Optimal language policy for the preservation of a minority language

We develop a dynamic language competition model with dynamic state intervention. Parents choose the language(s) to raise their children based on the communicational value of each language as well as on their emotional attachment to the languages at hand. Languages are thus conceptualized as tools for communication as well as carriers of cultural identity. The model includes a high and a low status language, and children can be brought up as monolinguals or bilinguals. Through investment into language policies, the status of the minority language can be increased. The aim of the intervention is to preserve the minority language in a bilingual subpopulation at low costs. We investigate the dynamic structure of the optimally controlled system as well as the optimal policy, identify stable equilibria and provide numerical case studies

Propagation of a Solitary Fission Wave

Reaction-diffusion phenomena are encountered in an astonishing array of natural systems. Under the right conditions, self stabilizing reaction waves can arise that will propagate at constant velocity. Numerical studies have shown that fission waves of this type are also possible and that they exhibit soliton like properties. Here, we derive the conditions required for a solitary fission wave to propagate at constant velocity. The results place strict conditions on the shapes of the flux, diffusive, and reactive profiles that would be required for such a phenomenon to persist, and this condition would apply to other reaction diffusion phenomena as well. Numerical simulations are used to confirm the results and show that solitary fission waves fall into a bistable class of reaction diffusion phenomena. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4729927]United States Nuclear Regulatory Commission NRC-38-08-946Mechanical Engineerin

Palmitate induces mRNA translation and increases ER protein load in islet β-cells via activation of the mammalian target of rapamycin pathway

Saturated free fatty acids (FFAs) have complex effects on the islet β-cell, acutely promoting adaptive hyperplasia but chronically impairing insulin release. The acute effects of FFAs remain incompletely defined. To elucidate these early molecular events, we incubated mouse β-cells and islets with palmitate and then studied mRNA translation by polyribosomal profiling and analyzed signaling pathways by immunoblot analysis. We found that palmitate acutely increases polyribosome occupancy of total RNA, consistent with an increase in mRNA translation. This effect on translation was attributable to activation of mammalian target of rapamycin (mTOR) pathways via L-type Ca(2+) channels but was independent of insulin signaling. Longer incubations led to depletion of polyribosome-associated RNA, consistent with activation of the unfolded protein response (UPR). Pharmacologic inhibition of mTOR suppressed both the acute effects of palmitate on mRNA translation and the chronic effects on the UPR. Islets from mice fed a high-fat diet for 7 days showed increases in polyribosome-associated RNA and phosphorylation of S6K, both consistent with activation of mTOR. Our results suggest that palmitate acutely activates mRNA translation and that this increase in protein load contributes to the later UPR

Moving beyond physical education subject knowledge to develop knowledgeable teachers of the subject

All knowledge is socially constructed, including physical education teachers’ knowledge of their subject. It is acquired from other people either formally and deliberately (e.g. by being taught) or informally and casually (e.g. by interacting with physical education teachers or playing in a sports team). The social aspects of learning appear to be particularly strong in physical education. This has implications for the development of knowledge for teaching, with trainee teachers focusing on the development of subject, and particularly content, knowledge. Focusing on subject knowledge reinforces a traditional view of physical education as it is, not as it might be to meet the needs of young people today. It is argued that attention needs to be given not only to the knowledge, skills and competencies that trainee teachers ought to develop but also to the social aspects of their learning and development and the context in which they learn. Attention also needs to be given to how the ability to think critically can be developed so that trainee teachers can become reflective practitioners able to challenge and, where appropriate, change the teaching of the subject. Only by doing this can the particularly strong socialisation which shapes the values and beliefs of physical education teachers begin to be challenged. However, as the process of developing knowledgeable teachers is ongoing it is also necessary to look beyond teacher training to continuing professional development

Moving beyond physical education subject knowledge to develop knowledgeable teachers of the subject

All knowledge is socially constructed, including physical education teachers’ knowledge of their subject. It is acquired from other people either formally and deliberately (e.g. by being taught) or informally and casually (e.g. by interacting with physical education teachers or playing in a sports team). The social aspects of learning appear to be particularly strong in physical education. This has implications for the development of knowledge for teaching, with trainee teachers focusing on the development of subject, and particularly content, knowledge. Focusing on subject knowledge reinforces a traditional view of physical education as it is, not as it might be to meet the needs of young people today. It is argued that attention needs to be given not only to the knowledge, skills and competencies that trainee teachers ought to develop but also to the social aspects of their learning and development and the context in which they learn. Attention also needs to be given to how the ability to think critically can be developed so that trainee teachers can become reflective practitioners able to challenge and, where appropriate, change the teaching of the subject. Only by doing this can the particularly strong socialisation which shapes the values and beliefs of physical education teachers begin to be challenged. However, as the process of developing knowledgeable teachers is ongoing it is also necessary to look beyond teacher training to continuing professional development

Insulin regulates carboxypeptidase E by modulating translation initiation scaffolding protein eIF4G1 in pancreatic β cells

Insulin resistance, hyperinsulinemia, and hyperproinsulinemia occur early in the pathogenesis of type 2 diabetes (T2D). Elevated levels of proinsulin and proinsulin intermediates are markers of β-cell dysfunction and are strongly associated with development of T2D in humans. However, the mechanism(s) underlying β-cell dysfunction leading to hyperproinsulinemia is poorly understood. Here, we show that disruption of insulin receptor (IR) expression in β cells has a direct impact on the expression of the convertase enzyme carboxypeptidase E (CPE) by inhibition of the eukaryotic translation initiation factor 4 gamma 1 translation initiation complex scaffolding protein that is mediated by the key transcription factors pancreatic and duodenal homeobox 1 and sterol regulatory element-binding protein 1, together leading to poor proinsulin processing. Reexpression of IR or restoring CPE expression each independently reverses the phenotype. Our results reveal the identity of key players that establish a previously unknown link between insulin signaling, translation initiation, and proinsulin processing, and provide previously unidentified mechanistic insight into the development of hyperproinsulinemia in insulin-resistant states

In silico investigation of a KCNQ1 mutation associated with short QT syndrome

Short QT syndrome (SQTS) is a rare condition characterized by abnormally ‘short’ QT intervals on the ECG and increased susceptibility to cardiac arrhythmias and sudden death. This simulation study investigated arrhythmia dynamics in multi-scale human ventricle models associated with the SQT2-related V307L KCNQ1 ‘gain-of-function’ mutation, which increases slow-delayed rectifier potassium current (IKs). A Markov chain (MC) model recapitulating wild type (WT) and V307L mutant IKs kinetics was incorporated into a model of the human ventricular action potential (AP) for investigation of QT interval changes and arrhythmia substrates. In addition, the degree of simulated IKs inhibition necessary to normalize the QT interval and terminate re-entry in SQT2 conditions was quantified. The developed MC model accurately reproduced AP shortening and reduced effective refractory period associated with altered IKs kinetics in homozygous (V307L) and heterozygous (WT-V307L) mutation conditions, which increased the lifespan and dominant frequency of re-entry in 3D human ventricle models. IKs reductions of 58% and 65% were sufficient to terminate re-entry in WT-V307L and V307L conditions, respectively. This study further substantiates a causal link between the V307L KCNQ1 mutation and pro-arrhythmia in human ventricles, and establishes partial inhibition of IKs as a potential anti-arrhythmic strategy in SQT2

Measuring diversity in multilingual communication

This article develops new indices to measure linguistic diversity. It is new in two respects: firstly, existing indices to measure the probability that in a given multilingual context communication among people speaking different languages can successfully occur are based on the assumption that communication is possible only if at least one single language is shared. This study develops new indices that describe the probability that people with different linguistic repertoires can effectively communicate not only through one common language, but also by relying on their receptive competence in multiple languages, or a mix between the two communication strategies. Secondly, it develops indices to measure the degree of diversity of language policies aimed at providing multilingual communication (through translation and interpretation). The focus, therefore, is on the organisation as collective actors rather than individuals. The indices may be relevant to the study of the political and economic implications of linguistic diversity in multilingual countries, and in the management of diversity in multilingual organisations

CONCEPTT: Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial: A multi-center, multi-national, randomized controlled trial - Study protocol.

BACKGROUND: Women with type 1 diabetes strive for optimal glycemic control before and during pregnancy to avoid adverse obstetric and perinatal outcomes. For most women, optimal glycemic control is challenging to achieve and maintain. The aim of this study is to determine whether the use of real-time continuous glucose monitoring (RT-CGM) will improve glycemic control in women with type 1 diabetes who are pregnant or planning pregnancy. METHODS/DESIGN: A multi-center, open label, randomized, controlled trial of women with type 1 diabetes who are either planning pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to ≤ 86 mmol/mol) or are in early pregnancy (<13 weeks 6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to ≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible women will wear a CGM which does not display the glucose result for 6 days during the run-in phase. To be eligible for randomization, a minimum of 4 HGM measurements per day and a minimum of 96 hours total with 24 hours overnight (11 pm-7 am) of CGM glucose values are required. Those meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women will be recruited (110 planning pregnancy, 214 pregnant). This takes into account 15 and 20 % attrition rates for the planning pregnancy and pregnant cohorts and will detect a clinically relevant 0.5 % difference between groups at 90 % power with 5 % significance. Randomization will stratify for type of insulin treatment (pump or multiple daily injections) and baseline HbA1c. Analyses will be performed according to intention to treat. The primary outcome is the change in glycemic control as measured by HbA1c from baseline to 24 weeks or conception in women planning pregnancy, and from baseline to 34 weeks gestation during pregnancy. Secondary outcomes include maternal hypoglycemia, CGM time in, above and below target (3.5-7.8 mmol/l), glucose variability measures, maternal and neonatal outcomes. DISCUSSION: This will be the first international multicenter randomized controlled trial to evaluate the impact of RT- CGM before and during pregnancy in women with type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01788527 Registration Date: December 19, 2012