1,205 research outputs found
Chalcogenide Glass-on-Graphene Photonics
Two-dimensional (2-D) materials are of tremendous interest to integrated
photonics given their singular optical characteristics spanning light emission,
modulation, saturable absorption, and nonlinear optics. To harness their
optical properties, these atomically thin materials are usually attached onto
prefabricated devices via a transfer process. In this paper, we present a new
route for 2-D material integration with planar photonics. Central to this
approach is the use of chalcogenide glass, a multifunctional material which can
be directly deposited and patterned on a wide variety of 2-D materials and can
simultaneously function as the light guiding medium, a gate dielectric, and a
passivation layer for 2-D materials. Besides claiming improved fabrication
yield and throughput compared to the traditional transfer process, our
technique also enables unconventional multilayer device geometries optimally
designed for enhancing light-matter interactions in the 2-D layers.
Capitalizing on this facile integration method, we demonstrate a series of
high-performance glass-on-graphene devices including ultra-broadband on-chip
polarizers, energy-efficient thermo-optic switches, as well as graphene-based
mid-infrared (mid-IR) waveguide-integrated photodetectors and modulators
The first Keystone Symposia Conference on pulmonary vascular disease and right ventricular dysfunction: current concepts and future therapies
Nanofluids Containing Ξ³-Fe2O3 Nanoparticles and Their Heat Transfer Enhancements
Homogeneous and stable magnetic nanofluids containing Ξ³-Fe2O3 nanoparticles were prepared using a two-step method, and their thermal transport properties were investigated. Thermal conductivities of the nanofluids were measured to be higher than that of base fluid, and the enhanced values increase with the volume fraction of the nanoparticles. Viscosity measurements showed that the nanofluids demonstrated Newtonian behavior and the viscosity of the nanofluids depended strongly on the tested temperatures and the nanoparticles loadings. Convective heat transfer coefficients tested in a laminar flow showed that the coefficients increased with the augment of Reynolds number and the volume fraction
Core Site-Moiety Maps Reveal Inhibitors and Binding Mechanisms of Orthologous Proteins by Screening Compound Libraries
Members of protein families often share conserved structural subsites for interaction with chemically similar moieties despite low sequence identity. We propose a core site-moiety map of multiple proteins (called CoreSiMMap) to discover inhibitors and mechanisms by profiling subsite-moiety interactions of immense screening compounds. The consensus anchor, the subsite-moiety interactions with statistical significance, of a CoreSiMMap can be regarded as a βhot spotβ that represents the conserved binding environments involved in biological functions. Here, we derive the CoreSiMMap with six consensus anchors and identify six inhibitors (IC50<8.0 Β΅M) of shikimate kinases (SKs) of Mycobacterium tuberculosis and Helicobacter pylori from the NCI database (236,962 compounds). Studies of site-directed mutagenesis and analogues reveal that these conserved interacting residues and moieties contribute to pocket-moiety interaction spots and biological functions. These results reveal that our multi-target screening strategy and the CoreSiMMap can increase the accuracy of screening in the identification of novel inhibitors and subsite-moiety environments for elucidating the binding mechanisms of targets
Interferon-Ξ± Improves Phosphoantigen-Induced VΞ³9VΞ΄2 T-Cells Interferon-Ξ³ Production during Chronic HCV Infection
In chronic HCV infection, treatment failure and defective host immune response highly demand improved therapy strategies. VΞ³9VΞ΄2 T-cells may inhibit HCV replication in vitro through IFN-Ξ³ release after Phosphoantigen (PhAg) stimulation. The aim of our work was to analyze VΞ³9VΞ΄2 T-cell functionality during chronic HCV infection, studying the role of IFN-Ξ± on their function capability. IFN-Ξ³ production by VΞ³9VΞ΄2 T-cells was analyzed in vitro in 24 HCV-infected patients and 35 healthy donors (HD) after PhAg stimulation with or without IFN-Ξ±. The effect of in vivo PhAg/IFN-Ξ± administration on plasma IFN-Ξ³ levels was analyzed in M. fascicularis monkeys. A quantitative analysis of IFN-Ξ³ mRNA level and stability in VΞ³9VΞ΄2 T-cells was also evaluated. During chronic HCV infection, VΞ³9VΞ΄2 T-cells showed an effector/activated phenotype and were significantly impaired in IFN-Ξ³ production. Interestingly, IFN-Ξ± was able to improve their IFN-Ξ³ response to PhAg both in vitro in HD and HCV-infected patients, and in vivo in Macaca fascicularis primates. Finally, IFN-Ξ± increased IFN-Ξ³-mRNA transcription and stability in PhAg-activated VΞ³9VΞ΄2 T-cells. Altogether our results show a functional impairment of VΞ³9VΞ΄2 T-cells during chronic HCV infection that can be partially restored by using IFN-Ξ±. A study aimed to evaluate the antiviral impact of PhAg/IFN-Ξ± combination may provide new insight in designing possible combined strategies to improve HCV infection treatment outcome
EGFRvIV: a previously uncharacterized oncogenic mutant reveals a kinase autoinhibitory mechanism
Tumor cells often subvert normal regulatory mechanisms of signal transduction. This study shows this principle by studying yet uncharacterized mutants of the epidermal growth factor receptor (EGFR) previously identified in glioblastoma multiforme, which is the most aggressive brain tumor in adults. Unlike the well-characterized EGFRvIII mutant form, which lacks a portion of the ligand-binding cleft within the extracellular domain, EGFRvIVa and EGFRvIVb lack internal segments distal to the intracellular tyrosine kinase domain. By constructing the mutants and by ectopic expression in naive cells, we show that both mutants confer an oncogenic potential in vitro, as well as tumorigenic growth in animals. The underlying mechanisms entail constitutive receptor dimerization and basal activation of the kinase domain, likely through a mechanism that relieves a restraining molecular fold, along with stabilization due to association with HSP90. Phosphoproteomic analyses delineated the signaling pathways preferentially engaged by EGFRvIVb-identified unique substrates. This information, along with remarkable sensitivities to tyrosine kinase blockers and to a chaperone inhibitor, proposes strategies for pharmacological interception in brain tumors harboring EGFRvIV mutations.Goldhirsh FoundationNational Cancer Institute (U.S.) (CA118705)National Cancer Institute (U.S.) (CA141556)National Cancer Institute (U.S.) (U54-CA112967
Abnormal Pulmonary Artery Stiffness in Pulmonary Arterial Hypertension: In Vivo Study with Intravascular Ultrasound
BACKGROUND: There is increasing recognition that pulmonary artery stiffness is an important determinant of right ventricular (RV) afterload in pulmonary arterial hypertension (PAH). We used intravascular ultrasound (IVUS) to evaluate the mechanical properties of the elastic pulmonary arteries (PA) in subjects with PAH, and assessed the effects of PAH-specific therapy on indices of arterial stiffness. METHOD: Using IVUS and simultaneous right heart catheterisation, 20 pulmonary segments in 8 PAH subjects and 12 pulmonary segments in 8 controls were studied to determine their compliance, distensibility, elastic modulus and stiffness index Ξ². PAH subjects underwent repeat IVUS examinations after 6-months of bosentan therapy. RESULTS: AT BASELINE, PAH SUBJECTS DEMONSTRATED GREATER STIFFNESS IN ALL MEASURED INDICES COMPARED TO CONTROLS: compliance (1.50Β±0.11Γ10(-2) mm(2/)mmHg vs 4.49Β±0.43Γ10(-2) mm(2/)mmHg, p<0.0001), distensibility (0.32Β±0.03%/mmHg vs 1.18Β±0.13%/mmHg, p<0.0001), elastic modulus (720Β±64 mmHg vs 198Β±19 mmHg, p<0.0001), and stiffness index Ξ² (15.0Β±1.4 vs 11.0Β±0.7, p = 0.046). Strong inverse exponential associations existed between mean pulmonary artery pressure and compliance (r(2) = 0.82, p<0.0001), and also between mean PAP and distensibility (r(2) = 0.79, p = 0.002). Bosentan therapy, for 6-months, was not associated with any significant changes in all indices of PA stiffness. CONCLUSION: Increased stiffness occurs in the proximal elastic PA in patients with PAH and contributes to the pathogenesis RV failure. Bosentan therapy may not be effective at improving PA stiffness
Search for rare quark-annihilation decays, B --> Ds(*) Phi
We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context
of the Standard Model, these decays are expected to be highly suppressed since
they proceed through annihilation of the b and u-bar quarks in the B- meson.
Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected
with the BABAR detector at SLAC. We find no evidence for these decays, and we
set Bayesian 90% confidence level upper limits on the branching fractions BF(B-
--> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results
are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid
Communications
Interleukins, laminin and epstein - barr virus latent membrane protein 1 (EBV LMP1) Promote metastatic phenotype in nasopharyngeal carcinoma
<p>Abstract</p> <p>Background</p> <p>Nasopharyngeal carcinoma (NPC) is a type of neoplasm that is highly prevalent in East Asia and Africa with Epstein-Barr virus (EBV), genetic, and dietary factors implicated as possible aetiologic factors. Previous studies suggested the association of certain cytokines with the invasion and metastatic properties of NPC. The present study examined the roles of EBV latent membrane protein-1 (LMP1), interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-Ξ²1) and laminin in the regulation of matrix-metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) in NPC. The effects of these factors on <it>bmi-1</it>, an oncogene, and <it>ngx6</it>, a tumour suppressor gene, were also investigated.</p> <p>Methods</p> <p>TW01 cells expressing LMP1 (TW01-LMP1) were established via transfection with the B95.8 EBV LMP1 gene. Both TW01 and TW01-LMP1 cells were treated with 100 pg/ml IL-6, 1000 pg/ml IL-10 and 100 pg/ml TGF-Ξ²1, separately and also in combination at their respective concentration for 48 hours. Treated cells were subjected to laminin adherence assay. The cells were also cultured with and without laminin and assayed for MMP-3, MMP-9 and VEGF production using enzyme-linked immunosorbent assay (ELISA). The cellular apoptotic property was analysed using caspase-3 apoptosis assay. The expression of <it>bmi-1 </it>and <it>ngx6 </it>gene was investigated using real time reverse transcriptase polymerase chain reaction.</p> <p>Results</p> <p>LMP1 was found to reduce the adherence of NPC cells towards laminin (p < 0.05) as compared to control. Treatment with IL-6 at 100 pg/ml enhanced the production of MMP-9 in both TW01 and TW01-LMP1 cells (p < 0.05). When cultured on laminin, the levels of MMP-3 and VEGF were significantly increased (p < 0.05) in TW01-LMP1 cells. TW01-LMP1 cells had relatively greater resistance to apoptosis as compared to TW01 cells (p < 0.05). Laminin, IL-6 and LMP1 were found to up-regulate the expression of <it>bmi-1 </it>and suppressed the expression of <it>ngx6</it>.</p> <p>Conclusions</p> <p>We conclude that IL-6 reduced cell adherence towards laminin and increased MMP-9 production in NPC cells. Our data suggested that EBV LMP1 was able to confer resistance of apoptosis and increased MMP-9 production in NPC cells. When cultured on laminin, TW01 cells expressing the EBV LMP1 (TW0-LMP1) that were treated with IL-6 at 100 pg/ml displayed increased MMP-9 production, up-regulation of <it>bmi-1 </it>oncogene expression and down-regulation of <it>ngx6 </it>tumour suppressor gene expression. These findings implicate the roles of EBV LMP1, laminin and IL-6 in the promotion of invasion and metastasis in NPC.</p
Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV
The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of βs = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pTβ₯20 GeV and pseudorapidities {pipe}Ξ·{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}Ξ·{pipe}<0. 8) for jets with 60β€pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2β€{pipe}Ξ·{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. Β© 2013 CERN for the benefit of the ATLAS collaboration
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