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Carlsson-Wall, Martin. "Targeting target costing : cost management and inter-organizational product development of multi-technology products." Doctoral thesis, Handelshögskolan i Stockholm, Institutionen för Redovisning och finansiering, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:hhs:diva-1284.
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Improving product development is a complex task for many companies. One challenge is to avoid over-engineering and only include the functionality that customers are willing to pay for. Another challenge is to reduce costs in close co-operation with suppliers. This is a complex task because suppliers often have their own goals and are rarely located at the same physical place. Handling these two challenges is the domain of target costing. Emerging first from Japanese companies such as Toyota, Nissan and Olympus, target costing has become a critical element in achieving long-term profitability. Previous research on target costing has been paradoxical because even though it deals with product development, it has not incorporated the complexity of the product development process. More specifically, current models of target costing assume that the product development process can largely be planned and controlled by a single company. For complex multi-technology products, such as airplanes and industrial robots, this is far from true. By drawing on product development theories, and conducting an in-depth case study at ABB Robotics, this thesis explores target costing in the development of complex multi-technology products. The result is a framework that identifies challenges and problems in target costing processes, but also shows that target costing relies on both planning and improvisation to cope with tensions and contradictions in close customer and supplier relationships.Diss. Stockholm : Handelshögskolan i Stockholm, 2011
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Mohammed, Asjad Kaleem. "Anticancer natural products that target hypoxia-inducible factor-1 /." Full text available from ProQuest UM Digital Dissertations, 2005. http://0-proquest.umi.com.umiss.lib.olemiss.edu/pqdweb?index=0&did=1260789291&SrchMode=1&sid=4&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1185218250&clientId=22256.
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Fraser, Andrew Logan. "Target elucidation of novel trypanosomatid inhibitors." Thesis, University of St Andrews, 2018. http://hdl.handle.net/10023/15666.
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In 2010 the Florence group completed the total synthesis of the natural product chamuvarinin which, in collaboration with the Smith group, was found to be a potent inhibitor of the pathogenic parasite T. brucei. Several simplified analogues were found to maintain this inhibitory activity alongside activity against the related species T. cruzi and L. major. The mechanism of action and structural features of these compounds responsible for the observed biological activity remained elusive despite a large synthetic effort by the Florence group. With the aim of identifying protein targets in trypanosomatids to understand the mechanism of action, several photo-affinity labeling analogs have been successfully synthesised and utilised to identify a primary protein target. This protein target was fully validated and molecule docking to this protein was evaluated in-silico. This computational data was used to evaluate the mode of action and aided in the design of simplified compounds which were found to maintain the previously observed anti-parasitic activity but with decreased toxicity to mammalian cells alongside decreased synthetic complexity. The total synthesis of the natural product ascr#18 is also described alongside the synthesis of photo-affinity labeling analogs. This natural product is implicated in the modulation of pathogen resistance in plants and has potential application in crop production.
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Yan, Luping. "Bioactive marine natural products : analogue synthesis, SAR, and target identification." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/50069.
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3,6,7-trihydroxycoumarin C11 (2.14) was first isolated from the green alga Dasycladus vermicularis in 1983. C11 and 3,7,8-trihydroxycoumarin C21 (2.15), alongside their precursors C12 (2.18) and C22 (2.20), were synthesized for a target-based screen for anti-HCV drugs, where ideal hits eliminate fluorescence signals by inhibiting the proteolytic activity of HCV NS3pro/Pep4A against a synthetic peptide “BS-IQFS”. With C12 and C22 serving as negative controls, C11 and C21 inhibited the NS3pro/Pep4A activity in vitro. The IC₅₀’s of C11 and C21 were 3.07 μM and 2.10 μM, respectively.
A bioassay-guided fractionation identified sintokamides A – E (3.11 – 3.15) from extracts of the sponge Dysidea sp. in 2008. In a phenotypic screen, the chlorinated dipeptides showed strong to modest inhibition of luciferase activity caused by AR NTD transactivation in LNCaP cells. Larger quantities of sintokamides A and B were isolated from the sponge for further biological study. After developing a practical synthetic route, a comprehensive SAR of the sintokamides was available from the in vitro activities of 29 synthetic analogues/precursors based on a 1,17-dinorsintokamide skeleton. LPY26 [(4R,10R)-3.233] showed the best biological activity in the synthetic analogues prepared to date and it was selected as a drug lead. Mechanism of action study using synthetic probes LPY30 (4.7) and LPY31 (4.8) revealed that the hexachlorinated 1,17-dinorsintokamides covalently bound to the AR, but not to the same AF1 region in the AR NTD as EPI-001 (3.8).
The structure of latonduine A (5.1) isolated from the sponge Stylissa carteri and its total synthesis were published in 2003. Later, latonduine A was shown to be active in a phenotypic screen to find drug leads for the treatment of cystic fibrosis caused by the F508del mutation. Latonduine A could efficiently correct immunofluorescent F508del-CFTR trafficking from the endoplasmic reticulum to the plasma membrane in the engineered cells. Synthetic latonduine A and N-biotinylated latonduine A (5.17) were prepared to support biological studies aimed at identifying its cellular protein target(s). These studies culminated in the finding that latonduine A is an inhibitor of PARP-3 with an EC₅₀ of 400 pM in CFBE41o- cells.Science, Faculty of
Chemistry, Department of
Graduate
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Oselusi, Samson Olaitan. "Cheminformatic approaches to hit-prioritization and target prediction of potential anti-mrsa natural products." University of Western Cape, 2020. http://hdl.handle.net/11394/8209.
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Magister Pharmaceuticae - MPharmThe growing resistance of Methicillin-Resistant Staphylococcus aureus (MRSA) to currently prescribed drugs has resulted in the failure of prevention and treatment of different infections caused by the superbug. Therefore, to keep pace with the resistance, there is a pressing need for novel antimicrobial agents, especially from non-conventional sources. Several natural products (NPs) have displayed varying in vitro activities against the pathogen but few of these natural compounds have been studied for their prospects to be potential antimicrobial drug candidates. This may be due to the high cost, tedious, and time-consuming process of conducting the important preclinical tests on these compounds. Hence, there is a need for cost-effective strategies for mining the available data on these natural compounds. This would help to get the knowledge that may guide rational prioritization of “likely to succeed” natural compounds to be developed into potential antimicrobial drug candidates.
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Centko, Ryan Matthew. "Isolation, synthesis, and biological target identification of natural products from terrestrial and marine environments." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/50064.
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Natural products offer an unparalleled resource for the discovery and development of chemical tools to be used by humans. The terrestrial and marine environments contain unique niches where organisms chemically adapt to produce compounds that have proven useful medicinally and beyond. In the following chapters, several classes of novel natural products from terrestrial fungi and marine sponges will be presented. In some cases, synthetic methodology, biological activity and enzymatic target identification will also be presented.
Chapters 2 and 3 highlight ramariolides A–D (2.18–2.21) and dhilirolides A–N (3.9–3.22), two new fungal derived compound classes isolated from terrestrial sources. The structure elucidation of these compounds will be presented alongside their biological activities as antimycobacterial and insecticidal agents, respectively.
Chapter 4 contains the structure elucidation of three new members of the xestoquinone family of compounds, xestolactone A (4.19), xestosaprol O (4.20), and xestosaprol P (4.21) along with their potent inhibitory effect on human indolamine 2, 3-dioxygenase (hIDO). A new method for synthetic access to derivatives of these compounds is demonstrated in Chapter 5 along with a brief structure activity relationship (SAR) study.
Lastly, Chapter 6 discusses latonduine A (6.9), a sponge-derived alkaloid, which has shown promise as a lead structure for the correction of cystic fibrosis (CF). Probes derived from latonduine A (6.9) have led to identification of poly (ADP-ribose) polymerase (PARP) as the enzymatic target. Methodology for the probes’ construction and SAR studies resulting in simplified synthetic analogues of latonduine will be presented.Science, Faculty of
Chemistry, Department of
Graduate
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Horton, Kevin G. "The use of portfolio management with target costed process oriented products under conditions of uncertainty." Master's thesis, This resource online, 1995. http://scholar.lib.vt.edu/theses/available/etd-02022010-020227/.
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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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Duan, Yufeng. "Ex-post competitiveness assessment of Alberta agri-food exports in target products and markets, 1988-1996." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0019/MQ47022.pdf.
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Heuett, Nubia Vanesa. "Target and Non-target Techniques for the Quantitation of Drugs of Abuse, Identification of Transformation Products, and Characterization of Contaminants of Emergent Concern by High Resolution Mass Spectrometry." FIU Digital Commons, 2015. http://digitalcommons.fiu.edu/etd/2194.
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Development and application of target and non-target techniques for routine analysis, identification of transformation products, and characterization of unknown compounds in water matrices using liquid-chromatography high-resolution mass spectrometry (HRMS) were explored in this dissertation. A novel analytical method based on online-SPE-LC-HRMS was developed for the detection of 18 drugs of abuse (DOAs) in raw sewage water from a college campus. Results showed the presence of 14 DOAs for which amphetamine and 11-nor-9-carcoxy-THC (THC metabolite) were the most prevalent and had the highest potential consumption rates.
A second study dedicated to the identification of transformation products (TPs) generated from DOAs was conducted using a combination of HR-MS/MS and metabolic identification and structural elucidation software. Findings confirmed the presence of multiple phase I and II DOA TPs (n=35) in raw sewage influents. Concentrations of all TPs were estimated based on the parent DOAs response factors, and used to calculate the percent mole fraction contributions of each TP to the parent concentrations. High abundance and frequency (compared to the parent drug) was determined for 9 of the TPs coming from drugs like oxycodone, morphine, codeine, methadone, LSD, cocaine, and MDEA.
Non-target analysis using HRMS was explored as a tool to characterize, and compare a series of interconnected water matrices along a river system. Several thousands of formulae were generated using automated heuristic rules from the full-scan acquisition at 140,000 resolution. Samples were part of a trajectory covering upstream, effluent, effluent mixing zone, downstream, drinking water intake, and treated drinking water locations. Graphical representations of the data were used to evaluate commonalities among the system. Using this approach, a total of 64 recalcitrant components were identified throughout the samples downstream of the effluent release point. Using a combination of MS/MS and computer-aid software techniques 4 out of the 64 compounds were tentatively confirmed. In addition, comparison of drinking water intake and finalized treated drinking water sites showed the presence of 1,152 chemical entities that were common to both locations; and 1,857 that were unique to the treated drinking water. Therefore, this non-target technique could be used to identify the potential formation of treatment byproducts.
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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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Zhang, Wei, Xue Zhang, Yuling Tian, Yan Zhu, Yindong Tong, Ying Li, and Xuejun Wang. "Risk Assessment of Total Mercury and Methylmercury in Aquatic Products from Offshore Farms in China." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/2624.
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Contamination of methylmercury (MeHg) in aquatic products has been a wide spread health concern. The objective of this study is to determine total mercury (THg) and MeHg concentrations in different species of aquatic products from major offshore farms in China, and to assess health impacts from consumption. Results showed that the concentrations of THg and MeHg ranged 5.6–328.4 ng/g (wet weight) and 4.3–303.6 ng/g (wet weight) in aquatic products, respectively, and were very variable among species and origin sources. Target hazard quotient (THQ) suggested that MeHg exposure via consumption posed high health risks to children aged 2–7 and higher income families. Residents above the age of 13 and with low income have relatively lower health risk of MeHg exposure. Health impacts on heart attacks and newborns’ IQ from MeHg exposure were evaluated using dose-response relationships. Results showed that mother’s consumption of aquatic products (at 6 ounce per day) may cause a loss of 0.38 IQ points for newborns. For non-pregnant, consumption of aquatic products may cause an increase rate of mortality and morbidity of heart attacks at 10.59 and 78.45 per 100,000 persons, respectively. The negative health impact of consuming seawater fish was higher than freshwater fish.
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König, Stefanie [Verfasser], Oliver Gutachter] Werz, Dirk [Gutachter] [Hoffmeister, and Alexandra Kathrin [Gutachter] Kiemer. "Mode of action and target identification of anti-inflammatory natural products / Stefanie König ; Gutachter: Oliver Werz, Dirk Hoffmeister, Alexandra Kathrin Kiemer." Jena : Friedrich-Schiller-Universität Jena, 2020. http://d-nb.info/1212509137/34.
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König, Stefanie [Verfasser], Oliver [Gutachter] Werz, Dirk [Gutachter] Hoffmeister, and Alexandra Kathrin [Gutachter] Kiemer. "Mode of action and target identification of anti-inflammatory natural products / Stefanie König ; Gutachter: Oliver Werz, Dirk Hoffmeister, Alexandra Kathrin Kiemer." Jena : Friedrich-Schiller-Universität Jena, 2020. http://nbn-resolving.de/urn:nbn:de:gbv:27-dbt-20200618-115401-005.
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Williams, Karen Lindsay. "Personas in the Design Process: A tool for understanding others." Thesis, Available online, Georgia Institute of Technology, 2006, 2006. http://etd.gatech.edu/theses/available/etd-07102006-101208/.
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Deeb, Ahmad Atef Said [Verfasser], and Torsten Claus [Akademischer Betreuer] Schmidt. "Target and suspect screening of organic micropollutants and their transformation products in aqueous samples / Ahmad Atef Said Deeb ; Betreuer: Torsten Claus Schmidt." Duisburg, 2017. http://d-nb.info/113557281X/34.
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Zetterström, Caroline E. "Small Molecules as Tools in Biological Chemistry : Effects of Synthetic and Natural Products on the Type III Secretion System." Doctoral thesis, Umeå universitet, Kemiska institutionen, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-70281.
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The increasing use of antibiotics has led to a huge problem for society, as some bacteria have developed resistance towards many of the antibiotics currently available. To help find solutions to this problem we studied small molecules that inhibit bacterial virulence, the ability to cause disease. The type III secretion system (T3SS) is a conserved virulence system found in several gram-negative bacteria, including human and plants pathogens, such as Yersinia spp., Pseudomonas aeruginosa, Chlamydia spp., Salmonella spp., Shigella spp, enteropathogenic Escherichia coli (EPEC), enterohemorrhagic Escherichia coli (EHEC), and Erwinia spp. One class of virulence-blocking compounds is the salicylidene acylhydrazides. They were first identified in a screen towards the T3SS in Yersinia pseudotuberculosis and have since been shown to block the T3SS in a panel of gram-negative bacteria such as Chlamydia spp. Salmonella enterica, Shigella flexneri and EPEC. We designed and synthesized a library of 58 salicylidene acylhydrazides and evaluated their activity as virulence-blocking compounds in Y. pseudotuberculosis followed by calculations of quantitative structure activity relationships (QSARs). Four QSAR models were calculated, and when used in consensus they correctly classified between five out of eight compounds for Y. pseudotuberculosis as active or inactive and six out of eight compounds for C. trachomatis. Since the target and mode of action of the salicylidene acylhydrazides were unknown, we used solution and solid phase synthesis to synthesize three different affinity reagents. One of these affinity reagents was used in affinity chromatography experiments, where 19 putative target proteins from an E. coli O157 bacterial lysate were identified. We studied four of the proteins, Tpx, WrbA, FolX, and AdhE, in more detail in Y. pseudotuberculosis and E. coli O157. We believe that the salicylidene acylhydrazides act on multiple targets that together result in down-regulation of T3SS functions. A knockout of AdhE in E. coli O157 showed a similar phenotype as salicylidene acylhydrazide treated E. coli, suggesting that this protein may be particularly interesting as a drug target. Many of the antibiotics used today originate form natural sources. In contrast, most virulence-blocking compounds towards the T3SS are small synthetic organic molecules. Therefore, a prefractionated natural product library with marine and terrestrial biota samples was screened towards the T3SS in Y. pseudotuberculosis. Neohopeaphenol A was identified as a hit and shown to have micromolar activity towards Y. pseudotuberculosis and P. aeruginosa in cell-based infection models.Det ökande användandet av antibiotika har lett till stora problem för samhället. Många bakterier har utvecklat resistens mot de antibiotika som finns tillgängliga. För att försöka hitta en möjlig lösning på detta problem, arbetar vi med en strategi där vi med hjälp av små organiska molekyler inhiberar bakteriernas virulenssystem, deras förmåga att orsaka sjukdom. Traditionella antibiotika är antingen, bakteriocida, avdödande eller bakteriostatiska, tillväxthämmande. Bakteriernas enda sätt för att överleva antibiotikabehandlingen är att utveckla resistens. Forskarvärlden tror att molekyler som inhiberar bakteriernas virulenssystem, leder till ett minskat tryck att utveckla resistens mot dessa molekyler, eftersom de inte dödar eller hämmar bakterietillväxten, utan bara avväpnar bakterierna. Typ III sekretionssystemet är ett virulenssystem som finns i många gram-negativa bakterier, t.ex., Yersinia spp., Pseudomonas aeruginosa, Chlamydia spp., Salmonella spp., Shigella spp, enteropatogena Escherichia coli (EPEC) och Erwinia spp. Salicylidenacylhydraziderna är en substansklass virulensblockare som inhiberar typ III sekretionssystemet i de ovan nämnda bakterierna. I denna avhandling har vi designat och syntetiserat ett bibliotek med 58 salicylidenacylhydrazider och utvärderat deras biologiska aktivitet som virulensblockare i Y. pseudotuberculosis. Vi relaterade den biologiska aktiviteten till de kemiska egenskaperna hos salicylidenacylhydraziderna i kvantitativa strukturaktivitetssamband. Med hjälp av dessa samband kunde vi prediktera och validera aktiviteten till aktiv eller inaktiv för fem av åtta nya salicylidenacylhydrazider i Y. pseudotuberculosis och sex av åtta i C. trachomatis. Eftersom verkningsmekanismen för salicylidenacylhydraziderna var okänd, så syntetiserade vi tre olika affinitetsmolekyler med kombinerad lösnings- och fastfas-syntes. En av affinitetsmolekylerna användes sedan för att ”fiska ut” och identifiera 19 potentiella målproteiner i ett bakterielysat från E. coli. Fyra av dessa proteiner, TpX, WrbA, FolX och AdhE har vi studerat vidare i Y. pseudotuberculosis och E. coli. Utifrån resultaten tror vi att salicylidenacylhydraziderna interagerar med flera proteiner som tillsammans resulterar i en nedreglering av type III sekretionssystemen. Vår samarbetspartner, Andrew Roe och hans forskargrupp (Universitetet i Glasgow), har studerat AdhE i E. coli. De har visat att E. coli som saknar genen för proteinet AdhE, har samma fenotyp som E. coli behandlad med salicylidenacylhydraziderna, d.v.s. ett nedreglerat T3SS, vilket gör AdhE till ett speciellt intressant målprotein. I jämförelse med många av våra nuvarande antibiotika som har ett naturligt ursprung så är de flesta studerade virulensblockare små syntetiska organiska molekyler. Därför testades en stor kollektion av naturprodukter från marina och landlevande växter och invertebrater från Sydostasien, för att hitta nya inhibitorer mot typ III sekretionssystemet i Y. pseudotuberculosis. Neohopeaphenol A som kommer från barken på Hopea hainanensis, ett träd som växer i sydostasiens regnskogar, identifierades som en ny virulensblockare. Neohopeaphenol A visade sig vara en potent virulensblockare i in vitro infektionsförsök med Y. psudotuberkulosis eller Pseudomonas aeruginosa. Forskningen i denna avhandling visar att virulensblockare kan hjälpa oss att förstå hur bakterier orsakar sjukdom. Förhoppningsvis kan det i framtiden leda till nya typer av läkemedel mot infektionssjukdomar.
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Jacobo-Herrera, Nadia Judith. "Anti-inflammatory properties and bioactive natural products from Witheringia solanacea, Withania frutescens (Solanaceae) and Valeriana officinalis (Valerianaceae) using NF-kappa as a molecular target." Thesis, University College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.420313.
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Melo, Reymard Savio Sampaio de 1983. "Guidelines for target costing introduction in the real estate products development proces = Diretrizes para introdução do custeio-meta no processo de desenvolvimento de produtos imobiliários." [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/258729.
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Orientador: Ariovaldo Denis GranjaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Civil, Arquitetura e Urbanismo
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Resumo: Os problemas relacionados com a prática tradicional de redução de custos na construção civil e a necessidade de aumentar a competitividade de empresas do setor de real estate nortearam essa pesquisa. Neste sentido, o custeio-meta é uma abordagem promissora para melhorar a competitividade de empresas garantindo que os produtos lançados no mercado não comprometam a margem de lucro da empresa nem a entrega de valor para os clientes. No entanto, há uma escassez de pesquisas visando apoiar as organizações do setor imobiliário que desejam implementar de forma gradual os princípios do custeio-meta no processo de desenvolvimento de produtos imobiliários destinados à venda. Diante disso, o principal objetivo da pesquisa foi propor diretrizes para introdução do custeio-meta no processo de desenvolvimento de produtos imobiliários destinados à venda. A design science foi o método de pesquisa utilizado. A pesquisa foi dividida em três fases: incubação da solução, refinamento da solução e explanação. As diretrizes propostas estão relacionadas as três principais seções do processo do custeio-meta: custeio orientado ao mercado, custeio-meta no nível de produto e custeio-meta no nível de componente.
Abstract: The problems associated with the traditional practice of reducing costs in construction and the need to increase business competitiveness in the real estate sector guided this research. In this sense, the target costing is a promising approach to improving the competitiveness of companies by ensuring that products launched on the market do not jeopardize the company's profit margin or the value delivery to customers. However, there is little research to support the real estate industry organizations wishing to implement gradually the target costing principles in real estate product development process. Thus, the main objective of the research was to propose guidelines for introduction of target costing in the real estate products development process. Design science was the research method applied. The research was divided into three phases: solution incubation, solution refinement and explanation. The proposed guidelines are related to the three main sections of target costing process: market-driven costing, product-level target costing and component-level target costing
Doutorado
Doutor em Engenharia Civil
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Cockroft, Nicholas T. "Applications of Cheminformatics for the Analysis of Proteolysis Targeting Chimeras and the Development of Natural Product Computational Target Fishing Models." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu156596730476322.
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Lambert, Claire. "Young children's fast food brand knowledge, preference and equity." University of Western Australia. Faculty of Economics and Commerce, 2009. http://theses.library.uwa.edu.au/adt-WU2009.0116.
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Today's children are a multi-billion dollar consumer market that not only has the power to spend their own money but directly influences the spending for household consumer purchases. They present an extremely healthy and potentially long term wealthy consumer market for marketers to target and reap the benefits from their loyalty. However, the area of young children's consumer behaviour is significantly under researched. Very little is known about how young children develop preferences, make brand choices, and develop equity towards a brand. This study investigates the brand knowledge elements associated with brand preference and brand equity for young children. An experimental procedure was employed utilising personal interviews and collecting data from five Australian Day Care facilities and four Australian Community Pre-school Centres. The respondents were three and four year old children, who performed a game involving questions about fast food brands. The hypotheses explored various aspects of brand knowledge (e.g., brand awareness) and, their influence on the child's initial preference between fast food choices (brand preference), and their loyalty when tempted by a toy and their second choice (brand equity). The study's analysis was divided into two parts. The first part determined whether there were any significant differences evident between three and four year old children in relation to the effect of brand awareness, affect toward, and brand image in brand preference and brand equity using chi-square analyses. The second part of the analysis employed binary logistic regression analyses to determine which elements of brand knowledge influenced a child's brand preference and brand equity regarding fast foods. 2 The study found there were no major differences between a three year old and a four year old in relation to the influences of brand awareness, affect toward, and brand image in brand preference or brand equity. The binary logistic regression analysis found that brand images provided the greatest effect in explaining and predicting brand preference and provided a contributing influence in brand equity. Brand awareness was found to provide the second greatest effect on brand preference and the greatest effect on brand equity, and affect towards the brand or main menu item provided the least amount of effect in explaining and predicting brand preference and brand equity for 3 and 4 year old children. The research also comments on the use of a toy as a marketing tool to lure children to a brand and provides suggestions for future research. Marketing, managerial and public policy implications are also provided.
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Brown, Dustin Paul. "TARGET-DIRECTED BIOSYNTHETIC EVOLUTION: REDIRECTING PLANT EVOLUTION TO GENOMICALLY OPTIMIZE A PLANT’S PHARMACOLOGICAL PROFILE." UKnowledge, 2015. http://uknowledge.uky.edu/neurobio_etds/13.
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The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity at this therapeutic target, i.e. the human DAT. This was achieved by expressing the human DAT protein in transgenic plant cells and selecting gain-of-function mutants for survival on medium containing a neurotoxin that is accumulated by the human DAT. This created a sub-population of mutants with increased DAT inhibitory activity. Some of the active metabolites in these mutants are novel (i.e. not detectable in wild-type cells). Others are cytoprotective, and also protect DAergic neurons against the neurotoxin. This provides proof-of-concept for a novel plant drug discovery platform, which is applicable to many different therapeutic target proteins and plant species.
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Peterson, Denis Desmond. "An analysis of financial literacy in the target market of a state–owned bank / Peterson D.D." Thesis, North-West University, 2011. http://hdl.handle.net/10394/8167.
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The South African Postbank Limited has been tasked by Government with a social mandate to provide basic financial services to people receiving low income and people living in rural areas. Personal financial literacy is an essential element which affects financial inclusion in the target market of a state–owned bank. To achieve the bank?s social mandate and its objective, it would be vital to determine whether people in low income and rural demographics are financially literate. Financial literacy is defined as the ability to manage your money on a day–to–day basis, do future financial planning, choose sound financial products and have appropriate financial knowledge and understanding. Various factors influence the level of financial literacy of a person and in order to improve the financial literacy of a person, cognisance should be taken of that person?s age, gender, living conditions, income–level and socio–economic elements. It will be beneficial for a state–owned bank, in order to reach its social mandate, to implement financial educational programmes to increase financial literacy. The latter will increase the amount of potential customers and thus promote financial inclusion in the long run. The sample in low income and rural areas has been found to be the most wanting in financial literacy and therefore it is crucial to address this shortcoming in the target market of the state–owned bank in order to reach the social mandate of financial inclusion.Thesis (M.B.A.)--North-West University, Potchefstroom Campus, 2012.
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Osburg, Victoria-Sophie [Verfasser], Waldemar [Akademischer Betreuer] Toporowski, Lutz M. [Akademischer Betreuer] Kolbe, and Margarete [Akademischer Betreuer] Boos. "Products consisting of materials based on renewable resources: Drivers of purchase intention, consumers' information needs and target groups / Victoria-Sophie Osburg. Gutachter: Waldemar Toporowski ; Lutz M. Kolbe ; Margarete Boos. Betreuer: Waldemar Toporowski." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2015. http://d-nb.info/1071713507/34.
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King, Larrie Leon Jr. "Private Labels and Personal Care: A Focus on Store Brand Package Design, Branding Design and Consumer Attitudes Towards Private Label Personal Care Products." Kent State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=kent1400330956.
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Tavares, Ricardo Matos. "Plano de negócios para criação de loja online Kyuubit." Master's thesis, Instituto Superior de Economia e Gestão, 2018. http://hdl.handle.net/10400.5/16559.
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Mestrado em Ciências EmpresariaisO presente trabalho tem como objetivo a criação de um plano de negócios para a loja online, a Kyuubit, que dedica à venda de produtos relacionados com a cultura pop. A implementação de um plano de negócios irá sem dúvida contribuir para a obtenção de investidores para este projeto. E, neste caso, os investidores potenciais irão querer analisar o plano de negócios, bem como todas as medidas para chegar ao sucesso do investimento. A internet é uma rede pública aberta com infinitas oportunidades comerciais. O ambiente excitante do comércio eletrónico inclui um conjunto amplo de processos de interação entre os vários participantes do mercado. Uma típica transação de e-commerce consiste em fornecedores e consumidores que reúnem informação que lhes permita explorar potenciais parceiros de mercado para bens e serviços. O plano de negócios foi realizado utilizando uma junção das metodologias de Kuratko (2009) e Harvard (2007). Estas metodologias irão dar-nos todas as guidelines e informações chave necessárias para a realização do plano de negócios. Neste plano foram utilizadas informações sobre envolventes externas, estratégias financeiras e operacionais. Foram também efetuadas recolhas de dados, através da realização de um inquérito. Os resultados financeiros do projeto revelaram-se bastante positivos o que torna o projeto atrativo.
The present work aims at the creation of a business plan for the Kyuubit online store. The implementation of a business plan will undoubtedly contribute to the acquisition of investors in this sector. So being, potential investors will want to analyze the business plan as well as all the steps to make the investment a success. The internet is an open public network with unlimited business opportunities. The exciting environment of e-commerce includes a broad set of interaction processes among various market participants, such as order, shipping and delivery, mediation. A typical e-commerce transaction consisting of suppliers and consumers that gather information and exploit potential market partners for goods and services. The business plan was carried out based on the methodologies of Kuratko (2009) and Harvard (2007). Those methodologies will give us all the guidelines and orientations necessary to carry out the business plan. In this business plan, information was collected about external environment, financial and operational strategies. Data collection was also carried out by conducting surveys. The financial results of the project proved to be very positive, which makes the project attractive.
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Heydenreuter, Wolfgang [Verfasser], Stephan A. [Akademischer Betreuer] [Gutachter] Sieber, and Tobias A. M. [Gutachter] Gulder. "Target identification of natural products by activity based protein profiling and a whole proteome inventory of background photocrosslinker binding / Wolfgang Heydenreuter ; Gutachter: Tobias A. M. Gulder, Stephan A. Sieber ; Betreuer: Stephan A. Sieber." München : Universitätsbibliothek der TU München, 2016. http://d-nb.info/1137624582/34.
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Walldén, Marcus. "Shooting Target - Design : Product Development." Thesis, Högskolan i Halmstad, Sektionen för ekonomi och teknik (SET), 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:hh:diva-25887.
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The project has involved the development of two kinds of shooting targets in partnership with Marcus Bergkvist and Christopher Åkerblom. The project from the client was divided into two parts. This thesis discusses solutions for hands-on transport, development of tripods and an overall design. The second thesis affect resetting systems for the products. The work was done with a process and methodology based on design perspectives. This process has involved the search of relevant data which has provided the platform and opportunity for appropriate and purposeful design work. Concept development has been done using hand sketches and Photoshop, where a simple visualization of different concepts for the tripods has been produced. The next step relies on evaluating concepts in relation to the requirements and likings collected and the best concept has been chosen and developed. The design work was based primarily on work in SolidWorks to simultaneously maintain an ongoing partnership in the project, involving development of the resetting and design features. In this way, a link between design and construction has been active through the whole project. Where design at first took account for the changes made in the construction based developments. In this way, the products has been optimized and developed in a context where the design meets the construction to achieve the best results. Design developments that’s been done required an expression of keywords within the semantics and other design features. This has resulted in two products in terms of concepts and prototypes which were developed with help from clients and sponsors. The prototypes showed good results and has fulfilled the required specifications.
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Bergkvist, Marcus, and Christopher Åkerblom. "Shooting Target - Konstruktion : Product Development." Thesis, Högskolan i Halmstad, Maskinteknisk produktframtagning (MTEK), 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:hh:diva-25899.
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The shooting sport is one of the most widespread sports in the world and it is being practice in most countries. Based on their own experiences, in competition - and hobby shooting, the client M4Solutions found a demand and need for a shooting target that is manufactured in Sweden. The purpose of the project has been to develop, with the help of Marcus Walldén, two shooting targets from idea to finished product. These two shooting targets, Plate Rack Target and Dueling Tree, would each be equipped with a mechanical resetting system but will in the future have the ability to be provided with an electronic resetting system. The project from the client was divided into two theses. One of these two, written by Marcus Walldén, focused on the tripod parts and the overall design work for both Plate Rack Target and Dueling Tree. The thesis that is presented in this report have focused on resetting systems, the design of protective plates and other peripherals for both shooting targets. This work has primarily been in CAD environment where design, construction and development has been given free rein. Calculations, test shootings and choice of materials has been made in order to reach the best possible solutions. The thesis resulted in two complete 3D models and two full-scale prototypes of steel.
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Amara, Vamsee. "Target Costing for Product Redesigning." Master's thesis, Virginia Tech, 1998. http://hdl.handle.net/10919/37071.
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Increased competition and increased costs of designing made it important for the firms to identify the right products and the right methods for manufacturing the products. Firms should focus on customers and identify customer demands accurately to design the right products. Several management methods and techniques that are currently available improve one or more functions or processes in an industry and do not take the complete product life cycle into consideration. On the other hand target costing is a method / philosophy that takes financial, manufacturing and customer aspects into consideration during designing phase and helps firms in making product design decisions to increase the profit / value of the company. It uses various techniques to identify customer demands, to decrease costs of manufacturing and finally to achieve strategic goals. Target costing does not replace any technique that is currently in practice for product design. But it forms an integral part of total product design / redesign based on strategic plans. The current report details the process of target costing along with some associated techniques and applies the process to the designing of the Caterpillar's D10 tractor in the late 70sMaster of Engineering
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Бухкало, Светлана Ивановна, and Оксана Игоревна Ольховская. "Анализ возможностей комплексных технологий утилизации полимерной части твердых бытовых отходов." Thesis, Московский государственный университет дизайна и технологии, 2016. http://repository.kpi.kharkov.ua/handle/KhPI-Press/22983.
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Рассмотрены основные системы газификационных агрегатов большой единичной мощности. Выделены основные логистические факторы, влияющие на технологические схемы газификационных агрегатов такие, как природа, качество и состав газифицирующего сырья, номенклатура целевых продуктов, экологические требования по вредным выбросам и эмиссии парниковых газов, местоположение агрегата относительно крупных производственных комплексов, возможности конверсии отходов в полезные продукты.The basic heat exchangers networks of big gasification plants with entrained-flow fuel gasification are considered. The main logistical factors that influence on process of gasification plants are underlined such fs nature quality and components content of fuel to be gasified, range of target products, environmental legislation and demands including greenhouse gases emission, location relatively to big industrial sites, possibilities of wastes conversion into saleable products.
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Wallock-Richards, Daynea Juaneckah. "Natural products : biosynthesis, antimicrobial properties and protein targets." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/14188.
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The diversity of biosynthetic pathways in prokaryotes and eukaryotes has led to numerous bioactive natural products (NPs) which occupy a vast chemical space. Despite the current challenges in NP research, these molecules are still relevant today as they are a major source of human medicine as well as being useful biological tools. The elucidation of their biosynthetic pathways has also provided information about the biochemical and biophysical properties of fascinating enzyme families such as the α- oxoamine synthases (AOSs). The AOSs are an expanding group of pyridoxal 5’- phosphate (PLP)-dependent enzymes, which are involved in the biosynthesis of several important NP, including those essential for life. This study reports the characterization and structural analysis of a unique AOS denoted as TamD from Pseudoalteromonas tunicata. This enzyme plays a major role in tambjamine biosynthesis and consists of both an acyl carrier protein (ACP) domain and a PLP-binding catalytic domain. UV/vis spectroscopy and mass spectrometry (MS) of the recombinant TamD purified from E. coli revealed that the enzyme forms a Schiff base with PLP via Lys380, which is responsible for its characteristic yellow colour. It binds L-serine as a natural substrate with a Kd of 5.01 ± 0.64 mM. This thesis also reports structural data for TamD from xray crystallography at a resolution of 4.98 Å, which shows four molecules in the asymmetric unit (ASU) suggesting the enzyme exist as a dimer. The absence of the Nterminal region where the ACP domain is located in the crystal strucuture also suggests intrinsic flexibility and disorder within that region. With the increasing demand for new anti-infective therapies, investigations of the molecular interactions between NPs and their protein targets are vital in understanding the inhibition or activation properties of these molecules. The cysteine transpeptidases known as sortases produced by Gram positive bacteria have been identified as attractive targets for NP inhibitors. In this thesis, the molecular basis for the inhibition of Streptococcus mutans sortase A (SrtA) by the plant flavonoid, trans-chalcone is explored, using a combination of MS, enzyme kinetics, molecular modelling and x-ray crystallography. This study reports the first high resolution crystal structure of the H139A mutant of S. mutans SrtA, which reveals a unique N-terminal α-helix domain. Trans-chalcone was found to inhibit the in vitro activity of S. mutans SrtA in a slow, tight–binding manner, with a half maximal inhibitory concentration (IC50) of 5.0 ± 0.6 μM. The interaction resulted in a covalent adduct with the active site cysteine residue (Cys205) via a Michael addition mechanism. Additionally, trans-chalcone showed evidence of S. mutans anti-biofilm activity in a concentration dependent manner up to 250 μM with an efficacy cut-off point at higher concentations. These results indicate that chalcone flavonoids are worth further investigation as potential antibiofilm inhibitors. A renewed interest in plant NPs has also led to a collaborative investigation on the antimicrobial potential of garlic-derived allicin, against Burkholderia cepacia complex (Bcc), the major bacterial phytopathogen for alliums and an intrinsically multiresistant and life-threatening human pathogen. Allicin is the principal antibacterial agent in fresh preparations of garlic extracts. This investigation reports the first evidence that allicin and allicin-contaning garlic extracts possess inhibitory and bactericidal activities against Bcc. The minimum inhibitory concentrations (MICs) of aqueous garlic extract (AGE) against 38 Bcc isolates ranged from 0.5 to 3% (v/v). An investigation into the possible molecular mechanisms of allicin with a recombinant thiol-dependent peroxiredoxin (BCP) from B. cenocepacia revealed that allicin and AGE modify an essential BCP catalytic cysteine residue and suggests a role for allicin as a general electrophilic reagent that targets protein thiols. Present therapeutic options against these life-threatening pathogens are limited; thus, allicin-containing compounds merit further investigation as adjuncts to existing antibiotics.
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Gimeno-Fabra, Miquel. "Tailored continuous hydrothermal synthesis of targeted products." Thesis, University of Nottingham, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.716843.
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Continuous flow hydrothermal synthesis offers a cost-efficient, environmentally friendly and highly scalable route to produce a wide range of materials. Recent advances in reactor design at Nottingham have led to the development of a high-throughput, continuous flow synthesis (CFS) method that has already proven suitable for the controlled production of various inorganic micro- and nanomaterials, mainly metal oxide based particles. In this thesis, the scope of this technology has been widened to include materials never before produced using flow systems.
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Vieira, Henry Silva, and +55-92-98165-9404. "Recognition and Linking of Product Mentions in User-generated Contents." Universidade Federal do Amazonas, 2018. https://tede.ufam.edu.br/handle/tede/6686.
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CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
FAPEAM - Fundação de Amparo à Pesquisa do Estado do Amazonas
A mídia social online tornou-se uma parte essencial de nossa vida diária. Por meio dessas mídias, os usuários trocam informações que geram usando diversos mecanismos de comunicação. Nesse contexto, mais e mais usuários transmitem e confiam em informações publicadas por outros usuários sobre uma grande variedade de tópicos, incluindo opiniões e informações sobre produtos. A extração e o processamento automáticos de informações geradas pelo usuário nas mídias sociais podem fornecer informações e conhecimento relevantes para uma variedade de aplicativos interessantes. Em particular, uma das técnicas de análise de conteúdo mais aplicadas às mídias sociais é a de mineração de opinião. Uma das tarefas básicas associadas à mineração de opinião é extrair e categorizar as entidades de destino, ou seja, identificar as menções de entidade no texto e vincular essas menções de entidade a entidades do mundo real sobre as quais as opiniões são feitas. Em nosso trabalho, nos concentramos em entidades-alvo de um tipo específico e atualmente relevante: produtos eletrônicos de consumo. Tais produtos são o principal assunto de opiniões postadas pelos usuários em várias postagens em fóruns de discussão e sites de varejo na Web. Neste trabalho, estamos interessados em usar o conteúdo textual não estruturado gerado por usuários de mídia social para permitir continuamente enriquecer o conhecimento sobre produtos representados em catálogos de produtos. Portanto, a tarefa que abordamos aqui é como reconhecer e vincular menções a produtos em conteúdo textual gerado pelo usuário para o produto, de um catálogo, ao qual eles se referem. Afirmamos que duas sub-tarefas básicas surgem: primeiro, a extração de entidades alvo mencionada em conteúdo textual não-estruturado; segundo, a desambiguação de entidades extraídas, isto é, ligação menções extraídas à sua contraparte do mundo real. Neste trabalho, desenvolvemos métodos para abordar essas duas subtarefas. Esta tese detalha essas tarefas, discute nossas ideias para os métodos que desenvolvemos e apresenta nossas contribuições e resultados para esse objetivo.
Online social media has grown into an essential part of our daily life. Through these media, users exchange information that they generate by using many different communication mechanisms. In this context, more and more users pass on and trust information published by other users on a large variety of topics, including opinion and information about products. Automatically extracting and processing user-generated information in social media can provide relevant information and knowledge to a variety of interesting applications. In particular, one of the content analysis techniques most often applied to social media is that of opinion mining. One of the basic tasks associated with opinion mining is extracting and categorizing target entities, i.e., identifying entity mentions in text, and linking these entity mentions to unique real world entities about which the opinions are made. In our work, we focus on target entities of a specific, and currently relevant, type: consumer electronic products. Such products are the main subject of opinions posted by users on a number of posts in discussion forums and retail sites over the Web. In this work, we are interested in using the unstructured textual content generated by social media users to continuously allow enriching the knowledge about products represented in product catalogs. Therefore, the task we address here is how to recognize and link mentions to products in user generated textual content to the product, from a catalog, they refer to. We claim that two basic sub-tasks arise: first, extraction of target entities mentions from unstructured textual content; second, disambiguation of extracted entities, i.e., linking extracted mentions to their real world counterpart. In this work, we developed methods to address these two sub-tasks. This thesis details these tasks, discusses our ideas for the methods we developed, and presents our contributions and results towards this goal.
Não tive dificuldades, tudo funcionou corretamente.
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Hjortman, Robin, and Kristian Harrysson. "Driveline : Moving infantry target (MIT)." Thesis, Tekniska Högskolan, Högskolan i Jönköping, JTH, Maskinteknik, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-30695.
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This report is part of a bachelor thesis implemented at Saab training systems AB in Huskvarna. It treats the concept development of the driveline on Moving infantry target, MIT. Today Saab has a problem in the shape of that their customers uses the wrong moment when tightening the cog belt of the driveline. As a consequence the cog belt has a high risk of snapping if it is too tight or pluck off if it is too loose. Thereto the electrical motors used in the MIT has gone out of production. The task boiled down to produce a number of proposals that improves the chucking or driveline solution together with finding a new electrical motor to replace the outdated one. A concept study was made containing detailed examinations together with Saab. To answer the problems questions, several product development methods were used, like Quality function deployment and Pugh’s matrix, to reach a final concept. The last concepts were modeled in a 3D-program for an easier comparison between their feasibility. The chosen solution consisted of two motors that via a gearing actuates the respective axle. By replacing the belt drive and choosing more lubrication free gears the maintenance is expected to be improved. In addition the product price is lowered by careful choices of components. The production of a prototype could not be implemented due to lack of time.
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Andersson, Jan. "Development of PET radioligands synthesized from in-target produced [¹¹C] methane." Stockholm, 2010. http://diss.kib.ki.se/2010/978-91-7409-797-9/.
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Clulow, James. "Unravelling the targets of electrophilic natural products in cancer with chemical proteomics." Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/44878.
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Electrophilic natural products that are found in dietary sources such as curcumin, piperlongumine and sulforaphane have attracted considerable interest on account of their broad range of biological activities, leading to their assessment as therapeutics for a number of diseases. Despite extensive research, the mode of action and biological targets of these compounds remain poorly understood. These compounds are clearly not 'single target' molecules; dissecting their complex polypharmacology to determine the key targets and pathways presents a major challenge, and has limited progress in the clinic. In this study, a chemical proteomics approach using activity-based probes (ABPs) based on these small molecules has been applied to allow the profiling of their molecular targets in breast cancer cellular systems, identifying the range and relative importance of targets that these molecules bind to covalently, across the entire system in an unbiased way for the very first time. Hundreds of high confidence targets have been unravelled, providing the most comprehensive protein target set for curcumin, piperlongumine and sulforaphane to date. Translation of these targets to the mode(s) of action displayed by these compounds reveals new mediators that help to explain their anticancer effects. The previous limited target information has been a major hindrance in determining how best to apply such electrophilic natural products as therapeutics. These studies address this void and help to provide greater clarity into the underlying mechanisms of curcumin, piperlongumine and sulforaphane, as well as electrophilic natural products more generally.
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Akhbari, Mohammad Reza, and Eric Wennberg. "Target Costing i Large Cap : -." Thesis, Linnéuniversitetet, Ekonomihögskolan, ELNU, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-20379.
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Master Thesis G3 in Business Administration, Business School at Linnaeus University, Management Control, 4FE90E, Spring 2012 Authors: Mohammad Akhbari och Eric Wennberg Tutor: Jan Alpenberg Title: Target Costing in Large Cap Background and problem formulation: Since the 1980s, the product of the company has become increasingly important, because of increased competition and rapid technological development. To succeed in the Product development, “Target Costing” can be used as an important financial tool to calculate costs based on an established price and profit margin. Research shows that the method widely has been applied in Japan, but studies of the method’s prevalence in Sweden, however, are quite limited. Objectives: The purpose of this paper is to describe and analyze the Swedish companies applying “Target Costing” in their product development process. Furthermore, the study aims to analyze respondents’ dysfunctional, performance related, successfulness and dynamic experiences of the method. Finally, the intention is to interpret the correlation between the use and experiences of the method in relation to the corporate influential factors. The essay is limited to the companies listed on the “Large Cap” on the Stockholm Stock Exchange and engaged in activities related to product development. Theory: We have studied a variety of literature and articles that treat the Target Costing in its entirety within the product development processes. In our theoretical references one can find Ansari et al, Cooper, Robinson and several other researcher describing the implementation and performance factors of Target Costing. Method: The study is based on a quantitative survey carried out to 40 companies. The empirical data have been analyzed by theoretical studies and research in this area. Study findings and conclusions are finally discussed based on the thesis of reference. Conclusion: Target Costing is used by 22 of 32 companies on Large Cap, which amounts to 69 percent. The use is influenced by the factors; industrial type, sales orientation, profit margin, revenue and staff numbers. Correlations have also been established between their experiences and the factors mentioned above, where the sales approach excels.Examensarbete G3 i företagsekonomi, Ekonomihögskolan vid Linnéuniversitet, ekonomistyrning, 4FE90E, VT 2012 Författare: Mohammad Akhbari och Eric Wennberg Handledare: Jan Alpenberg Titel: Target Costing i Large Cap Bakgrund: Sedan 1980-talet har produktutveckling i företag blivit allt viktigare på grund av ökad internationell konkurrens samt en snabbare teknisk utveckling. För att lyckas i produktionsutvecklingen framställs ”Target Costing” som ett viktigt ekonomistyrningsmedel för att kalkylera kostnader utifrån ett fastslaget pris och vinstmarginal. Forskning visar på att metoden i stor utsträckning tillämpas i Japan, där studier kring metodens förekomst i Sverige däremot är tämligen begränsat. Syfte: Syftet med denna uppsats är att beskriva och analysera tillämpning av ”Target Costing” i produktutvecklingsprocess hos svenska börsbolag. Vidare syftar studien till att analysera respondenternas dysfunktionella, prestationsmässiga, framgångsmässiga och dynamiska erfarenheter kring metoden. Slutligen är avsikten att tolka samband mellan företagens användning och erfarenheter kring metoden gentemot företagens påverkande faktorer. Uppsatsen är begränsad till att omfatta börsbolag noterade vid ”Large Cap” på stockholmsbörsen och som bedriver verksamhet som innefattar produktutveckling. Referensram: Vi har studerat en mängd litteratur och artiklar som behandlar “Target Costing” i sin helhet inom produktutvecklingsprocessen. I våra teoretiska referenser återfinns bland annat Ansari et al, Cooper, Robinson, och flera andra forskare som beskriver implementering och prestationsfaktorer av ”Target Costing”. Metod: Studien baseras på en kvantitativ enkätundersökning som genomförts på 40 företag. Det empiriska materialet har analyserats efter teoretiska studier samt tidigare forskning på området. Studiens resultat och slutsatser har avslutningsvis diskuterats utifrån uppsatsens referensram. Slutsatser: Förekomst av ”Target Costing” i bolag på ”Large Cap”, uppgår till 69 procent. Användningen påverkas av följande faktorer: industrityp, försäljningsinriktning, vinstmarginal, omsättning och antalet anställda. Samband har även påvisats mellan företagens erfarenheter och ovanstående faktorer, där försäljningsinriktning utmärker sig.
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Kelley, Karen Corzine. "Gadolinium-148 and Other Spallation Production Cross Section Measurements for Accelerator Target Facilities." Diss., Georgia Institute of Technology, 2004. http://hdl.handle.net/1853/5143.
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At the Los Alamos Neutron Science Center accelerator complex, protons are accelerated
to 800 MeV and directed to two tungsten targets, Target 4 at the Weapons Neutron Research
facility and the 1L target at the Lujan Center. The Department of Energy requires hazard
classification analyses to be performed on these targets and places limits on certain radionuclide
inventories in the targets to avoid characterizing the facilities as nuclear facilities.
Gadolinium-148 is a radionuclide created from the spallation of tungsten. Allowed isotopic
inventories are particularly low for this isotope because it is an alpha-particle emitter with
a 75-year half-life. The activity level of Gadolinium-148 is low, but it encompasses almost
two-thirds of the total dose burden for the two tungsten targets based on present yield estimates.
From a hazard classification standpoint, this severely limits the lifetime of these
tungsten targets. The cross section is not well-established experimentally and this is the
motivation for measuring the Gadolinium-148 production cross section from tungsten.
In a series of experiments at the Weapons Neutron Research facility, Gadolinium-148
production was measured for 600- and 800-MeV protons on tungsten, tantalum, and gold.
These experiments used 3 m thin tungsten, tantalum, and gold foils and 10 m thin aluminum
activation foils. In addition, spallation yields were determined for many short-lived
and long-lived spallation products with these foils using gamma and alpha spectroscopy and
compared with predictions of the Los Alamos National Laboratory codes CEM2k+GEM2
and MCNPX.
The cumulative Gadolinium-148 production cross section measured from tantalum, tungsten,
and gold for incident 600-MeV protons were 15.24.0, 8.310.92, and 0.5910.155,
respectively. The average production cross sections measured at 800 MeV were 28.63.5,
19.41.8, and 3.690.50 for tantalum, tungsten, and gold, respectively. These cumulative
measurements compared best with Bertini and were within a factor of two to three of
CEM2k+GEM2.
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Laguecir, Aziza. "Pour une approche sémiologique de la dynamique du target costing : une application à l'industrie française." Université Louis Pasteur (Strasbourg) (1971-2008), 2004. http://www.theses.fr/2004STR1EC04.
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Ce travail porte sur la dynamique d'un outil de gestion du processus de conception et de développement de nouveau produits : le Target Costing. En premier lieu, cette recherche vise à renouveler la conception théorique du Target Costing (et des outils de gestion en général), en adoptant une approche sémiologique de celui-ci et du processus dans lequel il s'insère. Cette approche nous a permis de développer un modèle instrumental de la dynamique du Target Costing. En second lieu, ce modèle est mis à l'épreuve par une application à l'industrie française. Cette application repose sur une méthodologie de traitement originale en Sciences de Gestion : l'Analyse Quali-Quantitative Comparée. Ce type de méthodologie permet de combiner les caractéristiques des approches qualitatives et quantitativesThis research aims to study a Cost Management Tools, the Target Costing; and the process where it take place : the New Product Development Process, through a semiotical approach. This semiotical approach leads to develop an instrumental framework built on the distinction between instrument, tools and users. This framework is used to analyse to what extend individuals influence and determine the way the tools are used, that is to say the instrument. Based on this framework, an instrumental model of Target Costing dynamics is developed. An experimentation of this model has been done in the French system-based industry. This experimentation consists in an original treatment in the field of management sciences : the Q. C. A. (Qualitative Comparative Analysis). This treatment methodology allows to combine the advantages of both qualitative and quantitative methods
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Andino, Alexandra Elizabeth. "Price Risk Management Strategies for Virginia Dairy Producers." Master's thesis, Virginia Tech, 2004. http://hdl.handle.net/10919/37159.
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The 1996 and 2002 Farm Bill changes in milk support price legislation
deregulated the market and milk prices are more volatile than ever. The use of a
mechanism to reduce farmers' exposure to volatile milk prices has therefore become
essential. This study evaluates the impact of two hedging strategies, one conservative and
the other an intermediate one (more sophisticated). Optimal parameters for the two
strategies are searched over a period of 5 years. Then, the performance, in terms of
increased profitability and reduced variation, is assessed and the best performer is chosen
and applied to an out-of-sample dataset.
With the in-sample data, both strategies generate higher mean monthly profits than
with the no-hedging option. Comparison of both strategies indicates that the intermediate
strategy outperforms the conservative one in terms of higher profitability and lower
variance. Out-of-sample results confirm the findings of the in-sample results. The
additional profits and the reduction in volatility can make the difference between keeping
a farm profitable and bankruptcy.Master of Science
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Jezequel, Gwenaëlle. "Synthèse et pharmacomodulation de composés antitumoraux naturels à motif hexahydroxanthène." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS424.
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Les ORPphilins regroupent plusieurs familles de molécules naturelles, à forte activité cytotoxique qui présentent un mécanisme d'action original, en inhibant OSBP, une protéine responsable du transport intra-cellulaire du cholestérol. Cependant, elles sont toutes difficiles d’accès, que ce soit par extraction à partir des organismes dont elles sont issues ou par synthèse chimique.Les schweinfurthines (SWs), isolées de plantes du genre Macaranga, font partie de ces ORPphilins, et sont étudiées par notre équipe depuis plusieurs années. Lors de ces études, il a notamment été montré qu’un analogue non actif, mais bioprécurseur probable de ces SWs était présent en grande quantité dans ces plantes. Le premier objectif de cette thèse a été de faire l’hémisynthèse des SWs et d’analogues non naturels à partir de ce bioprécurseur.Les SWs sont particulièrement actives sur le glioblastome multiforme (GBM), qui est actuellement de très mauvais pronostic. Le traitement consiste aujourd’hui en une chirurgie suivie d’une radiothérapie combinée à une chimiothérapie utilisant le témozolomide (TMZ), un agent alkylant de l’ADN. De nombreuses résistances au TMZ se développent et les récidives sont fréquentes. Or, il a été montré qu’une molécule duale liant de manière covalente deux molécules anti-cancéreuses présentant un mode d’action complémentaire pouvait présenter une synergie d’effets. Le deuxième objectif de cette thèse a donc été de synthétiser et d’évaluer biologiquement différentes molécules duales SW-TMZ.Enfin, une nouvelle molécule de structure originale a été isolée et identifiée des plantes du genre Macaranga. Ce composé présente une activité cytotoxique sur le glioblastome similaire à celle des SWs, et a la même cible protéique que les ORPphilins. Le dernier volet de cette thèse a eu pour objet la synthèse totale de cette molécule, et d’analogues, leur évaluation biologique et la détermination de premières relations structure-activité sur cette nouvelle série chimique.En conclusion, les travaux menés au cours de cette thèse ont permis la synthèse de molécules cytotoxiques, naturelles ou inspirées de produits naturels, ciblant OSBP. Ces molécules pourront ultérieurement servir d’outils moléculaires pour mettre en lumière leur mécanisme d’action encore mal connus et identifier les liens entre transport du cholestérol et cancerORPphilins are a set of several families of natural molecules with strong cytotoxic activity, that have an original mechanism of action by inhibiting OSBP, a protein responsible for the intracellular transport of cholesterol. However, they are all difficult to access, either by extraction from the organisms from which they are derived or by chemical synthesis.Schweinfurthins (SWs), isolated from plants of the genus Macaranga, are part of these ORPphilins, and have been studied by our team for several years. In these studies, it was shown that a non-active but probable bioprecursor analogue of these SWs was present in large amounts in these plants. The first objective of this thesis was to hemisynthezise SWs, and non-natural analogues from this bioprecursor.SWs are particularly active on multiform glioblastoma, which is currently a very poor prognosis. Today, the treatment consists of surgery followed by radiotherapy combined with chemotherapy using temozolomide (TMZ), an alkylating agent of DNA. Many resistances to TMZ develop and recurrences are frequent. However, it has been shown that a dual molecule covalently binding two anti-cancer molecules with a complementary mode of action may present a synergy of effects. The second objective of this thesis was therefore to synthesize and biologically evaluate different SW-TMZ dual molecules.Finally, a new molecule with an original structure has been isolated and identified from plants of the genus Macaranga. This compound has cytotoxic activity on glioblastoma similar to that of SWs, and has the same protein target as ORPphilins. The last part of this thesis focused on the total synthesis of this molecule, and of analogues, their biological evaluation and the determination of the first structure-activity relationships on this new chemical series.In conclusion, the work carried out during this thesis made it possible to synthesize cytotoxic molecules that are either natural or inspired by natural products, targeting OSBP. These molecules can later be used as molecular tools to highlight their as yet poorly understood mechanism of action and identify the links between cholesterol transport and cancer
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Ellenberger, Urs. "X-ray diagnostics of laser-produced plasma in cylindrical and slab target geometry /." [S.l : s.n.], 1994. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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OLIVEIRA, INEZ C. de. "Recuperacao e purificacao do uranio utilizado em alvos para a producao de Mosup99." reponame:Repositório Institucional do IPEN, 1998. http://repositorio.ipen.br:8080/xmlui/handle/123456789/10688.
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Made available in DSpace on 2014-10-09T12:43:03Z (GMT). No. of bitstreams: 0Made available in DSpace on 2014-10-09T14:05:37Z (GMT). No. of bitstreams: 1 06178.pdf: 4301800 bytes, checksum: 8ef60a5fb58c4649ffd7c1a0c70dc421 (MD5)
Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP
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Alku, Jeton, and Judita Rashiti. "Target Costing i produktutvecklingsprocessen : En studie på Volvo Construction Equipment i Braås." Thesis, Linnéuniversitetet, Institutionen för ekonomistyrning och logistik (ELO), 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-40693.
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Bakgrund: Produktutvecklingsprocessen har på senare tid kommit att ses som en strategisk aktivitet som är avgörande för företagets överlevnad eftersom produktens utförande och kostnader till stor del fastställs innan tillverkning påbörjas. ”Target Costing” har sitt ursprung från Toyota i Japan och är en metod för strategisk kostnadsstyrning som har vuxit fram för att tidigt styra kostnader. Metoden används för att integrera kostnadsstyrning i produktutvecklingsprocessen i samstämmighet med kundkrav och företagets egna vinstkrav. Syfte: Syftet med studien är att beskriva och analysera hur ”Target Costing” används i produktutvecklingsprocessen på Volvo Construction Equipment i Braås för att ge kunskap till nya potentiella användare. Studien syftar även till att analysera ”Target Costing”-processen på Volvo CE för att identifiera utvecklingsmöjligheter. Ett bisyfte är att ge förbättringsförslag. Metodval: Data samlades in genom ostrukturerade och semi-strukturerade intervjuer, direkt observation samt dokumentation där intervjuer var den huvudsakliga informationskällan. Slutsatser: ”Target Costing” används som ett kostnadsreduceringsprogram på Volvo CE inom deras produktutvecklingsprocess i syfte att bibehålla sin konkurrenskraft och möta prispress från konkurrenter. ”Target Costing” används inte i enlighet med karaktärsdragen eftersom deras kostnadsreduceringsmål representerar kostnadsgapet och är deras utgångspunkt.Background: The product development process has recently come to be seen as a strategic activity that is critical to its survival since the product's performance and costs are largely fixed before production begins. Target Costing originates from Toyota in Japan and is a method of strategic cost management that has emerged for the early control costs. The method is used to integrate cost management in the product development process in concert with customer requirements and the company's own profit requirements. Purpose: The study aims to describe and analyze how target costing is used in the product development process at Volvo Construction Equipment in Braås to give knowledge to new potential users. The study also aims to analyze Target Costing process at Volvo CE to identify development opportunities. A secondary purpose is to provide suggestions for improvement. Methodology: Data were collected through unstructured and semi-structured interviews, direct observation, and documentation where interviews were the main source of information. Conclusion: Target Costing is used as a cost-reduction program at Volvo CE in their product development process in order to remain competitive and meet price pressure from competitors. Target Costing is not used in accordance with the characteristics because their objectives of cost-reduction represent the cost gap and is their starting point.
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Devenish, Sean. "Studies of natural product derivatives: targeted polymer drug conjugates." Thesis, University of Canterbury. Chemistry, 2004. http://hdl.handle.net/10092/6661.
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Polymer drug conjugates are an emerging class of therapeutic agent that offer advantages in the treatment of cancer through long circulation times and passive targeting. A further benefit of using a polymeric framework is that it readily allows attachment of targeting motifs to enhance the drug specificity, as well as allowing variation of the drug component. In this work a series of targeted polymer drug conjugates were prepared that incorporated different drugs via peptide linkers designed to be stable in circulation but degradable at the target site.
In order to ensure stability in circulation, it was necessary to ensure the drugs were conjugated to the biodegradable linkers via amides, which required the introduction of amine functionalities to the natural-product drugs. The required hemisyntheses were successfully carried out, although yields were sometimes disappointing.
An effort to allow an assessment of the pharmacokinetic effects of using a polymeric scaffold was made through the attempted synthesis of low molecular weight analogues of the polymer drug conjugates, with success in some cases.
A recently developed polymeric precursor was used in the preparation of the polymer drug conjugates but was found to undergo an unexpected side-reaction, which may prevent the long term development of this particular precursor. The desired conjugates were nonetheless successfully produced on a scale suitable for initial biological testing.
Both the high and low molecular weight constructs synthesised showed reduced cytotoxicities to P388 murine leukemia cells and are currently awaiting in vitro testing to truly evaluate their utility.
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Fung, Ying-Kit (Richard). "An intelligent hybrid model for customer requirements interpretation and product design targets determination." Thesis, Loughborough University, 1997. https://dspace.lboro.ac.uk/2134/7419.
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The transition of emphasis in business competition from a technology-led age to a market-oriented era has led to a rapid shift from the conventional "economy of scale" towards the "economy of scope" in contemporary manufacturing. Hence, it is necessary and essential to be able to respond to the dynamic market and customer requirements systematically and consistently. The central theme of this research is to rationalise and improve the conventional means of analysing and interpreting the linguistic and often imprecise customer requirements in order to identify the essential product features and determine their appropriate design targets dynamically and quantitatively through a series of well proven methodologies and techniques. The major objectives of this research are: a) To put forward a hybrid approach for decoding and processing the Voice of Customer (VoC) in order to interpret the specific customer requirements and market demands into definitive product design features, and b) To quantify the essential product design features with the appropriate technical target values for facilitating the downstream planning and control activities in delivering the products or services. These objectives would be accomplished through activities as follows: • Investigating and understanding the fundamental nature and variability of customer attributes (requirements); • Surveying and evaluating the contemporary approaches in handling customer attributes; • Proposing an original and generic hybrid model for categorising, prioritising and interpreting specific customer attributes into the relevant product attributes with tangible target values; • Developing a software system to facilitate the implementation of the proposed model; • Demonstrating the functions of the hybrid model through a practical case study. This research programme begins with a thorough overview of the roles, the changing emphasis and the dynamic characteristics of the contemporary customer demand with a view to gaining a better understanding on the fundamental nature and variability of customer attributes. It is followed by a review of a number of well proven tools and techniques including QFD, HoQ, Affinity Diagram and AHP etc. on their applicability and effectiveness in organising, analysing and responding to dynamic customer requirements. Finally, an intelligent hybrid model amalgamating a variety of these techniques and a fuzzy inference sub-system is proposed to handle the diverse, ever-changing and often imprecise VoC. The proposed hybrid model is subsequently demonstrated in a practical case study.
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Brown, Gary Robert. "Use of phenotypic target objectives in beef cattle crossbreeding strategies to increase uniformity in production and product." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0015/MQ55657.pdf.
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Cairo, Stefano. "The promyelocytic leukaemia gene product PML interacts with Myc and influences the expression of Myc target genes." Thesis, Open University, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406451.
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Kleyner, Andre V. "Determining optimal reliability targets through analysis of product validation cost and field warranty data." College Park, Md. : University of Maryland, 2005. http://hdl.handle.net/1903/3107.
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Thesis (Ph. D.) -- University of Maryland, College Park, 2005.Thesis research directed by: Mechanical Engineering. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.