Correction of the neuropathogenic human apolipoprotein E4 (APOE4) gene to APOE3 in vitro using synthetic RNA/DNA oligonucleotides (chimeraplasts)

Apolipoprotein E (apoE) is a multifunctional circulating 34-kDa protein, whose gene encodes single-nucleotide polymorphisms linked to several neurodegenerative diseases. Here, we evaluate whether synthetic RNA/DNA oligonucleoticles (chimeraplasts) can convert a dysfunctional gene, APOE4 (C -> T, Cys112Arg), a risk factor for Alzheimer's disease and other neurological disorders, into wild-type APOE3. In preliminary experiments, we treated recombinant Chinese hamster ovary (CHO) cells stably secreting apoE4 and lymphocytes from a patient homozygous for the epsilon 4 allele with a 68-mer apoE4-to-apoE3 chimeraplast, complexed to the cationic delivery reagent, polyethyleneimine. Genotypes were analyzed after 48 h by routine polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and by genomic sequencing. Clear conversions of APOE4 to APOE3 were detected using either technique, although high concentrations of chimeraplast were needed (>= 800 nM). Spiking experiments of PCR reactions or CHO-K1 cells with the chimeraplast confirmed that the repair was not artifactual. However, when treated recombinant CHO cells were passaged for 10 d and then subcloned, no conversion could be detected when > 90 clones were analyzed by locus-specific PCR-RFLP. We conclude that the apparent efficient repair of the APOE4 gene in CHO cells or lymphocytes 48 h post-treatment is unstable, possibly because the high levels of chimeraplast and polyethyleneimine that were needed to induce nucleotide substitution are cytotoxic

Unveiling the planet population at birth

The radius distribution of small, close-in exoplanets has recently been shown to be bimodal. The photoevaporation model predicted this bimodality. In the photoevaporation scenario, some planets are completely stripped of their primordial H/He atmospheres, whereas others retain them. Comparisons between the photoevaporation model and observed planetary populations have the power to unveil details of the planet population inaccessible by standard observations, such as the core mass distribution and core composition. In this work, we present a hierarchical inference analysis on the distribution of close-in exoplanets using forward models of photoevaporation evolution. We use this model to constrain the planetary distributions for core composition, core mass, and initial atmospheric mass fraction. We find that the core-mass distribution is peaked, with a peak-mass of ∼4M⊕. The bulk core-composition is consistent with a rock/iron mixture that is ice-poor and ‘Earth-like’; the spread in core-composition is found to be narrow (⁠≲16 per cent variation in iron-mass fraction at the 2σ level) and consistent with zero. This result favours core formation in a water/ice poor environment. We find the majority of planets accreted a H/He envelope with a typical mass fraction of ∼4 per cent⁠; only a small fraction did not accrete large amounts of H/He and were ‘born-rocky’. We find four times as many super-Earths were formed through photoevaporation, as formed without a large H/He atmosphere. Finally, we find core-accretion theory overpredicts the amount of H/He cores would have accreted by a factor of ∼5, pointing to additional mass-loss mechanisms (e.g. ‘boil-off’) or modifications to core-accretion theory

Thermodynamic insights and assessment of the ‘circular economy’

This study analyses the effect on energy use of applying a wide range of circular economy approaches. By collating evidence on specific quantifiable approaches and then calculating and analyzing their combined full supply chain impacts through input-output analysis, it provides a more complete assessment of the overall potential scope for energy savings that these approaches might deliver than provided elsewhere. Assessment is conducted globally, across the EU-27 and in the UK. Overall, the identified opportunities have the potential to save 6%–11% of energy used to support economic activity, worldwide and in the EU, and 5%–8% in the UK. Their potential is equivalent to the total scope for other industrial energy efficiency savings. The potential savings are further divided into those due to sets of approaches relating to food waste, steel production, other materials production, product refurbishment, vehicle provision, construction and other equipment manufacture. Each of these sets of approaches can make a key contribution to the total savings that are possible. Complementary use of energy and exergy metrics illustrates the way in which energy use might change and for the first time provides indication that in most cases other energy efficiency measures are unlikely to be adversely affected by the circular economy approaches. Potential for savings in the energy embodied in each key product input to each major sector is assessed, enabling prioritization of the areas in which the circular economy approaches have the greatest scope for impact and identification of supply chains for which they are underrepresented

Thermodynamic insights and assessment of the ‘circular economy’

This study analyses the effect on energy use of applying a wide range of circular economy approaches. By collating evidence on specific quantifiable approaches and then calculating and analyzing their combined full supply chain impacts through input-output analysis, it provides a more complete assessment of the overall potential scope for energy savings that these approaches might deliver than provided elsewhere. Assessment is conducted globally, across the EU-27 and in the UK. Overall, the identified opportunities have the potential to save 6%–11% of energy used to support economic activity, worldwide and in the EU, and 5%–8% in the UK. Their potential is equivalent to the total scope for other industrial energy efficiency savings. The potential savings are further divided into those due to sets of approaches relating to food waste, steel production, other materials production, product refurbishment, vehicle provision, construction and other equipment manufacture. Each of these sets of approaches can make a key contribution to the total savings that are possible. Complementary use of energy and exergy metrics illustrates the way in which energy use might change and for the first time provides indication that in most cases other energy efficiency measures are unlikely to be adversely affected by the circular economy approaches. Potential for savings in the energy embodied in each key product input to each major sector is assessed, enabling prioritization of the areas in which the circular economy approaches have the greatest scope for impact and identification of supply chains for which they are underrepresented

Photoevaporation versus core-powered mass-loss: model comparison with the 3D radius gap

The extreme ultraviolet (EUV)/X-ray photoevaporation and core-powered mass-loss models are both capable of reproducing the bimodality in the sizes of small, close-in exoplanets observed by the Kepler space mission, often referred to as the ‘radius gap’. However, it is unclear which of these two mechanisms dominates the atmospheric mass-loss that is likely sculpting the radius gap. In this work, we propose a new method of differentiating between the two models, which relies on analysing the radius gap in 3D parameter space. Using models for both mechanisms, and by performing synthetic transit surveys we predict the size and characteristics of a survey capable of discriminating between the two models. We find that a survey of ≳5000 planets, with a wide range in stellar mass and measurement uncertainties at a ≲5 per cent level is sufficient. Our methodology is robust against moderate false positive contamination of ≲10 per cent⁠. We perform our analysis on two surveys (which do not satisfy our requirements): the California-KeplerSurvey and the Gaia–KeplerSurvey and find, unsurprisingly, that both data sets are consistent with either model. We propose a hypothesis test to be performed on future surveys that can robustly ascertain which of the two mechanisms formed the radius gap, provided one dominates over the other

Accidental blood exposure: risk and prevention in interventional radiology

There is a growing concern about the transmission of bloodborne pathogens during medical procedures among health care workers and patients. Over the last three decades, radiological services have undergone many changes with the introduction of new modalities. One of these new disciplines is interventional radiology (IR) which deals with procedures such as arteriography, image-guided biopsies, intravascular catheter insertions, angioplasty and stent placements. Despite these developments, the potential for accidental blood exposure and exposure to other infectious material continues to exist. Therefore, it is important for all radiologists who perform invasive procedures to observe specific recommendations for infection control. In this review, we look at the different policies for protection and universal standards on infection control

The California-Kepler survey. X. The radius gap as a function of stellar mass, metallicity, and age

In 2017, the California-Kepler Survey (CKS) published its first data release (DR1) of high-resolution optical spectra of 1305 planet hosts. Refined CKS planet radii revealed that small planets are bifurcated into two distinct populations, super-Earths (smaller than 1.5 R⊕) and sub-Neptunes (between 2.0 and 4.0 R⊕), with few planets in between (the "radius gap"). Several theoretical models of the radius gap predict variation with stellar mass, but testing these predictions is challenging with CKS DR1 due to its limited M⋆ range of 0.8–1.4 M⊙. Here we present CKS DR2 with 411 additional spectra and derived properties focusing on stars of 0.5–0.8 M⊙. We found that the radius gap follows Rp ∝ Pm with m = −0.10 ± 0.03, consistent with predictions of X-ray and ultraviolet- and core-powered mass-loss mechanisms. We found no evidence that m varies with M⋆. We observed a correlation between the average sub-Neptune size and M⋆. Over 0.5–1.4 M⊙, the average sub-Neptune grows from 2.1 to 2.6 R⊕, following ${R}_{p}\propto {M}_{\star }^{\alpha }$ with α = 0.25 ± 0.03. In contrast, there is no detectable change for super-Earths. These M⋆–Rp trends suggest that protoplanetary disks can efficiently produce cores up to a threshold mass of Mc, which grows linearly with stellar mass according to Mc ≈ 10 M⊕(M⋆/M⊙). There is no significant correlation between sub-Neptune size and stellar metallicity (over −0.5 to +0.5 dex), suggesting a weak relationship between planet envelope opacity and stellar metallicity. Finally, there is no significant variation in sub-Neptune size with stellar age (over 1–10 Gyr), which suggests that the majority of envelope contraction concludes after ∼1 Gyr

Sorting of chromosomes by magnetic separation

Chromosomes were isolated from Chinese hamster x human hybrid cell lines containing four and nine human chromosomes. Human genomic DNA was biotinylated by nick translation and used to label the human chromosomes by in situ hybridization in suspension. Streptavidin was covalently coupled to the surface of magnetic beads and these were incubated with the hybridized chromosomes. The human chromosomes were bound to the magnetic beads through the strong biotin-streptavidin complex and then rapidly separated from nonlabeled Chinese hamster chromosomes by a simple permanent magnet. The hybridization was visualized by additional binding of avidin-FITC (fluorescein) to the unoccupied biotinylated human DNA bound to the human chromosomes. After magnetic separation, up to 98% of the individual chromosomes attached to magnetic beads were classified as human chromosomes by fluorescence microscopy

Narratives of self and identity in women's prisons: stigma and the struggle for self-definition in penal regimes

A concern with questions of selfhood and identity has been central to penal practices in women's prisons, and to the sociology of women's imprisonment. Studies of women's prisons have remained preoccupied with women prisoners’ social identities, and their apparent tendency to adapt to imprisonment through relationships. This article explores the narratives of women in two English prisons to demonstrate the importance of the self as a site of meaning for prisoners and the central place of identity in micro-level power negotiations in prisons