Quantifying the Impact of Altered Hemodynamics and Vascular Biomechanics to Changes in Structure and Function in Native and Corrected Aortic Coarctation

Coarctation of the aorta (CoA) is associated with substantial cardiovascular morbidities despite successful treatment through surgical or catheter-based intervention. Although specific mechanisms leading to these morbidities remain elusive, abnormal hemodynamics and vascular biomechanics are implicated. We used a novel animal model that facilitates quantification of CoA-induced hemodynamic and vascular biomechanics alterations and their impact on vascular structure and function, independent of genetic or confounding factors. Rabbits underwent thoracic CoA at 10 weeks of age (~9 human years) to induce a 20 mmHg blood pressure (BP) gradient using permanent or dissolvable suture thereby replicating untreated and corrected CoA. Computational fluid dynamics (CFD) was performed using subject-specific imaging and BP data at 32 weeks to quantify velocity, strain, and wall shear stress (WSS). Vascular structure and function were evaluated at proximal and distal locations by histology, immunohistochemistry, and myograph analysis. Results revealed proximal systolic and mean BP was elevated in CoA compared to corrected and control rabbits leading to vascular remodeling, endothelial dysfunction proximally and distally, and increased stiffness and reduced active force response proximally. Corrected rabbits had reduced but significant medial thickening, endothelial dysfunction, and stiffening limited to the proximal region despite 12 weeks of alleviated systolic and mean BP (~4 human years) after the suture dissolved. Proximal arteries of CoA and corrected groups demonstrated increased non-muscle myosin expression and decreased myosin heavy chain expression, and this dedifferentiation may influence vascular remodeling and aortic stiffening. CFD analysis of untreated CoA rabbits demonstrated significantly reduced WSS proximal to CoA and markedly elevated WSS distally due to the presence of a stenotic velocity jet. Results from corrected rabbits indicate the velocity jet may have persistent effects on hemodynamics, as WSS remained significantly reduced. These hemodynamic and morphological observations are consistent with alterations in human patients. Using these coupled imaging and experimental results, we may determine changes in structure and function specific to CoA and correction and how they are influenced by hemodynamics and vascular biomechanics. We are now poised to augment clinical treatment of CoA through several methods, including investigation of specific cellular mechanisms causing morbidity in CoA and the development of therapies to improve endothelial function and restore vascular stiffness

Natural Supersymmetry and Implications for Higgs physics

We re-analyze the LHC bounds on light third generation squarks in Natural Supersymmetry, where the sparticles have masses inversely proportional to their leading-log contributions to the electroweak symmetry breaking scale. Higgsinos are the lightest supersymmetric particles; top and bottom squarks are the next-to-lightest sparticles that decay into both neutral and charged Higgsinos with well-defined branching ratios determined by Yukawa couplings and kinematics. The Higgsinos are nearly degenerate in mass, once the bino and wino masses are taken to their natural (heavy) values. We consider three scenarios for the stop and sbottom masses: (I) $\tilde{t}_R$ is light, (II) $\tilde{t}_L$ and $\tilde{b}_L$ are light, and (III) $\tilde{t}_R$, $\tilde{t}_L$, and $\tilde{b}_L$ are light. Dedicated stop searches are currently sensitive to Scenarios II and III, but not Scenario I. Sbottom-motivated searches ($2 b + \rm{MET}$) impact both squark flavors due to \tilde{t} \ra b \charp_1 as well as \tilde{b} \ra b \neut_{1,2}, constraining Scenarios I and III with somewhat weaker constraints on Scenario II. The totality of these searches yield relatively strong constraints on Natural Supersymmetry. Two regions that remain are: (1) the "compressed wedge", where $(m_{\tilde{q}} - |\mu|)/m_{\tilde{q}} \ll 1$, and (2) the "kinematic limit" region, where m_{\tilde{q}} \gsim 600-750 GeV, at the kinematic limit of the LHC searches. We calculate the correlated predictions for Higgs physics, demonstrating that these regions lead to distinct predictions for the lightest Higgs couplings that are separable with \simeq 10% measurements. We show that these conclusions remain largely unchanged once the MSSM is extended to the NMSSM in order to naturally obtain a large enough mass for the lightest Higgs boson consistent with LHC data.Comment: 18 pages, 8 figure

Verständnis und Feinabstimmung der Art der Wechselwirkungen zwischen einwandigen Kohlenstoff-Nanoröhren und lichtaktiven Bausteinen

This thesis is highlighted in the area of photon- and charge-management with focus on non-covalent electron donor-acceptor systems built around several different photoactive building blocks, on one hand, and 1-dimensional (1D) single-walled carbon nanotubes (SWCNTs), on the other hand. Particular attention is paid to the ability of photoactive building blocks to individualize SWCNTs, doping of SWCNTs, mode of the interactions between the two individual constituents, and the overall stability of the hybrid systems. Moreover, the selective interactions / functionalization between photoactive building blocks and SWCNTs with specific chirality are discussed using two differently prepared mechanically interlocked nanotubes (MINTs) systems as examples. The latter revealed a correlation between chiral selectivity and the molecular structure of the corresponding photoactive building blocks. A complete photophysical characterization of the individual constituents and the corresponding SWCNT hybrid systems by means of a broad range of spectroscopic(steady-state absorption, fluorescence, and Raman spectroscopies) and microscopic (atomic force microscopy (AFM) and aberration corrected high resolution transmission electron microscopy (AC-HRTEM)) techniques were performed. In particular, time-resolved transient absorption experiments with tunable excitation wavelengths and energies, ranging from femtosecond (fs) to microsecond (µs) regime stand at the forefront. They assist in understanding the mechanism that is associated with the generation and fade of the photoexcited states. A number of steady-state spectroscopic techniques in combination with microscopic techniques compliment the time-resolved measurements and round off the quest for a better understanding of the involved processes. The first two projects demonstrated the ability of the photoactive building blocks to non-covalently self-assemble onto the surface of SWCNTs driven by charge-transfer (CT) interactions. To this end, polymethine-based NIR dyes and porphyrins were used. The third project introduced the concept of using SWCNTs to harvest energy from low lying excited singlet fission (SF) states from a SF chromophore (o-dibenzodiazahexaacene) without compromising the initial SF. After this, the focus was placed on two different strategically synthesized chiral selective MINTs and the impact of the mechanically bound macrocycles (zinc porphyrins (ZnPs) and π-extended tetrathiafulvalene (ex-TTF)) on the excited state dynamics of SWCNTs.Der Schwerpunkt dieser Arbeit liegt im Bereich des Photonen- und Ladungsmanagements mit dem Fokus auf nicht-kovalente Elektronen- Donor-Akzeptor-Systeme, die einerseits durch verschiedene lichtaktive Bausteine und andererseits durch 1-dimensionale (1D) einwandige Kohlenstoffnanoröhren (SWCNTs) aufgebaut sind. Besonderes Augenmerk wird auf die Fähigkeit der lichtaktiven Bausteine zur Individualisierung der SWCNTs, die Dotierung der SWCNTs, die Art der Wechselwirkungen zwischen den beiden einzelnen Bestandteilen und die Gesamtstabilität der Hybridsysteme gelegt. Darüber hinaus werden die selektiven Wechselwirkungen / Funktionalisierungen zwischen lichtaktiven Bausteinen und SWCNTs mit spezifischer Chiralität am Beispiel von zwei unterschiedlich präparierten Systemen mit mechanisch verzahnten Nanoröhrchen (MINTs) diskutiert. Letztere zeigten eine Korrelation zwischen chiraler Selektivität und der molekularen Struktur der entsprechenden lichtaktiven Bausteine. Im Rahmen dieser Arbeit wird eine vollständige photophysikalische Charakterisierung der einzelnen molekularen Bestandteile und der entsprechenden SWCNT-Hybridsysteme mittels einer breiten Palette von spektroskopischen (stationäre Absorption, Fluoreszenz- und Raman-Spektroskopie) sowie mikroskopischen (Rasterkraftmikroskopie (AFM) und aberrationskorrigierte hochauflösende Transmissionselektronenmikroskopie (AC-HRTEM)) Techniken durchgeführt. Insbesondere zeitaufgelöste transiente Absorptionsexperimente mit vorab definierten Anregungswellenlängen, die vom Femtosekunden-(fs) bis zum Mikrosekundenbereich (µs) reichen, stehen bei der Charakterisierung im Vordergrund. Sie helfen dabei, den Mechanismus zu verstehen, der mit der Erzeugung und dem Abklingen, der durch Licht angeregten Zustände, verbunden ist. Darüber hinaus ergänzen eine Reihe von stationären spektroskopischen Techniken in Kombination mit mikroskopischen Techniken die zeitaufgelösten Messungen und runden Aufklärung der beteiligten Prozesse ab. Die ersten beiden Projekte demonstrierten die Fähigkeit der lichtaktiven Bausteine zur nicht-kovalenten Selbstassemblierung auf der Oberfläche von SWCNTs, welche aufgrund von Wechselwirkungen durch Ladungstransfer (CT) ermöglicht wird. Zu diesem Zweck wurden NIR-Farbstoffe auf Polymethinbasis und Porphyrine verwendet. Das dritte Projekt führte das Konzept ein, SWCNTs zu nutzen, um Energie aus niedrig liegenden, angeregten Zuständen durch Singulettspaltung (SF) von einem SF-Chromophor (o-Dibenzodiazahexaacen) zu nutzen, ohne die anfängliche SF zu beeinträchtigen. Danach wurde der Fokus auf zwei verschiedene strategisch synthetisierte chirale selektive MINTs und die Auswirkungen der mechanisch gebundenen Makrozyklen (Zinkporphyrine (ZnPs) und π-erweitertes