Production of alkenes and novel secondary products by P450 OleT JE using novel H2O2-generating fusion protein systems

Jeotgalicoccus sp. 8456 OleTJE (CYP152L1) is a fatty acid decarboxylase cytochrome P450 that uses hydrogen peroxide (H2O2) to catalyse production of terminal alkenes, which are industrially important chemicals with biofuel applications. We report enzyme fusion systems in which Streptomyces coelicolor alditol oxidase (AldO) is linked to OleTJE. AldO oxidizes polyols (including glycerol), generating H2O2 as a co-product and facilitating its use for efficient OleTJE-dependent fatty acid decarboxylation. AldO activity is regulatable by polyol substrate titration, enabling control over H2O2 supply to minimise oxidative inactivation of OleTJE and prolong activity for increased alkene production. We also use these fusion systems to generate novel products from secondary turnover of 2-OH and 3-OH myristic acid primary products, expanding the catalytic repertoire of OleTJE

Development and validation of a NanoString BASE47 bladder cancer gene classifier

Background Recent molecular characterization of urothelial cancer (UC) has suggested potential pathways in which to direct treatment, leading to a host of targeted therapies in development for UC. In parallel, gene expression profiling has demonstrated that high-grade UC is a heterogeneous disease. Prognostic basal-like and luminal-like subtypes have been identified and an accurate transcriptome BASE47 classifier has been developed. However, these phenotypes cannot be broadly investigated due to the lack of a clinically viable diagnostic assay. We sought to develop and evaluate a diagnostic classifier of UC subtype with the goal of accurate classification from clinically available specimens. Methods Tumor samples from 52 patients with high-grade UC were profiled for BASE47 genes concurrently by RNAseq as well as NanoString. After design and technical validation of a BASE47 NanoString probeset, results from the RNAseq and NanoString were used to translate diagnostic criteria to the Nanostring platform. Evaluation of repeatability and accuracy was performed to derive a final Nanostring based classifier. Diagnostic classification resulting from the NanoString BASE47 classifier was validated on an independent dataset (n = 30). The training and validation datasets accurately classified 87% and 93% of samples, respectively. Results Here we have derived a NanoString-platform BASE47 classifier that accurately predicts basal-like and luminal-like subtypes in high grade urothelial cancer. We have further validated our new NanoString BASE47 classifier on an independent dataset and confirmed high accuracy when compared with our original Transcriptome BASE47 classifier. Conclusions The NanoString BASE47 classifier provides a faster turnaround time, a lower cost per sample to process, and maintains the accuracy of the original subtype classifier for better clinical implementation

Fabrication of photonic crystals in rare-earth doped chalcogenide glass films for enhanced upconversion

Gallium lanthanum oxysulfide (GLSO) is a promising host material for observing strong upconversion emission from trivalent rare-earth ions such as erbium (Er3+). Its attractive properties include high rare-earth solubility due to the lanthanum content of the glass former, a high refractive index (n = 2.2 at 550nm) for high radiative efficiency, and a low maximum phonon energy of approximately 425cm-1. Photonic crystals meanwhile can provide controlled light extraction, and may be capable of suppressing unwanted IR emission from lower lying metastable states. Here, we describe the fabrication of photonic crystals in annealed films of Er3+-doped GLSO deposited by RF sputtering. The most intense visible upconversion emission is observed in films annealed at 550°C, close to the bulk glass transition temperature. Hexagonal lattice photonic crystals are subsequently milled into the films using a focused ion beam (FIB). The milling parameters are optimized to produce the most vertical sidewall profile

Utility of TERT Promoter Mutations for Cutaneous Primary Melanoma Diagnosis

Telomerase reverse transcriptase (TERT) promoter mutations are commonly found in malignant melanomas but rare in melanocytic nevi. To assess its potential diagnostic utility for the distinction of melanoma from nevus, we determined the TERT promoter mutation status of 86 primary melanomas, 72 melanocytic nevi, and 40 diagnostically problematic melanocytic proliferations. Of the 86 melanomas, 67 (77.9%) were TERT-positive, defined as harboring a hotspot TERT promoter mutation at positions -124C>T, -124_125CC>TT, -138_139CC>TT, or -146C>T. Of the 72 nevi, only 1 (1.4%) was TERT-positive. Of the 40 diagnostically uncertain melanocytic proliferations, 2 (5.0%) were TERT-positive. TERT positivity as a test for melanoma versus nevus had an accuracy of 87.3% [95% confidence interval (CI), 81.1-92.1], a sensitivity of 77.9% (95% CI, 68.9-85.4), a specificity of 98.6% (95% CI, 95.8-100), a positive predictive value of 98.5% (95% CI, 95.6-100), and a negative predictive value of 78.9% (95% CI, 72.6-85.4). Our results indicate that hotspot TERT promoter mutation status may be a useful ancillary parameter for the diagnosis of melanoma. In particular, the high specificity of these mutations for melanoma indicates the presence of a TERT promoter mutation in a melanocytic neoplasm associated with diagnostic controversy, or uncertainty should increase concern for a melanoma

Simulations of galactic dynamos

We review our current understanding of galactic dynamo theory, paying particular attention to numerical simulations both of the mean-field equations and the original three-dimensional equations relevant to describing the magnetic field evolution for a turbulent flow. We emphasize the theoretical difficulties in explaining non-axisymmetric magnetic fields in galaxies and discuss the observational basis for such results in terms of rotation measure analysis. Next, we discuss nonlinear theory, the role of magnetic helicity conservation and magnetic helicity fluxes. This leads to the possibility that galactic magnetic fields may be bi-helical, with opposite signs of helicity and large and small length scales. We discuss their observational signatures and close by discussing the possibilities of explaining the origin of primordial magnetic fields.Comment: 28 pages, 15 figure, to appear in Lecture Notes in Physics "Magnetic fields in diffuse media", Eds. E. de Gouveia Dal Pino and A. Lazaria

The boomerang effect of radicalism in Discursive Psychology: A critical overview of the controversy with the Social Representations Theory.

This article provides a critical overview of the controversy between the Radical approach to Discursive Psychology (RDP) and the Social Representations Theory (SRT) and aims: a)?to show what is potentially complementary and contradictory in Discursive Psychology (DP) and the Social Representations Theory, when and why they are incompatible, and whether and how it is possible and/or desirable to integrate these two approaches. b)?to describe how the radicalism of the socio-constructionist thesis upheld by Discourse Analysis can give rise to several hard-to-solve problems, which may then be translated into a boomerang effect. In the final section, it highlights interest in dialog and “cross-fertilization” between researchers inspired by the less radical approach to discursive psychology and those inspired by the Social Representations Theory, pointing out the effect of methodological implications that would ensue

Effects of solute Nb atoms and Nb precipitates on isothermal transformation kinetics from austenite to ferrite

Nb is a very important micro-alloying element in low-carbon steels, for grain size refinement and precipitation strengthening, and even a low content of Nb can result in a significant effect on phase transformation kinetics from austenite to ferrite. Solute Nb atoms and Nb precipitates may have different effects on transformation behaviors, and these effects have not yet been fully characterized. This paper examines in detail the effects of solute Nb atoms and Nb precipitates on isothermal transformation kinetics from austenite to ferrite. The mechanisms of the effects have been analyzed using various microscopy techniques. Many solute Nb atoms were found to be segregated at the austenite/ferrite interface and apply a solute drag effect. It has been found that solute Nb atoms have a retardation effect on ferrite nucleation rate and ferrite grain growth rate. The particle pinning effect caused by Nb precipitates is much weaker than the solute drag effect

A new measurement of direct CP violation in two pion decays of the neutral kaon

The NA48 experiment at CERN has performed a new measurement of direct CP violation, based on data taken in 1997 by simultaneously collecting K_L and K_S decays into pi0pi0 and pi+pi-. The result for the CP violating parameter Re(epsilon'/epsilon) is (18.5 +/- 4.5(stat)} +/- 5.8 (syst))x10^{-4}.Comment: 18 pages, 6 figure

Affecting qualitative health psychology

The ‘affective turn’ is a contemporary movement within the humanities, social science and psychology to investigate affect, emotion and feeling as hybrid phenomena jointly constituted from both biological and social influences. Health and illness are themselves jointly constituted in this way, and many of the topics, concerns and methods of health psychology are strongly permeated by affective phenomena. Qualitative research in health psychology might therefore benefit by engaging with this work. This paper describes some features of the affective turn, and suggests theories, terminology and methods that might be useful