Entry Strategy Issues in the Ophthalmic Industry: Entry Mode, Pricing and Distribution

Maahantulostrategia asettaa yrityksen kansainvälisiä liiketoimintoja ohjaavat tavoitteet, päämäärät, resurssit ja toiminnan suuntaviivat. Tämä diplomityö käsittelee yrityksen maahantulostrategian elementeistä operaatiomuodon valintaa, hinnoittelua ja jakelua. Työssä rakennetaan teoriakehys elementteihin liittyvien päätösten tutkimiseksi lääketeollisuuden ominaispiirteet huomioiden. Lääketeollisuudella on muihin teollisuudenaloihin verrattuna useita erityispiirteitä, joihin työ perehdyttää. Lisäksi työn olennainen osa on selvittää lääketeollisuuden maakohtaisia säädöksiä ja toimintamalleja. Diplomityö on tehty silmäläkkeitä valmistavalle, kehittävälle ja markkinoivalle Santen Oy:lle, joka suunnittelee toimintansa laajentamista Keski- ja Etelä-Euroopan markkinoille. Tässä laajentumisprosessissa ensimmäisenä kohdemaana on Saksa, jonka markkinoille suuntautuvia toimenpiteitä työ tutkii. Teoriakehyksen, markkinoiden ominaispiirteiden sekä useiden erilaisten analyysien pohjalta työn tavoitteena on antaa operaatiomuotoa, tuotteiden hinnoittelua ja jakelua koskevia suosituksia.

The development of an information infrastructure for cost estimating in the automotive industry

Työn tavoitteena on luoda yleinen informaatioinfrastruktuuri autoteollisuuden valmistuskustannusten arviointiin. Nykyään tämä kustannusarviointi on laajassa käytössä oleva menetelmä. Se mahdollistaa tuotekustannusten hallitsemisen, mikä lisää autovalmistajien kilpailukykyä. Kustannusarvioinnissa tarvitaan laadukasta tietoa, mutta suoritetussa tutkimuksessa paljastui, että useat seikat haittaavat tätä arviointia. Erityisesti resurssien vähyys, tiedonhankinta ja tiedon luotettavuuden varmentaminen aiheuttavat ongelmia. Nämä seikat ovat johtaneet kokemusperäisen asiantuntemuksen laajaan käyttöön, minkä johdosta erityisesti kokemattomilla kustannusarvioijilla on vaikeuksia ymmärtää kustannusarvioiden tietovaatimuksia. Tämän johdosta tutkimus tuo esiin kokeneiden kustannusarvioijien käyttämiä tietoja ja tietolähteitä päämääränä lisätä kustannusarvioiden ymmärtämistä. Informaatioinfrastruktuuri, joka sisältää tarvittavan tiedon järkevien ja luotettavien kustannusarvioiden luontiin, perustuu tutkimuksen tuloksiin. Infrastruktuuri määrittelee tarvittavan kustannustiedon ja niiden mahdolliset tietolähteet. Lisäksi se selvittää miksi tieto on tarpeellista ja miten tiedon oikeellisuus pitäisi varmentaa. Infrastruktuuria käytetään yhdessä yleisen kustannusarvioprosessimallin kanssa. Tämä integrointi johtaa tarkempiin ja selkeämpiin kustannusarvioihin autoteollisuudessa.

From caging to rouse dynamics in polymer melts with intramolecular barriers: a critical test of the mode coupling theory

By means of computer simulations and solution of the equations of the mode coupling theory (MCT),we investigate the role of the intramolecular barriers on several dynamic aspects of nonentangled polymers. The investigated dynamic range extends from the caging regime characteristic of glass-formers to the relaxation of the chain Rouse modes. We review our recent work on this question,provide new results, and critically discuss the limitations of the theory. Solutions of the MCT for the structural relaxation reproduce qualitative trends of simulations for weak and moderate barriers. However, a progressive discrepancy is revealed as the limit of stiff chains is approached. This dis-agreement does not seem related with dynamic heterogeneities, which indeed are not enhanced by increasing barrier strength. It is not connected either with the breakdown of the convolution approximation for three-point static correlations, which retains its validity for stiff chains. These findings suggest the need of an improvement of the MCT equations for polymer melts. Concerning the relaxation of the chain degrees of freedom, MCT provides a microscopic basis for time scales from chain reorientation down to the caging regime. It rationalizes, from first principles, the observed deviations from the Rouse model on increasing the barrier strength. These include anomalous scaling of relaxation times, long-time plateaux, and nonmonotonous wavelength dependence of the mode correlators.

Nanocharacterization of Soft Biological Samples in Shear Mode with Quartz Tuning Fork Probes

Quartz tuning forks are extremely good resonators and their use is growing in scanning probe microscopy. Nevertheless, only a few studies on soft biological samples have been reported using these probes. In this work, we present the methodology to develop and use these nanosensors to properly work with biological samples. The working principles, fabrication and experimental setup are presented. The results in the nanocharacterization of different samples in different ambients are presented by using different working modes: amplitude modulation with and without the use of a Phase-Locked Loop (PLL) and frequency modulation. Pseudomonas aeruginosa bacteria are imaged in nitrogen using amplitude modulation. Microcontact printed antibodies are imaged in buffer using amplitude modulation with a PLL. Finally, metastatic cells are imaged in air using frequency modulation.

The role of intramolecular barriers on the glass transition of polymers: computer simulations versus mode coupling theory

We present computer simulations of a simple bead-spring model for polymer melts with intramolecular barriers. By systematically tuning the strength of the barriers, we investigate their role on the glass transition. Dynamic observables are analyzed within the framework of the mode coupling theory (MCT). Critical nonergodicity parameters, critical temperatures, and dynamic exponents are obtained from consistent fits of simulation data to MCT asymptotic laws. The so-obtained MCT λ-exponent increases from standard values for fully flexible chains to values close to the upper limit for stiff chains. In analogy with systems exhibiting higher-order MCT transitions, we suggest that the observed large λ-values arise form the interplay between two distinct mechanisms for dynamic arrest: general packing effects and polymer-specific intramolecular barriers. We compare simulation results with numerical solutions of the MCT equations for polymer systems, within the polymer reference interaction site model (PRISM) for static correlations. We verify that the approximations introduced by the PRISM are fulfilled by simulations, with the same quality for all the range of investigated barrier strength. The numerical solutions reproduce the qualitative trends of simulations for the dependence of the nonergodicity parameters and critical temperatures on the barrier strength. In particular, the increase in the barrier strength at fixed density increases the localization length and the critical temperature. However the qualitative agreement between theory and simulation breaks in the limit of stiff chains. We discuss the possible origin of this feature.

eBusiness Adoption in Metalforming SMEs in the Automotive Industry

Competition in the automotive industry has led the participants trying to find new ways of reducing costs, increasing efficiency and improve responsiveness to gain competitive advantage. It is not anymore single companies competing against each others, it is the whole supply chains competing. This has already earlier led the big multinational companies to gain benefits by using electronic means of doing business (eBusiness). Lower down the chain the smaller companies have not yet taken advantage of the potential benefits of eBusiness methods. Therefore, the full benefits from eBusiness methods have yet to be discovered. The aim of the Thesis is to find ways of taking advantage of eBusiness methods with their limited resources. Because small and medium sized enterprises (SME) many times lack of eBusiness knowledge this project also aims to clarify the idea of eBusiness, present the potential possibilities and benefits from eBusiness and the requirements needed to achieve them. The Thesis presents information of eBusines especially in the automotive industry. Together with this information and the information acquired from the case study company a simple route map is developed which SMEs can use gain competitive advantage by eBusiness methods.

Recombination dynamics in ZnO nanowires: Surfaces states versus mode quality factor

In this work, we investigate the influence of finite size on the recombinations dynamics of ZnO nanowires. We demonstrate that diameter as well as lenght of nanowires determine the lifetime of the neutral donor bound excitons. Our findings suggest that while the length is mainly responsible for different mode quality factors of the cavity-like nanowires, the diameter determines the influence of surface states as alternative recombinations channels for the optical modes trapped in the nanocavity. In addition, comparing nanowires grown using different catalyst we show that the surfaces states strongly depend on each precursor characteristics.

Structural Insight into the Mode of Action of a Direct Inhibitor of Coregulator Binding to the Thyroid Hormone Receptor.

The development of nuclear hormone receptor antagonists that directly inhibit the association of the receptor with its essential coactivators would allow useful manipulation of nuclear hormone receptor signaling. We previously identified 3-(dibutylamino)-1-(4-hexylphenyl)-propan-1-one (DHPPA), an aromatic β-amino ketone that inhibits coactivator recruitment to thyroid hormone receptor β (TRβ), in a high-throughput screen. Initial evidence suggested that the aromatic β-enone 1-(4-hexylphenyl)-prop-2-en-1-one (HPPE), which alkylates a specific cysteine residue on the TRβ surface, is liberated from DHPPA. Nevertheless, aspects of the mechanism and specificity of action of DHPPA remained unclear. Here, we report an x-ray structure of TRβ with the inhibitor HPPE at 2.3-Å resolution. Unreacted HPPE is located at the interface that normally mediates binding between TRβ and its coactivator. Several lines of evidence, including experiments with TRβ mutants and mass spectroscopic analysis, showed that HPPE specifically alkylates cysteine residue 298 of TRβ, which is located near the activation function-2 pocket. We propose that this covalent adduct formation proceeds through a two-step mechanism: 1) β-elimination to form HPPE; and 2) a covalent bond slowly forms between HPPE and TRβ. DHPPA represents a novel class of potent TRβ antagonist, and its crystal structure suggests new ways to design antagonists that target the assembly of nuclear hormone receptor gene-regulatory complexes and block transcription.

A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia.

Lactate has been shown to offer neuroprotection in several pathologic conditions. This beneficial effect has been attributed to its use as an alternative energy substrate. However, recent description of the expression of the HCA1 receptor for lactate in the central nervous system calls for reassessment of the mechanism by which lactate exerts its neuroprotective effects. Here, we show that HCA1 receptor expression is enhanced 24 hours after reperfusion in an middle cerebral artery occlusion stroke model, in the ischemic cortex. Interestingly, intravenous injection of L-lactate at reperfusion led to further enhancement of HCA1 receptor expression in the cortex and striatum. Using an in vitro oxygen-glucose deprivation model, we show that the HCA1 receptor agonist 3,5-dihydroxybenzoic acid reduces cell death. We also observed that D-lactate, a reputedly non-metabolizable substrate but partial HCA1 receptor agonist, also provided neuroprotection in both in vitro and in vivo ischemia models. Quite unexpectedly, we show D-lactate to be partly extracted and oxidized by the rodent brain. Finally, pyruvate offered neuroprotection in vitro whereas acetate was ineffective. Our data suggest that L- and D-lactate offer neuroprotection in ischemia most likely by acting as both an HCA1 receptor agonist for non-astrocytic (most likely neuronal) cells as well as an energy substrate.

The effects of some variables on CO2 laser-MAG hybrid welding

The CO2-laser-MAG hybrid welding process has been shown to be a productive choice for the welding industry, being used in e.g. the shipbuilding, pipe and beam manufacturing, and automotive industries. It provides an opportunity to increase the productivity of welding of joints containing air gaps compared with autogenous laser beam welding, with associated reductions in distortion and marked increases in welding speeds and penetration in comparison with both arc and autogenous laser welding. The literature study indicated that the phenomena of laser hybrid welding are mostly being studied using bead-on-plate welding or zero air gap configurations. This study shows it very clearly that the CO2 laser-MAG hybrid welding process is completely different, when there is a groove with an air gap. As in case of industrial use it is excepted that welding is performed for non-zero grooves, this study is of great importance for industrial applications. The results of this study indicate that by using a 6 kW CO2 laser-MAG hybrid welding process, the welding speed may also be increased if an air gap is present in the joint. Experimental trials indicated that the welding speed may be increased by 30-82% when compared with bead-on-plate welding, or welding of a joint with no air gap i.e. a joint prepared as optimum for autogenous laser welding. This study demonstrates very clearly, that the separation of the different processes, as well as the relative configurations of the processes (arc leading or trailing) affect welding performance significantly. These matters influence the droplet size and therefore the metal transfer mode, which in turn determined the resulting weld quality and the ability to bridge air gaps. Welding in bead-onplate mode, or of an I butt joint containing no air gap joint is facilitated by using a leading torch. This is due to the preheating effect of the arc, which increases the absorptivity of the work piece to the laser beam, enabling greater penetration and the use of higher welding speeds. With an air gap present, air gap bridging is more effectively achieved by using a trailing torch because of the lower arc power needed, the wider arc, and the movement of droplets predominantly towards the joint edges. The experiments showed, that the mode of metal transfer has a marked effect on gap bridgeability. Transfer of a single droplet per arc pulse may not be desirable if an air gap is present, because most of the droplets are directed towards the middle of the joint where no base material is present. In such cases, undercut is observed. Pulsed globular and rotational metal transfer modes enable molten metal to also be transferred to the joint edges, and are therefore superior metal transfer modes when bridging air gaps. It was also found very obvious, that process separation is an important factor in gap bridgeability. If process separation is too large, the resulting weld often exhibits sagging, or no weld may be formed at all as a result of the reduced interaction between the component processes. In contrast, if the processes are too close to one another, the processing region contains excess molten metal that may create difficulties for the keyhole to remain open. When the distance is optimised - i.e. a separation of 0-4 mm in this study, depending on the welding speed and beam-arc configuration - the processes act together, creating beneficial synergistic effects. The optimum process separation when using a trailing torch was found to be shorter (0-2 mm) than when a leading torch is used (2-4 mm); a result of the facilitation of weld pool motion when the latter configuration is adopted. This study demonstrates, that the MAG process used has a strong effect on the CO2-laser-MAG hybrid welding process. The laser beam welding component is relatively stable and easy to manage, with only two principal processing parameters (power and welding speed) needing to be adjusted. In contrast, the MAG process has a large number of processing parameters to optimise, all of which play an important role in the interaction between the laser beam and the arc. The parameters used for traditional MAG welding are often not optimal in achieving the most appropriate mode of metal transfer, and weld quality in laser hybrid welding, and must be optimised if the full range of benefits provided by hybrid welding are to be realised.