Stable one-step technetium-99m labeling of His-tagged recombinant proteins with a novel Tc(I)-carbonyl complex.

We have developed a technetium labeling technology based on a new organometallic chemistry, which involves simple mixing of the novel reagent, a 99m Tc(I)-carbonyl compound, with a His-tagged recombinant protein. This method obviates the labeling of unpaired engineered cysteines, which frequently create problems in large-scale expression and storage of disulfide-containing proteins. In this study, we labeled antibody single-chain Fv fragments to high specific activities (90 mCi/mg), and the label was very stable to serum and all other challenges tested. The pharmacokinetic characteristics were indistinguishable from iodinated scFv fragments, and thus scFV fragments labeled by the new method will be suitable for biodistribution studies. This novel labeling method should be applicable not only to diagnostic imaging with 99mTc, but also to radioimmunotherapy approaches with 186/188 Re, and its use can be easily extended to almost any recombinant protein or synthetic peptide.

An Engineering Study to Update the Iowa Transportation Laws Annotated: HR 324a January 1995

Research project HR-234A was sponsored by the Iowa Highway Research Board and the Iowa Department of Transportation. In the preparation of this compilation of highway and street laws of Iowa, an attempt has been made to include those sections of the Iowa Code Annotated and Iowa Digest to which reference is frequently required by the Department of Transportation, counties, cities and towns in their conduct of highway and street administration, construction and maintenance. This publication is offered with the hope and belief that it will prove to be of value and assistance to those concerned with the problems of establishing, maintaining and administering a highway and street program. Because of the broad scope of highway and street work and the many interrelated provisions of Iowa law, and usable size, some Code provision which are insignificant to the principal subject were omitted out of necessity; others were omitted to avoid repetition. A general index is provided at the end of the text of this volume. Each major topic is divided into subtopics and is accompanied by appropriate Code sections. Specific section numbers as they appear in the Code are in.

Connections between signal processing and complex analysis

We describe one of the research lines of the Grup de Teoria de Funcions de la UAB UB, which deals with sampling and interpolation problems in signal analysis and their connections with complex function theory.

Collaboration entre médecin de famille et psychiatre pour les problèmes de santé mentale [Family physicians and psychiatrists' collaborative care for mental health problems].

The burden of disease linked to mental disorders represents more than one-fifth of years lived with disability in the world. Less than half of people suffering from mental disorders are adequately treated. Three quarter of those who receive treatment are followed by primary care. Collaborative care aims to increase the efficiency of direct general practitioner's treatment. Main components are sustainable and individualized consultation-liaison relationship (1/2 day of psychiatrist by 15 days for 10-15 general practitioners), and support of a clinical case manager for complex situations. Collaboration is bidirectional: early or crisis access to specialist care and long-term followup by general practitioner. This model is a challenge for the doctor-patient dual relationship and requires incentives in a public health perspective.

MM-GBSA binding free energy decomposition and T cell receptor engineering.

Recognition by the T-cell receptor (TCR) of immunogenic peptides (p) presented by class I major histocompatibility complexes (MHC) is the key event in the immune response against virus infected cells or tumor cells. The major determinant of T cell activation is the affinity of the TCR for the peptide-MHC complex, though kinetic parameters are also important. A study of the 2C TCR/SIYR/H-2Kb system using a binding free energy decomposition (BFED) based on the MM-GBSA approach had been performed to assess the performance of the approach on this system. The results showed that the TCR-p-MHC BFED including entropic terms provides a detailed and reliable description of the energetics of the interaction (Zoete and Michielin, 2007). Based on these results, we have developed a new approach to design sequence modifications for a TCR recognizing the human leukocyte antigen (HLA)-A2 restricted tumor epitope NY-ESO-1. NY-ESO-1 is a cancer testis antigen expressed not only in melanoma, but also on several other types of cancers. It has been observed at high frequencies in melanoma patients with unusually positive clinical outcome and, therefore, represents an interesting target for adoptive transfer with modified TCR. Sequence modifications of TCR potentially increasing the affinity for this epitope have been proposed and tested in vitro. T cells expressing some of the proposed TCR mutants showed better T cell functionality, with improved killing of peptide-loaded T2 cells and better proliferative capacity compared to the wild type TCR expressing cells. These results open the door of rational TCR design for adoptive transfer cancer therapy.

Using spatially distributed parameters and multi-response objective functions to solve parameterization of complex applications of semi-distributed hydrological models

Application of semi-distributed hydrological models to large, heterogeneous watersheds deals with several problems. On one hand, the spatial and temporal variability in catchment features should be adequately represented in the model parameterization, while maintaining the model complexity in an acceptable level to take advantage of state-of-the-art calibration techniques. On the other hand, model complexity enhances uncertainty in adjusted model parameter values, therefore increasing uncertainty in the water routing across the watershed. This is critical for water quality applications, where not only streamflow, but also a reliable estimation of the surface versus subsurface contributions to the runoff is needed. In this study, we show how a regularized inversion procedure combined with a multiobjective function calibration strategy successfully solves the parameterization of a complex application of a water quality-oriented hydrological model. The final value of several optimized parameters showed significant and consistentdifferences across geological and landscape features. Although the number of optimized parameters was significantly increased by the spatial and temporal discretization of adjustable parameters, the uncertainty in water routing results remained at reasonable values. In addition, a stepwise numerical analysis showed that the effects on calibration performance due to inclusion of different data types in the objective function could be inextricably linked. Thus caution should be taken when adding or removing data from an aggregated objective function.

Engineering Study Automating Iowa's Speed Monitoring Program, HR-228, 1983

Excessive speed on State and County highways is recognized as a serious problem by many Iowans. Speed increases both the risk and severity of accidents. Studies conducted by the FHWA and NHTSA have concluded that if average speeds were increased by five MPH, fatalities would increase by at least 2,200 annually. Along with the safety problems associated with excessive speed are important energy considerations. When the national speed limit was lowered to 55 MPH in 1974, a tremendous savings in fuel was realized. The estimated actual savings for automobiles amounted to 2.2 billion gallons, an average of 20.75 gallons for each of the 106 million automobiles registered in 1975. These benefits prompted the Federal-Aid Amendment of 1974 requiring annual State enforcement certification as a prerequisite for approval of Federal-aid highway projects. In 1978, the United States D.O.T. recommended to Congress significant changes in speed limit legislation designed to increase compliance with the national speed limit. The Highway Safety Act of 1978 provides for both withholding Federal-aid highway funds and awarding incentive grants based on speed compliance data submitted annually. The objective of this study was to develop and make operational, an automatic speed monitoring system which would have flexible capabilities of collecting accurate speed data on all road systems in Iowa. It was concluded that the Automatic Speed Monitoring Program in Iowa has been successful and needed data is being collected in the most economical manner possible.

Engineering Fabric Repair Prior to Resurfacing - Roadglas - US 30, HR-525, 1992

In Iowa it is normal procedure to either use partial or full-depth patching to repair deteriorated areas of pavement prior to resurfacing. The Owens/Corning Corporation introduced a repair system to replace the patching process. Their Roadglas repair system was used in this research project on US 30 in Story County. It was installed in 1985 and has been observed annually since that time. There were some construction problems with slippage as the roller crossed the abundant Roadglas binder. It appears the Roadglas system has helped to control reflective cracking in the research areas. Since the time when this project was completed it has been reported that Owens/Corning has discontinued production of the Roadglas system.

Segmentation of foot and ankle complex based on kinematic criteria.

Although various foot models were proposed for kinematics assessment using skin makers, no objective justification exists for the foot segmentations. This study proposed objective kinematic criteria to define which foot joints are relevant (dominant) in skin markers assessments. Among the studied joints, shank-hindfoot, hindfoot-midfoot and medial-lateral forefoot joints were found to have larger mobility than flexibility of their neighbour bonesets. The amplitude and pattern consistency of these joint angles confirmed their dominancy. Nevertheless, the consistency of the medial-lateral forefoot joint amplitude was lower. These three joints also showed acceptable sensibility to experimental errors which supported their dominancy. This study concluded that to be reliable for assessments using skin markers, the foot and ankle complex could be divided into shank, hindfoot, medial forefoot, lateral forefoot and toes. Kinematics of foot models with more segments must be more cautiously used.

Improving component management in an electronics company

Elektroniikka alalla tuotteet sisältävät yhä enemmän ja enemmän komponentteja joiden käyttöä yrityksen tulee hallita. Viime-aikaiset ympäristömääräykset ja lainsäädännöt ovat lisänneet yritysten painetta hallita käyttämiään komponentteja ja niiden tietoa tehokkaasti. Tässä työssä on tutkittu kolmen palveluntarjoajan tarjoamaa komponentinhallinta palvelua verrattunamahdolliseen talon omaan komponentti-insinööriin. Jotta tutkittuja vaihtoehtoja pystyisi vertailemaan, selvitettiin asiantuntija haastatteluja käyttäen komponenttien hallinnan erityispiirteet. Erityispiirteet yhdessä yrityksen vaatimuksien kanssa muodostivat kriteristön johon tutkittuja palveluja vertaillaan. Kriteeristö koostuu kahdeksasta osasta jotka puolestaan voidaan jaotella kolmeen ryhmään niiden keston ja luonteen mukaan. Neljän kriteerin katsottiin olevan tärkeämpiä kuin toiset, joten niille annettiin suurempi painoarvo palveluja vertailtaessa. Kaikki tutkitut palvelut täyttävät osan kriteereistä mutta mikään ei yksistään tarjoa riittävän kattavaa ratkaisua kohdeyrityksen ongelmiin. Suurimmat ongelmat yrityksellä ovat sisäisessä tiedonkulussa ja tietokantojen ja järjestelmien ylläpidossa ja hallinnassa. Jotta nämä ongelmat saataisiin ratkaistua on yrityksen saatava komponenttiprosessit toimimaan sekä tietokanta ajantasalle. Nämä tavoitteet saavutetaan vain jos yrityksessä on joku hoitamassa asiaa sisältä päin. Tutkitut kolme palvelua eivät tällaista sisäistä resurssia tarjoa vaan keskittyvät vain ulkoapäin tapahtuvaan tiedon välitykseen ja hallinnointiin.

Conflict-based Method for Conceptual Process Synthesis

The changing business environment demands that chemical industrial processes be designed such that they enable the attainment of multi-objective requirements and the enhancement of innovativedesign activities. The requirements and key issues for conceptual process synthesis have changed and are no longer those of conventional process design; there is an increased emphasis on innovative research to develop new concepts, novel techniques and processes. A central issue, how to enhance the creativity of the design process, requires further research into methodologies. The thesis presentsa conflict-based methodology for conceptual process synthesis. The motivation of the work is to support decision-making in design and synthesis and to enhance the creativity of design activities. It deals with the multi-objective requirements and combinatorially complex nature of process synthesis. The work is carriedout based on a new concept and design paradigm adapted from Theory of InventiveProblem Solving methodology (TRIZ). TRIZ is claimed to be a `systematic creativity' framework thanks to its knowledge based and evolutionary-directed nature. The conflict concept, when applied to process synthesis, throws new lights on design problems and activities. The conflict model is proposed as a way of describing design problems and handling design information. The design tasks are represented as groups of conflicts and conflict table is built as the design tool. The general design paradigm is formulated to handle conflicts in both the early and detailed design stages. The methodology developed reflects the conflict nature of process design and synthesis. The method is implemented and verified through case studies of distillation system design, reactor/separator network design and waste minimization. Handling the various levels of conflicts evolve possible design alternatives in a systematic procedure which consists of establishing an efficient and compact solution space for the detailed design stage. The approach also provides the information to bridge the gap between the application of qualitative knowledge in the early stage and quantitative techniques in the detailed design stage. Enhancement of creativity is realized through the better understanding of the design problems gained from the conflict concept and in the improvement in engineering design practice via the systematic nature of the approach.

Particle transport method for convection-diffusion-reaction problems

Convective transport, both pure and combined with diffusion and reaction, can be observed in a wide range of physical and industrial applications, such as heat and mass transfer, crystal growth or biomechanics. The numerical approximation of this class of problemscan present substantial difficulties clue to regions of high gradients (steep fronts) of the solution, where generation of spurious oscillations or smearing should be precluded. This work is devoted to the development of an efficient numerical technique to deal with pure linear convection and convection-dominated problems in the frame-work of convection-diffusion-reaction systems. The particle transport method, developed in this study, is based on using rneshless numerical particles which carry out the solution along the characteristics defining the convective transport. The resolution of steep fronts of the solution is controlled by a special spacial adaptivity procedure. The serni-Lagrangian particle transport method uses an Eulerian fixed grid to represent the solution. In the case of convection-diffusion-reaction problems, the method is combined with diffusion and reaction solvers within an operator splitting approach. To transfer the solution from the particle set onto the grid, a fast monotone projection technique is designed. Our numerical results confirm that the method has a spacial accuracy of the second order and can be faster than typical grid-based methods of the same order; for pure linear convection problems the method demonstrates optimal linear complexity. The method works on structured and unstructured meshes, demonstrating a high-resolution property in the regions of steep fronts of the solution. Moreover, the particle transport method can be successfully used for the numerical simulation of the real-life problems in, for example, chemical engineering.

Cost information in engineering design -Potentials and limitations of activity-based costing

The purpose of this thesis is to analyse activity-based costing (ABC) and possible modified versions ofit in engineering design context. The design engineers need cost information attheir decision-making level and the cost information should also have a strong future orientation. These demands are high because traditional management accounting has concentrated on the direct actual costs of the products. However, cost accounting has progressed as ABC was introduced late 1980s and adopted widely bycompanies in the 1990s. The ABC has been a success, but it has gained also criticism. In some cases the ambitious ABC systems have become too complex to build,use and update. This study can be called an action-oriented case study with some normative features. In this thesis theoretical concepts are assessed and allowed to unfold gradually through interaction with data from three cases. The theoretical starting points are ABC and theory of engineering design process (chapter2). Concepts and research results from these theoretical approaches are summarized in two hypotheses (chapter 2.3). The hypotheses are analysed with two cases (chapter 3). After the two case analyses, the ABC part is extended to cover alsoother modern cost accounting methods, e.g. process costing and feature costing (chapter 4.1). The ideas from this second theoretical part are operationalized with the third case (chapter 4.2). The knowledge from the theory and three cases is summarized in the created framework (chapter 4.3). With the created frameworkit is possible to analyse ABC and its modifications in the engineering design context. The framework collects the factors that guide the choice of the costing method to be used in engineering design. It also illuminates the contents of various ABC-related costing methods. However, the framework needs to be further tested. On the basis of the three cases it can be said that ABC should be used cautiously when formulating cost information for engineering design. It is suitable when the manufacturing can be considered simple, or when the design engineers are not cost conscious, and in the beginning of the design process when doing adaptive or variant design. If the design engineers need cost information for the embodiment or detailed design, or if manufacturing can be considered complex, or when design engineers are cost conscious, the ABC has to be always evaluated critically.

Requirements Management in the Software Development Process

Ohjelmistokehitys on monimutkainen prosessi. Yksi keskeisistä tekijöistä siinä on ohjelmistolle asetettavat vaatimukset. Näitä vaatimuksia on hyvin monenlaisia, ja eri tasoisia; toivotusta toiminnallisuudesta hyvinkin yksityiskohtaisiin vaatimuksiin. Näiden vaatimusten hallinta on myöskin hyvin monitahoista, vaikkakin se on kirjallisuudessa esitetty selkeänä prosessissa, joka on sarja toisistaan erottuviavaiheita. Työn painopiste oli näiden vaatimusten muutoksen ja valmiiseen ohjelmistoon kohdistuvan palautteen hallinnassa, ja kuinka vaatimustenhallintaohjelmisto voisi olla avuksi näissä prosesseissa. Vaatimustenhallintatyökalun käyttö ei sinällään ratkaise mitään ongelmia, mutta se suo puitteet parantaa vaatimusten hallitsemista. Työkalun käytöstä on muun muassa seuraavia etuja: vaatimusten keskitetty varastointi, käyttäjäoikeuksien määrittely koskien eri käyttäjiä ja heidän pääsyään näkemään tai muuttamaan tietoa, muutoksenhallintaprosessin hallinta, muutosten vaikutuksen analysointi ja jäljitettävyys ja pääsy tietoihin web-selaimella.

Evolutionary computing in search-based software engineering

This master’s thesis aims to study and represent from literature how evolutionary algorithms are used to solve different search and optimisation problems in the area of software engineering. Evolutionary algorithms are methods, which imitate the natural evolution process. An artificial evolution process evaluates fitness of each individual, which are solution candidates. The next population of candidate solutions is formed by using the good properties of the current population by applying different mutation and crossover operations. Different kinds of evolutionary algorithm applications related to software engineering were searched in the literature. Applications were classified and represented. Also the necessary basics about evolutionary algorithms were presented. It was concluded, that majority of evolutionary algorithm applications related to software engineering were about software design or testing. For example, there were applications about classifying software production data, project scheduling, static task scheduling related to parallel computing, allocating modules to subsystems, N-version programming, test data generation and generating an integration test order. Many applications were experimental testing rather than ready for real production use. There were also some Computer Aided Software Engineering tools based on evolutionary algorithms.