Skills Requirements for the European Machine Tool Sector Emerging from Its Digitalization

Abstract The machine tool industry, which is the starting point of all the metal producing activities, is presently undergoing rapid and continuous changes as a result of the fourth industrial revolution Industry 4.0. Manufacturing models are profoundly transforming with emerging digitalization. Smart technologies like artificial intelligence (AI), big data, the Internet of Things (IoT), digital twin, allow the machine tool companies to optimize processes, increase efficiency and reduce waste through a new phase of automation. These technologies, as well, enable the machine tool producers to reach the aim of creating products with improved performance, extended life, high reliability that are eco-efficient. Therefore, Industry 4.0 could be perceived as an invaluable opportunity for the machine tool sector, only if the sector has a competent workforce capable of handling the implementation of new business models and technological developments. The main condition to create this highly qualified workforce is reskilling and upskilling of the current workforce. Once we define the expected evolution of skills requirements, we can clarify the skills mismatch between the workers and job profiles. Only then, we can reduce them by delivering well-developed trainings. For this purpose, this article identifies the current and foreseen skills requirements demanded by the machine tool industry workforce. To this end, we generated an integrated database for the sector with the present and prospective skills needs of the metal processing sector professionals. The presented sectoral database is a fundamental structure that will make the sector acquire targeted industrial reforms. It can also be an essential instrument for machine tool companies, policymakers, academics and education or training centers to build well-designed and effective training programs to enhance the skills of the labor forceThis research was partly funded by (a) the European Union through the Erasmus Plus Programme (Grant Agreement No. 2018-3019/001-001, Project No. 600886-1-2018-1-DE-EPPKA2-SSA-B). (b) the HAZITEK call of the Basque Government, project acronym Adit4All and (c) Accenture, Inzu Group, Fundación Telefónica and Fundación BBK, partners of the Deusto Digital Industry Chair

Customized Treatment in Non-Small-Cell Lung Cancer Based on EGFR Mutations and BRCA1 mRNA Expression

BACKGROUND: Median survival is 10 months and 2-year survival is 20% in metastatic non-small-cell lung cancer (NSCLC) treated with platinum-based chemotherapy. A small fraction of non-squamous cell lung cancers harbor EGFR mutations, with improved outcome to gefitinib and erlotinib. Experimental evidence suggests that BRCA1 overexpression enhances sensitivity to docetaxel and resistance to cisplatin. RAP80 and Abraxas are interacting proteins that form complexes with BRCA1 and could modulate the effect of BRCA1. In order to further examine the effect of EGFR mutations and BRCA1 mRNA levels on outcome in advanced NSCLC, we performed a prospective non-randomized phase II clinical trial, testing the hypothesis that customized therapy would confer improved outcome over non-customized therapy. In an exploratory analysis, we also examined the effect of RAP80 and Abraxas mRNA levels. METHODOLOGY/PRINCIPAL FINDINGS: We treated 123 metastatic non-squamous cell lung carcinoma patients using a customized approach. RNA and DNA were isolated from microdissected specimens from paraffin-embedded tumor tissue. Patients with EGFR mutations received erlotinib, and those without EGFR mutations received chemotherapy with or without cisplatin based on their BRCA1 mRNA levels: low, cisplatin plus gemcitabine; intermediate, cisplatin plus docetaxel; high, docetaxel alone. An exploratory analysis examined RAP80 and Abraxas expression. Median survival exceeded 28 months for 12 patients with EGFR mutations, and was 11 months for 38 patients with low BRCA1, 9 months for 40 patients with intermediate BRCA1, and 11 months for 33 patients with high BRCA1. Two-year survival was 73.3%, 41.2%, 15.6% and 0%, respectively. Median survival was influenced by RAP80 expression in the three BRCA1 groups. For example, for patients with both low BRCA1 and low RAP80, median survival exceeded 26 months. RAP80 was a significant factor for survival in patients treated according to BRCA1 levels (hazard ratio, 1.3 [95% CI, 1-1.7]; P = 0.05). CONCLUSIONS/SIGNIFICANCE: Chemotherapy customized according to BRCA1 expression levels is associated with excellent median and 2-year survival for some subsets of NSCLC patients , and RAP80 could play a crucial modulating effect on this model of customized chemotherapy. TRIAL REGISTRATION: (ClinicalTrials.gov) NCT00883480

Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydis

Ustilago maydis is a ubiquitous pathogen of maize and a well-established model organism for the study of plant-microbe interactions. This basidiomycete fungus does not use aggressive virulence strategies to kill its host. U. maydis belongs to the group of biotrophic parasites (the smuts) that depend on living tissue for proliferation and development. Here we report the genome sequence for a member of this economically important group of biotrophic fungi. The 20.5-million-base U. maydis genome assembly contains 6,902 predicted protein-encoding genes and lacks pathogenicity signatures found in the genomes of aggressive pathogenic fungi, for example a battery of cell-wall-degrading enzymes. However, we detected unexpected genomic features responsible for the pathogenicity of this organism. Specifically, we found 12 clusters of genes encoding small secreted proteins with unknown function. A significant fraction of these genes exists in small gene families. Expression analysis showed that most of the genes contained in these clusters are regulated together and induced in infected tissue. Deletion of individual clusters altered the virulence of U. maydis in five cases, ranging from a complete lack of symptoms to hypervirulence. Despite years of research into the mechanism of pathogenicity in U. maydis, no 'true' virulence factors had been previously identified. Thus, the discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi. Genomic analysis is, similarly, likely to open up new avenues for the discovery of virulence determinants in other pathogens. ©2006 Nature Publishing Group.J.K., M. B. and R.K. thank G. Sawers and U. Kämper for critical reading of the manuscript. The genome sequencing of Ustilago maydis strain 521 is part of the fungal genome initiative and was funded by National Human Genome Research Institute (USA) and BayerCropScience AG (Germany). F.B. was supported by a grant from the National Institutes of Health (USA). J.K. and R.K. thank the German Ministry of Education and Science (BMBF) for financing the DNA array setup and the Max Planck Society for their support of the manual genome annotation. F.B. was supported by a grant from the National Institutes of Health, B.J.S. was supported by the Natural Sciences and Engineering Research Council of Canada and the Canada Foundation for Innovation, J.W.K. received funding from the Natural Sciences and Engineering Research Council of Canada, J.R.-H. received funding from CONACYT, México, A.M.-M. was supported by a fellowship from the Humboldt Foundation, and L.M. was supported by an EU grant. Author Contributions All authors were involved in planning and executing the genome sequencing project. B.W.B., J.G., L.-J.M., E.W.M., D.D., C.M.W., J.B., S.Y., D.B.J., S.C., C.N., E.K., G.F., P.H.S., I.H.-H., M. Vaupel, H.V., T.S., J.M., D.P., C.S., A.G., F.C. and V. Vysotskaia contributed to the three independent sequencing projects; M.M., G.M., U.G., D.H., M.O. and H.-W.M. were responsible for gene model refinement, database design and database maintenance; G.M., J. Kämper, R.K., G.S., M. Feldbrügge, J.S., C.W.B., U.F., M.B., B.S., B.J.S., M.J.C., E.C.H.H., S.M., F.B., J.W.K., K.J.B., J. Klose, S.E.G., S.J.K., M.H.P., H.A.B.W., R.deV., H.J.D., J.R.-H., C.G.R.-P., L.O.-C., M.McC., K.S., J.P.-M., J.I.I., W.H., P.G., P.S.-A., M. Farman, J.E.S., R.S., J.M.G.-P., J.C.K., W.L. and D.H. were involved in functional annotation and interpretation; T.B., O.M., L.M., A.M.-M., D.G., K.M., N.R., V. Vincon, M. VraneŠ, M.S. and O.L. performed experiments. J. Kämper, R.K. and M.B. wrote and edited the paper with input from L.-J.M., J.G., F.B., J.W.K., B.J.S. and S.E.G. Individual contributions of authors can be found as Supplementary Notes

Contribució a l'estudi genètic de les malalties complexes: Asma i psoriasi a la població espanyola

[cat] En aquesta tesi s'ha realitzat un estudi genètic de les malalties complexes de forma específica en la població espanyola. El treball s'ha centrat en l'estudi de dues malalties inflamatòries, complementàries tant a nivell experimental, quant a l'aproximació realitzada en els mètodes de mapatge genètic, com també a nivell de l'etiopatogènia inflamatòria de la malaltia. L'estudi de la psoriasi en la població espanyola ha evidenciat la presència de dos loci de predisposició, un a la regió de 6p21 (PSORS1), definit com un locus de múltiples gens lligats (HLA-Cw*6, HCR, CDSN), i un altre possible a la regió 4q35 (PSORS3), que presenta una interacció positiva, però no epistàtica amb PSORS1, implicant dues vies diferents i independents en l'etiopatogènia de la malaltia. A més s'ha posat de manifest un efecte parental en l'herència de la predisposició genètica en PSORS1, possiblement mitjançant un efecte d'imprinting matern en la regió. D'altra banda, s'ha determinat la presència d'un haplotip comú en distintes poblacions, format per quatre de les variants codificants del gen HCR (HCR*WWCC), convertint-se en un dels determinants majors i més estesos dintre de PSORS1. L'estudi de l'asma ha demostrat la important heterogeneïtat fenotípica inclosa en la definició de la malaltia, posant de manifest però la important determinació genètica dels fenotips associats a la malaltia (principalment del control de la resposta de les IgEs). De forma clara s'ha evidenciat la important variació del risc genètic associat a determinades variants en els distints moments de l'evolució de la malaltia, sent en molts casos oposats en l'edat adulta i en l'edat infantil. A més s'ha pogut associar la predisposició a l'asma amb variants del gen CFTR (Cystic fibrosis transmenbrane conductance regulator gene), amb una alta prevalença de variants d'error de sentit en els individus (adults i infantils) amb asma. En resum, l'anàlisi genètica ha demostrat la utilitat de la combinació d'estudis d'anàlisi de lligament amb els mètodes d'associació, així com la necessitat d'una definició i restricció important en la definició del fenotip "genètic" a estudiar, això és la definició del tret fenotípic determinat genèticament. A més s'ha posat de manifest la importància del coneixement de les bases de predisposició genètica de determinats trets associats a la malaltia per a la millor definició de la mateixa, i també en el procés de la identificació de l'heterogeneïtat genètica de la malaltia. D'altra banda, encara que les variants estudiades difícilment poden ser utilitzades per a un diagnòstic genètic, sí que poden ser emprades com a pronòstic en l'evolució, o de la severitat de la malaltia, afavorint una intervenció mèdica més eficient i preventiva més que correctora

Influence of eicosapentaenoic to docosahexaenoic acid ratio of dietary lipids given to juvenile of gilthead seabream (Sparus aurata) on growth and fatty acid composition.

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Sequence diversity of the uniparentally transmitted portions of the genome in the resident population of Catalonia

Genomic reference databases of residing populations are available in different countries and regions. Since they represent the whole genetic diversity of a geographical region, they have wide applications, from biomedical studies to forensic identifications. Uniparentally transmitted portions of the genome specifically are highly suitable for kinship analyses, mixed DNA cases and geographical ancestry inferences. We have sampled 808 individuals currently residing in Catalonia within the GCAT cohort, from which we have generated 808 high-quality whole mitochondrial DNA (mtDNA) genomes and 399 sequences of the male-specific part of the Y chromosome (MSY). We observe higher genetic diversity than in classical population genetics datasets. We test the robustness of whole sequences for unequivocal identifications, and we found that they have higher resolution than mitochondrial control region and Y chromosome short tandem repeats (Y-STRs), and that most of the variants they present are at low frequencies, increasing the discrimination capacity between individuals. These results confirm the forensic applicability of whole uniparental sequences and provide one of the largest high-quality reference datasets ever published.This work was supported by the Spanish Ministry of Economy and Competitiveness and Agencia Estatal de Investigación (grant numbers CGL2016–75389-P (MINEICO/FEDER, UE), PID2019–106485 GB-I00/AEI/10.13039/501100011033 (MINEICO), and “Unidad María de Maeztu” (CEX2018–000792-M) to FC and DC; and Agència de Gestió d’Ajuts Universitaris i de la Recerca (Generalitat de Catalunya, grant 2017SGR00702). Computing time at Barcelona Supercomputing Centre was granted by Red Española de Supercomputación (BCV-2019–3-00002). NF-P was supported by a FPU17/03501 fellowship. This study makes use of data generated by the GCAT=Genomes for Life. Cohort study of the Genomes of Catalonia, Fundacio IGTP with registration number PI-2018–03. IGTP is part of the CERCA Program / Generalitat de Catalunya. GCAT is supported by Acción de Dinamización del ISCIII-MINECO and the Ministry of Health of the Generalitat of Catalunya (ADE 10/00026) and; the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR 529)

Resilience characterized and quantified from physical activity data: A tutorial in R

Consistent physical activity is key for health and well-being, but it is vulnerable to stressors. The process of recovering from such stressors and bouncing back to the previous state of physical activity can be referred to as resilience. Quantifying resilience is fundamental to assess and manage the impact of stressors on consistent physical activity. In this tutorial, we present a method to quantify the resilience process from physical activity data. We leverage the prior operationalization of resilience, as used in various psychological domains, as area under the curve and expand it to suit the characteristics of physical activity time series. As use case to illustrate the methodology, we quantified resilience in step count time series (length = 366 observations) for eight participants following the first COVID-19 lockdown as a stressor. Steps were assessed daily using wrist-worn devices. The methodology is implemented in R and all coding details are included. For each person’s time series, we fitted multiple growth models and identified the best one using the Root Mean Squared Error (RMSE). Then, we used the predicted values from the selected model to identify the point in time when the participant recovered from the stressor and quantified the resulting area under the curve as a measure of resilience for step count. Further resilience features were extracted to capture the different aspects of the process. By developing a methodological guide with a step-by-step implementation, we aimed at fostering increased awareness about the concept of resilience for physical activity and facilitate the implementation of related research

Y-chromosome target enrichment reveals rapid expansion of haplogroup R1b-DF27 in Iberia during the Bronze Age transition

The Y chromosome can yield a unique perspective into the study of human demographic history. However, due to the repetitive nature of part of its sequence, only a small set of regions are suitable for variant calling and discovery from short-read sequencing data. These regions combined represent 8.9 Mbp or 0.14% of a diploid human genome. Consequently, investing in whole-genome sequencing to resolve Y-chromosome questions is poorly efficient. Here we use, as an alternative, target enrichment technology to greatly increase sequencing effectiveness, validating and applying the technique to 181 males, for 162 of whom we obtained a positive result. Additionally, 75 samples sequenced for the whole genome were also included, for a total sample size of 237. These samples were chosen for their Y chromosome haplogroup: R1b-DF27. In the context of European populations, and particularly in Iberia, this haplogroup stands out for its high frequency and its demographic history. Current evidence indicates that the diffusion of this haplogroup is related to the population movements that mark the cultural Bronze Age transition, making it remarkably interesting for population geneticists. The results of this study show the effects of the rapid radiation of the haplogroup in Spain, as even with the higher discriminating power of whole sequences, most haplotypes still fall within the R1b-DF27* paragroup rather than in the main derived branches. However, we were able to refine the ISOGG 2019-2020 phylogeny, and its two main subbranches, namely L176.2 and Z272, which present geographical differentiation between the Atlantic and Mediterranean coasts of Iberia.This work was funded by the Spanish Ministry of Economy and Competitiveness and Agencia Estatal de Investigación (grant number PID2019-106485GB-I00/AEI/10.13039/501100011033), and “Unidad María de Maeztu” (CEX2018-000792-M); and Agència de Gestió d’Ajuts Universitaris i de la Recerca (Generalitat de Catalonia, grant 2017SGR00702).  E.L. is supported by funding from the CERCA Programme (Generalitat de Catalonia) and from Ministerio de Ciencia e Innovación, Spanish Government (PID2020-116908GB-100). I.O. is supported by a Ramón y Cajal grant from Ministerio de Ciencia e Innovación, Spanish Government (RYC2019-027909-I/AEI/10.13039/501100011033). This study makes use of data generated by the GCAT-Genomes for Life Cohort study of the Genomes of Catalonia, IGTP, with GCAT Cession reference number PI-2018-03. IGTP is part of the CERCA Program/Generalitat de Catalonia. GCAT is supported by Acción de Dinamización del ISCIII-MINECO and the Ministry of Health of the Generalitat of Catalonia (ADE 10/00026); the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR 529).We acknowledge the work of the GCAT project group, the Blood and Tissue Bank from Catalonia (BST) and all the GCAT volunteers that participated in the study. A full list of the investigators who contributed to the generation of the data is available from http://www.genomesforlife.com/

Altered brain-derived neurotrophic factor blood levels and gene variability are associated with anorexia and bulimia

Murine models and association studies in eating disorder (ED) patients have shown a role for the brain-derived neurotrophic factor (BDNF) in eating behavior. Some studies have shown association of BDNF -270C/T single-nucleotide polymorphism (SNP) with bulimia nervosa (BN), while BDNF Val66Met variant has been shown to be associated with both BN and anorexia nervosa (AN). To further test the role of this neurotrophin in humans, we screened 36 SNPs in the BDNF gene and tested for their association with ED and plasma BDNF levels as a quantitative trait. We performed a family-based association study in 106 ED nuclear families and analyzed BDNF blood levels in 110 ED patients and in 50 sib pairs discordant for ED. The rs7124442T/rs11030102C/rs11030119G haplotype was found associated with high BDNF levels (mean BDNF TCG haplotype carriers = 43.6 ng/ml vs. mean others 23.0 ng/ml, P = 0.016) and BN (Z = 2.64; P recessive = 0.008), and the rs7934165A/270T haplotype was associated with AN (Z =-2.64; P additive = 0.008). The comparison of BDNF levels in 50 ED discordant sib pairs showed elevated plasma BDNF levels for the ED group (mean controls = 41.0 vs. mean ED = 52.7; P = 0.004). Our data strongly suggest that altered BDNF levels modulated by BDNF gene variability are associated with the susceptibility to ED, providing physiological evidence that BDNF plays a role in the development of AN and BN, and strongly arguing for its involvement in eating behavior and body weight regulation

Bibliografía y notas [Derechos y Libertades: revista del Instituto Bartolomé de las Casas. Oct 1993-mar 1994. I (2)]

Norberto Bobbio. Igualdad y libertad / Ángel Llamas. -- Algunas reflexiones sobre la visión integral de los derechos. Comentario del libro de Gregorio Peces-Barba. Curso de derechos fundamentales (I. Teoría General) / Fco. Javier Ansuátegui Roig. -- Luis Prieto Sanchís "Sobre principios y normas" / Rafael Escudero Alday. -- A.A.V.V., "Derechos humanos" / José Manuel Rodríguez Uribes. -- AA.V.V., "Constitución y Derecho del Trabajo, 1981-1991" / Teresa Ena Ventura. -- "Los derechos fundamentales en las revistas italianas: 1990-1992" / Fco. Javier Ansuátegui Roig. -- "Los derechos humanos en la nueva etapa del Anuario de Filosofía del Derecho" / J. J. Santamaría Ibeas. -- Social Philosophy & Policy, vol. 10, n.° 1, 1993 / Andrea Greppi. -- Cahiers de Philosophie Politique et Juridique, n.° 21/1992 / Andrea Greppi. -- "Artículos publicados en revistas españolas sobre temas de derechos humanos (1991-1993)" / Elviro Aranda, Gema Rosado y Carlos Deocón.Publicad