Purification of pharmaceuticals and nutraceutical compounds by sub- and supercritical extraction and chromatography

This thesis discusses the use of sub- and supercritical fluids as the medium in extraction and chromatography. Super- and subcritical extraction was used to separate essential oils from herbal plant Angelica archangelica. The effect of extraction parameters was studied and sensory analyses of the extracts were done by an expert panel. The results of the sensory analyses were compared to the analytically determined contents of the extracts. Sub- and supercritical fluid chromatography (SFC) was used to separate and purify high-value pharmaceuticals. Chiral SFC was used to separate the enantiomers of racemic mixtures of pharmaceutical compounds. Very low (cryogenic) temperatures were applied to substantially enhance the separation efficiency of chiral SFC. The thermodynamic aspects affecting the resolving ability of chiral stationary phases are briefly reviewed. The process production rate which is a key factor in industrial chromatography was optimized by empirical multivariate methods. General linear model was used to optimize the separation of omega-3 fatty acid ethyl esters from esterized fish oil by using reversed-phase SFC. Chiral separation of racemic mixtures of guaifenesin and ferulic acid dimer ethyl ester was optimized by using response surface method with three variables per time. It was found that by optimizing four variables (temperature, load, flowate and modifier content) the production rate of the chiral resolution of racemic guaifenesin by cryogenic SFC could be increased severalfold compared to published results of similar application. A novel pressure-compensated design of industrial high pressure chromatographic column was introduced, using the technology developed in building the deep-sea submersibles (Mir 1 and 2). A demonstration SFC plant was built and the immunosuppressant drug cyclosporine A was purified to meet the requirements of US Pharmacopoeia. A smaller semi-pilot size column with similar design was used for cryogenic chiral separation of aromatase inhibitor Finrozole for use in its development phase 2.

Drops That Open Worlds : Image of Water in the Poetry of Euphrase Kezilahabi

Euphrase Kezilahabi on tansanialainen kirjailija, joka ensimmäisenä julkaisi swahilinkielisen vapaalla mitalla kirjoitetun runokokoelman. Perinteisessä swahilirunoudessa tiukat muotosäännöt ovat tärkeitä, ja teos synnytti kiivasta keskustelua. Runoteokset Kichomi ( Viilto , Kipu , 1974) ja Karibu Ndani ( Tervetuloa sisään , 1988) sekä Kezilahabin muu tuotanto voidaan nähdä uuden sukupolven taiteena. Kezilahabi on arvostettu runoilija, mutta hänen runojaan ei aiemmin ole käännetty englanniksi (yksittäisiä säkeitä lukuunottamatta), eikä juurikaan tutkittu yksityiskohtaisesti. Yleiskuvaan pyrkivissä lausunnoissa Kezilahabin runouden on hyvin usein määritelty olevan poliittista. Monet Kezilahabin runoista ottavatkin kantaa yhteiskunnallisiin kysymyksiin, mutta niiden pohdinta on kuitenkin runoissa vain yksi taso. Sen lisäksi Kezilahabin lyriikassa on paljon muuta ennen kartoittamatonta tämä tutkimus keskittyy veden kuvaan (the image of water). Kezilahabi vietti lapsuutensa saarella Victoria-järven keskellä, ja hänen vesikuvastonsa on rikasta. Tutkimuskysymyksenä on, mitä veden kuva runoteoksissa Kichomi ja Karibu Ndani esittää. Runojen analysoinnissa ja tulkinnassa on tarkasteltu myös sitä, miten äänteellinen taso osallistuu kuvien luomiseen. Tutkimuksen määritelmä kuvasta pohjautuu osittain Hugh Kennerin näkemykseen, jonka mukaan oleellista kuvassa on kirjaimellinen taso. Kennerin lähtökohtaan on yhdistetty John Shoptawin teoriaa, joka korostaa runon äänteellisen puolen tärkeyttä merkityksen muodostumisessa. Foneemien analyysissä vaikutteena on ollut Reuven Tsurin teoria. Analyysiosio osoittaa, että veden kuva edustaa ja käsittelee teoksissa lukuisia teemoja: elämää, kuolemaa, fyysistä vetovoimaa, runoutta, mielikuvitusta ja (ali)tajuntaa sekä moraalia. Veden kuvan tutkimuksen pohjalta on nähtävissä, että Kezilahabin filosofia asettuu elävä/kuollut- ja elämä/kuolema dikotomioiden ulkopuolelle.

Oral Immune Defense against Chronic Hyperplastic Candidosis

Candida yeast species are widespread opportunistic microbes, which are usually innocent opportunists unless the systemic or local defense system of the host becomes compromised. When they adhere on a fertile substrate such as moist and warm, protein-rich human mucosal membrane or biomaterial surface, they become activated and start to grow pseudo and real hyphae. Their growth is intricately guided by their ability to detect surface defects (providing secure hiding , thigmotropism) and nutrients (source of energy, chemotropism). The hypothesis of this work was that body mobilizes both non-specific and specific host defense against invading candidal cells and that these interactions involve resident epithelial cells, rapidly responding non-specific protector neutrophils and mast cells as well as the antigen presenting and responding den-dritic cell lymphocyte plasma cell system. It is supposed that Candida albicans, as a result of dar-winistic pressure, has developed or is utilizing strategies to evade these host defense reactions by e.g. adhering to biomaterial surfaces and biofilms. The aim of the study was to assess the host defense by taking such key molecules of the anti-candidal defense into focus, which are also more or less characteristic for the main cellular players in candida-host cell interactions. As a model for candidal-host interaction, sections of chronic hyperplastic candidosis were used and compared with sections of non-infected leukoplakia and healthy tissue. In this thesis work, neutrophil-derived anti-candidal α-defensin was found in the epithelium, not only diffusely all over in the epithelium, but as a strong α-defensin-rich superficial front probably able to slow down or prevent penetration of candida into the epithelium. Neutrophil represents the main host defence cell in the epithelium, to which it can rapidly transmigrate from the circulation and where it forms organized multicellular units known as microabscesses (study I). Neutrophil chemotactic inter-leukin-8 (IL-8) and its receptor (IL-8R) were studied and were surprisingly also found in the candidal cells, probably helping the candida to keep away from IL-8- and neutrophil-rich danger zones (study IV). Both leukocytes and resident epithelial cells contained TLR2, TLR4 and TLR6 receptors able to recognize candidal structures via utilization of receptors similar to the Toll of the banana fly. It seems that candida can avoid host defence via stimulation of the candida permissive TLR2 instead of the can-dida injurious TLR4 (study V). TLR also provides the danger signal to the immune system without which it will not be activated to specifically respond against candidal antigens. Indeed, diseased sites contained receptor activator of nuclear factor kappa B ligand (RANKL; II study), which is important for the antigen capturing, processing and presenting dendritic cells and for the T lymphocyte activation (study III). Chronic hyperplastic candidosis provides a disease model that is very useful to study local and sys-temic host factors, which under normal circumstances restrain C. albicans to a harmless commensal state, but failure of which in e.g. HIV infection, cancer and aging may lead to chronic infection.

Avuksi pyynnöstä ja pyytämättä : Tampereen Kaupunkilähetyksen kristillissosiaalinen työ ja sen toimintakentät muutoksissa vuosina 1939–1961

Tämän tutkimuksen päätarkoitus on hahmottaa Tampereen Kaupunkilähetyksen kristillissosiaalista työtä ja sen toimintakenttiä niitä kohdanneissa muutoksissa toisesta maailmansodasta 1960-luvun alkuun. Tutkimuksen päämetodi on geneettinen metodi, ja päälähteinä on käytetty tämän yhdistyksen ja sen yhteistyökumppanien arkistoja ja julkaisuja. Tutkimuksen erityisenä tukena ovat olleet tekijän aiemmat tutkimukset tästä tutkimuskohteesta. Tutkimuksessa on selvitetty myös toiminnan sukupuolittumista ja ammatillistumista, sekä toiminnan vaihtelevaa suhdetta Tampereen kaupunkiin ja muihin yhteistyötahoihin. Tampereen Kaupunkilähetys on pitänyt toimintaperiaatteena perinteistä sisälähetystä, johon on kuulunut karitatiivinen ja missionaarinen puoli. Toimintaan on kuulunut niin laitosdiakoniaa kuin avohuollollista työtä. Diakonian ja uuskansankirkollisuuden läpimurto muuttivat työtapoja yhdessä sodan luomien poikkeuksellisten yhteiskunnallisten olojen kanssa. Inflaatio, vuokra- ja hintasäännöstely aiheuttivat raskaita menetyksiä Kaupunkilähetyksen toiminnalle. Samaan aikaan yhteiskunnan sosiaalityö alkoi kehityksen kohti hyvinvointiyhteiskuntaa, mikä ammatillisti ja kohotti sosiaalityön tasoa. Nämä kaikki yhdessä loivat muutospaineita Kaupunkilähetykselle, joka ryhtyi tuottamaan uusia työmuotoja kristillisessä hengessä toteutettuina, kuten avioliittoneuvonnan, jota voi luonnehtia sosiaaliseksi innovaatioksi, sekä hengellistä teollisuustyötä, erilaisia lastensuojelullisia laitoksia, pullakirkon ja kehitysvammaisten teollista työtoimintaa. Samalla Kaupunkilähetyksenkin työ ammatillistui. Tampereen kaupungin kunnallispolitiikkaa hallinnut sosialidemokraattien ja kokoomuslaisten aseveliakseli tuki Tampereen Kaupunkilähetyksen työtä. Tampereen kaupungin sosiaaliviranomaiset, kuten Alpo Lumme, ehdottivat usein uusia työmuotoja Kaupunkilähetykselle. Näiden ehdotuksien mukana tuli lupaukset antaa tarvittava taloudellinen tuki. Kaupungista tuli Kaupunkilähetyksen merkittävin tukija ja yhteistyökumppani. Molemmat hyötyivät yhteistyöstä. Kaupunkilähetys pyrki vastaamaan näkemiinsä sosiaalisiin haasteisiin pikaisesti. Tämä oli myös menestyksen ydin, sillä suhteellisen nopea päätöksenteko uuden toiminnan kokeilusta oli Kaupunkilähetykselle helpompaa kuin kaupungille tai seurakunnille. Yhdistyksen uusille työmuodoille oli luonteenomaista, että joku asiaan perehtynyt henkilö ryhtyi niitä ajamaan voimakkaasti ja taitavasti kohti toteutusta. Toimintamuotojen jouduttua rahoitusvaikeuksiin tai kasvaessa selvästi julkishallinnon tehtäviksi, Kaupunkilähetys luopui tarvittaessa osuudestaan melko kivuttomasti aloittamalla usein jälleen uuden työmuodon. Tampereen Kaupunkilähetys voidaan sijoittaa sosiaalityön toimintakenttään kristillissosiaalista työtä tekevänä kolmannen sektorin toimijana. Yhdistyksen työssä ja hallinnossa oli havaittavissa sellaista sukupuolittumista, että varsinaista työtä tekivät pääosin naiset naisten johdolla. Mies-, poika- ja evankelioimistyötä tekivät puolestaan pääosin miehet. Myös johtokunnissa naisilla oli merkittävä asema, kuten jäsenistössäkin. Johtokuntatoiminta etääntyi seurakunnasta, sillä puheenjohtajaksi vaihtui maallikko jo 1940-luvulla, ja johtokunnassa oli vain vähän pappeja muutenkin. Toiminnan taloudellisena tukena olivat Tampereen kaupunki suurimpana rahoittajana, Tampereen Kaupunkilähetyksen osittain omistama hotelli Emmaus Oy, valtio, Tampereen seurakunnat, yksityiset lahjoittajat ja jäsenistö. Yhdistyksen omat kiinteistöt tuottivat välillä tappiota ja välillä voittoa, mutta niiden tärkein merkitys oli olla toimitiloina.

Essays on Banking Crises

This thesis aims at finding the role of deposit insurance scheme and central bank (CB) in keeping the banking system safe. The thesis also studies the factors associated with long-lasting banking crises. The first essay analyzes the effect of using explicit deposit insurance scheme (EDIS), instead of using implicit deposit insurance scheme (IDIS), on banking crises. The panel data for the period of 1980-2003 includes all countries for which the data on EDIS or IDIS exist. 70% of the countries in the sample are less developed countries (LDCs). About 55% of the countries adopting EDIS also come from LDCs. The major finding is that the using of EDIS increases the crisis probability at a strong significance level. This probability is greater if the EDIS is inefficiently designed allowing higher scope of moral hazard problem. Specifically, the probability is greater if the EDIS provides higher coverage to deposits and if it is less powerful from the legal point of view. This study also finds that the less developed a country is to handle EDIS, the higher the chance of banking crisis. Once the underdevelopment of an economy handling the EDIS is controlled, the EDIS separately is no longer a significant factor of banking crises. The second essay aims at determining whether a country s powerful CB can lessen the instability of the banking sector by minimizing the likelihood of a banking crisis. The data used include indicators of the CB s autonomy for a set of countries over the period of 1980-89. The study finds that in aggregate a more powerful CB lessens the probability of banking crisis. When the CB s authority is disentangled with respect to its responsibilities, the study finds that the longer tenure of CB s chief executive officer and the greater power of CB in assigning interest rate on government loans are necessary for reducing the probability of banking crisis. The study also finds that the probability of crisis reduces more if an autonomous CB can perform its duties in a country with stronger law and order tradition. The costs of long-lasting banking crises are high because both the depositors and the investors lose confidence in the banking system. For a rapid recovery of a crisis, the government very often undertakes one or more crisis resolution policy (CRP) measures. The third essay examines the CRP and other explanatory variables correlated with the durations of banking crises. The major finding is that the CRP measure allowing the regulation forbearance to keep the insolvent banks operative and the public debt relief program are respectively strongly and weakly significant to increase the durations of crises. Some other explanatory variables, which were found by previous studies to be related with the probability of crises to occur, are also correlated with the durations of crises.

Molecular line and continuum studies of the early stages of star formation

New stars form in dense interstellar clouds of gas and dust called molecular clouds. The actual sites where the process of star formation takes place are the dense clumps and cores deeply embedded in molecular clouds. The details of the star formation process are complex and not completely understood. Thus, determining the physical and chemical properties of molecular cloud cores is necessary for a better understanding of how stars are formed. Some of the main features of the origin of low-mass stars, like the Sun, are already relatively well-known, though many details of the process are still under debate. The mechanism through which high-mass stars form, on the other hand, is poorly understood. Although it is likely that the formation of high-mass stars shares many properties similar to those of low-mass stars, the very first steps of the evolutionary sequence are unclear. Observational studies of star formation are carried out particularly at infrared, submillimetre, millimetre, and radio wavelengths. Much of our knowledge about the early stages of star formation in our Milky Way galaxy is obtained through molecular spectral line and dust continuum observations. The continuum emission of cold dust is one of the best tracers of the column density of molecular hydrogen, the main constituent of molecular clouds. Consequently, dust continuum observations provide a powerful tool to map large portions across molecular clouds, and to identify the dense star-forming sites within them. Molecular line observations, on the other hand, provide information on the gas kinematics and temperature. Together, these two observational tools provide an efficient way to study the dense interstellar gas and the associated dust that form new stars. The properties of highly obscured young stars can be further examined through radio continuum observations at centimetre wavelengths. For example, radio continuum emission carries useful information on conditions in the protostar+disk interaction region where protostellar jets are launched. In this PhD thesis, we study the physical and chemical properties of dense clumps and cores in both low- and high-mass star-forming regions. The sources are mainly studied in a statistical sense, but also in more detail. In this way, we are able to examine the general characteristics of the early stages of star formation, cloud properties on large scales (such as fragmentation), and some of the initial conditions of the collapse process that leads to the formation of a star. The studies presented in this thesis are mainly based on molecular line and dust continuum observations. These are combined with archival observations at infrared wavelengths in order to study the protostellar content of the cloud cores. In addition, centimetre radio continuum emission from young stellar objects (YSOs; i.e., protostars and pre-main sequence stars) is studied in this thesis to determine their evolutionary stages. The main results of this thesis are as follows: i) filamentary and sheet-like molecular cloud structures, such as infrared dark clouds (IRDCs), are likely to be caused by supersonic turbulence but their fragmentation at the scale of cores could be due to gravo-thermal instability; ii) the core evolution in the Orion B9 star-forming region appears to be dynamic and the role played by slow ambipolar diffusion in the formation and collapse of the cores may not be significant; iii) the study of the R CrA star-forming region suggests that the centimetre radio emission properties of a YSO are likely to change with its evolutionary stage; iv) the IRDC G304.74+01.32 contains candidate high-mass starless cores which may represent the very first steps of high-mass star and star cluster formation; v) SiO outflow signatures are seen in several high-mass star-forming regions which suggest that high-mass stars form in a similar way as their low-mass counterparts, i.e., via disk accretion. The results presented in this thesis provide constraints on the initial conditions and early stages of both low- and high-mass star formation. In particular, this thesis presents several observational results on the early stages of clustered star formation, which is the dominant mode of star formation in our Galaxy.

Lypsylehmän energiataseen mallintaminen tuotoskauden alkuvaiheessa

Energiataseen mallinnus on osa KarjaKompassi-hankkeeseen liittyvää kehitystyötä. Tutkielman tavoitteena oli kehittää lypsylehmän energiatasetta etukäteen ennustavia ja tuotoskauden aikana saatavia tietoja hyödyntäviä matemaattisia malleja. Selittävinä muuttujina olivat dieetti-, rehu-, maitotuotos-, koelypsy-, elopaino- ja kuntoluokkatiedot. Tutkimuksen aineisto kerättiin 12 Suomessa tehdyistä 8 – 28 laktaatioviikon pituisesta ruokintakokeesta, jotka alkoivat heti poikimisen jälkeen. Mukana olleista 344 lypsylehmästä yksi neljäsosa oli friisiläis- ja loput ayshire-rotuisia. Vanhempien lehmien päätiedosto sisälsi 2647 havaintoa (koe * lehmä * laktaatioviikko) ja ensikoiden 1070. Aineisto käsiteltiin SAS-ohjelmiston Mixed-proseduuria käyttäen ja poikkeavat havainnot poistettiin Tukeyn menetelmällä. Korrelaatioanalyysillä tarkasteltiin energiataseen ja selittävien muuttujien välisiä yhteyksiä. Energiatase mallinnettiin regressioanalyysillä. Laktaatiopäivän vaikutusta energiataseeseen selitettiin viiden eri funktion avulla. Satunnaisena tekijänä mallissa oli lehmä kokeen sisällä. Mallin sopivuutta aineistoon tarkasteltiin jäännösvirheen, selitysasteen ja Bayesin informaatiokriteerin avulla. Parhaat mallit testattiin riippumattomassa aineistossa. Laktaatiopäivän vaikutusta energiataseeseen selitti hyvin Ali-Schaefferin funktio, jota käytettiin perusmallina. Kaikissa energiatasemalleissa vaihtelu kasvoi laktaatioviikosta 12. alkaen, kun havaintojen määrä väheni ja energiatase muuttui positiiviseksi. Ennen poikimista käytettävissä olevista muuttujista dieetin väkirehuosuus ja väkirehun syönti-indeksi paransivat selitysastetta ja pienensivät jäännösvirhettä. Ruokinnan onnistumista voidaan seurata maitotuotoksen, maidon rasvapitoisuuden ja rasva-valkuaissuhteen tai EKM:n sisältävillä malleilla. EKM:n vakiointi pienensi mallin jäännösvirhettä. Elopaino ja kuntoluokka olivat heikkoja selittäjiä. Malleja voidaan hyödyntää karjatason ruokinnan suunnittelussa ja seurannassa, mutta yksittäisen lehmän energiataseen ennustamiseen ne eivät sovellu.

Uutta, vanhaa ja lainattua : Tampereen Kaupunkilähetyksen kristillissosiaalisen työn asemoituminen hyvinvointivaltion rakentumisessa vuosina 1939−1973

The main purpose of this study was to provide a full account of the Christian social work carried out at the Tampere City Mission (TCM) as well as the Missions sphere of operations from the Second World War to the early 1970s, comprising a period of significant change. The study consists of charting the processes of change and connections within the activities of the TCM and how examining these were linked to the general tendencies of the period, in lay work, social work, professionalization and the representation of gender. The positioning of the activities is described on the basis of these tendencies. The main sources for the study were the archives of the Mission, for example the minutes of meetings, correspondences as well as annual reports, and the archives of its partners, such as the City of Tampere, the Evangelical Lutheran parishes of Tampere and the State Welfare Administration. The archives of the Helsinki, Turku and Stockholm Missions supplied comparison reference and other material. In particular, social welfare and Christian social work technical journals of were used as printed sources. The principal method used was the genetic method of historiology. The research subject was also evaluated from the point of view of third sector research in addition to that of professionalization studies and gender studies. By the beginning of the research period, the TCM had turned more and more dedicatedly into a multipurpose social service organization maintaining social services such as old people s homes and children´s homes. This development continued, even though new areas of activity emerged and older ones fell into disuse. Social innovations sprang up, marriage counseling being one of them. On the national level, the TCM pioneered the provision of sheltered industrial work for intellectually disabled persons as well as housing services for them. As new activities were initiated, they overlapped with the established ones, and the TCM handed some of its child protection functions over to the municipality, in accordance with the current adaptation theory. The use of its own property to produce ever-changing social services may be the reason why the association s work continued on with vitality. Functional networks and political aid in the field of social services also bolstered the association. As in other Nordic countries, nonprofit organizations served as partners rather than competitors, with the State establishing institutional welfare arrangements. In the 1960s the municipal takeover of social services impacted the TCM activities. Rules for government subsidies and municipal allowances were not well established; hence these funds were not easily available, making improvements difficult. The TCM was a community in which women had a relatively strong position and an opportunity to make a difference. Female staff were reasonably equal to men, and women worked as heads of a several institutions. Care work employed a number of men, which went against the traditional segregation of labour between the sexes. The TCM s operations were from early on very professionalized, and were developed with particular care. Keywords: Christian social work, third sector, professionalization, gender

Biomarkers in acute respiratory failure

Acute respiratory failure (ARF) is the most common type of organ failure leading to the need for intensive care. It is often secondary to acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS). ARF, and especially ALI and ARDS, cause increased morbidity, and mortality rates remain high (up to 40%). These disorders are characterised by inflammatory reaction and tissue damage. In some cases, inflammation continues and leads to an overwhelming repair process with ongoing fibrosis, accompanied by organ dysfunction and eventually a loss of function. Measuring the magnitude of the inflammation, and the repair process, would theoretically offer information concerning outcome. Early identification of patients whose disease process is likely to proceed unfavourably, would help clinicians to optimise their treatment. The aim of this study was to evaluate the epidemiology of ARF, its treatment, and outcome in Finland, with special interest in biomarkers, and their value in the prediction of mortality. Altogether, 958 adult patients treated with ventilatory support were prospectively included in this study during an eight week period in 2007 in 25 intensive care units. Plasma aminoterminal pro-brain natriuretic peptide (NT-pro-BNP) was assessed in 602 patients, and plasma cell-free DNA in 580 patients, to evaluate their prognostic value in ARF. Markers of collagen metabolism were studied in longitudinal serum samples in 68 patients in order to evaluate their evolution in ARF and the association to multiple organ dysfunction (MOD). Ventilatory support was used in 39% of all ICU patients. The estimated incidence of ARF was 149.5/100 000 per year. Median tidal volumes used were higher than recommended. Overall mortality at 90 days was 31%. Plasma NT-pro-BNP and cell-free DNA were highly increased in the majority of patients. Both markers were independent predictors of 90-day mortality, but their discriminative power was at most moderate when used separately. The mortality was highest in those patients, in whom both biomarkers were over their separate cut-off values. Thus, combined use of these biomarkers may increase their clinical value in the mortality prediction. The markers of collagen metabolism changed significantly over time in surviving patients. None of these markers did associate with MOD in these patients.