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1
Songjang, Khemika. "Peptides to inhibit crop predation." Thesis, University of Reading, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.428155.
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Chen, Shao Ru. "Andrographolide analogues inhibit acute inflammation." Thesis, University of Macau, 2018. http://umaclib3.umac.mo/record=b3953265.
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Subramanian, Gayatri. "TDRD7, a Novel Viral Restriction Factor, Inhibits Cellular AMP-dependent Kinase to Inhibit Virus Replication." University of Toledo Health Science Campus / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=mco1596574176173965.
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Starks, Kenneth Maurice. "Novel pyridinium salts which inhibit acetylcholinesterase." Thesis, Georgia Institute of Technology, 1994. http://hdl.handle.net/1853/26950.
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Hasan, Jurjees. "Heparin oligosaccharides inhibit angiogenesis in vivo." Thesis, University of Manchester, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.488657.
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The prototypic heparan sulfate (HS)-dependent angiogenic cytokine is FGF-2. Here we present the first in vivo study of size fractionated heparin oligosaccharides in 3 models of angiogenesis that are progressively less dependent on FGF-2. We developed the modified hollow fibre assay, a novel model for quantifying angiogenesis in vivo. We tested the ability of size defined oligosaccharides (dp 6-14) to inhibit FGF-2 in a sponge model of angiogenesis, where the process can be driven by a defined angiogenic molecule. Sponges were implanted subcutaneously and injected with FGF2 100 ng/day and oligosaccharides (20 mglkg/day). After 14 days the sponges were excised and the microvessel density (MVD) measured. Octasaccharides were the most potent species, reducing MVD to levels below those observed in saline treated implants. In a second experiment HEC-FGF2 human endometrial cancer cells that over-express FGF-2 were implanted in a hollow fibre placed subcutaneously in vivo. Oligosaccharides were administered at 20 mglkg/day for 2 weeks and the data again showed that octasaccharides significantly reduced MVD around the fiber. In a more complex model, where angiogenesis was induced by a broad spectrum of growth factors including VEGF, we implanted H460 lung carcinoma cells in hollow fibers and treated the animals with oligosaccharides at 20mglkg/day over three weeks. The data showed that octasaccharides were able to reduce the microvessel density to the level of angiogenesis present in empty hollow fibres. Preliminary investigation of 6-0-desulfated heparins showed that these also had anti-angiogenic activity. In summary, we have shown that heparin octasaccharides have antiangiogenic activity in vivo in several models of variable dependence on FGF-2. We have now embarked on a synthetic programme to produce and investigate oligosaccharides with predefined sulfation patterns and cytokine specificities as FGF inhibitors.
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Yuceer, Buse, Devin Narwani, and Sean Fox. "Does Alcaligenes inhibit other Staphylococcal species?" Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/157.
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Members of the Staphylococcus genus are a major health issue in the clinical environment and can cause a wide range of disease in humans. However, this genus is also found as a part of the normal flora in humans, usually on the skin, nasal cavities, or on the linings of the throat. Normal flora members of the Staphylococcus genus become an opportunistic infection when there is breach in the physical barriers or the immune status of the human host. Another challenge with the Staphylococcus genus is the increase in drug resistant strains, such as Methicillin resistant Staphylococcus aureus (MRSA), making simple infections difficult to treat and leading to severe toxic shock or even death. Recently, there have been numerous studies demonstrating normal flora bacterial interactions inhibiting bacteria that are potentially harmful to humans. Our research lab has previously demonstrated that the benign bacterium Alcaligenes faecalis has inhibitory effects against Staphylococcus aureus. In the present study, we wanted to explore: 1) if the inhibitory effect of A. faecalis would translate to other Staphylococcus species (S. capitis, S. saprophyticus, and S. epidermidis); 2) if this inhibitory effect was found in other Alcaligenes species (A. viscolactis). To determine this possible interactions, two parallel experimental projects were undertaken. A. faecalis and A. viscolactis were tested for their interactions with Staphylococcus species on both agar and liquid medium. For agar medium analysis, Staphylococcus lawns were grown on agar plates and either Alcaligenes cells, heat killed Alcaligenes, or Alcaligenes cell free supernatant were spotted onto the lawns and observed and scored for zones of inhibition (ZOI). It was demonstrated live cells of both A. faecalis and A. viscolactis were needed to produce ZOI on Staphylococcus lawns and that all Staphylococcus species were inhibited. For liquid medium analysis, Staphylococcus species were either inoculated alone (control) or in a co-culture with Alcaligenes, serially diluted, and colony forming units (CFU) were enumerated. Both A. faecalis and A. viscolactis inhibited all Staphylococcus species in liquid culture. Based on the results from these experiments, it is our conclusion that: 1) Alcaligenes faecalis and Alcaligenes viscolactis both possess the ability to inhibit Staphylococcus growth; 2) all Staphylococcus species are inhibited by Alcaligenes, but at varying levels. The exact mechanism of how Alcaligenes can inhibit Staphylococcus species is unknown, which will require further studies to analyze and understand the exact mechanism in order to create effective therapeutic targets to combat these increasingly resistant strains of Staphylococcus.
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Podugu, Sireesha P. Ferrari Michael B. "Long duration calcium transients inhibit sarcomere assembly." Diss., UMK access, 2006.
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Thesis (M.S.)--School of Biological Sciences. University of Missouri--Kansas City, 2006."A thesis in cellular and molecular biology." Typescript. Advisor: Michael B. Ferrari. Title from "catalog record" of the print edition Description based on contents viewed Nov. 1, 2007. Includes bibliographical references (leaves 48-52). Online version of the print edition.
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Gopakumar, Bhaskaran Nair. "Molecular strategies to inhibit vein graft disease." Thesis, University of Leeds, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426787.
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Hofmann, Ronald. "Using ammonia to inhibit bromate formation during ozonation." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0019/NQ53686.pdf.
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Pridham, Kevin James. "Investigating Novel Targets to Inhibit Cancer Cell Survival." Diss., Virginia Tech, 2004. http://hdl.handle.net/10919/82855.
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Cancer remains the second leading cause of death in the United States and the world, despite years of research and the development of different treatments. One reason for this is cancer cells are able to survive through adaptation to their environment and aberrantly activated growth signaling. As such, developing new therapies that overcome these hurdles are necessary to combat cancer. Previous work in our laboratory using RNA interference screening identified genes that regulate the survival of glioblastoma (GBM) or autophagy in chronic myelogenous leukemia (CML) cancer cells. One screen identified Phosphatidylinositol-4,5-bisophosphate 3-kinase catalytic subunit beta (PIK3CB) in the family of Phosphatidylinositol 3-kinases (PI3K) as a survival kinase gene in GBM. Work contained in this dissertation set out to study PIK3CB mediated GBM cell survival. We report that only PIK3CB, in its family of other PI3K genes, is a biomarker for GBM recurrence and is selectively important for GBM cell survival. Another screen identified the long non-coding RNA, Linc00467, as a gene that regulates autophagy in CML. Autophagy is a dynamic survival process used by all cells, benign and cancerous, where cellular components are broken down and re-assimilated to sustain survival. Work contained in this dissertation set out to characterize the role that Linc00467 serves in regulating autophagy in a myriad of cancers. Collectively our data have showed Linc00467 to actively repress levels of autophagy in cancer cells. Further, our data revealed an important role for Linc00467 in regulating the stability of the autophagy regulating protein serine-threonine kinase 11 (STK11). Because of the unique role that Linc00467 serves in regulating autophagy we renamed it as, autophagy regulating long intergenic noncoding RNA or ARLINC. Taken together the work in this dissertation unveils the inner-workings of two important cancer cell survival pathways and shows their potential for development into therapeutic targets to treat cancer.Ph. D.
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Bonsignore, Lindsay Ann. "SURFACE CONTAMINANTS INHIBIT THE OSSEOINTEGRATION OF ORTHOPAEDIC IMPLANTS." Case Western Reserve University School of Graduate Studies / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=case1341323221.
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Pridham, Kevin J. "Investigating Novel Targets to Inhibit Cancer Cell Survival." Diss., Virginia Tech, 2018. http://hdl.handle.net/10919/82855.
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Cancer remains the second leading cause of death in the United States and the world, despite years of research and the development of different treatments. One reason for this is cancer cells are able to survive through adaptation to their environment and aberrantly activated growth signaling. As such, developing new therapies that overcome these hurdles are necessary to combat cancer. Previous work in our laboratory using RNA interference screening identified genes that regulate the survival of glioblastoma (GBM) or autophagy in chronic myelogenous leukemia (CML) cancer cells. One screen identified Phosphatidylinositol-4,5-bisophosphate 3-kinase catalytic subunit beta (PIK3CB) in the family of Phosphatidylinositol 3-kinases (PI3K) as a survival kinase gene in GBM. Work contained in this dissertation set out to study PIK3CB mediated GBM cell survival. We report that only PIK3CB, in its family of other PI3K genes, is a biomarker for GBM recurrence and is selectively important for GBM cell survival. Another screen identified the long non-coding RNA, Linc00467, as a gene that regulates autophagy in CML. Autophagy is a dynamic survival process used by all cells, benign and cancerous, where cellular components are broken down and re-assimilated to sustain survival. Work contained in this dissertation set out to characterize the role that Linc00467 serves in regulating autophagy in a myriad of cancers. Collectively our data have showed Linc00467 to actively repress levels of autophagy in cancer cells. Further, our data revealed an important role for Linc00467 in regulating the stability of the autophagy regulating protein serine-threonine kinase 11 (STK11). Because of the unique role that Linc00467 serves in regulating autophagy we renamed it as, autophagy regulating long intergenic noncoding RNA or ARLINC. Taken together the work in this dissertation unveils the inner-workings of two important cancer cell survival pathways and shows their potential for development into therapeutic targets to treat cancer.Ph. D.
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Fowell, Andrew. "The investigation of strategies to inhibit liver fibrosis by targeting tissue inhibitor of metalloproteinases with RNA interference." Thesis, University of Southampton, 2010. https://eprints.soton.ac.uk/362765/.
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Current evidence suggests that tissue inhibitor of metalloproteinase (TIMP)-l and -2 are expressed by hepatic stellate cells (HSC during the course of their activation to a profibrotic myofibroblastic phenotype and play an important role in liver fibrogenesis. Therefore, inhibition of these key molecules represents an attractive strategy for treatment of liver fibrosis. RNA interference (RNAi) is a naturally occurring cellular mechanism involving sequence-dependent silencing of target gene expression througn degradation of messenger RNA {m RNA). Evidence has rapidly emerged that components of this native mechanism such as short interfering RNA (siRNA) and microRNA (miRNA) may be harnessed therapeutically. It was hypothesised that inhibition of hepatic stellate cell TIMP-l and -2 expression by RNA interference has an antifibrotic: effect both in vitro and in vivo. The aims of the study were to: i) Identify siRNA which effectively silence TlMP-l and -2 expression in rat activated HSC; ii) Examine the effect of TIMP silendng on HSC phenotype, in particular apoptosis and proliferation; Hi) Investigate the role of endogenous RNA intenernce acting via miRNA in the regulation of TIMP-l and -2 expression by HSC; iv} Using an acute liver injury model, establish a clinically relevant means of delivering siRNA l miRNA which effectively silences TIMP-l in vivo and if successful, apply this to a chronic model of liver fibrosis and recovery. Culture activated primary rat HSC were transfected with TIMp·1 and 2siRNA by elec.tloporal.ion and target mRNA and protein expression .determined. The effect of TIMP silencing on HSC MMP-2 inhibition, proliferation and apoptosis was examined. Global miRNA expression during MSC activation was examined and "the potential role of candidate miRNAs in HSC TIMP expression. proliferation and apoptosis studied by miRNA overexpression and inhibition. Finally, the efficacy of TIMP-l siRHA was tested in vivo using peripheral liposomal delivery in a ca~ model of acute liver injury TIMP-l and -2 siRNA elec:rroporation were highly effective means of silencing HSC llMP expression in vitro. Silencing ofllMP-l or -2 removed a functional MMP suppressive effect in HSC cultures but did not affect HSC apoptosis in response to serum·deprivation. TIMP-l silencing inhibid HSC pro1iferation and was associated with reduced Akt phosphorylation, suggesting an autocrine role for TIMP· 1 in enhancing proliferation in fibrosis. activation of rat HSC was accompanied by marked up- and down-regulation of multiple miRNAs miR-143 was markedly unregulated with HSC activation and functional studies Suggested a profibrotic role for this miRNA in HSC Acute CCI, injury in rats increased hepatic TIMP-l expression but this was not attenuated byllMP-l siRNA delivered peripherany under normal pressures using a liposomal vector., perhaps due to preferential uptake by resident liver macrophages. In conclusion, these data shed new light on the role of TIMP-I and of miRNAs in HSC function. The efficacy of a siRNA-mediated anti-TIMP-l strategy has been shown in vitro, although the mechanisms of efficient delivery of reagents capable of targeting hepatic TIMP-l expression in vivo await further elucidation.
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Maciejewski, Mateusz. "Structure and dynamics of proteins that inhibit complement activation." Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/8245.
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NMR studies have long been used as a tool to derive structural and dynamic information. Such information has a wide range of applications, and notably is used in the study of structure-activity relationships. The aims of this work were to use NMR spectroscopy to derive structures of the molecules inhibiting the activation of the alternative pathway of the complement portion of the innate immune system (namely, the N-terminus of factor H (FH) and two small peptides, Compstatin 10 and Compstatin 20) and to consider the interdomain dynamics of proteins consisting of three modules theoretically (in silico) and experimentally (for the three N-terminal domains of FH). We focused on the three N-terminal complement control protein (CCP) domains of the important complement regulator, human factor H (i.e. FH1-3). Its three-dimensional solution structure was derived based on nuclear Overhauser effects and residual dipolar couplings (RDCs). Each of the three CCP modules in this structure was similar to the corresponding CCP in the previously derived C3b-bound structure of FH1-4, but the relative orientations of the domains were different. These orientations were additionally different from the interdomain orientations in other molecules that interact with C3b, such as DAF2-4 and CR1-15-17. The measured RDC datasets, collected under three different conditions in media containing magnetically aligned bicelles (disk-like particles formed from phospholipids), were used to estimate interdomain motions in FH1-3. A method in which the data was fitted to a structural ensemble was used to analyze such interdomain flexibility. More than 80% of the conformers of this predominantly extended three-domain molecule exhibit flexions of < 40°. Such segmental flexibility (together with the local dynamics of the hypervariable loop within domain 3) could facilitate recognition of C3b via initial anchoring, as well as eventual reorganization of modules into the conformation captured in the previously solved crystal structure of a C3b complex with FH1-4. The NMR study of the Compstatin analogues revealed unique structural features that had not before been observed in this group of peptides. These features included two b-turns per peptide, neither of which was located in the ‘canonical’ regions in which b-turns were observed in previous molecular dynamics and NMR studies. The structures of Compstatin 10 and Compstatin 20 derived here were consistent with the isothermal calorimetry (ITC) and surface plasmon resonance (SPR) data recorded previously. In the in silico study of interdomain motion of three-domain proteins carried out here, the domains were represented as vectors attached to one another in a linear fashion. They were allowed to undergo Brownian motion biased by the potentials between the sequential vectors. The resulting trajectories were analyzed using model-free and extended model-free formalism. The degree of coupling of the interdomain motion with overall motion was determined, along with a representation of the overall motion. The similarity between the trajectories of the vectors transformed to this overall motion frame and the results obtained from the model-free analysis was determined.
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Nickson, Catherine Marie. "Development of polymer coating to inhibit in-stent restenosis." Thesis, University of Liverpool, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.540029.
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Kaminski, John J. III. "Suppressive Oligodeoxynucleotides Inhibit Cytosolic DNA Sensing Pathways: A Dissertation." eScholarship@UMMS, 2013. https://escholarship.umassmed.edu/gsbs_diss/669.
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The innate immune system provides an essential first line of defense against infection. Innate immune cells detect pathogens through several classes of Pattern Recognition Receptors (PRR) allowing rapid response to a broad spectrum of infectious agents. Activated receptors initiate signaling cascades that lead to the production of cytokines, chemokines and type I interferons all of which are vital for controlling pathogen load and coordinating the adaptive immune response. Detection of nucleic acids by the innate immune system has emerged as a mechanism by which infection is recognized. Recognition of DNA is complex, influenced by sequence, structure, covalent modification and subcellular localization.
Interestingly certain synthetic oligodeoxynucleotides comprised of the TTAGGG motif inhibit proinflammatory responses in a variety of disease models. These suppressive oligodeoxynucleotides (sup ODN) have been shown to directly block TLR9 signaling as well as prevent STAT1 and STAT4 phosphorylation. Recently AIM2 has been shown to engage ASC and assemble an inflammasome complex leading to the caspase-1-dependent maturation of IL-1β and IL-18. The AIM2 inflammasome is activated in response to cytosolic dsDNA and plays an important role in controlling replication of murine cytomegalovirus (MCMV). In the second chapter of this thesis, a novel role for the sup ODN A151 in inhibiting cytosolic nucleic acid sensing pathways is described. Treatment of dendritic cells and macrophages with the A151 abrogated type I IFN, TNF-α and ISG induction in response to cytosolic dsDNA. A151 also reduced INF-β and TNF-α induction in BMDC and BMDM responding to the herpesviruses HSV-1 and MCMV but had no effect on the responses to LPS or Sendai virus. In addition, A151 abrogated caspase-1-dependent IL-1β and IL-18 maturation in dendritic cells stimulated with dsDNA and MCMV. Although inhibition of interferon-inducing pathways and inflammasome assembly was dependent on backbone composition, sequence differentially affected these pathways. While A151 more potently suppressed the AIM2 inflammasome, a related construct C151, proved to be a more potent inhibitor of interferon induction. A151 suppressed inflammasome signaling by binding to AIM2 and competing with immune-stimulatory DNA. The interaction of A151 and AIM2 prevented recruitment of the adapter ASC and assembly of the macromolecular inflammasome complex. Collectively, these findings reveal a new route by which suppressive ODNs modulate the immune system and unveil novel applications for suppressive ODNs in the treatment of infectious and autoimmune diseases.
The innate immune response to HSV-1 infection is critical for controlling early viral replication and coordinating the adaptive immune response. The cytokines IL-1β and IL-18 are important effector molecules in the innate response to HSV-1 in vivo. However, the PRRs responsible for the production and maturation of these cytokines have not been fully defined. In the third chapter of this thesis, The TLR2-MyD88 pathway is shown to be essential for the induction of pro-IL-1β transcription in dendritic cells and macrophages responding to HSV-1. The HSV-1 immediate-early protein ICP0 has previously been shown to block TLR2 responses and in keeping with this finding, ICP0 blocked pro-IL-1β expression. Following translation, pro-IL-1β exists as an inactive precursor that must be proteolytically cleaved by a multiprotein complex known as the inflammasome to yield its active form. Inflammasomes are composed of cytoplasmic receptors such as NLRP3 or AIM2, the adapter molecule ASC, and pro-caspase-1. In the present study we found that the NLRP3 inflammasome is important for maturation of IL-1β in macrophages and dendritic cells responding to HSV-1. In contrast the related NLRP12 protein controls IL-1β production in neutrophils. These data indicate that sensing of HSV-1 by TLR2 drives pro-IL-1β transcription and infection activates the inflammasome to mature this cytokine. Moreover, these studies reveal cell type-specific roles for NLRP3 and NLRP12 in inflammasome assembly.
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Cavaleiro, Eliana Marisa dos Santos. "Development of polymeric materials to inhibit bacterial quorum sensing." Doctoral thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/14887.
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Doutoramento em BiologiaBacterial infections are an increasing problem for human health. In fact, an increasing number of infections are caused by bacteria that are resistant to most antibiotics and their combinations. Therefore, the scientific community is currently searching for new solutions to fight bacteria and infectious diseases, without promoting antimicrobial resistance. One of the most promising strategies is the disruption or attenuation of bacterial Quorum Sensing (QS), a refined system that bacteria use to communicate. In a QS event, bacteria produce and release specific small chemicals, signal molecules - autoinducers (AIs) - into the environment. At the same time that bacterial population grows, the concentration of AIs in the bacterial environment increases. When a threshold concentration of AIs is reached, bacterial cells respond to it by altering their gene expression profile. AIs regulate gene expression as a function of cell population density. Phenotypes mediated by QS (QSphenotypes) include virulence factors, toxin production, antibiotic resistance and biofilm formation. In this work, two polymeric materials (linear polymers and molecularly imprinted nanoparticles) were developed and their ability to attenuate QS was evaluated. Both types of polymers should to be able to adsorb bacterial signal molecules, limiting their availability in the extracellular environment, with expected disruption of QS. Linear polymers were composed by one of two monomers (itaconic acid and methacrylic acid), which are known to possess strong interactions with the bacterial signal molecules. Molecularly imprinted polymer nanoparticles (MIP NPs) are particles with recognition capabilities for the analyte of interest. This ability is attained by including the target analyte at the synthesis stage. Vibrio fischeri and Aeromonas hydrophila were used as model species for the study. Both the linear polymers and MIP NPs, tested free in solutions and coated to surfaces, showed ability to disrupt QS by decreasing bioluminescence of V. fischeri and biofilm formation of A. hydrophila. No significant effect on bacterial growth was detected. The cytotoxicity of the two types of polymers to a fibroblast-like cell line (Vero cells) was also tested in order to evaluate their safety. The results showed that both the linear polymers and MIP NPs were not cytotoxic in the testing conditions. In conclusion, the results reported in this thesis, show that the polymers developed are a promising strategy to disrupt QS and reduce bacterial infection and resistance. In addition, due to their low toxicity, solubility and easy integration by surface coating, the polymers have potential for applications in scenarios where bacterial infection is a problem: medicine, pharmaceutical, food industry and in agriculture or aquaculture.
Infeções bacterianas são um problema recorrente para a saúde pública. A maioria das infeções bacterianas tem aumentado devido ao facto das bactérias se tornarem resistentes aos antibióticos. A procura de estratégias para combater este facto, sem promover a resistência antimicrobiana, tem sido incessante. A atenuação ou até mesmo a disrupção do Quorum Sensing (QS), é uma estratégia promissora para enfrentar este problema. QS é um sistema de comunicação bacteriana, onde há produção e libertação de moléculas sinais específicas, denominadas de Auto Indutores (AIs) para o ambiente. Á medida que a população bacteriana aumenta, aumenta também a concentração de moléculas sinais no ambiente. Quando a concentração destas moléculas atinge um certo limite, há uma alteração a nível da expressão genética. A expressão de determinados genes relacionados com fatores de virulência, produção de toxinas, resistência a antibióticos e formação de biofilmes é intrinsecamente relacionada com QS. Neste estudo foram desenvolvidos dois tipos de polímeros (polímeros lineares e nanopartículas impressas molecularmente) com capacidade para atenuar QS. Ambos os polímeros têm como finalidade a absorção e consequente remoção de moléculas sinais do ambiente, com consequente disrupção de QS. Os polímeros lineares são compostos por dois tipos de monómeros (ácido itacónico e ácido metacrílico) que possuem afinidade para as moléculas sinais. Nanoparticulas impressas molecularmente são partículas específicas para o alvo de interesse, pois este é incluído no processo de síntese. Vibrio fischeri e Aeromonas hydrophila foram os microrganismos escolhidos para este estudo. A eficiência dos polímeros lineares e das nanopartículas foi testada quer em solução quer como revestimento de superfícies, evidenciando as suas capacidade de disrupção de QS através da diminuição da bioluminescência de V. fischeri e da formação de biofilme de A. hydrophila. O crescimento bacteriano não mostrou ser afetado pela presença destes materiais. A citotoxicidade foi avaliada, usando uma linha celular de fibroblastos, de modo a avaliar a biocompatibilidade. Os resultados mostraram que ambos os materiais não são citotóxicos. Em conclusão, este estudo demonstrou que os polímeros desenvolvidos podem ser uma estratégia efetiva de disrupção de QS e redução de infeções e de resistência bacteriana. Devido às suas características, reduzida citotoxicidade, solubilidade e facilidade de integração, estes materiais poderão ser aplicados de diversas formas, especialmente onde há predominância de infeções bacterianas, como ambientes clínicos, farmacêuticos, indústria alimentar, agricultura ou aquacultura.
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Rawlins, Owen. "Factors influencing middle managers to enable or inhibit change." Diss., University of Pretoria, 2017. http://hdl.handle.net/2263/64918.
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Organisations undergo various change initiatives as a result of both external and internal pressures in order to survive and prosper, yet it is estimated that approximately 70% of change initiatives fail. Middle managers play a vital role in change initiatives; however, little is known about their views regarding the factors that enable them to commit to change initiatives. The purpose of this study is to ascertain which factors influence middle managers to enable or inhibit change.
Qualitative, exploratory research methods were employed in this study, with the data being analysed utilising thematic content analysis. Fifteen semi-structured interviews were conducted with middle managers from four different industries, representing nine different companies in South Africa. The study was conducted in one city (Durban), with middle managers who had been through a change initiative in the past three years.
The findings identified four broad factors (categories) which enable or inhibit middle managers in their role as change agents, namely personal factors, social factors, organisational factors and change-specific factors. For each of these factors multiple contributing factors were identified. The underlying factor that enables middle managers to commit to change is good leadership that engages employees, i.e. leaders must provide consultation, communication, and support.
There is ample literature on the roles of middle managers in implementing change initiatives, but there is a lack of research on the factors that influence them to enable or inhibit change initiatives. Two models of enabling and inhibiting factors were thus developed to illustrate the myriad of factors contributing to middle managers acting as change agents. This will assist senior managers to prepare for successful change initiatives.Mini Dissertation (MBA)--University of Pretoria, 2017.
km2018
Gordon Institute of Business Science (GIBS)
MBA
Unrestricted
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Cavaleiro, Eliana Marisa dos Santos. "Development of polymeric materials to inhibit bacterial quorum sensing." Thesis, Cranfield University, 2014. http://dspace.lib.cranfield.ac.uk/handle/1826/9236.
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Bacterial infections are an increasing problem for human health. In fact, an increasing number of infections are caused by bacteria that are resistant to most antibiotics and their combinations. A new solution to fight bacteria and infectious diseases, without promoting antimicrobial resistance, is required. A promise strategy is the disruption or attenuation of bacterial Quorum Sensing (QS), a refined system that bacteria use to communicate. In a QS event, bacteria produce and release specific small chemicals, signal molecules - autoinducers (AIs) - into the environment. AIs regulate gene expression as a function of cell population density. Phenotypes mediated by QS (QS- phenotypes) include virulence factors, toxin production, antibiotic resistance and biofilm formation. In this work, two polymeric materials (linear polymers and molecularly imprinted nanoparticles) were developed and their ability to attenuate QS was evaluated. Both types of polymers should be able to adsorb bacterial signal molecules, limiting their availability in the extracellular environment, with expected disruption of QS. Linear polymers were composed by methyl methacrylate as backbone and itaconic acid or methacrylic acid as functional monomer. IA and MAA monomers were identified by computer modelling to have strong interactions with the AIs produced by Gram-negative bacteria. Cont/d.
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McCrary, Elizabeth C. "Attachment as Affirmation to Inhibit Health Risk Information Avoidance." TopSCHOLAR®, 2017. http://digitalcommons.wku.edu/theses/1955.
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Previous research on information avoidance has revealed that people choose to avoid negative health information, but that this effect is interrupted by self-affirmation (Howell & Shepperd, 2013). The current study aimed to contribute to the field’s understanding of the conditions under which self-affirmation reduces information avoidance by using a unique affirmation: secure attachment figures. I hypothesized that activating a secure attachment would serve as the affirmation necessary for participants to choose to view their risk information for a fictitious enzyme deficiency. However, when given a choice, participants in both the experimental and control conditions chose to view this information. At best, these results demonstrate that psychological resources of a social nature were effective in protecting people from undesirable health risk information. At worst, they present a failure to replicate previous research. Explanations for why the results were unexpected and future modifications to the paradigm are discussed.
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Kaminski, John J. III. "Suppressive Oligodeoxynucleotides Inhibit Cytosolic DNA Sensing Pathways: A Dissertation." eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/669.
Full textAbstract:
The innate immune system provides an essential first line of defense against infection. Innate immune cells detect pathogens through several classes of Pattern Recognition Receptors (PRR) allowing rapid response to a broad spectrum of infectious agents. Activated receptors initiate signaling cascades that lead to the production of cytokines, chemokines and type I interferons all of which are vital for controlling pathogen load and coordinating the adaptive immune response. Detection of nucleic acids by the innate immune system has emerged as a mechanism by which infection is recognized. Recognition of DNA is complex, influenced by sequence, structure, covalent modification and subcellular localization.
Interestingly certain synthetic oligodeoxynucleotides comprised of the TTAGGG motif inhibit proinflammatory responses in a variety of disease models. These suppressive oligodeoxynucleotides (sup ODN) have been shown to directly block TLR9 signaling as well as prevent STAT1 and STAT4 phosphorylation. Recently AIM2 has been shown to engage ASC and assemble an inflammasome complex leading to the caspase-1-dependent maturation of IL-1β and IL-18. The AIM2 inflammasome is activated in response to cytosolic dsDNA and plays an important role in controlling replication of murine cytomegalovirus (MCMV). In the second chapter of this thesis, a novel role for the sup ODN A151 in inhibiting cytosolic nucleic acid sensing pathways is described. Treatment of dendritic cells and macrophages with the A151 abrogated type I IFN, TNF-α and ISG induction in response to cytosolic dsDNA. A151 also reduced INF-β and TNF-α induction in BMDC and BMDM responding to the herpesviruses HSV-1 and MCMV but had no effect on the responses to LPS or Sendai virus. In addition, A151 abrogated caspase-1-dependent IL-1β and IL-18 maturation in dendritic cells stimulated with dsDNA and MCMV. Although inhibition of interferon-inducing pathways and inflammasome assembly was dependent on backbone composition, sequence differentially affected these pathways. While A151 more potently suppressed the AIM2 inflammasome, a related construct C151, proved to be a more potent inhibitor of interferon induction. A151 suppressed inflammasome signaling by binding to AIM2 and competing with immune-stimulatory DNA. The interaction of A151 and AIM2 prevented recruitment of the adapter ASC and assembly of the macromolecular inflammasome complex. Collectively, these findings reveal a new route by which suppressive ODNs modulate the immune system and unveil novel applications for suppressive ODNs in the treatment of infectious and autoimmune diseases.
The innate immune response to HSV-1 infection is critical for controlling early viral replication and coordinating the adaptive immune response. The cytokines IL-1β and IL-18 are important effector molecules in the innate response to HSV-1 in vivo. However, the PRRs responsible for the production and maturation of these cytokines have not been fully defined. In the third chapter of this thesis, The TLR2-MyD88 pathway is shown to be essential for the induction of pro-IL-1β transcription in dendritic cells and macrophages responding to HSV-1. The HSV-1 immediate-early protein ICP0 has previously been shown to block TLR2 responses and in keeping with this finding, ICP0 blocked pro-IL-1β expression. Following translation, pro-IL-1β exists as an inactive precursor that must be proteolytically cleaved by a multiprotein complex known as the inflammasome to yield its active form. Inflammasomes are composed of cytoplasmic receptors such as NLRP3 or AIM2, the adapter molecule ASC, and pro-caspase-1. In the present study we found that the NLRP3 inflammasome is important for maturation of IL-1β in macrophages and dendritic cells responding to HSV-1. In contrast the related NLRP12 protein controls IL-1β production in neutrophils. These data indicate that sensing of HSV-1 by TLR2 drives pro-IL-1β transcription and infection activates the inflammasome to mature this cytokine. Moreover, these studies reveal cell type-specific roles for NLRP3 and NLRP12 in inflammasome assembly.
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Sun, Ji. "Gangliosides mediate axon-myelin stability and inhibit neurite outgrowth." Available to US Hopkins community, 2003. http://wwwlib.umi.com/dissertations/dlnow/3080774.
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Lacayo, Buckley Nidia Patricia. "Factors that inhibit the acquisition of English by Hispanic adults." Muncie, Ind. : Ball State University, 2009. http://cardinalscholar.bsu.edu/706.
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Miller, Laurie Ann. "The ability to generate or inhibit responses after frontal lobectomy /." Thesis, McGill University, 1987. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75775.
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The ability to generate different responses, and the ability to inhibit inappropriate behaviour, were explored in patients with unilateral cerebral excisions. Site-of-lesion effects were found to interact with the sex of the subject, the time of test-administration, and the nature of the response criteria. In Part I, the Thurstone Word Fluency Test revealed impairments two weeks postoperatively in patients with frontal, temporal, or central-area lesions. In men, removals from the left cerebral hemisphere caused greater deficits than removals from the right, but only left central-area excisions resulted in long-lasting impairments. Patients with left frontal-lobe removals produced few words on a sentence-completion fluency task, but on visual-image fluency, no patient-group was impaired. In Part II, an inability to inhibit impulsive actions on risk-taking tasks was seen after frontal lobectomy, as was a tendency to disregard the instructions on a word-fluency task. These results are consistent with the fact that patients with frontal-lobe lesions described themselves on a behavioural-trait questionnaire as less flexible and more impulsive than did control subjects.
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Pearson, G. J. "Factors which facilitate and inhibit innovation in a mature industry." Thesis, University of Manchester, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233626.
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Much of innovation research focuses on the innovating individual or the environment in which the innovation takes place. Moreover, empirical work has predominantly been concentrated on apparently innovative sectors such as those engaged in new technologies or in the early growth phase of development. This research is concerned with organisational characteristics which affect innovativeness in a mature industry setting. This research is based on a subsector of the UK textile industry. The first phase of research sought to identify a ranking among firms in the sector in terms of their innovativeness. The second phase focussed on a small sample of these firms and identified which organisational characteristics appeared to be most associated with innovativeness. In the sample of firms investigated it appeared that innovativeness was very closely associated with a group of characteristics related to the firm's business strategy and how well this strategy was known and understood by members of the firm. Another group of characteristics which also appeared to be associated with innovativeness, though less closely, was related to the way the firm was managed and the degree to which individual members of the firm experienced freedom to use their own initiative. The implications of the study are discussed and some lines for future research are suggested.
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Zelaya, Rainel. "Identification of Small Molecules that Inhibit Prostate Cancer Cell Proliferation." Honors in the Major Thesis, University of Central Florida, 2014. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/1659.
Full textAbstract:
Prostate cancer is the second most often diagnosed cancer and internationally the sixth foremost cause of cancer death in males, as of 2011. Within the United States it is the most common form of cancer in men with 186,000 new cases and with an overall 28,600 deaths in 2008, and it is the second leading kind of cancer-related death in men. The widespread threat that prostate cancer poses against men across the globe cannot be understated, and its initiation and progression must be understood in order to truly comprehend its implicated risks and possible forms of treatment. As its name implies, prostate cancer is a form of cancer that develops in the prostate gland located in the male reproductive system. Its progress starts when standard semen-secreting prostate gland cells mutate into cancer cells. Although its developments may start at the prostate gland, cancer cells may metastasize to other parts of the body through circulation systems such as the lymph nodes. The main sites of metastasis for prostate cancer include the adrenal gland, the bones, the liver and the lungs. Although there are treatments available for prostate cancer, there is no definitive cure. The primary goal of this project was to find an alternative form of treatment, which is what will be necessary to combat this cancer.B.S.
Bachelors
Biomedical Sciences
Biomedical Sciences
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Abdulsattar, Ban Oday. "Coronavirus proteins and their directed evolution to inhibit virus replication." Thesis, University of Reading, 2017. http://centaur.reading.ac.uk/73736/.
Full textAbstract:
Coronaviruses are enveloped, positive sense, RNA viruses that infect many species of animals, including humans. Of the six coronaviruses that can infect humans, SARS-CoV and MERS-CoV are the etiological agents of most concern currently. Coronaviruses possess the most complex and largest RNA genomes among all RNA viruses. The genome contains up to 15 genes with multiple open reading frames (ORFs) encoding both structural and non-structural proteins. Coronaviruses encode about 30 proteins that play specific, and often essential, roles in viral replication and assembly. This thesis presents work done to express Murine hepatitis virus strain A59 (MHVA59) proteins such as Nucleoprotein and membrane genes, non-structural proteins (5,6,7,8,9,10,16) from gene1, part of non-structural proteins (Plpro, Y-domain from nsp3 and N-terminal from nsp12) and RdRp from C-terminal part of nsp12 in E. coli BL21 cells and mammalian 17clone-1 cells, the latter of which are permissive for MHV-A59. The efficiency of transfection and expression of the proteins in mammalian cells was evaluated. SUMOStar (small ubiquitin-like modifier) fusion technology was used to enhance protein expression in the eukaryotic system. Expressed proteins were detected by Western blot with an anti-His tag antibody. The ability of virus-expressed proteins to interfere with virus infection was tested and an inhibitory effect was detected by plaque assay. The coronavirus nucleoprotein (N) is an important component for both viral replication and transcription. Error-prone PCR (ep-PCR) was used with the N protein as template to introduce random error and the number of mutations introduced was calculated after 100 random colonies were sequenced to validate the mutagenesis. Transient expression of N protein was shown to increase the efficiency of infection and virus yield. The function of N was investigated by screening for dominant-negative N mutants, using a library of N variants constructed using ep-PCR. The cytotoxicity of N variants was tested by MTT assay. Expressed N variants showed a range of effects ranging from a 10-fold increase in virus yield associated with the wild type N to 10-fold inhibition of virus growth. One particular N variant, mut38, was non-toxic, but reproducibly inhibited virus growth. The potential to screen for dominant-negative N variants using cell survival was also assessed using different N libraries. The thesis also investigated different strategies aimed at purification of non-structural protein 16 (nsp16). The overall findings suggest an ability of virus-expressed proteins in eukaryotic cells to interfere with virus infection and demonstrate that such antiviral activity can be generated by mutating an important viral protein.
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Dewar, Rebecca Amy. "Targeting cellular nuclear export to inhibit influenza A virus replication." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31349.
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Influenza A virus (IAV) is a global health threat, causing seasonal epidemics and potential pandemics leading to morbidity, death and economic losses. Currently, there are two main classes of licensed antivirals against IAV available in the US and Europe; adamantanes and neuraminidase inhibitors, both of which are hindered by the generation of resistant virus variants. The viral polymerase has a high error rate leading to mutations that allow the virus to overcome selection pressures directed at its own genome from conventional antivirals. The prospect of inhibiting host proteins that the virus exploits to facilitate its replication is of increasing interest as an antiviral strategy as the emergence of resistance has been predicted to be slower when targeting a host cellular factor. IAV utilizes the host nuclear export protein CRM1 to transport viral ribonucleoproteins (vRNPs) from the nucleus to the cytoplasm of an infected cell, a critical late stage of the influenza lifecycle. Leptomycin B (LMB), a Streptomyces metabolite, has been previously shown to target this pathway, resulting in reduced viral propagation; however, LMB's potent cytotoxicity has limited its use as a therapeutic agent. This thesis examined two novel selective inhibitors of nuclear export (SINE), KPT-335 and KPT-185, with less cytotoxicity. In vitro, KPT-335 inhibited replication of human and animal IAV strains in a dose-dependent manner with minimal cytotoxicity. To assess the resistance potential of KPT-335, IAV viruses were serially passaged in the presence of a sub-optimal concentration of the compound and assayed for the development of resistance. Resistance to KPT-335 became evident at 8-10 rounds of passage. Sequencing analysis of independently derived resistant virus clones identified 4 single amino acid changes on a surface exposed patch of the viral nucleoprotein (NP). Introduction of these amino acid changes, into otherwise wild type viruses by reverse genetics, confirmed that changes Q311R and N309T conferred a drug-resistant phenotype. However, these substitutions came at a fitness cost to virus replication. The molecular basis for resistance was unclear but Q311R and N309T NP-mutant viruses produced increased levels of M1 during infection as well as producing virus particles with increased M1:NP ratios. Furthermore, the KPT-335-resistance mutations were surprisingly similar to NP sequence polymorphisms previously associated with susceptibility to the innate defence protein MxA. Consistent with this, viruses harbouring the Q311R mutation displayed increased susceptibility to MxA inhibition compared to wild-type virus. Altogether this study confirms that SINEs have the potential to be successful therapeutic agents against IAV replication and that although resistance could be generated, it may be difficult for the virus to overcome both drug selection pressures and the human innate immune response restrictions by escape mutations.
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Robinson, Timothy. "Targeting cFLIP to inhibit residual cancer stem cells after chemotherapy." Thesis, Cardiff University, 2017. http://orca.cf.ac.uk/107539/.
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The emergence of the cancer stem cell (CSC) hypothesis has helped to explain previously poorly understood clinical concepts such as metastases, late tumour recurrence and resistance to chemotherapy. Triple Negative Breast Cancer (TNBC) has the worst prognosis of all types of breast cancer with a more frequent relapse rate and reduced length of survival in metastatic disease. It has been shown to contain a higher proportion of CSCs than other types of breast cancer. Paclitaxel, a taxane in widespread use in breast cancer, induces apoptosis in a ligand-independent manner through the extrinsic apoptosis pathway. cFLIP is both an antagonist of this apoptosis pathway and can interfere with the ubiquitynation and subsequent degradation of both HIF1α and β-catenin, two molecules involved in CSC-signalling. Using a novel compound targeted against cFLIP, we wanted to assess whether its combination with paclitaxel effectively targeted CSCs. Using a combination of in vitro models of cancer stem/progenitor-like activity and the surrogate marker of CSCs, ALDH, we demonstrated that a number of chemotherapeutic agents, including paclitaxel, docetaxel and FEC increased CSC-like behaviour. A mathematical model demonstrated that paclitaxel increased the absolute number of CSCs after treatment suggesting that CSC-like activity was being induced. OH14, a novel inhibitor of c-FLIP developed in our laboratory, abrogated the paclitaxel-mediated induction of CSC-like activity in TNBC cell lines. While apoptosis may play a role in CSC viability in vitro, it did not appear to play a major role in OH14-mediated suppression of CSC acquisition following paclitaxel treatment. Instead, OH14 appeared to suppress CSCs through disruption of HIF1- α, as HIF1α-mediated signalling was increased by paclitaxel and abrogated by the addition of OH14. These beneficial effects of combinatorial OH14 were confirmed in vivo, where OH14 suppressed tumour initiation of TNBC xenografts and prevented relapse of paclitaxel treated tumours in a xenograft model of systemic treatment. cFLIP thus has a dual effect in both increasing apoptosis and targeting signalling in TNBC CSCs. In a breast cancer subtype in desperate need of novel therapeutic strategies, targeting cFLIP warrants further investigation and progression towards clinical trials.
30
Orf, Robert William. "Factors that Promote and Inhibit Client Disclosure of Suicidal Ideation." Antioch University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=antioch1405093698.
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Williams, Kelley J. "Silver Nanoparticles Inhibit the Binding and Replication of Dengue Virus." Wright State University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=wright1431880664.
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Wakamatsu, Takuhiko. "The intravenous anesthetics barbiturates inhibit hypoxia-inducible factor 1 activation." Kyoto University, 2010. http://hdl.handle.net/2433/120562.
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Natarajan, Radhika. "Vitamin D metabolites inhibit adipocyte differentiation in ₃T₃-L₁ preadipocytes." Connect to this title, 2008. http://scholarworks.umass.edu/theses/164/.
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Everett, Taryn. "Examining Barriers That Inhibit Student Achievement From a Teacher's Perspective." ScholarWorks, 2016. https://scholarworks.waldenu.edu/dissertations/3157.
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Teachers at an urban high school in the Southeast have failed to see an increase in classroom achievement or standardized test scores despite efforts to increase passing rates. If achievement rates do not increase, school restructuring will occur. While the site has implemented programs to reduce academic failure, data exists that external barriers may be affecting student achievement. Guided by Bandura's (1986) theory of metacognitive beliefs and self-efficacy as the conceptual framework, this qualitative case study explored teachers' perceptions about the root causes of poor student achievement. This study examines how to identify those causes to help students improve academically, while providing teacher recommendations to reducing the effects of those causes in order to improve student success. Five teachers were selected from the math and science content areas to participate in 1-on-1 interviews to identify external barriers to student success. Thematic coding and member checks allowed for data triangulation to analyze the findings. Seven themes emerged to increase student success by helping close the achievement gap through fostering support between teachers and the families of all students involved: socioeconomic status, ability of goal setting, having encouragement and motivation, seeing another environment, lacking parental support, building relationships with parents, and stress of taking state tests. Developing resources that will help students to overcome issues outside of the school day that leads to increased student academic achievement and graduation rates creates social change.
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Shirindza, Mxolisi. "Understanding factors that enable and inhibit strategic decision making effectiveness." Diss., University of Pretoria, 2015. http://hdl.handle.net/2263/52317.
Full textAbstract:
The literature review has revealed that strategic decisions are complex, ill-structured and require much of organizational resources. Organizations are dependent on strategic decisions for sustained performance or even survival. Strategic decision-making is important in an organization as it is the process used to implement the strategic intent of the firm. Literature has also revealed that managers fail to process optimally, information for effective strategic decision-making due to their cognitive limits. This study set out to explore and understand the enablers and inhibitors of strategic decision-making effectiveness.
The study was conducted using an exploratory qualitative method, which consisted of in-depth semi-structured interviews. A total of 14 executives and managers were interviewed from coal mining organizations operating in the Mpumalanga province of South Africa. Interviews were recorded then transcribed into text. Directed content and frequency analysis were used to analyze the data and extract common themes. ATLAS.ti was used for the coding process during data analysis.
The findings of this study were the enablers and inhibitors of strategic decision-making effectiveness being discussed in detail. An empirically based framework was developed using the findings on ensuring strategic decision-making effectiveness. The factors used for the framework are : having support from the superiors, have a competent team in strategic decision-making, considering the external business environment, considering and involving stakeholders, ensure the quality of data and continuously review strategic decision-making process.Mini Dissertation (MBA)--University of Pretoria, 2015.
sn2016
Gordon Institute of Business Science (GIBS)
MBA
Unrestricted
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Sidinile, Ayanda. "An analysis of the barriers that inhibit sustainable implementation of LEAN." Thesis, Nelson Mandela Metropolitan University, 2014. http://hdl.handle.net/10948/d1021192.
Full textAbstract:
With global advances in technology, many organizations are finding it difficult and quite challenging to do business as usual. Japanese companies are on top of the world economy, while many Western companies are struggling to find ways to compete with them (Womack, et al., 1990). The Japanese secret weapon “Lean Production” is no longer a secret; more and more western companies are now learning and adopting Lean techniques to remain relevant and competitive. Lean management is a consistent philosophy and a set of practices that must be maintained over time in order to see the gains (Losonci & Demeter, 2013). Lean is not a quick fix to reduce costs, but a continuous improvement journey that will transform an organization into a cost efficient value-driven system. Lean is still a fairly new phenomenon in South Africa, particularly in the Eastern Cape. The road towards the lean implementation is viewed by many as a challenging and yet rewarding journey. South African organizations are following the trend of implementing lean in order to eliminate waste, improve quality, speed, customer satisfaction and thereby increasing profits. It is however still a long journey towards achieving total perfection. The main challenge facing South African organizations is the ability to sustain the lean improvements over a longer period. This study will focus on identifying and analyzing the main barriers that inhibit many successful organizations from sustaining lean improvement efforts.
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Mansfield, Ian David. "The synthesis of novel agents which inhibit tumour-stimulated bone resorption." Thesis, Loughborough University, 1999. https://dspace.lboro.ac.uk/2134/27412.
Full textAbstract:
A range of conjugates which focused on bisphosphonates as delivery molecules and on oestrogens as resorption inhibitors were synthesised. Various moieties were coupled through an ester linkage to bisphosphonates which were then converted to the corresponding bisphosphonic acids. This ester linkage was considered to be readily hydrolysable under normal physiological conditions.
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Lu, Jennifer. "Interferon-induced transmembrane proteins inhibit human immunodeficiency virus type 1 replication." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=95120.
Full textAbstract:
Viral infection triggers production of interferon (IFN) that in turn leads to the expression of genes known as IFN-stimulated genes (ISGs), some of which possess antiviral activities. Previous studies have shown that IFN suppresses the replication of human immunodeficiency virus type I (HIV-1). While several ISGs have been linked to this specific antiviral activity with well-defined inhibitory mechanisms, others remain to be investigated. With the purpose of identifying novel ISGs capable of inhibiting HIV-1 replication, we have performed a shRNA screen of the genes upregulated by IFN in SupT1 cells. This study reports three ISGs, known as interferon-induced transmembrane proteins 1, 2 and 3 (IFITM1, 2 and 3), that substantially inhibit HIV-1 replication in SupT1 cells. Further studies suggest that HIV-1 entry is impaired. Collectively, these findings identify a small family of cellular restriction factors that serve as a barrier to HIV-1 entry into the host cell.Suite à une infection virale, les interférons (IFNs) sont produites et servent à induire l'expression de certains gènes, appelés gènes stimulés par l'interféron (ISGs), dont certains possèdent des effets antivirales. Plusieurs études ont démontré que l'IFN possède la capacité d'inhiber la réplication virale du virus de l'immunodéficience humaine de type I (VIH-1). Tandis que certains ISGs ont été associés à une activité antivirale spécifique avec un mécanisme d'action bien défini, d'autres ISGs sont moins bien caractérisés. Dans le but d'identifier de nouveaux ISGs responsables d'inhiber la réplication virale du VIH-1, nous avons réalisé un criblage par shRNA des gènes régulés par l'IFN dans les cellules SupT1. Cette étude rapporte trois ISGs, appelés «interferon-induced transmembrane proteins 1, 2 et 3» (IFITM1, 2, et 3), dont l'expression dans les cellules SupT1 peut inhiber la réplication virale du VIH-1 de façon significative. Les résultats indiquent que ces protéines agissent au niveau de l'entrée du virus dans la cellule. Collectivement, cette étude a identifié une famille de facteur de restriction cellulaire qui agit comme barrière pour prévenir l'entrée du VIH-1 dans la cellule hôte.
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GARCEZ, FELIPE. "WINE IN RESTAURANTS: ANALYSIS OF THE FACTORS THAT INHIBIT ITS CONSUMPTION." PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO, 2005. http://www.maxwell.vrac.puc-rio.br/Busca_etds.php?strSecao=resultado&nrSeq=7514@1.
Full textAbstract:
O brasileiro não tem o hábito de beber vinho. Pesquisas
mostram que o
crescimento do consumo de vinho no Brasil é vegetativo a
mais de 30 anos.
Dentro desse contexto, a presente pesquisa tem como
objetivo explorar os fatores
inibidores ao consumo do vinho, principalmente em
restaurantes. Barreiras ao
consumo, como o preço e o desconhecimento são analisadas,
assim como os
riscos associados ao consumo do vinho em restaurantes. As
conclusões inferem
que, em situações de exposição pública, o risco social e o
risco financeiro podem
ser considerados como fatores inibidores ao consumo.
Paralelamente, a pesquisa
identifica um consumidor interessado por uma forma de
consumo mais simples e
uma relação mais descontraída com o vinho. Esses
resultados contribuem para um
possível reposicionamento do produto, com o objetivo de
popularizar seu
consumo.Brazilian people don´t have the habit of drinking wine. Previous researches have shown that, for the last 30 years, the consumption-increasing rate is vegetative. The present research has the objective of describing the inhibition factors related to wine consumption, basically in restaurants. Consumption barriers, as price and the lack of knowledge, are analyzed, as well as the risks associated with the consumption in restaurants. Conclusions shows that, in situations were people face high public exposition, social and financial risk can be considered as consumption inhibition factors. Other important conclusion is that, the present research identifies a consumer interested in a simplest way of drinking wine. Interested in a more soft and smooth relation with wine. Those results contribute for a possible reposition of wine, in order to stimulate and popularize its consumption.
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Wragg, Rachel T. "Monoamines and Peptides Interact to Inhibit Glutamatergic Signaling in Caenorhabditis elegans." University of Toledo / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1279208105.
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Gleespen, Abney Varner. "The development of coworker relationships that support or inhibit continuous learning /." The Ohio State University, 1997. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487946103567439.
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Davis, Elizabeth A. "Diverse environmental Pseudomonas encode unique secondary metabolites that inhibit human pathogens." Bowling Green State University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1498481537530199.
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Basalla, Joseph. "Identifying biosynthetic gene clusters whose products inhibit cystic fibrosis derived pathogens." Bowling Green State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1530795688583696.
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Tyson, Katharine Rose De Silva Aravinda Manu. "A family of tick Ixodes scapularis salivary proteins that inhibit complement." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2008. http://dc.lib.unc.edu/u?/etd,1491.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2008.Title from electronic title page (viewed Sep. 16, 2008). "... in partial fulfillment of the requirement for the degree of Doctor of Philosophy in the Department of Microbiology and Immunology." Discipline: Microbiology and Immunology; Department/School: Medicine.
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Lee, Jeanette. "Factors which influence and inhibit women becoming faculty in AABC schools." Theological Research Exchange Network (TREN), 1998. http://www.tren.com.
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Chiwakata, M., la Mare Jo-Anne De, Adrienne Lesley Edkins, and Denzil R. Beukes. "Sarqaquinoic acid and related synthetic naphthoquinones inhibit the function of Hsp90." Georg Thieme Verlag KG, 2016. http://hdl.handle.net/10962/66324.
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publisher versionHeat shock protein 90 (Hsp90) is of critical importance in the proper folding of numerous proteins, including those involved in cancer. Consequently, there is significant interest in the discovery and development of Hsp90 inhibitors as anticancer drugs. In this study, we investigated the ability of sargaquinoic acid (SQA) and selected naphthoquinone derivatives to inhibit Hsp90 function. SQA was isolated and purified from Sargassum incisifolium while the naphthoquinones were synthesised via a straightforward sequence incorporating a Diels-Alder reaction between benzoquinone derivatives and myrcene followed by coupling with substituted alkyl or arylamines. Hsp90 inhibition was assessed by a client protein degradation assay. At a concentration of 1µM, SQA showed almost complete inhibition of Hsp90 but only moderate antiproliferative effects (IC50 658µM) against a Hs578T breast cancer carcinoma cell line. Interestingly, the most potent synthetic aminonaphthoquinone inhibited Hsp90 function by 50% at a concentration of 1µM but showed much improved activity against the Hs578T cell line (IC50 0.32µM). Furthermore, unlike geldanamycin, none of the compounds tested upregulates Hsp70 suggesting that these compounds may bind to the C-terminal end of Hsp90.
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Tkachenko, Olga. "Polydisperse chaperone proteins and the mechanisms by which they inhibit aggregation." Thesis, University of Oxford, 2018. http://ora.ox.ac.uk/objects/uuid:f9034c0c-e3ca-48df-8d0a-b5cd37da7de5.
Full textAbstract:
The small heat-shock proteins (sHSPs) are ATP-independent molecular chaperones, found in all kingdoms of life. In humans their malfunction is associated with neurodegenerative disease, cataracts, myopathies and cancer. Their molecular mechanism is contentious as sHSPs are challenging experimental targets: they typically exist as large, polydisperse and exchanging oligomers. This heterogeneity is com- pounded by that of aggregating substrates. Here I investigate the structure, dynamics and function of a major human sHSP, αB-crystallin (αBC), using nuclear magnetic resonance (NMR) and native mass spectrometry (MS). Following the introduction, Chapters 2 and 3 focus on structure and dynamics of αBC. In Chapter 2, I elucidate an allosteric communication network between two interfaces of the core α-crystallin domain within the oligomers. In Chapter 3, I show that the connectivity of oligomer vertices is consistent with polyhedral architectures, and present size measurements of individual αBC stoichiometries within the polydisperse ensemble. Chapters 4-7 link these insights to the chaperone function of αBC. Chapter 4 presents a new methodology to derive kinetic mechanisms of aggregation, using the model protein α-lactalbumin (αLac). I show that αLac aggregation proceeds along two pathways via an unstable dimeric nucleus. Chapter 5 derives a kinetic mechanism for the chaperone action of αBC on αLac. Remarkably, αBC disassembles the aggregation nuclei, and is in kinetic competition with αLac in large aggregates. In Chapter 6, I characterise the size and shape of these large αBC-αLac complexes. Chapter 7 identifies αBC residues affected by αLac, showing that the substrate engages a subset of the interactions regulating quaternary dynamics of αBC. Thus I have exploited the complementarity of NMR and native MS to obtain insight into function of αBC, by studying its structure and dynamics from atomic- resolution to quaternary level. The results expand the arsenal of mechanisms by which molecular chaperones maintain cellular proteostasis.
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Dyk, Patricia Hyjer. "Family Relations Factors that Facilitate or Inhibit Middle Adolescent Identity Development." DigitalCommons@USU, 1990. https://digitalcommons.usu.edu/etd/2350.
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The formation of a sense of personal identity is a major task of adolescence. An adolescent's experimentation with roles is carried out in social interactions, the family being one important context for development. Research evidence suggests that the family's ability to tolerate individuality and maintain connectedness has implications for the process of identity formation. The purpose of this study was to identify family relations factors that facilitate or inhibit patterns of identity development during middle adolescence (high school years). Self-report and observational data were obtained from 49 families with middle adolescents to tap behaviors conceptualized as enabling or constraining individuality and connectedness. Mothers, fathers, and adolescents females, 20 males) completed two questionnaires assessing their perceptions of child-rearing behaviors within the parent-adolescent dyad : the Parent-Adolescent Relationship Questionnaire (PARQ) and Ellis, Thomas, and Rollins subscales. Perceptions of f amily system functioning were measured by FACES II. All three family members participated in a family interaction task, and observed social interaction behaviors were coded by nonfamily members . Adolescents completed an ego identity questionnaire (EOM-EIS) in the first and third years of the study. Based upon changes in identity status, adolescents were categorized as progressive, stable, or regressive. Family relations factors were then compared for each of these three groups . Results identify several child-rearing perceptions and social interaction variables as factors associated with progressive or regressive identity development. Fathers' perceptions of moderate levels of affection in the fatheradolescent relationship appear to facilitate identity development, while high levels of companionship and support are inhibiting factors. Adolescents' perceptions of a moderate level of withdrawal in the father-adolescent relationship are another facilitative factor. Lower proportions of fathers' and adolescents' enabling individuality behaviors appear to inhibit development, as do high proportions of enabling connectedness behaviors by both parents. The results from both perceptual and behavioral data support the notion that to facilitate identity exploration during middle adolescence, there needs to be a balance of expression of individuality and moderate connectedness in the family environment.
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Shaibu, Akaeze Nana Aishat. "Revenue Losses: Exploring Strategies Required by Managers to Inhibit Movie Piracy." ScholarWorks, 2016. https://scholarworks.waldenu.edu/dissertations/2272.
Full textAbstract:
The piracy of movie products resulted in 72,000 lost jobs and $4.5 billion in lost wages to the United States economy in 2012. The purpose of this multiple case study was to explore what strategies movie corporation managers use to inhibit piracy of movie products to achieve profitability. The sample consisted of 6 movie industry managers who managed movie corporations for not less than 5 years in New York City. The conceptual framework for this study was based on the general systems theory. Data were collected through face-to-face semistructured interviews. Transcript review and member checking were used to ensure credibility and trustworthiness of the interpretation of participants' responses. The 3 major themes that emerged in the study include the perceived effects of movie industry managers' marketing management strategies, legal management strategies, and customer management strategies for inhibiting product piracy. Findings from this study contribute to social change by indicating strategies that other movie industry managers may use to prevent piracy of product, sustain business, and reduce the negative effects of job loss. The results of this study thus may contribute to the prosperity of movie industry leaders, employees, their families, communities, and the local economy.
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Angom, Georgia Evelyn. "Diversity in the Canadian public sector, understanding the factors that inhibit inclusion." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape15/PQDD_0013/MQ32899.pdf.
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