An improved single-step lysis protocol to measure luciferase bioluminescence in Plasmodium falciparum

This report describes the optimization and evaluation of a simple single-step lysis protocol to measure luciferase bioluminescence from genetically modified Plasmodium falciparum. This protocol utilizes a modified commercial buffer to improve speed of assay and consistency in the bioluminescence signal measured by reducing the manipulation steps required to release the cytoplasmic fraction. The utility of this improved assay protocol is demonstrated in typical assays that explore absolute and temporal gene expression activity

Illuminating the Effect of the Local Environment on the Performance of Organic Sunscreens : Insights From Laser Spectroscopy of Isolated Molecules and Complexes

Sunscreens are essential for protecting the skin from UV radiation, but significant questions remain about the fundamental molecular-level processes by which they operate. In this mini review, we provide an overview of recent advanced laser spectroscopic studies that have probed how the local, chemical environment of an organic sunscreen affects its performance. We highlight experiments where UV laser spectroscopy has been performed on isolated gas-phase sunscreen molecules and complexes. These experiments reveal how pH, alkali metal cation binding, and solvation perturb the geometric and hence electronic structures of sunscreen molecules, and hence their non-radiative decay pathways. A better understanding of how these interactions impact on the performance of individual sunscreens will inform the rational design of future sunscreens and their optimum formulations

Sodium cationization can disrupt the intramolecular hydrogen bond that mediates the sunscreen activity of oxybenzone

A key decay pathway by which organic sunscreen molecules dissipate harmful UV energy involves excited-state hydrogen atom transfer between proximal enol and keto functional groups. Structural modifications of this molecular architecture have the potential to block ultrafast decay processes, and hence promote direct excited-state molecular dissociation, profoundly affecting the efficiency of an organic sunscreen. Herein, we investigate the binding of alkali metal cations to a prototype organic sunscreen molecule, oxybenzone, using IR characterization. Mass-selective IR action spectroscopy was conducted at the free electron laser for infrared experiments, FELIX (600-1800 cm-1), on complexes of Na+, K+ and Rb+ bound to oxybenzone. The IR spectra reveal that K+ and Rb+ adopt binding positions away from the key OH intermolecular hydrogen bond, while the smaller Na+ cation binds directly between the keto and enol oxygens, thus breaking the intramolecular hydrogen bond. UV laser photodissociation spectroscopy was also performed on the series of complexes, with the Na+ complex displaying a distinctive electronic spectrum compared to those of K+ and Rb+, in line with the IR spectroscopy results. TD-DFT calculations reveal that the origin of the changes in the electronic spectra can be linked to rupture of the intramolecular bond in the sodium cationized complex. The implications of our results for the performance of sunscreens in mixtures and environments with high concentrations of metal cations are discussed

Thermal and ground-state entanglement in Heisenberg XX qubit rings

We study the entanglement of thermal and ground states in Heisernberg $XX$ qubit rings with a magnetic field. A general result is found that for even-number rings pairwise entanglement between nearest-neighbor qubits is independent on both the sign of exchange interaction constants and the sign of magnetic fields. As an example we study the entanglement in the four-qubit model and find that the ground state of this model without magnetic fields is shown to be a four-body maximally entangled state measured by the $N$-tangle.Comment: Four pages and one figure, small change

Photochemical Degradation of the UV Filter Octyl Methoxy Cinnamate Probed via Laser-Interfaced Mass Spectrometry

Octyl methoxycinnamate (OMC) is a common UVA and UVB filter molecule that is widely used in commercial sunscreens. Here, we used gas-phase laser photodissociation spectroscopy to characterise the intrinsic photostability and photodegradation products of OMC by studying the system in its protonated form, i.e., [OMC·H]+. The major photofragments observed were m/z 179, 161, and 133, corresponding to fragmentation on either side of the ether oxygen of the ester group (m/z 179 and 161) or the C–C bond adjacent to the ester carbonyl group. Additional measurements were obtained using higher-energy collisional dissociation mass spectrometry (HCD-MS) to identify fragments that resulted from the breakdown of the vibrationally hot electronic ground state. We found that the m/z 179 and 161 ions were the main fragments produced by this route. Notably, the m/z 133 ion was not observed through HCD-MS, revealing that this product ion is only produced through a photochemical route. Our results demonstrate that UV photoexcitation of OMC is able to access a dissociative excited-state surface that uniquely leads to the rupture of the C–C bond adjacent to the key ester carbonyl group

Laser Interfaced Mass Spectrometry of the Sunscreen Molecule Octocrylene Demonstrates that Protonation Does Not Impact Photostability

Octocrylene (OCR) is a widely used organic sunscreen molecules, and is a dominant component of many sunscreen formulations. Here, we perform the first measurements on the protonated form of OCR, i. e. [OCR+H]+, to probe whether protonation affects the molecule's photostability. The novel photochemical technique of UV laser-interfaced mass spectrometry is employed from 400–216 nm, revealing that the electronic absorption spectrum of OCR across the S1 and S2 states red shift by 40 nm upon protonation. Our measurements reveal that [OCR+H]+ predominantly undergoes photofragmentation into the m/z 250 and 232 ionic products, associated with loss of its bulky alkyl side chain, and subsequent loss of water, respectively. We compare the photochemical fragmentation results with higher-energy collisional dissociation results to investigate the nature of the photodynamics that occur following UV absorption. The excited state decay pathways over the S1 and S2 excited states of [OCR+H]+ are associated with statistical fragmentation in line with dominant ultrafast decay. This behaviour mirrors that of neutral OCR, demonstrating that protonation does not affect the ultrafast decay pathways of this sunscreen molecule. We discuss our results in the context of the known breakdown of OCR into benzophenone, identifying a potential photoactivated pathway to benzophenone formation in solution

Quantifying the combined effects of multiple extreme floods on river channel geometry and on flood hazards

Effects of flood-induced bed elevation and channel geometry changes on flood hazards are largely unexplored, especially in the case of multiple floods from the same site. This study quantified the evolution of river channel and floodplain geometry during a repeated series of hypothetical extreme floods using a 2D full hydro-morphodynamic model (LHMM). These experiments were designed to examine the consequences of channel geometry changes on channel conveyance capacity and subsequent flood dynamics. Our results revealed that extreme floods play an important role in adjusting a river channel to become more efficient for subsequent propagation of floods, and that in-channel scour and sediment re-distribution can greatly improve the conveyance capacity of a channel for subsequent floods. In our hypothetical sequence of floods the response of bed elevation was of net degradation, and sediment transport successively weakened even with floods of the same magnitude. Changes in river channel geometry led to significant impact on flood hydraulics and thereby flood hazards. We found that flood-induced in-channel erosion can disconnect the channel from its floodplain resulting in a reduction of floodwater storage. Thus, the frequency and extent of subsequent overbank flows and floodplain inundation decreased, which reduced downstream flood attenuation and increased downstream flood hazard. In combination and in summary, these results suggest that changes in channel capacity due to extreme floods may drive changes in flood hazard. The assumption of unchanging of river morphology during inundation modelling should therefore be open to question for flood risk management

MRI vastus lateralis fat fraction predicts loss of ambulation in Duchenne muscular dystrophy

ObjectiveWe studied the potential of quantitative MRI (qMRI) as a surrogate endpoint in Duchennemuscular dystrophy by assessing the additive predictive value of vastus lateralis (VL) fat fraction(FF) to age on loss of ambulation (LoA).MethodsVL FFs were determined on longitudinal Dixon MRI scans from 2 natural history studies inLeiden University Medical Center (LUMC) and Cincinnati Children’s Hospital MedicalCenter (CCHMC). CCHMC included ambulant patients, while LUMC included a mixedambulant and nonambulant population. We fitted longitudinal VL FF values to a sigmoidalcurve using a mixed model with random slope to predict individual trajectories. The additivevalue of VL FF over age to predict LoA was calculated from a Cox model, yielding a hazard ratio.ResultsEighty-nine MRIs of 19 LUMC and 15 CCHMC patients were included. At similar age,6-minute walking test distances were smaller and VL FFs were correspondingly higher inLUMC compared to CCHMC patients. Hazard ratio of a percent-point increase in VL FF forthe time to LoA was 1.15 for LUMC (95% confidence interval [CI] 1.05–1.26; p = 0.003) and0.96 for CCHMC (95% CI 0.84–1.10; p = 0.569).ConclusionsThe hazard ratio of 1.15 corresponds to a 4.11-fold increase of the instantaneous risk of LoA inpatients with a 10% higher VL FF at any age. Although results should be confirmed in a largercohort with prospective determination of the clinical endpoint, this added predictive value ofVL FF to age on LoA supports the use of qMRI FF as an endpoint or stratification tool inclinical trials.Development and application of statistical models for medical scientific researc

Incidence and outcome of acquired demyelinating syndromes in Dutch children: update of a nationwide and prospective study

Introduction: Acquired demyelinating syndromes (ADS) are immune-mediated demyelinating disorders of the central nervous system in children. A nationwide, multicentre and prospective cohort study was initiated in the Netherlands in 2006, with a reported ADS incidence of 0.66/100,000 per year and MS incidence of 0.15/100,000 per year in the period between 2007 and 2010. In this study, we provide an update on the incidence and the long-term follow-up of ADS in the Netherlands. Methods: Children < 18 years with a first attack of demyelination were included consecutively from January 2006 to December 2016. Diagnoses were based on the International Paediatric MS study group consensus criteria. Outcome data were collected by neurological and neuropsychological assessments, and telephone call assessments. Results: Between 2011 and 2016, 55/165 of the ADS patients were diagnosed with MS (33%). This resulted in an increased ADS and MS incidence of 0.80/100,000 per year and 0.26/100,000 per year, respectively. Since 2006 a total of 243 ADS patients have been included. During follow-up (median 55 months, IQR 28–84), 137 patients were diagnosed with monophasic disease (56%), 89 with MS (37%) and 17 with multiphasic disease other than MS (7%). At least one form of residual deficit including cognitive impairment was observed in 69% of all ADS patients, even in monophasic ADS. An Expanded Disability Status Scale score of ≥ 5.5 was reached in 3/89 MS patients (3%). Conclusion: The reported incidence of ADS in Dutch children has increased since 2010. Residual deficits are common in this group, even in monophasic patients. Therefore, long-term follow-up in ADS patients is warranted

Reorientation-effect measurement of the first 2+ state in 12C : Confirmation of oblate deformation

A Coulomb-excitation reorientation-effect measurement using the TIGRESS γ−ray spectrometer at the TRIUMF/ISAC II facility has permitted the determination of the 〈21 +‖E2ˆ‖21 +〉 diagonal matrix element in 12C from particle−γ coincidence data and state-of-the-art no-core shell model calculations of the nuclear polarizability. The nuclear polarizability for the ground and first-excited (21 +) states in 12C have been calculated using chiral NN N4LO500 and NN+3NF350 interactions, which show convergence and agreement with photo-absorption cross-section data. Predictions show a change in the nuclear polarizability with a substantial increase between the ground state and first excited 21 + state at 4.439 MeV. The polarizability of the 21 + state is introduced into the current and previous Coulomb-excitation reorientation-effect analyses of 12C. Spectroscopic quadrupole moments of QS(21 +)=+0.053(44) eb and QS(21 +)=+0.08(3) eb are determined, respectively, yielding a weighted average of QS(21 +)=+0.071(25) eb, in agreement with recent ab initio calculations. The present measurement confirms that the 21 + state of 12C is oblate and emphasizes the important role played by the nuclear polarizability in Coulomb-excitation studies of light nuclei