Use of physiological constraints to identify quantitative design principles for gene expression in yeast adaptation to heat shock

Background: Understanding the relationship between gene expression changes, enzyme activity shifts, and the corresponding physiological adaptive response of organisms to environmental cues is crucial in explaining how cells cope with stress. For example, adaptation of yeast to heat shock involves a characteristic profile of changes to the expression levels of genes coding for enzymes of the glycolytic pathway and some of its branches. The experimental determination of changes in gene expression profiles provides a descriptive picture of the adaptive response to stress. However, it does not explain why a particular profile is selected for any given response. Results: We used mathematical models and analysis of in silico gene expression profiles (GEPs) to understand how changes in gene expression correlate to an efficient response of yeast cells to heat shock. An exhaustive set of GEPs, matched with the corresponding set of enzyme activities, was simulated and analyzed. The effectiveness of each profile in the response to heat shock was evaluated according to relevant physiological and functional criteria. The small subset of GEPs that lead to effective physiological responses after heat shock was identified as the result of the tuning of several evolutionary criteria. The experimentally observed transcriptional changes in response to heat shock belong to this set and can be explained by quantitative design principles at the physiological level that ultimately constrain changes in gene expression. Conclusion: Our theoretical approach suggests a method for understanding the combined effect of changes in the expression of multiple genes on the activity of metabolic pathways, and consequently on the adaptation of cellular metabolism to heat shock. This method identifies quantitative design principles that facilitate understating the response of the cell to stress.

Méta-analyses d'essais randomisés sur données individuelles dans le traitement des cancers ORL non métastatiques : principes, résultats, perspectives [Individual patient data meta-analyses of randomized trials for the treatment of non-metastatic head and neck squamous cell carcinomas: Principles, results and perspectives].

Meta-analyses are considered as an important pillar of evidence-based medicine. The aim of this review is to describe the main principles of a meta-analysis and to use examples of head and neck oncology to demonstrate their clinical impact and methodological interest. The major role of individual patient data is outlined, as well as the superiority of individual patient data over meta-analyses based on published summary data. The major clinical breakthrough of head and neck meta-analyses are summarized, regarding concomitant chemotherapy, altered fractionated chemotherapy, new regimens of induction chemotherapy or the use of radioprotectants. Recent methodological developments are described, including network meta-analyses, the validation of surrogate markers. Lastly, the future of meta-analyses is discussed in the context of personalized medicine.

Production Control Principles in Printed Wiring Board Fabrication

Työn tavoitteena oli kuvata piirilevyvalmistaja Aspocomp Oy:n Espoon tehtaan tämän hetkinen tuotannonohjausperiaate ja tunnistaa siinä esiintyvät puutteet sekä kehittää vaihtoehtoinen tuotannonohjausperiaate piirilevyvalmistukseen. Vaihtoehtoisen ohjausperiaatteen lähtökohtana oli tuotannonohjauksen sopeuttaminen vaativaan ja jatkuvasti muuttuvaan liiketoimintaympäristöön. Työn teoreettinen osa keskittyi tuotannonohjauksen eri lähestymistapoihin. Kirjallisuuskatsauksessa esitetään eri tuotannonohjausperiaatteiden keskeiset sisällöt, jotka muodostavat rungon toimivalle tuotannonohjauskäytännölle. Työn kokeellinen osa keskittyi Espoon piirilevytehtaan tuotannonohjausperiaatteen selvittämiseen. Espoon piirilevytehtaan nykyisessä tuotannonohjausperiaatteessa havaittujen ongelmakohtien ja liiketoimintaympäristön vaatimusten perusteella kehitettiin vaihtoehtoinen tuotannonohjaustapa. Vaihtoehtoisen tuotannonohjaustavan päämääränä oli läpimenoajan lyhentäminen sekä tuotannon parempi hallittavuus. Vaihtoehtoinen toimintamalli tavoitteiden saavuttamiseksi perustuu pullonkaulateoriaan, jossa keskeisin muutos nykyiseen toimintamalliin oli puolivalmisteiden varastointi toimitusajan lyhentämiseksi sekä tuotantovolyymin heilahdusten vaikutusten vähentämiseksi. Työn kokeellisessa osassa ilmeni, että kysynnän muutokset ja kapasiteetin suunnittelun puute aiheuttivat ongelmia piirilevytehtaan tuotannonohjauksessa.

First principles analysis of the stability and diffusion of oxygen vacancies in meetal oxides

Oxygen vacancies in metal oxides are known to determine their chemistry and physics. The properties of neutral oxygen vacancies in metal oxides of increasing complexity (MgO, CaO, alpha-Al2O3, and ZnO) have been studied using density functional theory. Vacancy formation energies, vacancy-vacancy interaction, and the barriers for vacancy migration are determined and rationalized in terms of the ionicity, the Madelung potential, and lattice relaxation. It is found that the Madelung potential controls the oxygen vacancy properties of highly ionic oxides whereas a more complex picture arises for covalent ZnO.

MgO/Ag(001) interface structure and STM images from first principles

The interface of MgO/Ag(001) has been studied with density functional theory applied to slabs. We have found that regular MgO films show a small adhesion to the silver substrate, the binding can be increased in off-stoichiometric regimes, either by the presence of O vacancies at the oxide film or by a small excess of O atoms at the interface between the ceramic to the metal. By means of theoretical methods, the scanning tunneling microscopy signatures of these films is also analyzed in some detail. For defect free deposits containing 1 or 2 ML and at low voltages, tunnelling takes place from the surface Ag substrate, and at large positive voltages Mg atoms are imaged. If defects, oxygen vacancies, are present on the surface of the oxide they introduce much easier channels for tunnelling resulting in big protrusions and controlling the shape of the image, the extra O stored at the interface can also be detected for very thin films.

Dual-Energy CT: Basic Principles, Technical Approaches, and Applications in Musculoskeletal Imaging (Part 1).

In recent years, technological advances have allowed manufacturers to implement dual-energy computed tomography (DECT) on clinical scanners. With its unique ability to differentiate basis materials by their atomic number, DECT has opened new perspectives in imaging. DECT has been used successfully in musculoskeletal imaging with applications ranging from detection, characterization, and quantification of crystal and iron deposits; to simulation of noncalcium (improving the visualization of bone marrow lesions) or noniodine images. Furthermore, the data acquired with DECT can be postprocessed to generate monoenergetic images of varying kiloelectron volts, providing new methods for image contrast optimization as well as metal artifact reduction. The first part of this article reviews the basic principles and technical aspects of DECT including radiation dose considerations. The second part focuses on applications of DECT to musculoskeletal imaging including gout and other crystal-induced arthropathies, virtual noncalcium images for the study of bone marrow lesions, the study of collagenous structures, applications in computed tomography arthrography, as well as the detection of hemosiderin and metal particles.

Dual-Energy CT: Basic Principles, Technical Approaches, and Applications in Musculoskeletal Imaging (Part 2).

In recent years, technological advances have allowed manufacturers to implement dual-energy computed tomography (DECT) on clinical scanners. With its unique ability to differentiate basis materials by their atomic number, DECT has opened new perspectives in imaging. DECT has been successfully used in musculoskeletal imaging with applications ranging from detection, characterization, and quantification of crystal and iron deposits, to simulation of noncalcium (improving the visualization of bone marrow lesions) or noniodine images. Furthermore, the data acquired with DECT can be postprocessed to generate monoenergetic images of varying kiloelectron volts, providing new methods for image contrast optimization as well as metal artifact reduction. The first part of this article reviews the basic principles and technical aspects of DECT including radiation dose considerations. The second part focuses on applications of DECT to musculoskeletal imaging including gout and other crystal-induced arthropathies, virtual noncalcium images for the study of bone marrow lesions, the study of collagenous structures, applications in computed tomography arthrography, as well as the detection of hemosiderin and metal particles.

Tackling Societal Challenges Related to Ageing and Transport Transition: An Introduction to Philosophical Principles of Causation Adapted to the Biopsychosocial Model

In geriatrics, driving cessation is addressed within the biopsychosocial model. This has broadened the scope of practitioners, not only in terms of assessing fitness to drive, but also by helping to maintain social engagements and provide support for transport transition. Causes can be addressed at different levels by adapting medication, improving physical health, modifying behaviour, adapting lifestyle, or bringing changes to the environment. This transdisciplinary approach requires an understanding of how different disciplines are linked to each other. This article reviews the philosophical principles of causality between fields and provides a framework for understanding causality within the biopsychosocial model. Understanding interlevel constraints should help practitioners overcome their differences, and favor transversal approaches to driving cessation.

An analytic approach to distribution logistics strategic management

Logistics management is increasingly being recognised by many companies to be of critical concern. The logistics function includes directly or indirectly many of the new areas for achieving or maintaining competitive advantage that companies have been forced to develop due to increasing competitive pressures. The key to achieving a competitive advantage is to manage the logistics function strategically which involves determining the most cost effective method of providing the necessary customer service levels from the many combinations of operating procedures in the areas of transportation, warehousing, order processing and information systems, production, and inventory management. In this thesis, a comprehensive distribution logistics strategic management process is formed by integrating the periodic strategic planning process with a continuous strategic issues management process. Strategic planning is used for defining the basic objectives for a company and assuring co operation and synergy between the different functions of a company while strategic issues management is used on a continuous basis in order to deal with environmental and internal turbulence. The strategic planning subprocess consists of the following main phases: (1) situational analyses, (2) defining the vision and strategic goals for the logistics function, (3) determining objectives and strategies, (4) drawing up tactical action plans, and (5) evaluating the implementation of the plans and making the needed adjustments. The aim of the strategic issues management subprocess is to continuously scan the environment and the organisation for early identification of the issues having a significant impact on the logistics function using the following steps: (1) the identification of trends, (2) assessing the impact and urgency of the identified trends, (3) assigning priorities to the issues, and (4) planning responses to the, issues. The Analytic Hierarchy Process (AHP) is a systematic procedure for structuring any problem. AHP is based on the following three principles: decomposition, comparative judgements, and synthesis of priorities. AHP starts by decomposing a complex, multicriteria problem into a hierarchy where each level consists of a few manageable elements which are then decomposed into another set of elements. The second step is to use a measurement methodology to establish priorities among the elements within each level of the hierarchy. The third step in using AHP is to synthesise the priorities of the elements to establish the overall priorities for the decision alternatives. In this thesis, decision support systems are developed for different areas of distribution logistics strategic management by applying the Analytic Hierarchy Process. The areas covered are: (1) logistics strategic issues management, (2) planning of logistic structure, (3) warehouse site selection, (4) inventory forecasting, (5) defining logistic action and development plans, (6) choosing a distribution logistics strategy, (7) analysing and selecting transport service providers, (8) defining the logistic vision and strategic goals, (9) benchmarking logistic performance, and (10) logistic service management. The thesis demonstrates the potential of AHP as a systematic and analytic approach to distribution logistics strategic management.

First principles modeling of metallic alloys and alloy surfaces

By alloying metals with other materials, one can modify the metal’s characteristics or compose an alloy which has certain desired characteristics that no pure metal has. The field is vast and complex, and phenomena that govern the behaviour of alloys are numerous. Theories cannot penetrate such complexity, and the scope of experiments is also limited. This is why the relatively new field of ab initio computational methods has much to give to this field. With these methods, one can extend the understanding given by theories, predict how some systems might behave, and be able to obtain information that is not there to see in physical experiments. This thesis pursues to contribute to the collective knowledge of this field in the light of two cases. The first part examines the oxidation of Ag/Cu, namely, the adsorption dynamics and oxygen induced segregation of the surface. Our results demonstrate that the presence of Ag on the Cu(100) surface layer strongly inhibits dissociative adsorption. Our results also confirmed that surface reconstruction does happen, as experiments predicted. Our studies indicate that 0.25 ML of oxygen is enough for Ag to diffuse towards the bulk, under the copper oxide layer. The other part elucidates the complex interplay of various energy and entropy contributions to the phase stability of paramagnetic duplex steel alloys. We were able to produce a phase stability map from first principles, and it agrees with experiments rather well. Our results also show that entropy contributions play a very important role on defining the phase stability. This is, to the author’s knowledge, the first ab initio study upon this subject.

Integrating eco-innovation principles into regional strategy and policy: case of Päijät-Häme region, Finland

This study focuses on the integration of eco-innovation principles into strategy and policy at the regional level. The importance of regions as a level for integrating eco-innovative programs and activities served as the point of interest for this study. Eco-innovative activities and technologies are seen as means to meet sustainable development objective of improving regions’ quality of life. This study is conducted to get an in-depth understanding and learning about eco-innovation at regional level, and to know the basic concepts that are important in integrating eco-innovation principles into regional policy. Other specific objectives of this study are to know how eco-innovation are developed and practiced in the regions of the EU, and to analyze the main characteristic features of an eco-innovation model that is specifically developed at Päijät-Häme Region in Finland. Paijät-Häme Region is noted for its successful eco-innovation strategies and programs, hence, taken as casework in this study. Both primary (interviews) and secondary data (publicly available documents) are utilized in this study. The study shows that eco-innovation plays an important role in regional strategy as reviewed based on the experience of other regions in the EU. This is because of its localized nature which makes it easier to facilitate in a regional setting. Since regional authorities and policy-makers are normally focused on solving its localized environmental problems, eco-innovation principles can easily be integrated into regional strategy. The case study highlights Päijät-Häme Region’s eco-innovation strategies and projects which are characterized by strong connection of knowledge-producing institutions. Policy instruments supporting eco-innovation (e.g. environmental technologies) are very much focused on clean technologies, hence, justifying the formation of cleantech clusters and business parks in Päijät-Häme Region. A newly conceptualized SAMPO model of eco-innovation has been developed in Päijät-Häme Region to better capture the region’s characteristics and to eventually replace the current model employed by the Päijät-Häme Regional Authority. The SAMPO model is still under construction, however, review of its principles points to some of its three important spearheads – practice-based innovation, design (eco-design) and clean technology or environmental technology (environment).

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.