Nanostructured copper particles-incorporated Nafion-modified electrode for oxygen reduction

The electrocatalytic activity of nanostructured copper particles (represented as Cunano) incorporated Nafion (Nf) film-coated glassy carbon (GC) electrode (GC/Nf/Cunano) towards oxygen reduction was investigated in oxygenated 0.1 M phosphate buffer (pH 7.2). The electrodeposited Cunano in Nf film was characterized by atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). The electrocatalytic activity of Cunano at the modified electrode towards oxygen reduction was studied using cyclic voltammetry technique. The molecular oxygen reduction at the GC/Nf/Cunano-modified electrode started at a more positive potential than at a bare GC electrode. A possible reaction mechanism was proposed in which oxygen reduction may proceed through two-step two-electron processes at the GC/Nf/Cunano electrode. The GC/Nf/Cunano electrode shows higher stability for oxy gen reduction in neutral solution and the electrode may find applications in fuel cells

Educational Ideas in Moral Tamil Literature

In the Pathinenkilkanakku collection of books that arose in order to uphold righteousness, and in the moral books that followed them, the poets have expounded educational thoughts with interesting songs. Our forefathers have sung songs in Tamil texts even before western scholars have spoken about the importance of education. The kings of the Sangam age ruled the country with the help of learned men. An uneducated person, even if he had acquired a great deal of wealth, was treated with contempt. The authors of the moral books, who know the importance of education, have not only mentioned righteousness in their books but have also praised education in many songs. Thus, the songs of the poets of the moral book become the subject of study under the categories of merits of education, method of obtaining education, method of education, mode of expressing education, and the status of the unlearned

Electrochemical and in situ spectroelectrochemical studies of gold nanoparticles immobilized Nafion matrix modified electrode

Electrochemical and in situ spectroelectrochemical behaviours of phenosafranine (PS+) were studied at the gold nanoparticles (AuNps) immobilized Nafion (Nf) film coated glassy carbon (GC) and indium tin oxide (ITO) electrodes. Cyclic voltammetric studies showed that the PS+ molecules strongly interact with the AuNps immobilized in the Nf matrix through the electrostatic interaction. The presence of AuNps in the Nf film improved the electrochemical characteristics of the incorporated dye molecules. The emission spectra of Nf-AuNps-PS+ films showed that the incorporated PS+ was quenched by AuNps and it could be explained based on the electronic interaction between the AuNps and PS+ molecules. The in situ spectroelectrochemical study showed an improved electrochemical characteristic of the incorporated PS+ molecules at the ITO/Nf-AuNps electrode when compared to the ITO/Nf electrode

Cellular Target Deconvolution of Small Molecules Using a Selection-Based Genetic Screening Platform

Small-molecule drug target identification is an essential and often rate-limiting step in phenotypic drug discovery and remains a major challenge. Here, we report a novel platform for target identification of activators of signaling pathways by leveraging the power of a clustered regularly interspaced short palindromic repeats (CRISPR) knockout library. This platform links the expression of a suicide gene to the small-molecule-activated signaling pathway to create a selection system. With this system, loss-of-function screening using a CRISPR single-guide (sg) RNA library positively enriches cells in which the target has been knocked out. The identities of the drug targets and other essential genes required for the activity of small molecules of interest are then uncovered by sequencing. We tested this platform on BDW568, a newly discovered type-I interferon signaling activator, and identified stimulator of interferon genes (STING) as its target and carboxylesterase 1 (CES1) to be a key metabolizing enzyme required to activate BDW568 for target engagement. The platform we present here can be a general method applicable for target identification for a wide range of small molecules that activate different signaling pathways

Operational Challenges in Conducting a Subnational TB Prevalence Survey in India: Lessons Learned for Resource-Limited, High-Burden Settings

Estimating the burden of TB at the subnational level is critical to planning and prioritizing resources for TB control activities according to the local epidemiological situation. We report the experiences and operational challenges of implementing a TB prevalence survey at the subnational level in India. Information was collected from research reports that gathered data from periodic meetings, informal discussions with study teams, letters of communication, and various site visit reports. During the implementation of the survey, several challenges were encountered, including frequent turnover in human resources, lack of survey participation and community engagement, breakdown of X-ray machines, laboratory issues that delayed sputum sample testing, delays in X-ray reading, and network and Internet connectivity issues that impeded data management. To help ensure the survey was implemented in a timely manner, we developed several solutions, including planning ahead to anticipate challenges, ensuring timely communication, having a high commitment from all stakeholders, having strong team motivation, providing repetitive hands-on training, and involving local leaders to increase community engagement. This experience may help future states and countries that plan to conduct TB prevalence surveys to address these anticipated challenges and develop alternative strategies well in advance

Programmatic implications of a sub-national TB prevalence survey in India

Subnational TB estimates are crucial for making informed decisions to tailor TB control activities to local TB epidemiolog

A multi-disciplinary perspective on emergent and future innovations in peer review [version 1; peer review: 2 approved with reservations]

Peer review of research articles is a core part of our scholarly communication system. In spite of its importance, the status and purpose of peer review is often contested. What is its role in our modern digital research and communications infrastructure? Does it perform to the high standards with which it is generally regarded? Studies of peer review have shown that it is prone to bias and abuse in numerous dimensions, frequently unreliable, and can fail to detect even fraudulent research. With the advent of Web technologies, we are now witnessing a phase of innovation and experimentation in our approaches to peer review. These developments prompted us to examine emerging models of peer review from a range of disciplines and venues, and to ask how they might address some of the issues with our current systems of peer review. We examine the functionality of a range of social Web platforms, and compare these with the traits underlying a viable peer review system: quality control, quantified performance metrics as engagement incentives, and certification and reputation. Ideally, any new systems will demonstrate that they out-perform current models while avoiding as many of the biases of existing systems as possible. We conclude that there is considerable scope for new peer review initiatives to be developed, each with their own potential issues and advantages. We also propose a novel hybrid platform model that, at least partially, resolves many of the technical and social issues associated with peer review, and can potentially disrupt the entire scholarly communication system. Success for any such development relies on reaching a critical threshold of research community engagement with both the process and the platform, and therefore cannot be achieved without a significant change of incentives in research environments

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)$^{1,2}$. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive$^{1,2}$. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma$^{3}$. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy respons

Microfluidic Chip for Molecular Amplification of Influenza A RNA in Human Respiratory Specimens

A rapid, low cost, accurate point-of-care (POC) device to detect influenza virus is needed for effective treatment and control of both seasonal and pandemic strains. We developed a single-use microfluidic chip that integrates solid phase extraction (SPE) and molecular amplification via a reverse transcription polymerase chain reaction (RT-PCR) to amplify influenza virus type A RNA. We demonstrated the ability of the chip to amplify influenza A RNA in human nasopharyngeal aspirate (NPA) and nasopharyngeal swab (NPS) specimens collected at two clinical sites from 2008–2010. The microfluidic test was dramatically more sensitive than two currently used rapid immunoassays and had high specificity that was essentially equivalent to the rapid assays and direct fluorescent antigen (DFA) testing. We report 96% (CI 89%,99%) sensitivity and 100% (CI 95%,100%) specificity compared to conventional (bench top) RT-PCR based on the testing of n = 146 specimens (positive predictive value = 100%(CI 94%,100%) and negative predictive value = 96%(CI 88%,98%)). These results compare well with DFA performed on samples taken during the same time period (98% (CI 91%,100%) sensitivity and 96%(CI 86%,99%) specificity compared to our gold standard testing). Rapid immunoassay tests on samples taken during the enrollment period were less reliable (49%(CI 38%,61%) sensitivity and 98%(CI 98%,100%) specificity). The microfluidic test extracted and amplified influenza A RNA directly from clinical specimens with viral loads down to 103 copies/ml in 3 h or less. The new test represents a major improvement over viral culture in terms of turn around time, over rapid immunoassay tests in terms of sensitivity, and over bench top RT-PCR and DFA in terms of ease of use and portability