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.

Assessment of inflammatory Bowel Disease patient's needs and problems from a nursing perspective

BACKGROUND: In this study, we aimed at assessing Inflammatory Bowel Disease patients' needs and current nursing practice to investigate to what extent consensus statements (European Crohn's and Colitis Organization) on the nursing roles in caring for patients with IBD concur with local practice. METHODS: We used a mixed-method convergent design to combine quantitative data prospectively collected in the Swiss IBD cohort study and qualitative data from structured interviews with IBD healthcare experts. Symptoms, quality of life, and anxiety and depression scores were retrieved from physician charts and patient self-reported questionnaires. Descriptive analyses were performed based on quantitative and qualitative data. RESULTS: 230 patients of a single center were included, 60% of patients were males, and median age was 40 (range 18-85). The prevalence of abdominal pain was 42%. Self-reported data were obtained from 75 out of 230 patients. General health was perceived significantly lower compared with the general population (p < 0.001). Prevalence of tiredness was 73%; sleep problems, 78%; issues related to work, 20%; sexual constraints, 35%; diarrhea, 67%; being afraid of not finding a bathroom, 42%; depression, 11%; and anxiety symptoms, 23%. According to experts' interviews, the consensus statements are found mostly relevant with many recommendations that are not yet realized in clinical practice. CONCLUSION: Identified prevalence may help clinicians in detecting patients at risk and improve patient management. © 2015 S. Karger AG, Basel.

Generating highly balanced sudoku problems as hard problems

Sudoku problems are some of the most known and enjoyed pastimes, with a never diminishing popularity, but, for the last few years those problems have gone from an entertainment to an interesting research area, a twofold interesting area, in fact. On the one side Sudoku problems, being a variant of Gerechte Designs and Latin Squares, are being actively used for experimental design, as in [8, 44, 39, 9]. On the other hand, Sudoku problems, as simple as they seem, are really hard structured combinatorial search problems, and thanks to their characteristics and behavior, they can be used as benchmark problems for refining and testing solving algorithms and approaches. Also, thanks to their high inner structure, their study can contribute more than studies of random problems to our goal of solving real-world problems and applications and understanding problem characteristics that make them hard to solve. In this work we use two techniques for solving and modeling Sudoku problems, namely, Constraint Satisfaction Problem (CSP) and Satisfiability Problem (SAT) approaches. To this effect we define the Generalized Sudoku Problem (GSP), where regions can be of rectangular shape, problems can be of any order, and solution existence is not guaranteed. With respect to the worst-case complexity, we prove that GSP with block regions of m rows and n columns with m = n is NP-complete. For studying the empirical hardness of GSP, we define a series of instance generators, that differ in the balancing level they guarantee between the constraints of the problem, by finely controlling how the holes are distributed in the cells of the GSP. Experimentally, we show that the more balanced are the constraints, the higher the complexity of solving the GSP instances, and that GSP is harder than the Quasigroup Completion Problem (QCP), a problem generalized by GSP. Finally, we provide a study of the correlation between backbone variables – variables with the same value in all the solutions of an instance– and hardness of GSP.

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

Agency problems with non-smooth decision profiles: the case of monopoly under product quality

A method for dealing with monotonicity constraints in optimal control problems is used to generalize some results in the context of monopoly theory, also extending the generalization to a large family of principal-agent programs. Our main conclusion is that many results on diverse economic topics, achieved under assumptions of continuity and piecewise differentiability in connection with the endogenous variables of the problem, still remain valid after replacing such assumptions by two minimal requirements.

Papaya pulp gelling: is it premature ripening or problems of water accumulation in the apoplast?

Gelled aspect in papaya fruit is typically confused with premature ripening. This research reports the characterization of this physiological disorder in the pulp of papaya fruit by measuring electrolyte leakage, Pi content, lipid peroxidation, pulp firmness, mineral contents (Ca, Mg and K - in pulp and seed tissues), and histological analysis of pulp tissue. The results showed that the gelled aspect of the papaya fruit pulp is not associated with tissue premature ripening. Data indicate a reduction of the vacuole water intake as the principal cause of the loss of cellular turgor; while the waterlogged aspect of the tissue may be due to water accumulation in the apoplast.

Problems of the randomization test for AB designs

N = 1 designs imply repeated registrations of the behaviour of the same experimental unit and the measurements obtained are often few due to time limitations, while they are also likely to be sequentially dependent. The analytical techniques needed to enhance statistical and clinical decision making have to deal with these problems. Different procedures for analysing data from single-case AB designs are discussed, presenting their main features and revising the results reported by previous studies. Randomization tests represent one of the statistical methods that seemed to perform well in terms of controlling false alarm rates. In the experimental part of the study a new simulation approach is used to test the performance of randomization tests and the results suggest that the technique is not always robust against the violation of the independence assumption. Moreover, sensitivity proved to be generally unacceptably low for series lengths equal to 30 and 40. Considering the evidence available, there does not seem to be an optimal technique for single-case data analysis

Joustavan robotisoidun särmäyssolun käyttöönotto levytuotetahtaalla

Diplomityön ensimmäisenä tavoitteena on selvittää robotisoidun särmäyssolun tehokkaimmat käyttöalueet särmättävien kappaleiden muotojen ja laitteiston teknisten edellytysten perusteella. Toisena tavoitteena on tuoda esille robotisoidun särmäyssolun käyttöönottoon liittyviä ongelmia ja antaa käytännön ohjeita niiden ratkaisemiseksi. Tuloksia sovelletaan jatkossa kohdeyrityksen markkinoiman särmäyssolun tuotekehitykseen. Särmäyksen automatisoinnin pääpiirteitä tarkastellaan tutkimalla markkinoilla olevien robottisolujen toimintaperiaatteita ja ohjelmointitapoja. Työssä on myös esitetty kohdeyrityksen omat tavoitteet ja lähtökohdat särmäysmenetelmien kehittämiseen, joista tärkeimmät ovat integroitavuus joustavaan valmistusjärjestelmään ja solun kehittäminen myyntiartikkeliksi. Työssä esitellään robotisoidun särmäyssolun toimintaa kuvaamalla työkierron toiminnot pääpiirteissään. Samassa yhteydessä esitellään myös solun konekanta sekä koneiden välillä tapahtuva tiedon siirto. Erityisenä mielenkiinnon kohteena ovat olleet joustavan valmistusjärjestelmän soluohjaimen toiminnot ja särmäyssolun toimivuus FMS:n osana. Analyyttisessä osuudessa tutkitaan kappaleiden särmättävyyttä robotisoidussa tuotantoratkaisussa. Lähtökohdaksi on otettu särmäyspuristimen, robotin, lisälaitteiden ja kappaleen muotojen asettamat rajoitukset sekä toisaalta robotisoinnin tuomat uudet mahdollisuudet. Tulosten perusteella robotisointi soveltuu parhaiten painaville tai monimutkaisille kappaleille, joiden manuaalisärmäys vie paljon aikaa. Taloudellisia käyttöalueita kartoitettiin tutkimalla eräkokoon, ohjelmointiajan, kappaleajan ja särmien määrän vaikutusta valmistuskustannuksiin. Robotisoinnin on todettu kannattavan yrityksissä, joissa sarjat ovat usein toistuvia ja eräkoot yli 150 kappaleen suuruisia. Kappaleen muoto ja särmien määrä vaikuttaa monin tavoin kappaleaikaan ja siten myös valmistuskustannuksiin. Robotisoinnin kannattavuutta on näissä tapauksissa arvioitava aina tapauskohtaisesti työkierron vaatimien toimintojen perusteella.

ROBOTTIHITSAUKSEN KÄYTTÖÖNOTON EDELLYTYKSET ASIAKASOHJAUTUVASSA YKSITTÄIS- JA PIENSARJATUOTANNOSSA

Diplomityö koostuu teoria- ja tutkimusosasta. Teoriaosassa on käsitelty robottihitsaus-järjestelmän hankinnan edellytyksiä asiakasohjautuvan yksittäis- ja piensarjatuotannon lähtökohdista. Tarkastelun osa-alueita ovat asiakasohjautuva tuotanto, robottihitsaus yksittäis- ja piensarjatuotannossa, robottien ohjelmointimenetelmät, robottihitsauksen laatu ja laadunvarmistus, tehokkuus, tuottavuus, kannattavuus, robottihitsattavan tuotteen ja robottihitsausjärjestelmän suunnittelu, robottihitsausaseman turvallisuus sekä robotti-järjestelmän toteutus ja käyttöönotto. Teoriaosa on koottu siten, että sitä voidaan käyttää myös oppimateriaalina. Siinä esitetään myös sovellusesimerkki Imatran ammattikoululla toteutetusta robottihitsausaseman turvallisuusrakenneratkaisusta, jonka on suunnitellut ja toteuttanut diplomityön laatija. Diplomityön tutkimusosassa selvitetään kyselytutkimuksen avulla robottihitsauksen käyt-töönoton edellytyksiä asiakasohjautuvassa yksittäis- ja piensarjatuotannossa eteläkarjalai-sissa konepaja- ja metallialan yrityksissä. Tutkimukseen mukaan valituille 25 yritykselle ja yrityksistä valituille vastuuhenkilöille lähetettiin kirjallinen kyselytutkimus, johon vastaus saatiin 17 yritykseltä. Diplomityön tavoitteena oli selvittää robottihitsauksen käyttöönoton edellytyksiä. Tutkimuksella haettiin tietoja myös muusta yritysten suunnittelemasta hitsaus-tuotannon kehittämisestä kuten mekanisoinnista ja sen nykytilasta sekä muista mahdollisista hitsaukseen liittyvistä hankkeista. Tutkimustulosten perusteella on todettavissa, että Etelä-Karjalassa toimivista asiakas-ohjautuvista yksittäis- ja piensarjatuotantoa harjoittavista konepaja- ja metallialan yri-tyksistä löytyy yrityksiä, jotka ovat kiinnostuneita robottihitsausjärjestelmän hankinnasta, mutta saatujen tulosten perusteella voidaan todeta, että edellytyksiä siihen ei vielä näyttäisi olevan. Syiksi robottihitsausjärjestelmän hankinnan edellytysten puuttumiseen voidaan mainita muun muassa sopimaton tuoterakenne, liian yksilölliset tuotteet ja pienet sarjat, joilla ei ole toistuvuutta. Lisäksi yritykset toimivat pelkästään alihankintayrityksinä eikä niillä ole omaa tuotetta. Robottihitsausjärjestelmän hankinta voisi olla mahdollista niissä yrityksissä, jotka ovat verkottuneet, toimivat vakaavaraisesti ja joiden viennistä osa suuntautuu välillisesti tai välittömästi ulkomaille. Yhteistyöverkkojen voidaan olettaa parantavan robottihitsaus-järjestelmän hankinnan mahdollisuuksia. Tällöin kustannuksia voidaan jakaa usealle eri yritykselle ja siten voidaan tehostaa myös järjestelmän käyttöastetta sekä hankkia uusia asiakkaita. Kaksi yrityksistä on harkinnut joko oman tai leasing-robottihitsausjärjestelmän hankintaa. Ongelmina robottihitsausjärjestelmän yhteishankinnalle pidettiin esim. kenen tiloihin järjestelmä hankitaan, kuka huolehtii kunnossapidosta, miten palkat maksetaan työntekijöille ja miten käytössä oleva työaika jaetaan eri yrityksille. Diplomityön johtopäätökset ja suositukset osassa esitetään muutamia jatkotoimenpide-ehdotuksia siitä, kuinka tiettyjen yritysten osalta voitaisiin robottihitsauksen käyttöönottoa edistää. Tutkimuksen tuloksena saatua tietoa hyödynnetään muun muassa Lappeenrannan teknillisen yliopiston tutkimus- ja koulutushankkeissa sekä toisen asteen kone- ja metallitekniikan koulutuksen suunnittelussa ja toteutuksessa.

Involuntary outpatient treatment for mental health problems in Switzerland: a literature review.

BACKGROUND: In 2008, the Swiss Civil Code was amended. From 1 January 2013, each Swiss canton may propose specific provisions for involuntary outpatient treatment (community treatment orders (CTOs)) for individuals with mental disorders. AIM: This review catalogues the legal provisions of the various Swiss cantons for CTOs and outlines the differences between them. It sets this in the context of variations in clinical provisions between the cantons. METHODS: Databases were searched to obtain relevant publications about CTOs in Switzerland. The Swiss Medical Association, Swiss Federal Statistical Office, Swiss Health Observatory and all the 26 Cantonal medical officers were contacted to complete the information. Conférence des cantons en matière de protection des mineurs et des adultes (COPMA), the authority which monitors guardianship legislation, and Pro Mente Sana, a patients' right association, were also approached. RESULTS: Three articles about CTOs in Switzerland were identified. Psychiatric provisions vary considerably between cantons and only a few could provide complete or even partial figures for rates of compulsion in previous years. Prior to 2013, only 6 of the 20 cantons, for which information was returned, had any provision for CTOs. Now, every canton has some form of legal basis but the level of detail is often limited. In eight cantons, the powers of the measure are not specified (for example, use of medication). In 12 cantons, the maximum duration of the CTO is not specified. German speaking cantons and rural cantons are more likely to specify the details of CTOs. CONCLUSION: Highly variable Swiss provision for CTOs is being introduced despite the absence of convincing international evidence for their effectiveness or good quality data on current coercive practice. Careful monitoring and assessment of these new cantonal provisions are essential.

Verkkokäyttöliittymäohjelmiston toteuttaminen TradeXpress-tietojärjestelmään.

Työssä perehdytään verkkokäyttöliittymien suunnitteluun ja toteutukseen. Erityisen huomion kohteena ovat Java-ohjelmointikieli ja ohjelmistosuunnittelussa suurta huomiota herättäneet suunnittelumallit. Java on kehittynyt lyhyen elinikänsä aikana huomattavasti, ja viimeaikaiset vakioluokkakirjastot ovat mahdollistaneet monipuolisten ja siirrettävien ohjelmistojen toteuttamisen. Vaikka Java ei sovellukaan kaikkiin tarkoituksiin, on se luotettavuutensa, siirrettävyytensä ja luokkakirjastojensa ilmaisuvoiman ansiosta hyvin houkutteleva kieli käyttöliittymien tekemiseen. Suunnittelumallit ovat merkittävä osa ammattimaista oliosuunnittelua. Ne tarjoavat valmiita ratkaisuja yleisiin suunnitteluongelmiin ja säästävät siten aikaa suunnittelu- ja toteutusvaiheissa. Suunnittelumallit voidaan jakaa kolmeen ryhmään: luontimallit, rakennemallit ja toiminnalliset mallit. Käytännön osuudessa tarkastellaan Java-käyttöliittymän toteutusta olemassa olevaan Soneran TradeXpress-tietojärjestelmään. Tässä tehtävässä Java ja suunnittelumallit ovat olleet keskeisellä sijalla. Java-käyttöliittymä, JavaGUI, koostuu kahdesta osasta: asiakasappletista ja Jrls-palvelimesta. Näiden kahden väliseen tiedonsiirtoon käytetään pääasiassa Javan RMI-yhteyskäytäntöä. Jrls-palvelin toimii asiakkaana RLS-palvelimelle erityisen RLS-yhteyskäytännön avulla.

Simulation Supported Robot Programming using XML

The main objective of this master's thesis is to study robot programming using simulation software, and also how to embed the simulation software into company's own robot controlling software. The further goal is to study a new communication interface to the assembly line's components -more precisely how to connect the robot cell into this new communication system. Conveyor lines are already available where the conveyors use the new communication standard. The robot cell is not yet capable of communicating with to other devices using the new communication protocols. The main problem among robot manufacturers is that they all have their own communication systems and programming languages. There has not been any common programming language to program all the different robot manufacturers robots, until the RRS (Realistic Robot Simulation) standards were developed. The RRS - II makes it possible to create the robot programs in the simulation software and it gives a common user interface for different robot manufacturers robots. This thesis will present the RRS - II standard and the robot manufacturers situation for the RRS - II support. Thesis presents how the simulation software can be embedded into company's own robot controlling software and also how the robot cell can be connected to the CAMX (Computer Aided Manufacturing using XML) communication system.

Evolutionary computing in search-based software engineering

This master’s thesis aims to study and represent from literature how evolutionary algorithms are used to solve different search and optimisation problems in the area of software engineering. Evolutionary algorithms are methods, which imitate the natural evolution process. An artificial evolution process evaluates fitness of each individual, which are solution candidates. The next population of candidate solutions is formed by using the good properties of the current population by applying different mutation and crossover operations. Different kinds of evolutionary algorithm applications related to software engineering were searched in the literature. Applications were classified and represented. Also the necessary basics about evolutionary algorithms were presented. It was concluded, that majority of evolutionary algorithm applications related to software engineering were about software design or testing. For example, there were applications about classifying software production data, project scheduling, static task scheduling related to parallel computing, allocating modules to subsystems, N-version programming, test data generation and generating an integration test order. Many applications were experimental testing rather than ready for real production use. There were also some Computer Aided Software Engineering tools based on evolutionary algorithms.