No description available.

The catalytic properties of gold have been widely investigated. In Dr. Chao-Ming Chiang¡¦s study, department of chemistry of NSYSU, they found that the organic molecules, propanal, form heterocyclic 2, 4, 6- triethyl-1, 3, 5-trioxane ring on Au(110) missing row surface at 180 K by temperature programmed desorption (TPD) and reflection absorption infrared spectra (RAIR). In this study, we used low energy electron diffraction (LEED) and scanning tunneling microscopy (STM) to study the detailed catalytic process on surface. Residual gas analyzer (RGA) was used to measure the thermal desorption of the propanal on Au(110) at 130 K and 185 K. This can be used to calibrate the temperature on the surface, which can not be directly measured by the thermal couple on the manipulator. The combination between the LEED pattern from the experiment and the DFT model shows the propanal adsorbed on the inclined plane with about 64 deg. to 71 deg. companing the (110) plane. The STM results also show that some of the surface after adsorption have trench wider atomic rows. In our experiment, the real temperature of the sample was not exactly determined. More experiments need to be taken to confirm the temperature.

The development of a safe, effective prophylactic HIV vaccine remains a major global health priority. Stabilized, soluble trimers that mimic the native functional HIV trimer have been developed that elicit strain-specific neutralizing HIV antibodies in animal models, and are currently being evaluated in several human clinical trials. Identifying whether multiple immunogens could be administered to facilitate the broadening of responses represents a pivotal challenge. In this thesis, we characterized the antibody response in individuals infected with multiple HIV strains to inform the development of polyvalent and sequential HIV vaccine regimens. We found that conventional approaches to detect HIV co- and superinfection are confounded by recombination. Therefore, we developed an automated, Bayesian approach to detect superinfection explicitly accounting for recombination. Using simulated and real sequence data, we demonstrated that this approach is sensitive, highly specific, and robust to recombination. Furthermore, analyzing previously published sequence datasets, we identified cases of superinfection that previously went undetected, indicating that superinfection occurs more frequently than previously estimated. We characterized the development of antibodies in five superinfected individuals identified in the CAPRISA 002 acute infection cohort. Specifically, we evaluated whether superinfection re-engaged cross-reactive memory B cells, promoting the development of cross-neutralizing antibodies. By comparing the breadth of the neutralizing antibody response in superinfected individuals to those that typically develop in singly infected individuals, we showed that HIV superinfection was not sufficient to broaden responses. By characterizing the kinetics and specificity of autologous neutralizing antibody responses, we show that responses to the superinfecting viruses failed to efficiently recruit neutralizing memory B cells. Instead, the secondary infection elicited strain-specific, de novo responses. This occurred even though the superinfecting viruses were relatively closely related (from the same subtype). To determine whether the co-exposure to diverse Env antigens favours the development of cross-neutralizing antibodies better than sequential exposure, we characterized the development of neutralizing antibodies in HIV co-infected individuals where several divergent viruses were transmitted prior to seroconversion. We identified three cases of co-infection that encompassed immunological exposure to: (i) two diverse, unlinked Envs, (ii) two related Envs with diversity uniformly distributed over the trimer, and (iii) two diverse but recombined Envs such that clusters of high homology were preserved in the presence of high diversity elsewhere. We found that, like superinfection, co-infection was not sufficient to broaden neutralizing antibody responses. Co-exposure to two HIV Env antigens did not necessarily produce additive or cross-neutralizing antibody responses, and in some cases was subject to immunological interference. This was most evident in the case of co-infection with two related Envs where diversity was uniformly distributed across the Env trimer; in this case neutralizing antibody responses to one variant arose to the near exclusion of responses to the other. However, in the case of co-exposure to diverse Envs but where the trimer apex was conserved in both variants through recombination, potent neutralization of both variants was evident. This was the co-infected participant who developed the broadest neutralizing antibody response, and we show that cross-neutralization was mediated, in part, by trimer apextargeting neutralizing antibodies. In conclusion, we find that HIV superinfection fails to efficiently recruit neutralizing memory B cells and, at best, results in additive nAb responses rather than a synergistic effect leading to cross-neutralization; a distinction that is highly relevant for vaccine design. While sequential immunizations with heterologous Env immunogens may be able to improve the potency of elicited responses, alone, they are unlikely to promote the development of bnAbs. Our observations from cases of co-infection suggests that cocktails of divergent stabilized Env trimers are unlikely to drive the development of cross-neutralizing antibodies, and may be subject to interference. However, the rational design of more similar immunogen cocktails where conserved epitopes are preserved across immunogens may be able to facilitate neutralizing antibodies to these targets, as seen in one individual. Thus, the use of related, stabilized Env trimers with diversity introduced in key regions together with strategies to reduce the immunogenicity of immunodominant, strain-specific epitopes may represent one path to a cross-neutralizing antibody response to multiple Envs within a cocktail.

The receptor dimers that mediate bacterial chemotaxis form high-order signaling complexes with CheW and the kinase CheA. From the packing arrangement in two crystal structures of different receptor cytoplasmic fragments, two different models have been proposed for receptor signaling arrays: the trimers-of-dimers and hedgerow models. We identified an interdimer distance that differs substantially in the two models, labeled the atoms defining this distance through isotopic enrichment, and measured it with 13C-19F REDOR. This was done in two types of receptor samples: first, isolated bacterial membranes containing overexpressed, intact receptor, and second, soluble receptor fragments reconstituted into kinase-active signaling complexes. In both cases, the distance found was not compatible with the receptor dimer−dimer contacts observed in the trimers-of-dimers or in the hedgerow models. Comparisons of simulated and observed REDOR dephasing were used to deduce a closest-approach distance at this interface, which provides a constraint for the possible arrangements of kinase-competent receptor assemblies. An alternate model of receptor signaling is proposed, which reconciles this result with existing structural and biochemical data. Additionally, two advances to solid-state NMR methodology are described. The first is a set of strategies to protect protein samples against degradation by solid-state NMR analysis. Biochemical and spectroscopic techniques are prescribed to identify and isolate specific challenges to protein stability, allowing them to be addressed individually. For this purpose a new pulse sequence (Thermal Calibration Under Pulseload, or TCUP) is employed, which allows sample temperature to be measured with exceptional time resolution. The second NMR advance describes the creation and characterization of a 13C-19F REDOR distance-calibration standard. The inclusion compound of 4-fluorotoluene and tert-butylcalix[4]arene was used for this purpose. The compound is easily synthesized from commercially available materials, and provides a long, isolated 13C-19F distance of 4.1 Å. Dynamics within the compound allow direct observation of 19F resonances without 1H-decoupling, and provide exceptionally sharp 13C resonances; these characteristics speed the routine setup of REDOR experiments. Both methodological developments were important to performing accurate distance measurements on functionally relevant chemotaxis signaling complexes; they also pave the way for making similar measurements in other proteins of interest.

High molecular weight PBTTT-C₁₂ is blended with the pure trimer, BTTT-3, to enhance intergrain connectivity and charge transport. Analysis of the morphology and crystallinity of the blends shows that the polymer and oligomer are well-integrated, leading to high hole mobilities, greater than 0.1 cm² V⁻¹ s⁻¹, in films that contain as much as 83% oligomer.

Die vorliegende Dissertation beschäftigt sich mit der Herstellung und Charakterisierung einzelner Edelmetallnanopartikel-Cluster für die oberflächenverstärkte Raman-Streuung (engl. surface-enhanced Raman scattering; SERS). In Clustern treten stark lokalisierte Regionen mit sehr hohen Feldverstärkungen auf (engl. hot spots), die den SERS-Effekt extrem verstärken. In der Regel werden Metallnanopartikel in kolloidaler Suspension untersucht, so dass nur Aussagen über das gesamte Kolloid und nicht über einzelne Cluster getroffen werden können. Für die Identifizierung von Struktur-Eigenschafts-Korrelationen wurden in dieser Arbeit daher einzelne Cluster optisch und elektronenmikroskopisch charakterisiert. Der erste Teil der vorliegenden Arbeit beschreibt neue Ansätze zur Trennung von glasverkapselten SERS-Nanopartikel-Clustern mit Hilfe der Dichtegradientenzentrifugation sowie die Etablierung einer modifizierten Synthesevorschrift zur Herstellung von monodispersen Silbernanopartikeln. Der zweite Teil beschäftigt sich mit der optischen Charakterisierung einzelner SERS-Cluster und den dafür notwendigen experimentellen Umbauten eines bestehenden Versuchsaufbaus. Anschließend wird die oberflächenverstärkte Raman-Streuung von SERS-Clustern in Abhängigkeit der Polarisation gemessen und die lokalisierte Oberflächenplasmonenresonanz (engl. localized surface plasmon resonance; LSPR) von Nano- und Mikrostrukturen bestimmt.

No description available.

Chimie dynamique: reconnaissance de nucléobases par des récepteurs synthétiques et isomérie cis-trans d'hydrazones acylées.Ce travail traite du développement des systèmes moléculaires qui peuvent s'adapter à l'addition de substances qui agissent comme un gabarit. Cette approche permet d'isoler une espèce majeure à partir d'un mélange de composés par le biais de la chimie combinatoire dynamique (CCD). La première partie de ma thèse de doctorat inclus l'utilisation d'un ADN simple brin (ADNsb) comme un gabarit pour le transfert d'information par auto-assemblage de récepteurs sans avoir besoin d'enzyme. De nouveaux récepteurs de l'adénine et de la guanine (pinces A et G) solubles dans l'eau ont été conçues dans ce but. Une approche utilisant la résonance magnétique nucléaire (RMN) a été utilisée pour déterminer l'affinité de liaison comme preuve d'une reconnaissance spécifique et efficace. Une évaluation dans l'eau par dichroïsme circulaire (CD) et mesure de la température de fusion par UV (Tm) a été réalisée. Cela a permis de tester respectivement la capacité d'auto-assemblage entre les pinces et un modèle ADNsb, et la force du processus de coopérativité. La deuxième partie de ce travail est axée sur le tri spontanné de motifs pyridine acylhydrazone et sur les configurations intéressantes qu'ils adoptent. Nous avons étudié la synthèse d'une série de motifs pyridine acylhydrazone: dimère, trimères et pentamères. Des études RMN ont permis d'évaluer les changements dans l'équilibre configurationnel cis / trans de ces systèmes dynamiques. Les études ont montré que l'équilibre attendu est biaise la cis acylhydrazone pyridine isomère a été observée par diffraction des rayons X. / Dynamic chemistry: nucleobase recognition by synthetic receptors and cis-trans acylhydrazone isomerism. This work deals with the development of molecular systems which can adapt upon the addition of substances that act as templates. This approach enables one major species to be identified from a mixture of compounds through the use of dynamic combinatorial chemistry (DCC). The first part of my PhD included the use of a single stranded DNA (ssDNA) as a template for information transfer via the self-assembly of receptors without the need for enzymes. New water soluble adenine and guanine receptors (A and G clamps) were designed and synthesised for this purpose. Nuclear magnetic resonance (NMR) titration studies were carried out to calculate the binding affinity and as a proof of specific and efficient recognition. An assessment in water via circular dichroism (CD) and UV temperature melting (Tm) studies was carried out. This tested the ability for self-assembly between the clamps and a ssDNA template and the strength of the cooperative process respectively. The second part of my PhD focused on the self-sorting of acylhydrazone pyridine motifs and the interesting configurations they adopt. The feasibility to synthesise these acylhydrazone pyridine motifs (dimer, trimers and pentamers) was investigated. X-ray and NMR studies showed that the equilibrium was found to be biased in an unusual way, and the cis acylhydrazone pyridine isomer was observed.

A radio frequency (rf) quadrupole instrument, currently known as an Isobar Separator for Anions (ISA), has been integrated into an Accelerator Mass Spectrometry (AMS) system to facilitate anion–gas reactions before the tandem accelerator. An AMS Cs+ sputter source provided > 15 keV ions that were decelerated in the prototype ISA to < 20 eV for reaction in a single collision cell and re-accelerated for AMS analysis. Reaction based isobar suppression capabilities were assessed for smaller AMS systems and a new technique for gas–phase reaction studies was developed. Isobar suppression of 36S– and 12C3– for 36Cl analysis, and YF3– and ZrF3– for 90Sr analysis were studied in NO2 with deceleration to < 12 eV. Observed attenuation cross sections, σ [x 10^–15 cm^2], were σ(S– + NO2) = 6.6, σ(C3– + NO2) = 4.2, σ(YF3– + NO2) = 7.6, σ(ZrF3– + NO2) = 19. With 8 mTorr NO2, relative attenuations of S–/Cl– ~ 10^–6, C3–/Cl– ~ 10^–7, YF3–/SrF3– ~ 5 x 10^–5 and ZrF3–/SrF3– ~ 4 x 10^–6 were observed with Cl– ~ 30% and SrF3– > 90% transmission. Current isobar attenuation limits with < 1.75 MV accelerator terminal voltage and ppm impurity levels were calculated to be 36S–/Cl– ~ 4 x 10^–16, 12C3–/Cl– ~ 1.2 x 10^–16, 90YF3–/SrF3– ~ 10^–15 and 90ZrF3–/SrF3– ~ 10^–16. Using 1.75 MV, four 36Cl reference standards in the range 4 x 10^–13 < 36Cl/Cl < 4 x 10^–11 were analyzed with 8 mTorr NO2. The measured 36Cl/Cl ratios plotted very well against the accepted values. A sample impurity content S/Cl < 6 x 10^–5 was measured and a background level of 36S–/Cl < 9 x 10^–15 was determined. Useful currents of a wide variety of anions are produced in AMS sputter sources and molecules can be identified relatively unambiguously by stripping fragments from tandem accelerators. Reactions involving YF3–, ZrF3–, S– and SO– + NO2 in the ISA analyzed by AMS are described, and some interesting reactants are identified.

A radio frequency (rf) quadrupole instrument, currently known as an Isobar Separator for Anions (ISA), has been integrated into an Accelerator Mass Spectrometry (AMS) system to facilitate anion–gas reactions before the tandem accelerator. An AMS Cs+ sputter source provided > 15 keV ions that were decelerated in the prototype ISA to < 20 eV for reaction in a single collision cell and re-accelerated for AMS analysis. Reaction based isobar suppression capabilities were assessed for smaller AMS systems and a new technique for gas–phase reaction studies was developed. Isobar suppression of 36S– and 12C3– for 36Cl analysis, and YF3– and ZrF3– for 90Sr analysis were studied in NO2 with deceleration to < 12 eV. Observed attenuation cross sections, σ [x 10^–15 cm^2], were σ(S– + NO2) = 6.6, σ(C3– + NO2) = 4.2, σ(YF3– + NO2) = 7.6, σ(ZrF3– + NO2) = 19. With 8 mTorr NO2, relative attenuations of S–/Cl– ~ 10^–6, C3–/Cl– ~ 10^–7, YF3–/SrF3– ~ 5 x 10^–5 and ZrF3–/SrF3– ~ 4 x 10^–6 were observed with Cl– ~ 30% and SrF3– > 90% transmission. Current isobar attenuation limits with < 1.75 MV accelerator terminal voltage and ppm impurity levels were calculated to be 36S–/Cl– ~ 4 x 10^–16, 12C3–/Cl– ~ 1.2 x 10^–16, 90YF3–/SrF3– ~ 10^–15 and 90ZrF3–/SrF3– ~ 10^–16. Using 1.75 MV, four 36Cl reference standards in the range 4 x 10^–13 < 36Cl/Cl < 4 x 10^–11 were analyzed with 8 mTorr NO2. The measured 36Cl/Cl ratios plotted very well against the accepted values. A sample impurity content S/Cl < 6 x 10^–5 was measured and a background level of 36S–/Cl < 9 x 10^–15 was determined. Useful currents of a wide variety of anions are produced in AMS sputter sources and molecules can be identified relatively unambiguously by stripping fragments from tandem accelerators. Reactions involving YF3–, ZrF3–, S– and SO– + NO2 in the ISA analyzed by AMS are described, and some interesting reactants are identified.