Fetal programming of pulmonary vascular dysfunction in mice: role of epigenetic mechanisms.

Insults during the fetal period predispose the offspring to systemic cardiovascular disease, but little is known about the pulmonary circulation and the underlying mechanisms. Maternal undernutrition during pregnancy may represent a model to investigate underlying mechanisms, because it is associated with systemic vascular dysfunction in the offspring in animals and humans. In rats, restrictive diet during pregnancy (RDP) increases oxidative stress in the placenta. Oxygen species are known to induce epigenetic alterations and may cross the placental barrier. We hypothesized that RDP in mice induces pulmonary vascular dysfunction in the offspring that is related to an epigenetic mechanism. To test this hypothesis, we assessed pulmonary vascular function and lung DNA methylation in offspring of RDP and in control mice at the end of a 2-wk exposure to hypoxia. We found that endothelium-dependent pulmonary artery vasodilation in vitro was impaired and hypoxia-induced pulmonary hypertension and right ventricular hypertrophy in vivo were exaggerated in offspring of RDP. This pulmonary vascular dysfunction was associated with altered lung DNA methylation. Administration of the histone deacetylase inhibitors butyrate and trichostatin A to offspring of RDP normalized pulmonary DNA methylation and vascular function. Finally, administration of the nitroxide Tempol to the mother during RDP prevented vascular dysfunction and dysmethylation in the offspring. These findings demonstrate that in mice undernutrition during gestation induces pulmonary vascular dysfunction in the offspring by an epigenetic mechanism. A similar mechanism may be involved in the fetal programming of vascular dysfunction in humans.

Therapeutisches Drug-Monitoring in der Psychiatrie : Kurze Zusammenfassung des neuen Konsensuspapiers der Arbeitsgruppe TDM der AGNP [Therapeutic drug monitoring in psychiatry : A brief summary of the new consensus paper by the task force on TDM of the AGNP].

In October 2011 the Task Force Therapeutic Drug Monitoring of the Association for Neuropsychopharmacology and Pharmacopsychiatry (AGNP) published an update (Pharmacopsychiatry 2011, 44: 195-235) of the first version of the consensus paper on therapeutic drug monitoring (TDM) published in 2004. This article summarizes the essential statements to make them accessible to a wider readership in German speaking countries.

Task Support in Scenario Process: Case LUT 2016

This thesis attempts to find whether scenario planning supports the organizational strategy as a method for addressing uncertainty. The main issues are why, what and how scenario planning fits in organizational strategy and how the process could be supported to make it more effective. The study follows the constructive approach. It starts with examination of competitive advantage and the way that an organization develops strategy and how it addresses the uncertainty in its operational environment. Based on the conducted literature review, scenario methods would seem to provide versatile platform for addressing future uncertainties. The construction is formed by examining the scenario methods and presenting suitable support methods, which results in forming of the theoretical proposition for supporter scenario process. The theoretical framework is tested in laboratory conditions, and the results from the test sessions are used a basis for scenario stories. The process of forming the scenarios and the results are illustrated and presented for scrutiny

Adaptive changes in a radial maze task: Efficient selection of baited arms with reduced foraging in senescent hooded rats

Qualitative differences in strategy selection during foraging in a partially baited maze were assessed in young and old rats. The baited and non-baited arms were at a fixed position in space and marked by a specific olfactory cue. The senescent rats did more re-entries during the first four-trial block but were more rapid than the young rats in selecting the reinforced arms during the first visits. Dissociation between the olfactory spatial cue reference by rotating the maze revealed that only few old subjects relied on olfactory cues to select the baited arms and the remainder relied mainly on the visuo-spatial cues.

Python as a programming language for the introductory programming courses

Tämä kandidaatintyö tutkii tietotekniikan perusopetuksessa keskeisen aiheen,ohjelmoinnin, alkeisopetusta ja siihen liittyviä ongelmia. Työssä perehdytään ohjelmoinnin perusopetusmenetelmiin ja opetuksen lähestymistapoihin, sekä ratkaisuihin, joilla opetusta voidaan tehostaa. Näitä ratkaisuja työssä ovat mm. ohjelmointikielen valinta, käytettävän kehitysympäristön löytäminen sekä kurssia tukevien opetusapuvälineiden etsiminen. Lisäksi kurssin läpivientiin liittyvien toimintojen, kuten harjoitusten ja mahdollisten viikkotehtävien valinta kuuluu osaksitätä työtä. Työ itsessään lähestyy aihetta tutkimalla Pythonin soveltuvuutta ohjelmoinnin alkeisopetukseen mm. vertailemalla sitä muihin olemassa oleviin yleisiin opetuskieliin, kuten C, C++ tai Java. Se tarkastelee kielen hyviä ja huonoja puolia, sekä tutkii, voidaanko Pythonia hyödyntää luontevasti pääasiallisena opetuskielenä. Lisäksi työ perehtyy siihen, mitä kaikkea kurssilla tulisi opettaa, sekä siihen, kuinka kurssin läpivienti olisi tehokkainta toteuttaa ja minkälaiset tekniset puitteet kurssin toteuttamista varten olisi järkevää valita.

Studies on integrating kinematic design method with mechanical systems simulation techniques

Theultimate goal of any research in the mechanism/kinematic/design area may be called predictive design, ie the optimisation of mechanism proportions in the design stage without requiring extensive life and wear testing. This is an ambitious goal and can be realised through development and refinement of numerical (computational) technology in order to facilitate the design analysis and optimisation of complex mechanisms, mechanical components and systems. As a part of the systematic design methodology this thesis concentrates on kinematic synthesis (kinematic design and analysis) methods in the mechanism synthesis process. The main task of kinematic design is to find all possible solutions in the form of structural parameters to accomplish the desired requirements of motion. Main formulations of kinematic design can be broadly divided to exact synthesis and approximate synthesis formulations. The exact synthesis formulation is based in solving n linear or nonlinear equations in n variables and the solutions for the problem areget by adopting closed form classical or modern algebraic solution methods or using numerical solution methods based on the polynomial continuation or homotopy. The approximate synthesis formulations is based on minimising the approximation error by direct optimisation The main drawbacks of exact synthesis formulationare: (ia) limitations of number of design specifications and (iia) failure in handling design constraints- especially inequality constraints. The main drawbacks of approximate synthesis formulations are: (ib) it is difficult to choose a proper initial linkage and (iib) it is hard to find more than one solution. Recentformulations in solving the approximate synthesis problem adopts polynomial continuation providing several solutions, but it can not handle inequality const-raints. Based on the practical design needs the mixed exact-approximate position synthesis with two exact and an unlimited number of approximate positions has also been developed. The solutions space is presented as a ground pivot map but thepole between the exact positions cannot be selected as a ground pivot. In this thesis the exact synthesis problem of planar mechanism is solved by generating all possible solutions for the optimisation process ¿ including solutions in positive dimensional solution sets - within inequality constraints of structural parameters. Through the literature research it is first shown that the algebraic and numerical solution methods ¿ used in the research area of computational kinematics ¿ are capable of solving non-parametric algebraic systems of n equations inn variables and cannot handle the singularities associated with positive-dimensional solution sets. In this thesis the problem of positive-dimensional solutionsets is solved adopting the main principles from mathematical research area of algebraic geometry in solving parametric ( in the mathematical sense that all parameter values are considered ¿ including the degenerate cases ¿ for which the system is solvable ) algebraic systems of n equations and at least n+1 variables.Adopting the developed solution method in solving the dyadic equations in direct polynomial form in two- to three-precision-points it has been algebraically proved and numerically demonstrated that the map of the ground pivots is ambiguousand that the singularities associated with positive-dimensional solution sets can be solved. The positive-dimensional solution sets associated with the poles might contain physically meaningful solutions in the form of optimal defectfree mechanisms. Traditionally the mechanism optimisation of hydraulically driven boommechanisms is done at early state of the design process. This will result in optimal component design rather than optimal system level design. Modern mechanismoptimisation at system level demands integration of kinematic design methods with mechanical system simulation techniques. In this thesis a new kinematic design method for hydraulically driven boom mechanism is developed and integrated in mechanical system simulation techniques. The developed kinematic design method is based on the combinations of two-precision-point formulation and on optimisation ( with mathematical programming techniques or adopting optimisation methods based on probability and statistics ) of substructures using calculated criteria from the system level response of multidegree-of-freedom mechanisms. Eg. by adopting the mixed exact-approximate position synthesis in direct optimisation (using mathematical programming techniques) with two exact positions and an unlimitednumber of approximate positions the drawbacks of (ia)-(iib) has been cancelled.The design principles of the developed method are based on the design-tree -approach of the mechanical systems and the design method ¿ in principle ¿ is capable of capturing the interrelationship between kinematic and dynamic synthesis simultaneously when the developed kinematic design method is integrated with the mechanical system simulation techniques.

Procurement in Project Implementation

Tutkimus keskittyy hankintatoimen kehittämiseen osana laitosprojektien toteutusta. Työ pohjautuu empiiriseltä taustaltaan Pöyry Oyj:n projektiliiketoimintaan ja työn tarkastelunäkökulmaksi onvalittu projektihallinnosta vastaavan yrityksen näkökulma. Tutkimus on hyvin käytännönläheinen ¿ se lähtee hankinnan ja sen seurannan ongelmista ja pyrkii tarjoamaan niihin uudenlaisia ratkaisuja. Pohjimmiltaan tutkimus kuuluu teollisuustalouden piiriin, vaikka tietojärjestelmätieteellä on vahva tukirooli. Työn tavoitteet ja tulokset liittyvät teollisuustaloudelle ominaisesti yrityksen toiminnan kehittämiseen, käytetyt välineet ja ratkaisut puolestaan hyödyntävät tietojärjestelmätieteen antamia mahdollisuuksia. Tutkimuksessa on käytetty konstruktiivista tutkimusotetta, jonka mukaisesti on luotu innovatiivisia konstruktioita ratkaisemaan aitoja reaalimaailman ongelmia ja tätä kautta tuotettu kontribuutioita teollisuustaloudelle. Tavoitteena oli järjestää hankintatoimi ja sen seuranta suurissa laitosprojekteissa tehokkaammin. Tätä varten uudistettiin ensin projektihallinnon ja hankintatoimen toimintaohjeet vastaamaan paremmin nykyajan vaatimuksia. Toimintaohjeiden perusteella ryhdyttiin toteuttamaan hankintaohjelmistoa, joka pystyisi kattamaan kaikki toimintaohjeissa kuvatut piirteet. Lopulta hankintaohjelmisto toi mukanaan uusia piirteitä projektihallintoon ja hankintatoimeen ja nämä sisällytettiin toimintaohjeisiin. Tähän kehitystyöhön ryhdyttiin, jotta laitosprojektien projektihallinto ja hankintatoimi toimisivat paremmin, eli pienemmin kustannuksin tuottaen projekteissa tarvittavat tulokset nopeammin, tarkemmin ja laadukkaammin. Tutkimuksella on kolmenlaisia tuloksia: hankintatoimen parannetut metodit, hankintaohjelmiston pohjana olevat toiminta- ja laskentamallit sekä implementaationa hankintasovellus. Uudistetut projekti- ja hankintaohjeet kuvaavat hankintatoiminnan parannettuja metodeja. Hankintaohjelmistoasuunnitellessa ja kehitettäessä tehdyt kuvaukset sisältävät uusia malleja niin hankintaprosessille kuin hankinnan seuraamiseksi suurissa laitosprojekteissa. Itse ohjelmisto on tuloksena implementaatio, joka perustuu parannettuihin hankintametodeihin ja uusiin toiminta- ja laskentamalleihin. Uudistetut projekti- ja hankintaohjeet ovat olleet käytössä Pöyry Oyj:ssä vuodesta 1991. Vuosien varrella nämä toimintaohjeet ovat auttaneet ja tukeneet satojen laitosprojektientoteutusta ja ylläpitäneet Pöyry Oyj:n kilpailukykyä kansainvälisenä projektitalona. Hankintasovellus puolestaan on ollut käytössä useissa projekteissa ja sen on havaittu pienentävän hankintatoimen suoria työkustannuksia laitosprojekteissa. Sovelluksen katsotaan myös tuovan epäsuoria kustannussäästöjä parempien hankintapäätösten muodossa, mutta näiden säästöjen suuruutta ei pystytä luotettavasti arvioimaan.

Identifying quantitative operation principles in metabolic pathways: a systematic method for searching feasible enzyme activity patterns leading to cellular adaptive responses

Background: Optimization methods allow designing changes in a system so that specific goals are attained. These techniques are fundamental for metabolic engineering. However, they are not directly applicable for investigating the evolution of metabolic adaptation to environmental changes. Although biological systems have evolved by natural selection and result in well-adapted systems, we can hardly expect that actual metabolic processes are at the theoretical optimum that could result from an optimization analysis. More likely, natural systems are to be found in a feasible region compatible with global physiological requirements. Results: We first present a new method for globally optimizing nonlinear models of metabolic pathways that are based on the Generalized Mass Action (GMA) representation. The optimization task is posed as a nonconvex nonlinear programming (NLP) problem that is solved by an outer- approximation algorithm. This method relies on solving iteratively reduced NLP slave subproblems and mixed-integer linear programming (MILP) master problems that provide valid upper and lower bounds, respectively, on the global solution to the original NLP. The capabilities of this method are illustrated through its application to the anaerobic fermentation pathway in Saccharomyces cerevisiae. We next introduce a method to identify the feasibility parametric regions that allow a system to meet a set of physiological constraints that can be represented in mathematical terms through algebraic equations. This technique is based on applying the outer-approximation based algorithm iteratively over a reduced search space in order to identify regions that contain feasible solutions to the problem and discard others in which no feasible solution exists. As an example, we characterize the feasible enzyme activity changes that are compatible with an appropriate adaptive response of yeast Saccharomyces cerevisiae to heat shock Conclusion: Our results show the utility of the suggested approach for investigating the evolution of adaptive responses to environmental changes. The proposed method can be used in other important applications such as the evaluation of parameter changes that are compatible with health and disease states.

Formalizing argumentative reasoning in a possibilistic logic programming setting with fuzzy unification

Possibilistic Defeasible Logic Programming (P-DeLP) is a logic programming language which combines features from argumentation theory and logic programming, incorporating the treatment of possibilistic uncertainty at the object-language level. In spite of its expressive power, an important limitation in P-DeLP is that imprecise, fuzzy information cannot be expressed in the object language. One interesting alternative for solving this limitation is the use of PGL+, a possibilistic logic over Gödel logic extended with fuzzy constants. Fuzzy constants in PGL+ allow expressing disjunctive information about the unknown value of a variable, in the sense of a magnitude, modelled as a (unary) predicate. The aim of this article is twofold: firstly, we formalize DePGL+, a possibilistic defeasible logic programming language that extends P-DeLP through the use of PGL+ in order to incorporate fuzzy constants and a fuzzy unification mechanism for them. Secondly, we propose a way to handle conflicting arguments in the context of the extended framework.

A logic programming framework for possibilistic argumentation: formalization and logical properties

In the last decade defeasible argumentation frameworks have evolved to become a sound setting to formalize commonsense, qualitative reasoning. The logic programming paradigm has shown to be particularly useful for developing different argument-based frameworks on the basis of different variants of logic programming which incorporate defeasible rules. Most of such frameworks, however, are unable to deal with explicit uncertainty, nor with vague knowledge, as defeasibility is directly encoded in the object language. This paper presents Possibilistic Logic Programming (P-DeLP), a new logic programming language which combines features from argumentation theory and logic programming, incorporating as well the treatment of possibilistic uncertainty. Such features are formalized on the basis of PGL, a possibilistic logic based on G¨odel fuzzy logic. One of the applications of P-DeLP is providing an intelligent agent with non-monotonic, argumentative inference capabilities. In this paper we also provide a better understanding of such capabilities by defining two non-monotonic operators which model the expansion of a given program P by adding new weighed facts associated with argument conclusions and warranted literals, respectively. Different logical properties for the proposed operators are studied

What interventions facilitate client progress through the assimilation model? A task analysis of interventions in the psychodynamic treatment of depression.

A variation of task analysis was used to build an empirical model of how therapists may facilitate client assimilation process, described in the Assimilation of Problematic Experiences Scale. A rational model was specified and considered in light of an analysis of therapist in-session performances (N = 117) drawn from six inpatient therapies for depression. The therapist interventions were measured by the Comprehensive Psychotherapeutic Interventions Rating Scale. Consistent with the rational model, confronting interventions were particularly useful in helping clients elaborate insight. However, rather than there being a small number of progress-related interventions at lower levels of assimilation, therapists' use of interventions was broader than hypothesized and drew from a wide range of therapeutic approaches. Concerning the higher levels of assimilation, there was insufficient data to allow an analysis of the therapist's progress-related interventions.

Task-induced deactivation from rest extends beyond the default mode brain network

Activity decreases, or deactivations, of midline and parietal cortical brain regions are routinely observed in human functional neuroimaging studies that compare periods of task-based cognitive performance with passive states, such as rest. It is now widely held that such task-induced deactivations index a highly organized"default-mode network" (DMN): a large-scale brain system whose discovery has had broad implications in the study of human brain function and behavior. In this work, we show that common task-induced deactivations from rest also occur outside of the DMN as a function of increased task demand. Fifty healthy adult subjects performed two distinct functional magnetic resonance imaging tasks that were designed to reliably map deactivations from a resting baseline. As primary findings, increases in task demand consistently modulated the regional anatomy of DMN deactivation. At high levels of task demand, robust deactivation was observed in non-DMN regions, most notably, the posterior insular cortex. Deactivation of this region was directly implicated in a performance-based analysis of experienced task difficulty. Together, these findings suggest that task-induced deactivations from rest are not limited to the DMN and extend to brain regions typically associated with integrative sensory and interoceptive processes.

Task complexity, the Cognition Hypothesis and second language learning and performance

In this paper we describe a taxonomy of task demands which distinguishes between Task Complexity, Task Condition and Task Difficulty. We then describe three theoretical claims and predictions of the Cognition Hypothesis (Robinson 2001, 2003b, 2005a) concerning the effects of task complexity on: (a) language production; (b) interaction and uptake of information available in the input to tasks; and (c) individual differences-task interactions. Finally we summarize the findings of the empirical studies in this special issue which all address one or more of these predictions and point to some directions for continuing, future research into the effects of task complexity on learning and performance.

Joustava hitsausautomaatio piensarjatuotannossa

Kustannuspaineet, tuotteiden laatuvaatimukset ja lisääntyvässä määrin myös ammattitaitoisen työvoiman pula lisäävät robotisoinnin käyttötarvetta hitsauksessa. Tämä työ on tehty edellä mainituista lähtökohdista ja käsittelee robottihitsausjärjestelmän suunnitteluprojektia, joustavaa hitsausautomaatiota ja robotiikan soveltamista. Näkökohtana on Savonia-ammattikorkeakoulun sekä Pohjois-Savon alueen yritysten tutkimus-, kehitys- ja koulutustoiminnan tarpeet. Joustavuus on hitsausjärjestelmän päätavoite, jolla pyritään vastaamaan asiakasohjautuvan yksittäis- ja piensarjatuotannon haasteisiin. Ratkaisua yksittäis- ja piensarjatuotteiden kokonaistaloudelliseen hitsaukseen on haettu hitsausrobotin rinnalle lisätyllä apurobotilla, jonka päätehtävä on kappaleenkäsittely, mutta sitä voidaan käyttää myös mm. robotisoituun leikkauksen ja särmäykseen. Tavallisuudesta poikkeavaa järjestelmäratkaisua on perusteltu sillä, että ohjaus- ja ohjelmointitekniikan sekä kehittyneen anturoinnin myötä on robottien käytettävyys parantunut ja aiempaa haasteellisempien robottijärjestelmien toteuttaminen on tullut näin mahdolliseksi. Lisäksi virtuaalimallinnus, simulointi ja etäohjelmointi ovat työkaluja, joita voidaan käyttää mm. tuotannon laadun ja tehokkuuden parantamiseen. Työssä esitetty robottiaseman suunnittelu alkaa järjestelmän määrittelystä, vaatimuslistan laadinnasta sekä visioinnista ja päättyy kolmen järjestelmävaihtoehdon vertailuun. Esitetyillä järjestelmävaihtoehdoilla on haettu mahdollisuutta yhdistää yleensä erillisinä toteutettuja työvaiheita yhteiseen soluun. Tuotannon joustavuus on ollut tuotantokapasiteettia tärkeämpi laitteistokokoonpanon valintaperuste.