A Nonlinear Force-Free Magnetic Field Approximation Suitable for Fast Forward-Fitting to Coronal Loops. I. Theory

We derive an analytical approximation of nonlinear force-free magnetic field solutions (NLFFF) that can efficiently be used for fast forward-fitting to solar magnetic data, constrained either by observed line-of-sight magnetograms and stereoscopically triangulated coronal loops, or by 3D vector-magnetograph data. The derived NLFFF solutions provide the magnetic field components $B_x({\bf x})$, $B_y({\bf x})$, $B_z({\bf x})$, the force-free parameter $\alpha({\bf x})$, the electric current density ${\bf j}({\bf x})$, and are accurate to second-order (of the nonlinear force-free $\alpha$-parameter). The explicit expressions of a force-free field can easily be applied to modeling or forward-fitting of many coronal phenomena.Comment: Solar Physics (in press), 26 pages, 11 figure

Passenger transmission and productiveness of transit lines with high loads

Deterministic transit capacity analysis applies to planning, design and operational management of urban transit systems. The Transit Capacity and Quality of Service Manual (1) and Vuchic (2, 3) enable transit performance to be quantified and assessed using transit capacity and productive capacity. This paper further defines important productive performance measures of an individual transit service and transit line. Transit work (p-km) captures the transit task performed over distance. Passenger transmission (p-km/h) captures the passenger task delivered by service at speed. Transit productiveness (p-km/h) captures transit work performed over time. These measures are useful to operators in understanding their services’ or systems’ capabilities and passenger quality of service. This paper accounts for variability in utilized demand by passengers along a line and high passenger load conditions where passenger pass-up delay occurs. A hypothetical case study of an individual bus service’s operation demonstrates the usefulness of passenger transmission in comparing existing and growth scenarios. A hypothetical case study of a bus line’s operation during a peak hour window demonstrates the theory’s usefulness in examining the contribution of individual services to line productive performance. Scenarios may be assessed using this theory to benchmark or compare lines and segments, conditions, or consider improvements

Automated Detection of Coronal Loops using a Wavelet Transform Modulus Maxima Method

We propose and test a wavelet transform modulus maxima method for the au- tomated detection and extraction of coronal loops in extreme ultraviolet images of the solar corona. This method decomposes an image into a number of size scales and tracks enhanced power along each ridge corresponding to a coronal loop at each scale. We compare the results across scales and suggest the optimum set of parameters to maximise completeness while minimising detection of noise. For a test coronal image, we compare the global statistics (e.g., number of loops at each length) to previous automated coronal-loop detection algorithms

The Evolution of Sunspot Magnetic Fields Associated with a Solar Flare

Solar flares occur due to the sudden release of energy stored in active-region magnetic fields. To date, the pre-cursors to flaring are still not fully understood, although there is evidence that flaring is related to changes in the topology or complexity of an active region's magnetic field. Here, the evolution of the magnetic field in active region NOAA 10953 was examined using Hinode/SOT-SP data, over a period of 12 hours leading up to and after a GOES B1.0 flare. A number of magnetic-field properties and low-order aspects of magnetic-field topology were extracted from two flux regions that exhibited increased Ca II H emission during the flare. Pre-flare increases in vertical field strength, vertical current density, and inclination angle of ~ 8degrees towards the vertical were observed in flux elements surrounding the primary sunspot. The vertical field strength and current density subsequently decreased in the post-flare state, with the inclination becoming more horizontal by ~7degrees. This behaviour of the field vector may provide a physical basis for future flare forecasting efforts.Comment: Accepted for Publication in Solar Physics. 16 pages, 4 figure

Fibrin(ogen) engagement of S. aureus promotes the host antimicrobial response and suppression of microbe dissemination following peritoneal infection

The blood-clotting protein fibrin(ogen) plays a critical role in host defense against invading pathogens, particularly against peritoneal infection by the Gram-positive microbe Staphylococcus aureus. Here, we tested the hypothesis that direct binding between fibrin(ogen) and S. aureus is a component of the primary host antimicrobial response mechanism and prevention of secondary microbe dissemination from the peritoneal cavity. To establish a model system, we showed that fibrinogen isolated from FibγΔ5 mice, which express a mutant form lacking the final 5 amino acids of the fibrinogen γ chain (termed fibrinogenγΔ5), did not support S. aureus adherence when immobilized and clumping when in suspension. In contrast, purified wildtype fibrinogen supported robust adhesion and clumping that was largely dependent on S. aureus expression of the receptor clumping factor A (ClfA). Following peritoneal infection with S. aureus USA300, FibγΔ5 mice displayed worse survival compared to WT mice coupled to reduced bacterial killing within the peritoneal cavity and increased dissemination of the microbes into circulation and distant organs. The failure of acute bacterial killing, but not enhanced dissemination, was partially recapitulated by mice infected with S. aureus USA300 lacking ClfA. Fibrin polymer formation and coagulation transglutaminase Factor XIII each contributed to killing of the microbes within the peritoneal cavity, but only elimination of polymer formation enhanced systemic dissemination. Host macrophage depletion or selective elimination of the fibrin(ogen) β2-integrin binding motif both compromised local bacterial killing and enhanced S. aureus systemic dissemination, suggesting fibrin polymer formation in and of itself was not sufficient to retain S. aureus within the peritoneal cavity. Collectively, these findings suggest that following peritoneal infection, the binding of S. aureus to stabilized fibrin matrices promotes a local, macrophage-mediated antimicrobial response essential for prevention of microbe dissemination and downstream host mortality

Are Solar Active Regions with Major Flares More Fractal, Multifractal, or Turbulent than Others?

Multiple recent investigations of solar magnetic field measurements have raised claims that the scale-free (fractal) or multiscale (multifractal) parameters inferred from the studied magnetograms may help assess the eruptive potential of solar active regions, or may even help predict major flaring activity stemming from these regions. We investigate these claims here, by testing three widely used scale-free and multiscale parameters, namely, the fractal dimension, the multifractal structure function and its inertial-range exponent, and the turbulent power spectrum and its power-law index, on a comprehensive data set of 370 timeseries of active-region magnetograms (17,733 magnetograms in total) observed by SOHO's Michelson Doppler Imager (MDI) over the entire Solar Cycle 23. We find that both flaring and non-flaring active regions exhibit significant fractality, multifractality, and non-Kolmogorov turbulence but none of the three tested parameters manages to distinguish active regions with major flares from flare-quiet ones. We also find that the multiscale parameters, but not the scale-free fractal dimension, depend sensitively on the spatial resolution and perhaps the observational characteristics of the studied magnetograms. Extending previous works, we attribute the flare-forecasting inability of fractal and multifractal parameters to i) a widespread multiscale complexity caused by a possible underlying self-organization in turbulent solar magnetic structures, flaring and non-flaring alike, and ii) a lack of correlation between the fractal properties of the photosphere and overlying layers, where solar eruptions occur. However useful for understanding solar magnetism, therefore, scale-free and multiscale measures may not be optimal tools for active-region characterization in terms of eruptive ability or, ultimately,for major solar-flare prediction.Comment: 25 pages, 7 figures, 2 tables, Solar Phys., in pres

Assessment of systemic AAV-microdystrophin gene therapy in the GRMD model of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by the absence of dystrophin, a membrane-stabilizing protein encoded by the DMD gene. Although mouse models of DMD provide insight into the potential of a corrective therapy, data from genetically homologous large animals, such as the dystrophin-deficient golden retriever muscular dystrophy (GRMD) model, may more readily translate to humans. To evaluate the clinical translatability of an adeno-associated virus serotype 9 vector (AAV9)–microdystrophin (μDys5) construct, we performed a blinded, placebo-controlled study in which 12 GRMD dogs were divided among four dose groups [control, 1 × 1013 vector genomes per kilogram (vg/kg), 1 × 1014 vg/kg, and 2 × 1014 vg/kg; n = 3 each], treated intravenously at 3 months of age with a canine codon-optimized microdystrophin construct, rAAV9-CK8e-c-μDys5, and followed for 90 days after dosing. All dogs received prednisone (1 milligram/kilogram) for a total of 5 weeks from day-7 through day 28. We observed dose-dependent increases in tissue vector genome copy numbers; μDys5 protein in multiple appendicular muscles, the diaphragm, and heart; limb and respiratory muscle functional improvement; and reduction of histopathologic lesions. As expected, given that a truncated dystrophin protein was generated, phenotypic test results and histopathologic lesions did not fully normalize. All administrations were well tolerated, and adverse events were not seen. These data suggest that systemically administered AAV-microdystrophin may be dosed safely and could provide therapeutic benefit for patients with DMD

Prostate cancer and Hedgehog signalling pathway

[Abstract] The Hedgehog (Hh) family of intercellular signalling proteins have come to be recognised as key mediators in many fundamental processes in embryonic development. Their activities are central to the growth, patterning and morphogenesis of many different regions within the bodies of vertebrates. In some contexts, Hh signals act as morphogens in the dose-dependent induction of distinct cell fates within a target field, in others as mitogens in the regulation of cell proliferation or as inducing factors controlling the form of a developing organ. These diverse functions of Hh proteins raise many intriguing questions about their mode of action. Various studies have now demonstrated the function of Hh signalling in the control of cell proliferation, especially for stem cells and stem-like progenitors. Abnormal activation of the Hh pathway has been demonstrated in a variety of human tumours. Hh pathway activity in these tumours is required for cancer cell proliferation and tumour growth. Recent studies have uncovered the role for Hh signalling in advanced prostate cancer and demonstrated that autocrine signalling by tumour cells is required for proliferation, viability and invasive behaviour. Thus, Hh signalling represents a novel pathway in prostate cancer that offers opportunities for prognostic biomarker development, drug targeting and therapeutic response monitoring