Modulation of Atherothrombotic Factors: Novel Strategies for Plaque Stabilization

UBL - phd migration 201

Whistle source levels of free-ranging beluga whales in Saguenay-St. Lawrence marine park

International audienceWild beluga whistle source levels (SLs) are estimated from 52 three-dimensional (3D) localized calls using a 4-hydrophone array. The probability distribution functions of the root-mean-square (rms) SL in the time domain, and the peak, the strongest 3-dB, and 10-dB SLs from the spectrogram, were non-Gaussian. The average rms SL was 143.8 +- 6.7 dB re 1microPa at 1m. SL spectral metrics were, respectively, 145.8 +- 8 dB, 143.2 +-7.1 dB, and 138.5 +-6.9 dB re 1 microPa. 1microPa / Hz at 1m

Attouch-Th\'era duality revisited: paramonotonicity and operator splitting

The problem of finding the zeros of the sum of two maximally monotone operators is of fundamental importance in optimization and variational analysis. In this paper, we systematically study Attouch-Th\'era duality for this problem. We provide new results related to Passty's parallel sum, to Eckstein and Svaiter's extended solution set, and to Combettes' fixed point description of the set of primal solutions. Furthermore, paramonotonicity is revealed to be a key property because it allows for the recovery of all primal solutions given just one arbitrary dual solution. As an application, we generalize the best approximation results by Bauschke, Combettes and Luke [J. Approx. Theory 141 (2006), 63-69] from normal cone operators to paramonotone operators. Our results are illustrated through numerous examples

Dust in dwarf galaxies: The case of NGC 4214

We have carried out a detailed modelling of the dust heating and emission in the nearby, starbursting dwarf galaxy NGC 4214. Due to its proximity and the great wealth of data from the UV to the millimeter range (from GALEX, HST, {\it Spitzer}, Herschel, Planck and IRAM) it is possible to separately model the emission from HII regions and their associated photodissociation regions (PDRs) and the emission from diffuse dust. Furthermore, most model parameters can be directly determined from the data leaving very few free parameters. We can fit both the emission from HII+PDR regions and the diffuse emission in NGC 4214 with these models with "normal" dust properties and realistic parameters.Comment: 4pages, 3 figures. To appear in 'The Spectral Energy Distribution of Galaxies' Proceedings IAU Symposium No 284, 201

Circulating insulin-like growth factor I modulates mood and is a biomarker of vulnerability to stress:from mouse to man

Individual susceptibility to anxiety disorders after maladaptive responses to stress is not well understood. We now report that while exploring stress responses in mice after traumatic brain injury (TBI), a condition associated to stress susceptibility, we observed that the anxiogenic effects of either TBI or exposure to life-threatening experiences (predator) were blocked when both stressors were combined. Because TBI increases the entrance into the brain of serum insulin-like growth factor I (IGF-I), a known modulator of anxiety with a wide range of concentrations in the human population, we then determined whether circulating IGF-I is related to anxiety measures. In mice, anxiety-like responses to predator were inversely related to circulating IGF-I levels. Other indicators of mood regulation such as sensitivity to dexamethasone suppression and expression levels of blood and brain FK506 binding protein 5 (FKBP5), a co-chaperone of the glucocorticoid receptor that regulates its activity, were also associated to circulating IGF-I. Indeed, brain FKBP5 expression in mice was stimulated by IGF-I. In addition, we observed in a large human cohort (n = 2686) a significant relationship between plasma IGF-I and exposure to recent stressful life events, while FKBP5 expression in blood cells was significantly associated to plasma IGF-I levels. Collectively, these data indicate that circulating IGF-I appears to be involved in mood homeostasis across different species. Furthermore, the data in mice allow us to indicate that IGF-I may be acting at least in part by modulating FKBP5 expression

Adenosine A(2B) receptor agonism inhibits vascular smooth muscle cell proliferation and intimal hyperplasia in ApoE deficient mice

Biopharmaceutic

Agonistic anti-TIGIT treatment inhibits T cell responses in LDLr deficient mice without affecting atherosclerotic lesion development

OBJECTIVE: Co-stimulatory and co-inhibitory molecules are mainly expressed on T cells and antigen presenting cells and strongly orchestrate adaptive immune responses. Whereas co-stimulatory molecules enhance immune responses, signaling via co-inhibitory molecules dampens the immune system, thereby showing great therapeutic potential to prevent cardiovascular diseases. Signaling via co-inhibitory T cell immunoglobulin and ITIM domain (TIGIT) directly inhibits T cell activation and proliferation, and therefore represents a novel therapeutic candidate to specifically dampen pro-atherogenic T cell reactivity. In the present study, we used an agonistic anti-TIGIT antibody to determine the effect of excessive TIGIT-signaling on atherosclerosis. METHODS AND RESULTS: TIGIT was upregulated on CD4(+) T cells isolated from mice fed a Western-type diet in comparison with mice fed a chow diet. Agonistic anti-TIGIT suppressed T cell activation and proliferation both in vitro and in vivo. However, agonistic anti-TIGIT treatment of LDLr(-/-) mice fed a Western-type diet for 4 or 8 weeks did not affect atherosclerotic lesion development in comparison with PBS and Armenian Hamster IgG treatment. Furthermore, elevated percentages of dendritic cells were observed in the blood and spleen of agonistic anti-TIGIT-treated mice. Additionally, these cells showed an increased activation status but decreased IL-10 production. CONCLUSIONS: Despite the inhibition of splenic T cell responses, agonistic anti-TIGIT treatment does not affect initial atherosclerosis development, possibly due to increased activity of dendritic cells

Metabolomics Profile in Depression:A Pooled Analysis of 230 Metabolic Markers in 5283 Cases With Depression and 10,145 Controls

BACKGROUND: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was compared between depressed and nondepressed persons. METHODS: Nine Dutch cohorts were included, comprising 10,145 control subjects and 5283 persons with depression, established with diagnostic interviews or questionnaires. A proton nuclear magnetic resonance metabolomics platform provided 230 metabolite measures: 51 lipids, fatty acids, and low-molecular-weight metabolites; 98 lipid composition and particle concentration measures of lipoprotein subclasses; and 81 lipid and fatty acids ratios. For each metabolite measure, logistic regression analyses adjusted for gender, age, smoking, fasting status, and lipid-modifying medication were performed within cohort, followed by random-effects meta-analyses. RESULTS: Of the 51 lipids, fatty acids, and low-molecular-weight metabolites, 21 were significantly related to depression (false discovery rate q < .05). Higher levels of apolipoprotein B, very-low-density lipoprotein cholesterol, triglycerides, diglycerides, total and monounsaturated fatty acids, fatty acid chain length, glycoprotein acetyls, tyrosine, and isoleucine and lower levels of high-density lipoprotein cholesterol, acetate, and apolipoprotein A1 were associated with increased odds of depression. Analyses of lipid composition indicators confirmed a shift toward less high-density lipoprotein and more very-low-density lipoprotein and triglyceride particles in depression. Associations appeared generally consistent across gender, age, and body mass index strata and across cohorts with depressive diagnoses versus symptoms. CONCLUSIONS: This large-scale meta-analysis indicates a clear distinctive profile of circulating lipid metabolites associated with depression, potentially opening new prevention or treatment avenues for depression and its associated cardiometabolic comorbidity

Upwind sail aerodynamics: A RANS numerical investigation validated with wind tunnel pressure measurements

A novel method similar to marching technique was used to model wind tunnel tests. ► Sail trim criteria based on their interactive effect are identified. ► Areas of separated flow were characterised. ► Local flow field was correlated with sail surface pressures. ► An aerodynamic model based on potential flow with viscous correction is proposed.The aerodynamics of a sailing yacht with different sail trims are presented, derived from simulations performed using Computational Fluid Dynamics. A Reynolds-averaged Navier-Stokes approach was used to model sixteen sail trims first tested in a wind tunnel, where thepressure distributions on the sails were measured. An original approach was employed byusing two successive simulations: the first one on a large domain to model the blockage due to the wind tunnel walls and the sails model, and a second one on a smaller domain to model the flow around the sails model. A verification and validation of the computed aerodynamic forces and pressure distributions was performed. The computed pressure distribution is shown to agree well with the measured pressures. The sail surface pressure was correlated with the increase of turbulent viscosity in the laminar separation bubble, the flow reattachment and the trailing edge separation. The drive force distribution on both sails showed that the fore part of the genoa (fore sail) provides the majority of the drive force and that the effect of the aft sail is mostly to produce an upwash effect on the genoa. An aerodynamic model based on potential flow theory and a viscous correction is proposed. This model, with one free parameter to be determined, is shown to fit the results better than the usual form drag and induced drag only, even if no friction drag is explicitly considered.the third author received a financial support from Brest Métropole Océane and the ERASMUS scholarshi