Thermodynamic partial properties of Na2O in Nasicon solid solution, Na1+xZr2SixP3-xO12

The thermodynamic activity of sodium oxide (Na2O) in the Nasicon solid solution series, Na1+xZr2SixO12, has been measured in the temperature range 700�1100 K using solid state galvanic cells: Pt|CO2 + O2|Na2CO3?Na1+xZr2SixP3-xO12?(Y2O3)ZrO2?In + In2O3|Ta, Pt for 1 = ? = 2.5, and Pt?CO2 + O2?Na2CO3?ß-alumina?Na1+xZr2SixP3-xO12?Ar + O2?Pt for x = 0, 0.5, 2.5, and 3. The former cell, where the Nasicon solid solution is used as an electrolyte along with yttria-stabilized zirconia, is well suited for Nasicon compositions with high ionic conductivity. In the latter cell, ß-alumina is used as an electrolyte and the Nasicon solid solution forms an electrode. The chemical potential of Na2O is found to increase monotonically with x at constant temperature. The partial entropy of Na2O decreases continuously with x. However, the partial enthalpy exhibits a maximum at x = 2. This suggests that the binding energy is minimum at the composition where ionic conductivity and cell volume have maximum values.

Levosimendaanin vaikutusmekanismi ja nykyinen merkitys sydämen vajaatoiminnan hoidossa

Sydämen vajaatoiminta on erilaisista sydän- ja verisuonisairauksista aiheutuva monimuotoinen oireyhtymä, johon sairastuneiden ja kuolleiden potilaiden määrä on yhä suuri. Sen patofysiologiaan voi kuulua muun muassa sympaattisen hermoston ja reniini-angiotensiini-aldosteroni–järjestelmän aktiivisuutta, huonosti supistuva vasen kammio, sydämen uudelleenmuokkautumista, muutoksia [Ca2+]i:n säätelyssä, kardiomyosyyttien apoptoosia sekä systeeminen tulehdustila. Johonkin osaan sairauden patofysiologiasta eivät nykyiset lääkehoidot riittävästi vaikuta. Klassiset inotroopit lisäävät sydämen supistusvireyttä kasvattamalla solunsisäistä Ca2+-pitoisuutta, mutta ne lisäävät rytmihäiriöriskiä, sydämen hapenkulutusta sekä heikentävät ennustetta. Levosimendaani, kalsiumherkistäjä, lisää sydämen supistusvoimaa [Ca2+]i:ta kohottamatta herkistämällä sydänlihaksen kalsiumin vaikutuksille. Lisäksi levosimendaani avaa sarkolemmaalisia ja mitokondriaalisia K+-kanavia, jotka välittävät vasodilataatiota ja kardioprotektiota. Suurilla annoksilla levosimendaani on selektiivinen PDE3-estäjä. Levosimendaania suositellaan äkillisesti pahentuneen sydämen vajaatoiminnan hoitoon, mutta muitakin lupaavia indikaatioita sille on keksitty. Esimerkiksi kroonisesti annosteltu oraalinen levosimendaani on suojannut kardiovaskulaarijärjestelmää ja parantanut selviytymistä in vivo. Erikoistyössä selvitettiin kroonisesti annostellun oraalisen levosimendaanin, valsartaanin ja näiden kombinaatioterapian vaikutuksia selviytymiseen, verenpaineeseen sekä sydämen hypertrofioitumiseen Dahlin suolaherkillä (Dahl/Rapp) rotilla. Levosimendaanin suojavaikutus ilmeni vähäisempänä kuolleisuutena, mutta ero ei ollut tilastollisesti merkitsevä kontrolliryhmään nähden. Kombinaatioterapia suojasi rottia kardiovaskulaarikuolleisuudelta ja vähensi todennäköisesti verenpaineesta riippuvaisesti sydämen hypertofioitumista niin sydän/kehonpaino–suhteen kuin ultraäänitutkimuksenkin perusteella arvioituna paremmin kuin kumpikaan lääke monoterapiana. Lääkekombinaatio alensi additiivisesti hypertensiota kaikissa mittauspisteissä. Sydämen systolista toimintaa levosimendaani kohensi vain vähäisesti. Dahl/Rapp-rotille kehittyikin pääosin hypertension indusoimaa diastolista sydämen vajaatoimintaa kohonneen IVRT-arvon perusteella. Levosimendaani sekä monoterapiana että kombinaatioterapiana valsartaanin kanssa vähensi sydämen diastolista vajaatoimintaa.

Peritoneal dialysis and neurological outcome in infants and small children

Although improved outcomes for children on peritoneal dialysis (PD) have been seen in recent years, the youngest patients continue to demonstrate inferior growth, more frequent infections, more neurological sequelae, and higher mortality compared to older children. Also, maintain-ing normal intravascular volume status, especially in anuric patients, has proven difficult. This study was designed to treat and monitor these youngest PD patients, which are relatively many due to the high prevalence of congenital nephrotic syndrome of the Finnish type (CNF, NPHS1) in Finland, with a strict protocol, to evaluate the results and to improve metabolic balance, growth, and development. A retrospective analysis of 23 children under two years of age at onset of PD, treated between 1995 and 2000, was performed to obtain a control population for our prospective PD study. Respectively, 21 patients less than two years of age at the beginning of PD were enrolled in prospective studies between 2001 and 2005. Medication for uremia and nutrition were care-fully adjusted during PD. Laboratory parameters and intravascular volume status were regu-larly analyzed. Growth was analyzed and compared with midparental height. In a prospective neurological study, the risk factors for development and the neurological development was determined. Brain images were surveyed. Hearing was tested. In a retrospective neurological study, the data of six NPHS1 patients with a congruent neurological syndrome was analyzed. All these patients had a serious dyskinetic cerebral palsy-like syndrome with muscular dysto-nia and athetosis (MDA). They also had a hearing defect. Metabolic control was mainly good in both PD patient groups. Hospitalization time shortened clearly. The peritonitis rate diminished. Hypertension was a common problem. Left ventricular hypertrophy decreased during the prospective study period. None of the patients in either PD group had pulmonary edema or dialysis-related seizures. Growth was good and catch-up growth was documented in most patients in both patient groups during PD. Mortality was low (5% in prospective and 9% in retrospective PD patients). In the prospective PD patient group 11 patients (52%) had some risk factor for their neuro-development originating from the predialysis period. The neurological problems, detected be-fore PD, did not worsen during PD and none of the patients developed new neurological com-plications during PD. Brain infarcts were detected in four (19%) and other ischemic lesions in three patients (14%). At the end of this study, 29% of the prospectively followed patients had a major impairment of their neurodevelopment and 43% only minor impairment. In the NPHS1+MDA patients, no clear explanation for the neurological syndrome was found. The brain MRI showed increased signal intensity in the globus pallidus area. Kernic-terus was contemplated to be causative in the hypoproteinemic newborns but it could not be proven. Mortality was as high as 67%. Our results for young PD patients were promising. Metabolic control was acceptable and growth was good. However, the children were significantly smaller when compared to their midparental height. Although many patients were found to have neurological impairment at the end of our follow-up period, PD was a safe treatment whereby the neurodevelopment did not worsen during PD.

Oriin seminaaliplasman matriksimetalloproteinaasit

Siirto- ja pakastesiemennysten lisääntyessä tammojen hedelmällisyystulosten parantuminen on hevoskasvatuksen taloudellisuuden kannalta merkittävää. Oriitten spermoissa on eroja sekä siirto- että pakastekestävyydessä. Pelkällä orivalinnalla ei voida kuitenkaan vaikuttaa hedelmällisyystuloksiin, sillä yleensä valinta painottuu suorituskykyyn. Siittiöiden lisäksi seminaaliplasmalla on havaittu vaikutuksia siirto- ja pakastuskestävyyteen. Seminaaliplasma koostuu useista erilaisista biologisista komponenteista, joista matriksimetalloproteinaasit (MMP) ovat yksi. Ne ovat proteiiniperhe, johon kuluu useita jäseniä. MMP:t kykenevät hajottamaan muun muassa solun ulkoisia tukirakenteita sekä tyvikalvoa erilaisissa fysiologisissa ja patologisissa tiloissa. Matriksimetalloproteinaaseja on löydetty useista kudoksista ja myös seminaaliplasmasta. Työn tutkimusosuudessa haluttiin selvittää MMP-pitoisuuksia, niiden vaihteluita oriitten välillä ja mahdollisia vaikutuksia hedelmällisyystuloksiin. Seminaaliplasmanäytteitä tutkittiin yhteensä 43 oriista. Näytteet oli kerätty astutuskaudella 2006 erirotuisilta ja -ikäisiltä hevosilta sekä kahdelta ponilta. Keräysvaiheessa näytteet jaoteltiin 1-4 eri fraktioon. Jokaisesta näytteestä tutkittiin MMP:t zymografian avulla. Seminaaliplasmanäytteiden lisäksi oriilta kerättiin hedelmällisyystietoja siittoloista sekä Suomen raviurheilun ja hevoskasvatuksen keskusjärjestöltä (Suomen Hippos ry). Kaikki tulokset taulukoitiin ja laskettiin aktiiviselle (akt-MMP-2) ja pro-MMP-2:lle sekä kokonais-MMP-9:lle (tot-MMP-9) siittiörikkaassa (SR) ja siittiököyhässä fraktiossa (SK) sekä kokonaisejakulaatissa (KE): keskiarvot, keskihajonnat, mediaanit sekä maksimi- ja minimiarvot. Spearmanin järjestyskorrelaatiokertoimet laskettiin tammojen ensimmäiseen kiimaan tiinehtymisen ja eri MMP-pitoisuuksien välille SR:ssa ja KE:ssa. Oriilla oli havaittavia pitoisuuksia pro- ja akt-MMP-2:ta sekä tot-MMP-9:ää. MMP-pitoisuudet olivat suurimmat SR:ssa. Suurimpia olivat pro-MMP-2:n pitoisuudet ja orikohtaiset erot olivat siinä pieniä. Saadut tulokset vastasivat odotuksia, sillä miesten seminaaliplasmatutkimusten tulokset ovat samansuuntaisia. Eri MMP-pitoisuuksilla ei havaittu korrelaatiota tammojen tiinehtymiseen kanssa. Aineiston pienen koon takia sattumalla voi olla suuri vaikutus tuloksiin. Myös keräysvuodenaika ja yksilön ejakulaation koostumusvaihtelut saattavat vaikuttaa seminaaliplasman MMP-pitoisuuksiin, sillä sen useissa ominaisuuksissa tapahtuu muutoksia näiden muuttujien mukaan. Tulokset ovat suuntaa antavia ja toimivat apuna jatkotutkimuksia suunniteltaessa.

Evidence in European Asylum Procedures

This thesis explores the particular framework of evidentiary assessment of three selected appellate national asylum procedures in Europe and discusses the relationship between these procedures, on the one hand, and between these procedures and other legal systems, including the EU legal order and international law, on the other. A theme running throughout the thesis is the EU strivings towards approximation of national asylum procedures and my study analyses the evidentiary assessment of national procedures with the aim of pinpointing similarities and differences, and the influences which affect these distinctions. The thesis first explores the frames construed for national evidentiary solutions by studying the object of decision-making and the impact of legal systems outside the national. Second, the study analyses the factual evidentiary assessment of three national procedures - German, Finnish and English. Thirdly, the study explores the interrelationship between these procedures and the legal systems influencing them and poses questions in relation to the strivings of EU and methods of convergence. The thesis begins by stating the framework and starting points for the research. It moves on to establish keys of comparison concerning four elements of evidentiary assessment that are of importance to any appellate asylum procedure, and that can be compared between national procedures, on the one hand, and between international, regional and national frameworks, on the other. Four keys of comparison are established: the burden of proof, demands for evidentiary robustness, the standard of proof and requirements for the methods of evidentiary assessment. These keys of comparison are then identified in three national appellate asylum procedures, and in order to come to conclusions on the evidentiary standards of the appellate asylum procedures, relevant elements of the asylum procedures in general are presented. Further, institutional, formal and procedural matters which have an impact on the evidentiary standards in the national appellate procedures are analysed. From there, the thesis moves on to establish the relationship between national evidentiary standards and the legal systems which affect them, and gives reasons for similarities and divergences. Further, the thesis studies the impact of the national frameworks on the regional and international level. Lastly, the dissertation makes a de lege ferenda survey of the relationship between EU developments, the goal of harmonization in relation to national asylum procedures and the particular feature of evidentiary standards in national appellate asylum procedures. Methodology The thesis follows legal dogmatic methods. The aim is to analyse legal norms and legal constructions and give them content and context. My study takes as its outset an understanding of the purposes for legal research also regarding evidence and asylum to determine the contents of valid law through analysis and systematization. However, as evidentiary issues traditionally are normatively vaguely defined, a strict traditional normative dogmatic approach is not applied. For the same reason a traditionalist and strict legal positivism is not applied. The dogmatics applied to the analysis of the study is supported by practical analysis. The aim is not only to reach conclusions concerning the contents of legal norms and the requirements of law, but also to study the use and practical functioning of these norms, giving them a practcial context. Further, the study relies on a comparative method. A functionalist comparative method is employed and keys of comparison are found in evidentiary standards of three selected national appellate asylum procedures. The functioning equivalences of German, Finnish and English evidentiary standards of appellate asylum procedures are compared, and they are positioned in an European and international legal setting. Research Results The thesis provides results regarding the use of evidence in national appellate asylum procedures. It is established that evidentiary solutions do indeed impact on the asylum procedure and that the results of the procedure are dependent on the evidentiary solutions made in the procedures. Variations in, amongst other things, the interpretation of the burden of proof, the applied standard of proof and the method for determining evidentiary value, are analysed. It is established that national impacts play an important role in the adaptation of national appellate procedures to external requirements. Further, it is established that the impact of national procedures on as well the international framework as on EU law varies between the studied countries, partly depending on the position of the Member State in legislative advances at the EU level. In this comparative study it is, further, established that the impact of EU requirements concerning evidentiary issues may be have positive as well as negative effects with regard to the desired harmonization. It is also concluded that harmonization using means of convergence that primaly target legal frameworks may not in all instances be optimal in relation to evidentiary standards, and that more varied and pragmatic means of convergence must be introduced in order to secure harmonization also in terms of evidence. To date, legal culture and traditions seem to prevail over direct efforts at procedural harmonization.

Internet- karttapalveluiden arviointi ja kehitys strategisessa maankäytön suunnittelussa, tapaustutkimuksena Esikaupunkien renessanssi -hanke

Participation is located in a living and complex environment. Traditional means of participation are only partially able to meet the new environmental requirements. In need are forms of participation which take into account the new opportunities of the environment and residents expertise. Internet map applications are an important channel of participation which potential is in many respects as unexplored and unutilized. They are commonly in inventory the perspectives, bringing out the concerns of the area, and only little for discussing about solutions. Interpretation is usually made by designer. This study focuses on evaluation and development of Internet map applications in strategic land use planning. Subject matter is dealt from designer and the inhabitants point of view. City Planning Department of Helsinki s Esikau-punkien Renessanssi -project and the associated SoftGIS survey acts as the case study. In the beginning of the study I tried to recognize the new environment in which the Internet map applications are placed. The research question is, what kind of challenges and opportunities the e-participation confronts in information society, and what kind of requirements the environmental creates for development of an application. In chapter three I evaluate how successfully these requirements are met in Esikau-punkien Renessanssi -project. I m trying to examine how the application would look like if the environment and the characteristics of the project are met better. The approach is experimental and I try to find new ways to take advantage of Internet maps. I try not to be too limited to current projects and studies. For example, I try to examine how social media and Web 2.0 opportunities can be utilized, and how the learning and shaping nature of planning may be reached in Internet map environment. In chapter four I have developed a new concept for the Esikaupunkien Renessanssi map application, and made images to visualize its operation in practice. I collect all the data in the research and gather it into a new service. The aim is to create a better application for Esikaupunkien Renessanssi -project, which takes into account the living and complex environment of participation and responds to threats and opportunities arising from it. The presented outcome is in many respects different from the current query. In the new service the role of residents is to interact and learn. The traditional standing of the Internet maps and the position of resident as one-sided information donor are questioned. In the concept, the residents innovate and make interpretations too. Influences are taken from a number of modern applications and for example services that make use of social media. The user experience is intended to be interactive, fast and easy. The idea is that the service keeps you up to date with planning matters, not the other way around. Service guides inhabitants, striving to achieve a deeper knowledge of the project's objectives as well as the dynamics and realities that different individuals experience.

Detection, epidemiology and host spectrum of cowpox and Borna disease virus infections

Several orthopoxviruses (OPV) and Borna disease virus (BDV) are enveloped, zoonotic viruses with a wide geographical distribution. OPV antibodies cross-react, and former smallpox vaccination has therefore protected human populations from another OPV infection, rodent-borne cowpox virus (CPXV). Cowpox in humans and cats usually manifests as a mild, self-limiting dermatitis and constitutional symptoms, but it can be severe and even life-threatening in the immunocompromised. Classical Borna disease is a progressive meningoencephalomyelitis in horses and sheep known in central Europe for centuries. Nowadays the virus or its close relative infects humans and also several other species in central Europe and elsewhere, but the existence of human Borna disease with its suspected neuropsychiatric symptoms is controversial. The epidemiology of BDV is largely unknown, and the present situation is even more intriguing following the recent detection of several-million-year-old, endogenized BDV genes in primate and various other vertebrate genomes. The aims of this study were to elucidate the importance of CPXV and BDV in Finland and in possible host species, and particularly to 1) establish relevant methods for the detection of CPXV and other OPVs as well as BDV in Finland, 2) determine whether CPXV and BDV exist in Finland, 3) discover how common OPV immunity is in different age groups in Finland, 4) characterize possible disease cases and clarify their epidemiological context, 5) establish the hosts and possible reservoir species of these viruses and their geographical distribution in wild rodents, and 6) elucidate the infection kinetics of BDV in the bank vole. An indirect immunofluorescence assay and avidity measurement were established for the detection, timing and verification of OPV or BDV antibodies in thousands of blood samples from humans, horses, ruminants, lynxes, gallinaceous birds, dogs, cats and rodents. The mostly vaccine-derived OPV seroprevalence was found to decrease gradually according to the year of birth of the sampled human subjects from 100% to 10% in those born after 1977. On the other hand, OPV antibodies indicating natural contact with CPXV or other OPVs were commonly found in domestic and wild animals: the horse, cow, lynx, dog, cat and, with a prevalence occasionally even as high as 92%, in wild rodents, including some previously undetected species and new regions. Antibodies to BDV were detected in humans, horses, a dog, cats, and for the first time in wild rodents, such as bank voles (Myodes glareolus). Because of the controversy within the human Borna disease field, extra verification methods were established for BDV antibody findings: recombinant nucleocapsid and phosphoproteins were produced in Escherichia coli and in a baculovirus system, and peptide arrays were additionally applied. With these verification assays, Finnish human, equine, feline and rodent BDV infections were confirmed. Taken together, wide host spectra were evident for both OPV and BDV infections based on the antibody findings, and OPV infections were found to be geographically broadly distributed. PCR amplification methods were utilised for hundreds of blood and tissue samples. The methods included conventional, nested and real-time PCRs with or without the reverse transcription step and detecting four or two genes of OPVs and BDV, respectively. OPV DNA could be amplified from two human patients and three bank voles, whereas no BDV RNA was detected in naturally infected individuals. Based on the phylogenetic analyses, the Finnish OPV sequences were closely related although not identical to a Russian CPXV isolate, and clearly different from other CPXV strains. Moreover, the Finnish sequences only equalled each other, but the short amplicons obtained from German rodents were identical to monkeypox virus, in addition to German CPXV variants. This reflects the close relationship of all OPVs. In summary, RNA of the Finnish BDV variant could not be detected with the available PCR methods, but OPV DNA infrequently could. The OPV species infecting the patients of this study was proven to be CPXV, which is most probably also responsible for the rodent infections. Multiple cell lines and some newborn rodents were utilised in the isolation of CPXV and BDV from patient and wildlife samples. CPXV could be isolated from a child with severe, generalised cowpox. BDV isolation attempts from rodents were unsuccessful in this study. However, in parallel studies, a transient BDV infection of cells inoculated with equine brain material was detected, and BDV antigens discovered in archival animal brains using established immunohistology. Thus, based on several independent methods, both CPXV and BDV (or a closely related agent) were shown to be present in Finland. Bank voles could be productively infected with BDV. This experimental infection did not result in notable pathological findings or symptoms, despite the intense spread of the virus in the central and peripheral nervous system. Infected voles commonly excreted the virus in urine and faeces, which emphasises their possible role as a BDV reservoir. Moreover, BDV RNA was regularly reverse transcribed into DNA in bank voles, which was detected by amplifying DNA by PCR without reverse transcription, and verified with nuclease treatments. This finding indicates that BDV genes could be endogenized during an acute infection. Although further transmission studies are needed, this experimental infection demonstrated that the bank vole can function as a potential BDV reservoir. In summary, multiple methods were established and applied in large panels to detect two zoonoses novel to Finland: cowpox virus and Borna disease virus. Moreover, new information was obtained on their geographical distribution, host spectrum, epidemiology and infection kinetics.

Effect of V2O5 on the Surface and Structural Characteristics of Potassium Lithium Niobate

It has been suggested that materials with interesting and useful bulk non-linear optical properties might result by substituting vanadium, the lightest element in the group V of periodic table, for Nb or Ta atoms along with Li and three oxygens. It is with this motivation that we have been making attempts to grow single crystals of LiNbO3 doped with various concentrations of V2O5. Unfortunately the results obtained on the ceramic samples of this material have not been very encouraging, owing to their hygroscopic nature. However, our attempts to prepare both ceramic and single-crystalline samples of potassium lithium niobate (K3Li2Nb5O15; KLN) doped V2O5 were successful. In this letter we report the preliminary results concerning our studies on the effect of V2O5 doping on the structural as well as topographic features of both ceramic and single-crystalline samples of KLN.

Idén om en karriär - ett kulturellt manuskript för skapandet av det postmoderna självet:

Bakgrunden till denna undersökning utgörs av arbetslivets förändring och dess konsekvenser för konstrueringen av självidentiteten; hur avväger unga konsulter i början av sin karriär mellan olika diskurser för att skapa en förhandlad självidentitet som styrs av idén om en karriär och såvida är hållbar även i ett långtidsperspektiv? Undersökningen tar avstamp i de sociologiska diskussionerna om informationssamhällets framväxt och dess inverkan på arbetets karaktär. Undersökningen utgår från begreppet kunskapsarbete (Alvesson 2001; Blom, Melin & Pyöriä 2001) eftersom konsultyrket kan anses representera denna typ av arbete. Ett genomgående tema är flexibiliteten och det höga tempot som å ena sidan möjliggör självförverkligande men å andra sidan försvårar skapandet av en sammanhängande självidentitet (Sennett 2002). Denna problematik är viktigt att ta i beaktande då förlängandet av arbetskarriärerna och ökandet av arbetslivets attraktivitet blivit centrala mål för den finska samhällspolitiken (Julkunen & Pärnänen 2005) samtidigt som ett generationsskifte håller på att ske på den finländska arbetsmarknaden. Undersökningen utgår från idén om karriären som ett manuskript som ger upphov för identitetsförhandlingar och sammanbinder livets olika domäner till ett personligt liv inte bara i nuläget utan även i ett långtidsperspektiv. Enligt Alvesson & Willmot (2002) framkallas identitetsförhandlingar genom både samhälleliga och organisationsspecifika identitetsreglerande praktiker. Jag utgår från antagandet att självidentiteten fungerar som den sammanbindande knytpunkten mellan karriären och det övriga livet, vilket gör det intressant att koncentrera sig på de identitetsförhandlingar som informanterna utsätts för i förhållande till sitt arbete och idén om en karriär. Begreppet personligt liv ger utrymme för individuell aktivitet och personliga betydelser men behåller ändå föreställningen om individen som inbäddad och sammanbunden i och med det sociala och kulturella (Smart 2007). I bakgrunden finns teorierna om den nya form som makten antagit i organisationer (Foucault; Rose 1999; Grey 1994, Casey 1995) och förvandlat individen till en ett självstyrande subjekt som arbetar som en entreprenör (Rose 1999). Jag poängterar den subjektiva aspekten av karriären som någonting som individen själv konstruerar (Hughes 1997; Barley 1989) och uppfattar i likhet med Julkunen (2003) och Acker (1990; 2006) ålder och kön som sociala kategorier i organisationsstrukturen. Syftet med denna studie är att undersöka hur unga personer utför identitetsförhandlingar i förhållande till arbetet och idén om en karriär i nuläget, samt sammanbinder karriären, framtiden och livet över lag med sin självidentitet i ett karriärperspektiv. Jag har valt unga konsulter som forskningsobjekt, eftersom endast en liten del av den sociologiska arbetslivsforskningen intresserat sig för just unga. Konsultbranschen är ett intressant forskningsobjekt av samma orsak – denna bransch har behandlats i mycket liten skala i finländsk forskning. Det empiriska materialet består av kvalitativa intervjuer med unga, högutbildade män och kvinnor i konsultbranschen. Som analysmetod har jag använt mig av tema-analys inspirerad av diskursanalys. Genom att undersöka individers identitetsförhandlingar i ett karriärperspektiv hoppas jag kunna bidra med nya synpunkter och infallsvinklar samt bättre förståelse för det postindustriella arbetslivet som karakteriseras av kunskapsintensifiering och snabba förändringar i organisationer. Studien visar att idén om en karriär fungerar som ett medel för designandet av det postmoderna självet på samma sätt som till exempel konsumtionen av vissa varumärken. Enligt studien har den flexibla kapitalismen olika inverkan på män och kvinnors idéer om en karriär och betjänar den manliga karriären betydligt bättre än den kvinnliga, åtminstone så länge traditionella könskonstruktioner dominerar. För männen är det naturligt att totalt utesluta faderskapet från karriärkonstruktionen, vilket får dem att kapitulera inför organisationens krav. För kvinnorna är det lika naturligt att justera idén om den framtida karriären enligt möjliga barn i framtiden. Möjligheten att bejaka moderskapets krav verkar beskydda den kvinnliga självidentiteten från att totalt ge efter för organisationens försök att kontrollera subjektiviteten. De unga informanterna konstruerar sitt arbete i mycket annorlunda termer än vad som traditionellt förknippas med arbete; konsultarbetets projektbaserade karaktär konstrueras som äventyrligt, roligt, intressant och omväxlande. Eftersom avsaknad av långsiktighet och rutiner förknippas med den tid i livet då man är ung, underlättades sammanförandet av konsultarbetet med självidentiteten. Samtidigt visar studien hur svårt individen, som fungerar likt en entreprenör i förhållande till sin arbetsgivare, har att skilja mellan arbete och övrigt liv samtidigt som diskursen om balans mellan arbete och fritid dominerar i samhället. Detta ger upphov till en konstruktion av självet som en lycklig och autonom individ som är nöjd över sitt val av start på karriären och tycker om att jobba, medan de långa arbetsdagarna och kraven på ständig effektivitet och prestationer konstrueras som något naturligt. Slutligen efterlyser studien en omdefiniering av begreppet kunskapsarbete. Arbetssociologin i sin helhet har utgått från tanken om arbete som något ofrivilligt eller som tvång, medan informanterna i denna undersökning tvärtom konstruerar sitt arbete i termer som traditionellt förknippas med fritid och frivillighet . Man kan fråga sig ifall kunskapsarbetet håller på att slita sig loss från den traditionella uppfattningen om arbete och skapa en allt skarpare kontrast till det arbete som utförs i traditionell bemärkelse?

Functional expression and subcellular localization of the Cl- cotransporters KCC2 and NKCC1 in rodent hippocampal and neocortical neurons

The work presented here has focused on the role of cation-chloride cotransporters (CCCs) in (1) the regulation of intracellular chloride concentration within postsynaptic neurons and (2) on the consequent effects on the actions of the neurotransmitter gamma-aminobutyric acid (GABA) mediated by GABAA receptors (GABAARs) during development and in pathophysiological conditions such as epilepsy. In addition, (3) we found that a member of the CCC family, the K-Cl cotransporter isoform 2 (KCC2), has a structural role in the development of dendritic spines during the differentiation of pyramidal neurons. Despite the large number of publications dedicated to regulation of intracellular Cl-, our understanding of the underlying mechanisms is not complete. Experiments on GABA actions under resting steady-state have shown that the effect of GABA shifts from depolarizing to hyperpolarizing during maturation of cortical neurons. However, it remains unclear, whether conclusions from these steady-state measurements can be extrapolated to the highly dynamic situation within an intact and active neuronal network. Indeed, GABAergic signaling in active neuronal networks results in a continuous Cl- load, which must be constantly removed by efficient Cl- extrusion mechanisms. Therefore, it seems plausible to suggest that key parameters are the efficacy and subcellular distribution of Cl- transporters rather than the polarity of steady-state GABA actions. A further related question is: what are the mechanisms of Cl- regulation and homeostasis during pathophysiological conditions such as epilepsy in adults and neonates? Here I present results that were obtained by means of a newly developed method of measurements of the efficacy of a K-Cl cotransport. In Study I, the developmental profile of KCC2 functionality during development was analyzed both in dissociated neuronal cultures and in acute hippocampal slices. A novel method of photolysis of caged GABA in combination with Cl- loading to the somata was used in this study to assess the extrusion efficacy of KCC2. We demonstrated that these two preparations exhibit a different temporal profile of functional KCC2 upregulation. In Study II, we reported an observation of highly distorted dendritic spines in neurons cultured from KCC2-/- embryos. During their development in the culture dish, KCC2-lacking neurons failed to develop mature, mushroom-shaped dendritic spines but instead maintained an immature phenotype of long, branching and extremely motile protrusions. It was shown that the role of KCC2 in spine maturation is not based on its transport activity, but is mediated by interactions with cytoskeletal proteins. Another important player in Cl- regulation, NKCC1 and its role in the induction and maintenance of native Cl- gradients between the axon initial segment (AIS) and soma was the subject of Study III. There we demonstrated that this transporter mediates accumulation of Cl- in the axon initial segment of neocortical and hippocampal principal neurons. The results suggest that the reversal potential of the GABAA response triggered by distinct populations of interneurons show large subcellular variations. Finally, a novel mechanism of fast post-translational upregulation of the membrane-inserted, functionally active KCC2 pool during in-vivo neonatal seizures and epileptiform-like activity in vitro was identified and characterized in Study IV. The seizure-induced KCC2 upregulation may act as an intrinsic antiepileptogenic mechanism.

Genomic alterations in Myeloproliferative Neoplasms and Myelodysplastic Syndromes

Myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders whose etiology and molecular pathogenesis are poorly understood. During the past decade, enormous developments in microarray technology and bioinformatics methods have made it possible to mine novel molecular alterations in a large number of malignancies, including MPN and MDS, which has facilitated the detection of new prognostic, predictive and therapeutic biomarkers for disease stratification. By applying novel microarray techniques, we profiled copy number alterations and microRNA (miRNA) expression changes in bone marrow aspirate and blood samples. In addition, we set up and validated an miRNA expression test for bone marrow core biopsies in order to utilize the large archive material available in many laboratories. We also tested JAK2 mutation status and compare it with the in vitro growth pattern of hematologic progenitors cells. In the study focusing on 100 MPN cases, we detected a Janus kinase 2 (JAK2) mutation in 71 cases. We observed spontaneous erythroid colony growth in all mutation-positive cases in addition to nine mutation negative cases. Interestingly, seven JAK2V167F negative ET cases showed spontaneous megakaryocyte colony formation, one case of which also harbored a myeloproliferative leukemia virus oncogene (MPL) mutation. We studied copy number alterations in 35 MPN and 37 MDS cases by using oligonucleotide-based array comparative hybridization (array CGH). Only one essential thrombocythemia (ET) case presented copy number alterations in chromosomes 1q and 13q. In contrast, MDS cases were characterized by numerous novel cryptic chromosomal aberrations with the most common copy number losses at 5q21.3q33.1 and 7q22.1q33, while the most common copy number gain was trisomy 8. As for the study of the bone marrow core biopsy samples, we showed that even though these samples were embedded in paraffin and underwent decalcification, they were reliable sources of miRNA and suitable for array expression analysis. Further, when studying the miRNA expression profiles of the 19 MDS cases, we found that, compared to controls, two miRNAs (one human Epstein-Barr virus (miR-BART13) miRNA and one human (has-miR-671-5p) miRNA) were downregulated, whereas two other miRNAs (hsa-miR-720 and hsa-miR-21) were upregulated. However, we could find no correlation between copy number alterations and microRNA expression when integrating these two data. This thesis brings to light new information about genomic changes implicated in the development of MPN and MDS, and also underlines the power of applying genome-wide array screening techniques in neoplasias. Rapid advances in molecular techniques and the integration of different genomic data will enable the discovery of the biological contexts of many complex disorders, including myeloid neoplasias.

The role of p73 in cancer – a pathway towards more effective cancer therapy

The p53-family consists of three transcription factors, p53, p73 and p63. The family members have similar but also individual functions connected to cell cycle regulation, development and tumorigenesis. p53 and p73 act mainly as tumor suppressors. During DNA damage caused by anticancer drugs or irradiation, p53 and p73 levels are upregulated in cancer cells leading to apoptosis and cell cycle arrest. p53 is mutated in almost 50 per cent of the cancers, causing the cancer cells unable to undergo cell death. Instead, p73 is rarely mutated in cancer cells and because of that could be more viable target for anticancer therapy. The network surrounding the regulation of p73 is extensive and has several potential targets for cancer therapy. One of the most studied is Itch ligase, the negative regulator of p73 levels. Gene therapy directed towards knockdown of Itch ligase is a potential approach but in need for more in vivo proof. p73 has two isoforms, transactivating TA-forms and dominant-negative ΔN-forms. The specific regulation of these isoforms could also offer a possible way for more effective cancer treatment. The literature work includes information of structures, isoforms, functions and possible therapeutic targets of p73. Also the main therapeutic approaches to date are introduced. The experimental part is based on transfection and cytotoxicity studies done e.g. in pancreatic cancer cells (Mia PaCa-2, PANC1, BxPc-3 and HPAC). The aim of the experimental work was to optimize the conditions for effective transfection with DAB16 dendrimer nanoparticles and to measure the cytotoxicity of plain dendrimers and DAB16-pDNA complexes. Also the protein levels of p73 and Itch ligase were measured by Western blotting. The work was done as a part of a bigger project, which was aiming to down regulate Itch ligase (negative regulator of p73) by siRNA/shRNA. Tranfection results were promising, showing good transfection efficacy with DAB16 N/P30 in pancreatic cancer cells (except in BxPc-3). Pancreatic cancer cells showed recovery in 3 days after they were exposed to plain dendrimer solution or to DAB16-pDNA. Measurement of protein levels by Western blotting was not optimal and the proposals for the improvement regarding e.g. the gels and the extracted protein amounts have been done.

Eri maitohappobakteerien ja niiden annostustason vaikutus säilörehun käymislaatuun ja aerobiseen stabiilisuuteen

Tämän maisterin tutkielman tarkoituksena oli testata eri maitohappobakteerien ja niiden annostustason vaikutusta säilörehun käymislaatuun ja aerobiseen stabiilisuuteen. Biologisilla säilöntäaineilla eli ympeillä säilöttyjen rehujen laatua verrattiin kontrolleina toimiviin painorehuun ja muurahaishapolla tehtyyn rehuun. Koerehut tehtiin Helsingin yliopiston Maataloustieteiden laitoksella 7.6.2010. Timotei (Phleum pratense) - nurminata (Festuca pratensis) kasvusto korjattiin tähkimisen alkuvaiheessa D-arvon ollessa 711 g/kg ka. Nurmikasvuston kuiva-ainepitoisuus oli 170 g/kg heti niiton jälkeen määritettäessä ja neljän tunnin esikuivauksen jälkeen 208 g/kg. Rehuraaka-aine jaettiin kuuteen erään, joihin lisättiin säilöntäaine. Säilöntäainekäsittelyt olivat: 1) ei säilöntäainetta (painorehu), 2) muurahaishappo (100 %:na 4 l/t), 3) Lactobacillus plantarum ja Pediococcus acidilactici 1x10? pmy/g sekä pektinaasi-, ksylanaasi- ja sellulaasientsyymi, 4) L. plantarum 1x10? pmy/g, 5) L. plantarum 1x10? pmy/g ja 6) L. plantarum ja L. buchneri 2x10? pmy/g. Rehut säilöttiin laboratoriosiiloissa kolmena rinnakkaisena. Laboratoriosiilojen lisäksi rehua säilöttiin jokaisesta säilöntäainekäsittelystä kuuteen rinnakkaiseen minisiiloon säilönnän alkuajan fermentaation ja rehujen pH:n muutoksen seuraamiseksi. Minisiiloista seurattiin kaasuntuotantoa 21 päivän ajan. Raaka-aineen koostumus ja rehujen säilönnällinen laatu sekä aerobinen stabiilisuus määritettiin. Säilörehujen kuiva-ainepitoisuus oli suhteellisen pieni (n. 210 g/kg), jotta voitiin testata biologisten säilöntäaineiden tehoa märässä rehussa. Kosteassa rehussa biologisten säilöntäaineiden toiminnan onnistuminen on haastavaa. Koska raaka-aineen sokeripitoisuus oli kuitenkin erittäin suuri (196 g/kg ka), onnistui ymppirehujen säilöntä hyvin. Kaikkien koerehujen pH oli alle 4:n. Painorehu ei täyttänyt hyvän rehun kriteerejä ammoniumtypen osalta. Muurahaishapporehu oli laadultaan tyydyttävää etikkahapon pitoisuuden osalta. Rehussa tapahtui epätyypillistä etanolikäymistä hiivojen toimesta, jonka johdosta rehussa muodostui suuri määrä kaasua säilönnän aikana. Muurahaishapporehu ei kuitenkaan lämmennyt aerobisen stabiilisuuden mittauksen aikana, johtuen todennäköisesti suuresta etikkahapon määrästä ja toisaalta pienestä sokerin määrästä. Maitohappobakteerisäilöntäaineilla saatiin käymislaadultaan parempaa säilörehua verrattuna painorehuun, lukuun ottamatta maitohappobakteeri-entsyymirehua. Entsyymilisäyksestä ei todennäköisesti ollut hyötyä rehun säilöntälaadun kannalta. Raaka-aineen suuren sokeripitoisuuden johdosta säilörehussa oli koko säilönnän ajan tarpeeksi sokeria maitohappobakteerien käytettäväksi ja sokeri toimi siten substraattina haitallisille mikrobeille tuottaen suuren etikkahappopitoisuuden. Maitohappobakteeri-entsyymiseoksella tehty rehu oli etikkahappopitoisuuden perusteella heikkolaatuista. Lactobacillus plantarumin molemmilla annostustasoilla (1x10? ja 1x10? pmy/g rehua) saatiin laadultaan hyvää rehua. Suuri sokeripitoisuus molemmissa rehuissa johtui todennäköisesti raaka-aineen tavallista suuremmasta sokerin määrästä. Molempien rehujen maitohappo-etikkahappo-suhde oli melko korkea, viitaten homofermentatiiviseen maitohappokäymiseen. Lactobacillus buchneri –lisäyksellä rehu oli säilönnälliseltä laadultaan hyvää. Heterofermentatiivisen ympin lisäys nosti tyypillisesti rehun pH:ta sekä pienensi maitohappoetikkahappo-suhdelukua verrattuna homofermentatiiviseen ymppiin. L. buchneri –lisäys paransi hieman säilörehun aerobista stabiilisuutta verrattuna homofermentatiivisella maitohappobakteerilla säilöttyyn rehuun, mutta tulos ei ollut tilastollisesti merkitsevä.

Molekyylibiologisten menetelmien kehittäminen ihmisen suoliston sulfaattia pelkistävien bakteerien määrittämiseksi

Ihmisen ruuansulatuskanavan bakteeriston kehitys alkaa syntymästä, jolloin ensimmäiset bakteerit kansoittavat steriilin ruuansulatuskanavan. Bakteeristo kehittyy perimän, ympäristön ja varhaisen ruokavalion vaikutuksesta kohti monimuotoisempaa bakteeripopulaatiota. Aikuisen ruuansulatuskanavan normaalibakteeristo on varsin muuttumaton, mutta siihen vaikuttavat monet tekijät, kuten ikä, terveydentila, ruokavalio ja antibioottien käyttö. Bakteeriston koostumus vaihtelee ruuansulatuskanavan eri osissa ja bakteerimäärä kasvaa kohti paksusuolta, ollen paksusuolessa ja ulosteessa peräti 1010-1012 pmy/ml. Suurin osa ruuansulatuskanavan bakteereista on anaerobeja. Ruuansulatuskanavan bakteeristo vaikuttaa muun muassa suoliston kehittymiseen ja hiilihydraattien ja proteiinien hajotukseen sekä toimii osana immuunipuolustusta. Sulfaattia pelkistävät bakteerit (SRB) ovat monimuotoinen ryhmä pääosin anaerobisia bakteereita, jotka käyttävät aineenvaihdunnassaan elektronin vastaanottajana sulfaattia muuttaen sen lopulta sulfidiksi. SRB:t ovat sopeutuneet useisiin erilaisiin ympäristöihin. Niitä tavataan mm. vesistöjen sedimenteissä sekä ihmisen ruuansulatuskanavassa. Ihmisen ruuansulatuskanavassa on SRB:ta n. 105-108 pmy/g, ja niitä on löydetty erityisesti anaerobisista osista kuten suun ientaskuista ja paksusuolesta. SRB:t voivat olla haitaksi ruuansulatuskanavalle tuottamansa sulfidin vuoksi, joka esiintyy vesiliuoksessa vetysulfidina. Tämän on havaittu olevan toksista suoliston epiteelisoluille. Viimeaikoina on kiinnostuttu sulfaatinpelkistäjien yhteydestä suoliston sairaustiloihin, kuten tulehduksellisiin suolistosairauksiin (IBD). Pro gradu -tutkimukseni tavoitteena oli kehittää PCR-DGGE- ja qPCR-menetelmät ulosteen sulfaattia pelkistävien bakteerien määritykseen. Kohdegeeninä menetelmänkehityksessä käytettiin dsrAB-geeniä, joka koodaa dissimilatorista sulfiitinpelkistysentsyymiä. dsrAB-geeni on sulfaatinpelkistäjille ominainen konservoitunut geenialue, johon perustuvia tutkimuksia ei vielä ole paljon ihmispuolelta. qPCR-menetelmä saatiin optimoitua herkäksi ja spesifiseksi käyttäen dsrA-geenispesifisiä alukkeita, mutta PCR-DGGE-menetelmää ei saatu optimoitua käytössä olleilla alukkeilla, jotka monistivat PCR-DGGE:ssa myös negatiivikontrollikantoja. Tutkittaessa qPCR:lla IBD:tä (Crohn ja ulseratiivinen koliitti) sairastavien lasten ja terveiden kontrollihenkilöiden ulostenäytteistä eristettyä DNA:ta, merkittävää eroa SRB-määrissä ei havaittu eri ryhmien välillä. Crohnin tautia sairastavien aktiivisen vaiheen ja oireettoman vaiheen näytteiden välillä oli kuitenkin tilastollisesti merkitsevä ero (SRB-määrät; oireeton vaihe>oireellinen vaihe) (P <0,05).

A hypothesis on a specific sequence-dependent conformation of DNA and its relation to the binding of the lac-repressor protein

The structure and properties of the double-helical form of the alternating copolymer poly(dA-dT) are considered. Different lines of evidence are interpreted in terms of a structure in which every second phosphate-diester linkage has a conformation different from that of the normal B form. A rationale for this “alternating-B” structure is given which provides an explanation for the effects of chemical modifications of the T residues on the binding of the poly(dA-dT)· poly(dA-dT) to the lac repressor of Escherichia coli.