Propuesta estratégica para el desarrollo de actividades extraescolares en las instituciones educativas oficiales de básica secundaria del municipio de Pereira para el año 2015

El país en general existe una creciente preocupación por el desarrollo complementario de las actividades escolares para las niñas, niños y jóvenes; específicamente en lo pertinente a esta investigación, se emplearon como población de estudio las instituciones educativas de básica secundaria del sector público del municipio de Pereira, donde no existía un diagnóstico sobre el tipo de actividades extraescolares ya sea de carácter deportivo, recreativo o cultural; con qué tipo de infraestructura deportiva o escenarios propicios para la práctica de diferentes deportes se cuenta y quienes son las personas encargadas de dictar las actividades extraescolares al interior de las distintas planteles educativos. El mal empleo del tiempo libre por parte de los estudiantes, los expone a riesgos como la prostitución, drogadicción, vandalismo, deserción escolar, violencia intrafamiliar, empleo juvenil además de una serie de problemas físicos, que pueden ser abordados de manera más eficiente con el deporte, la recreación y la cultura, que son medidas de tipo correctiva, que atacan estas dificultades desde su origen, diferente a las actuales medidas represivas, que evidentemente funcionan de manera superficial y temporal. A pesar de existir la normativa para la estructuración de clubes deportivos que aporten a la solución de la problemática mencionado, no se contaba con una herramienta o modelo que facilitara la constitución de clubes deportivos, que se presenta como una de las finalidades de esta investigación

Continuous production of viral vaccines with a two-stage bioreactor system

Continuous processes can be particularly efficient for production of biologicals that are required in large amounts such as viral vaccines. One virus that has received much clinical attention is Modified Vaccinia Ankara virus (MVA), which is a potential platform for expression of recombinant viral antigens and can be used as a vector in gene therapy [1]. Recently, a new MVA virus strain has been successfully propagated at high yields in non-aggregated avian suspension cells [2] allowing the production of MVA virus in continuous bioreactors. MVA is a lytic DNA virus and therefore, continuous production strategies can be implemented using two-stage bioreactor systems, where cell growth and virus propagation occur in separated vessels [3]. However, a possible drawback for continuous virus production is the presence of defective interfering particles among the virus population that cause oscillations in virus levels and low production yields [3], known as Von Magnus effect. In this work, continuous production of MVA virus in a two-stage bioreactor (TSB) set-up (two 1 L stirred tank bioreactors) was evaluated. Subsequently, the set-up was scaled down to a non-instrumented semi-continuous cultivation system (two shaker flasks; small-scale culture, SSC) as approximation to a continuous cultivation [4] that would facilitate TSB screening. The virus strain MVA.CR19 and the duck cell line AGE1.CR.pIX (both from ProBioGen, Berlin) were used. The TSB system involved a bioreactor for cell growth and a second bioreactor in series for virus propagation [3]. The SSC system consisted of two shaker flasks, one for cell growth (120 mL working volume) and another for virus propagation (different residence times). Harvest, cell transfer, and addition of fresh medium were done manually twice a day. Continuous production of MVA-CR19 was maintained for 18 d with the TSB system. Virus titers showed 7 d of transient phase, followed by stable titers that suggested the absence of a Von Magnus effect over 18 d. A total production capacity of 2x1010 viruses/day was estimated (4x1010 viruses/day estimated for batch). The space-time yield of the TSB approached that of 2 parallel batches at 11 d post infection. The process was scaled down to the SSC system that resulted in stable production of cells, and virus titers that approached the dynamics and values obtained with the TSB system. Additional cultivations with the SSC system showed that different residence times in the virus bioreactor could influence virus titers. Overall, it was demonstrated that continuous production of MVA.CR19 virus in a TSB system is feasible. Also, a small scale two-stage semi-continuous cultivation was successfully established as a faster and cheaper tool for screening the TSB systems before scale-up

Propagation of influenza and MVA virus in cascades of continuous stirred tank bioreactors: challenging the Von Magnus effect

Moving from batch to fully continuously operated upstream processes is one of the big challenges for the coming decades in cell culture-based viral vaccine manufacturing. Continuous processes are known to be more efficient than batch systems for production of large volumes of product, and can therefore be an interesting option for production of highly demanded viral vaccines. One example is the seasonal influenza virus that causes annual epidemics in human populations worldwide and is currently produced in batch processes. Another virus of clinical interest is Modified Vaccinia Ankara (MVA) virus which is a potential platform for recombinant vaccines and can be used as a vector in gene therapy [1]. Continuous propagation of MVA virus seems to be feasible using a new MVA virus strain that can propagate at high yields in non-aggregated avian suspension cells [2]. Because both influenza and MVA are lytic viruses a continuous production strategy was employed that involves cascades of two stirred tank bioreactors, where cell growth and virus propagation occur in separated vessels [3]. However, a possible drawback for continuous virus production is the presence of defective interfering particles among the virus population that cause oscillations in virus levels and low production yields [3], known as Von Magnus effect. In this work, a small scale two-stage cultivation system (two 100 mL shaker flasks; semi-continuous; SSC) was established as screening tool for influenza and MVA virus propagation before scaling to a 1 L continuous two-stage bioreactor system (two 1 L stirred tank bioreactors; TSB). The MVA virus strains MVA-CR19 and MVA-CR19.GFP were used, and propagated 14 days in the duck cell line AGE1.CR.pIX (all three from ProBioGen, Berlin) using the SSC system. Similarly, the influenza virus strain A/PR/8/34 H1N1 (RKI) was propagated 14 days using two different cell lines (MDCK.SUS2 and AGE1.CR.pIX) in the SSC system. From the best screening result, scale-up to the 1 liter TSB was performed with successful virus production in continuous mode for three weeks. PCR analysis was used to monitor the stability of the viruses in continuous culture. The SSC system resulted in stable production of cells, and influenza virus titers that approached the oscillatory behavior observed in previous experiments [3]. Interestingly, MVA virus cultivated in the SSC system did not show oscillations in the virus titer. Additional cultivations of MVA virus in the SSC system showed that different residence times in the virus bioreactor could influence virus titers. Subsequently, production of MVA-CR19 was scaled to the TSB system and maintained for 18 days in continuous mode. MVA virus titers showed 7 days of a transient phase, followed by stable titers that confirmed the absence of a Von Magnus effect over 18 days. A yield comparison between an eight days batch-cycle process and the TSB showed that the space-time yield of the TSB cultivation approached that of two parallel batches at 11 days of virus production. PCR analysis indicated that the reporter gene in MVA-CR19.GFP was maintained stably for the complete cultivation period. Overall, it was demonstrated that production of influenza and MVA viruses in a SSC system is feasible and can be used as a fast and cost-efficient tool for optimizing continuous virus production. Finally, MVA virus is a very promising candidate for production of viral vaccines in cascades of continuous stirred tank bioreactors. [1] Verheust et al. 2012, Vaccine 30(16):2623–32. [2] Jordan et al. 2013, Viruses 5(1):321–39. [3] Frensing et al. 2013, PLOS ONE 8(9):e72288. [ 4] Westgate and Emery 1990, Biotech & Bioeng 35(5):437-53

Hollow fiber-based high-cell-density and two-stage bioreactor continuous cultivation: Options and limits towards process intensification for virus production

Availability of suspension cell lines and culture media for expansion of up to 20×106 cells/mL provide perfect starting points to develop process intensification strategies for vaccine production. Modern hollow fiber-based perfusion systems accomplish up to 500 ×106 cells/mL in CHO cell cultivations. Reaching 10 to 20 fold higher cell concentrations, while keeping cell specific virus yields constant, could make processes with very low cell specific virus yields (10-100 viruses/cell) already to feasible processes. Therefore, all possible process strategies using new media, cell lines and reactor equipment need revisiting. Data obtained from the production of the modified vaccinia Ankara virus strain MVA-CR19 as well as influenza A/PR/8 virus in either hollow fiber-based high-cell-density (HCD) cultivations (using an alternating tangential flow (ATF) perfusion system) or in two-stage bioreactor continuous cultivations of the suspension cell line AGE1.CR.pIX are presented and critically discussed. Options and limits are highlighted to allow an evaluation of both approaches with respect to scale-up and application to other virus-host cell systems. Both process strategies were successfully scaled-down into shaker flasks allowing parallel experiments. Accordingly, perfusion and semi-perfusion at a feeding rate of 0.05 nL/cell×d led to concentrations of AGE1.CR.pIX cells above 60×106 cells/mL with neither limitation nor overload of nutrients. For infections in 50 mL, a combined strategy comprising an initial fed-batch phase followed by a periodic virus harvest phase resulted in the highest product concentration. Compared to a conventional batch process at 4 to 8×106 cell/mL, maximum titer increased more than 10-fold. Additionally, a 3-fold increase in both cell-specific yield (virus/cell) and volumetric productivity (virus/L×d) could be obtained. The subsequent scale-up into a 1 L bioreactor with ATF perfusion was equally successful and besides allowed re-evaluation of hollow-fiber cut-off. Alternatively, a small scale semi-continuous two-stage cultivation system (100 mL scale, two shaker flasks) was established as an approximation for a genuine continuous bioreactor set-up (1 L scale, two-stage stirred tank bioreactor). MVA virus production at both scales resulted in stable titers of MVA-CR19 virus (approx. 1×108 IU/mL) for over 18 days suggesting an absence of the “von Magnus effect” compared to influenza virus. PCR analysis confirmed stable maintenance of the recombinant transgene in a MVA-CR19.GFP virus. Such a system may be of interest for continuous production of recombinant MVA-based vaccines and gene therapy vectors in the future. Please click Additional Files below to see the full abstract

Metodología de inducción para nuevos profesionales en el área de la ingeniería industrial en centros de distribución de materia seca

Desde los inicios de las empresas hasta los últimos días , los procesos de enseñanza/aprendizaje del personal operativo de fueron considerados superfluos, siendo vistos como un desperdicio de labores que a su vez consumía tiempo y recursos, llevándose de una manera muy ligera y algunas veces casi nula, además cuando hablamos de un centro de distribución logística no dimensionamos todos los procesos por el cual pasa la mercancía y/o materia prima para poder ir de un punto A hasta un punto B, o en su defecto desde un proveedor a un cliente final, haciendo una importante labor de la cadena de abastecimiento, siendo la empresa el canal de distribución autorizado, ya sea por autonomía propia o haciendo un outsourcing. La aproximación de las materias primas, sus productos y sub productos a los puntos de consumo o de atención al cliente es un proceso logístico que se ejecuta,, a través de actividades de transformación, almacenaje y transporte. Las actividades de transformación y transporte originan el movimiento físico del producto hasta que se produce la demanda.[1] Frente a esta situación, nace la necesidad de desarrollar una Metodología de Inducción para nuevos profesionales en el área de la ingeniería Industrial en centros de distribución de materia seca , por ende, buscaremos plasmar una dinámica del funcionamiento de un centro de distribución logística contemplando actividades de almacenaje y transporte.Until very recently, the processes of inducement and training of personnel were considered superfluous, seen as a waste of time and in turn of resources, being carried out in a very superficial and careless manner; and generally when we speak of a logistics distribution center we do not dimension all the processes through which the merchandise or raw material passes in order to go from point A to point B, or failing that from a supplier to an end customer, doing an important job of the supply chain, the company being the authorized distribution channel, either by its own autonomy or by outsourcing. The approximation of the product to the consumption points is a logistic process that is basically carried out through transformation, storage, and transport activities. The transformation and transport activities originate the physical movement of the product until demand is produced [1] Faced with this situation, it awakens the need to develop an Inducement Methodology for new professionals in the area of Industrial engineering in dry matter distribution centers, therefore, we will seek to capture a dynamic of the operation of a logistics distribution center, contemplating activities of storage and transportation.Rionegr

Metodología de inducción para nuevos profesionales en el área de la ingeniería industrial en centros de distribución de materia seca

Desde los inicios de las empresas hasta los últimos días , los procesos de enseñanza/aprendizaje del personal operativo de fueron considerados superfluos, siendo vistos como un desperdicio de labores que a su vez consumía tiempo y recursos, llevándose de una manera muy ligera y algunas veces casi nula, además cuando hablamos de un centro de distribución logística no dimensionamos todos los procesos por el cual pasa la mercancía y/o materia prima para poder ir de un punto A hasta un punto B, o en su defecto desde un proveedor a un cliente final, haciendo una importante labor de la cadena de abastecimiento, siendo la empresa el canal de distribución autorizado, ya sea por autonomía propia o haciendo un outsourcing. La aproximación de las materias primas, sus productos y sub productos a los puntos de consumo o de atención al cliente es un proceso logístico que se ejecuta,, a través de actividades de transformación, almacenaje y transporte. Las actividades de transformación y transporte originan el movimiento físico del producto hasta que se produce la demanda.[1] Frente a esta situación, nace la necesidad de desarrollar una Metodología de Inducción para nuevos profesionales en el área de la ingeniería Industrial en centros de distribución de materia seca , por ende, buscaremos plasmar una dinámica del funcionamiento de un centro de distribución logística contemplando actividades de almacenaje y transporte.Until very recently, the processes of inducement and training of personnel were considered superfluous, seen as a waste of time and in turn of resources, being carried out in a very superficial and careless manner; and generally when we speak of a logistics distribution center we do not dimension all the processes through which the merchandise or raw material passes in order to go from point A to point B, or failing that from a supplier to an end customer, doing an important job of the supply chain, the company being the authorized distribution channel, either by its own autonomy or by outsourcing. The approximation of the product to the consumption points is a logistic process that is basically carried out through transformation, storage, and transport activities. The transformation and transport activities originate the physical movement of the product until demand is produced [1] Faced with this situation, it awakens the need to develop an Inducement Methodology for new professionals in the area of Industrial engineering in dry matter distribution centers, therefore, we will seek to capture a dynamic of the operation of a logistics distribution center, contemplating activities of storage and transportation.Rionegr

A large language model-assisted education tool to provide feedback on open-ended responses

Open-ended questions are a favored tool among instructors for assessing student understanding and encouraging critical exploration of course material. Providing feedback for such responses is a time-consuming task that can lead to overwhelmed instructors and decreased feedback quality. Many instructors resort to simpler question formats, like multiple-choice questions, which provide immediate feedback but at the expense of personalized and insightful comments. Here, we present a tool that uses large language models (LLMs), guided by instructor-defined criteria, to automate responses to open-ended questions. Our tool delivers rapid personalized feedback, enabling students to quickly test their knowledge and identify areas for improvement. We provide open-source reference implementations both as a web application and as a Jupyter Notebook widget that can be used with instructional coding or math notebooks. With instructor guidance, LLMs hold promise to enhance student learning outcomes and elevate instructional methodologies

Measuring poverty in India with machine learning and remote sensing

In this paper, we use deep learning to estimate living conditions in India. We use both census and surveys to train the models. Our procedure achieves comparable results to those found in the literature, but for a wide range of outcomes

Fine-Tuning Language Models with Advantage-Induced Policy Alignment

Reinforcement learning from human feedback (RLHF) has emerged as a reliable approach to aligning large language models (LLMs) to human preferences. Among the plethora of RLHF techniques, proximal policy optimization (PPO) is of the most widely used methods. Despite its popularity, however, PPO may suffer from mode collapse, instability, and poor sample efficiency. We show that these issues can be alleviated by a novel algorithm that we refer to as Advantage-Induced Policy Alignment (APA), which leverages a squared error loss function based on the estimated advantages. We demonstrate empirically that APA consistently outperforms PPO in language tasks by a large margin, when a separate reward model is employed as the evaluator. In addition, compared with PPO, APA offers a more stable form of control over the deviation from the model's initial policy, ensuring that the model improves its performance without collapsing to deterministic output. In addition to empirical results, we also provide a theoretical justification supporting the design of our loss function