8,095 research outputs found
Multicritical Points in an Ising Random-Field Model
The phase diagram of the mean-field Ising model in a random field obeying a symmetric three-peak distribution is determined. This distribution is relevant to diluted antiferromagnets in a uniform magnetic field. The phase diagram includes a fourth-order point, tricritical points, ordered critical points, critical end points, and a double critical end point. An ordered phase persists for arbitrarily large random fields at low temperatures
Angiogenesis-dependent and independent phases of intimal hyperplasia.
BACKGROUND: Neointimal vascular smooth muscle cell (VSMC) proliferation is a primary cause of occlusive vascular disease, including atherosclerosis, restenosis after percutaneous interventions, and bypass graft stenosis. Angiogenesis is implicated in the progression of early atheromatous lesions in animal models, but its role in neointimal VSMC proliferation is undefined. Because percutaneous coronary interventions result in induction of periadventitial angiogenesis, we analyzed the role of this process in neointima formation. METHODS AND RESULTS: Local injury to the arterial wall in 2 different animal models induced periadventitial angiogenesis and neointima formation. Application of angiogenesis stimulators vascular endothelial growth factor (VEGF-A165) or a proline/arginine-rich peptide (PR39) to the adventitia of the injured artery induced a marked increase in neointimal thickening beyond that seen with injury alone in both in vivo models. Inhibition of either VEGF (with soluble VEGF receptor 1 [sFlt1]) or fibroblast growth factor (FGF) (with a dominant=negative form of FGF receptor 1 [FGF-R1DN]), respectively, signaling reduced adventitial thickening induced by VEGF and PR39 to the level seen with mechanical arterial injury alone. However, neither inhibitor was effective in preventing neointimal thickening after mechanical injury when administered in the absence of angiogenic growth factor. CONCLUSIONS: Our findings indicate that adventitial angiogenesis stimulates intimal thickening but does not initiate it
Distinct Functions for the Drosophila piRNA Pathway in Genome Maintenance and Telomere Protection
Transposons and other selfish DNA elements can be found in all phyla, and mobilization of these elements can compromise genome integrity. The piRNA (PIWI-interacting RNA) pathway silences transposons in the germline, but it is unclear if this pathway has additional functions during development. Here we show that mutations in the Drosophila piRNA pathway genes, armi, aub, ago3, and rhi, lead to extensive fragmentation of the zygotic genome during the cleavage stage of embryonic divisions. Additionally, aub and armi show defects in telomere resolution during meiosis and the cleavage divisions; and mutations in lig-IV, which disrupt non-homologous end joining, suppress these fusions. By contrast, lig-IV mutations enhance chromosome fragmentation. Chromatin immunoprecipitation studies show that aub and armi mutations disrupt telomere binding of HOAP, which is a component of the telomere protection complex, and reduce expression of a subpopulation of 19- to 22-nt telomere-specific piRNAs. Mutations in rhi and ago3, by contrast, do not block HOAP binding or production of these piRNAs. These findings uncover genetically separable functions for the Drosophila piRNA pathway. The aub, armi, rhi, and ago3 genes silence transposons and maintain chromosome integrity during cleavage-stage embryonic divisions. However, the aub and armi genes have an additional function in assembly of the telomere protection complex
Functional improvement of dystrophic muscle by repression of utrophin: let-7c interaction
Duchenne muscular dystrophy (DMD) is a fatal genetic disease caused by an absence of the 427kD muscle-specific dystrophin isoform. Utrophin is the autosomal homolog of dystrophin and when overexpressed, can compensate for the absence of dystrophin and rescue the dystrophic phenotype of the mdx mouse model of DMD. Utrophin is subject to miRNA mediated repression by several miRNAs including let-7c. Inhibition of utrophin: let-7c interaction is predicted to 'repress the repression' and increase utrophin expression. We developed and tested the ability of an oligonucleotide, composed of 2'-O-methyl modified bases on a phosphorothioate backbone, to anneal to the utrophin 3'UTR and prevent let-7c miRNA binding, thereby upregulating utrophin expression and improving the dystrophic phenotype in vivo. Suppression of utrophin: let-7c interaction using bi-weekly intraperitoneal injections of let7 site blocking oligonucleotides (SBOs) for 1 month in the mdx mouse model for DMD, led to increased utrophin expression along with improved muscle histology, decreased fibrosis and increased specific force. The functional improvement of dystrophic muscle achieved using let7-SBOs suggests a novel utrophin upregulation-based therapeutic strategy for DMD
Behaviour of three charged particles on a plane under perpendicular magnetic field
We consider the problem of three identical charged particles on a plane under
a perpendicular magnetic field and interacting through Coulomb repulsion. This
problem is treated within Taut's framework, in the limit of vanishing center of
mass vector , which corresponds to the strong magnetic
field limit, occuring for example in the Fractional Quantum Hall Effect. Using
the solutions of the biconfluent Heun equation, we compute the eigenstates and
show that there is two sets of solutions. The first one corresponds to a system
of three independent anyons which have their angular momenta fixed by the value
of the magnetic field and specified by a dimensionless parameter , the ratio of , the magnetic length, over , the Bohr
radius. This anyonic character, consistent with quantum mechanics of identical
particles in two dimensions, is induced by competing physical forces. The
second one corresponds to the case of the Landau problem when .
Finally we compare these states with the quantum Hall states and find that the
Laughlin wave functions are special cases of our solutions under certains
conditions.Comment: 15 pages, 3 figures, Accepeted in JP
P14-04. HIV-SELECTEST EIA and rapid test: a novel assay for differential diagnosis of HIV infections in the face of vaccine-generated antibodies
PIH42 Engaging Patients with E-Clinical Technology: Incorporating Patient Preferences into Disease Management and Care
Crystal structure of monomeric human Ξ²-2- microglobulin reveals clues to its amyloidogenic properties
Dissociation of human Ξ²-2-microglobulin (Ξ²(2)m) from the heavy chain of the class I HLA complex is a critical first step in the formation of amyloid fibrils from this protein. As a consequence of renal failure, the concentration of circulating monomeric Ξ²(2)m increases, ultimately leading to deposition of the protein into
amyloid fibrils and development of the disorder, dialysis-related amyloidosis. Here we present the crystal structure of a monomeric form of human Ξ²(2)m determined at 1.8-Γ
resolution that reveals remarkable structural changes relative to the HLA-bound protein. These involve the restructuring of a Ξ² bulge that separates two
short Ξ² strands to form a new six-residue Ξ² strand at one edge of this Ξ² sandwich protein. These structural changes remove key features proposed to have evolved to protect Ξ² sheet proteins from aggregation [Richardson, J.&Richardson, D. (2002) Proc. Natl. Acad.
Sci. USA 99, 2754β2759] and replaces them with an aggregationcompetent surface. In combination with solution studies using (1)H NMR, we show that the crystal structure presented here represents a rare species in solution that could provide important clues about the mechanism of amyloid formation from the normally highly
soluble native protein
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