Planteamiento estratégico del sector automotor de Colombia

El sector automotriz colombiano ha venido creciendo de manera constante siguiendo la tendencia general de la economía del país de los últimos años. Para el mediano y largo plazo se espera que la tendencia sea positiva en razón al bajo índice de penetración de vehículos en el país en comparación con mercados similares al colombiano. Lo anterior se debe en gran medida al buen ambiente político, la apertura de la economía y la estabilidad fiscal que protege e incentiva la inversión y el desarrollo económico. La presente tesis busca generar una visión holística para el sector automotriz colombiano, que a través de la implementación del proceso estratégico le permitirá lograr objetivos para Largo Plazo: OLP1 Crear para el año 2018 un gremio del sector automotor que agrupe por lo menos al 80% de los importadores y ensambladores de tal forma que a través de este se pueda tener una mejor influencia y representación frente a los stakeholders del sector. OLP2 Desarrollar dos nuevos segmentos de mercado amigables con el medio ambiente para el año 2018, produciendo e importando vehículos híbridos y eléctricos que tendrán mayor aceptación en el consumidor colombiano y que hoy en día son inexistentes. OLP3 Integrar las intenciones de sector y del Estado, con el fin de lograr que para el año 2018 se tengan al menos 4,000 km de doble calzada partiendo de 1,000 km a finales de 2012. OLP4 Incrementar la venta de unidades en un 15% para el año 2018 versus las ventas del 2012. OLP5 Incrementar la confianza inversionista del sector automotor en un 10% y alcanzar un margen financiero del 15% anual para el año 2018. Los anteriores objetivos con la mayor independencia de la volatilidad y cambios macroeconómicos que puedan afectar al país en el futuro. Siendo este sector un motor de desarrollo económico y social del país basándose en sus ventajas competitivas como son la existencia de plantas para el ensamblaje de vehículos, variedad de tratados de libre comercio con países claves en la producción de vehículos y el alto nivel educativo de la población; lograría posicionarse como un sector líder en la industria nacional y un ejemplo a seguir a nivel latinoamericano por su crecimiento sostenido y atractivo económico. Dentro del desarrollo del proceso estratégico, se identificaron y retuvieron diez sólidas estrategias que abarcan desde la creación de un instituto de fomento del sector automotriz, ampliar la capacidad instalada hasta lograr la integración de los diferentes actores del sector que para implementarse exitosamente se necesitará de un liderazgo positivo y unificador de los importadores, ensambladores de vehículos.The Colombian automotive industry has been showing a constant growth following the national economy trend in the last years. By mid and long term is been expected a positive growth according with the low vehicle penetration in comparison with other similar markets. The political stability, markets aperture and the fiscal steadiness have been key factors for these achievements. This work shows a general vision for the Colombian automotive vertical a how by mean of strategic process implementation it will reach its long term objectives independently of the economical and environmental volatility that can outcome in the future. Long Term Objective 1: For 2018, a new automotive association which aggregate at least 80% of assemblers and importers. Long Term Objective 2: Develop two new and high potential clean technologies segments by 2018, making and importing hybrid and electric vehicles. Long Term Objective 3: Reach 4.000 km of two lane and paved roads by 2018 starting from 1.000 km in 2012 Long Term Objective 4: To increase 15% unit sales for 2018 versus 2012 Long Term Objective 5: To increase 10% investor confidence and reach a 15% operational margin for 2018 This sector has become a social and economical engine due to its competitive advantages such as the local production of vehicles, the free trade agreements (FTA) with several countries and a high educational level of the population, could lead this sector to become a national industry leader and a reference for the Latin-American region for its growing and economical attractiveness. In this strategic process, were identified y retained ten solid strategies than varies from the establishment of a sector development institute, increase the national assembling capacity to archive the industry integration of the main stakeholders. All these require a high committed and positive leadership that unify the importers and national assemblers.Tesi

Aspectos genético-moleculares asociados con el desarrollo del carcinoma colorrectal

El presente trabajo es el resultado de la revisión bibliográfica en PubMed y ScienceDirect, de 62 artículos, relacionados con aspectos genético-moleculares del carcinoma colorrectal (CCR). El CCR constituye un problema de salud pública, agravado en los países en desarrollo, porque la mayoría de los casos se diagnostican en estados avanzados, al punto que, en Colombia, los datos de mortalidad se asemejan a los de incidencia, lo cual no es común en los países desarrollados. En consecuencia, es importante implementar métodos de detección temprana, tratamientos efectivos y procedimientos genético-moleculares, para diferenciar los casos y ofrecer tratamientos de acuerdo con el perfil genético del paciente.  Se hace referencia a las pruebas moleculares de inestabilidad microsatelital e inmunohistoquimica para proteínas del grupo mismatch repear (MMR),  que por su alta sensibilidad y especificidad resultan indispensables para la clasificación y tamizaje del CCR y la discriminación del mismo, entre esporádico y hereditario

Local delivery of optimized nanobodies targeting the PD-1/PD-L1 axis with a self-amplifying RNA viral vector induces potent antitumor responses

Despite the success of immune checkpoint blockade for cancer therapy, many patients do not respond adequately. We aimed to improve this therapy by optimizing both the antibodies and their delivery route, using small monodomain antibodies (nanobodies) delivered locally with a self-amplifying RNA (saRNA) vector based on Semliki Forest virus (SFV). We generated nanobodies against PD-1 and PD-L1 able to inhibit both human and mouse interactions. Incorporation of a dimerization domain reduced PD-1/PD-L1 IC50 by 8- and 40-fold for antiPD-L1 and anti-PD-1 nanobodies, respectively. SFV viral particles expressing dimeric nanobodies showed a potent antitumor response in the MC38 model, resulting in >50% complete regressions, and showed better therapeutic efficacy compared to vectors expressing conventional antibodies. These effects were also observed in the B16 melanoma model. Although a short-term expression of nanobodies was observed due to the cytopathic nature of the saRNA vector, it was enough to generate a strong proinflammatory response in tumors, increasing infiltration of NK and CD8+ T cells. Delivery of the SFV vector expressing dimeric nanobodies by local plasmid electroporation, which could be more easily translated to the clinic, also showed a potent antitumor effect

CAR density influences antitumoral efficacy of BCMA CAR T cells and correlates with clinical outcome

Identification of new markers associated with long-term efficacy in patients treated with CAR T cells is a current medical need, particularly in diseases such as multiple myeloma. In this study, we address the impact of CAR density on the functionality of BCMA CAR T cells. Functional and transcriptional studies demonstrate that CAR T cells with high expression of the CAR construct show an increased tonic signaling with up-regulation of exhaustion markers and increased in vitro cytotoxicity but a decrease in in vivo BM infiltration. Characterization of gene regulatory networks using scRNA-seq identified regulons associated to activation and exhaustion up-regulated in CARHigh T cells, providing mechanistic insights behind differential functionality of these cells. Last, we demonstrate that patients treated with CAR T cell products enriched in CARHigh T cells show a significantly worse clinical response in several hematological malignancies. In summary, our work demonstrates that CAR density plays an important role in CAR T activity with notable impact on clinical response

Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n=3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (p(combined)=5.66x10(-5); ORcombined=2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (p(combined)=1.02x10(-4); ORcombined=2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10D mRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p=0.01 and p<0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p=0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC

The European Hematology Association Roadmap for European Hematology Research: a consensus document

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine ‘sections’ in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients

The European Hematology Association Roadmap for European Hematology Research. A Consensus Document

Abstract The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at Euro 23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine sections in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. Received December 15, 2015. Accepted January 27, 2016. Copyright © 2016, Ferrata Storti Foundatio

Interactive Effect of UVR and Phosphorus on the Coastal Phytoplankton Community of the Western Mediterranean Sea: Unravelling Eco- Physiological Mechanisms

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CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research