El clima i la producció d'olives a la Catalunya seca: el cas de Cabacés (el Priorat)

[cat] En un context de canvi climàtic cal estudiar les vulnerabilitats del territori a escala local. En aquest treball s'analitza la producció d'oli de qualitat en un indret de la Catalunya seca, Cabacés (el Priorat), i es posa en relació amb la variabilitat climàtica. Els resultats mostren que el clima té una influència important en la producció d'olives, sobretot les temperatures màximes del mes d'abril i les precipitacions del mes més sec, juliol. S'obté un model de regressió múltiple a partir d'aquestes dues variables climàtiques més influents en la producció. No obstant això, els valors del model s'allunyen dels reals a partir de l'any 2003 a causa d'un creixement molt elevat de la producció per l'extensió del reg de suport. Les futures vulnerabilitats no només depenen del canvi climàtic, sinó dels efectes del canvi global, fenomen que també engloba tots aquells canvis en els usos, hàbits i consums del territori.[spa]En un contexto de cambio climático es necesario estudiar las vulnerabilidades del territorio a escala local. Este trabajo analiza la producción de aceite de calidad en una localidad de la Cataluña seca, Cabacés (Priorat), en relación con la variabilidad climática. Los resultados muestran que el clima tiene una influencia importante en la producción de aceitunas, sobre todo las temperaturas máximas de abril y las precipitaciones del mes más seco, julio. Se obtiene un modelo de regresión múltiple a partir de estas dos variables climáticas más influyentes en la producción. No obstante, los valores del modelo se alejan de los reales a partir de 2003 debido al importante aumento de la producción por la extensión del riego de soporte. Las futuras vulnerabilidades no dependen solamente del cambio climático, sino de los efectos del cambio global, fenómeno que también incluye todos aquellos cambios en los usos, hábitos y consumos del territorio.[eng] In the current context of climate change, proper studies of regional and local vulnerabilities are required. This study analyses the relationship between the high quality olive production in a municipality of southern Catalonia, Cabacés (Priorat), and climate variability. Results show the climate effects maximum temperature in April, and rainfall in July on olive production. Nevertheless, irrigation caused a high increase in olive production along the last decade. This fact leads to a disagreement in the multiple regressions, modelled by the climatic variables above-mentioned, after 2002. Thus, to define future vulnerabilities must be taken the global change into account, which considers climate change and other changes in land and water uses

Propuesta de procesos en la cadena de suministros, para mejorar la logística de las empresas distribuidoras de materiales de construcción, ferretería y otros artículos de la ciudad de San Salvador. Caso ilustrativo.

Entre las necesidades básicas según A Maslow, se encuentra la de contar con vivienda, y de acuerdo a la Organización Internacional del Trabajo, esta debe dar abrigo en condiciones saludables y que cuente con algunos enseres domésticos y muebles. En el país el sector construcción es de los más importantes ya que genera el 12% como aporte al PIB, además de generar empleo, este sector para cumplir con sus objetivos de construir viviendas de acuerdo a las necesidades de cada Salvadoreño y Salvadoreña, debe minimizar costos y construir con calidad, es por lo anterior mencionado surge la necesidad de adquirir materiales de construcción de calidad, esperando el mejor precio en sus productos, y una entrega a tiempo por parte de las empresa dedicadas a la comercialización y distribución de materiales ferreteros y de construcción, sin errores ni acciones que aumente los costos. Debido que en El Salvador no se fabrican la mayoría de materiales, los Almacenes distribuidores de materiales de construcción optaron por importarlos directamente, y buscaron alianzas para bajar los costos en los fletes, y así poder manejar grandes volúmenes de compra a sus proveedores, disminuyendo los costos y trasladarlo al mejor precio para los consumidores, manteniéndose competitivos en el mercado. El objetivo principal de la presente investigación, es proponer procesos que colaboren a la buena Administración de la Cadena de Suministros de las empresas distribuidoras de materiales de construcción, utilizando como caso ilustrativo a la empresa Almacenes Vidrí S.A de C.V. por medio de la elaboración de un diagnóstico de la situación actual dentro de la empresa. A partir de lo anterior se tomó como unidad de análisis a los empleados y clientes de los diferentes almacenes que conformaron el universo y utilizando instrumentos como el cuestionario para el desarrollo del diagnóstico aplicando el Método Analítico permitió descomponer cada elemento en sus partes separando los factores principales de sus procesos apoyándose en el método sintético permitió unir todos los elementos para poder concluir con un diagnóstico de las deficiencias y mejoras de estas apoyándose método deductivo para el diagnóstico de la situación actual. La propuesta se centra en la Planificación de procesos que consta de dos apartados, el primero es, los Procesos Estratégicos, los cuales son realizados a largo plazo y que son responsabilidad directa de la Gerencia el velar que se cumplan. Como segundo apartado, tenemos los Procesos de Complemento o Apoyo, los cuales se enfocan en ser un apoyo fundamental, dando soporte a las funciones operativas. Los procesos anteriormente mencionados, servirán como base de apoyo Estratégico para lograr la obtención de los resultados marcados por la empresa

A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis

We report a medium-throughput drug-screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug-screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere.Acknowledgments: This work was supported by MINECO (SAF2017-89643-R, SAF2014-57243-R, SAF2015-62547-ERC) (M.V.), Fundacion FERO (IX FERO Grant for Research in Oncology) (M.V.), Fundacio La Marato de TV3 (141) (M.V.), Melanoma Research Alliance (Bristol-Myers Squibb-Melanoma Research Alliance Young Investigator Award 2017 (https://doi.org/10.48050/pc.gr.75716)) (M.V.), Beug Foundation (Prize for Metastasis Research 2017) (M.V.), Fundacion Ramon Areces (CIVP19S8163) (M.V.) and CIVP20S10662 (E.O.P.), Worldwide Cancer Research (19-0177) (M.V.), H2020-FETOPEN (828972) (M.V.), Cancer Research Institute (Clinic and Laboratory Integration Program CRI Award 2018 (54545)) (M.V.), AECC (Coordinated Translational Groups 2017 (GCTRA16015SEOA) (M.V.), LAB AECC 2019 (LABAE19002-VALI) (M.V.), ERC CoG (864759) (M.V.), Sophien-Stiftung zur Förderung der klinischen Krebsforschung (T.W.), Promedica Stiftung (T.W.), Stiftung f€ur angewandte Krebsforschung (T.W.), Forschungskredit of the University of Zurich (FK-18-054) (T.W.), Betty and David Koetser Foundation for Brain Research (T.W.), Foundation for Applied Cancer Research in Zurich (T.W., M.W.), Comunidad de Madrid (S2017/BMD-3867 RENIM-CM and Y2018/NMT-4949 NanoLiver-CM) and European structural and investment funds (M.D.), ISCIII (PT20/00044) co-funded by FEDER “A way of making Europe” (M.D.), Ministero dell’Istruzione, dell’Universita e della Ricerca-MIUR, “Dipartimenti di Eccellenza 2018-2022”, (D15D18000410001) (L.B. and P.C.), Science Foundation Ireland Frontiers for the Future Award (19/FFP/6443) (L.Y.), Science Foundation Ireland Strategic Partnership Programme, Precision Oncology Ireland (18/SPP/3522) (L.Y.), Breast Cancer Now Fellowship Award/ with the generous support of Walk the Walk (2019AugSF1310) (D.V.), La Caixa-Severo Ochoa International PhD Program Fellowship (LCF/BQ/SO16/52270014) (L.Z.), La Caixa International PhD Program Fellowship-Marie Sklodowska-Curie (LCF/BQ/DI17/11620028) (P.G-G), MINECO-Severo Ochoa PhD Fellowship (BES-2017-081995) (L.A-E.), AECC Postdoctoral Fellowship (POSTD19016PRIE) (N.P.), Boehringer Ingelheim Fonds MD fellowship (L.M.). The contribution of the Experimental Therapeutics Programme was supported by core funding from the Spanish National Cancer Research Center (CNIO). CNIO is supported by the ISCIII, the Ministerio de Ciencia e Innovacion, and is a Severo Ochoa Center of Excellence (SEV-2015-0510). The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovacion and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). M.V. was named Ramon y Cajal Investigator (RYC-2013-13365) and is member of EMBO YIP (4053)

A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis

We report a medium‐throughput drug‐screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood–brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug‐screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere

Sprouty2 and Spred1-2 Proteins Inhibit the Activation of the ERK Pathway Elicited by Cyclopentenone Prostanoids

Sprouty and Spred proteins have been widely implicated in the negative regulation of the fibroblast growth factor receptor-extracellular regulated kinase (ERK) pathway. In considering the functional role of these proteins, we explored their effects on ERK activation induced by cyclopentenone prostanoids, which bind to and activate Ras proteins. We therefore found that ectopic overexpression in HeLa cells of human Sprouty2, or human Spred1 or 2, inhibits ERK1/2 and Elk-1 activation triggered by the cyclopentenone prostanoids PGA1 and 15d-PGJ2. Furthermore, we found that in HT cells that do not express Sprouty2 due to hypermethylation of its gene-promoter, PGA1-provoked ERK activation was more intense and sustained compared to other hematopoietic cell lines with unaltered Sprouty2 expression. Cyclopentenone prostanoids did not induce Sprouty2 tyrosine phosphorylation, in agreement with its incapability to activate tyrosine-kinase receptors. However, Sprouty2 Y55F, which acts as a defective mutant upon tyrosine-kinase receptor stimulation, did not inhibit cyclopentenone prostanoids-elicited ERK pathway activation. In addition, Sprouty2 did not affect the Ras-GTP levels promoted by cyclopentenone prostanoids. These results unveil both common and differential features in the activation of Ras-dependent pathways by cyclopentenone prostanoids and growth factors. Moreover, they provide the first evidence that Sprouty and Spred proteins are negative regulators of the ERK/Elk-1 pathway activation induced not only by growth-factors, but also by reactive lipidic mediators

Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America : the ESTAMPA screening study protocol

Q1Q1Introduction Human papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC. Methods and analysis Women aged 30–64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre. Ethics and dissemination The study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings. Trial registration number NCT01881659Revista Internacional - Indexad

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.info:eu-repo/semantics/publishedVersio

El recurso de revocatoria contra la resolución determinativa en el procedimiento de determinación de oficio de las obligaciones tributarias en el ordenamiento jurídico costarricense

Tesis (licenciatura en derecho)UCR::Vicerrectoría de Docencia::Ciencias Sociales::Facultad de Derech