1,938 research outputs found

    Reversible Modulation of Spontaneous Emission by Strain in Silicon Nanowires

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    We computationally study the effect of uniaxial strain in modulating the spontaneous emission of photons in silicon nanowires. Our main finding is that a one to two orders of magnitude change in spontaneous emission time occurs due to two distinct mechanisms: (A) Change in wave function symmetry, where within the direct bandgap regime, strain changes the symmetry of wave functions, which in turn leads to a large change of optical dipole matrix element. (B) Direct to indirect bandgap transition which makes the spontaneous photon emission to be of a slow second order process mediated by phonons. This feature uniquely occurs in silicon nanowires while in bulk silicon there is no change of optical properties under any reasonable amount of strain. These results promise new applications of silicon nanowires as optoelectronic devices including a mechanism for lasing. Our results are verifiable using existing experimental techniques of applying strain to nanowires

    Unique Responses of Stem Cell-Derived Vascular Endothelial and Mesenchymal Cells to High Levels of Glucose

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    Diabetes leads to complications in selected organ systems, and vascular endothelial cell (EC) dysfunction and loss is the key initiating and perpetuating step in the development of these complications. Experimental and clinical studies have shown that hyperglycemia leads to EC dysfunction in diabetes. Vascular stem cells that give rise to endothelial progenitor cells (EPCs) and mesenchymal progenitor cells (MPCs) represent an attractive target for cell therapy for diabetic patients. Whether these vascular stem/progenitor cells succumb to the adverse effects of high glucose remains unknown. We sought to determine whether adult vascular stem/progenitor cells display cellular activation and dysfunction upon exposure to high levels of glucose as seen in diabetic complications. Mononuclear cell fraction was prepared from adult blood and bone marrow. EPCs and MPCs were derived, characterized, and exposed to either normal glucose (5 mmol/L) or high glucose levels (25 mmol/L). We then assayed for cell activity and molecular changes following both acute and chronic exposure to high glucose. Our results show that high levels of glucose do not alter the derivation of either EPCs or MPCs. The adult blood-derived EPCs were also resistant to the effects of glucose in terms of growth. Acute exposure to high glucose levels increased caspase-3 activity in EPCs (1.4x increase) and mature ECs (2.3x increase). Interestingly, MPCs showed a transient reduction in growth upon glucose challenge. Our results also show that glucose skews the differentiation of MPCs towards the adipocyte lineage while suppressing other mesenchymal lineages. In summary, our studies show that EPCs are resistant to the effects of high levels of glucose, even following chronic exposure. The findings further show that hyperglycemia may have detrimental effects on the MPCs, causing reduced growth and altering the differentiation potential

    Visualization of Glutamine Transporter Activities in Living Cells Using Genetically Encoded Glutamine Sensors

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    Glutamine plays a central role in the metabolism of critical biological molecules such as amino acids, proteins, neurotransmitters, and glutathione. Since glutamine metabolism is regulated through multiple enzymes and transporters, the cellular glutamine concentration is expected to be temporally dynamic. Moreover, differentiation in glutamine metabolism between cell types in the same tissue (e.g. neuronal and glial cells) is often crucial for the proper function of the tissue as a whole, yet assessing cell-type specific activities of transporters and enzymes in such heterogenic tissue by physical fractionation is extremely challenging. Therefore, a method of reporting glutamine dynamics at the cellular level is highly desirable. Genetically encoded sensors can be targeted to a specific cell type, hence addressing this knowledge gap. Here we report the development of Föster Resonance Energy Transfer (FRET) glutamine sensors based on improved cyan and yellow fluorescent proteins, monomeric Teal Fluorescent Protein (mTFP)1 and venus. These sensors were found to be specific to glutamine, and stable to pH-changes within a physiological range. Using cos7 cells expressing the human glutamine transporter ASCT2 as a model, we demonstrate that the properties of the glutamine transporter can easily be analyzed with these sensors. The range of glutamine concentration change in a given cell can also be estimated using sensors with different affinities. Moreover, the mTFP1-venus FRET pair can be duplexed with another FRET pair, mAmetrine and tdTomato, opening up the possibility for real-time imaging of another molecule. These novel glutamine sensors will be useful tools to analyze specificities of glutamine metabolism at the single-cell level

    Mammographic density and risk of breast cancer by age and tumor characteristics

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    Introduction: Understanding whether mammographic density (MD) is associated with all breast tumor subtypes and whether the strength of association varies by age is important for utilizing MD in risk models. Methods: Data were pooled from six studies including 3414 women with breast cancer and 7199 without who underwent screening mammography. Percent MD was assessed from digitized film-screen mammograms using a computer-assisted threshold technique. We used polytomous logistic regression to calculate breast cancer odds according to tumor type, histopathological characteristics, and receptor (estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2)) status by age (51%) versus average density (11-25%). Women ages 2.1 cm) versus small tumors and positive versus negative lymph node status (P’s < 0.01). For women ages <55 years, there was a stronger association of MD with ER-negative breast cancer than ER-positive tumors compared to women ages 55–64 and ≥65 years (Page-interaction = 0.04). MD was positively associated with both HER2-negative and HER2-positive tumors within each age group. Conclusion: MD is strongly associated with all breast cancer subtypes, but particularly tumors of large size and positive lymph nodes across all ages, and ER-negative status among women ages <55 years, suggesting high MD may play an important role in tumor aggressiveness, especially in younger women

    Constitutive phosphorylation of the FOXO1 transcription factor in gastric cancer cells correlates with microvessel area and the expressions of angiogenesis-related molecules

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    <p>Abstract</p> <p>Background</p> <p>Although FOXO transcription factors may have an anti-angiogenic role, little is known about their role in tumor angiogenesis. The present study was performed to investigate the correlation between the constitutive expression of phosphorylated FOXO1 (pFOXO1) and angiogenesis in gastric cancer.</p> <p>Methods</p> <p>Immunohistochemistry was performed on tissue array slides containing 272 gastric carcinoma specimens, and the correlations between the cytoplasmic pFOXO1 expression in gastric cancer cells and CD34-immunopositive microvessel area (MVA) or the expressions of angiogenesis-related molecules were analyzed. <it>In vitro </it>analyses with Western blotting and semiquantitative reverse transcription-polymerase chain reaction were performed using the stable SNU-638 gastric cancer cell line transfected with lentivirus-delivered FOXO1 short hairpin RNA.</p> <p>Results</p> <p>The cytoplasmic expression of pFOXO1 in tumor cells was observed in 85% of gastric carcinoma cases, and was found to be positively associated with higher MVA (<it>P </it>= 0.048). Moreover, pFOXO1 expression was positively correlated with the expressions of several angiogenesis-related proteins, including hypoxia inducible factor-1α (HIF-1α, <it>P </it>= 0.003), vessel endothelial growth factor (<it>P </it>= 0.004), phosphorylated protein kinase B (<it>P </it>< 0.001), and nuclear factor-κB (<it>P </it>= 0.040). In contrast, the expression of pFOXO1 was not correlated with that of phosphorylated signal transducer and activator of transcription 3 or β-catenin. In addition, cell culture experiments showed that FOXO1 suppression increased the mRNA and protein expressions of HIF-1α.</p> <p>Conclusion</p> <p>Our results suggest that pFOXO1 expression in cancer cells plays a role in gastric cancer angiogenesis via mechanisms involving various angiogenesis-related molecules. Animal experiments are needed to confirm the anti-angiogenic role of FOXO1 in human gastric cancer.</p

    Durability of Mortar Incorporating Ferronickel Slag Aggregate and Supplementary Cementitious Materials Subjected to Wet–Dry Cycles

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    This paper presents the strength and durability of cement mortars using 0–100% ferronickel slag (FNS) as replacement of natural sand and 30% fly ash or ground granulated blast furnace slag (GGBFS) as cement replacement. The maximum mortar compressive strength was achieved with 50% sand replacement by FNS. Durability was evaluated by the changes in compressive strength and mass of mortar specimens after 28 cycles of alternate wetting at 23 °C and drying at 110 °C. Strength loss increased by the increase of FNS content with marginal increases in the mass loss. Though a maximum strength loss of up to 26% was observed, the values were only 3–9% for 25–100% FNS contents in the mixtures containing 30% fly ash. The XRD data showed that the pozzolanic reaction of fly ash helped to reduce the strength loss caused by wet–dry cycles. Overall, the volume of permeable voids (VPV) and performance in wet–dry cycles for 50% FNS and 30% fly ash were better than those for 100% OPC and natural sand

    A2BR Adenosine Receptor Modulates Sweet Taste in Circumvallate Taste Buds

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    In response to taste stimulation, taste buds release ATP, which activates ionotropic ATP receptors (P2X2/P2X3) on taste nerves as well as metabotropic (P2Y) purinergic receptors on taste bud cells. The action of the extracellular ATP is terminated by ectonucleotidases, ultimately generating adenosine, which itself can activate one or more G-protein coupled adenosine receptors: A1, A2A, A2B, and A3. Here we investigated the expression of adenosine receptors in mouse taste buds at both the nucleotide and protein expression levels. Of the adenosine receptors, only A2B receptor (A2BR) is expressed specifically in taste epithelia. Further, A2BR is expressed abundantly only in a subset of taste bud cells of posterior (circumvallate, foliate), but not anterior (fungiform, palate) taste fields in mice. Analysis of double-labeled tissue indicates that A2BR occurs on Type II taste bud cells that also express Gα14, which is present only in sweet-sensitive taste cells of the foliate and circumvallate papillae. Glossopharyngeal nerve recordings from A2BR knockout mice show significantly reduced responses to both sucrose and synthetic sweeteners, but normal responses to tastants representing other qualities. Thus, our study identified a novel regulator of sweet taste, the A2BR, which functions to potentiate sweet responses in posterior lingual taste fields

    Support Vector Machine Implementations for Classification & Clustering

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    BACKGROUND: We describe Support Vector Machine (SVM) applications to classification and clustering of channel current data. SVMs are variational-calculus based methods that are constrained to have structural risk minimization (SRM), i.e., they provide noise tolerant solutions for pattern recognition. The SVM approach encapsulates a significant amount of model-fitting information in the choice of its kernel. In work thus far, novel, information-theoretic, kernels have been successfully employed for notably better performance over standard kernels. Currently there are two approaches for implementing multiclass SVMs. One is called external multi-class that arranges several binary classifiers as a decision tree such that they perform a single-class decision making function, with each leaf corresponding to a unique class. The second approach, namely internal-multiclass, involves solving a single optimization problem corresponding to the entire data set (with multiple hyperplanes). RESULTS: Each SVM approach encapsulates a significant amount of model-fitting information in its choice of kernel. In work thus far, novel, information-theoretic, kernels were successfully employed for notably better performance over standard kernels. Two SVM approaches to multiclass discrimination are described: (1) internal multiclass (with a single optimization), and (2) external multiclass (using an optimized decision tree). We describe benefits of the internal-SVM approach, along with further refinements to the internal-multiclass SVM algorithms that offer significant improvement in training time without sacrificing accuracy. In situations where the data isn't clearly separable, making for poor discrimination, signal clustering is used to provide robust and useful information – to this end, novel, SVM-based clustering methods are also described. As with the classification, there are Internal and External SVM Clustering algorithms, both of which are briefly described
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