Photophysical studies of triarylamine dyes and an investigation into polyelectrolyte-DNA interactions.

The photophysics and thermal properties of a series of seven novel triarylamine (TAA) dyes are described. Fluorescence characteristics have been studied in solvents of various polarities at room temperature and at 77 K. High molar extinction coefficients of the magnitude of 3.0-4.0(+/-0.50)x104 M-1cm-1 were obtained for most compounds, and relatively short radiative lifetimes were observed. Fluorescence quantum yields of the dyes at room temperature in cyclohexane were found to be between 0.34-0.57 increasing to 0.67-0.95 at 77 K. It has been shown that while at room temperature, solvent shell relaxation around the excited state can occur, and emission is from an equilibrium excited state to a twisted ground state, at 77 K in a rigid matrix environment solvent shell relaxation cannot occur and emission is from a Franck-Condon excited state to a planar ground state. The TAAs studied have excellent thermal properties for possible use in devices with thermal decomposition temperatures of greater than 300 °C, they also do not crystallise readily. Three poly (9,9-bis[N,N-(trimethylammonium)hexyl] fluorene-co-l,4-phenylene), fluorescent cationic conjugated polymers (CCP), of average chain lengths- 6, 12 and 100 repeat units, and their interaction with DNA and guanine are reported. Fluorescence microscopy and atomic force microscopy have been utilised to visualise the interaction between the polymers and DNA. Results show both efficient compaction of DNA induced by the polymer and linking and bridging of DNA/polymer aggregates. CCPs are known to aggregate in water, and for the CCPs studied here this is reflected in a decrease in fluorescence. These aggregates can be broken up by mixtures of solvents, e.g. acetonitrile/water. Steady state and ps time resolved techniques have been used to study: (i) aggregation of CCPs in various acetonitrile/water mixtures, and (ii) fluorescence quenching by single and double strand DNA, and guanine. All CCPs are extremely sensitive to quenching by DNA or guanine, with sensitivity increasing with chain length of both the CCP and DNA. Stem-Volmer plots are sigmoidal and have initial quenching rates constants far in excess of the diffusion controlled limit. The results have been analysed in terms of energy migration and trapping within and between polymer chains. Quenching seems best analysed in terms of an equilibrium in which a CCP/DNA aggregate complex is formed which brings polymer chains into close enough proximity to allow interchain excitation energy migration and quenching at aggregate or DNA base traps. We also report preliminary results of modelling time resolved data, of both the aggregation and quenching, using a kinetic model in which energy migration and trapping are represented as a series of energy transfer steps between neighbours

Utilization of waste tea leaves as bio-surfactant in CdS quantum dots synthesis and their cytotoxicity effect in breast cancer cells

Green technology for nanoparticles synthesis is considered to be of great significance in biomedical applications. Recently, low dimensional semiconductor cadmium sulfide (CdS) quantum dots (QDs) have raised great attention due to their optical properties and wide usage in biomedical studies. In our present work, we demonstrate a simple green synthesis route for CdS QDs production using waste matured tea leaves (mother leaf) as bio-surfactant that are a waste product of the tea leaf industry and not suitable for drinking. The structural and morphological analysis showed waste tea leaf derived CdS QDs range from 2.5 to 4 nm in particle size with a cubic crystalline structure. Interestingly, these CdS QDs exhibit strong florescence emission with maximum around 670 nm. We explored the cytotoxic effect of waste tea leaf mediated CdS QDs (MT-CdS QDs) in breast cancer cell lines and compared their viability with standard drug - cisplatin. Our experimental studies strongly suggest that MT-CdS QDs exhibits cytotoxic effect on breast cancer cells and their performance was compared with standard drug cisplatin. To further understand the role of MT-CdS QDs towards cytotoxicity, the fluorescence microscopy and flow cytometry analysis were carried out. The flow cytometry results reveal that MT-CdS QDs induces cell death as it arrests the cell cycle at S phase as well as G2/M phase. Further the apoptosis mechanism was confirmed with the expression of anti-apoptotic and apoptotic proteins. These studies explored that waste tea leaves have dual advantage – both in controlling the particle size of CdS QDs as well as facilitates their cytotoxicity effect in breast cancer cell death. Therefore, it is anticipated that the utilization of MT-CdS QDs produced from waste tea leaves as bi-functional drug and delivery vehicle in cancer treatment will be a promising approach. Also, this is a simple and circular economic route for producing biocompatible QDs at low-cost, which could simultaneously benefit tea and biomedical industries

On the Use of Carbon Cables from Plastic Solvent Combinations of Polystyrene and Toluene in Carbon Nanotube Synthesis

For every three people on the planet, there are approximately two Tonnes (Te) of plastic waste. We show that carbon recovery from polystyrene (PS) plastic is enhanced by the coaddition of solvents to grow carbon nanotubes (CNTs) by liquid injection chemical vapour deposition. Polystyrene was loaded up to 4 wt% in toluene and heated to 780 °C in the presence of a ferrocene catalyst and a hydrogen/argon carrier gas at a 1:19 ratio. High resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and Raman spectroscopy were used to identify multiwalled carbon nanotubes (MWCNTs). The PS addition in the range from 0 to 4 wt% showed improved quality and CNT homogeneity; Raman “Graphitic/Defective” (G/D) values increased from 1.9 to 2.3; mean CNT diameters increased from 43.0 to 49.2 nm; and maximum CNT yield increased from 11.37% to 14.31%. Since both the CNT diameters and the percentage yield increased following the addition of polystyrene, we conclude that carbon from PS contributes to the carbon within the MWCNTs. The electrical contact resistance of acid-washed Bucky papers produced from each loading ranged from 2.2 to 4.4 Ohm, with no direct correlation to PS loading. Due to this narrow range, materials with different loadings were mixed to create the six wires of an Ethernet cable and tested using iPerf3; the cable achieved up- and down- link speeds of ~99.5 Mbps, i.e., comparable to Cu wire with the same dimensions (~99.5 Mbps). The lifecycle assessment (LCA) of CNT wire production was compared to copper wire production for a use case in a Boeing 747-400 over the lifespan of the aircraft. Due to their lightweight nature, the CNT wires decreased the CO2 footprint by 21 kTonnes (kTe) over the aircraft’s lifespan.We would like to thank Keysight Technologies for the use of a test model of the B2900A SMU. We would like to acknowledge the assistance provided by Swansea University College of Engineering AIM Facility. We would like to thank TRIMTABS Ltd. for purchasing equipment required for making ethernet cables. Thanks to Swansea Employability Academy (SEA) for the summer placements scheme. Thanks to the Swansea University Texas Strategic Partnership. R.E.P. acknowledges his work was associated with the IMPACT operation. We acknowledge pixabay for use of imagery in the graphical abstract (https://pixabay.com/vectors/airplane-boeing-747-transport-48 11157/ (accessed on 1 December 2021))

Driving and Parkinson’s Disease: A Survey of the Patient’s Perspective

Background: Parkinson’s disease (PD) is a multi-system disorder that can impact on driving ability. Little is known about how these changes in driving ability affect people with PD, making it difficult for clinicians and carers to offer appropriate support. Objective: To assess patient views concerning the effect of PD on their driving ability, the impact of these changes and how they manage them. Method: An online survey was created by a team of clinicians, people with PD, their carers, and representatives from Parkinson’s UK. People with PD throughout the United Kingdom were invited to participate through Parkinson’s UK’s website, newsletter and Parkinson’s Excellence Network email list. Results: 805 people with PD took part in the survey. We found that the loss of a driving licence had an adverse impact on employment, socialisation, travel costs and spontaneous lifestyle choices. Multiple changes in driving ability related to PD were described, including that impulse control disorders can have an adverse impact on driving. Changes in driving ability caused people to change their driving practices including taking shorter journeys and being less likely to drive at night. Participants advised managing changes in driving ability through planning, vehicle adaptions, maintaining skills and self-assessment. Conclusion: This study demonstrates the impact that changes in driving ability can have on the lifestyle of people with PD and reveals the strategies that individuals adopt to manage these changes

Parameterization Effects in the analysis of AMI Sunyaev-Zel'dovich Observations

Most Sunyaev--Zel'dovich (SZ) and X-ray analyses of galaxy clusters try to constrain the cluster total mass and/or gas mass using parameterised models and assumptions of spherical symmetry and hydrostatic equilibrium. By numerically exploring the probability distributions of the cluster parameters given the simulated interferometric SZ data in the context of Bayesian methods, and assuming a beta-model for the electron number density we investigate the capability of this model and analysis to return the simulated cluster input quantities via three rameterisations. In parameterisation I we assume that the T is an input parameter. We find that parameterisation I can hardly constrain the cluster parameters. We then investigate parameterisations II and III in which fg(r200) replaces temperature as a main variable. In parameterisation II we relate M_T(r200) and T assuming hydrostatic equilibrium. We find that parameterisation II can constrain the cluster physical parameters but the temperature estimate is biased low. In parameterisation III, the virial theorem replaces the hydrostatic equilibrium assumption. We find that parameterisation III results in unbiased estimates of the cluster properties. We generate a second simulated cluster using a generalised NFW (GNFW) pressure profile and analyse it with an entropy based model to take into account the temperature gradient in our analysis and improve the cluster gas density distribution. This model also constrains the cluster physical parameters and the results show a radial decline in the gas temperature as expected. The mean cluster total mass estimates are also within 1 sigma from the simulated cluster true values. However, we find that for at least interferometric SZ analysis in practice at the present time, there is no differences in the AMI visibilities between the two models. This may of course change as the instruments improve.Comment: 19 pages, 13 tables, 24 figure

Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts

Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.</p

Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex

Reticulocyte-binding protein homologue 5 (RH5), a leading blood-stage Plasmodium falciparum malaria vaccine target, interacts with cysteine-rich protective antigen (CyRPA) and RH5-interacting protein (RIPR) to form an essential heterotrimeric “RCR-complex”. We investigate whether RCR-complex vaccination can improve upon RH5 alone. Using monoclonal antibodies (mAbs) we show that parasite growth-inhibitory epitopes on each antigen are surface-exposed on the RCR-complex and that mAb pairs targeting different antigens can function additively or synergistically. However, immunisation of female rats with the RCR-complex fails to outperform RH5 alone due to immuno-dominance of RIPR coupled with inferior potency of anti-RIPR polyclonal IgG. We identify that all growth-inhibitory antibody epitopes of RIPR cluster within the C-terminal EGF-like domains and that a fusion of these domains to CyRPA, called “R78C”, combined with RH5, improves the level of in vitro parasite growth inhibition compared to RH5 alone. These preclinical data justify the advancement of the RH5.1 + R78C/Matrix-M™ vaccine candidate to Phase 1 clinical trial

The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer

© The Author 2015.Background: The management of NSCLC has been transformed by stratified medicine. The National Lung Matrix Trial (NLMT) is a UK-wide study exploring the activity of rationally selected biomarker/targeted therapy combinations. Patients and methods: The Cancer Research UK (CRUK) Stratified Medicine Programme 2 is undertaking the large volume national molecular pre-screening which integrates with the NLMT. At study initiation, there are eight drugs being used to target 18 molecular cohorts. The aim is to determine whether there is sufficient signal of activity in any drug-biomarker combination to warrant further investigation. A Bayesian adaptive design that gives a more realistic approach to decision making and flexibility to make conclusions without fixing the sample size was chosen. The screening platform is an adaptable 28-gene Nextera next-generation sequencing platform designed by Illumina, covering the range of molecular abnormalities being targeted. The adaptive design allows new biomarker-drug combination cohorts to be incorporated by substantial amendment. The pre-clinical justification for each biomarker-drug combination has been rigorously assessed creating molecular exclusion rules and a trumping strategy in patients harbouring concomitant actionable genetic abnormalities. Discrete routes of pathway activation or inactivation determined by cancer genome aberrations are treated as separate cohorts. Key translational analyses include the deep genomic analysis of pre- and post-treatment biopsies, the establishment of patient-derived xenograft models and longitudinal ctDNA collection, in order to define predictive biomarkers, mechanisms of resistance and early markers of response and relapse. Conclusion: The SMP2 platform will provide large scale genetic screening to inform entry into the NLMT, a trial explicitly aimed at discovering novel actionable cohorts in NSCLC

Author Correction:Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts (Nature Genetics, (2021), 53, 1, (86-99), 10.1038/s41588-020-00750-6)

This paper was originally published without open access. As of the date of this correction, the paper is available online as an open-access paper under a Creative Commons Attribution 4.0 International License. *Lists of authors and their affiliations appear online