G-quadruplex ligands exhibit differential G-tetrad selectivity.

A rapid and simple equilibrium-binding assay mediated by ligand-induced fluorescence quenching of fluorophore-labelled G-quadruplex (G4) structures enabled quantitative interrogation of mutually exclusive ligand binding interactions at opposed G-tetrads. This technique revealed that the ligands TmPyP4, PhenDC3, and PDS have differential chemotype-specific binding preferences for individual G-tetrads of a model genomic G4 structure.This work was supported by the following grants: Cancer Research UK Programme, BBSRC BB/K018043/1 and EPSRC EP/ K039520/1. We thank Dr Chris Lowe for his constructive comments and for proofreading the manuscript.This is the final published version. It was first made available by RSC at http://pubs.rsc.org/en/Content/ArticleLanding/2015/CC/c5cc02252e#!divAbstract

Tumour-derived exosomes and their role in cancer-associated T-cell signalling defects

Dendritic and lymphoid ‘exosomes' regulate immune activation. Tumours release membranous material mimicking these ‘exosomes,' resulting in deletion of reactive lymphocytes. Tumour-derived ‘exosomes' have recently been explored as vaccines, without analysis of their immunologic consequences. This investigation examines the composition of tumour-derived ‘exosomes' and their effects on T lymphocytes. Membranous materials were isolated from ascites of ovarian cancer patients (n=6) and Western immunoblotting was performed for markers associated with ‘exosomes.' Using cultured T cells, ‘exosomes' were evaluated for suppression of CD3-ζ and JAK 3 expressions and induction of apoptosis, measured by DNA fragmentation. ‘Exosome' components mediating suppression of CD3-ζ were isolated by continuous eluting electrophoresis and examined by Western immunoblotting. ‘Exosomes' were shown to be identical with previously characterised shed membrane vesicles by protein staining and TSG101 expression. ‘Exosomes' expressed class I MHC, placental alkaline phosphatase, B23/nucleophosmin, and FasL. ‘Exosomes' suppressed expression of T-cell activation signalling components, CD3-ζ and JAK 3 and induced apoptosis. CD3-ζ suppression was mediated by two components: 26 and 42 kDa. Only the 42 kDa component reacted with anti-FasL antibody. These results indicate that, while ‘exosomes' express tumour antigens, leading to their proposed utility as tumour vaccines, they also can suppress T-cell signalling molecules and induce apoptosis

Age-related macular degeneration and smoking cessation advice by eye care providers: a pilot study

This is the final version of the article. Available from the publisher via the link in this record.Smoking is a modifiable risk factor for age-related macular degeneration (AMD), the leading cause of irreversible vision loss in the United States. We conducted a pilot study among eye care providers and AMD patients to assess smoking cessation preferences and cessation services offered at a large academic medical center. Most patients who smoke reported never being advised to quit smoking, although most eye care providers reported that they had advised smokers to quit. Two-thirds of providers expressed a desire for additional training and resources to support patient quit attempts, indicating the need for the integration of smoking cessation opportunities in the clinic setting.Support for this study was provided in part by a National Eye Institute grant (no. R21-EY019096)

A hybrid constructed wetland for organic-material and nutrient removal from sewage: Process performance and multi-kinetic models

© 2018 Elsevier Ltd A pilot-scale hybrid constructed wetland with vertical flow and horizontal flow in series was constructed and used to investigate organic material and nutrient removal rate constants for wastewater treatment and establish a practical predictive model for use. For this purpose, the performance of multiple parameters was statistically evaluated during the process and predictive models were suggested. The measurement of the kinetic rate constant was based on the use of the first-order derivation and Monod kinetic derivation (Monod) paired with a plug flow reactor (PFR) and a continuously stirred tank reactor (CSTR). Both the Lindeman, Merenda, and Gold (LMG) analysis and Bayesian model averaging (BMA) method were employed for identifying the relative importance of variables and their optimal multiple regression (MR). The results showed that the first-order–PFR (M2) model did not fit the data (P > 0.05, and R2 0.5). The pollutant removal rates in the case of M1 were 0.19 m/d (CODCr) and those for M3 were 25.2 g/m2∙d for CODCr and 2.63 g/m2∙d for NH4-N. By applying a multi-variable linear regression method, the optimal empirical models were established for predicting the final effluent concentration of five days' biochemical oxygen demand (BOD5) and NH4-N. In general, the hydraulic loading rate was considered an important variable having a high value of relative importance, which appeared in all the optimal predictive models

Enhanced efficiency for better wastewater sludge hydrolysis conversion through ultrasonic hydrolytic pretreatment

© 2016 Taiwan Institute of Chemical Engineers The major requirements for accelerating the process of anaerobic digestion and energy production are breaking the structure of waste activated sludge (WAS), and transforming it into a soluble form suitable for biodegradation. This work investigated and analysed a novel bench-scale ultrasonic system for WAS disruption and hydrolysis using ultrasonic homogenization. Different commercial sonoreactors were used at low frequencies under a variety of operating conditions (intensity, density, power, sonication time, and total suspended solids) to evaluate the effects of the equipment on sludge hydrolysis and to generate new insights into the empirical models and mechanisms applicable to the real-world processing of wastewater sludge. A relationship was established between the operating parameters and the experimental data. Results indicated an increase in sonication time or ultrasonic intensity correlated with improved sludge hydrolysis rates, sludge temperature, and reduction rate of volatile solids (33.51%). It also emerged that ultrasonication could effectively accelerate WAS hydrolysis to achieve disintegration within 5–10 min, depending on the ultrasonic intensity. This study also determined multiple alternative parameters to increase the efficiency of sludge treatment and organic matter reduction, and establish the practicality of applying ultrasonics to wastewater sludge pretreatment

Implementation of Web-Based Respondent-Driven Sampling among Men who Have Sex with Men in Vietnam

Objective: Lack of representative data about hidden groups, like men who have sex with men (MSM), hinders an evidence-based response to the HIV epidemics. Respondent-driven sampling (RDS) was developed to overcome sampling challenges in studies of populations like MSM for which sampling frames are absent. Internet-based RDS (webRDS) can potentially circumvent limitations of the original RDS method. We aimed to implement and evaluate webRDS among a hidden population. Methods and Design: This cross-sectional study took place 18 February to 12 April, 2011 among MSM in Vietnam. Inclusion criteria were men, aged 18 and above, who had ever had sex with another man and were living in Vietnam. Participants were invited by an MSM friend, logged in, and answered a survey. Participants could recruit up to four MSM friends. We evaluated the system by its success in generating sustained recruitment and the degree to which the sample compositions stabilized with increasing sample size. Results: Twenty starting participants generated 676 participants over 24 recruitment waves. Analyses did not show evidence of bias due to ineligible participation. Estimated mean age was 22 year and 82% came from the two large metropolitan areas. 32 out of 63 provinces were represented. The median number of sexual partners during the last six months was two. The sample composition stabilized well for 16 out of 17 variables. Conclusion: Results indicate that webRDS could be implemented at a low cost among Internet-using MSM in Vietnam. WebRDS may be a promising method for sampling of Internet-using MSM and other hidden groups. Key words: Respondent-driven sampling, Online sampling, Men who have sex with men, Vietnam, Sexual risk behavio

A comparison of transgenic rodent mutation and in vivo comet assay responses for 91 chemicals.

A database of 91 chemicals with published data from both transgenic rodent mutation (TGR) and rodent comet assays has been compiled. The objective was to compare the sensitivity of the two assays for detecting genotoxicity. Critical aspects of study design and results were tabulated for each dataset. There were fewer datasets from rats than mice, particularly for the TGR assay, and therefore, results from both species were combined for further analysis. TGR and comet responses were compared in liver and bone marrow (the most commonly studied tissues), and in stomach and colon evaluated either separately or in combination with other GI tract segments. Overall positive, negative, or equivocal test results were assessed for each chemical across the tissues examined in the TGR and comet assays using two approaches: 1) overall calls based on weight of evidence (WoE) and expert judgement, and 2) curation of the data based on a priori acceptability criteria prior to deriving final tissue specific calls. Since the database contains a high prevalence of positive results, overall agreement between the assays was determined using statistics adjusted for prevalence (using AC1 and PABAK). These coefficients showed fair or moderate to good agreement for liver and the GI tract (predominantly stomach and colon data) using WoE, reduced agreement for stomach and colon evaluated separately using data curation, and poor or no agreement for bone marrow using both the WoE and data curation approaches. Confidence in these results is higher for liver than for the other tissues, for which there were less data. Our analysis finds that comet and TGR generally identify the same compounds (mainly potent mutagens) as genotoxic in liver, stomach and colon, but not in bone marrow. However, the current database content precluded drawing assay concordance conclusions for weak mutagens and non-DNA reactive chemicals

Gravitational detection of a low-mass dark satellite at cosmological distance

The mass-function of dwarf satellite galaxies that are observed around Local Group galaxies substantially differs from simulations based on cold dark matter: the simulations predict many more dwarf galaxies than are seen. The Local Group, however, may be anomalous in this regard. A massive dark satellite in an early-type lens galaxy at z = 0.222 was recently found using a new method based on gravitational lensing, suggesting that the mass fraction contained in substructure could be higher than is predicted from simulations. The lack of very low mass detections, however, prohibited any constraint on their mass function. Here we report the presence of a 1.9 +/- 0.1 x 10^8 M_sun dark satellite in the Einstein-ring system JVAS B1938+666 at z = 0.881, where M_sun denotes solar mass. This satellite galaxy has a mass similar to the Sagittarius galaxy, which is a satellite of the Milky Way. We determine the logarithmic slope of the mass function for substructure beyond the local Universe to be alpha = 1.1^+0.6_-0.4, with an average mass-fraction of f = 3.3^+3.6_-1.8 %, by combining data on both of these recently discovered galaxies. Our results are consistent with the predictions from cold dark matter simulations at the 95 per cent confidence level, and therefore agree with the view that galaxies formed hierarchically in a Universe composed of cold dark matter.Comment: 25 pages, 7 figures, accepted for publication in Nature (19 January 2012