Description: Crusts composed of nontronite and ferromanganese oxides were recovered from Explorer Ridge, a spreading ridge segment in the northeastern Pacific Ocean located off the west coast of Canada. The chemical and mineralogical composition of the crusts closely resembles that of the mound-like hydrothermal deposits recently discovered at the FAMOUS site on the Mid-Atlantic Ridge and on the Galapagos spreading centre. Compositional anomalies suggest that the crusts are precipitates of hydrothermal vent solutions which were ejected discontinuously and subsequently mixed with seawater.

Description: Concretions of iron and manganese oxides and hydrous oxidesóobjects commonly called manganese nodulesóare widely distributed not only on the deep-sea floor but also in shallow marine environments1. Such concretions were not known to occur north of Cape Mendocino in the shallow water zones bordering the North-East Pacific Ocean until the summer of 1966 when they were recovered by one of us (J. W. M.) in dredge samples from Jervis Inlet, a fjord approximately 50 miles north-west of Vancouver, British Columbia.

Description: Children with a brain tumor treated with high-dose busulfan-thiotepa with autologous stem cell transplantation (ASCT) and radiation therapy (RT) often experience radiographic changes during follow-up. The purpose of the study was to identify the incidence, time course, risk factors, and clinical outcome of this complication. From May 1988 through May 2007, 110 patients (median age, 3.6 years; range, 1 month to 15.3 years) with a brain tumor had received 1 course of high-dose busulfan-thiotepa with stem cell rescue, followed or preceded by RT as part of their treatment. All MRI follow-up examinations were systematically reviewed. Twenty-three patients (21%) developed neuroradiological abnormalities at a median time of 9.2 months (range, 5.6–17.3 months) after ASCT. All contrast-enhancing lesions appeared in patients who had received RT after ASCT and were localized inside the 50–55Gy isodoses. They disappeared in 14 of 23 patients after a median time of 8 months (range, 3–17 months), leaving microcalcifications in some cases. The presence of MRI abnormalities was an independent prognostic factor for overall survival in the multivariate analysis (hazard ratio, 0.12; 95% confidence interval [CI], 0.04–0.33), with a 5-year overall survival rate of 84% among patients with MRI abnormalities (95% CI, 62–94), compared with 27% (95% CI, 19–37) among those without lesions. MRI-detectable pseudoprogression is a common early finding in children treated with high-dose busulfan-thiotepa followed by radiation therapy and is correlated with a better outcome.

Description: Background.  The mechanisms underlying smallpox vaccine-induced variations in immune responses are not well understood, but are of considerable interest to a deeper understanding of poxvirus immunity and correlates of protection. Methods.  We assessed transcriptional messenger RNA expression changes in 197 recipients of primary smallpox vaccination representing the extremes of humoral and cellular immune responses. Results.  The 20 most significant differentially expressed genes include a tumor necrosis factor–receptor superfamily member, an interferon (IFN) gene, a chemokine gene, zinc finger protein genes, nuclear factors, and histones ( P  ≤ 1.06E –20 , q  ≤ 2.64E –17 ). A pathway analysis identified 4 enriched pathways with cytokine production by the T-helper 17 subset of CD4+ T cells being the most significant pathway ( P  = 3.42E –05 ). Two pathways (antiviral actions of IFNs, P  = 8.95E –05 ; and IFN-α/β signaling pathway, P  = 2.92E –04 ), integral to innate immunity, were enriched when comparing high with low antibody responders (false discovery rate, 〈 0.05). Genes related to immune function and transcription ( TLR8 , P  = .0002; DAPP1 , P  = .0003; LAMP3 , P  = 9.96E –05 ; NR4A2 , P  ≤ .0002; EGR3 , P  = 4.52E –05 ), and other genes with a possible impact on immunity ( LNPEP , P  = 3.72E –05 ; CAPRIN1 , P  = .0001; XRN1 , P  = .0001), were found to be expressed differentially in high versus low antibody responders. Conclusion.  We identified novel and known immunity-related genes and pathways that may account for differences in immune response to smallpox vaccination.

Description: Background Platelet-derived growth factor receptor A is altered by amplification and/or mutation in diffuse intrinsic pontine glioma (DIPG). We explored in vitro on new DIPG models the efficacy of dasatinib, a multi-tyrosine kinase inhibitor targeting this receptor. Methods Gene expression profiles were generated from 41 DIPGs biopsied at diagnosis and compared with the signature associated with sensitivity/resistance to dasatinib. A panel of 12 new DIPG cell lines were established from biopsy at diagnosis, serially passaged, and characterized by gene expression analyses. Effects of dasatinib (1–10 μM) on proliferation, invasion, and cytotoxicity were determined on 4 of these cell lines using live-cell imaging and flow cytometry assays. Downstream signaling and receptor tyrosine kinases (RTKs) were assessed by western blot and phospho-RTK array. The effect of the combination with the c-Met inhibitor cabozantinib was studied on cellular growth and invasion analyzed by the Chou–Talaly method. Results DIPG primary tumors and cell lines exhibited the gene expression signature of sensitivity to dasatinib. Dasatinib reduced proliferation (half-maximal inhibitory concentration = 10–100 nM) and invasion (30%–60% reduction) at 100 nM in 4/4 cultures and induced apoptosis in 1 of 4 DIPG cell lines. Activity of downstream effectors of dasatinib targets including activin receptor 1 was strongly reduced. Since multiple RTKs were activated simultaneously in DIPG cell lines, including c-Met, which can be also amplified in DIPG, the benefit of the combination of dasatinib with cabozantinib was explored for its synergistic effects on proliferation and migration/invasion in these cell lines. Conclusion Dasatinib exhibits antitumor effects in vitro that could be increased by the combination with another RTK inhibitor targeting c-Met.

Description: The crust of a neutron star is thought to be comprised of a lattice of nuclei immersed in a sea of free electrons and neutrons. As the neutrons are superfluid, their angular momentum is carried by an array of quantized vortices. These vortices can pin to the nuclear lattice and prevent the neutron superfluid from spinning down, allowing it to store angular momentum which can then be released catastrophically, giving rise to a pulsar glitch. A crucial ingredient for this model is the maximum pinning force that the lattice can exert on the vortices, as this allows us to estimate the angular momentum that can be exchanged during a glitch. In this paper, we perform, for the first time, a detailed and quantitative calculation of the pinning force per unit length acting on a vortex immersed in the crust and resulting from the mesoscopic vortex–lattice interaction. We consider realistic vortex tensions, allow for displacement of the nuclei and average over all possible orientations of the crystal with respect to the vortex. We find that, as expected, the mesoscopic pinning force becomes weaker for longer vortices and is generally much smaller than previous estimates, based on vortices aligned with the crystal. Nevertheless, the forces we obtain still have maximum values of the order of f pin 10 15 dyn cm –1 , which would still allow for enough angular momentum to be stored in the crust to explain large Vela glitches, if part of the star is decoupled during the event.