What is the smallest physically acceptable scale for 1D turbulence schemes?

In numerical weather prediction (NWP) models, at mesoscale, the subgrid convective boundary-layer turbulence is dominated by the uni-directional (1D) vertical thermal production. In Large-Eddy Simulations (LES), the thermal plumes are resolved and the residual subgrid turbulent motions are homogeneous and isotropic, thus three-dimensional (3D), resulting from the dynamical production.This article sets the critical horizontal resolution for which the usually 1D turbulence schemes of NWP models must be replaced by 3D turbulence schemes. LES from five dry and cumulus-topped free convective boundary layers and one forced convective boundary layer are performed. From these LES data, the thermal production and vertical and horizontal dynamicalproductions are calculated at several resolutions from LES to mesoscale. It appears that the production terms of both dry and cumulus-topped free convective boundary layers have the same behavior. A pattern emerges whenever data are ranked by the resolution scaled by the size of thermal plumes, (h + hc , where h is the boundary-layer height and hc is the depth of the cloud layer). In free onvective boundary layers, the critical horizontal resolution for which the horizontal motions must be represented is 0.5(h + hc ). However, the critical horizontal resolution in the forced convective boundary layer case is 3(h + hc )

Onset of experimental severe cardiac fibrosis is mediated by overexpression of angiotensin-converting enzyme 2

Angiotensin-converting enzyme (ACE) 2 is a recently identified homologue of ACE. There is great interest in the therapeutic benefit for ACE2 overexpression in the heart. However, the role of ACE2 in the regulation of cardiac structure and function, as well as maintenance of systemic blood pressure, remains poorly understood. In cell culture, ACE2 overexpression led to markedly increased myocyte volume, assessed in primary rabbit myocytes. To assess ACE2 function in vivo, we used a recombinant adeno-associated virus 6 delivery system to provide 11-week overexpression of ACE2 in the myocardium of stroke-prone spontaneously hypertensive rats. ACE2, as well as the ACE inhibitor enalapril, significantly reduced systolic blood pressure. However, in the heart, ACE2 overexpression resulted in cardiac fibrosis, as assessed by histological analysis with concomitant deficits in ejection fraction and fractional shortening measured by echocardiography. Furthermore, global gene expression profiling demonstrated the activation of profibrotic pathways in the heart mediated by ACE2 gene delivery. This study demonstrates that sustained overexpression of ACE2 in the heart in vivo leads to the onset of severe fibrosis

Dynamic changes in lung microRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline

<b>Objective</b>: MicroRNAs (miRNAs) are small noncoding RNAs that have the capacity to control protein production through binding "seed" sequences within a target mRNA. Each miRNA is capable of potentially controlling hundreds of genes. The regulation of miRNAs in the lung during the development of pulmonary arterial hypertension (PAH) is unknown.<p></p> <b>Methods and Results</b>: We screened lung miRNA profiles in a longitudinal and crossover design during the development of PAH caused by chronic hypoxia or monocrotaline in rats. We identified reduced expression of Dicer, involved in miRNA processing, during the onset of PAH after hypoxia. MiR-22, miR-30, and let-7f were downregulated, whereas miR-322 and miR-451 were upregulated significantly during the development of PAH in both models. Differences were observed between monocrotaline and chronic hypoxia. For example, miR-21 and let-7a were significantly reduced only in monocrotaline-treated rats. MiRNAs that were significantly regulated were validated by quantitative polymerase chain reaction. By using in vitro studies, we demonstrated that hypoxia and growth factors implicated in PAH induced similar changes in miRNA expression. Furthermore, we confirmed miR-21 downregulation in human lung tissue and serum from patients with idiopathic PAH.<p></p> <b>Conclusion</b>: Defined miRNAs are regulated during the development of PAH in rats. Therefore, miRNAs may contribute to the pathogenesis of PAH and represent a novel opportunity for therapeutic intervention.<p></p&gt

Use of in vivo phage display to engineer novel adenoviruses for targeted delivery to the cardiac vasculature

We performed in vivo phage display in the stroke prone spontaneously hypertensive rat, a cardiovascular disease model, and the normotensive Wistar Kyoto rat to identify cardiac targeting peptides, and then assessed each in the context of viral gene delivery. We identified both common and strain-selective peptides, potentially indicating ubiquitous markers and those found selectively in dysfunctional microvasculature of the heart. We show the utility of the peptide, DDTRHWG, for targeted gene delivery in human cells and rats in vivo when cloned into the fiber protein of subgroup D adenovirus 19p. This study therefore identifies cardiac targeting peptides by in vivo phage display and the potential of a candidate peptide for vector targeting strategies

Neuromyths and knowledge about intellectual giftedness in a highly educated multilingual country.

peer reviewed[en] INTRODUCTION: Understanding brain functioning and intellectual giftedness can be challenging and give rise to various misconceptions. Nonetheless, there seems to be a widespread fascination and appetite for these subjects among the lay public and diverse professionals. The present study is the first to investigate general knowledge about the brain, neuromyths and knowledge about giftedness in a highly multilingual and educated country. METHODS: Starting from and extending two seminal studies on neuromyths, several novel statements on intellectual giftedness have been included in order to explore knowledge and misconceptions concerning giftedness. Our sample (N = 200) was composed of Luxembourgish education professionals, including students in educational science and cognitive psychology, thus allowing to analyze responses in general and according to training and professional profiles. Specifically, Group 1 consisted of teachers and futures teachers (n = 152). Group 2 consisted of other education professionals and psychology students (n = 48). RESULTS: Despite the size and the unbalanced distribution of the sample, our findings indicate a good level of general knowledge about the brain and learning (71.3% of correct responses in average) which does, however, not preclude the presence of the typically observed original neuromyths. Thus, we replicate the classical finding that misconceptions on Learning Styles (70% of error rate) and the Multiple Intelligence Theory (71.5% of error rate) are the most represented, both in (future and in-service) teachers and other education professionals. Moreover, the present sample also revealed a high presence of misconceptions on intellectual giftedness. DISCUSSION: Limitations and future directions are discussed.4. Quality educatio

Genetic Pharmacotherapy as an Early CNS Drug Development Strategy: Testing Glutaminase Inhibition for Schizophrenia Treatment in Adult Mice

Genetic pharmacotherapy is an early drug development strategy for the identification of novel CNS targets in mouse models prior to the development of specific ligands. Here for the first time, we have implemented this strategy to address the potential therapeutic value of a glutamate-based pharmacotherapy for schizophrenia involving inhibition of the glutamate recycling enzyme phosphate-activated glutaminase. Mice constitutively heterozygous for GLS1, the gene encoding glutaminase, manifest a schizophrenia resilience phenotype, a key dimension of which is an attenuated locomotor response to propsychotic amphetamine challenge. If resilience is due to glutaminase deficiency in adulthood, then glutaminase inhibitors should have therapeutic potential. However, this has been difficult to test given the dearth of neuroactive glutaminase inhibitors. So, we used genetic pharmacotherapy to ask whether adult induction of GLS1 heterozygosity would attenuate amphetamine responsiveness. We generated conditional floxGLS1 mice and crossed them with global CAGERT2cre∕+ mice to produce GLS1 iHET mice, susceptible to tamoxifen induction of GLS1 heterozygosity. One month after tamoxifen treatment of adult GLS1 iHET mice, we found a 50% reduction in GLS1 allelic abundance and glutaminase mRNA levels in the brain. While GLS1 iHET mice showed some recombination prior to tamoxifen, there was no impact on mRNA levels. We then asked whether induction of GLS heterozygosity would attenuate the locomotor response to propsychotic amphetamine challenge. Before tamoxifen, control and GLS1 iHET mice did not differ in their response to amphetamine. One month after tamoxifen treatment, amphetamine-induced hyperlocomotion was blocked in GLS1 iHET mice. The block was largely maintained after 5 months. Thus, a genetically induced glutaminase reduction—mimicking pharmacological inhibition—strongly attenuated the response to a propsychotic challenge, suggesting that glutaminase may be a novel target for the pharmacotherapy of schizophrenia. These results demonstrate how genetic pharmacotherapy can be implemented to test a CNS target in advance of the development of specific neuroactive inhibitors. We discuss further the advantages, limitations, and feasibility of the wider application of genetic pharmacotherapy for neuropsychiatric drug development

Interviewer: 'Are women and girls ever responsible for the domestic violence they encounter?' Student: 'No, well, unless they did something really, really bad …'

Research shows the ‘gendered nature’ of domestic violence, with Women’s Aid (a UK-based charity) estimating that 1 in 4 women are affected (2014). This paper reports on a project - funded by Comic Relief, completed by Nottinghamshire Domestic Violence Forum (now known as Equation) and evaluated by Nottingham Trent University. The project adopts a Whole School Approach in seeking to prevent domestic violence. Students at three secondary schools attended between one and five blocks of work, and special events. There is evidence of positive developments - with young people showing understanding of domestic violence as well as the margins between healthy and unhealthy relationships. However, not all students could reply ‘never’ to the question of ‘are women and girls to blame for the domestic violence they experience?’, remarking that if the woman had done something ‘really, really bad’ then violence might be justified. We argue that young people’s uncertainties need to be situated within the gender-unequal socio-contexts of contemporary society, and further call for a WSA to domestic violence prevention to be a compulsory part of the UK national curriculum

The programming of sequences of saccades

Saccadic eye movements move the high-resolution fovea to point at regions of interest. Saccades can only be generated serially (i.e., one at a time). However, what remains unclear is the extent to which saccades are programmed in parallel (i.e., a series of such moments can be planned together) and how far ahead such planning occurs. In the current experiment, we investigate this issue with a saccade contingent preview paradigm. Participants were asked to execute saccadic eye movements in response to seven small circles presented on a screen. The extent to which participants were given prior information about target locations was varied on a trial-by-trial basis: participants were aware of the location of the next target only, the next three, five, or all seven targets. The addition of new targets to the display was made during the saccade to the next target in the sequence. The overall time taken to complete the sequence was decreased as more targets were available up to all seven targets. This was a result of a reduction in the number of saccades being executed and a reduction in their saccade latencies. Surprisingly, these results suggest that, when faced with a demand to saccade to a large number of target locations, saccade preparation about all target locations is carried out in paralle

Testing the cognitive-behavioural maintenance models across DSM-5 bulimic-type eating disorder diagnostic groups: A multi-centre study

The original cognitive-behavioural (CB) model of bulimia nervosa, which provided the basis for the widely used CB therapy, proposed that specific dysfunctional cognitions and behaviours maintain the disorder. However, amongst treatment completers, only 40–50 % have a full and lasting response. The enhanced CB model (CB-E), upon which the enhanced version of the CB treatment was based, extended the original approach by including four additional maintenance factors. This study evaluated and compared both CB models in a large clinical treatment seeking sample (N = 679), applying both DSM-IV and DSM-5 criteria for bulimic-type eating disorders. Application of the DSM-5 criteria reduced the number of cases of DSM-IV bulimic-type eating disorders not otherwise specified to 29.6 %. Structural equation modelling analysis indicated that (a) although both models provided a good fit to the data, the CB-E model accounted for a greater proportion of variance in eating-disordered behaviours than the original one, (b) interpersonal problems, clinical perfectionism and low self-esteem were indirectly associated with dietary restraint through over-evaluation of shape and weight, (c) interpersonal problems and mood intolerance were directly linked to binge eating, whereas restraint only indirectly affected binge eating through mood intolerance, suggesting that factors other than restraint may play a more critical role in the maintenance of binge eating. In terms of strength of the associations, differences across DSM-5 bulimic-type eating disorder diagnostic groups were not observed. The results are discussed with reference to theory and research, including neurobiological findings and recent hypotheses