1,054 research outputs found
Therapeutic Targeting Notch2 Protects Bone Micro-Vasculatures from Methotrexate Chemotherapy-Induced Adverse Effects in Rats
Intensive cancer chemotherapy is well known to cause bone vasculature disfunction and damage, but the mechanism is poorly understood and there is a lack of treatment. Using a rat model of methotrexate (MTX) chemotherapy (five once-daily dosses at 0.75 mg/kg), this study investigated the roles of the Notch2 signalling pathway in MTX chemotherapy-induced bone micro-vasculature impairment. Gene expression, histological and micro-computed tomography (micro-CT) analyses revealed that MTX-induced micro-vasculature dilation and regression is associated with the induction of Notch2 activity in endothelial cells and increased production of inflammatory cytokine tumour necrosis factor alpha (TNFα) from osteoblasts (bone forming cells) and bone marrow cells. Blockade of Notch2 by a neutralising antibody ameliorated MTX adverse effects on bone micro-vasculature, both directly by supressing Notch2 signalling in endothelial cells and indirectly via reducing TNFα production. Furthermore, in vitro studies using rat bone marrow-derived endothelial cell revealed that MTX treatment induces Notch2/Hey1 pathway and negatively affects their ability in migration and tube formation, and Notch2 blockade can partially protect endothelial cell functions from MTX damage.Yaser Peymanfar, Yu-Wen Su, Mohammadhossein Hassanshahi and Cory J. Xia
Functional interaction between the cytoplasmic leucine-zipper domain of HIV-1 gp41 and p115-RhoGEF
AbstractThe long cytoplasmic tail of the human immunodeficiency virus (HIV)-1 transmembrane protein gp41 (gp41C) is implicated in the replication and cytopathicity of HIV-1 [1]. Little is known about the specific functions of gp41C, however. HIV-1 or simian immunodeficiency virus (SIV) mutants with defective gp41C have cell-type- or species-dependent phenotypes [2–6]. Thus, host factors are implicated in mediating the functions of gp41C. We report here that gp41C interacted with the carboxy-terminal regulatory domain of p115-RhoGEF [7], a specific guanine nucleotide exchange factor (GEF) and activator of the RhoA GTPase, which regulates actin stress fiber formation, activation of serum response factor (SRF) and cell proliferation [8,9]. We demonstrate that gp41C inhibited p115-mediated actin stress fiber formation and activation of SRF. An amphipathic helix region with a leucine-zipper motif in gp41C is involved in its interaction with p115. Mutations in gp41C leading to loss of interaction with p115 impaired HIV-1 replication in human T cells. These findings suggest that an important function of gp41C is to modulate the activity of p115-RhoGEF and they thus reveal a new potential anti-HIV-1 target
Research on parameters optimization of bilateral ring gear blank-holder in thick-plate fine blanking
To compensate for the poor quality of thick-plate blanking parts in cross-section, this paper suggests using the optimizing bilateral ring gear holder parameters to increase burnish zone and improve cutting precision. With the bilateral gear ring, the hydrostatic pressure of shear deformation zone will increase, plasticity of the material will be lifted to maximum and quality of the cross section will be raised. This paper establishes 8mm AISI-1020 fine blanking model by DEFORM2D, analysis different ring gear parameters and clearance that are influenced the stress-strain and cross section quality to predict forming defects. By using the bilateral gear ring blank holder, the poor quality of thick-plate blanking section is successfully enhanced. Therefore, the bilateral gear ring blank holder is vital to improve the quality of blanking parts and provide the reliable theory basis for the practical engineering application
The Evolution of Sunspot Magnetic Fields Associated with a Solar Flare
Solar flares occur due to the sudden release of energy stored in
active-region magnetic fields. To date, the pre-cursors to flaring are still
not fully understood, although there is evidence that flaring is related to
changes in the topology or complexity of an active region's magnetic field.
Here, the evolution of the magnetic field in active region NOAA 10953 was
examined using Hinode/SOT-SP data, over a period of 12 hours leading up to and
after a GOES B1.0 flare. A number of magnetic-field properties and low-order
aspects of magnetic-field topology were extracted from two flux regions that
exhibited increased Ca II H emission during the flare. Pre-flare increases in
vertical field strength, vertical current density, and inclination angle of ~
8degrees towards the vertical were observed in flux elements surrounding the
primary sunspot. The vertical field strength and current density subsequently
decreased in the post-flare state, with the inclination becoming more
horizontal by ~7degrees. This behaviour of the field vector may provide a
physical basis for future flare forecasting efforts.Comment: Accepted for Publication in Solar Physics. 16 pages, 4 figure
Quantum logic between atoms inside a high Q optical cavity
We propose a protocol for conditional quantum logic between two 4-state atoms
inside a high Q optical cavity. The process detailed in this paper utilizes a
direct 4-photon 2-atom resonant process and has the added advantage of commonly
addressing the two atoms when they are inside the high Q optical cavity.Comment: 8 pages, 3 figs. submitte
One-Loop MHV Amplitudes in Supersymmetric Gauge Theories
Using CSW rules for constructing scalar Feynman diagrams from MHV vertices,
we compute the contribution of chiral multiplet to one-loop
MHV gluon amplitude. The result agrees with the one obtained previously using
unitarity-based methods, thereby demonstrating the validity of the MHV-diagram
technique, in the case of one-loop MHV amplitudes, for all massless
supersymmetric theories.Comment: 20 pages, 5 figure
Designing a therapeutic hepatitis B vaccine to circumvent immune tolerance
An effective prophylactic hepatitis B virus (HBV) vaccine has long been available but is ineffective for chronic infection. The primary cause of chronic hepatitis B (CHB) and greatest impediment for a therapeutic vaccine is the direct and indirect effects of immune tolerance to HBV antigens. The resulting defective CD4+/CD8+ T cell response, poor cytokine production, insufficient neutralizing anti-body (nAb) and poor response to HBsAg vaccination characterize CHB infection. The objective of this study was to develop virus-like-particles (VLPs) that elicit nAb to prevent viral spread and prime CD4+/CD8+ T cells to eradicate intracellular HBV. Eight neutralizing B cell epitopes from the envelope PreS1 region were consolidated onto a species-variant of the HBV core protein, the woodchuck hepatitis core antigen (WHcAg). PreS1-specific B cell epitopes were chosen because of preferential expression on HBV virions. Because WHcAg and HBcAg are not crossreactive at the B cell level and only partially cross-reactive at the CD4+/CD8+ T cell level, CD4+ T cells specific for WHcAg-unique T cell sites can provide cognate T-B cell help for anti-PreS1 Ab production that is not curtailed by immune tolerance. Immunization of immune tolerant HBV transgenic (Tg) mice with PreS1-WHc VLPs elicited levels of high titer anti-PreS1 nAbs equivalent to wildtype mice. Passive transfer of PreS1 nAbs into human-liver chimeric mice prevented acute infection and cleared serum HBV from mice previously infected with HBV in a model of CHB. At the T cell level, PreS1-WHc VLPs and hybrid WHcAg/HBcAg DNA immunogens elicited HBcAg-specific CD4+ Th and CD8+ CTL responses
Scalar diagrammatic rules for Born amplitudes in QCD
We show that all Born amplitudes in QCD can be calculated from scalar
propagators and a set of three- and four-valent vertices. In particular, our
approach includes amplitudes with any number of quark pairs. The quarks may be
massless or massive. The proof of the formalism is given entirely within
quantum field theory.Comment: 20 pages, references adde
Specific characters of 16S rRNA gene and 16S-23S rRNA internal transcribed spacer sequences of Xylella fastidiosa pear leaf scorch strains
Pear leaf scorch, the only Xylella fastidiosa-induced disease reported from Taiwan, was found in area where the variety Hengshan (Pyrus pyrifolia) was grown. Strains of pear leaf scorch Xyl. fastidiosa (XF-PLS) shared similarities to strains of other host origins in the requirement of complex medium and the exhibition of rippled cell walls, however, recent serological and molecular biology studies showed difference among them. Five strains of XF-PLS were compared with 20 other strains originally isolated from almond, oleander, pecan, plum, peach, mulberry, grapes, citrus, coffee, and sycamore by sequence analyses of the 16S rRNA gene and 16S-23S rRNA internal transcribed spacer region (ITS). When sequences of 16S rRNA gene based on fragment size of 1,537-1,540 bp were compared, the similarity index among 5 XF-PLS strains was 99.3-99.8%, whereas it was 97.8-98.6% between XF-PLS strains and strains from other hosts. When sequences of 16S-23S rRNA ITS based on fragment size of 510-540 bp were compared, the similarity index among 5 XF-PLS strains was 99.0-100%, whereas it was 80.7-82% between XF-PLS strains and strains from other hosts. Multiple sequence alignments led to the identification of 5 polymorphic nucleotides in the 16S rRNA gene among the 25 Xyl. fastidiosa strains, and there were considerable variations in the nucleotide sequences of 16S-23S rRNA ITS between XF-PLS and the other 20 Xyl. fastidiosa strains. The phylogenetic trees revealed that XF-PLS strains were separated from strains of other hosts. Strains of other hosts were divided into four subgroups: strains from (1) oleander, (2) grape, almond M23 and mulberry, (3) citrus and coffee, and (4) pecan, peach, plum, sycamore and almond M12. Results indicate that XF-PLS strains were not closely related to the above-mentioned strains from other hosts and could possibly belong to a new subspecies of Xyl. fastidiosa
- …