Bakgrund I det närmaste alla organisationer strävar efter att använda sina resurser så effektivt som möjligt. Vad som dock inte diskuterats i någon större utsträckning är att den starkt kopplade komplexa organisationen inte klarar av att bemöta ens den minsta avvikelsen utan att ägna den direkt uppmärksamhet. Den övergripande frågan är därför Hur hanteras avvikelser i starkt kopplade projekt? Det teoretiska ramverket är först och främst projektlitteratur men ramverket vidgas sedermera till att omfatta praktikansatslitteratur samt Weicks (1976) ”Loosely coupled systems”. Metod Givet ansatsen faller det sig naturligt att göra en fallstudie med observationer som huvudsaklig metod. Utöver tolv veckors observationer förlitar jag mig på 57 intervjuer och mängder av dokument. En organisation, två projektgrupper och 118 avvikelser observerades totalt under perioden. De data som samlades in analyserades med hjälp av dataprogrammet Nvivo. Resultat Analysen är uppdelad i tre integrerade kapitel. Det första kapitlet diskuterar avvikelser som företeelse och definierar begreppet närmare. En avvikelse definieras som en händelse som kräver såväl identitet som handlingskraft. Det andra analyskapitlet analyserar praktiken närmare. Allt som allt observerades 29 praktiker vilka kunde grupperas i åtta praktikmönster. Praktikmönstren kunde sedermera inordnas i två distinkta löskopplingsmönster i en teoretiskt underbyggd och empiriskt styrkt figur. Figuren och följaktligen praktikmönstren beskriver hur avvikelsen görs löst kopplad. Det tredje analyskapitlet diskuterar fem mekanismer som följer av med de löst kopplade avvikelserna. Dessa fem mekanismer kan sedermera betonas och utnyttjas av projektledaren. Slutsatser Slutsatserna följer två spår. Det ena spåret fokuserar på projekt i allmänhet och projektledning i synnerhet. Slutsatsen som kan dras där är att det finns en inneboende osäkerhet i projekt som kan utnyttjas för att hantera avvikelser. Alla avvikelser har inte stora konsekvenser men de besitter vissa gemensamma egenskaper. Det andra spåret är ett bidrag till teorin om löst kopplade system. Länge har en processuell och praktikbaserad studie saknats. Genom att undersöka löskopplingsprocesser i ljuset av en praktikansats har jag visat hur löskopplingsprocesser ser ut.

G protein-coupled receptors (GPCRs) are one of the largest protein families in mammals. GPCRs are instrumental for hormonal and neurotransmitter signalling and are important in all major physiological systems of the body. Paper I describes the repertoire of GPCRs in Branchiostoma floridae, which is one of the species most closely related species to vertebrates. Mining and phylogenetic analysis of the amphioxus genome showed the presence of at least 664 distinct GPCRs distributed among all the main families of GPCRs; Glutamate (18), Rhodopsin (570), Adhesion (37), Frizzled (6) and Secretin (16). Paper II contains studies of the Adhesion, Methuselah and Secretin GPCR families in nine genomes. The Adhesion GPCRs are the most complex gene family among GPCRs with large genomic size, multiple introns and a fascinating flora of functional domains. Phylogenetic analysis showed Adhesion group V (that contains GPR133 and GPR144) to be the closest relative to the Secretin family among the groups in the Adhesion family, which was also supported by splice site setup and conserved motifs. Paper III examines the repertoire of human transmembrane proteins. These form key nodes in mediating the cell’s interaction with the surroundings, which is one of the main reasons why the majority of drug targets are membrane proteins. We identified 6,718 human membrane proteins and classified the majority of them into 234 families of which 151 belong to the three major functional groups; Receptors (63 groups, 1,352 members), Transporters (89 groups, 817 members) or Enzymes (7 groups, 533 members). In addition, 74 Miscellaneous groups were shown to include 697 members. Paper IV clarifies the hierarchy of the main families and evolutionary origin of majority of the metazoan GPCR families. Overall, it suggests common decent of at least 97% of the GPCRs sequences found in humans, including all the main families.

Questions have been raised about the genomic complexity of the human genome, since it was reported that it only consisted of 32,000 genes. Alternative splicing is considered the explanation of the enormous difference between the number of genes and the number of proteins. Aligning expressed sequence tags (ESTs) to the genomic sequence has become a popular approach for gene prediction, revealing alternative splice variants. The aim in this thesis is to identify and analyse splice variants of the adhesion family of G protein-coupled receptors using EST data. 75% of the genes in the data set of 33 sequences were found to have a total of 51 splice variants. About half of the variants were considered functional.

The D1-class receptors (D1R, D5R) each possess distinct signaling characteristics; however, pharmacological selectivity between them remains elusive. The third intracellular loops (IL3) of D1R and D5R harbour divergent residues that may contribute to their individual signalling phenotypes. Here we probe the function of central region of IL3 of D1R and D5R using deletion mutagenesis. Radioligand binding and whole cell cAMP assays suggest that the N-terminal and C-terminal moieties of the central IL3 oppositely contribute to the constitutive and agonist-dependant activity of D1-Class receptors. Whereas the N-terminal deletions ablated constitutive activity and decreased DA-induced activation, C-terminal deletions induced robust increases. These data, interpreted in concert with structural predictions generated from homology modeling implicate the central IL3 as playing an important role in the activation and subtype-specific characteristics of the D1-class receptors. This study may serve as a basis for the development of novel drugs targeting the central IL3 region.

CAPA-related peptides belong to a family of neuropeptides localized to the central nervous system that can function in diverse roles in the regulation of water and salt homeostasis in insects. These peptides are known to stimulate fluid secretion by Malpighian tubules (MTs) in Dipteran species, thus serving a diuretic function. In contrast, this thesis demonstrates that members of this family of peptides in Rhodnius prolixus serve an anti-diuretic role and have multiple tissue targets, whereby they oppose the activity of diuretic hormones such as serotonin (5-Hydroxytryptamine hydrochloride; 5-HT). I have identified two genes each encoding three peptides in R. prolixus, suggesting this insect is capable of producing a greater number of CAPA-peptides compared to other insects that contain only a single CAPA gene. Interestingly, while the second peptide encoded in each R. prolixus gene (RhoprCAPA-α2/-β2) inhibits the stimulatory effects of serotonin on tissues such as the anterior midgut and Malpighian tubules, it appears the other CAPA-related and pyrokinin-related peptides do not play a major role in inhibiting the effects of serotonin on these tissues. More specifically, serotonin-stimulated fluid secretion by MTs and fluid absorption by the anterior midgut are reduced by the anti-diuretic peptide, RhoprCAPA-α2. In addition, I have also identified a G protein-coupled receptor which likely mediates the anti-diuretic effect associated with RhoprCAPA-α2 and have functionally characterized this receptor in Chinese hamster ovary cells. Spatial transcript expression analysis in fifth-instars reveals a wide distribution of the receptor in tissues associated with the rapid post-gorging diuresis. Thus, my findings suggest that numerous tissues are regulated by the CAPA peptides in R. prolixus. Gene structure and phylogenetic analyses demonstrate that this receptor is the orthologue of the D. melanogaster capa receptor (CG14575) with homologs in other insects. Taken together, my thesis demonstrates that the RhoprCAPA peptides play an integral role in the coordination and maintenance of anti-diuresis in R. prolixus. This mechanism is necessary following the rapid diuresis associated with blood-feeding by this medically-important insect.

With the advancement of technology, submicron CMOSonly process is available now for Application Specific Integrated Circuits (ASICs). The high integration leads to the need for high pin counts. However voltage supply and ground bounce due to many output drivers switching at the same time is becoming a major problem. In this thesis, a CMOS offchip buffer design which generates ECL logic levels with lower ground bounce noise is described and demonstrated. The technique used in designing this buffer to reduce voltage noise differs from conventional design techniques. Traditionally there are two general methods to reduce ground bounce. One approach tries to reduce the instantaneous current change (di/dt) by increasing (prolonging) the rise and fall time of the signals. The other approach attempts to reduce the parasitic inductance attributed to packaging by using multiple supply pins. Our technique reduces the voltage noise by controlling the instantaneous current change through the reduction of current difference during switching time. Based on this approach, a novel circuit structure is designed. This circuit has a fully symmetrical configuration and is being selfbiased through negative feedback. A current injection technique is also used to increase the stability of the circuit. SPICE simulation of the proposed circuit is performed. Comparison and tradeoffs with other approaches are studied. / Graduation date: 1994

Stationary wave theory elucidates the dynamics of the time mean zonally asymmetric component of the atmospheric circulation and separates it from the dynamics of the zonal mean climatological flow. This thesis focuses on the dynamics of stationary wave nonlinearity and its applications in stationary wave modelling and the stationary wave response to climate change. Stationary wave nonlinearity describes the self-interaction of stationary waves and is important in maintaining the observed zonally asymmetric atmospheric general circulation. Stationary wave nonlinearity is examined in quasi-geostrophic barotropic dynamics in both the presence and absence of transient waves. Stationary wave nonlinearity is shown to account for most of the difference between the linear and full nonlinear stationary waves, particularly if the zonal-mean flow adjustment to the stationary waves is taken into account. Wave activity analysis shows that stationary wave nonlinearity in this setting is associated with Rossby wave critical layer reflection. A time-integration type nonlinear stationary wave modelling technique is tested in this simple barotropic setting and is shown to be able to predict stationary wave nonlinearity and capture the basic features of the full nonlinear stationary wave. A baroclinic nonlinear stationary wave model is then developed using this technique and is applied to the problem of the stationary wave response to climate change. Previous stationary wave modelling has largely focused on the tropospheric circulation, but the stationary wave field extends into the stratosphere and plays an important dynamical role there. This stationary wave model is able to represent the stratospheric stationary wave field and is used to analyze the Northern Hemisphere stationary wave response to climate change simulated by the Canadian Middle Atmosphere Model (CMAM). In the CMAM simulation changes to the zonal mean basic state alone can explain much of the stationary wave response, which is largely controlled by changes of the zonal mean circulation in the Northern Hemisphere subtropical upper troposphere. However, details of the stratospheric wave driving response are also sensitive to other aspects of the zonal-mean response and to the heating response. Many climate change related effects appear to contribute robustly to an increased wave activity flux into the stratosphere.

Temperature gradient causes volume change (elongation/shortening) in concrete structures. If the movement of the structure is restrained, significant stresses may occur on the structure. These stresses may be so significant that they can cause considerable cracking at structural components of large concrete structures. Thus, during the design of a concrete structure, the actual temperature gradient in the structure should be obtained in order to compute the stress distribution on the structure due to thermal effects. This study focuses on the implementation of a solution procedure for coupled thermal and structural analysis with finite element method for such structures. For this purpose, first transient heat transfer analysis algorithm is implemented to compute the thermal gradient occurring inside the concrete structures. Then, the output of the thermal analysis is combined with the linear static solution algorithm to compute stresses due to temperature gradient. Several, 2D and 3D, finite elements having both structural and thermal analysis capabilities are developed. The performances of each finite element are investigated. As a case study, the top floor of two L-shaped reinforced concrete parking structure and office building are analyzed. Both structures are subjected to heat convection at top face of the slabs as ambient condition. The bottom face of the slab of the parking structure has the same thermal conditions as the top face whereas in the office building the temperature inside the building is fixed to 20 degrees. The differences in the stress distribution of the slabs and the internal forces of the vertical structural members are discussed.

The task of finding the beat in music is simple for most people, but surprisingly difficult to replicate in a robot. Progress in this problem has been made using various preprocessing techniques (Hitz 2008; Tomic and Janata 2008). However, a real-time method is not yet available. Methods using a class of oscillators called relay relaxation oscillators are promising. In particular, systems of forced Hopf oscillators (Large 2000; Righetti et al. 2006) have been used with relative success. This work describes current methods of beat tracking and develops a new method that incorporates the best ideas from each existing method and removes the necessity for preprocessing.

CAPA-related peptides belong to a family of neuropeptides localized to the central nervous system that can function in diverse roles in the regulation of water and salt homeostasis in insects. These peptides are known to stimulate fluid secretion by Malpighian tubules (MTs) in Dipteran species, thus serving a diuretic function. In contrast, this thesis demonstrates that members of this family of peptides in Rhodnius prolixus serve an anti-diuretic role and have multiple tissue targets, whereby they oppose the activity of diuretic hormones such as serotonin (5-Hydroxytryptamine hydrochloride; 5-HT). I have identified two genes each encoding three peptides in R. prolixus, suggesting this insect is capable of producing a greater number of CAPA-peptides compared to other insects that contain only a single CAPA gene. Interestingly, while the second peptide encoded in each R. prolixus gene (RhoprCAPA-α2/-β2) inhibits the stimulatory effects of serotonin on tissues such as the anterior midgut and Malpighian tubules, it appears the other CAPA-related and pyrokinin-related peptides do not play a major role in inhibiting the effects of serotonin on these tissues. More specifically, serotonin-stimulated fluid secretion by MTs and fluid absorption by the anterior midgut are reduced by the anti-diuretic peptide, RhoprCAPA-α2. In addition, I have also identified a G protein-coupled receptor which likely mediates the anti-diuretic effect associated with RhoprCAPA-α2 and have functionally characterized this receptor in Chinese hamster ovary cells. Spatial transcript expression analysis in fifth-instars reveals a wide distribution of the receptor in tissues associated with the rapid post-gorging diuresis. Thus, my findings suggest that numerous tissues are regulated by the CAPA peptides in R. prolixus. Gene structure and phylogenetic analyses demonstrate that this receptor is the orthologue of the D. melanogaster capa receptor (CG14575) with homologs in other insects. Taken together, my thesis demonstrates that the RhoprCAPA peptides play an integral role in the coordination and maintenance of anti-diuresis in R. prolixus. This mechanism is necessary following the rapid diuresis associated with blood-feeding by this medically-important insect.