 and 0.98 log cycles, respectively, after 15 and 30 days post treatment. These data suggest that nisin could appear as promising alternative to control the survival of the pathogen microorganisms in the foods, particularly, Staphylococcus in the refrigerated pizza doughs.<br>Este estudo avaliou a efetividade de nisaplin, produto comercial tendo nisina como componente ativo, em diminuir a população estafilocócica em massas de pizza refrigeradas. Pedaços de massa de pizza refrigerada foram randomicamente escolhidos e mergulhados em soluções de nisaplin com concentração de 1.0 10-3 g e 1.0 10-2 g nisaplin/mL, nomeados, respectivamente, tratamento A e B, e mantidos sob refrigeração (7 °C ± 1°C). Nos tempos 0, 15 e 30 dias pós-tratamento foram feitas as contagens de Staphylococcus spp. Os resultados mostraram que ambos os tratamentos diminuíram a contagem (UFC/g) de Staphylococcus spp. em massas de pizza refrigeradas. Entretanto, somente o tratamento B mostrou um efeito redutor estatisticamente significante (p < 0.05) sobre a contagem de Staphylococcus spp. causando uma diminuição de 1.0 e 0.98 ciclos logarítmicos, respectivamente, nos tempos 15 e 30 dias pós tratamento. Estes dados sugerem que nisina poderia apresentar-se como uma promissora alternativa para controlar o a sobrevivência de microrganismos patógenos em alimentos, particularmente, espécies de Staphylococcus em massas de pizza refrigerada

Atenção primária à saúde: diretrizes, desafios e recomendações. Revisão de bibliografia internacional Primary health care: guidelines, challenges and recommendations. A review of international literature

Apresentamos uma revisão de bibliografia internacional que teve por objetivo identificar e analisar a diversidade de temas associados à Atenção Primária à Saúde, especialmente o cotidiano de trabalho de seus profissionais, suas diretrizes e seus desafios políticos e clínicos. Analisamos os resumos de 105 artigos publicados entre 1999 e 2009. Selecionamos, para análise, 34 artigos identificados de acordo com critérios específicos. Criamos categorias temáticas e comparamos os dados com certa literatura brasileira sobre o tema. Os artigos centram-se no profissional de medicina e enfatizam a noção de medicina baseada em evidências. Abordam principalmente a implementação de diretrizes na Atenção Primária e as relações entre profissionais e usuários. Admitem a complexidade da Atenção Primária e a importância de aproximação à realidade dos pacientes. Entretanto, não abordam a intersetorialidade, não questionam radicalmente o especialismo curativista e não mencionam a promoção de cidadania, autonomia e cogestão junto aos usuários. Falam da necessidade de abordar problemas "humanos" nos níveis de implementação de diretrizes, encontro clínico etc., mas se mostram distanciados das ciências humanas.<br>We present a review of international literature, aiming at identifying and analyzing the diversity of themes associated to Primary Health Care. We focused on the characteristics of the work of health care personnel, its guidelines and its political and clinical challenges. We analyzed the abstracts of 105 articles published between 1999 and 2009. Then, we integrally read and analyzed 34 articles, creating thematic categories. We compared data to Brazilian literature on the subject. The articles focus on physician's work and emphasize the notion of evidence-based medicine. They mainly approach the implementation of guidelines to primary health care and the professional-patient relations. They acknowledge the complexity of Primary Care and the importance of patient-centered care. However, they do not mention integrated actions with other public policies. The authors do not radically overthrow the cure-centered specialism and they do not write about fostering patients' participation, autonomy and empowerment. They acknowledge the need to approach "human" issues at the levels of guidelines implementation, clinical practices etc. Nevertheless, in general, these authors are far from the social sciences

Observation of triple J/ψ meson production in proton-proton collisions

Protons consist of three valence quarks, two up-quarks and one down-quark, held together by gluons and a sea of quark-antiquark pairs. Collectively, quarks and gluons are referred to as partons. In a proton-proton collision, typically only one parton of each proton undergoes a hard scattering – referred to as single-parton scattering – leaving the remainder of each proton only slightly disturbed. Here, we report the study of double- and triple-parton scatterings through the simultaneous production of three J/ψ mesons, which consist of a charm quark-antiquark pair, in proton-proton collisions recorded with the CMS experiment at the Large Hadron Collider. We observed this process – reconstructed through the decays of J/ψ mesons into pairs of oppositely charged muons – with a statistical significance above five standard deviations. We measured the inclusive fiducial cross-section to be 272−104+141(stat)±17(syst)fb, and compared it to theoretical expectations for triple-J/ψ meson production in single-, double- and triple-parton scattering scenarios. Assuming factorization of multiple hard-scattering probabilities in terms of single-parton scattering cross-sections, double- and triple-parton scattering are the dominant contributions for the measured process

Strategies and performance of the CMS silicon tracker alignment during LHC Run 2

The strategies for and the performance of the CMS silicon tracking system alignment during the 2015–2018 data-taking period of the LHC are described. The alignment procedures during and after data taking are explained. Alignment scenarios are also derived for use in the simulation of the detector response. Systematic effects, related to intrinsic symmetries of the alignment task or to external constraints, are discussed and illustrated for different scenarios