Regulation of epidermal tight junctions by calcium ATPases and p38

The epidermis is the upper layer of the skin and keratinocytes are its most abundant cells. Tight junctions are cell junctions located in the granular layer of the epidermis. They maintain the polarity of the cells and regulate the movement of water-soluble molecules. Epidermal tight junctions may lose their integrity when there are defects in intercellular calcium regulation. Hailey-Hailey and Darier´s disease are dominantly inherited, blistering skin diseases. Hailey-Hailey disease is caused by mutations in the ATP2C1 gene encoding a calcium/manganese ATPase SPCA1 of the Golgi apparatus. Darier´s disease is caused by mutations in the ATP2A2 gene encoding a calcium ATPase SERCA2 of the endoplasmic reticulum. p38 regulates the differentiation of keratinocytes. The overall regulation of epidermal tight junctions is not well understood. The present study examined the regulation of tight junctions in the human epidermis with a focus on calcium ATPases and p38. Skin from Hailey-Hailey and Darier´s disease patients was studied by using immunofluorescence labeling which targeted intercellular junction proteins. Transepidermal water loss was also measured. ATP2C1 gene expression was silenced in cultured keratinocytes, by siRNA, which modeled Hailey-Hailey disease. Expression of intercellular junction proteins was studied at the mRNA and protein levels. Squamous cell carcinoma and normal human keratinocytes were used as a model for impaired and normal keratinocyte differentiation, and the role of p38 isoforms alpha and delta in the regulation of intercellular junction proteins was studied. Both p38 isoforms were silenced by adenovirus cell transduction, chemical inhibitors or siRNA and keratinocyte differentiation was assessed. The results of this thesis revealed that: i.) intercellular junction proteins are expressed normally in acantholytic skin areas of patients with Hailey-Hailey or Darier´s disease but the localization of ZO-1 expanded to the stratum spinosum; ii.) tight junction proteins, claudin-1 and -4, are regulated by ATP2C1 in non-differentiating keratinocytes; and iii.) p38 delta regulates the expression of tight junction protein ZO-1 in proliferating keratinocytes and in squamous cell carcinoma derived cells. ZO-1 silencing, however, did not affect the expression of other tight junction proteins, suggesting that they are differently regulated. This thesis introduces new mechanisms involved in the regulation of tight junctions revealing new interactions. It provides novel evidence linking intracellular calcium regulation and tight junctions.

Toimituskyvyn kehittäminen prosessin materiaalipuutteita hallitsemalla

Toimituskyky on yrityksen suorituskykyä kuvaava tekijä, jolla on merkittävä vaikutus asiakastyytyväisyyteen, erityisesti valmistusteollisuudessa. Toimituskyky muodostuu materiaalin saatavuudesta ja logistisen järjestelmän toimitusvarmuudesta, joten hyvä toimituskyky edellyttää materiaalipuutteiden hallintaa. Tämän diplomityön tavoitteena on esittää, miten toimituskykyä voidaan kehittää tilaus-toimitusprosessin materiaalipuutteita hallitsemalla. Tutkimus toteutettiin konstruktiivisella tutkimusotteella case-tutkimuksena havainnoimalla toimintaa case-yrityksessä sekä analysoimalla case-yrityksen kirjallista materiaalia ja arkistoja. Yrityksessä havaittuja materiaalipuutteisiin liittyviä ongelmia tarkasteltiin tilaus-toimitusprosessin näkökulmasta prosessijohtamisen ja systemaattisen ongelmanratkaisun teorioiden avulla. Tutkimuksen tuloksena laadittiin kolme käytännönläheistä ratkaisuehdotusta havaittuihin ongelmiin; (1) materiaalipuutteiden syy-seuraussuhteita kuvaavat ongelma-syy-seurausketjut, (2) materiaalipuutteiden ongelmanratkaisumalli systemaattisen ongelmanratkaisun tueksi sekä (3) visuaalinen tilaus-toimitusprosessimalli, joka painottaa osaprosessien yhteyttä koko prosessin toimituskykyyn ja toimitusvarmuuteen. Tulosten mukaan materiaalipuutteet tulisi käsittää prosessin laatuvirheinä, jotka antavat arvokasta tietoa siitä, että prosessissa on laatuongelmia. Tulosten perusteella yrityksen toimituskykyä voidaan kehittää havainnoimalla tilaus-toimitusprosessin laatuvirheitä, selvittämällä laatuvirheiden syy-seuraussuhteet systemaattisesti ongelmanratkaisumallia hyödyntäen sekä toimimalla prosessiajattelun mukaisesti tilaus-toimitusprosessin toimituskyvyn jatkuvaa parantamista tavoitellen. Tutkimusongelman tarkastelutapaa ja työn tuloksia voidaan soveltaa samankaltaisiin tapauksiin, joissa tilaus-toimitusprosessin laatuvirheet, esimerkiksi materiaalipuutteet, paljastavat kehittämistä vaativia epäkohtia prosessin toimintatavoissa. Tilaus-toimitusprosessin toimituskykyä voidaan kehittää vain, jos panostetaan ajan hallintaan ja kykyyn toimia asiakaslupausten ja sopimusten mukaisesti.

Usability comparison of open source content management systems

The purpose of this thesis is to study, investigate and compare usability of open source cms. The thesis examines and compares usability aspect of some open source cms. The research is divided into two complementary parts –theoretical part and analytical part. The theoretical part mainly describes open source web content management systems, usability and the evaluation methods. The analytical part is to compare and analyze the results found from the empirical research. Heuristic evaluation method was used to measure usability problems in the interfaces. The study is fairly limited in scope; six tasks were designed and implemented in each interface for discovering defects in the interfaces. Usability problems were rated according to their level of severity. Time it took by each task, level of problem’s severity and type of heuristics violated will be recorded, analyzed and compared. The results of this study indicate that the comparing systems provide usable interfaces, and WordPress is recognized as the most usable system.

Tukin mittaus ja optimointi sahalinjassa

Tukin mittaus ennen sahausta ja sahausasetteen optimointi on kehittynyt paljon viimeisen 10 vuoden aikana. Sahauksen kannattavuuden huonontuessa raaka-aineen tehokas hyödyntäminen on muodostunut tärkeäksi osaksi prosessia. Mittalaitteiden tekniikan kehityttyä on ollut mahdollista mitata tukin muoto ja halkaisijat eri kohdista entistä tarkemmin. Sahausasetteen optimoinnilla pyritään raaka-aineen mahdollisimman tehokkaaseen käyttöön eli saamaan mahdollisimman hyvä saanto jokaisesta yksittäisestä sahatusta tukista. Mittaustarkkuus on suoraan kytköksissä sahausasetteen optimointi tuloksen onnistumiseen. Yleisesti tukin mittaus ennen sahausta ja sahausasetteen optimointi tulevat samalta toimittajalta. Työssä tarkasteltiin kahden eri toimittajan tukkimittareita sekä optimoinnin onnistumista sen perusteella. Käytössä oli lasikuituinen mallitukki, jota mitattiin kummankin toimittajan mittareilla. Näin voitiin suoraan vertailla mittauksen ja optimoinnin onnistumista ja verrata sitä optimaalisiin tuloksiin. Työssä käytettiin kandidaatintyössä luomaani toimintamallia tukkimittarin tarkkuuden toteamiseksi. Mittaus- ja optimointivirheistä pystyttiin laskemaan, kuinka paljon tappiota sahalaitokselle aiheutui verrattuna optimaaliseen mittaus- ja optimointitulokseen. Jo pienetkin virheet optimoinnissa ja mittauksessa vaikuttavat sahauksen kannattavuuteen, kun tarkastellaan sahalaitosta jossa sahataan 8000 – 10 000 tukkia yhden työvuoron aikana. Tulosten perusteella mittarit mittaavat hieman virheellisesti, ja kummankin mittarin mittausten perusteella saatiin eri sahausasete optimointitulokseksi. Mittavirheen takia voitiin todeta, että parantamalla mittaustarkkuutta voidaan sahauksen kannattavuutta parantaa.

Spectroscopic Studies of III-V Semiconductor Materials for Improved Devices

Defects in semiconductor crystals and at their interfaces usually impair the properties and the performance of devices. These defects include, for example, vacancies (i.e., missing crystal atoms), interstitials (i.e., extra atoms between the host crystal sites), and impurities such as oxygen atoms. The defects can decrease (i) the rate of the radiative electron transition from the conduction band to the valence band, (ii) the amount of charge carriers, and (iii) the mobility of the electrons in the conduction band. It is a common situation that the presence of crystal defects can be readily concluded as a decrease in the luminescence intensity or in the current flow for example. However, the identification of the harmful defects is not straightforward at all because it is challenging to characterize local defects with atomic resolution and identification. Such atomic-scale knowledge is however essential to find methods for reducing the amount of defects in energy-efficient semiconductor devices. The defects formed in thin interface layers of semiconductors are particularly difficult to characterize due to their buried and amorphous structures. Characterization methods which are sensitive to defects often require well-defined samples with long range order. Photoelectron spectroscopy (PES) combined with photoluminescence (PL) or electrical measurements is a potential approach to elucidate the structure and defects of the interface. It is essential to combine the PES with complementary measurements of similar samples to relate the PES changes to changes in the interface defect density. Understanding of the nature of defects related to III-V materials is relevant to developing for example field-effect transistors which include a III-V channel, but research is still far from complete. In this thesis, PES measurements are utilized in studies of various III-V compound semiconductor materials. PES is combined with photoluminescence measurements to study the SiO2/GaAs, SiNx/GaAs and BaO/GaAs interfaces. Also the formation of novel materials InN and photoluminescent GaAs nanoparticles are studied. Finally, the formation of Ga interstitial defects in GaAsN is elucidated by combining calculational results with PES measurements.

To Divide or Not to Divide; MicroRNAs and Small Compounds as Modulators of Mitosis

Mitosis is under the stringent quality control of the spindle assembly checkpoint (SAC). However, in cancer cells this control can fail, leading to excessive cellular proliferation and ultimately to the formation of a tumor. Novel cancer cell selective therapies are needed to stop the uncontrolled cell proliferation and tumor growth. The aim of the research presented in this thesis was to identify microRNAs (miRNAs) that could play a role in cancer cell proliferation as well as low molecular weight (LMW) compounds that could interfere with cell division. The findings could be used to develop better cancer diagnostics and therapies in the future. First, a high-throughput screen (HTS) was performed to identify LMW compounds that possess a similar chemical interaction field as rigosertib, an anti-cancer compound undergoing clinical trials. A compound termed Centmitor-1 was discovered that phenocopied the cellular impact of rigosertib by affecting the microtubule dynamics. Next, another HTS aimed at identifying compounds that would target the Hec1 protein, which mediates the interaction between spindle microtubules and chromosomes. Perturbation of this connection should prevent cell division and induce cell death. A compound termed VTT-006 was discovered that abrogated mitosis in several cell line models and exhibited binding to Hec1 in vitro. Lastly, using a cell-based HTS two miRNAs were identified that affected cancer cell proliferation via Aurora B kinase, which is an important mitotic regulator. MiR-378a-5p was found to indirectly suppress the production of the kinase whereas let-7b showed direct binding to the 3’UTR of Aurora B mRNA and repressed its translation. The miRNA-mediated perturbation of Aurora B induced defects in mitosis leading to abnormal chromosome segregation and induction of aneuploidy. The results of this thesis provide new information on miRNA signaling in cancer, which could be utilized for diagnostic purposes. Moreover, the thesis introduces two small compounds that may benefit future drug research.

Alumiinin oksidikerroksen merkitys hitsauksessa

Tämä kandidaatintyö on kirjallisuuden pohjalta laadittu yhteenveto alumiinin oksidikerroksen vaikutuksesta hitsauksessa. Työssä käsitellään alumiinia alkuaineena, alumiinin oksidikerroksen muodostumista ja rakennetta, seosaineiden vaikutusta oksidikerrokseen, alumiinin hitsattavuutta teräkseen vertaillen, alumiiniseosten hitsattavuutta, oksidikerroksen merkitystä hitsauksessa, alumiinin yleisiä hitsausvirheitä, oksidikerroksen poistotapoja sekä alumiinin eri hitsausmenetelmiä. Hitsausmenetelmistä käsitellään pääasiassa alumiinin MIG-, TIG- ja plasmahitsausta.

Threat modeling a factory environment using Microsoft Security Development Lifecycle methodology

The number of security violations is increasing and a security breach could have irreversible impacts to business. There are several ways to improve organization security, but some of them may be difficult to comprehend. This thesis demystifies threat modeling as part of secure system development. Threat modeling enables developers to reveal previously undetected security issues from computer systems. It offers a structured approach for organizations to find and address threats against vulnerabilities. When implemented correctly threat modeling will reduce the amount of defects and malicious attempts against the target environment. In this thesis Microsoft Security Development Lifecycle (SDL) is introduced as an effective methodology for reducing defects in the target system. SDL is traditionally meant to be used in software development, principles can be however partially adapted to IT-infrastructure development. Microsoft threat modeling methodology is an important part of SDL and it is utilized in this thesis to find threats from the Acme Corporation’s factory environment. Acme Corporation is used as a pseudonym for a company providing high-technology consumer electronics. Target for threat modeling is the IT-infrastructure of factory’s manufacturing execution system. Microsoft threat modeling methodology utilizes STRIDE –mnemonic and data flow diagrams to find threats. Threat modeling in this thesis returned results that were important for the organization. Acme Corporation now has more comprehensive understanding concerning IT-infrastructure of the manufacturing execution system. On top of vulnerability related results threat modeling provided coherent views of the target system. Subject matter experts from different areas can now agree upon functions and dependencies of the target system. Threat modeling was recognized as a useful activity for improving security.