Systematic review of birth cohort studies in Africa

In sub-Saharan Africa, unacceptably high rates of mortality amongst women and children continue to persist. The emergence of research employing new genomic technologies is advancing knowledge on cause of disease. This review aims to identify birth cohort studies conducted in sub-Saharan Africa and to consider their suitability as a platform to support genetic epidemiological studies

CCL19-sorted mature dendritic cells have enhanced lymph node migratory capacity and function

No abstract available

The effects of natural convection on low temperature combustion

When a gas undergoes an exothermic reaction in a closed vessel, spatial temperature gradients can develop. If these gradients become sufficiently large, the resulting buoyancy forces will move the gas, i.e. there is natural convection. The nature of the resulting flow is determined by the Rayleigh number, Ra = (β g ΔT L^3) / (κ ν). The evolution of such a system will depend on the interactions of natural convection, diffusion of both heat and chemical species, and chemical reaction. This study is concerned with a gas-phase system undergoing Sal’nikov’s reaction: P → A → B, in the presence of natural convection. This kinetic scheme is used as a simplified representation of a cool flame, which is a feature of the low temperature combustion of a hydrocarbon vapour. Sal’nikov’s reaction is one of the simplest to display thermokinetic oscillations, such as those seen in cool flames. The behaviour of Sal’nikov’s reaction in the presence of natural convection was investigated using a combination of analytical and numerical techniques. First, a numerical model was developed to compute the temperature, velocity and concentrations when a simple exothermic reaction occurs in a spherical batch reactor, the results of which could be compared with previous experimental measurements. Subsequently, a scaling analysis of Sal’nikov’s reaction proceeding in a spherical reactor was performed. This yielded significant insight into the general behaviour of this and similar systems. The forms of the analytical scales were confirmed through comparison with the results from numerical simulations. These scales were used to predict how the system responds to changes in certain key process variables, such as the pressure and the size of the reactor. It was shown that the behaviour of this system is governed by the ratios of the characteristic timescales for diffusion, reaction and natural convection. These ratios were used to define a regime diagram describing the system. The behaviour in different parts of this regime diagram was characterised and regions in which oscillations occur were identified.Engineering and Physical Sciences Research Council and Society of Chemical Industr

An integrated circuit for chip-based analysis of enzyme kinetics and metabolite quantification

We have created a novel chip-based diagnostic tools based upon quantification of metabolites using enzymes specific for their chemical conversion. Using this device we show for the first time that a solid-state circuit can be used to measure enzyme kinetics and calculate the Michaelis-Menten constant. Substrate concentration dependency of enzyme reaction rates is central to this aim. Ion-sensitive field effect transistors (ISFET) are excellent transducers for biosensing applications that are reliant upon enzyme assays, especially since they can be fabricated using mainstream microelectronics technology to ensure low unit cost, mass-manufacture, scaling to make many sensors and straightforward miniaturisation for use in point-of-care devices. Here, we describe an integrated ISFET array comprising 216 sensors. The device was fabricated with a complementary metal oxide semiconductor (CMOS) process. Unlike traditional CMOS ISFET sensors that use the Si3N4 passivation of the foundry for ion detection, the device reported here was processed with a layer of Ta2O5 that increased the detection sensitivity to 45 mV/pH unit at the sensor readout. The drift was reduced to 0.8 mV/hour with a linear pH response between pH 2 – 12. A high-speed instrumentation system capable of acquiring nearly 500 fps was developed to stream out the data. The device was then used to measure glucose concentration through the activity of hexokinase in the range of 0.05 mM – 231 mM, encompassing glucose’s physiological range in blood. Localised and temporal enzyme kinetics of hexokinase was studied in detail. These results present a roadmap towards a viable personal metabolome machine

Cytometric analysis of T cell phenotype using cytokine profiling for improved manufacturing of an EBV-specific T cell therapy

Acknowledgements We gratefully acknowledge the voluntary donations of peripheral blood and leukapheresis samples used in this study. This study was supported by the staff of the Scottish National Blood Transfusion Service (SNBTS) Clinical Apheresis Unit, Aberdeen and medical colleagues at the New Zealand Blood Transfusion Service for collection of the donor leukapheresis material for the second iteration of the EBV-T cell bank. This work was supported by a Wellcome Trust Translational Award. The ongoing operation of the UK EBV-specific T cell bank is supported by cost-recovery fees and supported by SNBTS. Contributions RSC and AK were responsible for the acquisition and analysis of data, and RSC wrote the principal manuscript; GW and MV were involved in supply of material and interpretation of data; MLT, JDMC and ARF were responsible for study conception and design, data analysis and interpretation, and revision of the final manuscript.Peer reviewedPublisher PD

A colorimetric CMOS-based platform for rapid total serum cholesterol quantification

Elevated cholesterol levels are associated with a greater risk of developing cardiovascular disease and other illnesses, making it a prime candidate for detection on a disposable biosensor for rapid point of care diagnostics. One of the methods to quantify cholesterol levels in human blood serum uses an optically mediated enzyme assay and a bench top spectrophotometer. The bulkiness and power hungry nature of the equipment limits its usage to laboratories. Here, we present a new disposable sensing platform that is based on a complementary metal oxide semiconductor process for total cholesterol quantification in pure blood serum. The platform that we implemented comprises readily mass-manufacturable components that exploit colorimetric changes of cholesterol oxidase and cholesterol esterase reactions. We have shown that our quantification results are comparable to that obtained by a bench top spectrophotometer. Using the implemented device, we have measured cholesterol concentration in human blood serum as low as 29 μM with a limit of detection at 13 μM, which is approximately 400 times lower than average physiological range, implying that our device also has the potential to be used for applications that require greater sensitivity

Intracellular redox potential is correlated with miRNA expression in MCF7 cells under hypoxic conditions

Hypoxia is a ubiquitous feature of cancers, encouraging glycolytic metabolism, proliferation, and resistance to therapy. Nonetheless, hypoxia is a poorly defined term with confounding features described in the literature. Redox biology provides an important link between the external cellular microenvironment and the cell's response to changing oxygen pressures. In this paper, we demonstrate a correlation between intracellular redox potential (measured using optical nanosensors) and the concentrations of microRNAs (miRNAs) involved in the cell's response to changes in oxygen pressure. The correlations were established using surprisal analysis (an approach derived from thermodynamics and information theory). We found that measured redox potential changes reflect changes in the free energy computed by surprisal analysis of miRNAs. Furthermore, surprisal analysis identified groups of miRNAs, functionally related to changes in proliferation and metastatic potential that played the most significant role in the cell's response to changing oxygen pressure. © 2019 National Academy of Sciences. All rights reserved

The development and validation of a novel, parameter-free, modelling strategy for electromembrane processes: Electrodialysis

As the global water crisis worsens and natural resources of strategic inorganic elements dwindle, the need for efficient and effective salt separation methods is becoming ever more important. Electromembrane processes, and in particular electrodialysis, are emerging as efficient and effective separation technologies that use an electric field to drive the transport of ions against a concentration gradient. Modelling electromembrane processes allows for process design and optimisation, as well as the identification of what technological improvements would have the greatest effect. However, the wide use of empirical fitting parameters in most existing models greatly limits their globality. The presence of complex and confounding phenomena within electromembrane processes greatly exacerbates this. In this work, a novel, circuit-based modelling strategy for electromembrane processes is presented, avoiding the use of any fitting parameters. Conventional electrodialysis is adopted as a case study. The implementation of a novel transport number model and membrane resistance model are crucial for model accuracy over a wide range of process conditions. The model was experimentally validated and showed excellent agreement with experimental data across a range of concentrations and voltages. Consequently, this model will prove to be an excellent tool for researchers and process designers