Regulating our immediate feelings, needs, and urges is a task that we are faced with every day in our lives. The effective regulation of our emotions enables us to adapt to society, to deal with our environment, and to achieve long‐term goals. Deficient emotion regulation, in contrast, is a common characteristic of many psychiatric and neurological conditions. Particularly anxiety disorders and subclinical states of increased anxiety are characterized by a range of behavioral, autonomic, and neural alterations impeding the efficient down‐regulation of acute fear. Established fear network models propose a downstream prefrontal‐amygdala circuit for the control of fear reactions but recent research has shown that there are a range of factors acting on this network. The specific prefrontal cortical networks involved in effective regulation and potential mediators and modulators are still a subject of ongoing research in both the animal and human model. The present research focused on the particular role of different prefrontal cortical regions during the processing of fear‐relevant stimuli in healthy subjects. It is based on four studies, three of them investigating a different potential modulator of prefrontal top‐down function and one directly challenging prefrontal regulatory processes. Summarizing the results of all four studies, it was shown that prefrontal functioning is linked to individual differences in state anxiety, autonomic flexibility, and genetic predisposition. The T risk allele of the neuropeptide S receptor gene, a recently suggested candidate gene for pathologically elevated anxiety, for instance, was associated with decreased prefrontal cortex activation to particularly fear‐relevant stimuli. Furthermore, the way of processing has been found to crucially determine if regulatory processes are engaged at all and it was shown that anxious individuals display generally reduced prefrontal activation but may engage in regulatory processes earlier than non‐anxious subjects. However, active manipulation of prefrontal functioning in healthy subjects did not lead to the typical behavioral and neural patterns observed in anxiety disorder patients suggesting that other subcortical or prefrontal structures can compensate for an activation loss in one specific region. Taken together, the current studies support prevailing theories of the central role of the prefrontal cortex for regulatory processes in response to fear‐eliciting stimuli but point out that there are a range of both individual differences and peculiarities in experimental design that impact on or may even mask potential effects in neuroimaging research on fear regulation. / Tagtäglich sind wir gefordert, die Kontrolle über unsere unmittelbaren Gefühle und Bedürfnisse zu bewahren und diese zu regulieren. Die effektive Kontrolle unserer Emotionen ermöglicht es uns, uns unserer Umgebung und Gesellschaft anzupassen und langfristige Ziele zu erreichen. Defizitäre Emotionsregulation, im Gegensatz, charakterisiert eine Reihe von psychiatrischen und neurologischen Erkrankungen. Vor allem Angststörungen und subklinisch erhöhte Ängstlichkeit zeichnen sich durch eine Reihe von behavioralen, vegetativen und neuronalen Abweichungen aus, welche sich störend auf die effiziente Furchtregulation auswirken. Gängige Modelle des Furchtnetzwerks gehen davon aus, dass Furchtreaktionen durch eine top‐down Verschaltung von Präfrontalkortex und Amygdala reguliert werden. Neure Studien jedoch haben gezeigt, dass dieses Netzwerk durch eine Reihe von Faktoren beeinflusst wird. Die spezifischen präfrontalen kortikalen Netzwerke, die an einer effektiven Regulation beteiligt sind und deren potentielle Mediatoren und Modulatoren sind jedoch noch immer Gegenstand heutiger Forschung, sowohl im Tier‐, als auch im Menschenmodell. Der Fokus der vorliegenden Arbeit richtete sich speziell auf die Rolle verschiedener Regionen des Präfrontalkortex während der Verarbeitung furchtrelevanter Reize bei gesunden Probanden. Die Arbeit basiert auf vier Studien, von denen drei jeweils einen potentiellen Modulator präfrontaler top-down Funktion näher untersuchten, während jene regulatorischen Prozesse in einer weiteren Studie gezielt manipuliert wurden. Zusammenfassend konnte gezeigt werden, dass die Präfrontalfunktion mit individuellen Unterschieden in Ängstlichkeit, vegetativer Flexibilität und genetischer Prädisposition assoziiert ist. So wurde beispielsweise das T Risikoallel des Neuropeptid S Rezeptor Gens, ein erst kürzlich entdecktes Kandidatengen für pathologisch erhöhte Ängstlichkeit, speziell während der Darbietung furchtrelevanter Reize mit geringerer Präfrontalkortex Aktivierung in Verbindung gebracht. Des Weiteren konnte gezeigt werden, dass die Art der Verarbeitung im Wesentlichen bestimmt, ob überhaupt regulatorische Vorgänge in Gang gesetzt werden und dass insbesondere ängstliche Probanden eine allgemein verminderte präfrontale Aktivierung zeigen. Die Ergebnisse deuten jedoch auch darauf hin, dass diese regulatorischen Prozesse bei Ängstlichen möglicherweise früher aktiviert werden als bei weniger Ängstlichen. Das aktive Eingreifen in die Präfrontalfunktion bei Gesunden führte jedoch nicht zu den typischen neuronalen und Verhaltensmustern, wie sie bei Patienten mit Angststörungen beobachtet werden, was wiederum die Annahme nahe legt, dass andere subkortikale oder präfrontale Strukturen für eine Aktivitätsverringerung in einer bestimmten Region kompensieren können. Zusammenfassend kann gesagt werden, dass die vorliegenden Ergebnisse aktuelle Theorien einer zentralen Rolle des Präfrontalkortex in Bezug auf regulatorische Prozesse während der Konfrontation mit furchtrelevanten Reizen untermauern, jedoch auch zeigen, dass es eine Reihe an individuellen Charakteristika und Feinheiten im jeweiligen experimentellen Design gibt, die potentielle Effekte in Bildgebungsstudien zur Furchtregulation beeinflussen oder sogar maskieren können.

In Canada, flax (<i>Linum usitatissimum</i> L.) is grown for its seed oil. However, a major disadvantage associated with growing oilseed flax is that the straw is difficult to incorporate into the soil after harvest. Instead, the majority of flax straw is burned in the field, increasing the workload for farmers, as well as creating air pollution. Agronomic concerns are also associated with burning, since it leaves fields vulnerable to wind and water erosion. A small market exists for Canadian flax straw for making high quality paper products and some plastic composites. However, fibre-based and fibre-using industries are growing world wide, and flax straw fibre is becoming an important product. Flax straw fibre concentration varies among cultivars and environments. Consistently high fibre concentrations are essential if the fibre in oilseed flax is to become an important product for Canadian farmers. This study assembled the agronomic information necessary to select for increased straw fibre concentration in the Crop Development Centre (CDC) Flax Breeding Program. Three experiments were conducted to determine: how seeding rate and row spacing effects straw fibre concentration, the effects of seeding date on straw fibre concentration, and how nitrogen fertilizer rates effects straw fibre concentration. Seeding in mid-May at either an 18 or 36 cm row spacing at a seeding rate of 30 or 45 kg/ha resulted in high straw fibre concentration without reducing other important oilseed characteristics such as seed yield, oil content and straw fibre yield. Nitrogen fertilizer did not have an effect on either straw fibre concentration or straw fibre yield.

La industria farmacéutica necesita disponer de métodos analíticos rápidos y fiables para poder controlar de forma eficiente tanto las materias primas como los productos intermedios o finales y, en un sentido amplio, el proceso de fabricación. En esta memoria se presentan métodos de análisis aplicables a las distintas necesidades que existen en el control de calidad de la industria farmacéutica, utilizando como técnica la espectroscopia en el infrarrojo próximo (NIR). Esta técnica, implementada con métodos quimiómetricos de reconocimiento de pautas y de calibración multivariable, se ha aplicado tanto en análisis cualitativo como en análisis cuantitativo. La identificación de preparados farmacéuticos se ha llevado a cabo mediante la construcción de bibliotecas de espectros NIR. Como caso particular se ha estudiado si el método de identificación de un preparado farmacéutico era capaz de detectar pequeñas desviaciones en el nivel de concentración de alguno de sus componentes, así como la capacidad de éste para detectar la presencia de pequeñas contaminaciones del producto racémico al trabajar con preparados que presentan algún componente enantioméricamente puro.En el desarrollo de métodos cuantitativos para la determinación de principios activos en diversos preparados, se han tratado los problemas presentes cuando se analizan muestras que presentan heterogeneidad tanto en el tamaño de partícula como en el contenido de principio activo de los diferentes tamaños. También se ha estudiado el uso de muestras sintéticas con el de dopadas en la matriz de calibración, observándose que existen ciertas diferencias entre los dos tipos de muestras de laboratorio que no permiten su utilización de forma indistinta.Para que los métodos de análisis NIR de productos farmacéuticos sean aceptados como métodos de control por las autoridades sanitarias, es necesario realizar su validación. Debido a que no existen normativas específicas para la validación de métodos NIR se han adaptado las normas existentes de la International Conference on Harmonisation (ICH). Una vez desarrollado y validado un modelo de calibración, éste ya se puede utilizar como método de control en la industria farmacéutica. Sin embargo, es necesario llevar a cabo un estudio de los resultados obtenidos a lo largo del tiempo. Se ha propuesto efectuar una corrección del modelo cuando se detectan pequeñas variaciones sistemáticas en los resultados. / Pharmaceutical industry needs fast and reliable analytical methods in order to control raw materials, intermediates and final products efficiently. In this work, analysis methods applicable to the quality control needs of the pharmaceutical industry have been developed. The chosen technique was near-infrared spectroscopy (NIR). This technique, implemented with multivariate calibration and pattern recognition procedures, has been applied both in qualitative and quantitative analysis. The identification of pharmaceutical preparations has been done generating a NIR spectral library. In particular, it has been studied whether a pharmaceutical identification method was able to identify small deviations in the concentration level of its components, and also the capacity of the method to detect small contaminations of the racemic product when the preparations contain some pure enantiomer compound.In the development of quantitative methods for the determination of active compound in different preparations, the problems of the analysis of samples showing heterogeneity both in the particle size and in the active compound content of the different particle size have been studied. Also, the use of synthetic and doped samples in the calibration matrix has been compared in terms of performance, concluding that the two types of laboratory samples are therefore different in some aspects, which precludes using them indifferently.In order to get that NIR analysis methods of pharmaceutical preparations are accepted as control methods by sanity authorities, a validation must be done. Due to the lack of a specific normative for NIR methods validation, the International Conference on Harmonisation (ICH) normative has been adapted to the case.Once the calibration model has been developed and validated it can be used as a control method in the pharmaceutical industry. Nevertheless, there must be an study of the results obtained along the time. It has been proposed to implement a correction of the method when small systematic variations in the results are detected.

In Canada, flax (<i>Linum usitatissimum</i> L.) is grown for its seed oil. However, a major disadvantage associated with growing oilseed flax is that the straw is difficult to incorporate into the soil after harvest. Instead, the majority of flax straw is burned in the field, increasing the workload for farmers, as well as creating air pollution. Agronomic concerns are also associated with burning, since it leaves fields vulnerable to wind and water erosion. A small market exists for Canadian flax straw for making high quality paper products and some plastic composites. However, fibre-based and fibre-using industries are growing world wide, and flax straw fibre is becoming an important product. Flax straw fibre concentration varies among cultivars and environments. Consistently high fibre concentrations are essential if the fibre in oilseed flax is to become an important product for Canadian farmers. This study assembled the agronomic information necessary to select for increased straw fibre concentration in the Crop Development Centre (CDC) Flax Breeding Program. Three experiments were conducted to determine: how seeding rate and row spacing effects straw fibre concentration, the effects of seeding date on straw fibre concentration, and how nitrogen fertilizer rates effects straw fibre concentration. Seeding in mid-May at either an 18 or 36 cm row spacing at a seeding rate of 30 or 45 kg/ha resulted in high straw fibre concentration without reducing other important oilseed characteristics such as seed yield, oil content and straw fibre yield. Nitrogen fertilizer did not have an effect on either straw fibre concentration or straw fibre yield.

This thesis reports the synthesis of new near infrared dyes in three chapters. The first two chapters outline the synthetic procedure for synthesizing mono- and pentamethine cyanine dyes. The initial chapter encompasses the synthesis of asymmetric monomethine dyes with red-shifted optical properties. The second chapter involves the synthesis and assessment of new symmetrical quinolin-4-yl and phenanthridin-6-yl pentamethine dyes as potential oxidative DNA cleavage agents. The last chapter of the thesis details the synthesis and evaluation of new phenoxizinum dyes as contrast agents for insulunomia, a pancreatic cancer. Furthermore, all new compounds were characterized via NMR and their coherent optical properties were obtained.

Zugl.: Kassel, Univ., Diss., 2006

Zugl.: Kassel, Univ., Diss., 2006 / Download lizenzpflichtig

Universiẗat, Diss., 2003--München.

University, Diss., 2006--Kassel. / Download lizenzpflichtig.

University, Diss., 2001--Bremen.