Design and Validation of a Novel Generic Platform for the Production of Tetravalent IgG1-like Bispecific Antibodies.

We have designed and validated a novel generic platform for production of tetravalent IgG1-like chimeric bispecific Abs. The VH-CH1-hinge domains of mAb2 are fused through a peptidic linker to the N terminus of mAb1 H chain, and paired mutations at the CH1-CL interface mAb1 are introduced that force the correct pairing of the two different free L chains. Two different sets of these CH1-CL interface mutations, called CR3 and MUT4, were designed and tested, and prototypic bispecific Abs directed against CD5 and HLA-DR were produced (CD5xDR). Two different hinge sequences between mAb1 and mAb2 were also tested in the CD5xDR-CR3 or -MUT4 background, leading to bispecific Ab (BsAbs) with a more rigid or flexible structure. All four Abs produced bound with good specificity and affinity to CD5 and HLA-DR present either on the same target or on different cells. Indeed, the BsAbs were able to efficiently redirect killing of HLA-DR(+) leukemic cells by human CD5(+) cytokine-induced killer T cells. Finally, all BsAbs had a functional Fc, as shown by their capacity to activate human complement and NK cells and to mediate phagocytosis. CD5xDR-CR3 was chosen as the best format because it had overall the highest functional activity and was very stable in vitro in both neutral buffer and in serum. In vivo, CD5xDR-CR3 was shown to have significant therapeutic activity in a xenograft model of human leukemia.

Developing a Service-Oriented Software Platform

Tehokkaasti toimiva sähköinen tiedonvälitys yrityksen omien sovellusten välillä sekä sen liikekumppaneiden kanssa on kasvanut merkittäväksi yrityksen kilpailukykyä lisääväksi tekijäksi. Yritysten erilaiset tietojärjestelmät asettavat haasteita tehokkaalle tiedonvälitykselle näiden järjestelmien välillä. Perinteiset EDI teknologioihin perustuvat sähköisen tiedonvälityksen ratkaisut eivät pysty mukautumaan nykyisin nopeasti muuttuviin markkinatilanteisiin. Palvelukeskeiseen arkkitehtuuriin ja Web-palveluihin perustuvat teknologiat mahdollistavat mukautumisen erilaisiin muutoksiin liiketoiminnassa nopeammin ja helpommin. Lisäksi ne nopeuttavat tiedon integrointia erilaisten tietojärjestelmien välillä, koska tiedonvälityksessä käytetään yleisesti hyväksyttyihin standardeihin perustuvia tiedonsiirtoprotokollia sekä tietoformaatteja. Diplomityössä esitellään keskeiset teknologiat ja menetelmät sähköisen tiedonvälityksen toteuttamiseen. Lisäksi työssä vertaillaan erilaisia vaihtoehtoja, joilla sähköinen tiedonvälitys voidaan toteuttaa. Vaihtoehtoina työssä ovat tiedonvälityspalveluiden ostaminen toiselta yritykseltä, olemassa olevan valmiin ohjelmiston hyödyntäminen, tai kokonaan uuden sovellusalustan kehittäminen. Työssä kuvaillaan palvelukeskeisen sovellusalustan toteutus, joka mahdollistaa tehokkaan sekä joustavan tiedonvälityksen sovellusten välillä. Alustan tarjoamien palveluiden päälle voidaan rakentaa erilaisia liiketoimintaa tukevia palveluita, jotka voivat hyödyntää sovellusalustan tarjoamia toiminnallisuuksia. Alustan toteutusta arvioidaan kolmen liiketoimintaskenaarion toteutuksesta saatujen kokemusten perusteella.

eLab, a Personal Learning Environment for the Green Open Innovation Platform

Open Innovation is a relatively new concept which involves a change of paradigm in the R+D+i processes of companies whose aim is to create new technologies or new processes. If to this change, we add the need for innovation in the new green and sustainability economy, and we set out to create a collaborative platform with a learning space where this can happen, we will be facing an overwhelming challenge which requires the application of intelligent programming technologies and languages at the service of education.The aim of the Green IDI (Green Open Innovation) ¿ Economic development and job creation vector in SMEs, based on the environment and sustainability project is to create a platform where companies and individual researchers can perform open innovation processes in the field of sustainability and the environment.The Green IDI (Green Open Innovation) project is funded under the program INNPACTO by the Ministry of Science and Innovation of Spain and is being developed through a consortium formed by the following institutions: GRUPO ICA; COMPARTIA; GRUPO INTERCOM; CETAQUA and the Instituto de Investigación en Inteligencia Artificial (IIIA) from Consejo Superior de Investigaciones Científicas (CSIC). Also the consortium include FUNDACIÓ PRIVADA BARCELONA DIGITAL; PIMEC and UNIVERSITAT OBERTA DE CATALUNYA (UOC).Sustainability and positive action for the environment are considered the principle vector of economic development for companies. As Nicolás Scoli says (2007) ¿in short, preventing unnecessary consumption and the efficient consumption of resources means producing greater wealth with less. Both effects lead to reduced pollution linked to production and consumption¿.The Spanish Sustainable Development Strategy (EEDS) plan defends consumption and sustainable production linked to social and economic development by adhering to the commitment not to endanger ecosystems and abolishing the idea that economic growth is directly proportional to the deterioration of the environment.Uniting the Open Innovation and New Green Economy concepts leads to the "Green Open Innovation¿ Platform creation project.This article analyses the concept of open innovation and defines the importance of the new green and sustainable economy. Lastly, it proposes the creation of eLab. The eLab is defined as an Open Green Innovation Platform personal and collaborative education space which is fed by the interactions of users and which enables innovation processes based on new green economy concepts to be carried out.The creation of a personal learning environment such as eLab on the Green Open Innovation Platform meets the need to offer a collaborative space where platform users can improve their skills regarding the environment and sustainability based on collaborative synergies through Information and Communication Technologies.

Improving the Potentials of Logistics Processes: Identification and Solutions

The importance of logistics for companies is a well known and justified issue. Today, enterprises are developing their logistics processes in order to match their products and services to the requirements of the most important customers. Therefore there is a need for developing analysing tools for logistics and especially for analysing the significance of various customer service elements. The aim of this paper is to propose analytic tools for supporting strategic level logistics decision making by emphasizing service level elements on two levels: (1) to introduce and propose approaches to categorize the developing efforts of logistics and (2) to introduce and/or propose approaches for solving some customer service related strategic level logistics problems. This study consists of two parts. In the first part an overview of the work is presented, and the second part comprises eight research papers on the topic of the study. The overview includes an introduction, where strategic and tactical level logistics problems are discussed and the relation of logistics to marketing and customer service issues is presented. In the first part of the study the objectives, the structure, the research strategy and the contribution of the research are described, and the challenges for future research are discussed. In the second part the three first papers deal with the identification of objectives for logistics while the remaining five papaers concentrate on solving customer service related strategic level logistics problems.

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.

Integration of Real-Time Simulator, Motion Platform and Haptics

This thesis describes the process of the integration of a real-time simulator environment with a motion platform and a haptic device as a part of the Kvalive project. Several programs running on two computers were made to control the different devices of the environment. User tests were made to obtain information of needed improvements to make the simulator more realistic. Also new ideas for improving the simulator and directions of further research were obtained with the help of this research.

Introducing Continuous Integration for C and C++ Software Development Projects on Linux Platform

Software integration is a stage in a software development process to assemble separate components to produce a single product. It is important to manage the risks involved and being able to integrate smoothly, because software cannot be released without integrating it first. Furthermore, it has been shown that the integration and testing phase can make up 40 % of the overall project costs. These issues can be mitigated by using a software engineering practice called continuous integration. This thesis work presents how continuous integration is introduced to the author's employer organisation. This includes studying how the continuous integration process works and creating the technical basis to start using the process on future projects. The implemented system supports software written in C and C++ programming languages on Linux platform, but the general concepts can be applied to any programming language and platform by selecting the appropriate tools. The results demonstrate in detail what issues need to be solved when the process is acquired in a corporate environment. Additionally, they provide an implementation and process description suitable to the organisation. The results show that continuous integration can reduce the risks involved in a software process and increase the quality of the product as well.

PRELIMINARILY DEVELOPMENT OF A MOISTURE-ACTIVATED BIORESORBABLE POLYMERIC PLATFORM FOR DRUG DELIVERY

Bioresorbable polymeric films were prepared by solvent casting using a tyrosine-derived polycarbonate and metronidazole (MDZ) as the model drug at 2.5%, 5% and 10% (w/w). Drug loading did not affect the water uptake, drug release, polymer degradation or erosion profiles. All devices released approximately 85% (w/w) of the drug within a 1.5 h period. This may be attributed to the rapid water uptake of the polymer. An increase in the water uptake correlated with a linear rate increase of the polymer degradation (0.968 ≤ R2 ≤ 0.999). Moreover, MDZ presented a remarkable plasticizing effect for the polymer and drug loading exerted a significant impact on the mechanical properties of the obtained films. The results obtained can be used to further the development of novel biocompatible and biodegradable polymeric platforms for the delivery of metronidazole and other drugs in a broad range of pharmaceutical applications.

Performance Measurement of the Logistics Process

The objective of the thesis was to create a performance measurement system for the logistics process of a company. In addition, one goal was to make suggestions for improvements based on description and analysis of the process and current measures. The logistics process was described in detail, and the objectives for it were derived from the company strategy and goals. Suggestions for performance measurement system and process improvement were made based on current state analysis. As a result of the thesis, three new performance measures were decided to take into use. In addition, several improvements were suggested to the ERP system to make process smoother. Some of the improvements have already been added to the system and the rest will be added in the near future.

Supply chain costs of a small board lot: sheet cutting and logistics

Succeeding in small board lot (0-20 tons) deliveries, is not always prosperous and failures as well as extra costs compared to standard costs arise. Failure deliveries from converting plants to customer locations tie a lot of unwanted and unexpected costs. Extra costs are handled as quality costs and more precise, internal failure costs. These costs revolve from unsuccessful truck payloads, redundant warehousing or unfavorable routing as examples. Quality costs are becoming more and more important factor in company’s financial decision making. Actual, realized truck payload correlates with the extra costs occurring, so filling the truck payload all get-out well is a key to lower the extra costs. Case company in this study is Corporation A, business segment Boards. Boards have outsourced half of their converting in order to gain better customer service via flexibility, lead time reductions and logistics efficiency improvements. Examination period of the study is first two quarters of year 2008 and deliveries examined are from converters to the customer locations. In Corporation A’s case, the total loss in failure deliveries is hundreds of thousands of Euros during the examination period. So, the logistics goal of getting the right product to the right place and right time for the least cost, does not completely realize.

Demonstration Platform for Visual Quality Metrics

This thesis presents two graphical user interfaces for the project DigiQ - Fusion of Digital and Visual Print Quality, a project for computationally modeling the subjective human experience of print quality by measuring the image with certain metrics. After presenting the user interfaces, methods for reducing the computation time of several of the metrics and the image registration process required to compute the metrics, and details of their performance are given. The weighted sample method for the image registration process was able to signifigantly decrease the calculation times while resulting in some error. The random sampling method for the metrics greatly reduced calculation time while maintaining excellent accuracy, but worked with only two of the metrics.

Platform as a Service - new opportunities for software development companies

Today cloud computing is the next stage in development information-oriented society in field of information technologies. Great attention is paid to cloud computing in general, but the lack of scientific consideration to components brings to the problem, that not all aspects are well examined. This thesis is an attempt to consider Platform as a Service (a technology of providing development environment through the Internet) from divergent angles. Technical characteristics, costs, time, estimation of effectiveness, risks, strategies that can be applied, migration process, advantages and disadvantages and the future of the approach are examined to get the overall picture of cloud platforms. During the work literature study was used to examine Platform as a Service, characteristics of existent cloud platforms were explored and a model of a typical software development company was developed to create a scenario of migration to cloud technologies. The research showed that besides all virtues in reducing costs and time, cloud platforms have some significant obstacles in adoption. Privacy, security and insufficient legislation impede the concept to be widespread.