Multiobjective strategies for New Product Development in the pharmaceutical industry

New Product Development (NPD) constitutes a challenging problem in the pharmaceutical industry, due to the characteristics of the development pipeline. Formally, the NPD problem can be stated as follows: select a set of R&D projects from a pool of candidate projects in order to satisfy several criteria (economic profitability, time to market) while coping with the uncertain nature of the projects. More precisely, the recurrent key issues are to determine the projects to develop once target molecules have been identified, their order and the level of resources to assign. In this context, the proposed approach combines discrete event stochastic simulation (Monte Carlo approach) with multiobjective genetic algorithms (NSGAII type, Non-Sorted Genetic Algorithm II) to optimize the highly combinatorial portfolio management problem. In that context, Genetic Algorithms (GAs) are particularly attractive for treating this kind of problem, due to their ability to directly lead to the so-called Pareto front and to account for the combinatorial aspect. This work is illustrated with a study case involving nine interdependent new product candidates targeting three diseases. An analysis is performed for this test bench on the different pairs of criteria both for the bi- and tricriteria optimization: large portfolios cause resource queues and delays time to launch and are eliminated by the bi- and tricriteria optimization strategy. The optimization strategy is thus interesting to detect the sequence candidates. Time is an important criterion to consider simultaneously with NPV and risk criteria. The order in which drugs are released in the pipeline is of great importance as with scheduling problems

Multiobjective strategies for New Product Development in the pharmaceutical industry

New Product Development (NPD) constitutes a challenging problem in the pharmaceutical industry, due to the characteristics of the development pipeline. Formally, the NPD problem can be stated as follows: select a set of R&D projects from a pool of candidate projects in order to satisfy several criteria (economic profitability, time to market) while coping with the uncertain nature of the projects. More precisely, the recurrent key issues are to determine the projects to develop once target molecules have been identified, their order and the level of resources to assign. In this context, the proposed approach combines discrete event stochastic simulation (Monte Carlo approach) with multiobjective genetic algorithms (NSGAII type, Non-Sorted Genetic Algorithm II) to optimize the highly combinatorial portfolio management problem. In that context, Genetic Algorithms (GAs) are particularly attractive for treating this kind of problem, due to their ability to directly lead to the so-called Pareto front and to account for the combinatorial aspect. This work is illustrated with a study case involving nine interdependent new product candidates targeting three diseases. An analysis is performed for this test bench on the different pairs of criteria both for the bi- and tricriteria optimization: large portfolios cause resource queues and delays time to launch and are eliminated by the bi- and tricriteria optimization strategy. The optimization strategy is thus interesting to detect the sequence candidates. Time is an important criterion to consider simultaneously with NPV and risk criteria. The order in which drugs are released in the pipeline is of great importance as with scheduling problems

The environmental impact of artificial lighting in urban settings: gaps, challenges, and sustainable lighting design

Artificial light has significantly impacted the value and perception of the night in individuals who apply it, those who develop technologies to supply it, those who assess its environmental impact, and those who use and benefit from it. The unnatural illumination of nightscapes has become seamlessly integrated into society's fabric, making night-time bright and over-illuminated across landscapes where the natural light (e.g. emitted by the moon and stars) is masked by Artificial Light At Night (ALAN). In this way, ALAN has become a pollutant, known as light pollution (LP), that has emerged with the exponential increase of unnatural brightness and the change in spectral composition induced by improperly managed lighting technologies. ALAN has been shown to alter light environments of nocturnal terrestrial and aquatic habitats, which can impact many organisms' physiological processes, body functions and behaviour, affecting multiple intra- and interspecific interactions and even ecosystem processes. Current technological advances in outdoor lighting have the potential to develop light pollution reduction strategies that balance conflicting societal needs and environmental concerns. However, this potential remains largely untapped due to insufficient communication between ALAN researchers and lighting practitioners. The problem of reducing LP remains complex as it involves the active collaboration between ALAN researchers and lighting practitioners and a lingua franca between experts involved to transfer and translate research into practice. This thesis addresses the environmental impact of artificial lighting in urban settings, including existing communication and knowledge gaps, challenges posed by artificial light in aquatic realms and future perspectives towards sustainable lighting design. To mitigate the communication gaps between ALAN researchers and lighting practitioners, I propose a transdisciplinary framework between the experts in the practice, research, production, policy-making and planning of light and lighting. In collaboration with experts from ALAN research and the lighting practice, I suggest a four-step process to aid in establishing collaboration between the domains involved. Moreover, to set a shared understanding between ALAN research and the lighting practice, I propose a collaborative systematic review to aid in the transfer of diverse responses of plants, arthropods, insects, spiders, fish, amphibians, reptiles, birds, and non-human mammals (including bats, rodents, primates, and ungulates) when exposed to ALAN. As well as a mutual agreement on key terms set by representatives from both domains. The systematic review is based on finally 216 studies reporting behavioural and physiological responses across six relevant organism groups. To transfer the results between the research and the lighting practice, collaborative discussions between the experts of each domain resulted in establishing an ALAN lingua franca on key terminologies and definitions related to natural and artificial light as knowledge both domains should acquaint. The collaborative discussions also included a common language on relevant radiometric and photometric parameters that ALAN researchers must consider in their research and lighting practitioners in their day-to-day lighting practice. Also, the discussions led to the proposal of two communication strategies: a communication framework and a knowledge infrastructure scheme to set an ecological ceiling of awareness (responses to avoid) and a lighting foundation (essential knowledge to gain) for a better flow of information between the domains involved. The findings of this study also indicated that aquatic organisms and their realms remain understudied and that further studies on the impact of ALAN on aquatic habitats and their inhabiting biodiversity are needed. Furthermore, I explored the potential implications of bridge illumination on a river transect to confront the existing knowledge gap on the potential impact of ALAN on riverine systems with illuminated bridges. The light field of a river was quantified from a research vessel considering seven illuminated bridges. The results indicated that LP was induced by surrounding illumination and bridge illumination. Via a conceptual model, the unnatural light scenarios at illuminated bridges and their potential impact on the life history of two migrating fish species, Atlantic salmon and European silver eels, were addressed. Additionally, at the same river transect and illuminated bridges, patterns of polarised light pollution (PLP) reflecting at the water's surface were quantified near the illuminated bridges and their potential effects on aquatic insects were discussed. The findings of the four studies highlight the need for (i) better communication frameworks between experts of ALAN research and the lighting practice, (ii) transdisciplinary interfaces and collaborations to efficiently translate ecological research into the lighting practice, as well as the need for (iii) quantified ALAN and PLP across inland waters to develop sustainable lighting solutions to preserve riverine nightscapes. This thesis provides communication frameworks to bridge communication gaps, a knowledge infrastructure scheme to mitigate the transfer of knowledge between the domains, evidence on LP and PLP induced by surrounding and bridge illumination on a river transect, together with a conceptual model on ALAN as a potential barrier for migrating fish. Additionally, this thesis discusses transdisciplinary approaches, perspectives inclusive of natural environments, and a vision towards lighting approaches that require an urgent change and concludes with recommendations for the future of ALAN research and the lighting practice

The Evolution of Luminous Compact Blue Galaxies: Disks or Spheroids?

Luminous compact blue galaxies (LCBGs) are a diverse class of galaxies characterized by high luminosity, blue color, and high surface brightness that sit at the critical juncture of galaxies evolving from the blue to the red sequence. As part of our multi-wavelength survey of local LCBGs, we have been studying the HI content of these galaxies using both single-dish telescopes and interferometers. Our goals are to determine if single-dish HI observations represent a true measure of the dynamical mass of LCBGs and to look for signatures of recent interactions that may be triggering star formation in LCBGs. Our data show that while some LCBGs are undergoing interactions, many appear isolated. While all LCBGs contain HI and show signatures of rotation, the population does not lie on the Tully-Fisher relation nor can it evolve onto it. Furthermore, the HI maps of many LCBGs show signatures of dynamically hot components, suggesting that we are seeing the formation of a thick disk or spheroid in at least some LCBGs. There is good agreement between the HI and H-alpha kinematics for LCBGs, and both are similar in appearance to the H-alpha kinematics of high redshift star-forming galaxies. Our combined data suggest that star formation in LCBGs is primarily quenched by virial heating, consistent with model predictions.Comment: 4 pages, 2 figures, to appear in the proceedings of IAU Symposium 277, "Tracing the Ancestry of Galaxies on the Land of our Ancestors", eds. C. Carignan, K.C. Freeman, and F. Combe

Propuestas de Desarrollo Turístico comunitario, en la comunidad de Huehuete Municipio de Jinotepe, del Departamento de Carazo en el período de Agosto a Diciembre del 2012

El presente trabajo consiste en la elaboración de una propuesta de Desarrollo Turístico Comunitario en la Comunidad de Huehuete, municipio de Jinotepe del Departamento de Carazo, con el fin de generar dichas alternativas que ayuden al desarrollo económico de dicha comunidad. Se procedió a la recopilación de Información acerca de la situación actual comunitaria mediante el análisis Interno y Externo de la comunidad, los cuales describen el estado social, económico, cultural, infraestructura, equipamiento turístico y recursos con que cuenta la Comunidad. Con el presente trabajo se pretende proponer la implementación del Turismo Comunitario como una alternativa de aprovechamiento de los Recursos existentes de manera Sostenible, mediante la práctica de actividades turísticas que puedan generar ingresos económicos a cada una de las familias prestadoras de servicios que de cómo resultado el mejoramiento de la calidad de vida de las mismas. Así mismo este trabajo contiene Propuestas de Acciones Estratégicas Sostenibles en cuanto a productos y servicios, para tal fin se tiene que tomar en cuenta el aspecto Organizacional, ya que de tal manera habrá un mejor Desarrollo Sostenible y el beneficio llegara a todas las familias. De igual forma es importante tomar en cuenta el aspecto Medio Ambiente debido a que todos los beneficio económicos que se obtienen en la Industria Turística provienen mayormente de los Recursos Naturales, es por eso que es necesario presérvalos. De igual manera se identificaron las causas que impiden que esta comunidad no se esté desarrollando turísticamente, las cuales no permiten que empresas e inversionistas tengan el interés a invertir en proyectos turísticos que podrían ayudar a mejorar la calidad de vida de las familias de la comunida

Efecto de la proporción de pulpa de manzana: zumo de piña: extracto de zanahoria, en las características fisicoquímicas, contenido de compuestos fenólicos, olor y sabor de un batido funcional.

Se evaluó el efecto la proporción de pulpa de manzana, variedad Israel (0-100%), zumo de piña, variedad Golden (0-100%) y extracto de zanahoria, variedad Chantenay (0-100%) en las características pH, sólidos solubles, tono, croma, fenoles totales, apreciación del olor y sabor del batido funcional. Se aplicó un diseño de mezclas simplex centroide ampliado, con la finalidad de obtener el modelo matemático adecuado para representar el comportamiento de las variables en estudio y establecer la combinación estimada de los factores que permita optimizar las variables respuesta (pH, sólidos solubles, tono, croma, fenoles totales, apreciación del olor y sabor). El análisis estadístico indicó que el efecto de la proporción de pulpa de manzana, zumo de piña y extracto de zanahoria en el pH, sólidos solubles, croma, olor y sabor del batido funcional fue significativo. Un modelo lineal describió el comportamiento de las variables: sólidos solubles, olor y sabor, con valores de coeficientes de determinación R2 de 0.955, 0.917 y 0.912; respectivamente. El pH y croma se ajustaron a un modelo cuadrático, significativo, con coeficiente de determinación R2 de 0.991 y 0.956, respectivamente. Para fenoles totales y tono, ningún modelo pudo describir el fenómeno en estudio. La proporción de pulpa de manzana, zumo de piña, y extracto de zanahoria, que optimizaron las variables pH, sólidos solubles, croma, olor y sabor a partir de la superposición de contornos, fue de 83.62% de pulpa de manzana: 12.62% de zumo de piña: 3.70% de extracto de zanahoria, al obtener respuestas estimadas de pH: 3.54, sólidos solubles: 13.14 °Brix, croma: 48.49%, olor: 7.14, sabor: 7.01. Se validaron los resultados estimados para las variables pH: 3.51, sólidos solubles: 13.37 °Brix, olor: 7.11 y sabor: 7.34, al presentar desviaciones menores a 5% entre los valores estimados y experimentales. Los valores de croma no fueron validados por presentar una desviación mayor al 10%.The effect of the proportion of apple pulp, variety Israel (0-100%), pineapple juice, variety Golden (0-100%) and carrot extract, variety Chantenay (0-100%) in the characteristics pH, soluble solids, tone, chroma, total phenols, appreciation of the smell and flavor of the functional smoothie. An extended centroid simplex mix design was applied, in order to obtain the adequate mathematical model to represent the behavior of the variables under study and establish the estimated combination of the factors that allow optimizing the response variables (pH, soluble solids, tone, chroma, total phenols, appreciation of smell and taste). The statistical analysis indicated that the effect of the proportion of apple pulp, pineapple juice and carrot extract in the pH, soluble solids, chroma, odor and flavor of the functional shake was significant. A linear model described the behavior of the variables: soluble solids, odor and taste, with values of coefficients of determination R2 of 0.955, 0.917 and 0.912; respectively. The pH and chroma were adjusted to a significant quadratic model, with coefficient of determination R2 of 0.991 and 0.956, respectively. For total phenols and tone, no model could describe the phenomenon under study. The proportion of apple pulp, pineapple juice, and carrot extract, which optimized the variables pH, soluble solids, chroma, smell and taste from the superposition of contours, was 83.62% of apple pulp: 12.62% pineapple juice: 3.70% of carrot extract, obtaining estimated pH responses: 3.54, soluble solids: 13.14 ° Brix, chroma: 48.49%, odor: 7.14, taste: 7.01. The estimated results for the pH variables were validated: 3.51, soluble solids: 13.37 ° Brix, odor: 7.11 and taste: 7.34, with deviations of less than 5% between the estimated and experimental values. Chroma values were not validated due to a deviation greater than 10%.Tesi

A transitional disk around an intermediate mass star in the sparse population of the Orion OB1 Association

We present a detailed study of the disk around the intermediate mass star SO 411, aiming to explain the spectral energy distribution of this star. We show that this is a transitional disk truncated at $\sim$11 au, with $\sim$0.03 lunar masses of optically thin dust inside the cavity. Gas also flows through the cavity, since we find that the disk is still accreting mass onto the star, at a rate of $\sim 5x10^{-9}$ Msun/yr. Until now, SO 411 has been thought to belong to the $\sim$3 Myr old {$\sigma$} Orionis cluster. However, we analyzed the second Gaia Data Release in combination with kinematic data previously reported, and found that SO 411 can be associated with an sparse stellar population located in front of the {$\sigma$} Orionis cluster. If this is the case, then SO 411 is older and even more peculiar, since primordial disks in this stellar mass range are scarce for ages $>$5 Myr. Analysis of the silicate 10$\mu$m feature of SO 411 indicates that the observed feature arises at the edge of the outer disk, and displays a very high crystallinity ratio of $\sim$0.5, with forsterite the most abundant silicate crystal. The high forsterite abundance points to crystal formation in non-equilibrium conditions. The PAH spectrum of SO 411 is consistent with this intermediate state between the hot and luminous Herbig Ae and the less massive and cooler T Tauri stars. Analysis of the 7.7$\mu$m PAH feature indicates that small PAHs still remain in the SO 411 disk.Comment: Accepted in the Astrophysical Journal (17 pages, 9 Figures

High-quality photonic crystals with a nearly complete band gap obtained by direct inversion of woodpile templates with titanium dioxide

Photonic crystal materials are based on a periodic modulation of the dielectric constant on length scales comparable to the wavelength of light. These materials can exhibit photonic band gaps; frequency regions for which the propagation of electromagnetic radiation is forbidden due to the depletion of the density of states. In order to exhibit a full band gap, 3D PCs must present a threshold refractive index contrast that depends on the crystal structure. In the case of the so-called woodpile photonic crystals this threshold is comparably low, approximately 1.9 for the direct structure. Therefore direct or inverted woodpiles made of high refractive index materials like silicon, germanium or titanium dioxide are sought after. Here we show that, by combining multiphoton lithography and atomic layer deposition, we can achieve a direct inversion of polymer templates into TiO₂ based photonic crystals. The obtained structures show remarkable optical properties in the near-infrared region with almost perfect specular reflectance, a transmission dip close to the detection limit and a Bragg length comparable to the lattice constant