Convolutional neural networks for challenges in automated nuclide identification

Improvements in Radio-Isotope IDentification (RIID) algorithms have seen a resurgence in interest with the increased accessibility of machine learning models. Convolutional Neural Network (CNN)-based models have been developed to identify arbitrary mixtures of unstable nuclides from gamma spectra. In service of this, methods for the simulation and pre-processing of training data were also developed. The implementation of 1D multi-class, multi-label CNNs demonstrated good generalisation to real spectra with poor statistics and significant gain shifts. It is also shown that even basic CNN architectures prove reliable for RIID under the challenging conditions of heavy shielding and close source geometries, and may be extended to generalised solutions for pragmatic RIID

CRISPR/Cas9 Ablation of Integrated HIV-1 Accumulates Proviral DNA Circles with Reformed Long Terminal Repeats

Gene editing may be used to excise the human immunodeficiency virus type 1 (HIV-1) provirus from the host cell genome, possibly eradicating the infection. Here, using cells acutely or latently infected by HIV-1 and treated with long terminal repeat (LTR)-targeting CRISPR/Cas9, we show that the excised HIV-1 provirus persists for a few weeks and may rearrange in circular molecules. Although circular proviral DNA is naturally formed during HIV-1 replication, we observed that gene editing might increase proviral DNA circles with restored LTRs. These extrachromosomal elements were recovered and probed for residual activity through their transfection in uninfected cells. We discovered that they can be transcriptionally active in the presence of Tat and Rev. Although confirming that gene editing is a powerful tool to eradicate HIV-1 infection, this work highlights that, to achieve this goal, the LTRs must be cleaved in several pieces to avoid residual activity and minimize the risk of reintegration in the context of genomic instability, possibly caused by the off-target activity of Cas9. IMPORTANCE The excision of HIV-1 provirus from the host cell genome has proven feasible in vitro and, to some extent, in vivo. Among the different approaches, CRISPR/Cas9 is the most promising tool for gene editing. The present study underlines the remarkable effectiveness of CRISPR/Cas9 in removing the HIV-1 provirus from infected cells and investigates the fate of the excised HIV-1 genome. This study demonstrates that the free provirus may persist in the cell after editing and in appropriate circumstances may reactivate. As an episome, it might be transcriptionally active, especially in the presence of Tat and Rev. The persistence of the HIV-1 episome was strongly decreased by gene editing with multiple targets. Although gene editing has the potential to eradicate HIV-1 infection, this work highlights a potential issue that warrants further investigation

Doing cold smarter

Cold has been much neglected in the energy debate. Governments are developing strategies and policies to green everything from electricity to transport to heat, but the energy and environmental impacts of cooling have so far been largely ignored. This is a serious oversight, since making things cold is energy intensive and can be highly polluting, and demand for cooling in all its forms is booming worldwide – especially in developing countries. According to one projection, by the end of this century global demand for air conditioning alone could consume the equivalent of half our worldwide electricity generation today – and most of the increase will come in developing markets. The ‘greening’ of cold is clearly an urgent global problem – but it may also offer Britain a massive business opportunity. Cold may have been ignored but is vitally important to many aspects of modern life. An effective cold chain, for example, is essential for tackling problems such as food waste, food security, water conservation and public health. Cooling is also critical for many less obvious but essential functions: data centres couldn’t operate without it, nor for example MRI scanners in medicine or superconductors in power electronics. Cooling also provides modern levels of comfort in hot countries – and can make the difference between some regions being habitable or not. At the same time, vast amounts of cold are wasted – for instance during the regasification of LNG – which could in principle be recycled to satisfy some of this demand and start to reduce the environmental damage caused by cooling. Such a system-level approach – which starts by asking what energy services we need, and what is the least damaging way to provide them, rather than accepting existing practices as a fait accompli – has recently been coined the ‘Cold Economy’. It is clear the Cold Economy could unleash a wide range of innovative clean cold technologies and provide energy resilience, economic growth and environmental benefits, but there is an urgent need to develop a system-level analysis of this problem and the potential solutions to inform both industry and policymakers. The Birmingham Policy Commission: Doing Cold Smarter was convened to start this work

Homozygous NMNAT2 mutation in sisters with polyneuropathy and erythromelalgia.

We identified a homozygous missense mutation in the gene encoding NAD synthesizing enzyme NMNAT2 in two siblings with childhood onset polyneuropathy with erythromelalgia. No additional homozygotes for this rare allele, which leads to amino acid substitution T94M, were present among the unaffected relatives tested or in the 60,000 exomes of the ExAC database. For axons to survive, axonal NMNAT2 activity has to be maintained above a threshold level but the T94M mutation confers a partial loss of function both in the ability of NMNAT2 to support axon survival and in its enzymatic properties. Electrophysiological tests and histological analysis of sural nerve biopsies in the patients were consistent with loss of distal sensory and motor axons. Thus, it is likely that NMNAT2 mutation causes this pain and axon loss phenotype making this the first disorder associated with mutation of a key regulator of Wallerian-like axon degeneration in humans. This supports indications from numerous animal studies that the Wallerian degeneration pathway is important in human disease and raises important questions about which other human phenotypes could be linked to this gene

A novel absorptive/reflective solar concentrator for heat and electricity generation: an optical and thermal analysis.

The crossed compound parabolic concentrator (CCPC) is one of the most efficient non-imaging solar concentrators used as a stationary solar concentrator or as a second stage solar concentrator. In this study, the CCPC is modified to demonstrate for the first time a new generation of solar concentrators working simultaneously as an electricity generator and thermal collector. The CCPC is designed to have two complementary surfaces, one reflective and one absorptive, and is named as an absorptive/reflective CCPC (AR-CCPC). Usually, the height of the CCPC is truncated with a minor sacrifice of the geometric concentration. These truncated surfaces rather than being eliminated are instead replaced with absorbent surfaces to collect heat from solar radiation. The optical efficiency including absorptive/reflective part of the AR-CCPC was simulated and compared for different geometric concentration ratios varying from 3.6× to 4×. It was found that the combined optical efficiency of the AR-CCPC 3.6×/4× remained constant and high all day long and that it had the highest total optical efficiency compared to other concentrators. In addition, the temperature distributions of AR-CCPC surfaces and the assembled solar cell were simulated based on those heat flux boundary conditions. It was shown that the addition of a thermal absorbent surface can increase the wall temperature. The maximum value reached 321.5 K at the front wall under 50° incidence. The experimental verification was also adopted to show the benefits of using absorbent surfaces. The initial results are very promising and significant for the enhancement of solar concentrator systems with lower concentrations