The Protein quality control system manages plant defence compound synthesis

Jasmonates are ubiquitous oxylipin-derived phytohormones that are essential in the regulation of many development, growth and defence processes. Across the plant kingdom, jasmonates act as elicitors of the production of bioactive secondarymetabolites that serve in defence against attackers. Knowledge of the conserved jasmonate perception and early signalling machineries is increasing, but the downstream mechanisms that regulate defence metabolism remain largely unknown. Herewe showthat, in the legumeMedicago truncatula, jasmonate recruits the endoplasmic-reticulum-associated degradation (ERAD)quality control system tomanagethe production of triterpene saponins, widespread bioactive compounds that share a biogenic origin with sterols. An ERAD-type RING membraneanchor E3 ubiquitin ligase is co-expressed with saponin synthesis enzymes to control the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the rate-limiting enzyme in the supply of the ubiquitous terpene precursor isopentenyl diphosphate. Thus, unrestrained bioactive saponin accumulationis prevented and plant development and integrity secured. This control apparatus is equivalent to the ERAD system that regulates sterol synthesis in yeasts and mammals but that uses distinct E3 ubiquitin ligases, of the HMGR degradation 1 (HRD1) type, to direct destruction of HMGR. Hence, the general principles for the management of sterol and triterpene saponin biosynthesis are conserved across eukaryotes but can be controlled by divergent regulatory cues.

The Protein quality control system manages plant defence compound synthesis

Jasmonates are ubiquitous oxylipin-derived phytohormones that are essential in the regulation of many development, growth and defence processes. Across the plant kingdom, jasmonates act as elicitors of the production of bioactive secondarymetabolites that serve in defence against attackers. Knowledge of the conserved jasmonate perception and early signalling machineries is increasing, but the downstream mechanisms that regulate defence metabolism remain largely unknown. Herewe showthat, in the legumeMedicago truncatula, jasmonate recruits the endoplasmic-reticulum-associated degradation (ERAD)quality control system tomanagethe production of triterpene saponins, widespread bioactive compounds that share a biogenic origin with sterols. An ERAD-type RING membraneanchor E3 ubiquitin ligase is co-expressed with saponin synthesis enzymes to control the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the rate-limiting enzyme in the supply of the ubiquitous terpene precursor isopentenyl diphosphate. Thus, unrestrained bioactive saponin accumulationis prevented and plant development and integrity secured. This control apparatus is equivalent to the ERAD system that regulates sterol synthesis in yeasts and mammals but that uses distinct E3 ubiquitin ligases, of the HMGR degradation 1 (HRD1) type, to direct destruction of HMGR. Hence, the general principles for the management of sterol and triterpene saponin biosynthesis are conserved across eukaryotes but can be controlled by divergent regulatory cues.

The Protein quality control system manages plant defence compound synthesis

Jasmonates are ubiquitous oxylipin-derived phytohormones that are essential in the regulation of many development, growth and defence processes. Across the plant kingdom, jasmonates act as elicitors of the production of bioactive secondarymetabolites that serve in defence against attackers. Knowledge of the conserved jasmonate perception and early signalling machineries is increasing, but the downstream mechanisms that regulate defence metabolism remain largely unknown. Herewe showthat, in the legumeMedicago truncatula, jasmonate recruits the endoplasmic-reticulum-associated degradation (ERAD)quality control system tomanagethe production of triterpene saponins, widespread bioactive compounds that share a biogenic origin with sterols. An ERAD-type RING membraneanchor E3 ubiquitin ligase is co-expressed with saponin synthesis enzymes to control the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the rate-limiting enzyme in the supply of the ubiquitous terpene precursor isopentenyl diphosphate. Thus, unrestrained bioactive saponin accumulationis prevented and plant development and integrity secured. This control apparatus is equivalent to the ERAD system that regulates sterol synthesis in yeasts and mammals but that uses distinct E3 ubiquitin ligases, of the HMGR degradation 1 (HRD1) type, to direct destruction of HMGR. Hence, the general principles for the management of sterol and triterpene saponin biosynthesis are conserved across eukaryotes but can be controlled by divergent regulatory cues.

Development of Order-Delivery Process in Purchasing

Diplomityön tavoitteena oli kehittää Fazer Suklaan oston tilaus-toimitusprosesseja, jotta raaka-aineet ja pakkausmateriaalit pystytään hoitamaan mahdollisimman tehokkaasti. Ensin selvitettiin kirjallisuuden avulla tilaus-toimitusprosessin päävaiheet ja niihin vaikuttavat tekijät. Empiirisessä osassa lähdettiin liikkeelle käymällä läpi Fazer Suklaan oston nykytilanne, joka tehtiin ostajille suunnatun aikaselvityksen, haastatteluiden ja nykyisten tilaus-toimitusprosessien kuvaamisen avulla. Tavoitetilanteen rakentaminen aloitettiin ostettavien materiaalien ja toimittajien luokittelemisella. Tämän perusteella nämä materiaalit voitiin jakaa kolmen eri tilaus toimitusprosessin alle. Automaattisessa tilaus-toimitusprosessissa eri vaiheet automatisoidaan yhdessäavain toimittajien kanssa. Puoliautomaattinen prosessi perustuu systeemiin, jossa toimittaja näkee internetin kautta Fazerin tuotantosuunnitelman ja tekee tämän perusteella materiaalien täydennykset. Yksinkertaisessa prosessissa ostoarvoltaan alhaiset materiaalit hoidetaan mahdollisimman lähellä käyttöpistettä ja prosessin vaiheet tehdään mandollisimman pienellä työmäärällä. Tavoiteprosessien implementoinnilla todettiin suurimmiksi eduiksi prosessivaiheiden vähentyminen ja manuaalisen työn automatisoituminen. Tätä kautta saatiin prosessin eri vaiheiden työmäärää vähennettyä, sekä alennettua varastotasoja ja näin tilaus toimitusprosessin kokonaiskustannuksia pystyttiin pienentämään.

Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial.

BACKGROUND: Enteral nutrition (EN) is recommended for patients in the intensive-care unit (ICU), but it does not consistently achieve nutritional goals. We assessed whether delivery of 100% of the energy target from days 4 to 8 in the ICU with EN plus supplemental parenteral nutrition (SPN) could optimise clinical outcome. METHODS: This randomised controlled trial was undertaken in two centres in Switzerland. We enrolled patients on day 3 of admission to the ICU who had received less than 60% of their energy target from EN, were expected to stay for longer than 5 days, and to survive for longer than 7 days. We calculated energy targets with indirect calorimetry on day 3, or if not possible, set targets as 25 and 30 kcal per kg of ideal bodyweight a day for women and men, respectively. Patients were randomly assigned (1:1) by a computer-generated randomisation sequence to receive EN or SPN. The primary outcome was occurrence of nosocomial infection after cessation of intervention (day 8), measured until end of follow-up (day 28), analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00802503. FINDINGS: We randomly assigned 153 patients to SPN and 152 to EN. 30 patients discontinued before the study end. Mean energy delivery between day 4 and 8 was 28 kcal/kg per day (SD 5) for the SPN group (103% [SD 18%] of energy target), compared with 20 kcal/kg per day (7) for the EN group (77% [27%]). Between days 9 and 28, 41 (27%) of 153 patients in the SPN group had a nosocomial infection compared with 58 (38%) of 152 patients in the EN group (hazard ratio 0·65, 95% CI 0·43-0·97; p=0·0338), and the SPN group had a lower mean number of nosocomial infections per patient (-0·42 [-0·79 to -0·05]; p=0·0248). INTERPRETATION: Individually optimised energy supplementation with SPN starting 4 days after ICU admission could reduce nosocomial infections and should be considered as a strategy to improve clinical outcome in patients in the ICU for whom EN is insufficient. FUNDING: Foundation Nutrition 2000Plus, ICU Quality Funds, Baxter, and Fresenius Kabi.

Performance measurement oforder-delivery chain in SMEs: Case study

Tutkimus pyrkii selvittämään, kuinka tehokas suorituskykymittaristo voidaan parhaiten suunnitella pk-yrityksessä. Tutkimuksen tavoitteena on luoda suorituskykymittaristo pienen kohdeyrityksen johtajien tarpeisiin. Päähuomion kohteena on yrityksen tilaus-toimitusketju ja arvoverkko. Työ on luonteeltaan kvalitatiivinen toimintatutkimus, joka noudattaa toiminta-analyyttista tutkimusotetta. Työn teoriaosassa selvitetään, kuinka suorituskyvyn mittaaminen sekä materiaali-, tieto- ja rahavirtojen hallinta on kehittynyt viime vuosina pk-yrityksen näkökulmasta. Mittariston suunnittelu aloitetaan kohdeyrityksen perusteellisella analyysilla. Tämän pohjalta määritellään yrityksen kriittiset menestystekijät, joista lopulta johdetaan suorituskykymittarit. Tutkimuksen perusteella voidaan todeta, että yleinen asenne mittaamista kohtaan, strategian huomioinnin puute sekä tietojärjestelmien rajoitteet ovat päähaasteita pk-yrityksen suorituskyvyn mittaamisessa. Mittareiden tuleekin olla melko yksinkertaisia ja helppoja käyttää, jotta mittaamisen ei koettaisi kuluttavan rajallisia resursseja liikaa. Mittariston tulee kuitenkin antaa kokonaisvaltainen kuva yrityksen suorituskyvystä, johon vaikuttavat kaikki arvoverkon osapuolet ja heidän yhteistyö toistensa kanssa.

Working alliance in communication skills training for oncology clinicians: A controlled trial.

OBJECTIVE: The aim of this study was to evaluate the impact of communication skills training (CST) on working alliance and to identify specific communicational elements related to working alliance. METHODS: Pre- and post-training simulated patient interviews (6-month interval) of oncology physicians and nurses (N=56) who benefited from CST were compared to two simulated patient interviews with a 6-month interval of oncology physicians and nurses (N=57) who did not benefit from CST. The patient-clinician interaction was analyzed by means of the Roter Interaction Analysis System (RIAS). Alliance was measured by the Working Alliance Inventory - Short Revised Form. RESULTS: While working alliance did not improve with CST, generalized linear mixed effect models demonstrated that the quality of verbal communication was related to alliance. Positive talk and psychosocial counseling fostered alliance whereas negative talk, biomedical information and patient's questions diminished alliance. CONCLUSION: Patient-clinician alliance is related to specific verbal communication behaviors. PRACTICE IMPLICATIONS: Working alliance is a key element of patient-physician communication which deserves further investigation as a new marker and efficacy criterion of CST outcome.

On Modelling, System Identification and Control of Servo-Systems with a Flexible Load

The present study was done with two different servo-systems. In the first system, a servo-hydraulic system was identified and then controlled by a fuzzy gainscheduling controller. The second servo-system, an electro-magnetic linear motor in suppressing the mechanical vibration and position tracking of a reference model are studied by using a neural network and an adaptive backstepping controller respectively. Followings are some descriptions of research methods. Electro Hydraulic Servo Systems (EHSS) are commonly used in industry. These kinds of systems are nonlinearin nature and their dynamic equations have several unknown parameters.System identification is a prerequisite to analysis of a dynamic system. One of the most promising novel evolutionary algorithms is the Differential Evolution (DE) for solving global optimization problems. In the study, the DE algorithm is proposed for handling nonlinear constraint functionswith boundary limits of variables to find the best parameters of a servo-hydraulic system with flexible load. The DE guarantees fast speed convergence and accurate solutions regardless the initial conditions of parameters. The control of hydraulic servo-systems has been the focus ofintense research over the past decades. These kinds of systems are nonlinear in nature and generally difficult to control. Since changing system parameters using the same gains will cause overshoot or even loss of system stability. The highly non-linear behaviour of these devices makes them ideal subjects for applying different types of sophisticated controllers. The study is concerned with a second order model reference to positioning control of a flexible load servo-hydraulic system using fuzzy gainscheduling. In the present research, to compensate the lack of dampingin a hydraulic system, an acceleration feedback was used. To compare the results, a pcontroller with feed-forward acceleration and different gains in extension and retraction is used. The design procedure for the controller and experimental results are discussed. The results suggest that using the fuzzy gain-scheduling controller decrease the error of position reference tracking. The second part of research was done on a PermanentMagnet Linear Synchronous Motor (PMLSM). In this study, a recurrent neural network compensator for suppressing mechanical vibration in PMLSM with a flexible load is studied. The linear motor is controlled by a conventional PI velocity controller, and the vibration of the flexible mechanism is suppressed by using a hybrid recurrent neural network. The differential evolution strategy and Kalman filter method are used to avoid the local minimum problem, and estimate the states of system respectively. The proposed control method is firstly designed by using non-linear simulation model built in Matlab Simulink and then implemented in practical test rig. The proposed method works satisfactorily and suppresses the vibration successfully. In the last part of research, a nonlinear load control method is developed and implemented for a PMLSM with a flexible load. The purpose of the controller is to track a flexible load to the desired position reference as fast as possible and without awkward oscillation. The control method is based on an adaptive backstepping algorithm whose stability is ensured by the Lyapunov stability theorem. The states of the system needed in the controller are estimated by using the Kalman filter. The proposed controller is implemented and tested in a linear motor test drive and responses are presented.

Relevance of death receptors in nervous system: role in the pathogenesis of neurodegenerative diseases and targets for therapy

L’apoptosi és un procés fisiològic que controla el nombre de cèl·lules en organismes superiors. L’apoptosi està estrictament regulada i s’ha vist que està implicada en la patogènesi d’algunes malalties del sistema nerviós. En aquest sentit, un excés de mort cel·lular contribueix a les malalties neurodegenerati- ves, mentre que, el seu dèficit és una de les raons del desenvolupament de tumors. El punt principal de regulació del procés apoptòtic és l’activació de les caspases, cisteïna-proteases que tenen especificitat pels residus aspàrtic. Les caspases es poden activar per dos mecanismes principals: (1) alliberament de citocrom C dels mitocondris alterats al citoplasma i (2) l’activació dels receptors de la membrana anomenats receptors de mort (DR, de l’anglès death receptor). Aquests receptors s’han caracteritzat extensament en el sistema immunitari, mentre que en el sistema nerviós les seves funcions són encara desconegudes. El present article se centra en el paper dels DR en la patogènesi de malalties neurodegeneratives i suggereix el seu potencial des del punt de vista terapèutic. També es descriuen diverses molècules intracel·lulars caracteritzades per la seva habilitat en la modulació dels DR. Entre elles, presentem dues noves proteïnes – lifeguard i FAIM – que s’expressen específicament al sistema nerviós.

Interoperability of learning objects copyright in the LUISA semantic learning management system

Semantic Web technology is able to provide the required computational semantics for interoperability of learning resources across different Learning Management Systems (LMS) and Learning Object Repositories (LOR). The EU research project LUISA (Learning Content Management System Using Innovative Semantic Web Services Architecture) addresses the development of a reference semantic architecture for the major challenges in the search, interchange and delivery of learning objects in a service-oriented context. One of the key issues, highlighted in this paper, is Digital Rights Management (DRM) interoperability. A Semantic Web approach to copyright management has been followed, which places a Copyright Ontology as the key component for interoperability among existing DRM systems and other licensing schemes like Creative Commons. Moreover, Semantic Web tools like reasoners, rule engines and semantic queries facilitate the implementation of an interoperable copyright management component in the LUISA architecture.

An activator/repressor dual system allows tight tetracycline-regulated gene expression in budding yeast

We have developed an activator/repressor expression system for budding yeast in which tetracyclines control in opposite ways the ability of tetR-based activator and repressor molecules to bind tetO promoters. This combination allows tight expression of tetO-driven genes, both in a direct (tetracycline-repressible) and reverse (tetracycline-inducible) dual system. Ssn6 and Tup1, that are components of a general repressor complex in yeast, have been tested for their repressing properties in the dual system, using lacZ and CLN2 as reporter genes. Ssn6 gives better results and allows complete switching-off of the regulated genes, although increasing the levels of the Tup1-based repressor by expressing it from a stronger promoter improves repressing efficiency of the latter. Effector-mediated shifts between expression and non-expression conditions are rapid. The dual system here described may be useful for the functional analysis of essential genes whose conditional expression can be tightly controlled by tetracyclines.

Impact of case management on frequent users quality of life : a randomized controlled trial

BACKGROUND: Frequent emergency department users represent a small number of patients but account for a large number of emergency department visits. They should be a focus because they are often vulnerable patients with many risk factors affecting their quality of life (QoL). Case management interventions have resulted in a significant decrease in emergency department visits, but association with QoL has not been assessed. One aim of our study was to examine to what extent an interdisciplinary case management intervention, compared to standard emergency care, improved frequent emergency department users' QoL. METHODS: Data are part of a randomized, controlled trial designed to improve frequent emergency department users' QoL and use of health-care resources at the Lausanne University Hospital, Switzerland. In total, 250 frequent emergency department users (≥5 attendances during the previous 12 months; ≥ 18 years of age) were interviewed between May 2012 and July 2013. Following an assessment focused on social characteristics; social, mental, and somatic determinants of health; risk behaviors; health care use; and QoL, participants were randomly assigned to the control or the intervention group (n=125 in each group). The final sample included 194 participants (20 deaths, 36 dropouts, n=96 in the intervention group, n=99 in the control group). Participants in the intervention group received a case management intervention by an interdisciplinary, mobile team in addition to standard emergency care. The case management intervention involved four nurses and a physician who provided counseling and assistance concerning social determinants of health, substance-use disorders, and access to the health-care system.

Paperiteollisuuden tehdasjärjestelmien uusimisen vaatimukset usean tehtaan ympäristössä

Tässä diplomityössä tutkitaan tehdasjärjestelmien uusintaan vaikuttavia tekijöitä, kun tarkoituksena on siirtyä yhtenäisiin tuotepohjaisiin järjestelmäratkaisuihin usean paperitehtaan ympäristössä. Paperitehtaan tehdasjärjestelmän avulla hallitaan tehtaan toimintaa alkaen tilauksen saapumisesta tehtaalle aina valmiin tuotteen varastointiin sekä asiakkaalle toimitukseen saakka. Työn pääasiallinen tarkoitus on tutkia erilaisten teknisten arkkitehtuurien, kuten keskitetyn tai hajautetun palvelinympäristön vaikutusta järjestelmän käyttövarmuuteen, käytettävyyteen sekä järjestelmän elinkaaren aikaisiin kustannuksiin. Tietojärjestelmien keskittämiseen ja konsolidointiin liittyen tutkitaan mm. vaikutuksia liityntöjen ja raportoinnin hallintaan sekä tietoverkoille asetettavia vaatimuksia. Työssä tutkitaan myös tuotepohjaisten järjestelmien räätälöintitarpeita ja siihen liittyvää vaatimusmäärittelyä. Työssä esitettyjä näkemyksiä voidaan käyttää päätösten tukena, kun pohditaan toteutettavan tietojärjestelmän teknisen infrastruktuurin optimaalisinta rakennetta.

LAIPPATEHTAAN TOIMITUSVARMUUDEN JA LÄPIMENOAIKOJEN KEHITTÄMINEN AIKAPERUSTEISEN PROSESSIJOHTAMISEN KEINOIN

Yritysten sisäiset prosessit ovat usein pysyneet samanlaisina jo vuosia, ellei vuosikymmeniä. Tulevaisuuden haasteet löytyvät mitä suurimmassa määrin yritysten omista, monessa tapauksessa vielä tunnistamattomista prosesseista. Näiden haasteiden pohjalta, tämän diplomityön perusajatuksena on prosessijohtaminen. Diplomityön tutkimusongelma on laippatehtaan vaihteleva ja usein liian alhainen viikoittainen toimitusvarmuus, pitkät tilaus-toimitusketjun läpimenoajat ja alihankintalaippojen maahantuonnin vaikutus tehtaan toimitusvarmuuteen. Työn tarkoituksena on tutkia, kuvata ja analysoida tehtaan tuotannonohjauksen ja prosessien nykytilanne. Kirjallisuustutkimuksen ja analyysien pohjalta tavoitteena on tehdä ja toteuttaa erilaisia kehitysvaihtoehtoja toimitusvarmuuden, läpimenoaikojen ja tuotannon seurannan kehittämiseksi. Työssä analysoitiin Ferral Components Oy:n tuotannon nykytilaa, joka on perinteisesti ollut standardituotteiden varasto-ohjattua toimintaa. Analyysin perustietoina käytettiin yrityksen tuotannonohjausjärjestelmästä saatavia tilaus-toimitustietoja pääosin vuosilta 2003 ja 2004, joiltakin osin myös vuoden 2005 tietoja. ABC-analyysin tuloksena saatiin selville yrityksen tuotteiston rakenne ja sen pohjalta päätuoteryhmien tilaus-toimitusketjut. Päätuoteryhmien tilaus-toimitusketjujen selvittämisen jälkeen voitiin analysoida niiden nykytilanne. Nykytila-analyysin tulokset osoittivat, että tilaustoimitusketjut eivät ole suorituskykyisiä käytettyjen menetelmien ja mittareiden valossa ja kehitystarvetta on olemassa. Nykytila-analyysin, kirjallisuustutkimuksen ja projektikokousten avulla löydettiin kehityskohteita prosessien luomiseksi, sekä niiden kehittämiseksi. Pääasiallinen kehityskohde löydettiin analyysin pohjalta määritettyjen tilaus-toimitusketjujen eriyttämisestä omiksi ydinprosesseikseen. Ydinprosessit kuvattiin etulehtien, prosessikaavioiden ja tekstisivujen avulla. Lisäksi ydinprosesseille hahmoteltiin uusi prosessien mukainen tuotannon layout ja määriteltiin prosessien seurantaan soveltuvat mittarit. Lopuksi listattiin ydinprosesseille nykytila-analyysin pohjalta havaittuja kehitysideoita ja niiden mahdollisia positiivisia vaikutuksia sekä tehtiin taulukkolaskentaohjelmalla taulukko varasto-ohjattavien tuotteiden hälytysrajojen määrittämiseksi.