Development of simple and efficient synthetic strategies for production of fine chemicals of pharmaceutical relevance : metal-mediated allylation combined with applied catalysis

Den snart 200 år gamla vetenskapsgrenen organisk synteskemi har starkt bidragit till moderna samhällens välfärd. Ett av flaggskeppen för den organiska synteskemin är utvecklingen och produktionen av nya läkemedel och speciellt de aktiva substanserna däri. Därmed är det viktigt att utveckla nya syntesmetoder, som kan tillämpas vid framställningen av farmaceutiskt relevanta målstrukturer. I detta sammanhang är den ultimata målsättningen dock inte endast en lyckad syntes av målmolekylen, utan det är allt viktigare att utveckla syntesrutter som uppfyller kriterierna för den hållbara utvecklingen. Ett av de centralaste verktygen som en organisk kemist har till förfogande i detta sammanhang är katalys, eller mera specifikt möjligheten att tillämpa olika katalytiska reaktioner vid framställning av komplexa målstrukturer. De motsvarande industriella processerna karakteriseras av hög effektivitet och minimerad avfallsproduktion, vilket naturligtvis gynnar den kemiska industrin samtidigt som de negativa miljöeffekterna minskas avsevärt. I denna doktorsavhandling har nya syntesrutter för produktion av finkemikalier med farmaceutisk relevans utvecklats genom att kombinera förhållandevis enkla transformationer till nya reaktionssekvenser. Alla reaktionssekvenser som diskuteras i denna avhandling påbörjades med en metallförmedlad allylering av utvalda aldehyder eller aldiminer. De erhållna produkterna innehållende en kol-koldubbelbindning med en närliggande hydroxyl- eller aminogrupp modifierades sedan vidare genom att tillämpa välkända katalytiska reaktioner. Alla syntetiserade molekyler som presenteras i denna avhandling karakteriseras som finkemikalier med hög potential vid farmaceutiska tillämpningar. Utöver detta tillämpades en mängd olika katalytiska reaktioner framgångsrikt vid syntes av dessa molekyler, vilket i sin tur förstärker betydelsen för de katalytiska verktygen i organiska kemins verktygslåda.

Performance Comparison of Behavioral Finance -based Investment Strategies in the Finnish Stock Market 1996-2010

In this thesis traditional investment strategies (value and growth) are compared to modern investment strategies (momentum, contrarian and GARP) in terms of risk, performance and cumulative returns. Strategies are compared during time period reaching from 1996 to 2010 in the Finnish stock market. Used data includes all listed main list stocks, dividends and is adjusted in case of splits, and mergers and acquisitions. Strategies are tested using different holding periods (6, 12 and 36 months) and data is divided into tercile portfolios based on different ranking criteria. Contrarian and growth strategies are the only strategies with improved cumulative returns when longer holding periods are used. Momentum (52-week high price1) and GARP strategies based on short holding period have the best performance and contrarian and growth strategies the worst. Momentum strategies (52-week high price) along with short holding period contrarian strategies (52-week low price2) have the lowest risk. Strategies with the highest risk are both growth strategies and two momentum strategies (52-week low price). The empirical results support the efficiency of momentum, GARP and value strategies. The least efficient strategies are contrarian and growth strategies in terms of risk, performance and cumulative returns. Most strategies outperform the market portfolio in all three measures. 1 Stock ranking criterion (current price/52-week highest price) 2 Stock ranking criterion (current price/52-week lowest price)

Immunoprophylactic strategies against enterotoxemia caused by Clostridium perfringens type D in goats

The serological response to an experimental vaccine against Clostridium perfringens type D enterotoxemia was evaluated in four groups of goats. Group 1 received colostrum from unvaccinated cows and no vaccine. Groups 2, 3 and 4 received colostrum from vaccinated cows. In addition, Groups 3 and 4 received a vaccine dose at 80 days of age, and Group 4 received a second vaccine dose at 120 days of age. Serum antibody levels were determined by ELISA in cows before and after calving, and in goats at 3, 80, 120 and 160 days of age. No significant difference in serum antibody levels was observed between vaccinated and unvaccinated cows, or between the four groups of goats evaluated at 3 days of life. Groups 3 and 4 presented mean antibody titers of 0.6 and 1.1 IU/ml, respectively, 40 days after first vaccination. The vaccine response of Group 4 was 1.8 IU/ml 40 days after the booster dose and was higher than that observed for Group 3 (0.2 IU/ml). Thus, in the proposed regimen the use of heterologous colostrum did not induce passive immunization in goat kids. However, first vaccination and a booster dose after 40 days triggered satisfactory antibody levels.

Metabolic evaluation of dairy cows submitted to three different strategies to decrease the effects of negative energy balance in early postpartum

In early lactation dairy cattle suffer metabolic alterations caused by negative energy balance, which predisposes to fatty liver and ketosis. The aim of this study was to evaluate the metabolic condition of high yielding dairy cows subjected to three treatments for preventing severe lipomobilization and ketosis in early lactation. Fifty four multiparous Holstein cows yielding >30 L/day were divided into four groups: control (CN= no treatment), glucose precursor (PG= propylene-glycol), hepatic protector (Mp= Mercepton®), and energy supplement with salts of linolenic and linoleic faty acids (Mg-E= Megalac-E®). Treatments were administrated randomly at moment of calving until 8 weeks postpartum. Blood samples were collected on days 1, 7, 14, 21, 28, 35, 42 and 49 postpartum. Body condition score (BCS) was evaluated at the same periods and milk yield was recorded at 2nd, 4th, 5th, 6th, 7th, and 8th weeks of lactation. Concentrations of non-esterified fatty acids (NEFA), albumin, AST, ß-hydroxybutyrate (BHBA), cholesterol, glucose, total protein, urea and triglycerides were analyzed in blood samples. Cut-off points for subclinical ketosis were defined when BHBA >1.4 mmol/L and NEFA >0.7 mmol/L. General occurrence of subclinical ketosis was 24% during the period. An ascendant curve of cholesterol and glucose was observed from the 1st to the 8th week of lactation, while any tendency was observed with BHBA and NEFA, although differences among treatments were detected (p<0.05). BCS decreased from a mean of 3.85 at 1st week to 2.53 at 8th week of lactation (p=0.001). Milk yield was higher in the Mg-E group compared with the other treatment groups (p<0.05) Compared with the CN group, the treatments with Mp and PG did not show significant differences in blood biochemistry and milk yield. Cows receiving PG and Mg-E showed higher values of BHBA and NEFA (P<0.05), indicating accentuated lipomobilization. Supplementation with Mg-E also resulted in significant higher concentrations of cholesterol, BHBA, urea, AST and lower values of glycemia. This performance may be explained by the highest milk yield observed with this treatment. Treatments with PG and Mp did not improve milk yield, compared with control cows, but did not show metabolic evidence of ketosis, fat mobilization or fatty liver. These results suggest that treatment with Mg-E improves milk production but induces a higher negative energy balance leading to moderated lipomobilization and ketone bodies production, increasing the risk of fatty liver.

The Use of Systematic Value Strategies in Separating the Winners from the Losers: Evidence from the Finnish Markets

This study examines the Magic Formula and ERP5 value strategies in the Finnish stocks markets. Magic Formula ranks stocks based on EV/EBIT and ROA and ERP5 based on EV/EBIT, ROA, P/B and five-year trailing ROA. The purpose of the study is to examine whether the value strategies can be used to generate excess returns over the market index. The data has been collected from the Datastream database for the sample period from May 1997 to May 2010 and consists of the companies listed on the main list of Helsinki Stock Exchange. This study confirms the findings of previous research that value premium exists in the Finnish stock markets and that systematic value strategies can be used to form portfolios that outperform the market index with lower volatility.

Kinetics of epsilon antitoxin antibodies in different strategies for active immunization of lambs against enterotoxaemia

Enterotoxaemia, a common disease that affects domestic small ruminants, is mainly caused by the epsilon toxin of Clostridium perfringens type D. The present study tested four distinct immunization protocols to evaluate humoral response in lambs, a progeny of non-vaccinated sheep during gestation. Twenty-four lambs were randomly allocated into four groups according to age (7, 15, 30 and 45 days), receiving the first dose of epsilon toxoid commercial vaccine against clostridiosis with booster after 30 days post vaccination. Indirect ELISA was performed after the first vaccine dose and booster to evaluate the immune response of the lambs. Results showed that for the four protocols tested all lambs presented serum title considered protective (≥0.2UI/ml epsilon antitoxin antibodies) and also showed that the anticipation of primovaccination of lambs against enterotoxaemia conferred serum title considered protective allowing the optimization of mass vaccination of lambs.

Startup IPR strategies: Why should startup companies protect their intellectual property?

This thesis studies intellectual property right (also: IPR) strategies from the perspective of high growth startup companies. Due to technology development and intellectualization of business, large part of companies’ assets are nowadays intangible. At the same time, the importance of protection instruments designed to protect these intangible assets, intellectual property rights, is increasing. Utilization of these instruments, however, requires understanding of the functioning of the IPR system, as well as financial resources. Startup companies aiming for growth need to be able compete with more established companies also in relation to intangible assets, but they might not have the required knowledge ot resources to fully utilize IPRs in their business. This research aims to understand what are the benefits a startup company can have from protecting their IPRs, and how can the company achieve those benefits. Based on a review of previous literature, altogether 11 benefits of IPR registration were recognized. To answer to the research questions, six half-structured interviews were conducted with experts form different fields, all with experience in working with startup companies and IPR issues. The interviews were analyzed using different methods of qualitative data analysis, mainly derived from grounded theory and case study methods. As a result, out of the 11 benefits recognized from earlier literature, 8 were recognized to be relevant for startup companies. The most central benefits were recognized to be linked with the financial lifecycle of the startup company, including increasing credibility of the startup and stimulating an investment. In addition it was noticed, that startup companies are mainly able to utilize these benefits at later stages of their lifecycle. However, to be able to utilize the benefits at later stages, the startup company needs to be aware of the functioning of the IPR system and might need to apply for appropriate protection already early on. As a result of this study, a three-step model was formed to describe different levels of IPR utilization. The first level of the model represents the minimum level of understanding that every startup company should have regarding IPRs. The second level views IPR strategy from a risk management perspective, including securing the minimum protection of the company’s own IPRs, contract management and establishing processes for handling IPR issues. The last stage reflects strategic use of IPRs. At this third stage intellectual property rights have a central role in the startup company’s business, and they are used in the company’s value creation.

Solution of aerospace problems using structured and unstructured strategies

Products developed at industries, institutes and research centers are expected to have high level of quality and performance, having a minimum waste, which require efficient and robust tools to numerically simulate stringent project conditions with great reliability. In this context, Computational Fluid Dynamics (CFD) plays an important role and the present work shows two numerical algorithms that are used in the CFD community to solve the Euler and Navier-Stokes equations applied to typical aerospace and aeronautical problems. Particularly, unstructured discretization of the spatial domain has gained special attention by the international community due to its ease in discretizing complex spatial domains. This work has the main objective of illustrating some advantages and disadvantages of numerical algorithms using structured and unstructured spatial discretization of the flow governing equations. Numerical methods include a finite volume formulation and the Euler and Navier-Stokes equations are applied to solve a transonic nozzle problem, a low supersonic airfoil problem and a hypersonic inlet problem. In a structured context, these problems are solved using MacCormack’s implicit algorithm with Steger and Warming’s flux vector splitting technique, while, in an unstructured context, Jameson and Mavriplis’ explicit algorithm is used. Convergence acceleration is obtained using a spatially variable time stepping procedure.

Energy-efficient control strategies for variable speed driven parallel pumping systems based on pump operation point monitoring with frequency converters

The pumping processes requiring wide range of flow are often equipped with parallelconnected centrifugal pumps. In parallel pumping systems, the use of variable speed control allows that the required output for the process can be delivered with a varying number of operated pump units and selected rotational speed references. However, the optimization of the parallel-connected rotational speed controlled pump units often requires adaptive modelling of both parallel pump characteristics and the surrounding system in varying operation conditions. The available information required for the system modelling in typical parallel pumping applications such as waste water treatment and various cooling and water delivery pumping tasks can be limited, and the lack of real-time operation point monitoring often sets limits for accurate energy efficiency optimization. Hence, alternatives for easily implementable control strategies which can be adopted with minimum system data are necessary. This doctoral thesis concentrates on the methods that allow the energy efficient use of variable speed controlled parallel pumps in system scenarios in which the parallel pump units consist of a centrifugal pump, an electric motor, and a frequency converter. Firstly, the suitable operation conditions for variable speed controlled parallel pumps are studied. Secondly, methods for determining the output of each parallel pump unit using characteristic curve-based operation point estimation with frequency converter are discussed. Thirdly, the implementation of the control strategy based on real-time pump operation point estimation and sub-optimization of each parallel pump unit is studied. The findings of the thesis support the idea that the energy efficiency of the pumping can be increased without the installation of new, more efficient components in the systems by simply adopting suitable control strategies. An easily implementable and adaptive control strategy for variable speed controlled parallel pumping systems can be created by utilizing the pump operation point estimation available in modern frequency converters. Hence, additional real-time flow metering, start-up measurements, and detailed system model are unnecessary, and the pumping task can be fulfilled by determining a speed reference for each parallel-pump unit which suggests the energy efficient operation of the pumping system.

Variations in weed population densities, rate of change and community diversity in RR-soybeans and RR-maize strip crops under two herbicide strategies

Concerns about the sustainability of large-scale, direct-drilled RR-soybeans (Glycine max), and RR-maize (Zea mays) under monoculture in central Argentina are growing steadily. An experiment was conducted during three consecutive years to determine the effects of crops and systems (monocultures and strips) and herbicide strategy on weed density, population rate of change (l), b community diversity (H´), crop yields and Land Equivalent Ratio (LER). Not only crops but also crop systems differentially influenced weed densities along their growth and development. For crop harvests, weed densities increased in both maize crop systems as compared to in the one for soybeans, but the lowest increase occurred in soybean strips. Differences were leveled by both herbicide strategies, which achieved 73% efficacy during the critical periods in both crops. l of annual monocotyledonous increased, thus shifting the weed community composition. Species richness and H´ were not affected by crop systems, but both herbicide strategies, particularly POST, either in soybeans in monoculture or in maize strips, significantly enhanced H´. Crop yields significantly increased in the maize-strip system with POST (Year 1) or PRE (Years 2 and 3) strategies, thus increasing LER above 1. Herbicide Environmental Load treatments fall within very low or low field use rating.

Currency Carry Trades – Excess Returns and Performance Optimization of G10 Currency Carry Trade Strategies during the Euro Era

This study examines the excess returns provided by G10 currency carry trading during the Euro era. The currency carry trade has been a popular trade throughout the past decades offering excess returns to investors. The thesis aims to contribute to existing research on the topic by utilizing a new set of data for the Euro era as well as using the Euro as a basis for the study. The focus of the thesis is specifically on different carry trade strategies’ performance, risk and diversification benefits. The study finds proof of the failure of the uncovered interest rate parity theory through multiple regression analyses. Furthermore, the research finds evidence of significant diversification benefits in terms of Sharpe ratio and improved return distributions. The results suggest that currency carry trades have offered excess returns during 1999-2014 and that volatility plays an important role in carry trade returns. The risk, however, is diversifiable and therefore our results support previous quantitative research findings on the topic.

The Effect of Different Weed Management Strategies on the Growth and Yield of Direct-Seeded Dry Rice (Oryza sativa)

Weed management is a primary concern in direct seeded rice (DSR) cropping because weed growth becomes a major constraint on crop yield. A two year field study was set up to evaluate the effect of various weed control measures on crop growth, grain yield and grain quality of DSR. The experiment involved five different weed control measures: hand weeding, hoeing, inter-row tine cultivation, inter-row spike hoeing and herbicide treatment (Nominee 100 SC). The extent of weed control (compared to a non-weeded control) ranged from 50-95%. The highest crop yield was obtained using hand weeding. Hand weeding, tine cultivation and herbicide treatment raised the number of fertile rice tillers formed per unit area and the thousand grain weight. Tine cultivation provided an effective and economical level of weed control in the DSR crop.

Raise All Ships: Cooperative Repository Strategies in a Boot-Strap Culture

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