Thèses : « Science biological sciences biophysics »

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Nichols, Alexander J. « Optical Molecular Sensing in Complex Biological Environments ». Thesis, Harvard University, 2014. http://nrs.harvard.edu/urn-3:HUL.InstRepos:14226087.

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Although techniques in molecular imaging have advanced considerably over the past several decades, there remain numerous categories of biological molecular targets that are refractory to straightforward imaging. Among these is molecular oxygen, which is vital to a host of physiological as well as pathological processes, as well as the amorphous pigment pheomelanin, which may play a formerly unappreciated role in melanoma carcinogenesis. This thesis describes two related bodies of work that advance techniques in oxygen and pheomelanin imaging, respectively. First, inspired by a desire to understand how hypoxia affects cancer chemotherapy on a cellular level, we designed and synthesized a novel oxygen-sensitive, dendritic nanoconstruct that is capable of spontaneously penetrating through hundreds of microns of multiple cellular layers. After demonstrating our nanoconjugate's oxygen sensitivity using time-domain phosphorescence lifetime measurements, we demonstrate that it retains its oxygen sensitivity in a 3D spheroid in vitro model of ovarian cancer through the use of a custom-made, near infrared-optimized confocal phosphorescence imaging system. Drawing from this approach, we then describe the fabrication and calibration of a separate oxygen-sensing bandage platform for use in wound-healing applications, and demonstrate its use in ex vivo and in vivo animal systems. The second body of work describes the use of non-linear four-wave mixing techniques to facilitate straightforward imaging of the molecular pigment pheomelanin. Recent findings suggest that pheomelanin may play a previously unappreciated role in melanoma carcinogenesis, even in the complete absence of an ultraviolet light insult. However, due to its pale color, pheomelanin is difficult to visualize against a skin background, making its study challenging. After constructing a femtosecond-pulsed coherent anti-Stokes Raman scatter (CARS) microscopy imaging system, we use imaging and spectroscopy to provide proof-of-concept that pheomelanin can be imaged through a combination of CARS microscopy and electronically-enhanced four-wave mixing. We then use our non-linear imaging system to specifically observe pheomelanin in isolated "redhead" mouse melanocytes, and show through an siRNA gene knock-down strategy that our system can be used to observe changes in pheomelanin signal upon modification of biological pathways known to affect pheomelanin synthesis.

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Ramsey, Nicole B. « Bilayer perturbation is a distinct parameter for regulating the experimental use of biological probes and the development of antimalarials ». Thesis, Weill Medical College of Cornell University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3580196.

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The controlled production and degradation of cAMP allows for control of many different signaling pathways. cAMP is produced by genetically distinct transmembrane (tmAC) and soluble (sAC) adenylyl cyclases; cAMP is catabolized by phosphodiesterases (PDEs). The relative contributions of sAC and tmAC to cAMP production, and of the PDEs to cAMP catabolism, usually are explored using pharmacological interventions. Because the compounds used to manipulate intracellular cAMP levels must cross cell membranes, they need to partition into lipid bilayers, which raises the question whether they could alter cell function by mechanisms that are unrelated to the changes in cAMP turnover. Indeed, many of these compounds are known to alter the function of other membrane proteins at concentrations that overlap with those used to target cAMP metabolism. Moreover, the concentration range(s) used to obtain the same effect vary widely among experiments, suggesting that these compounds elicit off-target effects that do not involve conventional cAMP signaling pathways. I therefore explored the lipid bilayerperturbing effects of 17 commonly employed modifiers of sAC, tmAC and PDE activity using a GBFA. Twelve compounds perturbed the bilayer at commonly used concentrations. Thus, in addition to their effects on cAMP metabolism, these molecules may alter cell function by being promiscuous modifiers of membrane protein function, meaning they should be used with care. Effects that occur only at concentrations that are three or more times higher than those for half-maximal effect (on the intended target) should be interpreted with caution.

In addition to being important for the interpretation of experiments that explore biological function with small-molecule probes, bilayer perturbation is also an important parameter for drug discovery. In this thesis, I focused on how to improve the development of new malaria therapies, which is necessary due to the perpetual development of resistance to current therapies. The Medicines for Malaria Venture developed the Malaria Box to facilitate the drug development process (and reduce the cost) by providing pharmaceutical company-vetted drug candidates to academicians. To explore whether testing for membrane effects might reduce the expenses required for drug development, I tested the 80 potent compounds from the Malaria Box for bilayer-mediated effects on membrane protein conformational changes (as a measure of literature. However, some significant differences should be further examined in other international teaching environments.

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Lee, Peilun. « BIOLOGICAL FUNCTIONS OF THE NOVEL LYSOPHOSPHATIDIC ACID (LPA) RECEPTOR, LPA₄/p2y9/GPR23 ». VCU Scholars Compass, 2008. http://scholarscompass.vcu.edu/etd/1676.

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Lysophosphatidic acid (LPA), a naturally occurring phospholipid present in serum and malignant effusions, elicits diverse biological functions through binding and activating specific cell surface G-protein coupled receptors. In addition to the conventional LPA1/Edg2, LPA2/Edg4 and LPA3/Edg7 receptors of the endothelial differentiation gene (Edg) family, LPA4/p2y9/GPR23 of the purinergic receptor family and the related LPA5/GPR92 and LPA6/p2y5 have been identified as novel LPA receptors. These newly identified LPA receptors are structurally distant from the Edg LPA1-3 receptors and couple to Gq, G12/13 and probably Gs subunits. However, the roles of the LPA4-6 receptors in LPA signal transduction and physiology are poorly understood. This project has used biochemical and genetic approaches to study biological functions of LPA4. In the first part of the study, we confirmed that LPA4 is indeed a functional LPA receptor mediating some cellular and biochemical responses to LPA including stimulation of neurite retraction, protein tyrosine phosphorylation. LPA4 also physically binds to LPA when ectopically expressed in cell lines. Mammalian cells usually express multiple LPA receptor subtypes and respond to LPA, making it difficult to link LPA receptors to specific responses. Targeted deletion has become a necessary approach to probe functions of individual LPA receptors. We therefore disrupted LPA4-encoding gene (lpa4/p2y9/gpr23) in mice. LPA4-deficient mice were born at the expected frequency and displayed no apparent abnormalities at least at early ages, indicating that LPA4 is not required for fertility, embryonic development or normal physiology. This is similar to knockouts of other LPA receptors. The backup and/or redundant receptor subtypes of LPA may suffice to compensate for the loss of individual LPA receptors in vivo. Alternatively, LPA may not be the only or rate-limiting mediator physiologically required in vivo. LPA signaling may be more critical in pathophysiological conditions when levels of the lipid mediator are locally and temporally altered. The availability of LPA4-null mice provides a valued model to analyze the roles of LPA4 in pathophysiological processes. Despite the lack of apparent phenotypes in mice, we took advantage of the LPA4- negative mouse embryonic fibroblasts (MEFs) to evaluate the effects of lpa4 deletion on cellular responses to LPA. Strikingly, LPA4-deficient MEFs were hypersensitive to LPA induced migration. Consistent with negative modulation of the phosphatidylinositol 3 kinase (PI3K) pathway by LPA4, LPA4 deficiency potentiated AKT and Rac but decreased Rho activation induced by LPA. Reconstitution of LPA4 converted LPA4-negative cells into a less motile phenotype. In support of the biological relevance of these observations, ectopic expression of LPA4 strongly inhibited migration and invasion of human cancer cells. When coexpressed with LPA1 in B103 neuroblastoma cells devoid of endogenous LPA receptors, LPA4 attenuated LPA1-driven migration and invasion, indicating functional antagonism between the two subtypes of LPA receptors. These results provide genetic and biochemical evidence that LPA4 is a suppressor of LPA-dependent cell migration and invasion. LPA4 may thus play a role in negative regulation of LPA signal transduction and specific cellular responses.

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Burnette-Vick, Bonnie A. « Characterization of Two Temperature-sensitive Mutants of Escherichia Coli Exhibiting an Altered L22 Ribosomal Protein ». Digital Commons @ East Tennessee State University, 1991. https://dc.etsu.edu/etd/2645.

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Analysis of E. coli strains SK1047 and SK1048 have shown them to be temperature-sensitive, protein-synthesis deficient. An alteration in ribosomal protein L22 was detected in both strains using two dimensional gel electrophoresis. Protein L22 was purified from both strains by reversed phase high performance liquid chromatography and from two dimensional electrophoretic gels. Purified ribosomal protein L22 was labeled by reductive methylation and used in 23S RNA binding assays with and without ribosomal protein L4. At the permissive temperature, protein L22 from SK1047 bound less efficiently than the control while protein L22 from SK1048 bound as efficiently as the control. At the restrictive temperature, both forms of mutant protein L22 bound less efficiently than the control. In both mutants, temperature sensitivity was mapped to the chromosomal region containing the rplV gene for ribosomal protein L22 using bacteriophage P1 transduction and bacteriophage $\lambda$ complementation. The wild type rplV gene subcloned into plasmid pLF1.0 was also shown to complement temperature sensitivity. The partial diploid nature of strains complemented by $\lambda$fus2 and plasmid pLF1.0 was verified when both wild type and mutant protein L22 were found on two dimensional gels. Reisolation of protein L22 from gels of $\lambda$fus2 complemented cells showed that both forms of protein L22 were in equal proportion irrespective of growth temperature. Reisolation of protein L22 from gels of plasmid pLF1.0 complemented cells showed that incorporation of the mutant protein exceeded the control protein at the permissive temperature; while the reverse was seen at the restrictive temperature. Temperature-shift experiments were conducted on complemented mutant cells to determine the effect of increased gene dosage on the coordinated regulation of ribosomal protein synthesis. Mutants complemented with $\lambda$fus2 exhibited normal cell growth, indicating that regulation was not effected. Cells transformed with plasmid pLF1.0 exhibited a reduction in growth possibly due to the disruption of balanced synthesis. The wild type and both mutant rplV genes were amplified using polymerase chain reaction and the PCR product was sequenced using primer extension. Sequencing of DNA from both mutants revealed the codon CGC for the amino acid arginine at position 8 in the protein chain was mutated to the TGC codon for the amino acid cysteine. The wild type ribosomal protein L22 contains no cysteine residues. The mutation was confirmed by testing control and mutant protein L22 for the presence of sulfhydryls using 4,4$\sp\prime$-dithiodipyridine. Ribosomal protein L22 isolated from both mutant strains was found to contain one cysteine sulfhydryl group.

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Paccione, Rachel J. « Vimentin Overexpression Contributes To the Biological Properties of Metastatic Head and Neck Cancer Cells ». VCU Scholars Compass, 2005. http://scholarscompass.vcu.edu/etd/1084.

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Epithelial to mesenchymal transition occurs in the later stages of epithelial tumor progression, with cells expressing mesenchymal markers. Of these, the intermediate filament protein vimentin is frequently upregulated in metastatic carcinomas. Previously, microarray studies showed that the gene encoding vimentin is highly upregulated in metastatic HN12 cells compared to a related primary tumor cell line. In this study, we confirmed this difference using real-time quantitative PCR, western blot analysis, and immunostaining. Furthermore, EGF and TGF-β, growth factors that induce migration and invasion of HN12 cells, produced synergistic increases in vimentin expression. To assess the contribution of vimentin to the biological properties, HN12 cells were stably transfected with a plasmid that directs synthesis of vimentin shRNA. Clones expressing decreased amounts of vimentin were isolated and characterized. These cells showed significantly reduced proliferation compared to non-targeting controls. Moreover, downregulation of vimentin led to a decrease in cell motility, as well as reducing their ability to invade through a basement membrane substitute. Using transient transfection assays, vimentin promoter activity was determined in HN12 cells to define regulatory elements important for controlling vimentin upregulation in the absence or presence of EGF and TGF-β. Taken together, the data indicate that overexpression of vimentin is important for proliferation and invasion of metastatic HN12 cells, and suggest that EGF- dependent pathways target binding elements in the proximal vimentin promoter, while TGF-β is likely to act in an AP1-dependent manner. Furthermore, both growth factors appear to synergize by stimulating promoter activation through the ASE site, suggesting involvement of Stat-dependent pathways in regulation of vimentin expression in HN12 cells.

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Jain, Dharamdeep. « Humidity Driven Performance of Biological Adhesives ». University of Akron / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=akron1510053266807976.

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Rodriguez, Idaykis. « An Ethnographic Study : Becoming a Physics Expert in a Biophysics Research Group ». FIU Digital Commons, 2013. http://digitalcommons.fiu.edu/etd/938.

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Expertise in physics has been traditionally studied in cognitive science, where physics expertise is understood through the difference between novice and expert problem solving skills. The cognitive perspective of physics experts only create a partial model of physics expertise and does not take into account the development of physics experts in the natural context of research. This dissertation takes a social and cultural perspective of learning through apprenticeship to model the development of physics expertise of physics graduate students in a research group. I use a qualitative methodological approach of an ethnographic case study to observe and video record the common practices of graduate students in their biophysics weekly research group meetings. I recorded notes on observations and conduct interviews with all participants of the biophysics research group for a period of eight months. I apply the theoretical framework of Communities of Practice to distinguish the cultural norms of the group that cultivate physics expert practices. Results indicate that physics expertise is specific to a topic or subfield and it is established through effectively publishing research in the larger biophysics research community. The participant biophysics research group follows a learning trajectory for its students to contribute to research and learn to communicate their research in the larger biophysics community. In this learning trajectory students develop expert member competencies to learn to communicate their research and to learn the standards and trends of research in the larger research community. Findings from this dissertation expand the model of physics expertise beyond the cognitive realm and add the social and cultural nature of physics expertise development. This research also addresses ways to increase physics graduate student success towards their PhD. and decrease the 48% attrition rate of physics graduate students. Cultivating effective research experiences that give graduate students agency and autonomy beyond their research groups gives students the motivation to finish graduate school and establish their physics expertise.

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Chen, Yuejin. « Characterization of the Vasoactivity of Tachykinins in Isolated Rat Kidney : Functional Studies and in Vitro Receptor Autoradiography ». Digital Commons @ East Tennessee State University, 1994. https://dc.etsu.edu/etd/2892.

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Although tachykinins have potent vascular actions, their effect on renal resistance blood vessels is currently unknown. The vasoactive properties of tachykinins and related analogs were assessed in isolated perfused rat kidney. At a basal perfusion pressure (PP) of 75 $\pm$ 6 mm Hg (n = 5), bolus injections of substance P (SP) had no significant vasoactive effect. Following a sustained increase in baseline PP (134 $\pm$ 10 mm Hg) produced by phenylephrine (1 $\mu$M), SP evoked a dose-dependent increase in PP. The largest dose of SP increased PP by 60 $\pm$ 5 mm Hg. The vasoconstrictor response to SP was not blocked by phentolamine when angiotensin II was used to increase basal tone. Thus, the response to SP is not mediated by norepinephrine. Pressor responses to SP were not potentiated by peptidase inhibitors, captopril and thiorphan. SP(1-7) had no effect on PP, suggesting that the pressor response to SP is C-terminal dependent and tachykinin receptor mediated. The selective NK-1 receptor agonist, (Sar$\sp9$,Met(O$\sb2)\sp{11}\rbrack$SP, had no effect on PP. In contrast, both the selective NK-2 and NK-3 receptor agonists, GR-64349 and (MePhe$\sp7$) NKB, produced dose-dependent pressor responses (116 $\pm$ 8 and 134 $\pm$ 15 mm Hg increases in PP at 33 nmol, respectively) and were more potent than SP. Infusion of capsaicin (500 nM) produced an initial increase in PP following by a more prolonged decrease in PP. Clamping the renal vein produced a marked increase in PP. The localization of NK-3 receptors in rat kidney evaluated by film autoradiography using $\sp{125}$I- (MePhe$\sp7\rbrack$NKB revealed a high density of specific binding sites on the proximal ureter and renal pelvis, moderate density in the renal vein and its large branches, and a low density in the inner strip of outer medulla, but no specific binding on the renal artery system and cortex. High resolution autoradiograms demonstrated $\sp{125}$I- (MePhe$\sp7\rbrack$NKB binding sites on the tunica media of the renal vein and tunica muscularises of renal pelvis and ureter. Specific binding of $\sp{125}$I-BHSP was found in association with the renal artery and renal pelvis. No specific SP binding sites were associated with renal vein. These data indicate that the pressor effect of tachykinins in the isolated rat kidney can be mediated by NK-2 and/or NK-3 receptors. The latter may be on the vascular smooth muscle of the renal vein.

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Ratnasinghe, Duminda D. « Unusual Structure of a Human Middle Repetitive DNA ». Digital Commons @ East Tennessee State University, 1993. https://dc.etsu.edu/etd/2767.

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The L2Hs sequences are a polymorphic, interspersed, middle repetitive DNA family unique to human genomes. Genomic fingerprinting indicates that these DNAs vary from one individual to another and between tissues of the same individual. Sequence analysis reveals that they are AT-rich (76%) and contain many unusual sequence arrangements (palindromes, inverted and direct repeats). These sequence properties confer on the L2Hs elements the potential to fold into non-B-form structures, a characteristic of recombination hot spots. To test this hypothesis carbodiimide, osmium tetroxide and S$\sb1$ nuclease were used as single-strand specific probes to study a recombinant plasmid, pN6.4.39, containing a single L2Hs segment. Different forms of the plasmid substrate were analyzed, including linear molecules and circular forms of low, intermediate and high superhelical densities. In addition, plasmid DNA in growing E. coli cells were analyzed. Modified plasmid DNA was analyzed by primer extension in a sequencing-type reaction format. These studies demonstrate that the L2Hs sequences: (1) assume non-B-form structures both in vitro and in vivo, (2) map to predicted cruciform structures, (3) behave as C-type extrusion sequences, and (4) that these unusual DNA structures are dependent on plasmid superhelicity.

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Lu, Zhixin. « Investigations on Cancer Cell Biological Effects of CDK8 Inhibitor Q-12 ». Scholarly Commons, 2018. https://scholarlycommons.pacific.edu/uop_etds/3554.

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Over the past two decades, protein kinases have been intensively investigated as targets to treat neoplastic diseases. Many protein kinase inhibitors not only have therapeutic potential but are becoming invaluable reagents for the study of cell signaling. We aspired to use our Cyclin-Dependent Kinase 8 inhibitor, Q-12, as a probe for biomarker discovery for CDK8 inhibitor sensitive tumor types. Q-12 shows potent inhibition of cell viability and induction of apoptosis process in some triple-negative breast cancer and colorectal cancer cell lines in vitro. Western blot results indicate that the reduction of STAT1 phosphorylation could be a robust indicator of CDK8 target engagement in all three cancer cell lines used upon Q-12 treatment. Q-12 treatment of triple-negative breast cancer cell line (MDA-MB-468) decreases STAT1 phosphorylation but increases STAT3 phosphorylation. Q-12 activity in MDA-MB-468 cell is dependent on the activation of STAT3 phosphorylation. All results suggest that there may be a critical STAT1 to STAT3 ratio that may serve as a biomarker for CDK8 inhibitor sensitivity. In this precision medicine era, the discovery of biomarker is urgently needed to minimize the risks of severe side-effects by traditional chemotherapy and improve diagnosis and monitor therapy response across a wide spectrum of disease, especially heterogenous type of disease, like cancer.

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Conde, Pueyo Núria 1983. « Biological computation in yeast ». Doctoral thesis, Universitat Pompeu Fabra, 2014. http://hdl.handle.net/10803/320193.

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Ongoing efforts within synthetic biology have been directed towards the building of artificial computational devices using engineered biological units as basic building blocks. Such efforts, are limited by the wiring problem: each connection of the basic computational units (logic gates), must be implemented by a different molecule. We propose a non-standard way of implementing logic computations that reduces wiring requirements thanks to a multicellular design with distribution of the output among cells. Practical implementations are presented using a library of engineered yeast cells, in which each genetic construct defines a logic function. This shows the great potential for re-utilization of genetic elements to build distinct cells. The cells are combined in multiple ways to easyly build diferent complex synthetic circuits. In the first manuscript, we proposed a multi-layer design. The engineered cells can perform the IDENTITY, NOT, AND and N-IMPLIES logics and are able to communicate with two different wiring molecules. As a proof of principle, we have implemented many logic gates and more complex circuits such as a 1--bit adder with carry. In the second manuscript, a general architecture to engineer cellular consortia that is independent of the circuit’s complexity is proposed. This design involves cells, performing IDENTITY and NOT logics, organized in two layers. The key aspect of the architecture is the spatial insulation. That design, permits implementation of complex logical functions, such as 4to1—multiplexer only with one wire.
En el camp de la biologia sintètica els esforços s'han dirigit a construir dispositius computacionals artificials connectant les unitats lògiques bàsiques (portes lògiques). Aquests esforços, estan limitats per l'anomenat “wiring problem”: cada connexió entre les unitats lògiques s'ha d'implementar amb una molècula diferent. En aquesta tesi es mostra una manera no-estàndard d'implementar funcions lògiques que redueix el nombre de cables necessaris gràcies a un disseny multicel·lular amb una distribució de la sortida en diferents cèl·lules. Es presenta una implementació pràctica utilitzant una llibreria de cèl·lules de llevat enginyeritzades, on cada constructe genètic defineix una funció lògica. Això posa de manifest el gran potencial que suposa la re-utilització dels elements genètics per construir les diferents cèl·lules. Al mateix temps, les cèl·lules es poden combinar de múltiples maneres permetent la construcció fàcil de diferents circuits sintètics complexes. En el primer article, proposem un disseny en múltiples capes. Les cèl·lules modificades genèticament poden realitzar les lògiques: IDENTITY, NOT, AND i NIMPLIES i són capaces de comunicar-se utilitzant dues connexions diferents. Com a demostració experimental, s'han implementat varies portes lògiques i circuits més complexos tals com un sumador d'un bit. En el segon article, es proposa una arquitectura general, que defineix un consorci cèl·lular, capaç d'implementar qualsevol circuit independentment de la seva complexitat. Aquest disseny es basa en cèl·lules que realitzen les lògiques IDENTITY i NOT, organitzades en dues capes. L’aspecte clau d’aquesta arquitectura és l’aïllament espaial. Aquest disseny permet implementar funcions lògiques molt complexes tals com multiplexor—4a1 utilitzant una sola molècula cable.

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Unis, Melod. « Peroxide reactions of environmental relevance in aqueous solution ». Thesis, Northumbria University, 2010. http://nrl.northumbria.ac.uk/2284/.

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The main objective of this research programme was to determine the factors influencing the decolourisation of dyes at low pH by different peroxide species, both in the presence and absence of metal ion catalysts and, therefore, to find a set of optimal conditions for application to wastewater treatment processes. An additional study looked at whether peroxoborates were capable of acting as nucleophiles. The specific aims of the study were: to investigate the in-situ formation of peracetic acid from the equilibrium formed between hydrogen peroxide and acetic acid, and whether this can be achieved without the addition of an acid catalyst such as sulphuric acid; to study the comparative reactivity of in-situ generated peracetic acid and hydrogen peroxide towards a range of dyes used in industry; to investigate the catalytic potential of a range of metal ions towards the reaction between peroxides and dyes; to investigate the structural features of dyes that might influence reactivity (decolourisation); and to investigate the reactivities of other peracid-like peroxide species that can be generated from hydrogen peroxide (peroxoborates and peroxocarbonates).The novel aspects arising from this study were: (a) The development of a new method for the in-situ generation of peracetic acid that gives the same equilibrium yield as established methods yet does not require the addition of an acid catalyst;(the reaction was slow, but there was minimal decomposition and so it is ideal for circumstances that allow the preparation of peracetic acid well in advance of use). (b) The first comprehensive study of the bleaching potential of peracetic acid and hydrogen peroxide towards a wide structural range of dyes both in the presence and absence of metal ions (iron, manganese, silver and copper). (c) The inference that for iron-catalysed bleaching of azo dyes by peracetic acid the catalytic mechanism involves pre-complexation of iron and dye, followed by reaction of the 'activated' complex with peracetic acid rather than a free radical mechanism that might have been expected for such systems. (d) The evidence that, in contradiction to literature studies, peroxoborate species do not act as nucleophiles. As an introduction to this work the reactions of peroxyacids are described in general terms. The experimental work is divided in three parts. In Chapter two, the homogeneous preparation of peracetic acid (PAA) from acetic acid (AA) and hydrogen peroxide (H2O2) was investigated with and without the catalysis of sulphuric acid (H2SO4). The formation of PAA and total peroxide content was determined by iodimetric titration. The reaction was slow in the absence of a strong acid catalyst, and was faster with a sulphuric acid catalyst. There was no loss of total peroxide over the timescales of both reactions, whether a catalyst was used or not. The equilibrium constant for peracetic acid formation at temperature of 20 was found to be 2.04 with a catalyst, and 2.10 without catalyst. The rate constant for the hydrolysis of peracetic acid for both forward and reverse reactions increased when the sulphuric acid concentration was increased from 0.02 M to 0.32 M. Linear relationships were found between the observed rate constants and H+ concentrations at 25oC. Moreover, it was found that the preparation of peracetic acid showed a first-order dependence with respect to peroxide concentration. In Chapter three, the application of this preparation of peroxyacids to the degradation of different types of dyesstuffs was investigated. As we know, physical or other chemical methods for dye degradation are expensive and can generate secondary pollution. In this part of the study the reactions of dyes with hydrogen peroxide and peracetic acid in the absence and presence different metal ions (Fe3+, Cu2+, Mn2+ and Ag+) were investigated. The iron/peroxyacid system was found to be the most effective. Consequently, Chapter 4 evaluates the decolourization of five azo dyes under conditions of bleaching by peracetic acid in the presence of Fe3+ as a catalyst. The experiment was carried out in aqueous acidic media. Dye oxidation systems are complex because: they involve several different tautomers; there is the possibility of dye aggregation at lower dye concentrations; and the oxidant species involved can be either the undissociated peroxide acting as an electrophile, or the dissociated peroxide acting as a nucleophile. The results obtained for the reaction of azo dyes with peracetic acid without added iron, when converted to the second order rate constant for the electrophilic reaction, k2E gave a value of 4.5x10-6 dm3 mol-1 s-1 for orange II, which is very high. This may be due to trace metal ions still being present and catalysing the reaction, possibly from impurities in the dye itself. No metal ion chelators were used in the present study because the bulk of the study was designed to elucidate the effect of metal ions concentration on reaction rate. For the catalysed reactions a significantly increased rate of absorbance decrease with increasing iron concentration was observed. Saturation of iron was also demonstrated at high iron concentrations, suggesting the formation of an iron (III)-dye complex which then reacted with peracetic acid. The maximum rate of reaction was observed at an iron concentration of 0.012 M, and the results showed a reactivity order of Ponceau 4R > Amaranth > (Orange II & Carmosine) > Black PN; Orange 1 was unreactive under these conditions. Also one of the key objectives of this chapter was to determine the optimum conditions for dye degradation in terms of pH and oxidant and catalyst concentrations. The optimum conditions for maximum degradation occurred at the highest pH of 3.0 and at about 1x10-3 M iron. Evidence of the possible involvement of radicals in our studies comes from the observation of a lag phase followed by a more rapid bleaching phase in the oxidation of azo dyes by peracetic acid at the lowest iron concentrations (another possibility is that at these iron concentrations the reactive iron complex forms at a much slower rate). However, this process is slow by comparison with the rate of oxidation at higher iron concentrations that do not exhibit this lag phase; consequently, if free radical mechanisms are suggested then they are not significant compared to the proposed formation of a reactive iron-dye complex.ixThe work contained in final experimental Chapter aimed to clarify whether or not any of the peroxyborate species displayed nucleophilic characteristics and thus accelerated the rate of the reaction of hydrogen peroxide with p-nitrophenyl acetate. The pH range of 6.0 to 8.0 is critical in terms of the distribution of peroxide species for a hydrogen peroxide / boric acid system. The triganol peroxoboric acid, B(OH)2OOH, is the only significant peroxoborate species below pH 6.5. However, above this pH, increased concentrations of the monoperoxoborate anion, B(OH)3OOH, the peroxodiborate anion, (HO)3BOOB(OH)32-, and the diperoxodiborate anion (HO)2B(OO)2B(OH)22-, are formed, with diperoxoborate, B(OH)2(OOH)2- forming at higher hydrogen peroxide concentrations. Therefore this is the ideal pH range in which to elucidate any effects of borate on the reaction of hydrogen peroxide and PNPA. The observed second order rate constants (k2obs) for the reaction between p-nitrophenyl acetate and hydrogen peroxide, and the corresponding second order rate constants, k2, for the reaction of the perhydroxyl anion with p-nitrophenyl acetate was determined by equation:In borate buffer the k2 values were significantly reduced compared to other buffers; this reduction was consistent with the hydrogen peroxide complexing with borate to form a range of non-reactive (towards carbonyl groups) peroxoborate species, thus also reducing the equilibrium concentration of the perhydroxyl anion. There was no evidence for peroxoborate species that could act as nucleophiles, in contradiction of literature claims. Values of k2 in the case of phosphate buffer compared reasonably well with values in the literature of 3140 and 3520 dm3 mol-1 s-1 obtained at pH 6.8 in ionic strengths of 0.02 dm3 mol-1 and 0.1dm3 mol-1 respectively. In carbonate buffer the literature value is 3785 dm3 mol-1 s-1 at pH 10, ionic strength 0.1 M, in borate buffer.

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Seashols, Sarah. « Variation and Modulation of microRNAs in Prostate Cancer and Biological Fluids ». VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/3258.

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Prostate cancer is the second-most diagnosed and fatal carcinoma for males in the United States, and better diagnostic markers and potential therapies are needed. microRNAs are small, single-stranded RNA molecules that affect protein expression at the translational level, and dysregulation can dramatically affect cell metabolism. Comparison of 736 microRNA expression levels between the poorly metastatic SV40T immortalized prostate epithelial cell line P69 to its highly tumorigenic and metastatic subline M12 identified 231 miRs that were overexpressed and 150 miRs that showed loss of expression in the M12 cell line. Further evaluation of fourteen identified miRs was accomplished using other prostate cell lines as well as laser-capture microdissected prostate samples. Inhibition of miR-147b was found to affect proliferative, migratory and invasive capabilities of M12 cells, and reduced tumour growth in nude athymic mice. AATF, an activator of the cell-cycle inhibitor p21, was identified as a target. Overexpression of miR-9 was found to affect the epithelial to mesenchymal transition through suppression of e-cadherin, a protein characterized as lost in EMT, as well as suppression of SOCS5, an attenuator of JAK-STAT signaling. Inhibition of miR-9 resulted in reduction of migratory and invasive potential, and significant reduction of tumorigenesis and metastases in male nude athymic mice. miR-17-3p was previously identified as down-regulated in prostate cancer and loss of miR-17-3p shown to cause vimentin transcriptional activation. Reverse phase microarray analysis (RPMA) identified c-KIT as a potential second mRNA target for miR-17-3p. miR-17-3p was shown to modulate not only protein levels, but also messenger RNA levels of c-KIT. Four miR-17-3p binding sites in the c-KIT mRNA were identified. Thus, a number of microRNAs involved in prostate cancer were identified, and their targets found to be highly relevant to tumour progression and could potentially be used as targets for therapy or diagnostics. Stability of microRNAs in forensically relevant biological fluids was evaluated through heat treatment, ultraviolet radiation, and chemical treatment. The dried body fluids showed some susceptibility to harsh treatment, but in most cases microRNAs were still detectable in the samples. microRNAs could represent a highly stable species for body fluid identification methods in forensic science.

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Zhang, Meng. « Proteomic analysis of streptococcus pyogenes ». Thesis, Northumbria University, 2007. http://nrl.northumbria.ac.uk/842/.

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Streptococcus pyogenes (group A streptococcus, GAS) is a major human Gram-positive pathogen that causes infections that normally occur in the respiratory tract, the skin, the wound, the lung, the bloodstream and/or muscle tissues and result in millions of deaths every year. To cause such infections, S. pyogenes produces a wide range of virulence factors. The destruction of connective tissue and the hyaluronic acid therein plays an important role in pathogenesis. S. pyogenes was propagated in hyaluronic acid rich growth media in an attempt to create a simple biological system that could reflect some elements of the pathogenesis. The growth of bacteria was analyzed in the hyaluronic acid rich media and control media and a proteomic approach was applied to identify those proteins that were differentially expressed by the streptococcal pathogens growing in the different media. The techniques of two dimensional gel electrophoresis and static nanospray mass spectrometry were optimized and proteome maps for S. pyogenes grown in both media were constructed. The differentially expressed proteins by S. pyogenes were identified and analyzed using bioinformatics. Our results showed that several recognized virulence factors of S. pyogenes were upregulated in hyaluronic acid rich media, including the Ml protein, a collagen-like surface protein and the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase, which has been shown to play important roles in streptococcal pathogenesis. Interestingly, two hypothetical proteins of unknown function were also up-regulated and detailed bioinformatics analysis showed that at least one of these hypothetical proteins is likely to be involved in GAS pathogenesis. It was therefore concluded that this simple biological system provided a valuable tool for the identification of potential streptococcal pathogens virulence factors.

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Jing, Stanley Mofor. « Synthesis of Resveratrol Esters and Aliphatic Acids ». Digital Commons @ East Tennessee State University, 2011. https://dc.etsu.edu/etd/1382.

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Resveratrol (RV) is a naturally occurring phytoalexin of the stilbenoid family produced by some plant species, and present in grape skin, peanuts, and red wine. It has been found to exhibit anti-cancer, anti-inflammatory, anti-viral, anti-aging, cardio protective, and anti-oxidant properties. Bioavailability is a huge setback that limits the potentials of RV. As a result, efforts have been made to design and synthesize RV esters and aliphatic acids in an attempt to increase its bioavailability, solubility in water, and possibly improving its biological activities. Resveratrol esters, 3,5,4'-triacetyloxystilbene (2) and Methyl 1,1',1''- (3,4',5-stilbenyl)-1,6-hexanedioate (3) have been synthesized. Compound 3 is a new compound, synthetic yield is 88%, and purity is above 95% based on NMR integration. Both 2 and 3 are good candidates for biological evaluation. 3 was used as a precursor in the synthesis of resveratrol aliphatic acid, 8-(3',5'-dihydroxylstilbene-4''-oxy)-3,6-dioxocotanoic acid (9). First, 2 was hydrolyzed to resveratrol diester, 3,5-diacetyloxystilbene (4). Mitsunobu reaction of 4 and methyl 8-hydroxy-3,6-dioxooctanoate (7) was then carried out to afford methyl 8-(3',5'-diacetyoxystilben-4''-oxy)-3.6-dioxooctanoate (/5), which was then hydrolyzed to afford 9 in total 43.6 % yield. Structures of all newly synthesized compounds were confirmed by 1H and 13C NMR spectroscopy.

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Thinnes, Cyrille Christophe. « Chemical and biological studies on human oxygenases ». Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:455f2e65-f294-461b-b44f-cd53796b14a0.

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As depicted in Chapter I, 2-oxoglutarate- (2OG) dependent oxygenases are ubiquitous in living systems and display a wide range of cellular functions, spanning metabolism, transcription, and translation. Although functionally diverse, the 2OG oxygenases share a high degree of structural similarities between their catalytic sites. From a medicinal chemistry point of view, the combination of biological diversity and structural similarity presents a rather challenging task for the development of selective small molecules for functional studies in vivo. The non-selective metal chelator 8-hydroxyquinoline (8HQ) was used as a template for the generation of tool compound I for the KDM4 subfamily of histone demethylases via application of the Betti reaction. Structural analogue II was used as the corresponding negative control (Figure A). These compounds were characterised in vitro against a range of 2OG oxygenases and subsequently used for studies in cells. I displays selectivity for KDM4 and increases the level of the H3K9me3 histone mark in cells. It has an effect on the post-translational modification pattern of histone H3, but not other histones, and reduces the viability of lung cancer cells, but not normal lung cells, derived from the same patient. I also stabilises hypoxia-inducable factor HIF in cells via a mechanism which seems to be independent from prolyl hydroxylase inhibition. This work is described in Chapters II and III. The chemical biology research in epigenetics is complemented by qualitative analysis conducted in the social sciences at Said Business School. With a global view on how innovation occurs and may actively be fostered, Chapter IV focuses on the potential of epigenetics in drug discovery and how this process may actively be promoted within the framework of open innovation. Areas of focus include considerations of incremental and disruptive technology; how to claim, demarcate, and control the market; how knowledge brokering occurs; and insights about process, management, organisation, and culture of open innovation. In contrast to the open-skies approach adopted for the development of a tool compound in Chapters II and III, a focused-library approach was taken for the generation of a tool compound for the OGFOD1 ribosomal prolyl hydroxylase. The development of a suitable in vitro activity assay for OGFOD1 in Chapter V enabled the development of lead compound III in Chapter VI. III is selective for OGFOD1 against the structurally closely related prolyl hydroxylase PHD2.

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Aggrawal, Manali. « Study of DNA damage on DNA G-quadruplexes and biophysical evaluation of the effects of modified bases (lesions) on their conformation and stability ». Scholarly Commons, 2014. https://scholarlycommons.pacific.edu/uop_etds/134.

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Exposure of DNA to reactive oxygen species (ROS) results in the modified nucleobases (lesions) as well as strand scissions under physiological conditions. Due to its lowest oxidation potential (1.29 eV), guanine is the most easily oxidisable nucleobase. Furthermore, it has been observed that the 5'-guanine in G-tracts (e.g. GGG) has even lower oxidation potential (1.00 V vs. NHE). One of the representative G-rich examples is telomeres that consist of repeating units of 5'-d [TTAGGG]-3' found at the ends of chromosomes. Telomeres play an important role in biological functions, serving as guardians of genome stability; however, their G-rich nature implies that they can be readily oxidized. So how does nature protect these biologically important regions from oxidation? We believe the formation of a secondary structure known as G-Quadruplex in telomeric regions can partly serve as a protective role. In the first part of this work, we investigated DNA G-Quadruplex damage under various oxidation conditions and compare the damage results with single-stranded telomeric sequences. Damage to G-Quadruplex is generally less than single strands and is condition dependent. Guanines are the primary damage sites, but damage of adenine and thymine is also possible. Based on our studies, telomeric DNA can be readily oxidized to produce DNA lesions. How do DNA lesions affect the conformation and the stability of telomeric G-Quadruplex DNA? In the second part, we sought to address this question using various biophysical methods. Several native (OxodG, OxodA, and abasic site) and non-native (8-NH 2 -dA and 8-Br-dA) lesions were tested. UV thermal denaturation and circular dichroism revealed that the conformation and the stability of G-Quadruplex DNA are dependent on the location and the type of lesion in the sequence. G-Quadruplex DNA containing OxodG maintains its conformation with a decreased stability. Abasic site in the TTA loop affects the conformation of G-Quadruplex DNA but shows little effect on its stability. An unexpected stabilization of telomeric G-Quadruplex DNA was observed when deoxyadenosine (dA) in the loops was replaced with its native oxidized form OxodA. This is the first example of native DNA lesion that increases the stability of G-Quadruplex DNA. Like OxodA lesion, 8-NH 2 -dA (a non native DNA lesion) increases the stability of G-Quadruplex DNA while 8-Br-dA only affects the stability in KCl but has no significant effect in NaCl. In addition, studies of the effect of OxodA lesion on the human telomerase activity using TRAP assay will be discussed.

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Fu, Josephine K. Y. « Functional characterization of the teleost multiple tissue (tmt) opsin family and their role in light detection ». Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:39bc18bb-16cb-4549-94cd-5f872daafe7e.

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In addition to a central circadian clock in the suprachiasmatic nucleus (SCN), zebrafish (Danio rerio) have local clock systems in their peripheral tissues. These peripheral tissues express a complement of clock genes that can be synchronized with the 24 h light/dark cycle and thus may be entrained by light. To date, teleost multiple tissue (tmt) opsin identified from Fugu rubripes and Danio rerio is the only opsin that has been proposed as a candidate to mediate this cellular photoentrainment (Moutsaki et al., 2003). Here we report the discovery of a multigene family of tmt opsins found not only in the teleost fishes, but in vertebrates,including amphibians, birds, reptiles, and some mammals. Phylogenetic analysis demonstrated that this gene family consists of three main classes, tmtI, tmtII and tmtIII, with each duplicating further to give two paralogues in the zebrafish genome. Their predicted amino acid sequences contain most of the characteristic features for the function of a photopigment opsin, as well as seven transmembrane segments indicative of a G protein coupled receptor (GPCR) superfamily. Significantly, reverse transcription polymerase chain reaction (RT-PCR) reveals that the tmt opsin genes in zebrafish are both temporally and spatially regulated. To investigate if these tmt photopigments mediate light-activated currents in cells, each opsin was expressed in vitro and the responses characterised by calcium imaging, whole-cell patch clamp electrophysiology, UV-Vis spectrophotometric analysis, and bioluminescence reporter assay. Collectively, these data suggest that some of the opsin photoproteins signal via Gi-type G protein pathway. Interestingly, the spectral analysis obtained shows that most tmt opsins tested are UV-sensitive when reconstituted in vitro with 11-cis and all-trans retinal, indicating an intrinsic bistable dynamics. Using site directed mutagenesis on one of the tmt opsins, tmt10, the potential spectral tuning sites involved in UV detection were tested. As part of this study, tmt opsin cDNAs were isolated from three populations of Mexican tetra (Astyanax mexicanus): surface, Pachon and Steinhardt. This allowed for a direct comparison between the tmt opsins present in the dark adapted species (cavefish) versus those of the light adapted species (zebrafish). It is hoped that the findings from this project will contribute to our understanding of non-visual light detection in fish and the evolution of their non-image forming photoreception.

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Huisman, Maximiliaan. « Vision Beyond Optics : Standardization, Evaluation and Innovation for Fluorescence Microscopy in Life Sciences ». eScholarship@UMMS, 2019. https://escholarship.umassmed.edu/gsbs_diss/1017.

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Fluorescence microscopy is an essential tool in biomedical sciences that allows specific molecules to be visualized in the complex and crowded environment of cells. The continuous introduction of new imaging techniques makes microscopes more powerful and versatile, but there is more than meets the eye. In addition to develop- ing new methods, we can work towards getting the most out of existing data and technologies. By harnessing unused potential, this work aims to increase the richness, reliability, and power of fluorescence microscopy data in three key ways: through standardization, evaluation and innovation. A universal standard makes it easier to assess, compare and analyze imaging data – from the level of a single laboratory to the broader life sciences community. We propose a data-standard for fluorescence microscopy that can increase the confidence in experimental results, facilitate the exchange of data, and maximize compatibility with current and future data analysis techniques. Cutting-edge imaging technologies often rely on sophisticated hardware and multi-layered algorithms for reconstruction and analysis. Consequently, the trustworthiness of new methods can be difficult to assess. To evaluate the reliability and limitations of complex methods, quantitative analyses – such as the one present here for the 3D SPEED method – are paramount. The limited resolution of optical microscopes prevents direct observation of macro- molecules like DNA and RNA. We present a multi-color, achromatic, cryogenic fluorescence microscope that has the potential to produce multi-color images with sub-nanometer precision. This innovation would move fluorescence imaging beyond the limitations of optics and into the world of molecular resolution.

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Chavan, Archana G. « Exploring the molecular architecture of proteins| Method developments in structure prediction and design ». Thesis, University of the Pacific, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3609082.

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Proteins are molecular machines of life in the truest sense. Being the expressors of genotype, proteins have been a focus in structural biology. Since the first characterization and structure determination of protein molecule more than half a century ago1, our understanding of protein structure is improving only incrementally. While computational analysis and experimental techniques have helped scientist view the structural features of proteins, our concepts about protein folding remain at the level of simple hydrophobic interactions packing side-chain at the core of the protein. Furthermore, because the rate of genome sequencing is far more rapid than protein structure characterization, much more needs to be achieved in the field of structural biology. As a step in this direction, my dissertation research uses computational analysis and experimental techniques to elucidate the fine structural features of the tertiary packing in proteins. With these set of studies, the knowledge of the field of structural biology extends to the fine details of higher order protein structure.

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Hekman, Ryan Matthew. « Production of Synthetic Spider Silk ». Scholarly Commons, 2018. https://scholarlycommons.pacific.edu/uop_etds/3534.

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Spider silk is a material that both has impressive mechanical properties and is also environmentally friendly. Though there are limitless potential engineering applications for such materials, industrial production of spider silk has proven to be challenging. Farming silk from spiders, as is done with silkworms, is not a viable option for large-scale production of spider silk due to the venomous and predatory nature of spiders. Here, an attempt is made to express synthetic spider silk minifibroins heterologously in Escherichia coli, to purify the recombinant spidroins from cell lysate, and to spin them into artificial fibers through a biomimetic process. Silk minifibroins were designed to be similar to Major Ampullate Spidroin 1 from Latrodectus hesperus. Synthetic fibers were examined by scanning electron and light microscopy, and their mechanical properties were tested by a tensometer. Properties of synthetic silk were compared to those of native dragline silk from the same species from which their design was inspired, revealing synthetic silk fibers with lower breaking stress and breaking strain.

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Scarlett, Michael A. « Can a comprehensive transition plan to barefoot running be the solution to the injury epidemic in American endurance runners ? » Scholarship @ Claremont, 2018. http://scholarship.claremont.edu/cmc_theses/1830.

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Fossils belonging to the genus Homo, dating as far back as two million years ago, exhibit uniquely efficient features suggesting that early humans had evolved to become exceptional endurance runners. Although they did not have the cushion or stability-control features provided in our modern day running shoes, our early human ancestors experienced far less of the running-related injuries we experience today. The injury rate has been estimated as high as 90% annually for Americans training for a marathon and as high as 79% annually for all American endurance runners. There is an injury epidemic in conventionally shod populations that does not exist in the habitually unshod or minimally shod populations around the world. This has led many to conclude that the recent advent of highly technological shoes might be the problem. Although current literature has been inconclusive, there are two main limitations in virtually all of the studies: 1) transition phases of less than three months and 2) transition phases without rehabilitation exercises. These two aspects are key to the treatment of the structural consequences on the muscles and tendons of the foot and calf that habitually shod individuals have faced. This study includes a discussion of the cumulative consequences that lifelong shoe usage has on the development of the feet and lower legs. I propose a 78-week study that addresses the limitations of past studies by implementing a gradual, 32-week, multi-shoe transition complemented by an evidence-based rehabilitation program. I believe that this approach will restore strength and elasticity to muscles and tendons that have been inhibited by lifelong usage of overconstructed shoes and adequately prepare runners for the increased demand brought on by a changing running mechanic. This comprehensive, multifaceted transition plan to a fully minimalist shoe will provide novel insight into the ongoing barefoot debate. Can this approach finally demonstrate the proposed benefits of losing the shoes?

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Genevskiy, Vladislav. « Biophysical differences between COPD, CF and healthy airways mucus ». Thesis, Malmö universitet, Fakulteten för hälsa och samhälle (HS), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-24779.

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An improved understanding of the mucus biophysical alteration in chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) patients is a milestone towards a more accurate and effective treatment of these common and highly debilitating conditions. Little is known about the variations in mucus structure between ill and healthy individuals. An established fact, however, is the role of the mucus obstruction in the exacerbation of the two conditions which impairs the physiological cleaning mechanism of the airways (mucociliary clearance) and is assessed as the strongest predictor of mortality. Therefore, it appears relevant to investigate which properties and structural changes are responsible of the impaired clearance of airway mucus. This thesis presents investigations of mucus on the basis of mucin structure observed in healthy, COPD and cystic fibrosis bronchial mucus samples. AFM (atomic force microscopy) and synchrotron SAXS (small angle X-ray scattering) techniques were used to characterise the structural features of the mucin molecules and allowed to identify the dumbbell structure of airways mucin monomers. The analysis of structural and dimensional features of mucins, highlighted a greater similarity of COPD with the healthy sample rather than with cystic fibrosis. The water sorption analysis using QCM-D (quartz crystal microbalance with dissipation monitoring), established a divergent behaviour between COPD and cystic fibrosis. Compared to healthy specimen, the mucus from COPD donors, showed a greater tendency to absorb water while cystic fibrosis mucus, in contrast, displayed the lowest water absorption.

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Jonnalagadda, Sneha R. « Molecular Modulation of a-Subunit VISIT-DG Sequence Residue Asp-350 in the Catalytic sites of Escherichia coli ATP Synthase ». Digital Commons @ East Tennessee State University, 2011. https://dc.etsu.edu/etd/1296.

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ATP Synthase is the fundamental means of cellular energy production in animals, plants, and almost all microorganisms. In order to understand the mechanism of ATP catalysis, critical amino acid residues involved in Pi binding have to be identified. The αVISIT-DG sequence at the interface of α/β subunits that contains residues from 345-351 is highly conserved and αAsp-350 has been chosen because of its negative charge side chain and its close proximity (~2.8 Å) to the known phosphate binding residue αArg-376. The mutant's αD350R, αD350Q, αD350A, αR376A/D, and αG351R/A/D were generated by site directed mutagenesis and several biochemical assays were performed on them to understand the role played by the amino acid residues in Pi binding. Biochemical results suggest that αD350 may be involved in catalysis of ATP synthase and play an important role in Pi binding, whereas αG351 may be involved only in the structural integrity.

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Agostini, Matteo. « Surface-acoustic-wave based biosensors and microfluidic devices for Life-science applications ». Doctoral thesis, Scuola Normale Superiore, 2018. http://hdl.handle.net/11384/85916.

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In 2015 over half of the total deaths worldwide were due to the top ten causes of mortality, as stated by the World Health Organization. Heart disease, cancer, and diabetes are particularly prominent, especially in developing countries. In the last decades a significant amount of effort has been made by the scientific community in order to address these pathologies, from both the screening and the treatment points of view. To date, early-detection seems to be one of the most effective strategies in reducing the mortality. By diagnosing one of these pathologies at very early stages, the survival rate can be significantly enhanced. For example, the 5-year survival rate of women with breast cancer is ⇡72% for stage III (before metastasis), ⇡93% for stage II and close to 100% for stage I and 0 (American Cancer Society data). Automated, cheap, and portable devices that can help in diagnosing these illnesses would be a breakthrough for life-science applications, particularly for point-of-care (PoC) purposes. These devices are the so-called lab-on-chips (LoCs). LoCs are chips with a small surface (mm2–cm2) that embed many operations that are usually performed by trained personnel in a centralized laboratory facility. These operations include centrifugation, reagent mixing, heating, particle separation, cell counting, analyte detection, amongst many others. By making use of innovative plastic materials, piezoelectric substrates and cleanroom facilities for fabrication, it is possible to realize these novel devices that can potentially fulfill all the requirements for early-detection and PoC. In this PhD thesis, I present my research on this topic. During my studies, I exploited two promising technologies for LoCs, namely surface acoustic wave (SAW) and surface plasmon resonance (SPR), through which I explored novel configurations for microfluidics and biosensing on nanostructured devices. I started studying the effects of SAWs on liquid droplets, with particular attention to the heating and mixing and how these phenomena could be exploited for treating biological samples. I investigated how SAWs affect cell cultures and how they can improve cell-proliferation by generating fluid motion inside standard Petri dishes. Then, I demonstrated a microfluidic SPR biosensor enhanced by the presence of SAW-induced fluid mixing. By means of the SAW-generated fluid recirculation, this device can detect analytes in a significantly reduced time. Next, I demonstrated two different SAW-based biosensors, a cantilever with a SAW-based readout and a SAW-resonator. The performance of both of them were suitable for biomedical assays. In particular, the SAW-resonator is promising in the light of cancer biomarker detection, as it is almost ten times more sensitive than similar commercially available sensing units. Finally, I moved towards the development of a full-SAW microfluidic platform for biosensing, combining SAW-microfluidics and SAWbiosensing. I further improved the SAW-resonator chip design by integrating multiplexing and microfluidic channels for liquid sample handling. I also developed custom-made software for fast and reliable data acquisition and post-processing. The experiments presented here are performed with artificial fluids: biotin-avidin was chosen for the biorecognition model, as it is well known to mimic the biomolecular processes of biomarkers detection. In final chapters I show and discuss experiments in the presence of biological noise (i.e., non-specific binding molecules) and evaluate the biosensor performance with samples more similar to body fluids. The studies I carried out are promising in the light of development of versatile, portable, and sensitive SAW-based LoC for early-detection of pathologies, and show enhanced performance in both detection of biomolecules and reduced detection times with respect to traditional methods.

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Mueller, Christian. « Lack of CFTR in CD3+ Lymphocytes Leads to Aberrant Cytokine Secretion and Hyper-Inflammatory Adaptive Immune Responses : A Master's Thesis ». eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/595.

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Background: Cystic fibrosis (CF) remains the most common fatal monogenic disease in the US, affecting 1 in 3,300 live births. CF is the result of mutations in CFTR, a chloride channel and regulator of other ion channels. The mechanisms by which CFTR mutations cause chronic lung disease in CF are not fully defined, but may include the combined effects of altered ion and water transport across the airway epithelium and aberrant inflammatory and immune responses to pathogens within the airways. We have shown that Cftr-/- mice mount an exaggerated IgE response towards Aspergillus fumigatus (Af) when compared to Cftr+/+ mice. Along with the increased IgE levels, the Cftr-/- mice had higher levels of IL-13 and IL-4, mimicking both the Th-2 biased immune responses and predilection to mounting Af-specifc IgE seen in CF patients. Herein we hypothesize that these immune aberrations are primarily due to the lack of Cftr expression in lymphocytes rather than with Cftr deficiency in the epithelium. Results: Our results indicate that adoptive transfer experiments with Cf splenocytes confer higher IgE response to Af in host mice as compared to hosts receiving wild-type splenocytes. The predilection of Cftr-deficient lymphocytes to mount Th2 responses was confirmed by in vitro antigen recall experiments, where higher levels of IL-13 and IL-4 where seen only in the presence of Cftr-deficient lymphocytes. Conclusive data on this phenomenon were obtained with conditional Cftr knockout mice, where mice lacking Cftr in T-cell lineages developed the higher IgE titers as compared to their wild-type littermate controls. Further analysis of Cftr-deficient lymphocytes revealed an enhanced intracellular Ca 2+ flux in response to T cell receptor activation as compared to normal lymphocytes. This was accompanied by a significant increase in nuclear localization of the calcium-sensitive transcription factor NFAT, which could contribute to the enhanced secretion of IL-13 and other cytokines. Conclusions: In summary, our data identified that CFTR dysfunction in T cells can lead directly to aberrant immune responses. This is the first instance that a CF related phenotype has been entirely modeled in vivo by selectively knocking out CFTR in the immune system. Specifically, Cftr deficient lymphocytes directed skewed responses to Aspergillus fumigatus , leading to a higher than normal IgE response. These findings implicate the lymphocyte population as a potentially important target for therapeutics directed to the treatment of CF lung disease.

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Burrows, Andrea C. « A social study of women in contemporary biological sciences ». Diss., This resource online, 1991. http://scholar.lib.vt.edu/theses/available/etd-07282008-135540/.

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Wala, Zingfa Jantur. « Birds and people : studies based on citizen science and census data of Greater Gauteng, South Africa ». Doctoral thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29541.

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Global human population growth has been predicted to grow exponentially, to a point where it exceeds the capacity of available resources to sustain it. The consequences that such exponential increase will have on the environment has also been the focus of several research. The spatial pattern of human population has reveal uneven pattern of human population with the urban areas being subject of increased influx of human population from the rural areas in search of better economic factors. The United Nations in 2007 revealed that at least half of the world’s 6.6 billion human population was living in urban areas. This number is expected to increase to over 60% of the world's population by the end of 2050. Most of this population growth is occurring in developing countries. While the health, security and town planning amongst other consequences of this global explosion in urbanization have been well-studied and documented, the impact which urbanization is having and will have on the ecosystem and on biodiversity, especially at regional and local scales has remained an a field of knowledge that has continued to evolve especially given the variable patterns and drivers of urbanization in different regions of the world as well as the different environmental factors and biodiversity in these regions. Biodiversity monitoring has been shown to be crucial to conservation goals aimed at accessing the state and condition of biodiversity. The Second South African Bird Atlas Project (SABAP2) is a citizen science atlas project which commenced in 2007. Over a decade, SABAP2 has produced a rich source of data, capturing bird distributions in South Africa. This makes SABAP2 a powerful tool for monitoring observed changes in bird communities and by extension biodiversity through time. I examined the effect that urbanization is having on the avian biodiversity in South Africa, one of the most urbanized countries in Africa. My research was focused on the 576 pentads in the four one-degree grid cells (25S 27E, 25S 28E, 26S 27E and 26E 28E) centered on the Gauteng province, referred to as Greater Gauteng region. In addition to being very urbanized, Greater Gauteng is also the most populated area in the country, and is home to 30% of the country’s 51 million people. The region is the most atlased SABAP2 region in the country, with each pentad having a minimum of 11 full-protocol SABAP2 checklists. It thus provide opportunities for the development of tools to monitor the temporal dynamics of bird communities. The first chapter is the general introduction where I did an extensive literature review of the research subject and gave an overview of the data chapters that make up the thesis. In the second chapter, I examined spatial patterns of urbanization and avian biodiversity. I assess avian species composition in the urban and rural areas of Greater Gauteng. I categorized bird data from SABAP2 for Greater Gauteng Urban and Rural subgroups. The dataset for this chapter had 700 bird species. 644 showed no range preference for either urban or rural areas. Five species showed a preference for rural areas while 51 species showed a preference for urban areas. The higher species richness recorded in urban pentads highlights the often overlooked benefits of biodiversity conservation efforts in urban areas such as green spaces and parks, gardens and water bodies. This chapter highlights the need for conservation efforts to be targeted at birds and other biodiversity in urban spaces. It is also raises the need to further promote policies aimed at having conservation efforts incorporated into town planning. In the third and fourth chapters, I used data from SABAP2 to investigate how different protected areas such as Important Bird Areas (IBAs) are to their surrounding areas by demonstrating how different the Devon Grasslands (Chapter 3) and Suikerbosrand Nature Reserve (Chapter 4) IBAs are to their immediate surrounding areas in terms of avian species richness and assemblage. Atlas data from the pentads covering these two IBAs were compared with data from the surrounding pentads. Both IBAs stand out as having more bird species than their immediate surroundings. The simple yet effective method used in this chapters can be applied in identifying potential sites for biodiversity conservation. In the fifth chapter, using a variation of the Shannon-Weiner species diversity index which is known to reach an asymptote rapidly even while species richness keeps increasing, to investigate patterns of spatial distribution of species richness and proportional diversity in Greater Gauteng. The chapter provides insights into pentads with the richest bird communities and also provides a method which can be applied to citizen science data such as SABAP2 to discover areas where particular groups of species, such as waterbirds and threatened species, are concentrated in the region. The sixth chapter examines the relationship between reporting rates of birds and human population in Greater Gauteng. With Greater Gauteng being the most populated region in South Africa, it presented an ideal situation to investigate patterns of correlation between human population and the reporting rates of bird species in the region. Based on the results obtained, the species were grouped into 18 groups categorized by the relationship pattern revealed by species reporting rates and human population. The Seventh chapter follows a similar pattern with chapter six. However, chapter seven, examines patterns between a socio-economic index, mean income per person, and the reporting rates of birds in Greater Gauteng. The eighth chapter is the conclusion. It gives a synthesis of the thesis and presents the implications for conservation of avian biodiversity in Greater Gauteng. Overall, this thesis highlights the contribution of citizen science can make to research. It also makes for a strong case showing fundamental importance of large volumes of data such as SABAP2 data, and the useful information that can be harnessed from this data. The conservation-relevant studies in the chapters of this thesis are a result of the spatial distribution patterns of the avifauna revealed by SABAP2 data from Greater Gauteng. It showed how we can detect changes in species abundance, richness and composition in a pentad or in any area, a method we can extend further to detect when bird species are starting to decline or drop out of the species list for a pentad. The results reported in this thesis provides a rich field of study for future research, especially in the field of urban ecology.

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Grauby-Heywang, Christine. « Etude à l'interface air-eau de mélanges lipidiques susceptibles de former des RAFTS membranaires ». Habilitation à diriger des recherches, Université Sciences et Technologies - Bordeaux I, 2008. http://tel.archives-ouvertes.fr/tel-00685610.

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La première partie de ce manuscrit concerne l'étude en monocouches à l'interface air-eau de mélanges lipidiques susceptibles de former des "rafts" dans les membranes cellulaires, c'est-à-dire des domaines enrichis spécifiquement en certains lipides (glycolipides, sphingolipides, cholestérol) et certaines protéines. Du fait de leur composition spécifique, ces domaines sont caractérisés par une phase particulière ("liquid ordered phase") présentant des caractéristiques intermédiaires entre celles des phases fluides et condensées. Les principales méthodes mises en oeuvre dans cette étude sont des mesures de pression de surface (isothermes de compression, analyse des aires moléculaires moyennes, études de désorption en présence de beta-cyclodextrine), la microscopie de fluorescence (après marquage de la monocouche à l'aide d'une sonde fluorescente), ou la microscopie à l'angle de Brewster. Une des parties les plus importantes de ce travail concerne le comportement de monocouches constituées d'un glycolipide, le GM3, en présence de phospholipides (phase fluide), de sphingomyéline ou de cholestérol (phase "raft"). Les mesures montrent que le GM3 n'a pas d'affinité particulière pour la sphingomyéline. De même, son interaction avec le cholestérol induit une condensation de la monocouche similaire à celle observée avec les phospholipides en phase fluide, et ne permet pas le maintien du cholestérol dans la monocouche lors d'une désorption induite par la beta-cyclodextrine. Ce manque d'interaction spécifique du GM3 avec des lipides présents dans les "rafts" permet donc d'expliquer sa répartition assez large dans les membranes d'adipocytes, tant dans la phase fluide que dans les "rafts". La seconde partie concerne l'étude de molécules organiques de type hémicyanine organisées en monocouches de Langmuir et films de Langmuir-Blodgett, étudiés par des méthodes complémentaires (absorption, spectroscopie de fluorescence stationnaire et résolue en temps), mesures de pression de surface et microscopie de fluorescence. Ces hémicyanines comportent une chaîne hydrophobe nécessaire à la réalisation de films organisés stables. Ces derniers peuvent avoir de multiples applications dans la collecte et le transfert de l'énergie lumineuse ou les analyses chimiques ou biochimiques (reconnaissance sélective de cations lors de pollutions par exemple).

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Mishra, Avdesh. « Effective Statistical Energy Function Based Protein Un/Structure Prediction ». ScholarWorks@UNO, 2019. https://scholarworks.uno.edu/td/2674.

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Proteins are an important component of living organisms, composed of one or more polypeptide chains, each containing hundreds or even thousands of amino acids of 20 standard types. The structure of a protein from the sequence determines crucial functions of proteins such as initiating metabolic reactions, DNA replication, cell signaling, and transporting molecules. In the past, proteins were considered to always have a well-defined stable shape (structured proteins), however, it has recently been shown that there exist intrinsically disordered proteins (IDPs), which lack a fixed or ordered 3D structure, have dynamic characteristics and therefore, exist in multiple states. Based on this, we extend the mapping of protein sequence not only to a fixed stable structure but also to an ensemble of protein conformations, which help us explain the complex interaction within a cell that was otherwise obscured. The objective of this dissertation is to develop effective ab initio methods and tools for protein un/structure prediction by developing effective statistical energy function, conformational search method, and disulfide connectivity patterns predictor. The key outcomes of this dissertation research are: i) a sequence and structure-based energy function for structured proteins that includes energetic terms extracted from hydrophobic-hydrophilic properties, accessible surface area, torsion angles, and ubiquitously computed dihedral angles uPhi and uPsi, ii) an ab initio protein structure predictor that combines optimal energy function derived from sequence and structure-based properties of proteins and an effective conformational search method which includes angular rotation and segment translation strategies, iii) an SVM with RBF kernel-based framework to predict disulfide connectivity pattern, iv) a hydrophobic-hydrophilic property based energy function for unstructured proteins, and v) an ab initio conformational ensemble generator that combines energy function and conformational search method for unstructured proteins which can help understand the biological systems involving IDPs and assist in rational drugs design to cure critical diseases such as cancer or cardiovascular diseases caused by challenging states of IDPs.

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Walker, Michael John. « Safeguarding food : advances in forensic measurement science and the regulation of allergens, additives and authenticity ». Thesis, Kingston University, 2016. http://eprints.kingston.ac.uk/37907/.

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This commentary reports on work published between 2005 and 2015 forming a record of a varied career building technical competence alongside strategic skills in the analytical chemistry and molecular biology of food. The unifying theme is practice based problem solving in the scientific regulation and enforcement of food safety and authenticity. The work demonstrates advances in sound, forensically robust, measurement science addressing problems arising from food additives, food authenticity and food allergens. In particular the mature discipline that underpins the regulation and enforcement of food additives is shown to be needed for the management of food allergens. The background to food regulation and enforcement is described alongside technical appeals in the official food control system to develop societally meaningful food surveillance, supported by a sustainable UK based official food control infrastructure (Public Analyst service) at the interface between science and the law. For food additives, publication of previously un-collated results informs regulatory practice and demonstrates the value of scientific collaboration between both jurisdictions on the island of Ireland. A definitive strategy is reported for the chemical analysis and risk assessment of ‘jelly mini-cups’ in which gel forming additives have caused choking fatalities and solutions to problems in the analysis of two illegal toxic additives, morpholine and dimethyl yellow are described. For food allergens the portfolio includes the first study to assess in quantitative terms the level of risk to peanut allergic consumers in take-away catering, leading to better training and similar work on coeliac disease and the availability of ‘gluten-free’ food. Systematic assessment of food allergen analysis and a programme of analytical improvement to support allergen risk assessment and risk management are discussed. A narrative account of an allergen related food sabotage incident and the subsequent Crown Court case and previously uncollated reports of court-sanctions for allergen noncompliances, severe incidents and deaths make key policy and practice recommendations for improvement in these areas. Page 7 of 162 In the study of food authenticity a critical review describes the nitrogen content of important species in the food supply chain as a proxy in the quantitative estimation of high value flesh foods in compound products. An exemplar study follows determining previously unavailable nitrogen factor data for farmed salmon and salmon frame mince. A critical survey of the up skilling of the UK Official Food Control System in DNA food authenticity techniques and major historical and contemporary reviews of food fraud (butter and horsemeat) support substantial policy and analytical recommendations. Many threats to our food supply can be assessed and managed only with the assistance of measurement science. Integrating elements of chemico-legal practice including lessons learned from ‘referee analyses’ and metrology in chemistry this commentary concludes with a synthesis describing major changes in the UK scientific food control system stemming from the author’s involvement in the ‘Elliott Review’ and recommendations for an international programme of work on food allergen analysis with interconnected learning for the benefit of the analytical and regulatory communities and society at large.

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Murrel, Benjamin. « Improved models of biological sequence evolution ». Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71870.

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Thesis (PhD)--Stellenbosch University, 2012.
ENGLISH ABSTRACT: Computational molecular evolution is a field that attempts to characterize how genetic sequences evolve over phylogenetic trees – the branching processes that describe the patterns of genetic inheritance in living organisms. It has a long history of developing progressively more sophisticated stochastic models of evolution. Through a probabilist’s lens, this can be seen as a search for more appropriate ways to parameterize discrete state continuous time Markov chains to better encode biological reality, matching the historical processes that created empirical data sets, and creating useful tools that allow biologists to test specific hypotheses about the evolution of the organisms or the genes that interest them. This dissertation is an attempt to fill some of the gaps that persist in the literature, solving what we see as existing open problems. The overarching theme of this work is how to better model variation in the action of natural selection at multiple levels: across genes, between sites, and over time. Through four published journal articles and a fifth in preparation, we present amino acid and codon models that improve upon existing approaches, providing better descriptions of the process of natural selection and better tools to detect adaptive evolution.
AFRIKAANSE OPSOMMING: Komputasionele molekulêre evolusie is ’n navorsingsarea wat poog om die evolusie van genetiese sekwensies oor filogenetiese bome – die vertakkende prosesse wat die patrone van genetiese oorerwing in lewende organismes beskryf – te karakteriseer. Dit het ’n lang geskiedenis waartydens al hoe meer gesofistikeerde waarskynlikheidsmodelle van evolusie ontwikkel is. Deur die lens van waarskynlikheidsleer kan hierdie proses gesien word as ’n soektog na meer gepasde metodes om diskrete-toestand kontinuë-tyd Markov kettings te parametriseer ten einde biologiese realiteit beter te enkodeer – op so ’n manier dat die historiese prosesse wat tot die vorming van biologiese sekwensies gelei het nageboots word, en dat nuttige metodes geskep word wat bioloë toelaat om spesifieke hipotesisse met betrekking tot die evolusie van belanghebbende organismes of gene te toets. Hierdie proefskrif is ’n poging om sommige van die gapings wat in die literatuur bestaan in te vul en bestaande oop probleme op te los. Die oorkoepelende tema is verbeterde modellering van variasie in die werking van natuurlike seleksie op verskeie vlakke: variasie van geen tot geen, variasie tussen posisies in gene en variasie oor tyd. Deur middel van vier gepubliseerde joernaalartikels en ’n vyfde artikel in voorbereiding, bied ons aminosuur- en kodon-modelle aan wat verbeter op bestaande benaderings – hierdie modelle verskaf beter beskrywings van die proses van natuurlike seleksie sowel as beter metodes om gevalle van aanpassing in evolusie te vind.

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Patke, Usha. « Inquiry-based laboratory investigations and student performance on standardized tests in biological science ». Thesis, Walden University, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3600291.

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Achievement data from the 3rd International Mathematics and Sciences Study and Program for International Student Assessment in science have indicated that Black students from economically disadvantaged families underachieve at alarming rates in comparison to White and economically advantaged peer groups. The study site was a predominately Black, urban school district experiencing underachievement. The purpose of this correlational study was to examine the relationship between students’ use of inquiry-based laboratory investigations and their performance on the Biology End of Course Test, as well as to examine the relationship while partialling out the effects of student gender. Constructivist theory formed the theoretical foundation of the study. Students’ perceived levels of experience with inquiry-based laboratory investigations were measured using the Laboratory Program Variable Inventory (LPVI) survey. LPVI scores of 256 students were correlated with test scores and were examined by student gender. The Pearson correlation coefficient revealed a small direct correlation between students’ experience in inquiry-based laboratory investigation classes and standardized test scores on the Biology EOCT. A partial correlational analysis indicated that the correlation remained after controlling for gender. This study may prompt a change from teacher-centered to student-centered pedagogy at the local site in order to increase academic achievement for all students. The results of this study may also influence administrators and policy makers to initiate local, state, or nationwide curricular development. A change in curriculum may promote social change as students become more competent, and more able, to succeed in life beyond secondary school.

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Diallo, Abdoulaye. « Inference of insertion and deletion scenarios for ancestral genome reconstruction and phylogenetic analyses : algorithms and biological applications ». Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=40771.

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This thesis focuses on algorithms related to ancestral genome reconstruction and phylogenetics analyses. Specially, it studies insertion and deletion (indel) in genomic sequences, their utilities for (1) evolutionary studies of species families, (2) multiple alignment and phylogenetic trees reconstruction assessment, and (3) functional DNA sequence annotation. Here, the indel scenarios reconstruction problem is presented, in a likelihood framework, and it can be stated as follows: given a multiple alignment of orthologous sequences and a phylogenetic tree for these sequences, reconstruct the most likely scenario of insertions and deletions capable of explaining the gaps observed in the alignment. This problem, that we called the Indel Maximum Likelihood Problem (IMLP), is an important step toward the reconstruction of ancestral genomic sequences, and is important for studying evolutionary processes, genome function, adaptation and convergence. In this thesis, first, we showed that we can solve the IMLP using a new type of tree hidden Markov model whose states correspond to single-base evolutionary scenarios and where transitions model dependencies between neighboring columns. The standard Viterbi and Forward-backward algorithms are optimized to produce the most likely ancestral reconstruction and to compute the level of confidence associated to specific regions of the reconstruction. A heuristic is presented to make the method practical for large data sets, while retaining an extremely high degree of accuracy. The developed methods have been made available for the community through a web interface. Second we showed the utilities of the defined indel score for assessing the accuracy of multiple sequence alignment and phylogenetic tree reconstruction. Third, the provided method is included into the framework of the ancestral protein reconstruction of phages under a reticulate evolution and the evolutionary studies of the carcinogencity of the Human Papilloma Vir
Cette thèse traite d'algorithmes pour la reconstruction de génomes ancestraux et l'analyse phylogénétique. Elle étudie particulièrement les scénarios d'insertion et délétion (indels) dans les séquences génomiques, leur utilité (1) pour l'étude des familles d'espèces, (2) pour l'évaluation des alignements multiples de séquences et la reconstruction phylogénétique, (3) et pour l'annotation de séquences génomiques fonctionnelles. Dans cette thèse, le problème de la reconstruction du scénario d'indels est étudié en utilisant le critère de maximum de vraisemblance. Ce problème peut être défini de la manière suivante: étant donné un alignement multiple de séquences orthologues et un arbre phylogénétique traduisant l'histoire évolutive de ces séquences, reconstruire le scénario d'indels le plus vraisemblable capable d'expliquer les brèches présentes dans l'alignement. Ce problème, dénommé ''Indel Maximum Likelihood Problem (IMLP)'', est une importante étape de la reconstruction de séquences ancestrales. Il est également important pour l'étude des processus évolutifs, des fonctions des gènes, de l'adaptation et de la convergence.Dans une première étape de cette thèse, nous montrons que l'IMLP peut être résolu en utilisant un nouveau type de données combinant un arbre phylogénétique et un modèle de Markov caché. Les états de ce modèle de Markov caché correspondent à un scénario évolutif d'une colonne de l'alignement. Ses transitions modélisent la dépendance entre les colonnes voisines de l'alignement.Les algorithmes standard de Viterbi et de Forward-Backward ont été optimisés pour produire le scénario ancestral le plus vraisemblable et pour calculer le niveau de confiance associé aux prédictions. Dans cette thèse, Nous présentons également une heuristique qui permet d'adapter la méthode à des données de grandes tailles. En second, nous montrons l'utilité du score d'indel dans l'évaluatio

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Jones, Graeme Angus. « Stereoscopic correspondence processes applied to linear features ». Thesis, King's College London (University of London), 1994. http://eprints.kingston.ac.uk/7544/.

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Abbass, Jad. « Secondary structure-based template selection for fragment-assembly protein structure prediction ». Thesis, Kingston University, 2018. http://eprints.kingston.ac.uk/42106/.

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Proteins play critical biochemical roles in all living organisms; in human beings, they are the targets of 50% of all drugs. Although the first protein structure was determined 60 years ago, experimental techniques are still time and cost consuming. Consequently, in silico protein structure prediction, which is considered a main challenge in computational biology, is fundamental to decipher conformations of protein targets. This thesis contributes to the state of the art of fragment-assembly protein structure prediction. This category has been widely and thoroughly studied due to its application to any type of targets. While the majority of research focuses on enhancing the functions that are used to score fragments by incorporating new terms and optimising their weights, another important issue is how to pick appropriate fragments from a large pool of candidate structures. Since prediction of the main structural classes, i.e. mainly-alpha, mainly-beta and alpha-beta, has recently reached quite a high level of accuracy, we have introduced a novel approach by decreasing the size of the pool of candidate structures to comprise only proteins that share the same structural class a target is likely to adopt. Picking fragments from this customised set of known structures not only has contributed in generating decoys with higher level of accuracy but also has eliminated irrelevant parts of the search space which makes the selection of first models a less complicated process, addressing the inaccuracies of energy functions. In addition to the challenge of adopting a unique template structure for all targets, another one arises whenever relying on the same amount of corrections and fine tunings; such a phase may be damaging to "easy' targets, i.e. those that comprise a relatively significant percentage of alpha helices. Owing to the sequence-structure correlation based on which fragment-based protein structure prediction was born, we have also proposed a customised phase of correction based on the structural class prediction of the target in question. After using secondary structure prediction as a "global feature" of a target, i.e. structural classes, we have also investigated its usage as a "local feature" to customise the number of candidate fragments, which is currently the same at all positions. Relying on the known facts regarding diversity of short fragments of helices, sheets and loops, the fragment insertion process has been adjusted to make "changes" relative to the expected complexity of each region. We have proved in this thesis the extent to which secondary structure features can be used implicitly or explicitly to enhance fragment assembly protein structure prediction.

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Glenn, Steven W. « Alpine Biological Soil Crusts in theWashington North Cascades| a Distribution Study at Select Sites Across a Precipitation Gradient ». Thesis, Prescott College, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=3712344.

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One of the least researched phenomena within the alpine regions of mountain biomes is the combination of primitive plants, algae, fungi, and lichens that are generally referred to as biological soil crusts. Sites containing well-developed biological soil crusts were examined in a variety of alpine, non-forested, vegetated landscapes in the North Cascade Mountains of Washington, USA. For each site, data were recorded for percent ground cover of biological soil crusts, slope aspect, and slope gradient of the terrain where the crust communities were located. For all of the sites, biological soil crusts were common, with a percent ground cover median of 29% and a range of 11% to 73%. The arrangement of the biological soil crusts on all sites was quite similar: all were clumped, as opposed to single, and random, as opposed to uniform. All of the soil crusts were found on soil exposed to direct sunlight. Few, if any, crusts were found in the shade of heavy forbs, or forest, or under accumulations of organic litter. When biological soil crusts were found associated with higher-order vegetation, it was with sparse graminoids, ericaceous woody shrubs, and stunted or krummholz Pinaceae trees. The biological soil crusts from this study exist on all locally undisturbed soil slope-gradients from 0% to almost 100%, and occurred on all aspects except for those in the Southwest quadrant. This study contains an extended literature review for desert and high latitude circumpolar crusts, as well as alpine biological soil crusts. Studies of biological soil crusts in subalpine and alpine environments are not common; it is hoped that this study will stimulate more research interest in these often overlooked pioneer biotic communities.

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Shepard, Pamela Ann. « The Use of Part-Time Faculty in Associate Degree Nursing, Social Science, and Biological Science Programs ». Thesis, University of North Texas, 1990. https://digital.library.unt.edu/ark:/67531/metadc332403/.

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This study surveyed the opinions of academic administrators of associate degree nursing programs, community college social science programs, and community college biological science programs regarding major benefits and concerns associated with the employment of part-time faculty. This study found that most part-time social science faculty teach in the classroom, half participate in non-teaching faculty activities, and most are paid a contract amount per course or credit hour. Part-time biological science faculty differed only in that most teach a combination of classroom and lab/practicum. Part-time nursing faculty differed in all three areas. Most part-time nursing faculty teach in lab or practicum settings, most participate in more non-teaching activities than other part-time faculty, and most are paid an hourly wage. However, the benefits and concerns associated with the employment of part-time nursing faculty were not significantly different from those identified by academic administrators of the other programs with one exception. Academic administrators felt that part-time nursing faculty expose students to the latest technologies in specialty areas and part-time social science faculty do not. The benefits cited by the respondents, that were in addition to the benefits most frequently cited in the literature, include increased interaction with the community and the ability to "try out" prospective full-time faculty. The concerns cited by respondents, that were in addition to the concerns most frequently cited in the literature, include the inability to find qualified part-time faculty to fill available positions and the concern that the employment of part-time faculty causes resentment among full-time faculty. The results from this study indicate that the literature pertaining to the benefits and concerns associated with the employment of social science and biological science part-time faculty in community colleges can be used to develop policies regarding part-time faculty in associate degree nursing programs.

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Seier, Edith, et Karl H. Joplin. « Introduction to STATISTICS in a Biological Context ». Digital Commons @ East Tennessee State University, 2011. http://amzn.com/1463613377.

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Smith, Martha Anne. « The organizational culture of the academic department : A case study of a Department of Biological Sciences ». W&M ScholarWorks, 1992. https://scholarworks.wm.edu/etd/1539618811.

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The purpose of this study was to examine theories of organizational culture typically applied to the university level of organization and their applicability to the academic department. Chaffee and Tierney's (1988) theory of organizational culture, dimensions of culture, and leadership strategies became the basis for a qualitative case study of a Department of Biological Sciences in a metropolitan university.;Interviews of current faculty members, current and former deans, and other administrators were conducted. Observations were made of faculty meetings and retreats and of departmental governance committee meetings. Extensive review of documents and correspondence covering more that twenty years provided additional data.;Interview and observation transcripts and documents were analyzed in terms of Chaffee and Tierney's (1988) concepts of the structural, environmental, and values dimensions of the department. Linear, adaptive, and interpretive strategies of faculty members and the department chair were identified.;The department was found to have what Clark (1972) refers to as strong organizational saga, or a sense of unique accomplishment which serves to maintain and perpetuate the integrity of the culture. Central to the value system of the Department of Biological Sciences is the shared sense that the department is unique in the degree to which faculty members work together cooperatively for the good of the department. These strong values were rooted in an earlier era when the department was experiencing growth and development of its research programs under adverse circumstances.;The primary usefulness of the results of this study go far beyond the particular findings for this individual academic department. Most important is the demonstration of the value of using this method of organizational analysis to understand the role of culture in shaping and perpetuating the organization. Administrators, department chairs, and faculty members can enhance their understanding of the departmental organization by applying concepts of organizational culture.;Further study and analysis are needed to evaluate disciplinary and institutional similarities and differences in departmental culture and to expand the existing theory to accommodate the variety of academic departments in colleges and universities.

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Cope, James S. « Computational methods for the classification of plants ». Thesis, Kingston University, 2014. http://eprints.kingston.ac.uk/28759/.

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Plants are of fundamental importance to life on Earth. The shapes of leaves, petals and whole plants are of great significance to plant science, as they can help to distinguish between different species, to measure plant health, and even to model climate change. The current availability of botanists is increasingly failing to meet the growing demands for their expertise. These demands range from amateurs desiring help in identifying plants, to agricultural applications such as automated weeding systems, and to the cataloguing of biodiversity for conservational purposes. This thesis aims to help fill this gap, by exploring computational techniques for the automated analysis and classification of plants from images of their leaves. The main objective is to provide novel techniques and the required frame¬work for a robust, automated plant identification system. This involves firstly the accurate extraction of different features of the leaf and the generation of appropriate descriptors. One of the biggest challenges involved in working with plants is the high amounts of variation that may occur within a species, and high similarity that exists between some species. Algorithms are introduced which aim to allow accurate classification in spite of this. With many features of the leaf being available for use in classification, a suitable framework is required for combining them. An efficient method is proposed which selects on a leaf-by-leaf basis which of the leaf features are most likely to be of use. This decreases computational costs whilst increasing accuracy, by ignoring unsuitable features. Finally a study is carried out looking at how professional botanists view leaf images. Much can be learnt from the behaviour of experts which can be applied to the task at hand. Eye-tracking technology is used to establish the difference between how botanists and non-botanists view leaf images, and preliminary work is performed towards utilizing this information in an automated system.

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Welikala, Roshan Alex. « Automated detection of proliferative diabetic retinopathy from retinal images ». Thesis, Kingston University, 2014. http://eprints.kingston.ac.uk/30591/.

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Diabetic retinopathy (DR) is a retinal vascular disease associated with diabetes and it is one of the most common causes of blindness worldwide. Diabetic patients regularly attend retinal screening in which digital retinal images are captured. These images undergo thorough analysis by trained individuals, which can be a very time consuming and costly task due to the large diabetic population. Therefore, this is a field that would greatly benefit from the introduction of automated detection systems. This project aims to automatically detect proliferative diabetic retinopathy (PDR), which is the most advanced stage of the disease and poses a high risk of severe visual impairment. The hallmark of PDR is neovascularisation, the growth of abnormal new vessels. Their tortuous, convoluted and obscure appearance can make them difficult to detect. In this thesis, we present a methodology based on the novel approach of creating two different segmented vessel maps. Segmentation methods include a standard line operator approach and a novel modified line operator approach. The former targets the accurate segmentation of new vessels and the latter targets the reduction of false responses to non-vessel edges. Both generated binary vessel maps hold vital information which is processed separately using a dual classification framework. Features are measured from each binary vessel map to produce two separate feature sets. Independent classification is performed for each feature set using a support vector machine (SVM) classifier. The system then combines these individual classification outcomes to produce a final decision. The proposed methodology, using a dataset of 60 images, achieves a sensitivity of 100.00% and a specificity of 92.50% on a per image basis and a sensitivity of 87.93% and a specificity of 94.40% on a per patch basis. The thesis also presents an investigation into the search for the most suitable features for the classification of PDR. This entails the expansion of the feature vector, followed by feature selection using a genetic algorithm based approach. This provides an improvement in results, which now stand at a sensitivity and specificity 3 of 100.00% and 97.50% respectively on a per image basis and 91.38% and 96.00% respectively on a per patch basis. A final extension to the project sees the framework of dual classification further explored, by comparing the results of dual SVM classification with dual ensemble classification. The results of the dual ensemble approach are deemed inferior, achieving a sensitivity and specificity of 100.00% and 95.00% respectively on a per image basis and 81.03% and 95.20% respectively on a per patch basis.

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Fraz, Muhammad Moazam. « Retinal image segmentation and quantification of vessel width in non-standard retinal datasets ». Thesis, Kingston University, 2013. http://eprints.kingston.ac.uk/26056/.

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The human retina has the potential to reveal important information about retinal, ophthalmic, and even systemic diseases such as diabetes, hypertension, and arteriosclerosis. Automatic quantification of retinal vessel morphology and width is considered as a first step in computer assisted medical applications related to diagnosis and treatment planning. This work aims to quantify the blood vessels in noisy and pathological retinal images of school children with uneven illumination and containing complex vessel profiles. In this thesis, we have presented two methodologies of retinal vessel segmentation and an algorithm for vessel width measurement. The unsupervised method of retinal segmentation is based on detection of vessel centrelines and followed by computing the vessel shape and the orientation map using morphological bitplane slicing. A supervised method for segmentation of blood vessels by using an ensemble classifier of boosted and bagged decision trees is also presented. The feature vector encodes information to successfully handle both normal and pathological retinas with bright and dark lesions simultaneously. The obtained performance metrics illustrate that this method outperforms most of the state-of-the-art methodologies of retinal vessel segmentation. The method is computationally fast in training and classification and needs fewer samples for training than other supervised methods. It is training set robust as it offers a better performance even when it is trained and tested on different sets of retinal images. A new public database of the retinal images taken from multi-ethnic school children is presented along with the ground truths of vessel segmentation and width measurement. We have also introduced a robust and accurate methodology for measuring the calibre of vessel segments in retinal images of multi-ethnic children. The vessel centrelines are detected from the vessel probability map image resulting from ensemble classification. The vessel branch points and crossovers are identified and removed from the vessel centreline image to obtain vessel segments followed by computing the local vessel orientation of the vessel segments. The width of each vessel segment is estimated using a two dimensional model with incorporated Gaussian (for ordinary vessels) as well as Difference of Gaussian profiles (for vessels with a central reflex). The automated methods for quantification of retinal vessel morphology and width may be used as an alternative to the time consuming subjective clinical evaluation for monitoring the progression of retinopathies and their association with normal and abnormal vascular patterns. This may enable a quick diagnosis, treatment availability, prognosis, and facilitation of clinical heath-care procedures in remote areas.

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Esmaielbeiki, Reyhaneh. « Structural complex prediction based on protein interface recognition ». Thesis, Kingston University, 2013. http://eprints.kingston.ac.uk/28209/.

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This dissertation contributes to the state of the art in protein interface prediction and detection of native-like docked poses by re-ranking them using protein interface knowledge. We started by investigating binding site patterns among homologues of a target protein in order to create a 3D motif. This structural binding site descriptor enables the re-ranking of docked complexes of the target protein. Although 3D motifs provide biological insight of protein interactions and have usage in real applications, they are not suitable for high through-put analysis. Therefore, we introduced a novel protein interface prediction framework which uses a weighted scoring schema to detect interface residues of the target protein using its homologues. The weights quantify both homology closeness between the target protein and its homologues and the diversity between the interacting partners of these homologues. The main novelty of this predictor is that it takes into account the nature of homologues interacting partners. It was further exploited for the development of a method for re-ranking docked conformations using predicted interface residues. We have evaluated both our interface predictor and re-ranking of docked poses using standard benchmarks. Comparisons to current state-of-the-art methods reveal that the proposed approaches outperform all their competitors. However, similarly to current interface predictors, our framework does not explicitly refer to pairwise residue interactions which leaves ambiguity when assessing quality of complex conformations. In addition, the performance of our interface predictor generally does not outperform the best available homologue interfaces if it was used as prediction. Therefore, we investigated the detection of the best homologue using the 'binding site transitivity' concept: given two query protein chains, interfaces of the first query protein are structurally compared against binding sites of the homologues' partners of the second query chain. This method not only allows detection of the best homologue for a reasonable number of proteins but also produces a docked structure of the two query chains. Finally, experiment suggests a meta interface predictor combining the prediction of our former interface predictor with the latter predictor based on binding site transitivity could further improve interface prediction.

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Ferreira, Filipa. « Automatic and accurate segmentation of thoratic aortic aneurysms from X-ray CT angiography ». Thesis, Kingston University, 2012. http://eprints.kingston.ac.uk/26293/.

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The scoped of this dissertation is to procure and propose a novel fully automated computer aided detection and measurement (CAD/CAM) system of thoracic aortic aneurysms. More explicitly, the objective of the algorithm is to facilitate the segmentation of the thoracic aorta, as accurately as possible and detection of possible existing aneurysms in the Computer Tomography Angiography (CT) images. In biomedical imaging, the manual examination and analysis of aortic aneurysms is a particularly laborious and time-consuming undertaking. Humans are susceptible to committing errors and their analysis is usually subjective and qualitative due to the inter- and intra-observer variability issue. Objective and quantitative analysis facilitated by the application developed in this project leads to a more accurate diagnostic decision by the physician. In this context, the project is concerned with the automatic analysis of thoracic aneurysms from CTA images. The project initially examines the theoretical background of the anatomy of the aorta and aneurysms. The concepts of image segmentation and, in particular, segmentation of vessels methods are reviewed. An algorithm is then developed and implemented, such that it will conform to the requirements put forth in the stated objectives. For purposes of testing the proposed approach, a significant amount of 3D, clinical CTA datasets of thoracic aorta form the framework of the CAD/CAM system. It is followed by presentation and discussion of the results. The system has been validated on a clinical dataset of30 eTA scans of which 28 eTA scans contained aneurysms. There were 30 eTA scans used as training dataset for parameter selection and another 30 eTA scans uses as a test dataset, in total 60 for clinical evaluation. The radiologist visually inspected the CAD and CAM component results and confirmed it correctly detected and segmented the T AA on all datasets, proving to have 100% sensitivity. We were able to conclude that there is distinct potential for.use of our fully automated CAD/CAM system in a real clinical setting. Although other CAD/CAM systems have been developed for other organ detection and even small sections of the thoracic aorta, to this date no fully automated CAD/CAM of the entire thoracic aorta has been developed hence its novelty. To facilitate the proposed CAD/CAM system is integrated in a Medical Images Processing, Seamless and Secure Sharing Platform (MIPS3) which is a friendly user interface that has been developed alongside with this project.

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Bakas, Spyridon. « Computer-aided localisation, segmentation and quantification of focal liver lesions in contrast-enhanced ultrasound ». Thesis, Kingston University, 2014. http://eprints.kingston.ac.uk/30592/.

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The research presented in this thesis focuses on applications of Contrast Enhanced Ultrasound (CEUS) imaging and is coordinated to address current clinical requirements in the assessment, quantification and evaluation of liver cancer and in particular focal liver lesions (FLLs). The main outcomes of this research are methods to assist radiologists with automating these routinely performed manual image interpretation tasks, with the intention of supporting them to make their diagnostic decisions faster, more easily and with greater confidence. Such automatic analysis is challenging mainly because of the relative motion between the ultrasound transducer and the liver, the physiological motion of the patient and the dramatic intensity changes over time caused by the contrast-enhancing agents intravenously injected during a CEUS examination. The work described in this thesis can be divided into three principal themes. These are addressed in turn below. Firstly, a set of methods are proposed to assist in automating initialisation tasks required for the offline assessment of data acquired during CEUS liver scans. These tasks relate to the delineation of the area comprising the ultrasonographic image, the identification of the optimal reference frame for initialising an FLL, as well as the segmentation of the FLL boundaries on this frame. The potential clinical value of the proposed methods is that they can lead to easier and faster assessment of FLLs, whilst producing results less dependent on the human initialisation and hence improving the repeatability and reproducibility of the assessment of the examination and increasing the confidence of radiologists when making a diagnosis. Secondly, a variety of methods are investigated to estimate the motion observed within the ultrasonographic image of CEUS screening recordings and then compensate for this, allowing for an accurate quantification of the perfusion of tissue regions. Obtaining a perfusion curve for an image region, without compensating for the observed motion, may lead to erroneous diagnostic results as the specified image region may correspond to different tissue along the video sequence. Quantitative evaluation of the presented methods demonstrates their potential as reliable real-time motion compensation methods for such recordings. Finally, an alternative fully automatic method for the identification and localisation of potential malignancies is proposed. For such identification, and hence distinction between cases that include potentially malignant and benign lesions, an innovative assessment of the global spatial configuration of local variations of perfusion curves is presented. For the localisation of tissue regions of potential malignancy, a novel feature is proposed that encompasses spatio-temporal information (Le. the combination of both the variation in these local perfusion curves and the location they relate to) to cluster together neighbouring regions with similar dynamic behaviour. The clinical value of the identification part is the early diagnosis of an FLL’s type and the possibility for the discharge of patients with benign FLLs, leading to less distress to the patients and their families, as well as reduced healthcare costs. Additionally, the localisation part assists in enhancing the radiologist’s awareness of tissue regions with potentially malignant behaviour, as well as providing effortless localisation of such regions allowing for an objective initialisation of computer-aided segmentation methods improving the repeatability and reproducibility of the assessment of CEUS data. The key findings of this research indicate that: i) the optimal reference frame can be reliably identified in a fully automatic and deterministic manner, ii) the segmentation of an F LL can be performed in a rapid semi-automatic manner, which produces results that are, at worst, of comparable consistency as different manual annotations, iii) the apparent observed motion can be compensated in real-time, either locally or globally, and a simple translation is sufficient to achieve this, iv) the distinction between benign and malignant lesions can be performed in a fully automatic and deterministic manner, without missing a single malignancy, and v) potential malignancies can be localised reliably in a fully automatic manner. Quantitative analysis of all results on real clinical data, from a multi-centre study, is used to evaluate the level of confidence of the decision of the proposed methods and demonstrates the value of these methods in a diverse dataset acquired using the protocol of current standard care. A system incorporating the proposed methods could improve the current clinical practice for assessing, quantifying and evaluating FLLs in CEUS recordings. Specifically, it would be beneficial to radiologists, for cancer research, providing easier and faster assessment of FLLs whilst producing results less dependent on the human initialisation and therefore increasing the confidence of radiologists in their diagnostic decisions.

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Alsharif, Abdulla H. « Intelligent M-Health-CBT combined technology for an enhanced smoking cessation management system using data mining techniques with a case study in Saudi Arabia ». Thesis, Kingston University, 2016. http://eprints.kingston.ac.uk/37875/.

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Smoking has become one of the major global health concerns. Though there are various awareness activities being undertaken, the prevalence of smoking across the world is increasing at alarming levels. However, the extent of this increase varies among different countries. Even in culturally rich countries where smoking is considered as antagonistic behaviour both religiously and culturally, like Saudi Arabia, the prevalence of smoking is increasing at alarming levels. As smoking is mostly a behavioural aspect bundled with other factors, CBT (Cognitive Behavioural Therapy) integrated with m-health technologies represents a good strategy towards smoking cessation. This study focuses on developing a mobile smoking cessation management system - SMOKE MIND - using CBT intervention, and assessing its impact on achieving smoking cessation. This study uses mixed methods approach, where different methods are used at different stages of the research. Based on the systematic reviews and other literature reviewed, a questionnaire-based survey is conducted to assess the requirements of smokers in Saudi Arabia regarding the system for smoking cessation. The system developed uses CO readings of smokers, entered daily by participants through the mobile application, and assesses their improvement. Additionally, smokers enter CBT data if their CO readings are high, also through the mobile application. Based on these readings and CBT data, physicians recommend various activities and send motivational messages. The system is trailed for four weeks with an intervention group, who had access to the system, and a control group who did not. At the end of the study, another survey is conducted for evaluating the usability aspects of the SMOKE MIND system. The results achieved at the end of the study in evaluating the SMOKE MIND System reflect significant improvements in the participants in quitting smoking, and high satisfaction levels of the participants using the system. The values of p in both one-talied (0.0061) and two tailed (0.01) t-test are < 0.05, indicating that results are significant. 81.8% of the participants in intervention group and 40% participants in the control group quit smoking at the end of the study. A majority of the participants were highly satisfied with the various features used in the SMOKE MIND System.

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Ion, Adina Izabela. « Computer aided detection and measurement of peripheral arterial diseases from CTA images ». Thesis, Kingston University, 2013. http://eprints.kingston.ac.uk/26273/.

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Peripheral Arterial Disease (pAD) afflicts more than 2.7 million people in the U.K. per year, and it is projected to increase rapidly within the current decade. PAD is a product of obstruction (stenosis or occlusion) of vessels feeding the body's extremities, and it is most often encountered in the lower extremities. Treatment of the disease is dependent on the specific anatomic segments afflicted, the degree of stenosis and its length. A common technique for imaging PAD is Computed Tomography-Angiography (CTA). The acquired CTA images are then investigated by a radiologist for disease assessment. However due to the large size of the PAD CTA datasets (1000-2000 slices) the radiologist's examination is time consuming and laborious. This project brings a contribution to the investigation of PAD in CTA datasets by the development of a tool for the radiologist, a fully automatic system for the detection and measurement of PAD, as currently there are no such systems efficacious for the disease. The proposed system is comprised of two components: a Computer Aided Detection (CAD) component and a Computer Aided Measurement (CAM) component. The CAD component is designed for artery segmentation and stenosis detection. The stage of artery segmentation is accomplished by using a 3D region growing method and an innovative 3D fast morphology operation. CAD methodologies commonly employ morphological operations as a tool in the segmentation process, along with extended series of CTA images. This large dataset requires careful attention to be paid towards optimizing the computational process in terms of time efficiency. In order to meet this goal, an optimized morphology algorithm is presented, which reduces the computation time by a factor of 10. A skeletonization based centreline technique is applied on the detected artery, and it then provides the basis for the measurement stage. Orthogonal planes to the centreline are used in order to obtain cross sectional images. The artery profile is then built based on vessel areas measured in the cross sectional images and an automated process of stenosis detection is performed. The CAM component of the system accurately measures and quantifies the stenosis and overcomes the challenge brought by the partial volume effect. In this respect, a hybrid method for partial volume correction is employed locally, on the candidate areas of stenosis detected by the CAD component, based on Maximum a Posterior (MAP) and Markov Random Field (MRF) expectation maximization method. The CAD-CAM system has been successfully implemented and applied on phantom and patient data (twenty data sets from The University Hospital of Lausanne (CHUV)) and the evaluation was carried out through the visual judgment of two experienced radiologists. Within the CAD component, the artery segmentation was evaluated and a total of 15 peripheral arterial trees were correctly extracted. The proposed stenosis detection method was evaluated on 525 arterial segments (each dataset was partitioned into 35 segments) from which 132 exhibited stenosis caused by soft plaque. The system achieved a sensitivity of 88% and a specificity of 96%. The CAM component has been evaluated using phantom data, and the average error of the diameter measurement was 8%.

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Fattah, Zahra Ali. « Applications of bipolar electrochemistry : from materials science to biological systems ». Phd thesis, Université Sciences et Technologies - Bordeaux I, 2013. http://tel.archives-ouvertes.fr/tel-00917770.

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Bipolar electrochemistry deals with the exposure of an isolated conducting substrate that has no direct connection with a power supply except via an electric field. Therefore it can be considered as a "wireless technique". The polarization of the substrate with respect to the surrounding medium generates a potential difference between its opposite ends which can support localized electrochemical oxidation reduction reactions and break the surface symmetry of the substrate. The method was applied in the present thesis to materials science and biological systems. In the frame of designing asymmetric particles, also called "Janus" particles, bipolar electrochemistry was adapted for the bulk preparation of these objects. Conductive substrates with different nature, sizes and shapes have been modified with various materials such as metals, ionic and inorganic compounds using this approach. Moreover, a control over the deposit topology could be achieved for substrates at different length scales. Bipolar electrodeposition is also a good tool for investigating the generation of different metal morphologies. Further developments in the bipolar setup allowed us to use the technology for microstructuration of conductive objects. Furthermore the concept has shown to be very useful in the field of the induced motion of particles. The asymmetric objects that have been prepared by bipolar electrodeposition were employed as microswimmers which could show both translational and rotational motion. The application of electric fields in the bipolar setup can be used for the direct generation of motion of isotropic objects through bubble generation. A levitation motion of objects combined with light emission was possible using this concept. Finally, bipolar electrochemistry was also used for studying the intrinsic conductivity of biological molecules (DNA), which is of great importance in the nanotechnology.

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Bohec, Pierre. « Étude du comportement hors-équilibre du cortex cellulaire ». Phd thesis, Université Paris-Diderot - Paris VII, 2012. http://tel.archives-ouvertes.fr/tel-00870466.

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La cellule est capable, en consommant l'énergie issue de l'hydrolyse de l'ATP, d'exercer des forces qui prennent leurs origines dans des réactions biochimiques. Un élément important de la cellule est le cytosquelette, composé principalement de microtubules et de filaments d'actine, il en constitue l'architecture et lui donne l'essentiel de ses propriétés mécaniques. Il est composé de polymères réticulés et, du point de vue de la rhéologie, a un comportement viscoélastique. Au sein du cytosquelette, des processus tels que la polymérisation de l'actine ou des microtubules permettent d'exercer des forces. Des protéines, de la famille des moteurs moléculaires, ont pour rôle spécifique de convertir l'énergie stockée sous forme chimique en énergie mécanique. L'activité mécanique hors-équilibre de la cellule est donc directement reliée à ces forces d'origine biochimique. Dans ce travail, nous avons étudié la distribution statistique des forces d'origine biochimique s'exerçant sur une bille de taille micrométrique attachée au cortex d'actine par l'intermédiaire de récepteurs de l'adhésion cellulaire : les intégrines. L'étude des forces d'origine biologique est inséparable de la connaissance des forces d'origine thermique car à cette échelle microscopique la contribution des forces thermiques n'est pas négligeable. Les forces s'exerçant sur la sonde ont deux origines possibles : biologique ou thermique. Notre approche expérimentale est basée sur la combinaison de deux techniques de microrhéologie, active et passive, ce qui nous permet de calculer la fonction d'autocorrélation temporelle des forces exercées sur une sonde accrochée à l'actine corticale et de la comparer à la fonction d'autocorrélation des forces thermiques estimée via le théorème de fluctuation-dissipation. La différence entre ces deux spectres nous donne une idée de la contribution des forces d'origine biologique au mouvement de la bille et une mesure de l'écart du système à l'équilibre thermodynamique. Afin d'étudier plus en détail ce système de bille subissant des forces de la part de l'actine corticale, nous avons étudié l'effet de la variation de la densité de ligand recouvrant la bille. La question qui nous a animés tout au long de ce travail est l'origine de ces forces biologiques ou plus exactement la nature du composant du cytosquelette qui exerce ces forces athermiques. Dans un premier temps, nous avons étudié l'influence de la température sur ces forces biologiques. Nous avons ensuite étudié l'effet de la déplétion de l'ATP dans la cellule, de la dépolymérisation de l'actine et de l'inhibition des moteurs moléculaires de la famille des myosines.

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Thèses sur le sujet « Science biological sciences biophysics »

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