Regulating Mechanisms of Gonadal and Pituitary Tumorigenesis in Mice Producing Human Chorionic Gonadotropin

Human chorionic gonadotropin (hCG) and luteinizing hormone (LH) are structurally and functionally similar glycoprotein hormones acting through the same luteinizing hormone chorionic gonadotropin receptor (LHCGR). The functions of LH in reproduction and hCG in pregnancy are well known. Recently, the expression of LHCGR has been found in many nongonadal tissues and cancers, and this has raised the question of whether LH/hCG could affect the function or tumorigenesis of these nongonadal tissues. We have also previously generated an hCG expressing mouse model presenting nongonadal phenotypes. Using this model it is possible to improve our understanding of nongonadal action of highly elevated LH/hCG. In the current study, we analyzed the effect of moderately and highly elevated hCG levels on male reproductive development and function. The main finding was the appearance of fetal Leydig cell (FLC) adenomas in prepubertal males. However, the development and differentiation of FLCs were not significantly affected. We also show that the function of hCG is different in FLCs and in adult Leydig cells (ALC), because in the latter cells hCG was not able to induce tumorigenesis. In FLCs, LHCGR is not desensitized or downregulated upon ligand binding. In this study, we found that the testicular expression of two G protein-coupled receptor kinases responsible for receptor desensitization or downregulation is increased in adult testis. Results suggest that the lack of LHCGR desensitization or downregulation in FLCs protect testosterone (Te) synthesis, but also predispose FLCs for LH/hCG induced adenomas. However, all the hCG induced nongonadal changes observed in male mice were possible to explain by the elevated Te level found in these males. Our findings indicate that the direct nongonadal effects of elevated LH/hCG in males are not pathophysiologically significant. In female mice, we showed that an elevated hCG level was able to induce gonadal tumorigenesis. hCG also induced the formation of pituitary adenomas (PA), but the mechanism was indirect. Furthermore, we found two new potential risk factors and a novel hormonally induced mechanism for PAs. Increased progesterone (P) levels in the presence of physiological estradiol (E2) levels induced the formation of PAs in female mice. E2 and P induced the expression and nuclear localization of a known cell-cycle regulator, cyclin D1. A calorie restricted diet was also able to prevent the formation of PAs, suggesting that obesity is able to promote the formation of PAs. Hormone replacement therapy after gonadectomy and hormone antagonist therapy showed that the nongonadal phenotypes observed in hCG expressing female mice were due to ovarian hyperstimulation. A slight adrenal phenotype was evident even after gonadectomy in hCG expressing females, but E2 and P replacement was able to induce a similar phenotype in WT females without elevated LH/hCG action. In conclusion, we showed that the direct effects of elevated hCG/LH action are limited only to the gonads of both sexes. The nongonadal phenotypes observed in hCG expressing mice were due to the indirect, gonadal hormone mediated effects of elevated hCG. Therefore, the gonads are the only physiologically significant direct targets of LHCGR signalling.

Bio-inspired Mechanisms for Artificial Self-organised Systems

Self-organization is a growing interdisciplinary field of research about a phenomenon that can be observed in the Universe, in Nature and in social contexts. Research on self-organization tries to describe and explain forms, complex patterns and behaviours that arise from a collection of entities without an external organizer. As researchers in artificial systems, our aim is not to mimic self-organizing phenomena arising in Nature, but to understand and to control underlying mechanisms allowing desired emergence of forms, complex patterns and behaviours. Rather than attempting to eliminate such self-organization in artificial systems, we think that this might be deliberately harnessed in order to reach desirable global properties. In this paper we analyze three forms of self-organization: stigmergy, reinforcement mechanisms and cooperation. The amplification phenomena founded in stigmergic process or in reinforcement process are different forms of positive feedbacks that play a major role in building group activity or social organization. Cooperation is a functional form for self-organization because of its ability to guide local behaviours in order to obtain a relevant collective one. For each forms of self-organisation, we present a case study to show how we transposed it to some artificial systems and then analyse the strengths and weaknesses of such an approach

Developing the environmental marketing of an industrial company

The objective of this study was to examine how the customers of Larox Flowsys value environmental issues and how environmental issues affect their purchasing behaviour. A comparison between Larox peristaltic pumps and competing pump brands and types was also made in order to find out whether LPP pumps possess some more environmentally beneficial features that other pumps do not have. Finally, if the answers to the first two research questions show that a need for a new marketing message does exist, then the final stage is to select the most appropriate environmental arguments for Larox Flowsys. The empirical data in the study was collected from several different sources, but the main sources were the customer interviews and the outsourced market research. The data was analysed mainly by using content analysis, but theme formation and quantification were also utilized. The results showed that the customers do not consider environmental issues as a main purchasing criterion, but they may well be the criterion that differentiates the product from competing ones. The comparison proved that LPP pumps do possess some significant environmental benefits over competing pumps and therefore, the prerequisite for the use of environmental arguments exists. The final stage in the study was to select the proper environmental arguments for Larox Flowsys.

Moda en la red : Análisis del sector en el ámbito del marketing online

El éxito del comercio electrónico, el manejo de nuevas plataformas para llevar a cabo campañas de marketing online, la aparición de influenciadores como los blogs y las redes sociales o los nuevos formatos de publicidad de moda en la red son algunos de los puntos que se analizarán en esta disertación.

Role of references in international industrial marketing : a theory-building case study about supplier’s processes of utilizing references

Scientific studies regarding specifically references do not seem to exist. However, the utilization of references is an important practice for many companies involved in industrial marketing. The purpose of the study is to increase the understanding about the utilization of references in international industrial marketing in order to contribute to the development of a theory of reference behavior. Specifically, the modes of reference usage in industry, the factors affecting a supplier's reference behavior, and the question how references are actually utilized, are explored in the study. Due to the explorative nature of the study, a research design was followed where theory and empirical studies alternated. An Exploratory Framework was developed to guide a pilot case study that resulted in Framework 1. Results of the pilot study guided an expanded literature review that was used to develop first a Structural Framework and a Process Framework which were combined in Framework 2. Then, the second empirical phase of the case study was conducted in the same (pilot) case company. In this phase, Decision Systems Analysis (DSA) was used as the analysis method. The DSA procedure consists of three interviewing waves: initial interviews, reinterviews, and validating interviews. Four reference decision processes were identified, described and analyzed in the form of flowchart descriptions. The flowchart descriptions were used to explore new constructs and to develop new propositions to develop Framework 2 further. The quality of the study was ascertained by many actions in both empirical parts of the study. The construct validity of the study was ascertained by using multiple sources of evidence and by asking the key informant to review the pilot case report. The DSA method itself includes procedures assuring validity. Because of the choice to conduct a single case study, external validity was not even pursued. High reliability was pursued through detailed documentation and thorough reporting of evidence. It was concluded that the core of the concept of reference is a customer relationship regardless of the concrete forms a reference might take in its utilization. Depending on various contingencies, references might have various tasks inside the four roles of increasing 1) efficiency of sales and sales management, 2) efficiency of the business, 3) effectiveness of marketing activities, and 4) effectiveness in establishing, maintaining and enhancing customer relationships. Thus, references have not only external but internal tasks as well. A supplier's reference behavior might be affected by many hierarchical conditions. Additionally, the empirical study showed that the supplier can utilize its references as a continuous, all pervasive decision making process through various practices. The process includes both individual and unstructured decision making subprocesses. The proposed concept of reference can be used to guide a reference policy recommendable for companies for which the utilization of references is important. The significance of the study is threefold: proposing the concept of reference, developing a framework of a supplier's reference behavior and its short term process of utilizing references, and conceptual structuring of an unstructured and in industrial marketing important phenomenon to four roles.

Present-day deformation of the Pyrenees revealed by GPS surveying and earthquake focal mechanisms until 2011

The Pyrenean mountain range is a slowly deforming belt with continuous and moderate seismic activity. To quantify its deformation field, we present the velocity field estimated from a GPS survey of the Pyrenees spanning 18 yr. The PotSis and ResPyr networks, including a total of 85 GPS sites, were installed and first measured in 1992 and 1995 1997, respectively, and remeasured in 2008 and 2010. We obtain a deformation field with velocities less than 1 mm yr−1 across the range. The estimated velocities for individual stations do not differ significantly from zero with 95 per cent confidence. Even so, we estimate a maximum extensional horizontal strain rate of 2.0 ± 1.7 nanostrain per year in a N S direction in the western part of the range. We do not interpret the vertical displacements due to their large uncertainties. In order to compare the horizontal strain rates with the seismic activity, we analyse a set of 194 focal mechanisms using three methods: (i) the 'r' factor relating their P and T axes, (ii) the stress tensors obtained by fault slip inversion and (iii) the strain-rate tensors. Stress and strain-rate tensors are estimated for: (i) the whole data set, (ii) the eastern and western parts of the range separately, and (iii) eight zones, which are defined based on the seismicity and the tectonic patterns of the Pyrenees. Each of these analyses reveals a lateral variation of the deformation style from compression and extension in the east to extension and strike-slip in the west of the range. Although the horizontal components of the strain-rate tensors estimated from the seismic data are slightly smaller in magnitude than those computed from the GPS velocity field, they are consistent within the 2σ uncertainties. Furthermore, the orientations of their principal axes agree with the mapped active faults.

One, two, or many mechanisms? The brain's processing of complex words

The heated debate over whether there is only a single mechanism or two mechanisms for morphology has diverted valuable research energy away from the more critical questions about the neural computations involved in the comprehension and production of morphologically complex forms. Cognitive neuroscience data implicate many brain areas. All extant models, whether they rely on a connectionist network or espouse two mechanisms, are too underspecified to explain why more than a few brain areas differ in their activity during the processing of regular and irregular forms. No one doubts that the brain treats regular and irregular words differently, but brain data indicate that a simplistic account will not do. It is time for us to search for the critical factors free from theoretical blinders.

Neural mechanisms underlying adaptive actions after slips

An increase in cognitive control has been systematically observed in responses produced immediately after the commission of an error. Such responses show a delay in reaction time (post-error slowing) and an increase in accuracy. To characterize the neurophysiological mechanism involved in the adaptation of cognitive control, we examined oscillatory electrical brain activity by electroencephalogram and its corresponding neural network by event-related functional magnetic resonance imaging in three experiments. We identified a new oscillatory thetabeta component related to the degree of post-error slowing in the correct responses following an erroneous trial. Additionally, we found that the activity of the right dorsolateral prefrontal cortex, the right inferior frontal cortex, and the right superior frontal cortex was correlated with the degree of caution shown in the trial following the commission of an error. Given the overlap between this brain network and the regions activated by the need to inhibit motor responses in a stop-signal manipulation, we conclude that the increase in cognitive control observed after the commission of an error is implemented through the participation of an inhibitory mechanism.

Multichannel distribution strategy for electrical equipment marketing

The thesis examines System Integration and original equipment manufacturer (OEM) channel in the St. Petersburg drives market. The aim of the study was to increase understanding the relationship between OEM and SI and producers, problems and ongoing trends. The collected data was analyzed in order to find out which features of a power electronic drive product exercise a significant influence for the Russian companies decision. An essential part of this study was interviews as primary information sources, organized with SI and OEM companies which represented the basic SPb industry segments. The wholesalers and end users are left out from the analysis. The collected data was analyzed in order to find out which features of a power electronic drive product exercise a significant influence for the Russian companies decision.

Defining a Performance Measurement System for Technology Marketing Team by Using the Balanced Scorecard Method

This thesis was produced for the Technology Marketing unit at the Nokia Research Center. Technology marketing was a new function at Nokia Research Center, and needed an established framework with the capacity to take into account multiple aspects for measuring the team performance. Technology marketing functions had existed in other parts of Nokia, yet no single method had been agreed upon for measuring their performance. The purpose of this study was to develop a performance measurement system for Nokia Research Center Technology Marketing. The target was that Nokia Research Center Technology Marketing had a framework for separate metrics; including benchmarking for starting level and target values in the future planning (numeric values were kept confidential within the company). As a result of this research, the Balanced Scorecard model of Kaplan and Norton, was chosen for the performance measurement system for Nokia Research Center Technology Marketing. This research selected the indicators, which were utilized in the chosen performance measurement system. Furthermore, performance measurement system was defined to guide the Head of Marketing in managing Nokia Research Center Technology Marketing team. During the research process the team mission, vision, strategy and critical success factors were outlined.

The Management of Intellectual Capital in the Early Phases of Project Marketing

This study aims at enhancing understanding and deriving new constructs about the management of intellectual capital in the early phases of project marketing. The research methodology employed is deductive; conceptual reasoning is based on existing literature. The study's knowledge base is drawn from the bodies of literature dealing with project, relationship, and industrial marketing, as well as from the literature dealing with mechanical engineering, network approach, systems selling, R&D, project portfolio, strategic, financial, and knowledge management. As a result, three processes, 32 summaries and 19 conclusions give to the management of intellectual capital meaning in the context of project marketing. These conclusions and synthesis are proposed to improve the existing concepts and models in project marketing.

TransPromo communication as a part of company’s marketing communications when the e-bill is a medium

The goal of this thesis was to research what TransPromo is, why companies want to implement TransPromo communication, and what the elements of effective Transpromo communication are. Furthermore, the goal was to develop a TransPromo communication strategy and a normative model for TeliaSonera Finland, which depicts the elements of effective TransPromo communication when the electronic bill is a medium. Abductive reasoning was utilized in this thesis, which means that empirical and theoretical worlds are alternating in researcher’s reasoning process. This thesis didn’t rely on any specific theory nor did it utilize any previous theoretical model. However, certain theoretical connections existed so this thesis cannot be considered purely inductive. The empirical part of this thesis was conducted by examining secondary industry data and by conducting specialist interviews at TeliaSonera Finland and Strålfors. Grounded Theory approach was utilized in the analysis of the interview data and content analysis was used in the analysis of secondary industry data. This thesis increases knowledge in the area of TransPromo communication, and provides one definition of TransPromo communication. As a result of this thesis, a TransPromo communication strategy and a normative model for TeliaSonera Finland was built. The model depicts the elements of the effective TransPromo communication when the e-bill is a medium. The TranPromo communication objective is to utilize transaction documents, such as bills, in order to deliver targeted and personalized marketing messages to current customers. The aim is to strengthen the customer relationship, and to enforce up-sell and cross-sell opportunities and cost savings.

Marketing of Lappeenranta University of Technology energy auditing services

The objective of this study was to find out how LUT Energy should start marketing its energy audit services, what would be the optimal pricing policy for its services and how LUT Energy could manage customer expectations towards quality of its auditing services. In order to answer these questions, a quantitative survey questionnaire was sent by e-mail to 56 companies from the regions of South Karelia and Kymenlaakso. The empirical data of the study was the answers and opinions of the companies, previous researches about energy efficiency and articles and presentations about the current situation in the energy efficiency market. The results of the study were that there is a great potential for energy audit services and also the legislation requires companies to improve their energy efficiency. To start marketing its services, LUT Energy should first clarify its service concept and divide its service offering into two offers. It should also clarify the marketing message it wants to send its customers and then do the marketing with the help of three-way-model. The best pricing policy for the service would be that the price is proportioned to the future savings. In order to ensure the quality of its services, LUT Energy has to make sure that both dimensions of the quality are managed properly and to fade out customer expectations towards the quality the auditing work has to be monitored.

Branding and Marketing Communications of Lifestyle Prescription Drugs in a Strict Legislative Environment

This thesis discusses the different possibilities to brand and promote a patented prescription lifestyle drug through different marketing communications practices. This thesis aims in explaining how branding procedures can be built in circumstances, where the legislative environment is strickt and furthermore, the environment consists of both B-to-B and B-to-C market characteristics simultaneously.