Catalytic Intermolecular Hetero-Dehydro-Diels–Alder Cycloadditions: Regio- and Diasteroselective Synthesis of 5,6-Dihydropyridin-2-ones

A novel catalyzed intermolecular heterodehydro-Diels–Alder reaction between push–pull 1,3-dien-5-ynes and aldimines or silylaldimines is reported. The sequence is promoted both by gold(I) or silver(I) catalysts and leads to the diastereo- and regioselective formation of 5,6-dihydropyridin-2-onesMICINN (Spain) (grants CTQ2009-09949, CTQ2010-16790, PTA2008-1524-P contract to J.M.F.-G. and Ramon y Cajal postdoctoral contract to M.A.F.-R.) and FICYT (project IB08-088)This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/page/policy/articlesonrequest/index.htm

Healthy environments from a broad perspective : an overview of research performed at the unit Building Physics and Systems of Eindhoven University of Technology

The design and realization of a healthy indoor environment is a challenge that is investigated from different perspectives at the unit Building Physics and Systems (BPS; Faculty of Architecture, Building and Planning) of Eindhoven University of Technology. Performance requirements (for instance, with respect to air quality, thermal comfort and lighting) and performance based assessment methods are the point-of-departure, focusing at computational techniques supporting the design process. Different specific application fields such as dwellings, offices, schools, but also, operating theatres, churches, musea and multifunctional stadiums, underline the applied approach that is part of the research within the unit. In the design of healthy environments, the performance based design assessment is crucial in arriving at innovative design solutions and optimized indoor and outdoor environments. In this assessment computational support tools and experimental verification play an important role. However, assessing the right indicators in an objective way, applying the correct tools and correct application of these tools is not yet well established. Alongside, developments are still ongoing. The work performed in the unit by the different researchers relates to the research questions that can be derived from this notice. The paper gives an introduction to the Unit BPS and presents a brief overview of recent and ongoing research. An extensive list of references is provided for further reading and supports the conclusion that healthy environments can and should be addressed from a wide angle

Healthy environments from a broad perspective : an overview of research performed at the unit Building Physics and Systems of Eindhoven University of Technology

The design and realization of a healthy indoor environment is a challenge that is investigated from different perspectives at the unit Building Physics and Systems (BPS; Faculty of Architecture, Building and Planning) of Eindhoven University of Technology. Performance requirements (for instance, with respect to air quality, thermal comfort and lighting) and performance based assessment methods are the point-of-departure, focusing at computational techniques supporting the design process. Different specific application fields such as dwellings, offices, schools, but also, operating theatres, churches, musea and multifunctional stadiums, underline the applied approach that is part of the research within the unit. In the design of healthy environments, the performance based design assessment is crucial in arriving at innovative design solutions and optimized indoor and outdoor environments. In this assessment computational support tools and experimental verification play an important role. However, assessing the right indicators in an objective way, applying the correct tools and correct application of these tools is not yet well established. Alongside, developments are still ongoing. The work performed in the unit by the different researchers relates to the research questions that can be derived from this notice. The paper gives an introduction to the Unit BPS and presents a brief overview of recent and ongoing research. An extensive list of references is provided for further reading and supports the conclusion that healthy environments can and should be addressed from a wide angle

BIM aplicado ao projeto de fôrmas de madeira em estrutura de concreto armado

ResumoO Projeto Construtivo de Fôrmas de Madeira (PCFM) faz uso tradicionalmente de ferramentas CAD na representação bidimensional, limitando sua inserção no contexto de Building Information Modeling (BIM). Considerando que BIM se encontra em grande expansão no mercado nacional esta pesquisa visa apontar um caminho para se vencer esta limitação. Propõe-se uma biblioteca de componentes para o projeto de fôrmas de madeira, incluindo usos de BIM tais como a Modelagem, a Quantificação, a Simulação 4D e procedimentos associados. O método de pesquisa utilizado foi a Constructive Research. Os componentes para a biblioteca foram desenvolvidos na ferramenta BIM Revit Structure. A proposta foi validada: em ambiente de ensino, escritório de projeto e na prática. Verifica-se que a pesquisa é consonante com os poucos estudos internacionais pioneiros e semelhantes, sendo contextualizada para o cenário nacional. Observa-se também que todas as pesquisas que tratam de BIM associado a fôrmas requerem um modelo de informação que inclua a modelagem de fôrmas no mesmo. Desta forma, este estudo é também fundamental, pois amplia desdobramentos da incorporação de BIM na cadeia produtiva da construção civil

Sleep duration, vital exhaustion and perceived stress among pregnant migraineurs and non-migraineurs

<p>Abstract</p> <p>Background</p> <p>Migraine has been associated with sleep disorders in men and non-pregnant women, but little is known about sleep complaints among pregnant migraineurs.</p> <p>Methods</p> <p>A cohort of 1,334 women was interviewed during early pregnancy. At the time of interview we ascertained participants' migraine diagnosis status and collected information about sleep duration before and during early pregnancy, daytime sleepiness, vital exhaustion and perceived stress during early pregnancy. Multivariable logistic regression procedures were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of short/long sleep duration, excessive daytime sleepiness, vital exhaustion and elevated perceived stress associated with a history of migraine.</p> <p>Results</p> <p>Approximately 19.4% of the cohort (n = 259) reported having a medical diagnosis of migraine prior to the study pregnancy. Compared with women without migraine, the multivariable-adjusted ORs (95% CI) among migraineurs for short sleep duration before and during early pregnancy were 1.51 (1.09-2.09), and 1.57 (1.11-2.23), respectively. The corresponding OR (95% CI) for long sleep duration before and during pregnancy were 1.33 (0.77-2.31) and 1.31 (0.94-1.83), respectively. A modest and statistically insignificant association between migraine history and excessive daytime sleepiness in early pregnancy was noted (OR = 1.46; 95% CI 0.94-2.26). Migraineurs had an increased risk of vital exhaustion (OR = 2.04; 95% CI 1.52-2.76) and elevated perceived stress (OR = 1.57; 95% CI 1.06-2.31). Observed associations were more pronounced among overweight migraineurs.</p> <p>Conclusions</p> <p>These data support earlier research documenting increased risks of sleep disorders among migraineurs; and extends the literature to include pregnant women. Prospective studies are needed to more thoroughly explore factors that mediate the apparent migraine-sleep comorbidity among pregnant women.</p

Postoperative outcomes in oesophagectomy with trainee involvement

BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. RESULTS: Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). CONCLUSION: Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery

SOX9 Governs Differentiation Stage-Specific Gene Expression in Growth Plate Chondrocytes via Direct Concomitant Transactivation and Repression

Cartilage and endochondral bone development require SOX9 activity to regulate chondrogenesis, chondrocyte proliferation, and transition to a non-mitotic hypertrophic state. The restricted and reciprocal expression of the collagen X gene, Col10a1, in hypertrophic chondrocytes and Sox9 in immature chondrocytes epitomise the precise spatiotemporal control of gene expression as chondrocytes progress through phases of differentiation, but how this is achieved is not clear. Here, we have identified a regulatory element upstream of Col10a1 that enhances its expression in hypertrophic chondrocytes in vivo. In immature chondrocytes, where Col10a1 is not expressed, SOX9 interacts with a conserved sequence within this element that is analogous to that within the intronic enhancer of the collagen II gene Col2a1, the known transactivation target of SOX9. By analysing a series of Col10a1 reporter genes in transgenic mice, we show that the SOX9 binding consensus in this element is required to repress expression of the transgene in non-hypertrophic chondrocytes. Forced ectopic Sox9 expression in hypertrophic chondrocytes in vitro and in mice resulted in down-regulation of Col10a1. Mutation of a binding consensus motif for GLI transcription factors, which are the effectors of Indian hedgehog signaling, close to the SOX9 site in the Col10a1 regulatory element, also derepressed transgene expression in non-hypertrophic chondrocytes. GLI2 and GLI3 bound to the Col10a1 regulatory element but not to the enhancer of Col2a1. In addition to Col10a1, paired SOX9–GLI binding motifs are present in the conserved non-coding regions of several genes that are preferentially expressed in hypertrophic chondrocytes and the occurrence of pairing is unlikely to be by chance. We propose a regulatory paradigm whereby direct concomitant positive and negative transcriptional control by SOX9 ensures differentiation phase-specific gene expression in chondrocytes. Discrimination between these opposing modes of transcriptional control by SOX9 may be mediated by cooperation with different partners such as GLI factors