Epoxysuccinyl peptide-derived cathepsin B inhibitors: Modulating membrane permeability by conjugation with the C-terminal heptapeptide segment of penetratin

Besides its physiological role in lysosomal protein breakdown, extralysosomal cathepsin B has recently been implicated in apoptotic cell death. Highly specific irreversible cathepsin B inhibitors that are readily cellpermeant should be useful tools to elucidate the effects of cathepsin B in the cytosol. We have covalently functionalised the poorly cellpermeant epoxysuccinyl based cathepsin B inhibitor [RGlyGlyLeu(2S, 3S)tEpsLeuProOH; R=OMe] with the C-terminal heptapeptide segment of penetratin (R=εAhxArg ArgNleLysTrpLysLysNH(2)). The high inhibitory potency and selectivity for cathepsin B versus cathepsin L of the parent compound was not affected by the conjugation with the penetratin heptapeptide. The conjugate was shown to efficiently penetrate into MCF-7 cells as an active inhibitor, thereby circumventing an intracellular activation step that is required by other inhibitors, such as the prodruglike epoxysuccinyl peptides E64d and CA074Me

Nonlinear Force-Free Field Modeling of the Solar Magnetic Carpet and Comparison with SDO/HMI and Sunrise/IMaX Observations

In the quiet solar photosphere, the mixed polarity fields form a magnetic carpet, which continuously evolves due to dynamical interaction between the convective motions and magnetic field. This interplay is a viable source to heat the solar atmosphere. In this work, we used the line-of-sight (LOS) magnetograms obtained from the Helioseismic and Magnetic Imager (HMI) on the \textit{Solar Dynamics Observatory} (\textit{SDO}), and the Imaging Magnetograph eXperiment (IMaX) instrument on the \textit{Sunrise} balloon-borne observatory, as time dependent lower boundary conditions, to study the evolution of the coronal magnetic field. We use a magneto-frictional relaxation method, including hyperdiffusion, to produce time series of three-dimensional (3D) nonlinear force-free fields from a sequence of photospheric LOS magnetograms. Vertical flows are added up to a height of 0.7 Mm in the modeling to simulate the non-force-freeness at the photosphere-chromosphere layers. Among the derived quantities, we study the spatial and temporal variations of the energy dissipation rate, and energy flux. Our results show that the energy deposited in the solar atmosphere is concentrated within 2 Mm of the photosphere and there is not sufficient energy flux at the base of the corona to cover radiative and conductive losses. Possible reasons and implications are discussed. Better observational constraints of the magnetic field in the chromosphere are crucial to understand the role of the magnetic carpet in coronal heating.Comment: Accepted for publication in The Astrophysical Journal (13 pages, 10 figures

Observations of Subarcsecond Bright Dots in the Transition Region above Sunspots with the Interface Region Imaging Spectrograph

Observations with the Interface Region Imaging Spectrograph (IRIS) have revealed numerous sub-arcsecond bright dots in the transition region above sunspots. These bright dots are seen in the 1400\AA{} and 1330\AA{} slit-jaw images. They are clearly present in all sunspots we investigated, mostly in the penumbrae, but also occasionally in some umbrae and light bridges. The bright dots in the penumbrae typically appear slightly elongated, with the two dimensions being 300--600 km and 250--450 km, respectively. The long sides of these dots are often nearly parallel to the bright filamentary structures in the penumbrae but sometimes clearly deviate from the radial direction. Their lifetimes are mostly less than one minute, although some dots last for a few minutes or even longer. Their intensities are often a few times stronger than the intensities of the surrounding environment in the slit-jaw images. About half of the bright dots show apparent movement with speeds of $\sim$10--40~km~s$^{-1}$ in the radial direction. Spectra of a few bright dots were obtained and the Si~{\sc{iv}}~1402.77\AA{} line profiles in these dots are significantly broadened. The line intensity can be enhanced by one to two orders of magnitude. Some relatively bright and long-lasting dots are also observed in several passbands of the Atmospheric Imaging Assembly onboard the Solar Dynamics Observatory, and they appear to be located at the bases of loop-like structures. Many of these bright dots are likely associated with small-scale energy release events at the transition region footpoints of magnetic loops.Comment: 5 figures, will appear in ApJ

StemNet: An Evolving Service for Knowledge Networking in the Life Sciences

Up until now, crucial life science information resources, whether bibliographic or factual databases, are isolated from each other. Moreover, semantic metadata intended to structure their contents is supplied in a manual form only. In the StemNet project we aim at developing a framework for semantic interoperability for these resources. This will facilitate the extraction of relevant information from textual sources and the generation of semantic metadata in a fully automatic manner. In this way, (from a computational perspective) unstructured life science documents are linked to structured biological fact databases, in particular to the identifiers of genes, proteins, etc. Thus, life scientists will be able to seamlessly access information from a homogeneous platform, despite the fact that the original information was unlinked and scattered over the whole variety of heterogeneous life science information resources and, therefore, almost inaccessible for integrated systematic search by academic, clinical, or industrial users

Effect of Concave Wall Geometry on Heat Transfer in Hypersonic Boundary Layers

Heat transfer measurements are made to investigate the effects of concave surface curvature on a high-stagnation enthalpy boundary layer in a Mach 5.1 flow. Experiments are carried out using two curved models with 16 and 25 degree turning angles, and baseline planar models (at plate and linear ramp) for comparative study. Streamwise and spanwise cross-sections are obtained. Significant destabilization of the boundary layer is observed over the adverse pressure gradient geometries. For the curved surfaces, the heat flux distribution appears to exhibit a quadratic dependence with streamwise distance, in contrast with the linear dependence observed on the linear ramp

The Relation between Solar Eruption Topologies and Observed Flare Features I: Flare Ribbons

In this paper we present a topological magnetic field investigation of seven two-ribbon flares in sigmoidal active regions observed with Hinode, STEREO, and SDO. We first derive the 3D coronal magnetic field structure of all regions using marginally unstable 3D coronal magnetic field models created with the flux rope insertion method. The unstable models have been shown to be a good model of the flaring magnetic field configurations. Regions are selected based on their pre-flare configurations along with the appearance and observational coverage of flare ribbons, and the model is constrained using pre-flare features observed in extreme ultraviolet and X-ray passbands. We perform a topology analysis of the models by computing the squashing factor, Q, in order to determine the locations of prominent quasi-separatrix layers (QSLs). QSLs from these maps are compared to flare ribbons at their full extents. We show that in all cases the straight segments of the two J-shaped ribbons are matched very well by the flux-rope-related QSLs, and the matches to the hooked segments are less consistent but still good for most cases. In addition, we show that these QSLs overlay ridges in the electric current density maps. This study is the largest sample of regions with QSLs derived from 3D coronal magnetic field models, and it shows that the magnetofrictional modeling technique that we employ gives a very good representation of flaring regions, with the power to predict flare ribbon locations in the event of a flare following the time of the model

Hot Plasma Detected in Active Regions by HINODE/XRT and SDO/AIA

Multiple ratios of Hinode/XRT filters showed evidence of a minor very hot emission measure component in active regions. Recently also SDO/AIA detected hot plasma in the core of an active region. Here we provide estimates showing that the amount of emission measure of the hot component detected with SDO is consistent with that detected with Hinode/XRT