TLR3-Mediated CD8+ Dendritic Cell Activation Is Coupled with Establishment of a Cell-Intrinsic Antiviral State.

Because of their unique capacity to cross-present Ags to CD8(+) T cells, mouse lymphoid tissue-resident CD8(+) dendritic cells (DCs) and their migratory counterparts are critical for priming antiviral T cell responses. High expression of the dsRNA sensor TLR3 is a distinctive feature of these cross-presenting DC subsets. TLR3 engagement in CD8(+) DCs promotes cross-presentation and the acquisition of effector functions required for driving antiviral T cell responses. In this study, we performed a comprehensive analysis of the TLR3-induced antiviral program and cell-autonomous immunity in CD8(+) DC lines and primary CD8(+) DCs. We found that TLR3-ligand polyinosinic-polycytidylic acid and human rhinovirus infection induced a potent antiviral protection against Sendai and vesicular stomatitis virus in a TLR3 and type I IFN receptor-dependent manner. Polyinosinic-polycytidylic acid-induced antiviral genes were identified by mass spectrometry-based proteomics and transcriptomics in the CD8(+) DC line. Nanostring nCounter experiments confirmed that these antiviral genes were induced by TLR3 engagement in primary CD8(+) DCs, and indicated that many are secondary TLR3-response genes requiring autocrine IFN-β stimulation. TLR3-activation thus establishes a type I IFN-dependent antiviral program in a DC subtype playing crucial roles in priming adaptive antiviral immune responses. This mechanism is likely to shield the priming of antiviral responses against inhibition or abrogation by the viral infection. It could be particularly relevant for viruses detected mainly by TLR3, which may not trigger type I IFN production by DCs that lack TLR3, such as plasmacytoid DCs or CD8(-) DCs.

Context-based services for mobile devices

The subject of this master’s thesis was developing a context-based reminder service for mobile devices. Possible sources of context were identified and analyzed. One such source is geographical location obtained via a GPS receiver. These receivers consume a lot of power and techniques and algorithms for reducing power consumptions were proposed and analyzed. The service was implemented as an application on a series 60 mobile phone. The application requirements, user interface and architecture are presented. The end-user experiences are discussed and possible future development and research areas are presented.

Force Spectroscopy with Dual-Trap Optical Tweezers: Molecular Stiffness Measurements and Coupled Fluctuations Analysis

ABSTRACT Dual-trap optical tweezers are often used in high-resolution measurements in single-molecule biophysics. Such measurements can be hindered by the presence of extraneous noise sources, the most prominent of which is the coupling of fluctuations along different spatial directions, which may affect any optical tweezers setup. In this article, we analyze, both from the theoretical and the experimental points of view, the most common source for these couplings in dual-trap optical-tweezers setups: the misalignment of traps and tether. We give criteria to distinguish different kinds of misalignment, to estimate their quantitative relevance and to include them in the data analysis. The experimental data is obtained in a, to our knowledge, novel dual-trap optical-tweezers setup that directly measures forces. In the case in which misalignment is negligible, we provide a method to measure the stiffness of traps and tether based on variance analysis. This method can be seen as a calibration technique valid beyond the linear trap region. Our analysis is then employed to measure the persistence length of dsDNA tethers of three different lengths spanning two orders of magnitude. The effective persistence length of such tethers is shown to decrease with the contour length, in accordance with previous studies.

Phospholipid bilayer perturbing-properties underlying lysis induced by pH-sensitive cationic lysine-based surfactants in biomembranes

Many strategies for treating diseases require the delivery of drugs into the cell cytoplasm following internalization within endosomal vesicles. Thus, compounds triggered by low pH to disrupt membranes and release endosomal contents into the cytosol are of particular interest. Here, we report novel cationic lysine-based surfactants (hydrochloride salts of Nε- and Nα-acyl lysine methyl ester) that differ in the position of the positive charge and the length of the alkyl chain. Amino acid-based surfactants could be promising novel biomaterials in drug delivery systems, given their biocompatible properties and low cytotoxic potential. We examined their ability to disrupt the cell membrane in a range of pH values, concentrations and incubation times, using a standard hemolysis assay as a model of endosomal membranes. Furthermore, we addressed the mechanism of surfactant-mediated membrane destabilization, including the effects of each surfactant on erythrocyte morphology as a function of pH. We found that only surfactants with the positive charge on the α-amino group of lysine showed pH-sensitive hemolytic activity and improved kinetics within the endosomal pH range, indicating that the positive charge position is critical for pH-responsive behavior. Moreover, our results showed that an increase in the alkyl chain length from 14 to 16 carbon atoms was associated with a lower ability to disrupt cell membranes. Knowledge on modulating surfactant-lipid bilayer interactions may help us to develop more efficient biocompatible amino acid-based drug delivery devices.

Mechanisms underlying cytotoxicity induced by engineered nanomaterials: a review of in vitro studies

Engineered nanomaterials are emerging functional materials with technologically interesting properties and a wide range of promising applications, such as drug delivery devices, medical imaging and diagnostics, and various other industrial products. However, concerns have been expressed about the risks of such materials and whether they can cause adverse effects. Studies of the potential hazards of nanomaterials have been widely performed using cell models and a range of in vitro approaches. In the present review, we provide a comprehensive and critical literature overview on current in vitro toxicity test methods that have been applied to determine the mechanisms underlying the cytotoxic effects induced by the nanostructures. The small size, surface charge, hydrophobicity and high adsorption capacity of nanomaterial allow for specific interactions within cell membrane and subcellular organelles, which in turn could lead to cytotoxicity through a range of different mechanisms. Finally, aggregating the given information on the relationships of nanomaterial cytotoxic responses with an understanding of its structure and physicochemical properties may promote the design of biologically safe nanostructures.

Presenting HTML Content Using Mobile Devices

Tämä diplomityö käsittelee HTML-sivujen näyttämistä käytettävästi mobiililla päätelaitteella. Tutkimuskohteena on sivujen käytettävyyden parantaminen mobiilissa internetselaimessa. Diplomityössä esitetään havaittuja käytettävyysongelmia ja pohditaan ratkaisuja näihin selaimessa. Teoriataustaa tarkastellaan useista käytettävyyden näkökulmista, käyttäen apuna tutkimuksia ja teorioita. Tutkimuksiin ja teorioihin perustuen suunnitellaan selaimessa tapahtuvat muutokset, jotka mahdollistaisivat sivujen hyvän käytettävyyden. Tutkimusainestoa kerättiin aikaisimmista käytettävyystutkimuksista, suosituksista sekä tieteellisistä analyyseistä. Tarkastelun kohteena olivat myös nykyisten mobiilien internetselainten käyttämät ratkaisut havaittuihin käytettävyysongelmiin. Työn tuloksena esitetään mobiiliin selaimeen toteutettavat sääntöjoukot, jotka muovaisivat HTML-sivut käytettäväksi päätelaitteelle. Ratkaisuna annetaan ehdotuksia sisällön esittämistavalle ja pohditaan näissä syntyneitä ongelmia. Tulevaisuudessa kun sääntöjoukko on toteutettu selaimeen sillä suoritetaan käytettävyystestaukset.

Positioning Wireless Mobile Terminal Devices

Positioning techniques enable the positioning of mobile transportation vehicles. Location information can be used in transport planning as well as in vehicles. Information can also be transferred between vehicles and transport planning. For example, pickup and delivery information and route instructions can be exchanged wirelessly. In this thesis, techniques suitable for positioning vehicles are studied, as well as techniques enabling wireless connectivity of the vehicles to the transport planning system. A prototype based on one positioning and connectivity technique is implemented. As a result, a system capable of positioning vehicles is created. The vehicles can be located almost in real-time. The accuracy in positioning is sufficient to visualise the locations on a good quality 1:20000 city map.

Les programmes de prise en charge des maladies chroniques et de la multimorbidité en Suisse

Le nombre et la couverture des programmes de prise en charge des maladies chroniques est insuffisant en Suisse. Dans le cadre de la préparation du rapport national suisse sur la santé 2015, l'Observatoire suisse de la santé a fait réaliser un état des lieux des programmes de prise en charge des maladies chroniques et de la multimorbidité en Suisse. Une enquête téléphonique selon la méthode boule de neige a permis d'identifier 44 programmes actifs dans quatorze cantons; ces programmes sont décrits plus précisément dans l'étude. Il s'agit d'une augmentation marquée, si on compare ces résultats avec ceux d'une enquête similaire réalisée en 2007 et qui avait dénombré sept programmes. Le nombre et la couverture de ces programmes sont, selon les auteurs, largement insuffisants pour permettre un impact réel et mesurable sur la santé et la prise en charge de tous les patients chroniques résidant en Suisse.

Remote File Access with Wireless Symbian Devices

Erilaisten langattomien päätelaitteiden kuten älypuhelimien ja kommunikaattoreiden määrän lisääntyessä myös kiinnostus liikkuville käyttäjille lisäarvoa tuottavia verkkopalveluita ja -sovelluksia kohtaan kasvaa. Työn tarkoituksena oli tutkia kuinka langattomat Symbianin käyttöjärjestelmää käyttävät laitteet voivat hyödyntää verkkotiedostoja. Työssä arvioitiin eri tiedostojenjakoprotokollien käytettävyyttä langattomissa verkoissa, määriteltiin etätiedostoyhteyden Symbian-alustalle tarjoavan ohjelmiston vaatimukset ja tehtiin alustava suunnitelma ohjelmiston toteuttamiseksi. Läpinäkyvä tiedostojen etäkäyttö vaatii tiedostojenjakoprotokollan toteuttamista sovelluksille yhteisen tiedostosaantimekanismin alle. Tiedostojen etäkäyttö voi perustua eri tiedostojenjakoprotokolliin kuten IP:n päällä toimiviin NFS:ään tai CIFS:ään. Langattomuuden aiheuttamat rajoitukset laitteissa ja tiedonsiirrossa saattavat vähentää sovellutuksen käytettävyyttä ja on huomioitava ohjelmistoa toteutettaessa. Symbian-alusta perustuu asiakas-palvelin arkkitehtuuriin, jossa asiakassovellukset käyttävät tiedostopalveluita yhteisen tiedostopalvelimen kautta. Etätiedostoyhteys on mahdollista toteuttaa liittämällä uusi kirjastomoduuli tiedostopalvelimeen. Protokollan toteuttavan moduulin on muunnettava protokollan viestit tiedostopalvelimelle sopiviksi huolehtien samalla muista samanaikaisista tiedostotapahtumista. Suunniteltu moduulin arkkitehtuuri mahdollistaa eri protokollavaihtoehtojen käyttämisen etätiedostoyhteyden toteuttamiseen.