175 research outputs found
Hemispherical Emissivity of V, Nb, Ta, Mo, and W from 300 to 1000 K
The hemispherical emissivities of five transition elements, V, Nb, Ta, Mo, and W, have been measured from 300 to 1000 K, complementing earlier higher-temperature results. These low-temperature data, which are similar, are fitted to a Drude model in which the room-temperature parameters have been obtained from optical measurements and the temperature dependence of the dc resistivity is used as input to calculate the temperature dependence of the emissivity. A frequency-dependent free-carrier relaxation rate is found to have a similar magnitude for all these elements. For temperatures larger than 1200 K the calculated emissivity is always greater than the measured value, indicating that the high-temperature interband features of transition elements are much weaker than those determined from room-temperature measurements
Real-time analysis of the binding of fluorescent VEGFâââ a to VEGFR2 in living cells: Effect of receptor tyrosine kinase inhibitors and fate of internalized agonist-receptor complexes
Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis. Here we have used a novel stoichiometric protein-labeling method to generate a fluorescent variant of VEGF (VEGFâââ
a-TMR) labeled on a single cysteine within each protomer of the antiparallel VEGF homodimer. VEGFâââ
a-TMR has then been used in conjunction with full length VEGFR2, tagged with the bioluminescent protein NanoLuc, to undertake a real time quantitative evaluation of VEGFR2 binding characteristics in living cells using bioluminescence resonance energy transfer (BRET). This provided quantitative information on VEGF-VEGFR2 interactions. At longer incubation times, VEGFR2 is internalized by VEGFâââ
a-TMR into intracellular endosomes. This internalization can be prevented by the receptor tyrosine kinase inhibitors (RTKIs) cediranib, sorafenib, pazopanib or vandetanib. In the absence of RTKIs, the BRET signal is decreased over time as a consequence of the dissociation of agonist from the receptor in intracellular endosomes and recycling of VEGFR2 back to the plasma membrane
Ovarian VEGF165b expression regulates follicular development, corpus luteum function and fertility
Angiogenesis and vascular regression are critical for the female ovulatory cycle.
They enable progression and regression of follicular development, and corpora
lutea formation and regression. Angiogenesis in the ovary occurs under the
control of the vascular endothelial growth factor-A (VEGFA) family of proteins,
which are generated as both pro-(VEGF165) and
anti(VEGF165b)-angiogenic isoforms by alternative splicing. To
determine the role of the VEGF165b isoforms in the ovulatory cycle,
we measured VEGF165b expression in marmoset ovaries by
immunohistochemistry and ELISA, and used transgenic mice over-expressing
VEGF165b in the ovary. VEGF165b was expressed in the
marmoset ovaries in granulosa cells and theca, and the balance of
VEGF165b:VEGF165 was regulated during luteogenesis.
Mice over-expressing VEGF165b in the ovary were less fertile than
wild-type littermates, had reduced secondary and tertiary follicles after
mating, increased atretic follicles, fewer corpora lutea and generated fewer
embryos in the oviduct after mating, and these were more likely not to retain
the corona radiata. These results indicate that the balance of VEGFA isoforms
controls follicle progression and luteogenesis, and that control of isoform
expression may regulate fertility in mammals, including in primates
The endogenous anti-angiogenic VEGF isoform, VEGF165b inhibits human tumour growth in mice
Vascular endothelial growth factor-A is widely regarded as the principal stimulator of angiogenesis required for tumour growth. VEGF is generated as multiple isoforms of two families, the pro-angiogenic family generated by proximal splice site selection in the terminal exon, termed VEGFxxx, and the anti-angiogenic family formed by distal splice site selection in the terminal exon, termed VEGFxxxb, where xxx is the amino acid number. The most studied isoforms, VEGF165 and VEGF165b have been shown to be present in tumour and normal tissues respectively. VEGF165b has been shown to inhibit VEGF- and hypoxia-induced angiogenesis, and VEGF-induced cell migration and proliferation in vitro. Here we show that overexpression of VEGF165b by tumour cells inhibits the growth of prostate carcinoma, Ewing's sarcoma and renal cell carcinoma in xenografted mouse tumour models. Moreover, VEGF165b overexpression inhibited tumour cell-mediated migration and proliferation of endothelial cells. These data show that overexpression of VEGF165b can inhibit growth of multiple tumour types in vivo indicating that VEGF165b has potential as an anti-angiogenic, anti-tumour strategy in a number of different tumour types, either by control of VEGF165b expression by regulation of splicing, overexpression of VEGF165b, or therapeutic delivery of VEGF165b to tumours
Losartan alters osteoblast differentiation and increases bone mass through inhibition of TGFB signalling in vitro and in an OIM mouse model
Excessive production of Transforming Growth Factor ÎČ (TGFÎČ) is commonly associated with dominant and recessive forms of OI. Previous reports have indicated that administration of TGFÎČ-targeted antibodies maybe of potential therapeutic benefit to OI patients. However, direct targeting of TGFÎČ is likely to cause multiple adverse effects including simulation of autoimmunity. In the current study we use patient-derived normal and OI fibroblasts, osteoblasts and OIM mouse models to determine the effects of Losartan, an angiotensin II receptor type 1 (AT1) antagonist, on TGFÎČ signalling and bone morphology in OI. In OIM mice bred on a mixed background administration of 0.6âŻg/L losartan for 4âŻweeks was associated with a significant reduction in TGFÎČ from 79.2âŻg/L in the control to 60.0âŻng/ml following losartan (pâŻ<âŻ0.05), reduced osteoclast activity as measured by CTX from 275.9âŻng/ml in the control to 157.2âŻng/ml following 0.6âŻg/L of losartan (pâŻ<âŻ0.05) and increased cortical bone thickness (PâŻ<âŻ0.001). Furthermore in OIM mice bred on a C57BL/6 background 0.6âŻg/L losartan increased trabecular bone volume in the tibiae (PâŻ<âŻ0.05) and the vertebrae (PâŻ<âŻ0.01), increased cortical bone thickness (PâŻ<âŻ0.001) reduced the trabecular pattern factor (PâŻ<âŻ0.01 and PâŻ<âŻ0.001 for the tibiae and vertebrae respectively), reduced osteoclast (PâŻ<âŻ0.05) and osteoblast (PâŻ<âŻ0.01) numbers as well as reducing the area of bone covered by these cell types. Interestingly, losartan did not affect immune cells infiltrating into bone, nor did this drug alter TGFÎČ signalling in normal or OI fibroblasts. Instead, losartan reduced SMAD2 phosphorylation in osteoblasts, inhibiting their ability to differentiate. Our data suggest that losartan may be an effective treatment for the bone-associated dysmorphia displayed in OI whilst minimising potential adverse immune cell-related effects
VEGF-A165b is an endogenous neuroprotective splice isoform of vascular endothelial growth factor A in vivo and in vitro
Vascular endothelial growth factor (VEGF) A is generated as two isoform families by alternative RNA splicing, represented by VEGF-A165a and VEGF-A165b. These isoforms have opposing actions on vascular permeability, angiogenesis, and vasodilatation. The proangiogenic VEGF-A165a isoform is neuroprotective in hippocampal, dorsal root ganglia, and retinal neurons, but its propermeability, vasodilatatory, and angiogenic properties limit its therapeutic usefulness. In contrast, a neuroprotective effect of endogenous VEGF-A165b on neurons would be advantageous for neurodegenerative pathologies. Endogenous expression of human and rat VEGF-A165b was detected in hippocampal and cortical neurons. VEGF-A165b formed a significant proportion of total VEGF-A in rat brain. Recombinant human VEGF-A165b exerted neuroprotective effects in response to multiple insults, including glutamatergic excitotoxicity in hippocampal neurons, chemotherapy-induced cytotoxicity of dorsal root ganglion neurons, and retinal ganglion cells (RGCs) in rat retinal ischemia-reperfusion injury in vivo. Neuroprotection was dependent on VEGFR2 and MEK1/2 activation but not on p38 or phosphatidylinositol 3-kinase activation. Recombinant human VEGF-A165b is a neuroprotective agent that effectively protects both peripheral and central neurons in vivo and in vitro through VEGFR2, MEK1/2, and inhibition of caspase-3 induction. VEGF-A165b may be therapeutically useful for pathologies that involve neuronal damage, including hippocampal neurodegeneration, glaucoma diabetic retinopathy, and peripheral neuropathy. The endogenous nature of VEGF-A165b expression suggests that non-isoform-specific inhibition of VEGF-A (for antiangiogenic reasons) may be damaging to retinal and sensory neurons
Dielectric relaxations in PEEK by combined dynamic dielectric spectroscopy and thermally stimulated current
The molecular dynamics of a quenched poly (ether ether ketone) (PEEK) was studied over a broad frequency range from 10-3 to 106 Hz by combining dynamic dielectric spectroscopy (DDS) and thermo-stimulated current (TSC) analysis. The dielectric relaxation losses e00 KK has been determined from the real part e0 T(x) thanks to KramersâKronig transform. In this way, conduction and relaxation processes can be analyzed independently. Two secondary dipolar relaxations, the c and the b modes, corresponding to non-cooperative localized molecular mobility have been pointed out. The main a relaxation appeared close to the glass transition temperature as determined by DSC; it has been attributed to the delocalized cooperative mobility of the free amorphous phase. The relaxation times of dielectric relaxations determined with TSC at low frequency converge with relaxation times extracted from DDS at high frequency. This correlation emphasized continuity of mobility kinetics between vitreous and liquid state. The dielectric spectroscopy exhibits the ac relaxation, near 443 K, which has been associated with the rigid amorphous phase confined by crystallites. This present experiment demonstrates coherence of the dynamics of the PEEK heterogeneous amorphous phase between glassy and liquid state and significantly improve the knowledge of molecular/dynamic structure relationships
Comportamento do polipropileno em presença de monĂŽmeros trifuncionais no estado fundido e sua influĂȘncia na morfologia
A Review on the Mechanical Modeling of Composite Manufacturing Processes
© 2016, The Author(s). The increased usage of fiber reinforced polymer composites in load bearing applications requires a detailed understanding of the process induced residual stresses and their effect on the shape distortions. This is utmost necessary in order to have more reliable composite manufacturing since the residual stresses alter the internal stress level of the composite part during the service life and the residual shape distortions may lead to not meeting the desired geometrical tolerances. The occurrence of residual stresses during the manufacturing process inherently contains diverse interactions between the involved physical phenomena mainly related to material flow, heat transfer and polymerization or crystallization. Development of numerical process models is required for virtual design and optimization of the composite manufacturing process which avoids the expensive trial-and-error based approaches. The process models as well as applications focusing on the prediction of residual stresses and shape distortions taking place in composite manufacturing are discussed in this study. The applications on both thermoset and thermoplastic based composites are reviewed in detail
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