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Lasse, Samuel. "Tgif and Smad2 mutations increase mammalian sensitivity to retinoic acid teratogenesis." Connect to this title online, 2005. http://hdl.handle.net/1811/3543.
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Thesis (Honors)--Ohio State University, 2005.Title from first page of PDF file. Document formattted into pages: contains vi, 43 p.; also includes graphics. Includes bibliographical references (p. 41-43). Available online via Ohio State University's Knowledge Bank.
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Löser, Dana A. "Investigating the mechanisms by which PARP inhibitors increase sensitivity to DNA damaging agents." Thesis, University of Sussex, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.505912.
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Damage induced by ionising radiation (IR) is mainly repaired by classical non homologous end joining (D-NHEJ), but a small subset of DSBs is repaired with slow kinetics in an ATM (Ataxia telangiectasia mutated) and Artemis dependent manner. In addition, a PARP-1 dependent NHEJ backup pathway (B-NHEJ) was described, which is thought to function in the absence of D-NHEJ. Using ATM, Artemis or DNA ligase IV deficient mouse embryonic fibroblasts (MEFs) as a model system, the effect of the potent and specific PARP-1/-2 inhibitor KU-0059436 upon clonogenic survival after various types of damage that induce different spectra of SSBs and DSBs was measured. In Artemis or ATM deficient MEFs no sensitising effect of KU-0059436 was detected after neocarzinostatin (NCS) treatment; however PARP inhibition increased sensitivity to IR and methylmethane sulphonate (MMS) markedly. In these cell lines no specific single strand break repair (SSBR) defect was observed, and radio-sensitisation by KU-0059436 was replication dependent. Furthermore PARP inhibition led to increased formation of DSBs, an effect which was augmented in Artemis deficient cells. PARP inhibition in DNA ligase IV deficient cells led to increased sensitivity after damage induction to all agents. However, radiosensitisation by KU-0059436 was replication independent. Results show that PARP inhibition increases the dependence on Artemis and ATM after SSB induction, which is consistent with a model whereby DSBs that arise from SSBs during DNA replication in the presence of a PARP inhibitor require ATM and Artemis for their repair. In cells deficient for DNA ligase IV, PARP inhibition causes additional replication independent sensitisation both by abrogating B-NHEJ and promoting accumulation of replication independent DSBs.
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Salisbury, Tonya. "Using globally significant children's literature to increase fourth-grade students' global attitudes and intercultural sensitivity." ScholarWorks, 2010. https://scholarworks.waldenu.edu/dissertations/797.
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It is vital for future generations to clearly grasp what it means to be global citizens in order for them to be successful and for America to maintain its status as a world leader. The purpose of this mixed-method study was to measure and describe the growth of global attitudes and intercultural sensitivity that fourth-grade students acquire through reading and discussing globally significant children's literature which honors and celebrates diversity worldwide, in terms of culture, race, language, religion, and social status. According to Rosenblatt's transactional theory, readers experience aesthetic transactions with the text leading to an understanding of the world around them. The research question involved whether the use of globally significant children's literature created aesthetic transactions and would result in significant changes in fourth-grade students' intercultural sensitivity and global attitudes. Using literature as a catalyst for group discussions and personal responses related to global issues, 23 fourth-grade students participated in a 12-week study. Qualitative data included participants' personal reading response journals and audio taped group literature circle discussions, which were reviewed and coded for evidence of growth in intercultural sensitivity based on Bennett's developmental model of intercultural sensitivity. Two surveys were developed by the researcher to gather quantitative data. A dependent samples, two-tailed, t test at the p < .05 level was used to test the hypothesis that students' global attitudes and intercultural sensitivity would increase after participating in these literature circles. The statistical data gathered showed gains in both areas. It is recommended that teachers at all grade levels utilize globally significant literature and encourage literary exchanges to promote cultural understandings among their students. Developing a mindset of cultural sensitivity in elementary students can have a positive impact on the relationships between individuals and groups representing diverse cultures.
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Krahn, Alexander Philipp. "Hardware development to increase NMR sensitivity and spectral resolution by novel rf resonators and polarization transfer." Lyon, Ecole normale supérieure, 2010. http://www.theses.fr/2010ENSL0561.
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Dans cette thèse, de nouvelles méthodes sont analysées afin d’augmenter la sensibilité, faible, du phénomène d’induction nucléaire grâce l’optimisation de l’instrument lui-même et par le couplage au moyen la Polarisation Dynamique Nucléaire (PDN). La première partie, est axée sur la bobine de mesure en contact avec l’échantillon et le circuit de sonde de RMN de l’état solide sous très hauts champs magnétiques. Le principe de réciprocité et les calculs de champ électromagnétique permettent une description physique des bobines ainsi qu’une optimisation de la géométrie des bobines de mesure. Dans ce contexte la problématique des champs électriques limite auxquels sont soumis les échantillons aux fréquences de Larmor élevées est prise en compte. Ce phénomène a toujours posé de sérieuses difficultés au moment de l’irradiation RF par des impulsions de découplage, cause d’une augmentation sensible de la température des échantillons dispersifs. Pour y remédier, des bobines innovantes, appelées LLC (Loop-gap Loaded Coil), issues de l’analyse numérique de la distribution du champ électromagnétique, sont introduites. Elles réduisent la composante électrique de l’onde électromagnétique dans le volume de l’échantillon. Cette étude est illustrée par la comparaison entre la simulation et l’étude expérimentale réalisée dans un champ statique de 16. 4 T. Dans la seconde partie, des résonateurs adaptés sont présentés pour appliquer la technique de la PDN, afin d’augmenter la polarisation des spins nucléaires par transfert de polarisation à travers le couplage des spins électroniques. Le dispositif expérimental mis en oeuvre relève du défi technique et exige la construction de structures doublement résonantes pour travailler aux fréquences de Larmor de l’électron et du noyau simultanément. Une procédure d’ajustement des modes est détaillée, celui-ci permet le calcul de la distribution du champ électromagnétique l’intérieur des cavités cylindriques, en tenant compte explicitement des propriétés diélectriques de l’échantillon. A partir d’un ensemble de modes dans les cavités résonantes, deux structures possibles sont retenues. Elles présentent des avantages complémentaires pour deux approches différentes expérimentales de la PDN. Des données expérimentales préliminaires sont présentées grâce à un prototype expérimental dans un champ statique 0. 35 T et 3. 5 TIn this thesis, methods are investigated to increase the inherently low detection sensitivity of the NMR experiment by an optimization of the detection hardware and by DNP experiments. In the first part, the emphasis is put on the sample coil and the rf circuitry of the NMR probehead, especially for conditions typical in high-field solid-state experiments. Based on a reciprocity principle and by electromagnetic field calculations, generalized coil parameters are derived and used to optimize the geometry of solenoid sample coils. In this context, the problem of fringe electric fields experienced by a sample at high Larmor frequencies is addressed. In the past, this has put severe limitations on the possibility to apply strong decoupling field amplitudes to temperature sensitive and dispersive samples. Resulting from the numerical field analysis of common NMR coils a novel sample coil geometry – the LLC resonator – is presented that significantly reduces the rf electric field in the sample volume. To characterize the novel structure, a comparative numerical and experimental study for a static field of 16. 4 T is demonstrated. In the second part, dedicated resonators are discussed to apply the method of DNP to increase the nuclear spin polarization by polarization transfer from coupled electron spins. The experimental setup of these experiments is challenging and requires the construction of double resonant structures operated at the electron and nuclear Larmor frequencies. An efficient mode-matching method is implemented that allows the calculation of the electromagnetic field distribution inside cylindrical cavities considering explicitly the dielectric properties of the sample. From the set of cavity modes, two potential resonator geometries are derived that are advantageous for two different experimental DNP approaches. Preliminary experimental data are shown that are measured with prototype resonators in a static field of 0. 35 T and 3. 5 T
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Miller, Matthew P. "Strategies to increase the signal to noise ratio in three-dimensional positron emission tomography." Thesis, University of Surrey, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322456.
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Positron Emission Tomography (PET) is an imaging technique that uses biologically relevant molecules labelled with positron emitting radioisotopes to measure regional tissue function in living organisms. To maximise the detection efficiency, data are acquired in 3D, that is, all possible detector combinations in a scanner without inter-ring shielding (septa). The gain in sensitivity afforded by 3D PET is offset by the increase in random coincidences, scattered coincidences and deadtime. These problems must be overcome for the gain in sensitivity to be fully realised. The aim of this research project was to investigate strategies to increase the signal to noise ratio of the 3D PET data. Additional side shielding, both in neuro and body scanning, has been implemented and assessed. Large gains were achieved using the neuro shields in experimental and clinical studies. The potential of the body shields was tested in experimental and in-vivo studies which showed that they were scan dependent. For example, no gain was found for a cardiac blood flow (H2 IS0) study. A model-based scatter correction was assessed by companng compartment ratios within the 'Utah' phantom with radioactivity outside the field of view, with and without neuroshielding. Recovered ratios were within 6% of their actual values. The integration time was reduced in an effort to decrease the system deadtime. A peak increase of 150/0 in noise equivalent count rate was measured for a uniform cylinder inside the field of view. A random coincidence variance reduction technique was implemented and assessed to reduce the noise contained in the delayed window random coincidence estimate. The algorithm was evaluated using phantoms and tested on clinical data. A mean 16% reduction in coefficient of variation was measured for a C15O torso study.
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Kambavalasa, Sasi Kiran. "Feasibility study to increase the sensitivity of a microwave microstripline bandpass filter based biosensor for the detection of bacteria in water /." abstract and full text PDF (free order & download UNR users only), 2007. http://0-gateway.proquest.com.innopac.library.unr.edu/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:1447811.
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Thesis (M.S.)--University of Nevada, Reno, 2007."May, 2007." Includes bibliographical references (leaves 87-89). Online version available on the World Wide Web. Library also has microfilm. Ann Arbor, Mich. : ProQuest Information and Learning Company, [2007]. 1 microfilm reel ; 35 mm.
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Jones, Sandra Joyce. "How an after school environmental science club can increase environmental knowledge: Awareness and sensitivity towards the environment for third and fourth grade students." CSUSB ScholarWorks, 2008. https://scholarworks.lib.csusb.edu/etd-project/3377.
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Children today are disconnected from the natural environment around them, sometimes finding it annoying, lacking in excitement, and little use to them. Their attention and focus are spent inside watching TV, playing games on computers or a variety of other electronic devices. The purpose of this project was to see if after-school exposure to an Enirovnmental Science Club on the school grounds can impact student attitudes toward our local environment and to increase these third and fourth grade students' knowledge and awareness of their environment.
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Gragg, MaryAnne G. "The apparent increase in insulin sensitivity of leptin-treated rats appears to be due to a decrease in blood glucose concentrations in response to fasting l." Auburn, Ala., 2007. http://repo.lib.auburn.edu/07M%20Theses/GRAGG_MARYANNE_23.pdf.
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Moraes, Maria de Lourdes Leite de. "Avaliação comparativa das estratégias para um aumento de sensibilidade em eletroforese capilar." Universidade de São Paulo, 2001. http://www.teses.usp.br/teses/disponiveis/46/46133/tde-15022019-144605/.
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A Eletroforese Capilar (CE) é uma técnica de separação baseada na migração diferenciada de compostos iônicos ou ionizáveis em um campo elétrico, proporcionando alta resolução, eficiência e rapidez de análise. Para preservar a alta resolução, o volume injetado deve ser pequeno (da ordem de nanolitros), o que dificulta a análise de compostos em baixos níveis de concentração. O diminuto caminho óptico definido pelo diâmetro interno do capilar, associado ao pequeno volume injetado, compromete a detecção, principalmente quando se utiliza a absorbância em linha. Várias estratégias têm sido descritas para melhorar a sensibilidade em eletroforese capilar. Neste trabalho, as estratégias de pré-concentração (\"stacking\", amplificação de campo, isotacoforese, cela óptica de alta sensibilidade e extração em fase sólida em linha) foram aplicadas a dois sistemas químicos: o ácido tereftálico (matéria prima importante utilizada na síntese de poliésteres) e o besilato de atracúreo (um agente bloqueador neuromuscular), avaliando-se comparativamente os resultados. O primeiro sistema não se mostrou adequado para tai fim, pois o ácido tereftálico apresenta baixa solubilidade em água, sendo necessário adicionar hidróxido de sódio para dissolvê-lo, o que produzia um meio de alta condutividade, inviabilizando algumas das estratégias de pré-concentração. Porém, como o controle de impurezas no ácido tereftálico é de interesse industrial foi desenvolvido um método para a análise simultânea dos subprodutos principais: o ácido carboxibenzaldeído (4-CBA) e o ácido p-toluóico (pTO), que são controlados industrialmente por polarografia e cromatografia à gás, respectivamente. As análises foram realizadas em lotes industriais do ácido tereftálico cru (CTA) e do ácido tereftálico altamente purificado (PTA). As concentrações de 4-CBA e p-TOL (determinadas por CE) em ambos, CTA e PTA, estão de acordo com as especificações do produto. As análises mostraram a viabilidade da determinação das impurezas, sendo identificados ainda o ácido benzóico (BZ) e o 4-hidroximetilbenzóico (HMB). O segundo sistema químico escolhido, o besilato de atracúreo, foi adequado para avaliar as várias estratégias de pré-concentração, pois este composto é solúvel em água. A apresentação comercial deste produto consiste na mistura de três isômeros (cis-cis, cis-trans e trans-trans), cada um exibindo uma potência bloqueadora neuromuscular particular. Primeiramente foi desenvolvido um método para a separação dos três isômeros por CE e depois foi feito um estudo das impurezas presentes no sistema, avaliando-se a temperatura e o tempo de estocagem. Foram identificadas duas impurezas no composto: a laudanosina e o monoquaternário ácido. Foi escolhido o pico da laudanosina para avaliar as estratégias de aumento de sensibilidade devido este ser o principal composto de decomposição do atracúreo. O aumento de sensibilidade foi calculado em termos de ganho em sinal-ruído (S/R). O melhor resultado de aumento de sensibilidade para o \"stacking\" mediado por força iônica foi quando se dissolveu a amostra em água e comparou-se à mesma amostra dissolvida no tampão de corrida (o ganho em S/R foi da ordem de 25 vezes). Para as demais estratégias, a referência de partida foi uma amostra já dissolvida em água. Dentre todas as estratégias avaliadas, o maior ganho em sensibilidade foi obtido com os pré-concentradores (22,5 vezes de aumento em sinal-ruído (S/R)), mas a dificuldade de confecção não os tornam atrativos para as análises. A isotacoforese proporcionou o segundo maior aumento (7,6 vezes), comparável ao aumento de sensibilidade em campo amplificado (7,5 vezes) quando se utilizou um tampão com alta concentração de sal. Este ganho foi melhor que o da cela HS que teve aumento de 2,9 vezes em SIR, sugerindo que estas técnicas de pré-concentração podem ser utilizadas com vantagem em relação à cela HS proporcionando baixo custo. O aumento de sensibilidade não foi tão expressivo no \"stacking\" por injeção de grande volume (1,1), mas pode ser melhorado se o capilar inteiro for preenchido com a amostra.Capillary Electrophoresis (CE) is a separation technique based on differential migration of ionic compounds in a electric field, providing high efficiency, resolution and faster analysis. To preserve high resolution, the injected volume must be small (nanoliters), which compromises the analysis of samples components in a low concentration level. The little pathlenght defined by the capillary internal diameter and a small injected volume, place a large demand on detection, especially when on-line absorbance detectors is used. Some strategies have been described to improve the capillary electrophoresis sensitivity. At this work, preconcentration techniques (stacking, field amplification, isotachophoresis, high sensitivity optical cell, and on line solid extraction) were applied to two chemical systems: terephthalic acid (an important raw material used in a polyester synthesis) and atracurium besylate (a neuromuscular blocking agent), and the results were comparatively evaluated. The first selected system was not suitable for this purpose, due to poor solubility of terephthalic acid in water. lt was necessary to work with solutions of crude and purified products prepared in 0.15 mol /L NaOH and that produced a high conductivity medium, jeopardizing some preconcentration techniques. However, since impurities control in terephthalic acid is of industrial interest, it was developed a method to simultaneously analyze major byproducts: 4-carboxybenzaldehyde (4-CBA) and toluoic acid (pTO), industrialy controlled by polarography and gas chromatography, respectively. Analysis were conducted in industrial batches of crude terephthalic acid (CTA) and highly purified terephthalic acid (PTA). Concentrations of 4-CBA and p-TOL, in both, CTA and PTA, were in agreement with product specification. The results showed the viability to determine several impurities using CE. Additionally, two other contaminants, benzoic acid (BZ) and 4-hydroxymethyl benzoic acid (HMB), were identified. The second selected system, atracurium besylate, was useful to evaluate some preconcentration strategies, because of this water solubility and ionic character. Commercial presentation of this pharmaceutical consists in a mixture of three isomers (cis-cis, cis-trans e trans-trans), which one presenting a particular neuromuscular potency. First, it was developed a method to separate the three isomers by CE and then a study of the product impurities was conducted, evaluating the temperature tolerance and shelf life. Laudanosine and a monoquaternary acid were identified impurities in the pharmaceutical. Laudanosine was selected for the evaluation of preconcentration techniques because it is the major decomposition product of atracurium besylate. Sensitivity enhancement was calculated in terms of signal-noise increase (S/R). The best results of enhancement sensitivity with \"stacking\" mediated by ionic strange was obtained when the sample was dissolved in water and it was compared to the same sample dissolved in a running buffer (signal-noise increase was 25 times). To the other strategies, the reference sample was dissolved in water). Among all evaluated strategies, the major sensitivity enhancement was obtained with preconcentrators (22,5 times), but its difficult manufaturing makes them not attractive for routine analysis. Isotachophoresis, the second best in terms of signal-noise (S/R) values (7,6 times), was comparable to field amplification sensitivity enhancement (7,5 times), when buffers with high salt concentration were used. Its enhancement was better than that of HS cell, that was signal-noise increase of 2,9 times), suggesting that these preconcentration techniques can be used with advantage in relation to HS cell providing low cost. Sensitivity enhancement was not expressive, in the large injection volumes strategy (1, 1 times), but it can be improved if the whole capillar1 is filled with sample.
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Benson, Eric Ashley. "Loss of SIMPL increases TNFalpha sensitivity during hematopoiesis." Connect to resource online, 2008. http://hdl.handle.net/1805/1851.
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Thesis (Ph. D.)--Indiana University, 2008.Title from screen (viewed June 24, 2009). Department of Biochemistry and Molecular Biology, Indiana University-Purdue University Indianapolis (IUPUI). Advisor(s): Maureen Harrington. Includes vita. Non-Latin script record. Includes bibliographical references (leaves 126-132).
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Melchert, Wanessa Roberto. "Desenvolvimento de procedimentos analíticos limpos e com alta sensibilidade para a determinação de espécies de interesse ambiental." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/46/46133/tde-25062009-150929/.
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Procedimentos analíticos limpos e com alta sensibilidade foram desenvolvidos para a determinação de espécies de interesse ambiental (carbaril, sulfato e cloro livre). Os procedimentos foram baseados no acoplamento de sistemas de análises em fluxo com microbombas solenoides à espectrofotometria com longo caminho óptico ou em procedimentos de extração em ponto nuvem, visando a concentração das espécies de interesse sem o emprego de solventes tóxicos. A determinação de carbaril em águas naturais foi baseada em uma dupla extração em ponto nuvem: uma etapa de clean-up para a remoção de substâncias orgânicas interferentes e outra de pré-concentração do indofenol formado na reação com a forma oxidada do p-aminofenol. Resposta linear foi observada entre 10 e 500 µg L-1, com absortividade molar aparente estimada em 4,6x105 L mol-1 cm-1. O limite de detecção foi estimado em 7 µg L-1 e coeficiente de variação em 3,4% (n = 8). Recuperações entre 91 e 99% foram estimadas para adições de carbaril em amostras de águas naturais. Uma cela simples e de baixo custo com 30 cm de caminho óptico foi construída para medidas espectrofotométricas. A cela apresenta características desejáveis como baixa atenuação do feixe de radiação e volume interno (75 µL) comparável a de uma cela convencional. O desempenho da cela foi avaliado na determinação de fosfato utilizando o método azul de molibdênio com resposta linear obtida entre 0,05 e 0,8 mg L-1 de fosfato (r = 0,999). O aumento na sensibilidade (30,4 vezes) em comparação com o obtido com uma cela de fluxo convencional de 1 cm está de acordo com o estimado pela lei de Lambert-Beer. A formação do indofenol foi também explorada para a determinação de carbaril no procedimento em fluxo com celas de 30 e 100 cm. Respostas lineares; limite de detecção e coeficiente de variação foram estimados entre 50 - 750 e 5 - 200 µg L-1; 4,0 e 1,7 µg L-1 e 2,3 e 0,7%, respectivamente, para as celas de 30 e 100 cm. O procedimento proposto foi seletivo para a determinação de carbaril, sem interferências de outros pesticidas carbamatos. O resíduo gerado foi tratado com persulfato de potássio e irradiação ultravioleta, com redução de 94% do carbono orgânico total, não sendo o resíduo degradado considerado tóxico, frente às bactérias Vibrio-fischeri. A determinação de sulfato foi baseada em medidas turbidimétricas com cela de fluxo de 1 cm, com resposta linear observada entre 20 - 200 mg L-1. Deriva de linha base não foi observada em função do fluxo pulsado gerado pelas microbombas solenoides. O limite de detecção e o coeficiente de variação (n = 20) foram estimados em 3 mg L-1 e 2,4%, respectivamente, com frequência de amostragem de 33 determinações por hora. Para aumentar a sensibilidade, uma cela de fluxo de 100 cm foi empregada e deriva de linha base foi evitada utilizando uma etapa de limpeza periódica com EDTA em meio alcalino. Resposta linear foi observada entre 7 - 16 mg L-1 com limite de detecção de 150 µg L-1 e coeficiente de variação de 3,0% (n = 20). A frequência de amostragem foi estimada em 25 determinações por hora. Resultados obtidos para amostras de águas naturais e de chuva foram concordantes a nível de confiança de 95% com o procedimento turbidimétrico em batelada. A determinação de cloro livre em águas naturais e de torneira foi baseada na reação com N,N-dietil-p-fenilenodiamina, com resposta linear entre 5 e 100 µg L-1 de hipoclorito e limite de detecção e coeficiente de variação estimados em 0,23 µg L-1 e 3,4%, respectivamente. A frequência de amostragem foi estimada em 58 determinações por hora.Clean analytical procedures with high sensitivity for the determination of species of environmental interest (carbaryl, sulphate and chlorine) were developed. Flow systems with solenoid micropumps were coupled to long optical pathlength spectrophotometry or cloud point extraction procedures, aiming the concentration of species for determination without employing toxic solvents. Carbaryl determination in natural waters was based on a double cloud point extraction: a clean-up step for removal of interfering organic species and pre-concentration of the indophenol blue, formed in the reaction with the oxidized of p-aminophenol. Linear response was observed between 10 and 50 µg L-1, with apparent molar absortivity estimated as 4.6x105 L mol-1 cm-1. Detection limit was estimated as 7 mg L-1 and the coefficient of variation as 3.4% (n = 8). Recoveries between 91 and 99% were obtained for carbaryl spiked to natural waters. A simple and low cost flow cell with 30 cm optical path was constructed for spectrophotometric measurements. The cell shows desirable characteristics such as reduced attenuation of the radiation beam and internal volume (75 µL) comparable to conventional flow cells. The performance was evaluated by phosphate determination by the molibdenium blue method, with linear response between 0.05 and 0.8 mg L-1 of phosphate (r = 0.999). The increase in sensitivity (30.4 fold) in comparison to the obtained with a conventional 1 cm optical path flow cell agreed to theoretical value estimated by the Lambert-Beer law. The determination of carbaryl was also carried out in a flow system coupled to 30 and 100 cm optical path flow cells, also exploiting the formation of indophenol compound. Linear responses, detection limits and coefficients of variation were 50 - 750 and 5 - 200 µg L-1;4.0 and 1.7 µg L-1 and 2.3 and 0.7%, respectively, for 30 and 100 cm cells. The proposed procedure was selective for the determination of carbaryl, without interferences of other carbamate pesticides. The waste of the analytical procedure was treated with potassium persulphate and ultraviolet irradiation, with decrease of 94% of total organic carbon. The residue after treatment was not toxic for Vibrio-fischeri bacteria. Sulphate determination was based on turbidimetric measurements with 1-cm flow cell, with linear response between 20 and 200 mg L-1. Baseline drift was avoided in view of the pulsed flow related to the solenoid micropumps. The detection limit and the coefficient of variation were estimated as 3 mg L-11 and 2.4%, respectively, for a sampling rate of 33 determinations per hour. Aiming the increase in sensitivity, a 100 cm optical path flow cell was employed and baseline drift was avoided with a washing, step employing EDTA in alkaline medium. Linear response was observed between 7 - 16 mg L-1, with a detection limit of 150 µg L-1, coefficient of variation of 3.0% (n = 20) and sampling rate of 25 determinations per hour. Results obtained natural and rain for water samples agreed at 95% confidence level with the batch turbidimetric procedure. The determination of free chlorine in natural and tap waters was based on the reaction with N,N-diethyl-p-phenylenediamine, with linear response between 5 and 100 µg L-1, and detection limit and coefficient of variation estimated as 0.23 µg L-1 and 3.4%, respectively. Sampling rate was estimated as 58 determinations per hour.
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Jurgelucks, Benjamin [Verfasser]. "Increased sensitivity in parameter identification problems for piezoelectrics / Benjamin Jurgelucks." Paderborn : Universitätsbibliothek, 2019. http://d-nb.info/1183087462/34.
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Bankar, Girish. "Heterozygous rho kinase2 deficinecy increases whole body insulin sensitivity in mice." Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/44092.
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The incidence of obesity and type 2 diabetes is increasing worldwide. Impaired insulin sensitivity in peripheral tissues has been considered one of the major causes of whole body insulin resistance. Previous in vitro and in vivo studies have shown that the RhoA/ROCK pathway regulates the insulin signaling pathway. Two isoforms of Rho kinase (ROCK) have been identified, known as ROCK1 and ROCK2. It has recently been shown that in-vivo deletion of ROCK1 causes insulin resistance, whereas whether ROCK2 has a role in regulation of insulin sensitivity is unknown. In the current study, we investigated the physiological role of ROCK2 in the regulation of whole body insulin sensitivity in mice with heterozygous ROCK2 deficiency (ROCK2 +/-). ROCK2 +/- mice showed increased glucose tolerance and whole body insulin sensitivity compared to their wild-type littermates. Increased whole body insulin sensitivity in ROCK2 +/- mice was associated with increased activation of the insulin signaling in skeletal muscles and adipose tissues. To explore the mechanism of increased peripheral insulin sensitivity in ROCK2 +/- mice, we studied PPARγ and adiponectin signaling. We found selective upregulation of PPARγ and adiponectin signaling in skeletal muscles, whereas PPAR gamma levels were downregulated in adipose tissues of ROCK2 +/- mice. These findings suggest that partial ROCK2 deficiency increases insulin sensitivity in vivo through upregulation of PPARγ selectively in skeletal muscles. This suggests that ROCK2 is a potential therapeutic target in the development of new drugs for type 2 diabetes.
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Hau, Pok Man. "Polyploidization increases the sensitivity to DNA-damaging agents in mammalian cells /." View abstract or full-text, 2007. http://library.ust.hk/cgi/db/thesis.pl?BICH%202007%20HAU.
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Hikida, Takatoshi. "Increased sensitivity to cocaine by cholinergic cell ablation in nucleus accumbens." Kyoto University, 2002. http://hdl.handle.net/2433/149673.
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Riggs, Lace Marie. "KETAMINE EXPOSURE DURING ADOLESCENCE INCREASES SENSITIVITY TO REWARD-RELATED STIMULI IN ADULTHOOD." CSUSB ScholarWorks, 2016. https://scholarworks.lib.csusb.edu/etd/351.
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Major depressive disorder (MDD) is commonly diagnosed prior to adulthood, and when left untreated, may result in negative consequences that extend into adulthood. It is estimated that children and adolescents who suffer from MDD are more likely to develop conduct and anxiety disorders, and that up to 25% eventually develop substance abuse disorder. Consequently, this has resulted in a disproportionate increase in the prevalence of antidepressants prescribed to populations below 20 years of age, many of whom remain treatment-resistant. Recently, the non-competitive N-Methyl-D-aspartate (NMDA) receptor antagonist, ketamine, has been shown to alleviate symptoms of MDD in individuals that suffer from treatment-resistant depression. However, little is known about the potential long-term consequences of ketamine exposure during early development. This is important to examine at the preclinical level, given ketamine’s abuse potential, and the diffuseness of glutamatergic innervation within the reward circuit. We first demonstrate that juvenile ketamine treatment enhances preference for natural reward (i.e., 1% sucrose) three weeks post ketamine administration. In order to determine whether these long lasting increases in reward sensitivity extend to drugs of abuse, we examined whether adolescent ketamine treatment leads to an increased preference for cocaine later in life. Specifically, male c57BL/6 mice were exposed to ketamine (0 or 20 mg/kg) either during adolescence (postnatal days [PD] 35-49) or adulthood (PD70-84), and later assessed for sensitivity to cocaine (0.0, 2.5, 5.0, 7.5, or 10.0 mg/kg) place conditioning (CPP). We show that, when compared to saline pretreated controls, adult mice treated with ketamine during adolescence display an enhanced preference for environments previously paired with moderate doses of cocaine (5.0, 7.5, and 10.0 mg/kg). In contrast, mice that are pretreated with ketamine during adulthood do not show an enhanced preference for cocaine later in life. This study is the first to show that ketamine exposure during adolescence, but not adulthood, leads to a heightened preference for cocaine in adulthood. Future research is needed in order to determine to what extent ketamine exerts age-dependent functional modification of the reward circuit, and the mechanisms by which these responses are mediated.
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Frye, Jacob Nathaniel. "Increased arterial stiffness and reduced cardiovagal baroreflex sensitivity with anti cancer chemotherapy." Thesis, Kansas State University, 2017. http://hdl.handle.net/2097/36244.
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Master of ScienceDepartment of Kinesiology
Carl Ade
Background – Chemotherapy-induced left ventricular cardiotoxicity is associated with many cancer treatments; however, what is less known is how these treatments affect vascular health and autonomic control of blood pressure. Arterial stiffness and cardiovagal baroreflex sensitivity (BRS) are indicators of cardiovascular health and may provide insight into the adverse effects of anti-cancer chemotherapy. Therefore, the primary aims of the present study were to evaluate carotid artery stiffness and arterial BRS in cancer patients currently being treated with adjuvant chemotherapy. Methods – We performed a cross-sectional, case-control study involving 9 cancer patients and 9 age- and sex-matched controls. Carotid artery stiffness was assess via 2D ultrasonography. Cardiovagal BRS was assessed from the spontaneous changes in beat-to-beat time series of R-R interval and systolic blood pressure via the cross correlation technique. Results – Our findings indicated a significant decrease in cardiovagal BRS in cancer patients compared to controls (4.7 ± 0.6 vs 9.2 ± 1.7 msec mmHg⁻¹ respectively, P = 0.02). Carotid artery β-Stiffness was significantly higher in the cancer patients compared to control participants (9.2 ± 1.2 vs 6.6 ± 0.74 U respectively, P = 0.05). Conclusions – These data suggest that anti-cancer chemotherapy elicits significant decreases in the autonomic control of blood pressure and arterial stiffness, leaving cancer survivors with an increased risk of future cardiovascular disease.
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Reyes, de Corcuera José Ignacio. "Increased sensitivity of enzyme-based amperometric glucose biosensors and their application as time-temperature integrators." Online access for everyone, 2004. http://www.dissertations.wsu.edu/Dissertations/Spring2004/J%5FDe-Corcuera%5F050404.pdf.
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Dudgeon, Lori Snyder. "Elevated Temperatures Perturb Lipopolysaccharide Leading to Increased Serum Complement Sensitivity in Most Gram-Negative Bacteria." W&M ScholarWorks, 1995. https://scholarworks.wm.edu/etd/1539625965.
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Mailman, Matthew David. "Molecular analysis of patients with recessive 5q-spinal muscular atrophy : increased diagnostic and prognostic sensitivity /." The Ohio State University, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=osu1486572165277248.
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Marcantonio, Daniela. "The catecholamine extraneuronal uptake, transporter is associated with the increased sensitivity of gliomas to sarcosinamide chloroethylnitrosourea /." Thesis, McGill University, 1997. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=20273.
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SarCNU, a novel chloroethylnitrosourea analogue, is transported by the extraneuronal uptake2 transporter (uptake2). SK-MG-1 human glioma cells are sensitive to SarCNU cytotoxicity and express uptake 2 whereas SKI-1 glioma cells have no detectable transporter, and are relatively resistant. To clone uptake2, we detected differences in RNA expression utilizing differential display. With differential display, we detected a novel sequence expressed in SK-MG-1 cells but not in SKI-1 cells, having 62% homology to an expressed sequence tag clone from human brain, and could be a partial sequence of uptake2. In the treatment of SF-295 glioma xenografts in athymic mice, SarCNU had superior activity than 1,3-bis-(2-chloroethyl)-1-nitrosourea. This suggested that SF-295 cells express uptake2. We determined if expression of uptake2 in the established SF-295 cell line correlated with the enhanced activity of SarCNU in vivo. Transport of [3H]SarCNU was not decreased by inhibitors of uptake2 in the SF-295 cell line and its steady state accumulation was similar to that of SKI-1. The increased stability of SarCNU versus BCNU may account for its enhanced activity in vivo or the expression of uptake2 in vivo may differ from its expression in vitro.
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Carrigan, Shawn D. "Development of hydrogel platforms for increased QCM-D biointerface sensitivity in real-time immunoassay of sepsis-related biomarkers." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86068.
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This doctoral thesis describes the development of novel rapid deposition hydrogel platforms that serve as biointerfaces for real-time immunoassay using quartz crystal microgravimetry (QCM). Biointerface development was undertaken with the goal of developing a simple system relying on affordable technology to achieve real-time immunoassay performance equivalent to more complex and involved protocols.The primary advantage of the hydrogel biointerfaces developed herein lies in their rapid preparation using affordable, non-toxic reagents. Compositions developed over three sequential development cycles rely on chemically cross-linking carboxymethylcellulose, which serves to covalently immobilise recognition elements through amine coupling, to polyethyleneimine. The various compositions require 10 minutes or less to deposit, a substantial improvement over competing self-assembled monolayer protocols requiring incubations ranging from hours to days using highly toxic reagents. Additional benefit lies in the immunoassay functionality of the biointerface, as these compositions excel in the traditional performance criteria of surface regeneration, minimisation of non-specific protein binding, and assay detection limit.
The peak detection limit achieved using a sandwich assay for a 17 kDa cytokine was 25 ng/mL in buffer and 500 ng/mL in a 1:3 serum dilution, with generic immunoassay capability for other cytokines demonstrated. Reusability of the developed biointerfaces is equally strong, with up to twenty regeneration cycles demonstrated without diminished sensitivity. Finally, mass-based estimates of non-specific serum adsorption indicate that the composition developed during the final design iteration equals the performance of the best protein-resistant biointerfaces currently available in the literature.
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Мягкий, Олександр Валерійович. "Підвищення завадостійкості теплової дефектоскопії багатошарових конструкцій та трубопроводів." Thesis, Харківський національний університет радіоелектроніки, 2018. http://repository.kpi.kharkov.ua/handle/KhPI-Press/40779.
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Дисертаційна робота на здобуття наукового ступеня кандидата технічних наук за спеціальністю 05.11.13 – прилади і методи контролю та визначення складу речовини. – Харківський національний університет радіоелектроніки, Харків, 2019.
Дисертація присвячена підвищенню завадостійкості теплової дефектоскопії багатошарових стільникових конструкцій і трубопроводів шляхом зниження завад в тепловому неруйнівному контролі як за рахунок вибору режиму контролю за критерієм максимуму відношення сигнал / завада, так і за допомогою подальшої комп'ютерної обробки отриманих експериментальних даних. Запропоновано теплофізичні моделі багатошарових стільникових конструкцій і трубопроводів. Розроблено програмний пакет "TermoPro_TFH_Statistic" і на його основі проведено чисельні експерименти по вибору режимів теплової дефектоскопії. Проведено ряд натурних і лабораторних експериментів з дослідження впливу завад на тепловий неруйнівний контроль. Розроблено ряд фільтрів, а також послідовність їх застосування для істотного зниження рівня завад при проведенні ТДС. Завдяки цьому підвищилась чутливість теплової дефектоскопії до виявлення дефектів типу "непроклей" в стільникових структурах – розмір порогового дефекту знижений з 6 мм до 3 мм, а достовірність їх виявлення зросла на 17-20%.The dissertation on the receipt of scientific degree of candidate of engineering sciences on speciality 05.11.13 – devices and methods of testing and materials composition determination. Kharkiv National University of Radio Electronics, Kharkiv, 2019. The dissertation is devoted to the question of immunity to interference improvement in the thermal non-destructive testing of multilayered honeycomb constructions and pipelines, both by the monitoring mode selection with the criterion of maximum signal-to-interference ratio, and by the further computer processing of obtained experimental data. Thermophysical models of multilayered honeycomb constructions are proposed. The software package "TermoPro_TFH_Statistic" was worked out and number of experiments at the thermal flaw detection modes selection were performed on its basis. A number of full-size and laboratory-scale experiments were conducted to investigate the interference effect on thermal non-destructive testing. A number of filters have been worked out, as well as the sequence of their use to significantly reduce the interference level during the thermal flaw detection. Due to this, the sensitivity of thermal defectoscopy to detection of defects of the "non-adhesive" type in honeycomb structures increased – the size of the threshold defect was decreased from 6mm to 3mm, and the reliability of their detection increased by 17-20%.
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Ramos-Gómez, Minerva. "Sensitivity to carcinogenesis is increased and chemopreventive efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice." Available to US Hopkins community, 2002. http://wwwlib.umi.com/dissertations/dlnow/3080748.
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Parise, Cláudia Klose. "Sensitivity and memory of the current mean climate to increased Antarctic sea ice: The role of sea ice dynamics." Instituto Nacional de Pesquisas Espaciais (INPE), 2014. http://urlib.net/sid.inpe.br/plutao/2014/11.19.18.13.
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Esta tese estuda a sensibilidade e memória do clima global ao aumento do gelo marinho Antártico, levando em consideração o tempo de persistência dos máximos de gelo (concentração e espessura) sob condições climáticas atuais. A sensibilidade das \emph{storm tracks} no Hemisfério Sul e do clima da América do Sul ao aumento do gelo marinho também são analisadas, bem como o mecanismo envolvido na restauração do equilíbrio climático. Dois grupos de experimentos foram realizados. No primeiro o gelo marinho é simulado por um modelo de única camada que desconsidera a reologia do gelo, impedindo que o gelo mova quando espesso. No segundo, o gelo marinho é simulado por um modelo multi-camadas que resolve explicitamente a dinâmica do gelo. Cada clima é perturbado com um extremo de condições positivas (\emph{Max}) e climatológicas (\emph{ctl}) de concentração e espessura de gelo marinho Antártico em um conjunto de 30-membros integrados por 10 anos cada. Alterações nas \emph{storm tracks} são analisadas através de um método automatizado de identificação e rastreio de ciclones extratropicais com base em vorticidade relativa. Os resultados mostram que um extremo de gelo marinho Antártico é capaz de persistir $\sim$4-anos sob condições climáticas atuais. Nos 4 anos seguintes o gelo marinho nos experimentos \emph{Max} é semelhante àquele dos experimentos \emph{ctl} e nos últimos 2-anos as diferenças (\emph{max- ctl}) de gelo marinho são negativas. A persistência dos máximos de gelo marinho varia setorialmente e em função do tipo de modelo de gelo. A presença de máximos de gelo marinho Antártico reduz a temperatura do ar dos baixos aos médios níveis da troposfera. O resfriamento das altas latitudes aumenta o transporte de calor para sul e a convergência em baixos níveis. A pressão média ao nível do mar é reduzida (aumentada) sobre as altas (médias) latitudes, padrão típico da fase positiva do Modo Anular Sul. O fluxo de calor sensível do oceano para a atmosfera é intenso nas margens do gelo marinho, onde a baroclinia da atmosfera também aumenta. Os ventos de oeste se intensificam ao sul de $50^{0}$S e se enfraquecem entre $45^{0}$S e $10^{0}$S. A corrente de jato polar se intensifica em direção aos pólos enquanto o jato subtropical se enfraquece em direção ao equador. Em resposta ao fortalecimento do jato polar, a densidade de trajetóricas dos ciclones, ciclogênese e ciclólise aumenta sobre as altas (médias) latitudes. Com o deslocamento das tempestades para sul, a atividade dos distúrbios transientes é reduzida sobre a América do Sul, bem como a formação de ciclones sobre as duas principais regiões ciclogenéticas (em $30^{0}$S e $45^{0}$S). O enfraquecimento do jato subtropical contribui para aumentar a estabilidade estática da atmosfera e reduzir a taxa de precipitação sobre a América do Sul. Os fortes ventos de oeste fortalecem a Corrente Circumpolar Antártica e, conseqüentemente, a deriva de Ekman para o norte. O derretimento do máximo de gelo marinho gera uma entrada da água fria e pouco salina na camada de mistura do Oceano Austral. A medida que essa água superficial flui para o norte há ressurgência da água mais quente e salina (observada abaixo da camada de mistura do oceano) na Divergência Antártica ($60^{0}$S). A memória climática ($\sim$8-anos) armazenada nas camadas superiores do oceano modula a intensidade e duração da resposta atmosférica ao máximo de gelo marinho.This thesis explores the sensitivity and memory of the global climate to increased Antarctic sea ice, taking into account the persistence of sea ice maxima (in concentration and thickness) under current climate conditions. Moreover, the sensitivity of the Southern Hemisphere storm tracks and the South America climate to increasedAntartictic sea ice are also studied as well as the mechanisms involved in restoring the climate balance. In order to isolate the impacts of sea ice dynamics, two sets of sensitivity experiments are performed with the GFDL CM2.1 coupled climate model. In the first set the sea ice is simulated by a simple slab sea ice model which neglects the sea ice dynamics whereas in the second the sea ice is simulated by a sophisticated multi-layer model. The current climate is perturbed with maximum conditions of Antarctic sea ice (max) and compared to the respective control simulation (ctl). The four numerical experiments are integrated for 10 years each in a large 30-member ensemble. The changes to the Southern Hemisphere extratropical cyclones are analysed through an automated of cyclone identification and tracking based on relative vorticity. The impact of increased Antarctic sea ice on the South America climate is analysed through changes in the precipitation regime and the associated atmospheric systems. The results show that a maximum condition of Antarctic sea ice is able to persist $\sim$4-years under current climate conditions.In the following 4-years of model integration the sea ice in the max experiments is similar to that of the ctl experiments and in the last 2-years the (max-ctl) sea ice differences are negative. However, the persistence of Antarctic sea ice maxima varies sectorally and according to the sea ice model type. The Antarctic sea ice maxima reduce the air temperature from the low to mid-levels. This increases the poleward meridional temperature gradient, resulting in air ascending over the high-latitudes.The mean sea level pressure is reduced (increased) over the high (mid)-latitudes, a typical pattern of the Southern Annular Mode positive phase. The sensible heat flux from the ocean to the atmosphere is intensified at the sea ice edges increasing the atmospheric baroclinicity there. The westerly winds are intensified south of 50$^{°}$S and weakened from 45$^{°}$S to 10$^{°}$S. The polar jet stream intensifies poleward whereas the subtropical jet stream weakens toward the Equator. In response to the polar jet strengthening, the cyclone track density, cyclogenesis and cyclolysis have increased (decreased) over the high (mid)-latitudes. The eddy activity is reduced over South America as well as the cyclogenesis over the two main regions (at 30$^{°}$S and 45$^{°}$S ). The weaker subtropical jet contributes to enhanced atmospheric static stability and reduces the precipitation rate over South America. The stronger westerlies strengthen the Antarctic Circumpolar Current and, consequently, the Ekman drift northward. The melting of the sea maximum generates an imput of cold and fresh melt water into the ocean mixed-layer of the Southern Ocean (from the surface to 100 m ). As this surface water flows northward there is upwelling of the warmer and saltier water (observes below the ocean mixed-layer) on the Antarctic Divergence (60$^{°}$S). The climate memory stored in the upper ocean layers ($\sim$8-years) modulates the intensity and timing of the atmospheric response.
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Мягкий, Олександр Валерійович. "Підвищення завадостійкості теплової дефектоскопії багатошарових конструкцій та трубопроводів." Thesis, Національний технічний університет "Харківський політехнічний інститут", 2019. http://repository.kpi.kharkov.ua/handle/KhPI-Press/40777.
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Дисертаційна робота на здобуття наукового ступеня кандидата технічних наук за спеціальністю 05.11.13 - прилади і методи контролю та визначення складу речовини. – Харківський національний університет радіоелектроніки, Харків, 2019.
Дисертація присвячена підвищенню завадостійкості теплової дефектоскопії багатошарових стільникових конструкцій і трубопроводів шляхом зниження завад в тепловому неруйнівному контролі як за рахунок вибору режиму контролю за критерієм максимуму відношення сигнал / завада, так і за допомогою подальшої комп'ютерної обробки отриманих експериментальних даних. Запропоновано теплофізичні моделі багатошарових стільникових конструкцій і трубопроводів. Розроблено програмний пакет "TermoPro_TFH_Statistic" і на його основі проведено чисельні експерименти по вибору режимів теплової дефектоскопії. Проведено ряд натурних і лабораторних експериментів з дослідження впливу завад на тепловий неруйнівний контроль. Розроблено ряд фільтрів, а також послідовність їх застосування для істотного зниження рівня завад при проведенні ТДС. Завдяки цьому підвищилась чутливість теплової дефектоскопії до виявлення дефектів типу "непроклей" в стільникових структурах – розмір порогового дефекту знижений з 6 мм до 3 мм, а достовірність їх виявлення зросла на 17 -20%.The dissertation on the receipt of scientific degree of candidate of engineering sciences on speciality 05.11.13 – devices and methods of testing and materials composition determination. Kharkiv National University of Radio Electronics, Kharkiv, 2019. The dissertation is devoted to the question of immunity to interference improvement in the thermal non-destructive testing of multilayered honeycomb constructions and pipelines, both by the monitoring mode selection with the criterion of maximum signal-to-interference ratio, and by the further computer processing of obtained experimental data. Thermophysical models of multilayered honeycomb constructions are proposed. The software package "TermoPro_TFH_Statistic" was worked out and number of experiments at the thermal flaw detection modes selection were performed on its basis. A number of full-size and laboratory-scale experiments were conducted to investigate the interference effect on thermal non-destructive testing. A number of filters have been worked out, as well as the sequence of their use to significantly reduce the interference level during the thermal flaw detection. Due to this, the sensitivity of thermal defectoscopy to detection of defects of the "non-adhesive" type in honeycomb structures increased – the size of the threshold defect was decreased from 6mm to 3mm, and the reliability of their detection increased by 17-20%.
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Lloyd, Hayleigh Jayne. "Co-crystallisation of energetic materials : a step-change in the control of properties and performance of munitions." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28860.
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The research described in this thesis seeks to explore a concept that has the potential to make a step-change for the control of the properties of energetic materials (sensitivity, long-term storage, processability, performance, etc.), resulting in safer munitions with enhanced performance. This concept is co-crystallisation and involves crystallisation of the energetic material with one or more molecular components in order to modify the properties of the composition. The concept has been demonstrated in the pharmaceutical sector as a successful means of altering the physical properties of active pharmaceutical ingredients, e.g. solubility, bioavailability, stability to humidity. This project therefore aims to exploit the concepts of crystal engineering and co-crystallisation as applied to selected energetic materials in order to achieve the following objectives: (i) develop an enhanced understanding of how structure influences key properties such as sensitivity, (ii) control the sensitivity of existing, approved energetic materials, and (iii) identify new energetic materials with enhanced properties, e.g. reduced sensitivity, higher performance, and increased thermal stability. The compound 3,5-nitrotriazolone (NTO) was crystallised with a selection of co-formers to produce salts and co-crystals. The structure properties of these materials were explored using single-crystal and powder X-ray diffraction, and structural features were correlated with properties such as crystal density, difference in pKa of co-formers, thermal properties, and sensitivity to impact. Detonation velocities of the co-crystals were calculated based on densities, chemical composition, and heats of formation. Co-former molecules included a series of substituted anilines, substituted pyridines (including 4,4’-bipyridine, 2-pyridone), and substituted triazoles. A co-crystal was formed between NTO and 4,4’-bipyridine on crystallisation from ethanol, whilst a salt was formed when crystallised from water. Upon heating the salt to 50ºC, the co-crystal was formed. Structural differences between the salts formed by NTO with 3,5-DAT and 3,4- DAT were correlated with structural features. 3,5-DAT.NTO is substantially less impact sensitive than 3,4-DAT.NTO, and this is attributed to the layered structure of 3,5-DAT.NTO. An investigation into triazole-based NTO salts under high pressure was conducted. A new polymorph of 3,5-DAT.NTO was discovered upon increasing the pressure to 2.89 GPa. The high-pressure phase appears to retain the layered structure and remains in this phase up to 5.33 GPa, although it was not recoverable upon decompression to atmospheric pressure. The compression behaviour of the unit cell volume for phase I of 3,5-DAT.NTO has been fitted to a 3rd-order Birch- Murnaghan equation of state (EoS) with V0 = 957.7 Å3, B0 = 8.2 GPa and B’0 = 14.7. The unit cell was found to be most compressible in the a and c directions. Under high pressure 3,4-DAT.NTO does not give any indication of a phase change occurring up to 6.08 GPa. The coefficients of the 3rd-order Birch-Murnaghan EoS have been determined to be V0 = 915.9 Å3, B0 = 12.6 GPa and B’0 = 6.5.
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Guo, Yang. "Overexpression of Heat-Shock Protein 27 (HSP27) increases gemcitabine sensitivity in pancreatic cancer cells through s-phase arrest and apoptosis." Diss., Ludwig-Maximilians-Universität München, 2014. http://nbn-resolving.de/urn:nbn:de:bvb:19-176979.
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Rarick, Kevin Richard. "Cardiovascular end-organ damage in response to increased blood pressure variability : impact of oxidative stress." Diss., University of Iowa, 2012. https://ir.uiowa.edu/etd/3370.
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Baroreflex sensitivity (BRS) is often reduced in elderly populations and patients with chronic cardiovascular diseases leading to a concomitant rise in blood pressure variability (BPV) that is associated with increased cardiovascular related morbidity and mortality. Thus, there is a need to better understand the mechanisms by which BPV causes cardiovascular end-organ damage. Animal studies using sinoaortic denervation (SAD) to increase BPV have demonstrated pathologic changes in the structure of the heart and blood vessels; however, there is a paucity of data investigating changes in functional measures of the heart and smaller, resistance type arteries. Furthermore, the pathogenic mechanisms involved in BPV-induced cardiovascular end-organ damage remain unknown. Baroreceptor denervation results in multiple cardiac stressors, many of which are associated with production of reactive oxygen species. Oxidative stress is known to promote cardiovascular end-organ damage but it is unclear if it plays a role in models of increased BPV. Thus, this study was designed to investigate the functional responses of smaller resistance type arteries and the heart to chronic exposure to enhanced BPV. In addition, the role of oxidative stress on these functional responses in a normotensive rat model of increased BPV was also investigated. Rats were subjected to either SAD surgery or a sham procedure and were observed for six weeks. To determine the role of oxidative stress, SAD rats were either treated with the superoxide dismutase mimetic tempol or left untreated. During the observation period, mean blood pressure remained normotensive, whereas baroreflex sensitivity was reduced and BPV increased two to three fold. Weekly in vivo assessment of vascular function of the long posterior ciliary artery (LPCA) demonstrated a significant reduction in endothelial-dependent dilation starting three weeks after SAD surgery compared to the sham group. Endothelial-independent dilation was not affected by SAD. Structural changes were not evident in the LPCA following SAD. However, structural (wall thickness, wall area, and wall area/lumen area ratio) and functional (strain and distensibility) changes were observed in the aorta. Cardiac structural (hypertrophy) and functional (diastolic dysfunction) effects were also evident following six weeks of increased BPV. Antioxidant treatment with tempol did not have any effect on the SAD-induced increase in BPV or decrease in BRS. Nevertheless, chronic tempol treatment prevented or reduced the cardiovascular end-organ damage (endothelial-dependent vascular dysfunction, decreased aortic distensibility, cardiac and vascular hypertrophy, and cardiac dysfunction) observed in the untreated SAD group. These findings suggest that the pathology observed following SAD is at least partly mediated by oxidative stress. Antioxidant treatment in patients with increased BPV (e.g., hypertension, diabetes, heart failure) may prevent or ameliorate cardiovascular end-organ damage and reduce the overall risk for cardiovascular disease events.
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Perna, Marla K., and Russell W. Brown. "Adolescent Nicotine Sensitization and Effects of Nicotine on Accumbal Dopamine Release in a Rodent Model of Increased Dopamine D2 Receptor Sensitivity." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/956.
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Our laboratory has reported neonatal quinpirole (D2/D3 agonist) treatment to rats increases dopamine D2 receptor sensitivity that persists throughout the animal's lifetime. This model appears to have clinical relevance to schizophrenia, and smoking is common in this population. Male and female Sprague-dawley rats were neonatally treated with quinpirole from postnatal (P) days 1–21. After habituation from P30 to 32, animals were administered saline or nicotine (0.3, 0.5, or 0.7mg/kg free base) every other day from P33 to 49 and locomotor activity was assessed. Generally, animals neonatally treated with quinpirole and administered nicotine during adolescence demonstrated increased behavioral activity and/or sensitization compared to animals neonatally given saline and sensitized to nicotine as well as controls. However, animals neonatally treated with quinpirole and given the 0.7mg/kg dose of nicotine demonstrated elevated activity throughout testing but did not show sensitization, and only mild sex differences were reported. Therefore, microdialysis was performed on male rats sensitized to the 0.5mg/kg dose of nicotine, and results revealed that neonatal quinpirole sensitized dopamine overflow in response to nicotine to 500% above animals neonatally given saline and sensitized to nicotine at peak levels. In addition, neonatal quinpirole increased the accumbal BDNF in response to nicotine compared to all other groups, and nicotine alone also produced significant increases in striatal and accumbal BDNF. This study reveals that neonatal quinpirole enhanced adolescent nicotine sensitization, accumbal dopamine overflow, and BDNF protein in response to nicotine, which may be related to changes in the brain's reward system.
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Grant, Kerstin [Verfasser], and Anke [Akademischer Betreuer] Jentsch. "Sensitivity of mesic temperate grassland to increased climate variability : biomass production, forage quality and plant-plant interactions / Kerstin Grant. Betreuer: Anke Jentsch." Bayreuth : Universität Bayreuth, 2016. http://d-nb.info/1108404804/34.
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Kamphuis, Jasper. "Increased intake of fermentable carbohydrates induces IBS-like symptoms : a complementary understanding of mechanisms involved." Thesis, Toulouse, INPT, 2019. http://www.theses.fr/2019INPT0074.
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Le syndrome de l’intestin irritable (SII) est un trouble gastro-intestinal fonctionnel caractérisé par des douleurs abdominales, des ballonnements et des troubles du transit intestinal. Cette pathologie digestive a une prévalence mondiale importante d'environ 11%. Elle entraîne un coût économique important : perte de productivité et absentéisme au travail. De plus, elle entraine une forte dégradation de la qualité de la vie des patients. Les causes de ce trouble fonctionnel ne sont pas bien comprises rendant le traitement thérapeutique difficile. Au cours des dernières années, un régime alimentaire à faible teneur en FODMAPs (Fermentable Oligo-, Di-, Mono-saccharides And Polyols) s’est révélé efficace dans la réduction des symptômes du SII. Sur le plan mécanistique ces effets positifs restent à élucider. Toutefois, on cite le plus souvent une réduction de la distension entérique due à une réduction de la production de gaz et du volume d’eau intestinale par des effets osmotiques. Campbell et al. pose l’hypothèse qu’une fermentation anaérobie de carbohydrates non-absorbés par le microbiote intestinal provoque la formation endoluminale de métabolites tels que les alcools, les cétones et les aldéhydes, responsables d'intolérances alimentaires comme l'intolérance au lactose. Nous avons émis l’hypothèse que ce mécanisme pourrait être étendu aux FODMAPs pour expliquer l’efficacité du régime alimentaire pauvre en FODMAPs chez les patients SII. Nos études montrent un rôle complexe des FODMAPs sur des modèles murins qui reflètent la physiopathologie du SII. Les traitements par FODMAPs (lactose et fructo-oligosaccharides) provoquent une hypersensibilité viscérale et abdominale et une dysfonction de la barrière de mucus au niveau de la muqueuse intestinale. Nous avons démontré que ces effets étaient dûs à la production d’agents de glycation par le microbiote intestinal. En effet, ces effets étaient prévenus par un co-traitement à la pyridoxamine. Le nombre de mastocytes muqueux était également augmenté chez les animaux traités par FODMAPs et significativement réduit par un co-traitement à la pyridoxamine. Les mastocytes sont connus pour être impliqués dans l’hypersensibilité viscérale et dans la dysrégulation de la barrière de mucus de l’intestin. Par ailleurs, une augmentation du nombre et/ou de l'activité des mastocytes est retrouvée sur des biopsie de patients SII. Ce travail de thèse original permet donc de faire un lien entre l'efficacité du régime alimentaire à faible teneur en FODMAPs, la symptomatologie et l'implication des mastocytes intestinaux chez le patient SIIIrritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) characterized by abdominal pain, bloating, and erratic bowel habits. It is an affliction with a high prevalence of around 11% worldwide. It carries a significant economic cost in lost productivity and work absence, and more importantly, it has a strong negative impact on quality of life. Because it is a functional disorder of which the causes are not well understood, treatment is difficult. In recent years, a low-FODMAP diet (low in Fermentable Oligo-, Di-, Mono-saccharides And Polyols) has been successfully used to reduce symptoms of IBS. The efficacity of this approach is not completely understood, but a reduction in enteric distension by reduced gas production and small intestinal water bulk by osmotic effects are most often cited. The bacterial metabolic toxin hypothesis, proposed by Campbell et al. poses that anaerobic fermentation of unabsorbed carbohydrates by the colonic gut microbiota, producing such metabolites as alcohols, ketones, and aldehydes, are responsible for food intolerances such as lactose intolerance. We hypothesized that this same mechanism could be extended to FODMAPs to explain the efficacity of the low- FODMAP diet. In this thesis, we looked for complementary mechanisms on how FODMAPs could influence IBS symptoms, besides distension related complaints. Our studies in a healthy mouse model show a complex role for FODMAPs in IBS physiopathology; FODMAP treatments cause a visceral and abdominal hypersensitivity, and a mucus barrier dysregulation, characterized using an innovative approach. We hypothesized that this is due to generation of glycating agents by the intestinal microbiota, and the prevention of these effects by co-treatment with pyridoxamine indicates that this hypothesis is correct. Mucosal mast cell counts were increased in FODMAP treated animals, but not in animals co-treated with pyridoxamine. Mast cells are implicated in visceral hypersensitivity, as well as in mucus barrier dysregulation, and increased mucosal mast cell numbers or activity are often linked to IBS. This work thus offers a link between the efficacity of the low-FODMAP diet and the involvement of intestinal mast cells in IBS
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De, Blasio Miles Jonathon. "Placental restriction of fetal growth increases growth rate and sensitivity to insulin and insulin-like growth factor 1 (IGF-1) after birth in sheep /." Title page and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09SB/09sbd286.pdf.
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Thesis (B.Sc.(Hons.))--University of Adelaide, Dept. of Physiology, 1999.Spine title: Fetal gowth restriction increases insulin and IGF-1 sensitivity in neonatal sheep. Bibliography: leaves 21-24.
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Guo, Yang [Verfasser], and Max [Akademischer Betreuer] Schnurr. "Overexpression of Heat-Shock Protein 27 (HSP27) increases gemcitabine sensitivity in pancreatic cancer cells through s-phase arrest and apoptosis / Yang Guo. Betreuer: Max Schnurr." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2014. http://d-nb.info/1062877586/34.
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Driscoll, Donald D. Jr. "Development and Performance of Detectors for the Cryogenic Dark Matter Search Experiment with an Increased Sensitivity Based on a Maximum Likelihood Analysis of Beta Contamination." Case Western Reserve University School of Graduate Studies / OhioLINK, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=case1074098001.
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Lampinen, Salomonsson Matilda. "Chemical Derivatization in Combination with Liquid Chromatography Tandem Mass Spectrometry for Detection and Structural Investigation of Glucuronides." Doctoral thesis, Uppsala University, Analytical Pharmaceutical Chemistry, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8670.
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This thesis presents novel approaches for structural investigation of glucuronides using chemical derivatization in combination with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MSn).
Today, LC-ESI-MSn is the dominant technique for quantitative as well as qualitative analyses of metabolites, due to its high sensitivity and selectivity. However, for compounds without an easily ionizable group, e.g., steroids, the sensitivity is limited. In the work presented in this thesis, a derivatization procedure forming a basic oxime significantly increased the detection sensitivity for the altrenogest glucuronide.
Furthermore, in structural evaluations of glucuronides, the limitation of LC-MSn becomes evident due to the initial neutral loss of 176 u, i.e. monodehydrated glucuronic acid, which often makes it impossible to elucidate the structures of the conjugates. To solve this problem, the main part of the work described in this thesis was devoted to chemical derivatization as a means of facilitating the determination of the site of conjugation.
For the first time, the isomeric estriol glucuronides were evaluated using a combination of three reagents 2-chloro-1-methylpyridinium iodide (CMPI), 1-ethyl-3-(3-dimethyl- aminopropyl)-carbodiimide (EDC), and 2-picolylamine (PA). Interestingly, the derivatization gave a selective fragmentation pattern leading to differentiation of the isomers.
Another derivatization reagent, 1,2-dimethylimidazole-4-sulfonyl chloride (DMISC), was also tested for the first time in structural investigations. The isomeric glucuronides of morphine, formoterol, and hydroxypropranolol were evaluated. They can all be conjugated in aliphatic as well as aromatic positions. DMISC was proven to be useful in two ways. Firstly, the morphine and formoterol glucuronides that contained a free phenol could be differentiated from those that were conjugated in the aromatic position based on different reactivity. Secondly, for the aromatic O-glucuronide of 4’-hydroxypropranolol, DMISC was proven to react with the amine. This product gave a different fragmentation pattern compared to the corresponding derivative of the aliphatic glucuronide.
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Fournel, Ludovic. "Influence Du Cisplatine sur l'expression du Check-Point Immunitaire PD-1/PD-L1 Dans Le Cancer Broncho-Pulmonaire Non A Petites Cellules Cisplatin Increases PD-L1 Expression and Optimizes Immune Check-Point Blockade in Non-Small Cell Lung Cancer Modulation of Lung Cancer Cell Plasticity and Heterogeneity with the Restoration of Cisplatin Sensitivity by Neurotensin Antibody." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASS077.
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Malgré les nombreux progrés réalisés ces dernières années dans la prise en charge thérapeutique du cancer broncho-pulmonaire, cette pathologie reste la première cause de décès lié au cancer dans le monde. L’enjeu majeur pour cette maladie est donc de développer de nouveaux traitements et d’optimiser l’utilisation des drogues existantes, en particulier les sels de platine. Les protocoles combinant des inhibiteurs de points de contrôle immunitaire avec des sels de platine est actuellement en plein essor malgré un certain manque en études précliniques. Dans ce travail, j’ai cherché à évaluer l'impact du cisplatine sur l'expression de PD-L1 en analysant des patients ayant reçu une chimiothérapie néo-adjuvante à base de cisplatine. Le traitement d'induction augmentait considérablement le marquage PD-L1 des cellules tumorales et immunitaires du microenvironnement. Vingt-deux patients présentaient une variation positive du pourcentage de cellules tumorales PD-L1+ après chimiothérapie néoadjuvante; dont 9 (23,1%) passant de <50% à ≥50% des cellules tumorales marquées. Nous avons également confirmé la régulation positive de PD-L1 par le cisplatine, tant au niveau de l'ARNm qu’au niveau protéique, in-vitro et in-vivo sur des souris nude et des souris immunocompétentes greffées par des tumeurs expérimentales issues de lignées cellulaires de cancer du poumon A549, LNM-R ou LLC1. L’up-régulation de PD-L1 par le cisplatine fait intervenir la voie de signalisation PI3K/AKT. De plus, l'administration combinée d'anticorps anti-PD-L1 (3 mg / kg) et de cisplatine (1 mg / kg) à des souris portant un carcinome pulmonaire réduisait significativement la croissance tumorale par rapport aux traitements en monothérapie et par rapport aux contrôles. Le cisplatine augmente donc précocément et durablement l'expression de PD-L1 et pourrait donc agir de manière synergique avec un blocage de PD-1 / PD-L1 pour améliorer la réponse tumorale aux traitements. En parallèle, nous avons pu développer une thérapie ciblée anti-neurotensine permettant de bloquer ses effets paracrines stimulants la prolifération, la croissance, et les capacités d’invasion des cellules de tumeurs pulmonaires. Les anticorps anti-neurotensine amélioraient également la sensibilité au cisplatine de tumeurs préalablement résistantes par des mécanismes qui impliquent probablement l’augmentation de l’influx et la diminution de l’efflux de platine au niveau de sa cible intra-nucléaire qu’est l’ADN. L’ensemble de ces résultats apportent du rationnel à la réalisation d’essais cliniques impliquant le cisplatine et visant par différents biais à améliorer l’efficacité de traitements systémiques de cancers broncho-pulmonaires non à petites cellulesDespite many advances in the recent years in the therapeutic management of bronchopulmonary cancer, it remains the leading cause of death linked to cancer in the world. The major challenge for this disease is therefore to develop new treatments and optimize the use of existing drugs, in particular platinum salts. The number of clinical protocols testing combined therapies including immune check-point inhibitors and platinum salts is currently increasing in lung cancer treatment, however preclinical studies and rationale are often lacking. Here, we evaluated the impact of cisplatin treatment on PD-L1 expression analyzing the clinicopathological characteristics of patients who received cisplatin-based neoadjuvant chemotherapy followed by surgery and showed that cisplatin-based induction treatment significantly increased PD-L1 staining in both tumor and immune cells from the microenvironment. Twenty-two patients exhibited positive PD-L1 staining variation after neoadjuvant chemotherapy; including 9 (23.1%) patients switching from <50% to ≥50% of stained tumor-cells. We also confirmed the up-regulation of PD-L1 by cisplatin, at both RNA and protein levels, in nude and immunocompetent mice bearing tumors grafted with A549, LNM-R, or LLC1 lung cancer cell lines. Up-regulation of PD-L1 by cisplatin involved the PI3K / AKT signaling pathway.The combined administration of anti-PD-L1 antibodies (3mg/kg) and cisplatin (1mg/kg) to mice harboring lung carcinoma significantly reduced tumor growth compared to single agent treatments and controls. Overall, these results suggest that cisplatin treatment could synergize with PD-1/PD-L1 blockade to increase the clinical response, in particular through early and sustainable enhancement of PD-L1 expression. Simultaneously, we were able to develop a targeted anti-neurotensin therapy to block its paracrine effects which stimulate proliferation, growth, and metastatic potential of lung tumor cells. Anti-neurotensin antibodies also improved the sensitivity to cisplatin of previously resistant tumors by mechanisms which probably involve increased influx and decreased efflux of platinum at the intra-nuclear level where resides its target DNA. All of these results provide a rationale for carrying out clinical trials involving cisplatin and aiming, by various ways, to improve the effectiveness of systemic treatments for non-small cell broncho-pulmonary cancers
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Ginouves, Marine. "Phylogénie et implication du Leishmania RNA virus dans la leishmaniose cutanée due à L. guyanensis en Guyane Française Prevalence and Distribution of Leishmania RNA Virus 1 in Leishmania Parasites from French Guiana Unraveling the genetic diversity and phylogeny of Leishmania RNA virus 1 strains of infected Leishmania isolates circulating in French Guiana Comparison of tetrazolium salt assays for evaluation of drug activity against Leishmania spp In Vitro Sensitivity of Cutaneous Leishmania Promastigote Isolates Circulating in French Guiana to a Set of Drugs Presence of Leishmania RNA Virus 1 in Leishmania guyanensis Increases the Risk of First-Line Treatment Failure and Symptomatic Relapse Use of the intramuscular route to administer pentamidine isethionate in Leishmania guyanensis cutaneous leishmaniasis increases the risk of treatment failure Leishmaniavirus genetic diversity is not related to leishmaniasis treatment failure." Thesis, Guyane, 2020. http://www.theses.fr/2020YANE0009.
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Le Leishmania RNA virus (LRV), un virus à ARN double brin retrouvé chez certaines Leishmania, pourrait constituer un facteur d’aggravation des leishmanioses tégumentaires. En Guyane Française, ce virus est retrouvé dans plus de 80% des isolats de L. guyanensis, dont la plupart sont issus des communes de l’intérieur. La présence de ce virus dans les Leishmania ne semble pas influencer la sensibilité in vitro des parasites aux principaux antiparasitaires, mais pourrait augmenter de 27% le risque d’échec thérapeutique et de rechutes chez les patients traités à la pentamidine. L’analyse génétique des LRV, dont le but était d'identifier l’implication de clusters dans la maladie, a permis de déterminer six groupes, dont deux majoritaires. Toutefois, aucun de ces clusters ne semblait être associé aux échecs thérapeutiques primaires. Le LRV ne semble être impliqué que dans les réactivations de la maladie. Ainsi, l’étude d’un plus grand nombre de sujets présentant une réactivation de la maladie permettrait de confirmer l’implication du LRV dans ces rechutes et de déterminer si un génotype de LRV particulier serait impliquéLeishmania RNA virus (LRV), a double-stranded RNA virus found in some Leishmania, could be a factor of tegumentary leishmaniasis aggravation. In French Guiana, this virus is found in more than 80% of L. guyanensis isolates, most of which come from the inlands. The presence of this virus in Leishmania does not seem to influence Leishmania in vitro susceptibility to antiparasitics, but could increase the risk of treatment failure and relapses by 27% in patients treated with pentamidine. The genetic analysis of LRV, to identify LRV clusters involved in the disease, revealed six LRV groups, including two main groups. However, none of these clusters appeared to be associated with primary treatment failures. LRV appears to be involved only in disease reactivations. Thus, the study of a larger number of cases with disease reactivation would confirm the involvement of LRV in these relapses and determine if a particular LRV genotype is involved
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CHEN, HSUEH LING, and 陳雪玲. "Can Compensation Committee Increase Pay-Performance Sensitivity?" Thesis, 2013. http://ndltd.ncl.edu.tw/handle/82210081627118750059.
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碩士國立臺北商業技術學院
會計財稅研究所
101
Section 14-6 of Securities Exchange Act is amended in November 24, 2010 to stipulate that corporations shall set up compensation committees. This research explores whether the mandatory compensation committee can increase pay-performance sensitivity and to provide the Board the specification establishment of compensation committee and operation model of compensation committee. The subject of this research is publicly listed companies from 2007, 2010 and 2011. The empirical results show that pay-performance sensitivity of the companies with compensation committees does not significantly differ from companies without compensation committees. In addition, the effectiveness of board is negative and significantly associated with association of pay-performance sensitivity and existence of compensation committees.
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Feng, Chun Hao, and 馮俊豪. "Targeting DNA repair pathway to increase DNA damage sensitivity." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/u4f89s.
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You, Ciao Ying, and 游巧盈. "The Study of Inhibiting Homologous Recombination Repair Pathway to Increase DNA Damage Sensitivity in Cancer Cells." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/2myt49.
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Shen, Wan-I., and 沈婉宜. "The use of Glucose Biosensor Array and Readout Circuit to Increase its Sensitivity and Signal-to-Noise Ratio." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/98ez55.
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碩士國立暨南國際大學
光電科技碩士學位學程在職專班
102
The cause of diabetes is due to unable/insufficient production of insulin. Apart from genetic factors, dietary habit is also another important factor. The symptoms of diabetes include diuresis, loss of body weight and etc. Besides, diabetic patients’ blood normally has high blood glucose level and urine often contains glucose as well. Diabetes is a chronic disease and results in many complications. Moreover, diabetes may lead to patient’s amputation. The aim of this study is to develop a simple, novel and accurate glucose biosensor array in order to accurately detect the blood glucose level of patients. Results showed that glucose biosensor array has a significantly higher sensitivity and signal-to-noise ratio as compared to a single glucose biosensor.
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CHANG, PO-YA, and 張博雅. "Using Sandwich Method to Increase the Detection Sensitivity of Cardiac Troponin I in Fiber Optic Particle Plasmon Resonance Biosensor." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/xn8f3b.
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Hsu, Jen-Hao, and 許仁豪. "The Mechanisms of Glucose Lowering Activity and Increase of Insulin Sensitivity Induced by Traditional Chinese Medicine Liu- Wei-Die-Huang-Wan." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/30495643804718227094.
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博士高雄醫學大學
天然藥物研究所博士班
95
It has been documented that Die-Huang-Wan showed an ability to lower the plasma glucose in normal rats via an increase of insulin secretion. Then, the herb of cornus (Cornus officinalis Sieb.) that is also called as San-Zu-Yee in Chinese has been indicated as a major factor for an increase of insulin secretion induced by Die-Huang-Wan. The present study was then conducted to understand the role of oleanolic acid from cornus (Cornus officinalis Sieb.) as an active principle responsible for the release of insulin. After an intraperitoneal injection into the fasting Wistar rats after 90 min, oleanolic acid (20 mg/kg) decreased the plasma glucose in a dose-dependent manner in parallel to an increase of plasma levels of insulin as well as C-peptide. The effects of oleanolic acid was reversed by a blockade of muscarinic receptors with atropine, but not affected by the ganglionic nicotinic antagonists, pentolinium or hexamethonium. Disruption of synaptic available acetylcholine (ACh) using an inhibitor of choline uptake, hemicholinium-3, or vesicular acetylcholine transport, vesamicol, negated this action of oleanolic acid. Also, physostigmine at concentration sufficient to inhibit acetylcholinesterase enhanced the action of oleanolic acid. Mediation of ACh release from the nerve terminals to enhance insulin secretion of oleanolic acid can thus be considered. Both the plasma glucose lowering action and the raised plasma levels of insulin and C-peptide by oleanolic acid were also inhibited by 4-diphenylacetoxy-N-methylpiperdine methiodide (4-DAMP), indicating the mediation of muscarinic M3 receptors. The results suggest that oleanolic acid can raise the release of ACh from nerve terminals, which stimulate muscarinic M3 receptors in the pancreatic cells and augment the insulin release resulting in a plasma glucose lowering action. Thus, oleanolic acid can be considered as one of the active principles for the increase of plasma insulin produced by cornus in normal rats. In addition, administration of Die-Huang-Wan has been found to delay the formation of insulin resistance in rats. The major herb contained in Die-Huang-Wan for this action was also investigated. In rats with insulin resistance induced by fructose-rich food, dioscorea(4.2mg/kg) ( Dioscorea opposita Thunb.) named as San-Yaw in Chinese showed the plasma glucose lowering action (28.9 ± 7.6 % vs. 26.4 ± 4.6 %, n=8, p< 0.01)in a way similar to Die-Huang-Wan while another 5 herbs failed to produce same action. Also, deletion of dioscorea from Die-Huang-Wan negated the plasma glucose lowering action. Moreover, a similar action of dioscorea produced by Die-Huang-Wan was characterized using the reduction of glucose-insulin index. In STZ-induced diabetic rats, daily oral administration of Die-Huang-Wan caused an increase of response to exogenous insulin 7 days later, indicating an increase of insulin sensitivity. The present study found that oral administration of dioscorea can increase insulin sensitivity produced by Die-Huang-Wan and the absence of dioscorea in Die-Huang-Wan failed to produce this action. Thus, dioscorea can be considered as the major herb in Die-Huang-Wan for the improvement of insulin resistance. In conclusion, now we found the mechanism(s) for two actions of Die-Huang-Wan in the regulation of plasma glucose in rats. Oleanolic acid was observed to be one of the active principles for the increase of plasma insulin produced by cornus which is the major herb in Die-Huang-Wan for increase of insulin secretion. The main herb in Die-Huang-Wan for improvement of insulin resistance was identified as dioscorea. Therefore, cornus and discorea may be used as an adjuvant for the handling of diabetic patients with insulin resistance in clinics.
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Hutin, D., L. Tamblyn, A. Gomez, Giulia Grimaldi, H. Soedling, T. Cho, S. Ahmed, et al. "Hepatocyte-specific deletion of TIPARP, a negative regulator of the aryl hydrocarbon receptor, is sufficient to increase sensitivity to dioxin-induced wasting syndrome." 2018. http://hdl.handle.net/10454/18338.
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YesThe aryl hydrocarbon receptor (AHR) mediates the toxic effects of dioxin (2, 3, 7, 8-tetrachlorodibenzo-p-dioxin; TCDD), which includes thymic atrophy, steatohepatitis, and a lethal wasting syndrome in laboratory rodents. Although the mechanisms of dioxin toxicity remain unknown, AHR signaling in hepatocytes is necessary for dioxin-induced liver toxicity. We previously reported that loss of TCDD-inducible poly(adenosine diphosphate [ADP]-ribose) polymerase (TIPARP/PARP7/ARTD14), an AHR target gene and mono-ADP-ribosyltransferase, increases the sensitivity of mice to dioxin-induced toxicities. To test the hypothesis that TIPARP is a negative regulator of AHR signaling in hepatocytes, we generated Tiparpfl/fl mice in which exon 3 of Tiparp is flanked by loxP sites, followed by Cre-lox technology to create hepatocyte-specific (Tiparpfl/flCreAlb) and whole-body (Tiparpfl/flCreCMV; TiparpEx3−/−) Tiparp null mice. Tiparpfl/flCreAlb and TiparpEx3−/− mice given a single injection of 10 μg/kg dioxin did not survive beyond days 7 and 9, respectively, while all Tiparp+/+ mice survived the 30-day treatment. Dioxin-exposed Tiparpfl/flCreAlb and TiparpEx3−/− mice had increased steatohepatitis and hepatotoxicity as indicated by greater staining of neutral lipids and serum alanine aminotransferase activity than similarly treated wild-type mice. Tiparpfl/flCreAlb and TiparpEx3−/− mice exhibited augmented AHR signaling, denoted by increased dioxin-induced gene expression. Metabolomic studies revealed alterations in lipid and amino acid metabolism in liver extracts from Tiparpfl/flCreAlb mice compared with wild-type mice. Taken together, these data illustrate that TIPARP is an important negative regulator of AHR activity, and that its specific loss in hepatocytes is sufficient to increase sensitivity to dioxin-induced steatohepatitis and lethality.
This work was supported by Canadian Institutes of Health Research (CIHR) operating grants (MOP-494265 and MOP-125919), CIHR New Investigator Award, an Early Researcher Award from the Ontario Ministry of Innovation (ER10-07-028), an unrestricted research grant from the DOW Chemical Company, the Johan Throne Holst Foundation, Novo Nordic Foundation and the Norwegian Cancer Society to J.M.
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Benson, Eric Ashley. "Loss of SIMPL increases TNFα sensitivity during hematopoiesis." Thesis, 2008. http://hdl.handle.net/1805/1851.
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Indiana University-Purdue University Indianapolis (IUPUI)The innate and adaptive immune responses are critical for host survival. The TNFα/NF-κB signaling pathway is a major regulator of the immune response. The TNFα/NF-κB signaling pathway has also been proposed to play a role in the regulation of hematopoiesis. In the TNFα signaling pathway, full induction of NF-κB (specifically the p65 subunit) dependent transcription is regulated by a co-activator SIMPL. The biological significance of SIMPL in TNFα dependent responses is poorly understood. To study SIMPL in vitro and in vivo in mammalian cells, a knockdown system utilizing shRNA (short hairpin RNA) was used. Analysis of hematopoietic progenitor cells infected with a retrovirus encoding the SIMPL shRNA was used to study the role of SIMPL in hematopoiesis. The ability of progenitor cells lacking SIMPL to grow and differentiate was not compromised. In contrast in the progenitors cells lacking SIMPL, TNFα mediated inhibition of colony formation was significantly enhanced. These growth inhibitory effects of SIMPL were not due to an increase in apoptosis. The enhanced inhibitory affects were specific for TNFα and not found in other common hematopoietic inhibitors (TGF-β1 and IFNγ). Results of this work reveal that SIMPL is a component of the hematopoiesis that is required for TNFα dependent effects upon myeloid progenitors.
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Chu, Ying, and 朱萾. "A578E mutation increases the capsaicin sensitivity of chicken TRPV1." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/06810001416289653220.
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碩士國立陽明大學
生命科學系暨基因體科學研究所
103
Chili peppers produce capsaicin, the chemical principle that accounts for the “hotness” of our culinary experience. Capsaicin activates transient receptor potential cation channel subfamily V member 1 (TRPV1) on sensory neurons to alter the membrane potential to induce pain. Studies had identified residues important for capsaicin activation of TRPV1, but failed to explain differential capsaicin sensitivity of TRPV1 between avians and mammals. To determine the residue(s) dictating relative capsaicin sensitivity among species, I characterized chimeras composed of capsaicin-sensitive rat TRPV1 (rTRPV1) and capsaicin-insensitive chicken TRPV1 (cTRPV1) functionally. Unexpectedly, the chimera containing rat E570-V686 swap into chicken receptors displays capsaicin sensitivity. Through analysis of point mutations, I identify rTRPV1-E570 residue is critical for gaining capsaicin sensitivity. A578E mutation, the equivalent site on cTRPV1, is also sufficient to endow capsaicin sensitivity. Moreover, I can replace the glutamate with a lysine or a glutamine to install capsaicin sensitivity in cTRPV1-A578 and rTRPV1-E570 mutants. Zingerone failed to activate any A578 mutants that retained capsaicin sensitivity, suggesting that the vanilloid group alone is not sufficient for receptor activation. Comparing the derivatives Cap-EA and Cap-EMA with capsaicin, these two compounds with the hydrophilic vanilloid moiety are less capable of engaging the hydrophobic part of TRPV1 to aid receptor activation. Cap-EA successfully activates cTRPV1-A578E, suggesting that the A578 residue is exposed to cytosol and may participate in vanilloid binding.
48
Chang, Yao-Fei, and 詹堯斐. "The mechanism whereby taxane increases NSCLC sensitivity to gefitinib." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/02319692228199222397.
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Chen, Shiau-Mei, and 陳曉玫. "The MicroRNA-124 Overexpression Increases Sensitivity of Anti-tumor Drug." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/34212421018360790700.
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博士國防醫學院
生命科學研究所
103
MicroRNAs play critical roles in regulating various physiological processes, including growth and development. Previous studies have shown that microRNA-124 (miR-124) participates not only in regulation of early neurogenesis but also in suppression of tumorigenesis. In the present study, we found that overexpression of miR-124 was associated with reduced DNA repair capacity in cultured cancer cells and increased sensitivity of cells to DNA-damaging anti-tumor drugs, specifically those that cause the formation of DNA strand-breaks (SBs). We then examined which DNA repair–related genes, particularly the genes of SBs repair, were regulated by miR-124. Two SBs repair–related genes, encoding ATM interactor (ATMIN) and poly ADP-ribose polymerase 1 (PARP1), were strongly affected by miR-124 overexpression, by binding of miR-124 to the 3¢-untranslated region of their mRNAs. As a result, the capacity of cells to repair DNA SBs, such as those resulting from homologous recombination, was significantly reduced upon miR-124 overexpression. A particularly important therapeutic implication of this finding is that overexpression of miR-124 enhanced cell sensitivity to multiple DNA-damaging agents via ATMIN- and PARP1-mediated mechanisms. The translational relevance of this role of miR-124 in anti-tumor drug sensitivity is suggested by the finding that increased miR-124 expression correlates with better breast cancer prognosis, specifically in patients receiving chemotherapy. These findings suggest that miR-124 could potentially be used as a therapeutic agent to improve the efficacy of chemotherapy with DNA-damaging agents.
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吉井, 美穂, and Miho Yoshii. "Lipopolysaccharide-Deficient Mutants of Salmonella enterica Have Increased Sensitivity to Catechins." Thesis, 2013. http://hdl.handle.net/2237/19161.
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