Anomalous Diffusion at Edge and Core of a Magnetized Cold Plasma

Progress in the theory of anomalous diffusion in weakly turbulent cold magnetized plasmas is explained. Several proposed models advanced in the literature are discussed. Emphasis is put on a new proposed mechanism for anomalous diffusion transport mechanism based on the coupled action of conductive walls (excluding electrodes) bounding the plasma drain current (edge diffusion) together with the magnetic field flux "cutting" the area traced by the charged particles in their orbital motion. The same reasoning is shown to apply to the plasma core anomalous diffusion. The proposed mechanism is expected to be valid in regimes when plasma diffusion scales as Bohm diffusion and at high $B/N$, when collisions are of secondary importance.Comment: 9 pages, 4 figure

A Software Platform for Post-Processing Waveform-Based NDE

Ultrasonic, microwave, and terahertz nondestructive evaluation imaging systems generally require the acquisition of waveforms at each scan point to form an image. For such systems, signal and image processing methods are commonly needed to extract information from the waves and improve resolution of, and highlight, defects in the image. Since some similarity exists for all waveform-based NDE methods, it would seem a common software platform containing multiple signal and image processing techniques to process the waveforms and images makes sense where multiple techniques, scientists, engineers, and organizations are involved. This presentation describes NASA Glenn Research Center's approach in developing a common software platform for processing waveform-based NDE signals and images. This platform is currently in use at NASA Glenn and at Lockheed Martin Michoud Assembly Facility for processing of pulsed terahertz and ultrasonic data. Highlights of the software operation will be given. A case study will be shown for use with terahertz data. The authors also request scientists and engineers who are interested in sharing customized signal and image processing algorithms to contribute to this effort by letting the authors code up and include these algorithms in future releases

Dealing with mobility: Understanding access anytime, anywhere

The rapid and accelerating move towards the adoption and use of mobile technologies has increasingly provided people and organisations with the ability to work away from the office and on the move. The new ways of working afforded by these technologies are often characterised in terms of access to information and people ‘anytime, anywhere’. This paper presents a study of mobile workers that highlights different facets of access to remote people and information, and different facets of anytime, anywhere. Four key factors in mobile work are identified from the study: the role of planning, working in ‘dead time’, accessing remote technological and informational resources, and monitoring the activities of remote colleagues. By reflecting on these issues, we can better understand the role of technology and artefact use in mobile work and identify the opportunities for the development of appropriate technological solutions to support mobile workers

Potential Modes of Interaction of 9-Aminomethyl-9,10-dihydroanthracene (AMDA) Derivatives with the 5-HT 2A Receptor: A Ligand Structure-Affinity Relationship, Receptor Mutagenesis and Receptor Modeling Investigation

The effects of 3-position substitution of 9-aminomethyl-9,10-dihydroanthracene (AMDA) on 5-HT2A receptor affinity were determined and compared to a parallel series of DOB-like 1-(2,5-dimethoxyphenyl)-2-aminopropanes substituted at the 4-position. The results were interpreted within the context of 5-HT2A receptor models that suggest that members of the DOB-like series can bind to the receptor in two distinct modes that correlate with the compounds’ functional activity. Automated ligand docking and molecular dynamics suggest that all of the AMDA derivatives, the parent of which is a 5-HT2A antagonist, bind in a fashion analogous to that for the sterically demanding antagonist DOB-like compounds. The failure of the F3406.52L mutation to adversely affect the affinity of AMDA and the 3-bromo derivative is consistent with the proposed modes of orientation. Evaluation of ligand-receptor complex models suggest that a valine/threonine exchange between the 5-HT2A and D2 receptors may be the origin of selectivity for AMDA and two substituted derivatives

Genetic polymorphisms in DPF3 associated with risk of breast cancer and lymph node metastases

BACKGROUND: Several studies have identified rare genetic variations responsible for many cases of familial breast cancer but their contribution to total breast cancer incidence is relatively small. More common genetic variations with low penetrance have been postulated to account for a higher proportion of the population risk of breast cancer. METHODS AND RESULTS: In an effort to identify genes that influence non-familial breast cancer risk, we tested over 25,000 single nucleotide polymorphisms (SNPs) located within approximately 14,000 genes in a large-scale case-control study in 254 German women with breast cancer and 268 age-matched women without malignant disease. We identified a marker on chromosome 14q24.3-q31.1 that was marginally associated with breast cancer status (OR = 1.5, P = 0.07). Genotypes for this SNP were also significantly associated with indicators of breast cancer severity, including presence of lymph node metastases (P = 0.006) and earlier age of onset (P = 0.01). The association with breast cancer status was replicated in two independent samples (OR = 1.35, P = 0.05). High-density association fine mapping showed that the association spanned about 80 kb of the zinc-finger gene DPF3 (also known as CERD4). One SNP in intron 1 was found to be more strongly associated with breast cancer status in all three sample collections (OR = 1.6, P = 0.003) as well as with increased lymph node metastases (P = 0.01) and tumor size (P = 0.01). CONCLUSION: Polymorphisms in the 5' region of DPF3 were associated with increased risk of breast cancer development, lymph node metastases, age of onset, and tumor size in women of European ancestry. This large-scale association study suggests that genetic variation in DPF3 contributes to breast cancer susceptibility and severity

Differential Helical Orientations among Related G Protein-coupled Receptors Provide a Novel Mechanism for Selectivity: STUDIES WITH SALVINORIN A AND THE κ-OPIOID RECEPTOR

Salvinorin A, the active component of the hallucinogenic sage Salvia divinorum, is an apparently selective and highly potent kappa-opioid receptor (KOR) agonist. Salvinorin A is unique among ligands for peptidergic G protein-coupled receptors in being nonnitrogenous and lipid-like in character. To examine the molecular basis for the subtype-selective binding of salvinorin A, we utilized an integrated approach using chimeric opioid receptors, site-directed mutagenesis, the substituted cysteine accessibility method, and molecular modeling and dynamics studies. We discovered that helix 2 is required for salvinorin A binding to KOR and that two residues (Val-108(2.53) and Val-118(2.63)) confer subtype selectivity. Intriguingly, molecular modeling studies predicted that these loci exhibit an indirect effect on salvinorin A binding, presumably through rotation of helix 2. Significantly, and in agreement with our in silico predictions, substituted cysteine accessibility method analysis of helix 2 comparing KOR and the delta-opioid receptor, which has negligible affinity for salvinorin A, revealed that residues known to be important for salvinorin A binding exhibit a differential pattern of water accessibility. These findings imply that differences in the helical orientation of helix 2 are critical for the selectivity of salvinorin A binding to KOR and provide a structurally novel basis for ligand selectivity

CoMFA analyses of C-2 position Salvinorin A analogs at the kappa-opioid receptor provides insights into epimer selectivity

The highly potent and kappa-opioid receptor (KOR)-selective hallucinogen salvinorin A and selected analogs have been analyzed using the 3D quantitative structure-affinity relationship technique Comparative Molecular Field Analysis (CoMFA) in an effort to derive a statistically significant and predictive model of salvinorin affinity at the KOR and to provide additional statistical support for the validity of previously proposed structure-based interaction models. Two CoMFA models of salvinorin A analogs substituted at the C-2 position are presented. Separate models were developed based on the radioligand used in the kappa-opioid binding assay, [3H]diprenorphine or [125I]6β-iodo-3,14-dihydroxy-17-cyclopropylmethyl-4,5α-epoxymorphinan ([125I]IOXY). For each dataset, three methods of alignment were employed: a receptor-docked alignment derived from the structure-based docking algorithm GOLD, another from the ligand-based alignment algorithm FlexS, and a rigid realignment of the poses from the receptor-docked alignment. The receptor-docked alignment produced statistically superior results compared to either the FlexS alignment or the realignment in both datasets. The [125I]IOXY set (Model 1) and [3H]diprenorphine set (Model 2) gave q2 values of 0.592 and 0.620, respectively, using the receptor-docked alignment, and both models produced similar CoMFA contour maps that reflected the stereoelectronic features of the receptor model from which they were derived. Each model gave significantly predictive CoMFA statistics (Model 1 PSET r2 = 0.833; Model 2 PSET r2 = 0.813). Based on the CoMFA contour maps, a binding mode was proposed for amine-containing salvinorin A analogs that provides a rationale for the observation that the β-epimers (R-configuration) of protonated amines at the C-2 position have a higher affinity than the corresponding β-epimers (S-configuration)

Screening the receptorome to discover the molecular targets for plant-derived psychoactive compounds: a novel approach for CNS drug discovery

Abstract Because psychoactive plants exert profound effects on human perception, emotion, and cognition, discovering the molecular mechanisms responsible for psychoactive plant actions will likely yield insights into the molecular underpinnings of human consciousness. Additionally, it is likely that elucidation of the molecular targets responsible for psychoactive drug actions will yield validated targets for CNS drug discovery. This review article focuses on an unbiased, discovery-based approach aimed at uncovering the molecular targets responsible for psychoactive drug actions wherein the main active ingredients of psychoactive plants are screened at th

S100A8 and S100A9 in experimental osteoarthritis

INTRODUCTION: The objective was to evaluate the changes in S100A8 S100A9, and their complex (S100A8/S100A9) in cartilage during the onset of osteoarthritis (OA) as opposed to inflammatory arthritis. METHODS: S100A8 and S100A9 protein localization were determined in antigen-induced inflammatory arthritis in mice, mouse femoral head cartilage explants stimulated with interleukin-1 (IL-1), and in surgically-induced OA in mice. Microarray expression profiling of all S100 proteins in cartilage was evaluated at different times after initiation of degradation in femoral head explant cultures stimulated with IL-1 and surgically-induced OA. The effect of S100A8, S100A9 or the complex on the expression of aggrecan (Acan), collagen II (Col2a1), disintegrin and metalloproteases with thrombospondin motifs (Adamts1, Adamts 4 &Adamts 5), matrix metalloproteases (Mmp1, Mmp3, Mmp13 &Mmp14) and tissue inhibitors of metalloproteinases (Timp1, Timp2 &Timp3), by primary adult ovine articular chondrocytes was determined using real time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: Stimulation with IL-1 increased chondrocyte S100a8 and S100a9 mRNA and protein levels. There was increased chondrocyte mRNA expression of S100a8 and S100a9 in early but not late mouse OA. However, loss of the S100A8 staining in chondrocytes occurred as mouse OA progressed, in contrast to the positive reactivity for both S100A8 and S100A9 in chondrocytes in inflammatory arthritis in mice. Homodimeric S100A8 and S100A9, but not the heterodimeric complex, significantly upregulated chondrocyte Adamts1, Adamts4 and Adamts 5, Mmp1, Mmp3 and Mmp13 gene expression, while collagen II and aggrecan mRNAs were significantly decreased. CONCLUSIONS: Chondrocyte derived S100A8 and S100A9 may have a sustained role in cartilage degradation in inflammatory arthritis. In contrast, while these proteins may have a role in initiating early cartilage degradation in OA by upregulating MMPs and aggrecanases, their reduced expression in late stages of OA suggests they do not have an ongoing role in cartilage degradation in this non-inflammatory arthropathy