The synthesis of modified integrin-targeting peptides for incorporation into lipid/integrin-targeting peptide/DNA transfection complexes.

Integrin-targeting peptides have been shown to increase transfection efficiency when included in a number of different non-viral vectors. In the case of Lipofectin/DN A complexes (LD), transfection efficiency has been shown to increase on incorporation of an integrin- targeting peptide (Lipid/Integrin-targeting peptide/DNA complexes), as seen by a 100-fold increase in luciferase expression. Efforts to improve the Lipofectin component of Lipid/Integrin-targeting peptide/DNA complexes continue to be made and consequently ways of increasing transfection efficiency through modifications to the integrin-binding peptide are also been investigated. The integrin- targeting peptide component of Lipid/Integrin-targeting peptide/DNA complexes investigated by Hart et al. has effectively three functionalities a 'head' which is complimentary to a specific integrin, a 'tail' which can bind to and condense DNA and a 'spacer' which links the 'head' and 'tail'. Both alternative spacers and DNA-binding motifs have been synthesised and incorporated into integrin-targeting peptides with the intention of investigating the effects of these modifications on the transfection efficiency as well as physical properties of Lipid/Integrin-targeting peptide/DNA complexes. In this thesis are reported the structures of unnatural amino acids synthesised and incorporated into integrin-targeting peptides, as well as some of the transfection results obtained

Biomimetic surfaces via dextran immobilization : grafting density and surface properties

Biomimetic surfaces were prepared by chemisorption of oxidized dextran (Mw = 110 kDa) onto SiO2 substrates that were previously modified with aminopropyl-tri-ethoxy silane (APTES). The kinetics of dextran oxidation by sodium metaperiodate (NaIO4) were quantified by 1H NMR and pH measurements. The extent of oxidation was then used to control the morphology of the biomimetic surface. Oxidation times of 0.5, 1, 2, 4, and 24 hours resulted in \u3c20, ~30, ~40, ~50 and 100% oxidation, respectively. The surfaces were characterized by contact angle analysis and atomic force microscopy (AFM). Surfaces prepared with low oxidation times revealed a more densely packed brushy layer when imaged by AFM than those prepared at low oxidation times. Finally, the contact angle data revealed, quite unexpectedly, that the surface with the greatest entropic freedom (0.5 h) wetted the fastest and to the greatest extent (THETAAPTES \u3e THETA1h \u3e THETA2,4h \u3e THETA0.5h)

Chandra and FUSE spectroscopy of the hot bare stellar core H1504+65

H1504+65 is an extremely hot hydrogen-deficient white dwarf with an effective temperature close to 200,000 K. We present new FUV and soft X-ray spectra obtained with FUSE and Chandra, which confirm that H1504+65 has an atmosphere primarily composed of carbon and oxygen. The Chandra LETG spectrum (60-160 Angstroem) shows a wealth of photospheric absorption lines from highly ionized oxygen, neon, and - for the first time identified in this star - magnesium and suggests relatively high Ne and Mg abundances. This corroborates an earlier suggestion that H1504+65 represents a naked C/O stellar core or even the C/O envelope of an O-Ne-Mg white dwarf.Comment: 15 pages, 10 figures, accepted for publication in A&

On the robustness of H-deficient post-AGB tracks

We analyze the robustness of H--deficient post--AGB tracks regarding previous evolution of their progenitor stars and the constitutive physics of the remnants. Our motivation is a recent suggestion of Werner & Herwig (2006) that previous evolution should be important in shaping the final post--AGB track and the persisting discrepancy between asteroseismological and spectroscopical mass determinations. This work is thus complementary to our previous work (Miller Bertolami & Althaus 2006) and intends to shed some light on the uncertainty behind the evolutionary tracks presented there. We compute full evolutionary models for PG1159 stars taking into account different extramixing (overshooting) efficiencies and lifetimes on the TP-AGB during the progenitor evolution. We also assess the effect of possible differences in the opacities and equation of state by artificially changing them before the PG1159 stage. Also comparisons are made with the few H-deficient post--AGB tracks available in the literature. Contrary to our expectations, we found that previous evolution is not a main factor in shaping H--deficient post--AGB tracks. Interestingly enough, we find that only an increase of $\sim50$ in the intershell opacities at high effective temperatures may affect the tracks as to reconcile spectroscopic and asteroseismologic mass determinations. This forces us to conclude that our previous tracks (Miller Bertolami & Althaus 2006) are robust enough as to be used for spectroscopic mass determinations, unless opacities in the intershell region are substantially different. Our results, then, call for an analysis of possible systematics in the usually adopted asteroseismological mass determination methods.Comment: Accepted for publication in Astronomy and Astrophysc

New nonadiabatic pulsation computations on full PG1159 evolutionary models: the theoretical GW Vir instability strip revisited

We reexamine the theoretical instability domain of pulsating PG1159 stars (GW Vir variables). We performed an extensive g-mode stability analysis on PG1159 evolutionary models with stellar masses ranging from 0.530 to 0.741 Mo for which the complete evolutionary stages of their progenitors from the ZAMS, through the thermally pulsing AGB and born-again phases to the domain of the PG1159 stars have been considered. We found that pulsations in PG1159 stars are excited by the kappa-mechanism due to partial ionization of carbon and oxygen, and that no composition gradients are needed between the surface layers and the driving region, much in agreement with previous studies. We show, for the first time, the existence of a red edge of the instability strip at high luminosities. We found that all of the GW Vir stars lay within our theoretical instability strip. Our results suggest a qualitative good agreement between the observed and the predicted ranges of unstable periods of individual stars. Finally, we found that generally the seismic masses (derived from the period spacing) of GW Vir stars are somewhat different from the masses suggested by evolutionary tracks coupled with spectroscopy. Improvements in the evolution during the thermally pulsing AGB phase and/or during the core helium burning stage and early AGB could help to alleviate the persisting discrepancies.Comment: 10 pages, 8 figures. To be published in Astronomy and Astrophysic

The central star of the planetary nebula PB 8: a Wolf-Rayet-type wind of an unusual WN/WC chemical composition

A considerable fraction of the central stars of planetary nebulae (CSPNe) are hydrogen-deficient. As a rule, these CSPNe exhibit a chemical composition of helium, carbon, and oxygen with the majority showing Wolf-Rayet-like emission line spectra. These stars are classified as CSPNe of a spectral type [WC]. We perform a spectral analysis of CSPN PB 8 with the Potsdam Wolf-Rayet (PoWR) models for expanding atmospheres. The source PB 8 displays wind-broadened emission lines from strong mass loss. Most strikingly, we find that its surface composition is hydrogen-deficient, but not carbon-rich. With mass fractions of 55% helium, 40% hydrogen, 1.3% carbon, 2% nitrogen, and 1.3% oxygen, it differs greatly from the 30-50% of carbon which are typically seen in [WC]-type central stars. The atmospheric mixture in PB 8 has an analogy in the WN/WC transition type among the massive Wolf-Rayet stars. Therefore we suggest to introduce a new spectral type [WN/WC] for CSPNe, with PB 8 as its first member. The central star of PB 8 has a relatively low temperature of T=52kK, as expected for central stars in their early evolutionary stages. Its surrounding nebula is less than 3000 years old, i.e. relatively young. Existing calculations for the post-AGB evolution can produce hydrogen-deficient stars of the [WC] type, but do not predict the composition found in PB 8. We discuss various scenarios that might explain the origin of this unique object.Comment: 10 pages, 10 figure

Vasopressors and Inotropes in the Treatment of Human Septic Shock: Effect on Innate Immunity?

Catecholamines have been suggested to modulate innate immune responses in experimental settings. The significance hereof in the treatment of human septic shock is unknown. We therefore sought if and how vasopressor/inotropic doses relate to pro-inflammatory mediators during treatment of septic shock. We prospectively studied 20 consecutive septic shock patients. For 3 days after admission, hemodynamic variables, lactate and plasma levels of interleukins (IL)-6 and 8, tumor necrosis factor (TNF)-α, and elastase-α1-antitrypsin were measured six hourly. Doses of vasoactive drugs were recorded. Of the 20 patients, nine died in the intensive care unit. Dobutamine doses were positively associated and related to TNF-α plasma levels, independently of disease severity, hemodynamics, and outcome, in multivariable models. Dopamine doses were positively associated with IL-6, and norepinephrine was inversely associated with IL-8 and TNF-α levels. Our observations suggest that catecholamines used in the treatment of human septic shock differ in their potential modulation of the innate immune response to sepsis in vivo. Dobutamine treatment may contribute to circulating TNF-α and dopamine to IL-6, independently of activated neutrophils. Conversely, norepinephrine may lack pro-inflammatory actions

Self-assembled hydrogel fibers for sensing the multi-compartment intracellular milieu

Targeted delivery of drugs and sensors into cells is an attractive technology with both medical and scientific applications. Existing delivery vehicles are generally limited by the complexity of their design, dependence on active transport, and inability to function within cellular compartments. Here, we developed self-assembled nanofibrous hydrogel fibers using a biologically inert, low-molecular-weight amphiphile. Self-assembled nanofibrous hydrogels offer unique physical/mechanical properties and can easily be loaded with a diverse range of payloads. Unlike commercially available E. coli membrane particles covalently bound to the pH reporting dye pHrodo, pHrodo encapsulated in self-assembled hydrogel-fibers internalizes into macrophages at both physiologic (37°C) and sub-physiologic (4°C) temperatures through an energy-independent, passive process. Unlike dye alone or pHrodo complexed to E. coli, pHrodo-SAFs report pH in both the cytoplasm and phagosomes, as well the nucleus. This new class of materials should be useful for next-generation sensing of the intracellular milieu