MicroRNAs and the functional β cell mass: For better or worse.

Insulin secretion from pancreatic β cells plays a central role in the control of blood glucose levels. The amount of insulin released by β cells is precisely adjusted to match organism requirements. A number of conditions that arise during life, including pregnancy and obesity, can result in a decreased sensitivity of insulin target tissues and a consequent rise in insulin needs. To preserve glucose homoeostasis, the augmented insulin demand requires a compensatory expansion of the pancreatic β cell mass and an increase in its secretory activity. This compensatory process is accompanied by modifications in β cell gene expression, although the molecular mechanisms underlying the phenomenon are still poorly understood. Emerging evidence indicates that at least part of these compensatory events may be orchestrated by changes in the level of a novel class of gene regulators, the microRNAs. Indeed, several of these small, non-coding RNAs have either positive or negative impacts on β cell proliferation and survival. The studies reviewed here suggest that the balance between the actions of these two groups of microRNAs, which have opposing functional effects, can determine whether β cells expand sufficiently to maintain blood glucose levels in the normal range or fail to meet insulin demand and thus lead, as a consequence, towards diabetes manifestation. A better understanding of the mechanisms governing changes in the microRNA profile will open the way for the development of new strategies to prevent and/or treat both type 2 and gestational diabetes.

Vaatimustiedon hallinta rakennusteollisuuden tuotanto- ja suunnitteluyrityksessä

Diplomityön ensisijaisena tavoitteena on luoda yleinen vaatimustiedon hallinnan malli, jonka avulla yrityksen toimintaympäristössä vaikuttavat vaatimukset voidaan tunnistaa ja kommunikoida koko organisaation tietoisuuteen. Kohdeyrityksen näkökulmasta mielenkiinto kohdistuu erityisesti käytännön työn kautta saataviin lopputuloksiin. Tavoitteena on luoda yritykseen pohja vaatimustiedon hallinnalle sekä samalla kehittää sähköistä vaatimustietojärjestelmää. Diplomityö on toteutettu konstruktiivisena tutkimuksena. Tutkittavasta aiheesta on saatavilla teoriatietoa hyvin rajallisesti. Tämän vuoksi vaatimustiedon hallinnan malli toteutetaan vahvasti käytännön työn havaintojen ja analysoinnin pohjalta. Lähtökohdaksi käytännön työlle esitellään laadunhallinnan, tiedonhallinnan sekä prosessien näkökulmia sekä perinteisiä vaatimusten hallinnan teorioita. Tiedot, joiden avulla valmis malli on luotu, kerättiin haastattelemalla yrityksen prosessien omistajia. Työn tuloksina esitellään vaatimustiedon hallinnan malli sekä yrityksessä saatuja käytännön työn lopputuloksia. Vaatimustiedon hallinnalla tarkoitetaan yrityksen toimintaympäristössä, prosesseissa sekä tuotteissa vaikuttavien vaatimusten saattamista organisaation tietoisuuteen mahdollisimman käyttäjäystävällisellä tavalla. Mallissa esiintyvät vaatimukset ovat sidosryhmien tai yrityksen itsensä ilmaisuja liittyen tuotteen tai palvelun ominaisuuksiin sekä suorituskykyyn. Valmis malli voidaan jakaa neljään eri vaiheeseen, jotka ovat suunnittelu ja esitutkimus, toteutus, käyttöönotto, sekä muutostenhallinta ja ylläpito. Laajimmillaan toteutettuna vaatimustiedon hallinta auttaa yritystä parhaiden käytäntöjen tunnistamisessa ja prosessien kehittämisessä, mahdollistaa tasalaatuisen toiminnan ja tuotteet sekä toimivan tiedon ja osaamisen hallinnan.

Vaatimusmäärittelykäytäntöjen sovellettavuus talousohjauksen vaatimuksia kartoitettaessa

Vaatimusten määrittelyn tarkoitus on kartoittaa tietojärjestelmän käyttäjien työtehtäviä ja niihin liittyviä järjestelmän toiminnallisia ja ei-toiminnallisia vaatimuksia. Todellinen asiakasnäkökulma tulee esille yrityksen itse käynnistämässä vaatimusten määrittelyssä. Nykytilan selvittäminen ja kriittisten toimintojen havaitseminen käynnistävät kohdeyksikössä käytävän keskinäisen keskustelun, mikä on edellytyksenä järjestelmävaatimusten havaitsemiseen. Tämän työn teoriaosuudessa lähestytään eri näkökulmia vaatimustenmäärittelyyn. Tämän jälkeen esitellään muutamia asiakasyritykselle sopivia määrittelymenetelmiä, joita voidaan hyödyntää valmisohjelmistohankeen määrittelyssä. Työssä esitetään myös toiminnanohjaukseen ja tietovarastointiin tarkoitettujen järjestelmien tapaa kerätä taloudellista informaatiota ja luoda raportteja johdolle päätöksenteon tueksi. Työn empiirisessä osassa selvitetään mitkä ovat Lappeenrannan Energia Oy:n asettamat liiketoiminnalliset tarpeet ja vaatimukset uudelle talousohjauksen tietojärjestelmälle.

Pilot study about the effect of rt-PA administration on the excitotoxicity mediated brain damage and its repercussion on the functional prognosis of patients with ischaemic stroke: research protocol

Fibrinolytic therapy with Recombinant Tissue-Plasminogen Activator (rt-PA) is currently the only effective treatment for ischaemic stroke in its acute phase. Even though its use generally improves the prognosis of those patients likely to receive it, rt-PA administration is associated to several risks, such as haemorrhagic transformation ofthe ischaemic lesion and activation of excitotoxic mechanisms that may contribute to an increase in mortality or to a poor outcome in certain occasions, specially when arterial recanalization is not achieved or the rt-PA is lately administrated. Since in the last few years the role of glutamate in the neurotoxicity associated toischaemia has been widely studied and it is known that high plasma glutamate levels are predictors of ischaemic lesion growth and poor neurological outcome, it is necessary to find out which factors can contribute to glutamate release in the brain. The aim of this study is to determine if rt-PA administration is related to an increase in plasma glutamate levels, as well as to define if higher plasma glutamate levels at admission are related to different evolution and prognosis of our patients, both in those in which recanalisation is achieved and not. A series of cases of patients with hemispheric cerebral infarction admitted in our hospital during a year will be studied, and the data obtained from them will be compared to the data obtained from a control group, the samples of wich were takenyears ago, before rt-PA was routinely used

Tiedon tuottaminen ja vaikuttaminen: prosessi ja liitynnät tietolähteisiin

Diplomityön tavoitteena on helpottaa Energiamarkkinaviraston tietomassojen käsittelyä ja tehostaa organisaatiotiedon hallintaa. Keskeisin tavoite on määritellä ja kuvata viraston tiedon tuottamis- ja vaikuttamisprosessi sekä sen liitynnät sisäisiin ja ulkoisiin tietolähteisiin. Työssä perehdytään organisaatiotiedon nykytilanteeseen, tiedon tuottamiseen ja vaikuttamiseen sekä ehdotetaan useita keinoja olemassa olevan tietomassan tehokkaampaan hyödyntämiseen. Työssä analysoidaan millaista tietoa virastossa tarvitaan, missä tieto on saatavilla ajantasaisena sekä luotettavana ja mihin hankittua tietoa loppujen lopuksi käytetään. Nykytilanteen selvittämisen lisäksi työssa ehdotetaan keinoja, joiden avulla organisaatiotieto saadaan nostettua nykyiseltä, pääosin operatiiviselta tasolta vähintään täysin taktiselle tai jopa osin strategiselle tasolle. Lisaksi työssä selvitetään kuinka virasto pystyy hankkimaan tietoa uudenlaiseen tietotarpeeseen. Työn keskeisimmät tulokset ovat diplomityössä esille nostetut kehityskohteet liittyen tietolähteiden hyödyntämiseen, internetsivuston uudistamiseen, uusien analyysien tuottamiseen, tärkeiden ohjeistusten tekemiseen ja prosessien suunnitteluun sekä automatisointiin. Näihin voidaan puuttua prosessikeskeisen ajattelutavan ja proaktiivisuuden lisäämisellä.

Functional diversity of macrophyte communities within and between Pyrenean lakes

Submersed vegetation is a common feature in about 70% Pyrene an high mountain (>1500 m a.s.l.) lakes. Isoetids and soft-water elodeids are common elements of this underw ater flora and can form distinct vegetation units (i.e. patches of vegetation dominated by different species) within complex mosaics of vegetation in shallow waters (<7 m). Since is oetids exert a strong influence on sediment biogeochemistry due to high radial oxygen loss, we examined the small scale characteristics of the lake environment (water and sediment) associated to vegetation patches in order to ascertain potential functional differences among them. To do so, we characterised the species composition and biomass of the main vegetation units from 11 lakes, defined plant communities based on biomass data, and then related each community with sediment properties (redox and dissolved nutrient concentration in the pore water) and water nutrient concentration within plant canopy. We also characterised lake water and sediment in areas without vegetation as a reference. A total of twenty-one vegetation units were identified, ranging from one to five per lake. A cluster analysis on biomass species composition suggested seven different macrophyte communities that were named after the most dominant species:Nitella sp.,Potamogeton praelongus, Myriophyllum alterniflorum, Sparganium angustifolium , Isoetes echinospora,Isoetes lacustris and Carex rostrata . Coupling between macrophyte communities and their immediate environment (overlying water and sediment) was manifested mainly as variation in sediment redox conditions and the dominant form of inorganic nitrogen in pore-water. These effects depended on the specific compositi on of the community, and on the allocation between above- and belowground biomass, and could be predicted with a model relating the average and standard deviation of sediment redox potential from 0 down to -20 cm, across macrophyte communities. Differences in pore-water total dissolved phosphorus were related to the trophic state of the lakes. There was no correlation between sediment and water column dissolved nutrients. However, nitrate concentrations tended to be lower in the water overlaying isoetid communities, in apparent contradiction to the patterns of dissolved nitrates in the pore-water. These tendencies were robust even when comparing the water over laying communities within the same lake, thus pointing towards a potential effect of isoetids in reducing dissolved nitrogen in the lakes.

Assessing functional relations in single-case designs: Quantitative proposals in the context of the evidence-based movement

In the context of the evidence-based practices movement, the emphasis on computing effect sizes and combining them via meta-analysis does not preclude the demonstration of functional relations. For the latter aim, we propose to augment the visual analysis to add consistency to the decisions made on the existence of a functional relation without losing sight of the need for a methodological evaluation of what stimuli and reinforcement or punishment are used to control the behavior. Four options for quantification are reviewed, illustrated, and tested with simulated data. These quantifications include comparing the projected baseline with the actual treatment measurements, on the basis of either parametric or nonparametric statistics. The simulated data used to test the quantifications include nine data patterns in terms of the presence and type of effect and comprising ABAB and multiple baseline designs. Although none of the techniques is completely flawless in terms of detecting a functional relation only when it is present but not when it is absent, an option based on projecting split-middle trend and considering data variability as in exploratory data analysis proves to be the best performer for most data patterns. We suggest that the information on whether a functional relation has been demonstrated should be included in meta-analyses. It is also possible to use as a weight the inverse of the data variability measure used in the quantification for assessing the functional relation. We offer an easy to use code for open-source software for implementing some of the quantifications.

Long-term functional improvements in the 2-year treatment of schizophrenia outpatients with olanzapine long-acting injection

BACKGROUND: Little is known about the long-term changes in the functioning of schizophrenia patients receiving maintenance therapy with olanzapine long-acting injection (LAI), and whether observed changes differ from those seen with oral olanzapine. METHODS: This study describes changes in the levels of functioning among outpatients with schizophrenia treated with olanzapine-LAI compared with oral olanzapine over 2 years. This was a secondary analysis of data from a multicenter, randomized, open-label, 2-year study comparing the long-term treatment effectiveness of monthly olanzapine-LAI (405 mg/4 weeks; n=264) with daily oral olanzapine (10 mg/day; n=260). Levels of functioning were assessed with the Heinrichs-Carpenter Quality of Life Scale. Functional status was also classified as 'good', 'moderate', or 'poor', using a previous data-driven approach. Changes in functional levels were assessed with McNemar's test and comparisons between olanzapine-LAI and oral olanzapine employed the Student's t-test. RESULTS: Over the 2-year study, the patients treated with olanzapine-LAI improved their level of functioning (per Quality of Life total score) from 64.0-70.8 (P<0.001). Patients on oral olanzapine also increased their level of functioning from 62.1-70.1 (P<0.001). At baseline, 19.2% of the olanzapine-LAI-treated patients had a 'good' level of functioning, which increased to 27.5% (P<0.05). The figures for oral olanzapine were 14.2% and 24.5%, respectively (P<0.001). Results did not significantly differ between olanzapine-LAI and oral olanzapine. CONCLUSION: In this 2-year, open-label, randomized study of olanzapine-LAI, outpatients with schizophrenia maintained or improved their favorable baseline level of functioning over time. Results did not significantly differ between olanzapine-LAI and oral olanzapine.

Success factors of customer and supplier master data system

Especially in global enterprises, key data is fragmented in multiple Enterprise Resource Planning (ERP) systems. Thus the data is inconsistent, fragmented and redundant across the various systems. Master Data Management (MDM) is a concept, which creates cross-references between customers, suppliers and business units, and enables corporate hierarchies and structures. The overall goal for MDM is the ability to create an enterprise-wide consistent data model, which enables analyzing and reporting customer and supplier data. The goal of the study was defining the properties and success factors of a master data system. The theoretical background was based on literature and the case consisted of enterprise specific needs and demands. The theoretical part presents the concept, background, and principles of MDM and then the phases of system planning and implementation project. Case consists of background, definition of as is situation, definition of project, evaluation criterions and concludes the key results of the thesis. In the end chapter Conclusions combines common principles with the results of the case. The case part ended up dividing important factors of the system in success factors, technical requirements and business benefits. To clarify the project and find funding for the project, business benefits have to be defined and the realization has to be monitored. The thesis found out six success factors for the MDM system: Well defined business case, data management and monitoring, data models and structures defined and maintained, customer and supplier data governance, delivery and quality, commitment, and continuous communication with business. Technical requirements emerged several times during the thesis and therefore those can’t be ignored in the project. Conclusions chapter goes through these factors on a general level. The success factors and technical requirements are related to the essentials of MDM: Governance, Action and Quality. This chapter could be used as guidance in a master data management project.

Foodstuffs and medicines as legal categories in the EU and China. Functional foods as a borderline case

The thesis discusses the regulation of foodstuffs and medicines, and particularly the regulation of functional foods. Legal systems investigated are the EU and China. Both are members of the WTO and Codex Alimentarius, which binds European and Chinese rules together. The study uses three Chinese berries as case examples of how product development faces regulation in practice. The berries have traditional uses as herbal medicines. Europe and China have similar nutrition problems to be resolved, such as obesity, cardiovascular disease, and diabetes. The three berries might be suitable raw materials for functional foods. Consumer products with health-enhancing functions, such as lowering blood pressure, might legally be classifi ed either as foodstuffs or medicines. The classifi cation will depend on functions and presentation of the product. In our opinion, food and medicine regulation should come closer together so the classifi cation issue would no longer be an issue. Safety of both foodstuffs and medicines is strictly regulated. With medicines, safety is a more relative concept, where benefi ts of the product are compared to side-effects in thorough scientifi c tests and trials. Foods, on the other hand, are not allowed to have side-effects. Hygiene rules and rules on the use of chemicals apply. In China, food safety is currently at focus as China has had several severe food scandals. Newly developed foods are called novel foods, and are specifi cally regulated. The current European novel food regulation from 1997 treats traditional third country products as novel. The Chinese regulation of 2007 also defi nes novel foods as something unfamiliar to a Chinese consumer. The concepts of novel food thus serve a protectionist purpose. As regards marketing, foods are allowed to bear health claims, whereas medicines bear medicinal claims. The separation is legally strict: foods are not to be presented as having medicinal functions. European nutrition and health claim regulation exists since 2006. China also has its regulation on health foods, listing the permitted claims and how to substantiate them. Health claims are allowed only on health foods. The European rules on medicines include separate categories for herbal medicines, traditional herbal medicines, and homeopathic medicines, where there are differing requirements for scientifi c substantiation. The scientifi c and political grounds for the separate categories provoke criticism. At surface, the Chinese legal system seems similar to the European one. To facilitate trade, China has enacted modern laws. Laws are needed as the country moves from planned economy to market economy: ‘rule of law’ needs to replace ‘rule of man’. Instead of being citizens, Chinese people long were subordinates to the Emperor. Confucius himself advised to avoid confl ict. Still, Chinese people do not and cannot always trust the legal system, as laws are enforced in an inconsistent manner, and courts are weak. In China, there have been problems with confl icting national and local laws. In Europe, the competence of the EU vs. the competence of the Member States is still not resolved, even though the European Commission often states that free trade requires harmonisation. Food and medicine regulation is created by international organisations, food and medicine control agencies, standards agencies, companies and their organisations. Regulation can be divided in ‘hard law’ and ‘soft law’. One might claim that hard law is in crisis, as soft law is gaining importance. If law is out of fashion, regulation certainly isn’t. In the future, ‘law’ might mean a process where rules and incentives are created by states, NGOs, companies, consumers, and other stakeholders. ‘Law’ might thus refer to a constant negotiation between public and private actors. Legal principles such as transparency, equal treatment, and the right to be heard would still be important.

Combined experimental powder X-ray diffraction and DFT data to obtain the lowest energy molecular conformation of friedelin

Friedelin molecular conformers were obtained by Density Functional Theory (DFT) and by ab initio structure determination from powder X-ray diffraction. Their conformers with the five rings in chair-chair-chair-boat-boat, and with all rings in chair, are energy degenerated in gas-phase according to DFT results. The powder diffraction data reveals that rings A, B and C of friedelin are in chair, and rings D and E in boat-boat, conformation. The high correlation values among powder diffraction data, DFT and reported single-crystal data indicate that the use of conventional X-ray diffractometer can be applied in routine laboratory analysis in the absence of a single-crystal diffractometer.

Data Consistency by a Metadata Management Solution

This thesis consists of three main theoretical themes: quality of data, success of information systems, and metadata in data warehousing. Loosely defined, metadata is descriptive data about data, and, in this thesis, master data means reference data about customers, products etc. The objective of the thesis is to contribute to an implementation of a metadata management solution for an industrial enterprise. The metadata system incorporates a repository, integration, delivery and access tools, as well as semantic rules and procedures for master data maintenance. It targets to improve maintenance processes and quality of hierarchical master data in the case company’s informational systems. That should bring benefits to whole organization in improved information quality, especially in cross-system data consistency, and in more efficient and effective data management processes. As the result of this thesis, the requirements for the metadata management solution in case were compiled, and the success of the new information system and the implementation project was evaluated.

A direct potentiometric titration study of the dissociation of humic acid with selectively blocked functional groups

A direct potentiometric titration method was applied to commercial and soil humic acids in order to determine their carboxyl and phenol group concentrations and apparent and intrinsic pK. In that context, acid-base properties of humic acids are interpreted by selective blocking of carboxylic and phenolic groups by esterification and acetylation. Differences in underivatized and derivatized HA's acid-base properties are ascribed to carboxyl and phenol groups influence on total humic acidity. Potentiometric data were treated with the modified Henderson-Hasselbalch equation. Infra red results, the acidic group contents and the average values of apparent and intrinsic pK for underivatized and derivatized HAs confirmed the selectivity of esterification derivatization method. After blocking of the functional groups, the values of acidic group contents decreased, while the value of apparent pK increased after derivatization. Phenol groups cannot be specifically identified by the acetylation method, due to low selectivity of the acetylation method.

Kaupunkialueella toimivan sähkönjakeluverkkoyhtiön siirtohinnoittelun kehittäminen

Sähkönjakeluverkkoyhtiöllä on sähkön siirtopalveluun alueellinen monopoli. Siirtohinnoittelun reunaehdot tulevat sähkömarkkinalaista ja hintojen kohtuullisuutta valvoo ja sääntelee Energiamarkkinavirasto. Tässä työssä selvitetään Turku Energia Sähköverkot Oy:lle kustannusvastaavat aiheuttamisperiaatteen mukaiset siirtohinnat. Samalla muodostetaan yleis-, yö- ja kausituotteiden perusmaksuihin asiakkaan liittymispisteen pääsulakkeen kokoon perustuva porrastus. Sulakeporrastuksen käyttöönotolla pystytään kehittämään siirtohinnoittelun kustannusvastaavuutta ja noudattamaan aiheuttamisperiaatteen mukaista hinnoittelupolitiikkaa entistä paremmin. Työssä tutkitaan siirtohinnoittelun kehitysnäkymiä myös pidemmällä tähtäimellä. Älykkäiden sähköverkkojen kehittyminen ja erityisesti etäluettavien mittareiden käyttöönotto tulevat luomaan kehitysmahdollisuuksia siirtohinnoitteluun tulevaisuudessa. Laitteista saatavia tarkkoja sähkönkulutus- ja tehotietoja voidaan käyttää kustannusvastaavuuslaskennan taustalla. Jotta verkon käyttö olisi sen mitoitukseen nähden mahdollisimman tehokasta, tulisi kuorman jakautua mahdollisimman tasaisesti ajan suhteen. Verkossa esiintyviä kulutushuippuja pystytään tulevaisuudessa mahdollisesti tasoittamaan esimerkiksi kuorman ohjauksen avulla, jonka tehokeinona voidaan käyttää siirtohinnoittelua. Siirtohinnoilla voidaan mahdollisesti vaikuttaa myös esimerkiksi kulutuksen ja tuotannon ajoittamiseen sekä kannusta asiakkaita loistehon kompensointiin. Siirtotuotteiden täytyy myös kehittyä asiakkaiden tarpeiden kehittymisen rinnalla ja esimerkiksi sähkön laadun tuotteistaminen voi olla eräs keino vastaamaan tiukentuneisiin vaatimuksiin.

A cell spot microarray method for high-throughput biology

High-throughput screening of cellular effects of RNA interference (RNAi) libraries is now being increasingly applied to explore the role of genes in specific cell biological processes and disease states. However, the technology is still limited to specialty laboratories, due to the requirements for robotic infrastructure, access to expensive reagent libraries, expertise in high-throughput screening assay development, standardization, data analysis and applications. In the future, alternative screening platforms will be required to expand functional large-scale experiments to include more RNAi constructs, allow combinatorial loss-of-function analyses (e.g. genegene or gene-drug interaction), gain-of-function screens, multi-parametric phenotypic readouts or comparative analysis of many different cell types. Such comprehensive perturbation of gene networks in cells will require a major increase in the flexibility of the screening platforms, throughput and reduction of costs. As an alternative for the conventional multi-well based high-throughput screening -platforms, here the development of a novel cell spot microarray method for production of high density siRNA reverse transfection arrays is described. The cell spot microarray platform is distinguished from the majority of other transfection cell microarray techniques by the spatially confined array layout that allow highly parallel screening of large-scale RNAi reagent libraries with assays otherwise difficult or not applicable to high-throughput screening. This study depicts the development of the cell spot microarray method along with biological application examples of high-content immunofluorescence and phenotype based cancer cell biological analyses focusing on the regulation of prostate cancer cell growth, maintenance of genomic integrity in breast cancer cells, and functional analysis of integrin protein-protein interactions in situ.