Turbulent thermal diffusion in a multi-fan turbulence generator with the imposed mean temperature gradient

We studied experimentally the effect of turbulent thermal diffusion in a multi-fan turbulence generator which produces a nearly homogeneous and isotropic flow with a small mean velocity. Using Particle Image Velocimetry and Image Processing techniques we showed that in a turbulent flow with an imposed mean vertical temperature gradient (stably stratified flow) particles accumulate in the regions with the mean temperature minimum. These experiments detected the effect of turbulent thermal diffusion in a multi-fan turbulence generator for relatively high Reynolds numbers. The experimental results are in compliance with the results of the previous experimental studies of turbulent thermal diffusion in oscillating grids turbulence (Buchholz et al. 2004; Eidelman et al. 2004). We demonstrated that turbulent thermal diffusion is an universal phenomenon. It occurs independently of the method of turbulence generation, and the qualitative behavior of particle spatial distribution in these very different turbulent flows is similar. Competition between turbulent fluxes caused by turbulent thermal diffusion and turbulent diffusion determines the formation of particle inhomogeneities.Comment: 9 pages, 9 figure, REVTEX4, Experiments in Fluids, in pres

Metabolic state alters economic decision making under risk in humans

Background: Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores). Specifically, animals often express a preference for risky (more variable) food sources when below a metabolic reference point (hungry), and safe (less variable) food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans. Methodology/Principal Findings: We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake), and circulating leptin levels (providing an assay of energy reserves). We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively. Conclusions/Significance: We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity in human risk-preference to current metabolic state has significant implications for both real-world economic transactions and for aberrant decision-making in eating disorders and obesity

Lipids induce expression of serum-responsive transmembrane kinase EhTMKB1-9 in an early branching eukaryote Entamoeba histolytica

Mechanisms underlying the initiation of proliferative response are known only for a few organisms, and are not understood for the medically important organisms including Entamoeba histolytica. The trans membrane kinase EhTMKB1-9 of E. histolytica is one of the early indicators of proliferation and its' expression is regulated by serum, one of the components necessary for cellular proliferation in vitro. In this study we show that bovine serum albumin (BSA) can induce EhTMKB1-9 expression in place of serum, and that both follow the same mechanism. Both serum and BSA use the same promoter element and the activation process is initiated through a PI3 kinase-mediated pathway. We further show that BSA activates EhTMKB1-9 due to the lipids associated with it and that unsaturated fatty acids are responsible for activation. These results suggest that lipid molecules are ligand(s) for initiation of a signaling system that stimulates EhTMKB1-9 expression

B-cell-specific checkpoint molecules that regulate anti-tumour immunity.

The role of B cells in anti-tumour immunity is still debated and, accordingly, immunotherapies have focused on targeting T and natural killer cells to inhibit tumour growth1,2. Here, using high-throughput flow cytometry as well as bulk and single-cell RNA-sequencing and B-cell-receptor-sequencing analysis of B cells temporally during B16F10 melanoma growth, we identified a subset of B cells that expands specifically in the draining lymph node over time in tumour-bearing mice. The expanding B cell subset expresses the cell surface molecule T cell immunoglobulin and mucin domain 1 (TIM-1, encoded by Havcr1) and a unique transcriptional signature, including multiple co-inhibitory molecules such as PD-1, TIM-3, TIGIT and LAG-3. Although conditional deletion of these co-inhibitory molecules on B cells had little or no effect on tumour burden, selective deletion of Havcr1 in B cells both substantially inhibited tumour growth and enhanced effector T cell responses. Loss of TIM-1 enhanced the type 1 interferon response in B cells, which augmented B cell activation and increased antigen presentation and co-stimulation, resulting in increased expansion of tumour-specific effector T cells. Our results demonstrate that manipulation of TIM-1-expressing B cells enables engagement of the second arm of adaptive immunity to promote anti-tumour immunity and inhibit tumour growth

Simvastatin decreases the level of heparin-binding protein in patients with acute lung injury

Background: Heparin-binding protein is released by neutrophils during inflammation and disrupts the integrity of the alveolar and capillary endothelial barrier implicated in the development of acute lung injury and systemic organ failure. We sought to investigate whether oral administration of simvastatin to patients with acute lung injury reduces plasma heparin-binding protein levels and improves intensive care unit outcome. Methods: Blood samples were collected from patients with acute lung injury with 48 h of onset of acute lung injury (day 0), day 3, and day 7. Patients were given placebo or 80 mg simvastatin for up to 14 days. Plasma heparin-binding protein levels from patients with acute lung injury and healthy volunteers were measured by ELISA. Results: Levels of plasma heparin-binding protein were significantly higher in patients with acute lung injury than healthy volunteers on day 0 (p = 0.011). Simvastatin 80 mg administered enterally for 14 days reduced plasma level of heparin-binding protein in patients. Reduced heparin-binding protein was associated with improved intensive care unit survival. Conclusions: A reduction in heparin-binding protein with simvastatin is a potential mechanism by which the statin may modify outcome from acute lung injury

Am I just not good enough? The creation, development and questioning of a high performance coaching identity

While the career experiences and trajectories of various sports workers have received increased scholarly attention, those of professional coaches have, in comparison, received scant consideration. This paper focuses on the career experiences of Maeve (a pseudonym), a high performance coach, and the critical incidents related to the creation, development, and, ultimately, questioning of her professional identity. Data were collected through a series of narrative-biographical interviews and were subject to a process of iterative data analysis. The results indicated that her significant investment into her coaching self, combined with the vagaries and uncertain nature of work in high performance coaching, led her to experience a biographical disruption that interrupted the narrative coherence of her coaching life. The findings add further credence to recent critiques of only understanding and representing coaching careers in a linear and chronically staged fashion

Small Interfering RNA against Transcription Factor STAT6 Leads to Increased Cholesterol Synthesis in Lung Cancer Cell Lines

STAT6 transcription factor has become a potential molecule for therapeutic intervention because it regulates broad range of cellular processes in a large variety of cell types. Although some target genes and interacting partners of STAT6 have been identified, its exact mechanism of action needs to be elucidated. In this study, we sought to further characterize the molecular interactions, networks, and functions of STAT6 by profiling the mRNA expression of STAT6 silenced human lung cells (NCI-H460) using microarrays. Our analysis revealed 273 differentially expressed genes after STAT6 silencing. Analysis of the gene expression data with Ingenuity Pathway Analysis (IPA) software revealed Gene expression, Cell death, Lipid metabolism as the functions associated with highest rated network. Cholesterol biosynthesis was among the most enriched pathways in IPA as well as in PANTHER analysis. These results have been validated by real-time PCR and cholesterol assay using scrambled siRNA as a negative control. Similar findings were also observed with human type II pulmonary alveolar epithelial cells, A549. In the present study we have, for the first time, shown the inverse relationship of STAT6 with the cholesterol biosynthesis in lung cancer cells. The present findings are potentially significant to advance the understanding and design of therapeutics for the pathological conditions where both STAT6 and cholesterol biosynthesis are implicated viz. asthma, atherosclerosis etc