Aminoterminal amphipathic α-helix AH1 of hepatitis C virus nonstructural protein 4B possesses a dual role in RNA replication and virus production.

Nonstructural protein 4B (NS4B) is a key organizer of hepatitis C virus (HCV) replication complex formation. In concert with other nonstructural proteins, it induces a specific membrane rearrangement, designated as membranous web, which serves as a scaffold for the HCV replicase. The N-terminal part of NS4B comprises a predicted and a structurally resolved amphipathic α-helix, designated as AH1 and AH2, respectively. Here, we report a detailed structure-function analysis of NS4B AH1. Circular dichroism and nuclear magnetic resonance structural analyses revealed that AH1 folds into an amphipathic α-helix extending from NS4B amino acid 4 to 32, with positively charged residues flanking the helix. These residues are conserved among hepaciviruses. Mutagenesis and selection of pseudorevertants revealed an important role of these residues in RNA replication by affecting the biogenesis of double-membrane vesicles making up the membranous web. Moreover, alanine substitution of conserved acidic residues on the hydrophilic side of the helix reduced infectivity without significantly affecting RNA replication, indicating that AH1 is also involved in virus production. Selective membrane permeabilization and immunofluorescence microscopy analyses of a functional replicon harboring an epitope tag between NS4B AH1 and AH2 revealed a dual membrane topology of the N-terminal part of NS4B during HCV RNA replication. Luminal translocation was unaffected by the mutations introduced into AH1, but was abrogated by mutations introduced into AH2. In conclusion, our study reports the three-dimensional structure of AH1 from HCV NS4B, and highlights the importance of positively charged amino acid residues flanking this amphipathic α-helix in membranous web formation and RNA replication. In addition, we demonstrate that AH1 possesses a dual role in RNA replication and virus production, potentially governed by different topologies of the N-terminal part of NS4B.

A new ambulatory system for comparative evaluation of the three-dimensional knee kinematics, applied to anterior cruciate ligament injuries

The aim of this study was to develop an ambulatory system for the three-dimensional (3D) knee kinematics evaluation, which can be used outside a laboratory during long-term monitoring. In order to show the efficacy of this ambulatory system, knee function was analysed using this system, after an anterior cruciate ligament (ACL) lesion, and after reconstructive surgery. The proposed system was composed of two 3D gyroscopes, fixed on the shank and on the thigh, and a portable data logger for signal recording. The measured parameters were the 3D mean range of motion (ROM) and the healthy knee was used as control. The precision of this system was first assessed using an ultrasound reference system. The repeatability was also estimated. A clinical study was then performed on five unilateral ACL-deficient men (range: 19-36 years) prior to, and a year after the surgery. The patients were evaluated with the IKDC score and the kinematics measurements were carried out on a 30 m walking trial. The precision in comparison with the reference system was 4.4 degrees , 2.7 degrees and 4.2 degrees for flexion-extension, internal-external rotation, and abduction-adduction, respectively. The repeatability of the results for the three directions was 0.8 degrees , 0.7 degrees and 1.8 degrees . The averaged ROM of the five patients' healthy knee were 70.1 degrees (standard deviation (SD) 5.8 degrees), 24.0 degrees (SD 3.0 degrees) and 12.0 degrees (SD 6.3 degrees for flexion-extension, internal-external rotation and abduction-adduction before surgery, and 76.5 degrees (SD 4.1 degrees), 21.7 degrees (SD 4.9 degrees) and 10.2 degrees (SD 4.6 degrees) 1 year following the reconstruction. The results for the pathologic knee were 64.5 degrees (SD 6.9 degrees), 20.6 degrees (SD 4.0 degrees) and 19.7 degrees (8.2 degrees) during the first evaluation, and 72.3 degrees (SD 2.4 degrees), 25.8 degrees (SD 6.4 degrees) and 12.4 degrees (SD 2.3 degrees) during the second one. The performance of the system enabled us to detect knee function modifications in the sagittal and transverse plane. Prior to the reconstruction, the ROM of the injured knee was lower in flexion-extension and internal-external rotation in comparison with the controlateral knee. One year after the surgery, four patients were classified normal (A) and one almost normal (B), according to the IKDC score, and changes in the kinematics of the five patients remained: lower flexion-extension ROM and higher internal-external rotation ROM in comparison with the controlateral knee. The 3D kinematics was changed after an ACL lesion and remained altered one year after the surgery

Load Testing and Load Rating Eight State Highway Bridges in Iowa, 1999

This main report provides a general discussion of the load testing, structural evaluation, and load rating procedures. Specific details for each bridge are provided in individual report sections. Additional supporting information on load testing, analyses, and load rating are also provided in the attached appendices.

The contribution of a pollinating seed predator to selection on Silene latifolia females.

Interactions, antagonistic or mutualistic, can exert selection on plant traits. We explored the role of Hadena bicruris, a pollinating seed predator, as a selective agent on its host, the dioecious plant Silene latifolia. We exposed females from artificial-selection lines (many, small flowers (SF) vs. few, large flowers (LF)) to this moth. Infestation did not differ significantly between lines, but the odds of attacked fruits aborting were higher in SF females. We partitioned selection between that caused by moth attack and that resulting from all other factors. In both lines, selection via moth attack for fewer, smaller flowers contrasted with selection via other factors for more flowers. In LF females, selection via the two components was strongest and selection via moth attack also favoured increased fruit abortion. This suggests that the moths act as more of a selective force on flower size and number via their predating than their pollinating role.

Control hardware and Condition Monitoring System for Intersector Weld/Cut Robot

Työ sisältää ohjaislaitteiston vertailun ja valinnan rinnakkaisrakenteista robottia varten sekä kunnonvalvontajärjestelmän periaatteiden laadinnan kyseistä robottia varten. Ohjauslaitteisto sisältää teollisuustietokoneen sekä kenttäväylän. Sekä tietokoneesta että väylästä on teoriaosuus ja yksityiskohtaisempi valintaosuus. Teoriaosuudessa selitetään tarkemmin laitteiden toimintaperiaatteista. Valintaosuudessa kerrotaanmiksi jokin tietty laite on valittu käytettäväksi robotin ohjauksessa. Kunnonvalvontateoria ja rinnakkaisrakenteisen robotin kunnonvalvonnan keinot ovat työn toinen osa. Teoriaosa sisältää yleisluonteisen selvityksen vikaantumisesta ja valvonnasta. Erikoisrobotin kunnonvalvonnan keinot esitetään työssä tietyssä järjestyksessä. Ensin esitetään mahdolliset vikatilanteet. Toisessa kohdassa havainnollistetaan vikojen havaitseminen.

Evaluation of Routing solution for Next Generation Open Platform

Verkkoon kytkettävien laitteiden määrä on lisääntynyt viime vuosina, joka luo tarpeen reitittimille ja niiden ominaisuuksille. On muodostunut uusi tarve laitteille, jotka voivat yhdistää erilaisia verkkoja toisiinsa. Tällaisen reitittimen rakentamiseen tarvitaan vakaa alusta. Tällaisella alustalla luodaan mahdollisuus kuormittaa järjestelmää ilman suuria ongelmia. Tällainen alusta on Open Platform, joka on suunniteltu tällaisille toiminnoille ja yhdessä oikeanlaisen verkkoratkaisun kanssa sitä voidaan käyttää sille suunnitellussa ympäristössä. Tämän diplomityön tarkoituksena on arvioida neljää eri reititysohjelmistoa ja kahta eri IP pinoa. Työssä käytetyt testit on suunniteltu arviointia varten ja niiden tarkoituksena on tuoda esille ohjelmistoissa esiintyvät viat ja ongelmat. Kaikki testit ovat samoja kaikille ohjelmille ja tehdään samassa ympäristössä. Testit analysoidaan niiden ajon jälkeen ja niiden tulosten avulla tehdään päätös mitä näistä ohjelmistoista tullaan käyttämään seuraavan sukupolven avoimella alustalla, joka tulee toimimaan Nokian Intelligent Service Nodessa. Tämä verkon laite toimii yhdyskäytävänäerilaisten verkkojen välillä.

La dépression majeure en hôpital général: adaptation et mise en oeuvre de recommandations pour la pratique clinique [Major depression in the general hospital: adaptation and implementation of guidelines]

Major depression IMD) is highly prevalent in the general hospital and adds a considerable burden to affected patients, but remains under detected and under treated. In an attempt to improve this situation, existing guidelines on MD were retrieved, systematically evaluated with the instrument AGREE (Appraisal of guidelines for research and evaluation), and adapted to the needs of the general hospital. These guidelines were made available on intranet, and actively implemented in two wards, where their impact on clinical practice was evaluated.

Language variation in source texts and their translations: the case of L3 in film translation

In addition to the two languages essentially involved in translation, that of the source text (L1) and that of the target text (L2), we propose a third language (L3) to refer to any other language(s) found in the text. L3 may appear in the source text (ST) or the target text (TT), actually appearing more frequently inSTs in our case studies. We present a range of combinations for the convergence and divergence of L1, L2 and L3, for the case of feature films and their translations using examples from dubbed and subtitled versions of films, but we are hopeful that our tentative conclusions may be relevant to other modalities of translation, audiovisual and otherwise. When L3 appears in an audiovisual ST,we find a variety of solutions whereby L3 is deleted from or adapted to the TT.In the latter case, L3 might be rendered in a number of ways, depending on factors such as the audience’s familiarity with L3, and the possibility that L3 inthe ST is an invented language.

Transsexualisme: enjeux et spécificités liés à la prise en charge d'une demande de réassignation sexuelle [Gender identity disorder: challenges and specificity in the treatment of requests for sexual reassignment].

Gender identity disorder is defined as a permanent desire to relieve one's own sexual features to acquire the sexual features and line to life of the opposite sex. The diagnosis is based on the psychiatric evaluation and treatment on an interdisciplinary approach by endocrinologists, surgeons and psychiatrists, and can be conceptualized into distinct phases: diagnostic evaluation, real life experience, hormonal treatment and surgery. Multiples challenges have to be faced, especially by the psychiatrist who follows the patient during the whole process.

Business competence and training needs in Finnish companies operating in the Leningrad Region

Tässä pro gradu -työssä tutkitaan Leningradin alueella, Venäjällä, toimivien suomalaisyritysten liiketoimintaosaamisen koulutustarpeita. Tavoitteena on ollut tutkia, millaisia yritysten koulutustarpeet ovat, sekä lisäksi selvittää yleisemmällä tasolla, miten liiketoimintaosaaminen määritellään. Useat tutkimusta varten haastatellut johtajat pitävät liiketoimintaosaamista erityisesti markkinoilla toimimiseen liittyvänä osaamisena. Myös johtaminen, sekä tuotteet ja teknologia nähdään liiketoimintaosaamisen tärkeinä osina. Yrityksillä on koulutustarpeita seuraavilla alueilla: johtaminen; myynti, markkinat ja asiakkaat; yrityksen sisäinen yhteistyö; kielet, sekä juridiikka ja laskentatoimi. Haastateltavien mukaan markkinoiden nopea kehitys sekä yrityksen kasvu luovat yrityksille koulutustarpeita. Yllättäen myös Venäjän koulutusjärjestelmää itsessään pidetään koulutustarpeiden syynä. Tutkimuksessa mukana olleiden yritysten koulutuskäytännöt ovat keskenään melko erilaisia: koulutusbudjetti, koulutuspäivien määrä ja koulutusorganisaation valintakriteerit vaihtelevatyrityksestä riippuen. Joka tapauksessa yleisin koulutusmuoto näyttää olevan yrityksen sisäinen koulutus. Monet haastateltavat painottavat suuresti uusien työntekijöiden kouluttamista. Selvästikin rekrytointi ja uusien työntekijöiden koulutus vievät suuren osan tutkimusta varten haastateltujen johtajien ajasta. Tärkeä huomio koulutusmarkkinoihin liittyen on se, että lyhyiden, kaikille avoimien koulutusten kohdalla markkinat ovat Pietarissa täynnä. Suurimpana uhkana nähdään alalla vallitseva kouluttajapula.

Web Presence Building and Performance Measuring in Business-to-Business Markets

Tutkimuksen tavoite oli selvittää yrityksen web toiminnan rakentamisen vaiheita sekä menestyksen mittaamista. Rakennusprosessia tutkittiin viisiportaisen askelmallin avulla. Mallin askeleet ovat; arviointi, strategian muotoilu, suunnitelma, pohjapiirros ja toteutus. Arviointi- ja toteutusvaiheiden täydentämiseksi sekä erityisesti myös internet toiminnan onnistumisen mittaamisen avuksi internet toiminnan hyödyt (CRM,kommunikointi-, myynti-, ja jakelukanava hyödyt markkinoinnin kannalta) käsiteltiin. Toiminnan menestyksen arvioinnin avuksi esiteltiin myös porrasmalli internet toimintaan. Porrasmalli määrittelee kauppakulissi-, dynaaminen-, transaktio- ja e-businessportaat. Tutkimuksessa löydettiin menestystekijöitä internet toimintojen menestykselle. Nämä tekijät ovat laadukas sisältö, kiinnostavuus, viihdyttävyys, informatiivisuus, ajankohtaisuus, personoitavuus, luottamus, interaktiivisuus, käytettävyys, kätevyys, lojaalisuus, suoriutuminen, responssiivisuus ja käyttäjätiedon kerääminen. Mittarit jaettiin tutkimuksessa aktiivisuus-, käyttäytymis- ja muunnosmittareihin. Lisäksi muita mittareita ja menestysindikaattoreita esiteltiin. Nämä menestyksen elementit ja mittarit koottiin yhteen uudessa internet toimintojen menestyksenarviointimallissa. Tutkielman empiirisessä osuudessa,esitettyjä teorioita peilattiin ABB:n (ABB:n sisällä erityisesti ABB Stotz-Kontakt) web toimintaan. Apuna olivat dokumenttianalyysi sekä haastattelut. Empiirinen osa havainnollisti teoriat käytännössä ja toi ilmi mahdollisuuden teorioiden laajentamiseen. Internet toimintojen rakentamismallia voidaan käyttää myös web toimintojen kehittämiseen ja porrasmalli sopii myös nykyisten internet toimintojen arvioimiseen. Mittareiden soveltaminen käytännössä toi kuitenkin ilmi tarpeen niiden kehittämiseen ja aiheen lisätutkimukseen. Niiden tulisi olla myös aiempaatiiviimmin liitetty kokonaisvaltaisen liiketoiminnan menestyksen mittaamiseen.

Does the working environment influence health care professionals' values, meaning in life and religiousness? Palliative care units compared with maternity wards.

CONTEXT: Increased altruism, self-transcendence, and quests for meaning in life (MiL) have been found in palliative care (PC) patients and their families who experience the finiteness of life. Similar changes were observed in healthy subjects who were experimentally confronted with their mortality. OBJECTIVES: The study investigated how daily experiences of the transitoriness of life influence PC health care professionals' (HCPs) values, MiL, and religiousness. METHODS: In a cross-sectional study, the Schwartz Value Survey, the Schedule for Meaning in Life Evaluation, and the Idler Index of Religiosity were used to investigate personal values, MiL, and private religiousness. HCPs working in PC (confronted with death) were compared with a control group of HCPs working at maternity wards (MWs) using multivariate models. Differences were considered to be statistically significant at P < 0.05. RESULTS: Seventy PC- and 70 MW-HCPs took part in the study (response rate 74.0%). No differences between the groups were found in overall MiL satisfaction scores. PC-HCPs were significantly more religious than MW-HCPs; they listed spirituality and nature experience more often as areas in which they experience MiL. Furthermore, hedonism was more important for PC-HCPs, and they had higher scores in openness-to-change values (stimulation and self-direction). MW-HCPs were more likely to list family as a MiL area. They assigned more importance to health and scored higher in conservation values (conformity and security). Duration of professional experience did not influence these results. CONCLUSION: Basic differences in values, MiL, and religiousness between PC-HCPs and MW-HCPs might have influenced the choice of working environment because no effect of job duration was observed. Longitudinal research is needed to confirm this hypothesis.

Artificial evolution on network structures : how time and space influence dynamics

Abstract The main objective of this work is to show how the choice of the temporal dimension and of the spatial structure of the population influences an artificial evolutionary process. In the field of Artificial Evolution we can observe a common trend in synchronously evolv¬ing panmictic populations, i.e., populations in which any individual can be recombined with any other individual. Already in the '90s, the works of Spiessens and Manderick, Sarma and De Jong, and Gorges-Schleuter have pointed out that, if a population is struc¬tured according to a mono- or bi-dimensional regular lattice, the evolutionary process shows a different dynamic with respect to the panmictic case. In particular, Sarma and De Jong have studied the selection pressure (i.e., the diffusion of a best individual when the only selection operator is active) induced by a regular bi-dimensional structure of the population, proposing a logistic modeling of the selection pressure curves. This model supposes that the diffusion of a best individual in a population follows an exponential law. We show that such a model is inadequate to describe the process, since the growth speed must be quadratic or sub-quadratic in the case of a bi-dimensional regular lattice. New linear and sub-quadratic models are proposed for modeling the selection pressure curves in, respectively, mono- and bi-dimensional regu¬lar structures. These models are extended to describe the process when asynchronous evolutions are employed. Different dynamics of the populations imply different search strategies of the resulting algorithm, when the evolutionary process is used to solve optimisation problems. A benchmark of both discrete and continuous test problems is used to study the search characteristics of the different topologies and updates of the populations. In the last decade, the pioneering studies of Watts and Strogatz have shown that most real networks, both in the biological and sociological worlds as well as in man-made structures, have mathematical properties that set them apart from regular and random structures. In particular, they introduced the concepts of small-world graphs, and they showed that this new family of structures has interesting computing capabilities. Populations structured according to these new topologies are proposed, and their evolutionary dynamics are studied and modeled. We also propose asynchronous evolutions for these structures, and the resulting evolutionary behaviors are investigated. Many man-made networks have grown, and are still growing incrementally, and explanations have been proposed for their actual shape, such as Albert and Barabasi's preferential attachment growth rule. However, many actual networks seem to have undergone some kind of Darwinian variation and selection. Thus, how these networks might have come to be selected is an interesting yet unanswered question. In the last part of this work, we show how a simple evolutionary algorithm can enable the emrgence o these kinds of structures for two prototypical problems of the automata networks world, the majority classification and the synchronisation problems. Synopsis L'objectif principal de ce travail est de montrer l'influence du choix de la dimension temporelle et de la structure spatiale d'une population sur un processus évolutionnaire artificiel. Dans le domaine de l'Evolution Artificielle on peut observer une tendence à évoluer d'une façon synchrone des populations panmictiques, où chaque individu peut être récombiné avec tout autre individu dans la population. Déjà dans les année '90, Spiessens et Manderick, Sarma et De Jong, et Gorges-Schleuter ont observé que, si une population possède une structure régulière mono- ou bi-dimensionnelle, le processus évolutionnaire montre une dynamique différente de celle d'une population panmictique. En particulier, Sarma et De Jong ont étudié la pression de sélection (c-à-d la diffusion d'un individu optimal quand seul l'opérateur de sélection est actif) induite par une structure régulière bi-dimensionnelle de la population, proposant une modélisation logistique des courbes de pression de sélection. Ce modèle suppose que la diffusion d'un individu optimal suit une loi exponentielle. On montre que ce modèle est inadéquat pour décrire ce phénomène, étant donné que la vitesse de croissance doit obéir à une loi quadratique ou sous-quadratique dans le cas d'une structure régulière bi-dimensionnelle. De nouveaux modèles linéaires et sous-quadratique sont proposés pour des structures mono- et bi-dimensionnelles. Ces modèles sont étendus pour décrire des processus évolutionnaires asynchrones. Différentes dynamiques de la population impliquent strategies différentes de recherche de l'algorithme résultant lorsque le processus évolutionnaire est utilisé pour résoudre des problèmes d'optimisation. Un ensemble de problèmes discrets et continus est utilisé pour étudier les charactéristiques de recherche des différentes topologies et mises à jour des populations. Ces dernières années, les études de Watts et Strogatz ont montré que beaucoup de réseaux, aussi bien dans les mondes biologiques et sociologiques que dans les structures produites par l'homme, ont des propriétés mathématiques qui les séparent à la fois des structures régulières et des structures aléatoires. En particulier, ils ont introduit la notion de graphe sm,all-world et ont montré que cette nouvelle famille de structures possède des intéressantes propriétés dynamiques. Des populations ayant ces nouvelles topologies sont proposés, et leurs dynamiques évolutionnaires sont étudiées et modélisées. Pour des populations ayant ces structures, des méthodes d'évolution asynchrone sont proposées, et la dynamique résultante est étudiée. Beaucoup de réseaux produits par l'homme se sont formés d'une façon incrémentale, et des explications pour leur forme actuelle ont été proposées, comme le preferential attachment de Albert et Barabàsi. Toutefois, beaucoup de réseaux existants doivent être le produit d'un processus de variation et sélection darwiniennes. Ainsi, la façon dont ces structures ont pu être sélectionnées est une question intéressante restée sans réponse. Dans la dernière partie de ce travail, on montre comment un simple processus évolutif artificiel permet à ce type de topologies d'émerger dans le cas de deux problèmes prototypiques des réseaux d'automates, les tâches de densité et de synchronisation.

Ideal and reality: do countries adopt and follow recommended procedures in comprehensive multiyear planning guidelines for national immunization programmes?

BACKGROUND: Meticulous steps and procedures are proposed in planning guidelines for the development of comprehensive multiyear plans for national immunization programmes. However, we know very little about whether the real-life experience of those who adopt these guidelines involves following these procedures as expected. Are these steps and procedures followed in practice? We examined the adoption and usage of the guidelines in planning national immunization programmes and assessed whether the recommendations in these guidelines are applied as consistently as intended. METHODS: We gathered information from the national comprehensive multiyear plans developed by 77 low-income countries. For each of the 11 components, we examined how each country applied the four recommended steps of situation analysis, problem prioritization, selection of interventions, and selection of indicators. We then conducted an analysis to determine the patterns of alignment of the comprehensive multiyear plans with those four recommended planning steps. RESULTS: Within the first 3 years following publication of the guidelines, 66 (86%) countries used the tool to develop their comprehensive multiyear plans. The funding conditions attached to the use of these guidelines appeared to influence their rapid adoption and usage. Overall, only 33 (43%) countries fully applied all four recommended planning steps of the guidelines. CONCLUSIONS: Adoption and usage of the guidelines for the development of comprehensive multiyear plans for national immunization programmes were rapid. However, our findings show substantial variation between the proposed planning ideals set out in the guidelines and actual use in practice. A better understanding of factors that influence how recommendations in public health guidelines are applied in practice could contribute to improvements in guidelines design. It could also help adjust strategies used to introduce them into public health programmes, with the ultimate goal of a greater health impact.

Lack of support for the association between facial shape and aggression: a reappraisal based on a worldwide population genetics perspective

Antisocial and criminal behaviors are multifactorial traits whose interpretation relies on multiple disciplines. Since these interpretations may have social, moral and legal implications, a constant review of the evidence is necessary before any scientific claim is considered as truth. A recent study proposed that men with wider faces relative to facial height (fWHR) are more likely to develop unethical behaviour mediated by a psychological sense of power. This research was based on reports suggesting that sexual dimorphism and selection would be responsible for a correlation between fWHR and aggression. Here we show that 4,960 individuals from 94 modern human populations belonging to a vast array of genetic and cultural contexts do not display significant amounts of fWHR sexual dimorphism. Further analyses using populations with associated ethnographical records as well as samples of male prisoners of the Mexico City Federal Penitentiary condemned by crimes of variable level of inter-personal aggression (homicide, robbery, and minor faults) did not show significant evidence, suggesting that populations/individuals with higher levels of bellicosity, aggressive behaviour, or power-mediated behaviour display greater fWHR. Finally, a regression analysis of fWHR on individual"s fitness showed no significant correlation between this facial trait and reproductive success. Overall, our results suggest that facial attributes are poor predictors of aggressive behaviour, or at least, that sexual selection was weak enough to leave a signal on patterns of between- and within-sex and population facial variation.