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
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
We present first-principles studies on the orbital states of the layered
perovskites CaSrRuO. The crossover from antiferromagnetic (AF)
Mott insulator for to nearly ferromagnetic (FM) metal at is
characterized by the systematic change of the orbital occupation. For the
AF side (), we present firm evidence for the ferro-orbital
ordering. It is found that the degeneracy of (or ) states is
lifted robustly due to the two-dimensional (2D) crystal-structure, even without
the Jahn-Teller distortion of RuO. This effect dominates, and the
cooperative occupation of 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 (), however, the orbital with half filling opens a
pseudo-gap in the FM state and contributes to the spin =1/2 moment (rather
than =1 for =0.0 case) dominantly, while states are itinerant
with very small spin polarization, explaining the recent neutron data
consistently.Comment: 17 pages, 5 figure
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Sensitivity of OMI SO2 measurements to variable eruptive behaviour at Soufrière Hills Volcano, Montserrat
Since 2004, the satellite-borne Ozone Mapping Instrument (OMI) has observed sulphur dioxide (SO2) plumes during both quiescence and effusive eruptive activity at Soufrière Hills Volcano, Montserrat. On average, OMI detected a SO2 plume 4-6 times more frequently during effusive periods than during quiescence in the 2008-2010 period. The increased ability of OMI to detect SO2 during eruptive periods is mainly due to an increase in plume altitude rather than a higher SO2 emission rate. Three styles of eruptive activity cause thermal lofting of gases (Vulcanian explosions; pyroclastic flows; a hot lava dome) and the resultant plume altitudes are estimated from observations and models. Most lofting plumes from Soufrière Hills are derived from hot domes and pyroclastic flows. Although Vulcanian explosions produced the largest plumes, some produced only negligible SO2 signals detected by OMI. OMI is most valuable for monitoring purposes at this volcano during periods of lava dome growth and during explosive activity
CD36 promotes vasculogenic mimicry in melanoma by mediating adhesion to the extracellular matrix
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
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
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]
Proteasome Nuclear Import Mediated by Arc3 Can Influence Efficient DNA Damage Repair and Mitosis in Schizosaccharomyces Pombe
Proteasomes must efficiently remove their substrates throughout the cells in a timely manner as many of these proteins can be toxic. This study shows that proteasomes can do so efficiently because they are highly mobile. Furthermore this study uncovers that proteasome mobility requires functional Arc3, a subunit of the Arp2/3 complex
The delivery of personalised, precision medicines via synthetic proteins
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
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