Extreme-Ultraviolet-Initated High-Order Harmonic Generation: Driving Inner-Valence Electrons Using Below-Threshold-Energy Extreme-Ultraviolet Light

We propose a novel scheme for resolving the contribution of inner- and outer-valence electrons in XUV-initiated high-harmonic generation in neon. By probing the atom with a low energy (below the 2s ionisation threshold) ultrashort XUV pulse, the 2p electron is steered away from the core, while the 2s electron is enabled to describe recollision trajectories. By selectively suppressing the 2p recollision trajectories we can resolve the contribution of the 2s electron to the high-harmonic spectrum. We apply the classical trajectory model to account for the contribution of the 2s electron, which allows for an intuitive understanding of the process.

Noncollinear Polarization Gating of Attosecond Pulse Trains in the Relativistic Regime

High order harmonics generated at relativistic intensities have long been recognized as a route to the most powerful extreme ultraviolet pulses. Reliably generating isolated attosecond pulses requires gating to only a single dominant optical cycle, but techniques developed for lower power lasers have not been readily transferable. We present a novel method to temporally gate attosecond pulse trains by combining noncollinear and polarization gating. This scheme uses a split beam configuration which allows pulse gating to be implemented at the high beam fluence typical of multi-TW to PW class laser systems. Scalings for the gate width demonstrate that isolated attosecond pulses are possible even for modest pulse durations achievable for existing and planned future ultrashort high-power laser systems. Experimental results demonstrating the spectral effects of temporal gating on harmonic spectra generated by a relativistic laser plasma interaction are shown.

How curvature-generating proteins build scaffolds on membrane nanotubes

Bin/Amphiphysin/Rvs (BAR) domain proteins control the curvature of lipid membranes in endocytosis, trafficking, cell motility, the formation of complex sub-cellular structures, and many other cellular phenomena. They form three-dimensional assemblies, which act as molecular scaffolds to reshape the membrane and alter its mechanical properties. It is unknown, however, how a protein scaffold forms and how BAR domains interact in these assemblies at protein densities relevant for a cell. In this work, we employ various experimental, theoretical and simulation approaches to explore how BAR proteins organize to form a scaffold on a membrane nanotube. By combining quantitative microscopy with analytical modeling, we demonstrate that a highly curving BAR protein endophilin nucleates its scaffolds at the ends of a membrane tube, contrary to a weaker curving protein centaurin, which binds evenly along the tube’s length. Our work implies that the nature of local protein-membrane interactions can affect the specific localization of proteins on membrane-remodeling sites. Furthermore, we show that amphipathic helices are dispensable in forming protein scaffolds. Finally, we explore a possible molecular structure of a BAR-domain scaffold using coarse-grained molecular dynamics simulations. Together with fluorescence microscopy, the simulations show that proteins need only to cover 30–40% of a tube’s surface to form a rigid assembly. Our work provides mechanical and structural insights into the way BAR proteins may sculpt the membrane as a high-order cooperative assembly in important biological processes. 

Inter-Laboratory Evaluation of a Next-Generation Sequencing Panel for Acute Myeloid Leukemia

INTRODUCTION: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder often associated with dismal overall survival. The clinical diversity of AML is reflected in the range of recurrent somatic mutations in several genes, many of which have a prognostic and therapeutic value. Targeted next-generation sequencing (NGS) of these genes has the potential for translation into clinical practice. In order to assess this potential, an inter-laboratory evaluation of a commercially available AML gene panel across three diagnostic centres in the UK and Ireland was performed.

METHODS: DNA from six AML patient samples was distributed to each centre and processed using a standardised workflow, including a common sequencing platform, sequencing chips and bioinformatics pipeline. A duplicate sample in each centre was run to assess inter- and intra-laboratory performance.

RESULTS: An average sample read depth of 2725X (range 629-5600) was achieved using six samples per chip, with some variability observed in the depth of coverage generated for individual samples and between centres. A total of 16 somatic mutations were detected in the six AML samples, with a mean of 2.7 mutations per sample (range 1-4) representing nine genes on the panel. 15/16 mutations were identified by all three centres. Allelic frequencies of the mutations ranged from 5.6 to 53.3 % (median 44.4 %), with a high level of concordance of these frequencies between centres, for mutations detected.

CONCLUSION: In this inter-laboratory comparison, a high concordance, reproducibility and robustness was demonstrated using a commercially available NGS AML gene panel and platform.

The mental health and wellbeing of first generation migrants: a systematic-narrative review of reviews

Background
First generation migrants are reportedly at higher risk of mental ill-health compared to the settled population. This paper systematically reviews and synthesizes all reviews on the mental health of first generation migrants in order to appraise the risk factors for, and explain differences in, the mental health of this population.
Methods
Scientific databases were searched for systematic reviews (inception-November 2015) which provided quantitative data on the mental ill-health of first generation migrants and associated risk factors. Two reviewers screened titles, abstracts and full text papers for their suitability against pre-specified criteria, methodological quality was assessed.
Results
One thousand eight hundred twenty articles were identified, eight met inclusion criteria, which were all moderate or low quality. Depression was mostly higher in first generation migrants in general, and in refugees/asylum seekers when analysed separately. However, for both groups there was wide variation in prevalence rates, from 5 to 44 % compared with prevalence rates of 8–12 % in the general population. Post-Traumatic Stress Disorder prevalence was higher for both first generation migrants in general and for refugees/asylum seekers compared with the settled majority. Post-Traumatic Stress Disorder prevalence in first generation migrants in general and refugees/ asylum seekers ranged from 9 to 36 % compared with reported prevalence rates of 1–2 % in the general population. Few studies presented anxiety prevalence rates in first generation migrants and there was wide variation in those that did. Prevalence ranged from 4 to 40 % compared with reported prevalence of 5 % in the general population. Two reviews assessed the psychotic disorder risk, reporting this was two to three times more likely in adult first generation migrants. However, one review on the risk of schizophrenia in refugees reported similar prevalence rates (2 %) to estimates of prevalence among the settled majority (3 %). Risk factors for mental ill-health included low Gross National Product in the host country, downward social mobility, country of origin, and host country.
Conclusion
First generation migrants may be at increased risk of mental illness and public health policy must account for this and influencing factors. High quality research in the area is urgently needed as is the use of culturally specific validated measurement tools for assessing migrant mental health.