Neurocognitive changes in early-stage Parkinson's disease : functional and structural brain correlates of memory and verbal functions

Resultaten påvisade små, men mätbara försämringar i minnes- och verbal förmåga hos personer som haft Parkinsons sjukdom under tre år. Jämfört med en kontrollgrupp uppvisade Parkinsonpatienter avvikande responser i hjärnans elektriska aktivitet under en korttidsminnesuppgift, och de presterade även sämre i olika typer av andra minnesuppgifter. Försämring i en specifik typ av minnesuppgift korrelerade med förminskad volym i höger hjärnhalva. Samband hittades också mellan sämre verbal förmåga och förminskad volym i djupa hjärnstrukturer. Förminskad hjärnvolym har tidigare påvisats hos dementa patienter i senare sjukdomsstadier. Forskningsresultaten bidrar med ny kunskap om kognitiva symptom och deras neurala bakgrund vid Parkinsons sjukdom. De tyder också på att tidig kognitiv funktionsnedsättning kan identifieras, vilket kan bidra till utvecklingen av sjukdomens behandling. Parkinsons sjukdom är den näst vanligaste neurogeriatriska sjukdomen efter Alzheimers sjukdom. Symptomen uppstår som följd av förminskad produktion av hjärnans transmittorämne dopamin. Parkinsons sjukdom har traditionellt betraktats som en progressiv motorisk sjukdom. Ny forskning tyder på att multipla hjärnsystem skadas, vilket resulterar i att även tankeprocesser påverkas. 75-80% uppskattas insjukna i demens 10-15 år efter diagnos, men det kognitiva sjukdomsförloppet och orsaken till demenssymptomen är tillsvidare okänd. I Finland uppskattas ca 10-12 000 personer ha Parkinsons sjukdom, varav ca 3 000 uppskattas ha demens. ----------------------------------------------------------------------------------------------------------------------------------------------------- Tutkimuksessa todettiin lieviä muutoksia muisti- ja kielellisissä toiminnoissa alle kolme vuotta sairastaneilla Parkinson-potilailla. Potilailla havaittiin poikkeavia aivosähkötoiminnan vasteita lyhytkestoista muistia mittaavan tehtävän aikana. Potilaat suoriutuivat myös verrokkiryhmää heikommin useissa muistitehtävissä. Heikentynyt tahaton muisti liittyi pienempään aivokuoren harmaan aineen paikalliseen tilavuuteen. Heikompi kielellinen suoriutuminen liittyi pienempään harmaan aineen tilavuuteen aivojen syvissä rakenteissa. Pienentyneitä aivorakenteiden tilavuuksia on aiemmin todettu dementoituneilla Parkinson-potilailla sairauden myöhemmissä vaiheissa. Tutkimustulokset tuovat uutta tietoa Parkinsonin taudin kognitiivisista oireista ja niiden aivoperäisestä taustasta. Tulosten perusteella on mahdollista tunnistaa jo varhaisia kognitiivisia muutoksia, mikä voi mahdollistaa tehokkaamman hoidon kohdentamisen. Parkinsonin tauti on Alzheimerin taudin jälkeen toiseksi yleisin neurogeriatrinen sairaus. Oirekuva liittyy aivojen dopaminergisen järjestelmän rappeutumiseen. Perinteisesti liikehäiriösairaudeksi luokiteltu sairaus vaurioittaa lukuisia muita aivojärjestelmiä aiheuttaen muutoksia myös mm. ajattelutoiminnoissa. Pitkään sairastaneista 75–80 prosentilla esiintyy dementiaoireita, mutta oireiden syy ja kehityskaari tunnetaan toistaiseksi huonosti. Suomessa on arviolta 10–12 000 Parkinson-potilasta, joista noin 3 000 arvioidaan kärsivän dementiaoireista.

Excessive functions, Appell polynomials and optimal stopping

The main topic of the thesis is optimal stopping. This is treated in two research articles. In the first article we introduce a new approach to optimal stopping of general strong Markov processes. The approach is based on the representation of excessive functions as expected suprema. We present a variety of examples, in particular, the Novikov-Shiryaev problem for Lévy processes. In the second article on optimal stopping we focus on differentiability of excessive functions of diffusions and apply these results to study the validity of the principle of smooth fit. As an example we discuss optimal stopping of sticky Brownian motion. The third research article offers a survey like discussion on Appell polynomials. The crucial role of Appell polynomials in optimal stopping of Lévy processes was noticed by Novikov and Shiryaev. They described the optimal rule in a large class of problems via these polynomials. We exploit the probabilistic approach to Appell polynomials and show that many classical results are obtained with ease in this framework. In the fourth article we derive a new relationship between the generalized Bernoulli polynomials and the generalized Euler polynomials.

Vesicular Trafficking in Osteoclasts

Osteoclasts are multinucleated bone-degrading cells that undergo large changes in their polarisation and vesicular trafficking during the bone resorption cycle. Rab proteins are small GTPases that offer both temporal and spatial regulation to the transport between membranous organelles. Previously the presence and function of only few of the currently known 60 Rab proteins in osteoclasts have been reported. In this study, the expression of 26 Rab genes in bone-resorbing osteoclasts was demonstrated with gene-specific primer pairs. The further analysis of three Rab genes during human osteoclast differentiation revealed that Rab13 gene is highly induced during osteoclastogenesis. The presence of Rab13 protein in the secretory vesicles directed towards the ruffled border and in the endocytotic or transcytotic pathways in resorbing osteoclasts was excluded. The localisation of Rab13 suggests that that it is associated with a previously unknown vesicle population travelling between the trans-Golgi network and the basolateral membrane in bone resorbing osteoclasts. Rab proteins convey their functions by binding to specific effector proteins. We found a novel Rab13 interaction with endospanins-1 and -2 that are yet poorly characterised small transmembrane proteins. The Rab13 subfamily member Rab8 also bound to endospanins, while Rab10 and unrelated Rabs did not. Rab13 and endospanin-2 co-localised in perinuclear vesicles in transfected cells, demonstrating the interaction also in vivo. The inhibition of Rab13 did not interfere with the localisation of endospanin-2 nor did it affect the cell surface expression of growth hormone receptor, as has been previously described for endospanins. The physiological role of this novel protein-protein interaction thus remains to be clarified. The analysis of the transcytotic route in bone resorbing osteoclasts revealed that multiple vesicle populations arise from the ruffled border and transport the bone degradation products for exocytosis. These vesicles are directed to the functional secretory domain that is encircled by an actin-based molecular barrier. Furthermore, the transcytotic vesicles contain abundant Helix pomatia lectin binding sites and represent lipid raft concentrates. Finally, autophagosomal compartments may also be involved in the transcytosis.

Bio-ethanol valorization towards C4s including 1-butanol over metal modified alumina and zeolite catalysts

Bio-ethanol has been used as a fuel additive in modern society aimed at reducing CO2-emissions and dependence on oil. However, ethanol is unsuitable as fuel supplement in higher proportions due to its physico-chemical properties. One option to counteract the negative effects is to upgrade ethanol in a continuous fixed bed reactor to more valuable C4 products such as 1-butanol providing chemical similarity with traditional gasoline components. Bio-ethanol based valorization products also have other end-uses than just fuel additives. E.g. 1-butanol and ethyl acetate are well characterised industrial solvents and platform chemicals providing greener alternatives. The modern approach is to apply heterogeneous catalysts in the investigated reactions. The research was concentrated on aluminium oxide (Al2O3) and zeolites that were used as catalysts and catalyst supports. The metals supported (Cu, Ni, Co) gave very different product profiles and, thus, a profound view of different catalyst preparation methods and characterisation techniques was necessary. Additionally, acidity and basicity of the catalyst surface have an important role in determining the product profile. It was observed that ordinary determination of acid strength was not enough to explain all the phenomena e.g. the reaction mechanism. One of the main findings of the thesis is based on the catalytically active site which originates from crystallite structure. As a consequence, the overall evaluation of different by-products and intermediates was carried out by combining the information. Further kinetic analysis was carried out on metal (Cu, Ni, Co) supported self-prepared alumina catalysts. The thesis gives information for further catalyst developments aimed to scale-up towards industrially feasible operations.

PDM system functions and utilizations analysis to improve efficiency of sheet metal product design and manufacturing

This study will concentrate on Product Data Management (PDM) systems, and sheet metal design features and classification. In this thesis, PDM is seen as an individual system which handles all product-related data and information. The meaning of relevant data is to take the manufacturing process further with fewer errors. The features of sheet metals are giving more information and value to the designed models. The possibility of implementing PDM and sheet metal features recognition are the core of this study. Their integration should make the design process faster and manufacturing-friendly products easier to design. The triangulation method is the basis for this research. The sections of this triangle are: scientific literature review, interview using the Delphi method and the author’s experience and observations. The main key findings of this study are: (1) the area of focus in triangle (the triangle of three different point of views: business, information exchange and technical) depends on the person’s background and their role in the company, (2) the classification in the PDM system (and also in the CAD system) should be done using the materials, tools and machines that are in use in the company and (3) the design process has to be more effective because of the increase of industrial production, sheet metal blank production and the designer’s time spent on actual design and (4) because Design For Manufacture (DFM) integration can be done with CAD-programs, DFM integration with the PDM system should also be possible.

Possibility to add a barrier layer to a fibre tray package in the moulding stage

The main objective of the present study was to analyze the best approach on how to coat paperboard trays at the pressing stage. The coating gives the paperboard enhanced barrier and mechanical properties. The whole process chain of the barrier coating development was studied in the research. The methodology applied includes obtaining the optimum temperature at which good adhesion and bonding is formed between paperboard and skin film. Evaluation of mechanical properties after the coatings; such as cracking, curling and barrier properties was performed.

Modified nano- and microcellulose based adsorption materials in water treatment

In recent decades, industrial activity growth and increasing water usage worldwide have led to the release of various pollutants, such as toxic heavy metals and nutrients, into the aquatic environment. Modified nanocellulose and microcellulose-based adsorption materials have the potential to remove these contaminants from aqueous solutions. The present research consisted of the preparation of five different nano/microcellulose-based adsorbents, their characterization, the study of adsorption kinetics and isotherms, the determination of adsorption mechanisms, and an evaluation of adsorbents’ regeneration properties. The same well known reactions and modification methods that were used for modifying conventional cellulose also worked for microfibrillated cellulose (MFC). The use of succinic anhydride modified mercerized nanocellulose, and aminosilane and hydroxyapatite modified nanostructured MFC for the removal of heavy metals from aqueous solutions exhibited promising results. Aminosilane, epoxy and hydroxyapatite modified MFC could be used as a promising alternative for H2S removal from aqueous solutions. In addition, new knowledge about the adsorption properties of carbonated hydroxyapatite modified MFC as multifunctional adsorbent for the removal of both cations and anions ions from water was obtained. The maghemite nanoparticles (Fe3O4) modified MFC was found to be a highly promising adsorbent for the removal of As(V) from aqueous solutions due to its magnetic properties, high surface area, and high adsorption capacity . The maximum removal efficiencies of each adsorbent were studied in batch mode. The results of adsorption kinetics indicated very fast removal rates for all the studied pollutants. Modeling of adsorption isotherms and adsorption kinetics using various theoretical models provided information about the adsorbent’s surface properties and the adsorption mechanisms. This knowledge is important for instance, in designing water treatment units/plants. Furthermore, the correspondence between the theory behind the model and properties of the adsorbent as well as adsorption mechanisms were also discussed. On the whole, both the experimental results and theoretical considerations supported the potential applicability of the studied nano/microcellulose-based adsorbents in water treatment applications.

Operations management in courts of justice - outlining functions, challenges and development possibilities

Professional services are an increasingly important group of economy and related to them there has been identified a fairly new concept called professional service operations management. However professional service operations management is still quite under-researched area which needs further research especially in specific contexts. This study aims to respond to that need by examining courts as an environment for operations management. As a result there is a preliminary structured description of what operations management is and could be in courts. The study also aims to inspire and tentatively classify possible areas for future research. Courts are examined based on three common perspectives for typical characteristics of professional services which can be identified in literature: the nature of customer role, the nature of professional work and the nature of process and product. The examination is based on research data from several research projects conducted in Finland and other European countries. Based on the examination it can be said that the operational environment of courts is highly complex and demanding because the case as an object of operations management tasks is challenging, the process sets strict requirements to the handling of the cases and the workforce is hard to direct.

Genetically Modified Organisms (GMOs) and Agroecology in Agricultural Production in the United States - A Comparative Analysis.

The world’s population is growing at a rapid rate and one of the primary problems of a growing is food supply. To ensure food supply and security, the biggest companies in the agricultural sector of the United States and all over the world have collaborated to produce genetically modified organisms, including crops, that have a tendency to increase yields and are speculated to reduce pesticide use. It’s a technology that is declared to have a multitude of benefits. During the same time period another set of practices has risen to the horizon by the name of agroecology. It spreads across many different sectors such as politics, sociology, environment, health and so on. Moreover, it involves primitive organic techniques that can be applied at farm level to enhance the performance of an ecosystem to effectively decrease the negative effect on environment and health of individuals while producing good quality foods. Since both the processes proclaim sustainable development, a natural question may come in mind that which one seems more favorable? During the course of this study, genetically modified organisms (GMOs) and agroecology are compared within the sphere of social, environmental and health aspects. The results derived upon a comparative analysis of scientific literature tend to prove that GMOs pose a greater threat to the environment, health of individuals and the generalized social balance in the United States compared to agroecological practices. Economic indicators were not included in the study and more studies might be needed in the future to get a broader view on the subject.

Arduino-pohjainen OBD2-lukija SAE J1850 VPW protokollatuella

Kandidaatintyössä toteutetaan OBD2 (On-Board Diagnostics 2) -lukija ajoneuvon päästöjenhallintajärjestelmän diagnostiikkatiedoille yleiskäyttöisellä mikro-ohjaimella. Lukija tukee tiedonsiirtoprotokollana SAE J1850 VPW protokollaa. Mikro-ohjaimena on Atmel Corporationin AVR ATMega328. Työn tavoitteena on havainnoida vastaantulevia käytännön ongelmia ja haasteita mikro-ohjaimen käytöllä tiedonsiirtoprotokollan toteutukseen, ja verrata toteutettua järjestelmää kaupallisiin OBD2-lukijoihin. Työn johtopäätöksenä havaitaan mikro-ohjaimen suorituskyvyn rajoitteet ja sen tuomat toiminnan epävarmuustekijät. Työssä myös todetaan, että mikro-ohjain soveltuu tiedonsiirtoprotokollan toteutukseen kun rajoitteet otetaan huomioon. Kaupallisiin lukijoihin verrattuna yleiskäyttöiseen mikro-ohjaimeen perustuva toteutettu järjestelmä on kalliimpi ja toiminnoiltaan suppeampi. Mikro-ohjaimeen perustuva järjestelmä on kuitenkin muokattavissa ja laajennettavissa tarvittaessa, jolloin toteutukseen voidaan saada kaupallisista järjestelmistä mahdollisesti puuttuvia ominaisuuksia, kuten valmistajakohtaisia protokollia ja toimintoja, joita ei ole määritelty OBD2:ssa. Yhtenä esimerkkinä tällaisesta toiminnosta voi mainita ajoneuvoissa yleistyvän sähköisen käsijarrun säätöä ohjaavat komennot jarruhuoltoa varten.

Metal-Ion-Binding Oligonucleotides: High-Affinity Probes for Nucleic Acid Sequences

Small non-coding RNAs have numerous biological functions in cell and are divided into different classes such as: microRNA, snoRNA, snRNA and siRNA. MicroRNA (miRNA) is the most studied non-coding RNA to date and is found in plants, animals and some viruses. miRNA with short sequences is involved in suppressing translation of target genes by binding to their mRNA post-transcriptionally and silencing it. Their function besides silencing of the viral gene, can be oncogenic and therefore the cause of cancer. Hence, their roles are highlighted in human diseases, which increases the interest in using them as biomarkers and drug targets. One of the major problems to overcome is recognition of miRNA. Owing to a stable hairpin structure, chain invasion by conventional Watson-Crick base-pairing is difficult. One way to enhance the hybridization is exploitation of metal-ion mediated base-pairing, i. e. oligonucleotide probes that tightly bind a metal ions and are able to form a coordinative bonds between modified and natural nucleobases. This kind of metallo basepairs containing short modified oligonucleotides can also be useful for recognition of other RNA sequences containing hairpin-like structural motives, such as the TAR sequence of HIV. In addition, metal-ion-binding oligonucleotides will undoubtedly find applications in DNA-based nanotechnology. In this study, the 3,5-dimethylpyrazol-1-yl substituted purine derivatives were successfully incorporated within oligonucleotides, into either a terminal or non-terminal position. Among all of the modified oligonucleotides studied, a 2-(3,5-dimethylpyrazol-1-yl)-6-oxopurine base containing oligonucleotide was observed to bind most efficiently to their unmodified complementary sequences in the presence of both Cu2+ or Zn2+. The oligonucleotide incorporating 2,6-bis(3,5-dimethylpyrazol-1-yl)purine base also markedly increased the stability of duplexes in the presence of Cu2+ without losing the selectivity.

Hävittäjäohjaajan kognitiivisen kuormituksen tason mittaaminen NASA-Task Load Index ja Modified Cooper-Harper -mittareilla F/A-18 virtuaalisimulaattorissa

F/A-18-monitoimihävittäjän ohjaajan tehtävän kognitiiviset vaatimukset ovat korkeat. Kognitiivisen kuormituksen taso vaikuttaa hävittäjäohjaajan suoritustasoon ja subjektiivisiin tun-temuksiin. Yerkesin ja Dodsonin periaatteen mukaisesti erittäin matala tai erittäin korkea kuormituksen taso laskee suoritustasoa. Optimaalinen kuormituksen taso ja suoritustaso saa-vutetaan jossain ääripäiden välillä. Hävittäjäohjaajan kognitiivisen kuormituksen tasoon vaikuttaa lentotehtävän suorittamiseen vaadittava henkinen ponnistelu. Vaadittavan ponnistelun taso riippuu tehtävien vaatimustasosta ja määrästä, tehtäviin käytettävissä olevasta ajasta sekä yksilöllisistä ominaisuuksista. Tutkimuksessa mitattiin kognitiivisen kuormituksen tasoa subjektiivisen arvioinnin menetelmällä NASA-TLX (National Aeronautics and Space Administration - Task Load Index) ja MCH (Modified Cooper-Harper) -mittareilla. Tutkimuksessa selvitettiin mittareiden havaintoarvojen muutosta, sensitiivisyyttä ja yhdenmukaisuutta kognitiivisen kuormituksen tason muuttuessa. Tutkimuksen mittauksiin osallistui 35 Suomen ilmavoimien aktiivisessa palveluksessa olevaa F/A-18-monitoimihävittäjäohjaajaa. Koehenkilöiden lentotuntien keskiarvo F/A-18-monitoimihävittäjällä oli 598 tuntia ja keskihajonta 445 tuntia. Koehenkilöiden tehtävänä oli lentää F/A-18-virtuaalisimulaattorilla 11 ILS (Instrument Landing System) -mittarilähestymistä eri aloitusetäisyyksiltä kiitotien kynnyksestä. Kognitiivisesti kuormitta-van mittarilähestymistehtävän aikana kuormituksen tasoa nostettiin lisätehtävillä ja vähentä-mällä tehtäviin käytettävissä olevaa aikaa. Koehenkilöitä pyydettiin ponnistelemaan mahdollisimman paljon tehtävien suorittamisen aikana hyvän suoritustason ylläpitämiseksi. Tulosten perusteella mittareiden havaintoarvot muuttuivat kognitiivisen kuormituksen tason muuttuessa. Käytettävissä olevan ajan vaikutus kognitiivisen kuormituksen tasoon oli tilastollisesti erittäin merkitsevä. Mittarit olivat sensitiivisiä kognitiivisen kuormituksen tason muutokselle ja antoivat yhdenmukaisia havaintoarvoja.

Customer Need Assessment for Differentiation in Building Information Modeling

Building Information Modeling – BIM is widely spreading in the Architecture, Engineering, and Construction (AEC) industries. Manufacturers of building elements are also starting to provide more and more objects of their products. The ideal availability and distribution for these models is not yet stabilized. Usual goal of a manufacturer is to get their model into design as early as possible. Finding the ways to satisfy customer needs with a superior service would help to achieve this goal. This study aims to seek what case company’s customers want out of the model and what they think is the ideal way to obtain these models and what are the desired functionalities for this service. This master’s thesis uses a modified version of lead user method to gain understanding of what the needs are in a longer term. In this framework also benchmarking of current solutions and their common model functions is done. Empirical data is collected with survey and interviews. As a result this thesis provides understanding that what is the information customer uses when obtaining a model, what kind of model is expected to be achieved and how is should the process optimally function. Based on these results ideal service is pointed out.