Bondgraph modelling and simulation of the dynamic behaviour of above-knee prostheses

A mathematical model was used to investigate the dynamic behaviour of an above-knee (AK) prosthesis in the swing phase and to analyse the influence of mass and mass distribution on the maximal stump load and the required energy. The model consists of a bondgraph model of the prosthesis and a “walking” model which predicts the walking velocity, step length and the femoral trajectory. Equipment was developed to measure the inertial properties of the components of the prosthesis. \ud \ud Through computer simulation, stickdiagrams of the swing phase and graphs of the variation with time of the hip and stump forces were obtained. It was found that for a normal AK prosthesis with a knee-lock mechanism the axial stump load is greatest at the beginning and at the end of the swing phase. At a walking velocity of 5 km/hr the maximum axial stump load amounts to 2.1 times the static weight of the prosthesis. \ud \ud The maximum axial stump force appeared to be almost directly proportional to the total mass of the prosthesis but independent of the mass distribution. The required energy also increased with the mass of the prosthesis but is' dependent on mass distribution. \ud \ud Because of their comparable weights the influence of the shoe is almost equal to the influence of the prosthetic foot. Thus lightweight shoes should be used with lightweight prosthetic feet in order to add to their advantages

New small molecule inhibitors of histone methyl transferase DOT1L with a nitrile as a non-traditional replacement for heavy halogen atoms

A number of new nucleoside derivatives are disclosed as inhibitors of DOT1L activity. SARs established that DOT1L inhibition could be achieved through incorporation of polar groups and small heterocycles at the 5-position (5, 6, 12) or by the application of alternative nitrogenous bases (18). Based on these results, CN-SAH (19) was identified as a potent and selective inhibitor of DOT1L activity where the polar 5-nitrile group was shown by crystallography to bind in the hydrophobic pocket of DOT1L. In addition, we show that a polar nitrile group can be used as a non-traditional replacement for heavy halogen atoms

Permanent Occlusion of Feeding Arteries and Draining Veins in Solid Mouse Tumors by Vascular Targeted Photodynamic Therapy (VTP) with Tookad

Antiangiogenic and anti-vascular therapies present intriguing alternatives to cancer therapy. However, despite promising preclinical results and significant delays in tumor progression, none have demonstrated long-term curative features to date. Here, we show that a single treatment session of Tookad-based vascular targeted photodynamic therapy (VTP) promotes permanent arrest of tumor blood supply by rapid occlusion of the tumor feeding arteries (FA) and draining veins (DV), leading to tumor necrosis and eradication within 24–48 h.A mouse earlobe MADB106 tumor model was subjected to Tookad-VTP and monitored by three complementary, non-invasive online imaging techniques: Fluorescent intravital microscopy, Dynamic Light Scattering Imaging and photosensitized MRI. Tookad-VTP led to prompt tumor FA vasodilatation (a mean volume increase of 70%) with a transient increase (60%) in blood-flow rate. Rapid vasoconstriction, simultaneous blood clotting, vessel permeabilization and a sharp decline in the flow rates then followed, culminating in FA occlusion at 63.2 sec±1.5SEM. This blockage was deemed irreversible after 10 minutes of VTP treatment. A decrease in DV blood flow was demonstrated, with a slight lag from FA response, accompanied by frequent changes in flow direction before reaching a complete standstill. In contrast, neighboring, healthy tissue vessels of similar sizes remained intact and functional after Tookad-VTP.Tookad-VTP selectively targets the tumor feeding and draining vessels. To the best of our knowledge, this is the first mono-therapeutic modality that primarily aims at the larger tumor vessels and leads to high cure rates, both in the preclinical and clinical arenas

Recovering 3D structural properties of galaxies from SDSS-like photometry

Because of the 3D nature of galaxies, an algorithm for constructing spatial density distribution models of galaxies on the basis of galaxy images has many advantages over surface density distribution approximations. We present a method for deriving spatial structure and overall parameters of galaxies from images and estimate its accuracy and derived parameter degeneracies on a sample of idealised model galaxies. The test galaxies consist of a disc-like component and a spheroidal component with varying proportions and properties. Both components are assumed to be axially symmetric and coplanar. We simulate these test galaxies as if observed in the SDSS project through ugriz filters, thus gaining a set of realistically imperfect images of galaxies with known intrinsic properties. These artificial SDSS galaxies were thereafter remodelled by approximating the surface brightness distribution with a 2D projection of a bulge+disc spatial distribution model and the restored parameters were compared to the initial ones. Down to the r-band limiting magnitude 18, errors of the restored integral luminosities and colour indices remain within 0.05 mag and errors of the luminosities of individual components within 0.2 mag. Accuracy of the restored bulge-to-disc ratios (B/D) is within 40% in most cases, and becomes worse for galaxies with low B/D, but the general balance between bulges and discs is not shifted systematically. Assuming that the intrinsic disc axial ratio is < 0.3, the inclination angles can be estimated with errors < 5deg for most of the galaxies with B/D < 2 and with errors < 15deg up to B/D = 6. Errors of the recovered sizes of the galactic components are below 10% in most cases. In general, models of disc components are more accurate than models of spheroidal components for geometrical reasons.Comment: 15 pages, 13 figures, accepted for publication in RA

Gamma Lines without a Continuum: Thermal Models for the Fermi-LAT 130 GeV Gamma Line

Recent claims of a line in the Fermi-LAT photon spectrum at 130 GeV are suggestive of dark matter annihilation in the galactic center and other dark matter-dominated regions. If the Fermi feature is indeed due to dark matter annihilation, the best-fit line cross-section, together with the lack of any corresponding excess in continuum photons, poses an interesting puzzle for models of thermal dark matter: the line cross-section is too large to be generated radiatively from open Standard Model annihilation modes, and too small to provide efficient dark matter annihilation in the early universe. We discuss two mechanisms to solve this puzzle and illustrate each with a simple reference model in which the dominant dark matter annihilation channel is photonic final states. The first mechanism we employ is resonant annihilation, which enhances the annihilation cross-section during freezeout and allows for a sufficiently large present-day annihilation cross section. Second, we consider cascade annihilation, with a hierarchy between p-wave and s-wave processes. Both mechanisms require mass near-degeneracies and predict states with masses closely related to the dark matter mass; resonant freezeout in addition requires new charged particles at the TeV scale.Comment: 17 pages, 8 figure

Axion-mediated dark matter and Higgs diphoton signal

We consider axion-mediated dark matter models motivated by Fermi gamma ray line at 130 GeV, where anomaly interactions of an axion-like scalar mediate a singlet Dirac fermion dark matter (DM) to electroweak gauge bosons. In these models, extra vector-like leptons generate anomaly interactions for the axion and can also couple to the SM Higgs boson to modify the Higgs-to-diphoton rate. We can distinguish models by the branching fraction of the DM annihilation into a photon pair, favoring the model with a triplet fermion. From the condition that the lighter charged extra lepton must be heavier than dark matter for no tree-level DM annihilations, we also show that the ratio of Higgs-to-diphoton rate to the SM value is constrained by vacuum stability to 1.4(1.5) for the cutoff scale of 10(1) TeV.Comment: 29 pages, 6 figures, references adde

Exact exchange-correlation potential of a ionic Hubbard model with a free surface

We use Lanczos exact diagonalization to compute the exact exchange-correlation (xc) potential of a Hubbard chain with large binding energy ("the bulk") followed by a chain with zero binding energy ("the vacuum"). Several results of density functional theory in the continuum (sometimes controversial) are verified in the lattice. In particular we show explicitly that the fundamental gap is given by the gap in the Kohn-Sham spectrum plus a contribution due to the jump of the xc-potential when a particle is added. The presence of a staggered potential and a nearest-neighbor interaction V allows to simulate a ionic solid. We show that in the ionic regime in the small hopping amplitude limit the xc-contribution to the gap equals V, while in the Mott regime it is determined by the Hubbard U interaction. In addition we show that correlations generates a new potential barrier at the surface

Centralized Modularity of N-Linked Glycosylation Pathways in Mammalian Cells

Glycosylation is a highly complex process to produce a diverse repertoire of cellular glycans that are attached to proteins and lipids. Glycans are involved in fundamental biological processes, including protein folding and clearance, cell proliferation and apoptosis, development, immune responses, and pathogenesis. One of the major types of glycans, N-linked glycans, is formed by sequential attachments of monosaccharides to proteins by a limited number of enzymes. Many of these enzymes can accept multiple N-linked glycans as substrates, thereby generating a large number of glycan intermediates and their intermingled pathways. Motivated by the quantitative methods developed in complex network research, we investigated the large-scale organization of such N-linked glycosylation pathways in mammalian cells. The N-linked glycosylation pathways are extremely modular, and are composed of cohesive topological modules that directly branch from a common upstream pathway of glycan synthesis. This unique structural property allows the glycan production between modules to be controlled by the upstream region. Although the enzymes act on multiple glycan substrates, indicating cross-talk between modules, the impact of the cross-talk on the module-specific enhancement of glycan synthesis may be confined within a moderate range by transcription-level control. The findings of the present study provide experimentally-testable predictions for glycosylation processes, and may be applicable to therapeutic glycoprotein engineering

PAMELA and FERMI-LAT limits on the neutralino-chargino mass degeneracy

Searches for Dark Matter (DM) particles with indirect detection techniques have reached important milestones with the precise measurements of the anti-proton and gamma-ray spectra, notably by the PAMELA and FERMI-LAT experiments. While the gamma-ray results have been used to test the thermal Dark Matter hypothesis and constrain the Dark Matter annihilation cross section into Standard Model (SM) particles, the anti-proton flux measured by the PAMELA experiment remains relatively unexploited. Here we show that the latter can be used to set a constraint on the neutralino-chargino mass difference. To illustrate our point we use a Supersymmetric model in which the gauginos are light, the sfermions are heavy and the Lightest Supersymmetric Particle (LSP) is the neutralino. In this framework the W^+ W^- production is expected to be significant, thus leading to large anti-proton and gamma-ray fluxes. After determining a generic limit on the Dark Matter pair annihilation cross section into W^+ W^- from the anti-proton data only, we show that one can constrain scenarios in which the neutralino-chargino mass difference is as large as ~ 20 GeV for a mixed neutralino (and intermediate choices of the anti-proton propagation scheme). This result is consistent with the limit obtained by using the FERMI-LAT data. As a result, we can safely rule out the pure wino neutralino hypothesis if it is lighter than 450 GeV and constitutes all the Dark Matter.Comment: 22page