870 resultados para lock and key model


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There is increasing evidence that glial cells, in particular astrocytes, interact dynamically with neurons. The well-known anatomofunctional organization of neurons in the barrel cortex offers a suitable and promising model to study such neuroglial interaction. This review summarizes and discusses recent in vitro as well as in vivo works demonstrating that astrocytes receive, integrate, and respond to neuronal signals. In addition, they are active elements of brain metabolism and exhibit a certain degree of plasticity that affects neuronal activity. Altogether these findings indicate that the barrel cortex presents glial compartments overlapping and interacting with neuronal compartments and that these properties help define barrels as functional and independent units. Finally, this review outlines how the use of the barrel cortex as a model might in the future help to address important questions related to dynamic neuroglia interaction.

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Työn tavoitteena on kehittää Microsoft Excel -taulukkolaskentaohjelmaan pohjautuva arvonmääritysmalli. Mallin avulla osaketutkimusta tekevät analyytikot ja sijoittajat voivat määrittää osakkeen fundamenttiarvon. Malli kehitetään erityisesti piensijoittajien työkaluksi. Työn toisena tavoitteena on soveltaa kehitettyä arvonmääritysmallia case-yrityksenä toimivan F-Securen arvonmäärityksessä ja selvittää mallin avulla onko F-Securen osake pörssissä fundamentteihin nähden oikein hinnoiteltu. Työn teoriaosassa esitellään arvonmäärityksen käyttökohteet ja historia, arvonmääritysprosessin vaiheet (strateginen analyysi, tilinpäätösanalyysi, tulevaisuuden ennakointi, yrityksen arvon laskeminen), pääoman kustannuksen määrittäminen ja sijoittajan eri arvonmääritysmenetelmät, joita ovat diskontattuun kassavirtaan perustuvassa arvonmäärityksessä käytettävät mallit sekä suhteellisen arvonmäärityksentunnusluvut. Empiirinen osa käsittää arvonmääritysmallin kehittämisen ja rakenteen kuvauksen sekä F-Securen arvonmääritysprosessin. Vaikka F-Securen tulevaisuus näyttää varsin valoisalta, osake on hinnoiteltu markkinoilla tällä hetkellä(23.02.2006) korkeammalle kuin näihin odotuksiin nähden olisi järkevää. Eri menetelmät antavat osakkeelle arvoja 2,25 euron ja 2,97 euron väliltä. Kehitetty Excel -malli määrittää F-Securen osakkeen tavoitehinnaksi eri menetelmien mediaanina 2,29 euroa. Tutkimuksen tuloksena F-Securen osaketta voidaan pitää yliarvostettuna, sillä sen hinta pörssissä on 3,05 euroa.

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Yrityksen sisäisten rajapintojen tunteminen mahdollistaa tiedonvaihdon hallinnan läpi organisaation. Idean muokkaaminen kannattavaksi innovaatioksi edellyttää organisaation eri osien läpi kulkevaa saumatonta prosessiketjua sekä tietovirtaa. Tutkielman tavoitteena oli mallintaa organisaation kahden toiminnallisesti erilaisen osan välinen tiedon vaihto. Tiedon vaihto kuvattiin rajapintana, tietoliittymänä. Kolmiulotteinen organisaatiomalli muodosti tutkimuksen pääteorian. Se kytkettiin yrityksen tuotanto- ja myyntiosiin, kuten myös BestServ-projektin kehittämään uuteen palvelujen kehittämisen prosessiin. Uutta palvelujen kehittämisen prosessia laajennettiin ISO/IEC 15288 standardin kuvaamalla prosessimallilla. Yritysarkkitehtuurikehikoita käytettiin mallintamisen perustana. Tietoliittymä nimenä kuvastaa näkemystä siitä, että tieto [tietämys] on olemukseltaan yksilöiden tai ryhmien välistä. Mallinnusmenetelmät eivät kuitenkaan vielä mahdollista tietoon [tietämykseen] liittyvien kaikkien ominaisuuksien mallintamista. Tietoliittymän malli koostuu kolmesta osasta, joista kaksi esitetään graafisessa muodossa ja yksi taulukkona. Mallia voidaan käyttää itsenäisesti tai osana yritysarkkitehtuuria. Teollisessa palveluliiketoiminnassa sekä tietoliittymän mallinnusmenetelmä että sillä luotu malli voivat auttaa konepajateollisuuden yritystä ymmärtämään yrityksen kehittämistarpeet ja -kohteet, kun se haluaa palvelujen tuottamisella suuremman roolin asiakasyrityksen liiketoiminnassa. Tietoliittymän mallia voidaan käyttää apuna organisaation tietovarannon ja tietämyksen mallintamisessa sekä hallinnassa ja näin pyrkiä yhdistämään ne yrityksen strategiaa palvelevaksi kokonaisuudeksi. Tietoliittymän mallinnus tarjoaa tietojohtamisen kauppatieteelliselle tutkimukselle menetelmällisyyden tutkia innovaatioiden hallintaa sekä organisaation uudistumiskykyä. Kumpikin tutkimusalue tarvitsevat tarkempaa tietoa ja mahdollisuuksia hallita tietovirtoja, tiedon vaihtoa sekä organisaation tietovarannon käyttöä.

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Tämän pro gradu -tutkielman aiheena on yritysverkostojen kehittäminen sekä siihen liittyvät käsitteet ja menetelmät. Tutkielman tavoitteena on selkiyttää verkostoitumiseen, verkostosuhteen kehittymiseen ja yritysverkoston kehittämiseen liittyviä käsitteitä. Tutkielmassa verkostoitumista tarkastellaan transaktiokustannusteorian, resurssiperusteisen näkemyksen ja IMP-tutkimusryhmän vuorovaikutusnäkökulman mukaisesti. Verkostoituminen nähdään osana organisaation uudistumisprosessia ja sitä mallinnetaan verkostosuhteen kehittymisprosessin avulla. Verkoston kehittäminen on jatke organisaation uudistumisprosessille ja osa verkostosuhteen kehittymisprosessia. Verkoston kehittämiseen liittyen tutkielmassa tarkastellaan, miten verkoston kehittäminen eroaa yrityksen sisäisestä kehittämisestä, ja millaisia haasteita ja menestystekijöitä yhteisestä kehittämistoiminnasta on löydettävissä. Tutkielmassa luokitellaan myös kehittämiskohteita sekä tarkastellaan, millaisella kehittämistyön organisoitumismallilla sekä työkaluilla ja menetelmillä yritysverkoston kehittämistä voidaan tukea.

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The aim of the paper is to describe some of the challenges faced by schools, or by formal education in general, as a consequence of today"s mobilecentric society (henceforth MCS), the term we will use to denote the new, networked learning ecology that has arisen from the massive penetration of digital media in everyday life. After revisiting some of the ideas of McLuhan and Vygotsky in the light of this new technological scenario, we describe five traits of the MCS and the challenges illustrated through educational practices that we believe schools will face if they wish to preserve their function of individualization and socialization. We believe that despite the emergence of the MCS, the main function of the school is still to provide the"box of tools" (a set of psychological instruments, such as reading, writing, mathematical notation, digital literacy, etc.) that enables people to develop their learning skills and life projects and to become part of communities and groups. However, the complexity and mobility of the new learning environments means that the position held by schools needs to be reevaluated in the face of the informal learning paths and experiences both online and offline to which learners now have access. We also need to reevaluate the meaning of the school itself as an institution and the model of learner it should be training

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The goal of this dissertation is to find and provide the basis for a managerial tool that allows a firm to easily express its business logic. The methodological basis for this work is design science, where the researcher builds an artifact to solve a specific problem. In this case the aim is to provide an ontology that makes it possible to explicit a firm's business model. In other words, the proposed artifact helps a firm to formally describe its value proposition, its customers, the relationship with them, the necessary intra- and inter-firm infrastructure and its profit model. Such an ontology is relevant because until now there is no model that expresses a company's global business logic from a pure business point of view. Previous models essentially take an organizational or process perspective or cover only parts of a firm's business logic. The four main pillars of the ontology, which are inspired by management science and enterprise- and processmodeling, are product, customer interface, infrastructure and finance. The ontology is validated by case studies, a panel of experts and managers. The dissertation also provides a software prototype to capture a company's business model in an information system. The last part of the thesis consists of a demonstration of the value of the ontology in business strategy and Information Systems (IS) alignment. Structure of this thesis: The dissertation is structured in nine parts: Chapter 1 presents the motivations of this research, the research methodology with which the goals shall be achieved and why this dissertation present a contribution to research. Chapter 2 investigates the origins, the term and the concept of business models. It defines what is meant by business models in this dissertation and how they are situated in the context of the firm. In addition this chapter outlines the possible uses of the business model concept. Chapter 3 gives an overview of the research done in the field of business models and enterprise ontologies. Chapter 4 introduces the major contribution of this dissertation: the business model ontology. In this part of the thesis the elements, attributes and relationships of the ontology are explained and described in detail. Chapter 5 presents a case study of the Montreux Jazz Festival which's business model was captured by applying the structure and concepts of the ontology. In fact, it gives an impression of how a business model description based on the ontology looks like. Chapter 6 shows an instantiation of the ontology into a prototype tool: the Business Model Modelling Language BM2L. This is an XML-based description language that allows to capture and describe the business model of a firm and has a large potential for further applications. Chapter 7 is about the evaluation of the business model ontology. The evaluation builds on literature review, a set of interviews with practitioners and case studies. Chapter 8 gives an outlook on possible future research and applications of the business model ontology. The main areas of interest are alignment of business and information technology IT/information systems IS and business model comparison. Finally, chapter 9 presents some conclusions.

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The changing business environment demands that chemical industrial processes be designed such that they enable the attainment of multi-objective requirements and the enhancement of innovativedesign activities. The requirements and key issues for conceptual process synthesis have changed and are no longer those of conventional process design; there is an increased emphasis on innovative research to develop new concepts, novel techniques and processes. A central issue, how to enhance the creativity of the design process, requires further research into methodologies. The thesis presentsa conflict-based methodology for conceptual process synthesis. The motivation of the work is to support decision-making in design and synthesis and to enhance the creativity of design activities. It deals with the multi-objective requirements and combinatorially complex nature of process synthesis. The work is carriedout based on a new concept and design paradigm adapted from Theory of InventiveProblem Solving methodology (TRIZ). TRIZ is claimed to be a `systematic creativity' framework thanks to its knowledge based and evolutionary-directed nature. The conflict concept, when applied to process synthesis, throws new lights on design problems and activities. The conflict model is proposed as a way of describing design problems and handling design information. The design tasks are represented as groups of conflicts and conflict table is built as the design tool. The general design paradigm is formulated to handle conflicts in both the early and detailed design stages. The methodology developed reflects the conflict nature of process design and synthesis. The method is implemented and verified through case studies of distillation system design, reactor/separator network design and waste minimization. Handling the various levels of conflicts evolve possible design alternatives in a systematic procedure which consists of establishing an efficient and compact solution space for the detailed design stage. The approach also provides the information to bridge the gap between the application of qualitative knowledge in the early stage and quantitative techniques in the detailed design stage. Enhancement of creativity is realized through the better understanding of the design problems gained from the conflict concept and in the improvement in engineering design practice via the systematic nature of the approach.

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Concerning process control of batch cooling crystallization the present work focused on the cooling profile and seeding technique. Secondly, the influence of additives on batch-wise precipitation process was investigated. Moreover, a Computational Fluid Dynamics (CFD) model for simulation of controlled batch cooling crystallization was developed. A novel cooling model to control supersaturation level during batch-wise cooling crystallization was introduced. The crystallization kinetics together with operating conditions, i.e. seed loading, cooling rate and batch time, were taken into account in the model. Especially, the supersaturation- and suspension density- dependent secondary nucleation was included in the model. The interaction between the operating conditions and their influence on the control target, i.e. the constant level of supersaturation, were studied with the aid of a numerical solution for the cooling model. Further, the batch cooling crystallization was simulated with the ideal mixing model and CFD model. The moment transformation of the population balance, together with the mass and heat balances, were solved numerically in the simulation. In order to clarify a relationship betweenthe operating conditions and product sizes, a system chart was developed for anideal mixing condition. The utilization of the system chart to determine the appropriate operating condition to meet a required product size was introduced. With CFD simulation, batch crystallization, operated following a specified coolingmode, was studied in the crystallizers having different geometries and scales. The introduced cooling model and simulation results were verified experimentallyfor potassium dihydrogen phosphate (KDP) and the novelties of the proposed control policies were demonstrated using potassium sulfate by comparing with the published results in the literature. The study on the batch-wise precipitation showed that immiscible additives could promote the agglomeration of a derivative of benzoic acid, which facilitated the filterability of the crystal product.

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This thesis investigates the strategy implementation process of enterprices; a process whichhas lacked the academic attentioon compared with a rich strategy formation research trdition. Strategy implementation is viewed as a process ensuring tha the strtegies of an organisation are realised fully and quickly, yet with constant consideration of changing circumstances. The aim of this sudy is to provide a framework for identifying, analysing and removing the strategy implementation bottleneck af an organization and thus for intesifying its strategy process.The study is opened by specifying the concept, tasks and key actors of strategy implementation process; especially arguments for the critical implementation role of the top management are provided. In order to facilitate the analysis nad synthetisation of the core findings of scattered doctrine, six characteristic approaches to strategy implementation phenomenon are identified and compared. The Bottleneck Framework is introduced as an instrument for arranging potential strategy realisation problems, prioritising an organisation's implementation obstacles and focusing the improvement measures accordingly. The SUCCESS Framework is introduced as a mnemonic of the seven critical factors to be taken into account when promoting sttrategy implementation. Both frameworks are empirically tested by applying them to real strategy implementation intesification process in an international, industrial, group-structured case enterprise.

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Salmonella is distributed worldwide and is a pathogen of economic and public health importance. As a multi-host pathogen with a long environmental persistence, it is a suitable model for the study of wildlife-livestock interactions. In this work, we aim to explore the spill-over of Salmonella between free-ranging wild boar and livestock in a protected natural area in NE Spain and the presence of antimicrobial resistance. Salmonella prevalence, serotypes and diversity were compared between wild boars, sympatric cattle and wild boars from cattle-free areas. The effect of age, sex, cattle presence and cattle herd size on Salmonella probability of infection in wild boars was explored by means of Generalized Linear Models and a model selection based on the Akaike’s Information Criterion. Prevalence was higher in wild boars co-habiting with cattle (35.67%, CI 95% 28.19–43.70) than in wild boar from cattle-free areas (17.54%, CI 95% 8.74–29.91). Probability of a wild boar being a Salmonella carrier increased with cattle herd size but decreased with the host age. Serotypes Meleagridis, Anatum and Othmarschen were isolated concurrently from cattle and sympatric wild boars. Apart from serotypes shared with cattle, wild boars appear to have their own serotypes, which are also found in wild boars from cattle-free areas (Enteritidis, Mikawasima, 4:b:- and 35:r:z35). Serotype richness (diversity) was higher in wild boars co-habiting with cattle, but evenness was not altered by the introduction of serotypes from cattle. The finding of a S. Mbandaka strain resistant to sulfamethoxazole, streptomycin and chloramphenicol and a S. Enteritidis strain resistant to ciprofloxacin and nalidixic acid in wild boars is cause for public health concern.

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Nokian Matkapuhelimien tuotantoprosessit on suunniteltu tukemaan massaräätälöintiä perustuen assembly-to-order tekniikkaan (ATO). Tämän työn tehtävänä oli kehittää toimitusmallit ATO-materiaaleille paikallisilta alihankkijoilta matkapuhelintehtaalle. Aluksi analysoitiin nykyiset toimintamallit perustun Nokia Komarom Kft:n työntekijöiden ja toimittajien haastatteluihin. Ongelmiksi havaittiin toimintatapojen monimuotoisuus, dokumentoinnin puute, puutteelliset laskut ja riittämätön toimitusseuranta.Malleille asetettavien joustavuusvaatimusten selvittämiseksi suoritettiin laajamittainen näkyvyysvälineiden ja tuotantokapasiteetin tutkimus. Vaatimukset tilauksesta toimitukseen läpimenoajoille ja kuljetustoiminnoille johdettiin joustavuusvaatimuksista. Työn lopussa muodostetaan toimitusmallit perustuen nykytilan analyysiin, havaittuihin ongelmiin ja malleille asetettuihin vaatimuksiin. Materiaalit jaetaan eri malleilla ohjattaviksi niiden ominaisuuksiin perustuen. Ensimmäinen malleista implementoidaan kahden pilottitoimittajan kanssa ja esitetään tulokset. Toista mallia hyödynnetään lähitulevaisuudessa Nokia Komarom Kft:n aloittaessa yhteistyön uusien paikallistoimittajien kanssa.

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Tutkimuksen tavoitteina oli rakentaa pelastuslaitoksen tuloksellisuuden arvioimiseen tasapainotettu mittaristo sekä valita mittareita, joiden avulla voidaan vertailla pelastuslaitoksia keskenään. Tutkimuksessa selvitetään, miten julkisen sektorin palveluiden tuloksellisuutta arvioidaan erityisesti kuntasektorilla, mitä tarkoitukseen soveltuvia mittausjärjestelmiä on olemassa, miten tasapainotetun mittausjärjestelmän rakentamisprosessi etenee, miten henkilöstön aikaansaannoskyky voidaan ottaa huomioon kuntien tuloksellisuuden arvioinnissa, minkälaisilla mittareilla voidaan parhaiten arvioida pelastuslaitoksen toimintaa ja mitkä mittareista soveltuvat pelastuslaitosten vertailuun. Teoriaosuudessa käsitellään julkisten palvelujen erityispiirteitä, suositusta kunnallisten palvelujen tuloksellisuuden arvioimisesta sekä henkilöstön aikaansaannoskyvyn mittaamista. Työssä esitellään joitakin tasapainotetun mittaamisen malleja sekä kuvataan mittariston rakentamisprosessin vaiheita. Teorian pohjalta rakennettiin tasapainotettu tunnuslukujärjestelmä Etelä-Karjalan pelastuslaitokselle. Kunnalliselle organisaatiolle voidaan rakentaa tasapainotettu mittaristo, mutta yksittäisen pelastuslaitoksen osalta on lähdettävä sen omista kriittisistä menestystekijöistä ja noudatettava kunnallisen sektorin suosituksia. Yhteisiä mittareita pelastuslaitosten käyttöön löytyy, mutta pääosin yksikön tuloksellisuutta ohjaavat mittarit soveltuvat vain sisäiseen käyttöön.

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A role for the NADPH oxidases NOX1 and NOX2 in liver fibrosis has been proposed, but the implication of NOX4 is poorly understood yet. The aim of this work was to study the functional role of NOX4 in different cell populations implicated in liver fibrosis: hepatic stellate cells (HSC), myofibroblats (MFBs) and hepatocytes. Two different mice models that develop spontaneous fibrosis (Mdr2−/−/p19ARF−/−, Stat3Δhc/Mdr2−/−) and a model of experimental induced fibrosis (CCl4) were used. In addition, gene expression in biopsies from chronic hepatitis C virus (HCV) patients or non-fibrotic liver samples was analyzed. Results have indicated that NOX4 expression was increased in the livers of all animal models, concomitantly with fibrosis development and TGF-β pathway activation. In vitro TGF-β-treated HSC increased NOX4 expression correlating with transdifferentiation to MFBs. Knockdown experiments revealed that NOX4 downstream TGF-β is necessary for HSC activation as well as for the maintenance of the MFB phenotype. NOX4 was not necessary for TGF-β-induced epithelial-mesenchymal transition (EMT), but was required for TGF-β-induced apoptosis in hepatocytes. Finally, NOX4 expression was elevated in patients with hepatitis C virus (HCV)-derived fibrosis, increasing along the fibrosis degree. In summary, fibrosis progression both in vitro and in vivo (animal models and patients) is accompanied by increased NOX4 expression, which mediates acquisition and maintenance of the MFB phenotype, as well as TGF-β-induced death of hepatocytes.

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Tuotteiden elinkaaret elektroniikkateollisuudessa ovat lyhentyneet entisestään. Paineet uusien kehittyneempien tuotteiden lanseeraamiselle ovat kasvaneet. Huonosti hoidettu tuotevaihto voi aiheuttaa merkittäviä kustannuksia yritykselle mikäli alasajon kustannusvaikutusta tulokseen aliarvioidaan. Työ käsittelee markkinoilta poistuvan tuotteen materiaalivirtojen hallintaa tuotevaihdon aikana. Lähtökohtana työssä oli kehittää toimintatapa miten tuotteen alasajon aikana tulisi toimia sekä mallintaa hankintaketju riskien ja pullonkaulojen löytämiseksi. Päätavoitteena oli materiaalivaraston arvon minimoiminen sekä ylijäämämateriaalien hyödyntäminen. Työn merkittävimpiä tuloksia oli hankintaketjun materiaalivirtojen seurantaan kehitetty Excel työkalu sekä alasajon liittyvien työvaiheiden kuvaaminen.

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Maximum entropy modeling (Maxent) is a widely used algorithm for predicting species distributions across space and time. Properly assessing the uncertainty in such predictions is non-trivial and requires validation with independent datasets. Notably, model complexity (number of model parameters) remains a major concern in relation to overfitting and, hence, transferability of Maxent models. An emerging approach is to validate the cross-temporal transferability of model predictions using paleoecological data. In this study, we assess the effect of model complexity on the performance of Maxent projections across time using two European plant species (Alnus giutinosa (L.) Gaertn. and Corylus avellana L) with an extensive late Quaternary fossil record in Spain as a study case. We fit 110 models with different levels of complexity under present time and tested model performance using AUC (area under the receiver operating characteristic curve) and AlCc (corrected Akaike Information Criterion) through the standard procedure of randomly partitioning current occurrence data. We then compared these results to an independent validation by projecting the models to mid-Holocene (6000 years before present) climatic conditions in Spain to assess their ability to predict fossil pollen presence-absence and abundance. We find that calibrating Maxent models with default settings result in the generation of overly complex models. While model performance increased with model complexity when predicting current distributions, it was higher with intermediate complexity when predicting mid-Holocene distributions. Hence, models of intermediate complexity resulted in the best trade-off to predict species distributions across time. Reliable temporal model transferability is especially relevant for forecasting species distributions under future climate change. Consequently, species-specific model tuning should be used to find the best modeling settings to control for complexity, notably with paleoecological data to independently validate model projections. For cross-temporal projections of species distributions for which paleoecological data is not available, models of intermediate complexity should be selected.