Design and Validation of a Novel Generic Platform for the Production of Tetravalent IgG1-like Bispecific Antibodies.

We have designed and validated a novel generic platform for production of tetravalent IgG1-like chimeric bispecific Abs. The VH-CH1-hinge domains of mAb2 are fused through a peptidic linker to the N terminus of mAb1 H chain, and paired mutations at the CH1-CL interface mAb1 are introduced that force the correct pairing of the two different free L chains. Two different sets of these CH1-CL interface mutations, called CR3 and MUT4, were designed and tested, and prototypic bispecific Abs directed against CD5 and HLA-DR were produced (CD5xDR). Two different hinge sequences between mAb1 and mAb2 were also tested in the CD5xDR-CR3 or -MUT4 background, leading to bispecific Ab (BsAbs) with a more rigid or flexible structure. All four Abs produced bound with good specificity and affinity to CD5 and HLA-DR present either on the same target or on different cells. Indeed, the BsAbs were able to efficiently redirect killing of HLA-DR(+) leukemic cells by human CD5(+) cytokine-induced killer T cells. Finally, all BsAbs had a functional Fc, as shown by their capacity to activate human complement and NK cells and to mediate phagocytosis. CD5xDR-CR3 was chosen as the best format because it had overall the highest functional activity and was very stable in vitro in both neutral buffer and in serum. In vivo, CD5xDR-CR3 was shown to have significant therapeutic activity in a xenograft model of human leukemia.

Gridifying IBM's Generic Log Adapter to Speed-Up the Processing of Log Data

Peer-reviewed

Combining Generic Programming and Service-Oriented Architectures for the Effective and Timely Development of Complex e-Learning Systems

Peer-reviewed

Generic features of eighteenth-century American runaway slave advertisements

Pro-gradu –tutkielmani aiheena ovat 1700-luvun ”karanneet orjat” – sanomalehtiilmoitusten genrelle ominaiset piirteet. Tutkimusaineisto koostuu 190 ilmoituksesta, jotka ovat alkuperäisesti ilmestyneet virginialaisissa, pennsylvanialaisissa ja newyorkilaisissa sanomalehdissä 1730-luvulta 1770-luvulle. Tutkimuksen kohteeksi on rajattu ilmoitukset, joissa yksityishenkilöt ilmoittavat orjan/orjien karanneet ja lupaavat kiinniottajalle palkkion. Tutkielman tarkoituksena on tarkastella, millaisia ovat tyypilliset kielelliset piirteet näissä teksteissä ja millainen on prototyyppinen genren edustaja. Genreteorian lisäksi teoriaosuudessa käsittelen jonkin verran 1700- luvun englannin kielen yleisiä piirteitä sekä orjuuden ja sanomalehtien syntyhistoriaa Amerikassa taustoittaakseni tutkimusta. Analyysissa hyödynnän mm. Swalesin ja Bhatian käyttämää käsitettä siirroista (moves). Tutkin ilmoituksien tyypillistä rakennetta jakamalla ne yhdeksään siirtoon, joilla kaikilla on oma tehtävänsä ilmoituksessa. Jotkut siirrot, kuten karkulaisen kuvailu ja palkkion lupaaminen, esiintyvät kaikissa ilmoituksissa, kun taas toiset siirrot ovat läsnä harvemmin. Muita tälle genrelle tyypillisiä ominaisuuksia ovat esim. ilmoituksissa toistuvat kiinteät fraasit ja tietyt sanastolliset erikoisuudet. Lisäksi tutkin ilmoituksissa käytettäviä tapoja viitata asiaan liittyviin henkilöihin, sekä erilaisia toimia, joita ilmoitusten jättäjät ilmoituksien avulla suorittavat. Genressä on havaittavissa pieniä reilun neljänkymmenen vuoden kuluessa tapahtuneita muutoksia, mutta myös eroavaisuuksia eri siirtokuntien ilmoitusten välillä. Yleisesti voidaan todeta, että vaikka ”karanneet orjat” –ilmoitukset voivat vaihdella rakenteeltaan ja sanavalinnoiltaan, suuri osa ilmoituksista seuraa kuitenkin melko prototyyppistä muottia.

Generic and professional caring in a Chinese setting: an ethnopraphic study

The objective of the present study is to describe the cultural care practices, meanings, values and beliefs which form the basis of caring in a Chinese context. The research has its starting point in a caring science perspective and a qualitative research approach with interpretative ethnography as methodological guideline. The theoretical perspective is formed by elements of the theory of caritative caring, developed by Eriksson, and the theory of Culture Care Diversity and Universality, developed by Leininger. Previous research of suffering, culture and caring is described and also a presentation of actual transcultural nursing research as well as a presentation of the social structure dimensions of Chinese culture is included in the theoretical background. The empirical part includes patients and relatives, nurses and Hu Gongs as informants. The data collected are analysed based on Geertz’s idea of forming “thick descriptions” through examining the “what, how and why” of people’s actions. The findings show that the family has a prominent position in Chinese caring practices. The patient plays an unobtrusive role and a mutual dependence between the patient and the family members is evident. The professional nursing care is an extended act which includes the family in the caring relationship. The care practices of the Chinese nurse are characterized by great professional nursing skills. Suffering is described by the informants as being caused by disease, pain and social circumstances. “Social suffering” is described as worse than physical or mental suffering. Culturally competent and congruent care is a prerequisite for avoiding cultural pain, imposition and blindness when caring for the suffering human being. The findings of the present study necessitate a broadening in caring theory to include the family in the caring relationship. A further conclusion is that a broadening in our perception and understanding of culture would promote the delivery of culturally competent and congruent care. Suffering need to be seen as enclosed in cultural patterns of how it is expressed, interpreted, understood and relieved. Care and caring need to be seen as embedded in culture and the care practices values and beliefs have to be congruent with the cultural patterns where the care is provided.

Generic Life Cycle Cost Model and Cost-effective Solutions

Life cycle costing (LCC) practices are spreading from military and construction sectors to wider area of industries. Suppliers as well as customers are demanding comprehensive cost knowledge that includes all relevant cost elements through the life cycle of products. The problem of total cost visibility is being acknowledged and the performance of suppliers is evaluated not just by low acquisition costs of their products, but by total value provided through the life time of their offerings. The main purpose of this thesis is to provide better understanding of product cost structure to the case company. Moreover, comprehensive theoretical body serves as a guideline or methodology for further LCC process. Research includes the constructive analysis of LCC related concepts and features as well as overview of life cycle support services in manufacturing industry. The case study aims to review the existing LCC practices within the case company and provide suggestions for improvements. It includes identification of most relevant life cycle cost elements, development of cost breakdown structure and generic cost model for data collection. Moreover, certain cost-effective suggestions are provided as well. This research should support decision making processes, assessment of economic viability of products, financial planning, sales and other processes within the case company.

Development of Generic Simulation Model for Mobile Working Machines

This master’s thesis has been done for Drive! –project in which a new electric motor solution for mobile working machines is developed. Generic simulation model will be used as marketing and development tool. It can be used to model a wide variety of different vehicles with and without electric motor and to show customer the difference between traditionally build vehicles and those with new electric motor solution. Customers can also use simulation model to research different solutions for their own vehicles. At the start of the project it was decided that MeVEA software would be used as main simulation program and Simulink will only be used to simulate the operation of electrical components. Development of the generic model started with the research of these two software applications, simulation models which are made with them and how these simulation models can be build faster. Best results were used for building of generic simulation model. Finished generic model can be used to produce new tractor models for real-time simulations in short notice. All information about model is collected to one datasheet which can be easily filled by the user. After datasheet is filled a script will automatically build new simulation model in seconds. At the moment generic model is capable of building simulation models for wide variety of different tractors but it can be easily altered for other vehicle types too which would also benefit greatly from electric drive solution. Those could be for example wheel loaders and harvesters.

Nursing staffs' perceptions of a generic service manager position

The recent reengineering within the health care industry has challenged many assumptions regarding traditional structures and roles. Within a product-line management structure, the traditional viewpoint that those who manage patient care areas must have a nursing background, is an example of one such assumption being challenged. The nursing profession is often seen as the greatest obstacle to the implementation of a product-line management structure and generic manager positions (does not require a nursing background), due to the perceived loss of professional identity. This qualitative study focused on how nursing staff within a chronic care and rehabilitation facility perceived a generic service manager position. Focus groups were conducted in three phases, over a 14 month period of time. The data collected from the focus groups were then coded according to common themes. Each phase was analyzed independently, with the study concluding with an analysis and interpretation of the collective results. The results of this study revealed a significant shift in how the nursing staff perceived their professional identity and accountability in light of the implementation of the generic Service Manager position. Initial reactions of personal and professional vulnerability and resentment were seen to transform into an increased ability to explicitly articulate the role of nursing. Changes in behavior that were described included: increased consultation and collaboration with other

One of Us or One of Them: A Generic Qualitative Study on the Efficacy of the Funds of Knowledge Strategy to Reduce Teacher Ethnocentrism

The purpose of this study was to examine whether English a Second Language (ESL) instructors’ ethnocentrism could be reduced using multicultural education (MCE) principles. There were three focus group discussions and a Likert scale questionnaire. The findings demonstrated that while ESL instructors were conscious of systemic barriers, media stereotypes, and bullying, more diversity training is required in order to improve teachers’ attitudes, responses, and instructional strategies regarding integration issues due to the increasing diversity of learners present in classrooms today. The findings of the study also demonstrated that MCE principles could be used to effectively raise the awareness of ESL instructors when dealing with integration and assimilation issues. When immigration, human rights, and multicultural policies were examined critically, ESL instructors were able to improve their cross-cultural skills in the classroom to be more inclusive towards diverse ethnic groups by giving learners greater opportunities to express themselves. As a result, learners’ knowledge, experience, and skills were validated in the classroom leading to a more meaningful learning experience.

Des typologies mécaniques à l'expérience esthétique : fonctions et mutations du genre dans le jeu vidéo

Cette thèse examine en profondeur la nature et l’application du concept de genre en jeu vidéo. Elle se divise en trois parties. La première fait l’inventaire des théories des genres en littérature et en études cinématographiques. Les propriétés essentielles du genre comme concept sont identifiées : il s’agit d’une catégorisation intuitive et irraisonnée, de nature discursive, qui découle d’un consensus culturel commun plutôt que de systèmes théoriques, et qui repose sur les notions de tradition, d’innovation et d’hybridité. Dans la deuxième partie, ces constats sont appliqués au cas du genre vidéoludique. Quelques typologies sont décortiquées pour montrer l’impossibilité d’une classification autoritaire. Un modèle du développement des genres est avancé, lequel s’appuie sur trois modalités : l’imitation, la réitération et l’innovation. Par l’examen de l’histoire du genre du first-person shooter, la conception traditionnelle du genre vidéoludique basée sur des mécanismes formels est remplacée par une nouvelle définition centrée sur l’expérience du joueur. La troisième partie développe l’expérience comme concept théorique et la place au centre d’une nouvelle conception du genre, la pragmatique des effets génériques. Dans cette optique, tout objet est une suite d’amorces génériques, d’effets en puissance qui peuvent se réaliser pourvu que le joueur dispose des compétences génériques nécessaires pour les reconnaître. Cette nouvelle approche est démontrée à travers une étude approfondie d’un genre vidéoludique : le survival horror. Cette étude de cas témoigne de l’applicabilité plus large de la pragmatique des effets génériques, et de la récursivité des questions de genre entre le jeu vidéo, la littérature et le cinéma.

Generic finite-size enhancement of pairing in mesoscopic Fermi systems

The finite-size-dependent enhancement of pairing in mesoscopic Fermi systems is studied under the assumption that the BCS approach is valid and that the two-body force is size independent. Different systems are investigated such as superconducting metallic grains and films as well as atomic nuclei. It is shown that the finite size enhancement of pairing in these systems is in part due to the presence of a surface which accounts quite well for the data of nuclei and explains a good fraction of the enhancement in Al grains.