DNA nanoparticles as ocular drug delivery platform

The field of DNA nanotechnology has progressed rapidly in recent years and now offers facile fabrication of a large variety of nanostructures of different shapes and geometries. In this thesis, short nucleic acid sequences are functionalized with hydrophobic units to form the basis of an ocular drug delivery platform. These DNA amphiphiles self-assemble into micellar nanoparticles (NPs) that exhibit a high affinity to the ocular surface. After selecting the best carrier, loading of the medication can easily be performed by employing drug specific aptamers that are hybridized on the NP. The developed platform shows a significantly prolonged availability of the drug compared to the free medication. In future applications, this allows for a lower dosing regime of the eye drop and a reduced drug concentration, which greatly improve the treatment of ophthalmic diseases

DNA nanoparticles as ocular drug delivery platform

The field of DNA nanotechnology has progressed rapidly in recent years and now offers facile fabrication of a large variety of nanostructures of different shapes and geometries. In this thesis, short nucleic acid sequences are functionalized with hydrophobic units to form the basis of an ocular drug delivery platform. These DNA amphiphiles self-assemble into micellar nanoparticles (NPs) that exhibit a high affinity to the ocular surface. After selecting the best carrier, loading of the medication can easily be performed by employing drug specific aptamers that are hybridized on the NP. The developed platform shows a significantly prolonged availability of the drug compared to the free medication. In future applications, this allows for a lower dosing regime of the eye drop and a reduced drug concentration, which greatly improve the treatment of ophthalmic diseases

On the Putative Detection of z>0 X-ray Absorption Features in the Spectrum of Markarian 421

In a series of papers, Nicastro et al. have reported the detection of z>0 OVII absorption features in the spectrum of Mrk421 obtained with the Chandra Low Energy Transmission Grating Spectrometer (LETGS). We evaluate this result in the context of a high quality spectrum of the same source obtained with the Reflection Grating Spectrometer (RGS) on XMM-Newton. The data comprise over 955ks of usable exposure time and more than 26000 counts per 50 milliAngstrom at 21.6 Angstroms. We concentrate on the spectrally clean region (21.3 < lambda < 22.5 Angstroms) where sharp features due to the astrophysically abundant OVII may reveal an intervening, warm--hot intergalactic medium (WHIM). We do not confirm detection of any of the intervening systems claimed to date. Rather, we detect only three unsurprising, astrophysically expected features down to the Log(N_i)~14.6 (3 sigma) sensitivity level. Each of the two purported WHIM features is rejected with a statistical confidence that exceeds that reported for its initial detection. While we can not rule out the existence of fainter, WHIM related features in these spectra, we suggest that previous discovery claims were premature. A more recent paper by Williams et al. claims to have demonstrated that the RGS data we analyze here do not have the resolution or statistical quality required to confirm or deny the LETGS detections. We show that our careful analysis resolves the issues encountered by Williams et al. and recovers the full resolution and statistical quality of the RGS data. We highlight the differences between our analysis and those published by Williams et al. as this may explain our disparate conclusions.Comment: 19 pages/7 figures/4 tables. 060424 submitted to ApJ 060522 re-submitted following ApJ reques

Transfinite reductions in orthogonal term rewriting systems

Strongly convergent reduction is the fundamental notion of reduction in infinitary orthogonal term rewriting systems (OTRSs). For these we prove the Transfinite Parallel Moves Lemma and the Compressing Lemma. Strongness is necessary as shown by counterexamples. Normal forms, which we allow to be infinite, are unique, in contrast to ω-normal forms. Strongly converging fair reductions result in normal forms. In general OTRSs the infinite Church-Rosser Property fails for strongly converging reductions. However for Böhm reduction (as in Lambda Calculus, subterms without head normal forms may be replaced by ⊥) the infinite Church-Rosser property does hold. The infinite Church-Rosser Property for non-unifiable OTRSs follows. The top-terminating OTRSs of Dershowitz c.s. are examples of non-unifiable OTRSs

Infinitary lambda calculus

In a previous paper we have established the theory of transfinite reduction for orthogonal term rewriting systems. In this paper we perform the same task for the lambda calculus. From the viewpoint of infinitary rewriting, the Böhm model of the lambda calculus can be seen as an infinitary term model. In contrast to term rewriting, there are several different possible notions of infinite term, which give rise to different Böhm-like models, which embody different notions of lazy or eager computation