Exercise-Induced Changes in Exhaled NO Differentiates Asthma With or Without Fixed Airway Obstruction From COPD With Dynamic Hyperinflation.

Asthmatic patients with fixed airway obstruction (FAO) and patients with chronic obstructive pulmonary disease (COPD) share similarities in terms of irreversible pulmonary function impairment. Exhaled nitric oxide (eNO) has been documented as a marker of airway inflammation in asthma, but not in COPD. To examine whether the basal eNO level and the change after exercise may differentiate asthmatics with FAO from COPD, 27 normal subjects, 60 stable asthmatics, and 62 stable COPD patients were studied. Asthmatics with FAO (n = 29) were defined as showing a postbronchodilator FEV(1)/forced vital capacity (FVC) ≤70% and FEV(1) less than 80% predicted after inhaled salbutamol (400 μg). COPD with dynamic hyperinflation (n = 31) was defined as a decrease in inspiratory capacity (ΔIC%) after a 6 minute walk test (6MWT). Basal levels of eNO were significantly higher in asthmatics and COPD patients compared to normal subjects. The changes in eNO after 6MWT were negatively correlated with the percent change in IC (r = −0.380, n = 29, P = 0.042) in asthmatics with FAO. Their levels of basal eNO correlated with the maximum mid-expiratory flow (MMEF % predicted) before and after 6MWT. In COPD patients with air-trapping, the percent change of eNO was positively correlated to ΔIC% (rs = 0.404, n = 31, P = 0.024). We conclude that asthma with FAO may represent residual inflammation in the airways, while dynamic hyperinflation in COPD may retain NO in the distal airspace. eNO changes after 6MWT may differentiate the subgroups of asthma or COPD patients and will help toward delivery of individualized therapy for airflow obstruction

LNK (SH2B3): paradoxical effects in ovarian cancer.

LNK (SH2B3) is an adaptor protein studied extensively in normal and malignant hematopoietic cells. In these cells, it downregulates activated tyrosine kinases at the cell surface resulting in an antiproliferative effect. To date, no studies have examined activities of LNK in solid tumors. In this study, we found by in silico analysis and staining tissue arrays that the levels of LNK expression were elevated in high-grade ovarian cancer. To test the functional importance of this observation, LNK was either overexpressed or silenced in several ovarian cancer cell lines. Remarkably, overexpression of LNK rendered the cells resistant to death induced by either serum starvation or nutrient deprivation, and generated larger tumors using a murine xenograft model. In contrast, silencing of LNK decreased ovarian cancer cell growth in vitro and in vivo. Western blot studies indicated that overexpression of LNK upregulated and extended the transduction of the mitogenic signal, whereas silencing of LNK produced the opposite effects. Furthermore, forced expression of LNK reduced cell size, inhibited cell migration and markedly enhanced cell adhesion. Liquid chromatography-mass spectroscopy identified 14-3-3 as one of the LNK-binding partners. Our results suggest that in contrast to the findings in hematologic malignancies, the adaptor protein LNK acts as a positive signal transduction modulator in ovarian cancers

Broadband on-chip polarization mode splitters in lithium niobate integrated adiabatic couplers

© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement. We report, to the best of our knowledge, the first broadband polarization mode splitter (PMS) based on the adiabatic light passage mechanism in the lithium niobate (LiNbO3) waveguide platform. A broad bandwidth of ~140 nm spanning telecom S, C, and L bands at polarization-extinction ratios (PER) of >20 dB and >18 dB for the TE and TM polarization modes, respectively, is found in a five-waveguide adiabatic coupler scheme whose structure is optimized by an adiabaticity engineering process in titanium-diffused LiNbO3 waveguides. When the five-waveguide PMS is integrated with a three-waveguide “shortcut to adiabaticity” structure, we realize a broadband, high splitting-ratio (ηc) mode splitter for spatial separation of TE- (H-) polarized pump (700-850 nm for ηc>99%), TM- (V-) polarized signal (1510-1630 nm for ηc>97%), and TE- (H-) polarized idler (1480-1650 nm for ηc>97%) modes. Such a unique integrated-optical device is of potential for facilitating the on-chip implementation of a pump-filtered, broadband tunable entangled quantum-state generator

Broadband On-Chip Adiabatic-Coupling Polarization Mode Splitters in Lithium Niobate Waveguides

© 2019 The Author(s) 2019 OSA. We report the first broadband (>120 nm at >97% splitting efficiency for both polarization modes) polarization mode-splitter in LiNbO3 adiabatic light-passage configuration. This device can facilitate the on-chip implementation of pump-filtered, broadband tunable Bell-state generators

Asymmetric adiabatic couplers for fully-integrated broadband quantum-polarization state preparation

© 2017 The Author(s). Spontaneous parametric down-conversion (SPDC) is a widely used method to generate entangled photons, enabling a range of applications from secure communication to tests of quantum physics. Integrating SPDC on a chip provides interferometric stability, allows to reduce a physical footprint, and opens a pathway to true scalability. However, dealing with different photon polarizations and wavelengths on a chip presents a number of challenging problems. In this work, we demonstrate an on-chip polarization beam-splitter based on z-cut titanium-diffused lithium niobate asymmetric adiabatic couplers (AAC) designed for integration with a type-II SPDC source. Our experimental measurements reveal unique polarization beam-splitting regime with the ability to tune the splitting ratios based on wavelength. In particular, we measured a splitting ratio of 17 dB over broadband regions (>60 nm) for both H-and V-polarized lights and a specific 50%/50% splitting ratio for a cross-polarized photon pair from the AAC. The results show that such a system can be used for preparing different quantum polarization-path states that are controllable by changing the phase-matching conditions in the SPDC over a broad band. Furthermore, we propose a fully integrated electro-optically tunable type-II SPDC polarization-path-entangled state preparation circuit on a single lithium niobate photonic chip

On-chip adiabatic couplers for broadband quantum-polarization state preparation

© 2018 OSA. We present a unique wavelength-dependent polarization splitter based on asymmetric adiabatic couplers designed for integration with type-II spontaneous parametric-down-conversion sources. The system can be used for preparing different quantum polarization-path states over a broad band

Nitrogen forms affect root structure and water uptake in the hybrid poplar

The study analyses the effects of two different forms of nitrogen fertilisation (nitrate and ammonium) on root structure and water uptake of two hybrid poplar (Populus maximowiczii x P. balsamifera) clones in a field experiment. Water uptake was studied using sap flow gauges on individual proximal roots and coarse root structure was examined by excavating 18 whole-root systems. Finer roots were scanned and analyzed for architecture. Nitrogen forms did not affect coarse-root system development, but had a significant effect on fine-root development. Nitrate-treated trees presented higher fine:coarse root ratios and higher specific root lengths than control or ammonium treated trees. These allocation differences affected the water uptake capacity of the plants as reflected by the higher sapflow rate in the nitrate treatment. The diameter of proximal roots at the tree base predicted well the total root biomass and length. The diameter of smaller lateral roots also predicted the lateral root mass, length, surface area and the number of tips. The effect of nitrogen fertilisation on the fine root structure translated into an effect on the functioning of the fine roots forming a link between form (architecture) and function (water uptake)

SUMO-2 promotes mRNA translation by enhancing interaction between eIF4E and eIF4G

Small ubiquitin-like modifier (SUMO) proteins regulate many important eukaryotic cellular processes through reversible covalent conjugation to target proteins. In addition to its many well-known biological consequences, like subcellular translocation of protein, subnuclear structure formation, and modulation of transcriptional activity, we show here that SUMO-2 also plays a role in mRNA translation. SUMO-2 promoted formation of the active eukaryotic initiation factor 4F (eIF4F) complex by enhancing interaction between Eukaryotic Initiation Factor 4E (eIF4E) and Eukaryotic Initiation Factor 4G (eIF4G), and induced translation of a subset of proteins, such as cyclinD1 and c-myc, which essential for cell proliferation and apoptosis. As expected, overexpression of SUMO-2 can partially cancel out the disrupting effect of 4EGI-1, a small molecule inhibitor of eIF4E/eIF4G interaction, on formation of the eIF4F complex, translation of the cap-dependent protein, cell proliferation and apoptosis. On the other hand, SUMO-2 knockdown via shRNA partially impaired cap-dependent translation and cell proliferation and promoted apoptosis. These results collectively suggest that SUMO-2 conjugation plays a crucial regulatory role in protein synthesis. Thus, this report might contribute to the basic understanding of mammalian protein translation and sheds some new light on the role of SUMO in this process. © 2014 Chen et al

A Semi-Lagrangian scheme for a modified version of the Hughes model for pedestrian flow

In this paper we present a Semi-Lagrangian scheme for a regularized version of the Hughes model for pedestrian flow. Hughes originally proposed a coupled nonlinear PDE system describing the evolution of a large pedestrian group trying to exit a domain as fast as possible. The original model corresponds to a system of a conservation law for the pedestrian density and an Eikonal equation to determine the weighted distance to the exit. We consider this model in presence of small diffusion and discuss the numerical analysis of the proposed Semi-Lagrangian scheme. Furthermore we illustrate the effect of small diffusion on the exit time with various numerical experiments

CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis

Macrophages abundantly found in the tumor microenvironment enhance malignancy(1). At metastatic sites a distinct population of metastasis associated macrophages (MAMs) promote tumor cell extravasation, seeding and persistent growth(2). Our study has defined the origin of these macrophages by showing Gr1+ inflammatory monocytes (IMs) are preferentially recruited to pulmonary metastases but not primary mammary tumors, a process also found for human IMs in pulmonary metastases of human breast cancer cells. The recruitment of these CCR2 (receptor for chemokine CCL2) expressing IMs and subsequently MAMs and their interaction with metastasizing tumor cells is dependent on tumor and stromal synthesized CCL2 (FigS1). Inhibition of CCL2/CCR2 signaling using anti-CCL2 antibodies blocks IM recruitment and inhibits metastasis in vivo and prolongs the survival of tumor-bearing mice. Depletion of tumor cell-derived CCL2 also inhibits metastatic seeding. IMs promote tumor cell extravasation in a process that requires monocyte-derived VEGF. CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer (Fig S2)(3-6). Our data provides the mechanistic link between these two clinical associations and indicates new therapeutic targets for treating metastatic breast disease