„Und frei erklär' ich alle meine Knechte“ : Höflichkeit als Ausdruck sozialer Utopie in Schillers Drama Wilhelm Tell.

My dissertation is an interdisciplinary study of the relationship between the Swiss peasants and nobles in Friedrich Schiller’s play Wilhelm Tell (1804). Changes to this relationship are of particular interest. Communication in the play is examined via a micro-analysis based on Penelope Brown’s and Stephen C. Levinson’s theoretical framework Politeness: Some universals in language usage. (1978, 1987). Brown and Levinson distinguish between positivepoliteness and negative-politeness strategies and their distinction is useful for my argument, since they claim that the use of positive-politeness strategies reflects the speaker’s intention to minimize the distance between the interlocutors (Brown and Levinson 1987: 103). Negative-politeness strategies, by contrast, result in social distancing (Brown and Levinson 1987: 130). In accordance with Brown’s and Levinson’s theory, it can be argued that the distribution of positive-politeness and negative-politeness strategies reflects changes in the distance between the fictional interlocutors as representatives of their social classes in Wilhelm Tell. The analysis of the communication in the play highlights that existing conflicts within the social groups are resolved and replaced with solidarity (cf. ‘Claim ’common ground’ and ‘Claim in-group membership with H’) before the peasants and noblemen appear on stage simultaneously in III, 3. In the scene in question, Geßler forces Tell to shoot the apple off his son’s head. Although both nobles and peasants are present, they do not communicate with each other. Thus, communication between the social classes occurs for the first time in IV, 2. This scene is crucial with regard to the changes in the relationship between the social classes in the play. The younger generation, with Rudenz as a representative of the nobility and Melchthal as a representative of the peasants, break with the prevailing conventions and initiate a new type of cooperation based on mutual helping and equality in the right and the duty to protect the country from the violent oppressors representing Habsburg (cf. ‘Convey that S and H are cooperators’, ‘Claim reflexivity’ and ‘Claim reciprocity’). The linguistic analysis reveals the crucial role of the Swiss nobility in the development of the social utopia, as well as the non-contribution of Wilhelm Tell. In fact, Tell never communicates with the Swiss noblemen. The role of the nobility and the role of Wilhelm Tell are further investigated in a comparison between Schiller’s Wilhelm Tell and four of Schiller’s historical sources. These sources, which contain earlier, non-dramatic versions of the establishment of the Swiss Confederation, are the following: Kronica von der loblichen Eydtgnoschaft compiled by Petermann Etterlin (1507), Gemeiner loblicher Eydgnoschafft Stetten Landen vnd Völckeren Chronik wirdiger thaaten beschreybung (1548) written by Johann Stumpf, Chronicon Helveticum of Aegidius Tschudi (the publication of Iselin from 1734 and 1736) and Johannes von Müller’s Geschichten schweizerischer Eidgenossenschaft (1786). Thecomparison sheds light on the fact that both Tschudi and von Müller emphasize unity among the Swiss and cooperation in their attempt to defeat the enemy. However, Schiller has reinforced the role of the nobility in the cooperation. In addition, the comparison between Schiller’s play and the historical sources reveals profound differences with regard to the role of Wilhelm Tell. In all of Schiller’s sources, Tell is present at Rütli, whereas he is absent from Rütli in Schiller’s play. In the play in general, Tell is conspicuously separated from the other peasants. Explanations of my linguistic results, which correspond to the above mentioned differences between the roles of the figures in Wilhelm Tell and the depictions in Schiller’s sources, are found by comparing the path of Schiller’s Swiss towards an egalitarian perspective with the kind of social evolution depicted by the German philosopher Johann Benjamin Erhard in his essay Über das Recht des Volks zu einer Revolution (1795). Aiming at considering Schiller’s social utopia within the larger cultural framework of the German response to the French Revolution, the comparison suggests that both authors depict the need for social change in terms of a change in social hierarchies (Erhard 1970: 95-96, cf. Foi 2005: 225). Erhard’s essay thus helps explain the political intention of Schiller’s play to keep the ideals of the French Revolution as crucial aims but profoundly change the means towards freedom and equality. In his attempt to claim the political resistance of the nobles and peasants as just, however, Schiller sacrificed the figure of Wilhelm Tell. Guilty of the murder of Geßler, Tell was no longer suitable for the righteous revolution imagined by Schiller (cf. Bloch 2008: 215 and Schulz 2005: 228). This explains Tell’s absence in the Rütli scene, his isolation in the plot, as well as his non-contribution to the social utopia. Together, the linguistic analysis and contextualisation of Schiller’s play support my hypothesis that Wilhelm Tell describes a process of change in the relationship between peasants and nobles. The interdisciplinary approach to the topic proved to be fruitful for all areas of the research involved.

Virtual communities : a virtual treasure trove for end-user developers

End-user development is a very common but often largely overlooked phenomenon in information systems research and practice. End-user development means that regular people, the end-users of software, and not professional developers are doing software development. A large number of people are directly or indirectly impacted by the results of these non-professional development activities. The numbers of users performing end-user development activities are difficult to ascertain precisely. But it is very large, and still growing. Computer adoption is growing towards 100% and many new types of computational devices are continually introduced. In addition, other devices not previously programmable are becoming so. This means that, at this very moment, hundreds of millions of people are likely struggling with development problems. Furthermore, software itself is continually being adapted for more flexibility, enabling users to change the behaviour of their software themselves. New software and services are helping to transform users from consumers to producers. Much of this is now found on-line. The problem for the end-user developer is that little of this development is supported by anyone. Often organisations do not notice end-user development and consequently neither provide support for it, nor are equipped to be able to do so. Many end-user developers do not belong to any organisation at all. Also, the end-user development process may be aggravating the problem. End-users are usually not really committed to the development process, which tends to be more iterative and ad hoc. This means support becomes a distant third behind getting the job done and figuring out the development issues to get the job done. Sometimes the software itself may exacerbate the issue by simplifying the development process, deemphasising the difficulty of the task being undertaken. On-line support could be the lifeline the end-user developer needs. Going online one can find all the knowledge one could ever need. However, that does still not help the end-user apply this information or knowledge in practice. A virtual community, through its ability to adopt the end-user’s specific context, could surmount this final obstacle. This thesis explores the concept of end-user development and how it could be supported through on-line sources, in particular virtual communities, which it is argued here, seem to fit the end-user developer’s needs very well. The experiences of real end-user developers and prior literature were used in this process. Emphasis has been on those end-user developers, e.g. small business owners, who may have literally nowhere to turn to for support. Adopting the viewpoint of the end-user developer, the thesis examines the question of how an end-user could use a virtual community effectively, improving the results of the support process. Assuming the common situation where the demand for support outstrips the supply.

Chlorophyll a fluorescence in rice plants exposed of herbicides of group imidazolinone

The objective of this work was to investigate the injuries caused to the photosynthetic apparatus of three types of rice exposed to application of imidazolinone group herbicides. Two experiments were conducted using herbicides Imazethapyr+imazapic and Imazapyr+imazapic, in a split-plot experimental design, and a 3 x 3 factorial, with six replications. The first factor (A) consisted of the herbicide rates 0, 100 e 200 g ha-1 of Imazethapyr+imazapic and 0, 140 e 280 g ha-1 of Imazapyr+imazapic; factor B consisted of type of rice (cv. Puitá Inta CL, sensitive red rice ecotype and red rice ecotype with suspected herbicide tolerance to Imidazolinone). Chlorophyll a fluorescence parameters were evaluated in plants at 30 days after herbicide application, using a portable fluorometer (HandyPEA, Hanstech). The photosynthetic metabolism of cv. Puitá Inta CL was found to tolerate commercial dosages of both herbicides. High sensitivity to the herbicides was observed for the sensitive red rice ecotype, while the photosynthetic apparatus of red rice ecotype with suspected herbicide tolerance showed high tolerance to both herbicides applied at rates higher than the commercial rate. The application of chemical herbicides of the imidazolinone group on rice plants causes changes in the photosynthetic metabolism of plants, detected by evaluating the emission of transient chlorophyll a fluorescence. This method can be useful in helping detect resistance and/or tolerance of red rice plants to herbicides of the imidazolinone group.

Helluntailaiset luokkakuvassa. uskontokulttuuri ja yksikön luokka-asema Turun Helluntaiseurakunnassa

Tässä tutkimuksessa analysoin sitä, miten helluntailainen uskontokulttuuri vaikuttaa yksilön valintoihin ja sen kautta siihen, mihin luokka-asemiin seurakuntalaiset ovat päätyneet Turun Helluntaiseurakunnassa. Tutkimus on uskontoantropologinen ja kuuluu uskontotieteen alaan. Siinä yhdistetään sosiologista luokkatutkimusta sekä rationaalisen valinnan ja toiminnan teorioita uskontoantropologisessa viitekehyksessä. Pääasialliseksi aineistoksi keräsin laajan etnografisen aineiston, joka koostuu systemaattisesta havainnoinnista, kyselyistä ja haastatteluista. Lisäksi olen tutkinut seurakunnan ja helluntailaisuutta koskevia arkistoja sekä kirjallisuutta. Tutkimuksen kohde on Turun helluntaiseurakunta, joka muodostaa tutkimusongelman kannalta mielekkään tutkimusasetelman. Tutkimus kertoo olennaista tietoa siitä, miten uskonto vaikuttaa yksilön valintoihin ja hänen yhteiskunnalliseen asemaansa. Tutkimusaineiston pohjalta laadin selittävän mallin kuvaamaan sitä prosessia, miten yksilöt tekevät valintojaan rationaalisina toimijoina eri kulttuurien vaikutuspiireissä. Antropologisena pohjana selitykselle toimii uskonnon rajojen rakentumisen, muuttamisen ja ylittämisen logiikka. Pyhän kategorisoinnin jäsentämä uskontokulttuuri ohjaa yksilöä suosimaan toisia kulttuureja, luokkakulttuureja ja tyylejä sekä vierastamaan toisia. Jos yksilö haluaa tehdä valinnan, joka nähdään arveluttavana, täytyy hänen oikeuttaa se kulttuurinsa sisäisillä symboleilla ja rituaaleilla. Turun Helluntaiseurakunnassa korostuvat auttamisen ja sivistämisen ammatit, kuten lääkäri, sairaanhoitaja ja opettaja. Nämä voidaan edelleen jäljittää seurakunnan opetuksiin sekä seurakuntalaisten käyttämiin diskursseihin ja oletuksiin hyväksytyistä elämäntyyleistä. Lisäksi diskursseissa korostuvat näkemykset ammatista kutsumuksena, koulutuksen itsestäänselvyys sekä asemaan liittyvän radikalismin välttäminen. Seurakunnan uskontokulttuurin keskiluokkaistava vaikutus näkyy ennen kaikkea toisen ja useamman polven helluntailaisissa, jotka sijoittuvat korkeampiin asemiin kuin ulkopuolelta kääntyneet. Seurakunnan uskontokulttuuri vähentää luokkatietoisuuden syntyä ja voi osaltaan ylläpitää yhteiskunnan luokkarakennetta, koska uskonnon ensisijaiset päämäärät eivät kohdistu yhteiskunnan rakenteen muuttamiseen Suomessa. Tutkimuksen mukaan yksilön omat ja häneen kohdistetut oletukset ja arvot, jotka hän kulttuurissa omaksuu, ohjaavat häntä myös kulttuurinsa näkökulmasta suosiollisiin asemiin.

Clonal growth and dispersal potential of Leiothrix flagellaris Ruhland (Eriocaulaceae) in the rocky grasslands of Southeastern Brazil

Leiothrix flagellaris is a small clonal plant that grows in sandy/rocky, nutrient poor soils in the rocky grasslands ("campos rupestres") of southeastern Brazil. In the rainy season most of their flower heads differentiate into small rosettes, produced by pseudovivipary, and connected to the mother-plant by flexible, elongated stalks that can reach up to 90cm. Most of these rosettes remain suspended over rocks or over the sparse herbaceous surrounding vegetation, while a few arch low enough to come into contact with the surrounding soil and take root. These suspended rosettes can reach diameters comparable to currently rooted and reproductively active rosettes produced during previous reproductive periods. As the rooted rosettes grow up, their potential to generate and disperse new pseudoviviparous rosettes increase rapidly. This unusual guerrilla strategy of L. flagellaris seems to congregate a suit of traits that promote a fast increase in photosynthetic area and improve recruitment, thereby helping to circumvent dispersal and establishment failures in its severe environment.

Ca2+ dependence of gluconeogenesis stimulation by glucagon at different cytosolic NAD+-NADH redox potentials

The influence of Ca2+ on hepatic gluconeogenesis was measured in the isolated perfused rat liver at different cytosolic NAD+-NADH potentials. Lactate and pyruvate were the gluconeogenic substrates and the cytosolic NAD+-NADH potentials were changed by varying the lactate to pyruvate ratios from 0.01 to 100. The following results were obtained: a) gluconeogenesis from lactate plus pyruvate was not affected by Ca2+-free perfusion (no Ca2+ in the perfusion fluid combined with previous depletion of the intracellular pools); gluconeogenesis was also poorly dependent on the lactate to pyruvate ratios in the range of 0.1 to 100; only for a ratio equal to 0.01 was a significantly smaller gluconeogenic activity observed in comparison to the other ratios. b) In the presence of Ca2+, the increase in oxygen uptake caused by the infusion of lactate plus pyruvate at a ratio equal to 10 was the most pronounced one; in Ca2+-free perfusion the increase in oxygen uptake caused by lactate plus pyruvate infusion tended to be higher for all lactate to pyruvate ratios; the most pronounced difference was observed for a lactate/pyruvate ratio equal to 1. c) In the presence of Ca2+ the effects of glucagon on gluconeogenesis showed a positive correlation with the lactate to pyruvate ratios; for a ratio equal to 0.01 no stimulation occurred, but in the 0.1 to 100 range stimulation increased progressively, producing a clear parabolic dependence between the effects of glucagon and the lactate to pyruvate ratio. d) In the absence of Ca2+ the relationship between the changes caused by glucagon in gluconeogenesis and the lactate to pyruvate ratio was substantially changed; the dependence curve was no longer parabolic but sigmoidal in shape with a plateau beginning at a lactate/pyruvate ratio equal to 1; there was inhibition at the lactate to pyruvate ratios of 0.01 and 0.1 and a constant stimulation starting with a ratio equal to 1; for the lactate to pyruvate ratios of 10 and 100, stimulation caused by glucagon was much smaller than that found when Ca2+ was present. e) The effects of glucagon on oxygen uptake in the presence of Ca2+ showed a parabolic relationship with the lactate to pyruvate ratios which was closely similar to that found in the case of gluconeogenesis; the only difference was that inhibition rather than stimulation of oxygen uptake was observed for a lactate to pyruvate ratio equal to 0.01; progressive stimulation was observed in the 0.1 to 100 range. f) In the absence of Ca2+ the effects of glucagon on oxygen uptake were different; the dependence curve was sigmoidal at the onset, with a well-defined maximum at a lactate to pyruvate ratio equal to 1; this maximum was followed by a steady decline at higher ratios; at the ratios of 0.01 and 0.1 inhibition took place; oxygen uptake stimulation caused by glucagon was generally lower in the absence of Ca2+ except when the lactate to pyruvate ratio was equal to 1. The results of the present study demonstrate that stimulation of gluconeogenesis by glucagon depends on Ca2+. However, Ca2+ is only effective in helping gluconeogenesis stimulation by glucagon at highly negative redox potentials of the cytosolic NAD+-NADH system. The triple interdependence of glucagon-Ca2+-NAD+-NADH redox potential reveals highly complex interrelations that can only be partially understood at the present stage of knowledge

Vahinkoeläinsodasta psykologiseen omistajuuteen. Petokonfliktien historiallinen tausta ja nykypäivän hallinta

Suurpetojen kannanhoitoon, ja etenkin suden kannanhoitoon liittyvä monitahoinen konfl ikti esiintyy jännitteinä paikallisyhteisöjen ja keskushallinnon, maaseudun ja kaupunkien sekä maallikoiden ja tutkijoiden välillä. Suurpetopolitiikan legitimiteettikriisi näkyy kansallisen kannanhoidon tavoitteiden ja toimenpiteiden kiistämisenä passiivisin ja aktiivisin toimin. Tällä ajankohtaisella ongelmalla on mittavat historialliset juuret. Luonnon ja ihmisen välinen suhde on ollut jatkuvaa tasapainottelua konfl iktien ja niiden hallinnan kanssa, ja suurpedot ovat väistämättä olleet konfl iktin keskiössä lajityypillisten piirteidensä vuoksi. Tämän tutkimuksen tavoitteena on osoittaa ympäristöhistoriallisen tutkimusotteen kautta suomalaisen vahinkoeläinhistorian keskeiset toimet ja toimijat, sekä ymmärtää vahinkoeläinten kannanhoidon tavoite- ja toimenpideasettelun vaikutukset eläinpopulaatioihin historiallisessa ja ekologisessa kontekstissa. Tutkimuksen toinen tavoite on tuottaa synteesi nykypäivän suurpetojen kannanhoidon tavoite- ja toimenpiteiden tarkoituksenmukaisuudesta ja vaikuttavuudesta historiallisessa kontekstissa ja esittää uudenlainen lähestymismalli sosiaalisesti kestävämmälle suurpetopolitiikalle. Vahinkoeläinhistoriaa käsitellään deduktiivisella ja rekonstruktiivisella tutkimusotteella käyttäen aineistona lakitekstejä, maksettuja tapporahoja, sanomalehtikirjoituksia, sidosryhmien kirjoituksia sekä eläintieteellisiä julkaisuja. Etenkin laeissa ja asetuksissa eri eläimistä asetetut tapporahat ja toisaalta saalistilastojen perusteella maksetut palkkiot on nostettu tässä tutkimuksessa merkittävään rooliin asenteiden tulkinnan välineenä. Tarkastelu ulotetaan nisäkkäiden lisäksi myös lintuihin, jotka ovat edellä mainitun aineiston valossa olleet merkittävä vainottu eläinryhmä. Nykypäivän petokonfl iktin tarkastelussa keskiöön nostetaan suurpetoasenteet, niiden muodostuminen ja vaikutus suurpetopolitiikan tavoitteiden ja toimenpiteiden kiistämisessä. Suurpetopolitiikan legitimiteettikriisiä tarkastellaan paikallisten uhmakkuutena hallintoa kohtaan ja tulkinta keinoista puuttua sosiopoliittiseen rikokseen rakennetaan tätä ajatusta vasten. Suurpetojen salakaatajat toimivat yhteisönsä puolesta ja saavat tukensa toimilleen yhteisöltään. Sosiopoliittinen rikos ei siten ole ainoastaan salakaatajien vaan sen sijaan yhteisön yhteinen. Salakaatajat ja paikallisyhteisö pyrkivät häivyttämään yhteiskunnassa viranomaisten ja sidosryhmien taholta toimintaan liittämää stigmaa ja siten oikeuttamaan tekonsa vallitsevissa olosuhteissa. Arvoristiriitoihin perustuvat konfl iktit ovat haasteellisia hallita ja lähtökohtana on oltava ymmärrys siitä, että etenkin suteen liittyvät jännitteet ja ristiriidat ihmisten välisissä suhteissa ovat väistämättömiä. Tunnistamalla historiallisen aineiston merkittävyys nykypäivän ongelmakeskeisen kannanhoidon ratkaisun tietopohjana on mahdollista rakentaa sosiaalisesti kestävämpää suurpetojen kannanhoitoa. Tässä väitöskirjatyössä painotetaan suurpetoihin liittyen ajatusta, jonka mukaan paikallisilta suurpetoalueilla eläviltä ihmisiltä tai sidosryhmien edustajilta ei edellytetä arvomaailman muuttumista, vaan hyväksytään heidän käsityksensä suurpetojen roolista vahingontekijöinä. Sen sijaan vahvistetaan suurpetojen välineellistä roolia paikallisyhteisöjen resurssina ja oleellisten sidosryhmien roolia yhteisön toimijoina psykologisen omistajuuden rakentamisen kautta. Suurpetojen kestävä kannanhoito vaatii siten riistahallinnon toimintakulttuurin muutosta ja uudenlaista suhdetta yhteiskunnan eri toimijoihin.

Anti-cyclic citrullinated peptide antibodies and rheumatoid factor in leprosy patients with articular involvement

The objective of the present research was to evaluate the usefulness of anti-cyclic citrullinated peptide (anti-CCP) antibodies and the IgM rheumatoid factor (IgM RF) test for the differential diagnosis of leprosy with articular involvement and rheumatoid arthritis (RA). Anti-CCP antibodies and IgM RF were measured in the sera of 158 leprosy patients (76 with and 82 without articular involvement), 69 RA patients and 89 healthy controls. Leprosy diagnosis was performed according to Ridley and Jopling classification criteria and clinical and demographic characteristics of leprosy patients were collected by a standard questionnaire. Leprosy patients with any concomitant rheumatic disease were excluded. Serum samples were obtained from all participants and frozen at _20°C. Measurement of anti-CCP antibodies and IgM RF were performed by ELISA, using a commercial second-generation kit, and the latex agglutination test, respectively. Anti-CCP antibodies and IgM RF were detected in low frequencies (2.6 and 1.3%, respectively) in leprosy patients and were not associated with articular involvement. Among healthy individuals both anti-CCP antibodies and IgM RF were each detected in 3.4% of the subjects. In contrast, in the RA group, anti-CCP antibodies were present in 81.2% and IgM RF in 62.3%. In the present study, both anti-CCP antibodies and IgM RF showed good positive predictive value for RA, helping to discriminate between RA and leprosy patients with articular involvement. However, anti-CCP antibodies were more specific for RA diagnosis in the population under study.

Proximal tubular dysfunction as an indicator of chronic graft dysfunction

New strategies are being devised to limit the impact of renal sclerosis on graft function. Individualization of immunosuppression, specifically the interruption of calcineurin-inhibitors has been tried in order to promote better graft survival once chronic graft dysfunction has been established. However, the long-term impact of these approaches is still not totally clear. Nevertheless, patients at higher risk for tubular atrophy and interstitial fibrosis (TA/IF) development should be carefully monitored for tubular function as well as glomerular performance. Since tubular-interstitial impairment is an early event in TA/IF pathogenesis and associated with graft function, it seems reasonable that strategies directed at assessing tubular structural integrity and function would yield important functional and prognostic data. The measurement of small proteins in urine such as α-1-microglobulin, N-acetyl-beta-D-glucosaminidase, alpha/pi S-glutathione transferases, β-2 microglobulin, and retinol binding protein is associated with proximal tubular cell dysfunction. Therefore, its straightforward assessment could provide a powerful tool in patient monitoring and ongoing clinical assessment of graft function, ultimately helping to facilitate longer patient and graft survival associated with good graft function.

Cognitive performance of young and elderly subjects on the free word recall memory test: effect of presentation order on recall order

The influence of aging on memory has been extensively studied, but the importance of short-term memory and recall sequence has not. The objective of the current study was to examine the recall order of words presented on lists and to determine if age affects recall sequence. Physically and psychologically healthy male subjects were divided into two groups according to age, i.e., 23 young subjects (20 to 30 years) and 50 elderly subjects (60 to 70 years) submitted to the Wechsler Adult Intelligence Scale-Revised and the free word recall test. The order of word presentation significantly affected the 3rd and 4th words recalled (P < 0.01; F = 14.6). In addition, there was interaction between the presentation order and the type of list presented (P < 0.05; F = 9.7). Also, both groups recalled the last words presented from each list (words 13-15) significantly more times 3rd and 4th than words presented in all remaining positions (P < 0.01). The order of word presentation also significantly affected the 5th and 6th words recalled (P = 0.05; F = 7.5) and there was a significant interaction between the order of presentation and the type of list presented (P < 0.01; F = 20.8). The more developed the cognitive functions, resulting mainly from formal education, the greater the cognitive reserve, helping to minimize the effects of aging on the long-term memory (episodic declarative).

Effect of hyperoxia on the intestinal IgA secretory component in neonatal rats and on intestinal epithelial cells in vitro

Oxygen therapy is essential for the treatment of some neonatal critical care conditions but its extrapulmonary effects have not been adequately investigated. We therefore studied the effects of various oxygen concentrations on intestinal epithelial cell function. In order to assess the effects of hyperoxia on the intestinal immunological barrier, we studied two physiological changes in neonatal rats exposed to hyperoxia: the change in intestinal IgA secretory component (SC, an important component of SIgA) and changes in intestinal epithelial cells. Immunohistochemistry and Western blot were used to detect changes in the intestinal tissue SC of neonatal rats. To detect intestinal epithelial cell growth, cells were counted, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Giemsa staining were used to assess cell survival. Immunohistochemistry was used to determine SC expression. The expression of intestinal SC in neonatal rats under hyperoxic conditions was notably increased compared with rats inhaling room air (P < 0.01). In vitro, 40% O2 was beneficial for cell growth. However, 60% O2 and 90% O2 induced rapid cell death. Also, 40% O2 induced expression of SC by intestinal epithelial cells, whereas 60% O2did not; however, 90% O2 limited the ability of intestinal epithelial cells to express SC. In vivo and in vitro, moderate hyperoxia brought about increases in intestinal SC. This would be expected to bring about an increase in intestinal SIgA. High levels of SC and SIgA would serve to benefit hyperoxia-exposed individuals by helping to maintain optimal conditions in the intestinal tract.

Molecular and cellular pathogenesis of autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common human life-threatening monogenic disorders. The disease is characterized by bilateral, progressive renal cystogenesis and cyst and kidney enlargement, often leading to end-stage renal disease, and may include extrarenal manifestations. ADPKD is caused by mutation in one of two genes, PKD1 and PKD2, which encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC2 is a non-selective cation channel permeable to Ca2+, while PC1 is thought to function as a membrane receptor. The cyst cell phenotype includes increased proliferation and apoptosis, dedifferentiation, defective planar polarity, and a secretory pattern associated with extracellular matrix remodeling. The two-hit model for cyst formation has been recently extended by the demonstration that early gene inactivation leads to rapid and diffuse development of renal cysts, while inactivation in adult life is followed by focal and late cyst formation. Renal ischemia/reperfusion, however, can function as a third hit, triggering rapid cyst development in kidneys with Pkd1 inactivation induced in adult life. The PC1-PC2 complex behaves as a sensor in the primary cilium, mediating signal transduction via Ca2+ signaling. The intracellular Ca2+ homeostasis is impaired in ADPKD, being apparently responsible for the cAMP accumulation and abnormal cell proliferative response to cAMP. Activated mammalian target for rapamycin (mTOR) and cell cycle dysregulation are also significant features of PKD. Based on the identification of pathways altered in PKD, a large number of preclinical studies have been performed and are underway, providing a basis for clinical trials in ADPKD and helping the design of future trials.

Serum metabolic profiling of human gastric cancer based on gas chromatography/mass spectrometry

Research on molecular mechanisms of carcinogenesis plays an important role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to non-invasively identify the potential biomarkers for the early diagnosis of human gastric cancer. The aims of this study were to explore the underlying metabolic mechanisms of gastric cancer and to identify biomarkers associated with morbidity. Gas chromatography/mass spectrometry (GC/MS) was used to analyze the serum metabolites of 30 Chinese gastric cancer patients and 30 healthy controls. Diagnostic models for gastric cancer were constructed using orthogonal partial least squares discriminant analysis (OPLS-DA). Acquired metabolomic data were analyzed by the nonparametric Wilcoxon test to find serum metabolic biomarkers for gastric cancer. The OPLS-DA model showed adequate discrimination between cancer and non-cancer cohorts while the model failed to discriminate different pathological stages (I-IV) of gastric cancer patients. A total of 44 endogenous metabolites such as amino acids, organic acids, carbohydrates, fatty acids, and steroids were detected, of which 18 differential metabolites were identified with significant differences. A total of 13 variables were obtained for their greatest contribution in the discriminating OPLS-DA model [variable importance in the projection (VIP) value >1.0], among which 11 metabolites were identified using both VIP values (VIP >1) and the Wilcoxon test. These metabolites potentially revealed perturbations of glycolysis and of amino acid, fatty acid, cholesterol, and nucleotide metabolism of gastric cancer patients. These results suggest that gastric cancer serum metabolic profiling has great potential in detecting this disease and helping to understand its metabolic mechanisms.

Scalable Feature Selection Applications for Genome-Wide Association Studies of Complex Diseases

Personalized medicine will revolutionize our capabilities to combat disease. Working toward this goal, a fundamental task is the deciphering of geneticvariants that are predictive of complex diseases. Modern studies, in the formof genome-wide association studies (GWAS) have afforded researchers with the opportunity to reveal new genotype-phenotype relationships through the extensive scanning of genetic variants. These studies typically contain over half a million genetic features for thousands of individuals. Examining this with methods other than univariate statistics is a challenging task requiring advanced algorithms that are scalable to the genome-wide level. In the future, next-generation sequencing studies (NGS) will contain an even larger number of common and rare variants. Machine learning-based feature selection algorithms have been shown to have the ability to effectively create predictive models for various genotype-phenotype relationships. This work explores the problem of selecting genetic variant subsets that are the most predictive of complex disease phenotypes through various feature selection methodologies, including filter, wrapper and embedded algorithms. The examined machine learning algorithms were demonstrated to not only be effective at predicting the disease phenotypes, but also doing so efficiently through the use of computational shortcuts. While much of the work was able to be run on high-end desktops, some work was further extended so that it could be implemented on parallel computers helping to assure that they will also scale to the NGS data sets. Further, these studies analyzed the relationships between various feature selection methods and demonstrated the need for careful testing when selecting an algorithm. It was shown that there is no universally optimal algorithm for variant selection in GWAS, but rather methodologies need to be selected based on the desired outcome, such as the number of features to be included in the prediction model. It was also demonstrated that without proper model validation, for example using nested cross-validation, the models can result in overly-optimistic prediction accuracies and decreased generalization ability. It is through the implementation and application of machine learning methods that one can extract predictive genotype–phenotype relationships and biological insights from genetic data sets.

Improving oral healthcare in Scotland with special reference to sustainability and caries prevention

Brett Duane Improving oral healthcare in Scotland with special reference to sustainability and caries prevention University of Turku, Faculty of Medicine, Institute of Dentistry, Community Dentistry, Finnish Doctoral Program in Oral Sciences (FINDOS-Turku), Turku, Finland Annales Universitatis Turkuensis, Sarja- Ser. D, Medica-Odontologica. Painosalama Oy, Turku, Finland, 2015. Dentistry must provide sustainable, evidence-based, and prevention-focused care. In Scotland oral health prevention is delivered through the Childsmile programme, with an increasing use of high concentration fluoride toothpaste (HCFT). Compared with other countries there is little knowledge of xylitol prevention. The UK government has set strict carbon emission limits with which all national health services (NHS) must comply. The purpose of these studies was firstly to describe the Scottish national oral health prevention programme Childsmile (CS), to determine if the additional maternal use of xylitol (CS+X) was more effective at affecting the early colonisation of mutans streptococci (MS) than this programme alone; secondly to analyse trends in the prescribing and management of HCFT by dentists; and thirdly to analyse data from a dental service in order to improve its sustainability. In all, 182 mother/child pairs were selected on the basis of high maternal MS levels. Motherswere randomly allocated to a CS or CS+X group, with both groups receiving Childsmile. Theintervention group consumed xylitol three times a day, from when the child was 3 months until 24 months. Children were examined at age two to assess MS levels. In order to understand patterns of HCFT prescribing, a retrospective secondary data analysis of routine prescribing data for the years 2006-2012 was performed. To understand the sustainability of dental services, carbon accounting combined a top-down approach and a process analysis approach, followed by the use of Pollard’s decision model (used in other healthcare areas) to analyse and support sustainable service reconfiguration. Of the CS children, 17% were colonised with MS, compared with 5% of the CS+X group. This difference was not statistically significant (P=0.1744). The cost of HCFT prescribing increased fourteen-fold over five years, with 4% of dentists prescribing 70% of the total product. Travel (45%), procurement (36%) and building energy (18%) all contributed to the 1800 tonnes of carbon emissions produced by the service, around 4% of total NHS emissions. Using the analytical model, clinic utilisation rates improved by 56% and patient travel halved significantly reducing carbon emissions. It can be concluded that the Childsmile programme was effective in reducing the risk for MS transmission. HCFT is increasing in Scotland and needs to be managed. Dentistry has similar carbon emissions proportionally as the overall NHS, and the use of an analytic tool can be useful in helping identify these emissions. Key words: Sustainability, carbon emissions, xylitol, mutans streptococci, fluoride toothpaste, caries prevention.