Dual role of cAMP in the transcriptional regulation of multidrug resistance-associated protein 4 (MRP4) in pancreatic adenocarcinoma cell lines

Cyclic AMP represents one of the most studied signaling molecules and its role in proliferation and differentiation processes has been well established. Intracellular cAMP levels are tightly regulated where the MRP4 transporter plays a major role. In the present study, we sought to establish whether cAMP modulated MRP4 expression in pancreatic adenocarcinoma cell lines. Quantitative PCR and western blot studies showed that cAMP-increasing agents enhanced MRP4 transcripts and protein levels in PANC-1 cells. Reporter luciferase experiments carried out in pancreatic AR42J cells showed that intracellular cAMP up-regulates MRP4 through an Epac2- and Rap1- mediated mechanism whereas extracellular cAMP reduced MRP4 promoter activity by a MEK/ERK-mediated pathway. Present results show that cAMP regulates MRP4 promoter activity, and further indicate that the balance between intracellular and extracellular cAMP levels determines MRP4 expression.Fil: Carozzo, Alejandro Enrique. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Diez, Federico Ruben. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gómez, Natalia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cabrera, Maia Diana Eliana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaFil: Shayo, Carina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaFil: Davio, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernández, Natalia Brenda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentin

El Recalentamiento Eléctrico por Termoconducción. Una Perspectiva Fisicoquímica del Calentamiento Eléctrico

El presente artículo recopila los comportamientos reales observados luego de cinco años de investigación, experimentación y modelado, con conductores eléctricos que fallan por alta conducción térmica, con el fin de rendir un aporte que pueda sumarse a las normativas existentes para la selección del cableado de proyectos eléctricos en baja tensión. Hasta ahora, los experimentos realizados con conductores eléctricos incendiados se limitan en su mayoría a tratar de determinar si el conductor produjo arco eléctrico o fue víctima del incendio, por medio de pruebas fisicoquímicas con los restos del conductor. Cuando se consideran factores como la intensidad de corriente, el tipo de instalación, la temperatura ambiental, fuentes cercanas generadoras de calor, condiciones de sobrecarga, y la sección transversal efectiva de conducción luego de considerar el efecto piel y los giros del cable, la selección del conductor adecuado se vuelve una decisión difícil. Estos factores, se consideran separadamente en normas españolas, americanas e internacionales; y los procesos de selección de cableado, desprecian ciertas condiciones que a veces son importantes causas de falla. El modelo presentado, es el resultado de la experimentación, en conjunto con un análisis global que tomó en cuenta todos estos factores simultáneamente; luego de revisar las conclusiones de las investigaciones químicas y físicas más relevantes.El presente artículo recopila los comportamientos reales observados luego de cinco años de investigación, experimentación y modelado, con conductores eléctricos que fallan por alta conducción térmica, con el fin de rendir un aporte que pueda sumarse a las normativas existentes para la selección del cableado de proyectos eléctricos en baja tensión. Hasta ahora, los experimentos realizados con conductores eléctricos incendiados se limitan en su mayoría a tratar de determinar si el conductor produjo arco eléctrico o fue víctima del incendio, por medio de pruebas fisicoquímicas con los restos del conductor. Cuando se consideran factores como la intensidad de corriente, el tipo de instalación, la temperatura ambiental, fuentes cercanas generadoras de calor, condiciones de sobrecarga, y la sección transversal efectiva de conducción luego de considerar el efecto piel y los giros del cable, la selección del conductor adecuado se vuelve una decisión difícil. Estos factores, se consideran separadamente en normas españolas, americanas e internacionales; y los procesos de selección de cableado, desprecian ciertas condiciones que a veces son importantes causas de falla. El modelo presentado, es el resultado de la experimentación, en conjunto con un análisis global que tomó en cuenta todos estos factores simultáneamente; luego de revisar las conclusiones de las investigaciones químicas y físicas más relevantes

Anthropogenic Effects on the Fouling Community: Impacts of Biological Invasions and Anthropogenic Structures on Community Structure

Coastal anthropogenic infrastructure has significantly modified nearshore environments. Because these structures often have a strong association with shipping as would be found in ports and harbors, they have been identified as invasion hotspots. Due to propagule pressure from shipping and recreational boating and suitable uncolonized substrate that provides a refuge from native predators, a greater number of non-native species have been found on these structures compared to nearby natural substrate. The mechanisms that limit the spread of non-native species from anthropogenic structures to natural substrate have been explored for several taxa at a species-specific level, but less so from an overall community perspective. Predation has been identified as one of the biotic interactions limiting invasion success. In addition to predation, dispersal ability may also prevent the spread of non-native species from anthropogenic structures to natural substrate. This thesis addresses how these two mechanisms interact to limit the spread of non-native species from anthropogenic structures to natural substrate and how that alters overall community composition. I aimed to explore differences between communities inside and outside of a marina and determine the extent to which predator and dispersal limitation were structuring these communities. I used a three-factor design, deploying seven unglazed ceramic tiles per each treatment combination of 1) inside versus outside a marina in Yaquina Bay, Oregon; 2) cage keeping out predators greater than the mesh size, no cage, or partial cage; 3) fixed near the substrata (benthic) versus suspended 1 meter below the surface. I also transplanted caged, suspended tiles of either adults or recruits from inside the marina to benthic and suspended caging treatments outside of the marina. These tiles allowed me to examine predation when dispersal limitation was not a factor for the community inside the marina, i.e. what happens to both recruits and adults if they can get outside of the marina. I found that the communities inside and outside of the marina were different and the data suggest that both predation and dispersal limitation interact to limit the spread of non-native species. Additionally, I found that mesopredators that could fit through the caging may be influencing predation results and community structure. This research addresses gaps in scientific knowledge regarding the mechanisms that prevent or facilitate the spread of non-native species. Future work could include the further exploration of mesopredation as an important factor in limiting the spread of non-native species and exploring dispersal limitation more in depth as well as broadening the geographic scope to see if the same trends hold true across bays and bioregions

Enseñanza de la Expresión Gráfica en las carreras de Diseño.

Ponencia al 10 Congreso Nacional de Expresión Gráfica en Ingeniería, Arquitectura y áreas afines.Los sistemas de representación son para el Diseñador Industrial un medio de vital importancia que establece un lenguaje universal, que posibilita mediante la utilización de un amplio espectro de herramientas poder comunicar, integrar y validar sus soluciones frente a todos los sistemas que deben interactuar con él durante el proyecto y en el desarrollo técnico productivo de un producto fabricado en serie. Los procesos de digitalización se consideran hoy como uno de los grupos de herramientas de representación más versátiles que confieren al Diseñador Industrial una herramienta versátil y actualizada, que interactúa con la situación a resolver desde una concepción integral y sistémica; al igual que los actuales procesos de Manufactura por Ingeniería Concurrente (secuencia de procesos) que se organizan mediante la planificación simultánea y la convergencia sinérgica de todos sus procesos. Estos tienen por objetivo proveer una variedad de piezas gráficas con fines representativos y de comunicación que permitan previsualizar el estado de avance del diseño según la etapa de proceso, siendo una actividad compleja que debe ser programada para asegurar la eficiencia y eficacia de la operación. En los procesos de digitalización se utilizan dos tipos de software, los CAD[1], (Dibujo Asistido por Computadora) y los sistemas CAM[2], (Mecanizado Asistido por Computadora) que además de generar un producto gráfico, permiten realizar comprobaciones mecánicas, estructurales y productivas, gracias a su motor tridimensional de programación y ser utilizados para procesos de fabricación. Es en este contexto universitario local; masivo y heterogéneo que la Cátedra Sistemas de Representación II de la Carrera de Diseño Industrial de la FAUD UNC, propone la experiencia de introducir a los alumnos a un recorrido multi-direccional por las herramientas digitales, software plataformas vectoriales y CAD-CAM, más utilizados en la formación autodidacta de los estudiantes avanzados de Diseño Industrial, destacando las ventajas de estas herramientas como simuladores de diversas técnicas y etapas del proceso de diseño, ayudando a optimizar el uso del tiempo y herramientas tanto analógicas como digitales, mejorando la relación tiempo de trabajo - calidad de resultado. Pretendiendo que desde un enfoque académico los Alumnos del nivel inicial de la carrera de Diseño Industrial, dispongan de un enfoque versátil y multidisciplinar.Mazzieri, Conrado Daniel. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaMontanaro Crivelli, Urías Ariel. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaLozano, Fabricio. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFernández Diez, María Sol. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaDepetris, Belén. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaBeck, Claudia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaMoreno, Facundo. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFuente de la, Federico. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaOtras Ciencias de la Computación e Informació

HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: a cross-sectional study

In HIV-1/HCV-coinfected patients, chronic HCV infection leads to an increased T-lymphocyte immune activation compared to HIV-monoinfected patients, thereby likely contributing to increase HIV-1 reservoir that is the major barrier for its eradication. Our objective was to evaluate the influence of HCV coinfection in HIV-1 viral reservoir size in resting (r) CD4+ T-cells (CD25-CD69-HLADR-). Multicenter cross-sectional study of 97 cART-treated HIV-1 patients, including 36 patients with HIV and HCV-chronic co-infection without anti-HCV treatment, 32 HIV patients with HCV spontaneous clearance and 29 HIV-monoinfected patients. rCD4+ T-cells were isolated and total DNA was extracted. HIV viral reservoir was measured by Alu-LTR qPCR. Differences between groups were calculated with a generalized linear model. Overall, 63.9% were men, median age of 41 years and Caucasian. Median CD4+ and CD8+ T-lymphocytes were 725 and 858 cells/mm 3 , respectively. CD4+ T nadir cells was 305 cells/mm 3 . Proviral HIV-1 DNA size was significantly increased in chronic HIV/HCV-coinfected compared to HIV-monoinfected patients (206.21 ± 47.38 vs. 87.34 ± 22.46, respectively; P = 0.009), as well as in spontaneously clarified HCV co-infected patients when compared to HIV-monoinfected individuals (136.20 ± 33.20; P = 0.009). HIV-1/HCV co-infected patients showed a larger HIV-1 reservoir size in comparison to HIV-monoinfected individuals. This increase could lead to a greater complexity in the elimination of HIV-1 reservoir in HIV-1/HCV-coinfected individuals, which should be considered in the current strategies for the elimination of HIV-1 reservoir.Financial support was provided by the Instituto de Salud Carlos III to VB (PI15CIII/00031), by the Spanish Ministry of Economy and Competitiveness to MC (SAF2016–78480-R) and The SPANISH AIDS Research Network RD16CIII/0002/0001, RD16CIII/0002/0002 and RD16/0025/0013 - ISCIII – FEDER. MRLP is supported by ISCIII - Subdirección General de Evaluacion and European Funding for Regional Development (FEDER) (PIE 13/00040 and RD12/0017/0017 RETIC de SIDA). C.P. is supported by the Portuguese Fundação para a Ciência e Tecnologia (FCT) (grant number SFRH/ BPD/77448/2011 is part of the EDCTP2 programme supported by the European Union). V.B., A.F.R. and N.R. are supported by the Miguel Servet programme from Fondo de Investigación Sanitaria (ISCIII) (grant number CP13/00098, CP14/CIII/00010 and CP14/00198, respectively)

Repeated pancreatic resection for pancreatic metastases from renal cell Carcinoma: A Spanish multicenter study (PANMEKID)

Background and objectives: Recurrent isolated pancreatic metastasis from Renal Cell Carcinoma (RCC) after pancreatic resection is rare. The purpose of our study is to describe a series of cases of relapse of pancreatic metastasis from renal cancer in the pancreatic remnant and its surgical treatment with a repeated pancreatic resection, and to analyse the results of both overall and disease -free survival. Methods: Multicenter retrospective study of patients undergoing pancreatic resection for RCC pancreatic metastases, from January 2010 to May 2020. Patients were grouped into two groups depending on whether they received a single pancreatic resection (SPS) or iterative pancreatic resection. Data on short and long-term outcome after pancreatic resection were collected. Results: The study included 131 pancreatic resections performed in 116 patients. Thus, iterative pancreatic surgery (IPS) was performed in 15 patients. The mean length of time between the first pancreatic surgery and the second was 48.9 months (95 % CI: 22.2-56.9). There were no differences in the rate of postoperative complications. The DFS rates at 1, 3 and 5 years were 86 %, 78 % and 78 % vs 75 %, 50 % and 37 % in the IPS and SPS group respectively (p = 0.179). OS rates at 1, 3, 5 and 7 years were 100 %, 100 %, 100 % and 75 % in the IPS group vs 95 %, 85 %, 80 % and 68 % in the SPS group (p = 0.895). Conclusion: Repeated pancreatic resection in case of relapse of pancreatic metastasis of RCC in the pancreatic remnant is justified, since it achieves OS results similar to those obtained after the first resection

Pancreatic metastases from renal cell carcinoma. Postoperative outcome after surgical treatment in a Spanish multicenter study (PANMEKID)

Background: Renal Cell Carcinoma (RCC) occasionally spreads to the pancreas. The purpose of our study is to evaluate the short and long-term results of a multicenter series in order to determine the effect of surgical treatment on the prognosis of these patients. Methods: Multicenter retrospective study of patients undergoing surgery for RCC pancreatic metastases, from January 2010 to May 2020. Variables related to the primary tumor, demographics, clinical characteristics of metastasis, location in the pancreas, type of pancreatic resection performed and data on short and long-term evolution after pancreatic resection were collected. Results: The study included 116 patients. The mean time between nephrectomy and pancreatic metastases' resection was 87.35 months (ICR: 1.51-332.55). Distal pancreatectomy was the most performed technique employed (50 %). Postoperative morbidity was observed in 60.9 % of cases (Clavien-Dindo greater than IIIa in 14 %). The median follow-up time was 43 months (13-78). Overall survival (OS) rates at 1, 3, and 5 years were 96 %, 88 %, and 83 %, respectively. The disease-free survival (DFS) rate at 1, 3, and 5 years was 73 %, 49 %, and 35 %, respectively. Significant prognostic factors of relapse were a disease free interval of less than 10 years (2.05 [1.13-3.72], p 0.02) and a history of previous extrapancreatic metastasis (2.44 [1.22-4.86], p 0.01). Conclusions: Pancreatic resection if metastatic RCC is found in the pancreas is warranted to achieve higher overall survival and disease-free survival, even if extrapancreatic metastases were previously removed. The existence of intrapancreatic multifocal compromise does not always warrant the performance of a total pancreatectomy in order to improve survival. (C) 2021 The Authors. Published by Elsevier Ltd

The relationship between gut and nasopharyngeal microbiome composition can predict the severity of COVID-19

Background: Coronavirus disease 2019 (COVID-19) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that displays great variability in clinical phenotype. Many factors have been described to be correlated with its severity but no specific determinants of infection outcome have been identified yet, maybe due the complex pathogenic mechanisms. The microbiota could play a key role in the infection and in the progression and outcome of the disease. Hence, SARS-CoV-2 infection has been associated with nasopharyngeal and gut dysbiosis and higher abundance of opportunistic pathogens. Methods: To identify new prognostic markers for the disease, a multicenter prospective observational cohort study was carried out in COVID-19 patients that were divided in three cohorts according to their symptomatology: mild (n=24), moderate (n=51) and severe/critical (n=31). Faecal and nasopharyngeal samples were taken and the microbiota was analysed. Results: Microbiota composition could be associated with the severity of the symptoms and the linear discriminant analysis identified the genera Mycoplasma and Prevotella as severity biomarkers in nasopharyngeal samples, and Allistipes, Enterococcus and Escherichia in faecal samples. Moreover, M. salivarium was defined as a unique microorganism in COVID-19 patients' nasopharyngeal microbiota while P. bivia and P. timonensis were defined in faecal microbiota. A connection between faecal and nasopharyngeal microbiota in COVID-19 patients was also identified as a strong positive correlation between P. timonensis (faeces) towards P. dentalis and M. salivarium(nasopharyngeal) was found in critically ill patients. Conclusions: This ratio could be used as a novel prognostic biomarker for severe COVID-19 patients.The research project was sup-ported by Government of Andalucia (Spain) (CV20-99908).N

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio