Sustained-release formulations for compounds underlying intestinal drug efflux

ZusammenfassungDie Sekretion von Arzneistoffen aus Darmzellen zurück ins Darmlumen, die durch intestinale Transporter wie P-Glykoprotein (P-GP) vermittelt wird, stellt eine bekannte Quelle für unvollständige und variable Bioverfügbarkeiten und für Interaktionen mit anderen Arzneimitteln und Nahrungsbestandteilen dar. Dennoch liegen bisher keine Veröffentlichungen vor, die sich mit daraus resultierenden Konsequenzen für die Entwicklung neuer peroraler Darreichungsformen befassen. Ziel der vorliegenden Arbeit war es, deutlich zu machen, dass dem Auftreten von intestinalen Sekretionsphänomenen bei der Entwicklung von Retardarzneimitteln Rechnung getragen werden muss.Dazu wurden effektive Permeabilitäten für den Modellarzneistoff Talinolol in unterschiedlichen Darmabschnitten anhand eines Rattendarmperfusionsmodells bestimmt.Des weiteren wurde eine Retardformulierung für den Modellarzneistoff Talinolol entwickelt. Dabei wurde gezeigt, dass die Verwendung unterschiedlicher Puffer als Wirkstofffreisetzungmedien zur Ausbildung unterschiedlicher Talinolol-Kristallstrukturen führt.Die neu entwickelten Retardmatrixtabletten wurden mit Hilfe des Pharmakokinetik-Computersoftwareprogrammes Gastro Plus® evaluiert. Das Zusammenspiel von verlangsamter Wirkstofffreigabe aus der Arzneiform und intestinaler Sekretion führte zu einer deutlich verringerten Bioverfügbarkeit der Modellsubstanz Talinolol aus der Retardformulierung im Vergleich zu schnellfreisetzenden Arzneiformen.Daher sollte der Einfluß intestinaler sekretorischer Transporter wie P-GP bei der Entwicklung von Retardarzneiformen unbedingt berücksichtigt werden.

Vantaggi e limiti dell'integrazione tra sistemi di traduzione assistita e sistemi di traduzione automatica

Computer-assisted translation (or computer-aided translation or CAT) is a form of language translation in which a human translator uses computer software in order to facilitate the translation process. Machine translation (MT) is the automated process by which a computerized system produces a translated text or speech from one natural language to another. Both of them are leading and promising technologies in the translation industry; it therefore seems important that translation students and professional translators become familiar with this relatively new types of technology. Whether used together, not only might these two different types of systems reduce translation time, but also lead to a further improvement in the field of translation technologies. The dissertation consists of four chapters. The first one surveys the chronological development of MT and CAT tools, the emergence of pre-editing, post-editing and controlled language and the very last frontiers in this sector. The second one provide a general overview on the four main CAT tools that are used nowadays and tested hereto. The third chapter is dedicated to the experimentations that have been conducted in order to analyze and evaluate the performance of the four integrated systems that are the core subject of this dissertation. Finally, the fourth chapter deals with the issue of terminological equivalence in interlinguistic translation. The purpose of this dissertation is not to provide an objective and definitive solution to the complex issues that arise at any time in the field of translation technologies, this aim being well away from being achieved, but to supply information about the limits and potentiality that are typical of those instruments which are now essential to any professional translator.

Angiofil-mediated visualization of the vascular system by microcomputed tomography: a feasibility study

Visualization of the vascular systems of organs or of small animals is important for an assessment of basic physiological conditions, especially in studies that involve genetically manipulated mice. For a detailed morphological analysis of the vascular tree, it is necessary to demonstrate the system in its entirety. In this study, we present a new lipophilic contrast agent, Angiofil, for performing postmortem microangiography by using microcomputed tomography. The new contrast agent was tested in 10 wild-type mice. Imaging of the vascular system revealed vessels down to the caliber of capillaries, and the digital three-dimensional data obtained from the scans allowed for virtual cutting, amplification, and scaling without destroying the sample. By use of computer software, parameters such as vessel length and caliber could be quantified and remapped by color coding onto the surface of the vascular system. The liquid Angiofil is easy to handle and highly radio-opaque. Because of its lipophilic abilities, it is retained intravascularly, hence it facilitates virtual vessel segmentation, and yields an enduring signal which is advantageous during repetitive investigations, or if samples need to be transported from the site of preparation to the place of actual analysis, respectively. These characteristics make Angiofil a promising novel contrast agent; when combined with microcomputed tomography, it has the potential to turn into a powerful method for rapid vascular phenotyping.

Effect of progressive mandibular advancement on pharyngeal airway size in anesthetized adults.

BACKGROUND: General anesthesia in adult humans is associated with narrowing or complete closure of the pharyngeal airway. The purpose of this study was to determine the effect of progressive mandibular advancement on pharyngeal airway size in normal adults during intravenous infusion of propofol for anesthesia. METHODS: Magnetic resonance imaging was performed in nine normal adults during wakefulness and during propofol anesthesia. A commercially available intraoral appliance was used to manually advance the mandible. Images were obtained during wakefulness without the appliance and during anesthesia with the participants wearing the appliance under three conditions: without mandibular advancement, advancement to 50% maximum voluntary advancement, and maximum advancement. Using computer software, airway area and maximum anteroposterior and lateral airway diameters were measured on the axial images at the level of the soft palate, uvula, tip of the epiglottis, and base of the epiglottis. RESULTS: Airway area across all four airway levels decreased during anesthesia without mandibular advancement compared with airway area during wakefulness (P < 0.007). Across all levels, airway area at 50% advancement during anesthesia was less than that at centric occlusion during wakefulness (P = 0.06), but airway area with maximum advancement during anesthesia was similar to that during wakefulness (P = 0.64). In general, anteroposterior and lateral airway diameters during anesthesia without mandibular advancement were decreased compared with wakefulness and were restored to their wakefulness values with 50% and/or maximal advancement. CONCLUSIONS: Maximum mandibular advancement during propofol anesthesia is required to restore the pharyngeal airway to its size during wakefulness in normal adults.

Whole-Genome Sequencing of a Canine Family Trio Reveals a FAM83G Variant Associated with Hereditary Footpad Hyperkeratosis

Over 250 Mendelian traits and disorders, caused by rare alleles have been mapped in the canine genome. Although each disease is rare in the dog as a species, they are collectively common and have major impact on canine health. With SNP-based genotyping arrays, genome-wide association studies (GWAS) have proven to be a powerful method to map the genomic region of interest when 10-20 cases and 10-20 controls are available. However, to identify the genetic variant in associated regions, fine-mapping and targeted re-sequencing is required. Here we present a new approach using whole-genome sequencing (WGS) of a family trio without prior GWAS. As a proof-of-concept, we chose an autosomal recessive disease known as hereditary footpad hyperkeratosis (HFH) in Kromfohrl änder dogs. To our knowledge, this is the first time this family trio WGS-approach, has successfully been used to identify a genetic variant that perfectly segregates with a canine disorder. The sequencing of three Kromfohrl änder dogs from a family trio (an affected offspring and both its healthy parents) resulted in an average genome coverage of 9.2X per individual. After applying stringent filtering criteria for candidate causative coding variants, 527 single nucleotide variants (SNVs) and 15 indels were found to be homozygous in the affected offspring and heterozygous in the parents. Using the computer software packages ANNOVAR and SIFT to functionally annotate coding sequence differences and to predict their functional effect, resulted in seven candidate variants located in six different genes. Of these, only FAM83G:c155G>C (p.R52P) was found to be concordant in eight additional cases and 16 healthy Kromfohrl änder dogs.

El color en las aceitunas negras naturales de mesa : nueva técnica de mensura digitalizada para optimizar el método de oscurecimiento natural

Se aplicó un nuevo método para la evaluación objetiva del color en aceitunas de mesa, basado en el análisis de la intensidad de reflexión de cada uno de los colores primarios que componen la luz blanca (rojo, verde y azul), según las longitudes de onda del Sistema RGB. Se trabajó con programas informáticos para el análisis de imágenes digitales color tipo BMP de 24 bits. Este trabajo proporciona mayor información sobre el pardeamiento de las aceitunas naturales en salmuera, lo que sería muy útil para incrementar la efectividad del proceso. El método propuesto es rápido y no destructivo, prometiendo ser muy práctico ya que permite que una misma muestra pueda ser evaluada en el tiempo. Se investigaron los cambios de color en aceitunas elaboradas naturalmente, con diferentes grados de madurez (pintas, rojas y negras) y a diferentes valores de pH (3,6 - 4,0 - 4,5), expuestas al aire durante períodos crecientes de tiempo. Se cuantificó el grado de oscurecimiento a través de Índices de Intensidad de Reflexión. La evolución del índice de reflexión en función del tiempo generó una curva polinomial de 4° grado que reveló el comportamiento sigmoidal del fenómeno de pardeamiento enzimático, con la máxima correlación a las 8 horas de aireación. Esta función permitiría predecir el fenómeno de pardeamiento en las aceitunas negras y representa una medición objetiva del grado relativo de pardeamiento. La evolución del color rojo (λ = 700,0 nm) exhibió la mayor correlación con el proceso de pardeamiento. Las aceitunas rojas naturales a pH 4,5 presentaron óptimo pardeamiento. El espectro de reflexión para el color azul (λ = 435,8 nm) se sugiere como medida de la actividad de la enzima PPO (polifenoloxidasa).

Mensura digitalizada de la evolución del color en aceitunas según el grado de madurez del fruto

Se desarrolló un nuevo método para la valoración objetiva del color en las aceitunas, mediante el análisis de la intensidad de la reflexión de los colores primarios (rojo, verde y azul) que componen la luz blanca. Se trabajó con programas informáticos para el análisis de imágenes digitales color tipo BMP de 24 bits. Este método es rápido, objetivo, no destructivo y puede ser muy útil cuando se requiere una técnica eficiente para determinar el grado de madurez de las aceitunas o de otros alimentos.

IT Clusters in India

One of the facilitating factors that enabled the rise of IT industry in India is the evolution of IT clusters. A study of these clusters can provide interesting insights. The rise of the Banglaore IT cluster was due, among other things, to some of the policies the Indian government took three decades or earlier. It would be difficult to talk of "benign neglect" of the government towards this sector. Different factors worked in the case of Hyderabad. A comparison between the IT clusters in India has much to tell the new emerging IT clusters in India as well as those outside of it.

IT Offshoring and India: Some Implications

There has been a large spurt in the offshore outsourcing of Information Technology (IT) recently. India has been a major recipient of such work. There have been loud protests against the "loss" of jobs in the US as work was shifted to India. The large inflow of IT related work has also had major impact on the Indian economy. There are implications on the foreign policy level as well. While the economic implications are well known, we try to see a little of the foreign policy implications in this paper.

A Semantic Scraping Model for Web Resources - Applying Linked Data to Web Page Screen Scraping

In spite of the increasing presence of Semantic Web Facilities, only a limited amount of the available resources in the Internet provide a semantic access. Recent initiatives such as the emerging Linked Data Web are providing semantic access to available data by porting existing resources to the semantic web using different technologies, such as database-semantic mapping and scraping. Nevertheless, existing scraping solutions are based on ad-hoc solutions complemented with graphical interfaces for speeding up the scraper development. This article proposes a generic framework for web scraping based on semantic technologies. This framework is structured in three levels: scraping services, semantic scraping model and syntactic scraping. The first level provides an interface to generic applications or intelligent agents for gathering information from the web at a high level. The second level defines a semantic RDF model of the scraping process, in order to provide a declarative approach to the scraping task. Finally, the third level provides an implementation of the RDF scraping model for specific technologies. The work has been validated in a scenario that illustrates its application to mashup technologies

A survey of agent-oriented methodologies

This article introduces the current agent-oriented methodologies. It discusses what approaches have been followed (mainly extending existing object oriented and knowledge engineering methodologies), the suitability of these approaches for agent modelling, and some conclusions drawn from the survey.

Realización de un procedimiento para la medida del coeficiente de absorción sonora normal

El objetivo de este trabajo es la elaboración de un procedimiento para la medida del coeficiente de absorción sonora normal en un tubo de impedancia. Para ello se han estudiado los fundamentos básicos de la ecuación de ondas y sus soluciones. Se han considerado las soluciones pertinentes que describen el comportamiento de una onda sonora dentro de un tubo rígido. Se ha considerado también la teoría básica de funciones de transferencia. Estas teorías son claves a la hora de poder desarrollar el procedimiento de medida, ya que el coeficiente de absorción acústica se obtendrá con la ayuda de un tubo de impedancias que mide las funciones de transferencia entre dos posiciones de micrófonos incorporados en una de las caras del tubo. La utilización de esta técnica tiene como principal ventaja, la necesidad de poco espacio en un laboratorio y el empleo de muestras pequeñas de material. La implementación de los visto teóricamente a su aplicación práctica se ha hecho a través de un procedimiento de medida que sigue la Norma UNE-EN ISO 10534-2 (2002) “Determinación del coeficiente de absorción sonoro y la impedancia en tubos de impedancia Parte 2: método función de transferencia”. El valor del coeficiente de absorción se puede obtener a través de una instrumentación específica y un programa computador. Para poder validar los cálculos que realiza el programa utilizado, se ha realizado una batería de medidas del coeficiente de absorción a diferentes tipos de materiales acústicos, y los cálculos se han hecho por la vía del programa y por la vía de una hoja de cálculo. Como parte del procedimiento de medida se ha calculado la incertidumbre en las medidas. En definitiva se pretende contribuir con este trabajo a establecer un procedimiento de medida del comportamiento acústico de diversos materiales. SUMMARY. The aim of this work is the development of a procedure for measuring the sound absorption coefficient normal of an impedance tube. To this end we have studied the basics of the wave equation and its solutions. We have considered the relevant solutions that describe the behavior of a sound wave in a rigid tube. It has also considered the basic theory of transfer functions. These theories are key when we want to develop the measurement method, since the absorption coefficient is obtained with the aid of an impedance tube measuring transfer functions between two positions of microphones incorporated into one side of the tube. The use of this technique has the main advantage, the need of little space on a laboratory and use of small samples of material. The implementation of theoretically seen to his practical application has been made through a measurement procedure following the UNE-EN ISO 10534-2 (2002) "Determination of sound absorption coefficient and impedance in impedance tubes Part 2 : transfer function method ". The value of the absorption coefficient can be obtained through a specific instrumentation and computer software. In order to validate the calculations performed by the program used, there has been realized a series of measures of the absorption coefficient at different types of acoustical materials, and calculations were made by means of the program and by means of a spreadsheet. As part of the measurement procedure has been estimated uncertainty in the measurements. Ultimately it’s tried to contribute with this work to establish a procedure measuring the acoustic behavior of various materials.

Análisis comparativo de series temporales de precio de diferentes metales : obtención de una serie -resumen

El objetivo de este proyecto de investigación es analizar el conjunto de las diez series temporales, relativas a los precios de diez metales (plata, aluminio, oro, cobre, níquel, paladio, plomo, platino, estaño y zinc), comprendidos en el periodo de enero de 2008 a septiembre de 2013, con el objetivo de reducir la dimensionalidad del conjunto de datos y facilitar la comparación de los mismos y la predicción de valores futuros. Para ello pretendemos aplicar una metodología, que nos permitirá deducir, a partir de una serie resumen y de unos coeficientes multiplicativos, la evolución del comportamiento de cualquier otro metal. Pese a la escasísima documentación existente al respecto, se valorará e intentará aplicarse una reciente metodología denominada “Metodología del haz de rectas” Como herramienta de trabajo para los programas informáticos desarrollados y para representar las gráficas asociadas al proyecto, se utilizó Matlab®, habida cuenta de su enorme potencia y por disponer de un lenguaje de programación sencillo y lo suficientemente versátil para las tareas que necesitamos. Abstract. The objective of this research project is to analyze the set of ten time series on prices of the ten metals (silver, aluminum, gold, copper, nickel, palladium, lead, platinum, tin and zinc), included in the period January 2008 to September 2013, with the aim of reducing the dimensionality of the data set and to facilitate comparison of the data and the prediction of future values To apply this methodology, allowing us to predict, from a series summarizes the evolution of the behavior of any other metal. This methodology is called "straight beam Methodology" As a tool for developing computer software and associated graphs to represent the project, Matlab® was used in view of its enormous power and have a simple programming language and versatile enough for the tasks we need

Enhancement of a body area network to support smart health monitoring at the digital home

The deployment of home-based smart health services requires effective and reliable systems for personal and environmental data management. ooperation between Home Area Networks (HAN) and Body Area Networks (BAN) can provide smart systems with ad hoc reasoning information to support health care. This paper details the implementation of an architecture that integrates BAN, HAN and intelligent agents to manage physiological and environmental data to proactively detect risk situations at the digital home. The system monitors dynamic situations and timely adjusts its behavior to detect user risks concerning to health. Thus, this work provides a reasoning framework to infer appropriate solutions in cases of health risk episodes. Proposed smart health monitoring approach integrates complex reasoning according to home environment, user profile and physiological parameters defined by a scalable ontology. As a result, health care demands can be detected to activate adequate internal mechanisms and report public health services for requested actions.

Increasing the Intelligence of Virtual Sales Assistants through Knowledge Modeling Techniques

Shopping agents are web-based applications that help consumers to find appropriate products in the context of e-commerce. In this paper we argue about the utility of advanced model-based techniques that recently have been proposed in the fields of Artificial Intelligence and Knowledge Engineering, in order to increase the level of support provided by this type of applications. We illustrate this approach with a virtual sales assistant that dynamically configures a product according to the needs and preferences of customers.