Epitaxial Y1Ba2Cu3O7 thin films on CeO2 buffer layers on sapphire substrates

Pulsed laser deposition has been used to deposit Y1Ba2Cu3O7 layer on CeO2 buffer layers on (1102) sapphire. Both layers are epitaxial with the (110) direction of the CeO2 layer aligned with the direction of the sapphire substrate. The c-axis Y1Ba2Cu3O7 layer has its direction aligned with the direction of the CeO2. Cross-sectional transmission electron microscopy shows the epitaxy to be coherent and the interfaces to be abrupt at an atomic level. The best films have a critical current of 9 e6 A/cm2 at 4.2 K and lower microwave surface resistance than copper at 77 K and at a frequency of 31 GHz.Comment: 3 pages, 2 figures, journal articl

Regulation of NF-κB by PML and PML-RARα

Promyelocytic Leukemia (PML) is a nuclear protein that forms sub-nuclear structures termed nuclear bodies associated with transcriptionally active genomic regions. PML is a tumour suppressor and regulator of cell differentiation. We demonstrate that PML promotes TNFα-induced transcriptional responses by promoting NF-κB activity. TNFα-treated PML−/− cells show normal IκBα degradation and NF-κB nuclear translocation but significantly reduced NF-κB DNA binding and phosphorylation of NF-κB p65. We also demonstrate that the PML retinoic acid receptor-α (PML-RARα) oncofusion protein, which causes acute promyelocytic leukemia, inhibits TNFα induced gene expression and phosphorylation of NF-κB. This study establishes PML as an important regulator of NF-κB and demonstrates that PML-RARα dysregulates NF-κB

"Isn't All of Oncology Hermeneutic?"

In this paper, we describe an event during a pediatric oncology research meeting that prompted the discussion of the ways in which hermeneutics brings a different kind of understanding to both research and practice. We claim that oncology is the practical science of handling natural science research and as such practice in oncology is deeply hermeneutic in character in its recognition of the importance, vitality, and generativity of the “individual case†even in the face of amassed, verified, and aggregate knowledge that is given from the natural science research. Oncology is always contingent, next case handling, and is not identifiable simply as something determined and guided by natural sciences alone. In the face of this, we propose that there is an obvious, profound, and natural fit of hermeneutic research in understanding the lives, relationships, suffering, and experiences that are affected by cancer.   Keywords: childhood cancer, Gadamer, hermeneutics, pediatric oncology, Robert Buckman Â

Slow Slip Events and Time-Dependent Variations in Locking Beneath Lower Cook Inlet of the Alaska-Aleutian Subduction Zone

We identify a series of abrupt changes in GPS site velocities in Lower Cook Inlet, Alaska, in late 2004, early 2010, and late 2011. The site motions during each time period are nearly linear. The surface deformations inferred from GPS for pre-2004 and 2010–2011 are similar to each other, as are 2004–2010 and post-2011. We estimate the slip distribution on the Alaska-Aleutian subduction plate interface accounting for upper plate block rotations and interpret this toggling between two deformation patterns as caused by transient slip. We find that by allowing negative slip deficit rates (i.e., creep rates in excess of relative plate motion), the data in Lower Cook Inlet are fit significantly better during pre-2004 and 2010–2011, suggesting the occurrence of slow slip events (SSEs) there during those time periods. The earlier SSE lasted at least 9 years (observations in that area began in 1995) with Mw ~7.8. The latter SSE had almost the same area as the earlier one and a duration of ~2 years with Mw ~7.2. During 2004–2010 and post-2011, the inversions result in only positive slip deficit rates (i.e., locking) in Lower Cook Inlet. Slip rates are nearly constant during the Lower Cook Inlet SSEs, and the events start and stop abruptly. Both of these properties contrast with observations of SSEs in Upper Cook Inlet and elsewhere. The Lower Cook Inlet SSEs are consistent with previously proposed duration-magnitude scaling laws and demonstrate that slow slip events can last as long as a decade

Rab-coupling protein coordinates recycling of α5β1 integrin and EGFR1 to promote cell migration in 3D microenvironments

Here we show that blocking the adhesive function of αvβ3 integrin with soluble RGD ligands, such as osteopontin or cilengitide, promoted association of Rab-coupling protein (RCP) with α5β1 integrin and drove RCP-dependent recycling of α5β1 to the plasma membrane and its mobilization to dynamic ruffling protrusions at the cell front. These RCP-driven changes in α5β1 trafficking led to acquisition of rapid/random movement on two-dimensional substrates and to a marked increase in fibronectin-dependent migration of tumor cells into three-dimensional matrices. Recycling of α5β1 integrin did not affect its regulation or ability to form adhesive bonds with substrate fibronectin. Instead, α5β1 controlled the association of EGFR1 with RCP to promote the coordinate recycling of these two receptors. This modified signaling downstream of EGFR1 to increase its autophosphorylation and activation of the proinvasive kinase PKB/Akt. We conclude that RCP provides a scaffold that promotes the physical association and coordinate trafficking of α5β1 and EGFR1 and that this drives migration of tumor cells into three-dimensional matrices

Fault Locking, Block Rotation and Crustal Deformation in the Pacific Northwest

We interpret Global Positioning System (GPS) measurements in the northwestern United States and adjacent parts of western Canada to describe relative motions of crustal blocks, locking on faults and permanent deformation associated with convergence between the Juan de Fuca and North American plates. To estimate angular velocities of the oceanic Juan de Fuca and Explorer plates and several continental crustal blocks, we invert the GPS velocities together with seafloor spreading rates, earthquake slip vector azimuths and fault slip azimuths and rates. We also determine the degree to which faults are either creeping aseismically or, alternatively, locked on the block-bounding faults. The Cascadia subduction thrust is locked mainly offshore, except in central Oregon, where locking extends inland. Most of Oregon and southwest Washington rotate clockwise relative to North America at rates of 0.4-1.0 ° Myr-1. No shear or extension along the Cascades volcanic arc has occurred at the mm/yr level during the past decade, suggesting that the shear deformation extending northward from the Walker Lane and eastern California shear zone south of Oregon is largely accommodated by block rotation in Oregon. The general agreement of vertical axis rotation rates derived from GPS velocities with those estimated from palaeomagnetic declination anomalies suggests that the rotations have been relatively steady for 10-15 Ma. Additional permanent dextral shear is indicated within the Oregon Coast Range near the coast. Block rotations in the Pacific Northwest do not result in net westward flux of crustal material¿the crust is simply spinning and not escaping. On Vancouver Island, where the convergence obliquity is less than in Oregon and Washington, the contractional strain at the coast is more aligned with Juan de Fuca¿North America motion. GPS velocities are fit significantly better when Vancouver Island and the southern Coast Mountains move relative to North America in a block-like fashion. The relative motions of the Oregon, western Washington and Vancouver Island crustal blocks indicate that the rate of permanent shortening, the type that causes upper plate earthquakes, across the Puget Sound region is 4.4 ± 0.3 mm yr-1. This shortening is likely distributed over several faults but GPS data alone cannot determine the partitioning of slip on them. The transition from predominantly shear deformation within the continent south of the Mendocino Triple Junction to predominantly block rotations north of it is similar to changes in tectonic style at other transitions from shear to subduction. This similarity suggests that crustal block rotations are enhanced in the vicinity of subduction zones possibly due to lower resisting stress

Predictors of High On-Aspirin Platelet Reactivity in Elderly Patients with Coronary Artery Disease.

Objectives Previous studies have illustrated the link between high on-aspirin platelet reactivity (HAPR) with increasing thrombotic risks. The aim of our study was to investigate relative risk factors of HAPR in elderly patients with coronary artery disease. Methods Elderly, hospitalized coronary artery disease patients on regular aspirin treatment were enrolled from January 2014 to September 2016. Medical records of each patient were collected, including demographic information, cardiovascular risk factors, concomitant drugs and routine biological parameters. Arachidonic acid (AA, 0.5 mg/mL) and adenosine diphosphate (ADP, 5 µmol/L) induced platelet aggregation were measured via light transmission assay (LTA) to evaluate antiplatelet responses, referred as LTA–AA and LTA–ADP. Results A total of 275 elderly patients were included, with mean age of 77.2±8.1 years, and males accounted for 81.8%. HAPR was defined as LTA–AA in the upper quartile of the enrolled population. HAPR patients tended to have lower renal function (P=0.052). Higher serum uric acid (SUA) level, as well as lower platelet count, hemoglobin and hematocrit were observed in HAPR patients, with a higher proportion of diuretics use (P\u3c0.05). Multivariate analysis revealed that SUA (OR: 1.004, 95% CI: 1.000–1.007, P=0.048), platelet count (OR: 0.994, 95% CI: 0.989–1.000, P=0.045), hematocrit (OR: 0.921, 95% CI: 0.864–0.981, P=0.011) and concomitant P2Y12 receptor inhibitors use (OR: 1.965, 95% CI: 1.075–3.592, P=0.028) were correlated with HAPR. Spearman’s correlation analysis demonstrated an inverse association of LTA–AA with hematocrit (r=−0.234, P\u3c0.001), hemoglobin (r=−0.209, P\u3c0.001) and estimated glomerular filtration rate (r=−0.132, P=0.031). Conclusion SUA, platelet count, hematocrit and P2Y12 receptor inhibitors use were independently correlated with HAPR. These parameters might provide novel therapeutic targets for optimizing antiplatelet therapy