Ion dynamics and coherent structure formation following laser pulse self-channeling

The propagation of a superintense laser pulse in an underdense, inhomogeneous plasma has been studied numerically by two-dimensional particle-in-cell simulations on a time scale extending up to several picoseconds. The effects of the ion dynamics following the charge-displacement self-channeling of the laser pulse have been addressed. Radial ion acceleration leads to the ``breaking'' of the plasma channel walls, causing an inversion of the radial space-charge field and the filamentation of the laser pulse. At later times a number of long-lived, quasi-periodic field structures are observed and their dynamics is characterized with high resolution. Inside the plasma channel, a pattern of electric and magnetic fields resembling both soliton- and vortex-like structures is observed.Comment: 10 pages, 5 figures (visit http://www.df.unipi.it/~macchi to download a high-resolution version), to appear in Plasma Physics and Controlled Fusion (Dec. 2007), special issue containing invited papers from the 34th EPS Conference on Plasma Physics (Warsaw, July 2007

Transgenic neuronal overexpression reveals that stringently regulated p23 expression is critical for coordinated movement in mice

<p>Abstract</p> <p>Background</p> <p>p23 belongs to the highly conserved p24 family of type I transmembrane proteins, which participate in the bidirectional protein transport between the endoplasmic reticulum and Golgi apparatus. Mammalian p23 has been shown to interact with γ-secretase complex, and modulate secretory trafficking as well as intramembranous processing of amyloid precursor protein in cultured cells. Negative modulation of β-amyloid production by p23 in cultured cell lines suggested that elevation of p23 expression in neurons might mitigate cerebral amyloid burden.</p> <p>Results</p> <p>We generated several lines of transgenic mice expressing human p23 in neurons under the control of <it>Thy-1.2 </it>promoter. We found that even a 50% increase in p23 levels in the central nervous system of mice causes post-natal growth retardation, severe neurological problems characterized by tremors, seizure, ataxia, and uncoordinated movements, and premature death. The severity of the phenotype closely correlated with the level of p23 overexpression in multiple transgenic lines. While the number and general morphology of neurons in Hup23 mice appeared to be normal throughout the brain, abnormal non-Golgi p23 localization was observed in a subset of neurons with high transgene expression in brainstem. Moreover, detailed immunofluorescence analysis revealed marked proliferation of astrocytes, activation of microglia, and thinning of myelinated bundles in brainstem of Hup23 mice.</p> <p>Conclusions</p> <p>These results demonstrate that proper level of p23 expression is critical for neuronal function, and perturbing p23 function by overexpression initiates a cascade of cellular reactions in brainstem that leads to severe motor deficits and other neurological problems, which culminate in premature death. The neurological phenotype observed in Hup23 mice highlights significant adverse effects associated with manipulating neuronal expression of p23, a previously described negative modulator of γ-secretase activity and β-amyloid production. Moreover, our report has broader relevance to molecular mechanisms in several neurodegenerative diseases as it highlights the inherent vulnerability of the early secretory pathway mechanisms that ensure proteostasis in neurons.</p

Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts

BIN1 is not expressed in human brain microglial cells. (A) Immunohistochemical staining of adjacent sections of normal human brain cortex with antibodies against BIN1 or Iba1 reveals that BIN1 immunoreactive cells that are morphologically distinct from microglia. The boxed region is shown at a higher magnification on the right. (B) Single and two-color immunostaining of the human brain using antibodies against BIN1 and CD45 reveals that perivenular CD45-positive cells of the hematopoietic lineage do not express BIN1. (TIFF 4392 kb

Role of p73 in Alzheimer disease: lack of association in mouse models or in human cohorts.

BACKGROUND: P73 belongs to the p53 family of cell survival regulators with the corresponding locus Trp73 producing the N-terminally distinct isoforms, TAp73 and DeltaNp73. Recently, two studies have implicated the murine Trp73 in the modulation in phospho-tau accumulation in aged wild type mice and in young mice modeling Alzheimer's disease (AD) suggesting that Trp73, particularly the DeltaNp73 isoform, links the accumulation of amyloid peptides to the creation of neurofibrillary tangles (NFTs). Here, we reevaluated tau pathologies in the same TgCRND8 mouse model as the previous studies. RESULTS: Despite the use of the same animal models, our in vivo studies failed to demonstrate biochemical or histological evidence for misprocessing of tau in young compound Trp73+/- + TgCRND8 mice or in aged Trp73+/- mice analyzed at the ages reported previously, or older. Secondly, we analyzed an additional mouse model where the DeltaNp73 was specifically deleted and confirmed a lack of impact of the DeltaNp73 allele, either in heterozygous or homozygous form, upon tau pathology in aged mice. Lastly, we also examined human TP73 for single nucleotide polymorphisms (SNPs) and/or copy number variants in a meta-analysis of 10 AD genome-wide association datasets. No SNPs reached significance after correction for multiple testing and no duplications/deletions in TP73 were found in 549 cases of AD and 544 non-demented controls. CONCLUSION: Our results fail to support P73 as a contributor to AD pathogenesis.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

DNA DSB Repair Dynamics following Irradiation with Laser-Driven Protons at Ultra-High Dose Rates

Protontherapy has emerged as more effective in the treatment of certain tumors than photon based therapies. However, significant capital and operational costs make protontherapy less accessible. This has stimulated interest in alternative proton delivery approaches, and in this context the use of laser-based technologies for the generation of ultra-high dose rate ion beams has been proposed as a prospective route. A better understanding of the radiobiological effects at ultra-high dose-rates is important for any future clinical adoption of this technology. In this study, we irradiated human skin fibroblasts-AG01522B cells with laser-accelerated protons at a dose rate of 10 9 Gy/s, generated using the Gemini laser system at the Rutherford Appleton Laboratory, UK. We studied DNA double strand break (DSB) repair kinetics using the p53 binding protein-1(53BP1) foci formation assay and observed a close similarity in the 53BP1 foci repair kinetics in the cells irradiated with 225 kVp X-rays and ultra- high dose rate protons for the initial time points. At the microdosimetric scale, foci per cell per track values showed a good correlation between the laser and cyclotron-accelerated protons indicating similarity in the DNA DSB induction and repair, independent of the time duration over which the dose was delivered

Plasma polymers as targets for laser-driven proton-boron fusion

Laser-driven proton-boron (pB) fusion has been gaining significant interest for energetic alpha particles production because of its neutron-less nature. This approach requires the use of B- and H-rich materials as targets, and common practice is the use of BN and conventional polymers. In this work, we chose plasma-assisted vapour phase deposition to prepare films of oligoethylenes (plasma polymers) on Boron Nitride BN substrates as an advanced alternative. The r.f. power delivered to the plasma was varied between 0 and 50 W to produce coatings with different crosslink density and hydrogen content, while maintaining the constant thickness of 1 μm. The chemical composition, including the hydrogen concentration, was investigated using XPS and RBS/ERDA, whereas the surface topography was analyzed using SEM and AFM. We triggered the pB nuclear fusion reaction focusing laser pulses from two different systems (i.e., the TARANIS multi-TW laser at the Queen’s University Belfast (United Kingdom) and the PERLA B 10-GW laser system at the HiLASE center in Prague (Czech Republic)) directly onto these targets. We achieved a yield up to 108 and 104 alpha particles/sr using the TARANIS and PERLA B lasers, respectively. Radiative-hydrodynamic and particle-in-cell PIC simulations were performed to understand the laser-target interaction and retrieve the energy spectra of the protons. The nuclear collisional algorithm implemented in the WarpX PIC code was used to identify the region where pB fusion occurs. Taken together, the results suggest a complex relationship between the hydrogen content, target morphology, and structure of the plasma polymer, which play a crucial role in laser absorption, target expansion, proton acceleration and ultimately nuclear fusion reactions in the plasma

Studies on neuropeptides in the nervous system with emphasis on their distribution on sensory and motor pathways in normal and experimental animal models of sensory and motor dysfunction

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