162 research outputs found
The person of architect Vojtěch Dvořák (1852-1925)
No full textThis bachelor work tries to clarify life and work of Ing. Arch. Vojtech Dvorak. The work follows his roots, praxes and teaching activities. Whereas there hasn't been paid much attention to this figure, the content of the work is mostly based on contemporary sources and archives. As Dvorak's work was mostly connected with Brno Czech industrial school, most of materials come from Archive of Brno city. The first chapter of the work describes environment and Dvorak's family background. The next chapter follows Dvorak's education, gaining praxes and important people in his life. The main part of the work contains list of the architect's realizations and take up cooperation between him and his colleague Karel Welzl (12. 3. 1854-22. 11. 1918). The bachelor work also describes Vojtech Dvorak as a person, who left indelible mark in history of the first industrial school in Moravia and outlines him from the perspective of his colleagues, friends and family
Chemical targeting of the membrane transporter for lactate SLC16A3
No full textDie Solute Carrier (SLC)-Superfamilie ist eine vielfältige Gruppe von mehr als 450 Membrantransportern, die in Menschen eine entscheidende Rolle beim Austausch von Molekülen zwischen der Zelle und ihrer Umgebung sowie den einzelnen subzellulären Kompartimenten spielen. Eine Vielzahl von Studien hat die einzelnen Mitglieder der SLC-Superfamilie mit einem breiten Spektrum physiologischer Prozesse und Krankheiten in Verbindung gebracht. Darüber hinaus gelten SLCs als pharmakologisch modulierbare („druggable") und vielversprechende therapeutische Ziele in vielen verschiedenen Krankheiten. Trotzdem bleibt das therapeutische Potential der SLC-Superfamilie zu großen Teilen ungenutzt, hauptsächlich aufgrund mangelnden Verständnisses der biologischen Funktionen vieler SLCs und der begrenzten Verfügbarkeit von Werkzeugen wie biologischen Assays oder niedermolekularer Werkzeuge („tool compounds“), die für eine effektive Untersuchung erforderlich wären.Der einführende Abschnitt dieser Arbeit beleuchtet kurz einige der allgemeinen Charakteristika von SLCs, wobei der Schwerpunkt insbesondere auf der SLC-Pharmakologie und den Assay-Technologien liegt. Jüngste Fortschritte - insbesondere im strukturbiologischen Verständnis von SLCs – ermöglichen die Untersuchung der Wirkungsweise bestehender SLC-Medikamente und somit ein präziseres Verständnis der SLC-Pharmakologie. Anschließend geben wir einen Überblick über die bestehenden SLC-spezifischen Assays und diskutieren ihre breitere Anwendbarkeit sowie SLC-Eigenschaften, die für die molekularbiologische Untersuchung von SLCs und entsprechende Assay-Entwicklung zentral sind.Letztendlich konzentriert sich diese Arbeit auf die Entwicklung einer vielseitigen Assay-Strategie zur SLC-orientierten Identifizierung potentieller SLC-bindender Moleküle und zur anschließenden Entwicklung spezifischer und selektiver Moleküle zur gezielten Bindung und Inhibition einzelner SLCs zu entwickeln. Zu diesem Zweck haben wir ein Assay-System namens "Paralog-dependent isogenic cell assay" oder PARADISO entwickelt, das genetische Interaktionen und funktionaler Überschneidungen zwischen Paralog-Genen gezielt ausnutzt. Das Grundprinzip beruht auf der Konstruktion einer Reihe von Zelllinien, die jeweils individuell auf ein einzelnes Paralog-Gen der Familie für ihr Wachstum oder ihre Überlebensfähigkeit angewiesen sind. Diese Zelllinien werden dann in einer schrittweise Screening-Kampagne verwendet, um hoch selektive Inhibitoren zu identifizieren. Wir konzentrierten uns auf Laktat-Transporter der SLC16-Familie und entwickelten einen hochselektiven und potenten chemischen Inhibitor für SLC16A3. SLC16A3, auch als MCT4 (Monocarboxylat-Transporter 4) bekannt, ist ein Laktat-Transporter mit einer wichtigen und zunehmend anerkannten Rolle in verschiedenen Pathologien, einschließlich Krebs. Der in dieser Arbeit beschriebene Ansatz kann grundsätzlich für andere SLCs, aber auch für andere Proteine verwendet werden und kann besonders nützlich sein, wenn der Zugang zu anderen Assays und molekularen Werkzeugen begrenzt ist.The Solute Carrier (SLC) superfamily is a diverse group of more than 450 membrane transporters which in humans have a crucial role in chemical exchange between the cell and its environment as well as individual subcellular compartments. A multitude of studies connected the individual members of the SLC superfamily to a diverse spectrum of physiological processes and diseases. Moreover, SLCs are considered to be pharmacologically tractable (“druggable”) and promising therapeutic targets in many and diverse diseases. Despite this, the SLC superfamily remains pharmacologically underexploited, mainly due to poor understanding of the biological functions of many SLCs and limited availability of tools such as biological assays or tool compounds that would be required to study them effectively.The introductory section of this thesis briefly reviews some of the general characteristics of SLCs, with a particular focus on the SLC druggability and assay technologies. The recent progress, particularly in structural biology of SLCs, provided an opportunity to survey the mode of actions of existing SLC targeting drugs and thus re-fine the scope of SLC druggability. Subsequently, we provide an overview of the existing kind for SLC-focused assays and discuss their wider applicability as well as SLC characteristics that are important to assess SLC properties that can be monitored.Ultimately, the focus of this thesis is developing a versatile assay strategy for SLC-oriented identification of cognate chemical compounds and consequent development of specific and selective probes targeting individual SLCs. To this end, we developed an assay system called Paralog-dependent isogenic cell assay, or PARADISO, which is based on exploiting the genetic interactions and functional overlap among paralog genes. The core principle relies on engineering a series of cell lines, each individually dependent on a particular paralog gene for its growth or survival fitness. These cell lines are then used in a logical cascade of screening steps that provide for high selectivity. We focused on lactate transporters of the SLC16 family and developed a highly selective and potent small molecule chemical inhibitor targeting SLC16A3. SL16A3, also known as MCT4 (monocarboxylate transporter 4) is a lactate transporter with an important and increasingly recognized role in several disease areas including cancer. The approach described in this thesis can in principle be used for other SLCs, but also other proteins, and can be especially useful when the access to other assays and tool compounds is limited.Abweichender Titel laut Übersetzung der Verfasserin/des VerfassersDissertation Medizinische Universität Wien 202
Vascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages
No full textGenetic depletion of macrophages in Polyoma Middle T oncoprotein (PyMT)-induced mammary tumors in mice delayed the angiogenic switch and the progression to malignancy. To determine whether vascular endothelial growth factor A (VEGF-A) produced by tumor-associated macrophages regulated the onset of the angiogenic switch, a genetic approach was used to restore expression of VEGF-A into tumors at the benign stages. This stimulated formation of a high-density vessel network and in macrophage-depleted mice, was followed by accelerated tumor progression. The expression of VEGF-A led to a massive infiltration into the tumor of leukocytes that were mostly macrophages. This study suggests that macrophage-produced VEGF regulates malignant progression through stimulating tumor angiogenesis, leukocytic infiltration and tumor cell invasion
Dvorak in Spillville
No full textThis is a podcast from Dr. James Schaap\u27s Small Wonders, a series of historical vignettes about regional history for KWIT/KOIA public radio in Sioux City, Iowa. Podcasts of these and other stories from the collection, read by the author, can also be found on the station\u27s website, www.KWIT.org, by entering Professor Schaap\u27s name in the search field
Simulation-based assessment of data center waste heat utilization using aquifer thermal energy storage of a university campus
No full textPublisher Copyright: © 2020, The Author(s).The global energy consumption of data centers (DCs) has experienced exponential growth over the last decade, that is expected to continue in the near future. Reasonable utilization of DC waste heat, which is dissipated during the computational process, can potentially be an effective solution to mitigate the environmental impact. However, the practical implementation of waste heat utilization in the DC environment is a very challenging task. The possible benefits of waste heat utilization are uncertain and difficult to quantify with the methods that are common in practice. This paper introduces a feasibility study in which dynamic simulation tools were used to predict the energy performance of a university campus resulting from the integration of a proposed DC system with an existing aquifer thermal energy storage (ATES). The presented study utilizes building energy simulation (BES) to evaluate uncertainty of the waste heat potential associated to various thermal management strategies of the proposed DC. Further in the feasibility study, the carbon footprint of the integrated approach is assessed for both the current and future situation based on measured data from the existing university campus and its district ATES system.Peer reviewe
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