1,697 research outputs found
Cultural Democracy in Higher Education ¬Beyond the Deficit Model of Compensatory Education
Promoting cultural democracy in the teaching, service, and research missions of higher education is being advanced as a model to integrate and empower minorities to become agents of change
Marco teórico sobre los factores que inciden en la internacionalización de proveedores automotrices en el noreste de México
El propósito de este estudio fue el de integrar el marco teórico y explorar las relaciones entre la orientación emprendedora, las redes de relaciones, la innovación y la capacidad de producción con la internacionalización de los proveedores automotrices Tier 1 del noreste de México. El enfoque de la investigación que se utilizó en este estudio fue cuantitativo con un alcance exploratorio, así como el uso de métodos de investigación descriptivos para este artículo. El diseño de la investigación fue no experimental y transeccional. Como resultado, se integró el marco teórico donde analizaron diferentes teorías y modelos teóricos que estudian el fenómeno de la internacionalización y se destacaron las investigaciones empíricas que vincularon la internacionalización con la orientación emprendedora, las redes de relaciones, la innovación y la capacidad de producción. En conclusión, para conocer los factores que inciden en la internacionalización de los proveedores automotrices Tier 1 es necesario considerar los modelos y teorías de la internacionalización listadas en el marco teórico
Versatile Graphene-Based Platform for Robust Nanobiohybrid Interfaces
Technologically useful and robust graphene-based interfaces for devices
require the introduction of highly selective, stable, and covalently bonded
functionalities on the graphene surface, whilst essentially retaining the
electronic properties of the pristine layer. This work demonstrates that highly
controlled, ultrahigh vacuum covalent chemical functionalization of graphene
sheets with a thiol-terminated molecule provides a robust and tunable platform
for the development of hybrid nanostructures in different environments. We
employ this facile strategy to covalently couple two representative systems of
broad interest: metal nanoparticles, via S-metal bonds, and thiol-modified DNA
aptamers, via disulfide bridges. Both systems, which have been characterized by
a multi-technique approach, remain firmly anchored to the graphene surface even
after several washing cycles. Atomic force microscopy images demonstrate that
the conjugated aptamer retains the functionality required to recognize a target
protein. This methodology opens a new route to the integration of high-quality
graphene layers into diverse technological platforms, including plasmonics,
optoelectronics, or biosensing. With respect to the latter, the viability of a
thiol-functionalized chemical vapor deposition graphene-based solution-gated
field-effect transistor array was assessed
1118-78 Primary angioplasty versus facilitated intervention (tenecteplase plus stenting) in patients with ST elevated acute myocardial infarction: Final results of the GRACIA-2 trial
p38γ/δ activation alters cardiac electrical activity and predisposes to ventricular arrhythmia
We gratefully acknowledge L. Sen-Martín, J. Alegre-Cebollada
(CNIC, Madrid) and L. Carrier (University Medical Center HamburgEppendorf and DZHK, Hamburg) for the cMyBP3-C KO cardiac tissue; D. Roiz-Valle and C. López-Otín (IUOPA; Universidad de Oviedo,
Oviedo) for the LmnaG609G/G609G cardiac tissue; and R. J. Davis for the
MKK6 KO mice. We thank G. Giovinazzo and the CNIC Pluripotent
Cell Technology Unit (CNIC, Madrid) for the hiPSCs. We thank
S. Bartlett and F. Chanut (CNIC, Madrid) for English editing, and
R. R. Mondragon (University of Michigan, Ann Arbor) for technical
support. We are grateful to R. J. Davis (University of Massachusetts
Chan Medical School, Worcester), A. Padmanabhan (University
of California, San Francisco) and M. Costa and C. López-Otín
(IUOPA; Universidad de Oviedo, Oviedo) for critical reading of
the manuscript. We thank the staf at the CNIC Genomics and
Bioinformatics Units for technical support and help with data analysis
and A. C. Silva for help with figure editing and design. This work was
funded by a CNIC Intramural Project Severo Ochoa (Expediente 12-
2016 IGP) to G.S. and J.J. G.S. is supported by the following projects:
PMP21/00057 IMPACT-2021, funded by the Instituto de Salud Carlos
III (ISCIII), and PDC2021-121147-I00 and PID2019-104399RB-I00,
funded by MCIN/AEI/10.13039/501100011033—all funded by the
European Union (FEDER/FSE); ‘Una manera de hacer Europa’/‘El
FSE invierte en tu futuro’/Next Generation EU and co-funded by the
European Union/Plan de Recuperación, Transformación y Resiliencia
(PRTR). R.R.B. is a fellow of the FPU Program (FPU17/03847).
B.G.T. was a fellow of the FPI Severo Ochoa CNIC Program
(SVP‐2013‐067639) and an American Heart Association Postdoctoral
Fellow (18POST34080175). The following grants provided
additional funding: Instituto de Salud Carlos III, PDC2021-121147-I00
Convocatoria: Proyectos Prueba de Concepto 2021 Ministerio de
Ciencia e Innovación and PID2022-138525OB-I00 Ministerio de
Ciencia e Innovación; US National Heart, Lung, and Blood Institute
(R01 grant HL122352); Fondos FEDER, Madrid, Spain, and Fundación
Bancaria ‘La Caixa (project HR19/52160013) to J.J.; American
Heart Association Postdoctoral Fellowship 14POST17820005 to
D.P.B.; and MICINN PGC2018-097019-B-I00, ISCIII-SGEFI/ERDF
(PRB3-IPT17/0019, ProteoRed), the Fundació Marató TV3 (grant
122/C/2015) and ‘la Caixa’ Banking Foundation (project code HR17-
00247) to J.V. The CNIC is supported by the Instituto de Salud Carlos
III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro
CNIC Foundation and is a Severo Ochoa Center of Excellence (grant
CEX2020-001041-S, funded by MICIN/AEI/10.13039/501100011033).S
p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1
During the first weeks of postnatal heart development, cardiomyocytes undergo a major adaptive metabolic shift from glycolytic energy production to fatty acid oxidation. This metabolic change is contemporaneous to the up-regulation and activation of the p38γ and p38δ stress-activated protein kinases in the heart. We demonstrate that p38γ/δ contribute to the early postnatal cardiac metabolic switch through inhibitory phosphorylation of glycogen synthase 1 (GYS1) and glycogen metabolism inactivation. Premature induction of p38γ/δ activation in cardiomyocytes of newborn mice results in an early GYS1 phosphorylation and inhibition of cardiac glycogen production, triggering an early metabolic shift that induces a deficit in cardiomyocyte fuel supply, leading to whole-body metabolic deregulation and maladaptive cardiac pathogenesis. Notably, the adverse effects of forced premature cardiac p38γ/δ activation in neonate mice are prevented by maternal diet supplementation of fatty acids during pregnancy and lactation. These results suggest that diet interventions have a potential for treating human cardiac genetic diseases that affect heart metabolism.G.S. is a YIP EMBO member. B.G.T. was a fellow of the FPI Severo Ochoa CNIC program (SVP-2013-067639) and currently is funded by the AHA-CHF (AHA award number: 818798). V.M.R. is a FPI fellow (BES-2014-069332) and A.M.S. is a fellow of the FPI Severo Ochoa CNIC program (BES-2016-077635). This work was funded by the following grants: to G.S.: funding from the EFSD/Lilly European Diabetes Research Programme Dr Sabio, from Spanish Ministry of Science, Innovation and Universities (MINECO-FEDER SAF2016-79126-R and PID2019-104399RB-I00), Comunidad de Madrid (IMMUNOTHERCAN-CM S2010/BMD-2326 and B2017/BMD-3733) and Fundación Jesús Serra; to P.A.: Ayudas para apoyar grupos de investigación del sistema Universitario Vasco (IT971-16 to P.A.), MCIU/AEI/FEDER, funding from Spanish Ministry of Science, Innovation and Universities (RTI2018-095134-B-100); Excellence Network Grant from MICIU/AEI (SAF2016-81975-REDT and 2018-PN188) to PA and GS; to J.V.: funding from Spanish Ministry of Science, Innovation and Universities (PGC2018-097019-B-I00), the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria grant PRB3 (PT17/0019/0003- ISCIII-SGEFI / ERDF, ProteoRed), and “la Caixa” Banking Foundation (project code HR17-00247); to J.P.B.: funding from Spanish Ministry of Science, Innovation and Universities (PID2019-105699RB-I00, RED2018‐102576‐T) and Escalera de Excelencia (CLU-2017-03); to J.A.E.: funding from Spanish Ministry of Science, Innovation and Universities MINECO (RED2018-102576-T, RTI2018-099357-B-I00), CIBERFES (CB16/10/00282), and HFSP (RGP0016/2018). RAP (XPC/BBV1602 and MIN/RYC1102). The CNIC is supported by the Ministry of Science, Innovation and Universities and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
wKinMut: An integrated tool for the analysis and interpretation of mutations in human protein kinases
BACKGROUND: Protein kinases are involved in relevant physiological functions and a broad number of mutations in this superfamily have been reported in the literature to affect protein function and stability. Unfortunately, the exploration of the consequences on the phenotypes of each individual mutation remains a considerable challenge. RESULTS: The wKinMut web-server offers direct prediction of the potential pathogenicity of the mutations from a number of methods, including our recently developed prediction method based on the combination of information from a range of diverse sources, including physicochemical properties and functional annotations from FireDB and Swissprot and kinase-specific characteristics such as the membership to specific kinase groups, the annotation with disease-associated GO terms or the occurrence of the mutation in PFAM domains, and the relevance of the residues in determining kinase subfamily specificity from S3Det. This predictor yields interesting results that compare favourably with other methods in the field when applied to protein kinases. Together with the predictions, wKinMut offers a number of integrated services for the analysis of mutations. These include: the classification of the kinase, information about associations of the kinase with other proteins extracted from iHop, the mapping of the mutations onto PDB structures, pathogenicity records from a number of databases and the classification of mutations in large-scale cancer studies. Importantly, wKinMut is connected with the SNP2L system that extracts mentions of mutations directly from the literature, and therefore increases the possibilities of finding interesting functional information associated to the studied mutations. CONCLUSIONS: wKinMut facilitates the exploration of the information available about individual mutations by integrating prediction approaches with the automatic extraction of information from the literature (text mining) and several state-of-the-art databases. wKinMut has been used during the last year for the analysis of the consequences of mutations in the context of a number of cancer genome projects, including the recent analysis of Chronic Lymphocytic Leukemia cases and is publicly available at http://wkinmut.bioinfo.cnio.es
Observation of an Excited Bc+ State
Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+π+π- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bc∗(2S31)+ state reconstructed without the low-energy photon from the Bc∗(1S31)+→Bc+γ decay following Bc∗(2S31)+→Bc∗(1S31)+π+π-. A second state is seen with a global (local) statistical significance of 2.2σ (3.2σ) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date
Bose-Einstein correlations of same-sign charged pions in the forward region in pp collisions at √s=7 TeV
Bose-Einstein correlations of same-sign charged pions, produced in protonproton collisions at a 7 TeV centre-of-mass energy, are studied using a data sample collected
by the LHCb experiment. The signature for Bose-Einstein correlations is observed in the
form of an enhancement of pairs of like-sign charged pions with small four-momentum
difference squared. The charged-particle multiplicity dependence of the Bose-Einstein correlation parameters describing the correlation strength and the size of the emitting source
is investigated, determining both the correlation radius and the chaoticity parameter. The
measured correlation radius is found to increase as a function of increasing charged-particle
multiplicity, while the chaoticity parameter is seen to decreas
Measurement of the inelastic pp cross-section at a centre-of-mass energy of 13TeV
The cross-section for inelastic proton-proton collisions at a centre-of-mass energy of 13TeV is measured with the LHCb detector. The fiducial cross-section for inelastic interactions producing at least one prompt long-lived charged particle with momentum p > 2 GeV/c in the pseudorapidity range 2 < η < 5 is determined to be ϭ acc = 62:2 ± 0:2 ± 2:5mb. The first uncertainty is the intrinsic systematic uncertainty of the measurement, the second is due to the uncertainty on the integrated luminosity. The statistical uncertainty is negligible. Extrapolation to full phase space yields the total inelastic proton-proton cross-section ϭ inel = 75:4 ± 3:0 ± 4:5mb, where the first uncertainty is experimental and the second due to the extrapolation. An updated value of the inelastic cross-section at a centre-of-mass energy of 7TeV is also reported
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