AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model

Limitless replicative potential is one of the hallmarks of cancer that is mainly due to the activity of telomerase. This holoenzyme maintains telomere length, adding TTAGGG repetitions at the end of chromosomes in each cell division. In addition to this function, there are extratelomeric roles of telomerase that are involved in cancer promoting events. It has been demonstrated that TERT, the catalytic component of telomerase, acts as a transcriptional modulator in many signaling pathways. Taking into account this evidence and our experience on the study of azidothymidine (AZT) as an inhibitor of telomerase activity, the present study analyzes the effect of AZT on some telomeric and extratelomeric activities. To carry out the present study, we evaluated the transcription of genes that are modulated by the Wnt/β-catenin pathway, such as c-Myc and cyclin-D1 (Cyc-D1) and cell processes related with their expression, such as, proliferation, modifications of the actin cytoskeleton, cell migration and cell cycle in a mammary carcinoma cell line (F3II). Results obtained after treatment with AZT (600 µM) for 15 passages confirmed the inhibitory effect on telomerase. Regarding extratelomeric activities, our results showed a decrease of 64, 38 and 25% in the transcription of c-Myc, Cyc-D1 and TERT, respectively (p<0.05) after AZT treatment. Furthermore, we found an effect on cell migration, reaching an inhibition of 48% (p<0.05) and a significant passage-dependent increase on cell doubling time during treatment. Finally, we evaluated the effect on cell cycle, obtaining a decline in G0/G1 in AZT-treated cells. These results allow us to postulate that AZT is not only an inhibitor of telomerase activity, but also a potential modulator of extratelomeric processes involved in cancer promotion.Fil: Armando, Romina Gabriela. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Methodological Approach for the Development of a Simplified Residential Building Energy Estimation in Temperate Climate

Energy ratings and minimum requirements for thermal envelopes and heating and air conditioning systems emerged as tools to minimize energy consumption and greenhouse gas emissions, improve energy e ciency and promote greater transparency with regard to energy use in buildings. In Latin America, not all countries have building energy e ciency regulations, many of them are voluntary and more than 80% of the existing initiatives are simplified methods and are centered in energy demand analysis and the compliance of admissible values for di erent indicators. However, the application of these tools, even when simplified, is reduced. The main objective is the development of a simplified calculation method for the estimation of the energy consumption of multifamily housing buildings. To do this, an energy model was created based on the real use and occupation of a reference building, its thermal envelope and its thermal system’s performance. This model was simulated for 42 locations, characterized by their climatic conditions, whilst also considering the thermal transmittance fulfilment. The correlation between energy consumption and the climatic conditions is the base of the proposed method. The input data are seven climatic characteristics. Due to the sociocultural context of Latin America, the proposed method is estimated to have more possible acceptance and applications than other more complex methods, increasing the rate of buildings with an energy assessment. The results have demonstrated a high reliability in the prediction of the statistical models created, as the determination coe cient (R2) is nearly 1 for cooling and heating consumption

Self-organized criticality in boson clouds around black holes

Boson clouds around black holes exhibit interesting physical phenomena through the Penrose process of superradiance, leading to black hole spin-down. Axionic clouds are of particular interest, since the axion Compton wavelength could be comparable to the Schwarzschild radius, leading to the formation of "gravitational atoms" with a black hole nucleus. These clouds collapse under certain conditions, leading to a "Bosenova". We model the dynamics of such unstable boson clouds by a simple cellular automaton and show that it exhibits self-organized criticality. Our results suggest that the evolution through the black hole Regge plane is due to self-organized criticality

Changing organizational culture in terms of information and communications technologies

Organizational change can be considered a genuine moment of evolution and development of the entire organization and decision of change is closely related to the company's mission, the objectives that wish to achieve in order to ensure their competitive advantage. At the same time, information and communication technologies as well as growing competition, changes in both production methods and organizational structures of companies. New forms of organization and management models based on different concepts and skills involving clear needs of employees with new skills, new roles, behaviors and values. It appears, therefore, a new culture of the organizationorganization, organizational culture, communications technologies

Albendazole Solid Dispersions: Influence of Dissolution Medium Composition on In Vitro Drug Release

The rate-limiting step to drug absorption is often dissolution from the dosage form, especially for poorly soluble com-pounds. Two possibilities for improving the dissolution of these drugs are to increase the available surface area and to im-prove their apparent solubilities under physiologically relevant conditions with surfactants as wetting agents. Albendazole (ABZ), one of the most effective broad-spectrum antihelminthic agents, has a very low aqueous solubility, which leads to an erratic availability. Solid dispersions (SD) with different amounts of carriers (P188 and PEG6000) were formulated to improve the ABZ dissolution rate. When the dissolution test is used to infer biopharmaceutical properties of the dosage form, it is es-sential that the method simulates the gastrointestinal conditions. The objective of this study was to examine the applicabil-ity of different dissolution media to the evaluation of ABZ and ABZ-SD dissolution rates. Dissolution profiles were performed by the official method (0.1 N HCl) and Simulated Gastric Fluid modified with a surfactant. Wetting was evaluated through the determination of surface tension and contact angle of the solutions. The dissolution rate of ABZ was clearly affected by the variables assessed in this study. These results have implications in the design of physiologically based dissolution media.Fil: González Vidal, Noelia Luján. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Control de Calidad de Medicamentos; ArgentinaFil: Castro, Silvina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Sanchez Bruni, Sergio Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Allemandi, Daniel Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Palma, Santiago Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentin

Rational certificates of non-negativity on semialgebraic subsets of cylinders

Let $g_1,\dots, g_s \in \mathbb{R}[X_1,\dots, X_n,Y]$ and $S = \{(\bar{x},y)\in \mathbb{R}^{n+1} \mid g_1(\bar{x},y) \ge 0, \dots, g_s(\bar{x}, y) \ge 0\}$ be a non-empty, possibly unbounded, subset of a cylinder in $\mathbb{R}^{n+1}$. Let $f \in \mathbb{R}[X_1, \dots, X_n, Y]$ be a polynomial which is positive on $S$. We prove that, under certain additional assumptions, for any non-constant polynomial $q \in \mathbb{R}[Y]$ which is positive on $\mathbb{R}$, there is a certificate of the non-negativity of $f$ on $S$ given by a rational function having as numerator a polynomial in the quadratic module generated by $g_1, \dots, g_s$ and as denominator a power of $q$

Measuring the efficiency of public schools in Uruguay: main drivers and policy implications

The aim of this research is to explore the existence of inefficient behaviors in public high schools in Uruguay and identify its potential drivers. To do so, we perform a two-stage model using PISA 2009 and 2012 databases. In the first stage, we use Data Envelopment Analysis (DEA) to estimate efficiency scores, which are then regressed on school and student contextual variables. This second stage is carried out using four alternative models: a conventional censored regression and three different regression models based on the use of bootstrapping recently proposed in the literature. Our results show that educational efficiency in Uruguayan high schools significantly dropped in nine percentage points between 2009 and 2012. In terms of educational policy recommendations, in order to reduce the inefficiencies in the evaluated public schools in Uruguay, the focus should be put on reducing grade-retention levels and promoting teaching–learning techniques that enhance student’s mathematics study skills and assessing students continuously through test and homework throughout the academic year. In this vein, our findings also show positive effects on public schools’ efficiency of providing the responsibility in the distribution of the school budget to school principals