Perfluoroalkanesulfonyl linker units for solid phase organic synthesis

Diversity linker units exploit the cleavage step in solid phase synthesis for the incorporation of further diversity into target molecules. A solid-supported perfluorosulfonyl linker unit would allow cleavage of substrates using transition-metal- catalysed cross-coupling reactions. This thesis describes several approaches towards a perfluoroalkanesulfonyl diversity linker from diiodoperfluoroalkanes. Early work concentrated on the reaction of diiodoperfluoroalkanes with eugenol. The resulting perfluoroalkyliodides were attached to Wang resin using Mitsunobu chemistry. However, stability problems prevented the generation of resin bound perfluoroalkanesulfonic acids and the route was abandoned. A bis-perfluoroalkanesulfonyl chloride linker unit was prepared from diiodoperfluoroalkanes by generation of the bis-sodium sulfite salt and subsequent chlorination. Optimisation studies using design software allowed preparation of multigram quantities in 60 - 70% yield. Model solution phase synthesis of bis- perfluoroalkanesulfonamides and bis-perfluoroalkanesulfonate esters showed the feasibility of attaching the bis-sulfonyl chloride to amino resins and loading phenols. Diversity cleavage was demonstrated using Suzuki and Stille reactions and optimised by screening parallel arrays of reaction conditions. Loading the bis-sulfonyl chloride onto TentaGel® gave access to solid supported porfluorosulfonate osters and diversity cleavage was shown using Suzuki reactions. However, the linkage to solid supports proved to be unstable and an additional spacer unit was required if the linker was to find widespread use. To this end, a second generation perfluoroalkanesulfonyl linker unit was developed from ally I alcohol and diiodoperfluoroalkanes. Oxidation to a perfluoroalkanesulfonyl chloride was achieved using a novel reaction employing N- chlorosuccinimide. Several methods for loading this linker unit onto a solid support were investigated but none were successful and this chemistry requires further development before it offers a practical perfluoroalkanesulfonyl diversity linker

Non-Gaussianity and Excursion Set Theory: Halo Bias

We study the impact of primordial non-Gaussianity generated during inflation on the bias of halos using excursion set theory. We recapture the familiar result that the bias scales as $k^{-2}$ on large scales for local type non-Gaussianity but explicitly identify the approximations that go into this conclusion and the corrections to it. We solve the more complicated problem of non-spherical halos, for which the collapse threshold is scale dependent.Comment: 13 pages, 3 figures. v2 references added. Matches published versio

Post-processing partitions to identify domains of modularity optimization

We introduce the Convex Hull of Admissible Modularity Partitions (CHAMP) algorithm to prune and prioritize different network community structures identified across multiple runs of possibly various computational heuristics. Given a set of partitions, CHAMP identifies the domain of modularity optimization for each partition ---i.e., the parameter-space domain where it has the largest modularity relative to the input set---discarding partitions with empty domains to obtain the subset of partitions that are "admissible" candidate community structures that remain potentially optimal over indicated parameter domains. Importantly, CHAMP can be used for multi-dimensional parameter spaces, such as those for multilayer networks where one includes a resolution parameter and interlayer coupling. Using the results from CHAMP, a user can more appropriately select robust community structures by observing the sizes of domains of optimization and the pairwise comparisons between partitions in the admissible subset. We demonstrate the utility of CHAMP with several example networks. In these examples, CHAMP focuses attention onto pruned subsets of admissible partitions that are 20-to-1785 times smaller than the sets of unique partitions obtained by community detection heuristics that were input into CHAMP.Comment: http://www.mdpi.com/1999-4893/10/3/9

Neue Strategien für die 18 F‐Radiochemie

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90201/1/1132_ftp.pd

[11C]Carbon Dioxide: Starting Point for Labeling PET Radiopharmaceuticals

Positron emission tomography (PET) is a powerful in vivo imaging technique capable of providing dynamic information on biochemical processes in the living human subject. Applications of PET in oncology, neurology, psychiatry, cardiology and other medical specialties continue to grow. The use of PET relies on the characteristics and availability of appropriately labeled radiopharmaceuticals. Carbon-11 is one of the most useful radionuclides for PET chemistry, since its introduction into a biologically active molecule dose not modify the biochemical properties of the compound. [11C]Carbon dioxide (11CO2), produced by cyclotron, is the most common and versatile primary labeling precursor in the production of 11C–labeled radiopharmaceuticals

Reionization and the large-scale 21 cm-cosmic microwave background cross correlation

Of the many probes of reionization, the 21 cm line and the cosmic microwave background (CMB) are among the most effective. We examine how the cross-correlation of the 21 cm brightness and the CMB Doppler fluctuations on large angular scales can be used to study this epoch. We employ a new model of the growth of large scale fluctuations of the ionized fraction as reionization proceeds. We take into account the peculiar velocity field of baryons and show that its effect on the cross correlation can be interpreted as a mixing of Fourier modes. We find that the cross-correlation signal is strongly peaked toward the end of reionization and that the sign of the correlation should be positive because of the inhomogeneity inherent to reionization. The signal peaks at degree scales (l~100) and comes almost entirely from large physical scales (k~0.01 Mpc). Since many of the foregrounds and noise that plague low frequency radio observations will not correlate with CMB measurements, the cross correlation might appear to provide a robust diagnostic of the cosmological origin of the 21 cm radiation around the epoch of reionization. Unfortunately, we show that these signals are actually only weakly correlated and that cosmic variance dominates the error budget of any attempted detection. We conclude that the detection of a cross-correlation peak at degree-size angular scales is unlikely even with ideal experiments.Comment: 15 pages, 4 figures, submitted to MNRA

An RF-powered micro-reactor for the detection of astrobiological target molecules on planetary bodies

We describe a sample-processing micro-reactor that utilizes 60 GHz RF radiation with approximately 730 mW of output power. The instrument design and performance characterization are described and then illustrated with modeling and experimental studies. The micro-reactor's efficiency on affecting hydrolysis of chemical bonds similar to those within large complex molecules was demonstrated: a disaccharide—sucrose—was hydrolyzed completely under micro-reactor conditions. The products of the micro-reactor-facilitated hydrolysis were analyzed using mass spectroscopy and proton nuclear magnetic resonance analytical techniques

TrkA expression decreases the in vivo aggressiveness of C6 glioma cells

We stably expressed the nerve growth factor receptor trkA or a truncated trkA lacking the kinase domain (trkA delta) in a highly tumorigenic rat glioma cell line, C6. Survival of rats with large intrastriatal inocula of C6trkA cells was significantly longer than for rats bearing C6 or C6trkA delta cells. Histological studies revealed that C6trkA cells were much less invasive than C6 or C6trkA delta cells and had a greater rate of apoptosis. There was no apparent induction of differentiation of C6 cells by trkA. Therefore, unlike what is observed in neuroblastomas, trkA decreases tumorigenicity by modulating invasiveness and tumor cell death independent of inducing differentiation. This novel mechanism suggests a new therapeutic strategy for malignant gliomas