Computational Methods Generating High-Resolution Views of Complex Structure-Activity Relationships

The analysis of structure-activity relationships (SARs) of small bioactive compounds is a central task in medicinal chemistry and pharmaceutical research. The study of SARs is in principle not limited to computational methods, however, as data sets rapidly grow in size, advanced computational approaches become indispensable for SAR analysis. Activity landscapes are one of the preferred and widely used computational models to study large-scale SARs. Activity cliffs are cardinal features of activity landscape representations and are thought to contain high SAR information content. This work addresses major challenges in systematic SAR exploration and specifically focuses on the design of novel activity landscape models and comprehensive activity cliff analysis. In the first part of the thesis, two conceptually different activity landscape representations are introduced for compounds active against multiple targets. These models are designed to provide an intuitive graphical access to compounds forming single and multi-target activity cliffs and displaying multi-target SAR characteristics. Further, a systematic analysis of the frequency and distribution of activity cliffs is carried out. In addition, a large-scale data mining effort is designed to quantify and analyze fingerprint-dependent changes in SAR information. The second part of this work is dedicated to the concept of activity cliffs and their utility in the practice of medicinal chemistry. Therefore, a computational approach is introduced to search for detectable SAR advantages associated with activity cliffs. In addition, the question is investigated to what extent activity cliffs might be utilized as starting points in practical compound optimization efforts. Finally, all activity cliff configurations formed by currently available bioactive compounds are thoroughly examined. These configurations are further classified and their frequency of occurrence and target distribution are determined. Furthermore, the activity cliff concept is extended to explore the relation between chemical structures and compound promiscuity. The notion of promiscuity cliffs is introduced to deduce structural modifications that might induce large-magnitude promiscuity effects

The Benefits of Privatizing Banks to Strategic Foreign Investors: A Survey of Central and Eastern Europe

The last decade witnessed the biggest privatization initiative so far that transitioned the markets of Central and Eastern Europe from centrally planned to competitive and western oriented. As a result, an increasing share of the banking sector in many of the transitional states is controlled by foreign capital. This study examines the effect of privatizing banks to foreign owners as opposed to domestic owners on bank performance. Using the ratio approach and the stochastic frontier approach, the paper concludes that although the effects of new ownership are not very pronounced due to the recent nature of the transition, banks privatized to foreign owners outperform these sold to domestic owners across all measures: profitability level, portfolio quality and managerial efficiency

DPPH antiradical activity and total phenolic content of methanol and ethanol extracts from macroalgae (Ulva rigida) and microalgae (Chlorella)

Introduction: Algae are widely popular as dietary supplement. Furthermore, they can be a great source of antioxidants (pigments, alkaloids, carotenoids, phenolic acids, sulfated polysaccharides and long-chain polyunsaturated fatty acids etc.) and can be used instead of synthetic ones. The different nutrient compositions of algae depend on class, species, habitats, maturity, and environmental conditions.Aim: The present study aims to investigate the differences in the antioxidant activity (AOA) and total phenolic content (TPC) of macroalgae Ulva rigida from the Black Sea and microalgae Chlorella. In addition, the obtained results will show their potential as natural sources of antioxidants.Materials and Methods: The marine macroalgae Ulva rigida and the microalgae Chlorella were used to perform different solvent extracts, which were analyzed for antiradical activity and total phenol content.Results and Discussion: All analyzed extracts (methanol and ethanol) showed positive results of the DPPH test and TPC. Both methanol extracts of microalgae Chlorella and macroalgae Ulva rigida had higher scavenging effect on used radicals for antioxidant activity compared to both ethanol extracts of the same plant material. The results show high potential as natural source of antioxidants of both algae species due perhaps to the phenolic content and other compounds having antioxidant activity.Conclusion: Both Ulva rigida and Chlorella can be used as a source of antioxidants and phenolic acids, which can be added to new functional foods and supplements, as well as be the basis of pharmaceutical and cosmetic products

Въпроси на конкурентоспособността на земеделските стопанства на България

A holistic approach for understanding, evaluating and improving the competitiveness of agricultural holdings in Bulgaria has been refined and applied. A multi-criteria assessment of the competitiveness of farms of different types is made by using survey information. A multi-criteria assessment of the level of competitiveness of agricultural holdings as a whole and with different types of product specialization was also made by using statistical data and applying the method of principal components. A comparative analysis of the level and dynamics of competitiveness of Bulgarian farms in general and with different specializations for the period 2010-2020 was also carried out. A comparative analysis of the results of the assessment of competitiveness based on survey and statistical data was made and the advantages and disadvantages of the various approaches. An assessment was made of the level and factors of competitiveness of agricultural holdings with organic production, the relationships with the main characteristics of the farmer (gender, age, etc.) were established, the most significant factors and political instruments affecting competitiveness were highlighted and the intentions were identified of organic farms in the near future. A model of CPR factor analysis and an index method for measuring competitiveness in the sheep meat sector were applied. The restructuring and diversification of agricultural cooperatives for the period after the country's integration into the EU was analyzed and a comparative assessment was made with other forms of business organizations in agriculture. The multi-criteria evaluation of alternative business models and strategies for managing the agricultural enterprise and risk was carried out, and the factors of the competitiveness of Bulgarian farms were identified. A theoretical analysis of the meso-economic level of management was made, the attitudes of alternative farmers in our country for the use of meso-institutions were established, and the relationship with agrarian competitiveness at the current stage of development of the industry was rethought. The development of agricultural holdings for the period 2007–2020 in the country was analyzed and the development of rural areas and the agrarian sector in the South Central region was compared with the general situation, by means of the Localization Index. The new trends in agricultural marketing (digitalization, intelligent marketing, etc.) are revealed, the impact on the relationship between agricultural producers and end users and the effect on the competitiveness of farms are assessed. An algorithm for the development and implementation of new models for innovative activity of small and medium-sized enterprises in agriculture is proposed, which allows effective management decisions at different levels, quantification of the index for innovative activity and easy adaptation when developing an automated system. General conclusions have been drawn up about the level, trends and factors of competitiveness of Bulgarian farms of different types and recommendations have been made for improving the scientific and evaluation methods, the system for gathering agro-information, public policies, programs and forms of intervention, and of farming strategies to improve competitiveness

Холистичен подход за дефиниране, оценяване и подобряване на конкурентоспособността на земеделските стопанства в България

The report presents the results of the first stage of the research project "Competitiveness of agricultural farms in Bulgaria" funded by the Agricultural Academy and implemented by a team from the Institute of Agrarian Economics, UNWE, NBU and IPAZR "N. Pushkarov ”in Sofia. A holistic framework for understanding, evaluating, and improving the competitiveness of agricultural holdings in Bulgaria has been elaborated. The achievements of the interdisciplinary New Institutional Economics, Theory of Economic Organizations, Theory of Competitiveness and other scientific methods such as: study of literature and experience, summary, synthesis, design, comparative and institutional analysis, multicriteria analysis, groupings, discrete structural analysis, value -measuring, qualitative analysis, expert evaluation, survey, Shift-share Analysis, VTOPSIS and statistical analysis, localization analysis, etc. Numerous publications and experience in the country and the world for understanding and assessing the competitiveness of agricultural holdings have been studied. On this basis, a (more) adequate definition of the competitiveness of the farm is given, it is justified that it has four equally important pillars (economic efficiency, financial capability, adaptability and sustainability), and a hierarchical system is developed to assess its level consisting of adequate criteria, indicators and reference values, and an approach to integration and interpretation. The new evaluation system is being experimented with, using survey information from managers of "typical" farms of different types, production specializations and geographical locations. The theoretical bases of business models are summarized and an innovative model of competitiveness of agricultural holdings is developed. An approach to assessing market and factor competitiveness has been adapted and tested in the dairy sector. The regional differences in the competitiveness of agriculture in the EU countries have been identified. The competitive positions and forms of management of alternative farms in the conditions of the Kovid pandemic are assessed. The peculiarities in determining the competitiveness of organic farms are highlighted. The advantages of strategic partnerships and network structures as a tool for increasing the competitiveness of small and medium farms were assessed. The possibilities of the "new" forms of marketing (green, niche, sustainable, etc.) and digitalization to increase the competitiveness of farms are assessed. A regional analysis of agricultural holdings and employees in the South Central region was made. Alternative forms of financing agriculture from banks and leasing companies to improve the competitiveness of farms have been assessed. Conclusions and recommendations for improving public policies and farming strategies have been prepared. The performed activity and the achieved results in terms of volume and quality fully correspond (and exceed) the planned for all tasks. More information can be obtained from the project website https://cfb.alle.bg

The role of consumer leverage in financial crises

This thesis demonstrates that consumer leverage can contribute to financial crises such as the subprime mortgage crisis characterised by increased bankruptcy prospects and tightened credit access. A recession may follow even when the leveraged sector is not a production sector and can be triggered by seeming positive events such as a technological innovation and a relaxation of borrowing conditions. The first preliminary chapter updates the Bernanke, Gertler and Gilchrist (1999) approach with financial frictions in the production sector to a two-sector model with consumption and housing. It shows that credit frictions in the capital financing decisions of housing firms are not sufficient to capture the negative consumer experience with falling housing prices and relaxed credit access during the recession. The second chapter brings the model closer to the subprime mortgage crisis by shifting credit constraints to the consumer mortgage market. Increased supply of houses lowers asset prices and reduces the value of the real estate collateral used in the mortgage which in turn worsens the leverage of indebted consumers. A relaxation of borrowing conditions turns credit-constrained households into a potential source of disturbances themselves when market optimism allows them to raise their leverage with little downpayment. Both cases demonstrate that although households are not production agents, their worsening debt levels can trigger a lasting financial downturn. The third chapter develops a chained mortgage contracts model where both homeowner consumers and the financial institutions that securitize their mortgage loan are credit-constrained. Adding credit constraints to the financial sector that provides housing mortgages creates opportunities for risk sharing where banks shift some of the downturn onto indebted consumers in order to hasten their own recovery. This consequence is especially evident in the case of relaxed credit access for banks. Financial institutions repair their debt position relatively fast at the expense of consumers whose borrowing ability is squeezed for a long period despite the fact that they may not be the source of the disturbance. The result mirrors the recent subprime mortgage crisis characterised by a sharp but brief decline for banks and a protracted recovery for mortgaged households.</p

The role of consumer leverage in financial crises

This thesis demonstrates that consumer leverage can contribute to financial crises such as the subprime mortgage crisis characterised by increased bankruptcy prospects and tightened credit access. A recession may follow even when the leveraged sector is not a production sector and can be triggered by seeming positive events such as a technological innovation and a relaxation of borrowing conditions. The first preliminary chapter updates the Bernanke, Gertler and Gilchrist (1999) approach with financial frictions in the production sector to a two-sector model with consumption and housing. It shows that credit frictions in the capital financing decisions of housing firms are not sufficient to capture the negative consumer experience with falling housing prices and relaxed credit access during the recession. The second chapter brings the model closer to the subprime mortgage crisis by shifting credit constraints to the consumer mortgage market. Increased supply of houses lowers asset prices and reduces the value of the real estate collateral used in the mortgage which in turn worsens the leverage of indebted consumers. A relaxation of borrowing conditions turns credit-constrained households into a potential source of disturbances themselves when market optimism allows them to raise their leverage with little downpayment. Both cases demonstrate that although households are not production agents, their worsening debt levels can trigger a lasting financial downturn. The third chapter develops a chained mortgage contracts model where both homeowner consumers and the financial institutions that securitize their mortgage loan are credit-constrained. Adding credit constraints to the financial sector that provides housing mortgages creates opportunities for risk sharing where banks shift some of the downturn onto indebted consumers in order to hasten their own recovery. This consequence is especially evident in the case of relaxed credit access for banks. Financial institutions repair their debt position relatively fast at the expense of consumers whose borrowing ability is squeezed for a long period despite the fact that they may not be the source of the disturbance. The result mirrors the recent subprime mortgage crisis characterised by a sharp but brief decline for banks and a protracted recovery for mortgaged households.This thesis is not currently available via ORA