Nonlinear Transient Field Problems with Phase Change using the Boundary Element Method

Peer reviewe

A distributed algorithm for European options with nonlinear volatility

A distributed algorithm is developed to solve nonlinear Black-Scholes equations in the hedging of portfolios. The algorithm is based on an approximate inverse Laplace transform and is particularly suitable for problems that do not require detailed knowledge of each intermediate time steps

Microtubule organization within mitotic spindles revealed by serial block face scanning electron microscopy and image analysis

Serial block face scanning electron microscopy (SBF-SEM) is a powerful method to analyze cells in 3D. Here, working at the resolution limit of the method, we describe a correlative light-SBF-SEM workflow to resolve microtubules of the mitotic spindle in human cells. We present four examples of uses for this workflow that are not practical by light microscopy and/or transmission electron microscopy. First, distinguishing closely associated microtubules within K-fibers; second, resolving bridging fibers in the mitotic spindle; third, visualizing membranes in mitotic cells, relative to the spindle apparatus; and fourth, volumetric analysis of kinetochores. Our workflow also includes new computational tools for exploring the spatial arrangement of microtubules within the mitotic spindle. We use these tools to show that microtubule order in mitotic spindles is sensitive to the level of TACC3 on the spindle

The challenges for graphic design in establishing an academic research culture: lessons from the Research Excellence Framework 2014

This paper examines why graphic design has struggled to establish an academic research culture, despite significant gains in design research over the last 20 years. It considers the criticisms levelled against graphic design research submitted to the 2014 Research Excellence Framework (REF2014). Through analysis of publicly available data, we identify a low volume of graphic design research adhering to traditional academic, non-practice-based forms, and concentrated amongst few institutions. Results confirm graphic design is yet to establish an academic research culture that accords with its widespread standing in higher education. We identify the absence of consensual nomenclature, lack of confidence and exemplars with practice-based graphic design research, the uncertain expectations of research audits, lack of venues for dissemination, heavy teaching loads and few established career pathways for research. In response we make a series of recommendations towards a sustainable graphic design research change agenda

Polymerase I and Transcript Release Factor Regulates Lipolysis via a Phosphorylation-Dependent Mechanism

OBJECTIVE: Polymerase I and transcript release factor (PTRF) is a protein highly expressed in adipose tissue and is an integral structural component of caveolae. Here, we report on a novel role of PTRF in lipid mobilization. RESEARCH DESIGN AND METHODS: PTRF expression was examined in different adipose depots of mice during fasting, refeeding, and after administration of catecholamines and insulin. Involvement of PTRF during lipolysis was studied upon PTRF knockdown and overexpression and mutation of PTRF phosphorylation sites in 3T3-L1 adipocytes. RESULTS: PTRF expression in mouse white adipose tissue (WAT) is regulated by nutritional status, increasing during fasting and decreasing to baseline after refeeding. Expression of PTRF also is hormonally regulated because treatment of mice with insulin leads to a decrease in expression, whereas isoproterenol increases expression in WAT. Manipulation of PTRF levels revealed a role of PTRF in lipolysis. Lentiviral-mediated knockdown of PTRF resulted in a marked attenuation of glycerol release in response to isoproterenol. Conversely, overexpressing PTRF enhanced isoproterenol-stimulated glycerol release. Mass-spectrometric analysis revealed that PTRF is phosphorylated at multiple sites in WAT. Mutation of serine 42, threonine 304, or serine 368 to alanine reduced isoproterenol-stimulated glycerol release in 3T3-L1 adipocytes. CONCLUSIONS: Our study is the first direct demonstration for a novel adipose tissue–specific function of PTRF as a mediator of lipolysis and also shows that phosphorylation of PTRF is required for efficient fat mobilization

Stimulation of glucose utilization in 3T3 adipocytes and rat diaphragm in vitro by the sulphonylureas, glimepiride and glibenclamide, is correlated with modulations of the cAMP regulatory cascade

The long-term hypoglycemic activity of sulphonylurea drugs has been attributed, in part at least, to the stimulation of glucose utilization in extra-pancreatic tissues. The novel sulphonylurea, glimepiride, gives rise to a longer lasting reduction in the blood sugar level in dogs and rabbits compared to glibenclamide (Geisen K, Drug Res38: 1120–1130, 1988). This cannot be explained adequately by elevated plasma insulin levels. This study investigated whether this prolonged hypoglycemic phase was based on the drug's abilities to stimulate glucose utilization and affect the underlying regulatory mechanisms in insulin-sensitive cells in vitro. It was found that in the absence of added insulin, glimepiride and glibenclamide (1–50 μM) stimulated lipogenesis (3T3 adipocytes) and glycogenesis (isolated rat diaphragm) not, vert, similar4.5- and 2.5-fold, respectively, and reduced the isoproterenol-stimulated lipolysis (rat adipocytes) up to 40–60%. The increased glucose utilization was correlated with a 3–4-fold higher 2-deoxyglucose transport rate and amount of GLUT4 at the plasma membrane, as well as with increased activities of key metabolic enzymes (glycerol-3-phosphate acyltransferase, glycogen synthase) within the same concentration range. Furthermore, the low Km cAMP-specific phosphodiesterase was activated 1.8-fold, whereas the cytosolic cAMP level and protein kinase A activity ratios were significantly lowered after incubation of isoproterenol-stimulated rat adipocytes with the sulphonylureas. In many of the aspects studied the novel sulphonylurea, glimepiride, exhibited slightly lower ed50-values than glibenclamide. This study demonstrates correlations existing between drug-induced stimulation of glucose transport/metabolism and cAMP degradation/protein kinase A inhibition as well as between the relative efficiencies of glimepiride and glibenclamide in inducing thse extra-pancreatic processes. Therefore, it is suggested that the stimulation of glucose utilization by sulphonylureas is mediated by a decrease of cAMP-dependent phosphorylation of GLUT4 and glucose metabolizing enzymes. The therapeutic relevance of extra-pancreatic effects of sulphonylureas, in general, and of the differences between glimepiride and glibenclamide as observed in vitro in this work, in particular, remain to be elucidated

Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease

Background: Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. Objectives: To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials. Date of latest search of the registers: 25 June 2015. Date of latest search of all other sources: 10 December 2014. Selection criteria: Any randomised or quasi-randomised control trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease when compared to usual care. Data collection and analysis: We identified 19 papers, describing 13 unique trials which were potentially eligible for inclusion in the review. However, after assessment, no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found. Main results: No randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found. Authors' conclusions: As no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis, or Tay-Sachs disease were found for inclusion in this review, the research evidence for current policy recommendations is limited to non-randomised studies. Information from well-designed, adequately powered, randomised trials is desirable in order to make more robust recommendations for practice. However, such trials must also consider the legal, ethical, and cultural barriers to implementation of preconception genetic risk assessment