A modular tethering complex for endosomal recycling.

How proteins migrate through the interconnected organelles of the endolysosomal system is poorly understood. A piece of the puzzle has been added with the identification of a complex of tethering factors that functions in the recycling of proteins towards the cell surface.

Agent-augmented process automation system in a panel board factory

Kiristyvä kansainvälinen kilpailu pakottaa automaatiojärjestelmien valmistajat ottamaan käyttöön uusia menetelmiä, joiden avulla järjestelmien suorituskykyä ja joustavuutta saadaan parannettua. Agenttiteknologiaa on esitetty käytettäväksi olemassa olevien automaatiojärjestelmien kanssa vastaamaan automaatiolle asetettaviin uusiin haasteisiin. Agentit ovat itsenäisiä yhteisöllisiä toimijoita, jotka suorittavat niille ennalta määrättyjä tehtäviä. Ne tarjoavat yhtenäisen kehyksen kehittyneiden toimintojen toteutukselle. Agenttiteknologian avulla automaatiojärjestelmä saadaan toimimaan joustavasti ja vikasietoisesti. Tässä työssä selostetaan agenttiteknologian ajatuksia ja käsitteitä. Lisäksi selvitetään sen soveltuvuutta monimutkaisten ohjausjärjestelmien kehittämiseen ja etsitään käyttökohteita sen soveltamiselle levytehtaassa. Työssä käsitellään myös aatteita, jotka ovat johtaneet agenttiteknologian käyttöön automaatiojärjestelmissä, sekä selostetaan agenttiavusteisen esimerkkisovelluksen rakenne ja testitulokset. Tutkimuksen tuloksena löydettiin useita kohteita agenttiteknologian käytölle levytehtaassa. Esimerkkisovellus osoittaa sen sopivan hyvin kehittyneiden toimintojen toteutukseen automaatiojärjestelmissä.

Integrating Financial Perspective to Quality Orientated Management System. Case: ALSTOM Finland Oy

Tutkimuksen päätavoitteena on tutkia taloudellisen näkökulman integroimista laatuajatteluun pohjautuvaan johtamisjärjestelmään esimerkkiyrityksessä. Johtamisjärjestelmän tulee tuottaa tietoa johdon strategiselle päätöksenteolle ja lisäksi täyttää laatujärjestelmän (ISO 9001:2000) asettamat vaatimukset. Tutkimuksen kohteena oleva työkalu on balanced scorecard (tasapainotettu tuloskortti). Työn tarkoituksena on ehdottaa balanced scorecard- talouden tunnuslukuja esimerkkiyritykselle. Tutkimuksen tavoitteisiin päästään empiiristä tutkimusta varten tehdyn teoreettisen viitekehyksen avulla. Empiiristä tutkimustietoa kerätään osallistuvan havainnoinnin, haastattelujen ja keskustelujen avulla. Tutkimusmenetelmänä on laadullinen case -tutkimus. Balanced scorecardin eri näkökulmille ehdotettiin tunnuslukuja empiirisen tutkimuksen pohjalta. Lisäksi talouden näkökulmaa tutkittiin tarkemmin. Tutkimuksen johtopäätöksenä esitettiin, että taloudelliset tunnusluvut mittaavat ensisijaisesti strategiaa eivätkä laatua. Lisäksi huomioitiin, että tuloskorttien tulisi olla koekäytössä ennen bonuspalkkauksen ja balanced scorecardin yhdistämistä.

Customer relationship management and central bank payment system services

Tutkimuksen tavoitteena on selvittää, miten kirjallisuudessa kuvattua asiakkuuden hallintaa voitaisiin soveltaa keskuspankin maksuliikepalveluissa. Tarkasteltavana ovat yleiset toimintatavat, sekä asiakkuuden hallintaa tukevat järjestelmät. Tutkimuksen päätavoitteena on Help Desk toiminnan kehittäminen. Tutkimuksessa tarkastellaan asiakkuuden hallinnan eri osa-alueita ottaen huomioon sekä asiakkaan, että palvelun tarjoajan näkökulmat. Asiakkuuden hallinta ymmärretään strategiana, jolla kyetään kuvaamaan kuinka koko organisaatio toimii asiakkaiden kanssa. Asiakkuuden hallinnan ydin on asiakkaan arvontuotantoprosessin ymmärtäminen. Käytettyjä lähdeaineistoja ovat olleet alan kirjallisuus, artikkelit sekä Internet-lähteet. Empirian taustan ovat muodostaneet asiantuntijahaastattelut sekä keskuspankin julkaisut, sisäiset toimintaohjeet ja vakiintuneet käytännöt. Tutkimuksen keskeinen tulos on, että asiakkuudenhallinnan perusajatukset ovat monin tavoin sovellettavissa keskuspankin melko ainutkertaiseen, teknisesti ja viestinnällisesti vaativaan maksuliikepalveluympäristöön, vaikka asiakkaiden lukumäärä onkin pieni. Hyötyjä voidaan saavuttaa jo asiakkuudenhallinnan peruskomponenttien ml. strategianäkökulma tuntemuksella ja melko pieniltäkin näyttävillä toimintatapa-, työnkulku- ja asennemuutoksilla. Asiakkuuden hallintaa tukevan tietoteknologian jonkinasteinen käyttöönotto voi tuoda lisäarvoa, mutta sen kustannukset ja hyödyt on punnittava tämäntyyppisessä ympäristössä tarkoin.

Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2.

CREB-binding protein (CBP) and p300 are transcriptional coactivators involved in numerous biological processes that affect cell growth, transformation, differentiation, and development. In this study, we provide evidence of the involvement of homeodomain-interacting protein kinase 2 (HIPK2) in the regulation of CBP activity. We show that HIPK2 interacts with and phosphorylates several regions of CBP. We demonstrate that serines 2361, 2363, 2371, 2376, and 2381 are responsible for the HIPK2-induced mobility shift of CBP C-terminal activation domain. Moreover, we show that HIPK2 strongly potentiates the transcriptional activity of CBP. However, our data suggest that HIPK2 activates CBP mainly by counteracting the repressive action of cell cycle regulatory domain 1 (CRD1), located between amino acids 977 and 1076, independently of CBP phosphorylation. Our findings thus highlight a complex regulation of CBP activity by HIPK2, which might be relevant for the control of specific sets of target genes involved in cellular proliferation, differentiation and apoptosis.

Improving ERP change tool processes to align business processes and ERP system

Nopea teknologian kehitys sekä kansainvälistymisen mukana tuoma kilpailupaine pakottavat yritykset jatkuvaan liiketoimintaprosessien kehittämiseen. Muutoksista organisaation rakenteissa sekä yrityksen prosesseissa on tullut yleisiä toimenpiteitä. Yksi näkyvimmistä toiminnallisista uudistuksesta on ollut toiminnanohjausjärjestelmän käyttöönotto. Toiminnanohjausjärjestelmän rakenne ja kehitys aiheuttaa yleensä suurimmat vaikeudet pyrittäessä rakentamaan liiketoimintaprosessien läpinäkyvyyttä esittävä tietojärjestelmäympäristö. Tässä tutkimuksessa liiketoiminnan sekä toiminnanohjausjärjestelmän prosessien yhdistäminen on tehty ns. toiminnanohjausjärjestelmä muutostyökaluilla. Kyseiset muutostyökalut on järjestetty yrityksissä tietojärjestelmä ympäristöön ja niiden avulla voidaan korjata teknisiä ongelmia sekä muuttaa itse prosesseja. Tutkimuksen empiria osuudessa on käytetty case-tutkimusmenetelmää Kone Oyj:n prosessien kehittämisosastolla. Tutkimuksen tavoitteena oli parantaa toiminnanohjausjärjestelmän muutostyökalujen prosesseja, liiketoimintaprosessien sekä toiminnanohjausjärjestelmän yhdistämiseksi ja harmonisoimiseksi. Tutkimuksen tavoitteiden täyttämiseksi, prosessijohtamisen käsitteitä käytettiin muutostyökaluprosessien parannusehdotusten löytymiseksi. Prosessijohtamisen käsitteet tarkoittavat prosessikartan, prosessin toimintojen, sekä prosessin kustannusten tutkimista ja hyväksikäyttöä. Prosessijohtamisen käsitteeseen kuuluu myös liiketoimintaprosessien jatkuvan parantamisen sekä uudelleenjärjestämisen mallien kuvaus. Toiminnanohjausjärjestelmäympäristön kuvaus teorian toisena osuutena antaa pohjaa muutostyökalujen prosessien käytölle. Tutkimuksen tuloksina voidaan todeta että tutkimusalue on hyvin monimutkainen ja vaikea. Toimintajärjestelmistä ei ole kirjoitettu teoriaa kovinkaan runsaasti, lukuunottamatta yritysten itse tekemiä tutkimuksia. Tutkimuksessa tarkasteltaville prosesseille löytyi kuitenkin parannusehdotuksia sekä ns. optimaalisen prosessimallin ominaisuuksia.

Implementation of counter testing in Nokia Automation System

In this study the performance measurement, a part of the research and development of the RNC, was improved by implementing counter testing to the Nokia Automation System. The automation of counter testing is a feature the customer ordered, because performing counter testing manually is rather complex. The objective was to implement an automated counter testing system, which once configured correctly, would manage to run the testing and perform the analysis. The requirements for the counter testing were first studied. It was investigated if the auto-mation of the feature was feasible in the meetings with the customer. The basic functionality required for the automation was also drawn. The technologies used in the architecture of the Nokia Automation System were studied. Based on the results of the study, a new technology, wxWidgets, was introduced. The new technology was necessary to facilitate the implementing of the required feature. Finally the implementation of the counter testing was defined and implemented. The result of this study was the automation of the counter testing method developed as a new feature for the Nokia Automation System. The feature meets the specifications and requirements set by the customer. The performing of the counter testing feature is totally automated. Only configuration of the test cases is done by the user. The customer has presented new requests to further develop the feature and there are plans by the Nokia Automation System developers to implement those in the near future. The study describes the implementation of the counter testing feature introduced. The results of the study give guidelines for further developing the feature.

A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia.

Lactate has been shown to offer neuroprotection in several pathologic conditions. This beneficial effect has been attributed to its use as an alternative energy substrate. However, recent description of the expression of the HCA1 receptor for lactate in the central nervous system calls for reassessment of the mechanism by which lactate exerts its neuroprotective effects. Here, we show that HCA1 receptor expression is enhanced 24 hours after reperfusion in an middle cerebral artery occlusion stroke model, in the ischemic cortex. Interestingly, intravenous injection of L-lactate at reperfusion led to further enhancement of HCA1 receptor expression in the cortex and striatum. Using an in vitro oxygen-glucose deprivation model, we show that the HCA1 receptor agonist 3,5-dihydroxybenzoic acid reduces cell death. We also observed that D-lactate, a reputedly non-metabolizable substrate but partial HCA1 receptor agonist, also provided neuroprotection in both in vitro and in vivo ischemia models. Quite unexpectedly, we show D-lactate to be partly extracted and oxidized by the rodent brain. Finally, pyruvate offered neuroprotection in vitro whereas acetate was ineffective. Our data suggest that L- and D-lactate offer neuroprotection in ischemia most likely by acting as both an HCA1 receptor agonist for non-astrocytic (most likely neuronal) cells as well as an energy substrate.

Alternatively spliced proline-rich cassettes link WNK1 to aldosterone action.

The thiazide-sensitive NaCl cotransporter (NCC) is important for renal salt handling and blood-pressure homeostasis. The canonical NCC-activating pathway consists of With-No-Lysine (WNK) kinases and their downstream effector kinases SPAK and OSR1, which phosphorylate NCC directly. The upstream mechanisms that connect physiological stimuli to this system remain obscure. Here, we have shown that aldosterone activates SPAK/OSR1 via WNK1. We identified 2 alternatively spliced exons embedded within a proline-rich region of WNK1 that contain PY motifs, which bind the E3 ubiquitin ligase NEDD4-2. PY motif-containing WNK1 isoforms were expressed in human kidney, and these isoforms were efficiently degraded by the ubiquitin proteasome system, an effect reversed by the aldosterone-induced kinase SGK1. In gene-edited cells, WNK1 deficiency negated regulatory effects of NEDD4-2 and SGK1 on NCC, suggesting that WNK1 mediates aldosterone-dependent activity of the WNK/SPAK/OSR1 pathway. Aldosterone infusion increased proline-rich WNK1 isoform abundance in WT mice but did not alter WNK1 abundance in hypertensive Nedd4-2 KO mice, which exhibit high baseline WNK1 and SPAK/OSR1 activity toward NCC. Conversely, hypotensive Sgk1 KO mice exhibited low WNK1 expression and activity. Together, our findings indicate that the proline-rich exons are modular cassettes that convert WNK1 into a NEDD4-2 substrate, thereby linking aldosterone and other NEDD4-2-suppressing antinatriuretic hormones to NCC phosphorylation status.

MHC/Peptide-Specific Interaction of the Humoral Immune System: A New Category of Antibodies.

Abs bind to unprocessed Ags, whereas cytotoxic CD8(+) T cells recognize peptides derived from endogenously processed Ags presented in the context of class I MHC complexes. We screened, by ELISA, human sera for Abs reacting specifically with the influenza matrix protein (IMP)-derived peptide58-66 displayed by HLA-A*0201 complexes. Among 653 healthy volunteers, blood donors, and women on delivery, high-titered HLA-A*0201/IMP58-66 complex-specific IgG Abs were detected in 11 females with a history of pregnancies and in 1 male, all HLA-A*0201(-). These Abs had the same specificity as HLA-A*0201/IMP58-66-specific cytotoxic T cells and bound neither to HLA-A*0201 nor the peptide alone. No such Abs were detected in HLA-A*0201(+) volunteers. These Abs were not cross-reactive to other self-MHC class I alleles displaying IMP58-66, but bound to MHC class I complexes of an HLA nonidentical offspring. HLA-A*0201/IMP58-66 Abs were also detected in the cord blood of newborns, indicating that HLA-A*0201/IMP58-66 Abs are produced in HLA-A*0201(-) mothers and enter the fetal blood system. That Abs can bind to peptides derived from endogenous Ags presented by MHC complexes opens new perspectives on interactions between the cellular and humoral immune system.

A cellular system for spatial signal decoding in chemical gradients.

Directional cell growth requires that cells read and interpret shallow chemical gradients, but how the gradient directional information is identified remains elusive. We use single-cell analysis and mathematical modeling to define the cellular gradient decoding network in yeast. Our results demonstrate that the spatial information of the gradient signal is read locally within the polarity site complex using double-positive feedback between the GTPase Cdc42 and trafficking of the receptor Ste2. Spatial decoding critically depends on low Cdc42 activity, which is maintained by the MAPK Fus3 through sequestration of the Cdc42 activator Cdc24. Deregulated Cdc42 or Ste2 trafficking prevents gradient decoding and leads to mis-oriented growth. Our work discovers how a conserved set of components assembles a network integrating signal intensity and directionality to decode the spatial information contained in chemical gradients.

Social insurances system's shortcomings : the example of the low-income young retirees' access to healthcare [Imperfections du système d'assurances sociales : l'exemple de l'accès aux soins des jeunes retraité(e)s à revenu modeste]

This article presents the results of a study involving 2445 recently retired persons from the Canton of Vaud in Switzerland who choose to forego health care. These persons of modest means barely qualify for government assistance programs and do not benefit from the social safety net that is provided to the truly destitute. 17.9% of the respondents to the questionnaire said that they forego health care for financial reasons. Interviews reveal the complex reasons that lie behind such a choice, as well as the compensation strategies that are sometimes used to get medical treatment. These strategies show that the people are able to act when the circumstances require them to do so. Despite that, their situation remains insecure. Cet article analyse les résultats d'une étude sur le renoncement aux soins menée auprès de 2445 Vaudois∙e∙s récemment retraité∙e∙s. Ces personnes de situation modeste sont proches des limites d'accès aux aides étatiques et ne bénéficient pas du même filet de protection sociale que d'autres plus démunies. 17.9% des répondant∙e∙s au questionnaire déclarent renoncer à des soins pour raisons financières. Des entretiens mettent en évidence la complexité du renoncement, ainsi que les stratégies compensatoires que les personnes adoptent pour accéder à certains soins. Ces dernières démontrent une capacité d'agir en situation qui reste toutefois précaire.

Spatiotemporal Aspects of Environmental Monitoring in the Complex Coastal Region of Southwest Finland

The management and conservation of coastal waters in the Baltic is challenged by a number of complex environmental problems, including eutrophication and habitat degradation. Demands for a more holistic, integrated and adaptive framework of ecosystem-based management emphasize the importance of appropriate information on the status and changes of the aquatic ecosystems. The thesis focuses on the spatiotemporal aspects of environmental monitoring in the extensive and geomorphologically complex coastal region of SW Finland, where the acquisition of spatially and temporally representative monitoring data is inherently challenging. Furthermore, the region is subject to multiple human interests and uses. A holistic geographical approach is emphasized, as it is ultimately the physical conditions that set the frame for any human activity. Characteristics of the coastal environment were examined using water quality data from the database of the Finnish environmental administration and Landsat TM/ETM+ images. A basic feature of the complex aquatic environment in the Archipelago Sea is its high spatial and temporal variability; this foregrounds the importance of geographical information as a basis of environmental assessments. While evidence of a consistent water turbidity pattern was observed, the coastal hydrodynamic realm is also characterized by high spatial and temporal variability. It is therefore also crucial to consider the spatial and temporal representativeness of field monitoring data. Remote sensing may facilitate evaluation of hydrodynamic conditions in the coastal region and the spatial extrapolation of in situ data despite their restrictions. Additionally, remotely sensed images can be used in the mapping of many of those coastal habitats that need to be considered in environmental management. With regard to surface water monitoring, only a small fraction of the currently available data stored in the Hertta-PIVET register can be used effectively in scientific studies and environmental assessments. Long-term consistent data collection from established sampling stations should be emphasized but research-type seasonal assessments producing abundant data should also be encouraged. Thus a more comprehensive coordination of field work efforts is called for. The integration of remote sensing and various field measurement techniques would be especially useful in the complex coastal waters. The integration and development of monitoring system in Finnish coastal areas also requires further scientific assesement of monitoring practices. A holistic approach to the gathering and management of environmental monitoring data could be a cost-effective way of serving a multitude of information needs, and would fit the holistic, ecosystem-based management regimes that are currently being strongly promoted in Europe.

Corporate Social and Regional Responsibility - The View of Small and Medium-sized Enterprises

The objective of this research was to understand and describe what corpo-rate social and regional responsibility is in SMEs and define the meaning of these concepts to the community and region. Corporate social respon-sibility (CSR) creates a basis for regional responsibility. Regional respon-sibility is a new concept and this research examines it from SMEs’ view-point. This is a theoretical research and the aim is to create a theoretical framework of SMEs’ corporate social and regional responsibility. This framework supports the future research on the subject. The research results show that CSR of SMEs is practical, informal and dependent on the scarce resources of SMEs. CSR is a complex and deep concept and SMEs have their own way of interpreting it. It can be stated that CSR-practises in SMEs are closely connected to employment, envi-ronment, community and supply chain. The challenge is to find motivation to socially and regionally responsible behaviour in SMEs. Benefiting from responsible behaviour and the attitude of SME’s owner-manager are the key reasons for SMEs to involve in CSR and regional responsibility. The benefits of this involvement are for example improved image, reputation and market position. CSR can also be used in SMEs as risk management tool and in cost reduction. This study indicates also that creation of strate-gic partnerships, local government participation, a proper legal system and financial support are the basic issues which support CSR of SMEs. This research showed that regional responsibility of SMEs includes active participation in regional strategy processes, L&RED initiatives and regional philanthropy. For SMEs regional responsibility means good relationships with the community and other related stakeholders, involvement in L&RED initiatives and acting responsibly towards the operating environment. In SMEs’ case this means that they need to understand the benefits of this kind of involvement in order to take action and participate. As regional responsibility includes the relationships between firm and the community, it can be stated that regional responsibility extends CSR’s view of stakeholders and emphasises both, the regional stakeholders and public-private partnerships. Community engagement and responsible be-haviour towards community can be seen as a part of SMEs’ social and regional responsibility. This study indicates that social and regional re-sponsibility of SMEs have a significant influence on the community and region where they are located. Better local and regional relationships with regional and community actors are the positive impacts of social and re-gional responsibility of SMEs. Socially and regionally responsible behav-iour creates a more positive environment and deepens the involvement of SMEs to community and L&RED initiatives.

Tabagisme et système digestif: une relation complexe. Partie 2: Microbiote intestinal et tabagisme [Smoking and digestive tract: a complex relationship. Part 2: Intestinal microblota and cigarette smoking].

Le système digestif est colonisé dès la naissance par une population bactérienne, le microbiote, qui influence le développement du système immunitaire. Des modifications dans sa composition sont associées à des pathologies comme l'obésité et les maladies inflammatoires chroniques de l'intestin. Outre les antibiotiques, des facteurs environnementaux comme le tabagisme semblent aussi avoir une influence sur la composition de la flore intestinale, pouvant en partie expliquer la prise de poids à l'arrêt du tabac avec une modification de la composition du microbiote proche de celle observée chez des personnes obèses (profil microbiotique montrant des capacités accrues d'extraction calorique des aliments ingérés). Ces découvertes permettent d'imaginer de nouvelles approches diagnostiques et thérapeutiques via la régulation de ce microbiome. The digestive tract is colonized from birth by a bacterial population called the microbiota which influences the development of the immune system. Modifications in its composition are associated with problems such as obesity or inflammatory bowel diseases. Antibiotics are known to influence the intestinal microbiota but other environmental factors such as cigarette smoking also seem to have an impact on its composition. This influence might partly explain weight gain which is observed after smoking cessation. Indeed there is a modification of the gut microbiota which becomes similar to that of obese people with a microbiotical profile which is more efficient to extract calories from ingested food. These new findings open new fields of diagnostic and therapeutic approaches through the regulation of the microbiota.