Fastidious intracellular bacteria as causal agents of community-acquired pneumonia.

Intracellular bacteria are common causes of community-acquired pneumonia that grow poorly or not at all on standard culture media and do not respond to beta-lactam antibiotic therapy. Apart from well-established agents of pneumonia such as Legionella pneumophila, Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci and Coxiella burnetii, some new emerging pathogens have recently been recognized, mainly Parachlamydia acanthamoebae and Simkania negevensis, two Chlamydia-related bacteria. Most of them are causes of benign and self-limited infections. However, they may cause severe pneumonia in some cases (i.e., Legionnaires' disease) and they may cause outbreaks representing a public health problem deserving prompt recognition and appropriate therapy. Although extrapulmonary manifestations are often present, no clinical features allow them to be distinguished from classical bacterial agents of pneumonia such as Streptococcus pneumoniae. Thus, specific molecular diagnostic tools are very helpful for early recognition of the offending bacteria, whereas serology often only allows retrospective or late diagnosis. Macrolides remain the best empirical treatment of intracellular respiratory pathogens, although some observational studies suggest that quinolones may be superior for the treatment of legionellosis.

Bootstrapping a statistical speech translator from a rule-based one

We describe a series of experiments in which we start with English to French and English to Japanese versions of an Open Source rule-based speech translation system for a medical domain, and bootstrap correspondign statistical systems. Comparative evaluation reveals that the rule-based systems are still significantly better than the statistical ones, despite the fact that considerable effort has been invested in tuning both the recognition and translation components; also, a hybrid system only marginally improved recall at the cost of a los in precision. The result suggests that rule-based architectures may still be preferable to statistical ones for safety-critical speech translation tasks.

Immune sensing of nucleic acids in inflammatory skin diseases.

Endosomal and cytosolic nucleic acid receptors are important immune sensors required for the detection of infecting or replicating viruses. The intracellular location of these receptors allows viral recognition and, at the same time, avoids unnecessary immune activation to self-nucleic acids that are continuously released by dying host cells. Recent evidence, however, indicates that endogenous factors such as anti-microbial peptides have the ability to break this protective mechanism. Here, we discuss these factors and illustrate how they drive inflammatory responses by promoting immune recognition of self-nucleic acids in skin wounds and inflammatory skin diseases such as psoriasis and lupus.

Optinen merkintunnistus satamaliikenteessä ja junavaunujen tunnistamisessa

Optisella merkintunnistuksella on tärkeä rooli nykypäivän automaatiossa. Optisen merkintunnistuksen eri sovellusalueet vaihtelevat dokumenttien tekstin tunnistamisesta ajoneuvojen tunnistamiseen ja erilaisten tuotanto- ja kokoonpanolinjojen automaatioon ja laadun tarkkailuun. Tässä työssä keskitytään optisen merkintunnistuksen käyttöön satamaliikenteessä. Työ jakaantuu kahteen osaan. Ensimmäisessä osassa esitellään satamien kannalta kaksi yleisintä ja samalla tärkeintä optisen merkintunnistuksen sovellusaluetta: rekisterikilpien tunnistus ja konttien tunnistus. Työn jälkimmäinen osa käsittelee junavaunujen tunnistamista optisen merkintunnistuksen avulla. Satamissa toimiva vaunukalusto ja niissä esiintyvät tunnisteet esitellään. Vaunujen tunnistamisen toteuttava konenäköjärjestelmä, sen vaativat laitteet sekä kuvankäsittelyn ja kuva-analyysin vaiheet käydään läpi. Kuva-analyysion jaettu työssä neljään päävaiheeseen: esikäsittely, segmentointi, piirreirrotus ja luokittelu. Kustakin vaiheesta esitetään useita eri menetelmiä, joiden käyttökelpoisuutta esitettyyn ongelmaan arvioidaan työn lopussa.

The relative salience of facial features when differentiating faces based on an interference paradigm

Research on face recognition and social judgment usually addresses the manipulation of facial features (eyes, nose, mouth, etc.). Using a procedure based on a Stroop-like task, Montepare and Opeyo (J Nonverbal Behav 26(1):43-59, 2002) established a hierarchy of the relative salience of cues based on facial attributes when differentiating faces. Using the same perceptual interference task, we established a hierarchy of facial features. Twenty-three participants (13 men and 10 women) volunteered for the experiment to compare pairs of frontal faces. The participants had to judge if the eyes, nose, mouth and chin in the pair of images were the same or different. The factors manipulated were the target-distractive factor (4 face components 9 3 distractive factors), interference (absent vs. present) and correct answer (the same vs. different). The analysis of reaction times and errors showed that the eyes and mouth were processed before the chin and nose, thus highlighting the critical importance of the eyes and mouth, as shown by previous research.

Tien rakentajan ja kunnossapitäjän ympäristöriskit ja -vastuut moottoritien elinkaarihankkeessa

Diplomityössä on tarkasteltu moottoritien rakentajan ja kunnossapitäjän ympäristöriskejä ja -vastuita moottoritien elinkaarihankkeessa. Työssä esitellään malli ympäristöriskien analysoimiseksi. Mallin avulla tuotetun tiedon pohjalta yrityksessä on mahdollista päättää ympäristöriskien hallintastrategiasta. Työssä on tutustuttu keskeiseen ympäristölainsäädäntöön ja sen yrityksen ympäristövastuulle asettamiin vaatimuksiin. Imagotekijöitä on käsitelty osana ympäristövastuuseen liittyvää yrityskohtaista päätöksentekoa. Hankekohtainen ympäristöriskien tunnistaminen ja arviointi on tehty E18 Muurla – Lohja moottoritiehankkeen tarjouslaskentavaiheessa. Tarjousvaiheessa tehty riskianalyysi palvelee päätöksentekoa yrityksessä valittaessa ympäristöriskien hallintastrategiaa. Analyysillä tuotetun tiedon avulla voidaan ohjata suunnittelua, tarjouksen hinnoittelua ja tarjouksen liitteeksi tuotettavan ympäristömateriaalin sisältöä. Tien rakentamisen ja kunnossapidon aikana materiaalia voidaan edelleen hyödyntää ympäristöasioiden hallinnassa.

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.

Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individuals

Background The MPER region of the HIV-1 envelope glycoprotein gp41 is targeted by broadly neutralizing antibodies. However, the localization of this epitope in a hydrophobic environment seems to hamper the elicitation of these antibodies in HIV infected individuals. We have quantified and characterized anti-MPER antibodies by ELISA and by flow cytometry using a collection of mini gp41-derived proteins expressed on the surface of 293T cells. Longitudinal plasma samples from 35 HIV-1 infected individuals were assayed for MPER recognition and MPER-dependent neutralizing capacity using HIV-2 viruses engrafted with HIV-1 MPER sequences. Results Miniproteins devoid of the cysteine loop of gp41 exposed the MPER on 293T cell membrane. Anti-MPER antibodies were identified in most individuals and were stable when analyzed in longitudinal samples. The magnitude of the responses was strongly correlated with the global response to the HIV-1 envelope glycoprotein, suggesting no specific limitation for anti-MPER antibodies. Peptide mapping showed poor recognition of the C-terminal MPER moiety and a wide presence of antibodies against the 2F5 epitope. However, antibody titers failed to correlate with 2F5-blocking activity and, more importantly, with the specific neutralization of HIV-2 chimeric viruses bearing the HIV-1 MPER sequence; suggesting a strong functional heterogeneity in anti-MPER humoral responses. Conclusions Anti-MPER antibodies can be detected in the vast majority of HIV-1 infected individuals and are generated in the context of the global anti-Env response. However, the neutralizing capacity is heterogeneous suggesting that eliciting neutralizing anti-MPER antibodies by immunization might require refinement of immunogens to skip nonneutralizing responses.

Domains of importance to the quality of life of older people from two Swiss regions

BACKGROUND: quality of life (QoL) is a subjective perception whose components may vary in importance between individuals. Little is known about which domains of QoL older people deem most important. OBJECTIVE: this study investigated in community-dwelling older people the relationships between the importance given to domains defining their QoL and socioeconomic, demographic and health status. METHODS: data were compiled from older people enrolled in the Lc65+ cohort study and two additional, population-based, stratified random samples (n = 5,300). Principal components analysis (PCA) was used to determine the underlying domains among 28 items that participants defined as important to their QoL. The components extracted were used as dependent variables in multiple linear regression models to explore their associations with socioeconomic, demographic and health status. RESULTS: PCA identified seven domains that older persons considered important to their QoL. In order of importance (highest to lowest): feeling of safety, health and mobility, autonomy, close entourage, material resources, esteem and recognition, and social and cultural life. A total of six and five domains of importance were significantly associated with education and depressive symptoms, respectively. The importance of material resources was significantly associated with a good financial situation (β = 0.16, P = 0.011), as was close entourage with living with others (β = 0.20, P = 0.007) and as was health and mobility with age (β = -0.16, P = 0.014). CONCLUSION: the importance older people give to domains of their QoL appears strongly related to their actual resources and experienced losses. These findings may help clinicians, researchers and policy makers better adapt strategies to individuals' needs.

Référentiel de pratiques professionnelles: soins et surveillance des accès veineux centraux de l'adulte pour la nutrition parentérale [Formative assessment in clinical nutrition: Care management of parenteral nutrition central venous access]

Les voies veineuses centrales (VVC) sont essentielles pour l'administration de la nutrition parentérale. Le risque de complications est dépendant de la qualité des soins apportés à la VVC qui influence de ce fait la qualité de vie des patients et le coût des soins. Beaucoup de complications des VVC, infectieuses ou non, peuvent être prévenues par l'existence de protocoles de soins appropriés et standardisés. L'information sur les soins des VVC et les éventuelles complications est essentielle pour le dépistage et le traitement précoce de ces complications ; elle doit faire l'objet de protocoles partagés entre les patients et les soignants. Cet article décrit une évaluation des pratiques professionnelles sous la forme d'un audit clinique destiné à améliorer la qualité de soins des patients en nutrition parentérale porteurs de VVC. Central venous access devices (CVAD) are essential for the administration of parenteral nutrition. The quality of the care of CVAD influences the risk of complications and so the quality of life of the patients and the costs of care. Numerous infectious or non-infectious complications of CVAD can be prevented by appropriate, standardized protocols of care. Information about the care of CVAD and complications is essential for the early recognition and treatment of complications and should be shared between patients and caregivers. This article describes an audit for CAVD care that can be used to improve quality of care in a professional practice evaluation program.

Evaluation of Implementation of BSc IT Curriculum at Tumaini University

In Tanzania computer knowledge is vital to supplement the pace fast growing economic and development activities, which demands high and reliable level of expertise in com- puting field. In 2006, a research carried out at Tumaini University with purpose to design and implement a contextualized curriculum that can supplement for such needs hence facilitate development in Tanzanian context. A contextualized curriculum took advantage of six principles namely curriculum contex- tualization, projects, practical, interdisciplinary orientation, international recognition and continuous research for the program’s formative and development. Implementation of the curriculum followed the CATI (Contextualize, Apply, Transfer, and Import) model with emphasis on students to identify societal expectations at the early stage in learning process, in which case the graduates will potentially cater for societal expertise needs on ICT. This study adopts an emergent exploratory cross-section research design, while employ- ing a qualitative approach. This study was conducted at Tumaini University in Iringa where by purposeful sampling was used to obtain participants such as students, teach- ers, administrators and employers who participated in several focus group discussions, in-depth interviews and participant observation. The study reveals that six principles are satisfactorily met,despite of bottlenecks such as incompatibility in pedagogical thinking and technology availability for e-learning, learning attitudes, insufficient experts with actual skills and experience,in academic field among the others. The study recommends that iterative longitudinal study should be car- ried out to design for proper intervention in response to these problems which will help in improving and stabilize the curriculum.

Osakeperusteinen palkitseminen: maksuttoman osakkeen hyödyntäminen kannustinjärjestelmissä

Tutkielman tavoitteena on selvittää osakeyhtiön palkitsemisjärjestelmiin liittyviä kysymyksiä päämies–agenttisuhteiden ja osakeyhtiöoikeudellisten periaatteiden kautta. Tutkielmassa selvitetään, kuinka maksuttomia osakkeita voidaan hyödyntää julkisen osakeyhtiön palkitsemisjärjestelmissä ja mitä haasteita ja mahdollisuuksia niiden käyttöön liittyy. Tutkimusmetodi työssä on lainopillinen ja aihetta lähestytään luontevasti kauppatieteellisen ja oikeustieteellisen näkökulman yhdistävän oikeustaloustieteen kautta. Ensisijaisena aineistona tutkielmassa käytetään voimassaolevaa lainsäädäntöä valmisteluaineistoineen ja näkökulmaa syvennetään aiemmin voimassa olleen lainsäädännön tarkastelulla. Toissijaisena aineistona tutkielmassa käytetään sekä eri asiantuntijoiden oikeudellista kirjallisuutta että palkitsemisen asiantuntijoiden laatimaa kirjallisuutta Suomesta ja muista länsimaista. Teoreettista työtä on syvennetty asiantuntijahaastattelulla ja yhtiöiden sijoittajatiedosta saatavalla informaatiolla. Merkittävin osakeyhtiön johdon ja yhtiön välisen suhteen tehokkuutta alentava seikka on päämies–agenttisuhteen valvontaongelma. Tämä liittyy päämies - agenttisuhteeseen, joka ilmenee negatiivisesti yhtiön ja yhtiön johdon intressien ristiriitatilanteissa. Valvontaongelma voi aiheuttaa ylimääräisiä transaktiokustannuksia ja tämä näkyy yhtiön toiminnan tehokkuuden laskemisena. Päämies–agenttisuhteen ratkaisuna lainsäädäntö ja erilaiset valvonnan keinot ovat tehottomia ja nykyisen yhtiöoikeudellisen ajattelun vastaisia. Tehokkaimmin valvontaongelma saadaan ratkaistua erilaisin kannustimin tapahtuvalla johdon ohjauksella. Osakesidonnainen palkitseminen on suosituin johdon ja yhtiön intressien yhdistämisen keino. Osakesidonnainen palkitseminen on parhaimmillaan eri osapuolien näkökulmasta sitouttavaa ja kannustavaa mutta osakepalkitsemisen käyttöön liittyy myös riskejä. Eräs keskeisistä yhtiöoikeudellisista periaatteista on yhdenvertaisuus, jota saatetaan loukata eri palkitsemisjärjestelmiä käytettäessä. Varojen jakoon ja järjestelmien rahoitukseen liittyy niin ikään riskejä, jotka saattavat vaarantaa järjestelmän onnistumisen. Liian avokätiset palkkiojärjestelmät taas saattavat aiheuttaa yhtiön eri sidosryhmien piirissä tyytymättömyyttä joka taas alentaa järjestelmän tehokkuutta. Yhtiön johto vastaa yhtiön strategian toteutumisesta ja linjaa Corporate Governance käytännön mukaisesti johdon palkitsemisen tavat. Yhtiön johto on kuitenkin päätöksistään vastuussa yhtiön residuaalioikeuden omaaville päämiehille, eli osakkeenomistajille. Vaikka yhtiön johto vastaa viime kädessä yhtiön toiminnasta, sen on huomioitava toiminnassaan yhtiön toiminnan tarkoitus ja sitä kautta yksittäisen osakkeenomistajan etu. Vaikka osakeyhtiössä toteutettaisiin enemmistöomistajan valitsemaa toimintalinjaa, osakeyhtiön yhdenvertaisuusperiaate korostaa juuri vähemmistöosakkeenomistajan asemaa. Johdon fidusiaaristen velvoitteiden voidaankin nähdä korostuvan johdon suhteessa vähemmistöosakkeenomistajaan. Tämä on huomioitava myös palkitsemisjärjestelmissä. Johdon palkitsemisjärjestelmien suunnittelussa ja toteutuksessa on suunnattava keskeinen huomio sen tavoitteiden toteutumiseen, eli yksittäisen osakkeenomistajan omistuksen arvon kasvattamiseen pidemmällä aikavälillä, pitäen huolta osakeyhtiön kantavista periaatteista.

New Distance Transforms for Gray Level Image Compression

This thesis deals with distance transforms which are a fundamental issue in image processing and computer vision. In this thesis, two new distance transforms for gray level images are presented. As a new application for distance transforms, they are applied to gray level image compression. The new distance transforms are both new extensions of the well known distance transform algorithm developed by Rosenfeld, Pfaltz and Lay. With some modification their algorithm which calculates a distance transform on binary images with a chosen kernel has been made to calculate a chessboard like distance transform with integer numbers (DTOCS) and a real value distance transform (EDTOCS) on gray level images. Both distance transforms, the DTOCS and EDTOCS, require only two passes over the graylevel image and are extremely simple to implement. Only two image buffers are needed: The original gray level image and the binary image which defines the region(s) of calculation. No other image buffers are needed even if more than one iteration round is performed. For large neighborhoods and complicated images the two pass distance algorithm has to be applied to the image more than once, typically 3 10 times. Different types of kernels can be adopted. It is important to notice that no other existing transform calculates the same kind of distance map as the DTOCS. All the other gray weighted distance function, GRAYMAT etc. algorithms find the minimum path joining two points by the smallest sum of gray levels or weighting the distance values directly by the gray levels in some manner. The DTOCS does not weight them that way. The DTOCS gives a weighted version of the chessboard distance map. The weights are not constant, but gray value differences of the original image. The difference between the DTOCS map and other distance transforms for gray level images is shown. The difference between the DTOCS and EDTOCS is that the EDTOCS calculates these gray level differences in a different way. It propagates local Euclidean distances inside a kernel. Analytical derivations of some results concerning the DTOCS and the EDTOCS are presented. Commonly distance transforms are used for feature extraction in pattern recognition and learning. Their use in image compression is very rare. This thesis introduces a new application area for distance transforms. Three new image compression algorithms based on the DTOCS and one based on the EDTOCS are presented. Control points, i.e. points that are considered fundamental for the reconstruction of the image, are selected from the gray level image using the DTOCS and the EDTOCS. The first group of methods select the maximas of the distance image to new control points and the second group of methods compare the DTOCS distance to binary image chessboard distance. The effect of applying threshold masks of different sizes along the threshold boundaries is studied. The time complexity of the compression algorithms is analyzed both analytically and experimentally. It is shown that the time complexity of the algorithms is independent of the number of control points, i.e. the compression ratio. Also a new morphological image decompression scheme is presented, the 8 kernels' method. Several decompressed images are presented. The best results are obtained using the Delaunay triangulation. The obtained image quality equals that of the DCT images with a 4 x 4

Um paradigma da química medicinal: a flexibilidade dos ligantes e receptores

In general, molecular modeling techniques applied in medicinal chemistry have been static and drug based. However the active site geometry and the intrinsic flexibility of both receptor and ligand are fundamental properties for molecular recognition and drug action. As a consequence, the use of dynamic models to describe the ligand-receptor complex is becoming a more common procedure. In this work we discuss the relevance of considering the receptor structure in medicinal chemistry studies as well as the flexibility of the ligand-receptor complex.

Creating dynamic continuous improvement system for Larox Corporation

Today´s organizations must have the ability to react to rapid changes in the market. These rapid changes cause pressure to continuously find new efficient ways to organize work practices. Increased competition requires businesses to become more effective and to pay attention to quality of management and to make people to understand their work's impact on the final result. The fundamentals in continmuois improvement are systematic and agile tackling of indentified individual process constraints and the fact tha nothin finally improves without changes. Successful continuous improvement requires management commitment, education, implementation, measurement, recognition and regeneration. These ingredients form the foundation, both for breakthrough projects and small step ongoing improvement activities. One part of the organization's management system are the quality tools, which provide systematic methodologies for identifying problems, defining their root causes, finding solutions, gathering and sorting of data, supporting decision making and implementing the changes, and many other management tasks. Organizational change management includes processes and tools for managing the people in an organizational level change. These tools include a structured approach, which can be used for effective transition of organizations through change. When combined with the understanding of change management of individuals, these tools provide a framework for managing people in change,