4,182 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
A Novel Strategy to Screen Bacillus Calmette-GuΓ©rin Protein Antigen Recognized by Ξ³Ξ΄ TCR
BACKGROUND: Phosphoantigen was originally identified as the main Ξ³Ξ΄ TCR-recognized antigen that could activate Ξ³Ξ΄ T cells to promote immune protection against mycobacterial infection. However, new evidence shows that the Ξ³Ξ΄ T cells activated by phosphoantigen can only provide partial immune protection against mycobacterial infection. In contrast, whole lysates of Mycobacterium could activate immune protection more potently, implying that other Ξ³Ξ΄ TCR-recognized antigens that elicit protective immune responses. To date, only a few distinct mycobacterial antigens recognized by the Ξ³Ξ΄ TCR have been characterized. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we established a new approach to screen epitopes or protein antigens recognized by the Ξ³Ξ΄ TCR using Bacillus Calmette-GuΓ©rin- (BCG-) specific Ξ³ TCR transfected cells as probes to pan a 12-mer random-peptide phage-displayed library. Through binding assays and functional analysis, we identified a peptide (BP3) that not only binds to the BCG-specific Ξ³Ξ΄ TCR but also effectively activates Ξ³Ξ΄ T cells isolated from human subjects inoculated with BCG. Importantly, the Ξ³Ξ΄ T cells activated by peptide BP3 had a cytotoxic effect on THP-1 cells infected with BCG. Moreover, the oxidative stress response regulatory protein (OXYS), a BCG protein that matches perfectly with peptide BP3 according to bioinformatics analysis, was confirmed as a ligand for the Ξ³Ξ΄ TCR and was found to activate Ξ³Ξ΄ T cells from human subjects inoculated with BCG. CONCLUSIONS/SIGNIFICANCE: In conclusion, our study provides a novel strategy to identify epitopes or protein antigens for the Ξ³Ξ΄ TCR, and provides a potential means to screen mycobacterial vaccines or candidates for adjuvant
Observation of Coalescence Process of Silver Nanospheres During Shape Transformation to Nanoprisms
In this report, we observed the growth mechanism and the shape transformation from spherical nanoparticles (diameter ~6 nm) to triangular nanoprisms (bisector length ~100 nm). We used a simple direct chemical reduction method and provided evidences for the growth of silver nanoprisms via a coalescence process. Unlike previous reports, our method does not rely upon light, heat, or strong oxidant for the shape transformation. This transformation could be launched by fine-tuning the pH value of the silver colloidal solution. Based on our extensive examination using transmission electron microscopy, we propose a non-point initiated growth mechanism, which is a combination of coalescence and dissolutionβrecrystallization process during the growth of silver nanoprisms
Nuclear receptors in vascular biology
Nuclear receptors sense a wide range of steroids and hormones (estrogens, progesterone, androgens, glucocorticoid, and mineralocorticoid), vitamins (A and D), lipid metabolites, carbohydrates, and xenobiotics. In response to these diverse but critically important mediators, nuclear receptors regulate the homeostatic control of lipids, carbohydrate, cholesterol, and xenobiotic drug metabolism, inflammation, cell differentiation and development, including vascular development. The nuclear receptor family is one of the most important groups of signaling molecules in the body and as such represent some of the most important established and emerging clinical and therapeutic targets. This review will highlight some of the recent trends in nuclear receptor biology related to vascular biology
Thrombomodulin expression in colorectal carcinoma is protective and correlates with survival
Thrombomodulin (TM) is an endothelial receptor that exhibits anticoagulant, antifibrinolytic and anti-inflammatory activity by inhibiting thrombin and cellular adhesion. In this study, the expression and significance of TM was examined in primary colorectal cancer and its prognostic implications explored. TM immunostaining was performed on formalin-fixed, paraffin-embedded tissue sections, from primary lesions of 200 patients with colorectal carcinoma. Institutional Ethical approval was granted and clinical data retrieved from patients' records. All normal colonic tissue expressed TM on endothelial cells. TM tumour cell expression was demonstrated in 53 (26.5%) cases and 147 (73.5%) showed no neoplastic cell staining. On univariate and multivariate analysis TM expression on tumour cells correlated significantly with tumour stage, differentiation, Jass score and 5 year survival. TM expression decreases as overall stage and tumour size increase (P=0.03). In all, 91% TM positive tumours were well differentiated and 85% of TM negative tumours were poorly differentiated (P<0.01). Five year survival rates of patients with positive and negative TM expression were 71 and 41%, respectively. Survival rate was poorer in those patients who were TM negative compared with those who were positive (P<0.01). A total of 101 (50.5%) of the cases were node negative. In this group, 5 year survival rates of patients with positive and negative TM expression were 87.5 and 37.8%, respectively, demonstrating a poorer survival rate for those who are node negative and TM negative at the time of surgery (P<0.001). This study demonstrates that loss of TM is a key indicator in tumour biology and prognosis
A peridynamic based machine learning model for one-dimensional and two-dimensional structures
With the rapid growth of available data and computing resources, using data-driven models is a potential approach in many scientific disciplines and engineering. However, for complex physical phenomena that have limited data, the data-driven models are lacking robustness and fail to provide good predictions. Theory-guided data science is the recent technology that can take advantage of both physics-driven and data-driven models. This study presents a novel peridynamics based machine learning model for one and two-dimensional structures. The linear relationships between the displacement of a material point and displacements of its family members and applied forces are obtained for the machine learning model by using linear regression. The numerical procedure for coupling the peridynamic model and the machine learning model is also provided. The numerical procedure for coupling the peridynamic model and the machine learning model is also provided. The accuracy of the coupled model is verified by considering various examples of a one-dimensional bar and two-dimensional plate. To further demonstrate the capabilities of the coupled model, damage prediction for a plate with a pre-existing crack, a two-dimensional representation of a three-point bending test, and a plate subjected to dynamic load are simulated
Anti-Inflammatory Activities of Inotilone from Phellinus linteus through the Inhibition of MMP-9, NF-ΞΊB, and MAPK Activation In Vitro and In Vivo
Inotilone was isolated from Phellinus linteus. The anti-inflammatory effects of inotilone were studied by using lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells and Ξ»-carrageenan (Carr)-induced hind mouse paw edema model. Inotilone was tested for its ability to reduce nitric oxide (NO) production, and the inducible nitric oxide synthase (iNOS) expression. Inotilone was tested in the inhibitor of mitogen-activated protein kinase (MAPK)Β [extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal kinase (JNK), p38], and nuclear factor-ΞΊB (NF-ΞΊB), matrix-metalloproteinase (MMP)-9 protein expressions in LPS-stimulated RAW264.7 cells. When RAW264.7 macrophages were treated with inotilone together with LPS, a significant concentration-dependent inhibition of NO production was detected. Western blotting revealed that inotilone blocked the protein expression of iNOS, NF-ΞΊB, and MMP-9 in LPS-stimulated RAW264.7 macrophages, significantly. Inotilone also inhibited LPS-induced ERK, JNK, and p38 phosphorylation. In in vivo tests, inotilone decreased the paw edema at the 4th and the 5th h after Carr administration, and it increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). We also demonstrated that inotilone significantly attenuated the malondialdehyde (MDA) level in the edema paw at the 5th h after Carr injection. Inotilone decreased the NO and tumor necrosis factor (TNF-Ξ±) levels on serum at the 5th h after Carr injection. Western blotting revealed that inotilone decreased Carr-induced iNOS, cyclooxygenase-2 (COX-2), NF-ΞΊB, and MMP-9 expressions at the 5th h in the edema paw. An intraperitoneal (i.p.) injection treatment with inotilone diminished neutrophil infiltration into sites of inflammation, as did indomethacin (Indo). The anti-inflammatory activities of inotilone might be related to decrease the levels of MDA, iNOS, COX-2, NF-ΞΊB, and MMP-9 and increase the activities of CAT, SOD, and GPx in the paw edema through the suppression of TNF-Ξ± and NO. This study presents the potential utilization of inotilone, as a lead for the development of anti-inflammatory drugs
Wide-Scale Analysis of Human Functional Transcription Factor Binding Reveals a Strong Bias towards the Transcription Start Site
We introduce a novel method to screen the promoters of a set of genes with
shared biological function, against a precompiled library of motifs, and find
those motifs which are statistically over-represented in the gene set. The gene
sets were obtained from the functional Gene Ontology (GO) classification; for
each set and motif we optimized the sequence similarity score threshold,
independently for every location window (measured with respect to the TSS),
taking into account the location dependent nucleotide heterogeneity along the
promoters of the target genes. We performed a high throughput analysis,
searching the promoters (from 200bp downstream to 1000bp upstream the TSS), of
more than 8000 human and 23,000 mouse genes, for 134 functional Gene Ontology
classes and for 412 known DNA motifs. When combined with binding site and
location conservation between human and mouse, the method identifies with high
probability functional binding sites that regulate groups of biologically
related genes. We found many location-sensitive functional binding events and
showed that they clustered close to the TSS. Our method and findings were put
to several experimental tests. By allowing a "flexible" threshold and combining
our functional class and location specific search method with conservation
between human and mouse, we are able to identify reliably functional TF binding
sites. This is an essential step towards constructing regulatory networks and
elucidating the design principles that govern transcriptional regulation of
expression. The promoter region proximal to the TSS appears to be of central
importance for regulation of transcription in human and mouse, just as it is in
bacteria and yeast.Comment: 31 pages, including Supplementary Information and figure
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
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