<p>Systems development projects and their documents are more or less standardized and can mainly be applied on systems that are supposed to be built from scratch, or updated. In pace with the number of IT-systems are increasing worldwide there is no need for every organization to build their own IT-system. Nowadays it is also possible to purchase licenses which allow the purchaser to modify or add functions to the system. Along with those changes, there have been an increased amount of “rapid development methods” such as Agile and “Quick and Dirty” solutions, but these methods and perspectives are mainly focusing on entire systems development processes, as the old ones, but quicker.</p><p>If a company purchases an off-the-shelf system with source code available, there is no real need to go through a proper systems development process. During interviews with a small company that has acquired a system as mentioned above, the researcher realized that only one single document is needed, the requirements specification. Today’s requirements specifications can be either well detailed or less, but a project still needs the details specified. Combining a known agile development process with IEEE’s standardized requirements specification, a new way to proceed with projects based on one single document (the requirements specification) has been made. This document also has a focus on simplicity for the inexperienced readers, but with the depth that every developer has got a use for.</p>

Diss. Stockholm : Handelshögsk.

The olfactory system is important for social behaviors, feeding and avoiding predators. Detection of odorous molecules is made by odorant receptors on specialized sensory neurons in the olfactory epithelial sheet. The olfactory sensory neurons are organized into a few regions or “zones” based on the spatially limited expression of odorant receptors. In this thesis the zonal division and functional specificity of olfactory sensory neurons have been studied in the mouse. We find that zones 2-4 show overlapping expression of odorant receptors while the border between the regions that express a zone 1 and a zone 2 odorant receptor, respectively, is sharp. This result indicates that zone 1 and zones 2-4 are inherently different from each other. In cDNA screens, aimed at finding genes whose expression correlate to the zonal expression pattern of odorant receptors, we have identified a number of signaling proteins implicated in neural-tissue organogenesis in other systems. The differential expression pattern of identified genes suggests that regional organization is maintained during the continuous neurogenesis in the olfactory epithelium as a result of counter gradients of positional information. We show that the gene c-fos is induced in olfactory sensory neurons as a result of cell activation by odorant exposure. A zonal and scattered distribution of c-Fos-positive neurons resembled the pattern of odorant receptor expression and a change of odorant results in a switch in which zone that is activated. Whereas earlier studies suggest that the odorant receptors are relatively broadly tuned with regard to ligand specificity, the restricted patterns of c-Fos induction suggests that low concentrations of odorous molecules activate only one or a few ORs. Studies on olfactory detection abilities of mice with zonal-restricted lesions in the olfactory epithelium show that loss of a zone has severe effects on the detection of some odorants but not others. These findings lend support to a hypothesis that odorant receptors are tuned to more limited numbers of odorants. Regional differences in gene expression and differences in response to toxic compounds between the zones indicate that there may be differences in tissue homeostasis within the epithelium. We have found that there are differences in proliferation and survival of olfactory sensory neurons in regions correlating to receptor expression zones. Identified differences with regard to gene expression, tissue homeostasis and odorant detection show that the olfactory epithelium is divided into regions that transduce different stimulus features.

The transformation of an initially uniform population of epiblast cells into an intricately complex central nervous system (CNS) is one of the most fascinating processes during embryonic development. Presumptive neural cells are initially specified as cells of forebrain character. Studies in various vertebrates have indicated that cells of more caudal neural character, that will generate the brain stem and spinal cord, are generated through the reprogramming of these initial rostral cells. The initial regionalization of these neural progenitor cells is central to all further diversification of neuronal cell types and the subsequent formation of functional euronal circuits. The aim of this thesis has been to enhance our understanding of which stages of embryonic development that are critical for the initial rostrocaudal regionalization of neural precursor cells, and which signaling mechanisms that orchestrate this early diversification. Both human and chick embryos have the shape of a flat disc during gastrulation. At this early stage, the chick neural plate is already regionalized and cells positioned at distinct rostrocaudal levels are specified to generate cells exhibiting a gene expression profile characteristic of the forebrain, midbrain, rostral hindbrain and caudal spinal cord, respectively. In addition, the Isthmic organizer (IsO), a secondary signaling centre at the midbrain–hindbrain border that is required for the further development of this region, is also specified already at the gastrula stage. Caudal neural character is induced by signals from adjacent tissues - the primitive streak and the paraxial mesoderm. Wingless/Wnts, Fibroblastic growth factors (FGFs) and retinoids (RA) are signaling molecules that have been proposed to promote caudal embryonic development, and exhibit spatio- emporal expression patterns that coincide with early caudalizing activities. The caudalizing activity that emanates from the gastrula stage paraxial mesoderm is mediated by Wnt signals, and the induction of caudal neural character by Wnts results from a direct action on neural precursor cells. In the presence of FGF activity, graded Wnt signaling is sufficient to induce cells exhibiting caudal forebrain, midbrain and rostral hindbrain character. The discrimination between rostral hindbrain and caudal spinal cord character appear to depend on a gradient of both Wnt and FGF signals. At hindbrain and spinal cord levels the patterned generation of neural progenitor cells along the rostrocaudal axis controls the generation of different classes of motor neurons in response to diffusible Sonic hedgehog (Shh) signals. Gastrula stage Wnt signaling is also required for this subsequent generation of motor neuron subtypes characteristic of the hindbrain and spinal cord. Later, at the early somite stage, cells characteristic of the caudal hindbrain and rostral spinal cord are specified adjacent to RA producing paraxial mesoderm. Opponent RA and FGF signals appear to act on, and refine the rostrocaudal identity of the initial hindbrain and spinal cord cells induced by gastrula stage Wnt based signals. Consistently, combinatorial Wnt, FGF and/or RA signals are sufficient to reconstruct neural progenitor cells that differentiate into motor neurons characteristic of the caudal hindbrain, rostral spinal cord and caudal spinal cord, respectively, in response to Shh. / Transformationen av en initialt uniform cellpopulation till något så komplext som det centrala nervsystemet (CNS) är en av de mest fascinerande processerna under fosterutvecklingen. Anlaget till neuronala celler är initialt programmerade att generera nervceller som är typiska för den blivande hjärnan (cerebrum). Forskning på olika vertebrata modell-organsimer har klargjort att nedre regioner av CNS, hjärnstammen lillhjärnan och ryggmärgen, genereras genom reprogrammering av dessa initiala celler. Målet med avhandlingsarbetet har varit att öka förståelsen för vilka perioder under fosterutveckingen som är kritiska för den initiala induktionen av neuronala celltyper som är specifika för dessa olika regioner, samt vilka signalerings mekanismer som styr den initiala re-programmeringen. Under gastruleringen bildar anlaget till neuronala celler en, till synes uniform, platta medialt i ektodermet i både humana-, och kyckling embryon. Anlaget till neuronal vävnad är dock redan under detta tidiga utvecklingsstadie indelat i regioner. Celler inom en specifik region är programmerade att generera celler med en genexpressions-profil som är specifik för anlaget till hjärnan, de övre delarna av hjärnstammen (diencephalon, mesencephalon, metencephalon) eller den nedre delen av ryggmärgen. Även Isthmus – ett sekundärt organisations centra som bildas i konstriktionen mellan mesencephalon och metencephalon, och som behövs för den senare utvecklingen av dessa regioner – specificeras redan på gastrula stadiet. Dessa nedre neuronala celltyper induceras av signal molekyler från närliggande vävnader som t.ex. primitivstrimman och det paraxiala mesodermet. Wingless/Wnt, Fibroblast tillväxtfaktorer (FGFs) samt vitamin A metaboliter (retinoider, RA) är exempel på signalmolekyler som påverkar de nedre vävnaderna under tidig embryonal utveckling. Dessutom indikerar spatialt och temporalt reglerade genexpressionsmönster att närvaro av dessa signalerings proteiner sammanträffar med när och var nedre neuronala celltyper specificeras. Den signal aktivitet som avges från det paraxiala mesodermet i det gastrulerande embryot medieras av Wnt signalering. För induktion av nedre neuronala identiteter krävs Wnt signalering i de presumtivt neuronala cellerna. I närvaro av FGF signalerings aktivitet är det tillräckligt med en stigande gradient av Wnt signalering för att succesivt generera celler med en genexpressions profil som är specifik för diencephalon, mesencephalon och metencephalon. Distinktionen mellan, metencephalon och nedre ryggmärgs identitet verkar vara resultatet av en gradient av både Wnt och FGF signalering. När det paraxiala mesodermet börjar bilda somiter har även celler med en genexpressions-profil som är specifik för den förlängda märgen (myelencephalon) och den övre delen av ryggmärgen blivit specificerade. Dessa celltyper bildas i regioner där det närliggande paraxiala mesodermet producerar RA. En gradient av Wnt och FGF signalering ger upphov till en initial nedre celltyps identitet som krävs för att dessa celler ska kunna svara på RA signaleringen. Antagoniserande aktiviteter av RA och FGF signalering avgör vilka celler som sedermera kommer att ge upphov till förlängda märgen eller övre-, respektive, nedre ryggmärgen. Senare under utvecklingen bildas olika regionspecifika klasser av motorneuroner i bla. förlängda märgen och ryggmärgen. Den initiala, Wnt medierade, regionaliseringen av neuronala celltyper är central även för denna process. Dessutom kan olika klasser av motorneuroner, specifika för den förlängda märgen, respective övre-, och nedre ryggmärgs regionerna, rekonstrueras in vitro genom att reprogrammera naivt neuroepitel mha. en kombination av Wnt, RA och/eller FGF.

Specification for process oriented applications tends to use languages that suffer from infinite, intractable or unpredictably irregular state spaces that thwart exhaustive searches by verification heuristics. However, conceptual schemas based on FOL, offer techniques for both integrating and verifying specifications in finite spaces. It is therefore of interest to transform process based specifications into conceptual schemata. Process oriented languages have an additional drawback in that reliable inputs to the integration of diverse specifications can result in unreliable outputs. This problem can more easily be addressed in a logic representation in which static and dynamic properties can be examined separately. The first part of the text describes a translation method from the process based language SDL, to first order logic. The usefulness of the method for industrial application has been demonstrated in an implementation. The method devised is sufficiently general for application to other languages with similar characteristics. Main contributions consist of: formalising the mapping of state transitions to event driven rules in dynamic entity-relationship schemas; analysing the complexity of various approaches to decomposing transitions; a conceptual representation of the source language that distinguishes meta- and object models of the source language and domain respectively. The second part of the text formally describes a framework for the integration of schemata that allows the exploration of their properties in relation to each other and to a set of integration assertions. The main contributions are the formal framework; an extension to conflicts between agents in a temporal action logic; complexity estimates for various integration properties. / QC 20101004

<p>Specification and differentiation of a cell is accomplished by changing its gene expression profiles. These processes require temporally and spatially regulated transcription factors (TFs), to induce the genes that are necessary to a specific cell type. In each cell a set of TFs interact with each other or activate their targets; as development progresses, transcription factors receive regulatory inputs from other TFs and a complex gene regulatory network (GRN) is generated. Adding complexity, each TF can be regulated not only at the transcriptional level, but also by translational, and post-translational mechanisms. Thus, understanding a developmental process requires understanding the interactions between TFs, signaling molecules and target genes which establish the GRN.</p><p>In this thesis, two genes, FoxN2/3, a TF and FGFR1, a component of the FGF signaling pathway are investigated. FoxN2/3 and FGFR1 have different mechanisms that function in sea urchin development; FoxN2/3 regulates gene expression and FGFR1 changes phosphorylation of target proteins. However, their ultimate goals are the same: changing the state of an earlier GRN into the next GRN state. </p><p>First, we characterize FoxN2/3 in the primary mesenchyme cell (PMC) GRN. Expression of foxN2/3 begins in the descendants of micromeres at the early blastula stage; and then is lost from PMCs at the mesenchyme blastula stage. foxN2/3 expression then shifts to the secondary mesenchyme cells (SMCs) and later to the endoderm. Here we show that, Pmar1, Ets1 and Tbr are necessary for activation of foxN2/3 in the descendants of micromeres. The later endomesoderm expression is independent of the earlier expression of FoxN2/3 in micromeres and independent of signals from PMCs. FoxN2/3 is necessary for several steps in the formation of larval skeleton. A number of proteins are necessary for skeletogenesis, and early expression of at least several of these is dependent on FoxN2/3. Furthermore, knockdown (KD) of FoxN2/3 inhibits normal PMC ingression. PMCs lacking FoxN2/3 protein are unable to join the skeletogenic syncytium and they fail to repress the transfating of SMCs into the skeletogenic lineage. Thus, FoxN2/3 must be present for the PMC GRN to control normal ingression, expression of skeletal matrix genes, prevention of transfating, and control fusion of the PMC syncytium.</p><p>Second, we show that the FGF-FGFR1 signaling is required for the oral-aboral axis formation in the sea urchin embryos. Without FGFR1, nodal is induced in all of the cells at the early blastula stage and this ectopic expression of nodal requires active p38 MAP kinase. The loss of oral restriction of nodal expression results in the abnormal organization of PMCs and the larval skeleton; it also induces ectopic expression of oral-specific genes and represses aboral-specific genes. The abnormal oral-aboral axis formation also affected fgf and vegf expression patterns; normally these factors are expressed in two restricted areas of the ectoderm between the oral and the aboral side, but when FGFR1 is knocked down, Nodal expands, and in response the expression of the FGF and VEGF ligands expands, and this in turn affects the abnormal organization of larval skeleton.</p> / Dissertation

Das System der Geometrischen Produktspezifikation und -verifikation ist eine umfangreiche Zusammenstellung von Normen, die die geometrische Produktspezifikation und den Nachweis der Bauteileigenschaften regelt. Die vorliegende Arbeit stellt die im Jahr 2012 gültigen Normen und deren Inhalte dar. Den Schwerpunkt bildet die funktionsgerechte Spezifikation. Ausgehend von den in den Normen festgelegten Möglichkeiten und bisherigen Ansätzen werden ein funktionsgerechtes Spezifikationsmodell abgeleitet und die Grenzen des Systems aufgezeigt.

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To ensure compliance with specifications during construction, a formal review process, called the submittals process is typically implemented, whereby the contractor is required to submit proposals for materials, equipment, and processes for the owner’s approval within a short period of time. This procedure can be a difficult task because of lack of time, lack of information in the submittal package, difficulty in retrieving related data, and lack of defined criteria for evaluation. This research introduces development of a framework for submittal evaluation that considers the operational impact of any minor variation in the required specifications. The evaluation mechanism uses the Multi-Attribute Utility Theory (MAUT) approach, which is adaptable to the varying requirements of organizations. Through the process of analyzing the current submittal mechanism, a list of key submittals is defined and the top one (chiller) is selected to be the focus of the research. The governing criteria (evaluation parameters) are defined for the selected submittal item and categorized into two categories: inflexible and flexible. The inflexible parameters have been dealt with using checklists with predefined threshold that must be met without tolerance. Flexible parameters have been analyzed using utility functions that represent decision maker preferences and tolerance levels. Accordingly, the evaluation process considers multi-parameters to determine an overall utility for the submittal and the value-based condition for accepting it, incorporating LEED requirements. The investigation is based on data provided by three main organizations, as well as intensive meetings and interviews with experts from each participating organization. The outcome of this investigation is the development of evaluation criteria and checklist parameters that are used as the basis of a value-based evaluation, which is the core of the developed decision support system. In summary, it has been demonstrated that a decision support system for the evaluation of construction submittals can be constructed and that it will provide numerous benefits: an expedited decision process, an audit trail for decisions, more consistent and objective decisions, risk identification, internal alignment of organizational values, and improved lifecycle asset performance. The benefits were validated by demonstration, and by experts' evaluations.

In this thesis, a simulation study is held and a statistical model is fitted to the simulated data. This data is assumed to be the satisfaction of the customers who withdraw their salary from a particular bank. It is a longitudinal data which has bivariate and binary response. It is assumed to be collected from 200 individuals at four different time points. In such data sets, two types of dependence -the dependence within subject measurements and the dependence between responses- are important and these are considered in the model. The model is Marginalized Transition Random Effects Models, which has three levels. The first level measures the effect of covariates on responses, the second level accounts for temporal changes, and the third level measures the difference between individuals. Markov Chain Monte Carlo methods are used for the model fit. In the simulation study, the changes between the estimated values and true parameters are searched under two conditions, when the model is correctly specified or not. Results suggest that the better convergence is obtained with the full model. The third level which observes the individual changes is more sensitive to the model misspecification than the other levels of the model.