Defective monocyte-derived macrophage phagocytosis is associated with exacerbation frequency in COPD

Background Lower airway bacterial colonisation (LABC) in COPD patients is associated with increased exacerbation frequency and faster lung function decline. Defective macrophage phagocytosis in COPD drives inflammation, but how defective macrophage function contributes to exacerbations is not clear. This study investigated the association between macrophage phagocytosis and exacerbation frequency, LABC and clinical parameters. Methods Monocyte-derived macrophages (MDM) were generated from 92 stable COPD patients, and at the onset of exacerbation in 39 patients. Macrophages were exposed to fluorescently labelled Haemophilus influenzae or Streptococcus pneumoniae for 4 h, then phagocytosis measured by fluorimetry and cytokine release by ELISA. Sputum bacterial colonisation was measured by PCR. Results Phagocytosis of H. influenzae was negatively correlated with exacerbation frequency (r = 0.440, p < 0.01), and was significantly reduced in frequent vs. infrequent exacerbators (1.9 × 103 RFU vs. 2.5 × 103 RFU, p < 0.01). There was no correlation for S. pneumoniae. There was no association between phagocytosis of either bacteria with age, lung function, smoking history or treatment with inhaled corticosteroids, or long-acting bronchodilators. Phagocytosis was not altered during an exacerbation, or in the 2 weeks post-exacerbation. In response to phagocytosis, MDM from exacerbating patients showed increased release of CXCL-8 (p < 0.001) and TNFα (p < 0.01) compared to stable state. Conclusion Impaired COPD macrophage phagocytosis of H. influenzae, but not S. pneumoniae is associated with exacerbation frequency, resulting in pro-inflammatory macrophages that may contribute to disease progression. Targeting these frequent exacerbators with drugs that improve macrophage phagocytosis may prove beneficial

Decoupling of a Current-Biased Intrinsic Josephson Junction from its Environment

We have observed a dissipative phase diffusion branch in arrays of hysteretic high-Tc intrinsic Josephson junctions. By comparing the data with a thermal activation model we extract the impedance seen by the junction in which phase diffusion is occurring. At the plasma frequency this junction is isolated from its environment and it sees its own large (~ kilo Ohm) impedance. Our results suggest that stacks of Josephson junctions may be used for isolation purposes in the development of a solid state quantum computer

Spatial patterns of dissipative polariton solitons in semiconductor microcavities

We report propagating bound microcavity polariton soliton arrays consisting of multipeak structures either along (x) or perpendicular (y) to the direction of propagation. Soliton arrays of up to five solitons are observed, with the number of solitons controlled by the size and power of the triggering laser pulse. The breakup along the x direction occurs when the effective area of the trigger pulse exceeds the characteristic soliton size determined by polariton-polariton interactions. Narrowing of soliton emission in energy-momentum space indicates phase locking between adjacent solitons, consistent with numerical modeling which predicts stable multihump soliton solutions. In the y direction, the breakup originates from inhomogeneity across the wave front in the transverse direction which develops into a stable array only in the solitonic regime via phase-dependent interactions of propagating fronts.</p

A single nucleotide substitution in TaHKT1;5-D controls shoot Na+ accumulation in bread wheat

Improving salinity tolerance in the most widely cultivated cereal, bread wheat (Triticum aestivum L.), is essential to increase grain yields on saline agricultural lands. A Portuguese landrace, Mocho de Espiga Branca accumulates up to sixfold greater leaf and sheath sodium (Na+) than two Australian cultivars, Gladius and Scout, under salt stress in hydroponics. Despite high leaf and sheath Na+ concentrations, Mocho de Espiga Branca maintained similar salinity tolerance compared to Gladius and Scout. A naturally occurring single nucleotide substitution was identified in the gene encoding a major Na+ transporter TaHKT1;5-D in Mocho de Espiga Branca, which resulted in a L190P amino acid residue variation. This variant prevents Mocho de Espiga Branca from retrieving Na+ from the root xylem leading to a high shoot Na+ concentration. The identification of the tissue-tolerant Mocho de Espiga Branca will accelerate the development of more elite salt-tolerant bread wheat cultivars

Logic Gates with Bright Dissipative Polariton Solitons in Bragg-Cavity Systems

Optical solitons are an ideal platform for the implementation of communication lines, since they can be packed extremely close one to another without risking partial loss of the encoded information due to their interaction. On the other hand, soliton-soliton interactions are needed to implement computations and achieve all-optical information processing. Here we study how bright dissipative polariton solitons interact and exploit their interaction to implement AND and OR gates with state of the art technology. Moreover, we show that soliton-soliton interaction can be used to determine the sign of {\alpha}2, the parameter describing the interaction between polaritons with opposite spin

Clinical and Molecular Characteristics of Childhood-Onset Stargardt Disease.

To describe the clinical and molecular characteristics of patients with childhood-onset Stargardt disease (STGD)

Mixed micelles of lipoic acid-chitosan-poly(ethylene glycol) and distearoylphosphatidylethanolamine-poly(ethylene glycol) for tumor delivery

Many chemotherapeutics suffer from poor aqueous solubility and tissue selectivity. Distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG) micelles are a promising formulation strategy for the delivery of hydrophobic anticancer drugs. However, storage and in vivo instability restrict their use. The aim of this study was to prepare mixed micelles, containing a novel polymer, lipoic acid-chitosan-poly(ethylene glycol) (LACPEG), and DSPE-PEG, to overcome these limitations and potentially increase cancer cell internalisation. Drug-loaded micelles were prepared with a model tyrosine kinase inhibitor and characterized for size, surface charge, stability, morphology, drug entrapment efficiency, cell viability (A549 and PC-9 cell lines), in vivo biodistribution, ex vivo tumor accumulation and cellular internalisation. Micelles of size 30-130nm with entrapment efficiencies of 46-81% were prepared. LACPEG/DSPE-PEG mixed micelles showed greater interaction with the drug (condensing to half their size following entrapment), greater stability, and a safer profile in vitro compared to DSPE-PEG micelles. LACPEG/DSPE-PEG and DSPE-PEG micelles had similar entrapment efficiencies and in vivo tumor accumulation levels, but LACPEG/DSPE-PEG micelles showed higher tumor cell internalisation. Collectively, these findings suggest that LACPEG/DSPE-PEG mixed micelles provide a promising platform for tumor delivery of hydrophobic drugs