19 resultados para Moving Targets

em Doria (National Library of Finland DSpace Services) - National Library of Finland, Finland


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Verkostokeskeisessä sodankäynnissä tietojärjestelmien suurimpana haasteena on oikean tiedon hajauttaminen oikeaan paikkaan ja aikaan. Tietojärjestelmissä esitettävän ilmatilannekuvan tulee vastata reaalimaailman tilannetta parhaalla mahdollisella tavalla. Ilmatorjunnassa reaaliaikaisuus nousee erityisen suureen rooliin nopeasti liikkuvien kohteiden takia. Tämä diplomityö on tehty Insta DefSec Oy:ssä liittyen johtamisjärjestelmän uudistamishankkeeseen. Työn vaatimuksina olivat standardeihin perustuvat ratkaisut, joista keskeisimmäksi nousi Data Distribution Service -standardi (DDS) ja sen hyödyntäminen osana johtamisjärjestelmän tiedon hajautusta. Työssä esitellään johtamisjärjestelmien tiedon hajautukseen liittyviä haasteita sekä paikallisessa että maantieteellisesti hajautetussa toimintaympäristössä. Työssä toteutettiin liityntäohjelmisto nykyisen ja uuden johtamisjärjestelmän välille. Liityntäohjelmiston tehtävänä on tuottaa reaaliaikaista ilmatilannekuvaa nykyisestä johtamisjärjestelmästä uuteen johtamisjärjestelmään. DDS-standardin toteuttavana välikerrosarkkitehtuurina käytettiin OpenSplice DDS -tuotetta. Valittu teknologia tarjoaa edistykselliset julkaisija–tilaaja-mallin mukaiset menetelmät tiedon reaaliaikaiseen hajauttamiseen. DDS:n arkkitehtuuri ja palvelun laadun mekanismit mahdollistavat tiedon hajautuksen sodanajan johtamisjärjestelmille.

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ässä työssä on analysoitu UPM-Kymmene Oyj Voikkaan tehtaalla tapahtuneiden paperikoneiden 16 ja 17 ja SGW- hiomon pysäyttämisten vaikutuksia tehtaan sisäiseen infrastruktuuriin sekä tehdas- ja osastolayoutien uudelleen järjestelytarpeisiin. Diplomityön tavoitteena oli laatia koko tehdasalueen käsittävä, osastojen, laitosten ja laitteistojen lyhyen ja pitkän tähtäimen sijoitussuunnitelma. Suunnitelmassa on huomioitu vanhan tehtaan puolelle jäävien toimintojen siirto lähemmäs käyntiin jääneitä paperikoneita 11 ja 18 sekä PGW-hiomoa. Suunnitelmassa on myös otettu huomioon tiedossa olevat pitemmän tähtäimen kehityssuunnitelmat. Suunnitelman laatimisella tavoitellaan niin ikään pitkän tähtäimen suunnitelmallisuuden lisäämistä koko tehdasympäristössä. Työn teoriaosassa tarkastellaan tehdassuunnittelua yleensä, esitellään tehdasprojektin eri vaiheet sekä tehdassuunnitteluprojektin oleellisimmat päätöksentekovaiheet. Tarkemman tarkastelun kohteena on, minkä tasoista tilasuunnittelua tehdasprojektin eri vaiheissa tehdään. Kokeellisessa osassa tarkastellaan tutkimuskohteiden vaihtoehtoisia sijoituspaikkoja, vaihtoehtojen toteutuskelpoisuutta ja niiden tarkoituksenmukaisuutta. Loppuyhteenvedossa tehdään johtopäätöksiä tehtaan koko layoutin tarkoituksenmukaisuudesta ja verrataan sitä ns. mallitehtaan periaatteelliseen layoutiin sekä tehdään yhteenvetoa siitä, mitkä ovat tehtaan toiminnan kannalta tärkeimmät muutoskohteet.

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Työn tärkeimpänä tavoitteena oli edistää ympäristöjärjestelmän laatimista Kvaerner Pulping, Power divisioonan Kattilat-liiketoimintayksikölle. Lisäksi tavoitteena oli tarkastella yritykseen kohdistuvia ympäristövaatimuksia ja niiden vaikutusta yrityksen toimintaan. Aluksi työssä tarkasteltiin ympäristöjärjestelmästandardien sisältöjä ja niiden eroja. Työssä käsiteltiin myös erilaisia elinkaarijohtamisen malleja, joita voidaan hyödyntää yrityksen kokonaisvaltaisessa ympäristöjärjestelmässä. Työssä tarkasteltiin myös sidosryhmien vaikutusta yrityksen ympäristötoimintaan. Kattilalaitostoimittajan tärkeimpiä asiakkaita ovat sellu- ja paperiteollisuus. Näihin yrityksiin on kohdistunut runsaan kymmenen vuoden aikana paineita ympäristötoiminnan tehostamiseksi. Tämän kehityksen seurauksena vastaavat tehostamispaineet ovat siirtymässä myös alihankkijoille, kuten kattilaitostoimittajille. Tehokkaan ympäristöjohtamisen takaamiseksi työssä määriteltiin ympäristövastuut ja –valtuudet sekä ympäristöpäämäärät ja –tavoitteet. Lisäksi tunnistettiin yrityksen toimintaan liittyvät ympäristönäkökohdat ja –riskit. Työn yhteydessä laadittiin ympäristöjärjestelmän luonnos, ja se sisältää jatkuvan parantamisen periaatteen. Työn yhteydessä laadittiin lisäksi Kvaerner Pulping Oy:n koelaitokselle ympäristölupahakemus. Työssä on kuvattu koelaitosta ja sen ympäristölupahakemukseen liittyviä asioita esimerkkinä parantuneesta ympäristöasioiden hoidosta.

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Urateoriat ovat murroksessa, kun urat ovat muuttumassa perinteisistä urapoluista rajattomiin, monisuuntaisiin uriin. Samaan aikaan erilaisten trainee-ohjelmien määrä lisääntyy vauhdilla. Urapolkujen tutkiminen on tästä syystä erittäin ajankohtaista. Tämän tutkielman tarkoituksena on tutkia, miten S-ryhmässä työskentelevien kaupallisen kenttäkoulutuksen käyneiden ja sen käymättömien urapolut eroavat toisistaan. Viimeaikaisten teorioiden mukaan urat voidaan jakaa objektiivisiin ja subjektiivisiin uriin sekä perinteisiin ja rajattomiin uriin. Aikaisempien tutkimustulosten pohjalta tarkastellaan yksilöiden uravalintoja ja käsityksiä hyvästä urasta. Myös yksilön sosiaalistuminen organisaatioon vaikuttaa sitoutumiseen ja tätä kautta uraan. Tutkimuksessa on käytetty kvalitatiivisia menetelmiä ja havaintoaineisto on kerätty sähköpostikyselyiden avulla S-ryhmässä työskenteleviltä henkilöiltä. Tutkimustulokset osoittavat, että urapolut ovat erilaisia. Kaikki tutkimukseen osallistuneet kenttäkoulutetut ovat johtaja-asemassa, vertailuryhmän henkilöt asiantuntija- tai päällikköasemassa. Tulosten mukaan ei kuitenkaan voida todeta, että näiden kahden ryhmän urakäsitykset olisivat huomattavasti erilaisia. Onnistunut ura nähdään useimmin subjektiivisesti haastavana, omien tavoitteiden ja kehittymisen saavuttamisena.

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ErbB receptors (EGFR, ErbB2, ErbB3 and ErbB4) are growth factor receptors that regulate signals of cell differentiation, proliferation, migration and survival. Inappropriate activation of these receptors is associated with the development and severity of many cancers and has prognostic and predictive value in cancer therapy. Drugs, such as therapeutic antibodies, targeted against EGFR and ErbB2, are currently used in therapy of breast, colorectal and head and neck cancers. The role of ErbB4 in tumorigenesis has remained relatively poorly understood. Alternative splicing produces four different isoforms of one ErbB4 gene. These isoforms (JM-a, JM-b, CYT-1 and CYT-2) are functionally dissimilar and proposed to have different roles in carcinogenesis. The juxtamembrane form JM-a undergoes regulated intramembrane proteolysis producing a soluble receptor ectodomain and an intracellular domain that translocates into the nucleus and regulates transcription. Nuclear signaling via JM-a isoform stimulates cancer cell proliferation. This study aimed to develop antibodies targeting the proposed oncogenic ErbB4 JM-a isoform that show potential in inhibiting ErbB4 dependent tumorigenesis. Also, the clinical relevance of ErbB4 shedding in cancer was studied. The currently used monoclonal antibody trastuzumab, targeting ErbB2, has shown efficacy in breast cancer therapy. In this study novel tissues with ErbB2 amplification and trastuzumab sensitivity were analyzed. The results of this study indicated that a subpopulation of breast cancer patients demonstrate increased shedding and cleavage of ErbB4. A JM-a isoform-specific antibody that inhibited ErbB4 shedding and consequent activation of ErbB4 had anti-tumor activity both in vitro and in vivo. Thus, ErbB4 shedding associates with tumor growth and specific targeting of the cleavable JM-a isoform could be considered as a strategy for developing novel ErbB-based cancer drugs. In addition, it was demonstrated that ErbB2 amplification is common in intestinal type gastric cancers with poor clinical outcome. Trastuzumab inhibited growth of gastric and breast cancer cells with equal efficacy. Thus, ErbB2 may be a useful target in gastric cancer.

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Prostate cancers form a heterogeneous group of diseases and there is a need for novel biomarkers, and for more efficient and targeted methods of treatment. In this thesis, the potential of microarray data, RNA interference (RNAi) and compound screens were utilized in order to identify novel biomarkers, drug targets and drugs for future personalized prostate cancer therapeutics. First, a bioinformatic mRNA expression analysis covering 9873 human tissue and cell samples, including 349 prostate cancer and 147 normal prostate samples, was used to distinguish in silico prevalidated putative prostate cancer biomarkers and drug targets. Second, RNAi based high-throughput (HT) functional profiling of 295 prostate and prostate cancer tissue specific genes was performed in cultured prostate cancer cells. Third, a HT compound screen approach using a library of 4910 drugs and drug-like molecules was exploited to identify potential drugs inhibiting prostate cancer cell growth. Nine candidate drug targets, with biomarker potential, and one cancer selective compound were validated in vitro and in vivo. In addition to androgen receptor (AR) signaling, endoplasmic reticulum (ER) function, arachidonic acid (AA) pathway, redox homeostasis and mitosis were identified as vital processes in prostate cancer cells. ERG oncogene positive cancer cells exhibited sensitivity to induction of oxidative and ER stress, whereas advanced and castrate-resistant prostate cancer (CRPC) could be potentially targeted through AR signaling and mitosis. In conclusion, this thesis illustrates the power of systems biological data analysis in the discovery of potential vulnerabilities present in prostate cancer cells, as well as novel options for personalized cancer management.

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The thesis examines the profitability of DMAC trading rules in the Finnish stock market over the 1996-2012 period. It contributes to the existing technical analysis literature by comparing for the first time the performance of DMAC strategies based on individual stock trading portfolios to the performance of index trading strategies based on the trading on the index (OMX Helsinki 25) that consists of the same stocks. Besides, the market frictions including transaction costs and taxes are taken into account, and the results are reported from both institutional and individual investor’s perspective. Performance characteristic of DMAC rules are evaluated by simulating 19,900 different trading strategies in total for two non- overlapping 8-year sub-periods, and decomposing the full-sample-period performance of DMAC trading strategies into distinct bullish- and bearish-period performances. The results show that the best DMAC rules have predictive power on future price trends, and these rules are able to outperform buy-and-hold strategy. Although the performance of the DMAC strategies is highly dependent on the combination of moving average lengths, the best DMAC rules of the first sub-period have also performed well during the latter sub-period in the case of individual stock trading strategies. According to the results, the outperformance of DMAC trading rules over buy-and-hold strategy is mostly attributed to their superiority during the bearish periods, and particularly, during stock market crashes.

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Recurrent castration resistant prostate cancer remains a challenge for cancer therapies and novel treatment options in addition to current anti-androgen and mitosis inhibitors are needed. Aberrations in epigenetic enzymes and chromatin binding proteins have been linked to prostate cancer and they may form a novel class of drug targets in the future. In this thesis we systematically evaluated the epigenenome as a prostate cancer drug target. We functionally silenced 615 known and putative epigenetically active protein coding genes in prostate cancer cell lines using high throughput RNAi screening and evaluated the effects on cell proliferation, androgen receptor (AR) expression and histone patterns. Histone deacetylases (HDACs) were found to regulate AR expression. Furthermore, HDAC inhibitors reduced AR signaling and inhibited synergistically with androgen deprivation prostate cancer cell proliferation. In particular, TMPRSS2- EGR fusion gene positive prostate cancer cell lines were sensitive to combined HDAC and AR inhibition, which may partly be related to the dependency of a fusion gene induced epigenetic pathway. Histone demethylases (HDMs) were identified to regulate prostate cancer cell line proliferation. We discovered a novel histone JmjC-domain histone demethylase PHF8 to be highly expressed in high grade prostate cancers and mediate cell proliferation, migration and invasion in in vitro models. Additionally, we explored novel HDM inhibitor chemical structures using virtual screening methods. The structures best fitting to the active pocket of KDM4A were tested for enzyme inhibition and prostate cancer cell proliferation activity in vitro. In conclusion, our results show that prostate cancer may efficiently be targeted with combined AR and HDAC inhibition which is also currently being tested in clinical trials. HDMs were identified as another feasible novel drug target class. Future studies in representative animal models and development of specific inhibitors may reveal HDMs full potential in prostate cancer therapy

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The purpose of this thesis was to study the design of demand forecasting processes. A literature review in the field of forecasting was conducted, including general forecasting process design, forecasting methods and techniques, the role of human judgment in forecasting and forecasting performance measurement. The purpose of the literature review was to identify the important design choices that an organization aiming to design or re-design their demand forecasting process would have to make. In the empirical part of the study, these choices and the existing knowledge behind them was assessed in a case study where a demand forecasting process was re-designed for a company in the fast moving consumer goods business. The new target process is described, as well as the reasoning behind the design choices made during the re-design process. As a result, the most important design choices are highlighted, as well as their immediate effect on other processes directly tied to the demand forecasting process. Additionally, some new insights on the organizational aspects of demand forecasting processes are explored. The preliminary results indicate that in this case the new process did improve forecasting accuracy, although organizational issues related to the process proved to be more challenging than anticipated.

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The three alpha2-adrenoceptor (alpha2-AR) subtypes belong to the G protein-coupled receptor superfamily and represent potential drug targets. These receptors have many vital physiological functions, but their actions are complex and often oppose each other. Current research is therefore driven towards discovering drugs that selectively interact with a specific subtype. Cell model systems can be used to evaluate a chemical compound's activity in complex biological systems. The aim of this thesis was to optimize and validate cell-based model systems and assays to investigate alpha2-ARs as drug targets. The use of immortalized cell lines as model systems is firmly established but poses several problems, since the protein of interest is expressed in a foreign environment, and thus essential components of receptor regulation or signaling cascades might be missing. Careful cell model validation is thus required; this was exemplified by three different approaches. In cells heterologously expressing alpha2A-ARs, it was noted that the transfection technique affected the test outcome; false negative adenylyl cyclase test results were produced unless a cell population expressing receptors in a homogenous fashion was used. Recombinant alpha2C-ARs in non-neuronal cells were retained inside the cells, and not expressed in the cell membrane, complicating investigation of this receptor subtype. Receptor expression enhancing proteins (REEPs) were found to be neuronalspecific adapter proteins that regulate the processing of the alpha2C-AR, resulting in an increased level of total receptor expression. Current trends call for the use of primary cells endogenously expressing the receptor of interest; therefore, primary human vascular smooth muscle cells (SMC) expressing alpha2-ARs were tested in a functional assay monitoring contractility with a myosin light chain phosphorylation assay. However, these cells were not compatible with this assay due to the loss of differentiation. A rat aortic SMC cell line transfected to express the human alpha2B-AR was adapted for the assay, and it was found that the alpha2-AR agonist, dexmedetomidine, evoked myosin light chain phosphorylation in this model.

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Ambitious energy targets set by EU put pressures to increase share of renewable electricity supply in this and next decades and therefore, some EU member countries have boosted increasing renewable energy generation capacity by implementing subsidy schemes on national level. In this study, two different change approaches to increase renewable energy supply and increase self-sufficiency of supply are assessed with respect to their impacts on power system, electricity market and electricity generation costs in Finland. It is obtained that the current electricity generation costs are high compared to opportunities of earnings from present-day investor’s perspective. In addition, the growth expectations of consumptions and the price forecasts do not stimulate investing in new generation capacity. Revolutionary transition path is driven by administrative and political interventions to achieve the energy targets. Evolutionary transition path is driven by market-based mechanisms, such as market itself and emission trading scheme. It is obtained in this study that in the revolutionary transition path operation of market-based mechanisms is distorted to some extent and it is likely that this path requires providing more public financial resources compared to evolutionary transition path. In the evolutionary transition path the energy targets are not achieved as quickly but market-based mechanisms function better and investment environment endures more stable compared to revolutionary transition path.