John Rawls-Jürgen Habermas: A normative and procedural solution to the tension between the democratic state and the ethnic, cultural and religious plurality

En este artículo se expone la forma como John Rawls y Jürgen Habermas ofrecen una salida normativa y procedimental para abordar los conflictos que se producen de la tensión entre el Estado y la pluralidad política, étnica y cultural. Dicha salida implica, por una parte, superar los déficits del liberalismo en cuanto a la consolidación de vínculos cívicos, solidarios y participativos entre los ciudadanos; por otra, buscar un pegamento que viabilice la cohesión social, el proceso político democrático y la solución de los asuntos públicos de manera consensuada. En el caso de John Rawls, la salida versa sobre la idea del consenso traslapado y la razón pública, y en el caso de Jürgen Habermas sobre el concepto de patriotismo constitucional. La tesis que se defenderá es que ambas salidas implican la construcción de un vínculo moral que se fundamenta en valores políticos y principios del constitucionalismo moderno, los cuales se encuentran anclados en la cultura política de regímenes democráticos con revisión constitucional. Dicho vínculo supone ir más allá de un modus vivendi o de la simple tolerancia entre la pluralidad étnica, religiosa, cultural y sexual que existe en una comunidad política

Comunicação táctil para todo público: sistema braille usando verniz poli(metacrilato de metila) em relevo polimerizável por ultravioleta (UV) impresso junto com texto e imagens em tinta (i-Br/Vza-UVxmf)

This paper presents an innovation (invention) that is applied as a tool for education inclusion and of accessibility among visually impaired people, representing 6.98% of the Brazilian population. The simultaneous printing using the Braille system along with its equivalent in Portuguese (or any other language) is proposed. A text printed in Portuguese (e.g., using offset printing) will then be printed in Braille applied using acrylic varnish that is dried with ultraviolet (UV) rays. This printing approach has been named i-Br/Vza-UVxmf and may be present in packages or publishing products. The proposed system eliminates the use of micro-holes left by traditional printing in Braille. Moreover, the system of micro-holes presents the risk of contamination (or the passage of contaminating substances) in the case of food packaging, personal use or cleansing items, which will not happen in the i-Br/Vza-UVxmf process. Since the proposed process can be applied to any editorial product (as a document, book or package), this printed material will be useful either to the normal sighted (who will read the material printed in Portuguese) as the visually impaired (who read Braille thanks to the embossing generated by the acrylic varnish). It’s Tiflotegnologics the art and Technique to write and editing for impaired people Then, this approach is intended to facilitate the living and the relationship among visually impaired and normal sighted people; leading them to better living and education standards. Moreover, this study may contribute to the implementation of existing legislation that requires the disclosure of information on medicine, food, personal use or cleansing items packaging. Current legislation demands the communication of name, content, specifications and expiration date of products. Finally, normal sighted people can benefit from the proposed system, making use of the fact that the material is printed in Portuguese and in Braille; and making them familiar with the use of tactile communication(written in Braille).O presente trabalho apresenta uma inovação (invenção) aplicada como uma ferramenta de inclusão à educação e de acessibilidade entre pessoas deficientes visuais, que representam 6,98% da população brasileira (IBGE, 2002). Propõe-se a impressão simultânea usando o sistema Braille tradicional aplicado com verniz poli(metacrilato de metila) em relevo polimerizável por ultravioleta (UV) junto com impressão tradicional em tinta (por exemplo, offset); sendo denominado pelo autor como i-Br/Vza-UVxmf e que pode estar presente em peças de embalagem, sinalização, rótulos, etiquetas, produtos editoriais e outros. O sistema proposto elimina o uso de alvéolos e microfuros deixados no sistema tradicional, que corresponde ao atual estado da arte, da impressão em Braille. Além disso, o sistema de microfuros apresenta o risco de contaminação (ou a passagem de substâncias) no caso de embalagens de alimentos, uso pessoal ou asseio; o que não ocorrerá no processo i-Br/Vza-UVxmf. Notou-se que, o processo proposto pode ser aplicado a qualquer produto promocional ou editorial (como um documento, livro ou embalagem). Este material impresso será útil tanto aos videntes normais (que lerão o que está impresso) como aos deficientes visuais (que “lerão” em Braille graças ao relevo gerado pelo verniz poli(metacrilato de metila)); aplicação de Tiflotecnologia que é a arte e técnica de escrever para cegos. Trata-se, então, de uma proposta facilitadora da convivência e relacionamento entre pessoas deficientes visuais com pessoas videntes normais, conduzindo-as para melhor nível de vida e educação. Além disso, o presente trabalho poderá contribuir com a aplicação da legislação vigente que exige a divulgação da informação nas embalagens de medicamentos, alimentos, material de uso pessoal e asseio; mediante a comunicação do nome, conteúdo, especificação, uso e validade de produtos, bens e serviços empacotados. Por fim, pessoas videntes normais poderão se beneficiar do sistema proposto, servindo-se do material impresso em tinta com caracteres gráficos e também em Braille, familiarizando-lhes no uso da comunicação táctil (escrita em Braille) Braille & Tinta

Expresión y secreción del ligando mortal TRAIL en células efectoras del sistema inmune

Los ligandos mortales juegan un papel importante en la regulación del sistema inmune. FasL/CD95L es quién realiza la mayor contribución en esta función, mientras que la actuación de Apo2L/ TRAIL no se halla completamente caracterizada. En los linfocitos T activados, ambos ligandos (FasL y TRAIL) se encuentran asociados con vesículas lipídicas denominadas exosomas, que preservan intacto su potencial citotóxico. Estos exosomas conteniendo los ligandos mortales, son almacenados en los cuerpos multivesiculares (MVB) y se secretan rápidamente al medio extracelular tras la re-estimulación de los linfocitos T activados. Se analizó mediante proteómica el contenido proteico de exosomas provenientes de la línea celular Jurkat y de los blastos T, observándose una expresión diferencial en la proteína VCP/p97. Entre los procesos celulares en los que VCP/p97 participa, resulta particularmente interesante su papel en el tráfico vesicular y podría estar involucrada en la diferente secreción de exosomas entre los linfocitos T normales y las células leucémicas. En este trabajo, se utilizó un inhibidor específico de VCP/p97 (DBeQ) con el propósito de profundizar en el papel de esta proteína en el transporte de los exosomas. Se analizó la expresión de TRAIL tanto en los linfocitos T activados como en las células Jurkat, así como su capacidad citotóxica y la de sus sobrenadantes tras el pre-tratamiento con DBeQ. Los resultados obtenidos sugieren que la VCP/p97 está implicada en el tráfico vesicular de las células Jurkat, pero no en el de los linfocitos T activados

Criterios de implementación ISO 14001:2015. Caso de Estudio Sector: Servicios de Compra y Distribución de Derivados de Petróleo. Estación de Servicio Guadalajara de Buga

Las estaciones de servicio realizan actividades como el almacenamiento y distribución de combustible, que pueden impactar de manera negativa el medio ambiente, de ahí la importancia de que se cuenten con medidas de seguridad y del cuidado del medio ambiente que estén enmarcadas en las normas colombianas e internacionales para la gestión del medio ambiente. El objetivo del presente estudio es realizar un análisis de la operación de la Estación de Servicio Guadalajara de Buga, identificando la problemática ambiental asociada y evaluar las acciones correctivas tomadas dentro del marco legal y de calidad aplicable. Para el desarrollo del estudio se realizó una matriz de evaluación de los principales aspectos e impactos ambientales de las actividades operativas, se analizaron los programas ambientales vigentes y se propuso un plan de mejora encaminado a mitigar dichos impactos. La realización del presente estudio nos permitió determinar los aspectos e impactos ambientales inherentes a la operación de una estación de servicio, la importancia de crear programas destinados al ahorro del agua, a la prevención de derrames o fugas de combustibles y al manejo adecuado de residuos sólidos y de esta manera generar procesos de mejora continua para que las actividades de la empresa se reformen o cambien, permitiendo que se incorporen nuevas estrategias, nuevas tecnologías, nuevos protocolos de procedimientos, encaminados en evitar un mayor impacto en el ambiente.Service stations carry out activities such as fuel storage and distribution, which can negatively impact the environment, hence the importance of having security measures and caring for the environment that are framed in Colombian and international standards for environmental management. The objective of this study is to carry out an analysis of the operation of the Guadalajara Buga Service Station, identifying the associated environmental problem and evaluating the corrective actions taken within the applicable legal and quality framework. For the development of the study, an evaluation matrix of the main environmental aspects and impacts of the operating activities was made, the current environmental programs were analyzed and an improvement plan was proposed to mitigate these impacts. Carrying out this study allowed us to determine the environmental aspects and impacts inherent to the operation of a service station, the importance of creating programs destinated for saving water, preventing fuel spills or leaks, and the proper management of solid waste and in this way generate continuous improvement processes so that the activities of the company are reformed or changed, allowing the incorporation of new strategies, new technologies, new procedure protocols, to avoid a greater impact on the environment

Plk1 overexpression induces chromosomal instability and suppresses tumor development

Polo-like kinase 1 (Plk1) is overexpressed in a wide spectrum of human tumors, being frequently considered as an oncogene and an attractive cancer target. However, its contribution to tumor development is unclear. Using a new inducible knock-in mouse model we report here that Plk1 overexpression results in abnormal chromosome segregation and cytokinesis, generating polyploid cells with reduced proliferative potential. Mechanistically, these cytokinesis defects correlate with defective loading of Cep55 and ESCRT complexes to the abscission bridge, in a Plk1 kinase-dependent manner. In vivo, Plk1 overexpression prevents the development of Kras-induced and Her2-induced mammary gland tumors, in the presence of increased rates of chromosome instability. In patients, Plk1 overexpression correlates with improved survival in specific breast cancer subtypes. Therefore, despite the therapeutic benefits of inhibiting Plk1 due to its essential role in tumor cell cycles, Plk1 overexpression has tumor-suppressive properties by perturbing mitotic progression and cytokinesis.We are indebted to Stephen Taylor for the Sgo1 antibody. We thank Simone Kraut, Jessica Steiner, and the DKFZ light microscopy unit for excellent technical assistance. The results published here are in part based on data generated by TCGA pilot project (https://cancergenome.nih.gov/established by the NCI and the National Human Gen- ome Research Institute. The data were retrieved through dbGaP authorization (accession no. phs000178.v9.p8). S.V.V. was supported by the Marie Curie Network Ploidynet, funded by the European Union Seventh Framework Programme (FP7/2007–2013) under Grant Agreement #316964. L.S. is supported by a postdoctoral fellowship from Funda- cion Ramon Areces. Work in the R.S. laboratory was supported by an ERC starting grant (#281614), Marie Curie PCIG09-GA-2011 –293745 and the Howard Hughes Medical Institute. G.d.C. is funded by AECC Scientific Foundation (LABAE16017DECA). Work in the M.M. laboratory was supported by grants from the MINECO (SAF2015 –69920-R cofunded by ERDF-EU), Worldwide Cancer Research (WCR no. 150278), and Comunidad de Madrid (iLUNG-CM; B2017/BMD3884). The CNIO is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0510).S

RAF1 kinase activity is dispensable for KRAS/p53 mutant lung tumor progression.

We thank Dr. Shiva Malek and her colleagues (Genentech Inc.) for sharing their results with us before publication. We also thank M. San Roman, R. Villar, M.C. Gonzalez, A. Lopez, N. Cabrera, P. Villanueva, J. Condo, O. Dominguez, and S. Ortega for excellent technical support. This work was supported by grants from the European Research Council (ERC-2015-AdG/695566, THERACAN); the Spanish Ministry of Science, Innovation, and Universities (RTC-2017-6576-1 and RTI2018094664-B-I00) and the Autonomous Community of Madrid (B2017/BMD-3884 iLUNG-CM) to M.B., as well as by a grant from the Spanish Ministry of Science, Innovation and Universities (RTI2018-094664-B-I00) to M.B. and M.M. M.B. is a recipient of an Endowed Chair from the AXA Research Fund. M.S., P.N., and F.F.-G. were supported by FPU fellowships from the Spanish Ministry of Education. L.E.-B. was a recipient of an FPI fellowship from the Spanish Ministry of Economy and Competitiveness. S.G.-A. is a recipient of a postdoctoral fellowship from the Asociacion Espanola Contra el Cancer (AECC).S

Tumor regression and resistance mechanisms upon CDK4 and RAF1 inactivation in KRAS/P53 mutant lung adenocarcinomas.

KRAS mutant lung adenocarcinomas remain intractable for targeted therapies. Genetic interrogation of KRAS downstream effectors, including the MAPK pathway and the interphase CDKs, identified CDK4 and RAF1 as the only targets whose genetic inactivation induces therapeutic responses without causing unacceptable toxicities. Concomitant CDK4 inactivation and RAF1 ablation prevented tumor progression and induced complete regression in 25% of KRAS/p53-driven advanced lung tumors, yet a significant percentage of those tumors that underwent partial regression retained a population of CDK4/RAF1-resistant cells. Characterization of these cells revealed two independent resistance mechanisms implicating hypermethylation of several tumor suppressors and increased PI3K activity. Importantly, these CDK4/RAF1-resistant cells can be pharmacologically controlled. These studies open the door to new therapeutic strategies to treat KRAS mutant lung cancer, including resistant tumors.We thank S. Ortega for the generation of the Cdk4FxKD mouse model; and M. San Roman, R. Villar, M. C. Gonzalez, A. Lopez, N. Cabrera, P. Villanueva, J. Condo, J. Klett, A. Cebria, A. Otero, O. Dominguez, G. Luengo, G. Garaulet, F. Mulero, and D. Megias for excellent technical support. This work was supported by European Research Council Grant ERC-2015-AdG/695566, THERACAN, Spanish Ministry of Science, Innovation, and Universities Grant RTC-2017-6576-1, and the Autonomous Community of Madrid Grant B2017/BMD-3884 iLUNG-CM (to M.B.); Spanish Ministry of Science, Innovation, and Universities Grant RTI2018-094664B-I00 (to M.B. and M.M.); and National Natural Science Foundation of China Grant 31771469 (to H.W.). M.B. is a recipient of an Endowed Chair from the AXA Research Fund. L.E.-B. is the recipient of an FPI fellowship from the Spanish Ministry of Economy and Competitiveness. F.F.-G., M.S., and P.N. were supported by an FPU fellowships from the Spanish Ministry of Education.S

Kras oncogene ablation prevents resistance in advanced lung adenocarcinomas

KRASG12C inhibitors have revolutionized the clinical management of patients with KRASG12C-mutant lung adenocarcinoma. However, patient exposure to these inhibitors leads to the rapid onset of resistance. In this study, we have used genetically engineered mice to compare the therapeutic efficacy and the emergence of tumor resistance between genetic ablation of mutant Kras expression and pharmacological inhibition of oncogenic KRAS activity. Whereas Kras ablation induces massive tumor regression and prevents the appearance of resistant cells in vivo, treatment of KrasG12C/Trp53-driven lung adenocarcinomas with sotorasib, a selective KRASG12C inhibitor, caused a limited antitumor response similar to that observed in the clinic, including the rapid onset of resistance. Unlike in human tumors, we did not observe mutations in components of the RAS-signaling pathways. Instead, sotorasib-resistant tumors displayed amplification of the mutant Kras allele and activation of xenobiotic metabolism pathways, suggesting that reduction of the on-target activity of KRASG12C inhibitors is the main mechanism responsible for the onset of resistance. In sum, our results suggest that resistance to KRAS inhibitors could be prevented by achieving a more robust inhibition of KRAS signaling mimicking the results obtained upon Kras ablation.This work was supported by grants from the European Research Council (ERC-GA 695566, THERACAN); the Agencia Estatal de Investigación, Ministerio de Ciencia e Innovación (MCIN/AEI/10.13039/501100011033) (grant RTC2017-6576-1), cofunded by ERDF “A way of making Europe”; the Autonomous Community of Madrid (B2017/BMD-3884 iLung-CM), cofunded by FSE and ERDF “A way of making Europe”; the CRIS Cancer Foundation, the Scientific Foundation of the Spanish Association Against Cancer (GC166173694BARB); an ERA PerMed grant, funded by the Instituto de Salud Carlos III (AC20/00114), the Scientific Foundation of the Spanish Association Against Cancer (PERME20707BARB) and the European Union’s Horizon 2020 program (779282) to MB; and the Agencia Estatal de Investigación, Ministerio de Ciencia e Innovación (grant RTI2018-094664-B-I00), cofunded by ERDF “A way of making Europe” to MM and MB. Additional funding included grants from the Spanish National Research and Development Plan, Instituto de Salud Carlos III, ERDF “A way of making Europe” (PI20/01837 and DTS19/00111); the Scientific Foundation of the Spanish Association Against Cancer (LABAE20049RODR) to SRP; the Instituto de Salud Carlos III (PI19/00514), cofunded by ERDF “A way of making Europe” to CG; the Agencia Estatal de Investigación, Ministerio de Ciencia e Innovación (grant PID2020-116705RB-I00); and the Scientific Foundation of the Spanish Association Against Cancer (LABAE211678DROS) to MD. MB is a recipient of an endowed chair from the AXA Research Fund. M Salmón was supported by a predoctoral contract “Severo Ochoa” (BES-2016-079096) from the Agencia Estatal de Investigación, Ministerio de Ciencia e Innovación. OB is a recipient of a fellowship from the Formación de Personal Investigador (FPI) program of the Agencia Estatal de Investigación, Ministerio de Ciencia e Innovación. FFG was supported by a Formación de Profesorado Universitario (FPU) fellowship from the Ministerio de Universidades

Telegrama de Manuel Antonio Sanclemente para Salvador Franco

1 páginaTelegrama del presidente Manuel Antonio Sanclemente en el que comunica a Salvador Franco su nombramiento como jefe civil y militar de Boyacá. Fechado en Tena