Improved Fast Neutron Spectroscopy via Detector Segmentation

Organic scintillators are widely used for fast neutron detection and spectroscopy. Several effects complicate the interpretation of results from detectors based upon these materials. First, fast neutrons will often leave a detector before depositing all of their energy within it. Second, fast neutrons will typically scatter several times within a detector, and there is a non-proportional relationship between the energy of, and the scintillation light produced by, each individual scatter; therefore, there is not a deterministic relationship between the scintillation light observed and the neutron energy deposited. Here we demonstrate a hardware technique for reducing both of these effects. Use of a segmented detector allows for the event-by-event correction of the light yield non-proportionality and for the preferential selection of events with near-complete energy deposition, since these will typically have high segment multiplicities.Comment: Accepted for publication in Nuclear Instruments and Methods in Physics Research Section

Experimental and Theoretical Investigation of Recombination Pumped X-ray Lasers Driven by High-Intensity, Short Pulse Lasers

We have experimentally investigated a recombination-pumped soft-x-ray laser on a Lyman-α transition (135 Å) of hydrogenlike lithium. Furthermore, we have modeled the dynamics of this system, including the effects of the multipeaked electron distribution function that is obtained from the sequential, optical-field ionization of an atom. We compare the predictions of our model and our experimental results

Annexin A2 mediates apical trafficking of renal Na(+)-K(+)-2Cl(-)-cotransporter

The furosemide-sensitive Na(+)-K(+)-2Cl(-)-cotransporter (NKCC2) is responsible for urine concentration, and helps maintain systemic salt homeostasis. Its activity depends on trafficking to, and insertion into, the apical membrane, as well as on phosphorylation of conserved N-terminal serine and threonine residues. Vasopressin (AVP), signaling via PKA and other kinases, activates NKCC2. Association of NKCC2 with lipid rafts facilitates its AVP-induced apical translocation and activation at the surface. Lipid raft microdomains typically serve as platforms for membrane proteins to facilitate their interactions with other proteins, but little is known about partners that interact with NKCC2. Yeast two-hybrid screening identified an interaction between NKCC2 and the cytosolic protein, annexin A2 (AnxA2). Annexins mediate lipid raft-dependent trafficking of transmembrane proteins, including the AVP-regulated water channel, aquaporin 2. Here, we demonstrate that AnxA2, which binds to phospholipids in a Ca(2+)-dependent manner and may organize microdomains, is co-distributed with NKCC2 to promote its apical translocation in response to AVP stimulation and low chloride hypotonic stress. NKCC2 and AnxA2 interact in a phosphorylation-dependent manner. Phosphomimetic AnxA2 carrying a mutant, Src-dependent phosphoacceptor (AnxA2-Y24D-GFP), enhanced surface expression and raft association of NKCC2 by 5-fold upon AVP stimulation, whereas PKC-dependent AnxA2-S26D-GFP did not. As the AnxA2 effect involved only non-phosphorylated NKCC2, it appears to affect NKCC2 trafficking. Overexpression or knockdown experiments further supported the role of AnxA2 in the apical translocation and surface expression of NKCC2. In summary, this study identifies AnxA2 as a lipid raft-associated trafficking factor for NKCC2 and provides mechanistic insight into the regulation of this essential cotransporter

Micron-Scale Resolution Radiography of Laser-Accelerated and Laser-Exploded Foils Using an Yttrium X-Ray Laser

The authors have imaged laser-accelerated foils and exploding foils on the few-micron scale using an yttrium x-ray laser (155 {angstrom}, 80 eV, {approximately}200 ps duration) and a multilayer mirror imaging system. At the maximum magnification of 30, resolution was of order one micron. The images were side-on radiographs of the foils. Accelerated foils showed significant filamentation on the rear-side (away from the driving laser) of the foil, although the laser beam was smoothed. In addition to the narrow rear-side filamentation, some shots revealed larger-scale plume-like structures on the front (driven) side of the Al foil. These plumes seem to be little-affected by beam smoothing and are likely a consequence of Rayleigh-Taylor instability. The experiments were carried out at the Nova two-beam facility

Statins Impair Antitumor Effects of Rituximab by Inducing Conformational Changes of CD20

Jakub Golab and colleagues found that statins significantly decrease rituximab-mediated complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity against B cell lymphoma cells

Heat treatment of cold-sprayed C355 Al for repair: microstructure and mechanical properties

Cold gas dynamic spraying of commercially pure aluminum is widely used for dimensional repair in the aerospace sector as it is capable of producing oxide-free deposits of hundreds of micrometer thickness with strong bonding to the substrate, based on adhesive pull-off tests, and often with enhanced hardness compared to the powder prior to spraying. There is significant interest in extending this application to structural, load-bearing repairs. Particularly, in the case of high-strength aluminum alloys, cold spray deposits can exhibit high levels of porosity and microcracks, leading to mechanical properties that are inadequate for most load-bearing applications. Here, heat treatment was investigated as a potential means of improving the properties of cold-sprayed coatings from Al alloy C355. Coatings produced with process conditions of 500 °C and 60 bar were heat-treated at 175, 200, 225, 250 °C for 4 h in air, and the evolution of the microstructure and microhardness was analyzed. Heat treatment at 225 and 250 °C revealed a decreased porosity (~ 0.14% and 0.02%, respectively) with the former yielding slightly reduced hardness (105 versus 130 HV0.05 as-sprayed). Compressive residual stress levels were approximately halved at all depths into the coating after heat treatment, and tensile testing showed an improvement in ductility

Optineurin Is Required for CYLD-Dependent Inhibition of TNFα-Induced NF-κB Activation

The nuclear factor kappa B (NF-κB) regulates genes that function in diverse cellular processes like inflammation, immunity and cell survival. The activation of NF-κB is tightly controlled and the deubiquitinase CYLD has emerged as a key negative regulator of NF-κB signalling. Optineurin, mutated in certain glaucomas and amyotrophic lateral sclerosis, is also a negative regulator of NF-κB activation. It competes with NEMO (NF-κB essential modulator) for binding to ubiquitinated RIP (receptor interacting protein) to prevent NF-κB activation. Recently we identified CYLD as optineurin-interacting protein. Here we have analysed the functional significance of interaction of optineurin with CYLD. Our results show that a glaucoma-associated mutant of optineurin, H486R, is altered in its interaction with CYLD. Unlike wild-type optineurin, the H486R mutant did not inhibit tumour necrosis factor α (TNFα)-induced NF-κB activation. CYLD mediated inhibition of TNFα-induced NF-κB activation was abrogated by expression of the H486R mutant. Upon knockdown of optineurin, CYLD was unable to inhibit TNFα-induced NF-κB activation and showed drastically reduced interaction with ubiquitinated RIP. The level of ubiquitinated RIP was increased in optineurin knockdown cells. Deubiquitination of RIP by over-expressed CYLD was abrogated in optineurin knockdown cells. These results suggest that optineurin regulates NF-κB activation by mediating interaction of CYLD with ubiquitinated RIP thus facilitating deubiquitination of RIP

Improved homology-driven computational validation of protein-protein interactions motivated by the evolutionary gene duplication and divergence hypothesis

<p>Abstract</p> <p>Background</p> <p>Protein-protein interaction (PPI) data sets generated by high-throughput experiments are contaminated by large numbers of erroneous PPIs. Therefore, computational methods for PPI validation are necessary to improve the quality of such data sets. Against the background of the theory that most extant PPIs arose as a consequence of gene duplication, the sensitive search for homologous PPIs, i.e. for PPIs descending from a common ancestral PPI, should be a successful strategy for PPI validation.</p> <p>Results</p> <p>To validate an experimentally observed PPI, we combine FASTA and PSI-BLAST to perform a sensitive sequence-based search for pairs of interacting homologous proteins within a large, integrated PPI database. A novel scoring scheme that incorporates both quality and quantity of all observed matches allows us (1) to consider also tentative paralogs and orthologs in this analysis and (2) to combine search results from more than one homology detection method. ROC curves illustrate the high efficacy of this approach and its improvement over other homology-based validation methods.</p> <p>Conclusion</p> <p>New PPIs are primarily derived from preexisting PPIs and not invented <it>de novo</it>. Thus, the hallmark of true PPIs is the existence of homologous PPIs. The sensitive search for homologous PPIs within a large body of known PPIs is an efficient strategy to separate biologically relevant PPIs from the many spurious PPIs reported by high-throughput experiments.</p