This study is a mixed methods investigation, based on a case study of The Ottawa Hospital’s recent and ongoing implementation of an integrated performance management system (IPMS). It is the first empirical investigation to identify the reasons why Canadian healthcare leaders choose to implement an IPMS in a hospital setting, the core components of hospital-based IPMSs, the challenges that senior leaders face when implementing such systems, and how these challenges might be mitigated to increase the likelihood of a successful implementation. Key findings include the need for senior leaders to carefully consider organizational culture prior to fully implementing an IPMS, engaging physicians early in the journey, and coordinating the implementation so that knowledge, skill, and expertise, as it relates to the IPMS, are distributed across the organization in tightly knit waves. Recommendations for future research include the development of frameworks for the design, implementation, and use of IPMSs

This study is a mixed methods investigation, based on a case study of The Ottawa Hospital’s recent and ongoing implementation of an integrated performance management system (IPMS). It is the first empirical investigation to identify the reasons why Canadian healthcare leaders choose to implement an IPMS in a hospital setting, the core components of hospital-based IPMSs, the challenges that senior leaders face when implementing such systems, and how these challenges might be mitigated to increase the likelihood of a successful implementation. Key findings include the need for senior leaders to carefully consider organizational culture prior to fully implementing an IPMS, engaging physicians early in the journey, and coordinating the implementation so that knowledge, skill, and expertise, as it relates to the IPMS, are distributed across the organization in tightly knit waves. Recommendations for future research include the development of frameworks for the design, implementation, and use of IPMSs

Die Diplomarbeit mit dem Thema: 'Konzeption und Herstellung von Systemdemonstratoren für miniaturisierte Im-Ohr-Lautsprecher mit drahtlosen Kommunikationsschnittstellen' konzentriert sich auf die Auslegung einer Schaltung eines neuartigen Lautsprechers, welche auf dem Prinzip der NED-Aktoren ('Nanoskaliger elektrostatischer Antrieb') arbeiten. Des Weiteren werden Gehäuse für die Im-Ohr-Anwendung als auch die Freifeldanwendung entwickelt.:Symbolverzeichnis Abkürzungsverzeichnis 1 Einleitung 2 Stand der Technik 2.1 Im-Ohr-Lautsprecher 2.2 Drahtlose Kommunikation 2.3 Kommerzielle Piezotreiber 3 Anforderungen an den Systemdemonstrator 4 Chipaufnahme 4.1 Anforderung 4.2 Konzeption und Umsetzung 5 Drahtlose Kommunikation 5.1 Anforderung 5.2 Konzept 5.3 Umsetzung 6 Verstärker 6.1 Anforderung 6.2 Konzeption und Umsetzung 6.2.1 Validierung des DRV2700 6.2.2 Thermisches Management der Verstärkerschaltung 6.3 Modellierung des Gehäuses für die Elektronik 7 Im-Ohr-Demonstrator 7.1 Anforderung 7.2 Konzeption und Umsetzung 8 Horn-Demonstrator 8.1 Anforderung 8.2 Konzeption und Umsetzung 9 Ergebnisse 9.1 Chipaufnahme 9.2 Verstärker 9.3 Gehäuse für Elektronik 9.4 Im-Ohr-Lautsprecher 9.5 Akustisches Horn 10 Realisierung mittels Entwicklungsplatine 11 Diskussion und Ausblick 12 Zusammenfassung Literatur Selbstständigkeitserklärung Anhang

The enzyme α-isopropylmalate synthase (IPMS) catalyses the reaction between acetyl coenzyme A (AcCoA) and α-ketoisovalerate (KIV) to produce free coenzyme A and α isopropylmalate (IPM). This reaction is a key control point in the biosynthesis of a leucine, a pathway absent in animals but present in plants, fungi and bacteria. As a result, IPMS is a antibiotic and herbicidal target that has been validated by knockout studies for M. tuberculosis, the causative agent of tuberculosis. Engineered IPMSs have also been used in the fermentative production of long chain alcohols for use as fuels. IPMS belongs to a family of related enzymes called α-ketoacid: AcCoA re-aldolases (KARAs), with each subfamily differing in the specific α-ketoacid that AcCoA is reacted with. The known KARA subfamilies are IPMS, citramalate synthases (CMSs), homocitrate synthases (HCSs), methylthioalkylmalate synthases (MAMSs) and re-citrate synthases (RCSs), respectively involved in the biosynthesis of isoleucine, lysine, glucosinolates and TCA cycle intermediates. This thesis describes work aimed at improving understanding of both specific subfamilies of KARA enzymes and also the genetic and functional relationships between the subfamilies. A particular emphasis is placed on relating primary structure to function, allowing the inference of function from a very small subset of residues. IPMSs are divided into two classes, the Mtu-like IPMSs and the much less studied Eco-like IPMSs. Chapter 2 details the expression and characterisation of the Eco like IPMS from N. meningitidis (NmeIPMS). Overall NmeIPMS showed similar properties to MtuIPMS, but unlike that enzyme NmeIPMS is inhibited by high divalent metal ion concentrations, does not require monovalent metal ions, and shows some activity with the α-ketoacid 3-methyl α ketovalerate. Several previous results showing inhibitory activity of Zn2+, Cd2+ and bromopyruvate were also found to be the results of interference with the assay system and all three were found to be much weaker inhibitors than previously determined.   Phylogenetic analysis of the different KARA subfamilies revealed certain specific positions that were believed to control substrate specificity. Chapter 3 details mutagenesis experiments on MtuIPMS that probe the function of these residues. Once the importance of the residues had been established, substitutions were made in which IPMS residues were replaced with their equivalents from HCSs and CMSs in order to change substrate specificity. The most successful result was the Y169L substitution based on HCS, which decreased the specificity constant with KIV by four orders of magnitude while improving other activities, successfully shifting the best activity to the unbranched α-ketoacid α-ketobutyrate. Chapter 4 of this thesis details the purification and functional testing of the RCS from C. saccharolyticus (CscRCS), the first thermophilic RCS characterised. CscRCS was found to have an extremely low Km for its substrate oxaloacetate (1.7 µM), believed to be an adaptation to the instability of oxaloacetate at the temperatures CscRCS operates at in vivo. The enzyme also showed competitive affinity by α-ketoglutarate, the end product of the pathway. Unlike other characterised RCSs, CscRCS showed no oxygen sensitivity. The phylogenetic analysis conducted for this thesis identified a subfamily of KARAs dubbed pseudo-IPMSs (PIPMSs) that showed no substantial homology to any studied subfamily. In Chapter 5 the PIPMS from T. thermophilus (TthPIPMS) was expressed and characterised. TthPIPMS showed many features of a CMS, being most active with the same substrate (pyruvate) and sensitive to the same inhibitor (isoleucine). Unlike the previously studied CMS subfamilies, TthPIPMS possesses a nanomolar IC50 for its inhibitor, and also shows substantial activity as an RCS. The results of these chapters are then drawn together in Chapter 6 to create a picture of the relationships between the KARA enzymes, in terms of their functional characteristics as well as the sequence and evolutionary relationships between them that have bought about their diverse functions.

α-Isopropylmalate synthase (α-IPMS) catalyses the first committed step in leucine biosynthesis in bacteria, including Neisseria meningitidis and Mycobacterium tuberculosis. It catalyses the condensation of α-ketoisovalerate (α-KIV) and acetyl coenzyme A (AcCoA) to form α-isopropylmalate (α-IPM). Like many key enzymes in biosynthesis, α-IPMS is inhibited by the end-product of the biosynthetic pathway, in this case leucine. α-IPMS is homodimeric, with monomers consisting of a (β/α)8-barrel catalytic domain, two subdomains and a C-terminal regulatory domain, responsible for binding leucine and providing feedback inhibition for leucine biosynthesis. The exact mechanism of feedback inhibition in this enzyme is unknown, despite the elucidation of crystal structures with and without leucine bound. This thesis explores the nature of allosteric regulation in α-IPMS, including the effects of the regulatory domain and the importance of structural asymmetry on catalytic activity. Chapter 2 details the characterisation of wild-type α-IPMS from N. meningitidis (NmeIPMS). This protein was successfully cloned, expressed and purified by metal-affinity and size-exclusion chromatography. NmeIPMS has similar characteristics to previously characterised α-IPMSs, being a dimer and demonstrating substrate binding affinities in the micromolar range. This enzyme has a turnover number of 13s⁻¹ and is sensitive to mixed, non-competitive inhibition by the amino acid leucine. Small angle X-ray scattering experiments reveal that the solution-phase structure of this protein is likely similar to existing crystal structures of other α-IPMSs. In Chapter 3, substitutions of residues potentially involved in the binding and transmission of the leucine regulatory mechanism are described. Most of these amino acid substituted variants reduce enzyme sensitivity to leucine, and one variant is almost entirely insensitive to this inhibitor. Another of these variants demonstrates an unexpected decrease in substrate affinity, despite the substituted residue being located far from the active site. The independence of α-IPMS domains is investigated in Chapter 4. The catalytic domains were isolated from NmeIPMS and the α-IPMS from M. tuberculosis (MtuIPMS), and found to be unable to catalyse the condensation of substrates, despite maintaining the wild-type structural fold. Complementation studies with Escherichia coli cells lacking the gene for α-IPMS show that the truncated variants are unable to rescue growth in these cells. Binding of α-KIV in the truncated NmeIPMS variant is much stronger than in the wild-type, and this may be the reason for lack of competent catalysis. A crystal structure was solved for the truncated variant of NmeIPMS and indicates that the regulatory domain is required for proper positioning of large regions of the protein. Two isolated regulatory domains from NmeIPMS were cloned, but with limited success in characterisation. Finally, Chapter 5 describes substitutions made in MtuIPMS to affect relative domain orientations within the protein. Dimer asymmetry is investigated by substituting residues at the domain interfaces. These substitutions did have some effect on catalysis and inhibition, but did not show any change in average solution-phase structure. These results are drawn together in the greater context of allostery in general in Chapter 6, along with ideas for future research in this field. This chapter reviews the insights gained into protein structure from this thesis, particularly the importance of residues at protein domain interfaces. The asymmetry in the α-IPMS structure is discussed, along with small-molecule binding regulatory domains.

<p>The purpose of this thesis is to explore what software evaluation methods are currently available that can assist organizations and companies in procuring a software solution for some particular task or purpose for a specific type of business. The thesis is based on a real-world scenario where a company, Volvo Technology Corporation (VTEC), is in the process of selecting a new intellectual property management system for their patent department. For them to make an informed decision as to which system to choose, an evaluation of market alternatives needs to be done. First, a set of software evaluation methods and techniques are chosen for further evaluation. An organizational study, by means of interviews where questions are based on the ISO 9126-1 Software quality model, is then conducted, eliciting user opinions about the current system and what improvements a future system should have. The candidate methods are then evaluated based on the results from the organizational study and other pertinent factors in order to reach a conclusion as to which method is best suited for this selection problem. The Analytical Hierarchy Process (AHP) is deemed the best choice.</p>

This dissertation concerns quasistatic torsional mirror's for optical applications. The intended main area of application is the use as switch in optical network's, replacing the conventional optical-electro-optical conversation. With these actuator's a new concept of electrostatic actuation has been realised. While the drive electrodes are integrated into the deflectable mirror, the whole counter electrode below the mirror plate remains at equal ground potential. The device is manufactured out of two parts using method's of silicon bulk mikro machining. A deflectable mirror plate, torsional spring's and the surrounding support structure are fabricated within the thin device layer at the top of BSOI material. The counter electrode is manufactured out of a highly doped silicon wafer. Both part's are assembled together by adhesive bonding at die level at the end. Since the driving potential is supplied to the mirror plate and the counter electrode is at ground level, lateral tolerances because of device assembly mismatches does not appear with the use of the new concept. In detail the mirror plate itself is divided into two seperate electrodes by a parallel arrangement of filled isolating trenches. The highly doped device layer provides electrical connection via the torsional spring's to the mirror electrodes. A quasistatic torsional actuation is performed if a dc-voltage is applied between one mirror side and the counter electrode. Several design's have been fabricated. The lateral dimension of the torsional mirror plate vary from 0,5 mm to 2,0 mm. The designed characteristic frequencies vary from 0,5 to 3 kHz. For quasistatic actuation the pull in angle vary from 1 to 5 degree and the pull in voltage goes up to several hundred volts. Accessorily the mirror plate is enclosed by a comb drive structure. So that the device could be used for low voltage resonant actuation or an capacitive position read out becomes feasible. Within this thesis the new concept has been verified and functionality has been demonstrated. Depending on their characteristic frequency, devices are suitable to perform quasistatic actuation within 10 ms. Experiments indicated that the electrical isolation damages irreversible at drive voltage's above 400 volt. It limits the maximum deflection of nearly all design's. At prototype actuators repeatability has been studied. No drift was observed in the static characteristic within several cycles for certain designs. Closed-loop position control is not mandatory for the actuators fabricated within this thesis. Mechanical stress inside the mirror plate causes deformation of the reflective surface larger than permitted by optical criteria. This paves the way for further device optimization, yield improvement and system integration.

The purpose of this thesis is to explore what software evaluation methods are currently available that can assist organizations and companies in procuring a software solution for some particular task or purpose for a specific type of business. The thesis is based on a real-world scenario where a company, Volvo Technology Corporation (VTEC), is in the process of selecting a new intellectual property management system for their patent department. For them to make an informed decision as to which system to choose, an evaluation of market alternatives needs to be done. First, a set of software evaluation methods and techniques are chosen for further evaluation. An organizational study, by means of interviews where questions are based on the ISO 9126-1 Software quality model, is then conducted, eliciting user opinions about the current system and what improvements a future system should have. The candidate methods are then evaluated based on the results from the organizational study and other pertinent factors in order to reach a conclusion as to which method is best suited for this selection problem. The Analytical Hierarchy Process (AHP) is deemed the best choice.

This dissertation concerns quasistatic torsional mirror's for optical applications. The intended main area of application is the use as switch in optical network's, replacing the conventional optical-electro-optical conversation. With these actuator's a new concept of electrostatic actuation has been realised. While the drive electrodes are integrated into the deflectable mirror, the whole counter electrode below the mirror plate remains at equal ground potential. The device is manufactured out of two parts using method's of silicon bulk mikro machining. A deflectable mirror plate, torsional spring's and the surrounding support structure are fabricated within the thin device layer at the top of BSOI material. The counter electrode is manufactured out of a highly doped silicon wafer. Both part's are assembled together by adhesive bonding at die level at the end. Since the driving potential is supplied to the mirror plate and the counter electrode is at ground level, lateral tolerances because of device assembly mismatches does not appear with the use of the new concept. In detail the mirror plate itself is divided into two seperate electrodes by a parallel arrangement of filled isolating trenches. The highly doped device layer provides electrical connection via the torsional spring's to the mirror electrodes. A quasistatic torsional actuation is performed if a dc-voltage is applied between one mirror side and the counter electrode. Several design's have been fabricated. The lateral dimension of the torsional mirror plate vary from 0,5 mm to 2,0 mm. The designed characteristic frequencies vary from 0,5 to 3 kHz. For quasistatic actuation the pull in angle vary from 1 to 5 degree and the pull in voltage goes up to several hundred volts. Accessorily the mirror plate is enclosed by a comb drive structure. So that the device could be used for low voltage resonant actuation or an capacitive position read out becomes feasible. Within this thesis the new concept has been verified and functionality has been demonstrated. Depending on their characteristic frequency, devices are suitable to perform quasistatic actuation within 10 ms. Experiments indicated that the electrical isolation damages irreversible at drive voltage's above 400 volt. It limits the maximum deflection of nearly all design's. At prototype actuators repeatability has been studied. No drift was observed in the static characteristic within several cycles for certain designs. Closed-loop position control is not mandatory for the actuators fabricated within this thesis. Mechanical stress inside the mirror plate causes deformation of the reflective surface larger than permitted by optical criteria. This paves the way for further device optimization, yield improvement and system integration.

<p>A new kind of lipid/polymer composite particle, consisting of a biodegradable polymer matrix with well-defined lipid domains, has been created. The lipid used is the water-swelling lipid monoolein (MO), which forms a reversed bicontinuous cubic diamond structure in aqueous solutions. The polymer is poly(d,l-lactide-co-glycolide) (PLG), which degrades into water-soluble monomers through hydrolysis. This new particle might be a good alternative for encapsulation of active substances intended to be released over a longer period of time, i.e. sustained/retained/controlled release.</p><p>To prepare such particles can be difficult. Suitable phase behaviour and a solvent with the right properties are needed. For this reason, the phase behaviours of several different lipid/polymer/solvent/water systems have been explored. From the phase behaviour of a suitable system (i.e. MO/PLG/ethyl acetate/water), a route for formation of lipid/polymer composite particles has been deduced. Particles have been formed and distinct, water-swelling, lipid domains have been confirmed by characterization by means of confocal laser scanning probe microscopy (CLSM). </p><p>The sample preparation process has been automated and a method based on using a robotic liquid handler has been developed. Phase diagrams have been determined by examination of macroscopic behaviours and the microstructures of the phases have been studied by small- and wide-angle X-ray scattering (L₃, V₂, L_α, L), nuclear magnetic resonance self-diffusion (L, L₃), viscosimetry (L) and rheology (L). Several different theoretical models have been applied for interpretation of the results. For example, the swelling of the reversed bicontinuous cubic phases and the sponge phase have been modelled by applying the theory of infinite periodical minimal surfaces, the sponge phase has been shown to be bicontinuous according to the theory of interconnected rods and the phase behaviour of the polymer has been described by the Flory-Huggins theory. The main focus of this work (4/5) concerns phase studies in multicomponent systems from a physical-chemical point of view.</p>