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LY3305677 (LY) is a synthetic peptide analog of mammalian oxyntomodulin with a fatty acyl side chain to extend time action. LY functions are mediated by binding and activation of both glucagon (GcgR) and glucagon-like peptide-1 (GLP-1R) receptors. LY is bound with potent binding affinity (Ki) to human and mouse GcgR (Ki: 17.7 nM and 15.9 nM, respectively) and GLP-1R (Ki: 28.6 nM and 25.1 nM, respectively). LY dose-dependently stimulated insulin secretion in mouse pancreatic islets (EC50: 5.2 nM) and in mice. In oral glucose tolerance tests of diet-induced obese (DIO) and streptozotocin-induced diabetic mice, a single subcutaneous (SC) dose of LY significantly reduced glucose area under the curve by up to 65%. SC injections of LY to DIO mice dose-dependently reduced serum triglycerides and PCSK9 (proprotein convertase subtilisin/kexin type 9) levels and dose-dependently increased FGF21 (fibroblast growth factor 21) levels. In DIO mice treated over 18 days, LY 30 nmol/kg reduced body weight to a greater extent (33%) than semaglutide 60 nmol/kg (12%), and decreased food intake by 50% compared to vehicle. At Day 18, LY 30 nmol/kg group lost 33% of initial bodyweight, which was primarily due to 70% reduced fat mass. LY reduced liver triglycerides by greater than 70% and increased serum ketones by more than 3-fold compared to vehicle, suggestive of increased fatty acid oxidation. LY decreased body weight in both GcgR knock-out (KO) and GLP-1R KO mice, indicating that activation of both receptors contributed to greater weight loss. To assess potential changes in energy expenditure, DIO mice were treated chronically with SC LY (15 nmol/kg), semaglutide (60 nmol/kg), or vehicle. LY, but not semaglutide, increased energy expenditure as compared with vehicle. These preclinical studies indicate that novel dual GcgR and GLP-1R agonist LY may have potential to enhance metabolic health by improving dyslipidemia, hyperglycemia, or obesity. Disclosure Y. Chen: None. H. Qu: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. A. Mezo: None. T. Coskun: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. M. Song: None. W. C. Roell: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. K. B. Bokvist: Employee; Self; Eli Lilly and Company, Sanofi-Aventis Deutschland GmbH, Stock/Shareholder; Self; Johnson & Johnson, Sanofi-Aventis Deutschland GmbH, Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. J. S. Moyers: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. M. K. Thomas: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. F. Valenzuela: None. Funding Eli Lilly and Company

La preocupación por el medio ambiente se ha incrementado significativamente en las últimas décadas. Son múltiples las convenciones, protocolos, pactos y objetivos establecidos por las instituciones a nivel mundial para frenar los efectos del denominado cambio climático mediante la reducción de las emisiones de CO2 y Gases de efecto invernadero (GEI), así como para conseguir un modelo de crecimiento sostenible y respetuoso con el medio ambiente. A pesar de los efectos de la pandemia del COVID-19, las energías renovables alcanzaron un récord de nueva capacidad energética instalada en 2020 y fueron la única fuente de generación de electricidad que registró un aumento neto de la capacidad total. Con el aumento de la concentración atmosférica de CO2 a niveles récord, incluso cuando las emisiones han disminuido, cada vez es más evidente que se necesita un cambio estructural para alcanzar los objetivos climáticos y de desarrollo a largo plazo. Esta preocupación ha llevado a las instituciones, tanto europeas como nacionales, a poner en marcha una serie de medidas y objetivos a cumplir en el medio y largo plazo que afectan a varios sectores productivos delimitando sus emisiones de GEI a la hora de desarrollar su actividad y establecer medidas para incentivar la inversión que permita un crecimiento más sostenible medioambientalmente. A medida que las fuentes de energía renovables alcanzan la paridad en precios y rendimiento con las fuentes de energía convencionales, demuestran su capacidad para mejorar las redes y ganan cada vez más competitividad gracias a las nuevas tecnologías. Por otro lado, la demanda de energías renovables aumenta rápidamente. Las energías solar y eólica se encuentran actualmente muy cerca de cumplir las tres prioridades de los consumidores de energía: fiabilidad, asequibilidad y respeto del medio ambiente. Sin embargo, las energías renovables no solo benefician al planeta y contribuyen a reducir el impacto del cambio climático, sino que además se han convertido en un sector con gran capacidad de generar empleos y nuevas profesiones entre profesionales cualificados y empresas que utilizan las nuevas tecnologías para prestar servicios a plantas eólicas o fotovoltaicas...

Members of the insulin/IGF superfamily are well conserved across the evolutionary tree. We recently showed that four viruses in theIridoviridaefamily possess genes that encode proteins highly homologous to human insulin/IGF-1. Using chemically synthesized single chain (sc), i.e. IGF-1-like, forms of the viral insulin/IGF-1 like peptides (VILPs), we previously showed that they can stimulate human receptors. Because these peptides possess potential cleavage sites to form double chain (dc), i.e. more insulin-like, VILPs, in this study, we have characterized dc forms of VILPs for Grouper iridovirus (GIV), Singapore grouper iridovirus (SGIV) and Lymphocystis disease virus-1 (LCDV-1). GIV and SGIV dcVILPs bind to both isoforms of human insulin receptor (IR-A, IR-B) and to the IGF1R, and for the latter show higher affinity than human insulin. These dcVILPs stimulate IR and IGF1R phosphorylation and post-receptor signaling in vitro and in vivo. Both GIV and SGIV dcVILPs stimulate glucose uptake in mice. In vivo infusion experiments in awake mice revealed that while insulin (0.015 nmol/kg/min) and GIV dcVILP (0.75nmol/kg/min) stimulated a comparable glucose uptake in heart, skeletal muscle and brown adipose tissue, GIV dcVILP stimulated ~2 fold higher glucose uptake in white adipose tissue (WAT) compared to insulin. This was associated with increased Akt phosphorylation and glucose transporter type 4 (GLUT4) gene expression compared to insulin. Taken together, these results show that GIV and SGIV dcVILPs are active members of the insulin superfamily with unique characteristics. Elucidating the mechanism of tissue specificity for GIV dcVILP will help us to better understand insulin action, design new analogues that specifically target the tissues, and provide new insights into their potential role in disease.

Objective The continuous endothelium of skeletal muscle (SkM) capillaries regulates insulin's access to skeletal myocytes. Whether impaired transendothelial insulin transport (EIT) contributes to SkM insulin resistance (IR), however, is unknown. Methods Male and female C57/Bl6 mice were fed either chow or a high-fat diet for 16 weeks. Intravital microscopy was used to measure EIT in SkM capillaries, electron microscopy to assess endothelial ultrastructure, and glucose tracers to measure indices of glucose metabolism. Results Diet-induced obesity (DIO) male mice were found to have a ~15% reduction in EIT compared with lean mice. Impaired EIT was associated with a 45% reduction in endothelial vesicles. Despite impaired EIT, hyperinsulinemia sustained delivery of insulin to the interstitial space in DIO male mice. Even with sustained interstitial insulin delivery, DIO male mice still showed SkM IR indicating severe myocellular IR in this model. Interestingly, there was no difference in EIT, endothelial ultrastructure, or SkM insulin sensitivity between lean female mice and female mice fed a high-fat diet. Conclusions These results suggest that, in male mice, obesity results in ultrastructural alterations to the capillary endothelium that delay EIT. Nonetheless, the myocyte appears to exceed the endothelium as a contributor to SkM IR in DIO male mice.

Objective Members of the insulin/insulin-like growth factor (IGF) superfamily are well conserved across the evolutionary tree. We recently showed that four viruses in the Iridoviridae family possess genes that encode proteins highly homologous to human insulin/IGF-1. Using chemically synthesized single-chain (sc), i.e., IGF-1-like, forms of the viral insulin/IGF-1-like peptides (VILPs), we previously showed that they can stimulate human receptors. Because these peptides possess potential cleavage sites to form double chain (dc), i.e., more insulin-like, VILPs, in this study, we have characterized dc forms of VILPs for Grouper iridovirus (GIV), Singapore grouper iridovirus (SGIV) and Lymphocystis disease virus-1 (LCDV-1) for the first time. Methods The dcVILPs were chemically synthesized. Using murine fibroblast cell lines overexpressing insulin receptor (IR-A or IR-B) or IGF1R, we first determined the binding affinity of dcVILPs to the receptors and characterized post-receptor signaling. Further, we used C57BL/6J mice to study the effect of dcVILPs on lowering blood glucose. We designed a 3-h dcVILP in vivo infusion experiment to determine the glucose uptake in different tissues. Results GIV and SGIV dcVILPs bind to both isoforms of human insulin receptor (IR-A and IR-B) and to the IGF1R, and for the latter, show higher affinity than human insulin. These dcVILPs stimulate IR and IGF1R phosphorylation and post-receptor signaling in vitro and in vivo. Both GIV and SGIV dcVILPs stimulate glucose uptake in mice. In vivo infusion experiments revealed that while insulin (0.015 nmol/kg/min) and GIV dcVILP (0.75 nmol/kg/min) stimulated a comparable glucose uptake in heart and skeletal muscle and brown adipose tissue, GIV dcVILP stimulated 2-fold higher glucose uptake in white adipose tissue (WAT) compared to insulin. This was associated with increased Akt phosphorylation and glucose transporter type 4 (GLUT4) gene expression compared to insulin in WAT. Conclusions Our results show that GIV and SGIV dcVILPs are active members of the insulin superfamily with unique characteristics. Elucidating the mechanism of tissue specificity for GIV dcVILP will help us to better understand insulin action, design new analogs that specifically target the tissues and provide new insights into their potential role in disease., Highlights • Viral insulin/IGF1-like peptides (VILPs) are microbial members of the insulin superfamily. • VILPs bind to human IR and IGF1R and stimulate post-receptor signaling. • Grouper iridovirus (GIV) VILP has white adipose tissue (WAT)-specific characteristics. • GIV VILP stimulates increased glucose uptake in WAT via increased GLUT4 expression.

Resumen: En este trabajo se propone que una lectura lacaniana puede enriquecer las aproximaciones al estudio de los procesos de organización de la subjetividad en el contexto (pos)neoliberal latinoamericano. Con el objetivo de responder a la pregunta sobre qué es lo que lleva a los sujetos-servidores-públicos a vincularse con el discurso de la forma-empresa y así sostener su hegemonía, se analizan entrevistas realizadas a gerentes públicos chilenos encargados de planificar y desarrollar políticas de emprendimiento para mostrar cómo los registros lacanianos de lo imaginario y lo simbólico permiten dar cuenta del incesante trabajo identitario de los sujetos con los inconsistentes recursos discursivos posburocráticos. Los hallazgos permiten abrir una perspectiva prácticamente inexplorada en los estudios organizacionales de la región y evaluar críticamente el presunto estadio posneoliberal latinoamericano. Abstract: This article contends that a Lacanian approach to the study of organizations can make a significant contribution to the analysis of subjectivity in the context of (post-)neoliberalism in Latin America. With aims at answering the question about what drives the public-servant-subject to insist on articulating the discourse of enterprise, and thus to reproduce its hegemonic status, we explore the interview testimonies of Chilean public managers in charge of designing and implementing entrepreneurship-fostering policies. Our analysis, based on Lacan’s conceptualization of the imaginary and symbolic registers of subjectivity, reveals how a continued work of identification is made possible by the subject’s reliance on both post-bureaucratic and bureaucratic discursive resources. Our findings contribute to expand a fairly unexplored line of research in organization and management studies in the Latin American context, and to critically evaluate claims about the emergence of a “post-neoliberal” era across the region.

Before insulin can stimulate glucose uptake in muscle, it must be delivered to skeletal muscle (SkM) through the microvasculature. Insulin delivery is determined by SkM perfusion and the rate of movement of insulin across the capillary endothelium. The endothelium therefore plays a central role in regulating insulin access to SkM. Nitric oxide (NO) is a key regulator of endothelial function and stimulates arterial vasodilation, which increases SkM perfusion and the capillary surface area available for insulin exchange. The effects of NO on transendothelial insulin efflux (TIE), however, are unknown. We hypothesized that acute reduction of endothelial NO would reduce TIE. However, intravital imaging of TIE in mice revealed that reduction of NO by l-NG-nitro-l-arginine methyl ester (l-NAME) enhanced the rate of TIE by ∼30% and increased total extravascular insulin delivery. This accelerated TIE was associated with more rapid insulin-stimulated glucose lowering. Sodium nitroprusside, an NO donor, had no effect on TIE in mice. The effects of l-NAME on TIE were not due to changes in blood pressure alone, as a direct-acting vasoconstrictor (phenylephrine) did not affect TIE. These results demonstrate that acute NO synthase inhibition increases the permeability of capillaries to insulin, leading to an increase in delivery of insulin to SkM.

Before insulin can stimulate myocytes to take up glucose, it must first move from the circulation to the interstitial space. The continuous endothelium of skeletal muscle (SkM) capillaries restricts insulin's access to myocytes. The mechanism by which insulin crosses this continuous endothelium is critical to understand insulin action and insulin resistance; however, methodological obstacles have limited understanding of endothelial insulin transport in vivo. Here, we present an intravital microscopy technique to measure the rate of insulin efflux across the endothelium of SkM capillaries. This method involves development of a fully bioactive, fluorescent insulin probe, a gastrocnemius preparation for intravital microscopy, an automated vascular segmentation algorithm, and the use of mathematical models to estimate endothelial transport parameters. We combined direct visualization of insulin efflux from SkM capillaries with modeling of insulin efflux kinetics to identify fluid-phase transport as the major mode of transendothelial insulin efflux in mice. Model-independent experiments demonstrating that insulin movement is neither saturable nor affected by insulin receptor antagonism supported this result. Our finding that insulin enters the SkM interstitium by fluid-phase transport may have implications in the pathophysiology of SkM insulin resistance as well as in the treatment of diabetes with various insulin analogs.

https://brasiliensis.cerm.org.br/index.php/brasiliensis/article/view/118/version/118 Our intention in this article and in the following ones is to go deep in the works of some authors who appear in the theological environment before the II Vatican Council, as a potent focus of light able to guide to a vision much more clear and pure of the catholicity as a characteristic property of the church and the vocation which she needs to answer in the history. We start with two professors of the Theological Dominican School Le Salchoir, A. de Poulpiquet and A. D. Sertillanges, they aren’t interested so much to demonstrate the catholicity “exterior and visible”, that during more than four centuries it was dominated the idea of catholicity, but to present it as an expression of universalism “internal and spiritual”, which throw its roots in the same being of the Church that is the mystery of Christ. It resplendence through the light of universalism of Christ the supernatural character of the Church that free all from any particularism and in the same time, it’s the Christian respect fundament of all values of the religions non-Christians and human nature in general.

Background Staphylococcus aureus produces 11 serotypes of endotoxins that may cause food poisoning. Aim To determine the prevalence of type A enterotoxigenic Staphylococcus aureus carriage among food service workers in Chillan, Chile. Material and Methods Pharyngeal swabs were obtained from 100 food service workers and were cultured in Agar plates. After identifying the presence of Staphylococcus aureus, DNA was extracted to identify type A toxin by conventional PCR. Results Thirty eight percent of samples were colonized with Staphylococcus aureus. Among these, 26% were toxin A producers. Conclusions Half of the sampled workers carried Staphylococcus aureus and a quarter of these produced type A enterotoxin.

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Programa Oficial de Doctorado en Humanidades, Presidente: Enrique Martinez Ruiz.- Secretario: Miguel Fernando Gómez Vozmediano.- Vocal: Magdalena de Pazzis

En el presente ensayo se describe el contexto en el que se ha dado el desarrollo educativo de las personas con diversidad funcional para caminar en México y el apoyo que reciben de organismos internacionales y del Gobierno Mexicano, ya que el mismo se ve truncado por diversas causas, siendo una de ellas, la dificultad para asistir a una institución educativa, principalmente por la deficiente infraestructura urbana y de transporte. Este trabajo se fundamenta en investigaciones realizadas por varias instituciones como: El Instituto Nacional de Estadística y Geografía (INEGI), Organización de las Naciones Unidas para la Educación la Ciencia y la Cultura (UNESCO), Observatorio Regional de la Sociedad de la Información, Consejo Nacional para el Desarrollo y la Inclusión de las Personas con Discapacidad (CONADIS), entre otras. Complementa este ensayo los resultados positivos de experiencias utilizando los desarrollos tecnológicos actuales, que hacen posible presentar una propuesta basada en videoconferencia de escritorio, la cual es económica, de fácil y rápida implementación y que puede utilizarse para atender la educación de las personas con diversidad funcional para caminar en búsqueda de su integración educativa. This essay describes the context of the educational development of people with disabilities to walk in Mexico and the support received from international organizations and Mexican government, because their educational development is truncated for different reasons, one being the difficulty to attend an educational institution, mainly due to poor urban and transport infrastructure. This work is based on research conducted by several institutions including: the National Institute of Statistics and Geography (INEGI), the United Nations Educational, Scientific and Cultural Organization (UNESCO), Regional Observatory for the Information Society, the National Council for Development and Inclusion of Persons with Disabilities (CONADIS), among others. This essay is complemented with the positive results of experiences using the current technological developments that make it possible to propose an option based on the desktop video conferencing, which is inexpensive, effective and easy to implement and can be used to attend to the educational needs of individuals with functional diversity in the seeking of their educational integration.

Sixty-nine Holstein heifers were used to evaluate the effect of progesterone supplementation after timed artificial insemination (TAI) on conception rates of heifers under heat stress. Heifers were randomly assigned to 1 of 3 treatments: 1) control treatment (C), visual detection of estrus. Heifers detected in estrous were inseminated according to the AM-PM procedure (n = 23); 2) TAI (n = 24), using a CIDR device (insert containing progesterone) placed intravaginally on day -10 and removed on day -2 with PGF2α given on day -3. Heifers were given 0.5 mg of ECP at CIDR insertion and a second injection (0.5 mg ECP) was given on day -2 and 48 h after all the heifers were inseminated (day 0); and 3) TAI with progesterone supplementation (TAI+S; n = 22), consisting of TAI plus progesterone supplementation with a used CIDR from day 4 to 14 after insemination. The maximum temperature humidity index during the study averaged 86, while the minimum was 77. Blood samples were collected from all heifers on days 5, 9, and 14 post-insemination for quantification of progesterone, thyroxine, and triiodothyronine levels. Respiration rate (RR) was measured at 1700 hours and rectal temperature (RT) at 1800 hours, 3 times per week. The conception rate did not differ (P > 0.05) among treatments (C = 40; TAI = 34.6; TAI+S = 44.4%). The levels of progesterone were not increased (P > 0.05) by progesterone supplementation. Values for RR, RT, and thyroid hormones were similar among treatments (P > 0.05). TAI combined with progesterone supplementation did not improve the conception rate of Holstein heifers under heat stress.

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Preeclampsia (PE) is one of the main causes of maternal and fetal morbidity and mortality in the world, causing nearly 40% of births delivered before 35 weeks of gestation. PE begins with inadequate trophoblast invasion early in pregnancy, which produces an increase in oxidative stress contributing to the development of systemic endothelial dysfunction in the later phases of the disease, leading to the characteristic clinical manifestation of PE. Numerous methods have been used to predict the onset of PE with different degrees of efficiency. These methods have used fetal/placental and maternal markers in different stages of pregnancy. From an epidemiological point of view, many studies have shown that PE is a disease with a strong familiar predisposition, which also varies according to geographical, socioeconomic, and racial features, and this information can be used in the prediction process. Large amounts of research have shown a genetic association with a multifactorial polygenic inheritance in the development of this disease. Many biological candidate genes and polymorphisms have been examined in their relation with PE. We will discuss the most important of them, grouped by the different pathogenic mechanisms involved in PE.

Con el fin de integrar a terceros y alcanzar la convergencia entre el mundo de las Telecomunicaciones y el mundo Web, fueron implantadas en el modelo de negocio de los operadores las SDP (Service Delivery Platform); éstas permiten la eficiente creación, despliegue, ejecución, orquestación y gestión de servicios, generando un puente entre el mundo Telco y el mundo de las Tecnologías de la Información (TI). Actualmente, las NGSDP constituyen la tercera generación de SDP, incorporando principios SOA (Service Oriented Architecture) relacionados con la orquestación y gestión de servicios, lo cual le permite a los operadores y terceros, desarrollar servicios y desplegarlos sobre diferentes arquitecturas. Sin embargo, uno de los grandes retos en este contexto, es mantener el porcentaje de disponibilidad de los servicios tradicionales de telecomunicaciones en los nuevos servicios convergentes. El presente artículo presenta una propuesta para mantener niveles de alta disponibilidad de servicio en el contexto de una NGSDP, a través del planteamiento de una serie de criterios y lineamientos técnicos relacionados con este contexto.

Let $f:M\rightarrow M$ be a biholomorphisms on two--dimensional a complex manifold, and let $X\subseteq M$ be a compact $f$--invariant set such that $f|X$ is asymptotically dissipative and without sinks periodic points. We introduce a solely dynamical obstruction to dominated splitting, namely critical point. Critical point is a dynamical object and capture many of the dynamical properties of their one--dimensional counterpart.

Antecedentes: Recientemente hemos propuesto en un modelo experimental de infarto al miocardio una significativa interregulación entre los niveles de la enzima convertidora de angiotensina I (ECA) y su homologa (ECA-2), junto con que angiotensina (Ang)-(1-9) más que Ang-(1-7) actuaría como un contrarregulador de Ang II. Sin embargo tal relación no se ha investigado en el remodelado aórtico hipertensivo. Objetivo: Determinar la expresion de ECA y ECA-2, los niveles de Angs I, II, (1-7) y (1-9) y los parámetros de remodelado de la pared aórtica de ratas hipertensas. Métodos: Ratas normotensas Lewis (n=18) fueron randomizadas a hipertension (HTA) por sobrecarga de presion (modelo Goldblatt, GB, 2 riñones-1 pinzado, n=9). Ratas pseudo-operadas se usaron como controles (S, n=9). A las 6 semanas post cirugía, se determinó la masa cardíaca relativa (MCR) y la presion arterial sistólica (PAS). En la aorta torácica se determinó el grosor de la túnica media (GTM), área de la TM (ATM), niveles de mRNA de ECA y ECA-2, factor de crecimiento transformante tipo ß (TGF-ß), inhibidor del activador de plasminógeno (PAI-1) y de la proteína quimioatractante de monocitos (MCP-1) por RT-PCR. La actividad y niveles proteicos de ECA y ECA-2 por fluorimetría y Western blot y los niveles de Angs I, II, (1-7) y (1-9) por HPLC y radioinmunoensayo. Resultados: La MCR y la PAS aumentaron significativamente (p), MCP-1 (53%,) junto con mayor actividad (89%,), niveles proteicos de ECA (130%,) y Ang II (48%,). Esos efectos se asociaron a una significativa disminución del mRNA, los niveles proteicos y actividad de ECA-2 (- 55%, -41%, y 54%, respectivamente) y a menores niveles aórticos (-25%,) de Ang- (1-9), sin diferencias en los niveles de ang-(1-7). Conclusion: Estos resultados fuertemente sugieren que en la hipertension arterial experimental, el remodelado de la pared aórtica está asociado a una interacción entre ECA y ECA-2 y los niveles de Ang II y Ang-(1-9), pero no de Ang-(1-7). Background: In experimental models of myocardial infarction we have recently proposed a significant inter-regulation between levels of Angiotensin I converting enzyme (ACE) and its homologous, ACE-2; in addition, we have proposed that Angiotensin 1-9 (Ang-(1-9)) rather than Ang-(1-7) counter regulates Ang II. These relations have not been investigated in hypertensive aortic wall remodeling. Aim: To measure de expression of ACE and ACE-2, the aortic wall levels of Ang I, Ang II, Ang-(1-7) and Ang-(1-9), along with parameters of aortic wall remodeling in hypertensive rats. Methods: 18 Lewis rats were randomized to Goldblatt (2 kidneys, 1 clamped) induced hypertension (n=9) or sham operation (controls, n=9). Six weeks after surgery, relative cardiac mass (RCM), systolic blood pressure (SBP), medial layer aortic wall thickness (MLT) and ML área (MLA) were measured. The aortic wall levels of ACE and ACE-2, tissue growth factor ß(TGF- ß), plasminogen activator inhibitor (PAI-1) and monocyte chemoattractant protein (MCP-1) were determined by RT-PCR. Activity and protein levels of ACE and ACE-2 were measured by fluorometry and Western Blot and ANG I, Ang II, Ang-(1-7) and Ang-(1-9) levels were determined using HPLC and radioimmunoassay. Results: RCM and SBP increased significantly in hypertensive as opossed to sham operated rats. Hypertensive rats had a significant (p

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La gran cantidad de procesos de fabricación con los que cuentan actualmente tanto ingenieros como diseñadores industriales hace necesaria la utilización de sistemas basados en ordenador como sistemas de análisis y selección de procesos tipo CAE o CAPP. Aunque la selección de alternativas de fabricación es una tarea trivial para centros con una variedad limitada de tecnologías o bien para profesionales con un alto nivel de especialización en un reducido número de procesos, el proceso de selección no resulta tan trivial cuando lo que interesa analizar son nuevas tecnologías o procesos para los cuales no existe el conocimiento práctico necesario. El presente trabajo en marcado en el proyecto MAQMA se encarga de modelar un sistema concurrente para la evaluación de procesos de Rapid Manufacturing apoyado en técnicas de inteligencia artificial como redes neuronales, lógica difusa y sistemas expertos. Se presentará la aplicación piloto a fin de ilustrar el funcionamiento de dichas herramientas en un sistema integrado para facilitar las decisiones en este innovador campo de la fabricación.

La intenció d'aquest projecte de recerca és anar més enllà de l' aconseguit pels sistemes existents de selecció i comparació de processos de Prototipat Ràpid, mitjançant la introducció d'una nova metodologia que tingui com a únic fi la 'Fabricació Final' de components. El sistema desenvolupat incorpora algunes de les eines més recents del camp de Intel·ligència Artificial, de manera que sigui possible aconseguir una metodologia concurrent que inclogui: · Sistemes experts, que s'executen durant el procés de presa de decisions amb alternatives múltiples. Els sistemes experts utilitzen típicament estructures del tipus: IF-THEN-ELSE o CASE, de manera que les opcions puguin ser 'cribrades' especialment durant les primeres etapes de la selecció. · Lògica difusa per a la presa de decisions. Normalment en l'àmbit de la fabricació, alguns termes lingüístics o paràmetres de tipus qualitatiu són utilitzats per definir estats o propietats. Per exemple és comú trobar termes qualitatius com ara: 'bones propietats mecàniques "o" alta taxa d'absorbència', en lloc de xifres i números puntuals. Per tant és necessari comptar amb un mètode per traduir i gestionar aquesta informació. La lògica difusa ha estat adoptada com a mitjà per traduir termes d'ordre qualitatiu a informació quantitativa de manera que a partir d'aquestes dades es pugui construir un sistema de classificació i rànquing de processos.· Presa de decisions Multi-criteri, agrupació (sumatòria) i classificació. Durant la investigació es van provar diferents mètodes per a la classificació d'alternatives i selecció final a partir de vectors d'ordre quantitatiu amb pesos ponderats. Per a aquesta finalitat es va adoptar la metodologia proposada per Lan et al. (2005) el qual es descriu en el capítol 5 d'aquest treball. · Xarxes Neuronals Artificials. Aquestes han estat aplicades per a la modelització i simulació d'alguns processos de Fabricació Ràpida prèviament seleccionats. Per exemple, el procés de Sinteritzat Selectiu Làser es va aconseguir modelar utilitzant Xarxes Neuronals amb un algorisme de "backpropagation", prenent com a informació base, les dades proporcionades pel software propietari de l'equip. Aquesta xarxa neuronal simula una màquina de sinteritzat làser model DTM Vanguard, disponible a la FundacioCIM-UPC a Barcelona. D'altra banda el procés de Fusió selectiva per làser ha estat modelat també mitjançant Xarxes Neuronals a partir de l'equip Concep Laser M2, disponible al laboratori d'Enginyeria mecànica de la Universitat Catòlica de Lovaina, Bèlgica. Els models extrets d'aquestes simulacions mostren una estimació del temps total de fabricació menor al 10% la qual cosa representa una millora substancial respecte a mètodes d'estimació paramètrics. · Finalment s'ha utilitzat la tècnica de bases de dades relacionals per a la gestió i emmagatzematge d'informació sobre materials. Aquestes bases de dades han estat creades en Ms Access, que proporciona la facilitat d'accés, filtrat, graficació i presentació de la informació requerida. Aquesta informació pot ser extreta automàticament mitjançant trucades ODBC, executades des de l'entorn Matlab.Per a il·lustrar el funcionament de les eines descrites en una forma integrada, s'ha optat per desenvolupar una aplicació pilot en Matlab, utilitzant alguns "Tool boxes" especialitzats com: Lògica difusa, Xarxes neuronals, Estadística, Utilitats de graficació, Creació d'interfície d'usuari (GUI), Bases de dades. El resultat d'aquesta integració és una aplicació pilot anomenada RMADS (Rapid Manufacturing Advice System), el qual compta amb una interfície gràfica d'usuari que es divideix en tres mòduls: · Requeriments generals de disseny. Aquest mòdul analitza els paràmetres usualment definits en les especificacions inicials de Producte, per exemple: tipus de material, toleràncies, acabat superficial, complexitat geomètrica, etc. · Mòdul de costos. Aquest mòdul utilitza paràmetres d'entrada prèviament introduïts com: volum de peça, mida de lot i dimensions totals, per a realitzar càlculs mitjançant mètodes paramètrics i models basats en xarxes neuronals. El resultat és una estimació del cost per peça i també el cost estès per volums grans. · Selecció de materials. Aquest mòdul mostra la natura iterativa del procés de selecció de materials, a través de criteris de "filtratge" o selecció, de manera que a cada iteració el nombre d'opcions sigui limitat a un nombre raonable d'alternatives., The intention of this research is to go beyond currently available systems for the assessment and selection of Rapid Prototyping processes, hence introducing a new methodology devoted to 'Manufacturing' applications. Specifically the system would include a number of state of the art artificial Intelligence techniques to comprise a fully concurrent methodology, namely:· Expert systems are included to aid in the decision making process with multiple alternatives. Expert systems typically use If-Then-Else or CASE structures so that the available options can be screened specially during the first selection stages.· Fuzzy logic for decision making. Usually in manufacturing, linguistic terms or qualitative parameters are used to define states of properties. For instance it is common to find terms such as 'Good mechanical properties' or 'High absortivity rates' therefore it is necessary to have a method to translate and manage such information. Fuzzy logic has been adopted as a means to translate qualitative terms to quantitative information.· Multi-criteria decision making, aggregation and ranking. Different methods for selecting and ranking alternatives were tested which allows the integration of quantitative vectors with weighting factors that reflect the user preferences. For this purpose the method proposed by Lan et al. (2005) has been adopted as discussed in Chapter 5.· Artificial Neural Networks (ANNs) are being applied for the modelling and simulation of a number of Rapid Manufacturing Methods. Selective Laser Sintering has been modelled using a back propagation algorithm ANN taking as a basis the information provided by the machine software. The ANN simulates a DTM Vanguard SLS machine available at Fundacio CIM-UPC, Barcelona, while the Selective Laser Melting has been modelled with the parameters and settings used by the Concept Laser M2 machine available at the Mechanical Engineering Lab of the Catholic University of Leuven, Belgium. The extracted models exhibit a build-time prediction error rate lower than 10%, which is a significant improvement compared to conventional parametric methods.· Finally, relational databases have been applied for storing and handling materials information. These databases have been stored as Ms Access data which provides the ease to access, filter, screen and plot the required information. This data can be automatically called and extracted by means of an ODBC call deployed within the Matlab environment.In order to illustrate the functionality of the previous tools put together, a pilot application was designed in Matlab, making use of a number of specialized toolboxes namely: Fuzzy logic, Neural Network, Statistics, Plotting utilities, GUI builder, Database.The result is a prototype system with a graphic user interface divided in three modules: · General design requirements: which deals with those parameters usually defined in the product PDS, for instance: material type, tolerances, surface roughness, geometrical complexity, etc.· Costing module: which makes use of parametric cost estimation and ANN-based models to perform the calculation of cost per part, and for low volumes· Materials selection: Shows the iterative nature of materials selection through screening steps so that the range of suitable options is limited.

Background: Melatonin receptors are widely distributed in human tissues but they have not been reported in human adrenal gland. Aim: To assess if the human adrenal gland expresses melatonin receptors and if melatonin affeets cortisol response to ACTH in dexamethasone suppressed volunteers. Material and methods: Adrenal glands were obtained from 4 patients undergoing unilateral nephrectomy-adrenalectomy for renal cáncer. Expression of mRNA MT1 and MT2 melatonin receptors was measured by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). The effect of melatonin on the response to intravenous (i.v.) ACTH was tested (randomized cross-over, double-blind, placebo-controlled tríal) in eight young healthy males pretreated with dexamethasone (1 mg) at 23:00 h. On the next day at 08:00 h, an i.v. Une was inserted, at 08:30 h, and after a blood sample, subjeets ingested 6 mg melatonin or placebo. At 09:00 h, 1-24 ACTH (Cortrosyn, 1µg/1.73 m² body surface área) was injected, drawing samples at 0, 15, 30, 45 and 60 minutes after. Melatonin, cortisol, cortisone, progesterone, aldosterone, DHEA-S, testosterone and prolactin were measured by immunoassay. Results: The four adrenal glands expressed only MT1 receptor mRNA. Melatonin ingestión reduced the cortisol response to ACTH from 14.6+1.45µg/dl at 60 min in the placebo group to 10.8+1.2µg/dl in the melatonin group (p

La miocardiopatía espongiforme, también conocida como ausencia aislada de compactación del ventrículo izquierdo, es una anomalía congénita recientemente descrita y que resulta de la interrupción en la morfogénesis embrionaria del miocardio ventricular izquierdo el cual permanece engrosado por grandes trabéculas y sinusoides y que suele expresarse clínicamente con manifestaciones de insuficiencia cardíaca, arritmias y eventos embólicos. Esta enfermedad suele detectarse en la infancia o en la adolescencia, menos frecuentemente en la vida adulta y muy excepcionalmente en la senectud. Presentamos aquí el caso de una mujer de 75 años de edad que corresponde a uno de los casos de miocardiopatía espongiforme de mayor edad entre los que se han publicado; sus manifestaciones clínicas y ecocardiográficas son típicas de esta variedad de miocaridopatía. El caso se comenta a la luz de los hechos más relevantes que existen en la escasa literatura publicada sobre esta interesante enfermedad.

Tesis (Ingeniero Comercial) El objeto de la investigación fue identificar y c;uantificar los costos en que incurren los empresarios de la locomoción colectiva de Santiago, para después lograr obtener la tarifa real del valor del pasaje y por último, se procede a la realizacióµ de una encuesta de medición de calidad y satisfacción del usuario de la locomoción colectiva. Este estudio se basa en la información público (INE, Instituciones fiscales) y privada (facturas, estudio de demanda) que están relacionados co:p el estudio en cuestión. Este estudio nace de la inquietud que tiene la po"Qlación por saber cual debería ser el valor real del precio del pasaje de buses licitados de la región metropolitana, pues este costo influye de manera significativa en el ingreso percápita mensualmente cada familia, cabe destacar que este informe no es con fines políticos ni lucrativo. En el presente año el gremio microbusero, el gobierno y los estudiantes han tenido grandes disputas para poder determinar cual debería ser el costo del pasaje tanto escolar como adulto. Este estudio se realizó teniendo como base estudios realizados anteriormente, como así también los datos recolectados y analizados. Este estudio esta dividido en dos partes medulares las cuales son la determinación de los costos en que incurren los empresarios de la locomoción colectiva de Santiago, los cuales fueron determinados a partir de los datos reco1ectados, y la segunda parte es un ejemplo para poder determinar la ecuación tarifaría y calcular la tarifa real del pasaje de la locomoción colectiva. Se realiza una encuesta a 50 usuarios y no-usuarios para evaluar la satisfacción y calificar el sistema de transporte en chile.

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The search to find ways to encourage library users and even those who are not, to to leverage content repositories, its location, assessment, understanding and use, is an end to the Librarianship. However, the term information literacy, with this concern is called, is relatively new, with the emergence of Internet, the use of intranets and extranets has risen to prominence. If literacy in information is involved in training students for a better life, any action undertaken must be directed to the development of information skills covering even the implied literacies to exclude with traditional forms of education to give way to those in which the web is central figure.

Se utilizaron 44 corderas Dorper x Pelibuey con peso vivo promedio de 24.56±0.70 kg para evaluar el efecto del clorhidrato de zilpaterol (CZ) sobre el comportamiento productivo y algunas características de canal en épocas de primavera (n=24) y verano (n=20), bajo condiciones áridas del noroeste de México. En cada época, las corderas fueron colocadas en corraletas individuales y divididas en dos grupos para ser alimentadas sin CZ (SCZ) o con 10 mg de CZ/ animal/día (CCZ) durante 32 días. Posteriormente, todas las corderas fueron sacrificadas. La información se sometió a un análisis de varianza con un diseño de bloques completamente al azar con arreglo factorial 2x2. Las corderas CCZ de primavera presentaron mayor (P0.05) por efecto del CZ; contrariamente, el peso de canal caliente y fría, y la área del músculo Longissimus dorsi fueron mayores (P

Supplemental material, Full_Appendix for The Enduring State: An analysis of governance-making in three mining conflicts by Rajiv Maher, Francisco Valenzuela and Steffen Böhm in Organization Studies

Supplemental material, Full_Appendix for The Enduring State: An analysis of governance-making in three mining conflicts by Rajiv Maher, Francisco Valenzuela and Steffen Böhm in Organization Studies

DOCTOR FONDECYT FONDECYT

DOCTOR EN BIOLOGIA C/M FISIOLOGIA FONDECYT FONDECYT