CHARACTERIZATION OF NOVEL CYP26B1-INHIBITOR, DX314, FOR THE TREATMENT OF KERATINIZATION DISORDERS

Our skin, particularly the barrier provided by the epidermis, functions as our primary protection from the harsh environment. It protects us from dangerous pathogens, allergens, ultraviolet radiation, and mechanical injury, as well as playing a major role in fluid and thermal regulation. Disruption of skin functions can lead to life-threatening consequences due to increased risk of infection, trans-epidermal water loss, and allergen sensitization. Many common skin disorders often result in a disrupted skin barrier placing patients at risk of complications. Retinoic acid (RA) is a major component of the vitamin A pathway, which critically controls multiple skin functions including cell proliferation and differentiation, barrier maintenance and immune regulation. Retinoid-based therapies have successfully been used to treat various skin disorders, such as ichthyosis and Darier’s disease, however, the prevalence of adverse effects, including dry skin, irritation, redness, photosensitivity, and barrier dysregulation, can result in complications and poor compliance. Novel, selective, retinoic acid metabolism blocking agents (RAMBAs), intended to minimize adverse effects and improve patient outcomes, have been designed and synthesized by our lab. In these studies, we first investigated whether our novel RAMBA, DX314, can potentiate the effects of RA, via inhibition of the RA-metabolizing enzyme, CYP26B1, in healthy human epidermis models. By studying the gene expression effects of RA, DX314, and two previous-generation RAMBAs (liarozole and talarozole), we show that DX314 does potentiate the effects of RA. Additionally, by studying its effect on epidermal histology and transepithelial electrical resistance, we discovered that DX314 displays a unique skin barrier-reinforcing property. In our second series of studies, we investigated DX314’s therapeutic potential in Darier’s disease and ichthyosis. These results confirm DX314’s ability to potentiate RA, and its barrier-reinforcing properties, in diseased skin models and suggest that DX314 has potential as a novel therapeutic agent for keratinization disorders. Together, the studies within this dissertation show our next-generation RAMBA, DX314, is a strong candidate for further drug development in the context of keratinization disorders. If successful, DX314 could fulfill the therapeutic need for an efficacious, selective RAMBA, providing improved patient outcomes and quality of life, with greatly reduced adverse effects relative to current treatment options

Digital Music Notation Data Model and Prototype Delivery System

The UVa Library requests $161,175 in outright funds from NEH to collaborate with the University of Paderborn in Detmold, Germany, to produce a Music Encoding Initiative (MEI) demonstration project and to engage in dissemination efforts that will establish MEI as the predominant academic encoding standard for music notation. The demonstration project will include basic software for transforming material into MEI, a searchable archive of representative MEI-encoded data, and a prototype delivery system for items in the archive. This will allow the scholarly community to overcome the limitations of today's printed editions by extending the potential of digital editions, implementing new methodological techniques for music research, and facilitating collaboration between musicologists

Thermal Energy Simulation of Buildings based on the CityGML Energy Application Domain Extension

The present paper describes a semi-automatic process, in which a typical CityGML 3D building model is enriched with explicit thermal energy related information and stored in a CityGML Application Domain Extension (ADE). Special emphasis is given to the discussion of suitability of existing CityGML models for city-wide energy simulations. Possible conflicts between the requirements of urban energy simulation systems, the capabilities of the CityGML Energy ADE and the available data are presented, which can be partly resolved by specific geometric / semantic corrections of the model data. For testing and evaluating the approach, interfaces for two building energy simulation systems have been developed

Stand und Perspektiven der Nutzung von MEI in der Musikwissenschaft und in Bibliotheken

Ausgehend von einer Darstellung der (an TEI angelehnten) Entwicklung von MEI werden die Forschungsperspektiven des Einsatzes dieses für wissenschaftliche Zwecke geschaffenen Formats und speziell das Potential seines umfangreichen Header-Bereichs beschrieben. Am Beispiel der Rolle von Faksimiles in Editionen wird deutlich, wie dieses Format zu einer neuen Zusammenarbeit von Wissenschaft und Bibliotheken beitragen kann.Starting from the description of the development of MEI (which has to be seen in parallel with TEI) the paper deals with the perspectives of the usage of this format, which was designed for scholarly purposes and, in the library context, has high potentials especially in the header-section. The role of facsimiles in editions illustrates how this format might contribute to a new way of collaboration between the scholarly and the library world

Digital Music Notation Data Model and Prototype Delivery System

The U.Va. Library requests $44,164 in outright funds from NEH to collaborate with the University of Paderborn in Detmold, Germany, in conducting two workshops, one to be held in summer 2009 and one in spring 2010, which will promote an international collaboration to create a music notation data model and prototype delivery system. We intend to engage a select group of international scholars and technologists with a broad range of expertise in discussing the features and functions required in a scholarly XML music notation model, critically evaluate the existing data models, discuss optimum solutions for achieving the desired features, and plan for future implementation of the solutions. Our long-term plans include applying for further grant funding to continue to develop this project after this basic collaboration is complete

Магнитоэлектрический двигатель для привода рулевой колонки автотранспортного средства

Научная квалификационная работа посещена исследованию пульсаций электромагнитного момента в магнитоэлектрическом двигателе рулевой колонки автотранспортного средства. В первой главе выполнен обзор исследований на тему магнитоэлектрических машин с различной компоновкой магнитов на роторе и осуществлена постановка задачи научной квалификационной работы. Во второй главе рассмотрены вопросы имитационного моделирования магнитоэлектрической машины в конечно-элементной компьютерной среде. Выполнено планирование эксперимента, получена взаимосвязь между количеством пазов ротора, зубцами статора, коэрцитивной силы магнитов с позиции значений электромагнитного момента. В третьей главе выполнен расчет связанной модели магнитоэлектрический двигатель-инвертор напряжения-система управления.Scientific qualification work is visited to a research of pulsations of the electromagnetic torque in the magnetoelectric motor of a steering column of the vehicle. In chapter 1 the review of researches on magnetoelectric machine with various configuration of magnets on a rotor is executed and problem definition of scientific qualification work is carried out. In chapter 2 questions of a simulation modeling of the magnetoelectric machine in the terminating and element computer environment are considered. Scheduling of an experiment is executed, the interrelation between quantity of poles of a rotor, tooths of a stator, a coercive force of magnets from a position of values of the electromagnetic torque is received. In a chapter 3 calculation of the bound model the magnetoelectric motor