Quantitative TCR:pMHC Dissociation Rate Assessment by NTAmers Reveals Antimelanoma T Cell Repertoires Enriched for High Functional Competence.

Experimental models demonstrated that therapeutic induction of CD8 T cell responses may offer protection against tumors or infectious diseases providing that T cells have sufficiently high TCR/CD8:pMHC avidity for efficient Ag recognition and consequently strong immune functions. However, comprehensive characterization of TCR/CD8:pMHC avidity in clinically relevant situations has remained elusive. In this study, using the novel NTA-His tag-containing multimer technology, we quantified the TCR:pMHC dissociation rates (koff) of tumor-specific vaccine-induced CD8 T cell clones (n = 139) derived from seven melanoma patients vaccinated with IFA, CpG, and the native/EAA or analog/ELA Melan-A(MART-1)(26-35) peptide, binding with low or high affinity to MHC, respectively. We observed substantial correlations between koff and Ca(2+) mobilization (p = 0.016) and target cell recognition (p < 0.0001), with the latter independently of the T cell differentiation state. Our strategy was successful in demonstrating that the type of peptide impacted on TCR/CD8:pMHC avidity, as tumor-reactive T cell clones derived from patients vaccinated with the low-affinity (native) peptide expressed slower koff rates than those derived from patients vaccinated with the high-affinity (analog) peptide (p < 0.0001). Furthermore, we observed that the low-affinity peptide promoted the selective differentiation of tumor-specific T cells bearing TCRs with high TCR/CD8:pMHC avidity (p < 0.0001). Altogether, TCR:pMHC interaction kinetics correlated strongly with T cell functions. Our study demonstrates the feasibility and usefulness of TCR/CD8:pMHC avidity assessment by NTA-His tag-containing multimers of naturally occurring polyclonal T cell responses, which represents a strong asset for the development of immunotherapy.

Forcing Usage Rules in PublicWireless LANs

Langattomien lähiverkkojen yleistyessä nopeasti suurten verkkojen teknologiana käyttösääntöjen valvonta tulee tarpeelliseksi. Tässä työssä kuvataan, kuinka käyttäjät voidaan pakottaa noudattamaan käyttösääntöjä julkisissa WLAN-verkoissa. Työssä käsiteltävät ongelmat koskevat menetelmiä epäluotettavien DHCP-palvelinten paljastamiseksi sekä omia IP-osoitteita käyttävien käyttäjien paljastamiseksi tilanteissa, jolloin IP-osoite ei ole virallisen DHCP-palvelimen myöntämä. Jokaisen menetelmän kohdalla pohditaan, kuinka tällaisia käyttäjiä voidaan estää rikkomasta käyttösääntöjä. Lisäksi pohditaan keskitetyn tietojen keruun hyödyntämistä kuvattujen tehtävien suorittamiseksi. Esitetyt ratkaisut on erityisesti suunniteltu testiverkkoa varten, mutta yleiset ideat ovat toimivia missä tahansa langattomassa verkossa.

Asiakassuuntautunut toimintatapa Osuuspankin Internet-pankkipalvelussa

Pankkien tavoitteena on tarjota asiakkaille kattava tuote- ja palveluvalikoima verkkopankissa. Verkkopalvelut ovat osa pankin asiakaslähtöistä toimintaa. Tässä tutkielmassa käsitellään niitä asioita, joita on mietittävä, määriteltävä ja selvitettävä, kun pankki kehittää verkkopalvelujaan. Näitä asioita ovat muun muassa palveluprosessin suunnittelu ja laajennetun palvelumallin rakentaminen osana verkkopalvelujen johtamista, valittavat strategiat ja hinnoittelu sekä asiakkaan ja organisaation oppiminen. Verkkomaailmassa asiakas on hyvin lähellä yritystä ja toimii yrityksen prosessissa. Asiakasta ei voi kuitenkaan johtaa suoraan - kuten henkilöstöä. Asiakkaan johtaminen tapahtuu asiakkuuden johtamisen kautta. Asiakkuuslähtöisessä ajattelussa asiakas osallistuu aktiivisesti palveluprosessiin ja pyrkii tuottamaan arvoa itselleen. Asiakkuuden johtamisessa voi soveltaen käyttää samoja menetelmiä kuin henkilön johtamisessa: kannusteita, palkitsemista, motivoimista, osaamisen ja asiakassuhteen kehittämistä sekä seurantaa. Verkon kautta asioivasta asiakkaasta on pidettävä huolta ja asiakkaan on tämä huolenpito itse huomattava ja koettava.

CREATING A MODEL FOR INVENTORY MANAGEMENT SYSTEM

Tutkielman tarkoituksena oli mallintaa varastonhallintajärjestelmä, joka olisi sopiva case yritykselle. Tutkimus aloitettiin case yrityksen varastonhallinan nykytilan kartoituksella, jonka jälkeen tutkittiin varastonhallinnan eri osa-alueisiin. Varastonhallinnan osa-alueista käsiteltiin varastotyyppejä, motiiveja, tavoitteita, kysynnän ennustamista sekä erilaisia varastonhallinnan työkaluja. Sen lisäksi tutkittiin erilaisia varaston täydennysmalleja. Teoriaosuudessa käsiteltiin lisäksi kolmea erilaista tietojärjestelmätyyppiä: toiminnanohjausjärjestelmää, sähköisen kaupankäynnin järjestelmää sekä räätälöityä järjestelmää. Tutkimussuunnitelmassa nämä kolme järjestelmää rajattiin vaihtoehdoiksi, joista jokin valittaisiin case yrityksen varastonhallintajärjestelmäksi. Teorian ja nykytilan pohjalta tehtiin viitekehys, jossa esiteltiin varastonhallintajärjestelmän tieto- ja toiminnallisuusominaisuuksia. Nämä ominaisuudet priorisoitiin neljään eri luokkaan ominaisuuden kriittisyyden mukaan. Järjestelmävaihtoehdot arvioitiin viitekehyksen kriteerien mukaisesti, miten helposti ominaisuudet olisivat toteutettavissa eri vaihtoehdoissa. Tulokset laskettiin näiden arviointien perusteella, jonka jälkeen tulosten analysoinnissa huomattiin, että toiminnanohjausjärjestelmä sopisi parhaiten case yrityksen varastonhallintajärjestelmäksi.

Radiographic volume analysis as a novel tool to determine nasopalatine duct cyst dimensions and its association with presenting symptoms and postoperative complications.

OBJECTIVES: The aims of the study were to use cone beam computed tomography (CBCT) images of nasopalatine duct cysts (NPDC) and to calculate the diameter, surface area, and 3D-volume using a custom-made software program. Furthermore, any associations of dimensions of NPDC with age, gender, presence/absence of maxillary incisors/canines (MI/MC), endodontic treatment of MI/MC, presenting symptoms, and postoperative complications were evaluated. MATERIAL AND METHODS: The study comprised 40 patients with a histopathologically confirmed NPDC. On preoperative CBCT scans, curves delineating the cystic borders were drawn in all planes and the widest diameter (in millimeter), surface area (in square millimeter), and volume (in cubic millimeter) were calculated. RESULTS: The overall mean cyst diameter was 15 mm (range 7-47 mm), the mean cyst surface area 566 mm(2) (84-4,516 mm(2)), and the mean cyst volume 1,735 mm(3) (65-25,350 mm(3)). For 22 randomly allocated cases, a second measurement resulted in a mean absolute aberration of ±4.2 % for the volume, ±2.8 % for the surface, and ±4.9 % for the diameter. A statistically significant association was found for the CBCT determined cyst measurements and the need for preoperative endodontic treatment to MI/MC and for postoperative complications. CONCLUSION: In the hands of a single experienced operator, the novel software exhibited high repeatability for measurements of cyst dimensions. Further studies are needed to assess the application of this tool for dimensional analysis of different jaw cysts and lesions including treatment planning. CLINICAL RELEVANCE: Accurate radiographic information of the bone volume lost (osteolysis) due to expansion of a cystic lesion in three dimensions could help in personalized treatment planning.

Inflammatory and metabolic responses to high-fat meals with and without dairy products in men.

Postprandial inflammation is an important factor for human health since chronic low-grade inflammation is associated with chronic diseases. Dairy products have a weak but significant anti-inflammatory effect on postprandial inflammation. The objective of the present study was to compare the effect of a high-fat dairy meal (HFD meal), a high-fat non-dairy meal supplemented with milk (HFM meal) and a high-fat non-dairy control meal (HFC meal) on postprandial inflammatory and metabolic responses in healthy men. A cross-over study was conducted in nineteen male subjects. Blood samples were collected before and 1, 2, 4 and 6 h after consumption of the test meals. Plasma concentrations of insulin, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and C-reactive protein (CRP) were measured at each time point. IL-6, TNF-α and endotoxin concentrations were assessed at baseline and endpoint (6 h). Time-dependent curves of these metabolic parameters were plotted, and the net incremental AUC were found to be significantly higher for TAG and lower for CRP after consumption of the HFM meal compared with the HFD meal; however, the HFM and HFD meals were not different from the HFC meal. Alterations in IL-6, TNF-α and endotoxin concentrations were not significantly different between the test meals. The results suggest that full-fat milk and dairy products (cheese and butter) have no significant impact on the inflammatory response to a high-fat meal.

Test automation of digital mammography device

Testing of a complex software is time consuming. Automated tools are available quite a lot for desktop applications, but for embedded systems a custom-made tool is required Building a complete test framework is a complicated task. Therefore, the test platform was built on top of an already existing tool, CANoe. CANoe is a tool for CAN bus analysis and node simulation. The functionality of CANoe was extended with LabVIEW DLL. The LabVIEW software was used for simulating hardware components of the embedded device As a result of the study, a platform was created where tests could be automated. Of the current test plan, 10 percent were automated and up to 60 percent could be automated with the current functionality.

Tullin tuonnin palvelujen epäyhtenäisten käytäntöjen analysointi

Työn tarkoituksena on analysoida Tulli tuonnin palveluissa esiintyviä epäyhtenäi siä käytäntöjä Tullihallituksen Ulkomaankauppaosaston asiakas- ja luotonhallin tayksikölle. Tutkimuksen pohjustamiseksi työssä on ensin määritelty palvelu, asiakashallinta ja Customer Relationship Management (CRM) kirjallisuuden pe rusteella sekä tutkimuksessa käytetty SERVQUAL-työkalu ja kuiluanalyysimalli. Näiden perusteella on luotu tutkimuksessa käytetty kysely. Kyselyssä kysyttiin missä tuonnin palveluissa epäyhtenäisiä käytäntöjä on havait tu, mistä ne johtuvat ja mandollisia keinoja niiden poistamiseen. SERVQUAL työkalulla tutkittiin koetun palvelun laatua 19 kysymyksellä Tullin tuonnin palve luiden odotuksista ja kokemuksista. Kyselyn tuloksista havaittiin Tullin tuonnin palveluissa olevan koetun palvelun kuilu eli odotettu palvelu ei ole vastannut ko kemuksia. Myös organisaatiosta johtuvia kuiluja havaittiin Tullin työntekijöille osoitetussa kyselyssä.

Reversal of a full-length mutant huntingtin neuronal cell phenotypeby chemical inhibitors of polyglutamine-mediated aggregation

Background: Huntington's disease (HD) is an inherited neurodegenerative disorder triggered by an expanded polyglutamine tract in huntingtin that is thought to confer a new conformational property on this large protein. The propensity of small amino-terminal fragments with mutant, but not wild-type, glutamine tracts to self-aggregate is consistent with an altered conformation but such fragments occur relatively late in the disease process in human patients and mouse models expressing full-length mutant protein. This suggests that the altered conformational property may act within the full-length mutant huntingtin to initially trigger pathogenesis. Indeed, genotypephenotype studies in HD have defined genetic criteria for the disease initiating mechanism, and these are all fulfilled by phenotypes associated with expression of full-length mutant huntingtin, but not amino-terminal fragment, in mouse models. As the in vitro aggregation of amino-terminal mutant huntingtin fragment offers a ready assay to identify small compounds that interfere with the conformation of the polyglutamine tract, we have identified a number of aggregation inhibitors, and tested whether these are also capable of reversing a phenotype caused by endogenous expressionof mutant huntingtin in a striatal cell line from the HdhQ111/Q111 knock-in mouse. Results: We screened the NINDS Custom Collection of 1,040 FDA approved drugs and bioactive compounds for their ability to prevent in vitro aggregation of Q58-htn 1¿171 amino terminal fragment. Ten compounds were identified that inhibited aggregation with IC50 < 15 ¿M, including gossypol, gambogic acid, juglone, celastrol, sanguinarine and anthralin. Of these, both juglone and celastrol were effective in reversing the abnormal cellular localization of full-length mutant huntingtin observed in mutant HdhQ111/Q111 striatal cells. Conclusions: At least some compounds identified as aggregation inhibitors also prevent a neuronal cellular phenotype caused by full-length mutant huntingtin, suggesting that in vitro fragment aggregation can act as a proxy for monitoring the disease-producing conformational property in HD. Thus, identification and testing of compounds that alter in vitro aggregation is a viable approach for defining potential therapeutic compounds that may act on the deleterious conformational property of full-length mutant huntingtin.

The composition of airborne and grain-dust fungal communities is shaped at regional scale by plant genotypes and farming practices

Chronic exposure to airborne fungi has been associated with different respiratory symptoms and pathologies in occupational populations, such as grain workers. However, the homogeneity in the fungal species composition of these bioaerosols on a large geographical scale and the different drivers that shape these fungal communities remain unclear. In this study, the diversity of fungi in grain dust and in the aerosols released during harvesting was determined across 96 sites at a geographical scale of 560 km(2) along an elevation gradient of 500 m by tag-encoded 454-pyrosequencing of the internal transcribed spacer (ITS) sequences. Associations between the structure of fungal communities in the grain dust and different abiotic (farming system, soil characteristics, geographic and climatic parameters) and biotic (wheat cultivar, previous crop culture) factors were explored. These analyses revealed a strong relationship between the airborne and grain dust fungal communities and showed the presence of allergenic and mycotoxigenic species in most samples, which highlights the potential contribution of these fungal species to work-related respiratory symptoms of grain workers. The farming system was the major driver of the alpha and beta phylogenetic diversity of fungal communities. In addition, elevation and soil CaCO3 concentrations shaped the alpha diversity whereas wheat cultivar, cropping history and the number of freezing days per year shaped the taxonomic beta diversity of these communities.

Enhanced capture of healthcare-related harms and injuries in the 11th revision of the International Classification of Diseases (ICD-11).

The World Health Organization (WHO) plans to submit the 11th revision of the International Classification of Diseases (ICD) to the World Health Assembly in 2018. The WHO is working toward a revised classification system that has an enhanced ability to capture health concepts in a manner that reflects current scientific evidence and that is compatible with contemporary information systems. In this paper, we present recommendations made to the WHO by the ICD revision's Quality and Safety Topic Advisory Group (Q&S TAG) for a new conceptual approach to capturing healthcare-related harms and injuries in ICD-coded data. The Q&S TAG has grouped causes of healthcare-related harm and injuries into four categories that relate to the source of the event: (a) medications and substances, (b) procedures, (c) devices and (d) other aspects of care. Under the proposed multiple coding approach, one of these sources of harm must be coded as part of a cluster of three codes to depict, respectively, a healthcare activity as a 'source' of harm, a 'mode or mechanism' of harm and a consequence of the event summarized by these codes (i.e. injury or harm). Use of this framework depends on the implementation of a new and potentially powerful code-clustering mechanism in ICD-11. This new framework for coding healthcare-related harm has great potential to improve the clinical detail of adverse event descriptions, and the overall quality of coded health data.

Travellers' profile, travel patterns and vaccine practices-a 10-year prospective study in a Swiss Travel Clinic.

BACKGROUND: The travel clinic in Lausanne serves a catchment area of 700 000 of inhabitants and provides pre- and post-travel consultations. This study describes the profile of attendees before departure, their travel patterns and the travel clinic practices in terms of vaccination over time. METHODS: We included all pre-travel first consultation data recorded between November 2002 and December 2012 by a custom-made program DIAMM/G. We analysed client profiles, travel characteristics and vaccinations prescribed over time. RESULTS: Sixty-five thousand and forty-six client-trips were recorded. Fifty-one percent clients were female. Mean age was 32 years. In total, 0.1% were aged <1 year and 0.2% ≥80 years. Forty-six percent of travellers had pre-existing medical conditions. Forty-six percent were travelling to Africa, 35% to Asia, 20% to Latin America and 1% (each) to Oceania and Europe; 19% visited more than one country. India was the most common destination (9.6% of travellers) followed by Thailand (8.6%) and Kenya (6.4%). Seventy-three percent of travellers were planning to travel for ≤ 4 weeks. The main reasons for travel were tourism (75%) and visiting friends and relatives (18%). Sixteen percent were backpackers. Pre-travel advice were sought a median of 29 days before departure. Ninety-nine percent received vaccine(s). The most frequently administered vaccines were hepatitis A (53%), tetanus-diphtheria (46%), yellow fever (39%), poliomyelitis (38%) and typhoid fever (30%). CONCLUSIONS: The profile of travel clinic attendees was younger than the general Swiss population. A significant proportion of travellers received vaccinations that are recommended in the routine national programme. These findings highlight the important role of travel clinics to (i) take care of an age group that has little contact with general practitioners and (ii) update vaccination status. The most commonly prescribed travel-related vaccines were for hepatitis A and yellow fever. The question remains to know whether clients do attend travel clinics because of compulsory vaccinations or because of real travel health concern or both.

Microscopy of Fission Yeast Sexual Lifecycle.

The fission yeast Schizosaccharomyces pombe has been an invaluable model system in studying the regulation of the mitotic cell cycle progression, the mechanics of cell division and cell polarity. Furthermore, classical experiments on its sexual reproduction have yielded results pivotal to current understanding of DNA recombination and meiosis. More recent analysis of fission yeast mating has raised interesting questions on extrinsic stimuli response mechanisms, polarized cell growth and cell-cell fusion. To study these topics in detail we have developed a simple protocol for microscopy of the entire sexual lifecycle. The method described here is easily adjusted to study specific mating stages. Briefly, after being grown to exponential phase in a nitrogen-rich medium, cell cultures are shifted to a nitrogen-deprived medium for periods of time suited to the stage of the sexual lifecycle that will be explored. Cells are then mounted on custom, easily built agarose pad chambers for imaging. This approach allows cells to be monitored from the onset of mating to the final formation of spores.

An Experimental Study on Peer Selection in a P2P Network over PlanetLab

Peer-reviewed

A Co-Processor Approach for Efficient Java Execution in Embedded Systems

This thesis deals with a hardware accelerated Java virtual machine, named REALJava. The REALJava virtual machine is targeted for resource constrained embedded systems. The goal is to attain increased computational performance with reduced power consumption. While these objectives are often seen as trade-offs, in this context both of them can be attained simultaneously by using dedicated hardware. The target level of the computational performance of the REALJava virtual machine is initially set to be as fast as the currently available full custom ASIC Java processors. As a secondary goal all of the components of the virtual machine are designed so that the resulting system can be scaled to support multiple co-processor cores. The virtual machine is designed using the hardware/software co-design paradigm. The partitioning between the two domains is flexible, allowing customizations to the resulting system, for instance the floating point support can be omitted from the hardware in order to decrease the size of the co-processor core. The communication between the hardware and the software domains is encapsulated into modules. This allows the REALJava virtual machine to be easily integrated into any system, simply by redesigning the communication modules. Besides the virtual machine and the related co-processor architecture, several performance enhancing techniques are presented. These include techniques related to instruction folding, stack handling, method invocation, constant loading and control in time domain. The REALJava virtual machine is prototyped using three different FPGA platforms. The original pipeline structure is modified to suit the FPGA environment. The performance of the resulting Java virtual machine is evaluated against existing Java solutions in the embedded systems field. The results show that the goals are attained, both in terms of computational performance and power consumption. Especially the computational performance is evaluated thoroughly, and the results show that the REALJava is more than twice as fast as the fastest full custom ASIC Java processor. In addition to standard Java virtual machine benchmarks, several new Java applications are designed to both verify the results and broaden the spectrum of the tests.