Oncogenic Gain of Function in Glioblastoma Is Linked to Mutant p53 Amyloid Oligomers.

Tumor-associated p53 mutations endow cells with malignant phenotypes, including chemoresistance. Amyloid-like oligomers of mutant p53 transform this tumor suppressor into an oncogene. However, the composition and distribution of mutant p53 oligomers are unknown and the mechanism involved in the conversion is sparse. Here, we report accumulation of a p53 mutant within amyloid-like p53 oligomers in glioblastoma-derived cells presenting a chemoresistant gain-of-function phenotype. Statistical analysis from fluorescence fluctuation spectroscopy, pressure-induced measurements, and thioflavin T kinetics demonstrates the distribution of oligomers larger than the active tetrameric form of p53 in the nuclei of living cells and the destabilization of native-drifted p53 species that become amyloid. Collectively, these results provide insights into the role of amyloid-like mutant p53 oligomers in the chemoresistance phenotype of malignant and invasive brain tumors and shed light on therapeutic options to avert cancer

In Situ Characterisation of Permanent Magnetic Quadrupoles for focussing proton beams

High intensity laser driven proton beams are at present receiving much attention. The reasons for this are many but high on the list is the potential to produce compact accelerators. However two of the limitations of this technology is that unlike conventional nuclear RF accelerators lasers produce diverging beams with an exponential energy distribution. A number of different approaches have been attempted to monochromise these beams but it has become obvious that magnetic spectrometer technology developed over many years by nuclear physicists to transport and focus proton beams could play an important role for this purpose. This paper deals with the design and characterisation of a magnetic quadrupole system which will attempt to focus and transport laser-accelerated proton beams.Comment: 20 pages, 42 figure

Manufacture, observation, and test of membranes with locatable single pores

A method for generating single pores down to 0.1 μm diameter in the center of a large circular foil is described, based on nuclear tracks. The foil is framed by a tension ring which enables one to handle the foils in a well‐defined precise way. The single pore has a lateral displacement of ±0.1 mm with respect to the tension ring center. The foils used are polycarbonate of the type Makrofol and have thicknesses between 2 and 10 μm. For calibration of the single pore diameters, multiple nuclear tracks between 0.1 and 3.5 μm diameter are etched and observed by microscopy. The microscopic observations are compared with gas‐flow measurements, using two alternative methods: multiple holes are tested under viscous flow conditions of N2 gas at normal temperature and pressure; single holes are tested under collisionless flow conditions of 4He gas at liquid‐nitrogen temperature, using a capacitance method.Peer reviewe

Supercooled confined water and the Mode Coupling crossover temperature

We present a Molecular Dynamics study of the single particle dynamics of supercooled water confined in a silica pore. Two dynamical regimes are found: close to the hydrophilic substrate molecules are below the Mode Coupling crossover temperature, $T_C$, already at ambient temperature. The water closer to the center of the pore (free water) approaches upon supercooling $T_C$ as predicted by Mode Coupling Theories. For free water the crossover temperature and crossover exponent $\gamma$ are extracted from power-law fits to both the diffusion coefficient and the relaxation time of the late $\alpha$ region.Comment: To be published, Phys. Rev. Lett., 4 pages, 3 figures, revTeX, minor changes in the figures, references added, changes in the tex

Electrodeposition of cobalt based ferro-magnetic metal nanowires in polycarbonate films with cylindrical nanochannels fabricated by heavy-ion-track etching

Polycarbonate films of thickness 30 μm were irradiated with heavy ions by applying a flux of 108 ions cm-2 to produce straight tracks perpendicular to the film surface. The tracks were preferentially etched in 6 M aqueous solution of sodium hydroxide to prepare cylindrical nanochannels. The channel diameters were tuned between 200 and 600 nm by varying the etching time. Co81Cu19 alloy nanowires were electrodeposited potentiostatically, while Co/Cu multilayered nanowires, consisting of alternating Co and Cu layers with thickness 10 nm, were synthesized by means of a pulse plating technique in channels of length 30 μm and diameter 200 nm. Co81Cu19 alloy nanowires showed an anisotropic magnetoresistance effect of 0.6%, and the giant magnetoresistance of Co/Cu multilayered nanowires reached up to 8.0%

X-ray Absorption Near-Edge Structure (XANES) at the O K-Edge of Bulk Co₃O₄: Experimental and Theoretical Studies

We combine theoretical and experimental X-ray absorption near-edge spectroscopy (XANES) to probe the local environment around cationic sites of bulk spinel cobalt tetraoxide (Co3O4). Specifically, we analyse the oxygen K-edge spectrum. We find an excellent agreement between our calculated spectra based on the density functional theory and the projector augmented wave method, previous calculations as well as with the experiment. The oxygen K-edge spectrum shows a strong pre-edge peak which can be ascribed to dipole transitions from O 1s to O 2p states hybridized with the unoccu- pied 3d states of cobalt atoms. Also, since Co3O4 contains two types of Co atoms, i.e., Co3+ and Co2+, we find that contribution of Co2+ ions to the pre-edge peak is solely due to single spin-polarized t2g orbitals (dxz, dyz, and dxy) while that of Co3+ ions is due to spin-up and spin-down polarized eg orbitals (dx2−y2 and dz2 ). Furthermore, we deduce the magnetic moments on the Co3+ and Co2+ to be zero and 3.00 μB respectively. This is consistent with an earlier experimental study which found that the magnetic structure of Co3O4 consists of antiferromagnetically ordered Co2+ spins, each of which is surrounded by four nearest neighbours of oppositely directed spins

Exploring the performance of the spectrometer prisma in heavy zirconium and xenon mass regions

We present results from two recent runs which illustrate the performance of the PRISMA spectrometer in the proximity of the upper limit of its operational interval, namely 96Zr + 124Sn at Elab = 500 MeV and 136Xe + 208Pb at Elab = 930 MeV. In the latter run, the γ array CLARA also allowed us to identify previously unknown γ transitions in the nuclides 136Cs and 134I

Magneto-sensitive nickel nanowires fabricated by electrodeposition into multi- and single-ion track templates

Polycarbonate templates of (30±1) μm thickness containing cylindrical etched-track nanochannels of (500±50) nm diameter were used for electrodeposition of Ni nanowires. Using 104 channels per cm2, the most favourable deposition potential of  − 1.0 V was determined in a potentiostatic mode by varying the deposition potential with respect to an Ag/AgCl reference electrode over a range between  − 0.1 V and  − 1.5 V. The deposition efficiency at  − 1.0 V was estimated around 10%. The resulting single wires had a resistance around 200 Ω and showed an anisotropic magnetoresistance (AMR) effect of 1%, applicable to directionally sensitive magnetic field sensors

Spectroscopic studies of Dy-168,170 using CLARA and PRISMA

Preliminary results from an experiment aiming at Dy-170. Submitted to the LNL Annual Report 2008.Comment: 2 pages, 4 figures, Submitted to the LNL Annual Report 200