GRAVITY: getting to the event horizon of Sgr A*

We present the second-generation VLTI instrument GRAVITY, which currently is in the preliminary design phase. GRAVITY is specifically designed to observe highly relativistic motions of matter close to the event horizon of Sgr A*, the massive black hole at center of the Milky Way. We have identified the key design features needed to achieve this goal and present the resulting instrument concept. It includes an integrated optics, 4-telescope, dual feed beam combiner operated in a cryogenic vessel; near infrared wavefront sensing adaptive optics; fringe tracking on secondary sources within the field of view of the VLTI and a novel metrology concept. Simulations show that the planned design matches the scientific needs; in particular that 10 microarcsecond astrometry is feasible for a source with a magnitude of K=15 like Sgr A*, given the availability of suitable phase reference sources.Comment: 13 pages, 11 figures, to appear in the conference proceedings of SPIE Astronomical Instrumentation, 23-28 June 2008, Marseille, Franc

Enhanced Pro-apoptotic Effects of Fe(II)-Modified IVIG on Human Neutrophils.

Mild modification of intravenous immunoglobulin (IVIG) has been reported to result in enhanced polyspecificity and leveraged therapeutic effects in animal models of inflammation. Here, we observed that IVIG modification by ferrous ions, heme or low pH exposure, shifted the repertoires of specificities in different directions. Ferrous ions exposed Fe(II)-IVIG, but not heme or low pH exposed IVIG, showed increased pro-apoptotic effects on neutrophil granulocytes that relied on a FAS-dependent mechanism. These effects were also observed in human neutrophils primed by inflammatory mediators or rheumatoid arthritis joint fluid in vitro, or patient neutrophils ex vivo from acute Crohn's disease. These observations indicate that IVIG-mediated effects on cells can be enhanced by IVIG modification, yet specific modification conditions may be required to target specific molecular pathways and eventually to enhance the therapeutic potential

Thymic Hyperplasia with Lymphoepithelial Sialadenitis (LESA)-Like Features: Strong Association with Lymphomas and Non-Myasthenic Autoimmune Diseases.

Thymic hyperplasia (TH) with lymphoepithelial sialadenitis (LESA)-like features (LESA-like TH) has been described as a tumor-like, benign proliferation of thymic epithelial cells and lymphoid follicles. We aimed to determine the frequency of lymphoma and autoimmunity in LESA-like TH and performed retrospective analysis of cases with LESA-like TH and/or thymic MALT-lymphoma. Among 36 patients (21 males) with LESA-like TH (age 52 years, 32-80; lesion diameter 7.0 cm, 1-14.5; median, range), five (14%) showed associated lymphomas, including four (11%) thymic MALT lymphomas and one (3%) diffuse large B-cell lymphoma. One additional case showed a clonal B-cell-receptor rearrangement without evidence of lymphoma. Twelve (33%) patients (7 women) suffered from partially overlapping autoimmune diseases: systemic lupus erythematosus (n = 4, 11%), rheumatoid arthritis (n = 3, 8%), myasthenia gravis (n = 2, 6%), asthma (n = 2, 6%), scleroderma, Sjögren syndrome, pure red cell aplasia, Grave's disease and anti-IgLON5 syndrome (each n = 1, 3%). Among 11 primary thymic MALT lymphomas, remnants of LESA-like TH were found in two cases (18%). In summary, LESA-like TH shows a striking association with autoimmunity and predisposes to lymphomas. Thus, a hematologic and rheumatologic workup should become standard in patients diagnosed with LESA-like TH. Radiologists and clinicians should be aware of LESA-like TH as a differential diagnosis for mediastinal mass lesions in patients with autoimmune diseases

Conformational dynamics and internal friction in homopolymer globules: equilibrium vs. non-equilibrium simulations

We study the conformational dynamics within homopolymer globules by solvent-implicit Brownian dynamics simulations. A strong dependence of the internal chain dynamics on the Lennard-Jones cohesion strength ε and the globule size N [subscript G] is observed. We find two distinct dynamical regimes: a liquid-like regime (for ε ε[subscript s] with slow internal dynamics. The cohesion strength ε[subscript s] of this freezing transition depends on N G . Equilibrium simulations, where we investigate the diffusional chain dynamics within the globule, are compared with non-equilibrium simulations, where we unfold the globule by pulling the chain ends with prescribed velocity (encompassing low enough velocities so that the linear-response, viscous regime is reached). From both simulation protocols we derive the internal viscosity within the globule. In the liquid-like regime the internal friction increases continuously with ε and scales extensive in N [subscript G] . This suggests an internal friction scenario where the entire chain (or an extensive fraction thereof) takes part in conformational reorganization of the globular structure.American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowshi

Olfactory perireceptor and receptor events in moths: a kinetic model revised

Modelling reveals that within about 3 ms after entering the sensillum lymph, 17% of total pheromone is enzymatically degraded while 83% is bound to the pheromone-binding protein (PBP) and thereby largely protected from enzymatic degradation. The latter proceeds within minutes, 20,000-fold more slowly than with the free pheromone. In vivo the complex pheromone–PBP interacts with the receptor molecule. At weak stimulation the half-life of the active complex is 0.8 s due to the postulated pheromone deactivation. Most likely this process is enzymatically catalysed; it changes the PBP into a scavenger form, possibly by interference with the C-terminus. The indirectly determined PBP concentration (3.8 mM) is close to direct measurements. The calculated density of receptor molecules within the plasma membrane of the receptor neuron reaches up to 6,000 units per μm2. This is compared with the estimated densities of the sensory-neuron membrane protein and of ion channels. The EC50 of the model pheromone–PBP complex interacting with the receptor molecules is 6.8 μM, as compared with the EC50 = 1.5 μM of bombykol recently determined using heterologous expression. A possible mechanism widening the range of stimulus intensities covered by the dose–response curve of the receptor-potential is proposed