The project proposes the production of devices to enhance the value or experience of a place as well as to allow research and education in history, collective memory and contemporary times of the city that we live in. Looking at the city through a specific type of architecture, concept or material, and hopefully giving an honest perspective of the space we inhabit. For this project the topic was contemporary ruins and their structural and visual values. Cataloging the timber barn, exploring it in an industrial hall and then exhibiting them on the concrete dolphins in the river, all buildings or structures created purely for convenience but have since lost all or some of this convenience, therefore becoming contemporary ruins. In the end creating structures with the purpose of learning, exhibiting them for others to learn as well; and in the end finding a place and purpose for the structure. Turning the building from a research project into a folly and then into a device for experience. Producing with the goal of learning, placing with the goal of enhancing, without designing specifically for the end product but rather for the process itself.

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The emergence of drug resistance towards existing drugs is a constant challenge in the fight against many diseases including Malaria and gonorrhoeae. To evade resistance, new targets must be engaged, and to do that, new structural classes of anti-infective must be prepared and evaluated. During the course of my PhD journey, I had the opportunity to investigate and optimize the antimalarial candidate (±)-2-3b, and salicylic acid (4-1a) as an anti-gonorrhea treatment. Malaria is a life-threatening mosquito-borne disease. In 2021, there were 247 million cases of malaria and the estimated number of malaria deaths stood at 619,000. Because of the rapid development of resistance to all current antimalarials, discovery of antimalarials with unexploited mechanisms of action is critical to reduce malaria mortality. In the Carlier group, our initial approach focused on discovery of inhibitors of the methylerythritol phosphate (MEP) pathway for isoprenoid precursor biosynthesis, since this pathway is essential for Plasmodium falciparum and absent in human. Application of the isopentenyl pyrophosphate (IPP) chemical rescue screen to the compounds of the Malaria Box, a collection of 400 antimalaria candidates with unknown mechanisms of action, identified tetrahydro-β-carboline 2-1 (MMV008138) as an inhibitor of the MEP pathway. Chapter 2 of this work discusses similarity searching of the Novartis portion of the hit set (5K compounds), from the original 20K compound hit set of the Malaria Box, and identifying tetrahydro-β-carboline GNF-Pf-5009, designated as (±)-2-3b. Preparation of pure enantiomers, by resolution, demonstrated the pharmacological superiority of (R)-2-3b over (S)-2-3b, which was found to have good asexual blood stage (ABS) inhibition potency against malarial parasites P. falciparum, and low general cytotoxicity. However, (R)-2-3b was found not orally efficacious in a P. berghei mouse model of malaria. We concluded that the lack of oral efficacy of (R)-2-3b was due to its poor drug-like qualities, in particular its high molecular weight and low solubility. Chapter 3 of this work explores modifications of (R)-2-3b ((R)-3-5Aa) that were expected to improve its properties. We show that the new compounds (R)-3-5Gm and (R)-3-5Gk not only are more potent in vitro than (R)-2-3b ((R)-3-5Aa), but also have molecular weights < 500 g/mol. Neisseria gonorrhoeae is the causative agent of the sexually transmitted disease gonorrhea. Due to the increased rates of infection as well as the prevalence of multidrug-resistant N. gonorrhoeae strains worldwide, the World Health Organization (WHO) and the U.S. Centers for Disease Control and Prevention (CDC) list N. gonorrhoeae at the highest possible threat level to public health. Dual therapy of azithromycin (AZM) and ceftriaxone has been the standard-of-care for treatment of gonococcal infections. However, due to increasing resistance to azithromycin (>33% in some regions) the CDC removed AZM from the treatment regimen for gonorrhea in 2020. Therefore, ceftriaxone remains the only recommended antibiotic for treatment of gonococcal infections. However, increasing resistance to this treatment option has been reported, consequently there is an urgent need to identify novel therapeutics against N. gonorrhoeae. Drug repurposing is a popular strategy that explores new therapeutic opportunities for approved drugs with available information on their pharmacokinetic data, dosages, and toxicity. Salicylic acid is a highly privileged chemical scaffold. Also, the use of salicylic acid to treat sexually transmitted diseases (including gonorrhea) was reported as early as the 19th century. Recently, Dr. Mohamed N. Seleem reported that salicylic acid (4-1a) exhibited modest activity against N. gonorrhoeae strains including the AZM-resistant strain (CDC-181). Chapter 4 of this work illustrates how the anti-gonococcal activity in this scaffold is easily lost by inopportune substitution. However, we found that substituted naphthyl analogs (4-3b,o,p) have superior activity to salicylic acid itself. In addition, the three analogs showed high selectivity, compared to AZM, against N. gonorrhoeae over the vaginal microbiota. / Doctor of Philosophy / In the fight against malaria and gonorrhea, two different diseases, we face one common challenge, which is the emergence of drug resistance towards existing drugs. Therefore, there is a pressing need for new antimalarial and anti-gonorrhea compounds with novel mechanisms of action. This dissertation encompasses my research on the investigation and optimization of the antimalarial candidate (±)-2-3b and Salicylic acid (4-1a) as anti-gonorrhea treatment. Malaria is a life-threatening mosquito-borne disease. It is transmitted through the bites of infected female Anopheles mosquitoes. In 2021, there were 247 million cases of malaria and the estimated number of malaria deaths stood at 619,000. Children under 5 accounted for about 80% of all malaria deaths. In the Carlier group, compound 2-1 (MMV008138) was identified and thoroughly studied as antimalaria candidate. It was found to be effective in killing the malaria parasite, P. falciparum, in red blood cells, in vitro. However, when tested on P. berghei mouse model of malaria, it was found not effective. Chapter 2 of this work discusses the discovery of (±)-2-3b after searching for a structurally similar analog of 2-1. The compound (±)-2-3b can exist in two distinct spatial arrangements (enantiomers) R and S. After preparation of pure enantiomers, we confirmed the pharmacological superiority of (R)-2-3b over (S)-2-3b. The compound (R)-2-3b showed good activity in vitro against malarial parasites P. falciparum, and low general cytotoxicity. However when tested orally on P. berghei mouse model of malaria, it was found not effective. We concluded that the lack of oral efficacy of (R)-2-3b was due to its poor drug-like qualities, such as high molecular weight and low solubility. Chapter 3 of this work explore modifications of (R)-2-3b ((R)-3-5Aa) that will improve its properties. We show that the new compounds (R)-3-5Gm and (R)-3-5Gk not only are more active in vitro than (R)-2-3b ((R)-3-5Aa), but also have lower molecular weights (< 500 g/mol). Neisseria gonorrhoeae is the causative agent of the sexually transmitted disease gonorrhea. The World Health Organization (WHO) and the U.S. Centers for Disease Control and Prevention (CDC) list N. gonorrhoeae at the highest possible threat level to public health because of the increased rates of infection and the appearance of multidrug-resistant N. gonorrhoeae strains worldwide. Dual therapy of azithromycin (AZM) and ceftriaxone has been the standard-of-care for treatment of gonococcal infections. However, due to increasing resistance to azithromycin the CDC removed AZM from the treatment regimen. Therefore, ceftriaxone remains the only recommended antibiotic for treatment of gonococcal infections. However, increasing resistance to this treatment option has been reported. Drug repurposing is a popular strategy that explores new therapeutic opportunities for approved drugs with available information on their pharmacokinetic data, dosages, and toxicity. Salicylic acid is a highly privileged chemical scaffold that has been used to treat sexually transmitted diseases (including gonorrhea) since the 19th century. Chapter 4 of this work illustrates our efforts to enhance the potency of salicylic acid (4- 1a). I performed chemical modifications on (4-1a) and concluded that anti-gonococcal activity is easily lost by inopportune substitution. However, we found that substituted naphthyl analogs (4-3b,o,p) have superior activity to salicylic acid itself. In addition, the three analogs showed high selectivity, compared to AZM, against N. gonorrhoeae over the vaginal microbiota.

Pagrindinis šio darbo tikslas buvo atlikti vizualinių dvinarių žvaigždžių TDSC katalogo statistinę analizę, iš šio katalogo atrinkti skirtingų žvaigždžių populiacijų rinkinius ir tuos rinkinius palyginti. Kataloge esantys žvaigždžių duomenys buvo skaičiuojami ir analizuojami pasinaudojant StatSoft STATISTICA kompiuterinių programų paketu. Siekiant atlikti TDSC katalogo statistinę analizę, nustatėme papildomus žvaigždžių parametrus: spalvos rodiklius (B - V)T, pilnus savuosius judėjimus μ, redukuotus savuosius judėjimus HvT. Be to, apskaičiavome šių parametrų absoliutines paklaidas. Visi šie duomenys vėliau buvo panaudoti atliekant statistinę analizę ir sudarant histogramas. Pasinaudoję Jones (1971) straipsnyje publikuotu būdu (pagal žvaigždžių spalvos rodiklių (B - V)T , redukuotų savųjų judėjimų HvT, ir tangentinių greičių Vtan ribas), iš katalogo atrinkome II populiacijos žvaigždes. Visų pirma, atrinkome tik tokias žvaigždes, kurių spalvos rodiklių ir redukuotų savųjų judėjimų reikšmės tenkina tokias sąlygas: HvT ≥ 8,68+4,4*(B-V)T, 0,30 ≤ (B-V)T ≤ 0,80; HvT ≥ 10,2571+2,4286*(B-V)T, 0,80 < (B-V)T ≤ 1,50; HvT ≥ 13,9, (B-V)T > 1,50; Vėliau, iš šių (atitinkančių anksčiau išvardintas sąlygas) žvaigždžių atrinkome tik tas, kurių tangentinių greičių reikšmės tenkino sąlygą Vtan ≥ 60 (km/s). Kadangi TDSC kataloge duomenų apie žvaigždžių atstumus nepateikta, tangentinių greičių nustatymui pasinaudojome paralaksų duomenimis, kuriuos radome kitame astronominių duomenų... [toliau žr. visą tekstą] / The main goals of this work were to perform the statistical analysis of visual binaries from the TDSC (Tycho Double Star Catalogue), divide this catalog into separated sets of stars by their populations, and finally, to compare these stellar populations. All of the catalog data were computed and analyzed by using StatSoft STATISTICA software. To perform the full statistical analysis of the TDSC catalog, we defined additional stellar parameters, like: color index (B – V)T, full proper motion μ, reduced proper motion HvT. In addition, the absolute errors for these parameters were estimated. After that, all of the data were used in statistical analysis, and part of it was used in the creation of histograms. The II population of stars was extracted from catalog using the technique published by Jones (1971). This extraction of II population stars was made by using the limited ranges of star color indexes (B – V)T, reduced proper motions HvT, and tangential velocities Vtan. At first, these ranges of star color index and reduced proper motion were used: HvT ≥ 8,68+4,4*(B-V)T, 0,30 ≤ (B-V)T ≤ 0,80; HvT ≥ 10,2571+2,4286*(B-V)T, 0,80 < (B-V)T ≤ 1,50; HvT ≥ 13,9, (B-V)T > 1,50; Second step, the limit of tangential velocity was added, where Vtan ≥ 60 (km/s). Because of lack of information in TDSC catalog about distances of stars, to determine the tangential velocity, we were forced to use the parallax information from additional catalog (van Leeuwen, 2007.). The... [to full text]

The document contains the catalog of earthquakes in Vogtland /West Bohemia within the period of 2008/10/19 -to- 2009/03/16. The events were recorded by a seismic mini-array operated by the Institute of Earthsciences, University of Postdam. / Das Dokument enthält einen Katalog von Erdbeben im Vogtland/Westböhmen im Zeitraum 2008/10/19 -bis- 2009/03/16. Die Erdbeben wurden mit Hilfe eines seismologischen Miniarrays, welches vom Institut für Geowissenschaften, Universität Potsdam, aufgestellt wurde, registriert.

The document contains the catalog of earthquakes in Vogtland /West Bohemia within the period of 2008/10/19 -to- 2009/03/16. The events were recorded by a seismic mini-array operated by the Institute of Earthsciences, University of Postdam. / Das Dokument enthält einen Katalog von Erdbeben im Vogtland/Westböhmen im Zeitraum 2008/10/19 -bis- 2009/03/16. Die Erdbeben wurden mit Hilfe eines seismologischen Miniarrays, welches vom Institut für Geowissenschaften, Universität Potsdam, aufgestellt wurde, registriert.

E-commerce applications generate and consume tremendous amount of online information that is typically available as textual documents. Observations of textual document management practices by organizations or individuals suggest the popularity of using categories (or category hierarchies) to organize, archive and access documents. On the other hand, an organization (or individual) also constantly acquires new documents from various Internet sources. Consequently, integration of relevant categorized documents into existent categories of the organization (or individual) becomes an important issue in the e-commerce era. Existing categorization-based approach for document-category integration (specifically, the Enhanced Na&#x00EF;ve Bayes classifier) incurs several limitations, including homogeneous assumption on categorization schemes used by master and source catalogs and requirement for a large-sized master categories as training data. In this study, we developed a Clustering-based Category Integration (CCI) technique to deal with integrating two document catalogs each of which is organized non-hierarchically (i.e., in a flat set). Using the Enhanced Na&#x00EF;ve Bayes classifier as benchmarks, the empirical evaluation results showed that the proposed CCI technique appeared to improve the effectiveness of document-category integration accuracy in different integration scenarios and seemed to be less sensitive to the size of master categories than the categorization-based approach. Furthermore, to integrate the document categories that are organized hierarchically, we proposed a Clustering-based category-Hierarchy Integration (referred to as CHI) technique extended the CCI technique and for category-hierarchy integration. The empirical evaluation results showed that the CHI technique appeared to improve the effectiveness of hierarchical document-category integration than that attained by CCI under homogeneous and comparable scenarios.