437 research outputs found

    Transcranial direct current stimulation (tDCS) as an intervention to improve empathic abilities and reduce violent behavior in forensic offenders: study protocol for a randomized controlled trial

    Get PDF
    Background: Recent studies show that changes in one of the brain areas related to empathic abilities (i.e. the ventromedial prefrontal cortex (vmPFC)) plays an important role in violent behavior in abusers of alcohol and cocaine. According to the models of James Blair, empathy is a potential inhibitor of violent behavior. Individuals with less empathic abilities may be less susceptible and motivated to inhibit violent behavior, which causes a higher risk of violence. Recent neuroscientific research shows that modulating (stimulation or inhibition) certain brain areas could be a promising new intervention for substance abuse and to reduce violent behavior, such as the neurostimulation technique transcranial direct current stimulation (tDCS). This study aims to investigate tDCS as a

    Orbital Dependent Phase Control in Ca2-xSrxRuO4

    Full text link
    We present first-principles studies on the orbital states of the layered perovskites Ca2x_{2-x}Srx_xRuO4_4. The crossover from antiferromagnetic (AF) Mott insulator for x<0.2x < 0.2 to nearly ferromagnetic (FM) metal at x=0.5x=0.5 is characterized by the systematic change of the xyxy orbital occupation. For the AF side (x<0.2x < 0.2), we present firm evidence for the xyxy ferro-orbital ordering. It is found that the degeneracy of t2gt_{2g} (or ege_g) states is lifted robustly due to the two-dimensional (2D) crystal-structure, even without the Jahn-Teller distortion of RuO6_6. This effect dominates, and the cooperative occupation of xyxy orbital is concluded. In contrast to recent proposals, the resulting electronic structure explains well both the observed X-ray absorption spectra and the double peak structure of optical conductivity. For the FM side (x=0.5x=0.5), however, the xyxy orbital with half filling opens a pseudo-gap in the FM state and contributes to the spin SS=1/2 moment (rather than SS=1 for xx=0.0 case) dominantly, while yz,zxyz,zx states are itinerant with very small spin polarization, explaining the recent neutron data consistently.Comment: 17 pages, 5 figure

    CD36 promotes vasculogenic mimicry in melanoma by mediating adhesion to the extracellular matrix

    Get PDF
    Background: The formation of blood vessels within solid tumors directly contributes to cancer growth and metastasis. Until recently, tumor vasculature was thought to occur exclusively via endothelial cell (EC) lined structures (i.e. angiogenesis), but a second source of tumor vasculature arises from the cancer cells themselves, a process known as vasculogenic mimicry (VM). While it is generally understood that the function of VM vessels is the same as that of EC-lined vessels (i.e. to supply oxygen and nutrients to the proliferating cancer cells), the molecular mechanisms underpinning VM are yet to be fully elucidated. Methods: Human VM-competent melanoma cell lines were examined for their VM potential using the in vitro angiogenesis assays (Matrigel), together with inhibition studies using small interfering RNA and blocking monoclonal antibodies. Invasion assays and adhesion assays were used to examine cancer cell function. Results: Herein we demonstrate that CD36, a cell surface glycoprotein known to promote angiogenesis by ECs, also supports VM formation by human melanoma cancer cells. In silico analysis of CD36 expression within the melanoma cohort of The Cancer Genome Atlas suggests that melanoma patients with high expression of CD36 have a poorer clinical outcome. Using in vitro ‘angiogenesis’ assays and CD36-knockdown approaches, we reveal that CD36 supports VM formation by human melanoma cells as well as adhesion to, and invasion through, a cancer derived extracellular matrix substrate. Interestingly, thrombospondin-1 (TSP-1), a ligand for CD36 on ECs that inhibits angiogenesis, has no effect on VM formation. Further investigation revealed a role for laminin, but not collagen or fibronectin, as ligands for CD36 expressing melanoma cells. Conclusions: Taken together, this study suggests that CD36 is a novel regulator of VM by melanoma cancer cells that is facilitated, at least in part, via integrin-α3 and laminin. Unlike angiogenesis, VM is not perturbed by the presence of TSP-1, thus providing new information on differences between these two processes of tumor vascularization which may be exploited to combat cancer progression.Carmela Martini, Mark DeNichilo, Danielle P. King, Michaelia P. Cockshell, Brenton Ebert, Brian Dale, Lisa M. Ebert, Anthony Woods, and Claudine S. Bonde

    Destruction of 18F via 18F(p,α) 15O burning through the Ec.m.=665 keV resonance

    Get PDF
    Knowledge of the astrophysical rate of the 18F(p,α)15O reaction is important for understanding the γ-ray emission expected from novae and heavy-element production in x-ray bursts. The rate of this reaction is dominated at temperatures above ∼0.4 GK by a resonance near 7.08 MeV excitation energy in 19Ne. The 18F(p,α)15O rate has been uncertain in part because of disagreements among previous measurements concerning the resonance strength and excitation energy of this state. To resolve these uncertainties, we have made simultaneous measurements of the 1H(18F,p)18F and 1H(18F,α)15O excitation functions using a radioactive 18F beam at the ORNL Holifield Radioactive Ion Beam Facility. A simultaneous fit of the data sets has been performed, and the best fit was obtained with a center-of-mass resonance energy of 664.7±1.6 keV (Ex = 7076±2 keV), a total width of 39.0±1.6 keV, a proton branching ratio of Γp/Γ = 0.39±0.02, and a resonance strength of ωγ= 6.2±0.3 keV

    Kinematically complete measurement of the 1H(18F,p)18F excitation function for the astrophysically important 7.08-MeV state in 19Ne

    Get PDF
    Knowledge of the astrophysical [Formula Presented] rate is important for understanding gamma-ray emission from novae and heavy-element production in x-ray bursts. A state with [Formula Presented] in [Formula Presented] provides an s-wave resonance and, depending on its properties, could dominate the [Formula Presented] rate. By measuring a kinematically complete [Formula Presented] excitation function with a radioactive [Formula Presented] beam at the ORNL Holifield Radioactive Ion Beam Facility, we find that the [Formula Presented] state lies at a center-of-mass energy of [Formula Presented] has a total width of [Formula Presented] and a proton partial-width of [Formula Presented]

    The delivery of personalised, precision medicines via synthetic proteins

    Get PDF
    Introduction: The design of advanced drug delivery systems based on synthetic and su-pramolecular chemistry has been very successful. Liposomal doxorubicin (Caelyx®), and liposomal daunorubicin (DaunoXome®), estradiol topical emulsion (EstrasorbTM) as well as soluble or erodible polymer systems such as pegaspargase (Oncaspar®) or goserelin acetate (Zoladex®) represent considerable achievements. The Problem: As deliverables have evolved from low molecular weight drugs to biologics (currently representing approximately 30% of the market), so too have the demands made of advanced drug delivery technology. In parallel, the field of membrane trafficking (and endocytosis) has also matured. The trafficking of specific receptors i.e. material to be recycled or destroyed, as well as the trafficking of protein toxins has been well characterized. This, in conjunction with an ability to engineer synthetic, recombinant proteins provides several possibilities. The Solution: The first is using recombinant proteins as drugs i.e. denileukin diftitox (Ontak®) or agalsidase beta (Fabrazyme®). The second is the opportunity to use protein toxin architecture to reach targets that are not normally accessible. This may be achieved by grafting regulatory domains from multiple species to form synthetic proteins, engineered to do multiple jobs. Examples include access to the nucleocytosolic compartment. Herein the use of synthetic proteins for drug delivery has been reviewed
    corecore