A public health approach to understanding and preventing violent radicalization

<p>Abstract</p> <p>Background</p> <p>Very recent acts of terrorism in the UK were perpetrated by 'homegrown', well educated young people, rather than by foreign Islamist groups; consequently, a process of violent radicalization was proposed to explain how ordinary people were recruited and persuaded to sacrifice their lives.</p> <p>Discussion</p> <p>Counterterrorism approaches grounded in the criminal justice system have not prevented violent radicalization. Indeed there is some evidence that these approaches may have encouraged membership of radical groups by not recognizing Muslim communities as allies, citizens, victims of terrorism, and victims of discrimination, but only as suspect communities who were then further alienated. Informed by public health research and practice, a new approach is proposed to target populations vulnerable to recruitment, rather than rely only on research of well known terrorist groups and individual perpetrators of terrorist acts.</p> <p>Conclusions</p> <p>This paper proposes public health research and practice to guard against violent radicalization.</p

A statistical framework for assessing pharmacological responses and biomarkers using uncertainty estimates

High-throughput testing of drugs across molecular-characterised cell lines can identify candidate treatments and discover biomarkers. However, the cells’ response to a drug is typically quantified by a summary statistic from a best-fit dose-response curve, whilst neglecting the uncertainty of the curve fit and the potential variability in the raw readouts. Here, we model the experimental variance using Gaussian Processes, and subsequently, leverage uncertainty estimates to identify associated biomarkers with a new Bayesian framework. Applied to in vitro screening data on 265 compounds across 1074 cancer cell lines, our models identified 24 clinically established drug-response biomarkers, and provided evidence for six novel biomarkers by accounting for association with low uncertainty. We validated our uncertainty estimates with an additional drug screen of 26 drugs, 10 cell lines with 8 to 9 replicates. Our method is applicable to any dose-response data without replicates, and improves biomarker discovery for precision medicine

Phenotype Enhancement Screen of a Regulatory spx Mutant Unveils a Role for the ytpQ Gene in the Control of Iron Homeostasis

Spx is a global regulator of genes that are induced by disulfide stress in Bacillus subtilis. The regulon that it governs is comprised of over 120 genes based on microarray analysis, although it is not known how many of these are under direct Spx control. Most of the Spx-regulated genes (SRGs) are of unknown function, but many encode products that are conserved in low %GC Gram-positive bacteria. Using a gene-disruption library of B. subtilis genomic mutations, the SRGs were screened for phenotypes related to Spx-controlled activities, such as poor growth in minimal medium and sensitivity to methyglyoxal, but nearly all of the SRG mutations showed little if any phenotype. To uncover SRG function, the mutations were rescreened in an spx mutant background to determine which mutant SRG allele would enhance the spx mutant phenotype. One of the SRGs, ytpQ was the site of a mutation that, when combined with an spx null mutation, elevated the severity of the Spx mutant phenotype, as shown by reduced growth in a minimal medium and by hypersensitivity to methyglyoxal. The ytpQ mutant showed elevated oxidative protein damage when exposed to methylglyoxal, and reduced growth rate in liquid culture. Proteomic and transcriptomic data indicated that the ytpQ mutation caused the derepression of the Fur and PerR regulons of B. subtilis. Our study suggests that the ytpQ gene, encoding a conserved DUF1444 protein, functions directly or indirectly in iron homeostasis. The ytpQ mutant phenotype mimics that of a fur mutation, suggesting a condition of low cellular iron. In vitro transcription analysis indicated that Spx stimulates transcription from the ytpPQR operon within which the ytpQ gene resides. The work uncovers a link between Spx and control of iron homeostasis

The green box: an electronically versatile perylene diimide macrocyclic host for fullerenes

The powerful electron accepting ability of fullerenes makes them ubiquitous components in biomimetic donor-acceptor systems that model the intermolecular electron transfer processes of Nature's photosynthetic centre. Exploiting perylene diimides (PDIs) as components in cyclic host systems for the non-covalent recognition of fullerenes is unprecedented, in part because archetypal PDIs are also electron deficient, making dyad assembly formation electronically unfavourable. To address this, we report the strategic design and synthesis of a novel large, macrocyclic receptor comprised of two covalently strapped electron-rich bis-pyrrolidine PDI panels, nicknamed the "Green Box" due to its colour. Through the principle of electronic complementarity, the Green Box exhibits strong recognition of pristine fullerenes (C60/70), with the non-covalent ground and excited state interactions that occur upon fullerene guest encapsulation characterised by a range of techniques including electronic absorption, fluorescence emission, NMR and time-resolved EPR spectroscopies, cyclic voltammetry, mass spectrometry and DFT calculations. Whilst relatively low polarity solvents result in partial charge transfer in the host donor-guest acceptor complex, increasing the polarity of the solvent medium facilitates rare, thermally allowed full electron transfer from Green Box to fullerene in the ground state. The ensuing charge separated radical ion paired complex is spectroscopically characterised, with thermodynamic reversibility and kinetic stability also demonstrated. Importantly, the Green Box represents a seminal type of C60/70 host where electron-rich PDI motifs are utilised as recognition motifs for fullerenes, facilitating novel intermolecular, solvent tuneable ground state electronic communication with these guests. The ability to switch between extremes of the charge transfer energy continuum is without precedent in synthetic fullerene-based dyads

Reputational Risk, Academic Freedom and Research Ethics Review

Drawing on scholarship around academic freedom and new public management, this article explores the way in which research ethics committees in UK universities (URECs) can come to exhibit behaviour – common in their US equivalents – that prioritises the reputational protection of their host institution over and above academic freedom and the protection of research subjects. Drawing on two case studies the article shows both how URECs can serve to restrict research that may be ‘embarrassing’ for a university and how, in high profile cases, university management come to use such committees as mechanisms for internal discipline