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1
Foxwell, Alice Ruth, and n/a. "Mechanisms of immunity to nontypeable Haemophilus influenzae in the lung." University of Canberra. Applied Science, 1998. http://erl.canberra.edu.au./public/adt-AUC20060710.142114.
Full textAbstract:
Pulmonary infection caused by nontypeable Haemophilus influenzae (NTHi) is a
significant cause of morbidity and mortality in both industrialised and developing
countries. Previous work from this group resulted in the development of a respiratory
model in rodents which has precipitated studies into the pathogenesis of infection by
NTHi and investigation of the humoral and cellular mechanisms by which the bacteria
are cleared from the lung. Comparison of mucosally immunised with non-immunised
animals has demonstrated that not only are bacteria cleared more rapidly from the lungs,
but there is a more rapid response and resolution of inflammatory factors in the
mucosally immunised animals following challenge with NTHi.
This inflammatory response is partially regulated by the ability of the mucosally
immunised animals to rapidly produce, then control the production of tumour necrosis
factor (TNF)-a. The TNF-a is produced by both macrophages and type I pneumocytes
in the alveoli and also by the endothelial cells lining the blood vessels in the lungs.
Immunocytochemical studies have identified cellular subsets accumulating in the lung
at various time points following infection. Marked differences in cellular infiltration
into the lung tissue were noted between immunised and non-immunised animals after
challenge with NTHi. Immunised animals demonstrated an early influx of
macrophages, CD8+ T cells and Y8+ T cells, followed by enhanced expression of the
MHC-II marker, cellular infiltration by polymorphonuclear leukocytes and finally an
increased number of both B cells and CD4+ T cells. In contrast, non-immunised
animals did not demonstrate any proliferation nor extravasation of lymphocytes or
increased expression of MHC-II before total bacterial clearance had occurred.
Polymorphonuclear leukocyte infiltration occurred in the non-immunised animals,
however at a later time than that seen in immunised animals.
Challenging rodents to establish persistent infection highlighted the inappropriately
aggressive white blood cell response to an initial challenge when bacteria may be
masked by other substances, followed by the inability to amplify the
polymorphonuclear leukocyte response on repeated challenge with NTHi. This
hyporesponsiveness in the macrophage population, shown by lack of detectable TNF-a
production, concomitant with low numbers of NTHi resulted in a continuously high
number of macrophages in the alveoli and the possibility of increased damage to the
lung tissue.
The requirement for cell surface TNF-a and CD8+ T cells to enhance the clearance of
NTHi from the lungs further strengthens previous in vitro and in vivo findings of the
possible significance of cellular invasion as a mechanism of pathogenicity for NTHi.
This thesis has contributed to the understanding of both the immune response to and the
pathogenicity mechanisms of pulmonary infection with NTHi. Kinetic studies
identifying cellular responses and cytokine levels have emphasised the ability of
mucosal immunisation to increase the rate of immune response and resolution of
inflammation to NTHi infection in the lung. Observations demonstrating a requirement
for macrophages and CD8+ T cells in mechanisms associated with enhancing NTHi
clearance from the lung will lead to further investigations.
2
McGrath, John Francis, and n/a. "Immunomodulation in the context of developing a nontypeable Haemophilus influenzae vaccine." University of Canberra. Health Sciences, 2007. http://erl.canberra.edu.au./public/adt-AUC20070726.152419.
Full textAbstract:
One of the major challenges of vaccine development is the conservation of immunogenicity
and protective efficacy through the stages of design, production, formulation and delivery.
The critical issue is that how and in what form an antigen is taken up by antigen presenting
cells for proteolytic processing and presentation to the immune system bound to MHC can
have dramatic effects on the activation of Th cells to drive clonal responses and induction of
immunological memory.
Nontypeable Haemophilus influenzae (NTHi) is a pathogenic commensal of the human
respiratory tract that causes diseases with enormous socioeoconomic burdens. There is no
licensed vaccine, although the potential for vaccination with outer membrane components to
reduce the incidence of disease caused by NTHi has recently been demonstrated in clinical
trials. The issue of immunomodulation was explored in this thesis in the context of the further
evaluation of a leading NTHi vaccine candidate, the outer membrane protein OMP26. The
efficacy of recombinant OMP26 (rOMP26) against NTHi challenge has been previously
demonstrated in mice, rats and chinchillas. In rats, efficacy was shown to be restricted to the
precursor form (containing the signal peptide) and not the mature form of rOMP26. The
immunodulatory effects of changes to the rOMP26 structure were further investigated in this
thesis. A range of structural variants of rOMP26 were constructed in view of reducing
extraneous plasmid-derived sequence from the antigen and to introduce a unique cysteine
residue as a potential conjugate site for multivalent vaccine development (Chapter 2). It was
demonstrated that minor structural changes to rOMP26 such as the addition, deletion,
modification or relative positioning of a single amino acid or bulky group, designed to
increase the efficiency of production or introduce (cysteine) conjugation sites, altered the
expression of the protein in E. coli and the immunogenicity in Balb/C mice. Furthermore, in
contradiction to the published report (El-Adhami et al. 1999) and a new study in rats (Chapter
3), there was no positive effect of the signal peptide in mice, with precursor and mature forms
of rOMP26 equally immunogenic (Chapter 2). Following confirmation of the need to retain
the signal peptide for the immunogenicity of rOMP26 in rats, a precursor form (rOMP26VTAL)
in which the conserved n-region of the signal peptide was deleted, and shown to reduce the
efficiency of the cleavage of the signal peptide by signal peptidase during protein overexpression
in E. coli (Chapter 3). Not only did this deletion result in an increase the yield and
stability of the purified precursor protein, but rOMP26VTAL was highly immunogenic and
enhanced the clearance of NTHi from the lungs of challenged rats. The potential for signal
peptides to be exploited as an immune-enhancing moiety in a proteinaceous vaccine is
discussed.
Following the development of rOMP26VTAL as a production optimised variant of rOMP26, the
next step was to test the feasibility of rOMP26VTAL as a component of a multivalent vaccine
(Chapter 4). Two chimeras were constructed with LB1(f)2,1,3, a trivalent synthetic B-cell
epitope from the extracellular loop 3 region of the P5 fimbrin protein of NTHi, positioned at
the N- or C-terminus of rOMP26VTAL. The solubility of rOMP26VTAL was affected by the
fusion, with both chimera constructs expressed only in the insoluble fraction, thus requiring a
denaturing protocol for purification. Although rLB1(f)2,1,3-OMP26VTAL was expressed and
purified as a more stable protein and in greater yield than rOMP26VTAL-LB1(f)2,1,3, the
relative positioning of the fusion was important and rOMP26VTAL-LB1(f)2,1,3 was significantly
more immunogenic in rats than rLB1(f)2,1,3-OMP26VTAL. In addition, rOMP26VTALLB1(
f)2,1,3, but not rLB1(f)2,1,3-OMP26VTAL induced a significant degree of bacterial clearance
following pulmonary challenge with NTHi, in levels comparable to the highly efficacious
rOMP26VTAL construct.
In the third part of the thesis, bacterial ghosts were evaluated as a novel mucosal delivery
technology for rOMP26VTAL and rOMP26VTAL-LB1(f)2,1,3, (Chapter 5). To mimic the natural
presentation of OMP26 and P5 fimbrin antigens on the cell surface of NTHi, an OmpA�
sandwich fusion surface display system was developed for the outer membrane expression of
the OMP26 constructs in E. coli ghosts. Following gut immunisation, but not intranasal
immunisation even when co-administered with the cholera toxin�derived adjuvant CTA1-DD,
bacterial ghosts were successful at presenting OMP26VTAL and rOMP26VTAL-LB1(f)2,1,3 to the
immune system for the induction of enhanced clearance of NTHi in the rat pulmonary
challenge model. Although this study was the first to demonstrate enhanced bacterial
clearance induced by heterologous antigens expressed in the outer membrane of bacterial
ghosts, future studies with ghosts will require optimisation of the expression levels of the
OmpA� fusion proteins possibly to avoid cross-reactive responses related to high doses of
ghosts in the inoculum.
This thesis presents data that both supports the further evaluation of rOMP26 constructs for
clinical trials, and has demonstrated the significant effects of structural changes, method of
production and delivery system can have on the immunogenicity of a candidate vaccine. Such
knowledge will contribute to and provide some new approaches for enhancing the efficiency
of vaccine development against a range of diseases including those caused by NTHi.
Major Outcomes:
1. Demonstration that the immunogenicity of rOMP26 antigen constructs is affected by
structural modifications and their positioning within the construct, and by the delivery
system.
2. Development of rOMP26VTAL, an rOMP26 construct with the KNIAK sequence
deletion of the signal peptide n-region. This protein retains the immunogenicity and
protective efficacy of rOMP26, but is produced with reduced cleavage of the signal
peptide, resulting in higher yields and a stable protein. Lacks extraneous plasmidderived
multiple cloning site sequence, and is produced in high yield as a stable
protein.
3. Construction of a NTHi rOMP26VTAL-LB1(f)2,1,3 chimera antigen that induced
enhanced clearance of NTHi in an acute pulmonary challenge model in rats.
4. Development of an OmpA� surface display system for the expression of rOMP26
antigen constructs in the outer membrane of E. coli/bacterial ghosts
5. Bacterial ghosts were successful as delivery vehicles for rOMP26 candidate vaccine
constructs when delivered in the gut.
3
Kunthalert, Duangkamol, and n/a. "Immunological and structural characterisation of the nontypeable Haemophilus influenzae vaccine protein OMP26." University of Canberra. Health Sciences, 2004. http://erl.canberra.edu.au./public/adt-AUC20060406.101830.
Full textAbstract:
Nontypeable Haemophilus influenzas (NTHi) is recognised as a significant human
pathogen causing mild to severe respiratory tract infections. At present, no vaccine is
available for prevention of infection caused by this pathogen. Several outer membrane
proteins (OMPs) of NTHi and its lipooligosaccharide have been investigated as possible
vaccine antigens against NTHi infections. Previous investigations in our laboratory
have shown that OMP26 from an NTHi 289 strain was able to significantly enhance
pulmonary clearance of NTHi in a rat model in which animals were immunised via
intestinal Peyer's patches and then boosted intratracheally (Kyd and Cripps, 1998; El-
Adhami et al., 1999). In recent studies, the OMP26, when used as a parenteral
immunogen, was also highly effective at inducing immune responses that led to
significantly enhanced clearance of the chinchilla nasopharynx (Kyd et al., 2003).
These studies indicate significant potential of the OMP26 as a candidate vaccine antigen
and warrant further investigations for development of a vaccine against NTHi.
This thesis focussed on the immunological and structural characterisation of the NTHi
vaccine candidate, OMP26. Peptides of OMP26 were used as tools to localise the
immunologically important regions of the OMP26. Two different E. coli expression
systems, the GST gene fusion and the 6xHis tagged systems, were employed to
construct the OMP26 peptides. It was found in this study that, despite efforts to
optimise the system, the GST-fusion protein system failed to produce consistent results
for the purification and storage of the OMP26 peptides. In contrast, the 6xHis tagged
system exhibited more reliable outcomes in the production of the recombinant OMP26
peptides and the stability of the stored purified peptides. As such, the purified OMP26
peptides from the 6xHis tagged system were chosen to map major regions of
immunological significance for the OMP26 protein.
The regions of the OMP26 which are involved in the induction of the acquired immune
responses have been identified in the present study. Based on the antigen specific
lymphocyte proliferation assay, the dominant T cell epitopes for OMP26 were located
between amino acid residues 95 and 197 (T3+T4 region). These identified T cell
epitopes exhibited the capability of efficient T cell activation, suggesting that the
epitopes within the T3+T4 region potentially had the highest affinity for binding to the
MHC molecules than did any other OMP26 region. Using two different assay systems,
ELISA and BIA, the predominant B cell epitopes of OMP26 were located between
amino acid residues 45 and 145 (T2+T3 region). This region was also found to be
immunodominant across all animal species tested, and with all immunisation regimens
used. Flow cytometry analysis also revealed that these particular epitopes were
expressed on the surface of NTHi cells. By integration of the data obtained from these
current experimental studies and the computational analysis of the OMP26 sequence,
two hypothetical models of the OMP26 were also proposed in this study.
The significant outcomes obtained in this thesis provide a better understanding of the
specificity of the host immune responses to the OMP26 protein These findings provide
great benefit not only for the development of a future NTHi vaccine but for the
development of the peptide-based immunodiagnostic reagents as well. These diagnostic
reagents will be valuable, in particular, for the evaluation of efficacy of an NTHi
vaccine in humans that may include OMP26 or specific conformational structures.
Future studies are still required to further define the minimum epitope length required
for the B and T cell responses identified in this study. The significance of these
responses in immune protection against NTHi infection also requires further
investigations. Human immune responses also need to be determined, but this can only
be achieved following clinical trial studies.
4
Heyl, Kerstin Andrea [Verfasser], Hortense [Akademischer Betreuer] Slevogt, Peter F. [Akademischer Betreuer] Zipfel, and Robert [Akademischer Betreuer] Bals. "Die Bedeutung von Dectin-1 für die durch Nontypeable Haemophilus Influenzae (NTHi) induzierte Immunantwort des humanen Lungenepithels / Kerstin Andrea Heyl. Gutachter: Hortense Slevogt ; Peter F. Zipfel ; Robert Bals." Jena : Thüringer Universitäts- und Landesbibliothek Jena, 2014. http://d-nb.info/1052020410/34.
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5
Santana, Estevan Alexis. "Identification of a Fur-regulated small regulatory RNA in nontypeable Haemophilus influenzae." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1410472201.
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6
Ng, Seang Khi Preston. "The Role of Distinct Host Glycans in the Evolution of Host Adapted Pathogens." Thesis, Griffith University, 2014. http://hdl.handle.net/10072/365445.
Full textAbstract:
Glycans are carbohydrate structures coating the cell surface of virtually all nucleated cells of vertebrates. A crucial function of glycans is in cell interaction and recognition, which is constantly exploited by bacteria and viral pathogens as targets for toxins, and as a receptor to aid recognition of and adhesion to host cells. Sialic acids, a 9-carbon compound commonly added as a terminal sugar on glycoconjugates
is crucial to both bacteria and viruses causing a successful infection. Bacterial pathogens utilize sialic acids as a component of LOS and capsule, both key virulence factors. The decoration of the bacterial cell surface with sialic acid glycoconjugates has two roles; first, to mimic host glycans to evade the host immune system, second, in reducing the efficiency of complement mediated lysis and opsonophagocytosis. Several key bacterial pathogens including Haemophilus influenzae and
Pneumococcus also utilize sialic acids as a carbon source. In viruses, host sialic acids glycoconjugates act as a receptor for viral recognition and adherence to host cells. In the case of influenza A virus, a viral neuraminidase is required to cleave and release newly formed viral particles from infected host cell. This thesis investigates the role of sialic acid glycoconjugates in pathogenesis to increase the understanding of sialic acid biology in human host adapted pathogens. The role sialic acids play in pathogenicity is investigated in the major human pathogens; non-typeable Haemophilus influenzae (NTHi) and Neisseria meningitidis and in human influenza A viral strains.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Institute for Glycomics
Science, Environment, Engineering and Technology
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7
Fernandes, Maria do Carmo de Alustau. "Caracterização do efeito vasodilatador dos nitratos orgânicos GTN, NTHF, NCOE e BIS-NTHF em artéria e veia isoladas de cordão umbilical humano." Universidade Federal da Paraíba, 2015. http://tede.biblioteca.ufpb.br:8080/handle/tede/8853.
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Human umbilical cord vessels (HUCV), often considered biological waste, are good models for evaluation of vasoactive substances. The effect of glyceryl trinitrate (GTN) has been characterized in several animal blood vessels, but this nitrate presents little effect on HUCV. The tetrahydrofurfuryl nitrate (NTHF) and 13-cis-9-octadecanoate acetate nitrate (NCOE) are nitric oxide (NO) donors, whose effect has been characterized in animal vessels. 1,2-bis (tetrahydrofuran-2-yl) ethane-1,2-diildinitrato (BIS-NTHF) is a novel compound (two molecules of NTHF) that has no pharmacological studies. The aim of this study was to implement and standardize the technique involving HUCV, and characterize the effect of these four organic nitrates both in artery (HUA) and vein (HUV) rings isolated from umbilical cord. The standardization of the technique showed that 3g and 3h are, respectively, the ideal voltage and time to experiment with the umbilical vessels, besides the fact that it presents a spontaneous decrease both basal tone as the contractile. The study of nitrates showed that these compounds have relaxed the basal tone of HUCV. All nitrate induced vasorelaxation in both umbilical vessels pre-contracted with serotonin (5-HT), with maximum effects than 90%, and more effectively in relaxing HUA than HUV. In this situation, GTN was the most potent nitrate in causing vasodilation, BIS NTHF presented an intermediate power value, while NCOE and NTHF were less potent in relaxing HUV and HUA, respectively. When HUA rings were pre-contracted with KCl 60 mM, there was an attenuation of vasodilation promoted by nitrates. GTN and the NTHF also showed decreased vasorelaxation in HUV rings contracted with KCl 60 mM, while NCOE and BIS-NTHF have effects similar to the rings pre-contracted with 5 HT. Preincubation of GTN, BIS-NTHF and NTHF attenuated contractions induced by 5-HT in HUA rings. Additionally, GTN and BIS-NTHF also inhibited contraction stimulated by 5-HT in HUV. In contrast, preincubation of NTHF in HUV, and NCOE both in HUV as HUA led to lower inhibition when compared with the other nitrates. GTN, NTHF and BIS-NTHF inhibited the phasic and tonic components of the contraction induced by 5-HT in the absence of extracellular Ca2+. NCOE was more effective to inhibit the tonic contraction. Pre-incubation of 10 μM of ODQ, inhibitor of soluble cyclase guanylyl, attenuated significantly the vasodilator response to GTN, NTHF, NCOE and BIS NTHF was. Preincubation of 10 mM TEA, a blocker of potassium channels, decreased the relaxant response of the four nitrates in HUA, while do not alter the effect in HUV. In view of what has been exposed here, it can be concluded that GTN, NTHF, NCOE and BIS-NTHF cause vasorelaxation of HUCV rings, both in basal tone as contractions induced by 5-HT or KCl. The mechanism of nitrates action in these human vessels involves activation of sCG and channels for potassium; and inhibition of calcium entry, release of stocks of this ion by sarcoplasmic reticulum and ROCK activity.
Vasos umbilicais humano (HUCV), muitas vezes considerado lixo biológico, são bons modelos para avaliação de substâncias vasoativas. O efeito do trinitrato de gliceril (GTN) já foi caracterizado em vários vasos sanguíneos animais, mas em HUCV foi apenas relatado que este nitrato apresenta pouco efeito. O nitrato de tetra-hidrofurfurilo (NTHF) e o 13-nitrato-cis-9-octadecanoato de etila (NCOE) são doadores de óxido nítrico (NO), cujo efeito foi caracterizado em vasos animais. O 1,2-bis(tetrahidrofuran-2-il)etano-1,2-diildinitrato (BIS-NTHF) é um composto inédito (duas moléculas de NTHF) que não possui estudos farmacológicos. O objetivo deste estudo foi implantar e padronizar a técnica envolvendo HUCV, e caracterizar o efeito desses quatro nitratos orgânicos tanto em anéis de artéria (HUA) como veia (HUV) isoladas de cordão. A padronização da técnica mostrou que 3 g e 3h são, respectivamente, a tensão e tempo ideais para experimentos com os vasos umbilicais, além do fato de que estes apresentam uma queda espontânea tanto do tônus basal como do contrátil. O estudo com os nitratos mostrou que esses compostos relaxaram o tônus basal de HUCV. Todos os nitratos induziram vasorrelaxamento, em ambos os vasos umbilicais pré-contraídos com serotonina (5-HT), com efeitos máximos superiores a 90%, e com maior eficácia em relaxar HUA do que HUV. Nesta situação, GTN foi o nitrato mais potente em causar vasodilatação, BIS-NTHF apresentou um valor de potência intermediário, enquanto que NCOE e NTHF foram os menos potentes em relaxar HUV e HUA, respectivamente. Quando os anéis de HUA foram pré-contraídos com KCl 60 mM, houve uma atenuação da vasodilatação promovida pelos nitratos. GTN e NTHF também apresentaram o vasorrelaxamento diminuído nos anéis de HUV pré-contraídos com KCl 60 mM, enquanto NCOE e BIS-NTHF tiveram seus efeitos de forma semelhante aos anéis pré-contraídos com 5-HT. A pré-incubação de GTN, NTHF e BIS-NTHF atenuou as contrações induzidas por 5-HT, em anéis de HUA. Adicionalmente, GTN e BIS-NTHF também inibiram a contração estimulada por 5-HT em HUV. Em contrapartida, a pré-incubação de NTHF, em HUV, e de NCOE, tanto em HUV como em HUA, levaram à inibição menor, quando comparados aos outros nitratos. GTN, NTHF e BIS-NTHF inibiram o componente fásico e tônico da contração induzida por 5-HT, na ausência do Ca2+ extracelular. NCOE, por sua vez, foi mais eficaz em inibir a contração tônica. A pré-incubação de 10 μM de ODQ, inibidor da ciclase de guanilil solúvel, fez com que a resposta vasodilatadora de GTN, NTHF, NCOE e BIS-NTHF fosse atenuada de maneira significativa. A pré-incubação de 10 mM de TEA, um bloqueador de canais para potássio, em HUA diminuiu a resposta relaxante dos quatro nitratos, não alterando o efeito em HUV. Diante do exposto, pode-se concluir que os nitratos orgânicos GTN, NTHF, NCOE e BIS-NTHF causam vasorrelaxamento de anéis de HUCV, tanto no tônus basal quanto de contrações induzidas por 5-HT ou KCl. O mecanismo de ação dos nitratos nestes vasos humanos envolve ativação da sGC e de canais para potássio; e inibição da entrada de cálcio, liberação dos estoques deste íon do retículo sarcoplasmático e da atividade da ROCK.
8
Ntho, Mokgadi Gloria. "An educational-psychological investigation of the attitude of Black learners to HIV/AIDS / Mokgadi Gloria Ntho." Thesis, North-West University, 2005. http://hdl.handle.net/10394/2361.
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Furtado, Fabiola Fialho. "Efeitos cardiovasculares induzidos por um novo doador de óxido nítrico, o nitrato tetrahidrofurfurílico (NTHF), em ratos." Universidade Federal da Paraíba, 2014. http://tede.biblioteca.ufpb.br:8080/handle/tede/6808.
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Previous studies have show that the organic nitrate tetrahydrofurfuryl (NTHF) induces vasorelaxation in mesenteric artery rings with involvement of the NO-sGC-PKG pathway. This study evaluated the action of NTHF on cardiovascular parameters in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, investigating: the nitric oxide (NO) release, acute toxicity, the NTHF effect on blood pressure and heart rate, its vasorelaxant effect and its ability to induce tolerance. NTHF increased NO levels in rat aortic smooth muscle cells (SMC) and cardiomyocites. In acute toxicity studies, a high single dose from NTHF showed low toxicity. In normotensive animals, NTHF induced hypotension after oral administration of NTHF, and bradycardic and hypotensive effects following administration of this nitrate. These results were similar that found using nitroglycerine (NTG). In addition, these effects were not altered by pretreatment with hexamethonium, a ganglionic blocker. However the treatment with methylene blue, a sGC inhibitor, promoted attenuation of both hypotensive and bradycardic effects, suggesting the involvement of the sGC pathway in these effects. In mesenteric artery rings from SHR and WKY rats precontracted with phenylephrine, NTHF induced concentration dependent vasodilatation in both intact and removed endothelium. This result suggests that the vasorelaxant effect is an endothelium derived relaxation factors (EDRFs) independent mechanism. Furthermore, in the presence of NO° scavenging (PTIO) or ODQ, a sGC inhibitor, the vasorelaxation induced by NTHF was decreased, indicating the involvement of NO-sGC pathway in this response in both SHR and WKY. In the presence of cyanamide, an aldehyde dehydrogenase (mtALDH) inhibitor, the vasorelaxant effect was diminished, suggesting that NTHF is metabolized by this enzyme. After exposure to depolarizing agent KCl, the nitrate effect was significantly attenuated, a characteristic of substances which acts by K+ channels activation. This effect was confirmed after using tetraetylamonium (TEA), a K+ channels inhibitor. In normotensive rats treated with NTHF, the acute administration of NTHF promoted bradycardia and hypotension were are not changed in relation to which those observed in vehicle-treated animals, suggesting that organic nitrate did not induce in vivo tolerance. In vitro tolerance was evaluated in both mesenteric artery rings from animals pretreated with NTHF as well as rings previously exposed to isolated concentrations of NTHF. The vasorelaxant effect was not modified by pretreatment or exposure to NTHF, unlike that observed with NTG. In rings treated with NTG, the effect induced by NTHF was not modified, indicating that NTHF did not promote in vitro tolerance. The results demonstrated that NTHF promoted hypotensive and bradycardic effects in both SHR and WKY rats, with involvement of sGC enzyme; NTHF induced a vasorelaxant effect with participation of NO-sGC-PKG pathway and K+ channels. These effects seem to be mediated by NO release from cardiomyocites and SMC. Finally this study will help to advance the field towards clinical trials, since NTHF caused low toxicity and this nitrate was devoid of in vivo and in vitro tolerance.
Estudos anteriores demonstraram que o nitrato orgânico tetra-hidrofurfurílico (NTHF), promoveu efeito vasorrelaxante em artéria mesentérica de ratos normotensos, com envolvimento da via NO-sGC-PKG. O objetivo deste trabalho foi avaliar os efeitos cardiovasculares induzidos pelo NTHF em ratos espontaneamente hipertensos (SHR) e normotensos Wistar Kyoto (WKY), investigando: a liberação de óxido nítrico (NO), a toxicidade aguda, o efeito do NTHF sobre pressão arterial (PA) e frequência cardíaca (FC), o efeito vasodilatador desse composto, além de sua capacidade em induzir tolerância. Em células musculares lisas vasculares (CMLV) de aorta de rato e cardiomiócitos, NTHF promoveu aumento dos níveis de NO. Na avaliação da toxicidade aguda, NTHF foi administrado por via oral numa dose elevada, e nestas condições o nitrato orgânico apresentou baixa toxicidade. Em animais normotensos, NTHF promoveu hipotensão quando administrado por via oral e efeito hipotensor e bradicárdico após a administração intravenosa, semelhante ao observado pelo gliceril trinitrato (GTN). Este efeito não foi alterado pelo prétratamento com hexametônio, um bloqueador nicotínico ganglionar. Porém, o tratamento com azul de metileno, inibidor da enzima ciclase de guanilil solúvel (sGC), promoveu diminuição da resposta, indicando a participação da sGC nos efeitos hipotensor e bradicárdico. Em animais WKY e SHR NTHF promoveu efeito hipotensor e bradicárdico. Em anéis de artéria mesentérica de ratos SHR e WKY, pré-contraídos com fenilefrina, NTHF promoveu vasodilatação concentraçãodependente, com endotélio vascular intacto ou removido, sugerindo um efeito independente da liberação dos fatores relaxantes derivados do endotélio (EDRFs). Na presença do sequestrador de NO radicalar (PTIO) ou do inibidor seletivo da sGC (ODQ), o efeito vasorrelaxante do NTHF foi atenuado, indicando a participação da via NO-sGC tanto em SHR quanto WKY. Na presença de cianamida, um inibidor da enzima aldeído desidrogenase mitocondrial (mtALDH), o efeito vasorrelaxante foi atenuado, indicando que o nitrato é metabolizado por esta enzima. Após a exposição ao agente despolarizante KCl e após adição de tetraetilamônio (TEA), inibidor de canais para K+, o efeito do NTHF foi diminuído. Em animais normotensos prétratados com NTHF, a administração aguda de NTHF hipotensão e bradicardia, comparáveis às observadas no grupo controle, sugerindo que o NTHF não induz tolerância in vivo. A tolerância in vitro foi avaliada em artéria mesentérica de animais tratados previamente com NTHF, quando previamente expostos a concentrações isoladas do nitrato. O efeito vasorrelaxante não foi modificado pelo tratamento ou exposição prévia ao NTHF. Efeito contrário ao obtido com GTN. Em anéis prétratados com GTN, o efeito induzido pelo NTHF não foi modificado, sugerindo que o nitrato em estudo não promove tolerância in vitro. Os resultados demonstram que o NTHF promoveu efeito hipotensor e bradicárdico em animais normotensos e hipertensos, com envolvimento da enzima sGC; apresentou efeito vasorrelaxante, com participação da via NO-sGC-PKG e também de canais para K+. Esses efeitos parecem ser mediados por meio da liberação de NO tanto em CMLV quanto em cardiomiócitos. Por fim, NTHF evidencia um potencial clínico por apresentar baixa toxicidade e não induzir tolerância in vivo e in vitro
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Martin, Florence. "Etude des distributions en masse, charge nucléaire et énergie cinétique des produits de fission de l'233U(nth,f) et du 241Pu(nth,f) mesurées auprès du spectromètre de masse Lohengrin (ILL)." Thesis, Grenoble, 2013. http://www.theses.fr/2013GRENI098/document.
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Les rendements des produits de fission font partie des données nucléaires sur lesquellesreposent les simulations neutroniques. L’objectif de cette thèse est d’apporter de nouvellesmesures de rendements de fission de deux noyaux fissiles : le 241Pu et l’233U. Ces noyauxappartiennent respectivement au cycle du combustible de l’uranium et à celui du thorium.Ces mesures ont été réalisées auprès du spectromètre de masse Lohengrin de l’InstitutLaue Langevin (ILL) à Grenoble. Le spectromètre est combiné avec une chambre d’ionisationpour mesurer les rendements en masse de l’233U et du 241Pu et avec un dispositif despectrométrie gamma pour déterminer les rendements isotopiques de l’233U.Une nouvelle procédure d’analyse innovante a été mise en place dans le but de maîtriserles systématiques et de réduire les biais expérimentaux. La matrice de variance-covarianceassociée à nos mesures de rendements a ainsi pu être calculée pour la première foisFission product yields are significant nuclear data for neutronic simulations. The purposeof this work is to improve fission yield knowledge for two fissile nuclei : 241Pu and 233U. Thoseare respectively involved in the uranium and thorium nuclear fuel cycle.The measurements are performed at the Lohengrin mass spectrometer of the InstitutLaue-Langevin (ILL) located in Grenoble. The spectrometer is combined with an ionizationchamber to measure mass yields of 241Pu and 233U and with a gamma spectrometry set-upto determine isotopic yields of 233U.A new analysis method of experimental data has been developed in order to controlsystematics and to reduce experimental biases. For the first time, the experimental variancecovariancematrix of our measured fission yields could be deduced
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SILVA, Nadja Medeiros Justino da. "Análise da eficácia dos serviços prestados pelo NTI, como gestor de TI, à UFPE." Universidade Federal de Pernambuco, 2009. https://repositorio.ufpe.br/handle/123456789/7405.
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Previous issue date: 2009Universidade Federal de Pernambuco
Este trabalho tem como objeto de estudo a eficácia. Tema sério e complexo, abordado com frequência nos estudos das organizações para analisar e identificar formas de otimização e maximização da produtividade, levando-se em consideração que o cenário organizacional ainda apresenta como foco principal a obtenção de seus objetivos propostos através do domínio da racionalidade funcional em suas ações administrativas, seja no âmbito público ou privado. De forma mais específica, a proposta da pesquisa foi analisar a eficácia dos serviços prestados pelo NTI, como gestor de Tecnologia da Informação da UFPE, aos seus usuários institucionais na visão de seus diretores do período de 2000 a 2009. A abordagem teórica adotada tomou como base os conceitos do fato administrativo e da ação administrativa, temas desenvolvidos pelo sociólogo Alberto Guerreiro Ramos, abrangendo a concepção de um sistema administrativo em equilíbrio dinâmico, associada ao reconhecimento de uma categoria de totalidade, com seus elementos constitutivos dispostos em diferentes camadas e em contínua inter-relação, interagindo com o ambiente externo reciprocamente, transformando, a partir desse contexto e através de ações administrativas, seus recursos e investimentos nos objetivos propostos, mas sem perder de vista o bem-estar dos indivíduos. A metodologia aplicada teve uma perspectiva qualitativa. Quanto aos fins a pesquisa foi exploratória e descritiva e quanto aos meios foi trabalhada como um estudo de caso, apresentando como delimitação o período de 2000 a 2009 que destaca a reestruturação do NTI. Evento que propôs mudanças em sua estrutura organizacional com vistas a realinhar estratégias para atender com eficácia às demandas de TI da UFPE, ao mesmo tempo em que se propunha a aproximar as instâncias gerenciais do quadro técnico profissional, através da redistribuição dos serviços e dos técnicos de TI em projetos. Nesse contexto, buscou responder ao questionamento de como o NTI, na visão de seus diretores no período referenciado, tem articulado seus elementos do fato administrativo e o tipo de racionalidade estabelecida na ação administrativa no seu ambiente interno com vistas à eficácia dos serviços de TI prestados à UFPE
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Benson, Alexis. "Akustik och elevers uppfattningav ljudmiljön i klassrum : En undersökning av akustiken på gymnasieskolan NTI." Thesis, KTH, Skolan för industriell teknik och management (ITM), 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-229836.
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Klassrumsakustik behandlar rumsliga förutsättningar för ljudutbredning där god talhörbarhet är av vikt för elevers och lärares välbefinnande och möjligheter till goda lärmiljöer. Även kognitiva förmågor som minnesfunktioner påverkas av ljudmiljöer, där lägre bakgrundsljudnivåer och kortare efterklangstider förordas av forskning och byggnadstekniska standarder. Bakgrundsljudnivåer, efterklangstider T20 och reflexnivåer C50 kan tillsammans ge en bild av en god ljudmiljö för lärande i klassrum. I denna undersökning har fem klassrums ljudmiljöer utvärderats och enkätundersökningar har använts för att undersöka elevers och lärares subjektiva upplevelser av dessa ljudmiljöer under aktuella lektionstillfällen. Det har inte kunnat dras några tydliga korrelationssamband mellan akustiska data och subjektiva upplevelser av ljudmiljön från denna undersökning. Dock har undersökningen erhållit akustiska mätvärden från de aktuella klassrummen och speciellt två av klassrummen har funnits undermåliga i jämförelse med riktvärden från standarder med avseende på efterklangstider.Classroom acoustics deal with spatial prerequisites for sound propagation, where good speech audibility is important for the well-being of students and teachers and provide opportunities for good learning environments. Cognitive abilities as memory functions are also influenced by sound environments, where lower background noise levels and shorter reverberation times are advocated by research and acoustical performance criteria for classrooms. Background noise levels, reverberation time T20 and room response C50 can together provide a picture of a good sound environment for classroom learning. In this survey, five classroom sound environments have been evaluated and questionnaires have been used to investigate the subjective experiences of pupils and teachers in these sound environments during current investigated lessons. There has been no clear correlation between acoustic data and subjective experiences of the audio environment from this survey. However, the survey has obtained acoustic measurements from the current classrooms and especially two of the classrooms have been found to be substandard in comparison with the guideline values of reverberation time from standards.
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Williams, Sarah. "Molecular mechanism of regulation of the cellular protein levels of endonuclease III homologue (NTH1) in response to DNA damage." Thesis, University of Liverpool, 2018. http://livrepository.liverpool.ac.uk/3026978/.
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Deoxyribonucleic acid (DNA) is the store of genetic material, needed for cellular survival and replication. Cellular DNA is under constant attack from genotoxic agents, arising endogenously or exogenously in relation to the cell. Maintaining the stability of the genome is imperative to ensure accurate inheritance of the genetic code for future progeny and ensures that crucial biological processes are undisturbed. To uphold the integrity of the genome, cells have developed numerous DNA surveillance and repair mechanisms. The base excision repair (BER) pathway is one of the pathways that has evolved to remove minor types of DNA damage. The main sub-pathway of BER involves recognition and removal of the oxidised DNA base lesion, incision of the phosphodiester backbone, followed by insertion of the correct complementary nucleotide, before the nick in the DNA backbone is restored. During BER, the recognition of damaged bases relies on DNA glycosylase enzymes. Human endonuclease III (NTH1) is a DNA glycosylase enzyme which specifically recognises oxidised base lesions, caused by reactive oxygen species (ROS). Crucially, NTH1 excises thymine glycol (Tg), which is a particularly mutagenic base lesion. Regulation of enzymes implicated in the BER pathway is important to prevent excessive DNA damage. Reports have demonstrated the importance of post translational modifications (PTMs) in controlling the levels, activity and interactivity of BER proteins. Ubiquitylation is a PTM that has been implicated in the regulation of several BER enzymes. Ubiquitylation is completed by the ubiquitin proteasome pathway (UPP); whereby E3 ligase enzymes attach of moieties of ubiquitin to lysine residues of substrate proteins. The attachment of multiple moieties of ubiquitin (polyubiquitylation) is associated with the regulation of protein levels, whereas, the attachment of singular subunits of ubiquitin (monoubiquitylation) can have variable consequences. Despite this understanding, evidence of PTMs that target human NTH1 are deficient. A proteomic study demonstrated that NTH1 is subject to ubiquitylation dependent regulation, but the specific UPP enzymes involved were not identified. The overarching aim of this project was to understand the molecular mechanisms employed by human cells to regulate levels of NTH1 via ubiquitylation, with specific emphasis on discovering the E3 ligase enzymes involved. Using a well refined purification technique, human cell extracts were fractionated using a series of column chromatography columns. Candidate E3 ligase activity was examined using in vitro ubiquitylation assays of chromatography fractions, with recombinant NTH1 as the substrate protein. Eventually, mass spectrometry analysis of an isolated ubiquitylated fraction, identified tripartite motif containing 26 (TRIM26) as the only candidate E3 ligase enzyme present in the active fraction. We strengthened this finding by repeating ubiquitylation assays using recombinant TRIM26. Together, these findings identify TRIM26 as the major E3 in human cell extracts that catalyses the ubiquitylation of NTH1. Following this, site directed mutagenesis identified lysine 67 as the major site of TRIM26 dependent ubiquitylation of NTH1. Aside to this, the cellular implications of TRIM26 dependent regulation of NTH1 were investigated. Elevated levels of cellular NTH1 following proteasome inhibition confirmed that NTH1 levels may be regulated in cells by ubiquitylation dependent degradation. However, depletion of cellular TRIM26 via siRNA had no significant impact on the steady state levels of the glycosylase. Fractionation of cellular extracts confirmed that cellular NTH1 is located primarily in the nucleus and may be associated with chromatin. Depletion of TRIM26 resulted in no alteration in the cellular distribution of the glycosylase. Since TRIM26 dependent ubiquitylation did not appear to regulate the steady state levels of NTH1, further examination using hydrogen peroxide as a DNA damaging agent showed that DNA damage responsive levels of NTH1 protein expression increased following TRIM26 depletion. The clonogenic assay demonstrated that cells had increased survival capacity in the absence of TRIM26. Importantly, this observation was recapitulated with a partial overexpression of NTH1. Similarly, the alkaline single gel electrophoresis (comet) assay, in combination with an siRNA mediated depletion of TRIM26, concluded that cells with reduced TRIM26 levels have improved ability to manage oxidative stress. Once more, a similar level of improved DNA repair kinetics could be achieved by partially overexpressing NTH1. Overall, I successfully purified and identified TRIM26 as the major E3 ligase that ubiquitylates NTH1. The major site of TRIM26 dependent ubiquitylation is lysine 67; as substitution of this residue substantially impeded in vitro ubiquitylation via TRIM26. Cellular studies confirmed that levels of NTH1 may be regulated by ubiquitylation dependent degradation, although, TRIM26 dependent ubiquitylation was not implicated in the regulation of steady state levels of NTH1. Rather, it appears that TRIM26 may be implicated in the regulation of DNA damage responsive levels of NTH1. Interestingly, a separate investigation in our laboratory previously identified TRIM26 as one of the major E3 ligase enzymes involved in regulation of the steady state levels of another BER glycosylase, endonuclease VIII-like protein 1 (NEIL1). Excitingly, the outcomes of this work have now been peer-reviewed and accepted for publication in the Molecular and Cellular Biology scientific journal (see appendix). In summary, an increasingly dynamic role of TRIM26 is now becoming apparent; whereby, the E3 ligase is involved in the regulation of multiple BER glycosylases with different effects in relation to the DNA damage response. Despite this increased perception, the cellular mechanism which dictates the outcome of ubiquitylation of either glycosylase under the regulation of TRIM26 remains to be fully understood and demands further inspection.
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Gippner, Peter, B. I. Andreev, Yu V. Pyatkov, Yu E. Penionzhkevich, A. A. Aleksandrov, R. A. Shekhmamet'ev, Wolfgang Wagner, Clauß-Michael Herbach, and H. G. Ortlepp. "Evidence for a supershort fission mode in the reactions 242mAm(nth,f) and 244Cm(sf)." Forschungszentrum Dresden, 2010. http://nbn-resolving.de/urn:nbn:de:bsz:d120-qucosa-31909.
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Gippner, Peter, B. I. Andreev, Yu V. Pyatkov, Yu E. Penionzhkevich, A. A. Aleksandrov, R. A. Shekhmamet'ev, Wolfgang Wagner, Clauß-Michael Herbach, and H. G. Ortlepp. "Evidence for a supershort fission mode in the reactions 242mAm(nth,f) and 244Cm(sf)." Forschungszentrum Rossendorf, 1995. https://hzdr.qucosa.de/id/qucosa%3A22017.
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Alustau, Maria do Carmo de. "Envolvimento da via do óxido nítrico na resposta vasodilatadora induzida pelo nitrato tetra-hidrofurfurilíco (NTHF) em artéria mesentérica superior de Rato/." Universidade Federal da Paraíba, 2010. http://tede.biblioteca.ufpb.br:8080/handle/tede/6856.
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Previous issue date: 2010-03-05Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
The organic nitrates are the most commonly nitric oxide (NO) donors used in the treatment of cardiovascular diseases, mainly due the pronounced vasodilator effect. The purpose of this study was to evaluate the vascular effects of tetrahydrofurfuryl nitrate (NTHF), an organic nitrate derivated from the sugarcane s synthetic route. In rat mesenteric artery rings, pre-contracted with phenylephrine 10 μM, NTHF induced concentration-dependent (1 pM-10 μM) vasodilatation, with intact endothelium (Maximum Response = 84 ± 5.3%, pD2 = 7.86 ± 0.22) or endothelium removal, NTHF effects were no attenuated (MR = 100 ± 6.1%, pD2 = 7.39 ± 0.15), suggesting an independent mechanism of endothelium-derived vasoactive factors. The subsequent experiments were performed in rings without endothelium. After pre-incubation of 3 mM NAC, a reactive oxygen species (ROS) scavenger, the response was potentiated (pD2 = 8.32 ± 0.18), a common profile of compounds producing NO. However, when pre-incubated with L-NAME 100 μM, a NOS inhibitor, there was a decrease in the potency (pD2 = 6.62 ± 0.15), suggesting an involvement of this enzyme in the NTHF vascular response. By using scavenger NO radical, hydroxocobalamin 30 μM or carboxy-PTIO 300 μM, the efficacy was attenuated (MR = 66 ± 9.2% and 32 ± 6.2%, respectively), suggesting an involvement of this NO form in the NTHF vasodilator response. In the presence of cyanamide 1 mM, an aldehyde dehydrogenase (ALDH) inhibitor, or ODQ 10 μM, a soluble guanylate cyclase (sGC) inhibitor, there was a significative maximum response s reduction (MR = 29 ± 9.5% and 22 ± 4.6, respectively), indicating an involvement of these enzymes in the NTHF vasodilator mechanism. After exposure to high concentrations of extracellular K+, KCl 80 or 20 mM, the NTHF effect was significantly attenuated (MR = 49 ± 3.8%; 59 ± 9.5%, respectively), a characteristic of substances that act by activating K+ channels. This effect was confirmed after the use of tetraethylammonium (TEA) 3 mM (MR = 31 ± 5.0%), a non-selective K+ channel blocker. In the presence of TEA 1 mM, which at this concentration selectively blocks the BKCa, the vasodilatation was significantly attenuated (MR = 38 ± 8.3%), suggesting the involvement of these channels in the nitrate vasorelaxant effect. This hypothesis was reinforced following the use of 4-aminopyridine 1 mM (MR = 81 ± 8.5%), a KV blocker, glibenclamide 10 μM (MR = 97 ± 9.0%), a KATP blocker, or BaCl2 30 μM (MR = 94 ± 4.9%), a KIR blocker, which did not alter the NTHF vasodilator response. After NTHF (10 μM) incubation for 60 min, the vasodilatation was not changed, indicating that in this concentration this nitrate does not induce vascular tolerance. In conclusion, the NTHF cause vasodilatation, probably by promoting the NO radical release, involving the activation of NOS, ALDH, sGC and BKCa.
Os nitratos orgânicos são compostos doadores de óxido nítrico (NO) mais utilizados no tratamento de distúrbios cardiovasculares, principalmente, devido ao pronunciado efeito vasorrelaxante. A finalidade deste estudo foi avaliar os efeitos vasculares do nitrato tetra-hidrofurfurílico (NTHF), um nitrato orgânico proveniente da rota sintética da cana-de-açúcar. Em anéis de artéria mesentérica superior de rato, pré-contraídos com fenilefrina 10 μM, o NTHF promoveu vasodilatação de maneira dependente de concentração (1 pM-10 μM), com o endotélio vascular intacto (Emáx = 84 ± 5,3%; pD2 = 7,86 ± 0,22) ou removido (Emáx = 100 ± 6,1%; pD2 = 7,39 ± 0,15), sugerindo um mecanismo independente dos fatores vasoativos derivados do endotélio. Todos os experimentos subsequentes foram realizados com remoção do endotélio. Após pré-incubação com N-acetilcisteína 3 mM, um sequestrador de espécies reativas do oxigênio, a resposta foi potencializada (pD2 = 8,32 ± 0,18), um perfil peculiar de substâncias que produzem NO. Entretanto, ao serem pré-incubados com L-NAME 100 μM, um inibidor da NO sintase (NOS), houve uma diminuição da potência (pD2 = 6,62 ± 0,15), sugerindo a participação desta enzima no efeito vasodilatador do NTHF. Ao utilizar sequestradores de NO radicalar, hidroxocobalamina 30 μM ou carboxi-PTIO 300 μM, a eficácia do efeito vasorrelaxante do NTHF foi atenuada (Emáx = 66 ± 9,2% e 32 ± 6,2%, respectivamente), indicando o envolvimento desta forma do NO na vasodilatação do nitrato em estudo. Na presença de cianamida 1 mM, um inibidor da aldeído desidrogenase (ALDH), e do ODQ 10 μM, um inibidor da ciclase de guanilil solúvel (sGC), a resposta máxima foi reduzida significativamente (Emáx = 29 ± 9,5% e 22 ± 4,6, respectivamente), indicando a participação destas enzimas no mecanismo vasorrelaxante do NTHF. Após a exposição a concentrações elevadas de K+ extracelular, KCl 80 ou 20 mM, o efeito do NTHF foi significantemente atenuado (Emáx = 49 ± 3,8% e 59 ± 9,5%, respectivamente), sendo esta uma característica de substâncias que agem por ativar canais para K+. Este efeito foi confirmado após utilização de tetraetilamônio (TEA) 3 mM (Emáx = 31 ± 5,0%), que nesta concentração bloqueia de modo não seletivo os canais para K+. Ao utilizar TEA 1 mM (Emáx = 38 ± 8,3%), que nesta concentração bloqueia seletivamente os BKCa, a vasodilatação foi atenuada de modo significante, sugerindo a participação destes canais neste efeito vasorrelaxante. Esta hipótese foi reforçada após a utilização de 4-aminopiridina 1 mM (Emáx = 81 ± 8,5%), um bloqueador dos KV, glibenclamida 10 μM (Emáx = 97 ± 9,0%), um bloqueador dos KATP, ou BaCl2 30 μM (Emáx = 94 ± 4,9%), um bloqueador dos KIR, que não alteraram a resposta vasodilatadora do NTHF. Após a incubação durante 60 min com o NTHF (10 μM), o vasorrelaxamento não foi alterado, sugerindo que nesta concentração este nitrato não induz tolerância vascular. Em conclusão, o NTHF causa vasodilatação, provavelmente, por promover a liberação de NO radicalar, envolvendo a ativação da NOS, ALDH, sGC e de BKCa.
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Couto, Patrícia Gonçalves Pereira. "Caracterização molecular de EGFR, KRAS, BRAF, PTEN E NTH1 em pacientes brasileiros com carcinoma de não-pequenas células de pulmão (NSCLC)." Universidade Federal de Minas Gerais, 2011. http://hdl.handle.net/1843/BUOS-97FF29.
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Lung cancer is the leading global cause of cancer -related mortality and the patients have poor prognosis . To improve the survival rate of lung cancer patients, a better understanding of tumor biology is required as well as the subsequent development of new therapeutic strategies. EGFR, KRAS, BRAF and PTEN genes play important role in the regulation of cell growth, proliferation, migration, survival and inhibition of apoptosis, while NTH1 function as a DNA glycosylase in DNA repair pathway. Somatic alterations in these genes may be associated with the development of lung cancer. To investigate these molecular alterations, we analyzed the targeted regions of NTH1 (exons 1-6), PTEN (exons 1-9), KRAS (exons 2 and 3), BRAF (exon 15) and EGFR (exons 18-21) in eighty-two Brazilian patients with non-small cell lung cancer (NSCLC). PTEN protein expression was evaluated in twenty -one samples by
immunohistochemistry. We analyzed the genomic ancestry of our patients through 40 biallelic indels. No mutations or polymorphisms were detected in PTEN and BRAF. The nuclear PTEN expression was higher in neoplastic cells compared to benign cells. The analysis detected the presence of KRAS mutation G228A in codon 12 in one patient (1.2%) and two patients (2.4%) showed polymorphism at codon 61 (rs17851045). In EGFR sequences we found 746_750 deletion (domain LREA) in exon 19 in 3.6% patients and no alterations in exons 18 and 21. In exon 20, two polymorphisms were identified: a silent substitution ( CAG> CAA) at position c.2538 (rs1050171) was detected in 54.9% of cases and a substitution 2284-60T> C upstream of exon 20
(rs10241451) was found in 13.4% of cases. The substitution 2284 -60T> C was significantly associated with the disease for both, allele and genotype frequency (p = 0.03 and p = 0.02, respectively). Ancestry analysis showed a greater African component in our sample. Analysis of NTH1, showed the G99T polymorphism (rs2302102), 140-17C> T (rs2233518) and 131 (C> A) in only two patients (4%), wich may be related to the disease. As shown, our data show a low frequency of mutations in EGFR, KRAS, BRAF and PTEN, which can be explained by the high African component of our patients. Our data highlight that the genetic heterogeneity of the EGFR pathw ay in NSCLC may differ between populations. Therefore, it underscores the need to reassess the use of therapeutic agents for the inhibition of this pathway in different populations. Futhermore, these results should be expanded and validated in studies of larger scope, focusing on Brazilian patients in general.O câncer de pulmão é a neoplasia que apresenta maior taxa de mortalidade mundial, sendo o prognóstico dos pacientes acometidos muito ruim. O desenvolvimento de novas estratégias terapêuticas e a melhor compreensão da tumorigênese relacionada a este tipo de câncer são necessários para aumentar a sobrevida dos doentes. Neste sentido, EGFR, KRAS, BRAF e PTEN são genes que atuam em vias de crescimento, proliferação, migração, sobrevivência celular e inibição de apoptose enquanto NTH1 é uma glicosilase que atua na via de reparo de DNA. Alterações somáticas nesses genes podem estar associadas ao desenvolvimento do câncer de pulmão . Para avaliar essas possíveis alterações, analisamos as regiões-alvo de NTH1 (exons 1-6), PTEN (exons 1-9), KRAS (exons 2 e 3), BRAF (exon 15) e EGFR (exon 18-21) em oitenta e dois pacientes brasileiros portadores de carcinoma de não-pequenas células de pulmão (NSCLC). A expressão da proteína PTEN foi investigada em vinte e uma amostras pelo método de imunohistoquímica. Analisamos a ancestralidade genômica dos nossos pacientes através de 40 indels bialélicos. Não foram detectadas mutações ou polimorfismos em PTEN e BRAF. A expressão de PTEN nuclear foi maior em células neoplásicas quando comparado com células benignas. Na análise de KRAS detectamos a presença da mutação G228A no códon 12 em um paciente (1.2%) e dois pacientes (2,4%) apresentaram polimorfismo no códon 61 (rs17851045). Em EGFR encontramos a presença da deleção 746_750 (domínio LREA) no exon 19 em 3.6% pacientes e não detectamos alterações nos exons 18 e 21. No exon 20, dois polimorfismos foram identificados: a substituição silenciosa (CAG> CAA) na posição c.2538 (rs1050171) detectada em 54,9% dos casos e a substituição 2284-60T>C a montante do exon 20 (rs10241451) encontrada em 13,4% dos casos. A substituição 2284-60T>C apresentou associação significativa com a doença tanto para freqüência alélica quanto genotípica (p = 0,03 e p = 0,02, respectivamente). Na análise de ancestralidade encontramos um maior componente africano em nossa amostra. Em NTH1 encontramos os polimorfismos G99T (rs2302102), 140-17C>T (rs2233518) e 131 (C> A) em apenas dois pacientes (4%) que podem estar relacionados ao desenvolvimento da doença. Como demonstrado, nossos dados apresentam uma baixa frequência de mutações em EGFR, KRAS, BRAF e PTEN, o que pode ser explicado pelo alto componente africano encontrado em nossos pacientes. Nossos dados destacam que a heterogeneidade genética da via de EGFR em NSCLC pode diferir entre as populações, ressaltando assim a necessidade de reavaliar a utilização de agentes terapêuticos destinados a inibição desta via. É importante destacar que esses resultados devem ser expandidos e validados em estudos de escopo mais largo, com foco em pacientes brasileiros em geral.
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Ukpo, Eugenia Onwu. "Learner support in distance education : a mixed method evaluation of the National Teachers' Institute (NTI) Nigeria student support system." Thesis, University of Bristol, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.419382.
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Vemuri, Achyut. "Estimation of Instantaneous Speed for Rotating Systems: New Processing Techniques." University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470671420.
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Jamerlan, Mona Lisa. "Establishing mating systems by microsatellite analysis in declining saltwater crocodile (Crocodylus porosus) hatchling production at Edward River Crocodile Farm (Nth. Queensland) /." [St. Lucia, Qld.], 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17070.pdf.
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Kaled, Said. "La fragilité du droit foncier comorien à la lumière de la pluralité des droits." Thesis, Perpignan, 2014. http://www.theses.fr/2014PERP1198.
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Les Comores sont un archipel de quatre îles situé dans l’Océan Indien à l’entrée nord du canal de Mozambique. Ce fut une colonie française jusqu’en 1975 date à laquelle elle a accédé à son indépendance. La mixité des systèmes juridiques applicables semble être à l’origine du marasme juridico institutionnel qui secoue le pays depuis son indépendance. En effet, les deux systèmes juridiques musulman et français sont venus se superposer au droit traditionnel local. Au départ, ces systèmes se sont fondus dans les pratiques locales, mais vont, par la suite, considérer que ces coutumes ne peuvent pas coexister avec les institutions d’un Etat moderne. Or, l’histoire récente montre que l’ignorance ou le mépris de la tradition et de son système de régulation sociale compromet les réformes sociales engagées par l’action publique car elle n’a pas l’adhésion de la société. Le droit foncier comorien est confronté également à cette pluralité juridique. Il est à l’origine des conflits fonciers qui gangrènent la société. Les villageois, les familles et même l’Etat se trouvent au centre de ces conflits. L’appareil judiciaire censé les régler est paralysé par son organisation complexe, l’insuffisance de ses moyens, mais surtout par une corruption généralisée. L’absence d’un droit positif unifié contribue à une insécurité juridique.Plusieurs tentatives de stabilisation ont échoué depuis l’époque coloniale, mais des réformes récentes, comme la législation OHADA et celle relative à l’organisation judiciaire (loi n° 05-016/AU), présentent un gage d’espoirThe Comoros is an archipelago of four islands in the Indian Ocean at the northern entrance of the Mozambique Channel. It was a French colony until 1975 when it gained its independence. The mix of applicable legal systems seems to be the origin of the legal and institutional stagnation gripping the country since its independence. Indeed, both Muslim and French legal systems have been superimposed local traditional law. Initially, these systems were merged into local practices, but will thereafter be considered that these customs can not coexist with the institutions of a modern state. But recent history shows that ignorance or contempt for tradition and its system of social regulation undermines social reforms introduced by the prosecution because it has no support from society. Comorian land law is also facing this legal pluralism. Itis the origin of land conflicts that plague society. The villagers, families and even the state are at the center of these conflicts. The judiciary is supposed to adjust paralyzed by its complex organization, its lack of resources, but also by widespread corruption. The lack of a unified positive law contributes to legal uncertainty. Several failed attempts to stabilize since the colonial era, but recent reforms, such as the OHADA legislation and that relating to the Judicature (Act No. 05-016 / AU), have a sign of hope
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Villagrán, Fernández Mario. "Juego, tecnología y tiempo libre : estudio cualitativo sobre el papel de las prácticas lúdicas digitales y su desarrollo como nuevas tecnologías de la comunicación y la información (NTCI) en Chile." Tesis, Universidad de Chile, 2007. http://www.repositorio.uchile.cl/handle/2250/106056.
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Lan, Yang. "Computational Approaches for Time Series Analysis and Prediction. Data-Driven Methods for Pseudo-Periodical Sequences." Thesis, University of Bradford, 2009. http://hdl.handle.net/10454/4317.
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Time series data mining is one branch of data mining. Time series analysis and prediction have always played an important role in human activities and natural sciences. A Pseudo-Periodical time series has a complex structure, with fluctuations and frequencies of the times series changing over time. Currently, Pseudo-Periodicity of time series brings new properties and challenges to time series analysis and prediction. This thesis proposes two original computational approaches for time series analysis and prediction: Moving Average of nth-order Difference (MANoD) and Series Features Extraction (SFE). Based on data-driven methods, the two original approaches open new insights in time series analysis and prediction contributing with new feature detection techniques. The proposed algorithms can reveal hidden patterns based on the characteristics of time series, and they can be applied for predicting forthcoming events. This thesis also presents the evaluation results of proposed algorithms on various pseudo-periodical time series, and compares the predicting results with classical time series prediction methods. The results of the original approaches applied to real world and synthetic time series are very good and show that the contributions open promising research directions.
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Corrêa, Ana Sílvia da Mota. "Avaliação da eficácia em curto prazo do uso de placas oclusais reposicionadoras e dispositivos NTI (nociceptive trigeminal inhibitory splint) no controle de Artralgia da Articulação Temporomandibular." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/25/25146/tde-21032012-155434/.
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O objetivo dessa pesquisa foi testar a hipótese de que o tratamento através de aparelhos oclusais (placas oclusais e dispositivo NTI) é benéfico na melhora dos sinais e sintomas de Artralgia da Articulação Temporomandibular (ATM) quando comparado a um grupo controle. Para isso, 60 indivíduos foram avaliados através de questionários e exames que determinaram a presença de Artralgia da ATM e sua intensidade. Essa amostra foi então dividida aleatoriamente em três grupos de 20 indivíduos cada um, sendo que, o primeiro grupo recebeu tratamento com placa reposicionadora rígida em uso parcial e técnicas de aconselhamento e mudanças comportamentais para pacientes com Disfunção Temporomandibular (DTM); o segundo, tratamento com NTI em uso parcial e técnicas de aconselhamento e mudanças comportamentais para pacientes com DTM; e o terceiro grupo, correspondente ao grupo controle, recebeu apenas técnicas de aconselhamento e mudanças comportamentais para pacientes com DTM. As placas foram instaladas e os controles realizados após duas, seis semanas e três meses. Os pacientes foram avaliados através de escala de análise visual de dor, presença de ruídos, abertura bucal ativa, algometria e conforto no uso dos aparelhos oclusais para os grupos experimentais. Os resultados foram analisados através dos testes estatísticos: Teste Kruskal-Wallis, ANOVA e Tukey, adotando nível de significância de 5%. Os três grupos apresentaram melhora nos sinais e sintomas de Artralgia da ATM sugerindo que o tratamento com aparelhos oclusais e técnicas de aconselhamento e mudanças comportamentais parece ser benéfico ao paciente. No entanto, o uso de aparelhos oclusais parece promover uma melhora ao primeiro momento mais rápida, sendo ainda, o uso das placas oclusais e posicionadoras mais confortável ao paciente logo no início do tratamento contribuindo para uma diminuição mais rápida da sua dor. Os dispositivos NTI necessitam de mais estudos em longo prazo para confirmar sua eficácia, assim como a ausência de efeitos adversos.The aim of this research was to test the hypothesis that the treatment with intraoral appliances (occlusal splints and device NTI) is beneficial to the control of symptoms and signs of arthralgy of temporomandibular joint (TMJ) when compared to a control group. Therefore, sixty patients were analyzed by questionnaires and tests that determined the presence of arthralgy of the TMJ and its intensity. Then this sample was randomly divided into three groups of 20 patients each: the first group was treated with repositioning occlusal splint and orientations; the second group received an anterior device (NTI nociceptive trigeminal inhibitory system), the third group of patients (the control group) just received counseling and orientations for behavioral changes. The devices were installed and used in partial time (only during sleep), and the follow-ups were performed after 2, 6 weeks and 3 months. In these sessions, patients were evaluated according the visual scale of pain (VAS), presence of noise, active mouth opening, temporomandibular joint algometry and comfort in the use of intraoral appliances for the experimental groups. The results were analyzed with Kruskal-Wallis, ANOVA and Tukey, adopting a significance level of 5%. All three groups showed improvement in signs and symptoms of temporomandibular joint arthralgy, suggesting that occlusal appliances and behavioural orientations may be beneficial in the treatment of this condition. However, the management with occlusal appliance and orientations seems to have an earlier effect. The use of occlusal repositioning splint is more comfortable at the beginning of the treatment of patients contributing to a faster reduction of their pain. Long - term studies with the NTI device are needed to establish its effectiveness and absence of adverse dental effects.
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Rochman, Dimitri. "Mesure et analyse de la distribution en masse et charge des produits de fission de 245Cm(nth, f) grâce au spectromètre de masse Lohengrin (ILL-Grenoble)." Université Louis Pasteur (Strasbourg) (1971-2008), 2001. http://www.theses.fr/2001STR13152.
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Butcher, Ronald K. "COMPOSITE DATA FROM CENTRIFUGAL EXPERIMENTATION REGARDING HUMAN INFORMATION PROCESSING." Wright State University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=wright1182285671.
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Birgersson, Evert. "Determination of binary fission-fragment yields in the reaction 251Cf(nth, f) and Verification of nuclear reaction theory predictions of fission-fragment distributions in the reaction 238U(n, f)." Doctoral thesis, Örebro : Institutionen för naturvetenskap Department of Natural Sciences, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-1474.
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Yamamoto, Mayumi Ya-Ya. "The influence of non-domestic factors on elite sport development and anti-doping policy : the cases of Japan and the UK/England." Thesis, Loughborough University, 2010. https://dspace.lboro.ac.uk/2134/15137.
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The aim of this thesis is to examine the extent to which selected aspects of sport policy in Japan and also UK/England are influenced by international forces. The objectives which underpin the research aim are to analyse the characteristics of the domestic policy areas and identify the varying degree of impact of external influences on domestic sport policy. The thesis examines the interactions between domestic and international factors that shape elite sport policy and anti-doping policy and seeks to identify how domestic institutional values and ideas have been shaped by global influences. Importantly, by analysing the nature and mechanisms of global influence that are manifest at the domestic level, it is intended to identify varying degree of impact external to national policy. To achieve the above objectives, a qualitative methodology and related documentary research methods are adopted in the empirical investigations. Policy document analysis and semi-structured interviews are employed. The cases of UK (or England where appropriate) are introduced in order to generate a deeper understanding of the development of Japanese elite sport and anti-doping policy. The thesis draws on a range of theoretical frameworks, including international relations theory, international regime theory and globalisation, to analyse the empirical data. By adopting these theoretical frameworks, it is aimed to identify the possible characteristics of international policy regimes in the policy areas of elite sport and anti-doping.
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Alencar, Eloisa Nassar de. "Avaliação da eficácia em curto prazo do uso de placas estabilizadoras oclusais de cobertura total e dispositivos NTI (nociceptive trigeminal inhibitory splint) no tratamento da dor miofascial da musculatura mastigatória." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/25/25146/tde-26072011-162157/.
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O objetivo dessa pesquisa foi testar a hipótese de que o tratamento através de aparelhos oclusais é benéfico na melhora dos sinais e sintomas da Dor Miofascial (DMF) de origem mastigatória quando comparado a um grupo controle. Para isso, 51 indivíduos foram avaliados segundo os critérios estabelecidos pelo Research Diagnostic Criteria for Temporomandibular Disorders (RDC/ TMD) para determinar a presença de Dor Miofascial. Essa amostra foi então dividida de maneira randomizada e estratificada em três grupos: 21 pacientes receberam tratamento com placa estabilizadora rígida com cobertura total e técnicas de aconselhamento e mudanças comportamentais para pacientes com DTM (Disfunção Temporomandibular), 16 receberam o dispositivo NTI e técnicas de aconselhamento e mudanças comportamentais para pacientes com DTM e 14 participaram como grupo controle, recebendo apenas técnicas de aconselhamento e mudanças comportamentais para pacientes com DTM. Os dispositivos foram instalados e utilizados em uso parcial (noturno), os controles realizados após duas, seis semanas e três meses. Nos retornos, os pacientes foram avaliados quanto a EAV (Escala de Análise Visual), abertura bucal ativa e algometria (exame para análise do limiar de dor a pressão (LDP) realizado com o auxílio de um algômetro da marca KRATOS capaz de medir a pressão em Kgf). Ainda foram avaliados possíveis efeitos colaterais como desconforto ao uso dos aparelhos oclusais. Os resultados foram analisados com os testes estatísticos: Teste Qui-Quadrado, Kruskal-Wallis, ANOVA e Turkey, adotando-se um nível de significância de 0,05. Os três grupos apresentaram melhora nos sinais e sintomas de DMF, sugerindo que o tratamento com aparelhos oclusais e técnicas de aconselhamento e mudanças comportamentais parece ser benéfico ao paciente. No entanto, o uso de aparelhos oclusais parece levar a uma melhora mais rápida. O tratamento através das placas estabilizadoras oclusais parece ser mais seguro e efetivo e os dispositivos NTI necessitam de mais estudos em longo prazo para confirmar sua eficácia, assim como a ausência de efeitos adversos.The aim of this research was to test the hypothesis that the treatment with intraoral appliances with different occlusal designs is beneficial in the management of symptoms and signs of masticatory Myofascial Pain (MMP) when compared to a control group. 51 patients were analyzed according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/ TMD) in order to obtain the diagnostic of Myofascial Pain. Then the sample was randomly divided into three groups: 21 patients were treated with acrylic stabilization occlusal splint ; 16 received an anterior device (NTI (Nociceptive Trigeminal Inhibitory System)) and 14 patients received couseling and orientations for behavioral changes (control group). The two previous groups also received orientations and counseling. The devices were installed and weared in partial time (only during sleep), and the follow-ups were performed after 2, 6 weeks and three months. In these sessions, patients were evaluated according the visual scale of pain (VAS), maximum mouth opening and masticatory muscle algometry, able to determine the pain pressure threshold (PPT)(KRATOS, Brazil). Possible adverse effects were also analyzed such as comfort in the use of the appliance and occlusal alterations. The results were analyzed with Chi-Square test, Kruskal-Wallis, ANOVA and Turkey, with significance level of 5%. The three groups showed improvement in signs and symptoms of MMP, suggesting that occlusal appliances and behavioural orientations may be benefical in the treatment of this condition. However, the management with occlusal appliance and orientations seems to have an earlier effect. Long term studies with the NTI device are needed to establish its safety and absence of adverse dental effects.
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中村, 允耶. "線虫の塩基除去修復関連遺伝子ung-1およびnth-1の同定とその機能解析." 京都大学 (Kyoto University), 2009. http://hdl.handle.net/2433/124453.
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Chang, Ya-Wen, and 張雅雯. "Non-typable Haemophilus influenzae (NTHi) has become a dominant microbial strain causing invasive diseases." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/97995285054005683437.
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碩士國立中山大學
生物科學系研究所
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Hemophilus influenzae (Hi) has been an important strain in clinical examination, but it is not clear about its subtype, non-typable Hi, in causing invasive diseases after years of application of vaccines against typable Hi. Thus, the study is to determine the major infected bacterium causing invasive diseases and investigate the genotype relationship between antibiotic resistance and active IgA1 protease. Practical approaches of the study include clone each microorganism from infected blood, pus, sputum, bronchial washing and thorax samples of patients with invasive diseases. Each of the organisms was assayed for IgA1 protease activity, the type of the enzyme and antibiotic resistance. Forty-five patients aged 1 to over 71 with invasive diseases of diagnosed pneumonia, sinusitis, bacteremia, bronchitis, chronic obstructive of pulmonary diseases (COPD), conjunctivitis or otitis media, were analyzed, and all the 45 Hi isolates contain iga gene but only 80% contain active IgA1 protease. Mutations to silence iga gene are common in Hi isolates. The dominant population of infected bacterium is Hi, 84% of which are non-typable (NTHi). About 76% of NTHi and 85% of typable Hi (THi) contained active IgA1 protease. PFGE analysis showed that none of the 45 Hi isolates had identical genome. Phenotypes of active IgA1 protease and antibiotic resistance of the 45 Hi isolates showed no close relations each other. This study clearly demonstrated that NTHi has become a dominant strain in causing invasive diseases. Antibiotic resistance and active IgA1 protease are two essential but independent phenotypes for NTHi to infect and colonize. Antibiotic resistance of NTHi is dependent on the presence of beta-lactamase.
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Atkinson, CT. "Acquired macrolide resistance genes in nontypeable Haemophilus influenzae." Thesis, 2017. https://eprints.utas.edu.au/23758/1/Atkinson_whole_thesis_ex_pub_mat.pdf.
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Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen that is associated with a range of respiratory infections, including acute exacerbations of chronic obstructive pulmonary disease (COPD), and community acquired pneumonia (CAP). Macrolide antibiotics such as azithromycin are being more frequently used to manage these conditions, including those where NTHi may be involved, despite macrolides having relatively poor antibiotic activity against H. influenzae (azithromycin MICs of wild-type strains typically cover the range of 0.25-4 μg/mL). The efficacy of these antibiotics in managing these conditions is further threatened by the emergence of strains of NTHi exhibiting high-level macrolide resistance.
A range of different mechanisms of macrolide resistance are recognised broadly within bacteria. Resistance has been attributed to the presence of mutations in structural components of the ribosomal binding site of macrolides. Such mutations can occur in the 23S rRNA gene, as well as in the L4 and L22 structural proteins. Increased expression of inherent macrolide efflux mechanisms such as acrAB resulting from mutations in regulatory regions of these efflux pumps have also been recognised as a potential cause of macrolide resistance. Finally, resistance has also been attributed to the acquisition of macrolide resistance genes (AMRGs), which are readily disseminated among species on mobile genetic elements. There are a large number of different AMRGs and associated proteins, and the mechanisms by which they produce resistance vary. For example, the erm genes encode enzymes which modify the ribosomal binding site, the mef genes encode alternate efflux systems, and an additional group of genes encode enzymes which directly deactivate the macrolide.
High-level macrolide resistance in NTHi is uncommon and has historically been attributed to chromosomal mutations in ribosomal structural elements or regulatory regions controlling acrAB. In contrast, AMRGs have not been widely associated with NTHi and a number of studies have failed to detect these genes in this particular species. There has been a single study in which these genes have been reported to be highly prevalent in NTHi. In that study, among a collection of 106 NTHi isolates from children with cystic fibrosis enrolled in a placebo-controlled azithromycin trial, all isolates had at least one AMRG, with many of the isolates carrying two or three of these genes. However, the phenotypic effect of these genes was not consistent; only 27 of the AMRG-carrying isolates exhibited phenotypic resistance to macrolides. While the findings of that study identify the emergence and potential spread of AMRGs in NTHi, it raises a number of questions regarding the prevalence of these genes within NTHi isolates more broadly and the role they play in generating a resistant phenotype.
In Chapter 4 of this thesis, a collection of 186 NTHi respiratory isolates of variable azithromycin resistance phenotype (azithromycin MIC range: 0.09 to >256 μg/mL; MIC50: 1.5 μg/mL; MIC90: 3 μg/mL) derived from both cystic fibrosis and non-cystic fibrosis patients was established and analysed for; 1) the presence of macrolide resistance-associated L4, L22 and 23S rRNA mutations, and 2) the presence of the AMRGs erm(A), erm(B), erm(C), erm(F), mef(A) and mef(E). For the detection of the AMRGs, two methods were used; 1) a novel PCR using locked nucleic acid dual-labelled hydrolysis probes, and 2) the original primer set used by the authors of the previous study. While L22 and 23S rRNA alterations were detected in 2 isolates with high-level macrolide resistance (azithromycin MIC ≥ 256 μg/mL), none of the isolates were found to carry any of the AMRGs using the novel PCR detection method. When using the primers described in the original study, mef(A) and erm(A) were detected in a number of isolates. Subsequent analysis of these amplicons. revealed them to be false positive results, raising questions as to the possibility of false positive results in the original study.
Over 100 different AMRGs have been recognised, and the development and increasing availability of whole genome sequencing (WGS) techniques now allows for efficient and thorough analysis of sequences for the detection of antibiotic resistance mechanisms. In Chapter 5 of this thesis, WGS was utilised to further investigate the presence of a broad selection of other AMRGs (n=72) in NTHi, using the SPANDx pipeline. WGSs of two isolates of NTHi exhibiting high-level macrolide resistance obtained from the study of Chapter 4, as well as an additional 89 publically available WGSs of NTHi isolates of variable resistance phenotype, were examined in the study. None of the specified AMRGs were detected among this collection of WGSs. In addition, the WGSs of the 2 isolates from Chapter 4 with high-level macrolide resistance were interrogated for any AMRGs using the Comprehensive Antibiotic Resistance Database (CARD), and none were detected. Both isolates underwent further WGS analysis to confirm the L22 and 23S findings in Chapter 4; one isolate carried R88P in L22 and C2611G in 23S rRNA and the other isolate carried A2058G in 23S rRNA, all previously associated with decreased macrolide susceptibility in H. influenzae. Alterations in regulatory regions of acrAB were also detected in both isolates. Finally, transformation studies using donor genomic DNA from these 2 isolates were performed on H. influenzae Rd KW20. While none of the transformants that were generated exhibited as high an azithromycin MIC as the donors, a number of different regions of donor origin were detected in various transformants. The role of these regions in generating resistance in individual transformants was not clear but, with respect to the lower MICs exhibited by these transformants, the findings suggested a multifactorial aetiology for the high-level macrolide resistance seen in the donor isolates.
In the Roberts et al. study, the effect of the AMRGs appeared to be inconsistent, with some isolates not exhibiting increased MICs (compared to a typical wild-type strain). The effect of these AMRGs on macrolide susceptibility in H. influenzae remains to be established. As a result, the aim of Chapter 6 was to transfer select AMRGs (erm(A), erm(B), erm(C), mef(A) and mef(E)) to H. influenzae Rd KW20 and examine the phenotypic effect of expression of these genes. Initially, attempts were made to conjugatively transfer these AMRGs from select Gram positive donors to H. influenzae Rd KW20. These attempts were unsuccessful. As a result, the AMRGs were cloned into the shuttle vector pLS88 and H. influenzae Rd KW20 was transformed with these constructed plasmids by electroporation. Clones were generated with a range of approaches, including with and without the native regulatory regions of the AMRG inserts, and in the former, tested for expression with and without the presence of an inducing agent. High-level expression of erm(A), erm(B) and erm(C) was demonstrated in at least some of the various conditions and resulted in increased macrolide resistance in these transformants. In contrast, expression of mef(A) and mef(E) did not have an effect on macrolide resistance. In the Roberts et al. study, conjugative transfer of mef(A) to H. influenzae Rd KW20 resulted in a moderate increase in azithromycin and erythromycin MICs; our findings therefore suggest that mef only increases MICs in combination with other macrolide resistance mechanisms such as msr(D) (found downstream of mef and not covered by our cloned inserts) or underlying chromosomal alterations.
The above AMRGs are commonly encountered among human pathogens which share a respiratory niche with NTHi, including Staphylococcus aureus and various respiratory Streptococcus spp.. A number of other AMRGs, such as erm(42), msr(E) and mph(E), are typically encountered among animal commensals and pathogens such as Pasteurella spp. and Mannheimia spp.. H. influenzae is closely related to these pathogens and previous studies have demonstrated that they are able to exchange resistance determinants, including beta-lactamases. Therefore, the work of Chapter 7 explored the potential for conjugative transfer of erm(42), msr(E) and mph(E) (carried on the mobile multiresistance integrative and conjugative element ICEPmu1) and associated macrolide resistance from a bovine Pasteurella multocida isolate to H. influenzae Rd KW20. Transconjugants generated in this study were found to carry a truncated form of ICEPmu1 that lacked msr(E) and mph(E) but carried erm(42); transconjugants were found to exhibit increased erythromycin and clindamycin resistance. This truncated ICEPmu1 was successfully transferred from primary transconjugants to secondary H. influenzae Rd KW20 recipients, indicating that transfer functions were retained during conjugation. The acquisition of ICEPmu1 did not appear to have an impact on the fitness of H. influenzae Rd KW20 and the ICE was found to be stable in the absence of antibiotic selective pressure.
In summary, the major findings of this thesis are that AMRGs are not widespread in NTHi and that the high prevalence of a selected set of these genes described in one recent study is probably unique to the circumstances of that study. Although complex regulatory regions in many AMRGs mean that expression and associated resistance may be dependent on the specific genetic context, we have shown that under favourable conditions, erm(A), erm(B) and erm(C) can produce macrolide resistance in H. influenzae in their own right, but this is unlikely for the mef genes. Although we were unable to demonstrate conjugative transfer of common AMRGs from respiratory Gram positive organisms to H. influenzae, we were able to demonstrate conjugative transfer of an AMRG encoding multi-resistance replicon from a closely related organism of animal origin. This replicon produced macrolide resistance, was stably maintained without a significant fitness cost and was capable of ongoing conjugative transfer within H. influenzae. This thesis concludes that there is little evidence for the imminent and widespread emergence of AMRG associated macrolide resistance in NTHi; however, the increasing use of macrolides in both animals and humans and the prevalence of AMRGs in other organisms suggest that it is prudent to undertake ongoing periodic surveillance for these genes in NTHi.
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Obaid, NA. "Application of infra-red spectroscopy to the evaluation of biofilm formation and pathogenesis of nontypeable Haemophilus influenzae." Thesis, 2016. https://eprints.utas.edu.au/23114/1/Obaid_whole_thesis.pdf.
Full textAbstract:
Biofilm formation has been recognised as an aggregation of bacterial cells surrounded
by extracellular polymeric substances (EPS) which are secreted from the cells.
Biofilm has a significant role in chronicity of infection and cells are recalcitrant to
antibacterial agents when biofilm is formed on abiotic or biotic surfaces. Nontypeable
Haemophilus influenzae (NTHi) has been investigated previously in terms of biofilm
production ability. This study examined NTHi biofilm formation using a staining
assay and relationship to pathogenicity, and an assessment of the spatial distribution
of the chemical components by Fourier Transform Infrared (FTIR) spectroscopy.
Firstly, a semi-quantitative microtitre plate (MTP) assay for NTHi biofilm formation
was developed and validated for in vitro formation of biofilm. This assay was used to
evaluate the effect of length of storage time on four fresh NTHi clinical isolates.
Isolates were stored at -80Cº for two, four, eight, 12, 24 and 48 weeks before
measuring biofilm production. Sixty clinical isolates of NTHi from different body
sites were also screened for biofilm formation ability and relationship with the body
site. FTIR microspectroscopy was applied to study NTHi biofilm formation and
pathogenesis by generating FTIR spectra. FTIR spectroscopy coupled with imaging of
the biofilm components were assessed for untreated biofilm, as well as the effect of
antibiotic treatment on new biofilm formation and treatment of mature NTHi biofilm.
The MTP showed consistent differences between the different NTHi isolates tested in
first part of the project with these categorised as high and low biofilm producers. The
MTP assay demonstrated that frozen storage of the isolates was not a determinant of
biofilm formation. No statistically significant differences in the in vitro biofilm
production were found across the clinical NTHi isolates from the nasopharynx
(normal flora), ears (otitis media), lung (community acquired pneumonia and
bronchiectasis in cystic fibrosis) or the isolates of Haemophilus haemolyticus (oropharynx, normal flora). However, the isolates from eyes (conjunctivitis)
demonstrated remarkably consistent low biofilm production compared to the isolates
from other body site (P<0.005). In the second part of this project, FTIR spectroscopy
was used to analyse the chemical constituents of the different biofilms. Unsupervised
multivariate analysis (PCA) of the spectral data showed a chemical distinction
between the two categories of biofilm formation (high and low). Analysis of
microscopic IR hyperspectral data highlighted the spatial distribution of the different
chemical components of the biofilm such as protein and carbohydrate. Analysis of
antibiotic treated biofilm by FTIR showed an increase of protein bands in NTHi
compared to standard Haemophilus influenzae isolate and untreated biofilm.
This project provides detailed information about ability of formation, pathogenesis
and chemical composition of biofilms produced by NTHi isolates. Spectral
information, with the effect of antibiotic on mature and newly formed NTHi biofilms
provides a spatial overview of chemical differences in the bacterial biofilm.
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Batista, Beatriz da Cunha. "Characterization and Biofilm Assessment of Haemophilus influenzae Isolates from Patients with Chronic Obstructive Pulmonary Disease and Otitis Media." Master's thesis, 2018. http://hdl.handle.net/10362/58090.
Full textAbstract:
Haemophilus influenzae is a commensal microorganism of the human nasopharynx,
responsible for both invasive and non-invasive diseases. This work focused on the study of 93 H. influenzae isolates, collected between 2013 and 2018, from patients with two epidemiologically relevant non-invasive diseases: Chronic Obstructive Pulmonary Disease (COPD) and Otitis Media (OM). Phenotypical and molecular characterizations were performed for the isolates, regarding capsular typing, β-lactamase production, antibiotic susceptibility, genetic diversity by MLST, presence/absence of virulence factors (pilA, hifA, hmw1A, hmw2A, hia and ompP5) and ability to produce biofilms.
COPD isolates were collected from adults (100%), while 98.2% of OM isolates were collected from children. Non-typeable H. influenzae (NTHi) was the aetiological agent in COPD (97.4%) and OM (100%). Regarding antibiotic susceptibility, it should be noticed that 15.1% of the isolates were β- lactamase producers. MLST revealed a high genetic diversity among COPD and OM isolates, with 31 STs in 41 analysed isolates. pilA and ompP5 genes were present in more than 50% of COPD and OM isolates. hifA and hia genes were identified in less than half of the isolates, with a higher prevalence of
these among OM isolates. hmw1A and hmw2A genes were respectively identified in 25.5% and 32.7% of OM isolates, while both hmw genes were present in 76.3% of COPD isolates. Biofilm production was observed for 14.0% and 29.0% of all isolates after 24h and 48h, respectively. No relationship between biofilm production and clinical source could be established, as well as with the presence of virulence factors (pilA, hmw1A e hmw2A) involved in biofilm production.
COPD and OM are frequently associated with NTHi. Since no vaccines are available,
monitoring of these diseases is highly recommended, as these constitute a Public Health threat associated with a high economic and social burden.
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Lee, Chi-Fan, and 李啟帆. "Nontypeable Haemophilus influenzae clearance by RAW624.7 cells is impaired by exposure to cigarette smoke extract and the change of inflammatory cell profiles in NTHi challenged whole-body cigarette smoke exposure mice model." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/tvurmr.
Full textAbstract:
碩士中國醫藥大學
基礎醫學研究所碩士班
105
From the data released by World Health Organization at 2012, Chronic Obstructive Pulmonary Disease (COPD) causes over three million deaths globally and is climbing up to the third of top ten cause of death at 2012. In many clinical studies, COPD patients usually have symptoms like sputum, long-lasting cough, chronic lung inflammation and air-flow limitation. COPD is an irreversible disease. This condition outdraws the importance of early diagnosis and the proper therapy to COPD. However, COPD is not the top ten cause of death in the low developed countries and undeveloped countries. This condition not only shows the high relation between COPD and the development of a country, but also shows the big health problem in developed country. In addition, the risk factors of COPD could come from air pollution(PM2.5、PM5、PM10、polycyclic aromatic hydrocarbons), cigarette smoke (smoke consumption or second-hand smoke), gene, infection, ageing and so on. In several research studies, cigarette smoke is the major risk factor to trigger COPD. After calculation, over 80 percentage of COPD patient have smoke behavior. Moreover, they are also vulnerable to infection. Nontypeable haemophilus influenzae (NTHi), which is gram-negative coccobacillus bacteria, is the most common pathogen found in sputum from COPD patients. In addition, both cigarette smoke and NTHi infection can lead to lung inflammation, COPD exacerbation and lung cancer. Therefore, we are curious about the immune response and the mechanism of this NTHi infection after cigarette smoke challenge. From the in vitro data, we found bacterial clearance is impaired in cigarette smoke extracts (CSE) treated Raw264.7 cells. The CCL-2, CXCL-2 and CXCL10 mRNA expression were reduced in CSE and NTHi dual treated RAW cells. Moreover, our lab member has previously found that NF-B promoter activity was also attenuated in CSE and NTHi dual treated RAW cells. In order to confirm in vitro results, we set up a whole-body cigarette smoke exposure mouse model. We found cigarette smoke indeed impair lung function within air-flow resistance experiment. The total cells found in BALF were increased in smoke-treated mice or NTHi challenged mice compared to control mice. Yet, this BALF cell increasement was impaired within smoke-treated mice after NTHi challenge.
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Kopecká, Miroslava. "Molekulární mechanismus regulace funkce neutrální trehalasy Nth1." Doctoral thesis, 2015. http://www.nusl.cz/ntk/nusl-352271.
Full textAbstract:
The yeast enzyme neutral trehalase (Nth1, EC 3.2.1.28) from the Saccharomyces cerevisiae helps these organisms to survive adverse living conditions. Nth1 hydrolyses a storage and protective disaccharide trehalose into two molecules of glucose. The activity of this enzyme is regulated by PKA phosphorylation, Ca2+ binding and the yeast 14-3-3 protein (Bmh1) binding. Ca2+ binds to the Ca-binding domain located within N-terminus of Nth1 and contains so called EF-hand motif (D114 TDKNYQITIED125 ) which is highly conserved among many Ca-binding proteins. The main aim of this project was to reveal the structural basis of the Bmh1- and calcium-dependent activation of Nth1. Other goals were to solve the structure of Nth1 itself and the structure of its complex with Bmh1. To reveal how the calcium regulates the Nth1 activity we prepared twelve mutant forms of Nth1 using site directed mutagenesis. These mutations were located within the region of EF-hand motif and its close vicinity. We estimated the enzymatic activity of all these mutants in the presence of Bmh1 and/or Ca2+ . The ability of Nth1 to form stable complexes with Bmh1 was verified using the native polyacrylamide gel electrophoresis and analytical ultracentrifugation. The impact of mutations on the structure and properties of Nth1 was tested using...
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Yang, Shu-Hua, and 楊淑華. "Accounting Service Quality: A Case Study of NTHU." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/56427432956987409034.
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Chang, Yen-Jung, and 張晏榕. "NTHU-Route 2.0: A Fast and Stable Global Router." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/50137316832522598547.
Full textAbstract:
碩士國立清華大學
資訊工程學系
96
We present in this thesis a fast and stable global router called NTHU-Route 2.0 that improves the solution quality and runtime of a state-of-the-art router, NTHURoute, by the following enhancements: (1) a new history based cost function, (2) new ordering methods for rip-up-and-reroute and congested region identification, and (3) two implementation techniques. The experimental results show that our router solves all ISPD98 benchmarks with very good quality. Besides, it routes 7 of 8 ISPD07 benchmarks without inducing any overflow. In particular, for one of the benchmarks which are thought to be difficult cases previously, our router is the only one that can completely eliminate its total overflow. Our router also successfully solves 12 of 16 ISPD08 benchmarks without causing any overflow and efficiently generates the best solutions for almost all benchmarks among all stateof-the-art global routers.
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Macáková, Eva. "Úloha Bmh proteinů v regulaci kvasničného enzymu neutrální trehalasy Nth1." Doctoral thesis, 2013. http://www.nusl.cz/ntk/nusl-321456.
Full textAbstract:
118 10. Summary Neutral trehalase 1 is a yeast enzyme from the family of hydrolases, which catalyzes hydrolysis of trehalose to two glucose molecules. Trehalose is a non-reducing disacharide, which serves as a carbon source in a yeast cells as well as a stress metabolite. When a cell is under stress conditions it accumulate trehalose and through the recovery process the trehalose is hydrolyses by trehalases. The main subject of our study was Nth1 from S. cerevisiae. It was published earlier (Panni, S., et al., 2008), that Nth1 must be phosphorylated by PKA and in the presence of 14-3-3 protein to be active. The activity of Nth1 also slightly increases in the presence of Ca2+ ions (Franco, A., et al., 2003). 14-3-3 proteins are family of acid regulatory proteins, which participates in variety of processes in the cells, like regulation of the cell-cycle, cell metabolism, transcription, apoptosis etc. They have more than 400 known binding partners, which include transcription factors, signalling molecules, enzymes and others. They control the regulation of their binding partners through phosphorylated motives in sequence by changing conformation of the binding partner, revealing or masking specific sequence or by mediation of protein-protein interactions. There are many isoforms of 14-3- 3 proteins through all...
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Li, An-Lun, and 李安倫. "DEVELOPMENT, VALIDATION, AND DEMONSTRATION OF THE NTHU FLIGHT DOSE CALCULATOR." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/497f32.
Full textAbstract:
碩士國立清華大學
核子工程與科學研究所
105
Galactic cosmic rays from outer space enter the Earth’s atmosphere and interact with air nuclei, leading to a phenomenon called the cosmic-ray air shower. Because the atmosphere provides scant protection to aircraft at high altitudes, aircrew are exposed to elevated levels of cosmic radiation. It’s necessary to evaluate receiving dose of aircrew. Aircrew in the European Union have been recognized as occupationally exposed workers since 1996. Several national and international organizations have published guidelines for monitoring and managing the doses received by aircrew. In line with this trend, the Atomic Energy Council in Taiwan has initiated research on improving aircrew exposure and regulatory control. Absolute intensities and energy spectra of secondary components in the atmosphere are complex and depend on numerous factors, including altitude, latitude, and solar activity. Numerical methods are extensively used to evaluate radiation exposure for aircraft crew and passengers. Literature on this topic is abundant, and various assessment codes are currently being used for aircrew dosimetry. To the authors’ knowledge, most flight routes investigated in the literature serve cities at intermediate and high latitudes; these routes do not include various flights of interest in Taiwan, although where the geomagnetic cutoff rigidity is nearly the highest in the world and the intensity of cosmic radiation is relatively low. Therefore, this study performed appropriate dose assessments for popular flights in Taiwan and developed a reliable and easy-to-use computer program (NTHU Flight Dose Calculator) for this purpose. 10 completed simulation projects which content electronic components was added to improve accuracy of database, following by previous work, which contain 50 simulation projects (44 simplified & 6 completed projects). Using newly developed NTHU flight dose calculator to compare 11 different software in 23 flight routes, which from EURADOS report. Also, choosing flight routes from Taipei to 11 cities worldwide to calculate flight dose of interest in Taiwan. The radiation components include neutron, proton, muon, photon, electron and positron. Finally, we use error propagation theory to analyze and confirm the accuracy. The software is available to public and authority, and can become a tool of cosmic radiation research.
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Wang, Fu-Yun, and 王復芸. "How to satisfy undergraduate students: using NTHU survey as example." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/wa6e8q.
Full text
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蔡文旗. "Evaluation of the dose distribution for the NTHU Co-60 irradiation facility." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/48777375736288992021.
Full text
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羅子傑. "A NTHU-3-like Layered Germanate and Sucrose-Induced Chiral Porous Zincophosphites." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/44372286787158201255.
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Chang, Bei-Hua, and 張倍華. "To Facilitate the Exploration of Institutes in NTHU Using Latent Dirichlet Allocation." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/demxn7.
Full textAbstract:
碩士國立清華大學
服務科學研究所
106
Cross field learning and multi-professions have become a trend in 21th century. People are gradually expected to possess knowledge and skills across different fields in order to communicate, cooperate, and solve complex problems. In universities, institutes provide learning resources, such as study programs and courses. However, during the process of making career plan and information seeking, the resources and knowledge networks need students who have motivations to explore disciplines beyond their current disciplines with additional efforts to explore and discover. In the past, though people payed attention on how to assist cross-field learning for students, it lacked the discussion about how to utilize information systems to facilitate this task in students' scenarios. This study aims to investigate the needs and the problems of students as target users of the service system, and develop an exploration prototype system as a minimum viable product to test the market. We also intend to make the value out of data from the institutional repository storing explicit knowledge. To achieve the goals and fulfil the needs of people, we take the framework of design science in the research. The exploration system, called Research Area Exploration System (RAES) applied Latent Dirichlet Allocation (LDA) to make connections across institutes and research areas. At the end, we evaluate the performance with quantitative and qualitative methods by comparing RAES with the Electronic Thesis and Dissertation System (eTDS) used by the library. The results show that RAES uniquely benefits users in different aspects from the existing eTDS, which indicates that RAES marginally contributes to facilitating students to cross disciplines in their studies.
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Wöstheinrich, Marcus [Verfasser]. "Emission von ternären Teilchen aus den Reaktionen 229Th(nth,f), 233U(nth,f) und 239Pu(nt-1tnh,f) / vorgelegt von Marcus Wöstheinrich." 1999. http://d-nb.info/963242830/34.
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Tseng, Yi-Ning, and 曾怡寧. "The effect of anti-commons in the post-STBL era: Evidence from NTHU." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/37166609821630211425.
Full textAbstract:
碩士國立清華大學
科技管理研究所
101
After The Bayh Dole Act in the US and related laws in other countries, the increasing commercialization of university discoveries has initiated a controversy on the impact for scientific research. It has been argued that an increasing orientation towards commercialization may have a negative impact on research work and publication. This paper empirically examines the emerging anti-commons effect of academic patenting on knowledge production after Taiwan after Science and Technology Basic Law. Through a panel dataset of 400 professors, including patent inventers and non-patent inventors, in National Tsing-Hua University during 1999~2010, the results reveal that the anti-commons effect is not happen in publication quantity, quality, and variety. In contrast, they reveal that the relationship between patent activities and publication performance is complementary, not substitute, in National Tsing-Hua University. Especially, this paper examines the pre-patent and post-patent period, and discovers that the change in the behavior of professors can be traced to the pre-patent period.
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Chang, Hai-Ting, and 張海定. "Design of nth-order voltage-mode notch filters using CCCIIs." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/6kwq74.
Full textAbstract:
碩士中原大學
電機工程研究所
91
Abstract In the thesis, we use the least number of current controlled conveyor (CCCII) and capacitors to realize an n•th-order voltage-mode notch filter structure. We apply the CCCII’s intrinsic resistance to design voltage mode notch filters. No need of passive resistors leads to a much simpler circuit structure. First we present a 2nd-order voltage mode notch filter circuit by using one positive type, one negative type current controlled conveyor (CCCII), two positive type CCCIIs, and two grounded capacitors. The proposed circuit enjoys the following advantages: no component matching conditions, employment of grounded passive elements, very low active and passive sensitivities. Secondly we develop a 3rd-order voltage-mode notch filter by adding one positive type CCCII and one grounded capacitor. Finally, we extend the technique to the n•th-oreder voltage-mode notch filter. The feasibility and accuracy of the proposed circuit has been verified by using Spice and Matlab. The simulation result agrees very well with the theoretical curve.
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Liu, Li-Yu, and 劉麗玉. "A Study on the architect''s implementation in design the NTHU Detached Housing Project." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/a267uu.
Full textAbstract:
碩士國立臺北科技大學
建築與都市設計研究所
97
As the development patterns of the Taiwan local housing, the buyers are only having the “ Right to Choose “, but not the “ Right to Determine “. The format of the “attendance design” will offer the power for the dweller to control the living space, avoid the monopoly from the builder/developer as well as the professional, but also provides a common understanding for the created environment through the dweller’s participation in the design build process. Such format also offers an opportunity for those, who wish to fulfill their ideal living space. As at the present time, there are few domestic models which could be offered as for further understanding as well as for the operational study. The author is using the NTHU Detached-faculty Housing Project, which she has been participating, as for the case study. From the integration between the architects, the Dweller (Owner) and the Steering Committee, it is visualized the actual “ Design with the User’s Participation” situation. And with the author’s expertise and also as the participant, the author analyzes the problems, and offers an alternative for the improvement opportunity. The fundamental findings: 1) Mutual respect & communication, 2) Working partnership, not conflict relationship, 3) Fairness is the principle of practice, 4) Using limited terminology with better understanding, 5) Avoid two dimensional presentation, adopt 3-D instead, 6) Avoid detailed discussion in the Schematic Phase.
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Kunkle, Thomas James. "A multivariate interpolant with nth derivatives not much larger than necessary." 1991. http://catalog.hathitrust.org/api/volumes/oclc/25287365.html.
Full textAbstract:
Thesis (Ph. D.)--University of Wisconsin--Madison, 1991.Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaf 54).
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Shih, Wei-Che, and 施維哲. "Design of the nth Order Adaptive Integral Variable Structure Derivative Estimator." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/qfje2k.
Full textAbstract:
碩士國立中山大學
電機工程學系研究所
97
Based on the Lyapunov stability theorem, a methodology of designing an nth order adaptive integral variable structure derivative estimator (AIVSDE) is proposed in this thesis. The proposed derivative estimator not only is an improved version of the existing AIVSDE, but also can be used to estimate the nth derivative of a smooth signal which has continuous and bounded derivatives up to n+1. Analysis results show that adjusting some of the parameters can facilitate the derivative estimation of signals with higher frequency noise. The adaptive algorithm is incorporated in the estimation scheme for tracking the unknown upper bounded of the input signal as well as their''s derivatives. The stability of the proposed derivative estimator is guaranteed, and the comparison between recently proposed derivative estimator of high-order sliding mode control and AIVSDE is also demonstrated.