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Lacombe, Laurie. "CRISPR-Cas9-based strategies for enhanced targeted integration." Electronic Thesis or Diss., université Paris-Saclay, 2024. http://www.theses.fr/2024UPASL047.
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La transplantation de cellules souches et progénitrices hématopoïétiques (CSPH) corrigées autologues est une stratégie prometteuse pour traiter les troubles génétiques sanguins, immunitaires et métaboliques en raison de leur capacité d'autorenouvellement et de différenciation en cellules sanguines variées. Une des méthodes les plus utilisées pour modifier les CSPH repose sur les outils d'édition de gènes comme les nucléases CRISPR/Cas9. L'intégration ciblée via CRISPR-Cas9 permet l'insertion précise de séquences thérapeutiques, offrant une source durable de cellules corrigées La cassure double brin (CDB) induite par Cas9 peut être réparée par trois voies principales : La jonction d'extrémités non homologues (NHEJ), où les brins libres générés sont ré-ligaturés, ou la recombinaison homologue dirigée (HDR) et la jonction d'extrémités médiée par microhomologie (MMEJ), qui utilise un modèle d'ADN pour la réparation. En fournissant un modèle d'ADN externe, la HDR et la MMEJ peuvent être détournées pour insérer des séquences curatives. Une plateforme de thérapie génique a été développée, avec des locus de refuge comme AAVS1 et HBA. Le locus HBA, en raison de sa forte expression d'α-globine et de sa perte de gène asymptomatique, est particulièrement prometteur pour l'expression de protéines thérapeutiques dans les cellules érythroïdes. Cependant, cette approche prometteuse soulève d'importants défis quant à l'amélioration et à l'évaluation de son efficacité et de sa sécurité.Pour aborder ces défis, divers aspects de l'intégration ciblée basée sur CRISPR/Cas9 ont été étudiés, notamment l'optimisation des méthodes d'administration du modèle ADN, la réduction de la toxicité cellulaire et l'exploitation des voies de réparation pour maximiser l'efficacité de l'intégration.L'un des principaux domaines d'investigation a porté sur la sélection et l'optimisation des méthodes d'administration pour l'introduction de modèles donneurs dans les cellules cibles. Les méthodes d'administration non virales et virales ont été explorées, l'AAV6 et l'IDLV se révélant les plus prometteuses.La toxicité cellulaire, souvent déclenchée par les outils d'intégration ciblée comme l'AAV et CRISPR/Cas9, diminue la viabilité cellulaire en activant la réponse aux dommages de l'ADN, affectant ainsi la capacité de greffe des CSPH. Pour atténuer ces effets génotoxiques, des protocoles visant à réduire la toxicité tout en atteignant des taux suffisants d'intégration ciblée ont été explorés.Les voies de réparation basées sur l'homologie, nécessaires à l'intégration des cassettes, sont limitées à des phases spécifiques du cycle cellulaire. La MMEJ opère pendant les phases G1/S, tandis que la HDR se produit pendant les phases S/G2. La NHEJ, active tout au long du cycle cellulaire, est responsable de la plupart des inconvénients de CRISPR, notamment les aberrations chromosomiques post-CDB.Pour favoriser l'utilisation de la HDR et de la MMEJ, un inhibiteur de la NHEJ a été testé, entraînant une augmentation significative de l'efficacité de l'intégration ciblée avec l'AAV et l'IDLV. Avec l'AAV6 identifié comme méthode optimale d'administration et l'inhibition de la NHEJ comme moyen d'améliorer l'intégration ciblée, la sécurité de la stratégie au niveau du site ciblé a été évaluée. En utilisant le séquençage ciblé à lecture longue, la caractérisation et la quantification des altérations génomiques induites par CRISPR/Cas9 et des événements d'intégration ciblée ont été réalisées, démontrant ainsi l'amélioration de la sécurité de notre approche.Ces résultats mettent en évidence le potentiel de l'inhibition de la NHEJ comme stratégie prometteuse pour améliorer l'édition du génome et l'intégration ciblée de l'ADNTransplantation of autologous corrected Hematopoietic Stem and Progenitor Cells (HSPCs) emerges as an attractive strategy for treating blood, immune, and metabolic genetic disorders due to their self-renewal capacity and ability to differentiate into any blood cell type. One popular approach to edit HSPCs relies on gene-editing tools such as CRISPR/Cas9 nucleases. Targeted homology-directed integration using CRISPR-Cas9 in HSPCs enables precise insertion of therapeutic sequences, providing a long-term source of corrected cells. The Cas9 induced double-stranded break (DSB) can be repaired via three main pathways: Non-Homologous End Joining (NHEJ), where generated free strands are re-ligated, or Homology Directed Repair (HDR) and Microhomology-mediated End Joining (MMEJ), which uses a template DNA for repair. By providing an external template of interest, MMEJ and HDR can be hijacked to insert curative sequences at a chosen site. A universal gene therapy platform has been developed, with safe harbor loci like AAVS1 and HBA allowing integration of any therapeutic sequence. The HBA locus, with its high α-globin expression and asymptomatic gene loss, is particularly promising allowing the development of a universal platform for expression and secretion of therapeutic proteins into erythroid cells.However, this promising approach raises important challenges about enhancing and evaluating its efficacy and safety. To address these questions, various aspects of CRISPR/Cas9-based targeted integration were investigated, focusing on optimizing delivery methods, minimizing cell toxicity, and exploiting repair pathways to maximize integration efficiency.One of the key areas of investigation centered on the selection and optimization of delivery methods for introducing donor templates into target cells. We explored both non-viral and viral-based delivery approaches.The potential of AAV6 and IDLV delivery methods was found to be the most promising.Cellular toxicity is triggered by numerous tools utilized in targeted integration using CRISPR-Cas9. AAV and CRISPR/Cas9-induced DSBs decrease cell viability by activating the DNA Damage Response, further impacting HSPC engraftment capacity. Concerns about potential genotoxic effects have led us to explore protocols aimed at reducing toxicity while achieving sufficient rates of targeted integration.Homology-based repair pathways necessary for cassette integration are restricted to specific phases of the cell cycle, reducing the window of action for this strategy. MMEJ operates during G1/S phases, while HDR occurs during S/G2 phases. NHEJ, active throughout the cell cycle, is responsible for most CRISPR drawbacks, particularly chromosomal aberrations post-DSB. To promote HDR and MMEJ utilization, a chemical compound known to inhibit NHEJ has been tested. NHEJ inhibition resulted in a significant increase in targeted integration efficiency with both AAV and IDLV-mediated delivery.Having identified AAV6 as the optimal template delivery method and NHEJ inhibition as a means of enhancing targeted integration, the safety of the strategy at the targeted site was assessed. Using targeted long-read sequencing, characterization and quantification of CRISPR/Cas9-induced genomic alterations and targeted integration events were achieved, demonstrating the improved safety of our approach.Overall, these data highlight the potential of NHEJ inhibition as a promising strategy for tuning genome editing and enhancing DNA targeted integration
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Collison, Sean Alfred. "Targeted gene integration for the production of recombinant pharmaceuticals in plants." Thesis, St George's, University of London, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.706519.
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Production of recombinant protein pharmaceuticals in plants is to become an important biotechnology for improving global health. In addition to having particular advantages for responding to pandemics it also addresses the need for affordable production of pharmaceuticals in developing countries. Whilst the development of transient expression systems has greatly improved the issue of recombinant protein yield from plants, improved expression vectors have also enhanced production from transgenic plants, and there are still drug products for which the technical simplicity of transgenic plant manufacture is important. For transgenic approaches, transgene insertion characteristics such as copy number and sites of insertion are known to affect transgene expression, so the random nature of transgenesis using agrobacterium is problematic, requiring massive screening campaigns to identify optimal lead plant lines. Furthermore, regulatory bodies require detailed characterisation of all genomic alterations resulting from the transformation process. Screening plant lines and genomic and phenotypic analysis is a significant time and cost burden. This thesis describes the design and construction of a series of vectors to develop a targeted gene integration TGI system, utilising the site-specific recombinases PhiC31 integrase and Cre to facilitate predictable gene expression and simplify genomic characterisation by inserting transgenes into predetermined target sites. PhiC31 was applied to perform recombinase- mediated cassette exchange (RMCE), using a promoter-trap system for selection for recombination of the incoming cassette in the correct orientation and allowing the generation of marker-free plants. Cre allowed potential excision of any ectopic integration events occurring during agrobacterium transformation. Over 89 TO target plant lines were generated and screened for recombinant protein production of the fluorescent marker protein, dsRED. They were self-fertilised and 43 T1 progeny were screened by segregation on selective medium. Expression analysis indicated higher transgene expression was associated with single-locus T-DNA insertion. The variation in dsRED expression at TO was also seen in T1 target plant lines, indicating that transgene integration sites are a determining factor for expression yields. Genomic analysis of 22 selected target lines was performed by Southern blot. Single copy T1 target plant lines were transformed with vectors for recombinases and an integration cassette by a novel strategy, to perform RMCE. Putative integrated plant lines were selected for the RMCE event. In a small number of regenerants, loss of dsRED and gain of GUS expression was observed at TO and subsequently in TO backcross plants, indicating successful exchange of the DNA cassettes. This thesis paves the way for a predictable and rapid approach to develop stable transgenic tobacco plants for the production of recombinant pharmaceutical proteins.
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Cortés, Ríos Julio César. "Targeted feedback collection for data source selection with uncertainty." Thesis, University of Manchester, 2018. https://www.research.manchester.ac.uk/portal/en/theses/targeted-feedback-collection-for-data-source-selection-with-uncertainty(3ce078e5-4e5a-4bf5-afb3-1ee51b863925).html.
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The aim of this dissertation is to contribute to research on pay-as-you-go data integration through the proposal of an approach for targeted feedback collection (TFC), which aims to improve the cost-effectiveness of feedback collection, especially when there is uncertainty associated with characteristics of the integration artefacts. In particular, this dissertation focuses on the data source selection task in data integration. It is shown how the impact of uncertainty about the evaluation of the characteristics of the candidate data sources, also known as data criteria, can be reduced, in a cost-effective manner, thereby improving the solutions to the data source selection problem. This dissertation shows how alternative approaches such as active learning and simple heuristics have drawbacks that throw light into the pursuit of better solutions to the problem. This dissertation describes the resulting TFC strategy and reports on its evaluation against alternative techniques. The evaluation scenarios vary from synthetic data sources with a single criterion and reliable feedback to real data sources with multiple criteria and unreliable feedback (such as can be obtained through crowdsourcing). The results confirm that the proposed TFC approach is cost-effective and leads to improved solutions for data source selection by seeking feedback that reduces uncertainty about the data criteria of the candidate data sources.
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Brady, Troy Leon. "The role of the integrase c-terminus in replication and targeted integration of the yeast retrotransposon Ty5." [Ames, Iowa : Iowa State University], 2007.
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Qiao, Junhua [Verfasser], and J. [Akademischer Betreuer] Bode. "Systematic Study on Generation of Mammalian Production Cell Lines by Targeted Integration (RMCE) / Junhua Qiao ; Betreuer: J. Bode." Braunschweig : Technische Universität Braunschweig, 2009. http://d-nb.info/1175828807/34.
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Hurlburt, Michael S. "An empirical framework for the evaluation of mental health care strategies targeted to community integration of severely mentally ill homeless individuals /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC IP addresses, 1997. http://wwwlib.umi.com/cr/ucsd/fullcit?p9722820.
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Hassan, Aamir Ul. "Integration of Genome Scale Data for Identifying New Biomarkers in Colon Cancer: Integrated Analysis of Transcriptomics and Epigenomics Data from High Throughput Technologies in Order to Identifying New Biomarkers Genes for Personalised Targeted Therapies for Patients Suffering from Colon Cancer." Thesis, University of Bradford, 2017. http://hdl.handle.net/10454/17419.
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Colorectal cancer is the third most common cancer and the leading cause of cancer deaths in Western industrialised countries. Despite recent advances in the screening, diagnosis, and treatment of colorectal cancer, an estimated 608,000 people die every year due to colon cancer. Our current knowledge of colorectal carcinogenesis indicates a multifactorial and multi-step process that involves various genetic alterations and several biological pathways. The identification of molecular markers with early diagnostic and precise clinical outcome in colon cancer is a challenging task because of tumour heterogeneity.
This Ph.D.-thesis presents the molecular and cellular mechanisms leading to colorectal cancer. A systematical review of the literature is conducted on Microarray Gene expression profiling, gene ontology enrichment analysis, microRNA and system Biology and various bioinformatics tools.
We aimed this study to stratify a colon tumour into molecular distinct subtypes, identification of novel diagnostic targets and prediction of reliable prognostic signatures for clinical practice using microarray expression datasets. We performed an integrated analysis of gene expression data based on genetic, epigenetic and extensive clinical information using unsupervised learning, correlation and functional network analysis. As results, we identified 267-gene and 124-gene signatures that can distinguish normal, primary and metastatic tissues, and also involved in important regulatory functions such as immune-response, lipid metabolism and peroxisome proliferator-activated receptors (PPARs) signalling pathways.
For the first time, we also identify miRNAs that can differentiate between primary colon from metastatic and a prognostic signature of grade and stage levels, which can be a major contributor to complex transcriptional phenotypes in a colon tumour.
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LLADO, SANTAEULARIA MANEL. "THERAPEUTIC GENOME EDITING IN RETINA AND LIVER." Doctoral thesis, Università degli Studi di Milano, 2020. http://hdl.handle.net/2434/696628.
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In vivo gene therapy with adeno-associated viral (AAV) vectors has been successful at treating several inherited diseases, specifically those caused by loss of function mutations which require transfer of a correct copy of a gene. This would not benefit dominant diseases due to gain of function mutations which produce toxic protein products. In addition, since AAV genomes persist as episomes in target cells, AAV mediated transgene expression might be short lived in tissues where cell proliferation occurs when newborn or after damage, like for example the liver. To overcome these challenges, I have developed AAV-based therapeutic approaches which use genome editing to introduce stable modifications at specific genomic loci. First, an allele-specific approach which targets the Rhodopsin P347S dominant mutation was developed and tested both in vitro and in vivo. I achieved allele-specific targeting of human P347S rhodopsin, which reduced mRNA levels and improved retinal electrical function in a mouse model of autosomal dominant retinitis pigmentosa. Second, I developed a mutation- and homology-independent targeted integration (HITI) approach for gene correction in photoreceptors. I demonstrated feasibility of this approach in mouse and pig photoreceptors using a reporter gene and characterized on-target precision of HITI in the murine rhodopsin locus. I then tested the therapeutic potential of this approach in a mouse model of autosomal dominant retinitis pigmentosa and observed mild and transient improvement of retinal function in treated eyes, which suggests that the levels of editing obtained need optimization. Third, I developed a HITI approach for expressing therapeutic genes from the liver by targeting the albumin locus, which is highly transcribed in hepatocytes. I demonstrated feasibility and efficiency of this approach using a reporter gene, and characterized on-target precision of HITI, as well as off-target integration due to Cas9 cleavage. I then tested the therapeutic potential of the integration of a copy of the human arylsulfatase B (ARSB) gene, which is mutated in a rare lysosomal storage disease, mucopolysaccharidosis type VI (MPS VI), in the albumin locus in the liver of newborn MPSVI mice. I demonstrated that this approach achieves stable expression of ARSB at levels that reduce glucosaminoglycan (GAG) urinary secretion, one of the main readouts of MPSVI phenotype. This stable expression of ARSB is contrary to the decrease of transgene expression observed in neonatal MPSVI mice injected with the same dose of a conventional gene therapy vector, thus overcoming the potential loss of transgene expression caused by hepatocyte proliferation. Overall, I have developed different genome editing approaches for conditions that are inherited as either dominant or recessive. I have tested these approaches in two relevant tissues for gene therapy like retina and liver and shown the potential to provide AAV with persistent transgene expression in proliferating tissues like the newborn liver.
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Tirovolis, Nikolaos Labros. "Integration of commercial aircraft economic targets into the initial design process." Thesis, Imperial College London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425793.
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Ewart, Steven. "Starting hand position effects on arm configuration for targeted reaching movements." Thesis, University of Iowa, 2014. https://ir.uiowa.edu/etd/4625.
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Mattsson, Johanna. "An integrative strategy for targeted evaluation of biomarker expression in non-small cell lung cancer." Doctoral thesis, Uppsala universitet, Molekylär och morfologisk patologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-285844.
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Despite improvements in therapy, the prognosis for non-small cell lung cancer (NSCLC) patients remains poor, and cure is only possible in localized tumors after surgical resection. A new generation of targeted cancer drugs has led to the expectation that lung cancer therapy can be significantly improved, but these drugs are today only an option in a small subset of NSCLC patients, and their effect is temporary. Therefore, the aim of this thesis was to characterize NSCLC in order to find new treatment targets and to evaluate biomarkers that further optimize therapy selection. In Paper I, the expression of the potential treatment targets claudin 6 and claudin 18.2 were evaluated based on immunohistochemical- and gene expression analysis. High ectopic protein and gene expression were demonstrated for both claudins in small subgroups of NSCLC. Clinical trials using humanized monoclonal antibodies against both proteins are ongoing in other cancer forms and may be extended to NSCLC. In Paper II, the prognostic impact of the inflammatory mediator cyclooxygenase 2 (COX-2) was evaluated. No prognostic significance was found in a meta-analysis incorporating gene expression data of 1337 NSCLC patients. Likewise, COX-2 protein expression in tumor cells was not associated with survival in two independent NSCLC cohorts. However, in one of the analyzed cohorts, higher COX-2 expression in the tumor stroma was associated with longer survival and may therefore be a subject for further investigation. In Paper III, tumor and stromal COX-2 protein expression was examined in patients treated with the COX-2 inhibitor celecoxib in order to evaluate if COX-2 expression is a predictive biomarker for benefit of celecoxib therapy. Celecoxib did not prolong overall survival neither in the whole cohort nor in patients stratified according to COX-2 expression in tumor or stromal cells. Noteworthy, a tendency towards longer survival was again demonstrated in patients with high COX-2 stromal expression. In Paper IV, the diagnostic methods for identification of ALK rearrangements were assessed in a large representative Swedish NSCLC population. Fluorescence in situ hybridization (FISH), as the diagnostic standard, was compared to two immunohistochemical assays. ALK gene expression levels were incorporated to supplement the molecular data. The frequency of ALK rearrangements was lower than previously reported. The different methods to detect the ALK fusion demonstrated overlapping results. However, the overlap was poor, so the methods cannot be regarded as interchangeable and should thereby be interpreted with caution when used in clinical diagnostics. In summary, this thesis applied an integrative translational approach to characterize potential new treatment targets and to evaluate the detection of existing predictive biomarkers in NSCLC.
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Khanafer, Sajida. "Sensory Integration During Goal Directed Reaches: The Effects of Manipulating Target Availability." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23422.
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When using visual and proprioceptive information to plan a reach, it has been proposed that the brain combines these cues to estimate the object and/or limb’s location. Specifically, according to the maximum-likelihood estimation (MLE) model, more reliable sensory inputs are assigned a greater weight (Ernst & Banks, 2002). In this research we examined if the brain is able to adjust which sensory cue it weights the most. Specifically, we asked if the brain changes how it weights sensory information when the availability of a visual cue is manipulated. Twenty-four healthy subjects reached to visual (V), proprioceptive (P), or visual + proprioceptive (VP) targets under different visual delay conditions (e.g. on V and VP trials, the visual target was available for the entire reach, it was removed with the go-signal or it was removed 1, 2 or 5 seconds before the go-signal). Subjects completed 5 blocks of trials, with 90 trials per block. For 12 subjects, the visual delay was kept consistent within a block of trials, while for the other 12 subjects, different visual delays were intermixed within a block of trials. To establish which sensory cue subjects weighted the most, we compared endpoint positions achieved on V and P reaches to VP reaches. Results indicated that all subjects weighted sensory cues in accordance with the MLE model across all delay conditions and that these weights were similar regardless of the visual delay. Moreover, while errors increased with longer visual delays, there was no change in reaching variance. Thus, manipulating the visual environment was not enough to change subjects’ weighting strategy, further i
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Etchells, Peter James. "The need for speed : target velocity integration in saccades to moving tatgets." Thesis, University of Bristol, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.535172.
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Mottram, Thomas. "The interdependency between motor programming and movement integration in multiple target aiming." Thesis, Bangor University, 2012. https://research.bangor.ac.uk/portal/en/theses/the-interdependency-between-motor-programming-and-movement-integration-in-multiple-target-aiming(01afcc7d-f3fa-4731-9ce5-8ef1b1f55983).html.
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Rapid aimed hand movements have been shown to be executed faster when the hand stops on a target than when it must proceed and hit a second target. This is known as the one-target advantage (OT A). This phenomenon has been shown to occur regardless of vision, practice, hand preference and hand use. Two hypotheses put forward to explain the OT A phenomenon have been the movement constraint hypothesis and movement integration hypothesis. Whilst previous research has focused on movements made with a single-limb, this thesis examined whether performing a two- target movement with two limbs had any effect on the OTA (chapters 2 and 3). The OTA materialised in both single-limb, and two-limb two target movements suggesting similar processes were used. By using kinematic analysis, this thesis has also shown that in movements performed using a single-limb and two-limbs, ellipse areas at the end of the first movement were typically smaller, showing support for the movement constraint hypothesis. Chapter 4 examined the interdependency between movements to target 1 and target 2. What role does movement amplitude, proximity of target 1 and 2, and target size have on movement times and spatial variability? Is there an optimal position of target 1 to optimise performance? Results indicated that when two targets are situated closer to each other, an advantage in terms of quicker total movement times is shown and the difference in total movement times was shown to be due to an advantage in the shorter movements compared to the long movements or in the pause times. A smaller second target also constrained variability at the first target, even though the first target size remained constant. This provides further support for the movement constraint hypothesis.
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Manson, Gerome Aleandro. "Examining the sensorimotor integration processes prior to and during movements to somatosensory targets." Thesis, Aix-Marseille, 2019. http://www.theses.fr/2019AIXM0072/document.
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La littérature sur les processus d’intégration multisensoriels (i.e., transformations sensorimotrice) avant et pendant des mouvements volontaires ont principalement utilisé des cibles visuelles. Considérant que la modalité d’une cible influence le cadre de référence utilisé pour contrôler un mouvement volontaire, l’objectif principal des trois expériences de la présente thèse était d’examiner ces processus de transformations sensorimotrices, et ce, spécifiquement pour des mouvements vers un cible somatosensorielle. Les deux premières expériences ont examiné les transformations sensorimotrices pendant la planification du mouvement. L’objectif de la troisième expérience était d’examiner les transformations sensorimotrices utilisée pour le contrôle du mouvement vers une cible somatosensorielle. Les résultats des deux premières expériences indiquent que des même des signaux auditifs peuvent faciliter l’utilisation d’un cadre de référence visuel du corps pour transformer la position de cibles somatosensorielles. Ces processus de transformation pourraient nécessiter des processus supplémentaires et engagent clairement des réseaux corticaux visuels et visuomoteurs. De plus, les résultats de la troisième expérience indique que des corrections apportées aux mouvements vers des cibles somatosensorielles perturbées prennent moins de temps pour être initiées en plus d’être plus efficaces et précises que des corrections apportées aux mouvement vers des cibles visuelles. De plus, cette troisième expérience indique que des cibles somatosensorielles ne sont pas nécessairement transformées dans un référentiel visuel avant de corriger un mouvement volontaire en cours d’exécutionResearch on multisensory integration for goal-directed movements has focused on targets external to the body. In this dissertation, three experiments were conducted to examine sensorimotor transformation processes for movements to body positions (i.e., somatosensory targets). The goal of the first experiment was to investigate if the modality of the cue used to indicate the location of a somatosensory target affects the body representation used to encode the target’s position during movement planning. The results showed that auditory cues prompted the use of an exteroceptive body representation for the encoding of movements to somatosensory targets in visual coordinates. The goal of the second experiment was expand on this finding and examine the neural processes associated with the visual remapping auditory-cued somatosensory targets. It was found that the sensorimotor transformation processes responsible for the conversion of somatosensory target positions to visual coordinates engages visuomotor cortical networks to a greater extent than movements to external visual targets. The goal of the third experiment was to examine the sensorimotor transformation processes employed for the online control of movements to somatosensory targets. These results provide evidence that the remapping of somatosensory targets into visual coordinates may not occur prior to online corrections. Altogether the findings of this thesis reveal that sensory cues can facilitate the remapping of somatosensory targets prior to goal directed actions. However, these remapping processes may be too costly to engage in during online control when there is no vision of the reaching limb
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Chou, Tsung-nan. "The integration of an ultrasonic phased array and a vision system for the 3D measurement of multiple targets." Thesis, University of Nottingham, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362887.
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Krarup, Troels Magelund. "Economic discourse and European market integration : the problem of financial market infrastructures." Thesis, Paris, Institut d'études politiques, 2016. http://www.theses.fr/2016IEPP0028/document.
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L’intégration européenne des marchés financiers semble se heurter de manière répétée à un certain type de problèmes concernant la substance et les limites conceptuelles de ce « marché » en cours d’intégration, ainsi que le statut et le rôle qu’y revêtent la monnaie, les infrastructures et la gouvernance publique. Ces problèmes et les controverses qu’ils soulèvent présentent un parallélisme avec des débats classiques de théorie économique tels que celui qui oppose les conceptions du marché comme espace sans frottements et comme processus de concurrence. Ce parallélisme est attribué ici à une « conception concurrentielle du marché » car celle-ci implique l’idée contradictoire d’une « intégration de la fragmentation ». La thèse repère ces thèmes et ces parallèles dans un grand projet récent d’intégration des infrastructures de marché financier : la plateforme paneuropéenne de règlement-livraison de titres Target2Securities (ou T2S), censée surmonter la fragmentation des systèmes qui réalisent les transferts de monnaie et de titres lors de transactions financières. L’analyse de ce projet permet en outre d’avancer une réponse à une énigme que les approches habituelles de l’intégration européenne en sociologie et en économie politique (political economy) – principalement centrées sur les intérêts et idées des acteurs les plus puissants – sont bien en peine d’éclaircir : à savoir la raison pour laquelle T2S sera de facto un monopole de la Banque centrale européenne, alors que les institutions européennes privilégient depuis le début l’intégration par les acteurs privés. La notion foucaldienne de « formation discursive » est mise à contribution pour conceptualiser ces thèsesEuropean integration of financial markets appears to repeatedly encounter specific kinds of problems about the substance and limits of the notion of “the market” undergoing integration, and about the status and role of money, market infrastructures, and government within it. Moreover, these problems and the controversies around them parallel classical discussions in economic theory such as that between conceptions of the market as a frictionless space and as a process of competition. A “competitive conception of the market” is identified as producing these parallel problems and controversies in European market integration and economic theory because it implies a contradictory “integration of fragmentation.” These themes and parallels can be specifically identified in a recent major project to integrate financial market infrastructures: a pan-European settlement platform – “Target2-Securities (T2S)” – to overcome existing fragmentation between the systems that perform the actual delivery of money and securities from financial transactions. Moreover, a close analysis of T2S answers a question that existing sociological and political economy approaches to European integration – focusing primarily on the interests and ideas of powerful players – struggle with: why T2S will become de facto a monopoly for the European Central Bank when early on in the integration process EU institutions emphasized an industry-led integration. Foucault’s notion of “discursive formation” is employed to conceptualize these arguments
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Nunes, André Filipe dos Santos Pereira. "Payment systems in the eurozone : an analysis of possibility of standardization." Master's thesis, Instituto Superior de Economia e Gestão, 2015. http://hdl.handle.net/10400.5/10464.
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Mestrado em FinançasEste projecto pretende realçar as vantagens que se obterão no âmbito dos sistemas de pagamento ao providenciar uma maior simplicidade ao processo, através de uma integração entre pelo menos dois sistemas de pagamentos, considerando apenas a Europa. Esta integração é vista como uma hipótese para alcançar o objectivo do projecto, considerando cinco sistemas de pagamento: SEPA, TARGET2, STEP1, EURO1 e sistemas de pagamento que considerem pagamentos em USD, não especificando um em concreto. De forma a obter resultados sustentáveis e válidos, o intervalo de tempo considerado para os dados numéricos recolhidos é desde 2009 até ao presente na maioria dos casos. Isto deve-se ao facto dos sistemas de pagamentos se encontrarem em constante evolução, do recente início de actividade do sistema SEPA (2009) e das novas necessidades criadas pela crise actual. O projecto descreve cada um dos sistemas individualmente e demonstra a possibilidade de tornar o processo de pagamento mais rápido e barato, beneficiando do decréscimo nos custos operacionais e da junção das diferentes características dos sistemas, através de uma integração entre, pelo menos, dois dos sistemas. Desta forma, a integração entre SEPA e TARGET2 foi considerada a mais viável, requisitando investimento e flexibilidade de todos os intervenientes no processo.
This project aims to show the advantages of getting an even higher simplicity in payment systems set, regarding Europe. In order to do so, the suggestion of merging at least two systems, was raised. Hence, the systems considered for this merger are SEPA, TARGET2, STEP1, EURO1 and systems that consider USD retail and large value payments (not considering a specific one). To obtain more suitable results, the range of the empirical data was defined from 2009 till present in most of the cases, given the constant evolution of payment systems, the recent beginning of SEPA (2009) and the emerging of the current crisis (creating new needs). This project presents and describes the five mentioned payments systems and shows the possibility of getting payments cheaper and simpler to process and faster to reach their destiny for the final clients, benefiting from the decrease in maintenance and operational costs and from the gathering of diverse features into one system, after the integration. Therefore, an integration between SEPA and TARGET2 was considered the most viable one, demanding investment and flexibility from the actors in the process.
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Balducci, Cristian. "Aggressive behavior at work: Investigating and integrating the target's and actor's perspectives." Doctoral thesis, Università degli studi di Trento, 2009. https://hdl.handle.net/11572/368344.
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Balducci, Cristian. "Aggressive behavior at work: Investigating and integrating the target's and actor's perspectives." Doctoral thesis, University of Trento, 2009. http://eprints-phd.biblio.unitn.it/139/1/Tesi_BalducciC.pdf.
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Tang, Chung Yiu Jonathan. "CIS-regulatory integration of intrinsic transcription factors with target-derived signals in neuronal differentiation." Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/24210.
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We now know that expression of the appropriate terminal differentiation gènes (TDG), such as neuropeptides, neurotransmitters, ion channels, etcetera, in maturing neurons is controlled by cell-specific combinations of transcription factors and by signals secreted from the neurons' target cells. However, it is unclear how thèse two regulatory inputs are integrated inside neurons. In Drosophila, target-derived Bone Morphogenetic Protein (BMP) signals and a well-characterized
combinatorial code of transcription factors activate expression of the FMRFa gene in the Tv neurons. Here, I performed a cis-regulatory analysis of FMRFa in order to understand how the two factors functionally intersect. Mutant analysis reveals that 4 of the 7 known FMRFa regulators, Apterous, BMP signalling, Dachshund and Zfhl, ail regulate the expression
of the Tv enhancer, a 446 bp cw-regulatory element that faithfully reproduces FMRFa expression in the Tv neurons. Within the Tv enhancer, I identified a functional module, termed HD/BRE-A, that is predicted to respond to both BMP signalling and the homeodomain transcription factor Apterous. I also verified that Apterous and the BMP factors, Mad and Medea, can directly bind to HD/BRE-A in vitro. Furthermore, transgenic analyse indicate that the positioning between the Apterous and Medea binding site is critical for Tv enhancer
activation, suggesting a strict physical requirement for simultaneous association of these factors. Taken together, my results supports a model of cis-regulatory integration of BMP signaling and homeodomain transcription factors in the regulation of TDGs.
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Yang, Sen. "Disease, Drug, and Target Association Predictions by Integrating Multiple Heterogeneous Sources." Case Western Reserve University School of Graduate Studies / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=case1342194249.
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Ngo, Mary Kim. "Facilitating visual target identification using non-visual cues." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:6e05bfc4-f049-43a3-8ecc-4db38f8cbb09.
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The research presented in this thesis was designed to investigate whether and how the temporal synchrony and spatial congruence of non-visual cues with visual targets could work together to improve the discrimination and identification of visual targets in neurologically-healthy adult humans. The speed and accuracy of participants’ responses were compared following the presence or absence of temporally synchronous and/or spatially congruent or incongruent auditory, vibrotactile, and audiotactile cues in the context of dynamic visual search and rapidly-masked visual target identification. The understanding of the effects of auditory, vibrotactile, and audiotactile cues derived from these laboratory-based tasks was then applied to an air traffic control simulation involving the detection and resolution of potential conflicts (represented as visual targets amidst dynamic and cluttered visual stimuli). The results of the experiments reported in this thesis demonstrate that, in the laboratory-based setting, temporally synchronous and spatially informative non-visual cues both gave rise to significant improvements in participants’ performance, and the combination of temporal and spatial cuing gave rise to additional improvements in visual target identification performance. In the real-world setting, however, only the temporally synchronous unimodal auditory and bimodal audiotactile cues gave rise to a consistent facilitation of participants’ visual target detection performance. The mechanisms and accounts proposed to explain the effects of spatial and temporal cuing, namely multisensory integration and attention, are examined and discussed with respect to the observed improvements in participants’ visual target identification performance.
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Bible, Paul W. "Integrating Heterogeneous Datasets for Functional Profiling of Transcription Factors and Their Target Genes." Thesis, University of Louisiana at Lafayette, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3589955.
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In this dissertation, computational approaches are developed which aim to characterize the behavior of transcription factor proteins (TFs) and their target genes. TFs are the main regulators of gene expression. Understanding their behavior is essential to developing novel strategies to fight genetic disease. The goals of this work were 1) to address gaps in the literature regarding the significance of DNA binding preferences of TFs, 2) to develop benchmarks and effective algorithms for predicting TF target genes, and 3) to integrate diverse knowledge to predict known and novel protein functions for TFs and their target genes in two types of cancer. Addressing the first goal, binding site similarity algorithms were compared to other types of similarity. This comparison found that binding site similarity is a good indication of structural similarity but a poor indicator of functional similarity. Addressing the second goal, data from the Encyclopedia of DNA Elements (ENCODE) was used to construct a set of target gene benchmarks to evaluate machine learning algorithms. These experiments established the Random Forest classifier as the most effective algorithm. Lastly addressing the third goal, a network flow simulation which integrated diverse data clustered proteins based on their likelihood of interacting. The inferred pathways of the clusters confirmed known biological pathway associations with the two cancer types and predicted novel pathway associations that could form the basis of further experimental research.
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Durgun, Ahmet Cemal. "Computation Of Radar Cross Sections Of Complex Targets By Physical Optics With Modified Surface Normals." Master's thesis, METU, 2008. http://etd.lib.metu.edu.tr/upload/12609810/index.pdf.
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In this study, a computer code is developed in MATLAB®to compute the Radar Cross Section (RCS) of arbitrary shaped complex targets by using Physical Optics (PO) and Modified PO. To increase the computational efficiency of the code, a novel fast integration procedure for oscillatory integrals, called Levin&rsquo
s integration, is applied to PO integrals. In order to improve the performance of PO near grazing angles and to model diffraction effects, a method called PO with Modified Surface Normal Vectors is implemented. In this method, new surface normals are defined to model the diffraction mechanism. Secondary scattering mechanisms like multiple scattering and shadowing algorithms are also included into the code to obtain a complete RCS prediction tool. For this purpose, an iterative version of PO is used to account for multiple scattering effects. Indeed, accounting for multiple scattering effects automatically solves the shadowing problem with a minor modification. Therefore, a special code for shadowing problem is not developed. In addition to frequency domain solutions of scattering problems, a waveform analysis of scattered fields in time domain is also comprised into this thesis. Instead of direct time domain methods like Time Domain Physical Optics, a Fourier domain approach is preferred to obtain the time domain expressions of the scattered fields. Frequency and time domain solutions are obtained for some simple shapes and for a complex tank model for differently polarized incident fields. Furthermore, a statistical analysis for the scattered field from the tank model is conducted.
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Berndt, Anthony Jason Erich. "Cis-regulatory integration of intrinsic and target-dependent regulators is required for terminal differentiation of Drosophila neurons." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/55193.
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Porterfield, Darwin Ben 1957. "Use of geodata integration techniques to target gold-silver mine mineralization at Twin Peaks, Owyhee County, Idaho." Thesis, The University of Arizona, 1993. http://hdl.handle.net/10150/278342.
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Various filtering and integration techniques were used to analyze geologic, geophysical and geochemical data from the Twin Peaks area located in the DeLamar mining district in Southwestern Idaho. In particular rank correlation and favorability analysis were employed in this study. The data analysis was used to delineate target areas considered favorable for epithermal gold-silver mineralization. The interpretation of geophysical data was emphasized because of the importance of subsurface geologic features and complications caused by post mineral cover. Field investigation of the target areas provides strong evidence supporting the potential for significant mineralization in four of the twelve target areas selected.
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Li, Zhe. "Fate of Pharmaceuticals and Their Transformation Products in Rivers : An integration of target analysis and screening methods to study attenuation processes." Doctoral thesis, Stockholms universitet, Institutionen för miljövetenskap och analytisk kemi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-123752.
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Pharmaceuticals are environmental contaminants causing steadily increasing concern due to their high usage, ubiquitous distribution in the aquatic environment, and potential to exert adverse effects on the ecosystems. After being discharged from wastewater treatment plants (WWTPs), pharmaceuticals can undergo transformation processes in surface waters, of which microbial degradation in river sediments is considered highly significant. In spite of a substantial number of studies on the occurrence of pharmaceuticals in aquatic systems, a comprehensive understanding of their environmental fate is still limited. First of all, very few consistent datasets from lab-based experiments to field studies exist to allow for a straightforward comparison of observations. Secondly, data on the identity and occurrence of transformation products (TPs) is insufficient and the relation of the behavior of TPs to that of their parent compounds (PCs) is poorly understood. In this thesis, these knowledge gaps were addressed by integrating the TP identification using suspect/non-target screening approaches and PC/TP fate determination. The overarching objective was to improve the understanding of the fate of pharmaceuticals in rivers, with a specific focus on water-sediment interactions, and formation and behavior of TPs. In paper I, 11 pharmaceutical TPs were identified in water-sediment incubation experiments using non-target screening. Bench-scale flume experiments were conducted in paper II to simultaneously investigate the behavior of PCs and TPs in both water and sediment compartments under more complex and realistic hydraulic conditions. The results illustrate that water-sediment interactions play a significant role for efficient attenuation of PCs, and demonstrate that TPs are formed in sediment and released back to surface water. In paper III the environmental behavior of PCs along stretches of four wastewater-impacted rivers was related to that of their TPs. The attenuation of PCs is highly compound and site specific. The highest attenuation rates of the PCs were observed in the river with the most efficient river water-pore water exchange. This research also indicates that WWTPs can be a major source of TPs to the receiving waters. In paper IV, suspect screening with a case-control concept was applied on water samples collected at both ends of the river stretches, which led to the identification of several key TPs formed along the stretches. The process-oriented strategies applied in this thesis provide a basis for prioritizing and identifying the critical PCs and TPs with respect to environmental relevance in future fate studies.At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Submitted. Paper 4: Manuscript.
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Baldo, Fatima Magdi Hamza. "Integrating chemical, biological and phylogenetic spaces of African natural products to understand their therapeutic activity." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/289714.
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This research aims to utilise ligand-based target prediction to (i) understand the mechanism of action of African natural products (ANPs), (ii) help identify patterns of phylogenetic use in African traditional medicine and (iii) elucidate the mechanism of action of phenotypically active small molecules and natural products with anti-trypanosomal activity. In Chapter 2 the objective was to utilise ligand-based target prediction to understand the mechanism of action of natural products (NPs) from African medicinal plants used against cancer. The Random Forest classifier used in this work compares the similarity of the input compounds from the natural product dataset with compound-target combinations in the training set. The more similar they are in structure, the more likely they are to modulate the same target. Natural products from plants used against cancer in Africa were predicted to modulate targets and pathways directly associated with the disease, thus understanding their mechanism of action e.g. "flap endonuclease 1" and "Mcl-1". The "Keap1-Nrf2 Pathway" and "apoptosis modulation by HSP70", two pathways previously linked to cancer (which are not currently targeted by marketed drugs, but have been of increasing interest in recent years) were predicted to be modulated by ANPs. In Chapter 3, we aimed to identify phylogenetic patterns in medicinal plant use and the role this plays in predicting medicinal activity. We combined chemical, predicted target and phylogenetic information of the natural products to identify patterns of use for plant families containing plant species used against cancer in African, Malay and Indian (Ayurveda) traditional medicine. Plant families that are close phylogenetically were found to produce similar natural products that act on similar targets regardless of their origin. Additionally, phylogenetic patterns were identified for African traditional plant families with medicinal species used against cancer, malaria and human African trypanosomiasis (HAT). We identified plant families that have more medicinal species than would statistically be expected by chance and rationalised this by linking their activity to their unique phyto-chemistry e.g. the napthyl-isoquinoline alkaloids, uniquely produced by Acistrocladaceae and Dioncophyllaceae, are responsible for anti-malarial and anti-trypanosome activity. In Chapter 4, information from target prediction and experimentally validated targets was combined with orthologue data to predict targets of phenotypically active small molecules and natural products screened against Trypanosoma brucei. The predicted targets were prioritised based on their essentiality for the survival of the T. brucei parasite. We predicted orthologues of targets that are essential for the survival of the trypanosome e.g. glycogen synthase kinase 3 (GSK3) and rhodesain. We also identified the biological processes predicted to be perturbed by the compounds e.g. "glycolysis", "cell cycle", "regulation of symbiosis, encompassing mutualism through parasitism" and "modulation of development of symbiont involved in interaction with host". In conclusion, in silico target prediction can be used to predict protein targets of natural products to understand their molecular mechanism of action. Phylogenetic information and phytochemical information of medicinal plants can be integrated to identify plant families with more medicinal species than would be expected by chance.
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Fischer, Martin, Patrick Grossmann, Megha Padi, and James A. DeCaprio. "Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks." Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-205936.
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Cell cycle (CC) and TP53 regulatory networks are frequently deregulated in cancer. While numerous genome-wide studies of TP53 and CC-regulated genes have been performed, significant variation between studies has made it difficult to assess regulation of any given gene of interest. To overcome the limitation of individual studies, we developed a meta-analysis approach to identify high confidence target genes that reflect their frequency of identification in independent datasets. Gene regulatory networks were generated by comparing differential expression of TP53 and CC-regulated genes with chromatin
immunoprecipitation studies for TP53, RB1, E2F, DREAM, B-MYB, FOXM1 and MuvB. RNA-seq data from p21-null cells revealed that gene downregulation by TP53 generally requires p21 (CDKN1A). Genes downregulated by TP53 were also identified as CC genes bound by the DREAM complex. The transcription factors RB, E2F1 and E2F7 bind to a subset of DREAM target genes that function in G1/S of the CC while B-MYB, FOXM1 and MuvB control G2/M gene expression. Our approach yields high confidence ranked target gene maps for TP53, DREAM, MMB-FOXM1 and RB-E2F and enables prediction and distinction of CC regulation. A web-based atlas at www.targetgenereg.org enables assessing the regulation of any human gene of interest.
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Stahl, Günter, Chei Hwee Chua, and Amy L. Pablo. "Does National Context Affect Target Firm Employees' Trust in Acquisitions? A Policy-Capturing Study." Springer, 2012. http://epub.wu.ac.at/3613/1/MIR_%2D_Employee_Reactions_to_Takeovers_(Final__April_23_2011).pdf.
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In this study, we test the assumption that the way target firm employees respond to a takeover is contingent on their national origin.
The antecedents of target firm member trust in the acquiring firm management were examined in a cross-national sample of German and Singaporean employees using a policy-capturing design. Five factors hypothesized to affect target firm member trust after a takeover were found to
be significant influences on employees' trust judgments in a decision-making simulation: (i)
combining firms' collaboration history, (ii) mode of takeover, (iii) whether it was a domestic
or cross-border acquisition, (iv) degree of autonomy removal, and (v) attractiveness of the
acquiring firm's human resource policies and reward system. Further analyses suggest that
the relative importance of these factors in predicting target firm employees' reactions to a
takeover varies depending on their national origin.
We conclude that companies engaged in cross-border acquisitions need to consider contingencies
in the cultural and institutional contexts in which the acquired firms are embedded and
adapt their approaches for integrating them accordingly.
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Mpangase, Phelelani Thokozani. "Integrating protein annotations for the in silico prioritization of putative drug target proteins in malaria." Diss., University of Pretoria, 2012. http://hdl.handle.net/2263/24715.
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Current anti-malarial methods have been effective in reducing the number of malarial cases. However, these methods do not completely block the transmission of the parasite. Research has shown that repeated use of the current anti-malarial drugs, which include artemisinin-based drug combinations, might be toxic to humans. There have also been reports of an emergence of artemisinin-resistant parasites. Finding anti-malarial drugs through the drug discovery process takes a long time and failure results in a great financial loss. The failure of drug discovery projects can be partly attributed to the improper selection of drug targets. There is thus a need for an eff ective way of identifying and validating new potential malaria drug targets for entry into the drug discovery process. The availability of the genome sequences for the Plasmodium parasite, human host and the Anopheles mosquito vector has facilitated post-genomic studies on malaria. Proper utilizationof this data, in combination with computational biology and bioinformatics techniques, could aid in the in silico prioritization of drug targets. This study was aimed at extensively annotating the protein sequences from the Plasmodium parasites, H. sapiens and A. gambiae with data from di fferent online databases in order to create a resource for the prioritization of drug targets in malaria. Essentiality, assay feasibility, resistance, toxicity, structural information and druggability were the main target selection criteria which were used to collect data for protein annotations. The data was used to populate the Discovery resource (http://malport. bi.up.ac.za/) for the in silico prioritization of potential drug targets. A new version of the Discovery system, Discovery 2.0 (http://discovery.bi.up.ac.za/), has been developed using Java. The system contains new and automatically updated data as well as improved functionalities. The new data in Discovery 2.0 includes UniProt accessions, gene ontology annotations from the UniProt-GOA project, pathways from Reactome and Malaria Parasite Metabolic Pathways databases, protein-protein interactions data from. IntAct as well as druggability data from the DrugEBIlity resource hosted by ChEMBL. Users can access the data by searching with a protein identi er, UniProt accession, protein name or through the advanced search which lets users filter protein sequences based on different protein properties. The results are organized in a tabbed environment, with each tab displaying different protein annotation data. A sample investigation using a previously proposed malarial target, S-adenosyl-Lhomocysteine hydrolase, was carried out to demonstrate the diff erent categories of data available in Discovery 2.0 as well as to test if the available data is su fficient for assessment and prioritization of drug targets. The study showed that using the annotation data in Discovery 2.0, a protein can be assessed, in a species comparative manner, on the potential of being a drug target based on the selection criteria mentioned here. However, supporting data from literature is also needed to further validate the findings.Dissertation (MSc)--University of Pretoria, 2012.
Biochemistry
unrestricted
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Regush, Murray M. "Development of a LIDAR for integration with the Naval Postgraduate School Infrared Search and Target Designation (NPS-IRSTD) system /." Monterey, Calif. : Springfield, Va. : Naval Postgraduate School ; Available from National Technical Information Service, 1993. http://handle.dtic.mil/100.2/ADA271847.
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Thesis (M.S. in Electrical Engineering) Naval Postgraduate School, June 1993.Thesis advisor(s): Alfred W. M. Cooper ; John P. Powers. "June 1993." Includes bibliographical references. Also available online.
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Regush, Murray Michael. "Development of a LIDAR for integration with the Naval Postgraduate School Infrared Search and Target Designation (NPS-IRSTD) system." Thesis, Monterey, California. Naval Postgraduate School, 1993. http://hdl.handle.net/10945/39835.
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Approved for public release; distribution is unlimited.A lidar was designed and manufactured at the Naval Postgraduate School, Monterey, CA, to provide range information to atmospheric features, such as clouds. It is further planned to integrate the lidar with the NPS-IRSTD system at some future date. The NPS-IRSTD uses two vertical linear focal plane arrays for target detection and target direction can be determined very accurately but the system does not provide any useful range information. The lidar was proposed as the solution for this shortcoming. The lidar used a frequency-doubled Nd:YAG laser which had an energy output of 2 millijoules. The laser beam was expanded to 17.75 inches using a Dall-Kirkham telescope to operate within laser safety limitations. The theoretical analysis of the 'Klett' method for the inversion of lidar returns was derived and a MATLAB program was written to demonstrate the process. A daytime and nighttime maximum range equation for the lidar was developed. The considerations for integrating the lidar with the NPS-IRSTD were listed and a solution was proposed to obtain the mean extinction coefficient along the path in the infrared spectrum using the lidar inversion extinction coefficient profile at 532 nanometers.
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Berlin, Sebastian [Verfasser], and Peter [Akademischer Betreuer] Horvath. "Integration der Kostenplanung ökologischer Produktfunktionen in das Target Costing dargestellt am Beispiel der Spielwarenindustrie / Sebastian Berlin. Betreuer: Péter Horváth." Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2015. http://d-nb.info/106567029X/34.
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Berlin, Sebastian [Verfasser], and Péter [Akademischer Betreuer] Horváth. "Integration der Kostenplanung ökologischer Produktfunktionen in das Target Costing dargestellt am Beispiel der Spielwarenindustrie / Sebastian Berlin. Betreuer: Péter Horváth." Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-97912.
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Melnyk, Richard V. "A framework for analyzing unmanned aircraft system integration into the national airspace system using a target level of safety approach." Diss., Georgia Institute of Technology, 2013. http://hdl.handle.net/1853/47572.
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Unmanned Aircraft Systems (UAS) represent a significant potential for growth in the aerospace industry. Their use in military operations has increased exponentially in the last decade alone, requiring a corresponding increase in training airspace in the United States. In addition to military usage, UAS have the potential to fulfill a myriad of roles for both the public and private sectors. However, the use of UAS has been limited in the National Airspace System (NAS) to military and public applications and only under fairly restrictive Certificates of Authorization or Waiver (COA). The only way to truly realize the potential of UAS is to fully integrate them into the NAS. The desire to integrate UAS was recently codified into law with the 2012 FAA Modernization Act, mandating integration by specific, fairly short timelines.
There are several challenges currently preventing the full integration of UAS that range from technological to procedural areas. However, the one common theme in all of these challenges is Safety. Across the literature on this topic there is no consensus on how safe UAS need to be to achieve integration, whether UAS can currently meet specified safety targets, and if not, what is the best way to achieve the safety goals.
The purpose of this effort was to demonstrate a comprehensive framework for analyzing UAS integration efforts using a Target Level of Safety (TLS) approach. Using reliability tools, aircraft encounter models, and data from a wide variety of sources ranging from manned aircraft safety, explosives, falling debris and earthquake damage, the primary outcome of the effort was a better understanding of the risk to second and third party persons as a result of UAS operations in the NAS.
This framework and associated models are validated using reliability and casualty data from manned aircraft operations. The framework is then applied to several relevant and specific cases to demonstrate the impact of policy decisions on UAS reliability and allowed operational areas. The supporting research and analysis can serve as a baseline for future integration analysis and decision-making efforts, and was designed to allow stakeholders and decision makers in this field to assess UAS safety, and set minimum system reliability requirements and mitigation system effectiveness standards.
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Joel, Sandé. "Jodivi: An Application to Target Sound Sensitivity Features in People with Autism Spectrum Disorder." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36516.
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The main objective of this research work is to provide a tool to prevent the severe hearing sensitivity to patients with Autism Spectrum Disorder (ASD) experience. The key element in our work is to identify commonalities between sounds that bother an ASD patient, and implement a procedure using PC or smartphone as platform - based on those results, which will lead to the prevention of “bothersome” sounds for the ASD sufferer and later to desensitization. To do so, we implemented a first application that evaluates the auditory sound sensitivity of a person, and a second application that determines those factors that are related to hearing sensitivity of the patient, suggest sounds in the preventive process, and proposes use of appropriate sounds in the desensitization process.
While the current implementation is a prototype, we are determined to pursue the development at professional level and implemented as very user friendly application, which we hope will become a popular tool used by medical personnel and ASD patients for the identification of an individual’s specific sound sensitivities and his/her desensitization to those sounds.
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Nyström, Johanna. "Integration som ömsesidig anpassning : En analys av idéerna bakom valet av målgrupp i den svenska integrationspolitiken." Thesis, Uppsala universitet, Statsvetenskapliga institutionen, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-279985.
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The Swedish policy for integration has been accused of wrongly targeting only immigrants and therefore resembling assimilation. In this bachelor thesis I show that there seems to be a general understanding between academics and politicians of how integration should be achieved. If integration is the opposite of assimilation an integrated society has to be achieved trough mutual adaptation. The purpose of this thesis is to identify if the Swedish government design their policy for integration according to the idea of integration as mutual adaptation or not. A frame analysis is used to identify the de target populations in the Swedish strategy for integration. Through analysing the choice of target populations I conclude that the Swedish policy for integration does not fulfil the idea of integration as mutual adaptation. Another important conclusion is that there can be two different target populations for every policy, one tied to the causal story and one tied to the solution of the problem with integration.Den svenska integrationspolitiken har anklagats för att felaktigt riktas mot endast invandrare och på så sätt mer likna assimilationspolitik. I den här kandidatuppsatsen visar jag att forskare och politiker på en övergripande nivå verkar vara överens om hur integration bör uppnås. Om integration är motsatsen till assimilation måste ett integrerat samhälle uppnås genom ömsesidig anpassning. Syftet med den här uppsatsen är att ta reda på om den svenska regeringen utformar sin integrationspolitik efter idén om integration som ömsesidig anpassning eller inte. Frameanalys används för att identifiera målgrupperna i den svenska strategin för integration. Genom att analysera valet av målgrupper drar jag slutsatsen att den svenska integrationspolitiken inte uppfyller idéen om integration som ömsesidig anpassning. En annan viktig slutsats är att det kan finnas två målgrupper för varje åtgärd, en knuten till orsaksförklaringen och en knuten till lösningen på problemet.
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Schumann, Frank Jens. "Methoden und Werkzeuge zur Integration der kundengerechten Wertgestaltung in die Konzeptphase des Produktentwicklungsprozesses." Doctoral thesis, Universitätsbibliothek Chemnitz, 2001. http://nbn-resolving.de/urn:nbn:de:bsz:ch1-200100287.
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Die für die Konzeptphase des Produktentwicklungsprozesses erarbeitete integrierte Vorgehensweise bietet durch Methoden und Werkzeuge zur Zielkostenspaltung und -erreichung eine systematische Unterstützung hinsichtlich der:
Funktionsprojektierung entsprechend den Kundenanforderungen
Ermittlung der Prioritäten des Kunden
Erarbeitung von Teilzielkostenvorgaben
Konzipierung prinzipieller Lösungen
Prognose deren voraussichtlicher Kosten
Auswahl alternativer Lösungskonzepte
Bewertung des technischen Potentials und des vergüteten Nutzens der Konzeptalternativen
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Kedaigle, Amanda Joy. "Integrating Omics data : a new software tool and its use in implicating therapeutic targets in Huntington's disease." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/119026.
Full textAbstract:
Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2018.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references.
High-throughput "omics" data are becoming commonplace in biological research and can provide important translational insights, but there is a need for well-crafted user-friendly tools for integrating and analyzing these data. In this thesis, I present versions 1 and 2 of Omics Integrator, a software tool designed to take advantage of the Prize-Collecting Steiner Forest algorithm from graph theory to provide users with high-confidence biological networks informed by their omics results. I show the results of using this flexible tool in several studies of Huntington's disease (HD), a fatal neurodegenerative disorder with no cure. By leveraging Omics Integrator on omics datasets from induced pluripotent stem cell (iPSC) derived models of HD, I discovered and highlighted several pathways that are altered in these cell line models, including neurodevelopment and glycolytic metabolism, which may lead to important therapeutic targets in the disease. Finally, I compare omics data derived from three iPSC-derived models differentiated towards a striatal neuron cell type using different protocols, and show that by performing this large comparative analysis I can implicate functions and pathways common to several models of HD. Future integrative and comparative studies like these will be made easier by the Omics Integrator tool.
by Amanda Joy Kedaigle.
Ph. D.
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Cattoglio, Claudia. "Target site selection of retroviral vectors in the human genome : viral and genomic determinants of non-random integration patterns in hematopoietic cells." Thesis, Open University, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494505.
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Integration of gamma-retroviruses (RV) and lehtiviruses (LV) follows different, non random patterns in mammalian genomes. To obtain information about the viral and genomic determinants of integration preferences, I mapped > 2,500 integration sites of RV and LV vectors carrying wild type or modified LTRs in human CD34+ hematopoietic cells. To investigate the role of transcriptional regulatory networks in directing RV and LV integration, 1 evaluated the local abundance and anangement of putative transcription factor binding sites (TFBSs) in the genomic regions flanking integrated proviruses.
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Wikle, Jared Kevin. "Integration of a Complete Detect and Avoid System for Small Unmanned Aircraft Systems." BYU ScholarsArchive, 2017. https://scholarsarchive.byu.edu/etd/6361.
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For unmanned aircraft systems to gain full access to the National Airspace System (NAS), they must have the capability to detect and avoid other aircraft. This research focuses on the development of a detect-and-avoid (DAA) system for small unmanned aircraft systems. To safely avoid another aircraft, an unmanned aircraft must detect the intruder aircraft with ample time and distance. Two analytical methods for finding the minimum detection range needed are described. The first method, time-based geometric velocity vectors (TGVV), includes the bank-angle dynamics of the ownship while the second, geometric velocity vectors (GVV), assumes an instantaneous bank-angle maneuver. The solution using the first method must be found numerically, while the second has a closed-form analytical solution. These methods are compared to two existing methods. Results show the time-based geometric velocity vectors approach is precise, and the geometric velocity vectors approach is a good approximation under many conditions. The DAA problem requires the use of a robust target detection and tracking algorithm for tracking multiple maneuvering aircraft in the presence of noisy, cluttered, and missed measurements. Additionally these algorithms needs to be able to detect overtaking intruders, which has been resolved by using multiple radar sensors around the aircraft. To achieve these goals the formulation of a nonlinear extension to R-RANSAC has been performed, known as extended recursive-RANSAC (ER-RANSAC). The primary modifications needed for this ER-RANSAC implementation include the use of an EKF, nonlinear inlier functions, and the Gauss-Newton method for model hypothesis and generation. A fully functional DAA system includes target detection and tracking, collision detection, and collision avoidance. In this research we demonstrate the integration of each of the DAA-system subcomponents into fully functional simulation and hardware implementations using a ground-based radar setup. This integration resulted in various modifications of the radar DSP, collision detection, and collision avoidance algorithms, to improve the performance of the fully integrated DAA system. Using these subcomponents we present flight results of a complete ground-based radar DAA system, using actual radar hardware.
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Karvir, Hrishikesh. "Design and Validation of a Sensor Integration and Feature Fusion Test-Bed for Image-Based Pattern Recognition Applications." Wright State University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=wright1291753291.
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Fonseca, Mateus Ramalho Ribeiro da. "Política monetária em um contexto de metas de inflação, câmbio flexível e mobilidade de capitais : uma investigação teórica, histórica e empírica." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2018. http://hdl.handle.net/10183/183071.
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A presente tese tenta avaliar a política monetária sob o Regime de Metas de Inflação (RMI), num contexto de flexibilidade cambial e integração financeira. No campo teórico, este trabalho avalia no primeiro ensaio, os aspectos teóricos do RMI e também do Novo Consenso Macroeconômico (NCM), assim como a crítica pós-keynesiana ao NCM. Na sequência, avalia-se a evolução do debate acerca da política monetária após a Crise Financeira Internacional, assim como os aspectos teóricos da integração financeira global e dos Ciclos Financeiros Globais, e suas consequências para a condução da política monetária. No aspecto histórico, avalia-se brevemente no segundo ensaio, o comportamento das principais variáveis macroeconômicas concernentes a política monetária, taxa de câmbio e crescimento econômico, assim como, os arranjos institucionais do RMI de cada país, evidenciando suas principais diferenças. O Brasil tem um dos RMI mais rígidos e as maiores taxas de juros entre os países analisados. No âmbito empírico, realizou-se três exercícios econométricos distintos. O primeiro, por meio do modelo VEC, comparam-se a eficiência do RMI brasileiro com outros 12 países selecionados, no que diz respeito ao controle inflacionário, ao repasse cambial e do crescimento econômico. O Brasil, assim como outros países em desenvolvimento, tem um dos RMI mais ineficientes, com evidencias da presença de price-puzzle, além de apresentar um elevado repasse cambial para o nível de preços e ter impactos no crescimento econômico. O segundo exercício econométrico buscou-se analisar a não-linearidade da política monetária brasileira com relação ao repasse cambial para o nível de preços, utilizando o modelo MS-VAR. O modelo mostrou fortes evidências empíricas de que há repasse cambial tanto em momentos de apreciação, quanto de depreciação cambial, configurando assim, uma política monetária com dois regimes cambiais. O terceiro exercício busca evidenciar, por meio do modelo VEC, os impactos que a integração financeira global, tem na condução da política monetária brasileira. Encontrou-se indícios de que a taxa de câmbio opera entre os ciclos financeiros globais e o nível de preços da economia brasileira, mostrando, assim, que a política monetária sob o RMI, tendo como base altas taxas de juros, é ineficiente. Tais fatos sugerem que a taxa de câmbio tem um papel fundamental no controle da inflação e no desempenho do próprio RMI; todavia, há a necessidade de uma reavaliação da política cambial que vêm sendo adotada no Brasil para além do papel de mecanismo de controle de preços.This study aims to evaluate the monetary evolution of the Inflation Target Regime (IT) in a context of exchange rate flexibility and financial integration. In the theoretical field, this work was evaluated in the first essay, the theoretical questions of the IT and also of the New Macroeconomic Consensus (NMC), as well as a post-Keynesian criticism to NMC. Following an assessment of the monetary policy debate following an International Financial Crisis, as well as the financial issues for the financial and global integration of Global Financials, and their consequences for the generation of monetary policy. The evaluation of the risk in the historical statistics, the evaluation of the risk changes the monetary changes, the risk must change the expansion policies, and the risk must have different conditions. Brazil has one of the most rigid ITs and the main interest rates among the analyzed countries. In the empirical context, the different econometric exercises are carried out. The first one, through the VEC model, compares the efficiency of the Brazilian IT with 12 other selected countries, than respect for inflationary control, exchange rate transfers and economic growth. Brazil, like other developing countries, has more inefficient IT, with evidence of the presence of price-puzzles, as well as a high exchange rate repayment for the price level and the impacts on economic growth. The second econometric exercise sought to analyze the non-linearity of the Brazilian monetary policy in relation to the pass-through to the price level, using the MS-VAR model. The model of empirical demonstrations that there is to change both in moments of appreciation and the exchange depreciation, thus forming a monetary policy with two exchange rate regimes. The third study seeks the evidence, through the VEC model, of the impacts that global financial integration has on Brazilian monetary policy. We find that the indexes of an exchange rate between the cycles and the level of prices of the Brazilian economy, thus showing a monetary policy on the IT, based on interest rates, is inefficient. Such facts should that an exchange rate has a key role in controlling the rate and performance of the IT itself; however, there is a reappraisal of the exchange rate policy that has been adopted in Brazil beyond the role of the price control mechanism.
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Younesi, Erfan [Verfasser]. "A Knowledge-based Integrative Modeling Approach for In-Silico Identification of Mechanistic Targets in Neurodegeneration with Focus on Alzheimer’s Disease / Erfan Younesi." Bonn : Universitäts- und Landesbibliothek Bonn, 2014. http://d-nb.info/1052582060/34.
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Capocchi, Ribeiro Maria Alice de Fatima. "A New Perspective into Languages for Specific Purposes (LSP) Syllabus Design : Target language learningpromoting thedevelopment of refugee employability competencies." Thesis, Linnéuniversitetet, Institutionen för kulturvetenskaper (KV), 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-106924.
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This thesis reports on a meta-analysis of the most relevant employabilitycompetencies to foster refugees’ labour integration which may be potentiallyleveraged through a target language for specific purposes (LSP)MOOCsyllabus. Italso suggests to group the thus identified employability competencies into threecategories tofurther supportLSPMOOC syllabus design and implementation.Themethodology of meta-analysis was based on Cooper’s (2017) five-stage model andguided by exploratory data analysis (EDA) of a dedicated research corpus that wasspecifically tailored for this study. Three data mining tools were used to performnatural language pre-processing and pattern extraction, directed by key terms(employability, competency, competencies, skill, ability, abilities, vocational,refugee,andlabour) used in various query combinations and limiters. IterativeEDApost-processing of metadata generated by these tools, based ontheoretical andsemantic sorting and integration, led to 21 re-aggregated clusters of employabilitycompetencies and the suggested categories for grouping them.The present studyshows that the broader capillarity of data and text mining tools, as well as ofEDA,can contribute toa more encompassing view of employability competencies and oftheLSP as a tool-competency, hence to a greater capillarity ofcompetency-basedVET(Vocational Education and Training) syllabus design, particularly the proposedinnovative type ofLSPMOOC syllabus.Examination Seminar held by Zoom given that it was a Distance Programme
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Loguercio, Salvatore. "Reductionist and Integrative approaches to explore the H.pylori genome." Doctoral thesis, Università degli studi di Padova, 2008. http://hdl.handle.net/11577/3425099.
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The reductionist approach of decomposing biological systems into their constituent parts has dominated molecular biology for half a century. Since organisms are composed solely of atoms and molecules without the participation of extraneous forces, it has been assumed that it should be possible to explain biological systems on the basis of the physico-chemical properties of their individual components, down to the atomic level. However, despite the remarkable success of methodological reductionism in analyzing individual cellular components, it is now generally accepted that the behavior of complex biological systems cannot be understood by studying their individual parts in isolation. To tackle the complexity inherent in understanding large networks of interacting biomolecules, the integrative viewpoint emphasizes cybernetic and systems theoretical methods, using a combination of mathematics, computation and empirical observation. Such an approach is beginning to become feasible in prokaryotes, combining an almost complete view of the genome and transcriptome with a reasonably extensive picture of the proteome.
Pathogenic bacteria are undoubtedly the most investigated subjects among prokaryotes. A paradigmatic example is the the human pathogen H.pylori, a causative agent of severe gastroduodenal disorders that infects almost half of the world population.
In this thesis, we investigated various aspects of Helicobacter pylori molecular physiology using both reductionist and integrative approaches.
In Section I, we have employed a reductionist, bottom-up perspective in studying the Cysteine oxidised/reduced state and the disulphide bridge pattern of an unusual GroES homolog expressed by H.pylori, Heat Shock protein A (HspA). This protein possesses a high Cys content, is involved in nickel binding and exhibits an extended subcellular localization, ranging from cytoplasm to cell surface. We have produced and characterized a recombinant HspA and mutants Cys94Ala and C94A/C111A. The disulphide bridge pattern has been assigned by integrating biochemical methodologies with mass spectrometry. All Cys are engaged in disulphide bonds that force the C-term domain to assume a peculiar closed loop structure, prone to host nickel ions. This novel Ni binding structural arrangement can be related to the Ni uptake/delivery to the extracellular urease, essential for the bacterium survival.
In Section II, we combined different computational methods with two main goals:
1) Analyze the H.pylori biomolecular interaction network in an attempt to select new molecular targets against H.pylori infection (Chapters 4 & 5);
2) Model and simulate the signaling perturbations induced by invading H.pylori proteins in the host ephitelial cells (Chapter 6).
Chapter 4 explores the 'robust yet fragile' feature of the H.pylori cell, viewed as a complex system in which robustness in response to certain perturbation is inevitably associated with fragility in response to other perturbations. With this in mind, we developed a general strategy aimed at identify control points in bacterial metabolic networks, which could be targets for novel drugs. The methodology is implemented on Helicobacter pylori 26695.
The entire metabolic network of the pathogen is analyzed to find biochemically critical points, e.g. enzymes which uniquely consume and/or produce a certain metabolite. Once identified, the list of critical enzymes is filtered in order to find candidate targets wich are non-homologous with the human enzymes. Finally, the essentiality of the identified targets is cross-validated by in silico deletion studies using flux-balance analysis (FBA) on a recent genome-scale metabolic model of H. pylori. Following this approach, we identified some enzymes which could be interesting targets for inhibition studies of H.pylori infection.
The study reported in Chapter 5 extends the previously described approach in light of recent theoretical studies on biological networks. These studies suggested that multiple weak attacks on selected targets are inevitably more efficient than the knockout of a single target, thus providing a conceptual framework for the recent success of multi-target drugs. We used this concept to exploit H.pylori metabolic robustness through multiple weak attacks on selected enzymes, therefore directing us toward target-sets discovery for combinatorial therapies.
We used the known metabolic and protein interaction data to build an integrated biomolecular network of the pathogen. The network was subsequently screened to find central elements of network communication, e.g. hubs, bridges with high betweenness centrality and overlaps of network communities. The selected enzymes were then classified on the basis of available data about cellular function and essentiality in an attempt to predict successful target-combinations. In order to evaluate the network effect triggered by the partial inactivation of candidate targets, robustness analysis was performed on small groups of selected enzymes using flux balance analysis (FBA) on a recent genome-scale metabolic model of H.pylori. In particular, the FBA simulation framework allowed to predict the growth phenotype associated to every partial inactivation set.
The preliminary results obtained so far may help to restrict the initial target-pool in search of target-sets for novel combinatorial drugs against H.pylori persistence. However, our long-term goal is to better understand the indirect network effects that lie at the heart of multi-target drug action and, ultimately, how multiple weak hits can perturb complex biological systems.
H.pylori produces various a cytotoxic protein, CagA, that interfere with a very important host signaling pathway, i.e. the epidermal growth factor receptor (EGFR) signaling network. EGFR signaling is one of the most extensively studied areas of signal transduction, since it regulates growth, survival, proliferation and differentiation in mammalian cells. In Chapter 6, we attempted to build an executable model of the EGFR-signaling core process using a process algebra approach. In the EGFR network, the core process is the heart of its underlying hour-glass architecture, as it plays a central role in downstream signaling cascades to gene expression through activation of multiple transcription factors. It consists in a dense array of molecules and interactions wich are tightly coupled to each other.
In order to build the executable model, a small set of EGFR core molecules and their interactions is tentatively translated in a BetaWB model. BetaWB is a framework for modelling and simulating biological processes based on Beta-binders language and its stochastic extension.
Once obtained, the computational model of the EGFR core process can be used to test and compare hypotheses regarding the principles of operation of the signaling network, i.e. how the EGFR network generates different responses for each set of combinatorial stimuli. In particular, probabilistic model checking can be used to explore the states and possible state changes of the computational model, whereas stochastic simulation (corresponding to the execution of the BetaWB model) may give quantitative insights into the dynamic behaviour of the system in response to different stimuli. Information from the above tecniques allows model validation through comparison within the experimental data available in the literature.
The inherent compositionality of the process algebra modeling approach enables further expansion of the EGFR core model, as well as the study of its behavior under specific perturbations, such as invading H.pylori proteins. This latter aspect might be of great value for H.pylori pathogenesis research, as signaling through the EGF receptors is intricately involved in gastric cancer and in many other gastroduodenal diseases.
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OLIVEIRA, AGATHA LOPES TOMMASI. "PROPOSAL OF A SYSTEMIC CONCEPTUAL MODEL TO DEFINE A COUNTRY S AGENDA 2030: PRIORITIZATION OF GLOBAL TARGETS INTEGRATING MULTICRITERIA METHODS, STRUCTURAL ANALYSIS, AND NETWORK THEORY." PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO, 2018. http://www.maxwell.vrac.puc-rio.br/Busca_etds.php?strSecao=resultado&nrSeq=35496@1.
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PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIROCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO
Uma questão fundamental na implementação da Agenda 2030 em nível nacional refere-se à análise das interrelações entre os Objetivos de Desenvolvimento Sustentável (ODS) e como suas respectivas metas interagem entre si. Diretamente ligadas a essa análise, surge outra questão de ordem metodológica, qual seja: como a integração de métodos multicritério de tomada de decisão, análise estrutural e teoria de redes poderá contribuir para que um país possa melhor definir que metas globais deverão ser incluídas na sua Agenda 2030, considerando-se aspectos críticos de seus contextos socioeconômico e político. Buscando responder essa questão, a presente dissertação tem por objetivo propor um modelo conceitual sistêmico para priorizar metas globais associadas aos ODS que irão compor a Agenda 2030 de um país, integrando-se métodos multicritério de apoio à decisão, análise estrutural e teoria de redes. A pesquisa pode ser considerada descritiva, metodológica e aplicada. Com base nos resultados da revisão bibliográfica e da análise documental de seus temas centrais e visando preencher as lacunas identificadas na literatura, desenvolveu-se um modelo conceitual sistêmico para priorizar as metas globais a serem incluídas na Agenda 2030 de um país. A aplicabilidade do modelo foi demonstrada mediante um experimento preliminar no contexto da Agenda 2030 brasileira. Acredita-se que o modelo conceitual resultante desta pesquisa possa ser replicado em outros contextos nacionais, particularmente em países que estão para definir as metas que integrarão suas respectivas Agendas para o Desenvolvimento Sustentável.
A fundamental question in the implementation of the 2030 Agenda at the national level is how the Sustainable Development Goals (SDGs) and their respective targets interact with each other. Directly linked to this concern, a methodological question arises – how can the integration of multicriteria decision making methods, structural analysis, and network theory contribute to a country to better define which global targets should be included in its 2030 Agenda, considering critical issues of its socio-economic and political contexts. With an attempt to answer this question, the dissertation aims to propose a systemic conceptual model to prioritize SDG s targets for a country s 2030 Agenda, by integrating multicriteria decision methods, structural analysis, and network theory. The research can be considered descriptive, methodological and applied. Based on the results of the bibliographic review and documentary analysis of its central themes, and seeking to fill the gaps identified in the specialized literature, a systemic conceptual model was developed for prioritizing global targets that should be included in a country s 2030 Agenda, considering critical issues of its socio-economic and political contexts. The model s applicability was demonstrated through a preliminary experiment concerning the definition of the Brazilian 2030 Agenda. It is believed that the conceptual model resulting from this research can be replicated in other national contexts, particularly in countries where the It is believed that the conceptual model resulting from this research can be replicated in other national contexts, particularly in those countries that are going to prioritize the targets that will integrate their respective Agendas for Sustainable Development.
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Zimmermann, Valentin, Christoph Kempf, Leo Hartmann, Nikola Bursac, and Albert Albers. "Umgang mit Marktunsicherheiten in der Zielsystementwicklung: Methode zur Reduktion von Definitionslücken bei der Konkretisierung des Initialen Zielsystems." Thelem Universitätsverlag & Buchhandlung GmbH & Co. KG, 2021. https://tud.qucosa.de/id/qucosa%3A75848.
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Der systematische Umgang mit Unsicherheiten, die in Form von Wissens- und Definitionslücken vorliegen, stellt eine zentrale Aktivität der Produktentwicklung dar. Im Zuge der Zielsystementwicklung liegen Unsicherheiten insbesondere in Form von aus Kunden- und Anwendersicht nichtzutreffender und fehlender oder unvollständiger Ziele und Anforderungen vor. Um bei der Konkretisierung des initialen Zielsystems dahingehend zu unterstützen, wurde eine Methode abgeleitet, welche die systematische Integration von Kunden und Anwendern in die Erhebung von Zielsystemelementen adressiert. Dabei formulieren Kunden und Anwender gemeinsam mit Produktentwicklern Ziele für das zu entwickelnde Produkt. Um dies zu unterstützen, werden die Ziele in Form von Satzschablonen formuliert, um die Vollständigkeit der Ziele zu gewährleisten. Weiter kann durch den Aufbau der Satzschablone sichergestellt werden, dass die Begründung in Form des Kunden- oder Anwendernutzens dokumentiert ist. Zusätzlich wurde ein Portfolio abgeleitet, welches die Ziele entsprechend der Zielgruppe und des relevanten Use-Cases strukturiert und damit fehlende Ziele darlegt. Im Rahmen einer Evaluation konnte gezeigt werden, dass durch die Anwendung der Methode in einem Entwicklungsprojekt von Hekatron Brandschutz die Vollständigkeit des Zielsystems gesteigert und die vorliegende Unsicherheit reduziert werden konnte.