Collagen is one of the major protein constituents in mammals and is present in all tissues and organs with the exceptions of keratin tissues such as hair and nails. Collagen monomers self-aggregate into a number of structures. In order to understand the physical bases for the structural polymorphism observed in collagen, a good starting point is one of the simplest collagen aggregates, segmental long spacing (SLS) collagen. Although SLS collagen formation induced by the presence of adenosine 5’-triphosphate is widely known, effects of other triphosphates, on the other hand, are much less studied. By varying the pH, it is discovered that all the nucleoside 5’-triphophsates, as well as inorganic triphosphate, are able to induce SLS formation over certain pH ranges. Adenosine 5’-diphosphate and para-nitrophenylphosphate cannot induce SLS formation at any pH. Based on the pH ranges at which SLS collagen can be formed, it is concluded the triphosphate functionality, with one negative charge per phosphate group, is primarily responsible for the formation of SLS collagen. Since inorganic triphosphate is able to induce SLS collagen formation, the presence of the nucleoside is optional for the assembly process; however if present, the assembly process prefers the nucleosides carrying acidic protons. Using electron spectroscopic imaging (ESI) technique, it is found phosphorus, present only in nucleotides but not in polypeptides, is localized in certain regions of SLS collagen, forming a unique banding pattern transverse the long axis of the SLS collagen. Nitrogen mapping indicates the localization of phosphorus is not due to accumulation of materials. The phosphorus banding pattern demonstrates an excellent consistency across SLS collagen assembled from both bovine and recombinant human collagen monomers. Results from molecular simulation are consistent with the experimental results. All threephosphate groups seem to be involved in the assembly process to some degree. In the last chapter of the thesis, a reliable protocol to synthesis native type collagen fibers is introduced.

Thesis (M.S.)--Indiana University, 2008. / Title from screen (viewed on June 3, 2009). Department of Earth Science, Indiana University-Purdue University Indianapolis (IUPUI). Advisor(s): Lin Li, Pierre Jacinthe, Gabriel M. Filippelli. Includes vita. Includes bibliographical references (leaves 78-81).

Thesis advisor: Ilija Zeljkovic / We used spectroscopic-imaging scanning tunneling microscopy (SI-STM) and spin-polarized STM (SP-STM) to unveil new electronic phenomena in several different quantum systems. We explored: (1) a potential topological superconductor heterostructure Bi₂Te₃/Fe(Te, Se), (2) high-Tc superconductors − Bi₂Sr₂CaCu₂O₈₊ₓ and Fe(Te, Se), and (3) doped spin-orbit Mott insulators Sr₂IrO₄ and Sr₃Ir₂O₇. In Bi₂Te₃/Fe(Te, Se), we observed superconductivity (SC) on the surface of Bi₂Te₃ thin film, induced by the iron-based superconductor substrate. By annealing the optimally-doped cuprate superconductor Bi₂Sr₂CaCu₂O₈₊ₓ, we drastically lowered the surface hole doping concentration to detect a unidirectional charge stripe order, the first reported charge order on an insulating (defined by the spectral gap with zero conductance spanning the Fermi level) cuprates surface. In the high-Tc SC Fe(Te, Se) single crystal, we found local regions of electronic nematicity, characterized by C₂ quasiparticle interference (QPI) induced by Fermi surface anisotropy and inequivalent spectral weight of dyz and dxz orbitals near Fermi level. Interestingly, the nematic order is locally strongly anti-correlated with superconductivity. Finally, utilizing SP-STM, we observed a short-range antiferromagnetic (AF) order near the insulator-metal transition (IMT) in spin-orbital Mott insulators Sr₂IrO₄ and Sr₃Ir₂O₇. The AF order inhomogeneity is found not to be strongly correlated with the charge gap. Interestingly, the AF order in the bi-layered Sr₃Ir₂O₇ shows residual memory behavior with temperature cycling. Overall, our work revealed new phenomena in a range of today’s most intriguing materials and set the stage for using SP-STM in other complex oxides. / Thesis (PhD) — Boston College, 2020. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Physics.

<p>The work in this thesis deals with pre-clinical development of rapid in vivo ³¹P mag- netic resonance spectroscopy (MRS) techniques. Current MRI literature of ³¹P spec- troscopy presents evidence of increased concentrations of phosphomonoesters (PME), and phosphodiester (PDE) as well as inorganic phosphate concentrations in tumor tissue. Human breast cancer studies have demonstrated correlation between disease progression and both PME and PDE peaks. Furthermore, ³¹P MRS can be used to detect, grade tumours and monitor response to chemo and radiation therapy.<br />Tumor measurements are typically static (i.e. single measurement per scan). In other experiments, on muscle for example, dynamic measures are required the purpose of which is to assess temporal function and recovery. In all ³¹P acquisitions there are problems surrounding RF coil design, pulse sequence speed, localization and system calibration. The work presented here focused on improving all these aspects and provide easy and reliable work flow to use ³¹P MRS in a clinical setting.<br />One of the aspects of this thesis lies in designing and construction of an RF coil that is well suited for integration with a clinical MRI breast imaging and biopsy system. The designed coil was tuned for simultaneous operation at ³¹P (51.73 MHz) and ¹H (127.88MHz) Larmor frequencies. This design has advantages in the fact that complex pulse sequences with heteronuclear decoupling could be performed easily. The additional features of the coil design is that it is possible to swap it into the breast imaging system without moving the patient. Along with the designed coil, custom software was written to assist with transmit gain calibration of ³¹P RF pulses, to ensure maximum MR signal. The automated prescan ensures easy work flow and minimizes the operator variability and patient time inside the MR scanner.<br />Another aspect of this thesis deals with rapid pulse sequence development, to further speed up the ³¹P MRS data acquisition. Echo planar spectroscopic imaging (EPSI) with a fly–back gradient trajectory is currently one of the most reliable and robust techniques for speeding up chemical shift imaging (CSI) acquisitions. A ³¹P EPSI sequence was written to acquire spectroscopic imaging data at 1, 2 and 2.6 cm spatial resolution and spectral bandwidth of 3125 Hz. The sequence showed an ability to speed up data acquisition up to 16 times, where SNR permits.<br />Phantom studies were used to verify the double tuned coil and EPSI sequence en- suring proper and safe operation. In vivo measurements of an exercising muscle demonstrated the ability of ³¹P EPSI to play an important role in rapidly acquiring spatially localized ³¹P spectroscopic data.<br />With these preclinical developments in place a clinical trial is possible using ³¹P MRS rapidly and efficiently. Furthermore the increased usability of ³¹P MRS provided by the tools developed in this thesis can prove to be beneficial by integrating ³¹P MRS into existing clinical protocols.</p> / Doctor of Science (PhD)

Mid-infrared spectroscopic imaging, which leverages the inherent vibrational contrast of chemical bonds, has been a powerful analytical tool for sample characterization. However, its use in studying living systems is limited by low spatial resolution and significant water absorption. Recently developed mid-infrared photothermal (MIP) microscopy addresses these limitations by probing the absorption-induced photothermal effect using visible light. MIP microscopy achieves sub-micrometer spatial resolution and reduces water background interference. Yet, the imaging speed of current MIP microscopy is constrained by the challenge of measuring a small modulation over the probe laser background. This low imaging throughput hinders the visualization of living dynamics, and the rich molecular information in the spectroscopic domain is obscured due to the slow acquisition process. This dissertation explores solutions for enhancing imaging speed and spectral throughput and extending MIP imaging into visualizing chemical dynamics in living systems. In the first part of the dissertation, the mid-infrared photothermal process is studied and modeled in the time, frequency, and spatial domains using heat transfer analysis. Photothermal dynamics imaging (PDI) is introduced with the ability to visualize nanosecond-scale thermodynamics in samples upon laser excitation. By capturing all higher-order harmonics, PDI achieves more than a four-fold improvement in signal-to-noise ratio compared to the lock-in method for detecting low-duty cycle photothermal signals. An imaging speed nearly two orders of magnitude faster than the lock-in counterpart has been reached. In addition, PDI captures the transient thermal field evolution, providing a tool to gauge the target’s physical properties and microenvironment. In the second part, a video-rate MIP microscope is introduced based on the PDI detection method. In the system, a synchronized IR and visible beam scanning scheme is developed, enabling photothermal detection with a single IR pulse at each pixel. Moreover, synchronized laser scanning allows uniform MIP imaging in a field of view over hundreds of micrometers while maintaining a high spatial resolution. This capability enabled the visualization of fast chemical dynamics inside living fungal cells, cancer cells, and living worms, providing an imaging platform for biology research. Having reached the speed limitation of single-pulse imaging, we further advanced the speed of spectroscopic imaging by moving beyond the conventional measurement of absorption contrast in the photothermal process. In the final part of this dissertation, we revisited the photothermal process from the perspective of energy deposition, discovering that the absorption coefficient is reflected in the slope of the heating process rather than its overall amplitude. We demonstrated mid-infrared energy deposition (MIRED) spectroscopy using a 32-channel quantum cascade laser array that emits a broadband pulse train in microseconds. With MIRED, we achieved hyperspectral mid-infrared imaging on a microsecond scale.

G-quadruplexes (G4s) are nucleic acid structures formed from π-stacked planar sets of four Hoogsteen hydrogen bonded guanine bases. G4s emerged as potential therapeutic targets based on their ability to modulate gene expression and inhibit the ability of telomerase to elongate chromosomal telomeres. Raman spectroscopy, polarized Raman spectroscopy, surface-enhanced Raman spectroscopy (SERS), and other optical spectroscopic techniques were used to characterize the G4s formed by four different DNA sequences: human telomeric (HT), thrombin-binding aptamer (TBA), nuclease hypersensitive element III1 region of the c- Myc gene promoter (Myc), and a single loop-isomer of Myc (MycL1). / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

Magnetic Resonance Spectroscopy (MRS) and Spectroscopic Imaging (MRSI) play an emerging role in clinical assessment, providing in vivo estimation of disease markers while being non-invasive and applicable to a large range of tissues. However, static magnetic field inhomogeneity, as well as eddy currents in the acquisition hardware, cause important distortions in the lineshape of acquired NMR spectra, possibly inducing significant bias in the estimation of metabolite concentrations. In the post-acquisition stage, this is classically handled through the use of pre-processing methods to correct the dataset lineshape, or through the introduction of more complex analytical model functions. This thesis concentrates on handling arbitrary lineshape distortions in the case of quantitation methods that use a metabolite basis-set as prior knowledge. Current approaches are assessed, and a novel approach is proposed, based on adapting the basis-set lineshape to the measured signal.Assuming a common lineshape to all spectral components, a new method is derived and implemented, featuring time domain local regression (LOWESS) filtering. Validation is performed on synthetic signals as well as on in vitro phantom data. Finally, a completely new approach to MRS quantitation is proposed, centred on the use of the compact spectral support of the estimated common lineshape. The new metabolite estimators are tested alone, as well as coupled with the more common residual-sum-of-squares MLE estimator, significantly reducing quantitation bias for high signal-to-noise ratio data.

The goals of the thesis were to, in pig models, (1) assess manganese-enhanced magnetic resonance imaging (MEMRI) in the characterization of acute and chronic ischemia-induced myocardial infarction (MI), (2) characterize cryoinjury-induced MI with contrast-enhanced MRI and optical methods, and (3) observe the effects of locally released angiogenic factors on the repair of cryoinjury-induced MI. Firstly, after acute MI was established by occlusion of the coronary artery branches, the pig hearts were isolated and mounted onto an ex vivo perfusion system inside a 7T magnet. After administration of MnCl2, T1-weighted MR images showed gradual enhancement of signal intensity within the normal myocardium, whereas the ischemic counterpart remained hypointense. During chronic MI progression, the intensity increased slowly after exposure to MnCl2 within the infarcted myocardium. Secondly, a new MI model was tested via direct 2-min contact of left ventricular epicardium with a liquid nitrogen-cooled aluminum bar. Subsequent in vivo Gd-enhanced MRI showed a uniform hypointense area (~10 mm in depth) surrounded by a hyperintense rim. Histology showed erythrocytes embolism within the cryolesion with a thin necrotic rim neighboring the normal myocardium. Four weeks later, the cryoinjured myocardium was replaced by scar tissue. Thirdly, in vivo MEMRI was tested on this cryoinjury model. After intravenous administration of MnCl2 via intermittent bolus or continuous infusion, normal myocardium showed prolonged hyperintense, which led to significant signal contrast between it and cryoinjured myocardium. Continuous infusion scheme minimized hemodynamic fluctuation. Finally, angiogenic therapy was assessed by anchoring of vascular growth factors-loaded alginate beads or adipose-derived stem cells (ADSCs)-loaded agarose patch on top of the cryoinjured myocardium. Gd-enhanced MRI revealed (1) growth of new tissue wrapping the growth factors-loaded alginate beads and (2) higher perfusion within the ADSCs-treated cryoinjured myocardium as compared with the growth factors-treated counterpart. Histological and fluorescent microsphere examination revealed that ADSCs induced more significant growth of mature microvasculature within the cryoinjured myocardium. These results indicate that MnCl2 could characterize MI ex vivo and in vivo. Epicardial implantation of ADSCs-loaded agarose hydrogel can induce angiogenesis within the cryoinjured myocardium, a form of MI with similar progression features as that induced by ischemia.

The goals of the thesis were to, in pig models, (1) assess manganese-enhanced magnetic resonance imaging (MEMRI) in the characterization of acute and chronic ischemia-induced myocardial infarction (MI), (2) characterize cryoinjury-induced MI with contrast-enhanced MRI and optical methods, and (3) observe the effects of locally released angiogenic factors on the repair of cryoinjury-induced MI. Firstly, after acute MI was established by occlusion of the coronary artery branches, the pig hearts were isolated and mounted onto an ex vivo perfusion system inside a 7T magnet. After administration of MnCl2, T1-weighted MR images showed gradual enhancement of signal intensity within the normal myocardium, whereas the ischemic counterpart remained hypointense. During chronic MI progression, the intensity increased slowly after exposure to MnCl2 within the infarcted myocardium. Secondly, a new MI model was tested via direct 2-min contact of left ventricular epicardium with a liquid nitrogen-cooled aluminum bar. Subsequent in vivo Gd-enhanced MRI showed a uniform hypointense area (~10 mm in depth) surrounded by a hyperintense rim. Histology showed erythrocytes embolism within the cryolesion with a thin necrotic rim neighboring the normal myocardium. Four weeks later, the cryoinjured myocardium was replaced by scar tissue. Thirdly, in vivo MEMRI was tested on this cryoinjury model. After intravenous administration of MnCl2 via intermittent bolus or continuous infusion, normal myocardium showed prolonged hyperintense, which led to significant signal contrast between it and cryoinjured myocardium. Continuous infusion scheme minimized hemodynamic fluctuation. Finally, angiogenic therapy was assessed by anchoring of vascular growth factors-loaded alginate beads or adipose-derived stem cells (ADSCs)-loaded agarose patch on top of the cryoinjured myocardium. Gd-enhanced MRI revealed (1) growth of new tissue wrapping the growth factors-loaded alginate beads and (2) higher perfusion within the ADSCs-treated cryoinjured myocardium as compared with the growth factors-treated counterpart. Histological and fluorescent microsphere examination revealed that ADSCs induced more significant growth of mature microvasculature within the cryoinjured myocardium. These results indicate that MnCl2 could characterize MI ex vivo and in vivo. Epicardial implantation of ADSCs-loaded agarose hydrogel can induce angiogenesis within the cryoinjured myocardium, a form of MI with similar progression features as that induced by ischemia.

La spectroscopie de plasma induit par laser, ou LIBS (acronyme anglais de Laser Induced Breakdown Spectroscopy) est une technique d'analyse élémentaire basée sur l'émission d'un plasma issu de l'interaction laser-matière. Elle permet en principe une détection de l'ensemble des éléments du tableau périodique avec une sensibilité typiquement de l'ordre du ppm et ce sur tout type de matériaux : solides, liquides ou gazeux. Sa capacité à exploiter aussi bien le signal élémentaire que moléculaire en fait un candidat crédible à l'identification des matériaux organiques, par exemple dans le domaine du tri des déchets plastiques où les techniques d'analyses usuelles peinent à remplir toutes les contraintes liées à cette question. Cependant, le plasma induit par laser est un phénomène transitoire et correspondant à un milieu inhomogène parfois difficile à maitriser, notamment en comparaison avec un plasma à couplage inductif. En conséquence, la LIBS reste aujourd'hui marginale dans les applications où une information fiable et souvent quantitative est requise. Ce travail doctoral, fruit d'un partenariat entre le CRITT Matériaux Alsace et l'Institut Lumière Matière de Lyon dans le cadre 'un financement CIFRE, se propose d'étudier ces deux problématiques. Un nouvel instrument LIBS est tout d'abord présenté. Articulé autour de nombreux outils de contrôle pilotés par un logiciel dédié, il a permis de limiter considérablement les fluctuations du signal LIBS liées aux divers paramètres impliqués dans le processus d'ablation laser (énergie du laser, position de l'échantillon, position de la détection…). L'efficacité de cet instrument est montrée à travers une étude de quantification d'éléments en trace dans des matrices de verre / Laser Induced Breakdown Spectroscopy (LIBS) is an analytical technique based on the emission of a plasma arising from the laser-matter interaction. All the elements of the periodic table can be detected with a detection limit close to the ppm, regardless of the nature of sample: solid, liquid or gas. LIBS can perform elemental as well as molecular analysis, which makes it a trustworthy technique for the identification of organic materials, especially with reference to plastic waste sorting where the established techniques experience some difficulties to fulfill all the requirements of this issue. Nevertheless, the laser-induced plasma is a transient and inhomogeneous process regularly hard to master in comparison with an inductively coupled plasma. As a consequence, LIBS technique still remains marginal for the applications demanding a reliable and frequently quantitative information. This doctoral research, which falls within the framework of a partnership between the CRITT Matériaux Alsace and the Institut Lumière Matière in Lyon, proposes to examine the two issues mentioned above. A new LIBS instrument is first given. It is organized around several monitoring tools driven by a dedicated software which allowed us to considerably reduce the fluctuations of the LIBS signal coming from the different factors involved in the process of laser ablation (laser energy, sample and detection positions, etc…). The efficiency of this new LIBS instrument is then illustrated through the example of the quantification of trace elements in glass matrices