Functional characterization of proteins required for mitotic progression and the spindle assembly checkpoint

During mitotic cell division, the genetic material packed into chromosomes is divided equally between two daughter cells. Before the separation of the two copies of a chromosome (sister chromatids), each chromosome has to be properly connected with microtubules of the mitotic spindle apparatus and aligned to the centre of the cell. The spindle assembly checkpoint (SAC) monitors connections between microtubules and chromosomes as well as tension applied across the centromere. Microtubules connect to a chromosome via kinetochores, which are proteinaceous organelles assembled onto the centromeric region of the sister chromatids. Improper kinetochore-microtubule attachments activate the SAC and block chromosome segregation until errors are corrected and all chromosomes are connected to the mitotic spindle in a bipolar manner. The purpose of this surveillance mechanism is to prevent loss or gain of chromosomes in daughter cells that according to current understanding contributes to cancer formation. Numerous proteins participate in the regulation of mitotic progression. In this thesis, the mitotic tasks of three kinetochore proteins, Shugoshin 1 (Sgo1), INCENP, and p38 MAP kinase (p38 MAPK), were investigated. Sgo1 is a protector of centromeric cohesion. It is also described in the tension-sensing mechanism of the SAC and in the regulation of kinetochore-microtubule connections. Our results revealed a central role for Sgo1 in a novel branch of kinetochore assembly. INCENP constitutes part of the chromosomal passenger complex (CPC). The other members of the core complex are the Aurora B kinase, Survivin and Borealin. CPC is an important regulatory element of cell division having several roles at various stages of mitosis. Our results indicated that INCENP and Aurora B are highly dynamic proteins at the mitotic centromeres and suggested a new role for CPC in regulation of chromosome movements and spindle structure during late mitosis. The p38 MAPK has been implicated in G1 and G2 checkpoints during the cell cycle. However, its role in mitotic progression and control of SAC signaling has been controversial. In this thesis, we discovered a novel function for p38γ MAPK in chromosome orientation and spindle structure as well as in promotion of viability of mitotic cells.

Modulaarinen kiinnitintekniikka alumiiniveneiden robottihitsauksessa

Tällä hetkellä hitsauksen automatisointiaste on hyvin pieni alumiinivenevalmistuksessa. Automatisointiasteen kasvattaminen on ensiarvoisen tärkeää kilpailukyvyn säilyttämiseksi, sekä edelleen nostamiseksi. Automatisointiasteen kasvattamisen esteenä ei ole teknologian puute, vaan suunnitellut tuotteet soveltuvat huonosti robotisoituun hitsaukseen. Lisäksi liitettävien osien tarkkuus on monissa tapauksissa puutteellinen, joten robottihitsaus on monessa tapauksessa mahdotonta. Robottihitsauksessa vaaditaan osien hyvää paikoittamista ja siihen tarvitaan kiinnittimiä. Kuitenkin alumiinivenevalmistuksessa valmistusmäärät ovat sen verran pieniä, että tuotekohtaisia kiinnittimiä ei kannata hankkia tai valmistaa. Siksi kiinnittimiltä vaaditaan joustavuutta ja modulaarisuutta, jotta samalla kiinnittimellä voi hitsata useita vastaavia piirteitä omaavia tuotteita. Tässä työssä tutkittiin modulaarisia kiinnittimiä, edistyneitä kiinnitinsuunnitteluprosesseja, osavalmistustarkkuuksia, tuotemoduloinnin hyödyntämistä ja alumiinin robottihitsauksen erityispiirteitä. Työssä suunniteltiin ja simuloitiin modulaarinen hitsauskiinnitin, jota käytetään tietyn alumiinivenemallin erillisenä osakokoonpanona valmistettavan jäykisterakennekonseptin hitsaamiseen. Suunnittelu ja simulointi tehtiin Delmia V5R20 -ohjelmistolla. Jäykisterakenne on modulaarinen tuoterakenne, jossa käytetään itsepaikoittavia liitoksia helpottamaan osien asettelua ja yksinkertaistamaan kiinnitintä. Kiinnitin soveltuu joustavasti erikokoisten jäykisterakenneosakokoonpanojen valmistukseen. Lisäksi suunniteltua kiinnitintä verrattiin kaupalliseen modulaariseen Demmeler -kiinnitinjärjestelmään. Jäykisterakenteen osakokoonpanon hitsaaminen robotilla lyhentää valmistusaikaa verrattuna nykytilaan, kun osat voidaan asettaa kiinnittimeen nopeasti ja luotettavasti. Samalla jäykisterakenteen tekeminen erillisenä osakokoonpanona lyhentää veneen rungon loppukokoonpanoaikaa ja mahdollistaa hitsausrobotin käytön myös veneen muiden hitsien hitsaamisessa. Modulaarisilla hitsauskiinnittimillä saavutetaan alumiiniveneiden nykyisillä valmistusmäärillä skaalaetuja, joita tuotekohtaisella kiinnittimellä ei voi saavuttaa.

Complexity Optimization in Product Development with Modularization

A company’s competence to manage its product portfolio complexity is becoming critically important in the rapidly changing business environment. The continuous evolvement of customer needs, the competitive market environment and internal product development lead to increasing complexity in product portfolios. The companies that manage the complexity in product development are more profitable in the long run. The complexity derives from product development and management processes where the new product variant development is not managed efficiently. Complexity is managed with modularization which is a method that divides the product structure into modules. In modularization, it is essential to take into account the trade-off between the perceived customer value and the module or component commonality across the products. Another goal is to enable the product configuration to be more flexible. The benefits are achieved through optimizing complexity in module offering and deriving the new product variants more flexibly and accurately. The developed modularization process includes the process steps for preparation, mapping the current situation, the creation of a modular strategy and implementing the strategy. Also the organization and support systems have to be adapted to follow-up targets and to execute modularization in practice.

Enhancement of water removal in the press section

The effectiveness of water removal on press section is very important for a paper and board machine’s functioning, efficiency and economy. Today, the most effective method for wet pressing is shoe press technology. Metso has carried out a number of studies concerning anew type of water removal method for a press section, which has also been patented. These studies include rough sketches and some test runs. These issues form the basis of this thesis. The objective of this work was to gather together information for a new and enhanced waterremoval method for a press section by studying the functioning of the device andcarrying out test runs. This method is referred to here as Hydronip. The main goal was tobuild a functional test site which fulfills all the necessary requirements and has all thenecessary information gathering devices. The design process was carried out by emphasizing the safety aspects. The goal was also to gather together information about the nip structure in running conditions, the seal function, and to carry out the nip tests with paper or board wads. This thesis consists of a theory part, the design and construction of the test site, and carrying out test runs through information gathering. The theory part consists of the principals of water removal from a press section, Hydronip construction, and the requirements for the test place. The safety aspects were taken into account especially in test runs, but also in the assembly stages. The design and construction of the test site includes the selection of equipment and surroundings that are needed for managing the test runs in the best possible way at certain premises. The test site included the equipment that was already on the premises. Some equipment could be used as it was but some equipment had to be manufactured or modified from existing equipment. A functional test site with information gathering devices was accomplished as a result of thethesis. Test runs demonstrated that the Hydronip concept is, at least on a small scale,functional. Short-term tests for seal functioning showed that the seal can be lubricatedsufficiently under different kinds of nip load situations. Wad tests demonstrated that the metal belt is durable against different sizes of external particles. The seal also endured wad tests even though the pressure impacts impaired the lubrication. MTS tests showing dry content increases, combined with a rough cost calculation and the basic function of the machine in test runs, show that with some further study Hydronip could be a promising new product for water removal from a paper or board machine’s press section.

The Role of Tactical Marketing Decisions on New Product Performance: The Moderating Effect of Entry Timing

This study focuses on observing how Finnish companies execute their new product launch processes. The main objective was to find out how entry timing moderates the relationship between launch tactics (namely product innovativeness, price and emotional advertising) and new product performance (namely sales volume and customer profitability). The empirical analysis was based on data collected in Lappeenranta University of Technology. The sample consisted of Finnish companies representing different industries and innovation activities. Altogether 272 usable responses were received representing a response rate of 37.67%. The measures were first assessed by using exploratory factor analysis (EFA) in PASW Statistics 18 and then further verified with confirmatory factor analysis (CFA) in LISREL 8.80. To test the hypotheses of the moderating effects of entry timing, hierarchical regression analysis was used in PASW Statistics 18. The results of the study revealed that the effect of product innovativeness on new product sales volume is dependent on entry timing. This implies that companies should carefully consider what would be the best time for entering the market when launching highly innovative new products. The results also depict a positive relationship between emotional advertising and new product sales volume. In addition, partial support was found for a positive relationship between pricing and new product customer profitability.

Integrating environmental aspects into product development process

Various regulations and customer requirements have made it necessary for Vacon Oyj to pay more attention to the environmental aspects in its processes. The main purpose of this master’s thesis project is to define how environmental aspects could be integrated into Vacon’s product development process. The aim is to find out the most important environmental aspects for the company to address, to examine how these could be taken into account during the development process and to map the critical factors that need consideration in order to ensure the successful integration of environmental aspects into the design process. Based on the customer requirements and evolving regulations the most important aspects for Vacon include minimizing the amount of harmful substances, improving the recyclability and energy efficiency of the product and moreover providing meaningful information related to these aspects. To tackle these issues, a new DfE process was developed, tasks in each phase were described and responsibilities were indicated. To ensure the success of the DfE process, management commitment, support of other processes and significant improvements in ways the information is managed are required. The developers should be provided with training and support. Environmental expertise and knowledge in-house should be developed and establishing meaningful environmental indicators is suggested.

Methods for construction and analysis of computational models in systems biology : applications to the modelling of the heat shock response and the self-assembly of intermediate filaments

Systems biology is a new, emerging and rapidly developing, multidisciplinary research field that aims to study biochemical and biological systems from a holistic perspective, with the goal of providing a comprehensive, system- level understanding of cellular behaviour. In this way, it addresses one of the greatest challenges faced by contemporary biology, which is to compre- hend the function of complex biological systems. Systems biology combines various methods that originate from scientific disciplines such as molecu- lar biology, chemistry, engineering sciences, mathematics, computer science and systems theory. Systems biology, unlike “traditional” biology, focuses on high-level concepts such as: network, component, robustness, efficiency, control, regulation, hierarchical design, synchronization, concurrency, and many others. The very terminology of systems biology is “foreign” to “tra- ditional” biology, marks its drastic shift in the research paradigm and it indicates close linkage of systems biology to computer science. One of the basic tools utilized in systems biology is the mathematical modelling of life processes tightly linked to experimental practice. The stud- ies contained in this thesis revolve around a number of challenges commonly encountered in the computational modelling in systems biology. The re- search comprises of the development and application of a broad range of methods originating in the fields of computer science and mathematics for construction and analysis of computational models in systems biology. In particular, the performed research is setup in the context of two biolog- ical phenomena chosen as modelling case studies: 1) the eukaryotic heat shock response and 2) the in vitro self-assembly of intermediate filaments, one of the main constituents of the cytoskeleton. The range of presented approaches spans from heuristic, through numerical and statistical to ana- lytical methods applied in the effort to formally describe and analyse the two biological processes. We notice however, that although applied to cer- tain case studies, the presented methods are not limited to them and can be utilized in the analysis of other biological mechanisms as well as com- plex systems in general. The full range of developed and applied modelling techniques as well as model analysis methodologies constitutes a rich mod- elling framework. Moreover, the presentation of the developed methods, their application to the two case studies and the discussions concerning their potentials and limitations point to the difficulties and challenges one encounters in computational modelling of biological systems. The problems of model identifiability, model comparison, model refinement, model inte- gration and extension, choice of the proper modelling framework and level of abstraction, or the choice of the proper scope of the model run through this thesis.

Recovery and refining of manganese as by-product from hydrometallurgical processes

The consumption of manganese is increasing, but huge amounts of manganese still end up in waste in hydrometallurgical processes. The recovery of manganese from multi-metal solutions at low concentrations may not be economical. In addition, poor iron control typically prevents the production of high purity manganese. Separation of iron from manganese can be done with chemical precipitation or solvent extraction methods. Combined carbonate precipitation with air oxidation is a feasible method to separate iron and manganese due to the fast kinetics, good controllability and economical reagents. In addition the leaching of manganese carbonate is easier and less acid consuming than that of hydroxide or sulfide precipitates. Selective iron removal with great efficiency from MnSO4 solution is achieved by combined oxygen or air oxidation and CaCO3 precipitation at pH > 5.8 and at a redox potential of > 200 mV. In order to avoid gypsum formation, soda ash should be used instead of limestone. In such case, however, extra attention needs to be paid on the reagents mole ratios in order to avoid manganese coprecipitation. After iron removal, pure MnSO4 solution was obtained by solvent extraction using organophosphorus reagents, di-(2-ethylhexyl)phosphoric acid (D2EHPA) and bis(2,4,4- trimethylpentyl)phosphinic acid (CYANEX 272). The Mn/Ca and Mn/Mg selectivities can be increased by decreasing the temperature from the commonly used temperatures (40 –60oC) to 5oC. The extraction order of D2EHPA (Ca before Mn) at low temperature remains unchanged but the lowering of temperature causes an increase in viscosity and slower phase separation. Of these regents, CYANEX 272 is selective for Mn over Ca and, therefore, it would be the better choice if there is Ca present in solution. A three-stage Mn extraction followed by a two-stage scrubbing and two-stage sulfuric acid stripping is an effective method of producing a very pure MnSO4 intermediate solution for further processing. From the intermediate MnSO4 some special Mn- products for ion exchange applications were synthesized and studied. Three types of octahedrally coordinated manganese oxide materials as an alternative final product for manganese were chosen for synthesis: layer structured Nabirnessite, tunnel structured Mg-todorokite and K-kryptomelane. As an alternative source of pure MnSO4 intermediate, kryptomelane was synthesized by using a synthetic hydrometallurgical tailings. The results show that the studied OMS materials adsorb selectively Cu, Ni, Cd and K in the presence of Ca and Mg. It was also found that the exchange rates were reasonably high due to the small particle dimensions. Materials are stable in the studied conditions and their maximum Cu uptake capacity was 1.3 mmol/g. Competitive uptake of metals and acid was studied using equilibrium, batch kinetic and fixed-bed measurements. The experimental data was correlated with a dynamic model, which also accounts for the dissolution of the framework manganese. Manganese oxide micro-crystals were also bound onto silica to prepare a composite material having a particle size large enough to be used in column separation experiments. The MnOx/SiO2 ratio was found to affect significantly the properties of the composite. The higher the ratio, the lower is the specific surface area, the pore volume and the pore size. On the other hand, higher amount of silica binder gives composites better mechanical properties. Birnesite and todorokite can be aggregated successfully with colloidal silica at pH 4 and with MnO2/SiO2 weight ratio of 0.7. The best gelation and drying temperature was 110oC and sufficiently strong composites were obtained by additional heat-treatment at 250oC for 2 h. The results show that silica–supported MnO2 materials can be utilized to separate copper from nickel and cadmium. The behavior of the composites can be explained reasonably well with the presented model and the parameters estimated from the data of the unsupported oxides. The metal uptake capacities of the prepared materials were quite small. For example, the final copper loading was 0.14 mmol/gMnO2. According to the results the special MnO2 materials are potential for a specific environmental application to uptake harmful metal ions.

Network effects: Scale development and implications for new product performance

More and more innovations currently being commercialized exhibit network effects, in other words, the value of using the product increases as more and more people use the same or compatible products. Although this phenomenon has been the subject of much theoretical debate in economics, marketing researchers have been slow to respond to the growing importance of network effects in new product success. Despite an increase in interest in recent years, there is no comprehensive view on the phenomenon and, therefore, there is currently incomplete understanding of the dimensions it incorporates. Furthermore, there is wide dispersion in operationalization, in other words, the measurement of network effects, and currently available approaches have various shortcomings that limit their applicability, especially in marketing research. Consequently, little is known today about how these products fare on the marketplace and how they should be introduced in order to maximize their chances of success. Hence, the motivation for this study was driven by the need to increase our knowledge and understanding of the nature of network effects as a phenomenon, and of their role in the commercial success of new products. This thesis consists of two parts. The first part comprises a theoretical overview of the relevant literature, and presents the conclusions of the entire study. The second part comprises five complementary, empirical research publications. Quantitative research methods and two sets of quantitative data are utilized. The results of the study suggest that there is a need to update both the conceptualization and the operationalization of the phenomenon of network effects. Furthermore, there is a need for an augmented view on customers’ perceived value in the context of network effects, given that the nature of value composition has major implications for the viability of such products in the marketplace. The role of network effects in new product performance is not as straightforward as suggested in the existing theoretical literature. The overwhelming result of this study is that network effects do not directly influence product success, but rather enhance or suppress the influence of product introduction strategies. The major contribution of this study is in conceptualizing the phenomenon of network effects more comprehensively than has been attempted thus far. The study gives an augmented view of the nature of customer value in network markets, which helps in explaining why some products thrive on these markets whereas others never catch on. Second, the study discusses shortcomings in prior literature in the way it has operationalized network effects, suggesting that these limitations can be overcome in the research design. Third, the study provides some much-needed empirical evidence on how network effects, product introduction strategies, and new product performance are associated. In general terms, this thesis adds to our knowledge of how firms can successfully leverage network effects in product commercialization in order to improve market performance.

SPECIES RICHNESS AND ABUNDANCE OF LOW-TRUNK HERB EPIPHYTES IN RELATION TO HOST TREE SIZE AND BARK TYPE, EASTERN AMAZONIA

ABSTRACTThe composition and structure of the low-trunk epiphytic herb assembly as well as its vertical distribution were studied. DBH of host tree and bark type influence species richness and abundance in a nonlooded lowland tropical rainforest in Eastern Amazonia (1º57’36"S 51º36’55"W). A total of 37 epiphytic herb species were identified, among which 60% were Araceae. Species richness and abundance of epiphytic herbs showed tendency of positive correlation with host tree size and no relationships with bark type. Low positive correlation may be a by-product of the predominance of trees with smaller diameter in our sample rather than a reflection of neutral relationship. The absence of relationships with bark type may be partially explained by the large number of secondary, generalist, hemi-epiphytes and also may reflect the absence of suitable substrate in trees with smaller diameter.

Suorakulmaisten palonrajoittimien valmistettavuuden kehittäminen

Palonrajoittimet ovat tuotteita, jotka estävät tulen ja savun leviämisen palo-osastosta toiseen ja mahdollistavat ihmisten turvallisen ulospääsyn palotilanteessa. Tämän diplomityön tavoitteena oli vähentää suorakulmaisten palonrajoittimien valmistuskustannuksia niiden valmistettavuutta kehittämällä. Työn teoriaosassa käsitellään valmistettavuutta ja kokoonpantavuutta kehittäviä menetelmiä DFM:ää (Design for Manufacturability) ja DFA:ta (Design for Assembly) sekä palonrajoittimien ja ohutlevytuotteiden erityispiirteitä. Käytännön osuudessa esitellään tutkimusta varten valmistetut kolme kehitettävää palonrajoitinta, joita vertaillaan myös kilpaileviin tuotteisiin. Tuotteista analysoidaan osamääriä, materiaalikustannuksia ja työaikoja. Palonrajoittimien ongelmakohtia olivat muun muassa liittäminen ja kokoonpantavuus. Työssä esitetään keinoja palonrajoitinten valmistusystävälliseen suunnitteluun ja uusi moduloitu tuoteperhemalli, jolla vähennetään varsinkin valmistuksesta aiheutuvia kiinteitä kustannuksia. Lisäksi työssä esitetään alustava runkoratkaisumalli uudelle tuoteperheelle.

Production of a product similar to gelatin from chicken feet collagen

Chicken feet can be used as an alternative source of collagen for the development of new products. In this sense, the aim of this study was the production of a product similar to gelatin from collagen extracted from chicken feet and the evaluation of sensory quality. The products were produced in two distinct flavors, with grape flavor called GU and pineapple flavor called GA. Subsequently, we compared these formulations with gelatin of a trademark established in the market. We used in the verification of sensory acceptability of products a hedonic scale of 9 points and the availability of consuming the product by 30 untrained tasters. According to the results, all formulations showed good levels of acceptability, indicating the collagen from chicken feet as an alternative source of high quality in the production of gelatin.

Effects of Country of Origin on Consumer Product Evaluations: Finnish clothing products in the minds of Russian tourists

Companies operating in today’s highly internationalized markets consider product differentiation the key priority in pursue to attain a constant competitive advantage in challenging global environment (Baker and Ballington 2002, 158). The main driver affecting companies’ differentiation actions was described as early as 1912 by one of the marketing pioneers A. W. Shaw (1912, 710) as meeting human wants more accurate than the competition, and thus increasing customers’ perceived value and satisfaction. Dickson and Ginter (1987, 2) point out in their study based on earlier research by Chamberlin (1965) and Porter (1976) that differentiation can be based on either tangible characteristics of a product such as design or intangible characteristics such as a brand name and country of origin (hereafter referred to as COO). The concept of COO and its impact on consumers’ evaluation of a product as an extrinsic product cue has been one of the most noteworthy topics in international marketing, having been voluminously examined by over 780 authors in more than 750 academic publications in the past 40 years (Papadopoulos and Heslop 2002, 294). Many of these studies accentuate the significant effect the COO has on consumers’ product attribute evaluations. People routinely associate country images with products and services in order to judge and categorize them based on perceived quality and risk levels; thereby COO can influence the likelihood of a purchase (Peterson and Jolibert 1995, 883-884; Verlegh and Steenkamp 1999, 523). Based on the vast research related to COO in the field of international business, it is widely recognized that the country associated with a product can act in a similar way as the name of a brand and even become a part of product’s total image. Thereby depending on customer’s values and perceptions, the product-country image can either increase or decrease perceived value.

Streamlining Launch Support Operations in a Product Platform

The new product development process is a massive investment to a company that aims to reduce their products’ time-to-market. Capability to shorter time-to market allows longer life-cycle to products which are introduced to market earlier but also give advantage to start product launch later while simultaneously learning from customer behavior and competitors. The product launch support operations are the last ramp-up activities before the product launching. This study defines what these operations mean in a product platform and how they can be streamlined to be more efficient. The methodology includes interviews, innovative group brainstorming and regular working group meetings. The challenges concerning the current situation of product launch support operations are allocated into four categories: General, Process, Project Resources and Project Management including altogether ten sub challenges. The challenges include issues related to technology and marketing management, branding strategy, organizing the global platform structure, harmonizing processes and clarifying handovers between shareholders in the process. The study makes a suggestion of a new Product Launch Support organization and clarification of its roles, responsibilities and tasks. In addition a new project management tool and Lessons Learned are suggested to improve the project management. The study can be seen as a pre-study when having an aim at combining technological and marketing know-how in the product ramp-up process before actual production. The future proceedings are suggested to include more detailed specifications and implementation in order to reach the long range target, reduced the time-to-market.

Making Sense of Software Product Requirements

One of the most crucial tasks for a company offering a software product is to decide what new features should be implemented in the product’s forthcoming versions. Yet, existing studies show that this is also a task with which many companies are struggling. This problem has been claimed to be ambiguous and changing. There are better or worse solutions to the problem, but no optimal one. Furthermore, the criteria determining the success of the solution keeps changing due to continuously changing competition, technologies and market needs. This thesis seeks to gain a deeper understanding of the challenges that companies have reportedly faced in determining the requirements for their forthcoming product versions. To this end, product management related activities are explored in seven companies. Following grounded theory approach, the thesis conducts four iterations of data analysis, where each of the iterations goes beyond the previous one. The thesis results in a theory proposal intended to 1) describe the essential characteristics of organizations’ product management challenges, 2) explain the origins of the perceived challenges and 3) suggest strategies to alleviate the perceived challenges. The thesis concludes that current product management approaches are becoming inadequate to deal with challenges that have multiple and conflicting interpretations, different value orientations, unclear goals, contradictions and paradoxes. This inadequacy continues to increase until current beliefs and assumptions about the product management challenges are questioned and a new paradigm for dealing with the challenges is adopted.