A mechanistic study of the EC′ mechanism – the split wave in cyclic voltammetry and square wave voltammetry

In this paper, a detailed investigation of electrochemical reactions coupled with homogenous chemical steps using cyclic voltammetry (CV) and square wave voltammetry (SWV) was carried out to study the electrocatalytic (EC’) mechanism. In CV, parameters including scan rate, electrode material and redox reactant were investigated while in SWV, parameters including substrate concentrations and frequencies were altered to demonstrate EC’ mechanism. Mechanistic studies focused on the EC’ mechanism using L-cysteine with ferrocenecarboxylic acid and 1,1 ′-ferrocenedicarboxylic acid respectively. Voltammetric responses were recorded and under conditions of high chemical rate constant and low substrate concentration, a split wave was observed in both CV and SWV studies

Evaporative Mass Loss Measurement as a Quality Control Tool for Quality Assurance in the Manufacture of Inks Suitable for High Speed (≥60 m/min) Printing

In any manufacturing environment, it is always important to be able to embrace a culture of traceability of any non-conformed product. For the case of ink manufacture, operator confusion, leading to the mixing-up of solvents, or connecting the incorrect solvent drum to solvent lines, can lead to disastrous consequences that are not trivial for a quality control/quality assurance team to unravel. Accordingly, simple methods for assessing whether the correct solvents were added in the correct ratios to products empower this QA/QC requirement. In this paper, we examine the use of a trivial measurement of evaporative mass loss as a protocol for validating the conformance of manufactured ink to specification. Inspired by the transport-limit that occurs at ultramicroelectrodes in electrochemistry, we develop theory to analyse evaporation rate measurements, and illustrate how vaporisation at the liquid | gas interface is dominated by a diffusion anisotropy, owing to natural convection for organic solvents, manufactured resins and commercialised inks that have been used, inter alia, for the underground transport tickets in the cities of London and Paris. We further demonstrate that the use of incorrect solvents is readily seen through evaporation rate transients, thereby enabling this measurement for human factor mitigation during the ink manufacture process

Performance of lyotropic liquid crystal-based photoelectrochemical capacitors for solar-to- electrical energy conversion

Regenerative photoelectrochemical capacitors, adapted from a experimental system previously reported (J. E. Halls, J. D. Wadhawan, Energy Environ. Sci., 2012, 5, 6541) and based on the doping of a lamellar lyotropic liquid crystal with visible light sensitizer tris(2,2'-bipyridyl)ruthenium(II), N-methylphenothiazine, zinc(II) ions and potassium chloride (as electrolyte) are examined in this work. The two dye species, by virtue of similarity in redox potentials and difference in size and lipophilicity, allow for electron transfer cascades to occur under illumination, which can be harnessed in a power-generating device through the use of a sacrificial counter electrode. In operation as a solar cell, a maximum light-to-electrical power conversion efficiency is reported as being ~5.0% under green light (530 nm centreband, 30 nm bandwidth, 2.2 mW cm-2 intensity), which extrapolates to the opportunistic value of 1% under one Sun conditions. The electrical characteristics of the devices under illumination afford specific capacitances of ca. 0.5-1.0 F g-1 and have fill factors ~20% which are close to the 25% expected for a perfect photogalvanic cell. The time constants of the reported devices (~1.5 s) are consistent with the notion of electroporation of the surfactant lamellae. The advantages of these mid-ranging photoelectrochemical capacitors are suggested as being their low cost and versatility afforded by their flexible liquid framework that appears to realign itself under conditions of open circuit

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Unravelling the Occurrence of Mediator-Blood Protein Interactions via the Redox Catalysis of the Physiological Gasotransmitter Hydrogen Sulfide

Ferrocenemethanol is employed as an aqueous, homogeneous redox mediator for hydrogen sulfide. The reaction is seen to follow an EC’ mechanism over the range 6≤pH≤9, with bisulfide reacting four times more rapidly than hydrogen sulfide. In the presence of 10 vol.% hæmolysed blood, greater concentrations of sulfide (as H2S or as HS−) are required to achieve the same degree of redox catalysis, compared with the absence of the blood proteins, at both pH 7 and pH 9. It is suggested that this phenomenon derives from a ferrocenemethanol/blood protein interaction, which is first titrated by the sulfide species. This can give rise to a titration-based electroanalytical assay for sulfide in blood, whilst being important for blood-based electrochemical bioassays involving hydrophilic ferrocene derivatives

Bronchial hyperresponsiveness and the bronchiolitis obliterans syndrome after lung transplantation

Because bronchial hyperresponsiveness has been linked to the bronchiolitis obliterans syndrome (BOS), we determined PD20 methacholine (PD20(M)), PD15 hypertonic saline (PD15(HS)) and their dose-response slopes (DRSM and DRSHS) in 8 single and 18 double lung transplant recipients within 1 year of lung transplantation and examined the relationship to bronchoalveolar lavage cell profiles and subsequent development of BOS. Twenty-two patients (81%) had a positive methacholine and 6 (25%) a positive hypertonic saline challenge. A positive PD15(HS) was associated with an increased risk for BOS at 2 years (odds ratio 12.6, 95% confidence interval 1.3–123.5, p \u3c 0.05), and time to BOS was significantly and negatively related to DRSHS (r = −0.5, p \u3c 0.05) — that is, the greater the response, the shorter the time to BOS. Interestingly, DRSHS correlated positively with recipient:donor total lung capacity ratio (r = 0.5, p \u3c 0.05), but there was no relationship between either challenge result and airway inflammation. Methacholine hyperresponsiveness is common after lung transplantation but is not prognostic, whereas response to hypertonic saline may reflect recipient:donor size matching and provide useful information regarding the potential for BOS development