Nonuniform irradiation of laser targets

Smoothing of plasma ablated from a laser target under weakly nonuniform irradiation is discussed. Conduction is assumed restricted to a quasisteady layer enclosing the critical surface (large pellet or focal spot, and long, low-intensity, short-wavelength pulse). Light refraction can make the ablated plasma unstable.

A fuzzy MCDA framework for safety assessment in the remediation of a uranium mill tailings site in Ukraine

The Pridneprovsky Chemical Plant was one of the largest uranium processing enterprises in the former USSR, producing a huge amount of uranium residues. The Zapadnoe tailings site contains most of these residues. We propose a theoretical framework based on multicriteria decision analysis and fuzzy logic to analyze different remediation alternatives for the Zapadnoe tailings, which simultaneously accounts for potentially conflicting economic, social and environmental objectives. We build an objective hierarchy that includes all the relevant aspects. Fuzzy rather than precise values are proposed for use to evaluate remediation alternatives against the different criteria and to quantify preferences, such as the weights representing the relative importance of criteria identified in the objective hierarchy. Finally, we suggest that remediation alternatives should be evaluated by means of a fuzzy additive multi-attribute utility function and ranked on the basis of the respective trapezoidal fuzzy number representing their overall utility.

Symmetry issues in Directly Irradiated Targets

In direct drive Inertial Confinement Fusion (ICF), the typical laser beam to laser beam angle is around 30o. This fact makes the study of the irradiation symmetry agenuine 3D problem. In this paper we use the three dimensional version of the MULTI hydrocode to assess the symmetry of such ICF implosions. More specifically, we study a shock-ignition proposal for the Laser-M´egajoule facility (LMJ) in which two of the equatorial beam cones are used to implode and pre compress a spherical capsule (the “reference” capsule of HiPER project) made of 0.59 mg of pure Deuterium-Tritium mixture. The symmetry of this scheme is analysed and optimized to get a design inside the operating limits of LMJ. The studied configuration has been found essentially axial-symmetric, so that the use of 2D hydrocodes would be appropriate for this specific situation

Study of the effects of moving targets in SAR images for their detection.

Synthetic Aperture Radar’s (SAR) are systems designed in the early 50’s that are capable of obtaining images of the ground using electromagnetic signals. Thus, its activity is not interrupted by adverse meteorological conditions or during the night, as it occurs in optical systems. The name of the system comes from the creation of a synthetic aperture, larger than the real one, by moving the platform that carries the radar (typically a plane or a satellite). It provides the same resolution as a static radar equipped with a larger antenna. As it moves, the radar keeps emitting pulses every 1/PRF seconds —the PRF is the pulse repetition frequency—, whose echoes are stored and processed to obtain the image of the ground. To carry out this process, the algorithm needs to make the assumption that the targets in the illuminated scene are not moving. If that is the case, the algorithm is able to extract a focused image from the signal. However, if the targets are moving, they get unfocused and/or shifted from their position in the final image. There are applications in which it is especially useful to have information about moving targets (military, rescue tasks,studyoftheflowsofwater,surveillanceofmaritimeroutes...).Thisfeatureiscalled Ground Moving Target Indicator (GMTI). That is why the study and the development of techniques capable of detecting these targets and placing them correctly in the scene is convenient. In this document, some of the principal GMTI algorithms used in SAR systems are detailed. A simulator has been created to test the features of each implemented algorithm on a general situation with moving targets. Finally Monte Carlo tests have been performed, allowing us to extract conclusions and statistics of each algorithm.

Fuzzy MCDA for remediation of a uranium tailing

The Pridneprovsky Chemical Plant was a largest uranium processing enterprises, producing a huge amount of uranium residues. The Zapadnoe tailings site contains the majority of these residues. We propose a theoretical framework based on Multi-Criteria Decision Analysis and fuzzy logic to analyse different remediation alternatives for the Zapadnoe tailings, in which potentially conflicting economic, radiological, social and environmental objectives are simultaneously taken into account. An objective hierarchy is built that includes all the relevant aspects. Fuzzy rather than precise values are proposed for use to evaluate remediation alternatives against the different criteria and to quantify preferences, such as the weights representing the relative importance of criteria identified in the objective hierarchy. Finally, it is proposed that remediation alternatives should be evaluated by means of a fuzzy additive multi-attribute utility function and ranked on the basis of the respective trapezoidal fuzzy number representing their overall utility.

5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats

Funding The research reported in this publication was supported by the Biotechnology and Biological Sciences Research Council (E007821/1 to M.S.M-G, R.L.C and E00797X/1; BB/K001418 /1 to L.K.H), the British Heart Foundation (FS/09/029/27902 to S.E.O.), the UK Medical Research Council Metabolic Diseases Unit (MC_UU_12012/4 to S.E.O and MC_UU_12012/1 to G.S.H.Y), the Wellcome Trust (WT081713 and WT098012 to L.K.H), the European Union (FP7-HEALTH-266408 Full4Health to G.S.H.Y) and the Helmholtz Alliance ICEMED to G.S.H.Y.

Oxidative damage during aging targets mitochondrial aconitase

The mechanisms that cause aging are not well understood. The oxidative stress hypothesis proposes that the changes associated with aging are a consequence of random oxidative damage to biomolecules. We hypothesized that oxidation of specific proteins is critical in controlling the rate of the aging process. Utilizing an immunochemical probe for oxidatively modified proteins, we show that mitochondrial aconitase, an enzyme in the citric acid cycle, is a specific target during aging of the housefly. The oxidative damage detected immunochemically was paralleled by a loss of catalytic activity of aconitase, an enzyme activity that is critical in energy metabolism. Experimental manipulations which decrease aconitase activity should therefore cause a decrease in life-span. This expected decrease was observed when flies were exposed to hyperoxia, which oxidizes aconitase, and when they were given fluoroacetate, an inhibitor of aconitase. The identification of a specific target of oxidative damage during aging allows for the assessment of the physiological age of a specific individual and provides a method for the evaluation of treatments designed to affect the aging process.

RanGTP Targets p97 to RanBP2, a Filamentous Protein Localized at the Cytoplasmic Periphery of the Nuclear Pore Complex

RanBP2, a protein containing FG repeat motifs and four binding sites for the guanosine triphosphatase Ran, is localized at the cytoplasmic periphery of the nuclear pore complex (NPC) and is believed to play a critical role in nuclear protein import. We purified RanBP2 from rat liver nuclear envelopes and examined its structural and biochemical properties. Electron microscopy showed that RanBP2 forms a flexible filamentous molecule with a length of ∼36 nm, suggesting that it comprises a major portion of the cytoplasmic fibrils implicated in initial binding of import substrates to the NPC. Using in vitro assays, we characterized the ability of RanBP2 to bind p97, a cytosolic factor implicated in the association of the nuclear localization signal receptor with the NPC. We found that RanGTP promotes the binding of p97 to RanBP2, whereas it inhibits the binding of p97 to other FG repeat nucleoporins. These data suggest that RanGTP acts to specifically target p97 to RanBP2, where p97 may support the binding of an nuclear localization signal receptor/substrate complex to RanBP2 in an early step of nuclear import.

Rapid evolution in plant chitinases: Molecular targets of selection in plant-pathogen coevolution

Many pathogen recognition genes, such as plant R-genes, undergo rapid adaptive evolution, providing evidence that these genes play a critical role in plant-pathogen coevolution. Surprisingly, whether rapid adaptive evolution also occurs in genes encoding other kinds of plant defense proteins is unknown. Unlike recognition proteins, plant chitinases attack pathogens directly, conferring disease resistance by degrading chitin, a component of fungal cell walls. Here, we show that nonsynonymous substitution rates in plant class I chitinase often exceed synonymous rates in the plant genus Arabis (Cruciferae) and in other dicots, indicating a succession of adaptively driven amino acid replacements. We identify individual residues that are likely subject to positive selection by using codon substitution models and determine the location of these residues on the three-dimensional structure of class I chitinase. In contrast to primate lysozymes and plant class III chitinases, structural and functional relatives of class I chitinase, the adaptive replacements of class I chitinase occur disproportionately in the active site cleft. This highly unusual pattern of replacements suggests that fungi directly defend against chitinolytic activity through enzymatic inhibition or other forms of chemical resistance and identifies target residues for manipulating chitinolytic activity. These data also provide empirical evidence that plant defense proteins not involved in pathogen recognition also evolve in a manner consistent with rapid coevolutionary interactions.

Ultrasensitive detection of pathological prion protein aggregates by dual-color scanning for intensely fluorescent targets

A definite diagnosis of prion diseases such as Creutzfeldt–Jakob disease (CJD) relies on the detection of pathological prion protein (PrPSc). However, no test for PrPSc in cerebrospinal fluid (CSF) has been available thus far. Based on a setup for confocal dual-color fluorescence correlation spectroscopy, a technique suitable for single molecule detection, we developed a highly sensitive detection method for PrPSc. Pathological prion protein aggregates were labeled by specific antibody probes tagged with fluorescent dyes, resulting in intensely fluorescent targets, which were measured by dual-color fluorescence intensity distribution analysis in a confocal scanning setup. In a diagnostic model system, PrPSc aggregates were detected down to a concentration of 2 pM PrPSc, corresponding to an aggregate concentration of approximately 2 fM, which was more than one order of magnitude more sensitive than Western blot analysis. A PrPSc-specific signal could also be detected in a number of CSF samples from patients with CJD but not in control samples, providing the basis for a rapid and specific test for CJD and other prion diseases. Furthermore, this method could be adapted to the sensitive detection of other disease-associated amyloid aggregates such as in Alzheimer's disease.

The small GTPase RalA targets filamin to induce filopodia

The Ras-related small GTPases Rac, Rho, Cdc42, and RalA bind filamin, an actin filament-crosslinking protein that also links membrane and other intracellular proteins to actin. Of these GTPases only RalA binds filamin in a GTP-specific manner, and GTP-RalA elicits actin-rich filopods on surfaces of Swiss 3T3 cells and recruits filamin into the filopodial cytoskeleton. Either a dominant negative RalA construct or the RalA-binding domain of filamin 1 specifically block Cdc42-induced filopod formation, but a Cdc42 inhibitor does not impair RalA’s effects, which, unlike Cdc42, are Rac independent. RalA does not generate filopodia in filamin-deficient human melanoma cells, whereas transfection of filamin 1 restores the functional response. RalA therefore is a downstream intermediate in Cdc42-mediated filopod production and uses filamin in this pathway.

Virus-encoded suppressor of posttranscriptional gene silencing targets a maintenance step in the silencing pathway

Certain plant viruses encode suppressors of posttranscriptional gene silencing (PTGS), an adaptive antiviral defense response that limits virus replication and spread. The tobacco etch potyvirus protein, helper component-proteinase (HC-Pro), suppresses PTGS of silenced transgenes. The effect of HC-Pro on different steps of the silencing pathway was analyzed by using both transient Agrobacterium tumefaciens-based delivery and transgenic systems. HC-Pro inactivated PTGS in plants containing a preexisting silenced β-glucuronidase (GUS) transgene. PTGS in this system was associated with both small RNA molecules (21–26 nt) corresponding to the 3′ proximal region of the transcribed GUS sequence and cytosine methylation of specific sites near the 3′ end of the GUS transgene. Introduction of HC-Pro into these plants resulted in loss of PTGS, loss of small RNAs, and partial loss of methylation. These results suggest that HC-Pro targets a PTGS maintenance (as opposed to an initiation or signaling) component at a point that affects accumulation of small RNAs and methylation of genomic DNA.

Structural code for DNA recognition revealed in crystal structures of papillomavirus E2-DNA targets

Transcriptional regulation in papillomaviruses depends on sequence-specific binding of the regulatory protein E2 to several sites in the viral genome. Crystal structures of bovine papillomavirus E2 DNA targets reveal a conformational variant of B-DNA characterized by a roll-induced writhe and helical repeat of 10.5 bp per turn. A comparison between the free and the protein-bound DNA demonstrates that the intrinsic structure of the DNA regions contacted directly by the protein and the deformability of the DNA region that is not contacted by the protein are critical for sequence-specific protein/DNA recognition and hence for gene-regulatory signals in the viral system. We show that the selection of dinucleotide or longer segments with appropriate conformational characteristics, when positioned at correct intervals along the DNA helix, can constitute a structural code for DNA recognition by regulatory proteins. This structural code facilitates the formation of a complementary protein–DNA interface that can be further specified by hydrogen bonds and nonpolar interactions between the protein amino acids and the DNA bases.