E1E_1-degeneration and d′d′′d'd''-lemma

For a double complex $(A, d', d'')$, we show that if it satisfies the $d'd''$-lemma and the spectral sequence $\{E^{p, q}_r\}$ induced by $A$ does not degenerate at $E_0$, then it degenerates at $E_1$. We apply this result to prove the degeneration at $E_1$ of a Hodge-de Rham spectral sequence on compact bi-generalized Hermitian manifolds that satisfy a version of $d'd''$-lemma

Partition Function of Chiral Boson on 2-Torus from Floreanini-Jackiw Lagrangian

We revisit the problem of quantizing a chiral boson on a torus. The conventional approach is to extract the partition function of a chiral boson from the path integral of a non-chiral boson. Instead we compute it directly from the chiral boson Lagrangian of Floreanini and Jackiw modified by topological terms involving auxiliary fields. A careful analysis of the gauge-fixing condition for the extra gauge symmetry reproduces the correct results for the free chiral boson, and has the advantage of being applicable to a wider class of interacting chiral boson theories.Comment: 31 pages, minor modificatio

Structural Basis of the Selective Block of Kv1.2 by Maurotoxin from Computer Simulations

The 34-residue polypeptide maurotoxin (MTx) isolated from scorpion venoms selectively inhibits the current of the voltage-gated potassium channel Kv1.2 by occluding the ion conduction pathway. Here using molecular dynamics simulation as a docking method, the binding modes of MTx to three closely related channels (Kv1.1, Kv1.2 and Kv1.3) are examined. We show that MTx forms more favorable electrostatic interactions with the outer vestibule of Kv1.2 compared to Kv1.1 and Kv1.3, consistent with the selectivity of MTx for Kv1.2 over Kv1.1 and Kv1.3 observed experimentally. One salt bridge in the bound complex of MTx-Kv1.2 forms and breaks in a simulation period of 20 ns, suggesting the dynamic nature of toxin-channel interactions. The toxin selectivity likely arises from the differences in the shape of the channel outer vestibule, giving rise to distinct orientations of MTx on block. Potential of mean force calculations show that MTx blocks Kv1.1, Kv1.2 and Kv1.3 with an IC(50) value of 6 µM, 0.6 nM and 18 µM, respectively.This work was supported by the National Health and Medical Research Council of Australia (http://www.nhmrc.gov.au). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Liquid biopsy genotyping in lung cancer: ready for clinical utility?

Liquid biopsy is a blood test that detects evidence of cancer cells or tumor DNA in the circulation. Despite complicated collection methods and the requirement for technique-dependent platforms, it has generated substantial interest due, in part, to its potential to detect driver oncogenes such as epidermal growth factor receptor (EGFR) mutants in lung cancer. This technology is advancing rapidly and is being incorporated into numerous EGFR tyrosine kinase inhibitor (EGFR-TKI) development programs. It appears ready for integration into clinical care. Recent studies have demonstrated that biological fluids such as saliva and urine can also be used for detecting EGFR mutant DNA through application other user-friendly techniques. This review focuses on the clinical application of liquid biopsies to lung cancer genotyping, including EGFR and other targets of genotype-directed therapy and compares multiple platforms used for liquid biopsy

A systematic review and meta-analysis of herbal medicine on chronic obstructive pulmonary diseases

Herbal medicine (HM) as an adjunct therapy has been shown to be promising for the chronic obstructive pulmonary disease (COPD). However, the role of herbs in COPD remains largely unexplored. In this present study, we conducted the systematic review to evaluate the efficacy of herbs in COPD. 176 clinical studies with reporting pulmonary function were retrieved from English and Chinese database. Commonly used herbs for acute exacerbations stage (AECOPD) and stable COPD stage (SCOPD) were identified. A meta-analysis conducted from 15 high quality studies (18 publications) showed that HM as an adjunct therapy had no significant improvement in pulmonary function (FEV1, FEV%, FVC, and FEV1/FVC) compared to conventional medicine. The efficacy of the adjunct HM on improving the arterial blood gas (PaCO2 and PaO 2) for AECOPD and SCOPD remains inconclusive due to the heterogeneity among the studies. However, HM as an adjunct therapy improved clinical symptoms and quality of life (total score, activity score, and impact score of St. George's Respiratory Questionnaire). Studies with large-scale and double-blind randomized controlled trials are required to confirm the role of the adjunct HM in the management of COPD. © 2014 Hai Yong Chen et al.published_or_final_versio

Elastic biodegradable starch/ethylene-co-vinyl alcohol fibre-mesh scaffolds for tissue engineering applications

The fabrication of a biomaterial scaffold, with adequate physical and structural properties for tissue engineering applications, is reported. A blend of starch with ethylene-vinyl alcohol (50/50 w/w, SEVA-C) is used to produce 3D fibre-mesh scaffolds by wet-spinning. The scaffolds are characterized in terms of morphology, porosity, interconnectivity, and pore size, using scanning electron microscopy (SEM) and microcomputed tomography (μCT). The degradation behavior, as well as the mechanical properties of the scaffolds, is investigated in presence of alpha-amylase enzyme at physiological concentration. Scaffolds with porosities ranging from 43 to 52%, interconnectivity of ∼70.5% and pore size between 118 and 159 μm, can be fabricated using the proposed methodology. The scaffolds exhibit an elastic behavior in the wet state with a compressive modulus of 7.96±0.32 MPa. Degradation studies show that SEVA-C scaffolds are susceptible to enzymatic degradation by alpha-amylase, confirmed by the increase of weight loss (40% of weight loss after 12 weeks) and presence of degradation products (reducing sugars) in solution. The diameter of SEVA-C scaffolds decreases with degradation time, increasing the overall porosity, interconnectivity and pore size. In vitro cell studies with human osteosarcoma cell line (SaOs-2) showed a nontoxic and cytocompatible behavior of the developed fibre mesh scaffolds. The positive cellular response, together with structural and degradable properties, suggests that 3D SEVA-C fibre-meshes may be good candidates as tissue engineering scaffolds. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40504. Copyright © 2014 Wiley Periodicals, Inc.This work was supported by national funds through the Portuguese Foundation for Science and Technology under the scope of the project PTDC/CTM/67560/2006 and by the European Regional Development Fund (ERDF) through the Operational Competitiveness Programme “COMPETE” (FCOMP-01-0124-FEDER-007148)