Transforming Growth Factor-b1 polymorphism is not associated with chronic graft disease: evidence from a meta-analysis

Kidney transplantation has been recognised as the optimal treatment choice for most end stage renal disease patients and the increase of allograft survival rates is achieved through the refinement of novel immunosuppressive agents. Chronic Graft Disease (CGD) is a multifactorial process that likely includes a combination of immunological, apoptotic and inflammatory factors. The application of individualised immunosuppressive therapies will also depend on the identification of risk factors that can influence chronic disease. Despite being the subject of several independent studies, investigations of the relationship between transforming growth factor-b1 (TGF-b1) polymorphisms and kidney graft outcome continue to be plagued by contradictory conclusions.

Toxin and Growth Responses of the Neurotoxic Dinoflagellate Vulcanodinium rugosum to Varying Temperature and Salinity

Vulcanodinium rugosum, a recently described species, produces pinnatoxins. The IFR-VRU-01 strain, isolated from a French Mediterranean lagoon in 2010 and identified as the causative dinoflagellate contaminating mussels in the Ingril Lagoon (French Mediterranean) with pinnatoxin-G, was grown in an enriched natural seawater medium. We tested the effect of temperature and salinity on growth, pinnatoxin-G production and chlorophyll a levels of this dinoflagellate. These factors were tested in combinations of five temperatures (15, 20, 25, 30 and 35 °C) and five salinities (20, 25, 30, 35 and 40) at an irradiance of 100 µmol photon m−2 s−1. V. rugosum can grow at temperatures and salinities ranging from 20 °C to 30 °C and 20 to 40, respectively. The optimal combination for growth (0.39 ± 0.11 d−1) was a temperature of 25 °C and a salinity of 40. Results suggest that V. rugosum is euryhaline and thermophile which could explain why this dinoflagellate develops in situ only from June to September. V. rugosum growth rate and pinnatoxin-G production were highest at temperatures ranging between 25 and 30 °C. This suggests that the dinoflagellate may give rise to extensive blooms in the coming decades caused by the climate change-related increases in temperature expected in the Mediterranean coasts.

Indole acetic acid and ACC deaminase fromendophytic bacteria improves the growth of Solanum lycopersicum

Background: Endophytic bacteria are ubiquitous in all plant species contributing in host plant\'s nutrient uptake and helping the host to improve its growth. Moringa peregrina which is a medicinal plant, growing in arid region of Arabia, was assessed for the presence of endophytic bacterial strains. Results: PCR amplification and sequencing of 16S rRNA of bacterial endophytes revealed the 5 endophytic bacteria, in which 2 strains were from Sphingomonas sp.; 2 strains from Bacillus sp. and 1 from Methylobacterium genus. Among the endophytic bacterial strains, a strain of Bacillus subtilis LK14 has shown significant prospects in phosphate solubilization (clearing zone of 56.71 mm after 5 d), ACC deaminase (448.3 ± 2.91 nM α-ketobutyrate mg-1 h-1) and acid phosphatase activity (8.4 ± 1.2 nM mg-1 min-1). The endophytic bacteria were also assessed for their potential to produce indole-3-acetic acid (IAA). Among isolated strains, the initial spectrophotometry analysis showed significantly higher IAA production by Bacillus subtilis LK14. The diurnal production of IAA was quantified using multiple reactions monitoring method in UPLC/MS–MS. The analysis showed that LK14 produced the highest (8.7 μM) IAA on 14th d of growth. Looking at LK14 potentials, it was applied to Solanum lycopersicum , where it significantly increased the shoot and root biomass and chlorophyll (a and b) contents as compared to control plants. Conclusion: The study concludes that using endophytic bacterial strains can be bio-prospective for plant growth promotion, which might be an ideal strategy for improving growth of crops in marginal lands.

Análisis de posicionamiento en el sector de servicios de hosterías en el Valle de Yunguilla y propuesta de diseño de un plan estratégico de marketing para la hostería “Los Cisnes” en el periodo 2015-2018

El proyecto está enfocado al desarrollo de un Plan Estratégico aplicado a Hostería “Los Cisnes”. Tiene como objetivo contribuir con el desarrollo organizacional de la empresa, hacer frente a la competencia con la finalidad de prestar un servicio de calidad.Para la consecución de lo mencionado anteriormente se realizó un esquema que contempla lo siguiente: Se Expone conceptos y definiciones básicos de marketing que se necesitarán a lo largo del desarrollo del proyecto para el entendimiento del mismo.Se realizó el estudio del sector mediante encuestas y entrevistas aplicadas a personas que hacen uso del servicio de hostería y a los administradores de estos establecimientos. Para la obtención de resultados se utilizó el programa SPSS donde se emplearon variables e indicadores. Se estableció un ranking de acuerdo al catastro de establecimientos otorgado por el Ministerio de Turismo, encontrándose Hostería Los Cisnes en el tercer lugar, esto de acuerdo a la encuesta aplicada por las autoras del trabajo de titulación. Se desarrolló la situación actual de la empresa mediante herramientas como: análisis del micro-entrono y macro-entorno, análisis FODA, matriz EFI, matriz EFE, matriz BCG. Se desarrolló el Plan Estratégico de Marketing que contempla: misión, visión, objetivos, implementación de estrategias, planes de acción y presupuestos, es decir, está formado por todos los recursos necesarios para posicionamiento de la empresa.Finalmente se presenta las conclusiones y recomendaciones que fortalezcan la realización de las estrategias planteadas y que a la vez determinen resultados óptimos para la hostería.

Two near-optimal layouts for trusslike bridge structures bearing uniform weight between supports

Although the primary objective on designing a structure is to support the external loads, the achievement of an optimal layout that reduces all costs associated with the structure is an aspect of increasing interest. The problem of finding the optimal layout for bridgelike structures subjected to a uniform load is considered. The problem is formulated following a theory on economy of frame structures, using the stress volume as the objective function and including the selection of appropriate values for statically indeterminate reactions. It is solved in a function space of finite dimension instead of using a general variational approach, obtaining near-optimal solutions. The results obtained with this profitable strategy are very close to the best layouts known to date, with differences of less than 2% for the stress volume, but with a simpler layout that can be recognized in some real bridges. This strategy could be a guide to preliminary design of bridges subject to a wide class of costs.

The Territorial Dimension: The Component of Business Strategy that Prevents the Generation of Social Conflicts

Taking advantage of economic opportunities has led to numerous conflicts between society and business in various geographies of the world. Companies have developed social responsibility programs to prevent and manage these types of problems. However, some authors comment that these programs lack a strategic vision. Starting with the Working with People model, created for the field of rural development planning, this paper proposes a methodology to prevent the generation of social conflicts from business strategy: the territorial dimension. The proposal emphasizes that local development support prevents the generation of social conflicts. Finally, an experience in Peru, a country that has been characterized in recent years by high economic growth and also by the presence of social conflicts that have stopped entrepreneurship is analyzed.

Feeding strategy with alternate fasting and refeeding: effects on farmed pacu production

P>A 36-day trial was conducted to determine the effects of repetitive periods of food restriction and refeeding on growth and energy metabolism in pacu (Piaractus mesopotamicus). A total 264 juvenile fish (36.9 +/- 2.8 g) were fed with the experimental diet for 36 days using three regimes: (i) feeding daily to satiation (FD); (ii) no feed for 3 days, then feeding the same amount offered to the control groups for the next 3 days (NF/R controlled); and (iii) no feed for 3 days, then feeding to apparent satiation for the next 3 days (NF/R at satiation). The treatments were distributed into four tanks each. WG and SGR were higher in FD group. Fish refed showed hyperphagia just up to the second day of refeeding. The worst feed conversion rate and the lowest protein efficiency ratio were found in fish NF/R controlled. The lowest values of visceral fat somatic index were found in both fasted fish groups, particularly in NF/R at satiation. The LL and glycogen concentrations, and the hepatosomatic index were all elevated in both feed restricted fish. Muscle lipid showed a tendency to decrease after the cycle of fasting and refeeding. Plasma free fatty acids and glucose levels were elevated in fish subjected to feeding restrictions while serum triglycerides levels were reduced. Triiodothyronine levels were significantly depressed in fish from the NF/R-controlled group and remained at the same levels as the control fish in fish NF/R at satiation. Results indicated that fish subjected to cyclic periods of 3-day satiation or controlled feeding after 3-days of fasting were unable to achieve the final body weight of fish fed to satiation after 36 days.

Use of Bioscreen C for growth of Mucor hiemalis in different carbon and nitrogen sources

O sistema automatizado Bioscreen C foi utilizado para o crescimento de quatro linhagens de Mucor hiemalis, isoladas do solo da Estação Ecológica de Juréia-Itatins (EEJI), estado de São Paulo, em meios líquidos com uma única fonte de carbono (2%) ou de nitrogênio (1%), pH 5,0, a 25ºC, e agitação de 150rpm por 5 dias. O meio com somente uma única fonte de nitrogênio foi adicionado com 2% de glicose. As leituras de densidade óptica foram realizadas a 540nm, em intervalos de 2h, por cinco dias. Os resultados foram analisados estatisticamente com o Teste de Friedman (alfa = 5%). Os melhores crescimentos foram obtidos com as linhagens M1, M2 e M3, que atingiram o início da fase log em 60 horas de cultivo. As melhores fontes de carbono variaram de acordo com a linhagem estudada, e extrato de levedura provou ser a melhor fonte de nitrogênio para todas as linhagens. Acetato de sódio inibiu o crescimento das quatro linhagens, sendo a M3 a mais afetada. O uso do sistema automatizado foi muito conveniente para as culturas em meio liquido, sendo rápido e automático, constituindo em uma boa técnica para a determinação das condições ambientais ótimas para crescimento de fungos filamentosos.

Revisión sistemática utilidad de asa y calcio con o sin vitamina d en la prevención de cáncer colorrectal y la recurrencia de pólipos adenomatosos en paciente con riesgo de padecer esta patología

Introducción: El cáncer colorrectal es una patología con alto impacto en la salud pública, debido a su prevalencia, incidencia, severidad, costo e impacto en la salud mental y física del individuo y la familia. Ensayos clínicos realizados en pacientes con antecedente de infarto al miocardio que consumían ácido acetil salicílico (asa), calcio con y sin vitamina D, mostraron asociación entre el consumo de estos medicamentos y disminución en la incidencia en cáncer colorrectal y pólipos adenomatosos. Objetivo: Evaluar la literatura sobre el uso de asa, calcio con y sin vitamina D con relación a su impacto en la prevención del cáncer colorrectal y pólipos adenomatosos. Métodos: Se realizó revisión sistemática buscando ensayos clínicos realizados en pacientes con factores de riesgo para cáncer colorrectal y pólipos adenomatosos que usaron asa, calcio con y sin vitamina D fueron incluidos. Resultados: se escogieron 105 para la revisión sistemática. Conclusiones: Es necesario desarrollar más estudios que lleven a evaluar el efecto protector de la aspirina, calcio y vitamina D. En los artículos revisados la aspirina a dosis de 81 a 325 mg día se correlaciona con reducción de riesgo de aparición de CRC aunque la dosis ideal, el tiempo de inicio y la duración de la ingesta continua no son claros. Hacen falta estudios que comparen poblaciones con ingesta de asa a diferentes dosis.

Design of experiment in drug development: optimal allocations in multi-arm clinical trials and design space for multi-step processes

In this thesis, we deal with the design of experiments in the drug development process, focusing on the design of clinical trials for treatment comparisons (Part I) and the design of preclinical laboratory experiments for proteins development and manufacturing (Part II). In Part I we propose a multi-purpose design methodology for sequential clinical trials. We derived optimal allocations of patients to treatments for testing the efficacy of several experimental groups by also taking into account ethical considerations. We first consider exponential responses for survival trials and we then present a unified framework for heteroscedastic experimental groups that encompasses the general ANOVA set-up. The very good performance of the suggested optimal allocations, in terms of both inferential and ethical characteristics, are illustrated analytically and through several numerical examples, also performing comparisons with other designs proposed in the literature. Part II concerns the planning of experiments for processes composed of multiple steps in the context of preclinical drug development and manufacturing. Following the Quality by Design paradigm, the objective of the multi-step design strategy is the definition of the manufacturing design space of the whole process and, as we consider the interactions among the subsequent steps, our proposal ensures the quality and the safety of the final product, by enabling more flexibility and process robustness in the manufacturing.

Development of Optimal Energy Management Strategies for a Hybrid Boat

The present work proposes different approaches to extend the mathematical methods of supervisory energy management used in terrestrial environments to the maritime sector, that diverges in constraints, variables and disturbances. The aim is to find the optimal real-time solution that includes the minimization of a defined track time, while maintaining the classical energetic approach. Starting from analyzing and modelling the powertrain and boat dynamics, the energy economy problem formulation is done, following the mathematical principles behind the optimal control theory. Then, an adaptation aimed in finding a winning strategy for the Monaco Energy Boat Challenge endurance trial is performed via ECMS and A-ECMS control strategies, which lead to a more accurate knowledge of energy sources and boat’s behaviour. The simulations show that the algorithm accomplishes fuel economy and time optimization targets, but the latter adds huge tuning and calculation complexity. In order to assess a practical implementation on real hardware, the knowledge of the previous approaches has been translated into a rule-based algorithm, that let it be run on an embedded CPU. Finally, the algorithm has been tuned and tested in a real-world race scenario, showing promising results.

Progettazione, modellazione e integrazione di risorse rinnovabili per promuovere lo sfruttamento dell'energia da moto ondoso e la Blue Growth.

L’energia da onda potrebbe assumere un ruolo fondamentale per la transizione energetica durante i prossimi decenni, grazie alla sua continuità nel tempo molto superiore rispetto ad altre risorse rinnovabili e alla sua vasta distribuzione nello spazio. Tuttavia, l’energia da onda è ancora lontana dall’essere economicamente sostenibile, a causa di diverse problematiche tecnologiche e alle difficoltà finanziarie associate. In questa ricerca, si è innanzitutto affrontata una delle maggiori sfide tecniche, nello specifico la progettazione e modellazione di sistemi di ancoraggio per i dispositivi galleggianti, proponendo possibili soluzioni per la modellazione numerica di sistemi di ancoraggio complessi e per l’ottimizzazione dei dispositivi stessi. Successivamente sono state analizzate le possibili sinergie strategiche di installazioni per lo sfruttamento della energia da onda con altre risorse rinnovabili e la loro applicazione nel contesto di aree marine multiuso. In particolare, una metodologia per la valutazione della combinazione ottimale delle risorse rinnovabili è stata sviluppata e verificata in due diversi casi studio: un’isola e una piattaforma offshore. Si è così potuto evidenziare l’importante contributo della risorsa ondosa per la continuità energetica e per la riduzione della necessità di accumulo. Inoltre, è stato concepito un metodo di supporto decisionale multicriteriale per la valutazione delle opzioni di riuso delle piattaforme offshore alla fine della loro vita operativa, come alternativa al decommissionamento, nell’ottica di una gestione sostenibile e della ottimizzazione dell’uso dello spazio marino. Sulla base dei criteri selezionati, l’inclusione di attività innovative come la produzione di energia da onda si è dimostrata essere rilevante per rendere vantaggioso il riuso rispetto al decommissionamento. Numerosi studi recenti hanno infatti sottolineato che, nell’ambito della “crescita blu”, i mercati come l’oil&gas, le attività offshore e le isole stimoleranno lo sviluppo di tecnologie innovative come lo sfruttamento dell’energia da onda, promuovendo la sperimentazione e fornendo un importante contributo all’avanzamento tecnico e alla commercializzazione.

A 3D biomimetic in vitro model: a novel strategy to investigate glioma biology

Gliomas are one of the most frequent primary malignant brain tumors. Acquisition of stem-like features likely contributes to the malignant nature of high-grade gliomas and may be responsible for the initiation, growth, and recurrence of these tumors. In this regard, although the traditional 2D cell culture system has been widely used in cancer research, it shows limitations in maintaining the stemness properties of cancer and in mimicking the in vivo microenvironment. In order to overcome these limitations, different three-dimensional (3D) culture systems have been developed to mimic better the tumor microenvironment. Cancer cells cultured in 3D structures may represent a more reliable in vitro model due to increased cell-cell and cell-extracellular matrix (ECM) interaction. Several attempts to recreate brain cancer tissue in vitro are described in literature. However, to date, it is still unclear which main characteristics the ideal model should reproduce. The overall goal of this project was the development of a 3D in vitro model able to reproduce the brain ECM microenvironment and to recapitulate pathological condition for the study of tumor stroma interactions, tumor invasion ability, and molecular phenotype of glioma cells. We performed an in silico bioinformatic analysis using GEPIA2 Software to compare the expression level of seven matrix protein in the LGG tumors with healthy tissues. Then, we carried out a FFPE retrospective study in order to evaluate the percentage of expression of selected proteins. Thus, we developed a 3D scaffold composed by Hyaluronic Acid and Collagen IV in a ratio of 50:50. We used two astrocytoma cell lines, HTB-12 and HTB-13. In conclusion, we developed an in vitro 3D model able to reproduce the composition of brain tumor ECM, demonstrating that it is a feasible platform to investigate the interaction between tumor cells and the matrix.

Growth performance, gut health, and metabolism of broilers under thermoneutral and heat stress conditions: multidisciplinary studies on the effects of nutritional strategies and genotype

This PhD project aimed to (i) investigate the effects of three nutritional strategies (supplementation of a synbiotic, a muramidase, or arginine) on growth performance, gut health, and metabolism of broilers fed without antibiotics under thermoneutral and heat stress conditions and to (ii) explore the impacts of heat stress on hypothalamic regulation of feed intake in three broiler lines from diverse stages of genetic selection and in the red jungle fowl, the ancestor of domestic chickens. Synbiotic improved feed efficiency and footpad health, increased Firmicutes and reduced Bacteroidetes in the ceca of birds kept in thermoneutral conditions, while did not mitigate the impacts of heat stress on growth performance. Under optimal thermal conditions, muramidase increased final body weight and reduced cumulative feed intake and feed conversion ratio in a dose-dependent way. The highest dose reduced the risk of footpad lesions, cecal alpha diversity, the Firmicutes to Bacteroidetes ratio, and butyrate producers, increased Bacteroidaceae and Lactobacillaceae, plasmatic levels of bioenergetic metabolites, and reduced the levels of pro-oxidant metabolites. The same dose, however, failed to reduce the effects of heat stress on growth performance. Arginine supplementation improved growth rate, final body weight, and feed efficiency, increased plasmatic levels of arginine and creatine and hepatic levels of creatine and essential amino acids, reduced alpha diversity, Firmicutes, and Proteobacteria (especially Escherichia coli), and increased Bacteroidetes and Lactobacillus salivarius in the ceca of thermoneutral birds. No arginine-mediated attenuation of heat stress was found. Heat stress altered protein metabolism and caused the accumulation of antioxidant and protective molecules in oxidative stress-sensitive tissues. Arginine supplementation, however, may have partially counterbalanced the effects of heat stress on energy homeostasis. Stable gene expression of (an)orexigenic neuropeptides was found in the four chicken populations studied, but responses to hypoxia and heat stress appeared to be related to feed intake regulation.

Trajectory planning of single and dual-arm robots for time-optimal handling of liquids and objects

This Thesis studies the optimal control problem of single-arm and dual-arm serial robots to achieve the time-optimal handling of liquids and objects. The first topic deals with the planning of time-optimal anti-sloshing trajectories of an industrial robot carrying a cylindrical container filled with a liquid, considering 1-dimensional and 2-dimensional planar motions. A technique for the estimation of the sloshing height is presented, together with its extension to 3-dimensional motions. An experimental validation campaign is provided and discussed to assess the thoroughness of such a technique. As far as anti-sloshing trajectories are concerned, 2-dimensional paths are considered and, for each one of them, three constrained optimizations with different values of the sloshing-height thresholds are solved. Experimental results are presented to compare optimized and non-optimized motions. The second part focuses on the time-optimal trajectory planning for dual-arm object handling, employing two collaborative robots (cobots) and adopting an admittance-control strategy. The chosen manipulation approach, known as cooperative grasping, is based on unilateral contact between the cobots and the object, and it may lead to slipping during motion if an internal prestress along the contact-normal direction is not prescribed. Thus, a virtual penetration is considered, aimed at generating the necessary internal prestress. The stability of cooperative grasping is ensured as long as the exerted forces on the object remain inside the static-friction cone. Constrained-optimization problems are solved for 3-dimensional paths: the virtual penetration is chosen among the control inputs of the problem and friction-cone conditions are treated as inequality constraints. Also in this case experiments are presented in order to prove evidence of the firm handling of the object, even for fast motions.