Дисертації з теми "Acid-sensitive"
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1
Jones, John I. W. "Characterisation of acid-sensitive dyspepsia." Thesis, Nottingham Trent University, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272811.
2
Gallovic, Matthew D. "Acid-Sensitive Polymer Microparticles for Subunit Vaccine Delivery." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1468803443.
3
Lamb, Justin. "Molecular aspects of amino acid sensitive cell cycle control." Thesis, University of Aberdeen, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245976.
Анотація:
The existence and molecular basis of an amino acid sensitive cell cycle control mechanism in human cells is described for the first time. Withdrawal of a single amino acid (arginine) from normal human fibroblast cultures caused a rapid cessation of proliferation characterised with a loss of accumulation of cells with G1 DNA content, consistent with a loss of cyclin D1-associated kinase activity and the predominance of hypo-phosphorylated pRb. Restoration of amino acid caused a synchronous reentry to cycle after a delay in excess of that for M to S transit in freely cycling populations, indicating exit from a quiescent-like state. The cellular response was thus consistent with Pardee's concept of a pivotal cell cycle control mechanism in G1, sensitive to extracellular conditions (ie the R-point) (Pardee, 1974). Inhibition of expression of the pRb phosphorylating kinase, cdk4, was identified as the key regulatory element in the response. A hypothetical cellular communication pathway coupling amino acid shortage to translational suppression of cdk4 (the '-Arg/cdk4 response pathway') has been synthesised from the known biochemical effects of deprivation and the recognised determinants of this suppression, including a 5'UTR mediated wild-type p53 dependency. A strategy for analysis and interrogation of this translational control mechanism, based upon the synthesis of epitope-tagged protein from full length or 5'URT truncated cdk4 cDNAs, and attempts to confirm the primacy of cdk4 suppression to the antiproliferative response by its enforced expression, are described. A highly deranged human tumour cell line (HeLa) was found to be deficient in amino acid sensitive cell cycle control. These cells continued in cycle after withdrawal but this was accompanied by a rapid loss of viability and cell disintegration. Simultaneous cell cycle blocks conferred partial protection from arginine deprivation induced cell death. The possibility that inappropriate cell cycle progression was the cause of cell death is discussed. Not all human tumour lines were vulnerable to arginine deprivation. This responsivity was found to be predicted by the status of the functional determinants identified or inferred (ie wild-type pRb, with cdk4 as the predominant phosphorylating kinase, intact'-Arg'cdk4 response pathway). This work describes a novel cellular response mechanism, complementing recent similar findings from elsewhere, to connect cellular biosynthetic capacity with control of cell cycle progression, with significance to the maintenance of normal cell growth regulation and suppression of the malignant phenotype, and providing a broader understanding of 'physiological' cell cycle control.
4
Agius, Ronald. "PH-sensitive binding of nickel(II) ions to aspartic acid." [S.l. : s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=971555737.
5
Roberge, Stéphane. "Conjugated Linoleic Acid/Styrene/Butyl Acrylate Bulk and Emulsion Polymerization." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/34536.
Анотація:
The potential for conjugated linoleic acid (CLA) incorporation into pressure-sensitive adhesive (PSA) formulations was evaluated. A series of free radical bulk copolymerizations of CLA/styrene (Sty) and CLA/butyl acrylate (BA) were designed to allow the estimation of reactivity ratios. Bulk terpolymerizations of CLA/Sty/BA were also evaluated before moving to emulsion terpolymerizations of CLA/Sty/BA. The polymers were characterized for composition, conversion, molecular weight and glass transition temperature while latexes were characterized for viscosity, particle size, tack, peel strength, and shear strength.
All experiments were performed at 80oC and monitored with attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. While bulk experiments were monitored off-line, the emulsion experiments were monitored in-line. Absorbance peaks related to the monomers and polymer were tracked to provide conversion and polymer composition data using a multivariate calibration method. Off-line measurements using gravimetry and 1H-NMR spectroscopy were compared to the ATR-FTIR data and no significant differences were detected between the measurement methods.
Pseudo-kinetic models, developed and validated with the copolymer experimental data, were used to estimate reactivity ratios. The copolymer pseudo-kinetic models were extended to a terpolymer pseudo-kinetic model and validated with experimental data. The pseudo-kinetic models incorporated the ability of oleic acid, a common impurity found in CLA, to trap electrons thus influencing the reaction kinetics significantly. The influence of terpolymer composition, chain transfer agent concentration, cross-linker concentration, molecular weight, viscosity and particle size on tack, peel strength and shear strength was investigated by using a constrained mixture design. The final forms of the resulting empirical models allowed the creation of 3D response surfaces for PSA performance optimization. The incorporation of 30 wt.% CLA into a practical PSA application suitable for the removable adhesives category was achieved.
6
Virdee, Susan. "The use of acid sensitive dyes to monitor acid generation and diffusion in thin polymer films." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ32562.pdf.
7
Goss, Heather Vanessa. "Contrasting Chemical Response to Experimental Acidification of Fice Acid-sensitive Streams." Fogler Library, University of Maine, 2006. http://www.library.umaine.edu/theses/pdf/GossHV2006.pdf.
8
Jadhav, Amol. "Paramagnetic microparticle manipulation for rapid and sensitive nucleic acid sequence identification." Thesis, University of Newcastle upon Tyne, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608361.
9
Evans, S. W. "The rate of release of aluminium from acidic and acid sensitive soils." Thesis, University of Nottingham, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308840.
10
Schweitzer, Lawrence D. (Lawrence David). "Identification of novel proteins that regulate the amino acid-sensitive mTORC1 pathway." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/103249.
Анотація:
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2016.Cataloged from PDF version of thesis. "February 2016."
Includes bibliographical references.
mTOR is a serine-threonine kinase that, as the catalytic subunit of mTORC1, promotes growth and anabolism. Due to its central role in metabolism, the local and systemic environment surrounding the cell tightly regulate mTORC1. Growth factors and nutrients are each required to activate mTORC1 and promote growth. Activation of mTORC1 by growth factors has been well-elucidated, but it is only recently becoming clear how nutrients, specifically amino acids, activate mTORC1. The presence of amino acids leads to the recruitment of mTORC1 from the cytosol to the surface of the lysosomal membrane, allowing it to be activated downstream of growth factors. This amino acid-induced translocation is mediated by the Rag GTPases and Ragulator (the scaffold for the Rag GTPases and mTORC1 on the lysosomal membrane). Here we describe the identification of two new components of Ragulator, HBXIP and c7orf59, that are required for the lysosomal localization of both the Rag GTPases and mTORC1 and that allowed us to identify new functions that Ragulator fulfills. We also characterized RagA-null mice and RagA-null mouse embryonic fibroblasts (MEFs). RagA is required for embryonic development, and, surprisingly, its deletion in adult mice leads to an expansion of monocytes. MEFs derived from RagA-null embryos display atypical, nutrient-insensitive mTORC1 activation. Finally, we identified c17orf59, a new Ragulator-interacting protein that inhibits the interaction between the Rag GTPases and Ragulator, inhibiting mTORC1 activation by amino acids. We report here our progress in characterizing the components of the amino acid-sensitive mTORC1 pathway and their physiological roles and we discuss the many open questions that remain to be studied regarding how amino acid sufficiency promotes the lysosomal localization of mTORC1.
by Lawrence D. Schweitzer.
Ph. D.
11
Lowry, Eleanor J. "14-3-3 mediated forward transport and heterodimerisation of acid-sensitive K2p channels." Thesis, University of Manchester, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.532256.
12
Alshaikh, Sana. "A novel and sensitive molecular method for nucleic acid discovery in CSF samples." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/a-novel-and-sensitive-molecular-method-for-nucleic-acid-discovery-in-csf-samples(65c2353b-40c2-4856-8af6-c64d86773e3e).html.
Анотація:
Encephalitis is a matter for serious public health concern because of the high morbidity and mortality associated with many cases. Epidemiological studies have shown that viral encephalitis (VE) is more common than the sum of encephalitis caused by all other pathogens. However, more than 95% of cases have no known cause. Thus, there is a significant need to develop a sensitive method for the diagnosis of these unknown cases. Previous sequence independent amplification (SIA) assays have proved successful in detecting new viruses in many biological samples but not in CSF samples. This may be due to the relatively low sensitivity of most available methods as CSF usually contains lower concentrations of pathogen than most other samples. A known problem with these types of assays is the annealing of the random primers to human DNA which facilitates preferential amplification of background human DNA. Thus, large scale sequencing is usually required to detect a virus, which in turn reduces the detection sensitivity to more than 1000 viral copies/µl, a CSF concentration that is rarely seen in cases of VE.This project was designed to develop a highly sensitive SIA assay for novel nucleic acid identification that could be used in testing CSF samples obtained from patients with neurological diseases of unknown cause. The study started with evaluation of two existing SIA assays commonly used for virus discovery; whole genome amplification (WGA) and random PCR (r-PCR). Sequential modification and adaptation of these methods was carried out to increase their sensitivity. Ultimately, a novel primer (Sa primer) that showed no binding to most human DNA sequences in GenBank was designed and synthesised. Its 3' end was tagged with 6 and 7 random nucleotides generating 2 r-primers; Sa-6 and Sa-7. The sensitivity of the r-primers was checked in a novel assay developed during this project and named Sa-SIA using known concentrations of HCMV and HSV-1. CSF samples from Malawian children were then tested using the developed assay. Results showed that adaptation of the existing WGA and r-PCR assays allowed detection of up to 1300 viral copies/µl. When the novel primers developed in this project were used in a random PCR assay (Sa-r-PCR), it was found that using Sa-6 primer 130, 13, and 1.3 HCMV copies/µl could be detected with 100, 60, and 50% efficiency respectively. When using Sa-7 primer, the same concentrations of virus were detected with 100, 42, and 28.6% efficiency. DNase-1 treatment of the samples pre-extraction resulted in an improvement in viral detection sensitivity in samples with a high background of host DNA. Starting with template concentrations of 11000, 110, 11, and 1.1 HSV-1 copies/µl, viral detection efficiency was increased from 33.3, 10, 0, and 0% to 92, 55.6, 16.7, and 0% respectively when pre-extraction DNase-1 treatment preceded Sa-r-PCR using Sa-6 primer. The final developed assay (Sa-SIA) consisted of centrifugation, DNase-1 treatment, DNA extraction, Sa-r-PCR using Sa-6 and Sa primers, gel electrophoresis, band excision, cloning, small scale sequencing (sequencing of ≤ 20 positive clones from one constructed DNA library), and bioinformatics. It had a detection sensitivity of 1.3-11 viral copies/µl. When this assay was applied to stored CSF samples, one 448bp sequence was identified which gave 96% coverage with 81% identity to Torque teno midi virus-1 and 93% coverage with 81% identity to small anellovirus-2. A 236bp sequence from another CSF sample showed 66% coverage with 97% homology to an unclassified sequence previously identified in a viral genomic survey of stool sample in an earlier published study. In conclusion, the standardised method had been shown to detect 1.3 to 11 viral copies/µl of two viruses; HCMV and HSV-1. The detection of these viruses was achieved with only small scale sequencing. Application of this method to CSF samples has shown promising results. However, this method could be followed by more advanced post amplification analyses such as next generation sequencing.
13
Bradbeer, Jennifer. "Self-structuring foods based on acid-sensitive gellan gum systems to impact on satiety." Thesis, University of Birmingham, 2014. http://etheses.bham.ac.uk//id/eprint/5169/.
Анотація:
A novel approach that may impact on satiety, whilst meeting the demands of consumers, is the use of hydrocolloids that respond to the environment (acidic) conditions inside the human stomach by self-structuring. This thesis seeks to investigate the in vitro acid-induced gelation (“structuring”) of the mixed biopolymer systems; low-acyl and high-acyl gellan gum, and low-acyl gellan fluid gels. To explore this concept, a variety of acid structures were obtained, which were characterised by texture analysis, rheology and dynamic scanning calorimetry. The gel structures were found to rely on the pH, hydrocolloid concentration, percentage weight of each hydrocolloid used and the processing conditions used during their production. It is suggested that the use of gel alone is more than capable of providing prolonged satiety but leads to unpleasant sensations for the consumer if there is no delivery of energy to the body to compliment the sensation of satiety. Materials should be included that will modulate the energy delivery and slowly release calories over time. This research shows that the addition of co-solutes such as sugar and the measurement of their subsequent release from hydrocolloid gels could provide a first step to tackling these issues.
14
Yaworsky, Karen Lynne. "Engagement of the insulin-sensitive pathway in the stimulation of glucose transport by Ã-lipoic acid." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0020/MQ45881.pdf.
15
He, Hongyan. "Multifunctional medical devices based on PH-sensitive hydrogels for controlled drug delivery." The Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=osu1148318906.
16
Löhrer, Daniel Verfasser], Dominik [Akademischer Betreuer] Wiemuth, and Marc [Akademischer Betreuer] [Spehr. "Proteinbiochemische und elektrophysiologische Charakterisierung des bile acid-sensitive ion channels BASIC / Daniel Löhrer ; Dominik Wiemuth, Marc Spehr." Aachen : Universitätsbibliothek der RWTH Aachen, 2017. http://d-nb.info/1162499036/34.
17
Löhrer, Daniel [Verfasser], Dominik Akademischer Betreuer] Wiemuth, and Marc [Akademischer Betreuer] [Spehr. "Proteinbiochemische und elektrophysiologische Charakterisierung des bile acid-sensitive ion channels BASIC / Daniel Löhrer ; Dominik Wiemuth, Marc Spehr." Aachen : Universitätsbibliothek der RWTH Aachen, 2017. http://d-nb.info/1162499036/34.
18
Hanafi-Bagby, Dalia. "Towards a fibre optic nucleic acid biosensor, thiazole orange derivatives as sensitive fluorescent probes to detect DNA hybridization." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0016/MQ45848.pdf.
19
Jakobsson, Emma. "Structural Studies of Echinococcus granulosus Fatty-acid-binding Protein 1 and Human Semicarbazide-sensitive Amine Oxidase." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis: Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5884.
20
Donnelly, Eilish Teresa. "An investigation of DNA repair in wild-type, amino acid auxotrophs and UV-sensitive mutants of Aspergillus nidulans." Thesis, University of Ulster, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243733.
21
Klein, Philipp Michael [Verfasser], and Ernst [Akademischer Betreuer] Wagner. "Redox-sensitive and receptor-targeted sequence-defined, cationic carriers for nucleic acid delivery / Philipp Klein ; Betreuer: Ernst Wagner." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2017. http://d-nb.info/1139977741/34.
22
Klein, Philipp [Verfasser], and Ernst [Akademischer Betreuer] Wagner. "Redox-sensitive and receptor-targeted sequence-defined, cationic carriers for nucleic acid delivery / Philipp Klein ; Betreuer: Ernst Wagner." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2017. http://d-nb.info/1139977741/34.
23
Helliwell, R. C. "Biogeochemical modelling of acid sensitive systems in Scotland : influence of scale and the potential role of enhanced nitrogen deposition." Thesis, University of Aberdeen, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.592556.
Анотація:
The focus of this thesis is on biogeochemical cycling in terrestrial ecosystems, and the effects on soil and surface water quality at a range of spatial scales throughout Scotland. The fundamental challenge of this research was to integrate the dynamic Model of Acidification of Groundwater In Catchments (MAGIC), within a spatial framework, by extrapolating knowledge of biogeochemical processes at the catchment scale to larger (i.e. regional and national) spatial units. The MAGIC model was applied to 9 Scottish sites in the U.K. Acid Waters Monitoring Network (UKAWMN), 59 sites in the region of Galloway and 733 sites throughout Scotland. Reduction in sulphur (S) emissions associated with the Second S Protocol and different forestry (land use) scenarios were modelled at these different scales to predict the existing and likely future extent of soil and surface water acidification in Scotland. The sensitivity of MAGIC to soil input data derived from two different methodologies was tested at the national scale. Anticipated reductions in S emissions are predicted to have a marginal beneficial effect on the reversibility of soil acidification at all spatial scales throughout Scotland, irrespective of the methodology used to determine the soil input parameters. With the exception of the most acid sensitive parts of Scotland, surface water Acid Neutralising Capacity (ANC) modelled at a national scale presents a picture of improving ANC in response to the Second S Protocol. From a policy perspective however, these results are potentially misleading. It is important that European legislation targets the most acid sensitive soils and surface waters as it is these ecosystems that require protection.
24
Renshaw, K. J. "Semi-natural vegetation characteristics and the prediction of hydrological and hydrochemical information within moorland, acid-sensitive catchments in upland Wales." Thesis, Swansea University, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.638645.
Анотація:
This study investigates the potential of utilizing semi-natural vegetation characteristics to predict hydrological and hydrochemical source areas in upland moorland catchments. It centres upon the intensive vegetational, hydrological and hydrochemical investigation of the Nant Gruffydd catchment, a tributary of the Camddwr at Llyn Brianne in upland, mid-Wales. A nested catchment approach was adopted and intensive monitoring during baseflows and stormflows was used to establish hydrological and hydrochemical source areas at stages through the storm hydrograph. The hydrological points raised include: 1) plateau peatlands ranked as the most important hydrological source during typical storm events, whilst the lower valley riparian peat areas ranked most important during very large storms and/or under very wet antecedent conditions. 2) isotopic investigations, although suggesting that 'old' pre-event water are dominant in the stream hydrograph in typical storm events, also demonstrate the invalidity of assumptions involved in conventional isotopic separation techniques. 3) hypotheses linking rapid runoff mechanisms with the delivery of pre-storm waters can be envisaged and are proposed. The hydrochemical points raised include: 1) the Nant Gruffydd catchment exhibits spatially variable levels of acidity and aluminium, specifically, plateau peatlands are characterised with low pH levels (4.2-4.4 pH units) and ranked as the most important source of Hydrogen, and the catchment slopes with mineral soils were identified as important sources of Aluminium (7 mmols/l) and supplied water of higher pH helping to account for the pH of 5.5 at the catchment outlet. 2) aluminium levels in the mid to upper catchment were as high as those recorded in acidified afforested catchments in the UK (Hornung et al. 1987). 3) changes in within-catchment sources of runoff, as opposed to at-a-point chemical changes exert a prime influence upon the hydrochemical dynamics of streamwater. 4) within-channel chemical reactions appear to influence runoff hydrochemistry more than hitherto has been recognised. The data gathered enabled associations between vegetation patterns and different hydrological/hydrochemical parameters to be explored at three scales. Whilst this demonstrated potentially useful associations, multiple-regression analysis failed to establish strong relationships.
25
Reinicker, Aaron D. "High Throughput Study of the Structure Sensitive Decomposition of Tartaric and Aspartic Acid on Surfaces Vicinal to Cu(111) and Cu(100)." Research Showcase @ CMU, 2015. http://repository.cmu.edu/dissertations/572.
Анотація:
There are many reactions that are sensitive to the surface structure of a catalyst. In order to obtain a comprehensive understanding of structure sensitive surface chemistry we use Surface Structure Spread Single Crystals (S4Cs) that expose a continuous distribution of crystal planes across their surfaces. Those crystal planes that lack mirror symmetry contain terraces, monatomic steps, and kinks and can be described as chiral with an R or an S orientation. When coupled with spatially resolved surface analysis techniques, S4Cs can be used to study the effects of surface structure and chirality on surface chemistry across a continuous distribution of crystal planes. A set of six Cu S4Cs has been created that spans all possible crystal planes of Cu. The Cu(111) S4C was used to study the structure sensitivity of L- and D-tartaric acid (TA) decomposition and the Cu(100) S4C was used to study the structure sensitivity of L-4-13C and D-aspartic acid (AA) decomposition. Isothermal Temperature Programmed Reaction Spectroscopy (TPRS) was implemented in which the S4Cs with monolayers of TA and AA were held at a temperature below the temperature of peak decomposition observed in a standard TPR experiment (heating at 1 K/s). At various times during isothermal heating, the surface was cooled to quench the reaction. Spatially resolved X-ray Photoelectron Spectroscopy (XPS) was performed to identify those regions on the surface in which the adsorbates had decomposed and those in which they were still intact. On the Cu(111) S4C which exposes both (100) and (110) step edges, TA decomposition is most sensitive to the density of (100) steps. AA decomposition on the Cu(100) S4C was enantioselective: L-AA-4-13C decomposed on S surfaces before R surfaces while D-AA decomposed on R surfaces before S surfaces. The decomposition of CH3CH2OH, CD3CD2OD, and CF3CH2OH on Zn was studied using temperature programmed reaction spectroscopy (TPRS). The decomposition products of each reaction were determined and a reaction mechanism was proposed for CH3CH2OH decomposition based on the product ratios and peak temperature locations. The CH3CH2OH decomposition mechanism includes the formation of two intermediate species on the surface: CH3CH2- to form CH2=CH2 and CH3CH2O- to form CH3CH=O.
26
Gagkas, Zisis. "Effects of broadleaf woodland cover on streamwater chemistry and risk assessments of streamwater acidification in acid-sensitive catchments in the UK." Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/2431.
Анотація:
Acidification of surface waters has been recognised as the major water quality problem in the UK uplands. The adverse effects of conifer afforestation on streamwater chemistry and ecology are well documented in acid-sensitive catchments and have mainly been attributed to the enhanced deposition of atmospheric pollutants onto conifer canopies (the “scavenging effect”). Currently, international and national policies promote the expansion of native broadleaf woodland in the UK. Pollutant deposition onto broadleaf canopies is considered less than onto the more aerodynamically rough conifers, but there is concern that largescale broadleaf planting could delay the recovery of acidified waters or lead to further acidification in most sensitive areas. However, there has been limited investigation of the influence of broadleaf woodland cover on streamwater chemistry in the UK. To investigate the effect of woodland cover 14 catchments with different (0-78%) percentages of broadleaf woodland cover were identified in representative acidsensitive areas in north-western and central Scotland (Glen Arnisdale and Loch Katrine area) and northern and south-western England (Ullswater area and Devon) using spatial datasets in a GIS. Streamwater was sampled at high flow from the catchment outlets in winter and spring 2005 and 2006 and was analysed for major cations, anions and trace metals using standard methods. The number of samples ranged from two in the Glen Arnisdale catchments to 10 in the Loch Katrine area catchments which were sampled more intensively. Significant positive correlations were found between percentage broadleaf woodland cover and streamwater NO3 (rs = 0.51) and soluble Al (rs = 0.64) concentrations. The greater NO3 leaching to streamwater in the three most forested catchments (> 50%) was probably due to enhanced N deposition onto woodland canopies and nitrification by alder in the Ullswater area forested catchments. Streamwater NO3 concentrations equalled or exceeded non-marine SO4 in the above catchments indicating that NO3 was the principal excess acidifying ion in catchments with greater woodland cover. The woodland effect on streamwater chemistry in the study catchments was masked to some extent by variability in acid deposition climate and soil type composition. Seasalt inputs were found to be a more important control than woodland cover for streamwater chemistry in the maritime Glen Arnisdale catchments. A risk assessment of acid-sensitivity in the study catchments was conducted by calculating streamwater critical load exceedances using the Steady-State Water Chemistry (SSWC) and First-order Acidity Balance (FAB) models and modelled pollutant deposition for 1995-97 and 2002. Critical loads were exceeded by 0.01 to 1.74 keq H ha-1 yr-1 in two catchments which had woodland covers > 50% and in the Devon control catchment. The remaining 11 study catchments were assessed to be not at risk of acidification, probably due to significantly reduced non-marine S deposition from 1986 to 2001, but seasalt inputs to the Glen Arnisdale catchments might cause acidic streamwater episodes. Acid-sensitivity was also assessed using macroinvertebrates sampled in 11 of the study catchments and the results generally agreed with the critical load assessments. More detailed estimates of the enhancement of dry S and N deposition onto birchwoods in the Loch Katrine area catchments using calculated roughness length within FRAME showed that it posed no risk for streamwater acidification in these catchments because of the high rainfall environment. However, in acid-sensitive areas of the UK with lower rainfall and closer to major pollution sources, enhanced pollutant scavenging by broadleaf woodland canopies could pose a greater risk of acidification to freshwaters. The finding that almost all study catchments with woodland covers less than 30% are well protected from acidification suggests that this is a sensible threshold value for use in risk assessments of the effects of broadleaf woodland planting conducted within the Forests and Water Guidelines. The results of a sensitivity analysis of the Guidelines’ methodology, conducted using parameters such as numbers and timing of streamwater sampling, different runoff estimates and critical acid neutralising capacity values, showed that the Guidelines should be able to protect sensitive freshwaters from acidification in areas where broadleaf woodland is expanding.
27
Horn, Christopher D. "Investigation of the effects of thermal enrichment and acid mine drainage on sensitive aquatic biota in the Stony River, Grant County, WV." Morgantown, W. Va. : [West Virginia University Libraries], 2005. https://etd.wvu.edu/etd/controller.jsp?moduleName=documentdata&jsp%5FetdId=3948.
Анотація:
Thesis (M.S.)--West Virginia University, 2005.Title from document title page. Document formatted into pages; contains vii, 101 p. : ill. (some col.), maps (part col.). Vita. Includes abstract. Includes bibliographical references.
28
Evans, Kate Florella. "The effects of acidosis, glutamine starvation and inhibition of the pH sensitive SNAT 2 amino acid transporter on protein metabolism in L6 muscle cells." Thesis, University of Leicester, 2009. http://hdl.handle.net/2381/7335.
Анотація:
Uraemia in end-stage renal disease patients leads to wasting of lean tissue, partly through the effects of acidosis that induce negative protein balance. Insulin resistance in these patients is also a major cause of muscle wasting, suggesting that low pH has a significant effect on insulin signalling in uraemic muscle. The pH sensitive SNAT2 amino acid transporter has been implicated in this because it is strongly inhibited by low pH, and amino acids are a well-established stimulus for the key protein kinase mTOR which regulates protein synthesis. The aims of this study were to determine: (a) the effects of amino acids, (especially L-Gln), and acidosis on insulin signalling and global protein synthesis/proteolysis rates; (b) whether these effects are mimicked by selective inhibition of SNAT2, and (c) whether intracellular amino acid depletion is sufficient to account for the functional effects of SNAT2 inhibition. In the L6 skeletal muscle cell-line, inhibition of SNAT2 with the nonmetabolisable SLC38 substrate methylaminoisobutyrate, metabolic acidosis (pH 7.1), or silencing of SNAT2 expression with smallinterfering RNAs, all decreased intracellular amino acid concentrations, mTOR activation, and global protein synthesis; and increased global proteolysis. Acidosis and small-interfering RNA inhibition both decreased phosphatidylinositol-3-kinase and protein kinase B activation, even though this is not regarded as an amino acid sensitive pathway. Extracellular amino acid depletion yielded decreases in intracellular amino acid levels similar to those observed during SNAT2 inhibition, but this failed to mimic the impairment of mTOR signalling observed when SNAT2 was inhibited. It is concluded that, in this muscle model, SNAT2 is able to regulate mTOR activation and protein synthesis rates; and that SNAT2 links acidosis, activity of the phosphatidylinositol-3-kinase/PKB signalling pathway and proteolysis, suggesting that SNAT2 is a key player in the acid-induced insulin resistance which is a prime cause of cachexia in acidotic uraemic patients.
29
Hu, Kang Dickson J. M. "Development and characterization of poly(vinylidene fluoride)-poly(acrylic acid) pore-filledpH-sensitive membranes and potential application on controlled drug release for ruminant animals." *McMaster only, 2007.
30
Phillipson, Mia. "Acid transport through gastric mucus : A study in vivo in rats and mice." Doctoral thesis, Uppsala University, Department of Medical Cell Biology, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3368.
Анотація:
The gastric mucosa is frequently exposed to endogenously secreted hydrochloric acid of high acidity. Gastric mucosal defense mechanisms are arranged at different levels of the gastric mucosa and must work in unison to maintain its integrity.
In this thesis, several mechanisms underlying gastric mucosal resistance to strong acid were investigated in anesthetized rats and mice. The main findings were as follows:
Only when acid secretion occurred did the pH gradient in the mucus gel withstand back-diffusion of luminal acid (100 mM or 155 mM HCl), and keep the juxtamucosal pH (pHjm) neutral. Thus, when no acid secretion occurred and the luminal pH was 0.8-1, the pH gradient was destroyed.
Bicarbonate ions, produced concomitant with hydrogen ions in the parietal cells during acid secretion and blood-borne to the surface epithelium, were carried transepithelially through a DIDS-sensitive transport.
Prostaglandin-dependent bicarbonate secretion seemed to be less important in maintaining a neutral pHjm.
Removal of the loosely adherent mucus layer did not influence the maintenance of the pHjm. Hence, only the firmly adherent mucus gel layer, approximately 80µm thick, seemed to be important for the pHjm.
Staining of the mucus gel with a pH-sensitive dye revealed that secreted acid penetrated the mucus gel from the crypt openings toward the gastric lumen only in restricted paths (channels). One crypt opening was attached to one channel, and the channel was irreversibly formed during acid secretion.
Gastric mucosal blood flow increased on application of strong luminal acid (155 mM HCl). This acid-induced hyperemia involved the inducible but not the neural isoform of nitric oxide synthase. These results suggest a novel role for iNOS in gastric mucosal protection and indicate that iNOS is constitutively expressed in the gastric mucosa.
It is concluded that a pH gradient in the gastric mucus gel can be maintained during ongoing acid secretion, since the acid penetrates the mucus only in restricted channels and bicarbonate is carried from the blood to the lumen via a DIDS-sensitive transporter.
31
Green, P., Ngozi G. Anyakoha, I. Gispan-Herman, G. Yadid, and Anna Nicolaou. "Arachidonic acid-containing phosphatidylcholine species are increased in selected brain regions of a depressive animal model: implications for pathophysiology." Elsevier, 2009. http://hdl.handle.net/10454/4584.
Анотація:
noThe Flinders Sensitive Line (FSL) rat is a genetic animal model of depression. Following recent findings that the brain fatty acid composition of FSL is characterised by increased arachidonic acid (AA), we used electrospray tandem mass spectrometry and 1H-NMR to examine lipid species in different brain areas. Cholesterol and sphingolipids were increased in the hypothalamus of the FSL rats. Furthermore, arachidonic acid-containing phosphatidylcholine species (AA-PC) were elevated with PC16:0/20:4, PC18:1/20:4 and PC18:0/20:4 (p<0.003) increased in the hypothalamus and striatum. In contrast, there was a decrease in some docosahexaenoic acid (DHA)-containing species, specifically PC18:1/22:6 (p<0.003) in the striatum and PE18:1/22:6 (p<0.004) in the prefrontal cortex. Since no significant differences were observed in the erythrocyte fatty acid concentrations, dietary or environmental causes for these observations are unlikely. The increase in AA-PC species which in this animal model may be associated with altered neuropathy target esterase activity, an enzyme involved in membrane PC homeostasis, may contribute to the depressive phenotype of the FSL rats.
32
Roberts, Terri Patricia. "Developmental failure in cochlear hair cells from mouse models of Usher syndrome and the identification of an acid sensitive ionic current in Inner and Outer hair cells." Thesis, University of Sussex, 2013. http://sro.sussex.ac.uk/id/eprint/46460/.
Анотація:
Inner hair cells (IHCs) are the primary sensory receptors of the mammalian cochlea. I employed the whole-cell patch-clamp technique to study voltage responses and ionic currents of IHCs in mice bearing mutations in hair bundle proteins. These mutations, all associated with Usher syndrome, lead to structural and functional defects of the mechanosensory hair bundle. I observed developmental failure in the electrical properties of IHCs from these mutants: a continuation of neonatal spiking instead of the graded receptor potentials seen in control adult IHCs. Voltage-clamp recordings revealed the main cause as the absence of the adult fast potassium (IK,f) current. Outer hair cells (OHCs) are required to amplify the travelling wave to be detected by the IHCs. Optical and whole-cell patch clamp techniques in these same mutants were employed to investigate the development of adult OHCs. I observed a developmental failure in the electrical properties of these OHCs, seen by an absence of the potassium current IK,n. Electromotility and the associated non-linear capacitance were however observed, indicating that prestin is expressed in the mutants. Acid sensitive ion channels (ASICs) have recently been found to be present within the organ of Corti. Here I present data showing the presence of an acid sensitive ion current in both IHCs and OHCs. ASIC1b knockout mice show a response to changes in the extracellular pH suggesting that the current may be carried through a different channel subtype or that compensatory changes occur. The electrical properties of the IHCs develop to maturity in these mice, however the OHCs appear to remain functionally immature displaying a lack of expression of the IK,n current and electromotily. This lack of electromotile function suggests that ASIC1b may be required either for the function of prestins electromotility or for the targeting of prestin to the cell membrane.
33
Smit, Michiel Johannes. "Development and validation of selective and sensitive LC-MS/MS Methods for determination of para-aminosalicyclic acid and cycloserine/terizidone applicable to clinical studies for the treatment of tuberculosis." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29814.
Анотація:
A method was validated for the quantification of para-aminosalicylic acid (PAS) in human plasma. The technique consisted of a protein precipitation extraction, followed by high performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) detection. Rilmenidine was used as the internal standard (ISTD). Analyte mean extraction yields determined were ~100.3% (CV % = 3.3). The extraction procedure was followed by liquid chromatographic separation using a Phenomenex Synergi Hydro-RP (150 x 2.0 mm, 4µm) analytical column. An isocratic mobile phase containing methanol, water and formic acid (40:59.8:0.2, v/v/v) was used at a flow-rate of 300 µl per minute. The retention times for PAS and rilmenidine were, ~2.4 and ~1.6 minutes, respectively. An AB Sciex API 3000 mass spectrometer at unit resolution in the multiple reaction monitoring (MRM) mode was used to monitor the transition of the protonated precursor ions m/z 154.1 and m/z 181.2 to the product ions m/z 80.2 and m/z 95.2 for PAS and the ISTD, respectively. Electro Spray Ionisation (ESI) was used for ion production. Accuracy and precision were assessed over three consecutive, independent runs. The calibration curve fits a quadratic (weighted by 1/x concentration) regression for PAS over the range 0.391 – 100 µg/ml, based on peak area ratios. A 1:1 and 1:4 dilution of the QC Dilution sample showed that concentrations of up to 160 µg/ml of PAS in plasma could be analysed reliably when diluted into the calibration range. Endogenous matrix components were found to have an insignificant effect on the reproducibility of the method, when human plasma originating from eight different sources were analysed. PAS was found to be stable in human plasma for 21 months kept at ~-80°C, for up to 21 hours at room temperature and when subjected to 3 freeze-thaw cycles. Stock solutions of PAS in methanol were stable for 2 days when stored at ~80°C and for 24 hours when stored at room temperature, ~4°C and ~-20°C. Plasma extracts of the analyte/ISTD ratio were shown to be stable on instrument over a period of ~55 hours. Reinjection reproducibility experiments indicated that an assay batch may be re-injected within 58 hours. Quantification of PAS in plasma was not significantly affected by the presence of haemolysed blood (2%) in plasma and when Lithium Heparin was used as anti-coagulant instead of K3EDTA. The best marker for terizidone pharmacokinetics is the analysis of cycloserine, a small polar drug with limited potential for absorbing UV that makes it difficult to analyse. A method was validated for the quantification of cycloserine in human plasma, and consisted of a protein precipitation extraction and derivatization, followed by high performance liquid chromatography with MS/MS detection. No ISTD was used as no suitable match could be found. The mean extraction yield determined was ~77% (CV% = 10.7). The extraction procedure was followed by liquid chromatographic separation using a Gemini NX C18 (50 x 2.0 mm, 5µ) analytical column. An isocratic mobile phase containing acetonitrile, water and formic acid (30:69.9:0.1, v/v/v) was used at a flow-rate of 300 µl per minute. The retention time for cycloserine was ~ 1.5 minutes. An AB Sciex API 3000 mass spectrometer at unit resolution in the MRM mode was used to monitor the transition of the protonated precursor ion m/z 335.9 to the product ion m/z 157.2 for cycloserine. ESI was used for ion production. Accuracy and precision were assessed over three consecutive, independent runs. The calibration curve fits a quadratic (weighted by 1/x concentration) regression for cycloserine over the range 0.313 – 40.0 µg/ml, based on peak areas. A 1:4 dilution of the QC Dilution sample showed that concentrations of up to 64.0 µg/ml of cycloserine in plasma could be analysed reliably when diluted into the calibration range and no carry over peaks were observed. Endogenous matrix components were found to have no effect on the reproducibility of the method when human plasma originating from six different sources was analysed. Cycloserine was found to be stable in human plasma for up to 18 hours at room temperature, and when subjected to 3 freeze-thaw cycles. Stock solutions of cycloserine in water and methanol were stable for 10 days when stored at ~ -80°C and for 18 hours when stored at room temperature, ~ 4°C and ~ -20°C. Long term stability in plasma has been proven for 17 months at -80°C. Plasma extracts of the analyte were shown to be stable on instrument over a period of ~ 29 hours. Reinjection reproducibility experiments indicate that an assay batch may be re-injected within 29 hours. Cycloserine is stable in whole blood (on ice) for up to 30 minutes. Both validated methods presented performed well on clinical samples generated from a multi drug resistant TB (MDR-TB) research study in children dosed with PAS and terizidone.
34
VERMA, SUJIT KUMAR [Verfasser], Sebastian [Akademischer Betreuer] Springer, Sebastian [Gutachter] Springer, Michael [Gutachter] Köhler, Mathias [Gutachter] Winterhalter, and Werner M. [Gutachter] Nau. "Polyelectrolyte Microcapsules: A versatile and sensitive tool for the detection of protein and nucleic-acid analytes / SUJIT KUMAR VERMA ; Gutachter: SEBASTIAN SPRINGER, MICHAEL KÖHLER, MATHIAS WINTERHALTER, WERNER M. NAU ; Betreuer: SEBASTIAN SPRINGER." Bremen : IRC-Library, Information Resource Center der Jacobs University Bremen, 2017. http://d-nb.info/114810397X/34.
35
Chen, Xiangke. "Vibrational Sum Frequency Generation Studies of Biological and Atmospheric Relevant Interfaces: Lipids, Organosulfur Species and Interfacial Water Structure." The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1282061999.
36
Sequeira, Reynold. "Sustainable Production Strategies for Environmentally Sensitive Industries." University of Cincinnati / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1288976134.
37
Adebayo, Olajumoke O. "Evaluation of bacterial polymers as protective agents for sensitive probiotic bacteria." Thesis, University of Wolverhampton, 2018. http://hdl.handle.net/2436/621096.
Анотація:
Probiotics are live microorganisms which when administered in adequate amounts confer one or more health benefits on the host. Different processing conditions, the acidic condition of the stomach and exposure to hydrolytic enzymes affect the viability and efficacy of probiotic organisms. This study investigated the protective effects of two biopolymers poly-gamma-glutamic acid (γ-PGA) and bacterial cellulose (BC) on probiotics during freeze drying and during exposure to simulated intestinal juices and bile salts. The antibacterial property of Bifidobacterium strains was also investigated against four pathogenic bacteria. γ-PGA, a naturally occurring biopolymer was produced by two bacteria (Bacillus subtilis ATCC 15245 and B. licheniformis ATCC 9945a) in GS and E media, γ-PGA yields of about 14.11g/l were achieved in shake flasks and molecular weight of up to 1620 k Da was recorded, γ-PGA production was scaled up in a fermenter with B. subtilis using GS medium. BC, an edible biopolymer was produced by Gluconacetobacter xylinus ATCC 23770 in HS medium and a modified HS (MHS) medium. A yield of about 1.37g/l was recorded and BC production with MHS medium was used for probiotic application. B. longum NCIMB 8809 B. breve NCIMB 8807 and B. animalis NCIMB 702716 showed the best antimicrobial properties against the investigated pathogens. Survival of Bifidobacterium strains was improved when protected with powdered BC (PBC) although γ-PGA offered better protection than PBC. Viability of B. longum NCIMB 8809, B. breve NCIMB 8807 and B. animalis NCIMB 702716 in simulated gastric juice (SGJ) and simulated intestinal juice with bile salts was improved when protected with 5% γ-PGA and 5% γ-PGA+PBC with a reduction of < 1 Log CFU/ml while a reduction of ≤2 Log CFU/ml was recorded in PBC protected cells. Protecting Bifidobacterium strains with γ-PGA, PBC or a novel γ-PGA + PBC combination is a promising method to deliver probiotic bacteria to the target site in order to confer their health benefits on the host.
38
Shah, Bhavik P. "Targeting Fat-Sensitive Pathways In Enteroendocrine Cells Using Nanoparticle-Mediated Drug Delivery." DigitalCommons@USU, 2009. https://digitalcommons.usu.edu/etd/432.
Анотація:
The current epidemic of obesity has been linked to an increase in fat intake associated with the Western diet. Nutrient-induced stimulation of enteroendocrine cells in the small intestine leads to the release of hormones that contribute to satiety and the control of food intake. In particular, ingested fat, specifically in the form of free fatty acids, is potent activator of enteroendocrine cells in the proximal small intestine. However, the underlying signaling cascade that free fatty acids initiate in these enteroendocrine cells, which leads to secretion of satiety hormones, is not known. In general, my research is focused on identifying nutrient-responsive pathways in enteroendocrine cells involved with the release of satiety signals and using this information to begin to develop novel drug delivery strategies to reduce food intake. In general, my results revealed that activation of the fatty acid receptor GPR120 was ecessary for the linoleic acid-induced intracellular calcium rise, a necessary precursor for hormone release. Using patch clamp recording, I discovered that linoleic acid activated enteroendocrine cells by inducing membrane depolarization, a process requiring the calcium-activated, monovalent cation permeable channel TRPM5, which is activated downstream of GPR120. To validate the unexpected finding that TRPM5 was involved in fattyacid signaling, I performed experiments using bitter compounds, whose transduction pathway is known to involve TRPM5. Enteroendocrine cells express the bitter taste receptors and release cholecystokinin in response to bitter stimuli, suggesting the probable role of gut in initiation of protective behavior against ingestion of potentially harmful substances. Armed with the data on the specifics of the fatty acid transduction, I performed experiments using nanoparticles to determine their utility for delivering pharmaceuticals specifically to the enteroendocrine cells. I fabricated and characterized PLGA nanoparticles and performed intracellular uptake studies in order to optimally delivery payloads inside cells. Finally, I validated their use by using cell-based assays to determine the effects of internalized PLGA nanoparticles on ion channels and signaling pathways involved in CCK release. Taken together, this dissertation research has identified the signaling pathways (pharmacological targets) involved in fatty acid-mediated satiety hormone release and validated the potential therapeutic use of nanoparticle-mediated drug delivery for the eventual control of food intake.
39
Turelli, Lorenzo. "Étude de nouveaux motifs d'espaceurs dans la construction de conjugués anticorps-médicaments." Electronic Thesis or Diss., Strasbourg, 2023. http://www.theses.fr/2023STRAF063.
Анотація:
La classe des conjugués anticorps-médicaments (ADC) représente l'un des traitements à la croissance la plus rapide en oncologie, permettant l'utilisation de composés hautement cytotoxiques liés de manière covalente à un anticorps monoclonal (mAb) qui peut se fixer sélectivement à un antigène exprimé à la surface de la cellule cancéreuse, assurant ainsi la précision de cette thérapie. Le motif de liaison, qui relie le mAb au médicament, est essentiel pour contrôler la libération du médicament ainsi que pour la pharmacocinétique et la pharmacodynamique de l'ensemble du conjugué. Cependant, le développement d'un nouveau linker est un processus long et coûteux, dans lequel le motif idéal doit assurer à la fois la stabilité en circulation sanguine et une cinétique rapide dans la libération du médicament à l'intérieur de la cellule cancéreuse. Le travail décrit ici vise à répondre aux limitations présentes dans ce domaine de deux manières différentes : premièrement, en introduisant un nouveau linker clivable sensible à l'acide avec une excellente stabilité extracellulaire et une clivabilité sélective dans la cellule cancéreuse ; deuxièmement, en adoptant une approche sans linker, en introduisant un nouveau format d'ADC, appelé Self Drugged Antibody (SDA), dans lequel le médicament est construit sur le mAb par une réaction multicomposant UgiThe class of Antibody Drug Conjugates (ADCs) represents one of the most fast-growing treatments in oncology therapeutics, enabling the use of highly cytotoxic compounds covalently linked to a monoclonal antibody (mAb) which can selectively get attached to an antigen expressed on the surface of the cancer cell, assuring the precision of this therapy. The linker motif, connecting the mAb to the drug, is key to dictate the modality of the drug’s release as for the pharmacokinetic and pharmacodynamic of the whole conjugate. However, the development of a novel linker is a costly and time-consuming process, in which the ideal motif has to assure both the stability in blood circulation and a fast kinetic in the release of the warhead inside the cancer cell. The work here described aims at addressing the limitations present in this field in two different ways: first by introducing a novel acid sensitive cleavable linker with excellent extracellular stability and selective cleavability in the cancer cell; secondly, embracing a linker-less approach, by introducing a new format of ADC, coined Self Drugged Antibody (SDA), in which the drug is built on the mAb through a Ugi multicomponent reaction
40
Nicolini, Ariana Marie, and Ariana Marie Nicolini. "Single-Step, Optical Biosensors for the Rapid and Sensitive Detection of Bacterial and Viral Pathogens." Diss., The University of Arizona, 2016. http://hdl.handle.net/10150/623158.
Анотація:
This dissertation discusses the development of inexpensive, easy-to-use, and field-deployable diagnostic techniques and devices for the early detection of various pathogens, commonly found in clinical samples and contaminated food and water. Infectious diseases account for about 90% of world health problems, killing approximately 14 million people annually, the majority of which reside in developing countries. In 2012, the World Health Organization (WHO) published data on the top 10 causes of death across the globe. Although communicable disease is a prevalent cause of fatality, both low-income and high-income countries, pathogen species and transmission are very different. Nearly 60% of deaths in developing countries are caused by food, water, air or blood-borne pathogens. The most prevalent illnesses are diarrheal disease, malaria, and HIV/AIDS. By contrast, the leading causes of death in developed countries (heart disease, cancer, and stroke) are not communicable and are often preventable. However, there is an increasing need for the development of rapid and accurate methods for pathogen identification in clinical samples, due to the growing prevalence of antibiotic-resistant strains. Incorrect, or unneeded antibiotic therapies result in the evolution of extremely aggressive nosocomial (hospital-acquired) infections, such as methicillin- (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA). The implementation of rapid, easy to use and cost-effective diagnostics will reduce the frequency of pathogen-related deaths in underdeveloped countries, and improve targeted antibiotic treatment in hospital settings, thus decreasing the potential development of more treatment-resistant "super bugs". This research includes novel techniques utilizing two major sensing modalities: serological (i.e. immunological), and nucleic acid amplification testing (NAATs). We first developed a highly sensitive (limit-of-detection = 100 CFU mL-1) particle immunoassay that takes advantage of elastic and inelastic light scatter phenomena, for optical detection of target antigens. This assay is performed upon a unique nanofibrous substrate that promotes multiplexing on a user-friendly platform. We then developed a novel technique, termed emulsion loop-mediated isothermal amplification (eLAMP), in which the target amplicon is detected in real-time, again utilizing light scattering detection and quantification. Both techniques require no sample pre-treatments, and can be combined with smartphone imaging for detection of targets in under 15 minutes. These methods have the potential to improve the speed and sensitivity of early pathogenic identification, thus leading to a reduction in preventative deaths and a decrease in global economic costs associated with infectious disease in clinical and other settings.
41
DURANTI, GUGLIELMO. "Oxidative stress resistance in skeletal muscle cells: role of vitamin C and redox sensitive transcription factors NF-KB and AP-1." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2005. http://hdl.handle.net/2108/48.
Анотація:
Durante l’esercizio fisico le cellule muscolari sono continuamente esposte allo stress ossidativo e necessitano quindi di efficaci sistemi di difesa antiossidante. Tramite l’attivazione di fattori trascrizionali, quali AP-1 e NF-kB, le cellule muscolari possono compensare le variazioni ambientali incrementando le risposte adattative (antiossidanti endogeni, enzimatici e non). Alle difese cellulari contribuiscono anche gli antiossidanti esogeni, quali la vitamina C. Il contenuto di vitamina C nelle cellule muscolari è determinato sia dall’efficienza dei sistemi di trasporto sia dal mantenimento della vitamina nella sua forma ridotta.
Lo scopo della tesi è stato quello di studiare in cellule muscolari scheletriche: i) specifici sistemi antiossidanti, quali il glutatione, la tioredossina reduttasi ed enzimi antiossidanti; ii) il ruolo di fattori di trascrizione sensibili allo stato redox quali AP-1 e NF-kB; iii) i meccanismi di trasporto sia per la forma ridotta (acido ascorbico, AA) che per la forma ossidata (acido deidroascorbico, DHA) della vitamina C; iiii) i sistemi enzimatici (NADH-, NADPH-, GSH-, acido lipoico-dipendenti) coinvolti nella rigenerazione della vitamina C. A tal fine sono state utilizzate cellule muscolari scheletriche di topo (C2C12) e di ratto (L6C5), sia in fase proliferativa che dopo differenziamento.
I risultati ottenuti dimostrano che il differenziamento è correlato all'aumento della capacità antiossidante, e tale fenomeno è maggiormente evidente nelle cellule L6C5. Le cellule C2C12 (mioblasti e miotubi), possedendo elevati livelli di NF-kB, di complessi AP-1 di tipo inibitorio e di tioredossina reduttasi, mostrano una maggiore espressione di enzimi antiossidanti; perciò, tali cellule sono maggiormente resistenti allo stress ossidativo. Al contrario, i mioblasti L6C5 mostrano un fenotipo sensibile, correlato a bassi livelli di tioredossina reduttasi, catalasi ed attività di NF-kB, ed alti livelli di glutatione ossidato e di complessi AP-1 attivi. Tuttavia, questa linea cellulare, se indotta a differenziare, acquista un fenotipo resistente all’apoptosi, accompagnato da drastici cambiamenti nel bilancio fra specie ossidanti ed antiossidanti. I miotubi L6C5, infatti, aumentano le attività di catalasi e NF-kB, e cambiano i complessi AP-1 da attivanti ad inibitori.
Gli esperimenti condotti per caratterizzare il metabolismo della vitamina C hanno evidenziato che il trasporto dell'AA è mediato dall'SVCT2 (trasportatore con elevata affinità), mentre il trasporto per il DHA è mediato dai trasportatori del glucosio GLUT1 e GLUT3. I mioblasti L6C5 sono più efficienti nel trasporto dell'acido ascorbico, mentre le cellule C2C12 sono più efficienti nel trasporto dell'acido deidroascorbico e mostrano maggiori attività DHA e AFR (radicale ascorbile) reduttasiche.
Lo stress ossidativo, indotto dalla deplezione di glutatione, induce un aumento dell'espressione di SVCT2 e dell'attività DHA reduttasica tioredossina-dipendente, specialmente nelle cellule differenziate. Da questi dati appare evidente che il trasportatore SVCT2 e l'attività DHA reduttasica NADPH-tioredossina-dipendente appartengono ad un sistema inducibile attivato in risposta allo stress ossidativo.During physical exercise skeletal muscle cells are continuosly exposed to oxidative stress. Thus, they compensate environmental challenges by increasing adaptive responses, characterized by AP-1- and NF-kB-mediated transcriptional up-regulation of endogenous enzymatic and non-enzymatic antioxidants. Also exogenous antioxidants, such as vitamin C contribute to cellular defences. The skeletal muscle cells content of vitamin C is determined both by the efficiency of transport systems and by the ability to maintain the vitamin in its reduced form. Aim of this thesis was to study, in skeletal muscle cells: i) specific antioxidants systems, including glutathione (GSH), thioredoxin reductase (TxR) and antioxidants enzymes; ii) the role of redox sensitive transcription factors, such as AP-1 and NF-kB; iii) the transport of vitamin C, both in the reduced (ascorbic acid, AA) and oxidized form (dehydroascorbic acid, DHA); iiii) the enzymatic systems (NADH-, NADPH-, GSH-, lipoic acid-dependent) involved in vitamin C recycling. To this end, two skeletal muscle cell lines were used (mouse C2C12 and rat L6C5 cells), in both proliferating and differentiated conditions. We found that muscle cell differentiation was associated with increase in antioxidant ability, and this phenomenon was more evident in the L6C5 cell line. C2C12 myoblasts and myotubes show high levels of NF-kB and thioredoxin reductase, together with AP-1 inhibitory complexes. Furthermore, C2C12 cells have antioxidant enzymes highly active thus allowing survival after exposure to oxidative insults. On the contrary, L6C5 myoblasts show a sensitive phenotype, correlated to low levels of thioredoxin reductase, catalase and NF-kB activity, together with high levels of oxidized glutathione (GSSG) and activating AP-1 complexes. Interestingly, this cell line acquires an apoptosis-resistant phenotype, accompanied by drastic changes in the oxidant/antioxidant balance, when induced to differentiate. Indeed, L6C5 myotubes enhance catalase and NF-kB activities and shift AP-1 complexes from an activating to an inhibitory behaviour. Concerning the experiments on vitamin C metabolism, our data show that both cell lines import AA by the SVCT2 transporter, while DHA transport is mediated by glucose carriers GLUT1 and GLUT3. L6C5 myoblasts are more efficient in ascorbic acid transport, while C2C12 cells are more efficient in dehydroascorbic acid transport and ascorbyl free radical/dehydroascorbic acid reduction. Oxidative stress, induced by glutathione depletion, increased SVCT2 expression and thioredoxin reductase-mediated dehydroascorbic acid reduction, especially in differentiated cells. From these data, SVCT2 and NADPH-thioredoxin dependent DHA reduction appear to belong to an inducible system activated in response to oxidative injury.
42
Liss, Petronella Francina. "Cloning of the gfp (green fluorescent protein) gene downstream of the ldh promoter in a bacteriocin-sensitive strain of Lactobacillus sakei to serve as a reporter strain in bacteriocin studies." Thesis, Stellenbosch : Stellenbosch University, 2003. http://hdl.handle.net/10019.1/53330.
Анотація:
Thesis (MSc)--Stellenbosch University, 2003.ENGLISH ABSTRACT: Lactobacillus plantarum 285, isolated from sorghum beer, produces bacteriocin 285, which displays activity against several food spoilage organisms. For future application of bacteriocin 285 in the food industry, it was important to characterize the peptide and identify the genes encoding its production. The effect of bacteriocin 285 on sensitive cells was determined through the use of an indicator (sensitive) organism, Lactobacillus sakei DSM 20017. The indicator strain was genetically modified to express GFP (green fluorescent protein), with the aim of quantifying the antibacterial activity of bacteriocin 285 as a function of GFP fluorescence. Bacteriocin 285 proved to be identical to plantaricin 423 produced by L. plantarum 423. Plantaricin 423 is a class lIa bacteriocin and displays antimicrobial activity towards a broad spectrum of bacteria, including several food spoilage organisms. The sensitivity of L. sakei DSM 20017 towards antibacterial peptides produced by Lactobacillus curvatus DF38, L. plantarum 285, Lactobacillus casei LHS and Lactobacillus salivarius 241 is not limited to the growth stage of the organism. Cells remained sensitive to all four of these bacteriocins, from lag phase to late exponential growth. To inhibit growth of up to 90% of the cells of L. sakei DSM 20017, 1 AU/ml bacteriocin 285 (7 ng/ml) of partially purified bacteriocin 285 was required. However, to kill all viable cells of L. sakei DSM 20017, 16 AU/ml (110 ng/ml) of partially purified bacteriocin 285 was required. The gfpuv gene, encoding GFPuv, was cloned downstream of the Idh promoter and successfully expressed in L. sakei DSM 20017. However, GFPuv fluorescence could not be used as a direct method to quantify the antimicrobial activity of bacteriocin 285, since cells of strain DSM 20017 remained fluorescent for prolonged periods after treatment with lethal concentrations of the bacteriocin. The non-viability of the cells was confirmed with epifluorescence microscopy and a L1VE/DEAD® Baclight™ Bacterial Viability Probe. Cells that were stained with the viability probe indicated that the majority of untreated L. sakei DSM 20017 cells were viable. However, treatment of strain DSM 20017 with 16 AU/ml bacteriocin 285 rendered all visible cells non-viable.
AFRIKAANSE OPSOMMING: Lactobacillus plantarum 285 wat uit sorgumbier geïsoleer is, produseer bakteriosien 285. Die bakteriosien toon aktiwiteit teen verskeie organismes wat voedselbederi veroorsaak. Vir toekomstige aanwending van bakteriosien 285 in die voedselindustrie was dit belangrik om die peptied te karakteriseer en die gene wat vir die produksie daarvan kodeer, te identifiseer. Die effek van bakteriosien 285 op sensitiewe selle is bepaal deur die gebruik van 'n indikator (sensitiewe)-organisme, Lactobacillus sakei DSM 20017. Die indikator-organisme is geneties verander om die GFP (groen fluoreserende proteïen) uit te druk. Die doel was om die antibakteriese aktiwiteit van bakteriosien 285 te kwantifiseer as 'n funksie van GFP fluorisensie. Bakteriosien 285 is identies aan plantarisien 423 wat deur L. plantarum 423 produseer word. Plantarisien 423 is 'n klas Iia bakteriosien en vertoon antimikrobiese aktiwiteit teenoor 'n wye verskeidenheid bakterieë, insluitende verskeie organismes wat voedsel bederf. Die sensitiwiteit van L. sakei DSM 20017 teenoor antibakteriese peptiede wat deur Lactobacillus cutveius DF38, L. plantarum 285, Lactobacillus casei LHS en Lactobacillus salivarius 241 geproduseer word, word nie beïnvloed deur die groeifase van die organisme nie. Selle het sensitief gebly teenoor al vier die bakteriosiene van sloer- tot laat eksponensiële groei. Om groei van tot 90% van L. sakei DSM 20017 selle te inhibeer, word 1 AU/ml (7 ng/ml) gedeeltelik gesuiwerde bakteriosien 285 benodig. Om alle lewensvatbare L. sakei DSM 20017 selle te dood, word 16 AU/ml (110 ng/ml) gedeeltelik gesuiwerde bakteriosien 285 benodig. Die gfpuv-geen, wat GFPuv kodeer is stroomaf van die Idh-promoter gekloneer en suksesvol in L. sakei DSM 20017 uitgedruk. GFPuv fluoresensie kon nie as direkte metode gebruik word om die antimikrobiese aktiwiteit van bakteriosien 285 te bepaal nie, aangesien die selle van L. sakei DSM 20017 fluoreserend gebly het lank na behandeling met dodelike konsentrasies van die bakteriosien. Die lewensvatbaarheid van die selle is bevestig deur epifluoresensiemikroskopie en 'n LlVE/DEAD® Bac/ight™ bakteriese lewensvatbaarheidspeiler. Selle van L. sakei DSM 20017 wat deur die peiler gekleur is, het gewys dat die meeste selle wat nie deur bakteriosien 285 behandel was nie, lewensvatbaar was. Behandeling van L. sakei DSM 20017 met 16 AU/ml bakteriosien 285 het al die sigbare selle gedood.
43
Vendrell, Arasa Alexandre. "SCF cdc4 regulates msn2 and msn4 dependent gene expression to counteract hog1 induced lethality." Doctoral thesis, Universitat Pompeu Fabra, 2009. http://hdl.handle.net/10803/7153.
Анотація:
L'activació sostinguda de Hog1 porta a una inhibició del creixement cel·lular. En aquest treball, hem observat que el fenotip de letalitat causat per l'activació sostinguda de Hog1 és parcialment inhibida per la mutació del complexe SCFCDC4. La inhibició de la mort causada per l'activació sostinguda de Hog1 depèn de la via d'extensió de la vida. Quan Hog1 s'activa de manera sostinguda, la mutació al complexe SCFCDC4 fa que augmenti l'expressió gènica depenent de Msn2 i Msn4 que condueix a una sobreexpressió del gen PNC1 i a una hiperactivació de la deacetilassa Sir2. La hiperactivació de Sir2 és capaç d'inhibir la mort causada per l'activació sostinguda de Hog1.També hem observat que la mort cel·lular causada per l'activació sostinguda de Hog1 és deguda a una inducció d'apoptosi. L'apoptosi induïda per Hog1 és inhibida per la mutació al complexe SCFCDC4. Per tant, la via d'extensió de la vida és capaç de prevenir l'apoptosi a través d'un mecanisme desconegut.
Sustained Hog1 activation leads to an inhibition of cell growth. In this work, we have observed that the lethal phenotype caused by sustained Hog1 activation is prevented by SCFCDC4 mutants. The prevention of Hog1-induced cell death by SCFCDC4 mutation depends on the lifespan extension pathway. Upon sustained Hog1 activation, SCFCDC4 mutation increases Msn2 and Msn4 dependent gene expression that leads to a PNC1 overexpression and a Sir2 deacetylase hyperactivation. Then, hyperactivation of Sir2 is able to prevent cell death caused by sustained Hog1 activation.
We have also observed that cell death upon sustained Hog1 activation is due to an induction of apoptosis. The apoptosis induced by Hog1 is decreased by SCFCDC4 mutation. Therefore, lifespan extension pathway is able to prevent apoptosis by an unknown mechanism.
44
Chang, Chia-Yu, and 張家瑜. "Isolation and Characterization of Acid Sensitive Mutants from Streptococcus mutans." Thesis, 1998. http://ndltd.ncl.edu.tw/handle/31736392427705344764.
Анотація:
碩士國立臺灣大學
微生物學研究所
86
Streptococcus mutans is an etiological agent of human dental caries. The bacterium expresses two important virulence traits for cariogenisity; the ability of the bacterium to colonize specifically on the tooth surface and to produce lactic acid resulting in demineralization of enamel surface. In addition, S. mutans can survive in acid environment, where the pH is below 3.0. It is the most acid tolerant species among the oral streptococci. The aim of this research is to identify genes are involved in acid tolerance(aciduricity) controlling of S. mutans to survive under the acidic environment. The strategy was construction a mutant library using a suicide vectors, pVA891. This plasmid was ligated with Sau3AI randomly digested chromosomal DNA fragment from S. mutans GS-5. The resultant plasmid pools were randomly integrated into the chromosome of strain GS-5. Acid sensitive mutants were screened by inability to survive on the acidic (pH5.5) agar plate, and confirmed by monitoring their growth under the pH5.5 condition. Acid sensitive mutants were analyzed for pVA891 integration by southern hybridization. Finally, mutant chromosomal DNA fragments flanking the plasmids were recovered by a marker rescue method in Escherichia coli and the flanking region was sequenced. In this study, we screened 2690 mutants, and one (74(3)-1-1) was an acid sensitive mutant. Interestingly, 74(3)-1-1, can not grow at acidic medium under the oxygen rich condition, but it restores acid tolerant ability under the anaerobic condition. The flanking regions of p74(3)H1, were partially sequenced, but it has no homology with other genes of the identical function.
45
Goss, Heather Vanessa. "Contrasting chemical response to experimental acidification of five acid-sensitive streams /." 2006. http://www.library.umaine.edu/theses/pdf/GossHV2006.pdf.
46
Agius, Ronald [Verfasser]. "PH-sensitive binding of nickel(II) ions to aspartic acid / Ronald Agius." 2004. http://d-nb.info/971555737/34.
47
Chien-Yi, Chang, and 張千益. "Characterization of an acid sensitive mutant of Streptococcus mutans with pVA891 integration." Thesis, 2000. http://ndltd.ncl.edu.tw/handle/98917073399957109634.
Анотація:
碩士國立臺灣大學
微生物學研究所
88
英文摘要 Streptococcus mutans is an etiological agent of human dental caries. The bacterium can metabolize many kinds of sugar and produce acidic products resulting in demineralization of tooth surface. Previous studies indicated that S. mutans can grow in acidic environment and survive below the pH value of 3.0. Acid production and acid tolerance are major virulence factors of S. mutans. Screening acid sensitive mutants with suicide vector pVA891 integration, we have identified strain 74(3)-1-1 which could not grow in pH value of 5.5 under aerobic condition, but could grow under the same acidic condition, if cultured anaerobically. The DNA fragments flanking the integrated plasmid were recovered from 74(3)-1-1 by marker rescue and the nucleotide sequence was determined. Using the rescued fragment as a probe to screen a S. mutans chromosomal library, several positive clones were identified. One of the clones, Zap7, was completely sequenced and contained three opene reading frames, cel, phsp, and tkt. Southern blot analysis confirmed the restriction maps of the genes and found that phsp was duplicated in 74(3)-1-1, and therefore, the integration of pVA891 did not inactivate the phsp gene. By monitoring the growth in bioreactor, we confirmed that 74(3)-1-1 can grow at pH of 5.0 under strictly anaerobic condition, but grow pooly under aerobic condition with oxygen tension of 30%. When tested in an in vitro assay system, 74(3)-1-1 exhibited enhanced ability to adhere to glass surfaces in the presence or absence of sucrose. In addition, 74(3)-1-1 cannot grow in a define medium in which glucose is the sole carbon source.
48
Sahoo, Anasurya. "PH sensitive fiber derived from copolymer of acrylonitrile and ocrylic acid derivative." Thesis, 2007. http://localhost:8080/xmlui/handle/12345678/3901.
49
Grell, Mary Ann Elizabeth. "Soil Chemistry Characterization of Acid Sensitive Watersheds in the Great Smoky Mountains National Park." 2010. http://trace.tennessee.edu/utk_gradthes/802.
Анотація:
Atmospheric acidic deposition has negatively impacted many Appalachian watersheds in the eastern United States and soils play a key role in the biogeochemical processes that govern the fate and transport of the acidic pollutants. Thus, the collection of soil chemistry data, a previously lacking component, is essential to understand the soil processes related to the retention or release of basic and acidic ions and is imperative for the prediction of ecosystem recovery. Soil chemical properties related to acidification were characterized for 25 sites within eight acid-sensitive watersheds located in the Great Smoky Mountains National Park (GRSM). Relationships were identified by comparing soil chemistry to watershed characteristics including site location, soil characteristics, forest type, geomorphic factors and the presence of Anakeesta. The Walker Camp Prong watershed had significantly higher soil base saturation, calcium and magnesium than all other study watersheds as a result of the application of dolomitic limestone to roadways for wintertime traction control. Significant differences in soil chemistry between the spatially close watersheds of Cosby and Rock Creek demonstrated how local factors can substantially influence the watershed acidification response. The chemical properties of the six study soil types, representing 60% of the entire GRSM, had no significant differences, suggesting soil chemistry must be governed by external inputs and basin characteristics, more so than parent material. This idea was strengthen by the ability to relate many soil chemical properties to forest type and identifying other chemical properties as functions of elevation, slope and soil depth. Also, the presence of unexposed Anakeesta did not seem to have any significant effect on soil chemical properties because all significant differences could be linked to factors unrelated to surficial geology. The majority of the soils of the GRSM study watersheds seem to be experiencing the deleterious effects of long-term exposure to acidic deposition and it could be assumed that soils in many other areas of the park may be enduring the same. The results provide a comparative baseline dataset and important input parameters for biogeochemical modeling. The relationships identified among watershed factors and soil chemical properties can aid in future study designs.
50
Lee, Yen Chen, and 李彥臻. "Applications of Thermo-sensitive Hydrogel Containing Gelatin and Hyaluronic Acid in Cartilage Tissue Engineering." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/45489401906653561499.
Анотація:
碩士長庚大學
化工與材料工程學系
98
Thermo-sensitive co-polymers based on poly(N-isopropylacrylamide) and contain hyaluronic acid (HPN) or hyaluronic acid and gelatin (HPN-G) were synthesized and characterized for applications in cartilage tissue engineering. Thermo-responsive characteristics of HPN and HPN-G and the feasibility of those polymers for chondrocytes cultures were studied. From in vitro cell culture experiments, the results showed that HPN-G hydrogel is preferred over HPN for differentiation and proliferation of chondrocytes. HPN-G hydrogel alone or by combining with porous polycaprolactone disk produced by laser sintering (G-P) were then used for in vivo animal studies using nude mice. The real-time PCR and staining results suggested that HPN-G scaffold not only helped chondrocytes maintain normal cell functions, but also supported excretion of type II collagen, SOX9, and aggregan. With its free flowing property at room temperature and reversible gelling property at physiological temperature, HPN-G polymer will be a suitable injectable scaffold for cartilage tissue engineering. By mixing polymer solution with chondrocytes at room temperature and cultured at physiological temperature, the hydrogel copolymer will provide a high cell loading efficiency and a suitable environment for chondrocytes proliferation and differentiation while maintaining high cell viability.