ESC Working Group on Myocardial Function Position Paper: how to study the right ventricle in experimental models

The right ventricle has become an increasing focus in cardiovascular research. In this position paper, we give a brief overview of the specific pathophysiological features of the right ventricle, with particular emphasis on functional and molecular modifications as well as therapeutic strategies in chronic overload, highlighting the differences from the left ventricle. Importantly, we put together recommendations on promising topics of research in the field, experimental study design, and functional evaluation of the right ventricle in experimental models, from non-invasive methodologies to haemodynamic evaluation and ex vivo set-ups.

Targeting myocardial remodelling to develop novel therapies for heart failure: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology

The failing heart is characterized by complex tissue remodelling involving increased cardiomyocyte death, and impairment of sarcomere function, metabolic activity, endothelial and vascular function, together with increased inflammation and interstitial fibrosis. For years, therapeutic approaches for heart failure (HF) relied on vasodilators and diuretics which relieve cardiac workload and HF symptoms. The introduction in the clinic of drugs interfering with beta-adrenergic and angiotensin signalling have ameliorated survival by interfering with the intimate mechanism of cardiac compensation. Current therapy, though, still has a limited capacity to restore muscle function fully, and the development of novel therapeutic targets is still an important medical need. Recent progress in understanding the molecular basis of myocardial dysfunction in HF is paving the way for development of new treatments capable of restoring muscle function and targeting specific pathological subsets of LV dysfunction. These include potentiating cardiomyocyte contractility, increasing cardiomyocyte survival and adaptive hypertrophy, increasing oxygen and nutrition supply by sustaining vessel formation, and reducing ventricular stiffness by favourable extracellular matrix remodelling. Here, we consider drugs such as omecamtiv mecarbil, nitroxyl donors, cyclosporin A, SERCA2a (sarcoplasmic/endoplasmic Ca(2 +) ATPase 2a), neuregulin, and bromocriptine, all of which are currently in clinical trials as potential HF therapies, and discuss novel molecular targets with potential therapeutic impact that are in the pre-clinical phases of investigation. Finally, we consider conceptual changes in basic science approaches to improve their translation into successful clinical applications.

Dickens, Hogarth and artistic perception: the case of Nicholas Nickleby

This essay considers the interest shared by William Hogarth and Charles Dickens on the idea of instrumentality in the art of realism. Taking his cue from eighteenth-century epistemological philosophy, Hogarth developed an idea of beauty and realism as insisting upon the need for human subjectivity or perspective. Naïve realism was a style that troubled both Hogarth and Dickens and both men developed forms in which caricature, melodrama and exaggeration is crucial to the development of verisimilitude. Considering the progress pieces and the writings of Hogarth as a preface to the style of Dickens, I argue that Nicholas Nickleby developed an extraordinary self-reflexivity. Both Nicholas and his uncle Ralph form part of a narrative study of the implications of filtering perception through the distorting lens of the individual.

Evaluation of simulated sea-ice concentrations from sea-ice/ocean models using satellite data and polynya classification methods

Sea-ice concentrations in the Laptev Sea simulated by the coupled North Atlantic-Arctic Ocean-Sea-Ice Model and Finite Element Sea-Ice Ocean Model are evaluated using sea-ice concentrations from Advanced Microwave Scanning Radiometer-Earth Observing System satellite data and a polynya classification method for winter 2007/08. While developed to simulate largescale sea-ice conditions, both models are analysed here in terms of polynya simulation. The main modification of both models in this study is the implementation of a landfast-ice mask. Simulated sea-ice fields from different model runs are compared with emphasis placed on the impact of this prescribed landfast-ice mask. We demonstrate that sea-ice models are not able to simulate flaw polynyas realistically when used without fast-ice description. Our investigations indicate that without landfast ice and with coarse horizontal resolution the models overestimate the fraction of open water in the polynya. This is not because a realistic polynya appears but due to a larger-scale reduction of ice concentrations and smoothed ice-concentration fields. After implementation of a landfast-ice mask, the polynya location is realistically simulated but the total open-water area is still overestimated in most cases. The study shows that the fast-ice parameterization is essential for model improvements. However, further improvements are necessary in order to progress from the simulation of large-scale features in the Arctic towards a more detailed simulation of smaller-scaled features (here polynyas) in an Arctic shelf sea.

Circadian Pattern of Wheel-Running Activity of a South American Subterranean Rodent (Ctenomys cf knightii)

Circadian rhythms are regarded as essentially ubiquitous features of animal behavior and are thought to confer important adaptive advantages. However, although circadian systems of rodents have been among the most extensively studied, most comparative biology is restricted to a few related species. In this study, the circadian organization of locomotor activity was studied in the subterranean, solitary north Argentinean rodent, Ctenomys knightii. The genus, Ctenomys, commonly known as Tuco-tucos, comprises more than 50 known species over a range that extends from 12S latitude into Patagonia, and includes at least one social species. The genus, therefore, is ideal for comparative and ecological studies of circadian rhythms. Ctenomys knightii is the first of these to be studied for its circadian behavior. All animals were wild caught but adapted quickly to laboratory conditions, with clear and precise activity-rest rhythms in a light-dark (LD) cycle and strongly nocturnal wheel running behavior. In constant dark (DD), the rhythm expression persisted with free-running periods always longer than 24h. Upon reinstatement of the LD cycle, rhythms resynchronized rapidly with large phase advances in 7/8 animals. In constant light (LL), six animals had free-running periods shorter than in DD, and 4/8 showed evidence of splitting. We conclude that under laboratory conditions, in wheel-running cages, this species shows a clear nocturnal rhythmic organization controlled by an endogenous circadian oscillator that is entrained to 24h LD cycles, predominantly by light-induced advances, and shows the same interindividual variable responses to constant light as reported in other non-subterranean species. These data are the first step toward understanding the chronobiology of the largest genus of subterranean rodents.

Recurrent Deletion of ZNF630 at Xp11.23 Is Not Associated With Mental Retardation

ZNF630 is a member of the primate-specific Xp11 zinc finger gene cluster that consists of six closely related genes, of which ZNF41, ZNF81, and ZNF674 have been shown to be involved in mental retardation. This suggests that mutations of ZNF630 might influence cognitive function. Here, we detected 12 ZNF630 deletions in a total of 1,562 male patients with mental retardation from Brazil, USA, Australia, and Europe. The breakpoints were analyzed in 10 families, and in all cases they were located within two segmental duplications that share more than 99% sequence identity, indicating that the deletions resulted from non-allelic homologous recombination. In 2,121 healthy male controls, 10 ZNF630 deletions were identified. In total, there was a 1.6-fold higher frequency of this deletion in males with mental retardation as compared to controls, but this increase was not statistically significant (P-value = 0.174). Conversely, a 1.9-fold lower frequency of ZNF630 duplications was observed in patients, which was not significant either (P-value = 0.163). These data do not show that ZNF630 deletions or duplications are associated with mental retardation. (C) 2010 Wiley-Liss, Inc.

Comparative genomics of the neglected human malaria parasite Plasmodium vivax

The human malaria parasite Plasmodium vivax is responsible for 25 - 40% of the similar to 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non- human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.

Carpentry Students at Work

Carpentry students from the New York Trade School at work during a class. Black and white photograph.

Multimodal Literacy as a form of Communication : What is the state of the students at Dalarna University multimodal literacy?

Literacy is an invaluable asset to have, and has allowed for communication, documentation and the spreading of ideas since the beginning of the written language. With technological advancements, and new possibilities to communicate, it is important to question the degree to which people’s abilities to utilise these new methods have developed in relation to these emerging technologies. The purpose of this bachelor’s thesis is to analyse the state of students’ at Dalarna University mulitimodal literacy, as well as their experience of multimodality in their education. This has led to the two main research questions: What is the state of the students at Dalarna University multimodal literacy? And: How have the students at Dalarna University experienced multimodality in education? The paper is based on a mixed-method study that incorporates both a quantitative and qualitative aspect to it. The main thrust of the research paper is, however, based on a quantitative study that was conducted online and emailed to students via their program coordinators. The scope of the research is in audio-visual modes, i.e. audio, video and images, while textual literacy is presumed and serves as an inspiration to the study. The purpose of the study is to analyse the state of the students’ multimodal literacy and their experience of multimodality in education. The study revealed that the students at Dalarna University have most skill in image editing, while not being very literate in audio or video editing. The students seem to have had mediocre experience creating meaning through multimodality both in private use and in their respective educational institutions. The study also reveals that students prefer learning by means of video (rather than text or audio), yet are not able to create meaning (communicate) through it.

Group photo at New York Trade School Commencement Ceremony, 1959

A group of administrators from the New York Trade School pose at the 1959 commencement ceremony held May 19, 1959. Original caption: "Front: (left to right) Wm. F. Vanderbeek - Kenneth Schweiger - Bernard Rosenstadt - Ralph D. Cole - George E. McLaughlin - Herbert Brod - Edward Hansen. Back: (left to right) James Wright - Lawrence Levenstein - Ronald B. Smith - Roy Wall."

Group Photo at a New York Trade School Commencement Ceremony

This is a group photo mainly comprised of the school's administrators taken at the 1958 commencement ceremony of the New York Trade School. Original caption reads, "Back Row - Left to Right: William F. Vanderbeek, Robert H. Scholl, Gurdon Simmon, Miss Marie Kaye, and Peter H. Vermilye. Front Row - Left to Right: Gilbert G. Weaver, George E. McLaughlin, John Clarke, Enders M. Voorhees, Ralph Cole, Frank Casino and Charles Leidig." Black and white photograph.

Planejamento estratégico e o controle da gestão pública: Desenvolvimento da ação de controle da gestão dos recursos públicos

Esta dissertação procura analisar o planejamento estratégico e a evolução do pensamento estratégico, objetivando identificar a possibilidade de adequação da utilização de suas técnicas, para contribuir no desenvolvimento da metodologia empregada no controle da gestão dos recursos públicos. Com esse propósito, a pesquisa bibliográfica é centrada no estudo do referencial teórico, e enfatiza a investigação das práticas e dos fenômenos organizadonais à luz da teoria da gestão estratégica. Nesse sentido, também é apresentada a análise dos resultados da pesquisa de campo, onde fica caracterizado a carência de estudo, pesquisa e desenvolvimento das práticas de controle; retratando a ausência de um pensamento estratégico voltado para o desenvolvimento dessa poUtica pública. As reflexões sobre as observaçôes colhidas no estudo, levaram à conclusão da necessidade fundamental da utilização do pensamento estratégico e da gestão estratégica, como um exercfcio contínuo de aperfeiçoamento da metodologia de ação de controle da gestão dos recursos públicos, voltada ao melhor cumprimento da missão institucional.

Affirmative action and interracial friendships

In two recent cases involving the University of Michigan, the Supreme Court examined whether race should be allowed to play an explicit role in the admission decisions of schools. The primary argument in these court cases and others has been that racial diversity strengthens the quality of education ofered to all students. Underlying this argument is the notion that educational benefits arise if interactions between students of different races improve preparation for life after college by, among other things, fostering mutual understanding and correcting misperceptions. A comprehensive study of this issue would ideally examine two conditions: first, whether students actually have incorrect perceptions about their friendship compatibility with students of other races at the time of college entrance; second, if misperceptions exist, whether diversity on campus is effective in changing students' beliefs about individuals of different races. In this paper we provide, to the best of our knowledge, the first direct evidence about both conditions by taking advantage of unique new data that was collected specifically for this purpose.

Inserção do Design em Micro e Pequenas Empresas: o caso de duas indústrias moveleiras no Estado do Rio Grande do Norte /

This work aims to promote design aspects into furniture Small and Medium Enterprises (SME s) at Rio Grande do Norte State. The final outcome will be an increasing on their competitiveness as well as consider design as key strategic aspect for their business. As a consequence, the results are based on two SME companies from the furniture sector located at Natal/RN. The study is based on a literature research followed by a management diagnosis for each company. The diagnosis was base don interviews with the entrepreneurs and their employees as well as meetings, participant observations and document analysis. Based on this analysis, specific aspects were implement in order to boost the production line as well as the product development process (PDP) and the development of a prototype. The results have indicated some limitation of these companies regarding their low technological on their production line, poor management and work skills as well as low perception of design as a competitive tool. Regardless these results, it was observed that design has brought an important contribution for cultural changes within companies as well as for the development of better quality and competitive products