Real-time broadening of non-equilibrium density profiles and the role of the specific initial-state realization

The real-time broadening of density profiles starting from non-equilibrium states is at the center of transport in condensed-matter systems and dynamics in ultracold atomic gases. Initial profiles close to equilibrium are expected to evolve according to linear response, e.g., as given by the current correlator evaluated exactly at equilibrium. Significantly off equilibrium, linear response is expected to break down and even a description in terms of canonical ensembles is questionable. We unveil that single pure states with density profiles of maximum amplitude yield a broadening in perfect agreement with linear response, if the structure of these states involves randomness in terms of decoherent off-diagonal density-matrix elements. While these states allow for spin diffusion in the XXZ spin-1/2 chain at large exchange anisotropies, coherences yield entirely different behavior.Comment: 7 pages, 7 figures, accepted for publication in Phys. Rev.

Orbital Period Determinations for Four SMC Be/X-ray Binaries

We present an optical and X-ray study of four Be/X-ray binaries located in the Small Magellanic Cloud (SMC). OGLE I-band data of up to 11 years of semi-continuous monitoring has been analysed for SMC X-2, SXP172 and SXP202B, providing both a measurement of the orbital period (Porb = 18.62, 68.90, and 229.9 days for the pulsars respectively) and a detailed optical orbital profile for each pulsar. For SXP172 this has allowed a direct comparison of the optical and X-ray emission seen through regular RXTE monitoring, revealing that the X-ray outbursts precede the optical by around 7 days. Recent X-ray studies by XMM-Newton have identified a new source in the vicinity of SXP15.3 raising doubt on the identification of the optical counterpart to this X-ray pulsar. Here we present a discussion of the observations that led to the proposal of the original counterpart and a detailed optical analysis of the counterpart to the new X-ray source, identifying a 21.7 d periodicity in the OGLE I-band data. The optical characteristics of this star are consistent with that of a SMC Be/X-ray binary. However, this star was rejected as the counterpart to SXP15.3 in previous studies due to the lack of H{\alpha} emission.Comment: Accepted for publication in MNRAS, 11 pages, 17 figure

XMM-Newton observations of the Small Magellanic Cloud: X-ray outburst of the 6.85 s pulsar XTE J0103-728

A bright X-ray transient was seen during an XMM-Newton observation in the direction of the Small Magellanic Cloud (SMC) in October 2006. The EPIC data allow us to accurately locate the source and to investigate its temporal and spectral behaviour. X-ray spectra covering 0.2-10 keV and pulse profiles in different energy bands were extracted from the EPIC data. The detection of 6.85 s pulsations in the EPIC-PN data unambiguously identifies the transient with XTE J0103-728, discovered as 6.85 s pulsar by RXTE. The X-ray light curve during the XMM-Newton observation shows flaring activity of the source with intensity changes by a factor of two within 10 minutes. Modelling of pulse-phase averaged spectra with a simple absorbed power-law indicates systematic residuals which can be accounted for by a second emission component. For models implying blackbody emission, thermal plasma emission or emission from the accretion disk (disk-blackbody), the latter yields physically sensible parameters. The photon index of the power-law of ~0.4 indicates a relatively hard spectrum. The 0.2-10 keV luminosity was 2x10^{37} with a contribution of ~3% from the disk-blackbody component. A likely origin for the excess emission is reprocessing of hard X-rays from the neutron star by optically thick material near the inner edge of an accretion disk. From a timing analysis we determine the pulse period to 6.85401(1) s indicating an average spin-down of ~0.0017 s per year since the discovery of XTE J0103-728 in May 2003. The X-ray properties and the identification with a Be star confirm XTE J0103-728 as Be/X-ray binary transient in the SMC.Comment: 5 pages, 4 figures, submitted to A&A on 21 Dec. 200

AGN in the XMM-Newton first-light image as probes for the interstellar medium in the LMC

The XMM-Newton first-light image revealed X-ray point sources which show heavily absorbed power-law spectra. The spectral indices and the probable identification of a radio counterpart for the brightest source suggest AGN shining through the interstellar gas of the Large Magellanic Cloud (LMC). The column densities derived from the X-ray spectra in combination with HI measurements will allow to draw conclusions on HI to H_2 ratios in the LMC and compare these with values found for the galactic plane.Comment: 4 pages, LaTex, 4 figures, Accepted for publication in A&A Letter

Alpha-particle emitting 213Bi-anti-EGFR immunoconjugates eradicate tumor cells independent of oxygenation

Hypoxia is a central problem in tumor treatment because hypoxic cells are less sensitive to chemo- and radiotherapy than normoxic cells. Radioresistance of hypoxic tumor cells is due to reduced sensitivity towards low Linear Energy Transfer (LET) radiation. High LET α-emitters are thought to eradicate tumor cells independent of cellular oxygenation. Therefore, the aim of this study was to demonstrate that the cell-bound α-particle emitting 213Bi immunoconjugates efficiently kill hypoxic just like normoxic CAL33 tumor cells. For that purpose CAL33 cells were incubated with 213Bianti- EGFR-MAb or irradiated with photons with a nominal energy of 6 MeV both under hypoxic and normoxic conditions. Oxygenation of cells was checked via the hypoxia-associated marker HIF-1α. Survival of cells was analysed using the clonogenic assay. Cell viability was monitored with the WST colorimetric assay. Results were evaluated statistically using a t-test and a Generalized Linear Mixed Model (GLMM). Survival and viability of CAL33 cells decreased both after incubation with increasing 213Bi-anti-EGFR-MAb activity concentrations (9.25 kBq/ml – 1.48 MBq/ml) and irradiation with increasing doses of photons (0.5 – 12 Gy). Following photon irradiation survival and viability of normoxic cells were significantly lower than those of hypoxic cells at all doses analysed. In contrast, cell death induced by 213Bianti- EGFR-MAb turned out to be independent of cellular oxygenation. These results demonstrate for the first time that α-particle emitting 213Bi-immunoconjugates eradicate hypoxic tumor cells as effective as normoxic cells. Therefore, 213Biradioimmunotherapy seems to be an appropriate strategy for treatment of hypoxic tumors.JRC.E.5-Nuclear chemistr

Proteasome alpha-type subunit C9 is a primary target of autoantibodies in sera of patients with myositis and systemic lupus erythematosus

Autoantibodies occur in low frequencies among patients with myositis characterizing only distinct subsets of this disease. Most of these known antibodies are directed to enzymatically active complexes. The 20S proteasome represents an essential cytoplasmatic protein complex for intracellular nonlysosomal protein degradation, and is involved in major histocompatibility complex class I restricted antigen processing. In this study we investigated whether the 20S proteasome complex is an antibody target in myositis and in other autoimmune diseases. 34 sera of poly/dermatomyositis patients were assayed for antiproteasomal antibodies using enzyme-linked immunosorbent assay, immunoblot, and two-dimensional non-equilibrium pH gradient electrophoresis (NEPHGE). Sera was from patients with systemic lupus erythematosus (SLE), mixed connective tissue disease, and rheumatoid arthritis; healthy volunteers served as controls. In 62% (21/34) of the cases sera from patients with myositis and in 58% (30/52) of the cases sera from patients with SLE reacted with the 20S proteasome. These frequencies exceeded those of sera from patients with mixed connective tissue disease, rheumatoid arthritis, and healthy controls. The alpha-type subunit C9 of the 20S proteasome was determined to be the predominant target of the autoimmune sera in myositis and SLE. Lacking other frequent autoantibodies in myositis, the antiproteasome antibodies are the most common humoral immune response so far detected in this disease entity

Duckweed production on diluted chicken manure

The aim of this study was to test chicken manure as duckweed (Lemna minor) fertiliser. Duckweed was grown using three different concentrations (low, medium and high; dilution factors 1:16, 1:12 and 1:8, respectively) of previously solubilised chicken manure. Subsequently, duckweed was evaluated for its fresh and dry biomass production, protein content and protein production capacity. Ammonium-nitrogen (NH4-N) concentrations increased in all substrates during an experimental week, with the increase being steeper in the treatments with higher chicken manure concentrations. However, duckweed populations were unable to fully utilise all the provided nitrogen. As the concentration of chicken manure increased, growth and protein production decreased. Adding the highest concentration of chicken manure (1:8 dilution) led to nearly complete die-off of the duckweed population. The low concentrated (1:16 dilution) chicken manure fertilisation resulted in acceptable growth (1.85 g dry matter (DM) per m2 and day) and high crude protein content (42.8% DM). The medium concentration (1:12 dilution) of chicken manure still stimulated growth, although it was significantly lower compared to duckweed grown on the low concentrated poultry manure and declined towards the end of the experiment (0.88 g DM per m2 and day). The biomass from this treatment also contained slightly lower protein content (40.6% DM). Duckweed cultivated using low and medium chicken manure concentrations produced an average of 0.79 and 0.36 g protein per m2 and day, respectively. Although solubilised chicken manure can serve as a potential fertiliser for duckweed, balancing the amount of chicken manure necessary to obtain a target NH4-N concentration when compared to cow or pig slurries is challenging

Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using 149Tb-rituximab

This study demonstrates high-efficiency sterilisation of single cancer cells in a SCID mouse model of leukaemia using rituximab, a monoclonal antibody that targets CD20, labelled with terbium-149, an alpha-emitting radionuclide. Radio-immunotherapy with 5.5MBq labelled antibody conjugate (1.11GBq/mg) 2 days after an intravenous graft of 5·106 Daudi cells resulted in tumour-free survival for >120 days in 89% of treated animals. In contrast, all control mice (no treatment or treated with 5 or 300µg unlabelled rituximab) developed lymphoma disease. At the end of the study period, 28.4%±4% of the long-lived daughter activity remained in the body, of which 91.1% was located in bone tissue and 6.3% in the liver. A relatively high daughter radioactivity concentration was found in the spleen (12%±2%/g), suggesting that the killed cancer cells are mainly eliminated through the spleen. This promising preliminary in vivo study suggests that targeted alpha therapy with 149Tb is worthy of consideration as a new-generation radio-immunotherapeutic approac

Dynamic undocking and the quasi-bound state as tools for drug discovery

There is a pressing need for new technologies that improve the efficacy and efficiency of drug discovery. Structure-based methods have contributed towards this goal but they focus on predicting the binding affinity of protein–ligand complexes, which is notoriously difficult. We adopt an alternative approach that evaluates structural, rather than thermodynamic, stability. As bioactive molecules present a static binding mode, we devised dynamic undocking (DUck), a fast computational method to calculate the work necessary to reach a quasi-bound state at which the ligand has just broken the most important native contact with the receptor. This non-equilibrium property is surprisingly effective in virtual screening because true ligands form more-resilient interactions than decoys. Notably, DUck is orthogonal to docking and other ‘thermodynamic’ methods. We demonstrate the potential of the docking–undocking combination in a fragment screening against the molecular chaperone and oncology target Hsp90, for which we obtain novel chemotypes and a hit rate that approaches 40