Protein kinase a distribution differentiates human glioblastoma from brain tissue

Brain tumor glioblastoma has no clear molecular signature and there is no effective therapy. In rodents, the intracellular distribution of the cyclic AMP (cAMP)-dependent protein kinase (Protein kinase A, PKA) R2Alpha subunit was previously shown to differentiate tumor cells from healthy brain cells. Now, we aim to validate this observation in human tumors. The distribution of regulatory (R1 and R2) and catalytic subunits of PKA was examined via immunohistochemistry and Western blot in primary cell cultures and biopsies from 11 glioblastoma patients. Data were compared with information obtained from 17 other different tumor samples. The R1 subunit was clearly detectable only in some samples. The catalytic subunit was variably distributed in the different tumors. Similar to rodent tumors, all human glioblastoma specimens showed perinuclear R2 distribution in the Golgi area, while it was undetectable outside the tumor. To test the effect of targeting PKA as a therapeutic strategy, the intracellular cyclic AMP concentration was modulated with different agents in four human glioblastoma cell lines. A significant increase in cell death was detected after increasing cAMP levels or modulating PKA activity. These data raise the possibility of targeting the PKA intracellular pathway for the development of diagnostic and/or therapeutic tools for human glioblastoma

Protein kinase a distribution in meningioma

Deregulation of intracellular signal transduction pathways is a hallmark of cancer cells, clearly differentiating them from healthy cells. Differential intracellular distribution of the cAMP-dependent protein kinases (PKA) was previously detected in cell cultures and in vivo in glioblastoma and medulloblastoma. Our goal is to extend this observation to meningioma, to explore possible differences among tumors of different origins and prospective outcomes. The distribution of regulatory and catalytic subunits of PKA has been examined in tissue specimens obtained during surgery from meningioma patients. PKA RI subunit appeared more evenly distributed throughout the cytoplasm, but it was clearly detectable only in some tumors. RII was present in discrete spots, presumably at high local concentration; these aggregates could also be visualized under equilibrium binding conditions with fluorescent 8-substituted cAMP analogues, at variance with normal brain tissue and other brain tumors. The PKA catalytic subunit showed exactly overlapping pattern to RII and in fixed sections could be visualized by fluorescent cAMP analogues. Gene expression analysis showed that the PKA catalytic subunit revealed a significant correlation pattern with genes involved in meningioma. Hence, meningioma patients show a distinctive distribution pattern of PKA regulatory and catalytic subunits, different from glioblastoma, medulloblastoma, and healthy brain tissue. These observations raise the possibility of exploiting the PKA intracellular pathway as a diagnostic tool and possible therapeutic interventions

Asymptotic behavior of the Kleinberg model

We study Kleinberg navigation (the search of a target in a d-dimensional lattice, where each site is connected to one other random site at distance r, with probability proportional to r^{-a}) by means of an exact master equation for the process. We show that the asymptotic scaling behavior for the delivery time T to a target at distance L scales as (ln L)^2 when a=d, and otherwise as L^x, with x=(d-a)/(d+1-a) for ad+1. These values of x exceed the rigorous lower-bounds established by Kleinberg. We also address the situation where there is a finite probability for the message to get lost along its way and find short delivery times (conditioned upon arrival) for a wide range of a's

Ultrafast Ge-Te bond dynamics in a phase-change superlattice

A long-standing question for avant-garde data storage technology concerns the nature of the ultrafast photoinduced phase transformations in the wide class of chalcogenide phase-change materials (PCMs). Overall, a comprehensive understanding of the microstructural evolution and the relevant kinetics mechanisms accompanying the out-of-equilibrium phases is still missing. Here, after overheating a phase-change chalcogenide superlattice by an ultrafast laser pulse, we indirectly track the lattice relaxation by time resolved x-ray absorption spectroscopy (tr-XAS) with a sub-ns time resolution. The approach to the tr-XAS experimental results reported in this work provides an atomistic insight of the mechanism that takes place during the cooling process; meanwhile a first-principles model mimicking the microscopic distortions accounts for a straightforward representation of the observed dynamics. Finally, we envisage that our approach can be applied in future studies addressing the role of dynamical structural strain in PCMs.M.M. acknowledges the support of the BACH beamline staff during the synchrotron experiments and Roberta Ciprian for insightful discussions. This work was supported by EU within FP7 project PASTRY [GA 317764]

Recipes for spin-based quantum computing

Technological growth in the electronics industry has historically been measured by the number of transistors that can be crammed onto a single microchip. Unfortunately, all good things must come to an end; spectacular growth in the number of transistors on a chip requires spectacular reduction of the transistor size. For electrons in semiconductors, the laws of quantum mechanics take over at the nanometre scale, and the conventional wisdom for progress (transistor cramming) must be abandoned. This realization has stimulated extensive research on ways to exploit the spin (in addition to the orbital) degree of freedom of the electron, giving birth to the field of spintronics. Perhaps the most ambitious goal of spintronics is to realize complete control over the quantum mechanical nature of the relevant spins. This prospect has motivated a race to design and build a spintronic device capable of complete control over its quantum mechanical state, and ultimately, performing computations: a quantum computer. In this tutorial we summarize past and very recent developments which point the way to spin-based quantum computing in the solid-state. After introducing a set of basic requirements for any quantum computer proposal, we offer a brief summary of some of the many theoretical proposals for solid-state quantum computers. We then focus on the Loss-DiVincenzo proposal for quantum computing with the spins of electrons confined to quantum dots. There are many obstacles to building such a quantum device. We address these, and survey recent theoretical, and then experimental progress in the field. To conclude the tutorial, we list some as-yet unrealized experiments, which would be crucial for the development of a quantum-dot quantum computer.Comment: 45 pages, 12 figures (low-res in preprint, high-res in journal) tutorial review for Nanotechnology; v2: references added and updated, final version to appear in journa

The Aquarius Superclusters - I. Identification of Clusters and Superclusters

We study the distribution of galaxies and galaxy clusters in a 10^deg x 6^deg field in the Aquarius region. In addition to 63 clusters in the literature, we have found 39 new candidate clusters using a matched-filter technique and a counts-in-cells analysis. From redshift measurements of galaxies in the direction of these cluster candidates, we present new mean redshifts for 31 previously unobserved clusters, while improved mean redshifts are presented for 35 other systems. About 45% of the projected density enhancements are due to the superposition of clusters and/or groups of galaxies along the line of sight, but we could confirm for 72% of the cases that the candidates are real physical associations similar to the ones classified as rich galaxy clusters. On the other hand, the contamination due to galaxies not belonging to any concentration or located only in small groups along the line of sight is ~ 10%. Using a percolation radius of 10 h^{-1} Mpc (spatial density contrast of about 10), we detect two superclusters of galaxies in Aquarius, at z = 0.086 and at z = 0.112, respectively with 5 and 14 clusters. The latter supercluster may represent a space overdensity of about 160 times the average cluster density as measured from the Abell et al. (1989) cluster catalog, and is possibly connected to a 40 h^{-1} Mpc filament from z ~ 0.11 to 0.14.Comment: LateX text (21 pages) and 12 (ps/eps/gif) figures; figures 5a, 5b and 6 are not included in the main LateX text; to be published in the Astronomical Journal, March issu

A Very Intense Neutrino Super Beam Experiment for Leptonic CP Violation Discovery based on the European Spallation Source Linac: A Snowmass 2013 White Paper

Very intense neutrino beams and large neutrino detectors will be needed in order to enable the discovery of CP violation in the leptonic sector. We propose to use the proton linac of the European Spallation Source currently under construction in Lund, Sweden to deliver, in parallel with the spallation neutron production, a very intense, cost effective and high performance neutrino beam. The baseline program for the European Spallation Source linac is that it will be fully operational at 5 MW average power by 2022, producing 2 GeV 2.86 ms long proton pulses at a rate of 14 Hz. Our proposal is to upgrade the linac to 10 MW average power and 28 Hz, producing 14 pulses/s for neutron production and 14 pulses/s for neutrino production. Furthermore, because of the high current required in the pulsed neutrino horn, the length of the pulses used for neutrino production needs to be compressed to a few $\mu$s with the aid of an accumulator ring. A long baseline experiment using this Super Beam and a megaton underground Water Cherenkov detector located in existing mines 300-600 km from Lund will make it possible to discover leptonic CP violation at 5 $\sigma$ significance level in up to 50% of the leptonic Dirac CP-violating phase range. This experiment could also determine the neutrino mass hierarchy at a significance level of more than 3 $\sigma$ if this issue will not already have been settled by other experiments by then. The mass hierarchy performance could be increased by combining the neutrino beam results with those obtained from atmospheric neutrinos detected by the same large volume detector. This detector will also be used to measure the proton lifetime, detect cosmological neutrinos and neutrinos from supernova explosions. Results on the sensitivity to leptonic CP violation and the neutrino mass hierarchy are presented.Comment: 28 page

HIFLUGCS: Galaxy cluster scaling relations between X-ray luminosity, gas mass, cluster radius, and velocity dispersion

We present relations between X-ray luminosity and velocity dispersion (L-sigma), X-ray luminosity and gas mass (L-Mgas), and cluster radius and velocity dispersion (r500-sigma) for 62 galaxy clusters in the HIFLUGCS, an X-ray flux-limited sample minimizing bias toward any cluster morphology. Our analysis in total is based on ~1.3Ms of clean X-ray XMM-Newton data and 13439 cluster member galaxies with redshifts. Cool cores are among the major contributors to the scatter in the L-sigma relation. When the cool-core-corrected X-ray luminosity is used the intrinsic scatter decreases to 0.27 dex. Even after the X-ray luminosity is corrected for the cool core, the scatter caused by the presence of cool cores dominates for the low-mass systems. The scatter caused by the non-cool-core clusters does not strongly depend on the mass range, and becomes dominant in the high-mass regime. The observed L-sigma relation agrees with the self-similar prediction, matches that of a simulated sample with AGN feedback disregarding six clusters with <45 cluster members with spectroscopic redshifts, and shows a common trend of increasing scatter toward the low-mass end, i.e., systems with sigma<500km/s. A comparison of observations with simulations indicates an AGN-feedback-driven impact in the low-mass regime. The best fits to the $L-M_{\rm gas}$ relations for the disturbed clusters and undisturbed clusters in the observational sample closely match those of the simulated samples with and without AGN feedback, respectively. This suggests that one main cause of the scatter is AGN activity providing feedback in different phases, e.g., during a feedback cycle. The slope and scatter in the observed r500-sigma relation is similar to that of the simulated sample with AGN feedback except for a small offset but still within the scatter.Comment: 45 pages, 28 figures, A&A proof-version, high-resolution figures in Appendix F can be found in the electronic version on the A&A we

Field-free deterministic ultra fast creation of skyrmions by spin orbit torques

Magnetic skyrmions are currently the most promising option to realize current-driven magnetic shift registers. A variety of concepts to create skyrmions were proposed and demonstrated. However, none of the reported experiments show controlled creation of single skyrmions using integrated designs. Here, we demonstrate that skyrmions can be generated deterministically on subnanosecond timescales in magnetic racetracks at artificial or natural defects using spin orbit torque (SOT) pulses. The mechanism is largely similar to SOT-induced switching of uniformly magnetized elements, but due to the effect of the Dzyaloshinskii-Moriya interaction (DMI), external fields are not required. Our observations provide a simple and reliable means for skyrmion writing that can be readily integrated into racetrack devices