366 research outputs found
Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis
Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene initiate a majority of colorectal cancers. Acquisition of chromosomal instability is an early event in these tumors. We provide evidence that the loss of APC leads to a partial loss of interkinetochore tension at metaphase and alters mitotic progression. Furthermore, we show that inhibition of APC in U2OS cells compromises the mitotic spindle checkpoint. This is accompanied by a decrease in the association of the checkpoint proteins Bub1 and BubR1 with kinetochores. Additionally, APC depletion reduced apoptosis. As expected from this combination of defects, tetraploidy and polyploidy are consequences of APC inhibition in vitro and in vivo. The removal of APC produced the same defects in HCT116 cells that have constitutively active β-catenin. These data show that the loss of APC immediately induces chromosomal instability as a result of a combination of mitotic and apoptotic defects. We suggest that these defects amplify each other to increase the incidence of tetra- and polyploidy in early stages of tumorigenesis
Gravitational quasinormal modes for Anti-de Sitter black holes
Quasinormal mode spectra for gravitational perturbations of black holes in
four dimensional de Sitter and anti-de Sitter space are investigated. The
anti-de Sitter case is relevant to the ADS-CFT correspondence in superstring
theory. The ADS-CFT correspondence suggests a prefered set of boundary
conditions.Comment: 12 pages, 6 figures in ReVTe
Ultrasound capsule endoscopy:sounding out the future
Video capsule endoscopy (VCE) has been of immense benefit in the diagnosis and management of gastrointestinal (GI) disorders since its introduction in 2001. However, it suffers from a number of well recognized deficiencies. Amongst these is the limited capability of white light imaging, which is restricted to analysis of the mucosal surface. Current capsule endoscopes are dependent on visual manifestation of disease and limited in regards to transmural imaging and detection of deeper pathology. Ultrasound capsule endoscopy (USCE) has the potential to overcome surface only imaging and provide transmural scans of the GI tract. The integration of high frequency microultrasound (µUS) into capsule endoscopy would allow high resolution transmural images and provide a means of both qualitative and quantitative assessment of the bowel wall. Quantitative ultrasound (QUS) can provide data in an objective and measurable manner, potentially reducing lengthy interpretation times by incorporation into an automated diagnostic process. The research described here is focused on the development of USCE and other complementary diagnostic and therapeutic modalities. Presently investigations have entered a preclinical phase with laboratory investigations running concurrently
Ultrasound mediated delivery of quantum dots from a proof of concept capsule endoscope to the gastrointestinal wall
Biologic drugs, defined as therapeutic agents produced from or containing components of a living organism, are of growing importance to the pharmaceutical industry. Though oral delivery of medicine is convenient, biologics require invasive injections because of their poor bioavailability via oral routes. Delivery of biologics to the small intestine using electronic delivery with devices that are similar to capsule endoscopes is a promising means of overcoming this limitation and does not require reformulation of the therapeutic agent. The efficacy of such capsule devices for drug delivery could be further improved by increasing the permeability of the intestinal tract lining with an integrated ultrasound transducer to increase uptake. This paper describes a novel proof of concept capsule device capable of electronic application of focused ultrasound and delivery of therapeutic agents. Fluorescent markers, which were chosen as a model drug, were used to demonstrate in vivo delivery in the porcine small intestine with this capsule. We show that the fluorescent markers can penetrate the mucus layer of the small intestine at low acoustic powers when combining microbubbles with focused ultrasound during in vivo experiments using porcine models. This study illustrates how such a device could be potentially used for gastrointestinal drug delivery and the challenges to be overcome before focused ultrasound and microbubbles could be used with this device for the oral delivery of biologic therapeutics
The development of a sub-atmospheric two-phase thermosyphon natural gas preheater using a lumped capacitance model and comparison with experimental results
Ultrasound mediated delivery of quantum dots from a capsule endoscope to the gastrointestinal wall
Biologic drugs, defined as therapeutic agents produced from or containing components of a living organism, are of growing importance to the pharmaceutical industry. Though oral delivery of medicine is convenient, biologics require invasive injections because of their poor bioavailability via oral routes. Delivery of biologics to the small intestine using electronic delivery with devices that are similar to capsule endoscopes is a promising means of overcoming this limitation and does not require reformulation of the therapeutic agent. The efficacy of such capsule devices for drug delivery could be further improved by increasing the permeability of the intestinal tract lining with an integrated ultrasound transducer to increase uptake. This paper describes a novel proof of concept capsule device capable of electronic application of focused ultrasound and delivery of therapeutic agents. Fluorescent markers, which were chosen as a model drug, were used to demonstrate in-vivo delivery in the porcine small intestine with this capsule. We show that the fluorescent markers can penetrate the mucus layer of the small intestine at low acoustic powers when combining microbubbles with focussed ultrasound. These findings suggest that the use of focused ultrasound together with microbubbles could play a role in the oral delivery of biologic therapeutics
Quantum Dynamics of Lorentzian Spacetime Foam
A simple spacetime wormhole, which evolves classically from zero throat
radius to a maximum value and recontracts, can be regarded as one possible mode
of fluctuation in the microscopic ``spacetime foam'' first suggested by
Wheeler. The dynamics of a particularly simple version of such a wormhole can
be reduced to that of a single quantity, its throat radius; this wormhole thus
provides a ``minisuperspace model'' for a structure in Lorentzian-signature
foam. The classical equation of motion for the wormhole throat is obtained from
the Einstein field equations and a suitable equation of state for the matter at
the throat. Analysis of the quantum behavior of the hole then proceeds from an
action corresponding to that equation of motion. The action obtained simply by
calculating the scalar curvature of the hole spacetime yields a model with
features like those of the relativistic free particle. In particular the
Hamiltonian is nonlocal, and for the wormhole cannot even be given as a
differential operator in closed form. Nonetheless the general solution of the
Schr\"odinger equation for wormhole wave functions, i.e., the wave-function
propagator, can be expressed as a path integral. Too complicated to perform
exactly, this can yet be evaluated via a WKB approximation. The result
indicates that the wormhole, classically stable, is quantum-mechanically
unstable: A Feynman-Kac decomposition of the WKB propagator yields no spectrum
of bound states. Though an initially localized wormhole wave function may
oscillate for many classical expansion/recontraction periods, it must
eventually leak to large radius values. The possibility of such a mode unstable
against growth, combined withComment: 37 pages, 93-
Identification of Endogenous Adenomatous Polyposis Coli Interaction Partners and β-Catenin-Independent Targets by Proteomics
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