Role of ErbB2 and ErbB4 in Cancer Growth, Prognosis and as Targets for Immunotherapy

ErbB receptors (EGFR, ErbB2, ErbB3 and ErbB4) are growth factor receptors that regulate signals of cell differentiation, proliferation, migration and survival. Inappropriate activation of these receptors is associated with the development and severity of many cancers and has prognostic and predictive value in cancer therapy. Drugs, such as therapeutic antibodies, targeted against EGFR and ErbB2, are currently used in therapy of breast, colorectal and head and neck cancers. The role of ErbB4 in tumorigenesis has remained relatively poorly understood. Alternative splicing produces four different isoforms of one ErbB4 gene. These isoforms (JM-a, JM-b, CYT-1 and CYT-2) are functionally dissimilar and proposed to have different roles in carcinogenesis. The juxtamembrane form JM-a undergoes regulated intramembrane proteolysis producing a soluble receptor ectodomain and an intracellular domain that translocates into the nucleus and regulates transcription. Nuclear signaling via JM-a isoform stimulates cancer cell proliferation. This study aimed to develop antibodies targeting the proposed oncogenic ErbB4 JM-a isoform that show potential in inhibiting ErbB4 dependent tumorigenesis. Also, the clinical relevance of ErbB4 shedding in cancer was studied. The currently used monoclonal antibody trastuzumab, targeting ErbB2, has shown efficacy in breast cancer therapy. In this study novel tissues with ErbB2 amplification and trastuzumab sensitivity were analyzed. The results of this study indicated that a subpopulation of breast cancer patients demonstrate increased shedding and cleavage of ErbB4. A JM-a isoform-specific antibody that inhibited ErbB4 shedding and consequent activation of ErbB4 had anti-tumor activity both in vitro and in vivo. Thus, ErbB4 shedding associates with tumor growth and specific targeting of the cleavable JM-a isoform could be considered as a strategy for developing novel ErbB-based cancer drugs. In addition, it was demonstrated that ErbB2 amplification is common in intestinal type gastric cancers with poor clinical outcome. Trastuzumab inhibited growth of gastric and breast cancer cells with equal efficacy. Thus, ErbB2 may be a useful target in gastric cancer.

Coopetitive advantage – How firms create and appropriate value by collaborating with their competitors

Collaboration between competing firms (coopetition) has emerged as an important issue forn business practice in many industries. Extant literature has examined coopetition on many levels of analysis, but lacks clarity in distinguishing it explicitly from cooperation between noncompeting organizations. Because of this, the performance implications of coopetition from the perspective of an individual firm are still ambiguous – some research suggests positive results whereas other studies suggest detrimental outcomes. The aim in this dissertation is to narrow these gaps by exploring how firms create and appropriate value through collaboration with their competitors. The dissertation is divided into two parts. The first part comprises an overview of the relevant literature, as well as the conclusions of the whole study, and the second part includes six research publications. Both qualitative and quantitative methodologies are utilized. The results suggest that coopetition embodies the distinctive logic of value creation and appropriation from the perspective of an individual firm, and thus differs in terms of performance implications from cooperation between non-competitors. The distinction comes from the fact that competitors have somewhat similar understanding, capabilities and interest related to certain markets, which is potentially both challenging and beneficial in terms of the individual firm’s competitiveness. It appears from the findings that there are distinctive firm-external and firm-specific factors affecting the success of a coopetition strategy. This study makes three main contributions. First, on the conceptual level it shows the distinction between coopetition and cooperation between non-rivals as a collaborative inter-organizational relationship. Secondly, it sets out a framework and propositions that enhance understanding of how value is created and appropriated in coopetition from the perspective of an individual firm. Thirdly, it offers empirical evidence of how coopetition affects firms’ innovation and market performance, and identifies the focal internal and external factors involved. In general terms, the thesis adds to our knowledge of how a firm can successfully utilize a coopetition strategy in its pursuit of improved performance.

Pretreatment in membrane filtration of wood hydrolysate

Interest in recovery of valuable components from process streams has increased in recent years. Purpose of biorefinery is to utilize components that otherwise would go to waste. Hemicelluloses, for example, could be utilized in production of many valuable products. One possible way to separate and fractionate hemicelluloses is membrane filtration. In the literature part of this work membrane fouling in filtration processes of pulp and paper process- and wastewaters was investigated. Especially purpose was to find out the possible fouling compounds, after which facilities to remove or modify such components less harmful were studied. In the experimental part different pretreatment methods, mainly to remove or degrade lignin from wood hydrolysate, were studied. In addition, concentration of hemicelluloses and separation from lignin were examined with two ultrafiltration membranes; UFX5 and RC70PP. Changes in feed solution, filtration capacity and fouling of membranes were used to evaluate the effects of pretreatment methods. Changes in hydrolysate composition were observed with different analysis methods. Filtration of hydrolysate proved to be challenging, especially with the UFX5 membrane. The more hydrophilic RC70PP membrane did not seem to be fouled as severely as the UFX5 membrane, according to pure water flux measurements. The UFX5 membrane retained hemicelluloses rather well, but problems arose from rapid flux decline resulting from concentration polarization and fouling of membrane. Most effective pretreatment methods in the case with the UFX5 membrane proved to be prefiltration with the RC70PP membrane, activated carbon adsorption and photocatalytic oxidation using titanium dioxide and UV radiation. An additional experiment with PHW extract showed that pulsed corona discharge treatment degraded lignin quite efficiently and thus improved filtration capacity remarkably, even over six times compared to the filtration with untreated extract.

Computational visual quality of digitally printed images

The problem of understanding how humans perceive the quality of a reproduced image is of interest to researchers of many fields related to vision science and engineering: optics and material physics, image processing (compression and transfer), printing and media technology, and psychology. A measure for visual quality cannot be defined without ambiguity because it is ultimately the subjective opinion of an “end-user” observing the product. The purpose of this thesis is to devise computational methods to estimate the overall visual quality of prints, i.e. a numerical value that combines all the relevant attributes of the perceived image quality. The problem is limited to consider the perceived quality of printed photographs from the viewpoint of a consumer, and moreover, the study focuses only on digital printing methods, such as inkjet and electrophotography. The main contributions of this thesis are two novel methods to estimate the overall visual quality of prints. In the first method, the quality is computed as a visible difference between the reproduced image and the original digital (reference) image, which is assumed to have an ideal quality. The second method utilises instrumental print quality measures, such as colour densities, measured from printed technical test fields, and connects the instrumental measures to the overall quality via subjective attributes, i.e. attributes that directly contribute to the perceived quality, using a Bayesian network. Both approaches were evaluated and verified with real data, and shown to predict well the subjective evaluation results.

Assessment of Coals from Russia and Countries of Former Soviet Union for Utility Fluidized Bed Boilers

With the occurrence of fossil fuels such as oil, gas and coal we found new sources of energy that have played a critical role in the progress of our modern society. Coal is very ample compared to the other two fossil fuels. Global coal reserves at the end of 2005 were estimated at 847,5 billion tones. Along with the major energy sources, coal is the most fast growing fuel on a global basis, it provides 26% of primary energy needs and remains essential to the economies of many developed and developing countries. Coal-fired power generation accounts for 41% of the world‘s total electricity production and in some countries, such as South Africa, Poland, China, Australia, Kazakhstan and India is on very high level. Still, coal utilization represents challenges related to high emissions of air pollutants such as sulphur and nitrogen dioxides, particulate matter, mercury and carbon dioxide. In relation to these a number of technologies have been developed and are in marketable use, with further potential developments towards ―Near Zero Emission‖ coal plants. In present work, coals mined in Russia and countries of Former Soviet Union were reviewed. Distribution of coal reserves on the territory of Russia and the potential for power generation from coal-fired plants across Russia was shown. Physical and chemical properties of coals produced were listed and examined, as main factor influencing on design of the combustion facility and incineration process performance. The ash-related problems in coal-fired boilers were described. The analysis of coal ash of Russia and countries of Former Soviet Union were prepared. Feasible combustion technologies also were reviewed.

Di-And Tri-Hydroxylated Kaurane Derivatives From Microbial Transformation Of Ent-Kaur-16-En-19-Ol By Cephalosporium Aphidicola And Their Allelopathic Activity On Lactuca Sativa (Lettuce)

The use of microorganisms to induce chemical modifications in organic molecules is a very useful tool in organic synthesis, to obtain biologically active substances. The fungus Cephalosporium aphidicola is known by its ability to hydroxylate several skeleton positions of many classes of organic compounds. In this work, the microbial transformation of ent-kaur-16-en-19-ol (1) by C. aphidicola, afforded two hydroxylated compounds, ent-kauran-16β,19-diol (2) and ent-kauran-16β,17,19-triol (3). Their structures were established by 1D and 2D-NMR studies. Both compounds were tested for their action on the growth of radical and shoot of Lactuca sativa.

Convergence and divergence in global economy and social development : global perspectives on the contents of economic and soical development policy and its effects on rich and poor countries

The study of convergence and divergence in global economy and social development utilises comparative indicators to investigate the contents of economic and social development policy and their effects on the global samples that represent the rich industrial, semi-industrial and the poor developing nations. The study searchesfor answers to questions such as "what are the objectives of economic growth policies in globalisation under the imperatives of convergence and divergence, and how do these affect human well-being in consideration to the objectives of social policy in various nations?" The empirical verification of data utilises the concepts of the `logic of industrialism´ for comparative analysis that focuses mainly on identifying the levels of well-being in world nations after the Second World War. The perspectives of convergence and divergence in global economy and social development critically examine the stages of early development processes in global economy, distinguish the differences between economy and social development, illustrate the contents of economic and social development policies, their effects on rich and poor countries, and the nature of convergence and divergence in propelling economic growth and unequal social development in world nations. The measurement of convergence and divergence in global economy and social development utilised both economic and social data that were combined into an index that measures the precise levels of the effects of economic and social development policies on human well-being in the rich and poor nations. The task of finding policy solutions to resolve the controversies are reviewed through empirical investigations and the analyses of trends indicated within economic and social indicators and data. These revealed how the adoption of social policy measures in translating the gains from economic growth, towards promoting education, public health, and equity, generate social progress and longer life expectancy, higher economic growth, and sustain more stable macro economy for the nations. Social policy is concerned with the translation of benefits from objectives of global economic growth policies, to objectives of social development policy in nation states. Social policy, therefore, represents an open door whereby benefits of economic growth policies are linked with the broader objectives of social development policy, thereby enhancing the possibility of extending benefits from economic growth to all human being in every nation.

TOWARDS A PHILOSOPHICAL UNDERSTANDING OF THE LOGICS OF FORMAL INCONSISTENCY

Abstract In this paper we present a philosophical motivation for the logics of formal inconsistency , a family of paraconsistent logics whose distinctive feature is that of having resources for expressing the notion of consistency within the object language in such a way that consistency may be logically independent of non-contradiction. We defend the view according to which logics of formal inconsistency may be interpreted as theories of logical consequence of an epistemological character. We also argue that in order to philosophically justify paraconsistency there is no need to endorse dialetheism, the thesis that there are true contradictions. Furthermore, we show that mbC , a logic of formal inconsistency based on classical logic, may be enhanced in order to express the basic ideas of an intuitive interpretation of contradictions as conflicting evidence.

Methods and Models for Accelerating Dynamic Simulation of Fluid Power Circuits

The objective of this dissertation is to improve the dynamic simulation of fluid power circuits. A fluid power circuit is a typical way to implement power transmission in mobile working machines, e.g. cranes, excavators etc. Dynamic simulation is an essential tool in developing controllability and energy-efficient solutions for mobile machines. Efficient dynamic simulation is the basic requirement for the real-time simulation. In the real-time simulation of fluid power circuits there exist numerical problems due to the software and methods used for modelling and integration. A simulation model of a fluid power circuit is typically created using differential and algebraic equations. Efficient numerical methods are required since differential equations must be solved in real time. Unfortunately, simulation software packages offer only a limited selection of numerical solvers. Numerical problems cause noise to the results, which in many cases leads the simulation run to fail. Mathematically the fluid power circuit models are stiff systems of ordinary differential equations. Numerical solution of the stiff systems can be improved by two alternative approaches. The first is to develop numerical solvers suitable for solving stiff systems. The second is to decrease the model stiffness itself by introducing models and algorithms that either decrease the highest eigenvalues or neglect them by introducing steady-state solutions of the stiff parts of the models. The thesis proposes novel methods using the latter approach. The study aims to develop practical methods usable in dynamic simulation of fluid power circuits using explicit fixed-step integration algorithms. In this thesis, twomechanisms whichmake the systemstiff are studied. These are the pressure drop approaching zero in the turbulent orifice model and the volume approaching zero in the equation of pressure build-up. These are the critical areas to which alternative methods for modelling and numerical simulation are proposed. Generally, in hydraulic power transmission systems the orifice flow is clearly in the turbulent area. The flow becomes laminar as the pressure drop over the orifice approaches zero only in rare situations. These are e.g. when a valve is closed, or an actuator is driven against an end stopper, or external force makes actuator to switch its direction during operation. This means that in terms of accuracy, the description of laminar flow is not necessary. But, unfortunately, when a purely turbulent description of the orifice is used, numerical problems occur when the pressure drop comes close to zero since the first derivative of flow with respect to the pressure drop approaches infinity when the pressure drop approaches zero. Furthermore, the second derivative becomes discontinuous, which causes numerical noise and an infinitely small integration step when a variable step integrator is used. A numerically efficient model for the orifice flow is proposed using a cubic spline function to describe the flow in the laminar and transition areas. Parameters for the cubic spline function are selected such that its first derivative is equal to the first derivative of the pure turbulent orifice flow model in the boundary condition. In the dynamic simulation of fluid power circuits, a tradeoff exists between accuracy and calculation speed. This investigation is made for the two-regime flow orifice model. Especially inside of many types of valves, as well as between them, there exist very small volumes. The integration of pressures in small fluid volumes causes numerical problems in fluid power circuit simulation. Particularly in realtime simulation, these numerical problems are a great weakness. The system stiffness approaches infinity as the fluid volume approaches zero. If fixed step explicit algorithms for solving ordinary differential equations (ODE) are used, the system stability would easily be lost when integrating pressures in small volumes. To solve the problem caused by small fluid volumes, a pseudo-dynamic solver is proposed. Instead of integration of the pressure in a small volume, the pressure is solved as a steady-state pressure created in a separate cascade loop by numerical integration. The hydraulic capacitance V/Be of the parts of the circuit whose pressures are solved by the pseudo-dynamic method should be orders of magnitude smaller than that of those partswhose pressures are integrated. The key advantage of this novel method is that the numerical problems caused by the small volumes are completely avoided. Also, the method is freely applicable regardless of the integration routine applied. The superiority of both above-mentioned methods is that they are suited for use together with the semi-empirical modelling method which necessarily does not require any geometrical data of the valves and actuators to be modelled. In this modelling method, most of the needed component information can be taken from the manufacturer’s nominal graphs. This thesis introduces the methods and shows several numerical examples to demonstrate how the proposed methods improve the dynamic simulation of various hydraulic circuits.

Integrating user experience into early phases of software development

The value and benefits of user experience (UX) are widely recognized in the modern world and UX is seen as an integral part of many fields. This dissertation integrates UX and understanding end users with the early phases of software development. The concept of UX is still unclear, as witnessed by more than twenty-five definitions and ongoing argument about its different aspects and attributes. This missing consensus forms a problem in creating a link between UX and software development: How to take the UX of end users into account when it is unclear for software developers what UX stands for the end users. Furthermore, currently known methods to estimate, evaluate and analyse UX during software development are biased in favor of the phases where something concrete and tangible already exists. It would be beneficial to further elaborate on UX in the beginning phases of software development. Theoretical knowledge from the fields of UX and software development is presented and linked with surveyed and analysed UX attribute information from end users and UX professionals. Composing the surveys around the identified 21 UX attributes is described and the results are analysed in conjunction with end user demographics. Finally the utilization of the gained results is explained with a proof of concept utility, the Wizard of UX, which demonstrates how UX can be integrated into early phases of software development. The process of designing, prototyping and testing this utility is an integral part of this dissertation. The analyses show statistically significant dependencies between appreciation towards UX attributes and surveyed end user demographics. In addition, tests conducted by software developers and industrial UX designer both indicate the benefits and necessity of the prototyped Wizard of UX utility. According to the conducted tests, this utility meets the requirements set for it: It provides a way for software developers to raise their know-how of UX and a possibility to consider the UX of end users with statistical user profiles during the early phases of software development. This dissertation produces new and relevant information for the UX and software development communities by demonstrating that it is possible to integrate UX as a part of the early phases of software development.

Identification and characterization of new genes and pathways regulating spermatogonial cell fate

Spermatogenesis, i.e sperm production in the seminiferous tubules of the testis, is a complex process that takes over one month to complete. Life-long ability of sperm production ultimately lies in a small population of undifferentiated cells, called spermatogonial stem cells (SSCs). These cells give rise to differentiating spermatogonia, which are committed to mature into spermatozoa. SSCs represent a heterogeneous population of cells and many aspects of their basic biology are still unknown. Understanding the mechanisms behind the cell fate decision of these cells is important to gain more insights into the causes of infertility and testis cancer. In addition, an interesting new aspect is the use of testis-derived stem cells in regenerative medicine. Our data demonstrated that adult mouse testis houses a population of Nanog-expressing spermatogonia. Based on mRNA and protein analysis these cells are enriched in stage XII of the mouse seminiferous epithelial cycle. The cells derived from this stage have the highest capacity to give rise to ES cell-like cells which express Oct4 and Nanog. These cells are under tight non- GDNF regulation but their fate can be dictated by activating p21 signalling. Comparative studies suggested that these cells are regulated like ES cells. Taken together these data imply that pluripotent cells are present in the adult mammalian testis. CIP2A (cancerous inhibitor of PP2A) has been associated with tumour aggressiveness and poor prognosis. In the testis it is expressed by the descendants of stem cells, i.e. the spermatogonial progenitor cells. Our data suggest that CIP2A acts upstream of PLZF and is needed for quantitatively normal spermatogenesis. Classification of CIP2A as a cancer/testis gene makes it an attractive target for cancer therapy. Study on the CIP2A deficient mouse model demonstrates that systemic inhibition of CIP2A does not severely interfere with growth and development or tissue or organ function, except for the spermatogenic output. These data demonstrate that CIP2A is required for quantitatively normal spermatogenesis. Hedgehog (Hh) signalling is involved in the development and maintenance of many different tissues and organs. According to our data, Hh signalling is active at many different levels during rat spermatogenesis: in spermatogonia, spermatocytes and late elongating spermatids. Localization of Suppressor of Fused (SuFu), the negative regulator of the pathway, specifically in early elongating spermatids suggests that Hh signalling needs to be shut down in these cells. Introduction of Hh signalling inhibitor resulted in an increase in germ cell apoptosis. Follicle-stimulating hormone (FSH) and inhibition of receptor tyrosine kinases resulted in down-regulation of Hh signalling. These data show that Hh signalling is under endocrine and paracrine control and it promotes germ cell survival.

Histopathological aspects of Bovine Enzootic Hematuria in Brazil

The bladder lesions of 59 cattle, from the States of Rio de Janeiro, São Paulo, Minas Gerais, Espírito Santo, Rio Grande do Sul, Santa Catarina, Paraná and Amazon, affected by Bovine Enzootic Haematuria (BEH), were studied histologically. The objective of this study was to describe and reclassify neoplastic and non-neoplastic alterations not yet reported, according to the more complete current nomenclature used in human medicine. There was an almost complete identity with alterations observed in the bladder of man. Due to the occurrence of two or more neoplasms in the same animal, differences in the methodology and in the concept of classification, a more precise comparison was not possible. Coexistence of different types of epithelial and/or mesenchymal tumour growth was frequently seen. Rare neoplasms or differentiations not previously described were found in the bladder of some animals affected by BEH. These were trabecular carcinoma with Paneth cells differentiation, mesonephroid adenoma, mesonephroid adenocarcinoma, "signet ring" cell carcinoma, plasmocytoid carcinoma, chromophobe cell carcinoma and nested type of transitional cell carcinoma. Haemangiosarcomas originating from haemangiomas were also observed. This study also revealed the occurrence of many tumors with anaplasia and pronounced infiltrative features, but which did not metastasize. The elucidation of the cause of this "barrier against metastases" and its relationship with chemical carcinogenesis induced by the ptaquiloside, the active principle of bracken fern (Pteridium aquilinum), could be of interest to future research on the control ofneoplasia in man and animals.

Effects of cytochrome P450 enzyme inhibitors and inducers on the metabolism of S-ketamine

The human body eliminates foreign compounds primarily by metabolizing them to hydrophilic forms to facilitate effective excretion through the kidneys. Cytochrome P450 (CYP) enzymes in the liver and intestine contribute to the metabolism of many drugs. Pharmacokinetic drugdrug interactions occur if the activity of CYPs are inhibited or induced by another drug. Prescribing multiple drugs to the improve effectiveness of therapy or to treat coexisting diseases is a common practice in clinical medicine. Polypharmacy predisposes patients to adverse effects because of the profound unpredictability in CYP enzymatic-mediated drug metabolism. S-ketamine is a phencyclidine derivative which functions as an antagonist of the N-methyl-Daspartate (NMDA) receptor in the central nervous system. It is a unique anaesthetic producing “dissociative anaesthesia” in high doses and analgesia in low doses. Studies with human liver microsomes suggest that ketamine is metabolized primarily via CYP3A4 and CYP2B6 enzymes. In this thesis, in healthy volunteers, randomized and controlled cross-over studies were conducted to investigate the effects of different CYP inducers and inhibitors on the pharmacokinetics and pharmacodynamics of oral and intravenous S-ketamine. The plasma concentrations of ketamine and its metabolite, norketamine, were determined at different timepoints over a 24 hour period. Other pharmacodynamic variables were examined for 12 hours. Results of these studies showed that the inhibition of the CYP3A4 pathway by clarithromycin or grapefruit juice increased the exposure to oral S-ketamine by 2.6- and 3.0-fold. Unexpectedly, CYP3A4 inhibition by itraconazole caused no significant alterations in the plasma concentrations of oral S-ketamine. CYP3A4 induction by St. John´s wort or rifampicin decreased profoundly the concentrations of oral S-ketamine. However, after rifampicin, there were no significant differences in the plasma concentrations of S-ketamine when it was administered intravenously. This demonstrated that rifampicin inhibited the metabolism of Sketamine at the intestinal level. When CYP2B6 was inhibited by ticlopidine, there was a 2.4- fold increase in the exposure of S-ketamine. These studies demonstrated that low dose oral Sketamine is metabolized both via CYP3A4 and CYP2B6 pathways. The concomitant use of drugs that affect CYP3A4 or CYP2B6, during oral S-ketamine treatment, may cause clinically significant drug-drug interactions.

Energy Efficiency of a Diesel-Electric MobileWorking Machine

The power demand of many mobile working machines such as mine loaders, straddle carriers and harvesters varies significantly during operation, and typically, the average power demand of a working machine is considerably lower than the demand for maximum power. Consequently, for most of the time, the diesel engine of a working machine operates at a poor efficiency far from its optimum efficiency range. However, the energy efficiency of dieseldriven working machines can be improved by electric hybridization. This way, the diesel engine can be dimensioned to operate within its optimum efficiency range, and the electric drive with its energy storages responds to changes in machine loading. A hybrid working machine can be implemented in many ways either as a parallel hybrid, a series hybrid or a combination of these two. The energy efficiency of hybrid working machines can be further enhanced by energy recovery and reuse. This doctoral thesis introduces the component models required in the simulation model of a working machine. Component efficiency maps are applied to the modelling; the efficiency maps for electrical machines are determined analytically in the whole torque–rotational speed plane based on the electricalmachine parameters. Furthermore, the thesis provides simulation models for parallel, series and parallel-series hybrid working machines. With these simulation models, the energy consumption of the working machine can be analysed. In addition, the hybridization process is introduced and described. The thesis provides a case example of the hybridization and dimensioning process of a working machine, starting from the work cycle of the machine. The selection and dimensioning of the hybrid system have a significant impact on the energy consumption of a hybrid working machine. The thesis compares the energy consumption of a working machine implemented by three different hybrid systems (parallel, series and parallel-series) and with different component dimensions. The payback time of a hybrid working machine and the energy storage lifetime are also estimated in the study.

The key practices of customer portfolio management (CPM) process in the medical and healthcare B2B industry

The goal of this study is to deepen the understanding of the customer portfolio management process. There are many models for the process, and they are not necessarily exclusive of each other. Consequently, the inclusion of many models might even prove out to be beneficial. Other theoretical framework include the current economical situation and its propose on customer portfolio management. With an understanding of the theoretical models as a background, the empirical part of this study compares Finnish multinational medical and healthcare technology companies’ customer portfolio management practices. The empirical research was carried out with theme interviews held with 11 sales and marketing managers or directors from four different companies. The goal was to discover the most essential practices of the process steps in the companies. The result of this study is that there is a lack of systematic customer portfolio management, but most companies are aiming to improve this in the near future. The most essential practices are analysis of sales, communication level, learning, and commitment to strategy of the focal company. Special characteristics of this industry include large business networks that include customers, professional end-users, institutions, universities, researchers, and key opinion leaders. The management and analysis of this comprehensive network has been seen to be extremely important for this industry.