Adenovirus-mediated gene transfer into selected liver segments using a vascular exclusion technique.

Adenovirus-mediated gene therapy is hampered by severe virus-related toxicity, especially to the liver. The aim of the present study was to test the ability of a vascular exclusion technique to achieve transgene expression within selected liver segments, thus minimizing both viral and transgene product toxicity to the liver. An E1-E3-deleted replication-deficient adenovirus expressing a green fluorescent protein (GFP) reporter gene was injected into the portal vein of BDIX rats, with simultaneous clamping of the portal vein tributaries to liver segments II, III, IV, V, and VIII. GFP expression and inflammatory infiltrate were measured in the different segments of the liver and compared with those of the livers of animals receiving the viral vector in the portal vein without clamping. The GFP expression was significantly higher in the selectively perfused segments of the liver as compared with the non-perfused segments (p < 0.0001) and with the livers of animals that received the vector in the portal vein without clamping (p < 0.0001). Accordingly, the inflammatory infiltrate was more intense in the selectively perfused liver segments as compared with all other groups (p < 0.0001). Fluorescence was absent in lungs and kidneys and minimal in spleen. The clinical usefulness of adenovirus-mediated gene transfer to the liver largely depends on the reduction of its liver toxicity. Clamping of selected portal vein branches during injection allows for delivery of genes of interest to targeted liver segments. Transgene expression confined to selected liver segments may be useful in the treatment of focal liver diseases, including metastases.

Fate of the herbicide glyphosate and its metabolite AMPA in soils and their transfer to surface waters: A multi-scale approach in the Lavaux vineyards, western Switzerland

The use of herbicides in agriculture may lead to environmental problems, such as surface water pollution, with a potential risk for aquatic organisms. The herbicide glyphosate is the most used active ingredient in the world and in Switzerland. In the Lavaux vineyards it is nearly the only molecule applied. This work aimed at studying its fate in soils and its transfer to surface waters, using a multi-scale approach: from molecular (10-9 m) and microscopic scales (10-6 m), to macroscopic (m) and landscape ones (103 m). First of all, an analytical method was developed for the trace level quantification of this widely used herbicide and its main by-product, aminomethylphosphonic acid (AMPA). Due to their polar nature, their derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl) was done prior to their concentration and purification by solid phase extraction. They were then analyzed by ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). The method was tested in different aqueous matrices with spiking tests and validated for the matrix effect correction in relevant environmental samples. Calibration curves established between 10 and 1000ng/l showed r2 values above 0.989, mean recoveries varied between 86 and 133% and limits of detection and quantification of the method were as low as 5 and 10ng/l respectively. At the parcel scale, two parcels of the Lavaux vineyard area, located near the Lutrive River at 6km to the east of Lausanne, were monitored to assess to which extent glyphosate and AMPA were retained in the soil or exported to surface waters. They were equipped at their bottom with porous ceramic cups and runoff collectors, which allowed retrieving water samples for the growing seasons 2010 and 2011. Results revealed that the mobility of glyphosate and AMPA in the unsaturated zone was likely driven by the precipitation regime and the soil characteristics, such as slope, porosity structure and layer permeability discrepancy. Elevated glyphosate and AMPA concentrations were measured at 60 and 80 cm depth at parcel bottoms, suggesting their infiltration in the upper parts of the parcels and the presence of preferential flow in the studied parcels. Indeed, the succession of rainy days induced the gradual saturation of the soil porosity, leading to rapid infiltration through macropores, as well as surface runoff formation. Furthermore, the presence of more impervious weathered marls at 100 cm depth induced throughflows, the importance of which for the lateral transport of the herbicide molecules was determined by the slope steepness. Important rainfall events (>10 mm/day) were clearly exporting molecules from the soil top layer, as indicated by important concentrations in runoff samples. A mass balance showed that total loss (10-20%) mainly occurred through surface runoff (96%) and, to a minor extent, by throughflows in soils (4%), with subsequent exfiltration to surface waters. Observations made in the Lutrive River revealed interesting details of glyphosate and AMPA dynamics in urbanized landscapes, such as the Lavaux vineyards. Indeed, besides their physical and chemical properties, herbicide dynamics at the catchment level strongly depend on application rates, precipitation regime, land use and also on the presence of drains or constructed channels. Elevated concentrations, up to 4970 ng/l, observed just after the application, confirmed the diffuse export of these compounds from the vineyard area by surface runoff during main rain events. From April to September 2011, a total load of 7.1 kg was calculated, with 85% coming from vineyards and minor urban sources and 15% from arable crops. Small vineyard surfaces could generate high concentrations of herbicides and contribute considerably to the total load calculated at the outlet, due to their steep slopes (~10%). The extrapolated total amount transferred yearly from the Lavaux vineyards to the Lake of Geneva was of 190kg. At the molecular scale, the possible involvement of dissolved organic matter (DOM) in glyphosate and copper transport was studied using UV/Vis fluorescence spectroscopy. Combined with parallel factor (PARAFAC) analysis, this technique allowed characterizing DOM of soil and surface water samples from the studied vineyard area. Glyphosate concentrations were linked to the fulvic-like spectroscopic signature of DOM in soil water samples, as well as to copper, suggesting the formation of ternary complexes. In surface water samples, its concentrations were also correlated to copper ones, but not in a significant way to the fulvic-like signature. Quenching experiments with standards confirmed field tendencies in the laboratory, with a stronger decrease in fluorescence intensity for fulvic-like fluorophore than for more aromatic ones. Lastly, based on maximum concentrations measured in the river, an environmental risk for these compounds was assessed, using laboratory tests and ecotoxicity data from the literature. In our case and with the methodology applied, the risk towards aquatic species was found negligible (RF<1).

management as a part of product lifecycle management

Tässä työssä käsitellään maailmanlaajuisen paperi- ja sellutehtaille laitteita toimittavan yrityksen Andritz:in dokumenttien hallintaa, keskittyen lähinnä yrityksen service- liiketoiminnan ja tuotteen elinkaaren hallinnan tarpeisiin. Tarkoituksena on selvittää kuinka aikaisemmin yritykselle muihin tarkoituksiin valittu dokumenttien hallinta-järjestelmä sopii Service-liiketoiminnan tarpeisiin. Työ perustuu kirjallisuutteen sekä tekijän työn ohella sekä haastatteluin keräämään näkemykseen liiketoiminnasta tällä alalla. Työssä käsitellään yleisellä tasolla dokumenttien hallintajärjestelmiä, niiden rakennetta ja perusominaisuuksia, sekä esitellään markkinoilla olevia erityylisiä ratkaisuja. Työssä esitellään myös Andritz:in dokumenttien hallinnan nykytilaa, tuotteen elinkaaren päävaiheet, dokumenttien hallinnan merkitys niissä ja nykyisin käytössä oleva dokumenttien hallintajärjestelmä. Näiden rinnalla pyritään tuomaan esille Service- liiketoiminnan erityispiirteet ja tarpeet dokumenttien hallinnalle niiden kannalta. Työhön on sisällytetty myös käytännön esimerkki dokumenttien hallinnasta suuressa käynnissä olevassa projektissa. Projektissa käytetään dokumenttihotelli palvelua dokumenttien projektin aikaiseen hallintaan. Hotellissa olevat dokumentit tulee siirtää myös Andritzin omaan järjestelmään, tämä siirto on tehty osana työtä.

Creating Global Competitive Advantage by Global Product Technology Transfers

Globalization is the trend which is realized in all areas in today’s business world. Pressure for cost reduction, changes in market situation and available scale economies have changed business environment more global than ever. To respond to new situation, companies are establishing global strategies. In this thesis, available global competitive advantages in electrical machine industry are studied in context of gaining them by global technology transfers. In theory part, establishing global strategy and competitive advantage is considered with connection to global sourcing and supply chain management. Additionally, market development in 21st century and its impact on global strategies is studied. In practice, global manufacturing is enabled by technology transfer projects. Smooth and fast project implementation enables faster and more flexible production ramp up. By starting the production available competitive advantages can be realized. In this thesis the present situation of technology transfer projects and the risks and advantages related to global manufacturing are analyzed. The analysis of implemented technology transfer projects indicates that project implementation is in good level. For further development of project execution 10 minor suggestions could be presented with two major ones: higher level standardization and development of product information model to support better global manufacturing.

Education export as a form of knowledge transfer : The potential of Finnish education export in Chile

Knowledge transfer is a complex process. Knowledge transfer in the form of exporting education products from one system of education to another is particularly complicated, because each system has been developed in a particular context to meet the requirements seen as relevant at each time. National innovation systems are often seen to form an essential framework within which the development of a country, its economy and level of knowledge are considered and promoted. These systems are orientated towards the future, and as such they also provide a framework for the knowledge transfer related to the development of education. In the best of circumstances they are able to facilitate and boost this transfer both from the viewpoint of the provider and the recipient. The leading thought and the idea of the study is that education export is a form of knowledge transfer, which is illustrated by the existing models included. The purpose of this study is to explore, analyze and describe the factors and phenomena related to education export, and more specifically, those related to the experiences and potential of Finnish education export to Chile. For better understanding, of the multiplicity of the issue involved, the current status of education export between Finland and Chile and he existing efforts within the Finnish innovation network will be outlined as well as new forms of co-operation between Finland and Chile in educational matters explored. Several countries have started to commercialize their education system in order to establish themselves as emerging education exporters. Moreover, the demand for education reform is accurate in many developing countries. This offers a good match between Finland and Chile to be the example countries of the research. The main research findings suggest that there are several business areas in education export. These include degrees in education, training services and education technologies for example The factors that influence education export can be divided into four groups, including academic, cultural, political and economic aspects. Challenges to overcome include the lack of product or services to be sold, lack of market and cultural knowledge of the buyer country, financing and lack of suitable pricing model. National innovation systems could be seen as enabling entities for successful education export. The extensive networks that national innovation systems aim to form, could operate as a basis for joining the forces in selling knowledge as well as receiving knowledge in a constructive way.

Industrial solution business – transition from product to solution offering

The business logic in the manufacturing industry has changed in the 21st century. In the current industrial market, manufacturers are driven to provide more comprehensive offerings that go beyond the traditional product-orientation by providing capacity and availability for their customers. From incidental merchandise, services have become the core of manufacturers’ offerings with long-lasting service agreements over the life-cycles of their products. This change is driven both by the need of providers to grow and gain competitive advantage and by increased customer demand caused by customers’ outsourcing trends. The three key drivers for manufacturers’ service strategies are outsourcing trends, saturation of the installed base, and commoditization in product markets. Thus, manufacturers focus on providing industrial solutions which are delivered through relational processes with customers by using solution-driven business models. In the management of marketing activities, this can be regarded as closer customer relationships, service-dominant business logic, and collaboration in solving customers’ problems. However, there are few studies on comprehensive conceptualizations of a solution offering that include different elements and their roles, especially in the context of capital goods industry. Also the transition process needs further studies in a real life context. This study explores the transition process of an industrial company from product to solution business and, as an aid to managing the solution business, explicates the structure and management of an industrial solution offering. There are two themes, the industrial transition process and industrial solution offering. Regarding the industrial transition process, the aim is to understand the supplier view on the process and its execution and to determine the challenges related to the transition process. The industrial solution offering is discussed by its elements and characteristics, as well as management. Furthermore, a special type of build-own-operate-transfer business model is presented and its suitability in the industrial context analyzed. The study includes findings achieved by qualitative methods and from four case companies. Based on the results, it is tentatively suggested that in the industrial solution business, the transition from product to solution business is not a linear project but an evolving process that varies according to customer needs, which suggests that companies need to possess an ability to develop new business models for different customer needs. The industrial solution offering is dynamic as it evolves in collaboration according to the prevailing and latent customer needs, which suggest restructuring of the organization from a product-centric to a customer-centric one. Furthermore, based on the findings, the concept of industrial solutions is defined as an ongoing relational process to satisfy a customer’s particular business or operational requirements, and the concept of industrial solution offering as an entity comprising the customized goods, services, collaboration, and finance needed to fulfill the industrial solution. Finally, the study offers several managerial implications for industrial managers involved in the transition and management of the solution business and its offering.

The requirements and needs of global data usage in product lifecycle management

This study was done for ABB Ltd. Motors and Generators business unit in Helsinki. In this study, global data movement in large businesses is examined from a product data management (PDM) and enterprise resource planning (ERP) point-of-view. The purpose of this study was to understand and map out how a large global business handles its data in a multiple site structure and how it can be applied in practice. This was done by doing an empirical interview study on five different global businesses with design locations in multiple countries. Their master data management (MDM) solutions were inspected and analyzed to understand which solution would best benefit a large global architecture with many design locations. One working solution is a transactional hub which negates the effects of multisite transfers and reduces lead times. Also, the requirements and limitations of the current MDM architecture were analyzed and possible reform ideas given.  

Customer Knowledge Transfer in MNCs

The purpose of this Master’s thesis was to study customer knowledge transfer processes in multinational corporations (MNCs). The main objective was to examine how customer knowledge is transferred in MNCs and what kind of factors enhance or inhibit the knowledge transfer process, and to create a framework on the basis of the existing literature and the empirical findings. In this thesis the factors were organized according to whether they are properties of the unit involved in knowledge management, properties of relationships between the units or properties of the knowledge itself. There are various properties that influence knowledge transfer but in this thesis the focus was on examining the relevant findings from the customer knowledge viewpoint. Empirical results show that internal fragmentation in the MNC seems to be inherent in this type of organization, and may cause many problems in customer knowledge transfer and utilization. These knowledge transfer inhibitors rise from the organization’s properties: it’s absorptive capacity, motivation, organizational culture, and the two dimensions of knowledge. However, in spite of the inherent forces causing internal fragmentation and inhibiting knowledge transfer, moderate customer knowledge and expertise codification, cooperative working practices among the experts, and socialization mechanisms posed by the headquarters seem to help maintain customer knowledge transfer, and value creation in the long-term relationship. This value creation can be seen to be based on accessing and integrating a wide variety of knowledge resources in order to create a coherent product and service offering.

Exploring the impact of celebrity endorsement and product class involvement on advertising effectiveness: an eye tracking approach

Celebrity endorsement has increased in popularity over the past decades and companies are willing to spend increasingly excessive amounts of money into it. Even though multiple studies support celebrity endorsement, further research on its impact on advertising effectiveness is called for. Fur-ther, the role of consumers’ product class involvement in advertising needs to be further studied. The purpose of this study is to explore if consumers’ product class involvement and exposure to celebrity endorsers affect consumers brand recall. Supported by earlier studies, brand recall was used as a measure for advertising effectiveness in this study. In general, a psychological approach was chosen for building the theoretical framework. Concept of classical conditioning was presented in order to understand why people act how they do. Balanced theory and meaning transfer model were presented in order to study how celebrities can be used effectively in advertising context. Further, the importance of product class involvement in advertising effectiveness was evaluated. Hypotheses were formulated based on a literature review of the existing research. Because of the versatility of the research design, a mixed methods approach for this study was adopted. Empirical part of the study was conducted in three stages. First, a pre-test was conducted in order to choose suitable product endorsers for the advertisement stimuli used in the experiment. Second, an eye-tracking experiment with 30 test subjects was conducted in order to study how people view advertisements and whether the familiarity of the product endorser and consumers’ product class involvement affects brand recall. For the experiment, a fictional brand was created in order to avoid bias on brand recall. Third, qualitative interviews for 15 test subjects were conducted in the post-experiment stage in order to gain deeper understating of the phenomenon and to make sense of the findings from the experiment. Findings from this study support celebrity endorsement by suggesting that a famous spokesperson does not steal attention from brand information more than a non-celebrity product endorser. As a result, the use of a celebrity endorser did not decrease brand recall. Results support earlier research as consumer’ higher product class involvement resulted in a better brand recall. Findings from the interviews suggest that consumers have positive perceptions of celebrity endorsement in general. However, the celebrity–brand congruence is a crucial factor when creating attitudes towards the advertisement. Future research ideas were presented based on the limitations and results of this study

Fostering product innovation by learning through exporting in Eastern Europe

This study discusses the importance of learning through the process of exporting, and more specifically how such a process can enhance the product innovativeness of a company. The purpose of this study is to investigate the appropriate sources of learning and to suggest an interactive framework for how new knowledge from exporting markets can materialize itself into product innovation. The theoretical background of the study was constructed from academic literature, which is related to concepts of learning by exporting, along with sources for learning in the market and new product development. The empirical research in the form of a qualitative case study was based on four semi-structured interviews and secondary data from the case company official site. The interview data was collected between March and April 2015 from case company employees who directly work in the department of exporting and product development. The method of thematic analysis was used to categorize and interpret the collected data. What was conclusively discovered, was that the knowledge from an exporting market can be an incentive for product innovation, especially an incremental one. Foreign customers and competitors as important sources for new knowledge contribute to the innovative process. Foreign market competitors’ influence on product improvements was high only when the competitor was a market leader or held a colossal market share, while the customers’ influence is always high. Therefore, involving a foreign customer in the development of a new product is vital to a company that is interested in benefiting from what is learned through exporting. The interactive framework, which is based on the theoretical background and findings of the study, suggests that exporting companies can raise their product innovativeness by utilizing newly gained knowledge from exporting markets. Except for input, in the form of sources of learning, and product innovation as an output, the framework contains a process of knowledge transfer, the absorptive capacity of a firm and a new product development process. In addition, the framework and the findings enhance the understanding of the disputed relationship between an exporting experience and product innovation. However, future research is needed in order to fully understand all the elements of the framework, such as the absorptive capacity of a firm as well as more case companies to be processed in order to increase the generalization of the framework

A DFT Guided/Experimental Approach to Asymmetric Allylation and Phase-Transfer Catalysis

The Dudding group is interested in the application of Density Functional Theory (DFT) in developing asymmetric methodologies, and thus the focus of this dissertation will be on the integration of these approaches. Several interrelated subsets of computer aided design and implementation in catalysis have been addressed during the course of these studies. The first of the aims rested upon the advancement of methodologies for the synthesis of biological active C(1)-chiral 3-methylene-indan-1-ols, which in practice lead to the use of a sequential asymmetric Yamamoto-Sakurai-Hosomi allylation/Mizoroki Heck reaction sequence. An important aspect of this work was the utilization of ortho-substituted arylaldehyde reagents which are known to be a problematic class of substrates for existing asymmetric allylation approaches. The second phase of my research program lead to the further development of asymmetric allylation methods using o-arylaldehyde substrates for synthesis of chiral C(3)-substituted phthalides. Apart from the de novo design of these chemistries in silico, which notably utilized water-tolerant, inexpensive, and relatively environmental benign indium metal, this work represented the first computational study of a stereoselective indium-mediated process. Following from these discoveries was the advent of a related, yet catalytic, Ag(I)-catalyzed approach for preparing C(3)-substituted phthalides that from a practical standpoint was complementary in many ways. Not only did this new methodology build upon my earlier work with the integrated (experimental/computational) use of the Ag(I)-catalyzed asymmetric methods in synthesis, it provided fundamental insight arrived at through DFT calculations, regarding the Yamamoto-Sakurai-Hosomi allylation. The development of ligands for unprecedented asymmetric Lewis base catalysis, especially asymmetric allylations using silver and indium metals, followed as a natural extension from these earlier discoveries. To this end, forthcoming as well was the advancement of a family of disubstituted (N-cyclopropenium guanidine/N-imidazoliumyl substituted cyclopropenylimine) nitrogen adducts that has provided fundamental insight into chemical bonding and offered an unprecedented class of phase transfer catalysts (PTC) having far-reaching potential. Salient features of these disubstituted nitrogen species is unprecedented finding of a cyclopropenium based C-H•••πaryl interaction, as well, the presence of a highly dissociated anion projected them to serve as a catalyst promoting fluorination reactions. Attracted by the timely development of these disubstituted nitrogen adducts my last studies as a PhD scholar has addressed the utility of one of the synthesized disubstituted nitrogen adducts as a valuable catalyst for benzylation of the Schiff base N-diphenyl methylene glycine ethyl ester. Additionally, the catalyst was applied for benzylic fluorination, emerging from this exploration was successful fluorination of benzyl bromide and its derivatives in high yields. A notable feature of this protocol is column-free purification of the product and recovery of the catalyst to use in a further reaction sequence.

Transfer effects in implicit memory and consumer choice

Two experiments investigated transfer effects in implicit memory and consumer choice, using a preference judgement task. Experiment 1 examined whether it is possible to obtain priming for unfamiliar food labels. Additionally, it investigated whether the experience of seeing a brand name with a particular product type would benefit subsequent processing of the brand name when linked with a different product type. Experiment 2 examined whether changes in modality between study and test would affect priming for unfamiliar brand names. Both questions are theoretically important, as well as pertaining to practical concerns in the consumer choice literature. Experiment 1 demonstrated significant priming for unfamiliar food labels, and established that priming was unaffected by changing the product type with which the brand name was associated. In Experiment 2, priming on both auditory and visual versions of the preference judgement task was reduced by changes in modality. The results and implications are discussed in relation to consumer choice and current theories of implicit memory.

De novo alanine synthesis by bacteroids of Mesorhizobium loti is not required for nitrogen transfer in the determinate nodules of Lotus corniculatus

Deletion of both alanine dehydrogenase genes (aldA) in Mesorhizobium loti resulted in the loss of AldA enzyme activity from cultured bacteria and bacteroids but had no effect on the symbiotic performance of Lotus corniculatus plants. Thus, neither indeterminate pea nodules nor determinate L. corniculatus nodules export alanine as the sole nitrogen secretion product.

The role of transfer in language variation and change: Evidence from contact varieties of French

In this Special Issue, the focus is on contact-induced language variation and change in situations of societal bilingualism that involve long-term contact between French and another language. As is well known, when two or more languages are spoken by groups of speakers in the same geographical area, over time, features from one language can be transferred to the other language, especially when the languages in question are unequal in terms of prestige, institutional support and demographic factors. The process that leads to the adoption of such features in the contact languages is generally known as INTERFERENCE or TRANSFER, and these terms are also used to describe the features in question (i.e. the end product of the process of transfer). In this issue we prefer to use the term TRANSFER over the use of the notion INTERFERENCE, as the former has fewer negative connotations than the latter.

A PRELIMINARY ANALYSIS OF THE ENERGY TRANSFER BETWEEN THE DARK SECTORS OF THE UNIVERSE

We study the mutual interaction between the dark sectors (dark matter and dark energy) of the Universe by resorting to the extended thermodynamics of irreversible processes and constrain the former with supernova type Ia data. As a by-product, the present dark matter temperature results are not extremely small and can meet the independent estimate of the temperature of the gas of sterile neutrinos.