Annual Report of Iowa Highway Research Board Research and Development Activities FY 2011, December 2011

The Highway Division of the Iowa DOT engages in research and development for two reasons: first, to find workable solutions to the many problems that require more than ordinary, routine investigation; and second, to identify and implement improved engineering and management practices. This report, entitled ―Iowa Highway Research Board Research and Development Activities FY2011‖ is submitted in compliance with Sections 310.36 and 312.3A, Code of Iowa, which direct the submission of a report of the Secondary Road Research Fund and the Street Research Fund, respectively. It is a report of the status of research and development projects in progress on June 30, 2011. It is also a report on projects completed during the fiscal year beginning July 1, 2010 and ending June 30, 2011. Detailed information on each of the research and development projects mentioned in this report is available from the Research and Technology Bureau, Highway Division, Iowa Department of Transportation. All approved reports are also online for viewing at: www.iowadot.gov/operationsresearch/reports.aspx.

Report of the ECCO workshop on anti-TNF therapy failures in inflammatory bowel diseases: biological roles and effects of TNF and TNF antagonists.

This second section of the first ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases addresses the biological roles of TNFα and the effects and mechanisms of action of TNFα antagonists. Mechanisms underlying their failure, including induction of TNF-independent inflammatory pathways and phenomena of paradoxical inflammation are discussed.

CARDIAC AND MUSCLE CHANNELOPATHIES: ROLES AND REGULATION OF VOLTAGE-GATED SODIUM CHANNELS

Abstract :The contraction of the heart or skeletal muscles is mainly due to the propagation, through excitable cells, of an electrical influx called action potential (AP). The AP results from the sequential opening of ion channels that generate inward or outward currents through the cell membrane. Among all the channels involved, the voltage-gated sodium channel is responsible for the rising phase of the action potential. Ten genes encode the different isoforms of these channels (from Nav1.1 to Nav1.9 and an atypical channel named NavX). Nav1.4 and Nav1.5 are the main skeletal muscle and cardiac sodium channels respectively. Their importance for muscle and heart function has been highlighted by the description of mutations in their encoding genes SCN4A and SCNSA. They lead respectively to neuromuscular disorders such as myotonia or paralysis (for Nav1.4), and to cardiac arrhythmias that can deteriorate into sudden cardiac death (for Nav1.5).The general aim of my PhD work has been to study diseases linked with channels dysfunction, also called channelopathies. In that purpose, I investigated the function and the regulation of the muscle and cardiac voltage-gated sodium channels. During the two first studies, I characterized the effects of two mutations affecting Nav1.4 and Nav1.5 function. I used the HEK293 model cells to express wild-type or mutant channels and then studied their biophysical properties with the patch-clamp technique, in whole cell configuration. We found that the SCN4A mutation produced complex alterations of the muscle sodium channel function, that could explain the myotonic phenotype described in patients carrying the mutation. In the second study, the index case was an heterozygous carrier of a SCNSA mutation that leads to a "loss of function" of the channel. The decreased sodium current measured with mutated Nay 1.5 channels, at physiological temperature, was a one of the factors that could explain the observed Brugada syndrome. The last project aimed at identifying a new potential protein interacting with the cardiac sodium channel. We found that the protein SAP97 binds the three last amino-acids of the C-terminus of Na,, 1.5. Our results also indicated that silencing the expression of SAP97 in HEK293 cells decreased the sodium current. Sodium channels lacking their three last residues also produced a reduced INa. These preliminary results suggest that SAP97 is implicated in the regulation of sodium channel. Whether this effect is direct or imply the action of an adaptor protein remains to be investigated. Moreover, our group has previously shown that Nav1.5 channels are localized to lateral membranes of cardiomyocytes by the dystrophin multiprotein complex (DMC). This suggests that sodium channels are distributed in, at least, two different pools: one targeted at lateral membranes by DMC and the other at intercalated discs by another protein such as SAP97.These studies reveal that cardiac and muscle diseases may result from ion channel mutations but also from regulatory proteins affecting their regulation.Résumé :La contraction des muscles et du coeur est principalement due à la propagation, à travers les cellules excitables, d'un stimulus électrique appelé potentiel d'action (PA). C'est l'ouverture séquentielle de plusieurs canaux ioniques transmembranaires, permettant l'entrée ou la sortie d'ions dans la cellule, qui est à l'origine de ce PA. Parmi tous les canaux ioniques impliqués dans ce processus, les canaux sodiques dépendant du voltage sont responsables de la première phase du potentiel d'action. Les différentes isoformes de ces canaux (de Nav1.1 à Nav1.9 et NavX) sont codées par dix gènes distincts. Nav1.4 et Nav1.5 sont les principaux variants exprimés respectivement dans le muscle et le coeur. Plusieurs mutations ont été décrites dans les gènes qui codent pour ces deux canaux: SCN4A (pour Nav1.4) et SCNSA (pour Nav1.5). Elles sont impliquées dans des pathologies neuromusculaires telles que des paralysies ou myotonies (SCN4A) ou des arythmies cardiaques pouvant conduire à la mort subite cardiaque (SCNSA).Mon travail de thèse a consisté à étudier les maladies liées aux dysfonctionnements de ces canaux, aussi appelées canalopathies. J'ai ainsi analysé la fonction et la régulation des canaux sodiques dépendant du voltage dans le muscle squelettique et le coeur. A travers les deux premières études, j'ai ainsi pu examiner les conséquences de deux mutations affectant respectivement les canaux Nav1.4 et Nav1.5. Les canaux sauvages ou mutants ont été exprimés dans des cellules HEK293 afin de caractériser leurs propriétés biophysiques par la technique du patch clamp en configuration cellule entière. Nous avons pu déterminer que la mutation trouvée dans le gène SCN4A engendrait des modifications importantes de la fonction du canal musculaire. Ces altérations fournissent des indications nous permettant d'expliquer certains aspects de la myotonie observée chez les membres de la famille étudiée. Le patient présenté dans la deuxième étude était hétérozygote pour la mutation identifiée dans le gène SCNSA. La perte de fonction des canaux Nav1.5 ainsi engendrée, a été observée lors d'analyses à températures physiologiques. Elle représente l'un des éléments pouvant potentiellement expliquer le syndrome de Brugada du patient. La dernière étude a consisté à identifier une nouvelle protéine impliquée dans la régulation du canal sodique cardiaque. Nos expériences ont démontré que les trois derniers acides aminés de la partie C-terminale de Nav1.5 pouvaient interagir avec la protéine SAP97. Lorsque que l'expression de la SAP97 est réduite dans les cellules HEK293, cela induit une baisse importante du courant sodique. De même, les canaux tronqués de leurs trois derniers acides aminés génèrent un flux ionique réduit. Ces résultats préliminaires suggèrent que SAP97 est peut-être impliquée dans la régulation du canal Na,,1.5. Des expériences complémentaires permettront de déterminer si ces deux protéines interagissent directement ou si une protéine adaptatrice est nécessaire. De plus, nous avons préalablement montré que les canaux Nav1.5 étaient localisés au niveau de la membrane latérale des cardiomyocytes par le complexe multiprotéique de la dystrophine (DMC). Ceci suggère que les canaux sodiques peuvent être distribués dans un minimum de deux pools, l'un ciblé aux membranes latérales pax le DMC et l'autre dirigé vers les disques intercalaires par des protéines telles que SAP97.L'ensemble de ces études met en évidence que certaines maladies musculaires et cardiaques peuvent être la conséquence directe de mutations de canaux ioniques, mais que l'action de protéines auxiliaires peut aussi affecter leur fonction.

Iowa Highway Research Board Research and Development Activities FY 2015

This report, entitled Iowa Highway Research and Development Activities FY 2015, is submitted in compliance with Iowa Code section 310.36 and 312.3A, which direct the submission of a report of the Secondary Road Research Fund and the Street Research Fund, respectively. It is a report of the status of research and development projects in process on June 30, 2015. It is also a report on projects completed during the fiscal year beginning July 1, 2014 and ending June 30, 2015. Detailed information on each of the research and development projects mentioned in this report is available from the office of Research and Analytics, Performance and Technology Division, Iowa Department of Transportation. All approved reports are also online for viewing at http://www.iowadot.gov/research/pdf/IHRBAnnualReport.pdf.

ePortfolio as a tool for reflexivity and skills' communication : learn how to communicate skills

This paper aims to present an ePortfolio project led for two years in a multilingual and interdisciplinary Master's program in public discourse and communication analysis offered by the Faculty of Arts of the University of Lausanne (Switzerland). Globally, the project - named Learn to communicate skills - offers a reflection about academic skills and their transferability to the professional world. More precisely, the aim of the project is to make students aware of the importance of reflexive learning to make their skills transferable to other contexts.

Balancing knowledge sharing and protection in collaborative innovation - The roles and dynamics of contracts, IPR's and trust

Pro-gradu tutkielman tavoitteena on tutkia, miten yritykset tasapainoilevat tiedon jakamisen ja suojaamisen välillä innovaatioyhteistyöprojekteissa, ja miten sopimukset, immateriaalioikeudet ja luottamus voivat vaikuttaa tähän tasapainoon. Yhteistyössä yritysten täytyy jakaa tarpeellista tietoa kumppanilleen, mutta toisaalta niiden täytyy varoa, etteivät ne menetä ydinosaamiseensa kuuluvaa tietoa ja kilpailuetuaan. Yrityksillä on useita keinoja tietovuodon estämiseen. Tutkielmassa keskitytään patenttien, sopimusten ja liikesalaisuuksien käyttöön tietoa suojaavina mekanismeina. Kyseiset suojamekanismit vaikuttavat luottamukseen kumppaneiden välillä, ja täten myös näiden halukkuuteen jakaa tietoa kumppaneilleen. Jos kumppanit eivät jaa tarpeeksi tietoa toisilleen, voi yhteistyö epäonnistua. Sopimusten, immateriaalioikeuksien ja luottamuksen rooleja ja vuorovaikutusta tutkitaan kahdenvälisissä yhteistyöprojekteissa. Tutkielmassa esitellään neljä case-esimerkkiä, jotka on koottu suomalaisen metsätoimialan yrityksen haastatteluista.

The roles and tasks of salespeople in Software-as-a-Service company's value-based sales process

Recent research in relationships marketing and sales and sales management emphasizes companies’ ability to create customer value as a core of all business-to-business relationships. The role of individual salespeople in business relation-ships is commonly acknowledged, but has been largely neglected in extant literature. This study offers especially more detailed perspective on salespeople’s roles and tasks in business-to-business value-based sales process. It focuses especially on Software-as-a-Service business environment. The objective of the study is to find out how salespeople can create value in Software-as-a-Service value-based sales process. It determines value-based sales process, salespeople’s roles and tasks in it, and combines value assessment in to process. The results indicate that salespeople have to adapt different selling roles and tasks in Software-as-a-Service value-based sales process to be able to support the customer’s value-in-use experience. The process itself is highly complex, consisting of multiple facets and selling behaviors, and involves relevant actors from both parties of relationship. The study concludes with a discussion of possibilities that provide interesting aspects for future research.

Exploring female graduate students' multifaceted and intersecting roles and identities in a complex educational milieu /

This qualitative phenomenological investigation explored six female Master of Education students' critical understandings of their identity and role negotiations, and their perceptions of environmental conditions that facilitated or impeded their identity explorations and negotiations within the institution. The interweaving of Feminist and Women's Development theories enabled the data to be examined under different, yet complementary, lenses. The data collection strategies included: four to five in-depth semistructured interviews, three take-home activities (involving identity mapping, object and metaphor identification, and strategy development), and the compilation of extensive interview notes as well as researcher reflections. The combination of a constant comparative method and a voice-centered method were used in tandem to analyze the data. Together they uncovered five emergent themes: (a) intricate understandings of key terms; (b) life-long learning and transformative pathways; (c) gender issues; (d) challenges, tensions, and possibilities; as well as (e) personal, professional, and educational implications. The findings underscored the possibility for both a singular static identity and dynamic multifaceted identities to exist in tandem, and the emergence of natural or logical identity intersections, as well as disjointed or colliding identity intersections. Ultimately, it is the continuous negotiation of internal and external spheres that contributes to the complexity and multidimensionality of graduate students' identities.

Doctoral Education and Skills Development : an International and Historical Perspective. 'Educación doctoral y desarrollo de competencias : una perspectiva internacional e histórica'.

Monográfico con el título: 'Competencias docentes en la Educación Superior'. Resumen basado en el de la publicación

Children's caring roles and responsibilities within the family in Africa

In many Sub-Saharan African countries, the care of chronically ill, disabled or elderly relatives is usually regarded as the responsibility of family members, within a broader landscape of often overburdened healthcare systems, the expense of medical fees, very limited access to social protection and policies that emphasise home-based care. Recent studies have demonstrated that children and youth, particularly girls and young women, take on considerable caring roles for chronically ill and elderly relatives in Africa. This article reviews the available research on young people’s caring roles and responsibilities within families affected by chronic illness and disability in Sub-Saharan Africa. I discuss how children’s caring roles challenge global and local constructions of childhood and suggest ways of conceptualising the socio-spatial and embodied dimensions of children’s everyday care work within diverse household forms. I analyse evidence on outcomes of care and children’s resilience in managing their caring responsibilities and examine the complex array of processes that influence whether children take on caring roles within the family. I argue that relational, intergenerational and lifecourse approaches to researching children’s caring responsibilities within the family have considerable potential for future geographical research and could provide further insights into the ways that care is embedded in social relations, cultural norms and structural inequalities operating in different configurations in particular places.

Potential roles and clinical utility of prebiotics in newborns, infants, and children: proceedings from a global prebiotic summit meeting, New York City, June 27-28, 2008

Initial bacterial colonization, including colonization with health-positive bacteria, such as bifidobacteria and lactobacilli, is necessary for the normal development of intestinal innate and adaptive immune defenses. The predominance of beneficial bacteria in the gut microflora of breast-fed infants is thought to be, at least in part, supported by the metabolism of the complex mixture of oligosaccharides present in human breast milk, and a more adult-type intestinal microbiota is found in formula-fed infants. Inadequate gut colonization, dysbiosis, may lead to an increased risk of infectious, allergic, and autoimmune disorders later in life. The addition of appropriate amounts of selected prebiotics to infant formulas can enhance the growth of bifidobacteria or lactobacilli in the colonic microbiota and, thereby, might produce beneficial effects. Among the substrates considered as prebiotics are the oligosaccharides inulin, fructo-oligosaccharides, galacto-oligosaccharides, and lactulose. There are some reports that such prebiotics have beneficial effects on various markers of health. For example, primary prevention trials in infants have provided promising data on prevention of infections and atopic dermatitis. Additional well-designed prospective clinical trials and mechanistic studies are needed to advance knowledge further in this promising field. (J Pediatr 2009;155:S61-70).

The roles and competencies of HR managers in Slovenian multinational companies

Purpose – The HRM literature provides various typologies of the HR managers’ roles in organizations. The purpose of this paper is to examine how the roles and required competencies of HR managers in Slovenian multinational companies change when these companies enter the international arena. Design/methodology/approach – The authors explored the total population of 25 Slovenian multinational companies (MNCs) operating in Serbia. In these companies the authors conducted interviews with 16 expatriates working in branches in Serbia, sent questionnaires to the CEOs, and conducted a survey of 50 HR managers and interviews with 15 of them. The authors used a triangulation approach and analyzed the results by multivariate methods and content analysis. Findings – The authors found that the complexity of HR managers’ roles, and expectations of their competencies, increases with an increasing level of internationalization of companies. Orientation to people and conflict resolution are seen as elementary competencies needed in all stages of internationalization. The key competence is seen to be strategic thinking that, according to CEOs and expatriates, goes hand in hand with cultural sensitivity, openness to change and a comprehensive understanding of the international environment and business processes. Practical implications – These results can potentially be used for assessing the HRM roles and competencies in different stages of company internationalization, especially MNCs operating in the ex-communist states of Europe, and will help HR managers to support expatriates, CEOs and other employees working in branches abroad more efficiently. Originality/value – This study contributes to the review and evaluation of the quite limited research on HR managers’ roles and competencies in MNCs. It focuses on MNCs and outward internationalization in the Central and Eastern European region. It contributes to studies of the HR managers’ roles and competencies and is the first study to establish a set of roles and competencies for HR managers in Slovenian MNCs.