Presenting dynamic information on mobile computers

A problem with mobile computing devices is the output of dynamic information owing to their small screens. This paper describes an experiment to investigate the use of non-speech sounds to present dynamic information without using visual display space. Results showed that non-speech sound could be used in a simple share-dealing scenario to present a “sound graph” of share prices. This allowed participants to reduce the workload they had to invest in share-price monitoring as they could listen to the graph whilst they worked in a share accumulation window

NuSTAR hard X-ray observation of a sub-A class solar flare

We report a NuSTAR observation of a solar microflare, SOL2015-09-01T04. Although it was too faint to be observed by the GOES X-ray Sensor, we estimate the event to be an A0.1 class flare in brightness. This microflare, with only 5 counts per second per detector observed by RHESSI, is fainter than any hard X-ray (HXR) flare in the existing literature. The microflare occurred during a solar pointing by the highly sensitive NuSTAR astrophysical observatory, which used its direct focusing optics to produce detailed HXR microflare spectra and images. The microflare exhibits HXR properties commonly observed in larger flares, including a fast rise and more gradual decay, earlier peak time with higher energy, spatial dimensions similar to the RHESSI microflares, and a high-energy excess beyond an isothermal spectral component during the impulsive phase. The microflare is small in emission measure, temperature, and energy, though not in physical size; observations are consistent with an origin via the interaction of at least two magnetic loops. We estimate the increase in thermal energy at the time of the microflare to be 2.4x10^27 ergs. The observation suggests that flares do indeed scale down to extremely small energies and retain what we customarily think of as "flarelike" properties.Comment: Status: Accepted by the Astrophysical Journal, 2017 July 1

Synthesis and evaluation of designed PKC modulators for enhanced cancer immunotherapy.

Bryostatin 1 is a marine natural product under investigation for HIV/AIDS eradication, the treatment of neurological disorders, and enhanced CAR T/NK cell immunotherapy. Despite its promising activity, bryostatin 1 is neither evolved nor optimized for the treatment of human disease. Here we report the design, synthesis, and biological evaluation of several close-in analogs of bryostatin 1. Using a function-oriented synthesis approach, we synthesize a series of bryostatin analogs designed to maintain affinity for bryostatin's target protein kinase C (PKC) while enabling exploration of their divergent biological functions. Our late-stage diversification strategy provides efficient access to a library of bryostatin analogs, which per our design retain affinity for PKC but exhibit variable PKC translocation kinetics. We further demonstrate that select analogs potently increase cell surface expression of CD22, a promising CAR T cell target for the treatment of leukemias, highlighting the clinical potential of bryostatin analogs for enhancing targeted immunotherapies

A MIQE-Compliant Real-Time PCR Assay for Aspergillus Detection

PMCID: PMC3393739This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Five years MIQE guidelines: The case of the Arabian countries

The quantitative real time polymerase chain reaction (qPCR) has become a key molecular enabling technology with an immense range of research, clinical, forensic as well as diagnostic applications. Its relatively moderate instrumentation and reagent requirements have led to its adoption by numerous laboratories, including those located in the Arabian world, where qPCR, which targets DNA, and reverse transcription qPCR (RT-qPCR), which targets RNA, are widely used for region-specific biotechnology, agricultural and human genetic studies. However, it has become increasingly apparent that there are significant problems with both the quality of qPCR-based data as well as the transparency of reporting. This realisation led to the publication of the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines in 2009 and their more widespread adoption in the last couple of years. An analysis of the performance of biomedical research in the Arabian world between 2001-2005 suggests that the Arabian world is producing fewer biomedical publications of lower quality than other Middle Eastern countries. Hence we have analysed specifically the quality of RT-qPCR-based peer-reviewed papers published since 2009 from Arabian researchers using a bespoke iOS/Android app developed by one of the authors. Our results show that compliance with 15 essential MIQE criteria was low (median of 40%, range 0-93%) and few details on RNA quality controls (22% compliance), assays design (12%), RT strategies (32%), amplification efficiencies (30%) and the normalisation process (3%). These data indicate that one of the reasons for the poor performance of Arabian world biomedical research may be the low standard of any supporting qPCR experiments and identify which aspects of qPCR experiments require significant improvements

The physiological target for LeuRS translational quality control is norvaline

The fidelity of protein synthesis depends on the capacity of aminoacyl-tRNA synthetases (AARSs) to couple only cognate amino acid-tRNA pairs. If amino acid selectivity is compromised, fidelity can be ensured by an inherent AARS editing activity that hydrolyses mischarged tRNAs. Here we show that the editing activity of Escherichia coli leucyl-tRNA synthetase (EcLeuRS) is not required to prevent incorrect isoleucine incorporation. Rather, as shown by kinetic, structural and in vivo approaches, the prime biological function of LeuRS editing is to prevent mis-incorporation of the non-standard amino acid norvaline. This conclusion follows from a reassessment of the discriminatory power of LeuRS against isoleucine and the demonstration that a LeuRS editing- deficient E. coli strain grows normally in high concentrations of isoleucine but not under oxygen deprivation conditions when norvaline accumulates to substantial levels. Thus, AARS- based translational quality control is a key feature for bacterial adaptive response to oxygen deprivation. The non-essential role for editing under normal bacterial growth has important implications for the development of resistance to antimicrobial agents targeting the LeuRS editing site

Technical transfer of a rapid microbial platform for vaccine production

The limited availability and affordability of vaccines to low- and middle-income countries (LMIC) has created a need for solutions that will ensure effective, affordable vaccine production technology. To establish a rapid and economical platform for the expression of viral proteins in high yield and purity by Pichia pastoris (X33), the receptor-binding domain (RBD) protein of the SARS-CoV2 was selected in this study. After fermentation at the 5 L scale, the protein was purified by a simplified chromatography, with minimal sample treatment. The purified protein was characterized biochemically, and after its formulation, the immunogenicity was evaluated in mice. Collectively, the data suggested that the vaccine candidate is a suitable COVID-19 vaccine candidate antigen for technology transfer. Furthermore, this study creates a robust foundation for industrial production at scale

Transportability without positivity: a synthesis of statistical and simulation modeling

When estimating an effect of an action with a randomized or observational study, that study is often not a random sample of the desired target population. Instead, estimates from that study can be transported to the target population. However, transportability methods generally rely on a positivity assumption, such that all relevant covariate patterns in the target population are also observed in the study sample. Strict eligibility criteria, particularly in the context of randomized trials, may lead to violations of this assumption. Two common approaches to address positivity violations are restricting the target population and restricting the relevant covariate set. As neither of these restrictions are ideal, we instead propose a synthesis of statistical and simulation models to address positivity violations. We propose corresponding g-computation and inverse probability weighting estimators. The restriction and synthesis approaches to addressing positivity violations are contrasted with a simulation experiment and an illustrative example in the context of sexually transmitted infection testing uptake. In both cases, the proposed synthesis approach accurately addressed the original research question when paired with a thoughtfully selected simulation model. Neither of the restriction approaches were able to accurately address the motivating question. As public health decisions must often be made with imperfect target population information, model synthesis is a viable approach given a combination of empirical data and external information based on the best available knowledge

Service evaluation of weight outcomes as a function of initial BMI in 34,271 adults referred to a primary care/commercial weight management partnership scheme

Peer reviewedPublisher PD

Fruit, vegetable and vitamin C intakes and plasma vitamin C: cross-sectional associations with insulin resistance and glycaemia in 9-10 year-old children.

AIM: To examine whether low circulating vitamin C concentrations and low fruit and vegetable intakes were associated with insulin resistance and other Type 2 diabetes risk markers in childhood. METHODS: We conducted a cross-sectional, school-based study in 2025 UK children aged 9-10 years, predominantly of white European, South-Asian and black African origin. A 24-h dietary recall was used to assess fruit, vegetable and vitamin C intakes. Height, weight and fat mass were measured and a fasting blood sample collected to measure plasma vitamin C concentrations and Type 2 diabetes risk markers. RESULTS: In analyses adjusting for confounding variables (including socio-economic status), a one interquartile range higher plasma vitamin C concentration (30.9 μmol/l) was associated with a 9.6% (95% CI 6.5, 12.6%) lower homeostatic model assessment of insulin resistance value, 0.8% (95% CI 0.4, 1.2%) lower fasting glucose, 4.5% (95% CI 3.2, 5.9%) lower urate and 2.2% (95% CI 0.9, 3.4%) higher HDL cholesterol. HbA1c concentration was 0.6% (95% CI 0.2, 1.0%) higher. Dietary fruit, vegetable and total vitamin C intakes were not associated with any Type 2 diabetes risk markers. Lower plasma vitamin C concentrations in South-Asian and black African-Caribbean children could partly explain their higher insulin resistance. CONCLUSIONS: Lower plasma vitamin C concentrations are associated with insulin resistance and could partly explain ethnic differences in insulin resistance. Experimental studies are needed to establish whether increasing plasma vitamin C can help prevent Type 2 diabetes at an early stage