SPH simulations of thixo-viscoplastic fluid flow past a cylinder

Thixotropic materials are complex fluids that display time-dependent viscosity and/or yield-stress response upon the application of a fixed deformation, while recovering their original structured-state when the deformation is discontinued. Thixotropic effects are presents in many different systems and applications, ranging from food products, such as ketchup, to metals, such as molten aluminum. In this work we present a first attempt to simulate the rheological properties of thixo-viscoplastic flows using a Smoothed Particle Hydrodynamic (SPH) method. The study set up is a 2D flow around a circular cylinder as well as a simple shear flow between parallel plates to validate our numerical results. SPH solutions are compared with simulations performed using the open-source Finite Volume Method solver RheoTool, based on OpenFOAM. The viscoplastic model used in this work is the Papanastasiou model combined with a recently developed microstructural one, in order to include thixotropy. In this thixo-viscoplastic framework, we analyze the flow properties in terms of yield-fronts, streamlines and structure-parameter fields at different Bingham and Thixotropy numbers, through microstructural thixotropic and yield-stress parameters variation. Obtained results show an important novelty: an asymmetry in the thixo-viscoplastic flow around the cylinder

Ionizing Radiation, an Instrument in Chemical Evolution Studies: Scope and Perspectives

The study of synthesis and stability of molecules in different environments it’s been part of chemistry evolution and origin of life studies for more than 70 years. Various kinds of ionizing radiation have been analyzed as possible sources of energy for the transformations undergone by the first organic molecules. Now experimental and computational simulation approaches continue with different groups of organic molecules, in search for more information that help us to understand and reconstruct somehow the mechanisms that toke place on early Earth and space. In that line, this paper presents first approach of keto acids stability to ionizing radiation, an interesting group of molecules involved in the Krebs cycle and glycolysis. Preliminary results obtained by HPLC/UV analysis of irradiating aqueous solutions of 5 keto acids ranging from 3 to 6 carbons with a 60Co gamma ray source, using doses up to 53 kGy, show different stabilities and a general tendency of shifting the keto-enol equilibrium to the enol tautomer before decomposition

Recognition of host Clr-b by the inhibitory NKR-P1B receptor provides a basis for missing-self recognition

The interaction between natural killer (NK) cell inhibitory receptors and their cognate ligands constitutes a key mechanism by which healthy tissues are protected from NK cell-mediated lysis. However, self-ligand recognition remains poorly understood within the prototypical NKR-P1 receptor family. Here we report the structure of the inhibitory NKR-P1B receptor bound to its cognate host ligand, Clr-b. NKR-P1B and Clr-b interact via a head-to-head docking mode through an interface that includes a large array of polar interactions. NKR-P1B:Clr-b recognition is extremely sensitive to mutations at the heterodimeric interface, with most mutations severely impacting both Clr-b binding and NKR-P1B receptor function to implicate a low affinity interaction. Within the structure, two NKR-P1B:Clr-b complexes are cross-linked by a non-classic NKR-P1B homodimer, and the disruption of homodimer formation abrogates Clr-b recognition. These data provide an insight into a fundamental missing-self recognition system and suggest an avidity-based mechanism underpins NKR-P1B receptor function

Estradiol valerate and alcohol intake: dose-response assessments

BACKGROUND: An injection of estradiol valerate (EV) provides estradiol for a prolonged period. Recent research indicates that a single 2.0 mg injection of EV modifies a female rat's appetite for alcoholic beverages. This research extends the initial research by assessing 8 doses of EV (from .001 to 2.0 mg/female rat), as well assessing the effects of 2.0 mg EV in females with ovariectomies. RESULTS: With the administration of EV, there was a dose-related loss of bodyweight reaching the maximum loss, when it occurred, at about 4 days after injections. Subsequently, rats returned to gaining weight regularly. Of the doses tested, only the 2.0 mg dose produced a consistent increase in intake of ethanol during the time previous research indicated that the rats would show enhanced intakes. There was, however, a dose-related trend for smaller doses to enhance intakes. Rats with ovariectomies showed a similar pattern of effects, to intact rats, with the 2 mg dose. After extensive histories of intake of alcohol, both placebo and EV-treated females had estradiol levels below the average measured in females without a history of alcohol-intake. CONCLUSION: The data support the conclusion that pharmacological doses of estradiol can produce enduring changes that are manifest as an enhanced appetite for alcoholic beverages. The effect can occur among females without ovaries

Results of the engineering run of the coherent neutrino nucleus interaction experiment (CONNIE)

The CONNIE detector prototype is operating at a distance of 30 m from the core of a 3.8 GWth nuclear reactor with the goal of establishing Charge-Coupled Devices (CCD) as a new technology for the detection of coherent elastic neutrino-nucleus scattering. We report on the results of the engineering run with an active mass of 4 g of silicon. The CCD array is described, and the performance observed during the first year is discussed. A compact passive shield was deployed around the detector, producing an order of magnitude reduction in the background rate. The remaining background observed during the run was stable, and dominated by internal contamination in the detector packaging materials. The in-situ calibration of the detector using X-ray lines from fluorescence demonstrates good stability of the readout system. The event rates with the reactor ON and OFF are compared, and no excess is observed coming from nuclear fission at the power plant. The upper limit for the neutrino event rate is set two orders of magnitude above the expectations for the standard model. The results demonstrate the cryogenic CCD-based detector can be remotely operated at the reactor site with stable noise below2 e RMS and stable background rates. The success of the engineering test provides a clear path for the upgraded 100 g detector to be deployed during 2016.Fil: Aguilar Arevalo, A.. Universidad Nacional Autónoma de México; MéxicoFil: Bertou, Xavier Pierre Louis. Comisión Nacional de Energía Atómica; Argentina. Comisión Nacional de Energía Atómica. Fundación José A. Balseiro; ArgentinaFil: Bonifazi, C.. Universidade Federal do Rio de Janeiro; BrasilFil: Butner, M.. Fermi National Accelerator Laboratory; Estados UnidosFil: Cancelo, G.. Fermi National Accelerator Laboratory; Estados UnidosFil: Castañeda Vazquez, A.. Universidad Nacional Autónoma de México; MéxicoFil: Cervantes Vergara, B.. Universidad Nacional Autónoma de México; MéxicoFil: Chavez, C. R.. Universidad Nacional de Asunción; ParaguayFil: Da Motta, H.. Centro Brasileiro de Pesquisas Físicas; BrasilFil: D'Olivo, J. C.. Universidad Nacional Autónoma de México; MéxicoFil: Dos Anjos, J.. Centro Brasileiro de Pesquisas Físicas; BrasilFil: Estrada, J.. Fermi National Accelerator Laboratory; Estados UnidosFil: Fernández Moroni, Guillermo. Universidad Nacional del Sur. Departamento de Ingeniería Eléctrica y de Computadoras. Instituto ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ford, R.. Fermi National Accelerator Laboratory; Estados UnidosFil: Foguel, A.. Centro Brasileiro de Pesquisas Físicas; Brasil. Universidade Federal do Rio de Janeiro; BrasilFil: Hernandez Torres, K. P.. Universidad Nacional Autónoma de México; MéxicoFil: Izraelevitch, F.. Fermi National Accelerator Laboratory; Estados UnidosFil: Kavner, A.. University of Michigan; Estados UnidosFil: Kilminster, B.. Universitat Zurich; SuizaFil: Kuk, K.. Fermi National Accelerator Laboratory; Estados UnidosFil: Lima Jr, H. P.. Centro Brasileiro de Pesquisas Físicas; BrasilFil: Makler, M.. Centro Brasileiro de Pesquisas Físicas; BrasilFil: Molina, J.. Universidad Nacional de Asunción; ParaguayFil: Moreno Granados, G.. Universidad Nacional Autónoma de México; MéxicoFil: Moro, Juan Manuel. Universidad Nacional del Sur. Departamento de Ingeniería; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paolini, Eduardo Emilio. Universidad Nacional del Sur. Departamento de Ingeniería Eléctrica y de Computadoras. Instituto ; ArgentinaFil: Sofo Haro, Miguel Francisco. Comision Nacional de Energia Atomica. Gerencia D/area de Energia Nuclear; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tiffenberg, Javier Sebastian. Fermi National Accelerator Laboratory; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Trillaud, F.. Universidad Nacional Autónoma de México; MéxicoFil: Wagner, S.. Centro Brasileiro de Pesquisas Físicas; Brasil. Pontificia Universidade Católica do Rio Grande do Sul; Brasi

Adipose Co-expression networks across Finns and Mexicans identify novel triglyceride-associated genes

BACKGROUND: High serum triglyceride (TG) levels is an established risk factor for coronary heart disease (CHD). Fat is stored in the form of TGs in human adipose tissue. We hypothesized that gene co-expression networks in human adipose tissue may be correlated with serum TG levels and help reveal novel genes involved in TG regulation. METHODS: Gene co-expression networks were constructed from two Finnish and one Mexican study sample using the blockwiseModules R function in Weighted Gene Co-expression Network Analysis (WGCNA). Overlap between TG-associated networks from each of the three study samples were calculated using a Fisher’s Exact test. Gene ontology was used to determine known pathways enriched in each TG-associated network. RESULTS: We measured gene expression in adipose samples from two Finnish and one Mexican study sample. In each study sample, we observed a gene co-expression network that was significantly associated with serum TG levels. The TG modules observed in Finns and Mexicans significantly overlapped and shared 34 genes. Seven of the 34 genes (ARHGAP30, CCR1, CXCL16, FERMT3, HCST, RNASET2, SELPG) were identified as the key hub genes of all three TG modules. Furthermore, two of the 34 genes (ARHGAP9, LST1) reside in previous TG GWAS regions, suggesting them as the regional candidates underlying the GWAS signals. CONCLUSIONS: This study presents a novel adipose gene co-expression network with 34 genes significantly correlated with serum TG across populations

CXCL6 is an important paracrine factor in the pro-angiogenic human cardiac progenitor-like cell secretome

Studies in recent years have established that the principal effects in cardiac cell therapy are associated with paracrine/autocrine factors. We combined several complementary techniques to define human cardiac progenitor cell (CPC) secretome constituted by 914 proteins/genes; 51% of these are associated with the exosomal compartment. To define the set of proteins specifically or highly differentially secreted by CPC, we compared human mesenchymal stem cells and dermal fibroblasts; the study defined a group of growth factors, cytokines and chemokines expressed at high to medium levels by CPC. Among them, IL-1, GROa (CXCL1), CXCL6 (GCP2) and IL-8 are examples whose expression was confirmed by most techniques used. ELISA showed that CXCL6 is significantly overexpressed in CPC conditioned medium (CM) (18- to 26-fold) and western blot confirmed expression of its receptors CXCR1 and CXCR2. Addition of anti-CXCL6 completely abolished migration in CPC-CM compared with anti-CXCR2, which promoted partial inhibition, and anti-CXCR1, which was inefficient. Anti-CXCL6 also significantly inhibited CPC CM angiogenic activity. In vivo evaluation also supported a relevant role for angiogenesis. Altogether, these results suggest a notable angiogenic potential in CPC-CM and identify CXCL6 as an important paracrine factor for CPC that signals mainly through CXCR2.This study was supported by funding from the European Commission (HEALTH-2009_242038) and by grants from the Spanish Ministry of Science and Innovation (SAF2012-34327 and SAF2015-70882-R to AB and BIO2012-37926 and BIO2015-67580-P to JV), the Research Program of the Comunidad Autónoma de Madrid (S2010/BMD-2420) and the Instituto de Salud Carlos III (RETICS-RD12/0019/0018 to AB and RETICS-RD12/0042/0056 to JV).S

In vitro Inhibition of Pancreatic Lipase by Polyphenols: A Kinetic, Fluorescence Spectroscopy and Molecular Docking Study

Svrha je ovog istraživanja bila ispitati molekulsko uklapanje i inhibicijski učinak četiri fenolna spoja pronađena u ljutim papričicama, i to: kavene kiseline, p-kumarne kiseline, kvercetina i kapsaicina, na aktivnost lipaze izolirane iz svinjske gušterače. Najjači inhibicijski učinak imao je kvercetin (IC50=(6.1±2.4) μM), zatim p-kumarna (170.2±20.6) μM) i kavena kiselina (401.5±32.1) μM), dok su kapsaicin i ekstrakt ljute papričice imali iznimno slab učinak. Svi polifenolni spojevi imali su inhibicijski učinak miješanog tipa. Mjerenjem fluorescencije utvrđeno je da su polifenolni spojevi ugasili prirođenu fluorescenciju lipaze izolirane iz gušterače, i to pomoću statičkog mehanizma. Sekvencija Stern-Volmerove konstante bila je: kvercetin, kavena kiselina, te p-kumarna kiselina. Rezultati ispitivanja molekulskih uklapanja pokazali su da se kavena kiselina, kvercetin i p-kumarna kiselina vežu blizu, za razliku od kapsaicina koji se veže daleko od aktivnog mjesta. Vodikove veze i hidrofobne pi-interakcije glavni su načini međusobnog povezivanja polifenolnih spojeva u lipazi izoliranoj iz gušterače.The inhibitory activity and binding characteristics of caffeic acid, p-coumaric acid, quercetin and capsaicin, four phenolic compounds found in hot pepper, against porcine pancreatic lipase activity were studied and compared to hot pepper extract. Quercetin was the strongest inhibitor (IC50=(6.1±2.4) μM), followed by p-coumaric acid ((170.2±20.6) μM) and caffeic acid ((401.5±32.1) μM), while capsaicin and a hot pepper extract had very low inhibitory activity. All polyphenolic compounds showed a mixed-type inhibition. Fluorescence spectroscopy studies showed that polyphenolic compounds had the ability to quench the intrinsic fluorescence of pancreatic lipase by a static mechanism. The sequence of Stern-Volmer constant was quercetin, followed by caffeic and p-coumaric acids. Molecular docking studies showed that caffeic acid, quercetin and p-coumaric acid bound near the active site, while capsaicin bound far away from the active site. Hydrogen bonds and π-stacking hydrophobic interactions are the main pancreatic lipase-polyphenolic compound interactions observed

A Systems Genetics Approach Implicates USF1, FADS3, and Other Causal Candidate Genes for Familial Combined Hyperlipidemia

We hypothesized that a common SNP in the 3' untranslated region of the upstream transcription factor 1 (USF1), rs3737787, may affect lipid traits by influencing gene expression levels, and we investigated this possibility utilizing the Mexican population, which has a high predisposition to dyslipidemia. We first associated rs3737787 genotypes in Mexican Familial Combined Hyperlipidemia (FCHL) case/control fat biopsies, with global expression patterns. To identify sets of co-expressed genes co-regulated by similar factors such as transcription factors, genetic variants, or environmental effects, we utilized weighted gene co-expression network analysis (WGCNA). Through WGCNA in the Mexican FCHL fat biopsies we identified two significant Triglyceride (TG)-associated co-expression modules. One of these modules was also associated with FCHL, the other FCHL component traits, and rs3737787 genotypes. This USF1-regulated FCHL-associated (URFA) module was enriched for genes involved in lipid metabolic processes. Using systems genetics procedures we identified 18 causal candidate genes in the URFA module. The FCHL causal candidate gene fatty acid desaturase 3 (FADS3) was associated with TGs in a recent Caucasian genome-wide significant association study and we replicated this association in Mexican FCHL families. Based on a USF1-regulated FCHL-associated co-expression module and SNP rs3737787, we identify a set of causal candidate genes for FCHL-related traits. We then provide evidence from two independent datasets supporting FADS3 as a causal gene for FCHL and elevated TGs in Mexicans