Дисертації: "MRI probe"

1

Wu, Faye Y. "Multi-probe robotic positioner for cryoablation in MRI." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/74953.

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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2012.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 116-118).
This thesis describes the design of a guidance device for faster and more accurate targeting of multiple probes during cryoablation and other percutaneous interventions performed in closed bore magnetic resonance (MR) imaging systems. The device is intended to be mounted onto a Siemens 110 mm MR loop coil that rests on the patient and contains a cable driven two-degree-of- freedom spherical mechanism that orientates the intervention probes about a remote center of motion located 15 mm above the skin entry point. A carriage, pulled by strong and low stretch cables, can position up to three intervention probes as it travels on a rotating hoop. Its motion is constrained by a custom designed roller bearing to minimize friction. A thumbscrew fastened latch allows a probe to be engaged in a guide that constrains the probe along a specific trajectory. The probe can also be disengaged from its track, freeing it to move with respiration and enabling the guide to be repositioned for another probe to be inserted. Compact MR compatible piezoelectric motors are used to actuate the system. A prototype was built from 3D printed ABS plastic as a proof of concept. Bench level evaluation demonstrated that each component of the device performs according to the design specifications. The device performance was characterized by analyzing still images taken before and after movement, which yielded sub-degree accuracy, sub-degree repeatability near vertical position, and an incremental step resolution of at least 0.5 degree. Upon further developments of the registration and calibration modules in 3D slicer to interface the robot with image data, evaluation of the device in MRI will be performed.
by Faye Y. Wu.
S.M.

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2

Khachaturian, Mark Haig 1979. "Advances in MRI to probe the functional and structural network of the macaque brain." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/44785.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, 2007.
Includes bibliographical references (leaves 95-103).
Diffusion MRI and fMRI have provided neuroscientists with non-invasive tools to probe the functional and structural network of the brain. Diffusion MRI is a neuroimaging technique capable of measuring the diffusion of water in neural tissue. It can reveal histological architecture irresolvable by conventional magnetic resonance imaging methods and has emerged as a powerful tool to investigate a wide range of neuropathologies. fMRI is a neuroimaging technique sensitive to hemodynamics which is indirectly linked to neural activity. Despite the applications of diffusion MRI and fMRI in basic and clinical neuroscience, the underlying biophysical mechanisms of cerebral diffusion and the hemodynamic response remain largely unknown. Also, these neurotechnqiues suffer from low SNR compared to conventional MRI. The challenges associated with the acquisition and interpretation of diffusion MRI and fMRI limit the application of these powerful non-invasive neuroimaging tools to study the functional and structural network of the brain. The purpose of this thesis is three fold; (1) improve the acquisition and reconstruction of the diffusion MRI and fMRI signals and (2) develop an MR-compatible cortical cooling system to reversibly deactivate cerebral glucose metabolism, and (3) apply the cortical cooling system to investigate the effect of cerebral glucose metabolism on cerebral diffusion and the hemodynamic response. First, I describe a novel phased array monkey coil capable of improving the resolution of diffusion MRI (4 fold increase) and fMRI (2 fold increase) in monkeys. Secondly, I present a novel reconstruction method to resolve complex white matter architecture which boosts the sampling efficiency of the diffusion MRI acquisition by 274-377%.
(cont.) Thirdly, I present a MR-compatible cortical cooling system capable of reversibly deactivating cerebral metabolism in monkeys. The cortical cooling system has been applied to study the effect of cerebral glucose metabolism on the cerebral diffusion of water. I use MR temperature maps to quantify the region and degree of deactivation (accuracy of ±1 °C in vivo). Then, I show that reversible deactivation of cerebral glucose metabolism affects the magnitude of cerebral diffusion (12-20%) but not the anisotropy. Finally, I apply the cortical cooling system to study the effect of reversibly deactivating cerebral glucose metabolism in V1 and its effect on the hemodynamic response in the visual system. Reversible deactivation of V1 decreased the hemodynamic response in visually driven regions upstream and downstream from V1. Compensatory effects were observed in V1 in both hemispheres and ipsilateral TEO with in 2 minutes of deactivation. Here I have described the tools to probe the functional and structural network of the macaque brain.
by Mark Haig Khachaturian.
Ph.D.

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3

Bortolotti, Laura. "Test of multiple sensor set-up for head motion characterization during MRI acquisition." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2017. http://amslaurea.unibo.it/14564/.

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L'Imaging a Risonanza Magnetica (MRI) è una tecnica di imaging ampiamente utilizzata in ambito medico. La ricerca in questo campo si sta focalizzando sullo sviluppo di scanner a campi molto intensi, come lo scanner a 7 T utilizzato in questa tesi. La risoluzione delle immagini e l'entità degli artefatti creati dai movimenti involontari del paziente sono proporzionali all'intensità di campo magnetico e diventano rilevanti ad intensità molto elevate. Le tecniche di Motion Correction, nota la cinetica dei movimenti, permettono di correggere queste distorsioni. La tesi è inserita in un progetto che ha come scopo la misura indiretta dei movimenti della testa durante la scansione MRI. In particolare, mi sono concentrata sui miglioramenti da apportare al set-up e sulla caratterizzazione dei tre strumenti usati per la misura: la telecamera di campo magnetico (Clip on Camera Head, CCH) formata da 16 sonde fissate in una struttura cilindrica posizionata attorno alla testa del paziente; la telecamera ottica (Moiré Phase Tracking System, MPT) che misura i movimenti tramite l'immagine di un marker olografico supportato da un bite tenuto nella bocca del volontario; il dispositivo (Physlog) dello scanner che fornisce i parametri fisiologici (respirazione e battito cardiaco). La comunicazione hardware degli strumenti avviene grazie a un segnale di trigger, di cui ho ottimizzato la sincronizzazione. Inoltre, abbiamo acquisito dataset completi di tre volontari, a diverse condizioni. I dati sono stati sincronizzati e analizzati, tramite analisi multivariate, per caratterizzare la risposta e la stabilità del sistema e la variabilità individuale dei pazienti. L'analisi ha permesso di capire meglio le proprietà dello strumento e ha consentito di associare le misure del campo magnetico al di fuori del cranio ai valori fisiologici dei volontari.

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4

FATEHBASHARZAD, PARISA. "Functionalized Concave Cube Gold Nanoparticles as Dual probe for Magnetic Resonance Imaging and Surface Enhanced Raman Scattering." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2020. http://hdl.handle.net/10281/273768.

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An innovative class of MRI CAs is represented by Gd-loaded gold nanoparticles. Differently from other nano-sized systems, the size, shape and chemical functionalization appear to affect the observed relaxation enhancement of water protons in their suspensions. The herein reported results shed more light on the determinants of the relaxation enhancement brought by Gd-loaded concave cube gold nanoparticles. It has been found that the role of the concave surface of these nanoparticles in the relaxivity is remarkable and it provides high contribution of second sphere water molecules. The specific shape of concave cube nanoparticles increases the relaxivity from 20.9 mM-1S-1 for spherical nanoparticles to 36.3 mM-1S-1. On the other hand, our studies prove that this special shape gold nanoparticles show high efficiency as a SERS probe. In the single-particle surface-enhanced Raman spectroscopy, the use of tunable plasmonic nanoparticles, having tipped surface structures, as being substrates revealed a highly feasible and promising approach to optimize SERS-based imaging and sensing applications. The concave cubic morphology has shown a remarkable plasmonic response, representing high sensitivity to the concavity degree. hence they can provide strong Raman signal which can be use in Raman imaging. Magnetic resonance and optical imaging are complementary techniques. By applying same nanoparticles as a contrast agent for both methods simultaniusly, screening total body with very clear identification become possible. This progress in imaging technologies associated with the advance of nanotechnology makes feasible the cancer detection and localization in its early stage.
An innovative class of MRI CAs is represented by Gd-loaded gold nanoparticles. Differently from other nano-sized systems, the size, shape and chemical functionalization appear to affect the observed relaxation enhancement of water protons in their suspensions. The herein reported results shed more light on the determinants of the relaxation enhancement brought by Gd-loaded concave cube gold nanoparticles. It has been found that the role of the concave surface of these nanoparticles in the relaxivity is remarkable and it provides high contribution of second sphere water molecules. The specific shape of concave cube nanoparticles increases the relaxivity from 20.9 mM-1S-1 for spherical nanoparticles to 36.3 mM-1S-1. On the other hand, our studies prove that this special shape gold nanoparticles show high efficiency as a SERS probe. In the single-particle surface-enhanced Raman spectroscopy, the use of tunable plasmonic nanoparticles, having tipped surface structures, as being substrates revealed a highly feasible and promising approach to optimize SERS-based imaging and sensing applications. The concave cubic morphology has shown a remarkable plasmonic response, representing high sensitivity to the concavity degree. hence they can provide strong Raman signal which can be use in Raman imaging. Magnetic resonance and optical imaging are complementary techniques. By applying same nanoparticles as a contrast agent for both methods simultaniusly, screening total body with very clear identification become possible. This progress in imaging technologies associated with the advance of nanotechnology makes feasible the cancer detection and localization in its early stage.

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5

Dalveren, Taylan. "A Study of Sensitivity Mapping Techniques for Multi-Channel MR Coils." University of Akron / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=akron1373403690.

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6

Hoang, Minh Dung. "Instrumentation and technical development for small animal micro-MRI studies at 7-Tesla." Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10284.

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L'IRM offre de nombreux avantages qui en font un outil d'imagerie attractif en comparaison avec d'autres modalités d'imagerie préclinique complémentaires telles que l'imagerie optique, la micro-tomographie aux rayons X (μ-scanner ou μ-CT), la micro- Tomographie par Emission de Positons (μ-TEP), l'échographie ultrasonore ou l'imagerie par photoluminescence et fluorescence. La nature tridimensionnelle de l'IRM sur une grande région d'intérêt en combinaison avec un contraste endogène tissulaire inégalé et qui est réalisable avec une résolution micrométrique en font un outil d'imagerie de haute importance en recherche biomédicale et plus particulièrement si l'on tient compte de la diversité des sources de contraste tissulaire possibles. Cependant, la principale limitation de lIRM reste sa sensibilité relativement faible et sa productivité réduite à un seul examen à la fois. L'objectif principal de ce travail de thèse a été le développement d'un ensemble de méthodologies en Imagerie par Résonance Magnétique (IRM), dédiées à des études sur des modèles expérimentaux. Une grande partie de nos efforts a été consacrée aux travaux suivants:-au développement et à l'optimisation d'instrumentations dédiées,-à la mise en place de protocoles IRM efficaces, L'ensemble de nos travaux a visé à surmonter tant les contraintes expérimentales rencontrées que celles liées a notre installation IRM. Particulièrement, l'amélioration d'images ex vivo et in vivo a été obtenu lors d'études précliniques utilisant des modèles animaux de la maladie d'Alzheimer. Les résultats obtenus ont été atteints logiquement et progressivement à partir d'expérimentations ex vivo et in vivo. La première étape a été consacré à l'amélioration de la composante clé en amont de la chaîne d'acquisition: la sonde RMN, également appelée résonateur radiofréquence (RF). Nous avons mené notre travail sur les trois aspects expérimentaux suivants: Conception et réalisation de sondes dédiées à l'imagerie in vivo de la souris tant pour l'étude du corps entier que pour l'IRM de la tête, - Développement et mise en oeuvre de sondes et d'instrumentation permettant l'acquisition simultanée de plusieurs cerveaux de souris ex vivo afin d'augmenter la productivité et l'efficacité de notre scanner, -Conception et réalisation d'un ensemble d'antennes spécialement adapté à l'imagerie directe de coupes de tissues histologiques de différentes tailles ainsi qu'a la mise au point des protocoles correspondants à la préparation des échantillons. Dans le chapitre d'introduction (chapitre 1), nous décrivons l'ensemble des outils et protocoles de caractérisation des sondes RMN conçues et réalisées pour les besoins de nos études. Cette caractérisation systématique effectuée aussi pour les antennes RMN commerciales du laboratoire a permis d'établir une étude comparative de leurs performances. Dans le chapitre 2, nous avons étudié des résonateurs RF homogènes avec une attention particulière pour les résonateurs de type cage d'oiseau. Après examen de leurs principaux avantages et des limites de chaque structure (passe-bas et passe-haut), nous détaillons les étapes pratiques nécessaires pour concevoir une antenne cage d'oiseau de type passe-haut dédiée à l'imagerie corps entier de souris. A titre d'exemple, nous présentons des séries d'images par IRM, illustrant l'excellente couverture RF et permettant l'identification (dans notre cas, de façon qualitative) des propriétés pharmacocinétiques d'agents de contraste nouvellement conçus [etc...]
The overarching goals of this work are to develop a set of magnetic resonance (MR) imaging methodologies to help study experimental models in the biomedical research. MRI offers a combination of attributes making it appealing as an imaging tool in biomedical research compared to other complementary preclinical imaging modalities such as optical imaging, micro-computed tomography, micro-Positron emission tomography or ultrasound bio-microscopy. The three-dimensional nature of MRI over a large region of interest and the unrivaled endogenous tissue contrast achievable in micrometric resolution make it a very important tool in biomedical research. This is particularly important with the expanding potentials of tissue contrast mechanism it can offer. However, one of the major limitations is its relative low sensitivity and slow throughput. A large part of our efforts have been dedicated to improve the MRI instrumentation and protocols to overcome some of these limitations around the existing MRI scanner in order help better screen both in vivo and ex vivo transgenic mouse models, -the most studied animal model of human diseases. This was assessed in our work with a particular focus on experimental models of Alzheimer’s disease.The description of our work and results build logically and incrementally from in vivo to ex vivo experimental set up starting with tackling the improvement of the first component of the acquisition chain: the MRI probe, also termed radiofrequency (RF) resonator or coil. The scope of the work expands from probes enabling in vivo whole mouse body to headonlyMRI as well as multiple ex vivo sample imaging in order to achieve higher throughput to dedicated instrumentation and set up for direct MR imaging of histology sections. In the introductory chapter (Chapter 1), we describe the set of tools and protocol that enable the characterization of each MRI probe used in our study. The systematic characterization for both existing commercial MRI coils and the one we develop in-house during this work allow for direct comparison of their performance. In chapter 2, we investigate the homogeneous RF resonators dedicated for in vivo studies with a particular focus on birdcage resonators. After examining the main advantages and limitations between low and high pass structures, we introduce the practical steps required to design a high pass birdcage structure aimed at whole mouse body imaging. Examples of serial imaging illustrate the excellent RF coverage of the whole mouse body in order to screen qualitatively the pharmacokinetic properties of newly designed contrast agents. For mouse head imaging, we aimed to increase the coil sensitivity relative to an existing commercial coil by reducing the geometry structure to closely fit the region of interest. The resulting gain in filling factor achieved without compromising the overall homogeneity of the RF field covering the brain region lead to 10% gain in Signal-to- Noise Ratio (SNR) or an equivalent 20% reduction in imaging time [etc...]

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7

Zimmeter, Katharina. "Développement de sondes IRM à base de peptides ou thiosemicarbazones pour la détection de cuivre(II) dans le milieu physiologique." Electronic Thesis or Diss., Strasbourg, 2024. http://www.theses.fr/2024STRAF046.

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Le cuivre échangeable, principalement lié à l'albumine sérique humaine (HSA) dans le sang, est un biomarqueur potentiel pour des maladies comme celles de Wilson et d’Alzheimer. Aucune méthode spécifique pour le détecter in vivo n'existant à ce jour, cette thèse présente des avancées dans la conception de sondes IRM (imagerie par résonance magnétique) responsives au CuII via deux approches : les agents de contraste (AC) de type q et τR, intégrant chacun un complexe de gadolinium et un ligand spécifique du CuII. Une partie de la thèse est dédiée à la synthèse et à l’étude de ligands adaptés à ces deux approches avec une affinité et une sélectivité suffisantes pour le CuII : des dérivés du motif peptidique ATCUN pour les sondes de type q et des α-pyridyl-thiosemicarbazones pour les sondes de type τR. L'autre partie porte sur leur association avec des agents IRM et leur caractérisation. Les sondes étudiées ont validé le principe des deux approches, bien que des optimisations restent nécessaires. Une relaxivité accrue de presque 400% a été observée pour l'AC de type q, DO3A-pyrGH, en présence de CuII, et une augmentation faible, mais notable pour les sondes τR en présence simultanée de CuII et de HSA
Exchangeable copper, which is primarily bound to human serum albumin (HSA) in the blood, is a potential biomarker for diseases such as Wilson's and Alzheimer's. To date, there is no specific method for its detection in vivo. This thesis presents progress in the design of CuII-responsive MRI (magnetic resonance imaging) probes through two approaches: q-based and τR-based contrast agents (CAs), each containing a gadolinium complex and a CuII-specific ligand. One part of the work is dedicated to the development of ligands adapted to these two approaches, with sufficient CuII-affinity and selectivity: derivatives of the peptidic ATCUN motif for q-based probes and α-pyridyl thiosemicarbazones for τR-based probes. The other part focuses on their incorporation into MRI CAs and their characterization. The probes studied proved the principle of both approaches, although optimizations are still needed. An increase in relaxivity of nearly 400% was observed for the q-based CA, DO3A-pyrGH, in the presence of CuII, and a small but notable increase for τR-type probes in the simultaneous presence of CuII and HSA

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8

Chalmers, Kirsten Hardie. "Fluorinated paramagnetic probes for 19-F and 1-H MRS/MRI." Thesis, Durham University, 2011. http://etheses.dur.ac.uk/879/.

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Novel CF3-labelled lanthanide(III) complexes have been synthesised for use as probes for 19-F and 1-H magnetic resonance spectroscopy and imaging. The syntheses and evaluation of two classes of fluorinated paramagnetic complexes are defined. Notably, the 19-F magnetic resonance relaxation processes for the complexes have been assessed, allowing for the analysis of the interplay between applied field, Ln(III) ion and rotational correlation time on relaxation properties. Strategies employed to enhance signal intensity are discussed, examining a number of different of fluorinated mono- and di-amide cyclen ligands. Systems incorporating phosphinate pendant arms are of particular interest, resulting in complexes with favourable isomer distributions, faster longitudinal relaxation rates and narrower linewidths. Finally, the synthesis of high molecular weight conjugates with paramagnetic fluorinated complexes is described. Three different classes of medium to high molecular adducts were considered, with the merits and limitations of each assessed. The desirable formation of one species in solution, ease of solubility and attractive 19F and 1H relaxometric properties render the chitosan conjugates promising candidates for future use as imaging probes.

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9

Leung, Ho-hon Arthur, and 梁浩瀚. "Lanthanide complexes for magnetic resonance imaging (MRI) contrast agents and fluorescence probes." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47752774.

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In this work, novel Gd(III) complexes endowed with non-steroidal anti-inflammatory drugs (NSAIDs) were synthesised and their targeting properties towards sites of inflammation were studied in U87 xenograft and rheumatoid arthritis animal models. The Tb(III) analogues were also synthesised and their photophysical properties were studied. Six new Gd(III) DO3A-amide complexes bearing different linkers, ethylenediamine (GdL1), hexamethylenediamine (GdL2), 2,2’-oxydiethylamine (GdL3), 4,7,10-trioxa-1,13-tridecanediamine (GdL4), trans-1,4-cyclohexanediamine (GdL5), and 1,4-phenylenediamine (GdL6) were incorporated to mefenamic acid (MA) moiety, a common NSAID. The syntheses, relaxometric properties by NMR techniques, hydration number determinations by luminescence lifetime measurements, lipophilicities by UV-Vis spectrometry, serum albumin binding properties by tryptophan emission-quenching experiments, cytotoxicities by MTT assay, cellular uptake properties; MRI scans on U87 sxenograft and rheumatoid arthritis animal models, and biodistributions of these new complexes were discussed. GdL1-L6 possess one bound water molecule and GdL2-L5 show higher relaxivities than Gd-DOTA (4.21 mM?1s?1, 300 MHz, 25oC), a clinically used MRI contrast agent (CA). The relaxivities at 300 and 400 MHz respectively at 25oC are in the descending order of GdL4 (5.70 and 4.87 mM?1?1) > GdL3 (4.94 and 4.07 mM?1s?1) > GdL2 (4.60 and 4.07 mM?1s?1) > GdL5 (4.41 and 4.12 mM?1s?1) > GdL6 (3.98 and 3.31 mM?1s?1) > GdL1 (3.96 and 3.56 mM?1s?1). GdL1-L5 show low cytotoxicities towards HeLa cells at 1000 μM. The MRI scans of GdL1-L6 on U87 xenograft show strong intensity boost immediately after administration. The intensity enhancements persist for more than 90 mins and complete clearances are found after 24 h post-administration. Their MRI scans on arthritis model also show prolonged retention. It is concluded that the retention is related to the targeting on inflammatory mediators of the complexes. All complexes show superior retention and intensity enhancements in kidney, liver, tumour and arthritis joint than Gd-DOTA. GdL1-L6 are therefore potential candidates as universal MRI CAs. Three new Gd(III) DO3A-amide complexes bearing respectively benzoic acid (GdL7), salicylic acid (GdL8), and methylated salicylic acid (GdL9), one known Gd(III) DTPA-bissalicylic acid (GdL10) complex and one new Gd(III) DTPA-bismethylated salicylic acid (GdL11) were synthesised and investigated. Their syntheses, relaxivities, hydration numbers, pH dependent photophysical properties, cytotoxicities, cellular uptake properties and MRI scans on arthritis rat model were discussed. All GaL7-L11 possess one bound water molecule and show lower relaxivities than Gd-DOTA. The relaxivities at 300 MHz at 25oC are in the descending order of GdL10 (3.64 mM?1s?1) > GdL9 (3.53 mM?1s?1) > GdL11 (2.69 mM?1s?1) > GdL8 (2.10 mM?1s?1) > GdL7 (1.99 mM?1s?1). Their Tb(III) analogue (TbL7-L11) show pH dependent UV-Vis and photoluminescence spectra which are consequences of protonation or deprotonation of the carboxylic acid, hydroxyl and amide groups. It is concluded that the pH change alters energy transfer efficiency and the ligand triplet energy level. GdL7-L11 show low cytotoxicities in MTT assay. Specifically, GdL8 is examined on arthritis rat model to give a comparable intensity at the arthritis joint to Gd-DOTA but having a longer retention time. LnL8 has therefore demonstrated its potential as both a MRI CA to target inflammation sites and a pH dependent luminescence probe.
published_or_final_version
Chemistry
Doctoral
Doctor of Philosophy

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10

Adhitiyawarman. "Pyridyltriazole-containing compounds as sinc-responsive MRI contrast agents and luminescence probes." Thesis, University of Leicester, 2018. http://hdl.handle.net/2381/43041.

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Magnetic resonance imaging (MRI) is a versatile imaging modality in modern clinical applications. The use of MRI started to be more powerful since the invention of smart contrast agents, which can selectively respond to a specific stimulus such as a metal ion. This study was focused on GdDO3A-based complexes designed to be zinc-responsive MRI contrast agents by exploiting a new pyridyltriazole moiety as an active arm for a zinc(II) chelator. This active arm was designed to have a coordination displacement ability to give a switch-on MR signal. A series of pyridyltriazole containing compounds were synthesized and examined sequentially. The primary compound containing pyrydyltriazole LnC2 (q = 0) exhibited no response towards zinc(II). Modification by changing the binding orientation of the pyridyltriazole, LnC4 had reduced the steric hindrance allowing one coordination site for water (q = 1); however, it still did not show any change in signal to the presence of zinc(II). Increasing the distance between the active arm and the lanthanide centre via additional carbon linkers (LnC5 and LnC6) gave complexes an open-structure (q = 2). This structure also had low affinity toward zinc(II) and did not provide a switch on response to the MR signal. Addition of a hydroxyl functional group to the pyridyltriazole (LnC7) did not change its coordination mode (q = 2). Incorporation of a carboxylic acid group (LnC8) provided coordination to give a q = 1 complex. Furthermore, it exhibited coordination displacement in response to zinc(II), by modulating its hydration number to give a "switch on" MR signal; the relaxivity increased by 30% from 6.5 to 8.6 mM-1s-1 as a response to one equivalent of zinc(II). Elongation of the linker by replacing it with the tri- and tetra-ethylene glycol (LnC9 and LnC10) changed their relaxivity in response to zinc(II) which was assumed to be a result of a different coordination mode. A series of emissive lanthanide complexes with high fluorescence quantum yields were also synthesized as luminescence probes namely; a click-ready complex (TbC1), water soluble complexes (TbC2a, TbC2b), a polymerizable complex (TbC2c), a dimer complex (TbC2-dimer), tridentate ligand complexes (Tb/Eu(27)3, Tb/Eu(32b)3) and a complex potential for dual-modal fluorescence/MR imaging probe (Tb(GdC8)3).

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11

FORGACS, Attila. "Thermodynamic, kinetic and NMR relaxometric studies of Mn(II) complexes as MRI probes." Doctoral thesis, Università del Piemonte Orientale, 2017. http://hdl.handle.net/11579/86962.

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The main goal of this thesis is the characterization in aqueous solutions of new Mn(II) complexes as MRI probes. Our investigation included thermodynamic, kinetic and detailed 1H and 17O NMR relaxometric measurements. We have taken into account Mn-complexes belonging to two different main types of structural units. One encompasses the Mn(II) complexes containing the pentadentate coordinating units 6,6-((methylazanediyl)bis(methylene))dipicolinic acid. We considered several derivatives of the monomeric DPAMA ligand, including mono-, bi- and trinuclear bis-hydrated complexes (Chapter 4). In addition, we investigated a number of derivatives featuring different side arms and a couple of lipophilic derivatives (Chapter 5). All these complexes represent a fairly homogeneous series that has allowed us to obtain useful information on the relationship between the molecular structure, the thermodynamic stability and the relaxation parameters. The other class of complexes are those containing the macrocyclic unit cyclen and two coordinating pendant arms. These macrocyclic derivatives have been studied in detail, considering the chemical nature of the pendant arms, their relative position (cis/trans), the possible presence of isomers with different states of hydration, the kinetic and thermodynamic stability of the complexes and their relaxometric properties (Chapter 6). The synthesis of two novel derivatives bearing hydrophobic pendant groups enabled the investigation of the binding association with human serum albumin (Chapter 7). The global set of experimental results has allowed us to deepen our understanding of the chemistry of Mn(II) complexes as potential MRI probes. We are confident that the new information gained will help in the future design and development of more effective and safer MRI contrast enhancing agents.

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12

Jülg, Peter [Verfasser], and Roland [Akademischer Betreuer] Zengerle. "Microfluidic automation of multiplex mediator probe PCR for leukaemia MRD monitoring." Freiburg : Universität, 2020. http://d-nb.info/121641758X/34.

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13

Li, Zizhen. "Synthesizing Multimodal Imaging Probes and Their Application in Non-Invasive Axonal Tracing by Magnetic Resonance Imaging." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/34414.

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Imaging techniques have become much more in demand in modern medicine, especially in fields of disease prognosis, diagnosis and therapeutics. This is because a better understanding of different diseases, characteristics of each patient and further optimizing treatment planning, are all enhanced by advanced imaging techniques. Since each imaging modality has its own merits and intrinsic limitations, combining two or more complementary imaging modalities has become an interesting research area. In this study, gadolinium (Gd3+) doped CdTe quantum dots (QDs) were synthesized and used as multimodal imaging probes of two highly complementary imaging modalities: optical imaging and magnetic resonance imaging. The new imaging probes were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), UV-vis absorbance spectra, fluorescence spectra (FL) and magnetic resonance imaging (MRI). The optical / MRI imaging probes were further functionalized by conjugating with the axonal tracer dextran amine (10 kDa) for non-invasive axonal tracing observations. Biocompatibility and MRI contrast effect of prepared multimodal imaging probes were investigated by in vitro cell experiments and MRI scanner. Ultimately, it is hoped that this imaging probe will help us better understand the regeneration mechanisms in real time without sacrificing animals at intervening time-points.

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14

Lingott, Jana. "Untersuchungen zur Aufnahme und Verteilung von gadoliniumbasierten Kontrastmitteln in biologischen Proben mittels Laserablation mit induktiv gekoppelter Plasma-Massenspektrometrie." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät, 2016. http://dx.doi.org/10.18452/17412.

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Gadoliumbasierte Kontrastmittel werden in der Magnetresonanztomographie verwendet und gelangen nach der Exkretion durch behandelte Patienten in Oberflächengewässer, da sie von Klärwerken nur unzureichend entfernt werden. Das Verhalten der Kontrastmittel in der Umwelt und deren Wechselwirkung mit Organismen wurde in dieser Arbeit aufgrund der Toxizität des freien Gd-Ions und der damit verbundenen möglichen Gefahren, wie der Anreicherung in der menschlichen Nahrungskette, näher untersucht. Die bildgebenden elementanalytischen Methoden Laserablation mit induktiv gekoppelter Plasmamassenspektrometrie (LA-ICP-MS) und Röntgenfluoreszenzanalyse mit Synchrotronstrahlung (SRXRF) wurden genutzt, um verschiedene biologische Systeme hinsichtlich ihrer Aufnahme, Verteilung und Abgabe von Gd-basierten Kontrastmitteln zu untersuchen. Zuvor wurden beide Methoden für diese Anwendung analytisch charakterisiert und verglichen. Die Nachweisgrenzen von Gadolinium wurden mittels LA-ICP-MS (0.78 pg) und SRXRF (89 pg) unter jeweils optimierten Bedingungen durch die Kalibrierung über Rückstände eingetrockneter Elementstandardtropfen bestimmt. Anhand von Fadenalgen konnte die Aufnahme und Abgabe der Gd-basierten Kontrastmittel gezeigt werden. Die Abhängigkeit von der Konzentration des Kontrastmittels in der Expositionslösung und die Unabhängigkeit der zeitlichen Aufnahme innerhalb eines Zeitraums von 1-7 Tagen wurden an Wasserlinsen studiert. Gadolinium konnte in einem Kresseblatt quantifiziert werden. Die Verifizierung der LA-ICP-MS-Ergebnisse erfolgte mit der SRXRF und der ICP-MS nach Aufschluss. Auch die Aufnahme und Abgabe von Gd in Wasserflöhen wurde beobachtet. Die Lokalisierung des Gds wurde mittels 3D µ-Computertomographie durch den Vergleich mit einem unbelasteten Wasserfloh aufgeklärt. In allen Untersuchungen wurde Gadolinium in den exponierten Modellorganismen nachgewiesen, woraus geschlussfolgert werden kann, dass die Kontrastmittel aus der Umgebung aufgenommen werden.
Gadolinium based contrast agents are used for magnetic resonance imaging. After their excretion by medicated patients they reach surface water passing waste water treat-ment plants where they are not removed sufficiently. The behavior of the contrast agents in the environment and the interaction with organisms was investigated in this work due to the toxicity of the free Gd3+ ion and the associated risks, such as accumulation in the human food chain. In this work, the two elemental analytical imaging methods laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and synchrotron radiation X-ray fluorescence analysis (SRXRF) have been used to investigate the uptake, distribution, and excretion of Gd-based contrast agents by various biological systems. Both methods were analytically characterized and compared for this application. The detection limits of gadolinium were determined under optimized conditions by LA-ICP-MS and SRXRF. With calibration by remains of dried elemental standard droplets detection limits of 0.78 pg absolute amount of gadolinium (LA-ICP-MS), respectively 89 pg (SRXRF) were reached. Based on filamentous algae as water plants the uptake and the excretion of Gd-based contrast agents were revealed. The dependence on concentration of the contrast agent in the exposition solution and the independence of temporal uptake within one to seven days were studied for duckweed. By LA-ICP-MS gadolinium was quantified in a leaf of cress plant. The verification of the results was performed by SRXRF and ICP-MS after digestion. Furthermore, the uptake and distribution of Gd-based contrast agents in higher organisms (water flea) were observed. The exact location of gadolinium was resolved by three-dimensional μ-computed tomography by the comparison of an exposed with a Gd-free water flea. In all studies, gadolinium was detected in the investigated exposed model organisms. It can be concluded that the contrast agents were taken from the environment.

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15

Llewellyn, P. L. "The MFI-type zeolites : an examination of the phenomena observed on adsorption of simple probe molecules." Thesis, Brunel University, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306326.

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16

Ding, Ning. "Development and evaluation of cancer-targeted pre-operative and intra-operative dual-imaging probes based on metal nanoparticles." Kyoto University, 2019. http://hdl.handle.net/2433/242668.

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17

Miyake, Yuka. "Synthesis and Functional Evaluation of Novel Chiral Dendrimer-triamine-coordinated Gd-MRI Contrast Agents That Can Act as Molecular Probes." 京都大学 (Kyoto University), 2016. http://hdl.handle.net/2433/215564.

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18

Reid, Emma. "An examination of ischaemic penumbra in the spontaneously hypertensive stroke-prone rat (SHRSP) using the MRI perfusion-diffusion mismatch model." Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3254/.

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Stroke accounts for 9% of all deaths worldwide and is a major cause of severe disability (Donnan et al, 2008). Following ischaemic stroke, the penumbra represents tissue which is hypoperfused and functionally impaired but is not yet irreversibly damaged. However, the penumbra has a finite lifespan and will proceed to infarction in the absence of swift reperfusion. Therefore, the identification and potential salvage of penumbral tissue in acute ischaemic stroke is the ultimate goal for both clinicians and experimental stroke researchers. Positron emission tomography (PET) is the ‘gold standard’ imaging modality for identifying the penumbra, but the complex logistics of PET limit its widespread use. Magnetic Resonance Imaging (MRI) is widely used for penumbra imaging in both clinical and pre-clinical research. The MRI perfusion-diffusion mismatch model provides an approximation of the penumbra, where diffusion weighted imaging (DWI) identifies the core of ischaemic injury and perfusion weighted imaging (PWI) reveals the perfusion deficit. The mismatch between the DWI and PWI provides a measure of penumbral tissue. However, there is no consensus on the perfusion and diffusion thresholds used to identify mismatch tissue in clinical and preclinical stroke research. Furthermore, in rodent stroke models differences in the evolution of ischaemic injury between strains may limit the use of a single set of threshold values. Therefore, the first aim of this thesis was to establish strain specific perfusion and diffusion thresholds to compare penumbra volume in the clinically relevant spontaneously hypertensive stroke-prone rat (SHRSP) and the normotensive control strain, Wistar-Kyoto (WKY) using 3 different methods. The SHRSP strain is characterised by the progressive development of severe hypertension which is followed by a tendency to spontaneous stroke and an increased sensitivity to experimental stroke. Experimental stroke was induced by permanent middle cerebral artery occlusion (MCAO) by the intraluminal filament method. DWI and PWI were obtained every hour from 1-4 hours post-MCAO. Strain-specific diffusion and perfusion thresholds were established from final infarct at 24 hours post-MCAO, as defined by T2 weighted imaging. The calculated ADC thresholds were comparable between the strains but the absolute perfusion threshold was significantly higher in SHRSP compared to WKY. This may be indicative of an increased sensitivity to ischaemia in the hypertensive strain. Furthermore, application of these thresholds to the acute MRI data revealed that the volume of ischaemic injury and the perfusion deficit were significantly larger in SHRSP compared to WKY and this was also reflected in the significantly larger infarct volume observed in SHRSP at 24 hours post-MCAO. Interestingly, there was evidence of a temporal increase in the volume of the perfusion deficit in SHRSP and WKY. This may indicate that there is a progressive failure of collateral blood supply in both strains following stroke. Penumbra volume was then assessed in SHRSP and WKY rats using the mismatch method and also indirectly by examining the growth of the volume of ADC derived ischaemic injury. Mismatch volume was determined by arithmetic subtraction of the volume of ischaemic injury from the volume of perfusion deficit (volumetric method) and also by manual delineation of mismatch on each of 6 coronal slices (spatial method). There was a limited volume of mismatch tissue in either strain from as early as 1 hour post-MCAO and the volumetric method generated smaller mismatch volumes than the spatial mismatch method. Mismatch volume was comparable in SHRSP and WKY from 1-4 hours post-MCAO. Penumbra was also determined retrospectively by subtracting the volume of ischaemic injury at each time point from final infarct volume. Using this method, penumbra volume was significantly larger in WKY compared to SHRSP at 30 minutes post-MCAO but penumbra volume was comparable at all later time points. This suggests that there is reduced potential for tissue salvage in SHRSP compared to WKY within the first hour following MCAO but from 1 hour onwards, there is limited potential for penumbra salvage in both strains. In addition, there was evidence of ‘negative’ mismatch tissue in SHRSP and WKY rats, where the ADC derived lesion expanded beyond the boundary of the perfusion deficit. The volume of negative mismatch tissue was comparable between the strains and was persistent over the 4 hour time course. This phenomenon may arise from the spread of toxic mediators from the ischaemic core. Oxidative stress is a major mediator of cellular injury following ischaemic stroke and reactive oxygen species, like superoxide, have multiple deleterious effects on the components of the neurovascular unit. It is well established that NADPH oxidase is the principal source of superoxide in acute ischaemic stroke and is therefore a target for potential neuroprotective strategies (Moskowitz et al, 2010). Consequently, the second aim of this thesis was to evaluate the potential neuroprotective effect of NADPH oxidase inhibition with low and high dose apocynin following permanent or transient ischaemia. Rats were administered apocynin at a dose of 5mg/kg or 30mg/kg or vehicle, at 5 minutes post-MCAO. Apocynin treatment had no significant effect on infarct volume or functional outcome at 24 hours following permanent MCAO in WKY rats. However, both low and high dose apocynin treatment significantly reduced infarct volume at 72 hours post-MCAO by 60% following 1 hour of ischaemia in Sprague-Dawley rats. Furthermore, functional outcome was improved in the low dose apocynin treated group, although this did not reach the level of statistical significance. On the basis of these results, low dose apocynin treatment was evaluated in SHRSP rats following 1 hour of ischaemia. However, apocynin treatment had no effect on the acute evolution of ischaemic injury and failed to improve stroke outcome, where the mortality rate was high in both the apocynin treated and the vehicle treated group. The conflicting effects of apocynin may be attributable to a differential expression of NADPH oxidase subunits in normotensive and hypertensive rat strains. These findings may also explain the failure of neuroprotective drugs to translate from bench to bedside, as therapies which are neuroprotective in young healthy animals may not demonstrate the same efficacy in animal models with stroke co-morbidities. Therefore, potential therapeutic strategies should be extensively evaluated in animal models with stroke risk factors before proceeding to clinical trial.

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19

Proba, Patrick [Verfasser]. "Nosokomiale Infektionen, Antibiotikaeinsatz und multiresistente Erreger (MRE) in Langzeitpflegeeinrichtungen im Rhein-Main-Gebiet / Patrick Proba." Gießen : Universitätsbibliothek, 2017. http://d-nb.info/1124387358/34.

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20

Barc´, Bartlomiej. "Hydrated clusters of nucleic acid bases in supersonic beams probed by multiphoton ionization (MPI) mass spectrometry." Thesis, Open University, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.576663.

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In the present thesis clusters of nucleic acid bases and water are used as model systems of cellular DNA to investigate UV induced radiation damage in the gas phase. A new experimental system has been designed and commissioned to perform rnultiphoton ionization experiments on hydrogen bonded clusters of the nucleic acid bases: adenine, thymine and uracil, as well as on the related chromciphores: 5-fluorouracil and hypoxanthine. As the result of pulsed nanosecond laser irradiation in the wavelength range of 220-230 nm. cluster, monomer and fragment ions were detected using a time-of-flight mass spectrometer. Possible multiphoton ionization pathways of clustered and isolated molecules including the role played by short (singlet) and long-lived (triplet) excited states as well as excited state tautomeric transitions are discussed. Signal intensities as a function of laser pulse fluence were measured. The slope of a logarithmic plot of the signal intensity versus fluence yields the so-called 'photon order' and provides information on the number of photons leading to the production of cluster, monomer and fragment ions. The results indicate two-photon ionization for uracil and thymine in dry molecular beams (i.e. photon orders equal to 1.9±0.2 and 1.4±O.1, respectively). An interesting result in the form of photon order equal to 3.0±0.5 has been measured for adenine in a dry molecular beam irradiated with an unfocused laser beam. This suggests a three photon ionization process, however further experimental work is required in order to exclude factors related to stability of the laser beam spatial profile. Hydrated cluster ions with up to 7 water molecules attached to a single uracil and 4 water molecules attached to adenine were unambiguously identified after adding water vapour to the molecular beam source. A maximum of 7 water molecules attached to adenine-uracil base pairs were detected. Possible ionization pathways of such hydrated clusters mediated by excited states tautomeric transitions are discussed. On the basis of photon orders measured under hydrated conditions, it is proposed that sequential MPI processes with 2, 3, and 4 photon absorption lead to production of cluster ions, cluster fragment ions (including protonated monomers), and molecular fragment ions, respectively.

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21

Kolanowski, Jacek Lukasz. "Bispidine-iron (II) complexes as a novel platform for the design of magentogenic probes." Phd thesis, Ecole normale supérieure de lyon - ENS LYON, 2013. http://tel.archives-ouvertes.fr/tel-01059820.

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This work concerns the development and characterization of molecular probes that respond to a chemical analyte in a liquid sample by turning from a diamagnetic to a paramagnetic state (off-on mode).With the aim of designing these tools, we focused on iron(II) chelates of bicyclic bispidines as they promised, among others, sufficient probe stability, even in competitive media like water. This manuscript describes new robust synthetic protocols for their large-scale preparation. Synthesized bispidine-iron(II) complexes were thoroughly characterized in solution (1D/2D NMR, MS, UV-Vis, CV) and in the solid state (X-ray and SQUID). In particular, I report here the first diamagnetic, low spin examples thereof, as well as pairs of structurally related diamagnetic-paramagnetic chelates. It now enables the design of responsive probes for various (bio)-chemical targets (including enzyme biomarkers), accessible by one-step functionalization of a key synthetic intermediate with suitable trigger moieties. The first two such probes are described herein, which respond to the presence of a particular kind of anion or a change in the pH.In addition in the course of my work, the unprecedented radioactive iron(II) (Fe-59 isotope) complex of a model water-insoluble ligand was prepared and used in an initial biodistribution study in mice. This original protocol can now be directly adapted to virtually all iron(II)-based probe candidates. Furthermore, the relaxivity data obtained for model MRI-silent and MRI-active chelates, in conjunction with the in vivo behavior of the active form in mice, bode well for a creation of an MRI probe functioning in a true off-on mode.Methodologies and molecular designs described herein enable the development of solution-operating magnetogenic molecular probes, which until now have not been synthesized. The availability of such tools would open up numerous perspectives for technological, environmental and biomedical applications.

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22

Godart, Estelle. "Synthèses de cryptophanes hydrosolubles adaptés à l’encapsulation du xénon, et d’hémicryptophanes fonctionnalisés pour la complexation de lanthanides (III), en vue d’applications en imagerie médicale." Thesis, Lyon, 2017. http://www.theses.fr/2017LYSEN041/document.

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Ce manuscrit détaille l’ensemble des travaux de recherches effectués au cours de mes trois années de thèse. Après un chapitre général portant sur les principes de la chimie supramoléculaire, et quelques unes de ces applications, nous nous sommes focalisés sur l’utilisation des propriétés de molécules cages (cryptophanes et hémicryptophanes) pour aller vers la conception de sondes en imagerie médicale. Nous évoquons successivement le cheminement vers la synthèse d’un hémicryptophane apte à complexer le Gadolinium(III), pour une utilisation en tant qu’agent de contraste en IRM du proton, puis à l’élaboration de cryptophanes hydrosolubles adaptés à la RMN et l’IRM du 129Xe. Cette thèse s’achève sur la synthèse d’un nouvel hémicryptophane fonctionnalisé pour former des complexes avec le Terbium(III) et l’Europium(III) dont les propriétés de fluorescence sont prometteuses
This book details all the research work that has been done during three years of Ph-D. After a chapter dedicated to the general principles of supramolecular chemistry, and some of its applications, we focalise on the use of cage-shapes molecules (cryptophanes and hemicrypto-phanes) in order to build probes for biological imaging. We successively mention the way toward the synthesis of a hemicryptophane able to complex Gadolinium(III), to use it it as a proton-MRI contrast agent, then toward the elaboration of hydrosoluble cryptophanes adapted to 129Xe NMR and MRI. This PhD manuscript ends with the synthesis of a new hemicryptophane functionnalized to form complexes with Terbium(III) and Europium(III), whose fluorescence properties are promising

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23

Freitas, Paula M?ssnich de. "A regula??o do MIR-10B e do MIR-603 pelas prote?nas HMGA tem papel cr?tico na transforma??o de c?lulas da tire?ide." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2012. http://tede2.pucrs.br/tede2/handle/tede/2685.

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HMGA overexpression, other than to be a feature of human malignant neoplasias, has a causal role in cell transformation. Then, the aim of our study has been to investigate the miRNAs regulated by the HMGA proteins in the process of cell transformation analyzing the miRNA expression profile of v-ras-ki oncogenetransformed thyroid cells expressing or not HMGA proteins. We demonstrate that, among the miRNAs regulated by cell transformation, there are miR-10b, miR-21, miR-125b, miR-221 and miR-222 that are positively and miR-34a and miR-603 that are negatively regulated, by HMGA expression. Then, we focused our attention on the miR-10b and miR-603 whose expression appeared to be dependent on the presence of the HMGA proteins also in other cell systems. We found that miR-10b is able to target the PTEN gene, whereas miR-603 targets CCND1 and CCND2 genes. Moreover, functional studies showed that miR-10b and miR-603 were able to regulate positively and negatively, respectively, cell proliferation and migration suggesting a role of their deregulation in thyroid cell transformation.
A super express?o das prote?nas HMGA (High Mobility Group A) al?m de ser uma caracter?stica de neoplasias humanas malignas tem uma papel essencial na transforma??o celular. O objetivo deste trabalho foi identificar os miRNAs associados as prote?nas HMGA no processo de transforma??o celular, analisando perfil de express?o de microRNAs (miRNAs) em c?lulas da tire?ide transformadas com o oncogene v-ras-ki, expressando ou n?o as prote?nas HMGA. Entre os miRNAs regulados pela transforma??o celular, observou-se que o miR-10b, miR-21, miR- 125b, miR-221 e o miR-222 s?o positivamente e o miR-34a and miR-603 s?o negativamente regulados pela express?o das prote?nas HMGA. Assim focamos nossa atencao no miR-10b e no miR-603 cuja express?o parece ser dependente da presen?a das prote?nas HMGA tamb?m em outros sistemas celulares. Igualmente, foi demonstrado que CCND1 e CCND2 s?o alvos do miR-603, e PTEN alvo do miR- 10b. Al?m disso, os estudos funcionais demonstraram que o miR-10b e o miR-603 s?o capazes de regular positiva e negativamente a prolifera??o celular e migra??o, sugerindo um papel da sua desregula??o na transforma??o de c?lulas da tire?ide.

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24

Dattola, Tiziano. "Caratterizzazione mediante tecniche di imaging a risonanza magnetica nucleare dello spiazzamento di fluidi non miscibili nei mezzi porosi." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2020. http://amslaurea.unibo.it/20013/.

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L’attività condotta in questo lavoro di tesi è stata rivolta alla caratterizzazione delle proprietà petrofisiche di campioni di roccia, mediante tecniche di imaging a risonanza magnetica (MRI). In particolare il lavoro si è focalizzato sullo studio dello spiazzamento di fluidi non miscibili in campioni di roccia per caratterizzarne le proprietà intrinseche, quale la permeabilità, e al contempo verificare il comportamento del fluido all’interno del mezzo poroso. Le prove di laboratorio classiche, sono state eseguite tramite cella triassiale collegata ad un apparato di flussaggio per determinare le proprietà di trasporto della roccia. Tale apparato, ha permesso anche l’applicazione di metodi a risonanza magnetica nucleare (NMR) per ottenere in modo non invasivo e non distruttivo indicazioni di carattere qualitativo sui mezzi porosi esaminati, attraverso la realizzazione di immagini create col tomografo Artoscan Esaote. Per analizzare le immagini acquisite, in modo anche quantitativo, è stato necessario utilizzare diversi software sviluppati ad hoc. In particolare si menziona il software ARTS per la comparazione quantitativa delle immagini e CorrelaIMG per misurare in modo oggettivo, l’avanzamento del fronte di spiazzamento. Tali analisi,sono state completate su due campioni rocciosi di differente litotipo. L’avanzamento del fronte, per ambedue i campioni, è risultato essere ben descrivibile mediante un semplice modello esponenziale. Il valore dei parametri del modello sono stati valutati mediante regressione non lineare col risolutore Solver di Excel®. I risultati ottenuti mostrano una piena corrispondenza fra le misure classiche e i risultati ottenuti per mezzo delle immagini MRI. Pertanto, il lavoro di tesi riconferma,come la tecnica MRI sia un ottimo strumento, per valutare le caratteristiche di un mezzo poroso sottoposto a flussaggio, specialmente quando si renda indispensabile minimizzare le alterazioni subite dal campione come conseguenza della tecnica adottata.

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25

Nitin, Nitin. "Optical and MR Molecular Imaging Probes and Peptide-based Cellular Delivery for RNA Detection in Living Cells." Diss., Available online, Georgia Institute of Technology, 2005, 2005. http://etd.gatech.edu/theses/available/etd-08102005-120350/.

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Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2006.
Dr. X. Hu, Committee Member ; Dr. Al Merrill, Committee Member ; Dr. Niren Murthy, Committee Member ; Dr. Gang Bao, Committee Chair ; Dr. Nicholas Hud, Committee Member. Includes bibliographical references.

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26

RIGGIO, VINCENZO ANDREA. "Valutazione di produzione di biogas da prove sperimentali di digestione anaerobica da differenti mix di scarti da biomassa agricola." Doctoral thesis, Politecnico di Torino, 2010. http://hdl.handle.net/11583/2500106.

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Nella sperimentazione si sono valutati alcuni aspetti tecnici e tecnologici relativi alla produzione di energia, in forma di biogas, ottenuta dalla digestione anaerobica di scarti provenienti principalmente da produzioni agricole – zootecniche. Questa tecnica è ben nota e utilizzata da diversi anni, ma a fronte di un crescente interesse da parte delle autorità locali, contrappone una certa stazionarietà nella risoluzione dei principali problemi che la accompagnano. Agendo su un territorio locale che fa dell’agricoltura, e della zootecnia, uno dei comparti produttivi maggiormente soggetto a rischi economici, questo studio fornisce alcune risposte pratiche, e attuabili, agli operatori locali volto sia a migliorare la produzione di metano da reattori esistenti, sia nella realizzazione di nuovi. La possibilità di risolvere problemi pratici come l’abbattimento dei cattivi odori e la gestione dei reflui zootecnici, a fronte di tempi di ritorno degli investimenti inferiori ai dieci anni, rende agricoltori e allevatori molto ben disposti verso soluzioni di questo tipo. L’obiettivo è stato quello di realizzare un digestore anaerobico sperimentale di medie dimensioni, e utilizzarlo per effettuare una serie di prove volte a testare le rese di differenti tipologie di mix. Il presente lavoro si articola in cinque capitoli; il primo affronta le tematiche relative al recupero di energia dalla biomassa. In particolare sono illustrati i molteplici benefici ambientali ed economici, e le diverse tecnologie legate alla digestione anaerobica. Quest’ultimo argomento viene esplicitato nel dettaglio nel capitolo successivo, dove si riportano i processi tecnologici che permettono la produzione di metano da biomassa organica. Nel terzo capitolo viene descritta la filiera del biogas, valutando la scelta della biomassa, e le principali linee di trattamento aziendali. Inoltre si approfondiscono le modalità di pretrattamento e successivo impiego del biogas, oltre al corretto utilizzo agronomico del digestato, in linea con la normativa vigente. Nel quarto capitolo si descrivono gli strumenti operativi impiegati per la realizzazione del presente lavoro: nella prima parte è presente un’approfondita descrizione del digestore anaerobico sperimentale, mentre nella successiva viene affrontato lo sviluppo degli strumenti informatici impiegati per l’analisi dei dati post-prova. Infine viene illustrato lo svolgimento dei test sui vari mix utilizzati: ad una prima fase di calibrazione con l’impiego di letame suino, è stata testata una miscela di letame bovino e siero di latte. Successivamente dopo una serie di modifiche tecniche all’impianto, sono stati effettuati dei test conoscitivi sul potenziale metanigeno di un mix di letame bovino e insilato di mais. Grazie ai risultati ottenuti si è deciso di effettuare delle prove sulla stessa miscela, ma a carico organico variabile. Seguono le considerazioni finali, e le prospettive future.

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MONTE, Zenaide Severina do. "Pirimidinas: de potenciais fármacos a marcadores fluorescentes." Universidade Federal de Pernambuco, 2016. https://repositorio.ufpe.br/handle/123456789/19607.

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Compostos heterocíclicos do tipo pirimidina são conhecidos pela enorme riqueza de seus potenciais biológicos e farmacológicos. Numerosas reações de heterociclização que permitem a obtenção dessa classe de compostos são igualmente reconhecidas, devido à diversidade de atividades e do conhecimento prévio de inúmeras viabilidades sintéticas. As modificações estruturais obtidas na busca da otimização das rotas sintéticas conferem às novas moléculas diferentes propriedades físicas e alteram a reatividade das moléculas, acarretando em mudanças na distribuição nas células e nos tecidos. Essas discretas modificações estruturais podem revelar efeitos biológicos que haviam estado latentes ou eclipsados pelos efeitos colaterais do composto protótipo. Sendo assim, o presente trabalho apresenta a síntese por método convencional dos derivados da pirimidina 3a-q e 5o-q. Estes compostos foram avaliados quanto às propriedades duais: Antimicrobiana e Fotoluminescência, estas apresentaram resultados promissores, podem atuar como boas sondas fluorescentes. Foram realizados também estudos Espectrofotométricos em diferentes solventes além de determinarmos o Cálculo do Orbital Molecular de Fronteira nesta série. Realizou-se também a nanoencapsulação em lipossomas para o composto 3o. Obtivemos também p-arilamidinas 3a-j por método convencional e avaliamos as propriedades Antimicrobiana e Citotóxica, as quais apresentaram resultados significativos. Realizamos a síntese dos derivados pirimidínicos 3a-f e 6a-f pelo método em Irradiação em micro-ondas, em fase sólida e em solução, respectivamente. Estudamos também para estes as propriedades Antimicrobiana e Antioxidante, cujos os resultados foram satisfatórios. Foram obtidos bons rendimentos para todos os compostos obtidos. Um estudo inédito de RMN bidimensional, COSY, HSQC e HMBC foram aplicados às pirimidinas foi realizado, proporcionando a caracterização estrutural destes compostos. Os resultados obtidos apresentaram significativa potencialidades biológicas, farmacológicas e fotofísicas.
Heterocyclic compounds of pyrimidine are known for rich biological and pharmacological potential. A number of heterociclic reactions that enable the obtention of this class of compounds are also recognized, due to the diversity of activities and prior knowledge of their various synthetic viabilities. The structural modifications obtained in search for the best synthetic routes confered different physical properties on the new molecules and altered the reactivity of the molecules, resulting in changes in the distribution in cells and tissues. These discrete structural changes may reveal biological effects that may have been latent or eclipsed by the side effects of the compound prototype. This work presents the synthesis by conventional method of derivatives from pyrimidine 3a-q and 5o-q. These compounds were evaluated for dual properties: antimicrobial and photoluminescence. They showed promising results can act as fluorescent probes. Spectroscopic studies were carried out with different solvents and the Frontier Molecular Orbital calculation for this series was determined. Nanoencapsulation of liposomes for the compound 3o was prepared. The conventional method was used to obtain 3a-j p-arilamidinas. Results were significant for the antimicrobial and cytotoxic properties. Finally, the synthesis of pyrimidines derivatives 3a-f and 6a-f by a new method, solid phase micro-wave and in solution, respectively was carried out. We have studied both the Antimicrobial and Antioxidant properties with satisfactory results. Good yields were obtained for all compounds obtained. New studies of two-dimensional NMR, COSY, HSQC and HMBC were performed besides the characterization of the compounds by standard methods. The results show that the compounds obtained have great biological, pharmacological potential and Photophysical.

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Salaam, Jeremy. "Sondes magnetogènes à base de Fe(II) répondantes à un analyte chimique par changement de spin électronique." Thesis, Lyon, 2020. http://www.theses.fr/2020LYSEN075.

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Cette thèse traite de molécules à base de Fe(II) capables d’un passage de spin sous l’action d’un analyte en solution, utilisées dans le domaine de l’imagerie moléculaire, notamment l’IRM (Imagerie par Résonance Magnétique). Depuis plusieurs années, la communauté scientifique autour de l’IRM a pris conscience de deux problématiques importantes : la faible sensibilité de l’IRM et la toxicité des agents de contrastes utilisés pour l’améliorer. Notre équipe répond à ces deux problématiques en développant des sondes magnétogènes spécifiques à un analyte biologique et supposées moins toxiques. Dans ce but, l’élaboration d’une méthodologie fiable permettant le greffage d’unités sulfonates en périphérie de complexes de coordination, et offrant un gain de solubilité et de compatibilité avec les milieux biologiques, a été réalisé. Puis, elle a été appliquée à un système de sonde déjà établi dans l’équipe afin d’augmenter son pH d’activation. En élargissant ces unités décoratives en périphérie a d’autre fonctions, une série de dérivés a été synthétisé, afin d’en extraire une tendance dans les performances d’activation du système en milieu acide.Dans le but de trouver un système de sonde s’activant à pH physiologique, deux complexes ont été synthétisés, portant des motifs d’activation nouveaux. La caractérisation poussée et l’étude d’activation de ces complexes ont offert de nouvelles données précieuses à équipe dans sa compréhension des concepts moléculaires et leur optimisation.La biocompatibilité in cellulo des systèmes développés a été explorée par l’étude de leur toxicité et de leur pénétration cellulaire. Un projet d’activation enzymatique dans l’estomac de rats, et première tentative de preuve de concept in vivo de l’équipe, a pu être initié. Les manipulations préliminaires s’avèrent prometteuses pour la suite du projet.Enfin, l’écart de signal IRM des objets chimiques synthétisés, écart entre la sonde avant rencontre avec son analyte et après, sont inédits dans le domaine. Ces résultats sont encourageants pour le développement d’une sonde suffisamment sensible pour permettre l’application à des expériences d’imagerie moléculaire de routine
This thesis deals with Fe(II) based molecules capable of a spin switch by interacting with an analyte in solution, which are used in the field of molecular imaging, in particular MRI (Magnetic Resonance Imaging). For several years now, the scientific community around MRI has become aware of two important issues: MRI’s low sensitivity and the toxicity of the contrast agents used to improve it. Our team responds to these two drawbacks by developing magnetogenic probes that are specific to a biological analyte and supposedly less toxic.For that purpose, the development of a reliable methodology allowing the incorporation of sulfonate units on the periphery of coordination complexes, offering a solubility and compatibility increase in biological media, was carried out. Then it was applied to a probe system already established in the team in order to increase its pH of activation. By expanding these peripheral decorative units to other functional groups, a series of derivatives have been synthesized, in order to extract a trend in the activation performance of the system in acidic conditions.With the aim of finding a system operating at physiological pH, two complexes were synthesized, carrying new activation motifs. The extensive characterization and activation studies of these complexes provided valuable data for the team in its understanding and optimization of the probe’s design.The in cellulo biocompatibility of the developed systems has been explored by studying their toxicity and their cellular absorption.An enzymatic activation project in the stomach of laboratory animals (rat), and the team's first in vivo proof of concept attempt, has been initiated. The preliminary manipulations are promising for the rest of the project. Finally, the difference in the MRI signal of the synthesized chemical objects, the difference between the probe before its encounter of the analyte and after, is unprecedented in the field. These results are encouraging for the development of a probe sensitive enough to allow application to routine molecular imaging experiments

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Paris, Jérémy. "Nanoparticules d'oxydes de fer et nanotubes de titanate pour l'imagerie multimodale et à destination de la thérapie anticancéreuse." Thesis, Dijon, 2013. http://www.theses.fr/2013DIJOS065/document.

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Les possibilités offertes par les applications en médecine des nanoparticules sont l’un des facteurs essentiels des progrès médicaux attendus pour ce XXIème siècle. Ainsi, le domaine de l’imagerie médicale est aussi touché par cette évolution technologique. Ce présent travail a consisté à élaborer des sondes théranostiques à base de nanoparticules d’oxydes de fer (SPIO) et de nanotubes de titanate (TiONts) pour l’imagerie multimodale (magnétique/nucléaire ou magnétique/optique) et possédant aussi un effet thérapeutique (hyperthermie/PDT ou radiosensibilisation/PDT).Les nanotubes de titanate de cette étude, d’une longueur moyenne d’environ 150 nm, ont été obtenus par synthèse hydrothermale selon la méthode de Kasuga. Ces nanotubes présentent un diamètre extérieur de l’ordre de 10 nm et une cavité interne de 4 nm. Les nanoparticules d’oxydes de fer ont quant à elles été synthétisées par méthode de co-précipitation "Massart". Ces nanoparticules d’oxydes de fer de structure spinelle possèdent des cristallites de 9 nm de diamètre et présentent un comportement superparamagnétique mis en évidence par des mesures FC/ZFC. Pour préparer ces nanoparticules à recevoir des molécules d’intérêt biologique, deux ligands possédant des fonctions organiques plus réactives (APTES : NH2 et PHA : COOH) ont été greffés à la surface de ces deux types de nanoparticules. La présence de l'un ou l'autre a été mise en évidence par différentes techniques d’analyses (XPS, IR, zêtamétrie). La quantité de molécules greffées a été déterminé par ATG, elle est dans tous les cas d’environ 5 molécules/nm2. Dans un premier temps, les nanotubes de titanate ont été fonctionnalisés par un agent macrocyclique (0,2 DOTA/nm2). Après radiomarquage à l’indium 111, les TiONts – DOTA[In] ont été injectés dans des souris Swiss mâle nude pour connaître leur biodistribution en imagerie SPECT/CT. Les images obtenues et le comptage de la radioactivité dans chaque organe ont montré qu’au bout d’une heure, les nanotubes se situent dans les poumons et dans l’urine. Ensuite, les nanotubes sont progressivement éliminés pour n’être plus présents que dans les urines à 24 heures. Ces mêmes agents chélatants ont été greffés à la surface des SPIO pour la création de sondes multimodales IRM/SPECT ou IRM/TEP. En parallèle de cette étude, un fluorophore (phtalocyanine de zinc, ZnPc) a été greffé à la surface des nanoparticules. Le nanohybride SPIO – Pc synthétisé possède les propriétés requises pour être une sonde utilisable en imagerie bimodale IRM/IO grâce à sa longueur d’émission vers 670 nm et sa relaxivité de l’ordre de 70 L.mmolFe3O4-1.s-1. De plus, les nanohybrides ont été fonctionnalisés par du PEG pour les rendre furtifs, biocompatibles et stables. La toxicité de certains de ces nanohybrides a été évaluée avec le modèle in vivo zebrafish. Les nanohybrides étudiés n’ont pas présenté de toxicité, n’ont pas perturbé l’éclosion et n’ont pas provoqué de malformations sur les larves des zebrafish
The new implementations of nanoparticles in the medical field are one of the essential factors of the medical progress expected at the beginning of this XXIst century. Thus, the domain of the medical imaging is also affected by this technological evolution. This work consisted in developing theranostic probes with iron oxides nanoparticles (SPIO) and titanate nanotubes (TiONts) for multimodal imaging (magnetic/nuclear or magnetic/optical) and also possessing a therapeutic effect (hyperthermia/PDT or radiosensitization/PDT).The titanate nanotubes of this study have an average length of about 150 nm and were obtained by Kasuga's hydrothermal synthesis. These nanotubes present an outside diameter of about 10 nm and an intern cavity of 4 nm. On the other hand, iron oxides nanoparticles were synthesized by soft chemistry ("Massart" method). These spinel-like iron oxides nanoparticles have a crystallite size of 9 nm in diameter and exhibit a superparamagnetic behavior which was highlighted by FC / ZFC measurements.To get these nanoparticles ready to receive molecules of biological interest, two linkers of more reactive organic functions (APTES: NH2 or PHA: COOH) were grafted to the surface of these two types of nanoparticles. Their presence was shown by different techniques (XPS, IR, UV-vis). The amount of grafted linkers was determined by TGA and in all cases this amount is close to 5 molecules/nm2. First, titanate nanotubes were coated by a macrocyclic chelating agent (0.2 DOTA/nm2). After radiolabelling with indium 111, the TiONts – DOTA[In] nanohybrids were injected in Swiss nude mice and observed by SPECT/CT imaging to characterize their biodistribution. The SPECT/CT images and the radioactivity measured in each organ showed that after one hour, nanotubes are located in lungs and in urine. Then, the nanotubes are gradually eliminated and are only found in urines after 24 hours. The same macrocyclic agent was grafted to the SPIO’s surface for the creation of multimodal probes MRI/SPECT or MRI/PET. Alongside this study, a fluorophore (Zinc phthalocyanine) was also grafted to the surface of nanoparticles. The synthesized SPIO – Pc nanohybrid has the required properties of bimodal imaging MRI/OI probe thanks to his emission wavelength around 670 nm and its relaxivity is about 70 L.mmolFe3O4-1.s-1. Furthermore, nanohybrids were coated by PEG to make them stealth, biocompatible and stable.In this study, the toxicity of most nanohybrids was evaluated by the in vivo zebrafish model. The studied nanohybrids did not present any toxicity, hatching disruption or malformation on zebrafish larvae

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30

Diarra, Myriam. "Figures et fictions d'auteur chez Lucien de Samosate." Thesis, Paris 4, 2017. http://www.theses.fr/2017PA040141.

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Partant du constat de l'omniprésence de Lucien dans son corpus, notre thèse se propose de dresser un panorama des autoreprésentations auctoriales dans l'ensemble de l'œuvre de Lucien de Samosate, mais dans une perspective résolument théorique. En effet, parce qu'il se constitue comme point focal de sa propre œuvre, Lucien a souvent tendance à faire l'objet d'une lecture biographique de la part de la critique. Cette thèse se donne pour objet de redonner à l'autoreprésentation de l'auteur son sens de geste poétique. En choisissant le terme de figure, auquel on donne ici un sens plus restreint qu'à celui de persona, on s'intéressera uniquement aux moments où l'auteur fait explicitement l'objet de son propre discours.La première partie de notre thèse consiste donc en une importante typologie des mises en scène de soi chez Lucien: on part des apparitions les plus explicites de l'auteur en contexte référentiel, dans le corpus oratoire ou biographique, pour traiter ensuite de la partie fictionnelle du corpus. L'un des objectifs de ce travail est en effet de redonner à Lucien sa place de pionnier dans l'invention de l'autofiction.La seconde partie de notre thèse tire les conclusions poétiques de cette typologie, en dégageant aux autoreprésentations de l'auteur une double fonction : d'abord, elles doivent dire l'individu social et intellectuel, mais dans une démarche qui transcende les genres et la séparation traditionnelle entre référentialité et fiction. Ensuite, les figures de l'auteur ont pour fonction de servir de vecteur à un message métapoétique extrêmement riche, qui va de la théorie de la fiction à celle de la réception
The starting point of this PhD thesis was the constatation of Lucian's omnipresence within his own corpus. This phenomenon often led critics to have an excessively biographical approach to this author. The aim of this thesis is thus to give an account of the vast scope of self-representations within Lucian's corpus, in a theoretical perspective, in order to show that the staging of the self can be seen as a poetical gesture. The first part of this work thus consists in a typology of all the auctorial self-representations that can be found within Lucian's œuvre. It ranges from the most explicit forms of authorial presence, in referential works, such as prolaliai and biographies, to the most fictional part of the corpus. The aim of this work is to establish Lucian's position as a pioneer in the invention of autofiction.The second part of this thesis draws the theoretical conclusions of this typology, by showing that authorial self-representations have two main functions : first, they help defining Lucian's social and intellectual identity, beyond generic boudaries ; second, they serve a metaliterary purpose : as vicarious surrogates, Lucian's doubles appear as a powerful means of expressing his aesthetical views

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31

Hontebeyrie, Micheline. "Paul Valéry et l'écriture de l'homme complet." Paris 12, 1994. http://www.theses.fr/1994PA120033.

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The aim of this four-part thesis is to show how, in spite of the fact that paul valery has been considered for a long time to have first and foremost prized the intellect, he did reveal other essential aspects of his "mortal" condition, through out works he did not, in their majority, really intend to publish. Excerpts from cahiers, manuscriots or posthumous publications, two groups of texts entitled le manuscrit trouve dans une cervelle (mnss) and alphabet (alpl. ) give the basis of our reflexion. Our first part takes into account the biographical background of this self-discorevy through writing. The second part dwells on the underlining structure of his work (musical as well as mathematical or scientific influences), while our third part analyses the semantic, lexical and graphic processes used in fragmented or peotical types of writing. The fourth part attempts to trace the labyrinth of themes expressed out of a number of key-poems taken from alphabet. The thesis concludes with the poet's perspectives on "l'homme complet" in their connexions with revealed possibilities of self-achievong through writing, in unfinished works
Le propos de cette thèse est de faire apparaître que, parallèlement à l'étude méthodique des capacités de l'Intellect et à la publication d'uune superbe poésie versifiée qui assura sa célébrité, P. Valéry suivit durant plus de 30 ans un secret parcours le conduisant à se mesurer avec succès aux artistes de génie dont l'ombre immense avait émerveillé et tout à la fois angoissé sa jeunesse poétique. A partir de deux ensembles de textes (extraits des "Cahiers", des manuscrits, ou de parutions posthumes), intitulés "Le Manuscrit trouvé dans une Cervelle" (soit : Mnss) et Alphabet (soit : Alph. ), notre réflexion prend d'abord en compte les conditions biographiques de l'exploration de soi par l'écriture, véritable Odyssée de l'aube. Notre seconde partie repère les axes sous-jacents d'une structuration interne (issus d'un héritage aussi bien musical que mathématico-scientifique), tandis que la troisième détaille les procédés sémantiques, lexicaux, et graphiques mis en oeuvre dans les divers blocs textuels (fragments ou poèmes en prose). La quatrième partie fait état des réseaux de signification tissés autour de quelques poèmes-clés d'"Alphabet", à l'instar d'une "musique à motifs". La conclusion, proposant une vision synthétique de ce que fut cette écriture de Soi, illustre comment étaient compatibles la notion d'"homme complet" et celle d'inachèvement

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32

Godley, Richard Franklin. "Investigation of Cryo-Cooled Microcoils for MRI." Thesis, 2011. http://hdl.handle.net/1969.1/ETD-TAMU-2011-08-9873.

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When increasing magnetic resonance imaging (MRI) resolution into the micron scale, image signal-to-noise ratio (SNR) can be maintained by using small radiofrequency (RF) coils in close proximity to the sample being imaged. Micro-scale RF coils (microcoils) can be easily fabricated on chip and placed adjacent to a sample under test. However, the high series resistance of microcoils limits the SNR due to the thermal noise generated in the copper. Cryo-cooling is a potential technique to reduce thermal noise in microcoils, thereby recovering SNR. In this research, copper microcoils of two different geometries have been cryo-cooled using liquid nitrogen. Quality-factor (Q) measurements have been taken to quantify the reduction in resistance due to cryo-cooling. Image SNR has been compared between identical coils at room temperature and liquid nitrogen temperature. The relationship between the drop in series resistance and the increase in image SNR has been analyzed, and these measurements compared to theory. While cryo-cooling can bring about dramatic increases in SNR, the extremely low temperature of liquid nitrogen is incompatible with living tissue. In general, the useful imaging region of a coil is approximately as deep as the coil diameter, thus cryo-cooling of coils has been limited in the past to larger coils, such that the thickness of a conventional cryostat does not put the sample outside of the optimal imaging region. This research utilizes a scheme of microfluidic cooling (developed in the Texas A&M NanoBio Systems Lab), which greatly reduces the volume of liquid nitrogen required to cryo-cool the coil. Along with a small gas phase nitrogen gap, this eliminates the need for a bulky cryostat. This thesis includes a review of the existing literature on cryo-cooled coils for MRI, as well as a review of planar pair coils and spiral microcoils in MR applications. Our methods of fabricating and testing these coils are described, and the results explained and analyzed. An image SNR improvement factor of 1.47 was achieved after cryo-cooling of a single planar pair coil, and an improvement factor of 4 was achieved with spiral microcoils.

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33

Lenich, Tobias. "Development and Application of an NMR Metabolic Imaging Technique based on CEST/NOE." 2018. https://ul.qucosa.de/id/qucosa%3A32395.

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For a thorough investigation of metabolic changes in cases of increased activity or disease, a high-resolution imaging modality would be of high-value. Conventional MR-based metabolite mapping techniques suffer from low spatial resolution and poor sensitivity to low concentrated metabolites. In this work, a novel optimization approach for high-resolution metabolic imaging by means of chemical exchange saturation transfer (CEST) and nuclear Overhauser effect (NOE) will be introduced. The general term of saturation transfer comprises CEST, NOE and magnetization transfer (MT). It describes the transfer of saturated magnetization from low concentrated solute metabolites to bulk water, after frequency selective RF irradiation was applied. The strong enhancement of attenuation effects—observed in a Z-spectrum—can be used to detect changes in metabolite concentrations. The vast complexity of in vivo tissue heavily distorts the baseline in Z-spectra. With a background spin system, modeled from a scout acquisition, saturation pulse amplitudes for each frequency offset were modulated, such that a speciﬁc target signal intensity was achieved. Further, a framework for a retrospective look-up correction of magnetic ﬁeld inhomogeneities and background spin system deviations was developed. The approach of a prospective baseline enhancement (PROBE) was investigated by means of sensitivity and speciﬁcity in vitro. It was subsequently translated into a clinical setting at 3 T. A high-resolution mapping of elevated lactate in ischemic regions of acute stroke patients became feasible.

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Ferreira, Ana Rita Rolo. "Synthesis and Characterization of a Biocompatible Fluorinated Mn(III)-Porphyrin as a Redox Responsive 19F-NMR/T1 Bimodal MRI Contrast Agent." Master's thesis, 2021. http://hdl.handle.net/10316/98191.

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Dissertação de Mestrado em Bioquímica apresentada à Faculdade de Ciências e Tecnologia
De entre as diferentes técnicas de imagem, a ressonância magnética nuclear de processos químicos e fisiológicos tem vindo a ganhar maior destaque. A MRI é uma técnica bastante vantajosa, dada a sua capacidade de gerar imagens de tecidos profundos com alta resolução temporal e sensibilidade. A vantagem de 19F MRI advêm da ausência de sinal de flúor in vivo e da extensa janela química de 19F, o que permite detetar simultaneamente mais do que uma sonda. O desenvolvimento da técnica de 19F MRI deve-se ao design de novas sondas perfluoradas, com parâmetros de imagem melhorados devido à incorporação de iões paramagnéticos. De acordo com a teoria de Bloch-Wangsness-Redfield, vários fatores podem afetar a sensibilidade das sondas perfluoradas, como a distância internuclear, tempos de correlação rotacional, geometria, bem como o estado de oxidação e estado de spin do ião metálico. Nesta dissertação foi sintetizada uma nova porfirina – Mn(III)TPP-p-CF3 para aplicação em 19F MRI como sonda “turn-off” redox. A incorporação com manganês, que é um ião paramagnético, tem como objetivo reduzir o tempo de relaxação T1, permitindo a aquisição de sinal com intensidade suficiente num período de tempo razoável. A sonda foi caracterizada por estudos de absorção UV-Vis e 1H/19F RMN. Para o desenvolvimento de sondas MRI sensíveis ao ambiente redox baseadas em MnIII/MnII, a complexação estável das formas reduzida e oxidada do metal, bem como o ajuste apropriado do potencial redox numa faixa biologicamente relevante são fatores essenciais. A porfirina sintetizada, que é insolúvel em água, satisfaz ambos os requisitos. Em solução aquosa, consegue alternar reversivelmente entre os estados de oxidação MnIII/MnII. Na presença de ácido ascórbico (um dos principais antioxidantes), o MnIII sofre uma redução lenta, que é revertida com a exposição ao oxigénio do ar. No entanto, o complexo não é reduzido pela glutationa. Este facto deve-se à coordenação dos grupos carboxilo da glutationa ao MnIII, em posição axial. A inclusão com γ-CD visa aumentar a hidrossolubilidade do complexo, considerando a sua capacidade de formar complexos de inclusão não covalentes com moléculas hóspedes hidrofóbicas. Através de 19F RMN foi confirmada a inclusão dos grupos CF3 da porfirina na cavidade hidrofóbica da γ-CD. Embora o complexo γ-CD*Mn(III)TPP-p-CF3 também seja reduzido na presença de ácido ascórbico, a inclusão com γ-CD estabiliza ambos os estados de oxidação MnIII/MnII, mesmo na ausência de ácido ascórbico, o que pode comprometer a sua aplicabilidade como sonda redox. Apesar de a estequiometria entre os dois compostos não ter sido determinada experimentalmente, é esperada uma estequiometria de 2:1 (γ-CD:Mn(III)TPP-p-CF3). De uma forma geral, não foi detetada citotoxicidade in vitro na linha celular humana Caco-2 para ambos os complexos, embora as concentrações utilizadas não cobrissem a faixa de concentrações típica para aplicação em MRI.
Among the different imaging techniques, magnetic resonance imaging of chemical and physiological processes is becoming widespread. MRI is a powerful tool given its ability to image deep inside tissue with high temporal resolution and sensitivity. The strength of 19F MRI comes from the negligible background signal in in vivo 19F MRI and the broad chemical shift window of 19F, making it possible to image more than one marker. Much of the grown of 19F MRI can be assigned to novel designs of 19F probes, which have improved imaging parameters due to the incorporation of paramagnetic ions. According to Bloch-Wangsness-Redfield theory, several parameters may affect the sensitivity of the fluorine-based probes, such as internuclear distance, rotational correlation times, geometry, as well as oxidation state and spin state of the metal ion. In this dissertation, a novel porphyrin – Mn(III)TPP-p-CF3 has been designed and synthesized to work as a “turn-off” redox probe for application in 19F MRI. The incorporation with manganese, which is a paramagnetic metal ion, has the purpose to reduce T1 relaxation time, allowing the acquisition of sufficient signal intensity in a reasonable period of time. The former probe was characterized by both UV-Vis absorption and 1H/19F NMR studies. For the development of redox responsive MRI probes based on the MnIII/MnII couple, it is mandatory a stable complexation of both reduced and oxidized forms of the metal and appropriate tuning of the redox potential in a biologically relevant range. The non-water-soluble fluorinated Mn-porphyrin derivative satisfies both requirements. In aqueous solution, it can reversibly switch between MnIII/MnII oxidation states. In the presence of ascorbic acid (one of the most important antioxidants), the MnIII undergoes a slow reduction, reversed in the presence of air oxygen. However, the complex is not reduced by glutathione. This event is prevented by the coordination of the glutathione carboxylate groups to the MnIII in the axial position. The inclusion of Mn(III)TPP-p-CF3 into γ-CD aims to increase the probe hydrosolubility, considering their ability to form noncovalent inclusion complexes with hydrophobic guest molecules. 19F NMR confirmed the inclusion of the meso aryl groups (CF3) of the porphyrin into the γ-CD hydrophobic cavity. Although the γ-CD*Mn(III)TPP-p-CF3 complex is also reduced by ascorbic acid, the inclusion with CD stabilizes both MnIII and MnII oxidation states even in the absence of ascorbic acid, which may compromise its application as a redox responsive probe. The stoichiometry between the two compounds was not possible to determine experimentally, but it is expected to have a 2:1 stoichiometry (γ-CD:Mn(III)TPP-p-CF3). Overall, no in vitro cytotoxicity in the human Caco-2 cell line was detectable for both complexes, even though the concentrations used were not in the typical MRI imaging concentration range.

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35

Martins, Andre Ferreira. "Multimodal Imaging Probes for the Diagnostics of Alzheimer’s Disease." Doctoral thesis, 2013. http://hdl.handle.net/10316/23523.

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Tese de doutoramento em Bioquímica, na especialidade de Biofísica Molecular, apresentada à Faculdade de Ciências e Tecnologia da Universidade de Coimbra
Alzheimer’s disease (AD) is the most frequent form of intellectual deterioration in elderly individuals, characterized by the brain deposition of amyloid plaques and neurofibrillary tangles. Early detection of the β-amyloid (Aβ) deposits in vivo is very difficult. Recently 11C-radiolabeled small-molecules have been developed, capable of entering the brain and specifically targeting amyloid plaques for imaging with PET, such as several Thioflavin T derivatives. In particular, the uncharged analogue 6-OH-BTA-1 (Pittsburgh compound B- PiB) is highly efficient both in crossing the BBB and in selective binding to AD amyloid aggregates. The use of Aβ marker linked to a MRI CA would constitute an attractive noninvasive in vivo imaging approach.
FCT - SFRH/BD/46370/2008 e CNRS - Orléans

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36

Carvalho, Henrique F. "Structural, physicochemical and photophysical studies of new cyclen derivatives and evaluation of their potential as MRI and MRI-NIR probes." Master's thesis, 2011. http://hdl.handle.net/10316/18848.

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Dissertação de mestrado em Bioquímica, apresentada à Faculdade de Ciências e Tecnologia da Universidade de Coimbra
Imagem por Ressonância Magnética (IRM) é uma modalidade de imagem onde um mapa multi-dimensional de sinais de Ressonância Magnética Nuclear (RMN) de 1H pertencentes a uma dada amostra é gerado. É bastante utilizada em investigação biomédica e em prática clínica pela sua capacidade de obter imagens de elevada resolução espacial de tecidos moles. Nestas, sinais RMN de 1H pertencentes a tecidos constitutivos são mapeados, principalmente os de 1H pertencentes a moléculas de água, dada a sua elevada abundância natural e sensibilidade da técnica ao sinal proveniente destes núcleos. Tem havido um grande interesse em melhorar a qualidade das imagens obtidas por IRM desde a sua implementação, nomeadamente através do aumento de contraste obtido entre unidades de volume. Isto é conseguido através da administração de Agentes de Contraste (AC), compostos que modulam a intensidade de sinal das imagens obtidas. Complexos de GdIII baseados em poliaminocarboxilatos cíclicos ou lineares são a classe de AC mais estudada e todos os AC disponíveis comercialmente são baseados neste tipo de complexos. No entanto, é possível aumentar a eficácia destes compostos. Este trabalho foca-se na caracterização físico-química, fotofísica e estrutural de dois tipos de sistemas. O primeiro tipo, consistindo em derivados de cicleno com três braços pendentes metilfosfonato – DO3P, DO3P1Pr e DO3P1ol – e os seus respectivos complexos de LnIII foram estudados de forma a determinar o seu potencial como AC para IRM e também para determinar qual o efeito de um braço pendente adicional nas suas propriedades físico-químicas e estruturais. Os estudos realizados permitiram avaliar qual o esquema de coordenação apresentado por estes complexos, em particular que um braço pendente adicional propionato ou propanol não estão envolvidos na coordenação do ião LnIII central quando outros três braços pendentes metilfosfonato o estão. O segundo tipo de sistema, consistindo em derivados de cicleno com braços pendentes piridina-N-óxido – DO2A-trans-(pyNO)2 – e respectivos complexos de LnIII foram também estudados e as suas propriedades físico-químicas, fotofísicas e estruturais foram analisadas. O potencial destes complexos como sondas de imagem para IRM e infra-vermelho próximo foram avaliados, nomeadamente a sua eficácia como AC de IRM e a capacidade sensibilizar luminescência de lantanídeos. Os resultados obtidos indicam que este sistema é um candidato potencial para estas aplicações uma vez que apresenta estabilidades termodinâmica e cinética favoráveis e que apresenta a capacidade de sensibilizar luminescência de iões LnIII (LnIII = EuIII, TbIII, YbIII, NdIII, HoIII and PrIII).
Magnetic Resonance Imaging (MRI) is an imaging modality where a multi-dimensional map of 1H Nuclear Magnetic Resonance (NMR) signals from a given sample is generated. It is widely used in biomedical research and clinical practice due to its ability to obtain high spatial resolution imaging of soft tissues. Here, 1H NMR signals from constitutive tissues are mapped, mainly the ones from water molecules, due to their high natural abundance in soft tissues and high relative sensibility of their NMR signal. There has been a great interest in increasing the quality of the obtained MRI images since its implementation as an imaging modality, namely through contrast enhancement between volume units. This can be done by administration of Contrast Agents, compounds that modulate the signal intensity of the obtained images. GdIII complexes based on macrocyclic or linear aminocarboxylates are the most studied class of CAs and all the commercially-available CAS are based on these complexes. However, there is the possibility of increasing their efficiency and much effort has been made in this direction. This work is focused on the structural, photophysical and physicochemical properties of two types of systems. The first type, cyclen derivatives with three methylphosphonate pendant arms - DO3P, DO3P1Pr and DO3P1ol – and their respective LnIII complexes were studied in order to determine their potential as MRI CAs and also to determine the role of additional pendant arms in their structural and physicochemical properties. The studies performed allowed for determination of the coordination scheme presented by these complexes, namely that an additional propionate and propanol pendant arms do not participate in central LnIII ion coordination when three methylphosphonate pendant arms are also involved. The second type, a cyclen derivative with pyridine-N-oxide pendant arms – DO2A-trans-(pyNO)2 – and its respective LnIII complexes were also studied and their physicochemical, photophysical and structural properties analyzed. The potential of these complexes as bimodal MRI and Near-Infrared Imaging probes was evaluated, namely its efficiency as a MRI CAs and the capacity to sensitize lanthanide luminescence. The obtained results indicate that this system is a potential candidate for such applications since its shows suitable thermodynamic and kinetic stabilities and the ability to efficiently sensitize LnIII luminescence (LnIII = EuIII, TbIII, YbIII, NdIII, HoIII and PrIII).

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37

Maafi, Foued. "Développement d'une sonde fluorescente bioactivable pour l'étude du rôle in vitro et in vivo des protéases dégradant l’apolipoprotéine A-I." Thèse, 2015. http://hdl.handle.net/1866/13427.

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38

LIU, HENG-YIN, and 劉恆吟. "Family Adaptation in Taiwan: Zhong Mei-yin’s Prose Writing." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/q52png.

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碩士
東海大學
中國文學系碩士在職專班
107
By analyzing numerous prose written by Zhong Mei-yin, a female Chinese writer who moved with her husband, Yu Bo-Qi, to Taiwan from China in March 1948, this study investigated the Chinese women who relocated to Taiwan with the government of the Republic of China (ROC). After reviewing the prose written by Zhong, this study explored how these women protected themselves and their families in turbulent times and further adapted themselves under regime changes. Additionally, this study investigated the reasons and unique context in which the great female writers who moved from the mainland emerged and thrived in Taiwan during the 1950s. This study first focused on Zhong’s unique life philosophies, which were developed in the complexities of her hardships in a turbulent time and her suffering from a chronic lung disease. The second focus is on Zhong’s psychological transition and adjustment process regarding her endeavor to adapt to life in Taiwan. Originally, the writer did not plan for a long stay in Taiwan and was eager to return her home in China at any time. However, after living in Taiwan for a long period of time, Zhong finally gave up going back to China and persuaded herself to treat Taiwan as her new home where she would dwell permanently. This study adopted the textural analysis method to review and analyze Zhong’s prose. As one of the Chinese women who relocated to Taiwan with the ROC government following the end of Chinese Civil War, Zhong was forced to leave her hometown and became separated from her family and relatives. The profound implications imparted by her writing revealed how Zhong adapted to a new life in Taiwan and how she rebuilt her home afterwards. This paper comprises five chapters. The first chapter describes the research rationale. The second chapter analyzes Zhong’s works from the perspective of the art and literature policies enforced by the ROC government in the 1950s. The third chapter summarizes Zhong’s medical history to explore the philosophies of life developed out of her chronic asthma. The fourth chapter focuses on the localized writing in Zhong’s works. The final chapter concludes the findings that sum up Zhong’s life and the complexity and characteristics of the literary world in Taiwan during the 1950s. The findings of this study can draw the attention of literature academics to study the essays written by female writers who relocated from China to Taiwan during the 1950s and thus bring more insightful reviews.

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39

Hong, Wen-Jie, and 洪文傑. "To Probe into the Process of Mei-Gin and the Effects on Serum Lipids of Hamsters." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/01794251480762349447.

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碩士
國立中興大學
食品科學系
93
Abstract Marketing Mei-Gin is a highly concentrated and dark black product made from squeeze juice of premature mei (Japanese apricot) via filtration. This product has been generally recognized as a food with several functional properties. In this study, Taiwan mei was used as raw materials to make Mei-Gin by traditional method which combined heating and concentration. Changes in quality during processing were observed and functional property for the final Mei-Gin was investigated by biological test of rat feeding. The results were as follows. 1. Heating and concentration were two necessary processes to obtain Mei-Gin of traditionally viscous and dark black appearance. The solution of diluted Mei-Gin which was concentrated to 10-fold in acidity by combined heating and concentration and then re-hydrated to original juice showed 46.95 for total color difference (ΔE) value. The value was quite high compared to that of circulated heating at normal pressure (3.62) and vacuum concentration (3.19). 2. Scavenging efficiency of DPPH for mei juice gradually increased with heating and concentration. The final Mei-Gin product was 33.24% higher than original juice, while no obvious changes for circulated heating at normal pressure method and little decrease for vacuum concentration method. The sediment fraction obtained from the diluted Mei-Gin solution by centrifugal fractionation showed 32~53% higher in DPPH scavenging efficiency original juice while decrease was observed for supernatant fraction. The changes became much more obvious with heating and concentration indicated that availably functional components were further produced during processing. 3. Diets mixed high cholesterol (0.2% cholesterol) with various concentrations (0.05%, 0.5%, 5%) of Mei-Gin were feed to rats. The blood biochemical assessment after 2, 4, and 8 weeks showed: No regular changes in both GPT and GOT;  Total cholesterol (TC) reduced from 210.92 to about 183 mg/dL at the 4th week, however, the decrease was not proportional to the concentrations Mei-Gin and was not significantly different with that of the 2nd and 8th week;  Total triglyceride (TG) obviously related to concentration of Bainiku-ekisu, it reduced from 115.03 to 70.75 mg/dL (closed to the normal group, 69.67 mg/dL) for the 2nd week, while from 119.32 to 47.2 mg/dL for the 4th week, and from 141.83 to 53.8 mg/dL for the 8th week;  No difference was observed in HDL for the 2nd week, but obviously increased for both 4th and 8th week though was not in proportion to the Mei-Gin concentrations;  There were no differences in LDL for any experimental groups at any weeks.

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40

Shih, Cheng-Mei, and 施呈玫. "The Concepts and Practice on Cheng-Mei Shih’s Four Composition Works：The probe into combination of composition skills and sound layers." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/39519076846830064150.

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Анотація:

碩士
國立臺北教育大學
音樂學系碩士班
98
The main purpose research of the thesis is to probe into several kinds of contemporary musical composition theories, including Twelve-tone technique, Modes of limited transposition, and Non-retrograde rhythm. To Probe into the composition skills and the feature of sound layers in four of my composition works, further more make the theories into practice to music composition. The analysis of the four works are the orchestral music “Journey”, the chamber music “Image and Color”, the chamber music “Lunar shadow”, the chamber music “Irregular and Asymmetry”. Make respective research adopted special performance with features from the set of music instruments, composition frame, composition skills, and the analysis of the score, based on Western musical theory make the composition into practice. Therefore I try to include, analyze and exert the theory on my four compositions for proof and reference. With conscientious probe process, then I gradually blend sophisticate music composition into my style.

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41

Liu, X., L. Hu, G. Ge, B. Yang, J. Ning, S. Sun, L. Yang, Klaus Pors, and J. Gu. "Quantitative analysis of cytochrome P450 isoforms in human liver microsomes by the combination of proteomics and chemical probe-based assay." 2014. http://hdl.handle.net/10454/10502.

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No
Cytochrome P450 (CYP) is one of the most important drug-metabolizing enzyme families, which participates in the biotransformation of many endogenous and exogenous compounds. Quantitative analysis of CYP expression levels is important when studying the efficacy of new drug molecules and assessing drug-drug interactions in drug development. At present, chemical probe-based assay is the most widely used approach for the evaluation of CYP activity although there are cross-reactions between the isoforms with high sequence homologies. Therefore, quantification of each isozyme is highly desired in regard to meeting the ever-increasing requirements for carrying out pharmacokinetics and personalized medicine in the academic, pharmaceutical, and clinical setting. Herein, an absolute quantification method was employed for the analysis of the seven isoforms CYP1A2, 2B6, 3A4, 3A5, 2C9, 2C19, and 2E1 using a proteome-derived approach in combination with stable isotope dilution assay. The average absolute amount measured from twelve human liver microsomes samples were 39.3, 4.3, 54.0, 4.6, 10.3, 3.0, and 9.3 (pmol/mg protein) for 1A2, 2B6, 3A4, 3A5, 2C9, 2C19, and 2E1, respectively. Importantly, the expression level of CYP3A4 showed high correlation (r = 0.943, p < 0.0001) with the functional activity, which was measured using bufalin-a highly selective chemical probe we have developed. The combination of MRM identification and analysis of the functional activity, as in the case of CYP3A4, provides a protocol which can be extended to other functional enzyme studies with wide application in pharmaceutical research.

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