Circulating markers of arterial thrombosis and late-stage age-related macular degeneration: a case-control study.

PURPOSE: The aim of this study was to examine the relation of late-stage age-related macular degeneration (AMD) with markers of systemic atherothrombosis. METHODS: A hospital-based case-control study of AMD was undertaken in London, UK. Cases of AMD (n=81) and controls (n=77) were group matched for age and sex. Standard protocols were used for colour fundus photography and to classify AMD; physical examination included height, weight, history of or treatment for vascular-related diseases and smoking status. Blood samples were taken for measurement of fibrinogen, factor VIIc (FVIIc), factor VIIIc, prothrombin fragment F1.2 (F1.2), tissue plasminogen activator, and von Willebrand factor. Odds ratios from logistic regression analyses of each atherothrombotic marker with AMD were adjusted for age, sex, and established cardiovascular disease risk factors, including smoking, blood pressure, body mass index, and total cholesterol. RESULTS: After adjustment FVIIc and possibly F1.2 were inversely associated with the risk of AMD; per 1 standard deviation increase in these markers the odds ratio were, respectively, 0.62 (95% confidence interval 0.40, 0.95) and 0.71 (0.46, 1.09). None of the other atherothrombotic risk factors appeared to be related to AMD status. There was weak evidence that aspirin is associated with a lower risk of AMD. CONCLUSIONS: This study does not provide strong evidence of associations between AMD and systematic markers of arterial thrombosis, but the potential effects of FVIIc, and F1.2 are worthy of further investigation

Digit-only sauropod pes trackways from China – evidence of swimming or a preservational phenomenon?

For more than 70 years unusual sauropod trackways have played a pivotal role in debates about the swimming ability of sauropods. Most claims that sauropods could swim have been based on manusonly or manus-dominated trackways. However none of these incomplete trackways has been entirely convincing, and most have proved to be taphonomic artifacts, either undertracks or the result of differential depth of penetration of manus and pes tracks, but otherwise showed the typical pattern of normal walking trackways. Here we report an assemblage of unusual sauropod tracks from the Lower Cretaceous Hekou Group of Gansu Province, northern China, characterized by the preservation of only the pes claw traces, that we interpret as having been left by walking, not buoyant or swimming, individuals. They are interpreted as the result of animals moving on a soft mud-silt substrate, projecting their claws deeply to register their traces on an underlying sand layer where they gained more grip during progression. Other sauropod walking trackways on the same surface with both pes and manus traces preserved, were probably left earlier on relatively firm substrates that predated the deposition of soft mud and silt . Presently, there is no convincing evidence of swimming sauropods from their trackways, which is not to say that sauropods did not swim at all

Electromagnetic wave diffraction by periodic planar metamaterials with nonlinear constituents

We present a theory which explains how to achieve an enhancement of nonlinear effects in a thin layer of nonlinear medium by involving a planar periodic structure specially designed to bear a trapped-mode resonant regime. In particular, the possibility of a nonlinear thin metamaterial to produce the bistable response at a relatively low input intensity due to a large quality factor of the trapped-mode resonance is shown. Also a simple design of an all-dielectric low-loss silicon-based planar metamaterial which can provide an extremely sharp resonant reflection and transmission is proposed. The designed metamaterial is envisioned for aggregating with a pumped active medium to achieve an enhancement of quantum dots luminescence and to produce an all-dielectric analog of a 'lasing spaser'.Comment: 18 pages, 13 figure

Chiral tunneling and the Klein paradox in graphene

The so-called Klein paradox - unimpeded penetration of relativistic particles through high and wide potential barriers - is one of the most exotic and counterintuitive consequences of quantum electrodynamics (QED). The phenomenon is discussed in many contexts in particle, nuclear and astro- physics but direct tests of the Klein paradox using elementary particles have so far proved impossible. Here we show that the effect can be tested in a conceptually simple condensed-matter experiment by using electrostatic barriers in single- and bi-layer graphene. Due to the chiral nature of their quasiparticles, quantum tunneling in these materials becomes highly anisotropic, qualitatively different from the case of normal, nonrelativistic electrons. Massless Dirac fermions in graphene allow a close realization of Klein's gedanken experiment whereas massive chiral fermions in bilayer graphene offer an interesting complementary system that elucidates the basic physics involved.Comment: 15 pages, 4 figure

Triassic chirotheriid footprints from the Swiss Alps: ichnotaxonomy and depositional environment (Cantons Wallis & Glarus)

Autochthonous Triassic sediments of the Vieux Emosson Formation near Lac d’Emosson, southwestern Switzerland, have yielded assemblages with abundant archosaur footprints that are assigned to chirotheriids based on pentadactyl pes and manus imprints with characteristic digit proportions. Tridactyl footprints formerly considered as those of dinosaurs are identified as incomplete extramorphological variants of chirotheriids. Recently discovered new sites, including a surface with about 1500 imprints, permit re-evaluation of ichnotaxonomy and modes of preservation. Most common are oval to circular impressions arranged in an ‘‘hourglass-like’’ shape, corresponding to pes-manus couples. Sediment displacement rims indicate the presence of true tracks rather than undertracks. A few well-preserved footprints with distinct digit traces allow closer assignments. Several chirotheriid ichnotaxa are present with Chirotherium barthii,?Chirotherium sickleri, Isochirotherium herculis, Chirotheriidae cf. Isochirotherium isp. and indeterminate forms. This corresponds with characteristic assemblages from the Buntsandstein of the Germanic Basin. In the study area, the Vieux Emosson Formation is an up to 10 m thick finingupward sequence with conglomerates, rippled sandstones, siltstones and mudstones and occasionally carbonate nodules. Sedimentological features such as high relief erosion, immature sediments, erosionally truncated metre-scale fining-upward sequences, palaeosols and unidirectional palaeocurrents clearly prove a fluvial depositional environment with sediment transport towards the northwest and the Germanic Basin. This contrasts with former assumptions of a coastal marine environment and a south-facing transport towards the Tethys. The footprints occur in the coarser lower portion of the sequence that is interpreted as a shallow braided river. From Obersand in the eastern Swiss Alps, a surface in dolomitic limestone (Ro¨ti Dolomite) is re-examined. The footprints are identified as Chirotherium barthii and were impressed in a carbonate tidal flat environment. Biostratigraphically, the occurrence of characteristic Buntsandstein assemblages with Chirotherium barthii supports an Anisian age of both locations

Two-dimensional Vortices in Superconductors

Superconductors have two key characteristics. They expel magnetic field and they conduct electrical current with zero resistance. However, both properties are compromised in high magnetic fields which can penetrate the material and create a mixed state of quantized vortices. The vortices move in response to an electrical current dissipating energy which destroys the zero resistance state\cite{And64}. One of the central problems for applications of high temperature superconductivity is the stabilization of vortices to ensure zero electrical resistance. We find that vortices in the anisotropic superconductor Bi$_{2}$Sr$_{2}$CaCu$_{2}$O$_{8+\delta}$ (Bi-2212) have a phase transition from a liquid state, which is inherently unstable, to a two-dimensional vortex solid. We show that at high field the transition temperature is independent of magnetic field, as was predicted theoretically for the melting of an ideal two-dimensional vortex lattice\cite{Fis80,Gla91}. Our results indicate that the stable solid phase can be reached at any field as may be necessary for applications involving superconducting magnets\cite{Has04,Sca04,COHMAG}. The vortex solid is disordered, as suggested by previous studies at lower fields\cite{Lee93,Cub93}. But its evolution with increasing magnetic field displays unexpected threshold behavior that needs further investigation.Comment: 5 pages and 4 figures. submitted to Nature Physic

Neurocognitive outcomes in neurofibromatosis clinical trials

Neurofibromatosis type 1 (NF1) is associated with neurocognitive deficits that can impact everyday functioning of children, adolescents, and adults with this disease. However, there is little agreement regarding measures to use as cognitive endpoints in clinical trials. This article describes the work of the Neurocognitive Committee of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration. The goal of this committee is to identify standardized and specific cognitive assessment tools for use in NF clinical trials. The committee first identified cognitive domains relevant to NF1 and prioritized attention as the first domain of focus given prior and current trends in NF1 cognitive clinical trials. Performance measures and behavioral rating questionnaires of attention were reviewed by the group using established criteria to assess patient characteristics, psychometric properties, and feasibility. The highest rated tests underwent side-by-side comparison. The Digit Span subtest from the Wechsler scales was given the highest ratings of the performance measures due to its good psychometrics, feasibility, utility across a wide age range, and extensive use in previous research. The Conners scales achieved the highest ratings of the behavioral questionnaires for similar reasons. Future articles will focus on other cognitive domains, with the ultimate goal of achieving agreement for cognitive endpoints that can be used across NF clinical trials

SUMO chain formation is required for response to replication arrest in S. pombe

SUMO is a ubiquitin-like protein that is post-translationally attached to one or more lysine residues on target proteins. Despite having only 18% sequence identity with ubiquitin, SUMO contains the conserved betabetaalphabetabetaalphabeta fold present in ubiquitin. However, SUMO differs from ubiquitin in having an extended N-terminus. In S. pombe the N-terminus of SUMO/Pmt3 is significantly longer than those of SUMO in S. cerevisiae, human and Drosophila. Here we investigate the role of this N-terminal region. We have used two dimensional gel electrophoresis to demonstrate that S. pombe SUMO/Pmt3 is phosphorylated, and that this occurs on serine residues at the extreme N-terminus of the protein. Mutation of these residues (in pmt3-1) results in a dramatic reduction in both the levels of high Mr SUMO-containing species and of total SUMO/Pmt3, indicating that phosphorylation of SUMO/Pmt3 is required for its stability. Despite the significant reduction in high Mr SUMO-containing species, pmt3-1 cells do not display an aberrant cell morphology or sensitivity to genotoxins or stress. Additionally, we demonstrate that two lysine residues in the N-terminus of S. pombe SUMO/Pmt3 (K14 and K30) can act as acceptor sites for SUMO chain formation in vitro. Inability to form SUMO chains results in aberrant cell and nuclear morphologies, including stretched and fragmented chromatin. SUMO chain mutants are sensitive to the DNA synthesis inhibitor, hydroxyurea (HU), but not to other genotoxins, such as UV, MMS or CPT. This implies a role for SUMO chains in the response to replication arrest in S. pomb

Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection

Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169+ sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4+CD25+ T cells and an increased number of B220+CD19+ B cells. The reduction in CD4+CD25+ T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome