Synthesis and biodistribution of immunoconjugates of a human IgM and polymeric drug carriers

The synthesis and purification of radiolabelled immunoconjugates, composed of a human IgM monoclonal antibody directed against an intracellular tumour-associated antigen and either poly (alpha-L-glutamic acid) (PGA) or poly[N5-(2-hydroxyethyl)-L-glutamine] (PHEG) is described. Coupling of polymers to the antibody was performed through disulfide bond formation involving a single thiol group at the C-terminus of the polymer chain and 2-pyridyldisulfide groups introduced onto the antibody. The antibody was iodinated with 131I before conjugation. The polymers contained tyrosinamide in a low degree of substitution and were radiolabelled with 125I. 125I-labelled PGA and PHEG were found to be stable for at least 3 days in murine and human plasma. The biodistribution in mice of the doubly labelled immunoconjugates was studied and was compared with the pharmacokinetics of the individual components.\ud \ud PHEG showed a relatively slow blood clearance, the half-life being approximately 10 h with low uptake in liver, kidneys and spleen. PGA was rapidly cleared from the circulation and was significantly taken up in liver, kidneys and spleen. The biodistribution of both immunoconjugates was indistinguishable from that of the IgM proper, with plasma half-lives of approximately 6 h, indicating that the pharmacokinetic properties of the immunoconjugates are largely determined by the antibody part

Gap Formation by Planets in Turbulent Protostellar Disks

The processes of planet formation and migration depend intimately on the interaction between planetesimals and the gaseous disks in which they form. The formation of gaps in the disk can severely limit the mass of the planet and its migration toward the protostar. We investigate the process of gap formation through magnetohydrodynamic simulations in which internal stress arises self-consistently from turbulence generated by the magnetorotational instability. The simulations investigate three different planetary masses and two disk temperatures to bracket the tidal (thermal) and viscous gap opening conditions. The results are in general qualitative agreement with previous simulations of gap formation, but show significant differences. In the presence of MHD turbulence, the gaps produced are shallower and asymmetrically wider than those produced with pure hydrodynamics. The rate of gap formation is also slowed, with accretion occurring across the developing gap. Viscous hydrodynamics does not adequately describe the evolution, however, because planets capable of producing gaps also may be capable of affecting the level MHD turbulence in different regions of the disk.Comment: accepted by Astrophysical Journal. For associated animations see http://www.astro.virginia.edu/VITA/papers/planet1

Observations of Binary Stars with the Differential Speckle Survey Instrument. VII. Measures from 2010 September to 2012 February at the WIYN Telescope

We report on speckle observations of binary stars carried out at the WIYN Telescope over the period from September 2010 through February 2012, providing relative astrometry for 2521 observations of 883 objects, 856 of which are double stars and 27 of which are triples. The separations measured span a range of 0.01 to 1.75 arc seconds. Wavelengths of 562 nm, 692 nm, and 880 nm were used, and differential photometry at one or more of these wavelengths is presented in most cases. Sixty-six components were resolved for the first time. We also estimate detection limits at 0.2 and 1.0 arc seconds for high-quality observations in cases where no companion was seen, a total of 176 additional objects. Detection limits vary based on observing conditions and signal-to-noise ratio, but are approximately 4 magnitudes at 0.2 arc seconds and 6 magnitudes at 1.0 arc seconds on average. Analyzing the measurement precision of the data set, we find that the individual separations obtained have linear measurement uncertainties of approximately 2 mas, and photometry is uncertain to approximately 0.1 magnitudes in general. This work provides fundamental, well-calibrated data for future orbit and mass determinations, and we present three first orbits and total mass estimates of nearby K-dwarf systems as examples of this potential

The light curve of the semiregular variable L2 Puppis: I. A recent dimming event from dust

The nearby Mira-like variable L2 Pup is shown to be undergoing an unprecedented dimming episode. The stability of the period rules out intrinsic changes to the star, leaving dust formation along the line of sight as the most likely explanation. Episodic dust obscuration events are fairly common in carbon stars but have not been seen in oxygen-rich stars. We also present a 10-micron spectrum, taken with the Japanese IRTS satellite, showing strong silicate emission which can be fitted with a detached, thin dust shell, containing silicates and corundum.Comment: MNRAS (accepted

High-resolution measurement of the time-modulated orbital electron capture and of the β+\beta^+ decay of hydrogen-like 142^{142}Pm60+^{60+} ions

The periodic time modulations, found recently in the two-body orbital electron-capture (EC) decay of both, hydrogen-like $^{140}$Pr$^{58+}$ and $^{142}$Pm$^{60+}$ ions, with periods near to 7s and amplitudes of about 20%, were re-investigated for the case of $^{142}$Pm$^{60+}$ by using a 245 MHz resonator cavity with a much improved sensitivity and time resolution. We observed that the exponential EC decay is modulated with a period $T = 7.11(11)$s, in accordance with a modulation period $T = 7.12(11)$ s as obtained from simultaneous observations with a capacitive pick-up, employed also in the previous experiments. The modulation amplitudes amount to $a_R = 0.107(24)$ and $a_P = 0.134(27)$ for the 245 MHz resonator and the capacitive pick-up, respectively. These new results corroborate for both detectors {\it exactly} our previous findings of modulation periods near to 7s, though with {\it distinctly smaller} amplitudes. Also the three-body $\beta^+$ decays have been analyzed. For a supposed modulation period near to 7s we found an amplitude $a = 0.027(27)$, compatible with $a = 0$ and in agreement with the preliminary result $a = 0.030(30)$ of our previous experiment. These observations could point at weak interaction as origin of the observed 7s-modulation of the EC decay. Furthermore, the data suggest that interference terms occur in the two-body EC decay, although the neutrinos are not directly observed.Comment: In memoriam of Prof. Paul Kienle, 9 pages, 1 table, 5 figures Phys. Lett. B (2013) onlin

Disk Planet Interactions and Early Evolution in Young Planetary Systems

We study and review disk protoplanet interactions using local shearing box simulations. These suffer the disadvantage of having potential artefacts arising from periodic boundary conditions but the advantage, when compared to global simulations, of being able to capture much of the dynamics close to the protoplanet at high resolution for low computational cost. Cases with and without self sustained MHD turbulence are considered. The conditions for gap formation and the transition from type I migration are investigated and found to depend on whether the single parameter M_p R^3/(M_* H^3), with M_p, M_*, R and H being the protoplanet mass, the central mass, the orbital radius and the disk semi-thickness respectively exceeds a number of order unity. We also investigate the coorbital torques experienced by a moving protoplanet in an inviscid disk. This is done by demonstrating the equivalence of the problem for a moving protoplanet to one where the protoplanet is in a fixed orbit which the disk material flows through radially as a result of the action of an appropriate external torque. For sustainable coorbital torques to be realized a quasi steady state must be realized in which the planet migrates through the disk without accreting significant mass. In that case although there is sensitivity to computational parameters, in agreement with earlier work by Masset & Papaloizou (2003) based on global simulations, the coorbital torques are proportional to the migration speed and result in a positive feedback on the migration, enhancing it and potentially leading to a runaway. This could lead to a fast migration for protoplanets in the Saturn mass range in massive disks and may be relevant to the mass period correlation for extrasolar planets which gives a preponderance of sub Jovian masses at short orbital period.Comment: To appear in Celestial Mechanics and Dynamical Astronomy (with higher resolution figures

An 800-million-solar-mass black hole in a significantly neutral Universe at redshift 7.5

Quasars are the most luminous non-transient objects known and as a result they enable studies of the Universe at the earliest cosmic epochs. Despite extensive efforts, however, the quasar ULAS J1120+0641 at z=7.09 has remained the only one known at z>7 for more than half a decade. Here we report observations of the quasar ULAS J134208.10+092838.61 (hereafter J1342+0928) at redshift z=7.54. This quasar has a bolometric luminosity of 4e13 times the luminosity of the Sun and a black hole mass of 8e8 solar masses. The existence of this supermassive black hole when the Universe was only 690 million years old---just five percent of its current age---reinforces models of early black-hole growth that allow black holes with initial masses of more than about 1e4 solar masses or episodic hyper-Eddington accretion. We see strong evidence of absorption of the spectrum of the quasar redwards of the Lyman alpha emission line (the Gunn-Peterson damping wing), as would be expected if a significant amount (more than 10 per cent) of the hydrogen in the intergalactic medium surrounding J1342+0928 is neutral. We derive a significant fraction of neutral hydrogen, although the exact fraction depends on the modelling. However, even in our most conservative analysis we find a fraction of more than 0.33 (0.11) at 68 per cent (95 per cent) probability, indicating that we are probing well within the reionization epoch of the Universe.Comment: Updated to match the final journal versio

Electronic detection of charged particle effects in a Penning trap

We present a thorough analysis of the electronic detection of charged particles, confined in a Penning trap, via image charges induced in the trap electrodes. Trapping of charged particles in an electrode structure leads to frequency shifts, which are due to image charge and space charge effects. These effects are of importance for Penning trap experiments which involve high charge densities or require high precision in the motional frequencies. Our analysis of image charges shows that only (higher order) odd powers of the particle displacement lead to induced charge differences, giving rise to a signal. This implies that, besides the centre-of-mass frequency of a trapped particle cloud, also higher order individual particle frequencies induce a signal, which can be picked up by an electronic detection circuit attached to the trap electrodes. We also derive analytic expressions for the image charge and space charge induced frequency shifts and perform simulations of space charge effects. In relation to this, we discuss the consequences of the shifted particle frequencies for resistive cooling of the particle motion.Comment: 16 pages, 4 figure

End-diastolic wall thickness as a predictor of recovery of function in myocardial hibernation Relation to rest-redistribution Tl-201 tomography and dobutamine stress echocardiography

AbstractOBJECTIVESThe study assessed whether end-diastolic wall thickness (EDWT), measured with echocardiography, is an important marker of myocardial viability in patients with suspected myocardial hibernation, and it compared this index to currently established diagnostic modalities of dobutamine stress echocardiography (DSE) and rest-redistribution thallium-201 (Tl-201) scintigraphy.BACKGROUNDBecause myocardial necrosis is associated with myocardial thinning, preserved EDWT may provide a simple index of myocardial viability that is readily available from the resting echocardiogram.METHODSAccordingly, 45 patients with stable coronary artery disease and ventricular dysfunction underwent rest 2D echocardiograms, DSE and rest-redistribution Tl-201 tomography before revascularization and a repeat resting echocardiogram ≥2 months later.RESULTSGlobal wall motion score index decreased from 2.38 ± 0.73 to 1.94 ± 0.82 after revascularization (p < 0.001). Thirty-eight percent of severely dysfunctional segments recovered resting function. Compared to segments without recovery of resting function, those with recovery had greater EDWT (0.94 ± 0.18 cm vs. 0.67 ± 0.22 cm, p ≤ 0.0001) and a higher Tl-201 uptake (78 ± 13% vs. 59 ± 21%; p < 0.0001). An EDWT >0.6 cm had a sensitivity of 94% and specificity of 48% for recovery of function. Similarly, a Tl-201 maximal uptake of ≥60% had a sensitivity of 91% and specificity of 50%. Receiver operating characteristic curves for prediction of recovery of regional and global function were similar for EDWT and maximum Tl-201 uptake. Combination of EDWT and any contractile reserve during DSE for recovery of regional function improved the specificity to 77% without a significant loss in sensitivity (88%).CONCLUSIONSEnd-diastolic wall thickness is an important marker of myocardial viability in patients with suspected hibernation, and it can predict recovery of function similar to Tl-201 scintigraphy. Importantly, a simple measurement of EDWT ≤0.6 cm virtually excludes the potential for recovery of function and is a valuable adjunct to DSE in the assessment of myocardial viability