Dissertations / Theses on the topic 'Human Biophysics'

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1

Ogilvie, Julian Andrew. "Functional specialisation in human visual processing." Thesis, Imperial College London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286444.

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2

Schluter, Nathaniel D. "Human premotor cortex : imaging and interference." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284344.

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3

Walker, Lloyd T. "The biomechanics of the human foot." Thesis, University of Strathclyde, 1991. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=21131.

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This thesis reports on work undertaken to study the biomechanics of the human foot during normal daily activity, particularly walking and standing. A literature review is presented on topics related to the subject and several of the areas demanding further investigation are highlighted. Three lines of enquiry were pursued to consider the kinematics, kinetics, passive structural properties and muscle activity associated with the foot. A dynamic pedobarograph with a synchronised video system was used to measure the forces and their distribution under the foot (based on seven marked areas) and six kinematic angles of the foot and lower leg. Sixty-one healthy subjects were assessed and the results are presented. Kinetic and kinematic parameters were found to be consistent and smooth for the test population. Several of the events of the gait cycle were found to be temporally different from values widely reported. In the second investigation, four cadaveric foot specimens were tested dynamically to determine the role of the plantar structures during loading in various positions. A method of sequential dissection was used and the results support many of the theories regarding ligament function. Tests on the effect of three extrinsic muscles on the foot load distribution also support previous studies while a preliminary investigation of two pathological feet partially clarifies the biomechanical effects of a hallux valgus deformity. Eight of the foot extrinsic and intrinsic muscles were assessed for the final investigation. Using electromyographic (EMG) recording techniques on six healthy subjects, the muscle EMG activity was quantified during walking a) barefoot, b) with a moulded heel plate, and c) with soft shoes. The results for the extrinsic muscles generally agree with previous work, while the intrinsic muscle activity is more variable. The intrinsic muscles were more active when shoes were worn and displayed unusual fatigue patterns.
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4

Schechtman, Helio. "Mechanical characterisation of fatigue failure in human tendons." Thesis, Queen Mary, University of London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297451.

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5

Alexopoulos, Evangelos Demetrios. "Extracellular matrix associated with human luteinizing granulosa cells." Thesis, University of Southampton, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369867.

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6

Scase, Mark O. "Studies on normal and impaired human colour vision." Thesis, Keele University, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.254775.

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7

Tha, Susan P. L. "Interaction forces between human red cells aggutinated by antibody." Thesis, McGill University, 1987. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75421.

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A theoretical and experimental method is described whereby the hydrodynamic forces, both normal and shear, acting on the spheres of a doublet can be calculated. This is applied to a system of sphered human red blood cells agglutinated by human hyperimmune anti-B antiserum undergoing Poiseuille flow and observed using the traveling microtube technique. The mean forces separating the cells of individual doublets were found to be proportional to antiserum concentration from 0.73 to 3.56% v/v, normal forces increasing from 0.060 to 0.197 nN and shear forces from 0.023 to 0.072 nN. It was impossible to determine which force was responsible for break-up. Measurements of the doublets' mean dimensionless period of rotation indicated that doublets were rigidly linked.
Micropipet aspiration was applied to the same red cell-antibody system. Separation forces were $ sim2{1 over2}$ fold greater than for normal forces of the traveling microtube technique. Non-uniformity of red cell adhesiveness was also demonstrated.
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8

Moran, Carmel Mary. "The physical basis for ultrasonic investigation of human skin." Thesis, Institute of Cancer Research (University Of London), 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246108.

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9

Quantock, Andrew James. "The stromal ultrastructure of normal and pathologic human corneas." Thesis, Open University, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293665.

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10

Jones, Simon Richard. "Non-invasive analysis of human retinal and cortical visual function." Thesis, Imperial College London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312379.

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11

Mansfield, John Stephen. "The influence of spatial contrast processing on human stereoscopic vision." Thesis, University of Oxford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.291325.

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12

Bell, David N. "Physical factors governing the aggregation of human platelets in sheared suspensions." Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75873.

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The effect of shear rate on the ADP-induced aggregation of human blood platelets in flow through tubes was studied over the full physiologically significant range. The extent of single platelet aggregation at 0.2 $ mu$M ADP in citrated platelet-rich plasma, PRP, was greatest at mean tube shear rate, G = 314 s$ sp{-1}$; however, aggregate size steadily decreased from G = 39.3 to 1800 s$ sp{-1}$. At 1.0 $ mu$M ADP the rate of aggregation increased up to G = 1800 s$ sp{-1}$ where virtually no unaggregated platelets remained after 43 s of flow, although, aggregate size was still limited by shear rate. A shear-dependent delay in the onset of aggregation and an increase in collision efficiency with time suggest the existence of a time and shear-dependency in the expression of bonds mediating aggregation. Greater aggregation of platelets from female donors than male donors was due to differences in the ionized calcium concentration, (Ca$ sp{2+}$), in the plasma of donors of different hematocrit when the chelating agent citrate is used as anticoagulant. At physiological (Ca$ sp{2+}$) aggregation was much greater in heparinized and hirudinized plasma than in citrated plasma and no sex difference was present. Aggregation in whole blood was much greater than in PRP due to a shear-dependent increase in the frequency of collision between activated platelets caused by the motion of red cells.
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13

Prince, Simon J. D. "Measurement and encoding of binocular disparity in the human visual system." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299231.

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14

Ho, Joseph Daniel. "Heterologous expression of human membrane protein drug targets and the X-ray crystallographic determination of the human aquaporin 4 structure." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3378489.

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15

Roberts, Stephen John. "Analysis of the human sleep electroencephalogram using a self-organising neural network." Thesis, University of Oxford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302898.

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16

Yu, Zhongbo. "Mechanochemistry of Human DNA G-quadruplexes Revealed by Single-molecule Optical Tweezers." Kent State University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=kent1369366966.

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17

Meadley, Stacey. "Investigation of the structure of healthy and diseased human ascending aorta by multiphoton microscopy." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66789.

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There have been relatively few examinations of the microstructure of the human ascending aorta and none relating it to the biochemical composition and the tissue mechanics. This study uses multiphoton microscopy, an innovative new tool in biological imaging, to study the structure of the two proteins elastin and collagen in the ascending aorta. Healthy and dilated ascending aortic tissue was examined at two regions, the inner curvature and outer curvature. Dilated aortas were classified by aortic valve type. The morphology of the fenestrations in the elastic laminae and the collagen fibers were quantified. The results show variation of microstructure by aortic valve type and also by region. Correlations between the microstructures and the biochemical composition and the tissue mechanics suggest that multiphoton microscopy could potentially be used for rapid determination of biochemistry and biomechanics of human ascending aortic tissue d uring surgery. This study demonstrates that vessel wall remodeling occurs with ascending aorta dilation.
Peu d'études portent sur la microstructure de l'aorte ascendante humaine et aucune relative à la composition biochimique et à la mécanique des tissus ont été réalisées. Cette étude utilise la microscopie multiphotonique, un nouvel outil employé en imagerie biologique, afin d'étudier la structure de deux protéines, l'élastine et le collagène, dans l'aorte ascendante. Des tissus en santé d'aortes ascendantes dilatées ont été examinés dans deux régions, la courbure intérieure et extérieure. Les aortes dilatées ont été classées par type de valve, bicuspide ou tricuspide. La morphologie des fenestrations dans les lames élastiques de l'aorte ainsi que les fibres de collagène ont été quantifiées. Les résultats démontrent une différence dans les divers types de valve aortique et également dans les différentes régions analysées. Les corrélations entre la microstructure et la composition biochimique ainsi que la mécanique des tissus suggèrent que la microscopie multiphotonique pourrait être utilisée pour la détermination rapide de la biochimie et la biomécanique de l'aorte ascendante humaine lors de chirurgies aortiques. Cette étude démontre que le remodelage de la paroi se produit simultanément avec la dilatation de l'aorte ascendante.
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18

Breen, Alan Clark. "The measurement of the kinematics of the human spine using videofluoroscopy and image processing." Thesis, University of Southampton, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.303090.

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19

Abbott, Heather Elizabeth. "Comparisons of the factors influencing intrinsic radiosensitivity between two isogenic human ovarian carcinoma cell lines." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0021/MQ57080.pdf.

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20

Levesque, Ives. "Quantitative magnetic resonance imaging of magnetization transfer and T2 relaxation in human white matter pathology." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66751.

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The primary aim of this thesis is the reconciliation of two seemingly disparate quantitative magnetic resonance imaging (MRI) techniques proposed to characterize human brain white matter (WM) in health and disease. Quantitative magnetization transfer imaging (QMTI) and multi-component analysis of T2 relaxation (QT2) both attempt to quantify myelin content in vivo, but are based on fundamentally different models of WM. QMTI probes the macromolecular component of tissue using a two-pool model of magnetization transfer, while QT2 isolates the water signal from distinct micro-anatomical compartments. The specific objectives were to determine the interrelationship between measurements made with both techniques in the context of potential pathological changes associated with multiple sclerosis (MS), and to apply both to track WM changes in the acute phase of MS lesions. First, simulations were used to evaluate the theoretical sensitivity of each technique to the characteristics of a model of WM that incorporates four pools of magnetization, based on published in vitro measurements. Next, the experimental reproducibility of each technique was investigated, and the impact of certain basic variations in the data acquisition and analysis procedures was evaluated. In the final stage, both methods were applied longitudinally in vivo to assess the dynamic changes that occur in acute, contrast-enhancing lesions of MS. The theoretical results illustrate the sensitivity and limitations of QMTI and QT2 to specific pathology-inspired modifications of WM, and shed new light on the potential specificity of often-neglected QMTI parameters. The reproducibility of both techniques is acceptable for use in repeated clinical measurements, and QMTI has lower variability overall. The importance of corrections for magnetic field inhomogeneity in QMTI is demonstrated, and a simple optimization of the QMTI data acquisition is introduc
L'objectif principal de cette thèse est la réconciliation de deux techniques quantitatives d'imagerie par résonance magnétique, en apparence difféerentes, utilisées pour la caractérisation de la susbtance blanche du cerveau humain en santé ou affectée par la maladie. Les techniques d'imagerie quantitative par transfert de magnétisation (QTM) et d'analyse de la relaxation T2 par de multiples composantes (QT2) proposent toutes deux des mesures in vivo de la quantitée de myéline, mais à l'aide de modèles fondamentalement différents. D'un côté, l'imagerie QTM sonde la composante macro-moléculaire des tissues à l'aide d'un modèle à deux réservoirs pour le transfert de magnétisation. De l'autre, l'imagerie QT2 sépare les signaux acqueux provenant de compartiments micro-anatomiques distincts. Plus spécifiquement, cet ouvrage cherche à mieux comprendre l'interdépendance des mesures de ces deux techniques dans le contexte pathologique de la sclérose en plaques (SEP), pour ensuite les appliquer à l' étude de lésions aigues de SEP. En premier lieu, des simulations ont été effectuées pour évaluer la sensibilité de chaque technique aux caractéristiques d'un modèle plus complet de la substance blanche, qui découle de résultats in vitro publiés et incorpore quatre réservoirs de magnétisation. Ensuite, la reproductibilité de chacune des techniques a été évaluée; de plus, quelques variations élémentaires des méthodes d'acquisition et d'analyse des données examinées. En dernier lieu, les deux techniques ont été utilisées in vivo afin de mesurer les changements dynamiques des lésions aigues de SEP, présentant un hyper-signal rehaussée par un agent de contraste. Les résultats des simulations démontrent d'un point de vue théorique la sensibilité et les limites de chacune de ces technique aux changements dans la substance blanche. Ces résultats apportent égalem
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21

Cohalan, Claire. "Cerebral blood volume changes during human neuronal activation: a comparative study of VASO and VERVE." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66871.

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In this research, two techniques which measure hemodynamic changes during neuronal activation in humans were studied. The Vascular Space Occupancy (VASO) technique indirectly measures changes in total cerebral blood volume (CBV) by measuring the decrease in grey matter signal during activation, in images in which the blood signal is nulled. The Venous Refocusing for Volume Estimation (VERVE) technique measures changes in venous blood volume by exploiting the dependence of partially-deoxygenated blood's T2¬ on the refocusing interval τ180. Using a simultaneous visual and motor task, a (ΔCBV/CBVrest)total of 25.0 ± 13.9 % and a (ΔCBV/CBVrest)¬venous of 3.9 ± 1.6 % were measured using VASO and VERVE, respectively. Though the VASO technique has a high CNR and is simple to implement, its signal has contributions from many compartments other than grey matter. VERVE has fewer deleterious effects, but suffers from a higher power deposition. The activated regions in VERVE overlap better with BOLD activation than the VASO regions do, which, combined with VERVE's specificity to venous CBV changes, make it more appropriate in an investigation of the blood volume contribution to the BOLD signal.
Deux techniques visant à mesurer les changements de volume sanguin cérébral durant l'activité neuronale sont étudiées. La première, Vascular Space Occupancy (VASO), mesure l'augmentation de l'ensemble du sang en mesurant la baisse du signal provenant de la matière grise, dans une image où la magnétisation du sang est nulle. La deuxième, Venous Refocusing for Volume Estimation (VERVE), mesure en particulier l'augmentation du volume sanguin veineux en exploitant la dépendance du T2 du sang partiellement deoxygéné sur l'intervalle de refocalisation τ180. Avec une tâche à la fois motrice et visuelle, un (ΔCBV/CBVrepos)totale de 25,0 ± 13,9 % et un (ΔCBV/CBVrepos)¬veineux de 3,9 ± 1,6 % ont été mesurés par VASO et VERVE, respectivement. La méthode VASO est facile à instrumenter, et jouit d'un ratio contraste-bruit plus élevé que VERVE, mais plusieurs compartiments autres que la matière grise contribuent à son signal. Moins d'effets gênants contribuent au signal de VERVE, mais celui-ci souffre d'un taux de puissance déposé élevé, parfois atteignant les limites imposées par la Commission Fédérale des Communications. Le volume activé de VERVE correspond mieux que le volume activé de VASO au volume activé de BOLD. Ce fait, et celui que VERVE mesure spécifiquement le volume veineux, prônent l'utilisation de cette technique dans une analyse de la contribution du volume sanguin au signal BOLD.
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22

Sheppard, Steven James. "Diagnosis from single photon emission tomography images of the human brain using artificial neural networks." Thesis, University of Warwick, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307348.

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23

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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24

Dumoulin, Serge O. "Motion mechanisms and cortical areas in human vision : psychophysics and fMRI." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82860.

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Our visual world contains both luminance- (first-order) and contrast-defined (second-order) information. Distinct mechanisms underlying the perception of first-order and second-order motion have been proposed from electrophysiological, psychophysical and neurological studies. In this thesis psychophysical and human brain imaging (fMRI) experiments are described that support the notion of distinct mechanisms, but extend the previous studies by providing evidence for a functional dissociation and a relative cortical specialization for first- and second-order motion.
Using psychophysical methods, a directional anisotropy was found for second-order but not first-order motion in peripheral vision. This anisotropy is interpreted as a functional dissociation implicating the second-order mechanism in optic flow processing.
Identification of early visual cortical areas is a prerequisite to any functional assessment of these visual areas. To this aim a novel human brain mapping method has been developed which automatically segments early human retinotopic visual areas. Unlike previous methods this procedure does not depend on a cortical surface reconstruction and thereby greatly simplifies the analysis.
In a combined psychophysical and fMRI study, distinct cortical regions, in occipital and parietal lobes, were preferentially activated by either first- or second-order motion. These results provide evidence for the idea that first-order motion is computed in V1 and second-order motion in later occipital visual areas. In addition the results suggest a functional dissociation of the two kinds of motion beyond the occipital lobe consistent with a role for the second-order mechanism in optic flow analysis.
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25

Taylor, David W. Jr. "Structural Basis for RNA Processing by Human Dicer." Thesis, Yale University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3578460.

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Dicer plays a central role in RNA interference pathways by cleaving double-stranded RNAs (dsRNAs) to produce small regulatory RNAs. Human Dicer can process long double-stranded and hairpin precursor RNAs to yield short interfering RNAs (siRNAs) or microRNAs (miRNAs), respectively. In humans, Argonaute2 (AGO2) assembles with the guide RNA-generating enzyme Dicer and either the RNA-binding protein TRBP or PACT to form a RISC-loading complex (RLC), which is necessary for efficient transfer of nascent siRNAs from Dicer to AGO2. Here, I have used electron microscopy and single particle analysis of human Dicer-RNA complexes and the RLC to gain insight into the structural basis for human Dicer's substrate preference and RISC-loading. My studies show that Dicer traps pre-siRNAs in a non-productive conformation, while interactions of Dicer with pre-miRNAs and dsRNA binding proteins induce structural changes in the enzyme that enable productive substrate recognition in the central catalytic channel. The RLC Dicer's N-terminal DExH/D domain, located in a short base branch, interacts with TRBP, whereas its C-terminal catalytic domains in the main body are proximal to AGO2. A model generated by docking the available atomic structures of Dicer and Argonaute homologs into the RLC reconstruction suggests a mechanism for siRNA transfer from Dicer to AGO2.

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Vera, Carlos D. "Functional Characterization of Disease-Causing Mutations in Human Myosin Heavy Chain Genes." Thesis, University of Colorado at Boulder, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10981347.

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Biophysical and biochemical imbalance of mechanisms relevant to muscle function, can result in morphological changes to the tissue. While the purpose of activities involving exercise is to modify the shape and size of skeletal muscle, and the length of these muscles allows wide ranges of stiffness and stretch to be applied, cardiac tissue is not meant to change much. However, stressful extrinsic factors (poor diet, chemotherapy, etc) or intrinsic factors like inherited mutations in muscle functioning genes can result in a myopathy or a disease of the muscle. In fact, another biological process that requires much compliance of many molecules is embryogenesis. Although the timeline of an embryonic structure is limited, compared to an adult heart and muscle composition, continuous and coordinated movement is essential, but cumulative, prolonged disruptions can be harmful. At the core of muscle biology is the myosin molecule which is a motor protein that hydrolyzes ATP, binds to actin, and the spatial dynamics of its function (contraction-relaxation) alter the length of muscle. Myosin cyclically follows specific steps and undertakes well-defined structural conformations during these events, but mutations can alter the time and stability of any of these aspects. In this thesis I did a comprehensive analysis of the ATPase cycle parameters for both embryonic and cardiac myosin and studied the effects of specific associated or linked mutations have on function. The multiple mutations were in the interest of cataloging common features and defects to identify mechanistic patterns. In a collaborative effort I also used these wet-lab measurements to simulate the cycle using a working kinetic model for the myosin ATPase cycle. We have found distinct differences between three different myopathies that will be discussed in the following chapters.

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27

Niese, Brandon A. "Fabrication of microfluidic devices to probe cell mechanical properties of MDA-MB-231 human breast cancer cells." Ohio University Honors Tutorial College / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1556626033175996.

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28

Roy, David Michael. "Gestural human-machine interaction using neural networks for people with severe speech and motor impairment due to cerebral palsy." Thesis, City University London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307917.

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29

Beck, Jennifer 1968. "Effects of chest wall configuration and electrode positioning on human diaphragmatic EMG." Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=22536.

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The measurement and analysis of the human diaphragm electromyogram (EMGdi), as obtained with an esophageal electrode, requires objective control of the disturbances and filtering effects which can influence the signal. One issue of importance is that an increase in the muscle-to-electrode distance (MEdist) acts as a low-pass filter, filtering out the high frequency components of the EMG power spectrum (the MEdist filter). Due to the numerous factors which can influence the EMGdi, control of signal quality is also of utmost importance. The aims of this study were: (1) to evaluate the effect of the MEdist filter on EMGdi, as measured with a multiple array esophageal electrode, (2) to take advantage of the MEdist filter in order to locate the position of the diaphragm with respect to the electrodes, and (3) to evaluate the influence of changes in chest wall configuration on EMGdi center frequency (CF) values, while controlling for both signal quality and the MEdist filter.
Five normal male subjects performed static contractions of the diaphragm at seven predetermined chest wall configurations. The EMGdi was measured with an array of eight steel rings mounted on a catheter, forming seven sequential pairs of electrodes, with an interelectrode distance of 10 mm. EMGdi signal quality was evaluated by computer algorithms. The pair of electrodes whose EMGdi signals (and power spectrums) were the least influenced by the MEdist filter was assumed to be closest to the diaphragm.
The results of the study indicated (1) EMGdi power spectrums and their associated CF values were strongly affected by the position of the diaphragm with respect to the multiple array esophageal electrode. CF decreased by approximately 1 Hz per mm displacement away from the diaphragm. (2) By controlling for the MEdist filter, there was no relationship found between changes in chest wall configuration and CF values. These data demonstrate that changes in chest wall configuration, and hence diaphragm length, do not influence the CF values of the EMGdi, if the distance between the electrodes and the diaphragm and signal quality are controlled for.
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30

Carter, Richard John. "Small-angle scattering studies of human growth hormone and its complexes with antibody fragments and X-ray crystallographic studies of chromatin." Thesis, Liverpool John Moores University, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337899.

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31

Oursler, Stephen Mark. "A proposed mechanical-metabolic model of the human red blood cell." Thesis, University of Maryland, College Park, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=1561025.

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The theoretical modeling and computational simulation of human red blood cells is of interest to researchers for both academic and practical reasons. The red blood cell is one of the simplest in the body, yet its complex behaviors are not fully understood. The ability to perform accurate simulations of the cell will assist efforts to treat disorders of the cell. In this thesis, a computational model of a human red blood cell that combines preexisting mechanical and metabolic models is proposed. The mechanical model is a coarse-grained molecular dynamics model, while the metabolic model considers the set of chemical reactions as a system of first-order ordinary differential equations. The models are coupled via the connectivity of the cytoskeleton with a novel method. A simulation environment is developed in MATLAB® to evaluate the combined model. The combined model and the simulation environment are described in detail and illustrated in this thesis.

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32

Seckler, James Malcolm. "The Structural Dynamics of Human Immunodeficiency Virus Type I Reverse Transcriptase." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1298562809.

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33

Saqar, Wedad Ali. "Characterization of Small Conductance Calcium-Activated Potassium Channels in a Human Lens Epithelium Cell Line (B3)." Wright State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=wright1401279427.

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34

Mercier, Jean-Francois. "New modelling tools for the human genome project: 1 A study of the Ogston regime for small analytes and 2 Models for solid phase DNA amplification." Thesis, University of Ottawa (Canada), 2004. http://hdl.handle.net/10393/29141.

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Now that the human genome project has been completed, the race is on to improve the existing sequencing techniques, or develop new ones, to allow affordable and reasonably quick personal DNA testing. This would help predict personal response to drugs and disease predisposition. The standard sequencing method is based on electrophoresis, which allows a sorting of molecules according to their size. In the first part of this thesis, I develop a new numerical method to rapidly obtain the continuum limit mobility of a migrating molecule, using results obtained on a lattice. I then use this technique to re-examine the theoretical foundation of the current model (the Ogston-Morris-Rodbard-Chrambach or OMRC model) used to describe the molecular size dependence of the electrophoresic mobility of small molecules during gel electrophoresis. I consider three-dimensional gels and electric field lines similar to the ones used in electrophoresis and show that the OMRC model could not reliably predict the mobility of a molecule in a gel. In the second part of this thesis, I present a computational study of a new technique that could be used to provide alternatives to electrophoresis-based sequencing. This technique, named solid phase DNA amplification, allows for the parallelization of DNA amplification (and ultimately, a new sequencing method). I use Monte Carlo and Brownian Dynamics simulations to model this new experimental technique. I show that it leads to a geometrical amplification of DNA molecules and sharp population size distributions.
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35

Sankeralli, Marcel John. "Investigation of the chromatic postreceptoral detection mechanisms of human colour vision using noise masking in cone contrast space." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0020/NQ44571.pdf.

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36

Buzan, Jonathan R. "Quantifying Human Heat Stress in Working Environments, and Their Relationship to Atmospheric Dynamics, Due to Global Climate Change." Thesis, Purdue University, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10809312.

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Heat stress is a global issue that crosses socioeconomic status. Heat stress leads to reduced worker capacity on seasonal scales, and weekly to sub-daily timescales, incapacitation, morbidity, and mortality. This dissertation focuses on 2 distinct parts: quantification methods of heat stress, and heat stress applications.

Quantification methods of heat stress: Chapters 1–3 focus on historical analysis of heat stress. Chapter 1 is a detailed assessment of previous work in heat stress—methods, history, and future research out- look. Chapter 2 focuses on the implementation and quantification of a battery of heat stress metrics within the global circulation model framework. The ultimate outcome is a Fortran module, the HumanIndexMod [1], that may be run independently on individual datasets, or used with the Community Earth System Model 1, Community Land Model Version 5 (released February 2018 w/HumanIndexMod). Chapter 3 is an analysis of a battery of heat stress metrics with the focus on showing their differences in global circulation models, and thermodynamic predictability and scalability.

Heat stress applications: Chapters 4 and 5 focus on applications for physical impact modeling and economic outcomes. Chapter 4 quantifies labor impacts from heat stress due to the covariance or temperature, humidity, and radiation. My predictions of labor productivity losses from heat stress are amenable to Integrated Assessment Modeling. Chapter 5 is a preliminary economic impacts analysis–a 1st order sensitivity perturbation study for labor impacts–which will guide a flagship application for the Purdue University Big Idea Project, GLASS: Global to Local Analysis of Systems Sustainability. My labor productivity losses from heat stress will become a boundary condition for a series of sensitivity assessments intended to inform the policy making process to help achieve the United Nations Sustainability Development Goals.

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37

Mao, Suifang. "Motile cilia of human airway epithelia mediate noncanonical hedgehog signaling." Diss., University of Iowa, 2018. https://ir.uiowa.edu/etd/6195.

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During embryogenesis, airway epithelial cells possess primary cilia, and HH signaling guides lung development. As epithelial cells mature, they produce hundreds of motile cilia and continue to produce the sonic hedgehog (SHH) ligand, which is found apically in the thin layer of liquid covering airways. However, whether ciliated airway cells express apical HH signaling components and what their function might be have remained unknown. Here we show that motile cilia are enriched for HH signaling proteins, including patched 1 and smoothened. These cilia are also enriched for proteins affecting cAMP-dependent signaling, including Gαi and adenylyl cyclase 5/6. Surprisingly, SHH in differentiated airway epithelia did not elicit the canonical SHH signaling pathway that regulates transcription during development. But instead, activating HH signaling decreases intracellular levels of cAMP, which reduces ciliary beat frequency and airway surface liquid pH, similar to changes that have been observed in the airway of people with chronic obstructive pulmonary disease (COPD). Furthermore, we observed that significant increase of SHH ligand expression in differentiated airway epithelia with COPD, suggesting a potential role of SHH signaling in the pathogenesis of airway disease. Collectively, our study indicates that airway cilia detect apical SHH to mediate airway physiology through noncanonical HH signaling. SHH may dampen defenses at the contact point between the environment and the lung, perhaps counterbalancing processes that stimulate airway defenses. This may suggest a potential role of SHH signaling in the pathogenesis of airway disease, such as COPD.
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Trikha, Saurabh. "Unraveling the Molecular Mechanisms of Human Amylin Binding, Turnover and Toxicity in Pancreatic Cells." Thesis, The George Washington University, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3590360.

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Islet amyloid polypeptide or amylin is a recently discovered 37 amino acid residue signaling protein (hormone) that is produced and co-secreted along with insulin by pancreatic beta-cells. In late onset of diabetes, amylin readily aggregates forming protein deposits or plaques that are toxic to beta-cells, resulting in beta-cell apoptosis. Given the well-known role of cholesterol and lipids in etiology of diabetes, I explored whether these two essential PM components regulate amylin assembly and aggregation on artificial (synthetic) membranes. Using high resolution imaging and spectroscopic approaches, I demonstrated that amylin undergoes facilitated aggregation and conformational changes in the presence of membranes composed of anionic lipids such as phosphatidylserine (PS). The presence of cholesterol on the other hand inhibited lipid-induced aggregation of amylin in solution and on model planar membranes. However, the patho-physiological consequence of cholesterol-regulated amylin polymerization on membranes, and biochemical mechanisms that protect beta-cells from amylin toxicity are poorly understood. Hence, in my subsequent study, I reported that PM cholesterol plays a key role in molecular recognition, sorting and internalization of toxic amylin oligomers but not monomers in pancreatic rat insulinoma and human islet cells. Depletion of PM cholesterol or the disruption of the cytoskeleton network inhibited internalization of amylin oligomers, which in turn enhanced extracellular oligomer accumulation and potentiated amylin toxicity. In contrast to oligomers, amylin monomers followed clathrin-dependent endocytosis, which was not sensitive to cholesterol depletion. Our studies identified an actin-mediated and cholesterol-dependent mechanism for selective uptake and clearance of amylin oligomers, impairment of which greatly potentiated amylin toxicity.

However, the exact uptake mechanism and trafficking routes of these molecular forms and their significance for amylin toxicity are yet to be determined. Hence, in my further study, I observed that pancreatic cells employed different strategies to eliminate amylin's toxic and non-toxic molecular forms. My study also revealed that macropinocytosis serves a major cyto-protective role in these cells, by clearing of amylin molecular forms. The overreaching goal was to fully elucidate the internalization and trafficking pathways of human amylin monomers and toxic oligomers in pancreatic cells.

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39

Zhu, Yueming. "Polychlorinated biphenyl (PCB)-induced oxidative stress mediates cytotoxicity in human breast and prostate epithelial cells." Diss., University of Iowa, 2011. https://ir.uiowa.edu/etd/3026.

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This thesis describes studies that are designed to investigates the hypothesis that mitochondrial production of reactive oxygen species (O2*- and H2O2) cause oxidative stress during PCB exposure and this increased production of ROS contributes to the biological effects of PCBs on cell proliferation in human breast and prostate epithelial cells. Exponentially growing non-malignant human breast epithelial cells (MCF-10A) and non-malignant human prostate epithelial cells (RWPE-1) were treated with selected PCBs and their metabolites (PCB3, 77, 153, Aroclor and 4ClBQ). Results showed that PCBs and their metabolites could significantly inhibit MCF-10A and RWPE-1 cell growth as well as inducing clonogenic cell killing. These PCBs were also found to increase steady-state levels of mitochondrial O2*- and H2O2. Furthermore, the same PCBs were also found to induce alterations in SOD activities in MCF-10A and RWPE-1 cells. Finally, treatment with either N-acetyl-cysteine (NAC), or the combination of polyethylene glycol (PEG) conjugated CuZnSOD and PEG-catalase added 1 hour after PCBs, significantly protected MCF-10A and RWPE-1 cells from PCB-induced toxicity even when added following PCB exposure. Similar experiments were also accomplished using airborne PCBs treated RWPE-1 cells. 4-OH-PCB11, a metabolite of airborne PCB 11 is shown to lead to steady-state increases in superoxide and hydroperoxides in exponentially growing RWPE-1 human nonmalignant prostate epithelial cells. This increased level of ROS was accompanied by the inhibition of cell growth and clonogenic cell killing. Furthermore treatment of cells with antioxidants one hour following exposure to 4-OH-PCB11 was able to significantly diminish the toxicity in human prostate epithelial cells. These results strongly supported the hypothesis that exposure to PCBs or their metabolites can induce the cytotoxicity and alterations in cellular proliferation as well as causing oxidative stress in exponentially growing human breast and prostate epithelial cells. More importantly, the data also provide clear evidence that antioxidant manipulations after PCB exposure are capable of protecting human cells against PCB-induced cytotoxicity. Based on these observations, the long term goal of this work is to develop a mechanism based biochemical rationale for the development of pharmaceutical manipulations to protect humans from PCB intoxication.
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40

Vittal, Rao Geeta. "Identifying Functional Epitopes In Site 1 Of Human Prolactin Hormone." The Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1226014118.

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41

Shikov, Sergei. "Structural Determinants for Heparin Binding in Human Coagulation Factor XI." Diss., Temple University Libraries, 2008. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/13460.

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Biochemistry
Ph.D.
Coagulation factor XI plays an important role in the consolidation phase of blood coagulation. Previous studies from our laboratory and others have demonstrated that zymogen factor XI (FXI) binds to heparin with moderate (KD~110 nM) affinity via residues (K252, K253 and K255) located in the apple 3 (A3) domain of the molecule. In contrast, the enzyme, factor XIa (FXIa), was shown to bind to heparin with significantly higher affinity (~1.5 nM by ELISA) via residues (K529, R530 and R532) within the catalytic domain (CD). The interaction between heparin and FXIa potentiates the inhibition of FXIa by protease nexin-2 by 10-fold. In addition, related polyanions heparin and dextran sulfate inhibit the catalytic activity of FXIa. The present study was designed to determine the relative contributions of positively charged residues as well as the dimeric structure of FXI in heparin binding. During this project, wtFXI, FXIR504A, FXIK505A, FXIR507A, FXIR529A, FXIR530A, FXIR532A, and FXIR586A have been expressed and purified. All mutants were homogenous and identical to wtFXI on SDS-PAGE, clotting assays and 1G5 monoclonal antibody binding studied by SPR. In addition, monomeric FXI C321S/K331A was expressed and purified. Utilizing an ELISA assay, no difference in the affinity for heparin between FXIa and FXI was found. Surface plasmon resonance (SPR) data collected for FXI clearly indicate a complex interaction which does not conform to a simple 1:1 Langmuir binding model making it difficult to obtain quantitative information. The complexity of FXI interactions with heparin is likely to arise from the multivalent nature of the binding, in which both protein and heparin have multiple binding sites. Two positively charged residues in the FXI catalytic domain, FXIR507A and FXIR532A, were found to be particularly important for interaction with heparin. The FXIR507A and FXIR532A mutants demonstrated ~ 65% and ~50% decreases respectively in total number of heparin binding sites based on ELISA. Also, the apparent dissociation constants for FXIR507A (KDapp ~13 nM) and FXIR532A (KDapp ~21 nM ) were 6 and 10-fold increased respectively compared with 2.1 nM for the wtFXI. Mutant FXIR586A also demonstrated a defect in affinity (KDapp ~ 13 nM) without an effect on the Bmax. The monomeric FXIC321S/R331A was also characterized for its ability to bind heparin compared with wtFXI. Surprisingly, the monomeric FXI displayed defective binding to heparin according to ELISA (KDapp ~ 30 nM) and SPR methods. Thus, the unique homodimeric structure of FXI in addition to the residues both in its catalytic and A3 domain chains are necessary for high-affinity heparin binding.
Temple University--Theses
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42

Everett, Judith Helen. "Structure of monolithic human insulin at 1.8A resolution and development of computer software for application in biophysics." Thesis, Liverpool John Moores University, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.290739.

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43

Mohanraj, Lathika. "REGULATION OF MDM2 MEDIATED NFκB2 PATHWAY IN HUMAN LUNG CANCER." VCU Scholars Compass, 2008. http://scholarscompass.vcu.edu/etd/1641.

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Overexpression of oncoprotein MDM2 and mutations of tumor suppressor p53 are frequently observed in human cancers. The NFκB pathway is one of the deregulated pathways in oncogenesis. The overall goal of the project was to study the regulation of NFκB pathway by MDM2 in lung cancer. Our first effort was to determine the frequency of MDM2 overexpression in human lung tumor samples and to identify co-occurring abnormal gene expression by studying the levels of MDM2 and members of NFκB pathway with respect to p53 status. Higher than normal levels of MDM2 were found in approximately 30% of the cancer samples harboring wild-type (WT) and mutant p53. Expression of NFκB2, a mutant p53 inducible gene showed significant statistical correlation with MDM2 in cancer samples that harbored WT p53. A downstream target gene of NFκB2, Bcl2, showed a significant correlation to MDM2 levels, independent of p53 status. Lung cancer samples harboring mutant p53 exhibited elevated levels of NFκB2 though not statistically significant. Our next step was to corroborate findings from lung tumor samples with data from lung cancer cell line harboring WT p53-H460. Consistent with lung tumor samples, ectopic overexpression of MDM2 in H460, showed elevated expression of NFκB2 and Bcl2 with promoter upregulation of NFB2. Silencing of MDM2 proportionally downregulated NFκB2 and Bcl2 in H460 cells. Domain analysis of MDM2 suggested that increase in the NFκB2 promoter activity was not confined to the p53 binding domain of MDM2 suggesting their interaction via p53-dependent and p53-independent mechanisms. A functional cell growth assay showed retarded cell proliferation with downregulation of MDM2. Data from human lung tumor samples and lung cancer cell line suggest that overexpression of MDM2 mediates NFB2 upregulation to confer growth advantage, thus favoring oncogenesis.
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44

Nguỹên, Quang. "Characterization of proteolytic agents involved in the degradation of human articular cartilage proteoglycan during aging and arthritis." Thesis, McGill University, 1990. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74620.

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Some of the age-related changes in the structure of human proteoglycan aggregate, and the depletion of proteoglycan in arthritic cartilage have been attributed to the action of proteolytic agents. However, the identity of these agents is still uncertain. In this study, the cartilage matrix protein, link protein, has been used as an in situ probe of endogenous proteolysis, due to its relative resistance to proteolysis and the accumulation of its proteolytically-modified form with age in the matrix. Stromelysin, a metalloproteinase secreted in a latent form by human articular cartilage in organ culture, was shown to play a major role in the matrix degradation of neonatal cartilage. In adult cartilage, additional proteolytic agents, besides stromelysin, are involved. The data are compatible with the action of cathepsins B and G, and probably cathepsin L and hydroxyl radicals. The same multiple proteolytic agents appear to have acted on the cartilage remaining in both osteoarthritic and rheumatoid arthritic joints. To further investigate the role of the stromelysin in the degradation of arthritic cartilage, relative steady-state mRNA levels of prostromelysin in normal and arthritic cartilage were also examined. Northern blots indicated that abundant amounts of prostromelysin mRNA were present in normal adult cartilage, whereas relatively lower levels were found in arthritic and neonatal cartilage. Relative to prostromelysin mRNA, little procollagenase and tissue inhibitor of metalloproteinases (TIMP) mRNA were expressed in vivo by chondrocytes in human articular cartilage. In situ hybridization revealed that the metalloproteinase message was being expressed predominantly in the superficial chondrocytes of normal adult and osteoarthritic cartilage. If the observed low levels of latent metalloproteinase precursor are characteristic of all phases of the disease process, then it would appear that the level of activation rather than the amount of the metalloproteinase pre
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45

Venius, Jonas. "Fluorescence spectroscopy and imaging studies of functionally different human heart tissues." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2013. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2013~D_20130124_081732-30187.

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Rhythmical contraction of the heart is controlled by the cardiac conduction system (CCS). However, this highly important system visually could not be distinguished from the surrounding heart tissues – myocardium (MC) and connective tissue (CT); therefore during surgical procedures CCS could be damaged. The reliable method for CCS identification either in vivo or ex vivo does not exist therefore there is a definite need for developing a CCS imaging method. Fluorescence spectroscopy studies of cardiac tissues revealed, that most distinct spectral differences between CCS and the surrounding tissues were observed in 400 nm – 550 nm region under excitation from 330 nm – 380 nm region. The visualization method, based on the intensity ratios calculated for two excitation wavelengths, has been established. The calculated ratio R = I(330)/I(380) is different for CCS, CT and MC tissues, therefore the method may be used for identification of CCS. Time resolved fluorescence spectroscopy revealed no significant difference in composition and lifetimes between CCS and MC. On the other hand, the lifetimes and the relative spectral composition of CT differed significantly from those of CCS. Reflection confocal microscopy allows visualizing MC, CT, Purkinje cells and CCS bundles because of different reflection properties of tissue components and their specific distribution inside the tissue. The results of in vivo performed procedure revealed, that the distribution of fluorescence intensities... [to full text]
Tvarkingą širdies darbą užtikrina širdies laidžioji sistema (ŠLS). Ją pažeidus sutrinka širdies darbas. Pažeidimo rizika atsiranda operacijos metu, kadangi ŠLS yra raumeninės kilmės audinys ir vizualiai neatskiriamas nuo aplinkinių audinių. ŠLS pažeidimo galima būtų išvengti, jei būtų žinomas tikslus ŠLS išsidėstymas arba egzistuotų ŠLS vaizdinimo metodika. Deja, bet atskirų ŠLS dalių tikslus išsidėstymas vis dar tikslinamas, o patologijų atvejais apskritai nėra žinomas. ŠLS vaizdinimo metodikos, tinkančios in vivo taikymams, taipogi nėra. Atlikus širdies audinių tyrimus nustoviąja fluorescencine spektroskopija nustatyti charakteringi intensyvumų skirtumai. Remiantis šiais skirtumais sukurta ŠLS atskyrimo metodika, paremta intensyvumų santykių skaičiavimu. Suskaičiuota vertė R = I(330)/I(380) yra skirtinga ŠLS, miokardui (MK) ir jungiamąjam audiniui (JA).Tokia metodika yra nejautri tyrimo sąlygoms ir gali būti naudojama ŠLS nustatymui. Ištyrus širdies audinius laikinės skyros spektroskopija nustatyta, kad ŠLS ir MK fluorescencijos gyvavimo trukmė bei santykinė sudėtis reikšmingai nesiskiria, tuo tarpu JA ir ŠLS tiek fluorescencijos gyvavimo trukmės, tiek santykinė komponentinė sudėtis yra skirtinga. Ištyrus širdies audinius konfokaliniu atspindžio mikroskopu nustatyta, jog dėl skirtingų šviesą atspindinčių komponentų bei skirtingo jų išsidėstymo galima identifikuoti MK, JA, Purkinje ląsteles ir ŠLS pluoštus. Atlikus tyrimus in vivo nustatyta, jog operacijos metu... [toliau žr. visą tekstą]
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46

Adams, Bret. "Double-Strand Break Repair Mechanisms in Human Embryonic Stem Cells." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/114.

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Central to the progression of all organisms is the maintenance of a stable genome despite continuous insults arising from genotoxic and environmental stresses. Embryonic stem cells show promise for treatment of a variety of diseases as well as for providing normal human tissue to conduct scientific research. A major obstacle for their application is that genomic instability arises in stem cells after prolonged cell culture. The most detrimental form of DNA damage is the DNA double-strand break (DSB), which is managed by cells through complex mechanisms, designated the DNA damage response. There are two major types of DSB repair; homologous recombination repair (HRR) and non-homologous end joining (NHEJ), both of which are regulated by members of the phosphatidyl-inositol-3’-kinase-related kinase (PIKK) family, including Ataxia Telangiectasia Mutated (ATM), Ataxia Telangiectasia Mutated and Rad3-related (ATR) and the DNA dependent protein kinase (DNA-PK). The aim of this study was to define the mechanisms and important proteins involved in repair of human embryonic stem cells. Here we have also described a system to differentiate hESCs into neural progenitors and astrocytes and were able to examine their DNA damage response. In both examining DNA repair markers and using a DNA repair reporter assay, this work shows that ATR is involved in DSB repair early in development, whereas ATM is essential in DSB repair in differentiated cells. We also show that HRR, a high fidelity form of repair, is used extensively by embryonic stem cells and HRR diminishes as cells differentiate. We also further defined the extent of NHEJ and the role of high fidelity NHEJ from the embryonic to differentiated state. These findings further the basic knowledge of repair fidelity in embryonic and mature human tissue. The data gives insight into what proteins maintain stem cell genomic stability and may be important to develop safe technologies for tissue engineering. Specifically, we have defined what DNA damage signaling pathways are used as embryologic cells progress to a mature, functional state.
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47

Lloyd, Kenneth P. "Understanding Human Erythrocyte Glucose Transporter (GLUT1) Mediated Glucose Transport Phenomena Through Structural Analysis." eScholarship@UMMS, 2018. https://escholarship.umassmed.edu/gsbs_diss/962.

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GLUT1-mediated, facilitated sugar transport is proposed to be an example of transport by a carrier that alternately presents exofacial (e2) and endofacial (e1) substrate binding sites, commonly referred to as the alternating access carrier model. This hypothesis is incompatible with observations of co-existent exo- and endofacial ligand binding sites, transport allostery, and e1 ligand (e.g. cytochalasin B) induced GLUT1 sugar occlusion. The fixed-site carrier model proposes co-existent, interacting e2 and e1 ligand binding sites but involves sugar translocation by geminate exchange through internal cavities. Demonstrations of membrane-resident dimeric and tetrameric GLUT1 and of e2, e1 and occluded GLUT conformations in GLUT crystals of monodisperse, detergent-solubilized proteins suggest a third model. Here, GLUT1 is an alternating access carrier but the transporter complex is a dimer of GLUT1 dimers, in which subunit interactions produce two e2 and two e1 conformers at any instant. The crystallographic structures in different conformations can be utilized to further understand the transport cycle, ligand binding behavior and complex kinetics observed in GLUT1. Specifically, the GLUT1 crystal structure and homology models based upon related major facilitator superfamily proteins were used in this study, to understand inhibitor binding, ligand binding induced GLUT1 transport allostery and the existence of helix packing/oligomerization motifs and glycine induced flexibility. These studies suggest that GLUT1 functions as an oligomeric allosteric carrier where cis-allostery is an intramolecular behavior and trans-allostery is an intermolecular behavior. Additionally, mutations of a dynamic glycine affect the turnover of the transporter while mutations to helix packing motifs affect affinity.
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48

Liu, Sheng. "NMR studies of RNA binding domains of human lysyl aminoacyl tRNA synthetase." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1353343207.

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49

Amunugama, Ravindra Bandara. "Insights into Regulation of Human RAD51 Nucleoprotein Filament Activity During Homologous Recombination." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1321984760.

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50

Peramo, Antonio. "Physical studies of glycosaminoglycans in relation to the adhesion properties of human cancer cells." [Tampa, Fla.] : University of South Florida, 2005. http://purl.fcla.edu/usf/dc/et/SFE0001414.

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