Development of advanced monitoring and control tools for rAAV production in the insect cell system

"Since the first publication introducing the concept in 1972, gene therapy has had a series of success stories and setbacks. However, the recent rise of awareness, public interest, promising results in clinical trials and recent market approvals indicate that gene therapy has come to stay. Currently there is a growing interest from the biopharmaceutical industry in gene and cell therapy, mostly using viral vectors. (...)

Evidence across different income groups of countries

The major motivation behind the present study is to analyze the interactions between food consumption, economic growth and sustainable development. Considering that high population and income growths will lead the coming decades, an increase in global food demand is expected. Not only in terms of feeding the population but also to satisfy their recent needs of more calorie- and protein-dense foods. Livestock products such a meat are closely related to this trend, but also associated with impacts on the environment and public health. From land and water depletion, to greenhouse gases emissions and higher risks of non-communicable diseases. Therefore, an answer to this problem is needed. The literature suggests that meat consumption should be reduced for the sake of the environment and global population Inspired by these facts, this study employs an empirical approach, analyzing through three income groups and applying a sustainable development indicator, analyze the interactions of food consumption, specially meat consumption as the literature highlights. And the impact on the economy of a possible reduction in meat consumption suggested by the literature. By analyzing for different income groups and using a sustainable development indicator, our findings suggest that meat consumption, economic growth and sustainable development have different relationships considering income level. Succinctly, meat consumption promotes economic growth following the GDP, but neglects the sustainable development ISEW. Evidencing a dilemma between economic growth and economic sustainability. Further research is needed with the objective of further understand which solutions are more effective, as with the intent to promote growth, while considering the environmental perspective.O presente trabalho tem como motivação principal perceber as interações entre o consumo alimentar, crescimento económico e desenvolvimento sustentável. Considerando o elevado crescimento populacional e o acentuado crescimento do rendimento disponível, espera-se que a procura global por alimentos aumente. Não só no sentido de alimentar as populações, mas também de satisfazer uma nova necessidade por produtos densos em calorias e proteínas. Alimentos de pecuária como a carne estão relativamente associados a esta nova tendência, mas também ligados a fortes impactos ambientais e de saúde pública. Perante esta situação, a literatura sugere que o consumo de carne deva ser reduzido pelo benefício do ambiente e da população mundial. Inspirado por estes factos, este estudo aplica uma análise empírica utilizando uma abordagem ARDL de curto- e longo-prazo, destacando uma análise dividida por 3 níveis de rendimento e recorrendo a um indicador de desenvolvimento sustentável, analisando assim o consumo alimentar, em destaque o consumo de carne maioritariamente abordado na literatura. Para além de abordar também o impacto de uma possível redução no consumo de carne, sugerida na literatura, no crescimento económico e desenvolvimento sustentável. Após analisar perante diferentes níveis de rendimento e utilizando um indicador de desenvolvimento que considera o impacto ambiental, os resultados sugerem que o consumo de carne, crescimento económico e desenvolvimento sustentável contemplam diferentes relações conforme o nível de rendimento analisado e a perspetiva crescimento/desenvolvimento abordada. Em resumo, o consumo de carne promove o crescimento económico enquanto, por outro lado, prejudica o desenvolvimento sustentável. Evidenciando um dilema entre as duas perspetivas abordadas. Investigação futura é necessária com objetivo de entender quais a soluções mais eficazes, no sentido de não por em causa o crescimento, salvaguardando a componente de desenvolvimento sustentável

Two-Dimensional Higher-Derivative Supergravity and a New Mechanism for Supersymmetry Breaking

We discuss the general form of quadratic (1,1) supergravity in two dimensions, and show that this theory is equivalent to two scalar supermultiplets coupled to non-trivial supergravity. It is demonstrated that the theory possesses stable vacua with vanishing cosmological constant which spontaneously break supersymmetry.Comment: 22 pages, LaTeX2e and AMS-LaTeX 1.

Algunhas aplicacións do análise funcional á teoría fundamental de EDO e outras ecuacións funcionais

Traballo Fin de Grao en Matemáticas. Curso 2018-2019.[GL] A análise matemática proporciona ferramentas para tratar certas cuestións sobre as ecuacións funcionais. Empréganse moito conceptos como converxencia, derivabilidade,... No primeiro capítulo, vése como, a partir dunha ecuación, chegar a unha solución equivale a atopar puntos fixos, bótando man de métodos iterativos, como o método das aproximaci óns sucesivas para atopalos. Ademáis, defínense termos como a diferenciabilidade, e trátanse resultados relacionados con ela como o problema do valor inicial. No seguinte capítulo, trabállase coas ecuacións integrais, e abórdanse varias formas para solucionalas, xa sexa con series ou empregando sistemas. Cabe destacar, que unha ecuación integral pode transformarse nunha diferencial, polo tanto, resolver ecuacións integrais, é útil para solucionar ecuacións funcionais en xeneral. No derradeiro capítulo, veranse algúns exemplos de ecuacións funcionais, vendo onde aparecen na vida real. Moitos destes exemplos englóbanse nos campos da física ou da estadística, ainda que como sucede coas matemáticas en xeneral, abarcan todos os campos.[ES] El análisis matemático proporciona ciertas herramientas para tratar ciertas cuestiones sobre las ecuaciones funcionales. Se usarán mucho conceptos como convergencia, derivabilidad,.. En el primer capítulo, se verá como, a partir de una ecuación, llegar a una solución equivale a encontrar puntos fijos, echando mano de métodos iterativos, como el método de las aproximaciones sucesivas para hallarlos. Además, se definen términos como la diferenciabilidad, y se tratan resultados relacionados con ella como el problema del valor inicial. En el siguiente capítulo, se trabajará con ecuaciones integrales, y se abordarán varias formas para solucionalas, ya sea con series o usando sistemas. Cabe destacar, que una ecuación integral, se puede transformar en una diferencial, por lo tanto, resolver ecuaciones integrales, es de utilidad para solucionar ecuaciones funcionales en general. En el último capítulo, se veran algunos ejemplos de ecuaciones funcionales, viendo donde aparecen en la vida real. Muchos de estos ejemplos, se engloban en los campos de la física o de la estadística, aunque como sucede con las matemáticas en general, abarcan todos los campos.[EN] Mathematic analysis gives tools to treat certain questions about functional equations. They will be used many terms like convergence, derivability,.. First chapter, it will see how, with a equation, arrive to a solution means find fixed points, using iterative methods, such as the method of successive approximations. In addition, they are defined terms such as differentiation, and results related to it as the problem of the initial value. In the next chapter, it will work with the integral equations, and it will find several paths to solve them, such as sums or using sistems. It should be noted that an integral equation can be transformed into a differential, therefore it focused how to look for solutions of a functional equation in general. In the last chapter, it will see some examples of integral equations, seeing where they happened in the daily life. Many os these examples are included in the fields of physics or statistics, although, as usually happens with maths, they can be seen in all the domains

Forestry harvest planning considering social impacts and soil compaction issues

Forest harvest planning implies great challenges for wood supply companies. This type of planning involves complex decision processes involving different stakeholders, as well as factors outside the stakeholders that directly affect the resolution of the problem. Within these factors that affect, one of special interest is the conditioning by risk of soil compaction. This factor can be decisive in planning since it functions as a restriction or prohibition on harvesting operations. This phenomenon depends on the hydrological balances of the soils, which in turn depends on the meteorological and climatic conditions. That is why to properly address these decision processes, stochastic approaches are required. On the other hand, there exists a large number of SMEs and micro-SMEs that are dedicated to forest harvesting operations, which work as contractors for industries and provide. These companies have a direct interference in the industrial matrix and in the labor offer in the regional economy of the Argentine Northwest. However, a purely utilitarian approach to forest harvesting would tend to prioritize the hiring of larger companies with superior technical capacity, which would allow production costs to be reduced. However, this would impede the possibility of growth of the regional economy, leaving out smaller companies, which do not have the resources for technological migration. This issue has gained relevance after United Nations included this topic in its Sustainable Development Goals agenda (ODS 8).To contribute to this line, an approach based on mathematical programming is proposed that allow addressing the stochastic complexity of the problem (due to the risk of soil compaction), but that balance the workload delivered to each contractor, ensuring compliance with the demand. For this, a goal programming model is developed, which contemplates the minimization of costs and the balancing of the workload among contractors.Fil: Rossit, Daniel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Matemática Bahía Blanca. Universidad Nacional del Sur. Departamento de Matemática. Instituto de Matemática Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería; ArgentinaFil: Broz, Diego Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Misiones. Facultad de Ciencias Forestales; ArgentinaFil: Pais, Cristóbal. University of California at Berkeley; Estados UnidosFil: Weintraub, Andrés. Universidad de Chile.; ChileXXI Latin Ibero-American Conference on Operations Research -CLAIO 2022Buenos AiresArgentinaUniversidad de Buenos Aires. Facultad de Ciencias Exactas y Naturale

Red-Emitting Tetracoordinate Organoboron Chelates: Synthesis, Photophysical Properties, and Fluorescence Microscopy

Seven tetracoordinate organoboron fluorophores with heterobiaryl N,O- or N,N-chelate ligands were prepared and photophysically characterized (in toluene). The electronic variation of the heteroaromatic moiety provided a means for the fine-tuning of the UV/vis absorption and emission spectra. In the most interesting cases, the spectra were red-shifted to maximum absorbance at wavelengths longer than 500 nm and emission maxima between 620 and 660 nm. The pronounced intramolecular charge-transfer character of the dyes yielded large Stokes shifts (3500-5100 cm), while maintaining appreciable fluorescence quantum yields of up to 0.2 for emission maxima longer than 600 nm. The lipophilic character of the dyes enabled their application as stains of vesicle substructures in confocal fluorescence microscopy imaging.Ministerio de Economía y Competitividad CTQ2014-54729 - C2 - 1 - P for U.P., CTQ2013 - 48164 - C2 - 1 - P , CTQ2013 - 48164 - C2 - 2 - P for A.R., CTQ2013 - 41339 - P, CTQ2015 - 71896 - REDT for E.P.I., Ramón y Cajal contract RYC - 2013 - 12585 for A.R.FEDER FundJunta de Andalucía 2012/FQM - 2140 for U.P., 2009/FQM - 4537 and 2012/FQM - 1078 for A.R

Soft Supersymmetry Breaking Induced by Higher-Derivative Supergravitation in the Electroweak Standard Model

We show how spontaneous supersymmetry breaking in the vacuum state of higher-derivative supergravity is transmitted, as explicit soft supersymmetry-breaking terms, to the effective Lagrangian of the standard electroweak model. The general structure of the soft supersymmetry breaking terms is presented and a new scenario for understanding the gauge hierarchy problem, based on the functional form of these terms, is discussed.Comment: LaTeX2e with AMS-LaTeX 1.2, 13 page

Monitoring the production of AAV vectors in insect cells by fluorescence spectroscopy

Adeno-associated viruses (AAV) are among the most promising viral vectors for gene therapy, since they can transduce non-dividing cells from several tissues while maintaining a long-term gene expression. Besides, AAVs possess low immunogenicity compared to other viral vectors, and are physically resistant, which makes them resilient to industrial manufacturing conditions, long-term storage, and in vivo administration. One of the systems available for large scale production of AAVs is the insect cell-baculovirus expression vector system (IC-BEVS). Insect cells grow in suspension to high cell densities with modest growth requirements and without the need of serum supplementation. Consequently, scaling up the production in order to achieve the large number of AAV needed for clinical trials is more straight‑forward than with transfection-based systems. However, methods for online monitoring of AAV production are still lacking. Such methods would allow determination of the best time of harvest in real-time, thus allowing recovery of AAV as soon as its concentration medium was higher. Here we apply Fluorescence Spectroscopy to baculovirus-infected insect cell cultures producing adeno‑associated virus vectors, correlating the spectra to critical process parameters like cell concentration, viability and AAV concentration. Sf9 cells were co-infected with two baculovirus (expressing AAV rep and cap and a CMV-GFP transgene) at low or high multiplicities of infection (MOI), and the culture was followed by Fluorescence Spectroscopy in situ through a bioreactor probe. After an exploratory calibration using data from only one bioreactor, we attested the aptitude of this technique to capture overall data trend: using a 3 component PLS model, we have obtained a calibration NRMSE of 2.9% for total AAV particles per cell, 5.9% for viable cell density and 0.9% for viability). Additional bioreactor productions using different infection parameters (CCI, MOI, time of infection) allowed testing the robustness of fluorescence monitoring to process variability. With this dataset, we tested several pre-treatment methods for the raw spectra, as well as different regression algorithms in order to establish a good predictive model. Ultimately, fluorescence spectroscopy provides a simple tool for online monitoring of key process variables in baculovirus-infected insect cell cultures. Acknowledgments: Funding from Fundação para a Ciência e a Tecnologia, projects EXPL/BBBBIO/1129/2013 and Daniel Pais’ PhD research grant PD/BD/105873/2014

On the properties of NiO powders obtained by different wet chemical methods and calcination

NiO powders were synthesized using coprecipitation, sol-gel, and hydrothermal synthesis methods. The powders were subjected to calcination in atmospheric air, followed by recalcination in an O2-rich atmosphere at 800°C for 2 h each. Characterization techniques, such as scanning electron microscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, and microRaman spectroscopy, were utilized. The coprecipitation and hydrothermal methods resulted in disaggregated submicrometric particles. The average size of particles obtained by the coprecipitation method after calcination in atmospheric air and recalcination in an O2-rich atmosphere was 360 ± 140 nm and 400 ± 130 nm, respectively. Regarding the particles obtained by the hydrothermal method, the average size was 190 ± 50 and 220 ± 80 nm for calcined in atmospheric air and recalcined in O2-rich atmosphere, respectively. Conversely, the sol-gel method produced particle aggregates with an average size of 430 ± 150 nm after calcination in atmospheric air and 500 ± 200 nm for calcination in an O2-rich atmosphere. X-ray diffraction analysis revealed that only the hydrothermal method yielded pure NiO without additional Ni-related phases, irrespective of the calcination procedure. In contrast, the coprecipitation sample exhibited a Ni2O3 phase after calcination in atmospheric air, which disappeared after recalcination in an O2-rich atmosphere. The sol-gel-derived sample maintained a Ni phase after both calcination processes. Analysis of the crystallite size demonstrated an increase after recalcination in an O2-rich atmosphere for the hydrothermal and sol-gel-derived samples, while a decrease was observed for the coprecipitation-derived sample. Raman spectra exhibited defect-enabled first-order forbidden phonon modes that were sensitive to the synthesis route. The two magnon phonon modes also demonstrated dependency on the route, indicating variations in defect structures. Photocatalytic evaluation using methylene blue degradation in aqueous solutions indicated better performance for the powders recalcined in an O2-rich atmosphere.Fil: Alastuey, Patricio. Universidad Nacional de Tucumán. Instituto de Física del Noroeste Argentino. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Física del Noroeste Argentino; ArgentinaFil: Pais Ospina, Daniel Humberto. Universidad Nacional de Tucumán. Instituto de Física del Noroeste Argentino. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Física del Noroeste Argentino; ArgentinaFil: Comedi, David Mario. Universidad Nacional de Tucumán. Instituto de Física del Noroeste Argentino. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Física del Noroeste Argentino; ArgentinaFil: Tirado, Monica Cecilia. Universidad Nacional de Tucumán. Instituto de Física del Noroeste Argentino. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Física del Noroeste Argentino; ArgentinaFil: Marín Ramírez, Oscar Alonso. Universidad Nacional de Tucumán. Instituto de Física del Noroeste Argentino. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Física del Noroeste Argentino; Argentin