Par4 is a coactivator for a splice isoform-specific transcriptional activation domain in WT1

The Wilms’ tumor suppressor protein WT1 is a transcriptional regulator involved in differentiation and the regulation of cell growth. WT1 is subject to alternative splicing, one isoform including a 17–amino acid region that is specific to mammals. The function of this 17–amino acid insertion is not clear, however. Here, we describe a transcriptional activation domain in WT1 that is specific to the WT1 splice isoform that contains the 17–amino acid insertion. We show that the function of this domain in transcriptional activation is dependent on a specific interaction with the prostate apoptosis response factor par4. A mutation in WT1 found in Wilms’ tumor disturbs the interaction with par4 and disrupts the function of the activation domain. Analysis of WT1 derivatives in cells treated to induce par4 expression showed a strong correlation between the transcription function of the WT1 17–amino acid insertion and the ability of WT1 to regulate cell survival and proliferation. Our results provide a molecular mechanism by which alternative splicing of WT1 can regulate cell growth in development and disease.

Refining animal models in fracture research: Seeking consensus in optimising both animal welfare and scientific validity for appropriate biomedical use

Background In an attempt to establish some consensus on the proper use and design of experimental animal models in musculoskeletal research, AOVET (the veterinary specialty group of the AO Foundation) in concert with the AO Research Institute (ARI), and the European Academy for the Study of Scientific and Technological Advance, convened a group of musculoskeletal researchers, veterinarians, legal experts, and ethicists to discuss, in a frank and open forum, the use of animals in musculoskeletal research. Methods The group narrowed the field to fracture research. The consensus opinion resulting from this workshop can be summarized as follows: Results & Conclusion Anaesthesia and pain management protocols for research animals should follow standard protocols applied in clinical work for the species involved. This will improve morbidity and mortality outcomes. A database should be established to facilitate selection of anaesthesia and pain management protocols for specific experimental surgical procedures and adopted as an International Standard (IS) according to animal species selected. A list of 10 golden rules and requirements for conduction of animal experiments in musculoskeletal research was drawn up comprising 1) Intelligent study designs to receive appropriate answers; 2) Minimal complication rates (5 to max. 10%); 3) Defined end-points for both welfare and scientific outputs analogous to quality assessment (QA) audit of protocols in GLP studies; 4) Sufficient details for materials and methods applied; 5) Potentially confounding variables (genetic background, seasonal, hormonal, size, histological, and biomechanical differences); 6) Post-operative management with emphasis on analgesia and follow-up examinations; 7) Study protocols to satisfy criteria established for a "justified animal study"; 8) Surgical expertise to conduct surgery on animals; 9) Pilot studies as a critical part of model validation and powering of the definitive study design; 10) Criteria for funding agencies to include requirements related to animal experiments as part of the overall scientific proposal review protocols. Such agencies are also encouraged to seriously consider and adopt the recommendations described here when awarding funds for specific projects. Specific new requirements and mandates related both to improving the welfare and scientific rigour of animal-based research models are urgently needed as part of international harmonization of standards.

Responding to rapid change in higher education : enabling university departments responsible for work related programs through boundary spanning

Boundary spanning links organisations to one another in order to create mutually beneficial relationships; it is a concept developed and used in organisational theory but rarely used to understand organisational structures in higher education (Pruitt & Schwartz, 1999). Yet understanding boundary spanning activity has the capacity to help universities respond to demands for continuous quality improvement, and to increase capacity to react to environmental uncertainty. At a time of rapid change characterised by a fluctuating economic environment, globalisation, increased mobility, and ecological issues, boundary spanning could be viewed as a key element in assisting institutions in effectively understanding and responding to such change. The literature suggests that effective boundary spanning could help universities improve organisational performance, use of infrastructure and resources, intergroup relations, leadership styles, performance and levels of job satisfaction, technology transfer, knowledge creation, and feedback processes, amongst other things. Our research aims to put a face on boundary spanning (Miller, 2008) by contextualising it within organisational systems and structures in university departments responsible for work related programs i.e. Work Integrated Learning (WIL) and Co-operative Education (Co-op). In this paper these approaches are referred to collectively as work related programs. The authors formed a research team in Victoria, British Columbia in 2009 at a sponsored international research forum, Two Days in June. The purpose of the invitation-only forum was to investigate commonalities and differences across programs and to formulate an international research agenda for work related programs over the next five to ten years. Researchers from Queensland University of Technology, University of Cincinnati, Baden-Wuerttemberg Cooperative State University, University of Ottawa,and Dublin City University agreed that further research was needed into the impact stakeholders, organisational systems, structures, policies, and practices have on departments delivering work related programs. This paper illustrates how policy and practice across the five institutions can be better understood through the lens of boundary spanning. It is argued that boundary spanning is an area of theory and practice with great applicability to a better understanding of the activity of these departments. The paper concludes by proposing topics for future research to examine how boundary spanning can be used to better understand practice and change in work related programs.

Simulation architecture for the design of cooperative collision warning systems

Simulation has been widely used to estimate the benefits of Cooperative Systems (CS) based on Inter-Vehicular Communications (IVC). This paper presents a new architecture built with the SiVIC simulator and the RTMaps™ multisensors prototyping platform. We introduce several improvements from a previous similar architecture, regarding IVC modelisation and vehicles’ control. It has been tuned with on-road measurements to improve fidelity. We discuss the results of a freeway emergency braking scenario (EEBL) implemented to validate our architecture’s capabilities.

Bioequivalence of two tablet formulations of capecitabine and exploration of age, gender, body surface area, and creatinine clearance as factors influencing systemic exposure in cancer patients

Purpose: The objective of the study was to assess the bioequivalence of two tablet formulations of capecitabine and to explore the effect of age, gender, body surface area and creatinine clearance on the systemic exposure to capecitabine and its metabolites. Methods: The study was designed as an open, randomized two-way crossover trial. A single oral dose of 2000 mg capecitabine was administered on two separate days to 25 patients with solid tumors. On one day, the patients received four 500-mg tablets of formulation B (test formulation) and on the other day, four 500-mg tablets of formulation A (reference formulation). The washout period between the two administrations was between 2 and 8 days. After each administration, serial blood and urine samples were collected for up to 12 and 24 h, respectively. Unchanged capecitabine and its metabolites were determined in plasma using LC/MS-MS and in urine by NMRS. Results: Based on the primary pharmacokinetic parameter, AUC(0-∞) of 5'-DFUR, equivalence was concluded for the two formulations, since the 90% confidence interval of the estimate of formulation B relative to formulation A of 97% to 107% was within the acceptance region 80% to 125%. There was no clinically significant difference between the t(max) for the two formulations (median 2.1 versus 2.0 h). The estimate for C(max) was 111% for formulation B compared to formulation A and the 90% confidence interval of 95% to 136% was within the reference region 70% to 143%. Overall, these results suggest no relevant difference between the two formulations regarding the extent to which 5'-DFUR reached the systemic circulation and the rate at which 5'-DFUR appeared in the systemic circulation. The overall urinary excretions were 86.0% and 86.5% of the dose, respectively, and the proportion recovered as each metabolite was similar for the two formulations. The majority of the dose was excreted as FBAL (61.5% and 60.3%), all other chemical species making a minor contribution. Univariate and multivariate regression analysis to explore the influence of age, gender, body surface area and creatinine clearance on the log-transformed pharmacokinetic parameters AUC(0-∞) and C(max) of capecitabine and its metabolites revealed no clinically significant effects. The only statistically significant results were obtained for AUC(0-∞) and C(max) of intact drug and for C(max) of FBAL, which were higher in females than in males. Conclusion: The bioavailability of 5'-DFUR in the systemic circulation was practically identical after administration of the two tablet formulations. Therefore, the two formulations can be regarded as bioequivalent. The variables investigated (age, gender, body surface area, and creatinine clearance) had no clinically significant effect on the pharmacokinetics of capecitabine or its metabolites.

Simulating cooperative systems applications : a new complete architecture

For a decade, embedded driving assistance systems were mainly dedicated to the management of short time events (lane departure, collision avoidance, collision mitigation). Recently a great number of projects have been focused on cooperative embedded devices in order to extend environment perception. Handling an extended perception range is important in order to provide enough information for both path planning and co-pilot algorithms which need to anticipate events. To carry out such applications, simulation has been widely used. Simulation is efficient to estimate the benefits of Cooperative Systems (CS) based on Inter-Vehicular Communications (IVC). This paper presents a new and modular architecture built with the SiVIC simulator and the RTMaps™ multi-sensors prototyping platform. A set of improvements, implemented in SiVIC, are introduced in order to take into account IVC modelling and vehicles’ control. These 2 aspects have been tuned with on-road measurements to improve the realism of the scenarios. The results obtained from a freeway emergency braking scenario are discussed.

Australia

Crisis management in the banking sector is a topical issue in Australia. This is not because financial institutions are facing a financial crisis. Indeed, in 2012, the International Monetary Fund (IMF) noted that ‘Australia has a history of few bank failures, even fewer financial crises, and its banking sector emerged from the global financial crisis relatively well.’ Rather, crisis management of banks is topical because there has been the first full review of Australia’s banking and financial system in nearly 20 years, which has examined and raised issues about the resilience and capacity of the Australian regime in this post GFC world. At the time of writing, the Report’s recommendations, including for Australian banks to meet capital standards in line with emerging international practice, are the subject of industry debate in advance of the Australian government’s decision.

”Waxaa i bartay hooyaday waawa u muhiim naaska caruurta.” Äitini opetti, että rintamaito on tärkeää lapselle. Osallistava tutkimus auktoritatiivisen tiedon omaksumisesta somalikulttuuritaustaisten naisten imetyskäytännöissä.

Suomessa asuvat somalitaustaiset maahanmuuttajaäidit luopuvat imetyksestä ja ruokkivat vauvojaan äidinmaidonkorvikkeella, vaikka somalikulttuurissa arvostetaan imetystä. Tuen ja tiedon puutetta on arveltu syyksi pulloruokinnan yleisyyteen. Tarkoituksenani on tutkia osallistavia menetelmiä käyttäen, minkälaisia imetykseen liittyviä tietojärjestelmiä somaliäidit pitävät auktoritatiivisina eli arvovaltaisina. Tarkastelen tiedon auktoritatiivisuutta etnografisten esimerkkien valossa hyödyntäen Brigitte Jordanin auktoritatiivisen tiedon käsitettä. Tutkin Jean Pierre Olivier de Sardanin teorian avulla, kuinka paikalliset populaarit tietojärjestelmät kohtaavat tieteellis-teknisen tiedon kehityksen kontekstissa. Tutkin myös, kuinka somaliäitien imetystietojärjestelmät kohtaavat suomalaisen terveydenhoitojärjestelmän edustaman imetystiedon. Osallistavien menetelmien tarkoituksena on saada heikkojen ja sorrettujen yhteisöjen ääni kuuluviin. Tutkimukseni tiedonantajina on seitsemäntoista somalimaahanmuuttajaäitiä ja yksi suomalainen äitiys- ja lastenneuvolan terveydenhoitaja. Käytän tiedonkeruumenetelminä puolistrukturoituja teemahaastatteluja, jonka lisäksi teen osallistuvaa havainnointia ja osallistavia menetelmiä kolmessa ryhmähaastattelutilanteessa. Käytän Rapi Rurad Appraisal (RRA) –menetelmiä, kuten Venn-diagrammia ja pisteytystä. Tutkimukseni tulos on, että somaliäitien imetykseen liittyvä tieto koostuu kolmesta tietojärjestelmästä, joita ovat sukuverkostoista tuleva perinteinen tietotaito, islaminuskon terveystieto sekä suomalaisen terveydenhoitojärjestelmän tieto. Näistä eri tietolähteistä tuleva imetystieto ei ole sisällöltään ristiriidassa. Imetykseen liittyvät vaikeudet ovat käytännön ongelmiin, kuten sukuverkoston hajoamiseen ja suomalaisen terveydenhoitojärjestelmän kanssa kommunikointiin liittyviä.

Reversible shear-induced crystallization above equilibrium freezing temperature in a lyotropic surfactant system

We demonstrate a unique shear-induced crystallization phenomenon above the equilibrium freezing temperature (T-K(o)) in weakly swollen isotropic (L-i) and lamellar (L-alpha) mesophases with bilayers formed in a cationic-anionic mixed surfactant system. Synchrotron rheological X-ray diffraction study reveals the crystallization transition to be reversible under shear (i.e., on stopping the shear, the nonequilibrium crystalline phase L-c melts back to the equilibrium mesophase). This is different from the shear-driven crystallization below T-K(o), which is irreversible. Rheological optical observations show that the growth of the crystalline phase occurs through a preordering of the L-i phase to an L-alpha phase induced by shear flow, before the nucleation of the Lc phase. Shear diagram of the L-i phase constructed in the parameter space of shear rate ((gamma)) over dot vs. temperature exhibits L-i -> L-c and L-i -> L-alpha transitions above the equilibrium crystallization temperature (T-K(o)), in addition to the irreversible shear-driven nucleation of L-c in the L-i phase below T-K(o). In addition to revealing a unique class of nonequilibrium phase transition, the present study urges a unique approach toward understanding shear-induced phenomena in concentrated mesophases of mixed amphiphilic systems.

Coral reef activity book

An activity book for children highlighting coral reef issues. The book includes coral reef information, fun facts, drawings to color, connect the dots, find a word, images, matching, etc. Target audience is K-6th graders.

Characterization and Comparison of the Tissue-Related Modules in Human and Mouse

Background: Due to the advances of high throughput technology and data-collection approaches, we are now in an unprecedented position to understand the evolution of organisms. Great efforts have characterized many individual genes responsible for the interspecies divergence, yet little is known about the genome-wide divergence at a higher level. Modules, serving as the building blocks and operational units of biological systems, provide more information than individual genes. Hence, the comparative analysis between species at the module level would shed more light on the mechanisms underlying the evolution of organisms than the traditional comparative genomics approaches. Results: We systematically identified the tissue-related modules using the iterative signature algorithm (ISA), and we detected 52 and 65 modules in the human and mouse genomes, respectively. The gene expression patterns indicate that all of these predicted modules have a high possibility of serving as real biological modules. In addition, we defined a novel quantity, "total constraint intensity,'' a proxy of multiple constraints (of co-regulated genes and tissues where the co-regulation occurs) on the evolution of genes in module context. We demonstrate that the evolutionary rate of a gene is negatively correlated with its total constraint intensity. Furthermore, there are modules coding the same essential biological processes, while their gene contents have diverged extensively between human and mouse. Conclusions: Our results suggest that unlike the composition of module, which exhibits a great difference between human and mouse, the functional organization of the corresponding modules may evolve in a more conservative manner. Most importantly, our findings imply that similar biological processes can be carried out by different sets of genes from human and mouse, therefore, the functional data of individual genes from mouse may not apply to human in certain occasions.

Der perfekte Auftritt

Biehl, Brigitte, 'Der perfekte Auftritt', Harvard Business Manager (2007) 29(5) pp.18-27 RAE2008

Rôle de la molécule CD81 dans le fonctionnement des lymphocytes B chez l'homme.

News