Homogeneous Assays for Simplified Screening of HLA-conferred Genetic Disease Risk

The increasing incidence of type 1 diabetes has led researchers on a quest to find the reason behind this phenomenon. The rate of increase is too great to be caused simply by changes in the genetic component, and many environmental factors are under investigation for their possible contribution. These studies require, however, the participation of those individuals most likely to develop the disease, and the approach chosen by many is to screen vast populations to find persons with increased genetic risk factors. The participating individuals are then followed for signs of disease development, and their exposure to suspected environmental factors is studied. The main purpose of this study was to find a suitable tool for easy and inexpensive screening of certain genetic risk markers for type 1 diabetes. The method should be applicable to using whole blood dried on sample collection cards as sample material, since the shipping and storage of samples in this format is preferred. However, the screening of vast sample libraries of extracted genomic DNA should also be possible, if such a need should arise, for example, when studying the effect of newly discovered genetic risk markers. The method developed in this study is based on homogeneous assay chemistry and an asymmetrical polymerase chain reaction (PCR). The generated singlestranded PCR product is probed by lanthanide-labelled, LNA (locked nucleic acid)-spiked, short oligonucleotides with exact complementary sequences. In the case of a perfect match, the probe is hybridised to the product. However, if even a single nucleotide difference occurs, the probe is bound instead of the PCR product to a complementary quencher-oligonucleotide labelled with a dabcyl-moiety, causing the signal of the lanthanide label to be quenched. The method was applied to the screening of the well-known type 1 diabetes risk alleles of the HLA-DQB1 gene. The method was shown to be suitable as an initial screening step including thousands of samples in the scheme used in the TEDDY (The Environmental Determinants of Diabetes in the Young) study to identify those individuals at increased genetic risk. The method was further developed into dry-reagent form to allow an even simpler approach to screening. The reagents needed in the assay were in dry format in the reaction vessel, and performing the assay required only the addition of the sample and, if necessary, water to rehydrate the reagents. This allows the assay to be successfully executed even by a person with minimal laboratory experience.

Sotkuinen näkökulma hallintoon

Kirjallisuusarvostelu

Tuotannonsuunnittelu- ja -ohjausprosessin kehittäminen konepajayrityksessä

Tehdyssä kirjallisuus- ja teoriakatsauksessa vuosien 2006 - 2010 välisenä aikana, Keski-Suomessa toimivan konepajateollisuuden järjestelmätoimittajayrityksen toimeksiannosta, pyrittiin muodostamaan kokonaiskuva laajasta tuotannonsuunnittelun ja -ohjauksen aihealueesta. Perustutkimuskysymykset liittyivät ns. MPC-systeemiin, jolla tarkoitetaan sitä, että tuotannonsuunnittelu- ja ohjauskysymyksissä on huomioitava aina henkilöiden, organisaation, teknologioiden ja prosessien muodostama kokonaisuus. Operatiivisen johtamisen tehtävänä on yrityksen tuotteita koskevan kysynnän ja tarjonnan tasapainottaminen niin, että resursseja käytettäisiin ja tarvittaisiin mahdollisimman vähän vastattaessa kysyntään asiakasvaatimukset huomioiden. Tuotantostrategian pohjalta on voitava rakentaa MPC-systeemi, jonka avulla ja jota kehittäen tuotanto saavuttaisi sille asetetut suorituskykytavoitteet mm. kustannusten, laadun, nopeuden, luotettavuuden sekä tuottavuuskehityksen osalta. Työssä tarkasteltiin yleisen kolmitasoisen viitekehyksen kautta ”perinteisistä MPC-systeemien perusratkaisuista” hierarkkisia, suunnittelu- ja laskentaintensiiviä, MRP-pohjaisia sekä yksinkertaistamiseen ja nopeuteen perustuvia JIT/Lean -menetelmiä. Tämä viitekehys käsittää: 1) kysynnän- ja resurssien hallinnan, 2) yksityiskohtaisemman kapasiteetin ja materiaalien hallinnan sekä 3) tarkemman tuotannon ja hankintojen ohjauksen sekä tuotannon lattiatason osa-alueet. Johtamisen ja MPC-systeemien kehittämisen ”uusina aaltoina ja näkökulmina” raportissa käsiteltiin myös johtamisen eri koulukuntia sekä em. viitekehyksen pohjalta tarvittavia tietojärjestelmiä. Olennaisimpana johtopäätöksenä todettiin, että MRP-pohjaisten ratkaisujen lisäksi, etenkin monimutkaisia tuotteita tilausohjautuvasti valmistavien kappaletavarateollisuuden yritysten, on mahdollisesti hyödynnettävä myös kehittyneempiä suunnittelu- ja ohjausjärjestelmiä. Lisäksi huomattiin, että ”perinteisten strategioiden” rinnalle yritysten on nostettava myös tieto- ja viestintäteknologiastrategiat. On tärkeää ymmärtää, että täydellistä MPC-systeemiä ei ole vielä keksitty: jokaisen yrityksen tehtäväksi ja vastuulle jää ”oman totuutensa” muodostaminen ja systeeminsä rakentaminen sen pohjalta.

Developing the Sourcing with the Purchasing Tool in the Chemical Company

The aim of this research was to investigate Tikkurila Oyj's Vantaa factories' current status in procurement and to develop the reporting of purchases and purchase warehouses, and to measure the activities during the implementation of the new purchasing tool. The implemented purchasing tool was based on ABC-analysis. Based on its reports the importance of performance measurements for the operations of the company, and the purpose of getting transparency to the company's supply chain on the part of purchasing were examined. A successful purchase- and material operation calls for accurate knowledge and professional skills. The research proved that with a separate purchasing tool, that analyses the existing information of the company's production management system, it is possible to get added value to whole supply chain's needs. The analyses and reports of the purchasing tool enable a more harmonized purchasing process at the operative level, and create a basis for internal targets and to their follow-up. At the same time the analyses clarify the current status and development trends of procurement fresh to the management. The increase of the possibilities of exploitation of information technology enables a perfect transparency to the case company's purchase department.

Seikkaillen kohti sukupuuttoa

Kirjallisuusarvostelu

Lähihistoriaa Kiinan johdon tuuliselta huipulta

Kahden Kiinan lähihistorian pääministerin elämänkerrat.

Verkkokaupan logistiikkaratkaisu

Tässä työssä selvitetään miten peltikattoja ja niiden oheistarvikkeita verkkokaupoissa myyvä yritys voi alkaa myydä ristiin eri valmistajien kattoja ja sadevesijärjestelmiä. Työssä tarkastellaan niin tehokkaan logistiikan kuin verkkokaupan vaatimuksia, sekä sitä miksi näitä tuotteita kannattaa myydä verkkokaupassa eikä perinteiseen tapaan rautakaupoissa. Tehokkaan logistiikan mahdollistamiseksi tuotteiden kokoa on muutettava – pitkien tuotteiden kuljettaminen on aina kallista. On pyrittävä käyttämään standardikokoisia kuljetus- ja käsittely-yksiköitä, jolloin kuljetuskustannukset alenevat ja käsittely helpottuu ja nopeutuu. Runkokuljetuksissa keskusvarastoihin pyritään täysiin kuormiin, kun taas jakelukuljetuksissa asiakkaille on pyrittävä kustannustehokkuuteen ja kattavaan palveluverkostoon, jollaisen tarjoaa esimerkiksi Matkahuolto. Verkkokaupoissa sadevesijärjestelmiä myydään kahdella eri tavalla. Kattopaketti.fi -verkkokaupassa asiakas käyttää kattonsa mitoittamisessa pienoisohjelmaa, johon hän syöttää pyydetyt mitat. Peltikauppa.com toimii tavalliseen tapaan, jolloin asiakas valitsee haluamansa tuotteet valikoimasta. Rakennustarvikkeet ovat puuttuneet verkkokaupoista niiden hankalan logistiikan vuoksi. Tuotteet ovat isoja, kömpelöitä ja niitä tarvitaan määrällisesti paljon. Keskittymällä yhteen tuoteryhmään ja hiomalla sen logistiikka kuntoon, on verkkokaupan kuitenkin mahdollista pystyä kilpailemaan perinteisiä hankintakanavia vastaan.

Risk-return trade-off and autocorrelation

A trade-off between return and risk plays a central role in financial economics. The intertemporal capital asset pricing model (ICAPM) proposed by Merton (1973) provides a neoclassical theory for expected returns on risky assets. The model assumes that risk-averse investors (seeking to maximize their expected utility of lifetime consumption) demand compensation for bearing systematic market risk and the risk of unfavorable shifts in the investment opportunity set. Although the ICAPM postulates a positive relation between the conditional expected market return and its conditional variance, the empirical evidence on the sign of the risk-return trade-off is conflicting. In contrast, autocorrelation in stock returns is one of the most consistent and robust findings in empirical finance. While autocorrelation is often interpreted as a violation of market efficiency, it can also reflect factors such as market microstructure or time-varying risk premia. This doctoral thesis investigates a relation between the mixed risk-return trade-off results and autocorrelation in stock returns. The results suggest that, in the case of the US stock market, the relative contribution of the risk-return trade-off and autocorrelation in explaining the aggregate return fluctuates with volatility. This effect is then shown to be even more pronounced in the case of emerging stock markets. During high-volatility periods, expected returns can be described using rational (intertemporal) investors acting to maximize their expected utility. During lowvolatility periods, market-wide persistence in returns increases, leading to a failure of traditional equilibrium-model descriptions for expected returns. Consistent with this finding, traditional models yield conflicting evidence concerning the sign of the risk-return trade-off. The changing relevance of the risk-return trade-off and autocorrelation can be explained by heterogeneous agents or, more generally, by the inadequacy of the neoclassical view on asset pricing with unboundedly rational investors and perfect market efficiency. In the latter case, the empirical results imply that the neoclassical view is valid only under certain market conditions. This offers an economic explanation as to why it has been so difficult to detect a positive tradeoff between the conditional mean and variance of the aggregate stock return. The results highlight the importance, especially in the case of emerging stock markets, of noting both the risk-return trade-off and autocorrelation in applications that require estimates for expected returns.

Negative refractive index materials and propagation

Negative refractive index materials and propagation of electromagnetic waves in them started to draw attention of scientists not so long ago. This review highlights historically important and recent papers on practical and theoretical aspects related to these issues. Namely, basic properties and peculiarities of such materials related to both their design and wave propagation in them, experimental verification of predictions theoretically made for them, possible practical applications and prospects in this area are considered.

Rising to the impossible challenge: the storage of all research data, forever?

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Predicting bankruptcy of Finnish limited liability companies from historical financial statements

This master’s thesis studies the probability of bankruptcy of Finnish limited liability companies as a part of credit risk assessment. The main idea of this thesis is to build and test bankruptcy prediction models for Finnish limited liability companies that can be utilized in credit decision making. The data used in this thesis consists of historical financial statements from 2112 Finnish limited liability companies, half of which have filed for bankruptcy. A total of four models are developed, two with logistic regression and two with multivariate discriminant analysis (MDA). The time horizon of the models varies from 1 to 2 years prior to the bankruptcy, and 14 different financial variables are used in the model formation. The results show that the prediction accuracy of the models ranges between 81.7% and 88.9%, and the best prediction accuracy is achieved with the one year prior the bankruptcy logistic regression model. However the difference between the best logistic model and the best MDA model is minimal. Overall based on the results of this thesis it can be concluded that predicting bankruptcy is possible to some extent, but naturally the results are not perfect.

Hoitokuluanalyysi Suomen yksityisen sektorin työeläkejärjestelmästä

Tämän pro gradu -tutkielman tavoitteena on tutkia Suomen työeläkevakuutusyhtiöiden työeläkevakuutusmaksun hoitokustannusosalla katettavia liikekuluja ja muodostaa analyysi Suomen työeläkevakuutusjärjestelmän liikekulujen kehittymisestä ja tehokkuuden tasosta. Tehokkuusnäkökulman lisäksi tarkastellaan työeläkejärjestelmän kilpailuolosuhteita. Tutkimusta motivoi työeläkealalle ajankohtainen asia, joka liittyy yhtiökohtaisen hinnoittelumallin mahdolliseen käyttöönottoon, jota parhaillaan suunnitellaan työeläkealan tehokkuuden ja kilpailullisuuden lisäämiseksi. Yhtiökohtaisessa hinnoittelumallissa työeläkeyhtiö voisi itsenäisesti vaikuttaa työeläkevakuutuksen hintaan hoitokustannusosan kautta, joka määräytyisi pitkälti sen mukaan kuinka tehokkaasti yhtiö pystyy toimintansa järjestämään. Empiirinen tutkimus on toteutettu kvalitatiivisena tapaustutkimuksena, jossa kuitenkin empiirinen analyysi perustuu kvantitatiiviseen aineistoon ja aineistoa on käsitelty kvantitatiivisen tutkimuksen menetelmin. Pääasiallisina tutkimusotteina on käytetty taulukointia ja erinäisten muuttujien välistä korrelaatiota. Tuloksien suhteen on käytetty aineistolähtöistä induktiivista päättelyä. Tutkimuksessa on tutkittu seitsemän yksityisen sektorin työeläkeyhtiön liikekuluja vuosilta 2006–2013. Tutkimustuloksien mukaan järjestelmätasolla tarkasteltuna työeläkeyhtiöiden toiminta on tehokasta, joskin yksittäisten yhtiöiden välillä on suuriakin tehokkuuseroja. Vakuutusten ja korvaustoiminnan hoito ovat suurimmat kustannusten aiheuttajat. Työeläkemarkkinat ovat hyvin keskittyneet ja muistuttavat enemmänkin oligopolisia markkinoita kuin täydellisen kilpailun markkinoita.

Artificial reflecting structures based on metamaterials

This thesis studies metamaterial-inspired mirrors which provide the most general control over the amplitude and phase of the reflected wavefront. The goal is to explore practical possibilities in designing fully reflective electromagnetic structures with full control over reflection phase. The first part of the thesis describes a planar focusing metamirror with the focal distance less than the operating wavelength. Its practical applicability from the viewpoint of aberrations when the incident angle deviates from the normal one is verified numerically and experimentally. The results indicate that the proposed focusing metamirror can be efficiently employed in many different applications due to its advantages over other conventional mirrors. In the second part of the thesis a new theoretical concept of reflecting metasurface operation is introduced based on Huygens’ principle. This concept in contrast to known approaches takes into account all the requirements of perfect metamirror operation. The theory shows a route to improve the previously proposed metamirrors through tilting the individual inclusions of the structure at a chosen angle from normal. It is numerically tested and the results demonstrate improvements over the previous design.

Organization of the marketing communication activities after fusion - the integration and the decision making processes

This master’s thesis was made in order to gain answers to the question of how the integration of the marketing communications and the decision making related to it in a geographically dispersed service organization could be improved in a situation where an organization has gone through a merger. The effects of the organizational design dimensions towards the integration of the marketing communications and the decision making related to it was the main focus. A case study as a research strategy offered a perfect frames for an exploratory study and the data collection was conducted by semi-structured interviews and observing. The main finding proved that from the chosen design dimensions, decentralization, coordination and power, could be found specific factors that in a geographically dispersed organization are affecting the integration of the marketing communications negatively. The effects can be seen mostly in the decision making processes, roles and in the division of responsibility, which are affecting the other dimensions and by this, the integration. In a post-merger situation, the coordination dimension and especially the information asymmetry and the information flow seem to have a largest affect towards the integration of the marketing communications. An asymmetric information distribution with the lack of business and marketing education resulted in low self-assurance and at the end in fragmented management and to the inability to set targets and make independent decisions. As conclusions it can be stated, that with the organizational design dimensions can the effects of a merger towards the integration process of the marketing communications to be evaluated.

Market anomalies and tactical asset allocation: Utilising market anomalies in multiple asset class portfolios with the Black−Litterman model

This thesis discusses the basic problem of the modern portfolio theory about how to optimise the perfect allocation for an investment portfolio. The theory provides a solution for an efficient portfolio, which minimises the risk of the portfolio with respect to the expected return. A central feature for all the portfolios on the efficient frontier is that the investor needs to provide the expected return for each asset. Market anomalies are persistent patterns seen in the financial markets, which cannot be explained with the current asset pricing theory. The goal of this thesis is to study whether these anomalies can be observed among different asset classes. Finally, if persistent patterns are found, it is investigated whether the anomalies hold valuable information for determining the expected returns used in the portfolio optimization Market anomalies and investment strategies based on them are studied with a rolling estimation window, where the return for the following period is always based on historical information. This is also crucial when rebalancing the portfolio. The anomalies investigated within this thesis are value, momentum, reversal, and idiosyncratic volatility. The research data includes price series of country level stock indices, government bonds, currencies, and commodities. The modern portfolio theory and the views given by the anomalies are combined by utilising the Black-Litterman model. This makes it possible to optimise the portfolio so that investor’s views are taken into account. When constructing the portfolios, the goal is to maximise the Sharpe ratio. Significance of the results is studied by assessing if the strategy yields excess returns in a relation to those explained by the threefactormodel. The most outstanding finding is that anomaly based factors include valuable information to enhance efficient portfolio diversification. When the highest Sharpe ratios for each asset class are picked from the test factors and applied to the Black−Litterman model, the final portfolio results in superior riskreturn combination. The highest Sharpe ratios are provided by momentum strategy for stocks and long-term reversal for the rest of the asset classes. Additionally, a strategy based on the value effect was highly appealing, and it basically performs as well as the previously mentioned Sharpe strategy. When studying the anomalies, it is found, that 12-month momentum is the strongest effect, especially for stock indices. In addition, a high idiosyncratic volatility seems to be positively correlated with country indices on stocks.