A multistep process of cancer associated fibroblasts determination under CSL-p53 control

Stromal fibroblast senescence has been linked to the aging-associated increase of tumors. However, in epithelial cancer, density and proliferation of cancer associated fibroblasts (CAF) are frequently increased, rather than decreased. We previously showed that genetic deletion or down-modulation of the canonical Notch effector CSL/RBP-JK in dermal fibroblasts is sufficient for CAF activation with consequent development of keratinocyte-derived tumors. We show here that CSL silencing induces senescence of primary fibroblasts from dermis, oral mucosa, breast and lung. CSL functions in these cells as direct repressor of multiple senescence- and CAF-effector genes. It also physically interacts with p53, repressing its activity. CSL is down-modulated in stromal fibroblasts of premalignant skin actinic keratosis lesions and squamous cell carcinomas (SCC), while p53 gene expression and function is down-modulated only in the latter, with paracrine influences of incipient cancer cells as a likely culprit. Concomitant loss of CSL and p53 overcomes fibroblast senescence, enhances CAF effector gene expression and promotes stromal and cancer cell expansion. The findings support a CAF activation/stromal co-evolution model under convergent CSL/p53 control of likely clinical relevance.

Judicialisation and Direct Democracy. Switzerland's Ban on Minaret Construction

Launched by representatives from the Union démocratique du centre (UDC) with the aim of circumventing political and judicial decisions made at both local and national levels, the 2009 federal popular initiative calling for a ban on the construction of minarets rekindled the stigmatisation of Muslims living in Switzerland. Within the prevalent institutional configuration it moreover revived controversies surrounding issues such as direct democracy versus fundamental rights, or "the will of the people" versus "the power of the judges", whether national or international. "Judicialisation" is a polysemous concept. It is not understood here as the transfer to the courts of matters of political significance - in this instance the public regulation of religion - but as a process of juridification (or juridicalisation) in which court rulings were constantly anticipated in the political debate provoked by the popular initiative.

On the dynamics of exports and FDI: The Spanish Internationalization Process

This paper provides further insights into the dynamics of exports and outward foreign direct investment (FDI) flows in Spain from a time-series approach. The contribution of the paper is twofold: 1) the existence of either substitution or a complementary relationship between Spanish outward investments and exports is empirically tested using a multivariate cointegrated model (VECM). The evolution in exchange flows (1993-2008) and country-specific variables (such as world demand - including Spain’s main recently growing foreign markets - for trade flows and the relative price of exports in order to proxy new global competitors) are taken into account for the first time. And 2) the growth in the trade of services in recent decades leads us to test a specific causality relationship by disaggregating between goods and services flows. Our results provide evidence of a positive (Granger) causality relationship running from FDI to exports of goods (stronger) and to exports of services (weaker) in the long run, the complementarity relation of which is consistent with vertical FDI strategies. In the short run, however, only exports of goods are affected (positively) by FDIs.

The transatlantic business community faced with US direct investment in Western Europe, 1958-1968

This article examines the position of US and European business in the debate about American direct investment in Western Europe in a historical perspective, from the establishment of the Common Market to the introduction of US regulation of foreign direct investment (FDI) a decade later. Based on abundant and diverse archival documents, it sheds new light on the process of Americanisation and contributes to existing research on transnational networks, by revealing the active role industrial leaders on both sides of the Atlantic played in shaping the political responses to problems raised by the American firms' massive presence in the Common Market.

Regulatory framework of local citizen participation: Instruments of Direct and Participative Democracy in the Municipal Field

This article focuses on the analysis of the regulatory framework of citizen participation in the local government, which organises direct and participatory democracy at the local level, and identifies the laws and mechanisms through which the constitutional requirements for participation are accomplished. Mu nicipalities, the authority closest to citizens, are the best level of government since they directly involve civil society in the decision-making process experiencing the scope and appropriateness of the instruments by which it is channeled.

Intracellular membrane trafficking in Osteoclasts The role of direct Rab protein – Rac 1 interactions in the targeting of intracellular vesicles

Osteoclasts are cells responsible for bone resorption. These cells undergo extensive membrane re-organization during their polarization for bone resorption and form four distinct membrane domains, namely the ruffled border, the basolateral membrane, the sealing zone and the functional secretory domain. The endocytic/biosynthetic pathway and transcytotic route(s) are important for the resorption process, since the endocytic/biosynthetic pathway brings the specific vesicles to the ruffled border whereas the transcytotic flow is believed to transport the degraded bone matrix away from the resorption lacuna to the functional secretory domain. In the present study, we found a new transcytotic route from the functional secretory domain to the ruffled border, which may compensate membrane loss from the ruffled border during the resorption process. We also found that lipid rafts are essential for the ruffled border-targeted late endosomal pathways. A small GTP-binding protein, Rab7, has earlier been shown to regulate the late steps of the endocytic pathway. In bone-resorbing osteoclasts it is involved in the formation of the ruffled border, which displays several features of late endosomal membranes. Here we discovered a new Rab7-interacting protein, Rac1, which is another small GTP-binding protein and binds to the GTP-form of Rab7 in vitro. We demonstrated further that Rab7 colocalizes with Rac1 at the fusion zone of the ruffled border in bone-resorbing osteoclasts. In other cell types, such as fibroblast-like cells, this colocalization is mainly perinuclear. Because Rac1 is known to control the actin cytoskeleton through its effectors, we suggest that the Rab7-Rac1 interaction may mediate late endosomal transport between microtubules and microfilaments, thus enabling endosomal vesicles to switch tracks from microtubules to microfilaments before their fusion to the ruffled border. We then studied the role of Rab-Rac1 interaction in the slow recycling pathway. We revealed that Rac1 also binds directly to Rab11 and to some other but not all Rab-proteins, suggesting that Rab-Rac1 interaction could be a general regulatory mechanism to direct the intracellular vesicles from microtubule mediated transport to actin filament mediated transport and vice versa. On the basis of our results we thus propose a new hypothesis for these GTPases in the regulation of intracellular membrane flow.

DIRECT INFUSION ESI-MS APPLIED IN THE DETECTION OF BYPRODUCTS DUE TO REDUCTIVE DEGRADATION OF ACETAMIPRID BY ZERO-VALENT IRON

This study investigated the reductive degradation of acetamiprid (5 mg L-1) in aqueous medium (at pH 2.0) induced by zero-valent iron (50 mg). The process was monitored using high-performance liquid chromatography (HPLC) to determine the degradation rate as a function of reaction time, and direct infusion electrospray ionization mass spectrometry (DI-ESI-MS) to search for (and potentially characterize) any possible byproducts formed during degradation. The results obtained via HPLC showed that after 60 min, the degradation of the substrate reached nearly 100% in an acidic medium, whereas the mineralization rate (as determined by total organic carbon measurements) was as low as 3%. Data obtained by DI-ESI-MS showed that byproducts were formed mainly by insertions of hydrogen atoms into the nitrile, imine, and pyridine ring moieties, in addition to the observation of chlorine substitution by hydrogen replacement (hydrodechlorination) reactions.

Salesperson's customer orientation in the personal selling process and in the use of personal selling techniques in the business-to-business setting

Selling is much maligned, often under-valued subject whose inadequate showing in business schools is in inverse proportion to the many job opportunities it offers and the importance of salespeople bringing incomes to companies. The purpose of this research is to increase the understanding of customer-oriented selling and examine the influence of customer-oriented philosophy on selling process, the applicability of selling techniques to this philosophy and the importance of them to salespeople. The empirical section of the study is two-fold. Firstly, the data of qualitative part was collected by conducting five thematic interviews among sales consultants and case company representatives. The findings of the study indicate that customer-oriented selling requires the activity of salespeople. In the customer-oriented personal selling process, salespeople invest time in the preplanning, the need analysis and the benefit demonstration stages. However, the findings propose that salespeople today must also have the basic capabilities for executing the traditional sales process, and the balance between traditional and consultative selling process will change as the duration of the relationship between the salesperson and customer increases. The study also proposes that selling techniques still belong to the customer-oriented selling process, although their roles might be modest. This thesis mapped 75 selling techniques and the quantitative part of the study explored what selling techniques are considered to be important by salespeople in direct selling industry when they make sales with new and existing customers. Response rate of the survey was 69.5%.

Cost evaluation process for competitors' products

A company’s capability to map out its cost position compared to other market players is important for competitive decision making. One aspect of cost position is direct product cost that illustrates the cost efficiency of a company’s product designs. If a company can evaluate and compare its own and other market players’ direct product costs, it can implement better decisions in product development and management, manufacturing, sourcing, etc. The main objective of this thesis was to develop a cost evaluation process for competitors’ products. This objective includes a process description and an analysis tool for cost evaluations. Additionally, process implementation is discussed as well. The main result of this thesis was a process description consisting of a sixteen steps process and an Excel based analysis tool. Since literature was quite limited in this field, the solution proposal was combined from many different theoretical concepts. It includes influences from reverse engineering, product cost assessment, benchmarking and cost based decision making. This solution proposal will lead to more systematic and standardized cost position analyses and result in better cost transparency in decision making.

CLONAL PROPAGATION OF NEEM (Azadirachta indica A. Juss.) VIA DIRECT AND INDIRECT IN VITRO REGENERATION

ABSTRACTThe study was conducted with shoot tip explants of neem (Azadirachta indica A. Juss) to identify a viable regenerative process. Shoot tips were obtained from neem embryos cultured alternatingly in DKW medium supplemented with BAP and medium without hormones. Initial shoot development was influenced by cotyledon presence. Basal callus, excised from in vitro stem base, also presented organogenic potential. In some cases, plant lines, obtained from each seed, presented different characteristics. The most common characteristic observed in vitro was callus formation at the stem base. However, the rarest characteristics were stem callus formation and leaf senescence. The regenerated shoot tips were further subculture and rooted on a medium supplemented with IBA so that complete plants could be obtained. The rooted plants were transplanted to a greenhouse and successfully acclimatized. No significant differences in in vivo development were observed between neem plants from callus and from shoot tip propagation.

A Bridge Builder or a Raconteur? How Japan Manoeuvres the Global Development Discourse within the TICAD Process

Japan has been a major actor in the field of development cooperation for five decades, even holding the title of largest donor of Official Development Assistance (ODA) during the 1990s. Financial flows, however, are subject to pre-existing paradigms that dictate both donor and recipient behaviour. In this respect Japan has been left wanting for more recognition. The dominance of the so called ‘Washington Consensus’ embodied in the International Monetary Fund (IMF) and the World Bank has long circumvented any indigenous approaches to development problems. The Tokyo International Conference on African Development (TICAD) is a development cooperation conference that Japan has hosted since 1993 every five years. As the main organizer of the conference Japan has opted for the leading position of African development. This has come in the wake of success in the Asian region where Japan has called attention to its role in the so called ‘Asian Miracle’ of fast growing economies. These aspirations have enabled Japan to try asserting itself as a major player in directing the course of global development discourse using historical narratives from both Asia and Africa. Over the years TICAD has evolved into a continuous process with ministerial and follow-up meetings in between conferences. Each conference has produced a declaration that stipulates the way the participants approach the question of African development. Although a multilateral framework, Japan has over the years made its presence more and more felt within the process. This research examines the way Japan approaches the paradigms of international development cooperation and tries to direct them in the context of the TICAD process. Supplementing these questions are inquiries concerning Japan’s foreign policy aspirations. The research shows that Japan has utilized the conference platform to contest other development actors and especially the dominant forces of the IMF and the World Bank in development discourse debate. Japan’s dominance of the process is evident in the narratives found in the conference documents. Relative success has come about by remaining consistent as shown by the acceptance of items from the TICAD agenda in other forums, such as the G8. But the emergence of new players such as China has changed the playing field, as they are engaging other developing countries from a more equal level.

The effects of the service process on satisfaction, trust and value as creators of customer loyalty in a daily deals concept

This study aims at applying the customer behaviour studies of satisfaction, trust, perceived value and loyalty to a daily deals concept. The goal is to find out whether the relationships are the same in this specific context when compared to previous e-commerce studies. The study examines how the daily deals service process affects customer satisfaction, trust and value, and how these in turn impact customer loyalty and each other. The data was collected via e-mail survey from case company customers, and research was conducted on a quantitative basis by using multivariate methods as tools. The results suggest that daily deals service process and service quality do have a direct and positive effect on customer satisfac-tion, trust and value. Additionally, positive correlations between the latter variables and customer loyalty were found. The results imply that the daily deals concept does not differ from other e-services when considering the studied factors. The results also emphasize the importance of recognizing what determinants have the greatest impact on customer loyalty in this specific context.

Improving the competitiveness of electrolytic Zinc process by chemical reaction engineering approach

This doctoral thesis describes the development work performed on the leachand purification sections in the electrolytic zinc plant in Kokkola to increase the efficiency in these two stages, and thus the competitiveness of the plant. Since metallic zinc is a typical bulk product, the improvement of the competitiveness of a plant was mostly an issue of decreasing unit costs. The problems in the leaching were low recovery of valuable metals from raw materials, and that the available technology offered complicated and expensive processes to overcome this problem. In the purification, the main problem was consumption of zinc powder - up to four to six times the stoichiometric demand. This reduced the capacity of the plant as this zinc is re-circulated through the electrolysis, which is the absolute bottleneck in a zinc plant. Low selectivity gave low-grade and low-value precipitates for further processing to metallic copper, cadmium, cobalt and nickel. Knowledge of the underlying chemistry was poor and process interruptions causing losses of zinc production were frequent. Studies on leaching comprised the kinetics of ferrite leaching and jarosite precipitation, as well as the stability of jarosite in acidic plant solutions. A breakthrough came with the finding that jarosite could precipitate under conditions where ferrite would leach satisfactorily. Based on this discovery, a one-step process for the treatment of ferrite was developed. In the plant, the new process almost doubled the recovery of zinc from ferrite in the same equipment as the two-step jarosite process was operated in at that time. In a later expansion of the plant, investment savings were substantial compared to other technologies available. In the solution purification, the key finding was that Co, Ni, and Cu formed specific arsenides in the “hot arsenic zinc dust” step. This was utilized for the development of a three-step purification stage based on fluidized bed technology in all three steps, i.e. removal of Cu, Co and Cd. Both precipitation rates and selectivity increased, which strongly decreased the zinc powder consumption through a substantially suppressed hydrogen gas evolution. Better selectivity improved the value of the precipitates: cadmium, which caused environmental problems in the copper smelter, was reduced from 1-3% reported normally down to 0.05 %, and a cobalt cake with 15 % Co was easily produced in laboratory experiments in the cobalt removal. The zinc powder consumption in the plant for a solution containing Cu, Co, Ni and Cd (1000, 25, 30 and 350 mg/l, respectively), was around 1.8 g/l; i.e. only 1.4 times the stoichiometric demand – or, about 60% saving in powder consumption. Two processes for direct leaching of the concentrate under atmospheric conditions were developed, one of which was implemented in the Kokkola zinc plant. Compared to the existing pressure leach technology, savings were obtained mostly in investment. The scientific basis for the most important processes and process improvements is given in the doctoral thesis. This includes mathematical modeling and thermodynamic evaluation of experimental results and hypotheses developed. Five of the processes developed in this research and development program were implemented in the plant and are still operated. Even though these processes were developed with the focus on the plant in Kokkola, they can also be implemented at low cost in most of the zinc plants globally, and have thus a great significance in the development of the electrolytic zinc process in general.

Ultrastructural analysis of in vitro direct and indirect organogenesis

This is a comparative study of the ultrastructural characteristics of the cells involved in the organogenesis in vitro of Bauhinia forficata Link (indirect system) and Glycine max (L.) Merrill (direct system). B. forficata calli after 30 days culture and G. max meristemoids after 10 days culture were prepared for ultrastructural analysis using conventional methods. Concentrically arranged rough endoplasmic reticulum (RER) and plastids containing starch grains were seen during G. max and B. forficata organogenesis. The amitotic process, the presence of plastids around the nucleus and nuclear envelope with conspicuous pores were found in B. forficata.

Catalytic direct synthesis of hydrogen peroxide in a novel microstructured reactor

The direct synthesis from hydrogen and oxygen is a green alternative for production of hydrogen peroxide. However, this process suffers from two challenges. Firstly, mixtures of hydrogen and oxygen are explosive over a wide range of concentrations (4-94% H2 in O2). Secondly, the catalytic reaction of hydrogen and oxygen involves several reaction pathways, many of them resulting in water production and therfore decreasing selectivity. The present work deals with these two challenges. The safety problem was dealed by employing a novel microstructured reactor. Selectivity of the reaction was highly improved by development a set of new catalysts. The final goal was to develop an effective and safe continuous process for direct synthesis of hydrogen peroxide from H2 and O2. Activated carbon cloth and Sibunit were examined as the catalysts’ supports. Palladium and gold monometallic and palladium-gold bimetallic catalysts were thoroughly investigated by numerous kinetic experiments performed in a tailored batch reactor and several catalyst charachterization methods. A complete set of data for direct synthesis of H2O2 and its catalytic decomposition and hydrogenation was obtained. These data were used to assess factors influencing selectivity and activity of the catalysts in direct synthesis of H2O2 as well as its decomposition and hydrogenation. A novel microstructured reactor was developed based on hydrodynamics and mass transfer studies in prototype microstractural plates. The shape and the size of the structural elements in the microreactor plate were optimized in a way to get high gas-liquid interfacial area and gas-liquid mass transfer. Finally, empirical correlations for the volumetric mass transfer coefficient were derived. A bench-scale continuous process was developed by using the novel microstructral plate reactor. A series of kinetic experiments were performed to investigate the effects of the gas and the liquid feed rates and their ratio, the amount of the catalyst, the gas feed composition and pressure on the final rate of H2O2 production and selectivity.