Increased Presence of FOXP3+ Regulatory T Cells in Inflamed Muscle of Patients with Active Juvenile Dermatomyositis Compared to Peripheral Blood.

Juvenile dermatomyositis (JDM) is an immune-mediated inflammatory disease affecting the microvasculature of skin and muscle. CD4+CD25+FOXP3+ regulatory T cells (Tregs) are key regulators of immune homeostasis. A role for Tregs in JDM pathogenesis has not yet been established. Here, we explored Treg presence and function in peripheral blood and muscle of JDM patients. We analyzed number, phenotype and function of Tregs in blood from JDM patients by flow cytometry and in vitro suppression assays, in comparison to healthy controls and disease controls (Duchenne's Muscular Dystrophy). Presence of Tregs in muscle was analyzed by immunohistochemistry. Overall, Treg percentages in peripheral blood of JDM patients were similar compared to both control groups. Muscle biopsies of new onset JDM patients showed increased infiltration of numbers of T cells compared to Duchenne's muscular dystrophy. Both in JDM and Duchenne's muscular dystrophy the proportion of FOXP3+ T cells in muscles were increased compared to JDM peripheral blood. Interestingly, JDM is not a self-remitting disease, suggesting that the high proportion of Tregs in inflamed muscle do not suppress inflammation. In line with this, peripheral blood Tregs of active JDM patients were less capable of suppressing effector T cell activation in vitro, compared to Tregs of JDM in clinical remission. These data show a functional impairment of Tregs in a proportion of patients with active disease, and suggest a regulatory role for Tregs in JDM inflammation.

Circulating Tumor-reactive CD8(+) T cells in melanoma patients contain a CD45RA(+)CCR7(-) effector subset exerting ex vivo tumor-specific cytolytic activity.

To defend the host from malignancies, the immune system can spontaneously raise CD8(+) T-cell responses against tumor antigens. Investigating the functional state of tumor-reactive cytolytic T cells in cancer patients is a key step for understanding the role of these cells in tumor immunosurveillance and for evaluating the potential of immunotherapeutic approaches of vaccination against cancer. In this study we identified a subset of circulating tumor-reactive CD8(+) T lymphocytes, which specifically secreted IFN-gamma after exposition to autologous tumor cell lines in stage IV metastatic melanoma patients. Additional phenotypic characterization using multicolor flow cytometry revealed that a significant fraction of these cells were CD45RA(+)CCR7(-), a phenotype that has been proposed recently to characterize cytolytic effectors potentially able to home into inflamed tissues. In the case of an HLA-A2-expressing patient, the antigen specificity of this population was identified by using HLA-A2/peptide multimers incorporating a tyrosinase-derived peptide. Consistently with their phenotypic characteristics, A2/tyrosinase peptide multimer(+) CD8(+) T cells, isolated by cell sorting, were directly lytic ex vivo and able to specifically recognize tyrosinase-expressing tumor cells. Overall, these results provide the first evidence that a proportion of melanoma patients have circulating tumor-reactive T cells, which are lytic effectors cells.

Tapping the innovation potential of corporate engagement with stakeholders

Summary This dissertation explores how stakeholder dialogue influences corporate processes, and speculates about the potential of this phenomenon - particularly with actors, like non-governmental organizations (NGOs) and other representatives of civil society, which have received growing attention against a backdrop of increasing globalisation and which have often been cast in an adversarial light by firms - as a source of teaming and a spark for innovation in the firm. The study is set within the context of the introduction of genetically-modified organisms (GMOs) in Europe. Its significance lies in the fact that scientific developments and new technologies are being generated at an unprecedented rate in an era where civil society is becoming more informed, more reflexive, and more active in facilitating or blocking such new developments, which could have the potential to trigger widespread changes in economies, attitudes, and lifestyles, and address global problems like poverty, hunger, climate change, and environmental degradation. In the 1990s, companies using biotechnology to develop and offer novel products began to experience increasing pressure from civil society to disclose information about the risks associated with the use of biotechnology and GMOs, in particular. Although no harmful effects for humans or the environment have been factually demonstrated even to date (2008), this technology remains highly-contested and its introduction in Europe catalysed major companies to invest significant financial and human resources in stakeholder dialogue. A relatively new phenomenon at the time, with little theoretical backing, dialogue was seen to reflect a move towards greater engagement with stakeholders, commonly defined as those "individuals or groups with which. business interacts who have a 'stake', or vested interest in the firm" (Carroll, 1993:22) with whom firms are seen to be inextricably embedded (Andriof & Waddock, 2002). Regarding the organisation of this dissertation, Chapter 1 (Introduction) describes the context of the study, elaborates its significance for academics and business practitioners as an empirical work embedded in a sector at the heart of the debate on corporate social responsibility (CSR). Chapter 2 (Literature Review) traces the roots and evolution of CSR, drawing on Stakeholder Theory, Institutional Theory, Resource Dependence Theory, and Organisational Learning to establish what has already been developed in the literature regarding the stakeholder concept, motivations for engagement with stakeholders, the corporate response to external constituencies, and outcomes for the firm in terms of organisational learning and change. I used this review of the literature to guide my inquiry and to develop the key constructs through which I viewed the empirical data that was gathered. In this respect, concepts related to how the firm views itself (as a victim, follower, leader), how stakeholders are viewed (as a source of pressure and/or threat; as an asset: current and future), corporate responses (in the form of buffering, bridging, boundary redefinition), and types of organisational teaming (single-loop, double-loop, triple-loop) and change (first order, second order, third order) were particularly important in building the key constructs of the conceptual model that emerged from the analysis of the data. Chapter 3 (Methodology) describes the methodology that was used to conduct the study, affirms the appropriateness of the case study method in addressing the research question, and describes the procedures for collecting and analysing the data. Data collection took place in two phases -extending from August 1999 to October 2000, and from May to December 2001, which functioned as `snapshots' in time of the three companies under study. The data was systematically analysed and coded using ATLAS/ti, a qualitative data analysis tool, which enabled me to sort, organise, and reduce the data into a manageable form. Chapter 4 (Data Analysis) contains the three cases that were developed (anonymised as Pioneer, Helvetica, and Viking). Each case is presented in its entirety (constituting a `within case' analysis), followed by a 'cross-case' analysis, backed up by extensive verbatim evidence. Chapter 5 presents the research findings, outlines the study's limitations, describes managerial implications, and offers suggestions for where more research could elaborate the conceptual model developed through this study, as well as suggestions for additional research in areas where managerial implications were outlined. References and Appendices are included at the end. This dissertation results in the construction and description of a conceptual model, grounded in the empirical data and tied to existing literature, which portrays a set of elements and relationships deemed important for understanding the impact of stakeholder engagement for firms in terms of organisational learning and change. This model suggests that corporate perceptions about the nature of stakeholder influence the perceived value of stakeholder contributions. When stakeholders are primarily viewed as a source of pressure or threat, firms tend to adopt a reactive/defensive posture in an effort to manage stakeholders and protect the firm from sources of outside pressure -behaviour consistent with Resource Dependence Theory, which suggests that firms try to get control over extemal threats by focussing on the relevant stakeholders on whom they depend for critical resources, and try to reverse the control potentially exerted by extemal constituencies by trying to influence and manipulate these valuable stakeholders. In situations where stakeholders are viewed as a current strategic asset, firms tend to adopt a proactive/offensive posture in an effort to tap stakeholder contributions and connect the organisation to its environment - behaviour consistent with Institutional Theory, which suggests that firms try to ensure the continuing license to operate by internalising external expectations. In instances where stakeholders are viewed as a source of future value, firms tend to adopt an interactive/innovative posture in an effort to reduce or widen the embedded system and bring stakeholders into systems of innovation and feedback -behaviour consistent with the literature on Organisational Learning, which suggests that firms can learn how to optimize their performance as they develop systems and structures that are more adaptable and responsive to change The conceptual model moreover suggests that the perceived value of stakeholder contribution drives corporate aims for engagement, which can be usefully categorised as dialogue intentions spanning a continuum running from low-level to high-level to very-high level. This study suggests that activities aimed at disarming critical stakeholders (`manipulation') providing guidance and correcting misinformation (`education'), being transparent about corporate activities and policies (`information'), alleviating stakeholder concerns (`placation'), and accessing stakeholder opinion ('consultation') represent low-level dialogue intentions and are experienced by stakeholders as asymmetrical, persuasive, compliance-gaining activities that are not in line with `true' dialogue. This study also finds evidence that activities aimed at redistributing power ('partnership'), involving stakeholders in internal corporate processes (`participation'), and demonstrating corporate responsibility (`stewardship') reflect high-level dialogue intentions. This study additionally finds evidence that building and sustaining high-quality, trusted relationships which can meaningfully influence organisational policies incline a firm towards the type of interactive, proactive processes that underpin the development of sustainable corporate strategies. Dialogue intentions are related to type of corporate response: low-level intentions can lead to buffering strategies; high-level intentions can underpin bridging strategies; very high-level intentions can incline a firm towards boundary redefinition. The nature of corporate response (which encapsulates a firm's posture towards stakeholders, demonstrated by the level of dialogue intention and the firm's strategy for dealing with stakeholders) favours the type of learning and change experienced by the organisation. This study indicates that buffering strategies, where the firm attempts to protect itself against external influences and cant' out its existing strategy, typically lead to single-loop learning, whereby the firm teams how to perform better within its existing paradigm and at most, improves the performance of the established system - an outcome associated with first-order change. Bridging responses, where the firm adapts organisational activities to meet external expectations, typically leads a firm to acquire new behavioural capacities characteristic of double-loop learning, whereby insights and understanding are uncovered that are fundamentally different from existing knowledge and where stakeholders are brought into problem-solving conversations that enable them to influence corporate decision-making to address shortcomings in the system - an outcome associated with second-order change. Boundary redefinition suggests that the firm engages in triple-loop learning, where the firm changes relations with stakeholders in profound ways, considers problems from a whole-system perspective, examining the deep structures that sustain the system, producing innovation to address chronic problems and develop new opportunities - an outcome associated with third-order change. This study supports earlier theoretical and empirical studies {e.g. Weick's (1979, 1985) work on self-enactment; Maitlis & Lawrence's (2007) and Maitlis' (2005) work and Weick et al's (2005) work on sensegiving and sensemaking in organisations; Brickson's (2005, 2007) and Scott & Lane's (2000) work on organisational identity orientation}, which indicate that corporate self-perception is a key underlying factor driving the dynamics of organisational teaming and change. Such theorizing has important implications for managerial practice; namely, that a company which perceives itself as a 'victim' may be highly inclined to view stakeholders as a source of negative influence, and would therefore be potentially unable to benefit from the positive influence of engagement. Such a selfperception can blind the firm from seeing stakeholders in a more positive, contributing light, which suggests that such firms may not be inclined to embrace external sources of innovation and teaming, as they are focussed on protecting the firm against disturbing environmental influences (through buffering), and remain more likely to perform better within an existing paradigm (single-loop teaming). By contrast, a company that perceives itself as a 'leader' may be highly inclined to view stakeholders as a source of positive influence. On the downside, such a firm might have difficulty distinguishing when stakeholder contributions are less pertinent as it is deliberately more open to elements in operating environment (including stakeholders) as potential sources of learning and change, as the firm is oriented towards creating space for fundamental change (through boundary redefinition), opening issues to entirely new ways of thinking and addressing issues from whole-system perspective. A significant implication of this study is that potentially only those companies who see themselves as a leader are ultimately able to tap the innovation potential of stakeholder dialogue.

Antigenicity and immunogenicity of Melan-A/MART-1 derived peptides as targets for tumor reactive CTL in human melanoma.

Some cancer patients mount spontaneous T- and B-cell responses against their tumor cells. Autologous tumor reactive CD8 cytolytic T lymphocyte (CTL) and CD4 T-cell clones as well as antibodies from these patients have been used for the identification of genes encoding the target antigens. This knowledge opened the way for new approaches to the immunotherapy of cancer. In this review, we describe the characterization of the structure-function properties of the melanocyte/melanoma tumor antigen Melan-A/MART-1, the assessment of the T-cell repertoire available against this antigen in healthy individuals, and the analysis of naturally acquired and/or vaccine-induced CTL responses to this antigen in patients with metastatic melanoma.

Sediment budget monitoring of a debris-flow torrent (French Prealps)

The Manival near Grenoble (French Prealps) is a very active debris-flow torrent equipped with a large sediment trap (25 000 m3) protecting an urbanized alluvial fan from debris-flows. We began monitoring the sediment budget of the catchment controlled by the trap in Spring 2009. Terrestrial laser scanner is used for monitoring topographic changes in a small gully, the main channel, and the sediment trap. In the main channel, 39 cross-sections are surveyed after every event. Three periods of intense geomorphic activity are documented here. The first was induced by a convective storm in August 2009 which triggered a debris-flow that deposited ~1,800 m3 of sediment in the trap. The debris-flow originated in the upper reach of the main channel and our observations showed that sediment outputs were entirely supplied by channel scouring. Hillslope debris-flows were initiated on talus slopes, as revealed by terrestrial LiDAR resurveys; however they were disconnected to the main channel. The second and third periods of geomorphic activity were induced by long duration and low intensity rainfall events in September and October 2009 which generate small flow events with intense bedload transport. These events contribute to recharge the debris-flow channel with sediments by depositing important gravel dunes propagating from headwaters. The total recharge in the torrent subsequent to bedload transport events was estimated at 34% of the sediment erosion induced by the August debris-flow.

Optimal use of SSR markers for varietal identification of upland cotton

Abstract: The objective of this work was to identify polymorphic simple sequence repeat (SSR) markers for varietal identification of cotton and evaluation of the genetic distance among the varieties. Initially, 92 SSR markers were genotyped in 20 Brazilian cotton cultivars. Of this total, 38 loci were polymorphic, two of which were amplified by one primer pair; the mean number of alleles per locus was 2.2. The values of polymorphic information content (PIC) and discrimination power (DP) were, on average, 0.374 and 0.433, respectively. The mean genetic distance was 0.397 (minimum of 0.092 and maximum of 0.641). A panel of 96 varieties originating from different regions of the world was assessed by 21 polymorphic loci derived from 17 selected primer pairs. Among these varieties, the mean genetic distance was 0.387 (minimum of 0 and maximum of 0.786). The dendrograms generated by the unweighted pair group method with arithmetic average (UPGMA) did not reflect the regions of Brazil (20 genotypes) or around the world (96 genotypes), where the varieties or lines were selected. Bootstrap resampling shows that genotype identification is viable with 19 loci. The polymorphic markers evaluated are useful to perform varietal identification in a large panel of cotton varieties and may be applied in studies of the species diversity.

Electric bicycles as a new active transportation modality to promote health.

GOJANOVIC, B., J. WELKER, K. IGLESIAS, C. DAUCOURT, and G. GREMION. Electric Bicycles as a New Active Transportation Modality to Promote Health. Med. Sci. Sports Exerc., Vol. 43, No. 11, pp. 2204-2210, 2011. Electrically assisted bicycles (EAB) are an emerging transportation modality favored for environmental reasons. Some physical effort is required to activate the supporting engine, making it a potential active commuting option. Purpose: We hypothesized that using an EAB in a hilly city allows sedentary subjects to commute comfortably, while providing a sufficient effort for health-enhancing purposes. Methods: Sedentary subjects performed four different trips at a self-selected pace: walking 1.7 km uphill from the train station to the hospital (WALK), biking 5.1 km from the lower part of town to the hospital with a regular bike (BIKE), or EAB at two different power assistance settings (EAB(high), EAB(std)). HR, oxygen consumption, and need to shower were recorded. Results: Eighteen sedentary subjects (12 female, 6 male) age 36 +/- 10 yr were included, with (V) over dotO(2max) of 39.4 +/- 5.4 mL.min(-1).kg(-1). Time to complete the course was 22 (WALK), 19 (EAB(high)), 21 (EAB(std)), and 30 (BIKE) min. Mean %(V) over dotO(2max) was 59.0%, 54.9%, 65.7%, and 72.8%. Mean%HR(max) was 71.5%, 74.5%, 80.3%, and 84.0%. There was no significant difference between WALK and EAB(high), but all other comparisons were different (P < 0.05). Two subjects needed to shower after EAB(high), 3 needed to shower after WALK, 8 needed to shower after EAB(std), and all 18 needed to shower after BIKE. WALK and EAB(high) elicited 6.5 and 6.1 METs (no difference), whereas it was 7.3 and 8.2 for EAB(std) and BIKE. Conclusions: EAB is a comfortable and ecological transportation modality, helping sedentary people commute to work and meet physical activity guidelines. Subjects appreciated ease of use and mild effort needed to activate the engine support climbing hills, without the need to shower at work. EAB can be promoted in a challenging urban environment to promote physical activity and mitigate pollution issues.

Extension of Murray's law using a non-Newtonian model of blood flow.

BACKGROUND: So far, none of the existing methods on Murray's law deal with the non-Newtonian behavior of blood flow although the non-Newtonian approach for blood flow modelling looks more accurate. MODELING: In the present paper, Murray's law which is applicable to an arterial bifurcation, is generalized to a non-Newtonian blood flow model (power-law model). When the vessel size reaches the capillary limitation, blood can be modeled using a non-Newtonian constitutive equation. It is assumed two different constraints in addition to the pumping power: the volume constraint or the surface constraint (related to the internal surface of the vessel). For a seek of generality, the relationships are given for an arbitrary number of daughter vessels. It is shown that for a cost function including the volume constraint, classical Murray's law remains valid (i.e. SigmaR(c) = cste with c = 3 is verified and is independent of n, the dimensionless index in the viscosity equation; R being the radius of the vessel). On the contrary, for a cost function including the surface constraint, different values of c may be calculated depending on the value of n. RESULTS: We find that c varies for blood from 2.42 to 3 depending on the constraint and the fluid properties. For the Newtonian model, the surface constraint leads to c = 2.5. The cost function (based on the surface constraint) can be related to entropy generation, by dividing it by the temperature. CONCLUSION: It is demonstrated that the entropy generated in all the daughter vessels is greater than the entropy generated in the parent vessel. Furthermore, it is shown that the difference of entropy generation between the parent and daughter vessels is smaller for a non-Newtonian fluid than for a Newtonian fluid.

Modelling of a Hydrogen Catalytic Recombiner for Nuclear Power Plant Containment Studies; Case: Siemens FR90/1-150 Recombiner in TONUS OD Code

Ydinvoimalaitokset on suunniteltu ja rakennettu niin, että niillä on kyky selviytyä erilaisista käyttöhäiriöistä ja onnettomuuksista ilman laitoksen vahingoittumista sekä väestön ja ympäristön vaarantumista. On erittäin epätodennäköistä, että ydinvoimalaitosonnettomuus etenee reaktorisydämen vaurioitumiseen asti, minkä seurauksena sydänmateriaalien hapettuminen voi tuottaa vetyä. Jäädytyspiirin rikkoutumisen myötä vety saattaa kulkeutua ydinvoimalaitoksen suojarakennukseen, jossa se voi muodostaa palavan seoksen ilman hapen kanssa ja palaa tai jopa räjähtää. Vetypalosta aiheutuvat lämpötila- ja painekuormitukset vaarantavat suojarakennuksen eheyden ja suojarakennuksen sisällä olevien turvajärjestelmien toimivuuden, joten tehokas ja luotettava vedynhallintajärjestelmä on tarpeellinen. Passiivisia autokatalyyttisiä vetyrekombinaattoreita käytetäänyhä useammissa Euroopan ydinvoimaitoksissa vedynhallintaan. Nämä rekombinaattorit poistavat vetyä katalyyttisellä reaktiolla vedyn reagoidessa katalyytin pinnalla hapen kanssa muodostaen vesihöyryä. Rekombinaattorit ovat täysin passiivisiaeivätkä tarvitse ulkoista energiaa tai operaattoritoimintaa käynnistyäkseen taitoimiakseen. Rekombinaattoreiden käyttäytymisen tutkimisellatähdätään niiden toimivuuden selvittämiseen kaikissa mahdollisissa onnettomuustilanteissa, niiden suunnittelun optimoimiseen sekä niiden optimaalisen lukumäärän ja sijainnin määrittämiseen suojarakennuksessa. Suojarakennuksen mallintamiseen käytetään joko keskiarvoistavia ohjelmia (Lumped parameter (LP) code), moniulotteisia virtausmalliohjelmia (Computational Fluid Dynamics, CFD) tai näiden yhdistelmiä. Rekombinaattoreiden mallintaminen on toteutettu näissä ohjelmissa joko kokeellisella, teoreettisella tai yleisellä (eng. Global Approach) mallilla. Tämä diplomityö sisältää tulokset TONUS OD-ohjelman sisältämän Siemens FR90/1-150 rekombinaattorin mallin vedynkulutuksen tarkistuslaskuista ja TONUS OD-ohjelmalla suoritettujen laskujen tulokset Siemens rekombinaattoreiden vuorovaikutuksista. TONUS on CEA:n (Commissariat à 1'En¬ergie Atomique) kehittämä LP (OD) ja CFD -vetyanalyysiohjelma, jota käytetään vedyn jakautumisen, palamisenja detonaation mallintamiseen. TONUS:sta käytetään myös vedynpoiston mallintamiseen passiivisilla autokatalyyttisillä rekombinaattoreilla. Vedynkulutukseen vaikuttavat tekijät eroteltiin ja tutkittiin yksi kerrallaan. Rekombinaattoreiden vuorovaikutuksia tutkittaessa samaan tilavuuteen sijoitettiin eri kokoisia ja eri lukumäärä rekombinaattoreita. Siemens rekombinaattorimalli TONUS OD-ohjelmassa laskee vedynkulutuksen kuten oletettiin ja tulokset vahvistavat TONUS OD-ohjelman fysikaalisen laskennan luotettavuuden. Mahdollisia paikallisia jakautumia tutkitussa tilavuudessa ei voitu havaita LP-ohjelmalla, koska se käyttäälaskennassa suureiden tilavuuskeskiarvoja. Paikallisten jakautumien tutkintaan tarvitaan CFD -laskentaohjelma.

Sediment budget monitoring of debris-flow and bedload transport in the Manival Torrent, SE France

Steep mountain catchments typically experience large sediment pulses from hillslopes which are stored in headwater channels and remobilized by debris-flows or bedload transport. Event-based sediment budget monitoring in the active Manival debris-flow torrent in the French Alps during a two-year period gave insights into the catchment-scale sediment routing during moderate rainfall intensities which occur several times each year. The monitoring was based on intensive topographic resurveys of low- and high-order channels using different techniques (cross-section surveys with total station and high-resolution channel surveys with terrestrial and airborne laser scanning). Data on sediment output volumes from the main channel were obtained by a sediment trap. Two debris-flows were observed, as well as several bedload transport flow events. Sediment budget analysis of the two debris-flows revealed that most of the debris-flow volumes were supplied by channel scouring (more than 92%). Bedload transport during autumn contributed to the sediment recharge of high-order channels by the deposition of large gravel wedges. This process is recognized as being fundamental for debris-flow occurrence during the subsequent spring and summer. A time shift of scour-and-fill sequences was observed between low- and high-order channels, revealing the discontinuous sediment transfer in the catchment during common flow events. A conceptual model of sediment routing for different event magnitude is proposed.

Logistics Development in Finnish and Swedish Companies with Respect of Russia and Four Asian Countries: Traffic Flow and Warehousing Analysis from Current Situation and Likely Development Trends

On selvää, että tänä päivänä maailmankaupan painopiste on hiljalleen siirtymässä Aasiaan ja varsinkin Kiina on ollut huomion keskipisteessä. Erityisesti valmistavien yritysten perspektiivistä muutos on ollut merkittävä ja tämä tosiasia kasvattaa yrityksissä paineita luoda kustannustehokkaita toimitusketjuratkaisuja,joiden vasteaika on mahdollisimman lyhyt. Samaan aikaan kun tarkastellaan kuljetusvirtoja, huomattaan että maanosien välillä on suuri epätasapaino. Tämä on enimmäkseen seurausta suurten globaalisti toimivien yritysten toimitusketjustrategioista. Useimmat näistä toimijoista optimoivat verkostonsa turvautumalla 'paikalliseen hankintaan', jotta he voisivat paremmin hallita toimitusketjujaan ja saada näitä reagointiherkimmiksi. Valmistusyksiköillä onkin monesti Euroopassa pakko käyttää kalliita raaka-aineita ja puolivalmisteita. Kriittisiksi tekijöiksi osoittautuvat kuljetus- ja varastointikustannukset sekä näiden seurauksena hukka-aika, joka aiheutuu viivästyksistä. Voidakseen saavuttaa optimiratkaisun, on tehtävä päätös miten tuotteet varastoidaan: keskitetysti tai hajautetusti ja integroida tämä valinta sopivien kuljetusmuotojen kanssa. Aasiasta Pohjois-Eurooppaan on halpaa käyttää merikuljetusta, mutta operaatio kestää hyvin pitkään - joissain tapauksessa jopa kahdeksan viikkoa. Toisaalta lentokuljetus on sekä kallis että rajoittaa siirrettävien tuotteiden eräkokoa.On olemassa kolmaskin vaihtoehto, josta voisi olla ratkaisuksi: rautatiekuljetus on halvempi kuin lentokuljetus ja vasteajat ovat lyhyemmät kuin merikuljetuksissa. Tässä tutkimuksessa tilannetta selvitetään kyselyllä, joka suunnattiin Suomessa ja Ruotsissa toimiville yrityksille. Tuloksien perusteella teemme johtopäätökset siitä, mitkä kuljetusmuotojen markkinaosuudet tulevat olemaan tulevaisuudessa sekä luomme kuvan kuljetusvirroista Euroopan, Venäjän, Etelä-Korea, Intian, Kiinan ja Japanin välillä. Samalla on tarkoitus ennakoida sitä, miten tarkastelun kohteena olevat yritykset aikovat kehittää kuljetuksiaan ja varastointiaan tulevien vuosien aikana. Tulosten perusteella näyttää siltä, että seuraavan viiden vuoden kuluessa kuljetuskustannukset eivät merkittävissä määrin tule muuttuman ja meri- sekä kumipyöräkuljetukset pysyvät suosituimpina vaihtoehtoina.Kuitenkin lentokuljetusten osuus laskee hiukan, kun taas rautatiekuljetusten painotus kasvaa. Tulokset paljastavat, että Kiinassa ja Venäjällä kuljetettava konttimäärä kasvaa; Intiassa tulos on saman suuntainen, joskaan ei niin voimakas. Analyysimme mukaan kuljetusvirtoihin liittyvä epätasapaino säilyy Venäjän kuljetusten suhteen: yritykset jatkavat tulevaisuudessakin vientiperusteista strategiaansa. Varastoinnin puolella tunnistamme pienemmän muutoksen, jonka mukaan pienikokoisten varastojen määrät todennäköisesti vähenevät tulevaisuudessa ja kiinnostus isoja varastoja kohtaan lisääntyy. Tässä kohtaa on mainittava, että suomalaisilla yrityksillä on enemmän varastoja Keski- ja Itä-Euroopassa verrattuna ruotsalaisiin toimijoihin, jotka keskittyvät selkeämmin Länsi-Euroopan maihin. Varastoja yrityksillä on molemmissa tapaukissa paljolti kotimaassaan. Valitessaan varastojensa sijoituskohteita yritykset painottavat seuraavia kriteereitä: alhaiset jakelukustannukset, kokoamispaikan/valmistustehtaan läheisyys, saapuvan logistiikan integroitavuus ja saatavilla olevat logistiikkapalvelut. Tutkimuksemme lopussa päädymme siihen, että varastojen sijoituspaikat eivät muutu satamien rakenteen ja liikenneyhteyksien takia kovinkaan nopeasti.

Validation Studies of Thermal-hydraulic Code for Safety Analysis of Nuclear Power Plants

This thesis gives an overview of the validation process for thermal hydraulic system codes and it presents in more detail the assessment and validation of the French code CATHARE for VVER calculations. Three assessment cases are presented: loop seal clearing, core reflooding and flow in a horizontal steam generator. The experience gained during these assessment and validation calculations has been used to analyze the behavior of the horizontal steam generator and the natural circulation in the geometry of the Loviisa nuclear power plant. The cases presented are not exhaustive, but they give a good overview of the work performed by the personnel of Lappeenranta University of Technology (LUT). Large part of the work has been performed in co-operation with the CATHARE-team in Grenoble, France. The design of a Russian type pressurized water reactor, VVER, differs from that of a Western-type PWR. Most of thermal-hydraulic system codes are validated only for the Western-type PWRs. Thus, the codes should be assessed and validated also for VVER design in order to establish any weaknesses in the models. This information is needed before codes can be used for the safety analysis. Theresults of the assessment and validation calculations presented here show that the CATHARE code can be used also for the thermal-hydraulic safety studies for VVER type plants. However, some areas have been indicated which need to be reassessed after further experimental data become available. These areas are mostly connected to the horizontal stem generators, like condensation and phase separation in primary side tubes. The work presented in this thesis covers a large numberof the phenomena included in the CSNI code validation matrices for small and intermediate leaks and for transients. Also some of the phenomena included in the matrix for large break LOCAs are covered. The matrices for code validation for VVER applications should be used when future experimental programs are planned for code validation.

Numerical and ExperimentalModelling of Gas Flow and Heat Transfer in the Air Gap of An Electric Machine

This work deals with the cooling of high-speed electric machines, such as motors and generators, through an air gap. It consists of numerical and experimental modelling of gas flow and heat transfer in an annular channel. Velocity and temperature profiles are modelled in the air gap of a high-speed testmachine. Local and mean heat transfer coefficients and total friction coefficients are attained for a smooth rotor-stator combination at a large velocity range. The aim is to solve the heat transfer numerically and experimentally. The FINFLO software, developed at Helsinki University of Technology, has been used in the flow solution, and the commercial IGG and Field view programs for the grid generation and post processing. The annular channel is discretized as a sector mesh. Calculation is performed with constant mass flow rate on six rotational speeds. The effect of turbulence is calculated using three turbulence models. The friction coefficient and velocity factor are attained via total friction power. The first part of experimental section consists of finding the proper sensors and calibrating them in a straight pipe. After preliminary tests, a RdF-sensor is glued on the walls of stator and rotor surfaces. Telemetry is needed to be able to measure the heat transfer coefficients at the rotor. The mean heat transfer coefficients are measured in a test machine on four cooling air mass flow rates at a wide Couette Reynolds number range. The calculated values concerning the friction and heat transfer coefficients are compared with measured and semi-empirical data. Heat is transferred from the hotter stator and rotor surfaces to the coolerair flow in the air gap, not from the rotor to the stator via the air gap, althought the stator temperature is lower than the rotor temperature. The calculatedfriction coefficients fits well with the semi-empirical equations and precedingmeasurements. On constant mass flow rate the rotor heat transfer coefficient attains a saturation point at a higher rotational speed, while the heat transfer coefficient of the stator grows uniformly. The magnitudes of the heat transfer coefficients are almost constant with different turbulence models. The calibrationof sensors in a straight pipe is only an advisory step in the selection process. Telemetry is tested in the pipe conditions and compared to the same measurements with a plain sensor. The magnitudes of the measured data and the data from the semi-empirical equation are higher for the heat transfer coefficients than thenumerical data considered on the velocity range. Friction and heat transfer coefficients are presented in a large velocity range in the report. The goals are reached acceptably using numerical and experimental research. The next challenge is to achieve results for grooved stator-rotor combinations. The work contains also results for an air gap with a grooved stator with 36 slots. The velocity field by the numerical method does not match in every respect the estimated flow mode. The absence of secondary Taylor vortices is evident when using time averagednumerical simulation.

Ion-exchange resins as stationary phase in reactive chromatography

Dynamic behavior of bothisothermal and non-isothermal single-column chromatographic reactors with an ion-exchange resin as the stationary phase was investigated. The reactor performance was interpreted by using results obtained when studying the effect of the resin properties on the equilibrium and kinetic phenomena occurring simultaneously in the reactor. Mathematical models were derived for each phenomenon and combined to simulate the chromatographic reactor. The phenomena studied includes phase equilibria in multicomponent liquid mixture¿ion-exchange resin systems, chemicalequilibrium in the presence of a resin catalyst, diffusion of liquids in gel-type and macroporous resins, and chemical reaction kinetics. Above all, attention was paid to the swelling behavior of the resins and how it affects the kinetic phenomena. Several poly(styrene-co-divinylbenzene) resins with different cross-link densities and internal porosities were used. Esterification of acetic acid with ethanol to produce ethyl acetate and water was used as a model reaction system. Choosing an ion-exchange resin with a low cross-link density is beneficial inthe case of the present reaction system: the amount of ethyl acetate as well the ethyl acetate to water mole ratio in the effluent stream increase with decreasing cross-link density. The enhanced performance of the reactor is mainly attributed to increasing reaction rate, which in turn originates from the phase equilibrium behavior of the system. Also mass transfer considerations favor the use ofresins with low cross-link density. The diffusion coefficients of liquids in the gel-type ion-exchange resins were found to fall rapidly when the extent of swelling became low. Glass transition of the polymer was not found to significantlyretard the diffusion in sulfonated PS¿DVB ion-exchange resins. It was also shown that non-isothermal operation of a chromatographic reactor could be used to significantly enhance the reactor performance. In the case of the exothermic modelreaction system and a near-adiabatic column, a positive thermal wave (higher temperature than in the initial state) was found to travel together with the reactive front. This further increased the conversion of the reactants. Diffusion-induced volume changes of the ion-exchange resins were studied in a flow-through cell. It was shown that describing the swelling and shrinking kinetics of the particles calls for a mass transfer model that explicitly includes the limited expansibility of the polymer network. A good description of the process was obtained by combining the generalized Maxwell-Stefan approach and an activity model that was derived from the thermodynamics of polymer solutions and gels. The swelling pressure in the resin phase was evaluated by using a non-Gaussian expression forthe polymer chain length distribution. Dimensional changes of the resin particles necessitate the use of non-standard mathematical tools for dynamic simulations. A transformed coordinate system, where the mass of the polymer was used as a spatial variable, was applied when simulating the chromatographic reactor columns as well as the swelling and shrinking kinetics of the resin particles. Shrinking of the particles in a column leads to formation of dead volume on top of the resin bed. In ordinary Eulerian coordinates, this results in a moving discontinuity that in turn causes numerical difficulties in the solution of the PDE system. The motion of the discontinuity was eliminated by spanning two calculation grids in the column that overlapped at the top of the resin bed. The reactive and non-reactive phase equilibrium data were correlated with a model derived from thethermodynamics of polymer solution and gels. The thermodynamic approach used inthis work is best suited at high degrees of swelling because the polymer matrixmay be in the glassy state when the extent of swelling is low.

Reduction of oxidative cellular damage by overexpression of the thioredoxin TRX2 gene improves yield and quality of wine yeast dry active biomass

Background: Wine Saccharomyces cerevisiae strains, adapted to anaerobic must fermentations, suffer oxidative stress when they are grown under aerobic conditions for biomass propagation in the industrial process of active dry yeast production. Oxidative metabolism of sugars favors high biomass yields but also causes increased oxidation damage of cell components. The overexpression of the TRX2 gene, coding for a thioredoxin, enhances oxidative stress resistance in a wine yeast strain model. The thioredoxin and also the glutathione/glutaredoxin system constitute the most important defense against oxidation. Trx2p is also involved in the regulation of Yap1p-driven transcriptional response against some reactive oxygen species. Results: Laboratory scale simulations of the industrial active dry biomass production process demonstrate that TRX2 overexpression increases the wine yeast final biomass yield and also its fermentative capacity both after the batch and fed-batch phases. Microvinifications carried out with the modified strain show a fast start phenotype derived from its enhanced fermentative capacity and also increased content of beneficial aroma compounds. The modified strain displays an increased transcriptional response of Yap1p regulated genes and other oxidative stress related genes. Activities of antioxidant enzymes like Sod1p, Sod2p and catalase are also enhanced. Consequently, diminished oxidation of lipids and proteins is observed in the modified strain, which can explain the improved performance of the thioredoxin overexpressing strain. Conclusions: We report several beneficial effects of overexpressing the thioredoxin gene TRX2 in a wine yeast strain. We show that this strain presents an enhanced redox defense. Increased yield of biomass production process in TRX2 overexpressing strain can be of special interest for several industrial applications.