Molecular diagnostics of rare inherited SYNDROMES with a view on diagnostic test development

CHARGE syndrome, Sotos syndrome and 3p deletion syndrome are examples of rare inherited syndromes that have been recognized for decades but for which the molecular diagnostics only have been made possible by recent advances in genomic research. Despite these advances, development of diagnostic tests for rare syndromes has been hindered by diagnostic laboratories having limited funds for test development, and their prioritization of tests for which a (relatively) high demand can be expected. In this study, the molecular diagnostic tests for CHARGE syndrome and Sotos syndrome were developed, resulting in their successful translation into routine diagnostic testing in the laboratory of Medical Genetics (UTUlab). In the CHARGE syndrome group, mutation was identified in 40.5% of the patients and in the Sotos syndrome group, in 34%, reflecting the use of the tests in routine diagnostics in differential diagnostics. In CHARGE syndrome, the low prevalence of structural aberrations was also confirmed. In 3p deletion syndrome, it was shown that small terminal deletions are not causative for the syndrome, and that testing with arraybased analysis provides a reliable estimate of the deletion size but benign copy number variants complicate result interpretation. During the development of the tests, it was discovered that finding an optimal molecular diagnostic strategy for a given syndrome is always a compromise between the sensitivity, specificity and feasibility of applying a new method. In addition, the clinical utility of the test should be considered prior to test development: sometimes a test performing well in a laboratory has limited utility for the patient, whereas a test performing poorly in the laboratory may have a great impact on the patient and their family. At present, the development of next generation sequencing methods is changing the concept of molecular diagnostics of rare diseases from single tests towards whole-genome analysis.

Repair of segmental bone defects with fiber-reinforced composite: a study of material development and an animal model on rabbits

The Repair of segmental defects in load-bearing long bones is a challenging task because of the diversity of the load affecting the area; axial, bending, shearing and torsional forces all come together to test the stability/integrity of the bone. The natural biomechanical requirements for bone restorative materials include strength to withstand heavy loads, and adaptivity to conform into a biological environment without disturbing or damaging it. Fiber-reinforced composite (FRC) materials have shown promise, as metals and ceramics have been too rigid, and polymers alone are lacking in strength which is needed for restoration. The versatility of the fiber-reinforced composites also allows tailoring of the composite to meet the multitude of bone properties in the skeleton. The attachment and incorporation of a bone substitute to bone has been advanced by different surface modification methods. Most often this is achieved by the creation of surface texture, which allows bone growth, onto the substitute, creating a mechanical interlocking. Another method is to alter the chemical properties of the surface to create bonding with the bone – for example with a hydroxyapatite (HA) or a bioactive glass (BG) coating. A novel fiber-reinforced composite implant material with a porous surface was developed for bone substitution purposes in load-bearing applications. The material’s biomechanical properties were tailored with unidirectional fiber reinforcement to match the strength of cortical bone. To advance bone growth onto the material, an optimal surface porosity was created by a dissolution process, and an addition of bioactive glass to the material was explored. The effects of dissolution and orientation of the fiber reinforcement were also evaluated for bone-bonding purposes. The Biological response to the implant material was evaluated in a cell culture study to assure the safety of the materials combined. To test the material’s properties in a clinical setting, an animal model was used. A critical-size bone defect in a rabbit’s tibia was used to test the material in a load-bearing application, with short- and long-term follow-up, and a histological evaluation of the incorporation to the host bone. The biomechanical results of the study showed that the material is durable and the tailoring of the properties can be reproduced reliably. The Biological response - ex vivo - to the created surface structure favours the attachment and growth of bone cells, with the additional benefit of bioactive glass appearing on the surface. No toxic reactions to possible agents leaching from the material could be detected in the cell culture study when compared to a nontoxic control material. The mechanical interlocking was enhanced - as expected - with the porosity, whereas the reinforcing fibers protruding from the surface of the implant gave additional strength when tested in a bone-bonding model. Animal experiments verified that the material is capable of withstanding load-bearing conditions in prolonged use without breaking of the material or creating stress shielding effects to the host bone. A Histological examination verified the enhanced incorporation to host bone with an abundance of bone growth onto and over the material. This was achieved with minimal tissue reactions to a foreign body. An FRC implant with surface porosity displays potential in the field of reconstructive surgery, especially regarding large bone defects with high demands on strength and shape retention in load-bearing areas or flat bones such as facial / cranial bones. The benefits of modifying the strength of the material and adjusting the surface properties with fiber reinforcement and bone-bonding additives to meet the requirements of different bone qualities are still to be fully discovered.

Goodrich "High test" drivrem

kuv., 8 x 15 cm

Goodrich "High-test" drivrem

kuv., 10 x 15 cm

Goodrich "High-test" konehihnat

kuv., 10 x 15 cm

Goodrich "High test" konehihna

kuv., 8 x 15 cm

Goodrich "High-test" drivrem

kuv., 10 x 15 cm

Goodrich "High-test" konehihnat

kuv., 10 x 15 cm

One chip solution for low-cost active magnetic bearing system

In this work the implementation of the active magnetic bearing control system in a single FPGA is studied. Requirements for the full magnetic bearing control system are reviewed. Different control methods for active magnetic bearings are described shortly. Flux and the current base controllers are implemented in a FPGA. Suitability of the con-trollers for a low-cost magnetic bearing application is studied. Floating-point arithmetic’s are used in the controllers to ease designing burden and improve calculation precision. Per-formance of the flux controller is verified with simulations.

Sähkömoottorin etäohjausjärjestelmän suunnittelu ja testaus

Tämä kandityön aihe liittyy LUT Energialla lukuvuonna 2012 – 2013 käynnissä olevaan tutkimukseen, jossa tutkitaan sähkömoottorin laakerivirtojen syntyä. Tätä tutkimusta varten tarvittiin sähkömoottorin etäohjausjärjestelmä, jonka avulla tutkimuksessa käytettävän sähkömoottorin käyttäytymistä voitaisiin tutkia erilaisien käyttöprofiileiden funktiona. Tässä kandityössä suunnitellaan ja toteutetaan edellä kuvattu järjestelmä. Toteutuksessa hyödynnetään nykyaikaista automaatiotekniikkaa, joka yhdessä Ethernet-lähiverkkotekniikan kanssa mahdollistaa etäohjauksen. Valmiin etäohjausjärjestelmän avulla käyttäjä pystyy sekä käynnistämään että sammuttamaan sähkömoottorin, ja määrittämään käyttöprofiilin ON- ja OFF-tilojen ajalliset kestot sekä käyntinopeudet.

Design of a Test Stand for a Centrifugal Compressor

The goal of the Master’s thesis is to design a test stand for a centrifugal compressor. Different theoretical aspects of flow parameters measurements and test rigs built for the similar purposes in other research units are described in the theoretical part of the work. The process of components selection and the description of chosen components are given in the second part of the thesis. Besides measuring and control stages, the designed test stand has a closed-loop piping, an aftercooler and a surge tank. Overview and layout of the test rig is presented in the last chapter of the work.

Unidirectional fiber-reinforced composite as an oral implant abutment material: Experimental studies of E-glass fiber/BisGMA-TEGDMA polymer in vitro

Fiber-reinforced composites (FRCs) are a new group of non-metallic biomaterials showing a growing popularity in many dental and medical applications. As an oral implant material, FRC is biocompatible in bone tissue environment. Soft tissue integration to FRC polymer material is unclear. This series of in vitro studies aimed at evaluating unidirectional E-glass FRC polymer in terms of mechanical, chemical, and biological properties in an attempt to develop a new non-metallic oral implant abutment alternative. Two different types of substrates were investigated: (a) Plain polymer (BisGMA 50%–TEGDMA 50%) and (b) Unidirectional FRC. The mechanical behavior of high fiber-density FRCs was assessed using a three-point bending test. Surface characterization was performed using scanning electron and spinning disk confocal microscopes. The surface wettability/energy was determined using sessile drop method. The blood response, including blood-clotting ability and platelet morphology was evaluated. Human gingival fibroblast cell responses - adhesion kinetics, adhesion strength, and proliferation activity - were studied in cell culture environment using routine test conditions. A novel tissue culture method was developed and used to evaluate porcine gingival tissue graft attachment and growth on the experimental composite implants. The analysis of the mechanical properties showed that there is a direct proportionality in the relationship between E-glass fiber volume fraction and toughness, modulus of elasticity, and load bearing capacity; however, flexural strength did not show significant improvement when high fiber-density FRC is used. FRCs showed moderate hydrophilic properties owing to the presence of exposed glass fibers on the polymer surface. Blood-clotting time was shorter on FRC substrates than on plain polymer. The FRC substrates also showed higher platelet activation state than plain polymer substrates. Fibroblast cell adhesion strength and proliferation rate were highly pronounced on FRCs. A tissue culture study revealed that gingival epithelium and connective tissue established an immediate close contact with both plain polymer and FRC implants. However, FRC seemed to guide epithelial migration outwards from the tissue/implant interface. Due to the anisotropic and hydrophilic nature of FRC, it can be concluded that this material enhances biological events related with soft tissue integration on oral implant surface.

Aktiivisen verkkosillan tuottaman yhteismuotoisen jännitteen vaimentaminen kaksitasoisessa, jännitevälipiirillisessä, taajuusmuuttajatopologiassa

Pulssinleveysmoduloidun vaihtosuuntaajan hyötysuhteen parantaminen ja kytkentätaajuuden suurentaminen ovat johtaneet lähtöjännitteen suuritaajuiseen taajuussisältöön kaksitasoisessa, jännitevälipiirillisessä taajuusmuuttajatopologiassa. Kasvava tarve siirtää tehoa myös verkkoon päin on lisännyt aktiivisen verkkosillan käyttöä. Kaksitasoisen aktiivisen verkkosillan vaikutuksesta DC-välipiirin keskipisteen ja kolmivaiheisen kuorman tähtipisteen välinen jännite on nollasta poikkeava aiheuttaen suurentuneen yhteismuotoisen jännitteen taajuusmuuttajan lähtöön ja verkon puolelle. Lisäksi yhteismuotoisten jännitteiden aiheuttamat kytkentätaajuiset häiriövirrat voivat aiheuttaa vikavirtasuojien tahatonta laukeamista, vaikeuttaa EMC-standardien vaatimusten täyttämistä, lisätä moottorin käämieristyksien rasitusta ja mahdollisuutta moottorin laakerivaurioille. Diplomityössä tutkitaan aktiivisen ja passiivisen verkkosillan tuottamaa yhteismuotoista jännitettä simuloinneilla. Esitellään aikaisempaa tutkimustietoa yhteismuotoisen jännitteen ja virran vaimennusratkaisuista aktiivista verkkosiltaa käytettäessä. Tutkimustiedon pohjalta suunnitellaan koelaitteistolle soveltuva suodin. Suotimen toiminta testataan simuloinnein sekä kokeellisin mittauksin. Tehdyt mittaukset osoittavat, että suunniteltu suodin vaimentaa yhteismuotoista jännitettä noin 20 dB verkkosillan kytkentätaajuudella ja tämän jälkeen yli 20 dB/dekadi taajuuteen 100 kHz asti. Lisäksi yhteismuotoisen virran suuruus syöttökaapelin kautta pieneni ehdotetun suotimen vaikutuksesta.