Sitagliptin improved glucose assimilation in detriment of fatty-acid utilization in experimental type-II diabetes: Role of GLP-1 isoforms in Glut4 receptor trafficking

Background: The distribution of glucose and fatty-acid transporters in the heart is crucial for energy consecution and myocardial function. In this sense, the glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, improves glucose homeostasis but it could also trigger direct cardioprotective actions, including regulation of energy substrate utilization. Methods: Type-II diabetic GK (Goto-Kakizaki), sitagliptin-treated GK (10 mg/kg/day) and wistar rats (n = 10, each) underwent echocardiographic evaluation, and positron emission tomography scanning for [ 18 F]-2-fluoro-2-deoxy-d-glucose ( 18 FDG). Hearts and plasma were isolated for biochemical approaches. Cultured cardiomyocytes were examined for receptor distribution after incretin stimulation in high fatty acid or high glucose media. Results: Untreated GK rats exhibited hyperglycemia, hyperlipidemia, insulin resistance, and plasma GLP-1 reduction. Moreover, GK myocardium decreased 18 FDG assimilation and diastolic dysfunction. However, sitagliptin improved hyperglycemia, insulin resistance, and GLP-1 levels, and additionally, enhanced 18 FDG uptake and diastolic function. Sitagliptin also stimulated the sarcolemmal translocation of the glucose transporter-4 (Glut4), in detriment of the fatty acyl translocase (FAT)/CD36. In fact, Glut4 mRNA expression and sarcolemmal translocation were also increased after GLP-1 stimulation in high-fatty acid incubated cardiomyocytes. PI3K/Akt and AMPKα were involved in this response. Intriguingly, the GLP-1 degradation metabolite, GLP-1(9-36), showed similar effects. Conclusions: Besides of its anti-hyperglycemic effect, sitagliptin-enhanced GLP-1 may ameliorate diastolic dysfunction in type-II diabetes by shifting fatty acid to glucose utilization in the cardiomyocyte, and thus, improving cardiac efficiency and reducing lipolysisThis work was supported by national grants from Ministerio de Educación y Ciencia (SAF2009-08367), Comunidad de Madrid (CCG10-UAM/BIO-5289), and PIE13/00051 and PI14/00386 (IS. Carlos III). Merck Sharp and Dohme (Darmstadt, Germany) provided sitagliptin and partial financial support to the conduct of the stud

Significant discharge of CO2 from hydrothermalism associated with the submarine volcano of El Hierro Island

The residual hydrothermalism associated with submarine volcanoes, following an eruption event, plays an important role in the supply of CO2 to the ocean. The emitted CO2 increases the acidity of seawater. The submarine volcano of El Hierro, in its degasification stage, provided an excellent opportunity to study the effect of volcanic CO2 on the seawater carbonate system, the global carbon flux, and local ocean acidification. A detailed survey of the volcanic edifice was carried out using seven CTD-pH-ORP tow-yo studies, localizing the redox and acidic changes, which were used to obtain surface maps of anomalies. In order to investigate the temporal variability of the system, two CTD-pH-ORP yo-yo studies were conducted that included discrete sampling for carbonate system parameters. Meridional tow-yos were used to calculate the amount of volcanic CO2 added to the water column for each surveyed section. The inputs of CO2 along multiple sections combined with measurements of oceanic currents produced an estimated volcanic CO2 flux = 6.0 105 ± 1.1 105 kg d−1 which is ~0.1% of global volcanic CO2 flux. Finally, the CO2 emitted by El Hierro increases the acidity above the volcano by ~20%.En prens

Transverse momentum spectra of charged particles in proton-proton collisions at s=900\sqrt{s} = 900 GeV with ALICE at the LHC

The inclusive charged particle transverse momentum distribution is measured in proton-proton collisions at $\sqrt{s} = 900$ GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region $(|\eta|<0.8)$ over the transverse momentum range $0.15<p_{\rm T}<10$ GeV/$c$. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for $|\eta|<0.8$ is $\left<p_{\rm T}\right>_{\rm INEL}=0.483\pm0.001$ (stat.) $\pm0.007$ (syst.) GeV/$c$ and \left_{\rm NSD}=0.489\pm0.001 (stat.) $\pm0.007$ (syst.) GeV/$c$, respectively. The data exhibit a slightly larger $\left<p_{\rm T}\right>$ than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET.Comment: 20 pages, 8 figures, 2 tables, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/390

Real-time simulation techniques for augmented learning in science and engineering

In this paper we present the basics of a novel methodology for the development of simulation-based and augmented learning tools in the context of applied science and engineering. It is based on the extensive use of model order reduction, and particularly, of the so-called Proper Generalized Decomposition (PGD) method. This method provides a sort of meta-modeling tool without the need for prior computer experiments that allows the user to obtain real-time response in the solution of complex engineering or physical problems. This real-time capability also allows for its implementation in deployed, touch-screen, handheld devices or even to be immersed into electronic textbooks. We explore here the basics of the proposed methodology and give examples on a few challenging applications never until now explored, up to our knowledge.Peer ReviewedPostprint (author's final draft

Space-time proper generalized decompositions for the resolution of transient elastodynamic models

In this paper, we investigate ability of proper generalized decomposition (PGD) to solve transient elastodynamic models in space-time domain. Classical methods use time integration schemes and an incremental resolution process. We propose here to use standard time integration methods in a non-incremental strategy. As a result, PGD gives a separated representation of the space-time solution as a sum of tensorial products of space and time vectors, that we interpret as space-time modes. Recent time integration schemes are based on multi-field formulations. In this case, separated representation can be constructed using state vectors in space and same vectors in time. However, we have experienced bad convergence order using this decomposition. Furthermore, temporal approximation must be the same for all fields. Thus, we propose an extension of classical separated representation for multi-field problems. This multi-field PGD (MF-PGD) uses space and time vectors that are different for each field. Calculation of decomposition is done using a monolithic approach in space and time, potentially allowing the use of different approximations in space and time. Finally, several simulations are performed with the transient elastodynamic problem with one dimension in space. Different approximations in time are investigated: Newmark scheme, single field time discontinuous Galerkin method and two fields time continuous and discontinuous Galerkin methods

Charged-particle multiplicity measurement in proton–proton collisions at sqrt(s)=0.9 and 2.36 TeV with ALICE at LHC

Charged-particle production was studied in proton–proton collisions collected at the LHC with the ALICE detector at centre-of-mass energies 0.9 TeV and 2.36 TeV in the pseudorapidity range |η| &lt; 1.4. In the central region (|η| &lt; 0.5), at 0.9 TeV, we measure charged-particle pseudorapidity density dNch/dη = 3.02 ± 0.01(stat.) +0.08 −0.05(syst.) for inelastic interactions, and dNch/dη = 3.58 ± 0.01 (stat.) +0.12 −0.12(syst.) for non-single-diffractive interactions. At 2.36 TeV, we find dNch/dη = 3.77 ± 0.01(stat.) +0.25 −0.12(syst.) for inelastic, and dNch/dη = 4.43 ± 0.01(stat.) +0.17 −0.12(syst.) for non-single-diffractive collisions. The relative increase in charged-particle multiplicity from the lower to higher energy is 24.7% ± 0.5%(stat.) +5.7 −2.8%(syst.) for inelastic and 23.7% ± 0.5%(stat.) +4.6 −1.1%(syst.) for non-single-diffractive interactions. This increase is consistent with that reported by the CMS collaboration for non-single-diffractive events and larger than that found by a number of commonly used models. The multiplicity distribution was measured in different pseudorapidity intervals and studied in terms of KNO variables at both energies. The results are compared to proton– antiproton data and to model predictions

Charged-particle multiplicity measurement in proton-proton collisions at root s=7 TeV with ALICE at LHC

The pseudorapidity density and multiplicity distribution of charged particles produced in proton-proton collisions at the LHC, at a centre-of-mass energy root s = 7 TeV, were measured in the central pseudorapidity region vertical bar eta vertical bar < 1. Comparisons are made with previous measurements at root s = 0.9 TeV and 2.36 TeV. At root s = 7 TeV, for events with at least one charged particle in |eta vertical bar| < 1, we obtain dN(ch)/d eta = 6.01 +/- 0.01(stat.)(-0.12)(+0.20) (syst.). This corresponds to an increase of 57.6%+/-0.4%(stat.)(-1.8%)(+3.6) (syst.) relative to collisions at 0.9 TeV, significantly higher than calculations from commonly used models. The multiplicity distribution at 7 TeV is described fairly well by the negative binomial distribution