The importance of neutralizing antibody in protection against influenza virus is well established but the role of early antibody response during the initial stage of infection affecting disease severity is unknown. The 2009 pandemic influenza provided a unique opportunity because most patients lacked preexisting neutralizing antibody. In this study, we compared the antibody response of 52 patients with severe or mild disease in their serum collected at admission. Microneutralization assay (MN) was used to detect neutralizing antibody. We have also developed an enzyme-linked immunosorbent assay (ELISA) which detects both neutralizing and non-neutralizing antibodies against viral antigens from a split-virion inactivated monovalent influenza virus vaccine. While the MN titer was not significantly different between the two groups (p=0.764), the ELISA titer and the ELISA:MN titer ratio were significantly higher in patients with severe disease than those with mild disease (p=0.004 and p=0.011, respectively). This finding suggested that in patients with severe disease, a higher proportion of their serum antibodies are the antibody with no detectable neutralizing activity. The antibody avidity was also significantly higher in patients with severe disease than those with mild disease (p<0.05). Among patients with severe disease, those who required positive pressure ventilation (PPV) had significantly higher ELISA titer than those who did not require PPV (p<0.05). Multivariate analysis showed that ELISA titer and antibody avidity were independently associated with severe disease. Higher titer of non-neutralizing antibody with higher avidity present at the early stage of influenza infection may be associated with worse clinical severity and poorer outcome.

Shwachman Diamond syndrome (SDS) is a rare inherited bone marrow failure syndrome (IBMFS) characterized by neutropenia, exocrine pancreatic dysfunction, and cancer predisposition. Patients are at risk for myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) but, unlike other IBMFS, there have been no reported cases of solid tumors. We report a novel case of a solid tumor in a patient with SDS and biallelic mutations in the Shwachman Bodian Diamond Syndrome gene (SBDS). Whether the development of breast cancer in this patient is due to SDS or an isolated case due to unknown factors requires further study. Pediatr Blood Cancer © 2011 Wiley Periodicals, Inc.

Background:  There is a need for the development of novel non-steroidal topical drugs for the treatment of atopic dermatitis. Objectives:  The primary objective was to evaluate the efficacy of WBI-1001 over 6 weeks of treatment of mild to severe AD. Methods:  Patients with atopic dermatitis (AD) affecting 3-20% of their body surface area (BSA) and with an Investigator's Global Assessment (IGA) of 2 to 4 were randomized (1:1:1) to receive placebo, 0.5% WBI-1001, or 1.0% WBI-1001 in a cream formulation applied twice daily for 6 weeks. At the end of this phase, patients receiving WBI-1001 continued the same treatment for an additional 6 weeks. Patients receiving placebo entered into a 6-week double-blind phase with re-randomization (1:1) to 0.5% or 1.0% WBI-1001 creams. The primary objective was to evaluate the efficacy of WBI-1001 over 6 weeks of treatment of mild to severe AD. The primary endpoint was the mean change from baseline in IGA at Day 42 (Week 6). Results:  A total of 148 patients were randomized and analyzed in the placebo (51), 0.5% WBI-1001 (50) and 1.0% WBI-1001 groups (47). There was a decrease of 1.3 (43%; p<0.001; 95%CI:-1.2; -0.5) and 1.8 (56.3%; p<0.001; 95%CI: -1.6; -0.9) in IGA at Day 42 in the 0.5% and 1.0% WBI-1001 groups, respectively as compared with a decrease of 0.5 (14.7%) in the placebo group. Adverse drug reactions included a few cases of folliculitis and contact dermatitis. Conclusions:  WBI-1001 is an efficacious novel topical anti-inflammatory molecule for the treatment of atopic dermatitis.

Kelvin-Helmholtz instability (KHI) driven by velocity shear is a generator of waves found away from the vicinity of the velocity-shear layers since the fast-mode waves radiated from the surface perturbation can propagate away from the transition layer. Thus the nonlinear evolution associated with KHI is not confined near the velocity-shear layer. To understand the physical processes in multiple velocity-shear layers, the interactions between two KHIs at a pair of tangential discontinuities are studied by two-dimensional magnetohydrodynamic simulations. It is shown that the interactions between two neighboring velocity-shear layers are dominated by the propagation of the fast-mode waves radiated from KHIs in a nonuniform medium. That is, the fast-mode Mach number of the surface waves M_{Fy}, a key factor of the nonlinear evolution of KHI, will vary with the nonuniform background plasma velocity due to the existence of two neighboring velocity-shear layers. As long as the M_{Fy} observed in the plasma rest frame across the neighboring velocity-shear layer is larger than one, newly formed fast-mode Mach-cone-like (MCL) plane waves generated by the fast-mode waves can be found in this region. As results of the interactions of two KHIs, reflection and distortion of the MCL plane waves generate the turbulence and increase the plasma temperature, which provide possible mechanisms of heating and accelerating local plasma between two neighboring velocity-shear layers.

The Visible, InfraRed, and Thermal Imaging Spectrometer (VIRTIS) on Rosetta obtained hyperspectral images, spectral reflectance maps, and temperature maps of the asteroid 21 Lutetia. No absorption features, of either silicates or hydrated minerals, have been detected across the observed area in the spectral range from 0.4 to 3.5 micrometers. The surface temperature reaches a maximum value of 245 kelvin and correlates well with topographic features. The thermal inertia is in the range from 20 to 30 joules meter(-2) kelvin(-1) second(-0.5), comparable to a lunarlike powdery regolith. Spectral signatures of surface alteration, resulting from space weathering, seem to be missing. Lutetia is likely a remnant of the primordial planetesimal population, unaltered by differentiation processes and composed of chondritic materials of enstatitic or carbonaceous origin, dominated by iron-poor minerals that have not suffered aqueous alteration.

Images obtained by the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) cameras onboard the Rosetta spacecraft reveal that asteroid 21 Lutetia has a complex geology and one of the highest asteroid densities measured so far, 3.4 ± 0.3 grams per cubic centimeter. The north pole region is covered by a thick layer of regolith, which is seen to flow in major landslides associated with albedo variation. Its geologically complex surface, ancient surface age, and high density suggest that Lutetia is most likely a primordial planetesimal. This contrasts with smaller asteroids visited by previous spacecraft, which are probably shattered bodies, fragments of larger parents, or reaccumulated rubble piles.

Monolayer graphene oxide (GO) sheets with sizes ranging from a few to ∼200 μm are synthesized based on a chemical method and are sorted out to obtain four different grades having uniform sizes. Transparent conductive films are produced using the ultralarge graphene oxide (UL-GO) sheets that are deposited layer-by-layer on a substrate using the Langmuir-Blodgett (LB) assembly technique. The density and degree of wrinkling of the UL-GO monolayers are turned from dilute, close-packed flat UL-GO to graphene oxide wrinkles (GOWs) and concentrated graphene oxide wrinkles (CGOWs) by varying the LB processing conditions. The method demonstrated here opens up a new avenue for high-yield fabrication of GOWs or CGOWs that are considered promising materials for hydrogen storage, supercapacitors, and nanomechanical devices. The films produced from UL-GO sheets with a close-packed flat structure exhibit exceptionally high electrical conductivity and transparency after thermal reduction and chemical doping treatments. A remarkable sheet resistance of ∼500 Ω/sq at 90% transparency is obtained, which outperforms the graphene films grown on a Ni substrate by chemical vapor deposition. The technique used in this work to produce transparent conductive UL-GO thin films is facile, inexpensive, and tunable for mass production.

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The neurofibromatosis type 2 tumor suppressor protein, merlin, is related to the ERM (ezrin, radixin, and moesin) family of plasma membrane-actin cytoskeleton linkers. For ezrin, phosphatidylinositol 4,5-bisphosphate (PIP(2)) binding to the amino-terminal FERM domain is required for its conformational activation, proper subcellular localization, and function, but less is known about the role of phosphoinositide binding for merlin. Current evidence indicates that association with the membrane is important for merlin to function as a growth regulator; however, the mechanisms by which merlin localizes to the membrane are less clear. Here, we report that merlin binds phosphoinositides, including PIP(2), via a conserved binding motif in its FERM domain. Abolition of FERM domain-mediated phosphoinositide binding of merlin displaces merlin from the membrane and releases it into the cytosol without altering the folding of merlin. Importantly, a merlin protein whose FERM domain cannot bind phosphoinositide is defective in growth suppression. Retargeting the mutant merlin into the membrane using a dual-acylated amino-terminal decapeptide from Fyn is sufficient to restore the growth-suppressive properties to the mutant merlin. Thus, FERM domain-mediated phosphoinositide binding and membrane association are critical for the growth-regulatory function of merlin.

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