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Neste ensaio, demonstra-se que qualquer grupo de difeomorfismos que preserve orientação e aja na 2-esfera, estendendo propriamente o grupo conforme das transformações de Möbius, precisa ser ao menos 4 transitivo ou, mais precisamente, 4-transitivo por arcos. Isso significa que quaisquer duas listas ordenadas de quatro pontos distintos podem ser aplicadas uma sobre a outra por alguma transformação do grupo, isotópica à identidade. Argumenta-se, também, que tais grupos apresentam sempre um elemento de entropia topológica positiva, para o qual é dada uma descrição como isotópico a um homeomorfismo pseudo-Anosov relativo da esfera 4-perfurada. Além disso, apresenta-se uma caracterização elementar em termos de transitividade das transformações de Möbius dentro do grupo total de difeomorfismos. It is proven in this essay that any group of orientation preserving diffeomorphisms acting on the 2-sphere and properly extending the conformal group of Möbius transformations must be at least 4-transitive or, more precisely, arc 4-transitive. This means that any two ordered lists of four distinct points can be mapped one onto the other via a transformation in the group, isotopic to the identity. In addition, it is shown that any such group must always contain an element of positive topological entropy, for which a description as isotopic to a relative pseudo-Anosov homeomorphism of the 4-punctured sphere is provided. Furthermore, an elementary characterisation of the Möbius transformations within the full group of sphere diffeomorphisms is given in terms of transitivity.

Measurements of wind strength and direction abstracted from European ships' logbooks during the recently finished CLIWOC project have been used to produce the first gridded Sea Level Pressure (SLP) reconstruction for the 1750?1850 period over the North Atlantic based solely on marine data. The reconstruction is based on a spatial regression analysis calibrated by using data taken from the ICOADS database. An objective methodology has been developed to select the optimal calibration period and spatial domain of the reconstruction by testing several thousands of possible models. The finally selected area, limited by the performance of the regression equations and by the availability of data, covers the region between 28° N and 52° N close to the European coast and between 28° N and 44° N in the open Ocean. The results provide a direct measure of the strength and extension of the Azores High during the 101 years of the study period. The comparison with the recent land-based SLP reconstruction by Luterbacher et al. (2002) indicates the presence of a common signal. The interannual variability of the CLIWOC reconstructions is rather high due to the current scarcity of abstracted wind data in the areas with best response in the regression. Guidelines are proposed to optimize the efficiency of future abstraction work.

This page details programming, registration and accessibility options, and volunteer efforts for the Open Science Special Interest Group's Open Science Room, a conference within a conference that is part of the Organization for Human Brain Mapping'd (OHBM) annual meeting.

Self-regulation, the ability to guide behavior according to one’s goals, plays an integral role in understanding loss of control over unwanted behaviors, for example in alcohol use disorder (AUD). Yet, experimental tasks that measure processes underlying self-regulation are not easy to deploy in contexts where such behaviors usually occur, namely outside the laboratory, and in clinical populations such as people with AUD. Moreover, lab-based tasks have been criticized for poor test–retest reliability and lack of construct validity. Smartphones can be used to deploy tasks in the field, but often require shorter versions of tasks, which may further decrease reliability. Here, we show that combining smartphone-based tasks with joint hierarchical modeling of longitudinal data can overcome at least some of these shortcomings. We test four short smartphone-based tasks outside the laboratory in a large sample (N = 488) of participants with AUD. Although task measures indeed have low reliability when data are analyzed traditionally by modeling each session separately, joint modeling of longitudinal data increases reliability to good and oftentimes excellent levels. We next test the measures’ construct validity and show that extracted latent factors are indeed in line with theoretical accounts of cognitive control and decision-making. Finally, we demonstrate that a resulting cognitive control factor relates to a real-life measure of drinking behavior and yields stronger correlations than single measures based on traditional analyses. Our findings demonstrate how short, smartphone-based task measures, when analyzed with joint hierarchical modeling and latent factor analysis, can overcome frequently reported shortcomings of experimental tasks.

OBJECTIVE: to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP). METHODS: PubMed and Dialog databases were searched (January 2000-October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected. RESULTS: prevalence of sarcopenia was, with regional and age-related variations, 1-29% in community-dwelling populations, 14-33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function. CONCLUSION: prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes.

O desenvolvimento de novas formas sólidas de ingredientes farmacêuticos ativos (API) é relevante tanto numa perspectiva fundamental como industrial. Para tal, a Engenharia de cristais tem desempenhado um papel importante nas ciências farmacêuticas. Dentre as estratégias, a formação de sais é a abordagem mais importante e implementada. Os sais de APIs são capazes de modular e ajustar a solubilidade e a estabilidade, a fim de proporcionar uso prático. Nesta tese, são reportados sais de dois fármacos Inibidores Seletivos de Recaptação de Serotonina, consolidados no tratamento da depressão e distúrbios de ansiedade, a Paroxetina (PRX) e a Fluoxetina (FLX). Brometo de Paroxetina hemiidratado ((PRXBr)0.5H2O), Nitrato de Paroxetina hidratado (PRXNO3H2O) e polimorfos de Nitrato de Fluoxetina (FLXNO3), síntese e protocolos de cristalização foram cuidadosamente delineados, com base na sistematização de dados estruturais e supramoleculares das moléculas e seus análogos, depositados no Cambridge Structural Database. Todos os sais foram caracterizados por Difração de Raios-X por Monocristal, Calorimetria Explanatória Diferencial (DSC), Análise termogravimétrica (TGA), Termomicroscopia, Espectroscopia vibracional na região do infravermelho (IR) e solubilidade. Considerando que a hidratação/desidratação induz mudanças de fases que comprometem a eficiência do API, a caracterização do (PRXBr)0.5H2O auxiliou no entendimento do processo de desidratação reversível que ocorre para esse fármaco. Estas mudanças de fase resultam também em implicações sobre a compreensão do processo de desidratação do sal isoestrutural de cloreto de PRX hemiidratado. Além disso, por meio da elucidação estrutural do (PRXNO3)H2O, foi possível analisar a diversidade conformacional e supramolecular da PRX. Quanto à FLX, verificou-se que sua quiralidade está relacionada com seu polimorfismo. Um racemato e uma estrutura não centrossimétrica com dois enatiômeros independentes na unidade assimétrica foram obtidos para o FLXNO3. A comparação destas estruturas permitiu mostrar a existência de arranjos supramoleculares racêmicos, constituídos por diferentes orientações de enatiômeros. A rara ocorrência de sistemas racêmicos em grupos espaciais não-centrossimétricos tornou este evento um caso notável. A partir das propriedades físico-químicas, os polimorfos puderam ser monotropicamente relacionados. Os resultados desta tese trazem importantes contribuições científicas para diversidade de formas sólidas e também define novas formulações sólidas para utilização como antidepressivos. The development of new solid forms of active pharmaceutical ingredients (API) is relevant both from fundamental as well as industrial perspectives. To this end, Crystal Engineering plays an ever-increasing important role in pharmaceutical sciences. Among the crystal engineering strategy, salt formation is the most important and implemented approach. The salt forms of API could be used to modulate and tuned the solubility and stability of API to provide optimal practical uses. Herein, we report pharmaceutical salts of two Selective Serotonin Reuptake Inhibitor antidepressants used in the treatment of depression and anxiety disorders, Paroxetine (PRX) and Fluoxetine (FLX). For this purpose, salt formers, supramolecular synthesis and crystallization protocols have been driven by the systematization of structural and supramolecular data of molecules and analogues from the Cambridge Structural Database. Paroxetine bromide hemihydrate ((PRXBr)0.5H2O), Paroxetine Nitrate hydrate (PRXNO3H2O) and two polymorphs of Fluoxetine Nitrate (FLXNO3) have obtained. All were characterized by a combination of techniques including Single Crystal X-ray Diffraction, Differential Scanning Calorimetry (DSC), Thermogravimetry analysis (TGA), Hot Stage Microscopy, Fourier transform infrared spectroscopy (IR) and solubility measurements. Since the hydration/dehydration process in APIs induces phase transitions that compromise its efficiency, the structural characterization of (PRXBr)0.5H2O help to understand its reversible dehydration process. Also, this study has implication in the understating of dehydration of isostructural PRX hydrochloride salt. Additionally, the (PRXNO3)H2O have shown the conformational flexibility and supramolecular diversity of PRX. On the other hand, the chirality of FLX is related to two nitrate salt polymorphs. A racemate and a non-centrosymmetric structure with independent enantiomers in the asymmetric unit were obtained for FLXNO3. Their packing have shown the existence of different racemic motifs, resulting in different enantiomer orientations The rare occurrence of racemic systems in non-centrosymmetric space groups becomes this event a noteworthy case. By their physicochemical properties, the polymorphs were monotropically related. The scientific contributions of this thesis show the diversity of the solid forms and define candidates to new antidepressants APIs solid formulations.

The "Malnutrition in the Elderly Knowledge Hub" (MaNuEL) is an action program as part of the Strategic Research Agenda of the Joint Programming Initiative "A Healthy Diet for a Healthy Life". In the MaNuEL project experts of 22 research groups from 7 countries (Austria, France, Germany, Ireland, Spain, the Netherlands and New Zealand) came together to bundle up all the knowledge on malnutrition.

Apoptosis of infected cells can limit virus replication and serves as an innate defense mechanism against viral infections. Consequently, viruses delay apoptosis by expressing antiapoptotic proteins, many of which structurally resemble the cellular antiapoptotic protein Bcl-2. Like Bcl-2, the viral analogs inhibit apoptosis by preventing activation and/or oligomerization of the proapoptotic mitochondrial proteins Bax and Bak. Here we show that cytomegaloviruses (CMVs) have adopted a different strategy. They encode two separate mitochondrial proteins that lack obvious sequence similarities to Bcl-2-family proteins and specifically counteract either Bax or Bak. We identified a small mitochondrion-localized protein encoded by the murine CMV open reading frame (ORF) m41.1, which functions as a viral inhibitor of Bak oligomerization (vIBO). It blocks Bak-mediated cytochrome c release and Bak-dependent induction of apoptosis. It protects cells from cell death-inducing stimuli together with the previously identified Bax-specific inhibitor viral mitochondria-localized inhibitor of apoptosis (vMIA) (encoded by ORF m38.5). Similar vIBO proteins are encoded by CMVs of rats, and possibly by other CMVs as well. These results suggest a non-redundant function of Bax and Bak during viral infection, and a benefit for CMVs derived from the ability to inhibit Bak and Bax separately with two viral proteins.