Platelets mediate lymphovenous hemostasis to maintain blood-lymphatic separation throughout life

Mammals transport blood through a high-pressure, closed vascular network and lymph through a low-pressure, open vascular network. These vascular networks connect at the lymphovenous (LV) junction, where lymph drains into blood and an LV valve (LVV) prevents backflow of blood into lymphatic vessels. Here we describe an essential role for platelets in preventing blood from entering the lymphatic system at the LV junction. Loss of CLEC2, a receptor that activates platelets in response to lymphatic endothelial cells, resulted in backfilling of the lymphatic network with blood from the thoracic duct (TD) in both neonatal and mature mice. Fibrin-containing platelet thrombi were observed at the LVV and in the terminal TD in wild-type mice, but not Clec2-deficient mice. Analysis of mice lacking LVVs or lymphatic valves revealed that platelet-mediated thrombus formation limits LV backflow under conditions of impaired valve function. Examination of mice lacking integrin-mediated platelet aggregation indicated that platelet aggregation stabilizes thrombi that form in the lymphatic vascular environment to prevent retrograde blood flow. Collectively, these studies unveil a newly recognized form of hemostasis that functions with the LVV to safeguard the lymphatic vascular network throughout life

Thermal performance of two heat exchangers for thermoelectric generators

Thermal performance of heat exchanger is important for potential application in integrated solar cell/module and thermoelectric generator (TEG) system. Usually, thermal performance of a heat exchanger for TEGs is analysed by using a 1D heat conduction theory which ignores the detailed phenomena associated with thermo-hydraulics. In this paper, thermal and mass transports in two different exchangers are simulated by means of a steady-state, 3D turbulent flow k -e model with a heat conduction module under various flow rates. In order to simulate an actual working situation of the heat exchangers, hot block with an electric heater is included in the model. TEG model is simplified by using a 1D heat conduction theory, so its thermal performance is equivalent to a real TEG. Natural convection effect on the outside surfaces of the computational model is considered. Computational models and methods used are validated under transient thermal and electrical experimental conditions of a TEG. It is turned out that the two heat exchangers designed have a better thermal performance compared with an existing heat exchanger for TEGs, and more importantly, the fin heat exchanger is more compact and has nearly half temperature rise compared with the tube heat exchanger

A comparison of 3D particle, fluid and hybrid simulations for negative streamers

In the high field region at the head of a discharge streamer, the electron energy distribution develops a long tail. In negative streamers, these electrons can run away and contribute to energetic processes such as terrestrial gamma-ray and electron flashes. Moreover, electron density fluctuations can accelerate streamer branching. To track energies and locations of single electrons in relevant regions, we have developed a 3D hybrid model that couples a particle model in the region of high fields and low electron densities with a fluid model in the rest of the domain. Here we validate our 3D hybrid model on a 3D (super-)particle model for negative streamers in overvolted gaps, and we show that it almost reaches the computational efficiency of a 3D fluid model. We also show that the extended fluid model approximates the particle and the hybrid model well until stochastic fluctuations become important, while the classical fluid model underestimates velocities and ionization densities. We compare density fluctuations and the onset of branching between the models, and we compare the front velocities with an analytical approximation

A phenomenological approach to the simulation of metabolism and proliferation dynamics of large tumour cell populations

A major goal of modern computational biology is to simulate the collective behaviour of large cell populations starting from the intricate web of molecular interactions occurring at the microscopic level. In this paper we describe a simplified model of cell metabolism, growth and proliferation, suitable for inclusion in a multicell simulator, now under development (Chignola R and Milotti E 2004 Physica A 338 261-6). Nutrients regulate the proliferation dynamics of tumor cells which adapt their behaviour to respond to changes in the biochemical composition of the environment. This modeling of nutrient metabolism and cell cycle at a mesoscopic scale level leads to a continuous flow of information between the two disparate spatiotemporal scales of molecular and cellular dynamics that can be simulated with modern computers and tested experimentally.Comment: 58 pages, 7 figures, 3 tables, pdf onl

Targeted online liquid chromatography electron capture dissociation mass spectrometry for the localization of sites of in vivo phosphorylation in human Sprouty2

We demonstrate a strategy employing collision-induced dissociation for phosphopeptide discovery, followed by targeted electron capture dissociation (ECD) for site localization. The high mass accuracy and low background noise of the ECD mass spectra allow facile sequencing of coeluting isobaric phosphopeptides, with up to two isobaric phosphopeptides sequenced from a single mass spectrum. In contrast to the previously described neutral loss of dependent ECD method, targeted ECD allows analysis of both phosphotyrosine peptides and lower abundance phosphopeptides. The approach was applied to phosphorylation analysis of human Sprouty2, a regulator of receptor tyrosine kinase signaling. Fifteen sites of phosphorylation were identified, 11 of which are novel

The SAMI Galaxy Survey: Gas Streaming and Dynamical M/L in Rotationally Supported Systems

Line-of-sight velocities of gas and stars can constrain dark matter (DM) within rotationally supported galaxies if they trace circular orbits extensively. Photometric asymmetries may signify non-circular motions, requiring spectra with dense spatial coverage. Our integral-field spectroscopy of 178 galaxies spanned the mass range of the SAMI Galaxy Survey. We derived circular speed curves (CSCs) of gas and stars from non-parametric Diskfit fits out to $r\sim2r_e$. For 12/14 with measured H I profiles, ionized gas and H I maximum velocities agreed. We fitted mass-follows-light models to 163 galaxies by approximating the radial starlight profile as nested, very flattened mass homeoids viewed as a S\'ersic form. Fitting broad-band SEDs to SDSS images gave median stellar mass/light 1.7 assuming a Kroupa IMF vs. 2.6 dynamically. Two-thirds of the dynamical mass/light measures were consistent with star+remnant IMFs. One-fifth required upscaled starlight to fit, hence comparable mass of unobserved baryons and/or DM distributed similarly across the SAMI aperture that came to dominate motions as the starlight CSC declined rapidly. The rest had mass distributed differently from starlight. Subtracting fits of S\'ersic profiles to 13 VIKING Z-band images revealed residual weak bars. Near the bar PA, we assessed m = 2 streaming velocities, and found deviations usually <30 km/s from the CSC; three showed no deviation. Thus, asymmetries rarely influenced our CSCs despite co-located shock-indicating, emission-line flux ratios in more than 2/3.Comment: 21 pages, 15 figures. Accepted to MNRA

Genetic risk for schizophrenia and psychosis in Alzheimer disease

Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD), affecting ~40 to 60% of individuals with AD (AD with psychosis (AD+P)). In comparison with AD subjects without psychosis, AD+P subjects have more rapid cognitive decline and poor outcomes. Prior studies have estimated the heritability of psychosis in AD at 61%, but the underlying genetic sources of this risk are not known. We evaluated a Discovery Cohort of 2876 AD subjects with (N=1761) or without psychosis (N=1115). All subjects were genotyped using a custom genotyping array designed to evaluate single-nucleotide polymorphisms (SNPs) with evidence of genetic association with AD+P and include SNPs affecting or putatively affecting risk for schizophrenia and AD. Results were replicated in an independent cohort of 2194 AD subjects with (N=734) or without psychosis (N=1460). We found that AD+P is associated with polygenic risk for a set of novel loci and inversely associated with polygenic risk for schizophrenia. Among the biologic pathways identified by the associations of schizophrenia SNPs with AD+P are endosomal trafficking, autophagy and calcium channel signaling. To the best of our knowledge, these findings provide the first clear demonstration that AD+P is associated with common genetic variation. In addition, they provide an unbiased link between polygenic risk for schizophrenia and a lower risk of psychosis in AD. This provides an opportunity to leverage progress made in identifying the biologic effects of schizophrenia alleles to identify novel mechanisms protecting against more rapid cognitive decline and psychosis risk in AD

The SAMI Galaxy Survey: Asymmetry in Gas Kinematics and its links to Stellar Mass and Star Formation

We study the properties of kinematically disturbed galaxies in the SAMI Galaxy Survey using a quantitative criterion, based on kinemetry (Krajnovic et al.). The approach, similar to the application of kinemetry by Shapiro et al. uses ionised gas kinematics, probed by H{\alpha} emission. By this method 23+/-7% of our 360-galaxy sub-sample of the SAMI Galaxy Survey are kinematically asymmetric. Visual classifications agree with our kinemetric results for 90% of asymmetric and 95% of normal galaxies. We find stellar mass and kinematic asymmetry are inversely correlated and that kinematic asymmetry is both more frequent and stronger in low-mass galaxies. This builds on previous studies that found high fractions of kinematic asymmetry in low mass galaxies using a variety of different methods. Concentration of star forma- tion and kinematic disturbance are found to be correlated, confirming results found in previous work. This effect is stronger for high mass galaxies (log(M*) > 10) and indicates that kinematic disturbance is linked to centrally concentrated star formation. Comparison of the inner (within 0.5Re) and outer H{\alpha} equivalent widths of asymmetric and normal galaxies shows a small but significant increase in inner equivalent width for asymmetric galaxies.Comment: 29 pages, 21 figure