SYNTHESIS AND BIOLOGICAL ACTIVITY OF NEW SERIES OF ORGANOTIN(IV) ESTERS WITH N,N-DIACETYLGLYCINE

A bioactive N,N-diacetylglycine (NNDAG) and new organotin(IV) complexes (OTCs) (1-7) were synthesized. Spectroscopic techniques were employed to characterize NNDAG and OTCs. FTIR was employed to verify N,N protection of glycine by acetyl groups. The disappearance of υ(OH) at 3000-2600 cm-1 showed de-protonation of free ligand. The Δυ 150<200 cm-1 of OTCs 4-7 verified bidentate coordination with tetrahedral geometry. The Δυ of OTCs1 and 3 was <200 cm-1 exhibitingtrans -octahedral geometry while OTC 2 dimer was assigned a unique sinusoidal view. The 1H NMR spectra of OTCs verified their synthesis by de-protonation of NNDAG and no chemical shift was found downfield for carboxylic acid proton. The 13C, 119Sn NMR and Mass spectrometric data also supported FTIR and 1H NMR descriptions. The OTCs 4, 5, 6 and7 (500 ppm) proved twice as active against Escherichia coli as the standard antibiotic enoxacin (1000 ppm). The promising property of the OTCs (4, 5, 6 and7) is clearly due to their tetrahedral. The OTCs 4and 5 exhibited excellent activity against M. minimum and good activity against T. castaneum.LD50 of all the compounds were determined and OTCs4, 5 and 7 were found to be active.

Defining the location factors of new manufacturing site in chemical industry

The objective of this thesis is to examine the factors that have an impact on the location decision of new manufacturing site and to create the relative order of importance of these factors by analytic hierarchy process (AHP). The decision making process especially related to the location selection and the measurement of the location factors are also examined. In theoretical part the character of decision making process and the relevant methods are introduced. Based on the previous studies of other researchers, the location factors are examined and the main research method, analytic hierarchy process, is also introduced. The empirical part of the study mainly follows the phases of decision making process and is emphasized on the main stages of analytic hierarchy process; building the hierarchy, defining the priorities and analyzing the results. The hierarchy is constructed from seven main criteria which all have several sub criteria. The evaluation of the hierarchy is implemented at the group decision making –laboratory and there can be seen significant differences between the importance of criteria. The final stage in the study is to create the appropriate measurement scales to the chosen criteria.

Synthesis of new disulfonamides from different substituted diamino pyridines

A series of novel disulfonamide derivatives were synthesized and characterized by FT-IR, ¹H NMR and MS techniques. In order to prepare new disulfonamides, at first we synthesized new diamines containing a pyridine ring. Then, they have been reacted with sulfonyl chlorides to give corresponding disulfonamides.

Stress testing and risk evaluation of new capacity payment algorithm proposed by Market Council

In the Russian Wholesale Market, electricity and capacity are traded separately. Capacity is a special good, the sale of which obliges suppliers to keep their generating equipment ready to produce the quantity of electricity indicated by the System Operator. The purpose of the formation of capacity trading was the maintenance of reliable and uninterrupted delivery of electricity in the wholesale market. The price of capacity reflects constant investments in construction, modernization and maintenance of power plants. So, the capacity sale creates favorable conditions to attract investments in the energy sector because it guarantees the investor that his investments will be returned.

Network effects: Scale development and implications for new product performance

More and more innovations currently being commercialized exhibit network effects, in other words, the value of using the product increases as more and more people use the same or compatible products. Although this phenomenon has been the subject of much theoretical debate in economics, marketing researchers have been slow to respond to the growing importance of network effects in new product success. Despite an increase in interest in recent years, there is no comprehensive view on the phenomenon and, therefore, there is currently incomplete understanding of the dimensions it incorporates. Furthermore, there is wide dispersion in operationalization, in other words, the measurement of network effects, and currently available approaches have various shortcomings that limit their applicability, especially in marketing research. Consequently, little is known today about how these products fare on the marketplace and how they should be introduced in order to maximize their chances of success. Hence, the motivation for this study was driven by the need to increase our knowledge and understanding of the nature of network effects as a phenomenon, and of their role in the commercial success of new products. This thesis consists of two parts. The first part comprises a theoretical overview of the relevant literature, and presents the conclusions of the entire study. The second part comprises five complementary, empirical research publications. Quantitative research methods and two sets of quantitative data are utilized. The results of the study suggest that there is a need to update both the conceptualization and the operationalization of the phenomenon of network effects. Furthermore, there is a need for an augmented view on customers’ perceived value in the context of network effects, given that the nature of value composition has major implications for the viability of such products in the marketplace. The role of network effects in new product performance is not as straightforward as suggested in the existing theoretical literature. The overwhelming result of this study is that network effects do not directly influence product success, but rather enhance or suppress the influence of product introduction strategies. The major contribution of this study is in conceptualizing the phenomenon of network effects more comprehensively than has been attempted thus far. The study gives an augmented view of the nature of customer value in network markets, which helps in explaining why some products thrive on these markets whereas others never catch on. Second, the study discusses shortcomings in prior literature in the way it has operationalized network effects, suggesting that these limitations can be overcome in the research design. Third, the study provides some much-needed empirical evidence on how network effects, product introduction strategies, and new product performance are associated. In general terms, this thesis adds to our knowledge of how firms can successfully leverage network effects in product commercialization in order to improve market performance.

Identification and characterization of new genes and pathways regulating spermatogonial cell fate

Spermatogenesis, i.e sperm production in the seminiferous tubules of the testis, is a complex process that takes over one month to complete. Life-long ability of sperm production ultimately lies in a small population of undifferentiated cells, called spermatogonial stem cells (SSCs). These cells give rise to differentiating spermatogonia, which are committed to mature into spermatozoa. SSCs represent a heterogeneous population of cells and many aspects of their basic biology are still unknown. Understanding the mechanisms behind the cell fate decision of these cells is important to gain more insights into the causes of infertility and testis cancer. In addition, an interesting new aspect is the use of testis-derived stem cells in regenerative medicine. Our data demonstrated that adult mouse testis houses a population of Nanog-expressing spermatogonia. Based on mRNA and protein analysis these cells are enriched in stage XII of the mouse seminiferous epithelial cycle. The cells derived from this stage have the highest capacity to give rise to ES cell-like cells which express Oct4 and Nanog. These cells are under tight non- GDNF regulation but their fate can be dictated by activating p21 signalling. Comparative studies suggested that these cells are regulated like ES cells. Taken together these data imply that pluripotent cells are present in the adult mammalian testis. CIP2A (cancerous inhibitor of PP2A) has been associated with tumour aggressiveness and poor prognosis. In the testis it is expressed by the descendants of stem cells, i.e. the spermatogonial progenitor cells. Our data suggest that CIP2A acts upstream of PLZF and is needed for quantitatively normal spermatogenesis. Classification of CIP2A as a cancer/testis gene makes it an attractive target for cancer therapy. Study on the CIP2A deficient mouse model demonstrates that systemic inhibition of CIP2A does not severely interfere with growth and development or tissue or organ function, except for the spermatogenic output. These data demonstrate that CIP2A is required for quantitatively normal spermatogenesis. Hedgehog (Hh) signalling is involved in the development and maintenance of many different tissues and organs. According to our data, Hh signalling is active at many different levels during rat spermatogenesis: in spermatogonia, spermatocytes and late elongating spermatids. Localization of Suppressor of Fused (SuFu), the negative regulator of the pathway, specifically in early elongating spermatids suggests that Hh signalling needs to be shut down in these cells. Introduction of Hh signalling inhibitor resulted in an increase in germ cell apoptosis. Follicle-stimulating hormone (FSH) and inhibition of receptor tyrosine kinases resulted in down-regulation of Hh signalling. These data show that Hh signalling is under endocrine and paracrine control and it promotes germ cell survival.

Identification of new flagellin-encoding fliC genes in Escherichia coli isolated from domestic animals using RFLP-PCR and sequencing methods

Identification of Escherichia coli requires knowledge regarding the prevalent serotypes and virulence factors profiles allows the classification in pathogenic/non-pathogenic. However, some of these bacteria do not express flagellar antigen invitro. In this case the PCR-restriction fragment length polymorphism (RFLP-PCR) and sequencing of the fliC may be suitable for the identification of antigens by replacing the traditional serology. We studied 17 samples of E. coli isolated from animals and presenting antigen H nontypeable (HNT). The H antigens were characterized by PCR-RFLP and sequencing of fliC gene. Three new flagellin genes were identified, for which specific antisera were obtained. The PCR-RFLP was shown to be faster than the serotyping H antigen in E. coli, provided information on some characteristics of these antigens and indicated the presence of new genes fliC.

Soil seed bank of plant species as a function of long-term soil management and sampled depth

This study aimed at assessing the level of weed infestation indifferent areas that were submitted to different soil management for 16 years. Four management systems were studied: (1) agriculture only under conventional tillage system; (2) agriculture only under no-till system; (3) crop-livestock integrationcrop-livestock integration; (4) livestock only. These areas were sampled at three soil depths (0-5, 5-10 and 10-15 cm), and soil was stored in plastic pots and taken to a greenhouse, where soil moisture and weight were standardized. Soil was kept near 70% moisture field capacity, being revolved every 20 days when all seedling emerged from soil were counted, identified and collected for dry mass assessment. The soil coverage by weeds, number of weed seedlings and dry mass of the weedy community were assessed. A phytoecological analysis was conducted. Weed composition is differentdifferent among management systems after 16 years. Areas with livestock showed much smaller number of weed species in comparison to systems where only grain crops are grown. The presence of livestock affects the potential of germination of soil seed bank. Agriculture systems are similar in terms of weed composition along soil profile, while systems involving livestock show little relation in what regards such sampled depths. Conservationist models of land exploration contribute to reduce severity of weed species occurrence in the long term.

Simulation of new p-type pixel strip detector with enhanced multiplication effect

This Master’s Thesis is dedicated to the simulation of new p-type pixel strip detector with enhanced multiplication effect. It is done for high-energy physics experiments upgrade such as Super Large Hadron Collider especially for Compact Muon Solenoid particle track silicon detectors. These detectors are used in very harsh radiation environment and should have good radiation hardness. The device engineering technology for developing more radiation hard particle detectors is used for minimizing the radiation degradation. New detector structure with enhanced multiplication effect is proposed in this work. There are studies of electric field and electric charge distribution of conventional and new p-type detector under reverse voltage bias and irradiation. Finally, the dependence of the anode current from the applied cathode reverse voltage bias under irradiation is obtained in this Thesis. For simulation Silvaco Technology Computer Aided Design software was used. Athena was used for creation of doping profiles and device structures and Atlas was used for getting electrical characteristics of the studied devices. The program codes for this software are represented in Appendixes.

Building Dynamic Data Centers for Fast Delivery of New Data and Data Updates

Poster at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Development of new heparin-like compounds and other antithrombotic drugs and their interaction with vascular endothelial cells

The anticlotting and antithrombotic activities of heparin, heparan sulfate, low molecular weight heparins, heparin and heparin-like compounds from various sources used in clinical practice or under development are briefly reviewed. Heparin isolated from shrimp mimics the pharmacological activities of low molecular weight heparins. A heparan sulfate from Artemia franciscana and a dermatan sulfate from tuna fish show a potent heparin cofactor II activity. A heparan sulfate derived from bovine pancreas has a potent antithrombotic activity in an arterial and venous thrombosis model with a negligible activity upon the serine proteases of the coagulation cascade. It is suggested that the antithrombotic activity of heparin and other antithrombotic agents is due at least in part to their action on endothelial cells stimulating the synthesis of an antithrombotic heparan sulfate.

Establishment of new murine embryonic stem cell lines for the generation of mouse models of human genetic diseases

Embryonic stem cells are totipotent cells derived from the inner cell mass of blastocysts. Recently, the development of appropriate culture conditions for the differentiation of these cells into specific cell types has permitted their use as potential therapeutic agents for several diseases. In addition, manipulation of their genome in vitro allows the creation of animal models of human genetic diseases and for the study of gene function in vivo. We report the establishment of new lines of murine embryonic stem cells from preimplantation stage embryos of 129/Sv mice. Most of these cells had a normal karyotype and an XY sex chromosome composition. The pluripotent properties of the cell lines obtained were analyzed on the basis of their alkaline phosphatase activity and their capacity to form complex embryoid bodies with rhythmically contracting cardiomyocytes. Two lines, USP-1 and USP-3, with the best in vitro characteristics of pluripotency were used in chimera-generating experiments. The capacity to contribute to the germ line was demonstrated by the USP-1 cell line. This cell line is currently being used to generate mouse models of human diseases.