Proteolysis of the endothelial cell protein C receptor by neutrophil proteinase 3

BACKGROUND: The endothelial cell protein C receptor (EPCR) presents protein C to the thrombin:thrombomodulin complex on the endothelium of large vessels, and enhances the generation of activated protein C (APC) and activation of protease-activated receptor-1. A previous report has demonstrated binding of soluble (s) EPCR to activated neutrophils via surface proteinase 3 (PR3). METHODS: We now report further characterization of this interaction. Activated neutrophils and purified PR3 both decrease endothelial cell (EC) surface EPCR, suggestive of its proteolysis. RESULTS: When added to purified recombinant sEPCR, PR3 produced multiple cleavages, with early products including 20 kDa N-terminal and C-terminal (after Lys(176)) fragments. The binding of active site blocked PR3 to sEPCR was studied by surface plasmon resonance. Estimates of the K(D) of 18.5–102 nm were obtained with heterogeneous binding, suggestive of more than a single interaction site. CONCLUSIONS: This work demonstrates PR3 binding to and proteolysis of EPCR and suggests a mechanism by which anticoagulant and cell protective pathways can be down-regulated during inflammation

Scaling-up climate services with users in Latin America

Latin America farmers are highly vulnerable to climate variability, with crop losses observed throughout the region on a virtually annual basis. For instance, as indicated by the United Nations’ Food and Agriculture Organization (FAO) and World Food Program (WFP), the 2014–2017 drought conditions in Central America affected over 3.5 million people in Guatemala, Honduras and El Salvador. At the same time, local stakeholders and farmers generally have limited access to existing climate and forecast information, do not have sufficient capacities to understand the climate information and/or mechanisms to relate this information to the impact that climate variations can generate at a local level. This precludes the translation of information into actionable knowledge, and therefore into action. In this study, we describe a process through which scientists and strategic partners have co-developed, tested and scaled out an approach to assess, co-produce, translate and transfer climate information to enable agricultural decision making –the Local Technical Agroclimatic Committees (LTAC). LTACs allow open and clear dialogues about climate variations at multiple timescales, how these can affect crops, and the design of measures to reduce crop loss, particularly providing agronomic recommendations to farmers. We systematically describe the process of evidence generation, creation, partner engagement, scaling up, and monitoring of the approach throughout Latin America. Currently, 35 LTACs exist in 9 Latin American countries, engaging more than 250 public and private institutions, increasing the resilience and food security of an estimated 330,000 farmers, and potentially transforming how Latin American farmers manage climate risk. The study illustrates changes in institutional and farmers' capacities to co-produce, translate and use climate information and explores how better climate and crop prediction models can effectively underpin this process. We show how strategic alliances with farmer organizations, national public, and private and regional climate outlook forums help deliver improved and accurate climate information to users. Finally, we document how LTACs and their integration with other local-scale processes have led to changes in farmers’ management practices to take better advantage of good climatic conditions or avoid losses

Modelo de aseguramiento de calidad para los procesos de desarrollo de software de las Pymes

Actualmente las Pequeñas y Medianas Empresas (Pymes) son de gran importancia en la economía, representando más del 90 % del total de empresas, generando entre el 60 y 70 por ciento del empleo a nivel mundial (ONU, 2017), y en particular en la industria software. Hoy en día, el uso de software es un recurso indispensable, sin embargo, todavía siguen subsistiendo grandes problemas durante su proceso de desarrollo debido al poco enfoque que se le da a la calidad durante la elaboración de un software. Esto se debe a que los modelos de calidad de procesos en este sector fueron orientadas a grandes empresas, por lo que adaptarlas a las pymes resulta difícil, debido a que conlleva una gran inversión en dinero, tiempo y recursos (Grados, 2015), que lo hace inaccesible. Como propuesta de solución se propone un modelo de aseguramiento de calidad para ayudar a las pymes a mejorar sus procesos de desarrollo de software, basado en el ciclo de Deming para la mejora continua y en las buenas prácticas del CMMI y la ISO 12207. El modelo propuesto se adapta a cualquier metodología de desarrollo y es fácil de implementar. El modelo fue probado en un proyecto dentro de una Pyme desarrolladora de software cuyos resultados fueron una mejor estabilidad y definición de requerimientos ya que estos no sufrieron modificaciones ni mostraban ambigüedad, una mejor construcción de software ya que las funcionalidades fueron probadas con éxito, mayor cobertura y madurez de pruebas y una menor densidad de defectos.As a proposed solution, a quality assurance model is proposed to help SMEs to improve their software development processes, based on the Deming cycle for continuous improvement and on the good practices of CMMI and ISO 12207. The model proposed adapts to any development methodology and is easy to implement. The model was tested in a project within a software developer SME whose results were a better stability and definition of requirements since they did not suffer modifications or showed ambiguity, a better software construction since the functionalities were tested successfully, greater coverage and test maturity and lower defect density.Tesi

Percepción del marketing multinivel en los promotores de empresas multiniveles: un estudio comparativo de Herbalife y Fuxion, Trujillo 2018

La investigación tuvo como objetivo determinar la percepción del marketing multinivel en los promotores de empresas multiniveles: Un estudio comparativo de Herbalife y Fuxion en Trujillo 2018.El tipo de investigación es no experimental, y el diseño aplicado fue un descriptivo- comparativo. La población establecida para este estudio fueron dos empresas, las cuales fueron: Herbalife y Fuxion, de las cuales a través de un muestreo aleatorio estratificado se determinó una muestra de 270 promotores. La herramienta para medir esta tesis fue un cuestionario en escala de Likert, en donde se logró medir los indicadores de percepción del marketing multivel, tales como; entendimiento del diseño de negocio, satisfacción del método de difusión, formalidad del proceso de reclutamiento, material suministrado por el promotor, grado de satisfacción del reclutado, superación personal y profesional, motivación, calidad de los instructores, satisfacción de la línea de soporte, eficacia en la solución de problemas, percepción de la calidad del producto o servicio. De acuerdo a los resultados obtenidos de la investigación se concluye que la percepción de los promotores de las empresas multiniveles tienen un nivel moderado siendo los promotores de la empresa Fuxion los que reflejan un porcentaje de nivel alto y moderado con 17% y 36% respectivamente, mientras que los promotores de la empresa Herbalife reflejaron un nivel alto de 4% y moderado de 12%

Mammographic Findings after Intraoperative Radiotherapy of the Breast

Intraoperative Radiotherapy (IORT) is a form of accelerated partial breast radiation that has been shown to be equivalent to conventional whole breast external beam radiotherapy (EBRT) in terms of local cancer control. However, questions have been raised about the potential of f IORT to produce breast parenchymal changes that could interfere with mammographic surveillance of cancer recurrence. The purpose of this study was to identify, quantify, and compare the mammographic findings of patients who received IORT and EBRT in a prospective, randomized controlled clinical trial of women with early stage invasive breast cancer undergoing breast conserving therapy between July 2005 and December 2009. Treatment groups were compared with regard to the 1, 2 and 4-year incidence of 6 post-operative mammographic findings: architectural distortion, skin thickening, skin retraction, calcifications, fat necrosis, and mass density. Blinded review of 90 sets of mammograms of 15 IORT and 16 EBRT patients demonstrated a higher incidence of fat necrosis among IORT recipients at years 1, 2, and 4. However, none of the subjects were judged to have suspicious mammogram findings and fat necrosis did not interfere with mammographic interpretation

IFN-γ-producing CD4+ T cells promote experimental cerebral malaria by modulating CD8+ T cell accumulation within the brain.

It is well established that IFN-γ is required for the development of experimental cerebral malaria (ECM) during Plasmodium berghei ANKA infection of C57BL/6 mice. However, the temporal and tissue-specific cellular sources of IFN-γ during P. berghei ANKA infection have not been investigated, and it is not known whether IFN-γ production by a single cell type in isolation can induce cerebral pathology. In this study, using IFN-γ reporter mice, we show that NK cells dominate the IFN-γ response during the early stages of infection in the brain, but not in the spleen, before being replaced by CD4(+) and CD8(+) T cells. Importantly, we demonstrate that IFN-γ-producing CD4(+) T cells, but not innate or CD8(+) T cells, can promote the development of ECM in normally resistant IFN-γ(-/-) mice infected with P. berghei ANKA. Adoptively transferred wild-type CD4(+) T cells accumulate within the spleen, lung, and brain of IFN-γ(-/-) mice and induce ECM through active IFN-γ secretion, which increases the accumulation of endogenous IFN-γ(-/-) CD8(+) T cells within the brain. Depletion of endogenous IFN-γ(-/-) CD8(+) T cells abrogates the ability of wild-type CD4(+) T cells to promote ECM. Finally, we show that IFN-γ production, specifically by CD4(+) T cells, is sufficient to induce expression of CXCL9 and CXCL10 within the brain, providing a mechanistic basis for the enhanced CD8(+) T cell accumulation. To our knowledge, these observations demonstrate, for the first time, the importance of and pathways by which IFN-γ-producing CD4(+) T cells promote the development of ECM during P. berghei ANKA infection

Cosecha de Alcances: Valoración de las transformaciones producidas por las Mesas Técnicas Agroclimáticas (MTA) en Latinoamérica

Durante el 2019 se realizó un proceso de análisis de las transformaciones que han generado las Mesas Técnicas Agroclimáticas (MTA), en los territorios en que han sido establecidas durante los últimos 6 años. El estudio se enfoca en los cambios observables de comunidades, organizaciones o instituciones que han modificado sus acciones, relaciones, políticas y prácticas en cuatro países de Latinoamérica. Cinco áreas de transformación han sido identificadas i) mayor confianza en la calidad de información climática y agroclimática en el nivel local; ii) información agroclimática más conocida, comprensible y conectada; iii) democratización de conocimiento climático; iv) transformaciones en las prácticas agrícolas, y v) incidencia política y transformación institucional. Se verifican más de 140 alcances o cambios sobre dichas áreas. Se evidencia que las MTA analizadas han promovido un mayor acercamiento de las Instituciones Meteorológicas Nacionales a las necesidades de los territorios, lo que, a su vez, ha propiciado la creación de comunidades de práctica locales sobre la aplicación de conocimientos de clima en la toma de decisiones. En efecto, se tiene evidencia que los agricultores adaptan sus prácticas productivas tomando decisiones basadas en información de variabilidad climática local, reduciendo pérdidas y aumentando rentabilidad. Se demuestra, además, que el desarrollo de alianzas inter-institucionales derivadas de las MTA en los países, ayudan a la construcción y fortalecimiento de políticas públicas locales y nacionales para la adaptación al cambio y la variabilidad climática en la agricultura. Finalmente, se identifican diversas oportunidades y desafíos relacionados con liderazgo y la sostenibilidad del proceso de establecimiento de las MTA en Latinoamérica.During 2019 a process of analysis of the effects or transformations that the Local Agro climatic Technical Committees (MTA) have been carried out, in the territories in which they have been established during the last 5 years. The study focuses on the observable changes of individuals, communities, organizations or institutions that have modified their actions, relationships, policies and practices in five Latin American countries. Five areas of transformation have been identified as outcomes of the MTAs, among which are analyzed: i) greater confidence in the quality of climate and agro climatic information at the local level; ii) best-known, understandable and connected agro climatic information; iii) democratization of climate knowledge; iv) transformations in agricultural practices, and v) political influence and institutional transformation. More than 140 scopes or changes over these areas are verified. There is evidence that the MTAs have promoted a closer approach of the national meteorological institutions to the need of the territories farmers, which in turn has led to the creation of local communities of practice on the application of climate knowledge in decision making agricultural. Indeed, evidence shows that farmers adapt their productive practices by making decisions based on information on local climate variability, reducing losses and increasing profitability. It is also demonstrated that the development of inter-institutional alliances derived from MTAs in the countries, helps to build and strengthen local and national public policies for adaptation to climate change and variability in agriculture. Finally, various opportunities and challenges related to leadership and the sustainability of the MTA establishment process in Latin America are identified

Where are the most vulnerable areas to climate induced insecurities and risks in Zimbabwe?

This factsheet gives answers on how climate exacerbates root causes of conflict in Zimbabwe, using spatial hotspot analysis. The findings show that the high/moderate conflict and harsh climate interactions co-occurred principally with low productivity, inequality, and undernutrition hotspots. This occurs in the following districts: Beitbridge, Chiredzi, Mwenezi, and Chipinge. This publication is part of a factsheet series reporting on the findings of the CGIAR FOCUS Climate Security Observatory work in Africa (Kenya, Mali, Nigeria, Senegal, Sudan, Uganda, Zimbabwe). The research is centered around 5 questions: 1. How does climate exacerbate root causes of conflict? 2. Where are hotspots of climate insecurities ? 3.What is the underlying structure of the climate, conflict, and socio-economic system? 4. Are climate and security policies coherent and integrated? 5. Are policy makers aware of the climate security nexus

Where are the most vulnerable areas to climate induced insecurities and risks in Sudan?

This factsheet gives answers on how climate exacerbates root causes of conflict in Sudan, using spatial hotspot analysis. The findings show that areas of high conflict and harsh climate interactions co-occurred with hotspots where socio-economic vulnerabilities (undernutrition, inequality, migration, low productivity) are present. This occurs in north of Uran, Sololo, and north of Obbu (hotspots of inequality and low production), Marsabit Central, Sagante/Jaldesa, and Karare (inequality and low production), and all the socio-economic hotspots in surroundings of Wajir East Township, Wagberi, and Barwago; surroundings of Bulla Mpya, and eastern of Khorof/Harar. This publication is part of a factsheet series reporting on the findings of the CGIAR FOCUS Climate Security Observatory work in Africa (Kenya, Mali, Nigeria, Senegal, Sudan, Uganda, Zimbabwe). The research is centered around 5 questions: 1. How does climate exacerbate root causes of conflict? 2. Where are hotspots of climate insecurities ? 3.What is the underlying structure of the climate, conflict, and socio-economic system? 4. Are climate and security policies coherent and integrated? 5. Are policy makers aware of the climate security nexus

Where are the most vulnerable areas to climate induced insecurities and risks in Uganda?

This factsheet gives answers on how climate exacerbates root causes of conflict in Uganda, using spatial hotspot analysis. The findings show that areas of high conflict and harsh climate interactions co-occurred with hotspots where migration, inequality, and low agricultural productivity are present. This occurs in Lakwor, Oryang Lalano, Palwo, and Parumu. This publication is part of a factsheet series reporting on the findings of the CGIAR FOCUS Climate Security Observatory work in Africa (Kenya, Mali, Nigeria, Senegal, Sudan, Uganda, Zimbabwe). The research is centered around 5 questions: 1. How does climate exacerbate root causes of conflict? 2. Where are hotspots of climate insecurities ? 3.What is the underlying structure of the climate, conflict, and socio-economic system? 4. Are climate and security policies coherent and integrated? 5. Are policy makers aware of the climate security nexus