Distributed computing and farm management with application to the search for heavy gauge bosons using the ATLAS experiment at the LHC (CERN)

The Standard Model of particle physics describes the strong, weak, and electromagnetic forces between the fundamental particles of ordinary matter. However, it presents several problems and some questions remain unanswered so it cannot be considered a complete theory of fundamental interactions. Many extensions have been proposed in order to address these problems. Some important recent extensions are the Extra Dimensions theories. In the context of some models with Extra Dimensions of size about $1 TeV^{-}1$, in particular in the ADD model with only fermions confined to a D-brane, heavy Kaluza-Klein excitations are expected, with the same properties as SM gauge bosons but more massive. In this work, three hadronic decay modes of some of such massive gauge bosons, Z* and W*, are investigated using the ATLAS experiment at the Large Hadron Collider (LHC), presently under construction at CERN. These hadronic modes are more difficult to detect than the leptonic ones, but they should allow a measurement of the couplings between heavy gauge bosons and quarks. The events were generated using the ATLAS fast simulation and reconstruction MC program Atlfast coupled to the Monte Carlo generator PYTHIA. We found that for an integrated luminosity of $3 × 10^{5} pb^{-}1$ and a heavy gauge boson mass of 2 TeV, the channels Z*->bb and Z*->tt would be difficult to detect because the signal would be very small compared with the expected backgrou nd, although the significance in the case of Z*->tt is larger. In the channel W*->tb , the decay might yield a signal separable from the background and a significance larger than 5 so we conclude that it would be possible to detect this particular mode at the LHC. The analysis was also performed for masses of 1 TeV and we conclude that the observability decreases with the mass. In particular, a significance higher than 5 may be achieved below approximately 1.4, 1.9 and 2.2 TeV for Z*->bb , Z*->tt and W*->tb respectively. The LHC will start to operate in 2008 and collect data in 2009. It will produce roughly 15 Petabytes of data per year. Access to this experimental data has to be provided for some 5,000 scientists working in 500 research institutes and universities. In addition, all data need to be available over the estimated 15-year lifetime of the LHC. The analysis of the data, including comparison with theoretical simulations, requires an enormous computing power. The computing challenges that scientists have to face are the huge amount of data, calculations to perform and collaborators. The Grid has been proposed as a solution for those challenges. The LHC Computing Grid project (LCG) is the Grid used by ATLAS and the other LHC experiments and it is analised in depth with the aim of studying the possible complementary use of it with another Grid project. That is the Berkeley Open Infrastructure for Network C omputing middle-ware (BOINC) developed for the SETI@home project, a Grid specialised in high CPU requirements and in using volunteer computing resources. Several important packages of physics software used by ATLAS and other LHC experiments have been successfully adapted/ported to be used with this platform with the aim of integrating them into the LHC@home project at CERN: Atlfast, PYTHIA, Geant4 and Garfield. The events used in our physics analysis with Atlfast were reproduced using BOINC obtaining exactly the same results. The LCG software, in particular SEAL, ROOT and the external software, was ported to the Solaris/sparc platform to study it's portability in general as well. A testbed was performed including a big number of heterogeneous hardware and software that involves a farm of 100 computers at CERN's computing center (lxboinc) together with 30 PCs from CIEMAT and 45 from schools from Extremadura (Spain). That required a preliminary study, development and creation of components of the Quattor software and configuration management tool to install and manage the lxboinc farm and it also involved the set up of a collaboration between the Spanish research centers and government and CERN. The testbed was successful and 26,597 Grid jobs were delivered, executed and received successfully. We conclude that BOINC and LCG are complementary and useful kinds of Grid that can be used by ATLAS and the other LHC experiments. LCG has very good data distribution, management and storage capabilities that BOINC does not have. In the other hand, BOINC does not need high bandwidth or Internet speed and it also can provide a huge and inexpensive amount of computing power coming from volunteers. In addition, it is possible to send jobs from LCG to BOINC and vice versa. So, possible complementary cases are to use volunteer BOINC nodes when the LCG nodes have too many jobs to do or to use BOINC for high CPU tasks like event generators or reconstructions while concentrating LCG for data analysis

Galileo Station Keeping Strategy

This paper presents analyses done for the design and implementation of the Maneuver Planning software of the Galileo Flight Dynamics Facility. The station keeping requirements of the constellation have been analyzed in order to identify the key parameters to be taken into account in the design and implementation of the software

Regulatory polymorphisms in extracellular matrix protease genes and susceptibility to rheumatoid arthritis: a case-control study

Many extracellular matrix (ECM) proteases seem to be important in rheumatoid arthritis (RA) and regulation of their transcription levels is a critical mechanism for controlling their activity. We have investigated, therefore, whether the best-characterized single nucleotide polymorphisms (SNPs) affecting transcription of the ECM proteases that have been related with joint pathology are associated with RA susceptibility. Nine SNPs in eight genes were selected by bibliographic search, including SNPs in the genes encoding matrix metalloproteinase (MMP)1, MMP2, MMP3, MMP7, MMP9, MMP13, plasminogen activator, tissue type (PLAT) and PAI-1. They were studied in a case-control setting that included 550 RA patients and 652 controls of Spanish ancestry from a single center. Genotyping was performed by single-base extension. Only two of the nine SNPs showed significant association with RA susceptibility. RA patients showed increased frequencies of the -7351 T allele of the gene encoding PLAT (36.4% versus 32.1% in controls, p = 0.026) and the -1306 T allele of the gene encoding MMP2 (24.5% versus 20.3% in controls, p = 0.013). These two alleles seemed to cooperate according to an additive model with respect to increased RA susceptibility (p = 0.004), and they were the low-expression alleles of the respective SNPs in a PLAT enhancer and the MMP2 promoter. These findings are in agreement with previous data suggesting that these two ECM proteases have a protective role in RA pathology. Confirmation of these associations will be needed to support these hypotheses. The remaining SNPs did not show association, either individually or collectively. Therefore, although regulatory SNPs in ECM proteases did not show any major effect on RA susceptibility, it was possible to find modest associations that, if replicated, will have interesting implications in the understanding of RA pathology

Gene expression changes in mononuclear cells from patients with metabolic syndrome after acute intake of phenol-rich virgin olive oil

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Previous studies have shown that acute intake of high-phenol virgin olive oil reduces pro-inflammatory, pro-oxidant and pro-thrombotic markers compared with low phenols virgin olive oil, but it still remains unclear whether effects attributed to its phenolic fraction are exerted at transcriptional level in vivo. To achieve this goal, we aimed at identifying expression changes in genes which could be mediated by virgin olive oil phenol compounds in the human. Results Postprandial gene expression microarray analysis was performed on peripheral blood mononuclear cells during postprandial period. Two virgin olive oil-based breakfasts with high (398 ppm) and low (70 ppm) content of phenolic compounds were administered to 20 patients suffering from metabolic syndrome following a double-blinded, randomized, crossover design. To eliminate the potential effect that might exist in their usual dietary habits, all subjects followed a similar low-fat, carbohydrate rich diet during the study period. Microarray analysis identified 98 differentially expressed genes (79 underexpressed and 19 overexpressed) when comparing the intake of phenol-rich olive oil with low-phenol olive oil. Many of these genes seem linked to obesity, dyslipemia and type 2 diabetes mellitus. Among these, several genes seem involved in inflammatory processes mediated by transcription factor NF-κB, activator protein-1 transcription factor complex AP-1, cytokines, mitogen-activated protein kinases MAPKs or arachidonic acid pathways. Conclusion This study shows that intake of virgin olive oil based breakfast, which is rich in phenol compounds is able to repress in vivo expression of several pro-inflammatory genes, thereby switching activity of peripheral blood mononuclear cells to a less deleterious inflammatory profile. These results provide at least a partial molecular basis for reduced risk of cardiovascular disease observed in Mediterranean countries, where virgin olive oil represents a main source of dietary fat. Admittedly, other lifestyle factors are also likely to contribute to lowered risk of cardiovascular disease in this region.Published versio

Regioirregular and catalytic Mizoroki-Heck reactions

[EN] The palladium-catalysed cross-coupling reaction between alkenes and aryl halides (the Mizoroki-Heck reaction) is a powerful methodology to construct new carbon-carbon bonds. However, the success of this reaction is in part hampered by an extremely marked regioselectivity on the double bond, which dictates that electron-poor alkenes react exclusively on the beta-carbon. Here, we show that ligand-free, few-atom palladium clusters in solution catalyse the alpha-selective intramolecular Mizoroki-Heck coupling of iodoaryl cinnamates, and mechanistic studies support the formation of a sterically encumbered cinnamate-palladium cluster intermediate. Following this rationale, the alpha-selective intermolecular coupling of aryl iodides with styrenes is also achieved with palladium clusters encapsulated within fine-tuned and sterically restricted zeolite cavities to produce 1,1-bisarylethylenes, which are further engaged with aryl halides by a metal-free photoredox-catalysed coupling. These ligand-free methodologies significantly expand the chemical space of the Mizoroki-Heck coupling.This work was supported by MINECO (Spain, projects CTQ 2017-86735-P, PID2019-105391GB-C22 and MAT2017-82288-C2-1-P, Severo Ochoa programme SEV-2016-0683 and the Juan de la Cierva programme). F.G.-P. and R.G. thank ITQ for the concession of a contract. J.O.-M. acknowledges the Juan de la Cierva programme for the concession of a contract, and R.P.-R. and J.C.-S. thank the Plan GenT programme (CIDEGENT/2018/044) funded by Generalitat Valenciana. HR STEM measurements were performed at DME-UCA in Cadiz University, with financial support from FEDER/MINECO (PID2019-110018GA-I00 and PID2019-107578GA-I00). We acknowledge ALBA Synchrotron for allocating beamtime and CL AE SS beamline staff for their technical support during our experiment.Garnes-Portoles, F.; Greco, R.; Oliver-Meseguer, J.; Castellanos-Soriano, J.; Jiménez Molero, MC.; Lopez-Haro, M.; Hernández-Garrido, JC.... (2021). Regioirregular and catalytic Mizoroki-Heck reactions. Nature Catalysis. 4(4):293-303. https://doi.org/10.1038/s41929-021-00592-3S2933034

EZH2 endorses cell plasticity to non-small cell lung cancer cells facilitating mesenchymal to epithelial transition and tumour colonization

CGL was funded by the Consejería de Salud y Familias, Junta de Andalucía (RH-0139-2020) and SG-P is funded by Instituto de Salud Carlos III (CP19/00029, PI15/00336, PI19/01533). JAM is supported by RTI2018.101309B-C22 funded by MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa” and by the Chair “Doctors Galera-Requena in cancer stem cell research”. PCS is funded by Ministerio de Ciencia e Innovación (grant PID2020-119032RB-I00) and FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidades (grants P20_00335 and B‐CTS‐40‐UGR20). The Landeira lab is supported by the Spanish ministry of science and innovation (PID2019-108108-100, EUR2021-122005), the Andalusian regional government (PC-0246-2017, PIER-0211-2019, PY20_00681) and the University of Granada (A-BIO-6-UGR20) grants.Reversible transition between the epithelial and mesenchymal states are key aspects of carcinoma cell dissemination and the metastatic disease, and thus, characterizing the molecular basis of the epithelial to mesenchymal transition (EMT) is crucial to find druggable targets and more effective therapeutic approaches in cancer. Emerging studies suggest that epigenetic regulators might endorse cancer cells with the cell plasticity required to conduct dynamic changes in cell state during EMT. However, epigenetic mechanisms involved remain mostly unknown. Polycomb Repressive Complexes (PRCs) proteins are well-established epigenetic regulators of development and stem cell differentiation, but their role in different cancer systems is inconsistent and sometimes paradoxical. In this study, we have analysed the role of the PRC2 protein EZH2 in lung carcinoma cells. We found that besides its described role in CDKN2A-dependent cell proliferation, EZH2 upholds the epithelial state of cancer cells by repressing the transcription of hundreds of mesenchymal genes. Chemical inhibition or genetic removal of EZH2 promotes the residence of cancer cells in the mesenchymal state during reversible epithelial–mesenchymal transition. In fitting, analysis of human patient samples and tumour xenograft models indicate that EZH2 is required to efficiently repress mesenchymal genes and facilitate tumour colonization in vivo. Overall, this study discloses a novel role of PRC2 as a master regulator of EMT in carcinoma cells. This finding has important implications for the design of therapies based on EZH2 inhibitors in human cancer patients.Junta de Andalucía (RH-0139-2020)Instituto de Salud Carlos III (CP19/00029, PI15/00336, PI19/01533)MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa” RTI2018.101309B-C22Chair “Doctors Galera-Requena in cancer stem cell research”Ministerio de Ciencia e Innovación (grant PID2020-119032RB-I00)FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidades (grants P20_00335 and B‐CTS‐40‐UGR20)Spanish ministry of science and innovation (PID2019-108108-100, EUR2021-122005)Andalusian regional government (PC-0246-2017, PIER-0211-2019, PY20_00681)University of Granada (A-BIO-6-UGR20

Metabolomics analysis of type 2 diabetes remission identifies 12 metabolites with predictive capacity: a CORDIOPREV clinical trial study.

Type 2 diabetes mellitus (T2DM) is one of the most widely spread diseases, affecting around 90% of the patients with diabetes. Metabolomics has proven useful in diabetes research discovering new biomarkers to assist in therapeutical studies and elucidating pathways of interest. However, this technique has not yet been applied to a cohort of patients that have remitted from T2DM. All patients with a newly diagnosed T2DM at baseline (n = 190) were included. An untargeted metabolomics approach was employed to identify metabolic differences between individuals who remitted (RE), and those who did not (non-RE) from T2DM, during a 5-year study of dietary intervention. The biostatistical pipeline consisted of an orthogonal projection on the latent structure discriminant analysis (O-PLS DA), a generalized linear model (GLM), a receiver operating characteristic (ROC), a DeLong test, a Cox regression, and pathway analyses. The model identified a significant increase in 12 metabolites in the non-RE group compared to the RE group. Cox proportional hazard models, calculated using these 12 metabolites, showed that patients in the high-score tercile had significantly (p-value < 0.001) higher remission probabilities (Hazard Ratio, HR, high versus low = 2.70) than those in the lowest tercile. The predictive power of these metabolites was further studied using GLMs and ROCs. The area under the curve (AUC) of the clinical variables alone is 0.61, but this increases up to 0.72 if the 12 metabolites are considered. A DeLong test shows that this difference is statistically significant (p-value = 0.01). Our study identified 12 endogenous metabolites with the potential to predict T2DM remission following a dietary intervention. These metabolites, combined with clinical variables, can be used to provide, in clinical practice, a more precise therapy. ClinicalTrials.gov, NCT00924937.The CORDIOPREV study is supported by the Ministerio de Economia y Competitividad, Spain, under the grants AGL2012/39615, PIE14/00005, and PIE14/00031 associated to J.L.-M.; AGL2015-67896-P to J.L.-M. and A.C.; CP14/00114 to A.C.; PI19/00299 to A.C.; DTS19/00007 to A.C.; FIS PI13/00023 to J.D.-L., PI16/01777 to F.P.-J. and P.P.-M.; Antonio Camargo is supported by an ISCIII research contract (Programa Miguel-Servet CPII19/00007); Marina Mora-Ortiz has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 847468; ‘Fundacion Patrimonio Comunal Olivarero’, Junta de Andalucía (Consejería de Salud, Consejeria de Agricultura y Pesca, Consejería de Innovacion, Ciencia y Empresa), ‘Diputaciones de Jaen y Cordoba’, ‘Centro de Excelencia en Investigación sobre Aceite de Oliva y Salud’ and ‘Ministerio de Medio Ambiente, Medio Rural y Marino’, Gobierno de España; ‘Consejeria de Innovación, Ciencia y Empresa, Proyectos de Investigación de Excelencia’, Junta de Andalucía under the grant CVI-7450 obtaiend by J.L.-M.; and we would also like to thank the ‘Fondo Europeo de Desarrollo Regional (FEDER)’.S

La vid silvestre en México. Actualidades y potencial

En ocho capítulos se aborda el estado del arte de la vid silvestre en MéxicoEl estudio de las especies vegetales nativas de México representa un reto que cada día más investigadores mexicanos asumen. Durante muchos años, el apoyo a la investigación pública ha sido mínimo; desde el punto de vista agronómico es insuficiente para avanzar a la velocidad que requiere nuestro país para afrontar problemas de producción y distribución de alimentos. Por esa razón, entre otras, me es grato presentar esta obra que compila parte de los trabajos de la Red de Vid Silvestre patrocinada por el Sistema Nacional de Recursos Fitogenéticos (sinarefi) dependiente de la sagarpa; trabajos apuntalados por investigadores que sin pertenecer a la red han colaborado en el estudio de las plantas del género Vitis. En este libro se muestra el potencial del país para aprovechar el recurso vid, empleado desde antes de la conquista española por nativos mexicanos que conocían sus bondades. Es necesario continuar el avance en el conocimiento de este recurso, por ello el presente libro pretende invitar a toda persona interesada en contribuir con el rescate y conservación de las vides mexicanas. Los autores y editores, así como las instituciones en donde laboramos y aquellas que patrocinan estas investigaciones, esperamos se cumpla este objetivo y que el lector, alumno, profesor, investigador, público en general, disfrute esta lectura y, sobre todo, se interese en el recurso VitisSEP, SINAREFI, UAEME