Design of a horizontal neutron reflectometer for the European Spallation Source

A design study of a horizontal neutron reflectometer adapted to the general baseline of the long pulse European Spallation Source (ESS) is presented. The instrument layout comprises solutions for the neutron guide, high-resolution pulse shaping and beam bending onto a sample surface being so far unique in the field of reflectometry. The length of this instrument is roughly 55 m, enabling $\delta \lambda / \lambda$ resolutions from 0.5% to 10%. The incident beam is focussed in horizontal plane to boost measurements of sample sizes of 1*1 cm{^2} and smaller with potential beam deflection in both downward and upward direction. The range of neutron wavelengths untilized by the instrument is 2 to 7.1 (12.2, ...) {\AA}, if every (second, ...) neutron source ulse is used. Angles of incidence can be set between 0{\deg} and 9{\deg} with a total accessible q-range from 4*10^{-3} {\AA}^{-1} up to 1 {\AA}^{-1}. The instrument operates both in {\theta}/{\theta} (free liquid surfaces) and {\theta}/2{\theta} (solid/liquid, air/solid interfaces) geometry. The experimental setup will in particular enable direct studies on ultrathin films (d ~ 10 {\AA}) and buried monolayers to multilayered structures of up to 3000 {\AA} total thickness. The horizontal reflectometer will further foster investigations of hierarchical systems from nanometer to micrometer length scale, as well as their kinetics and dynamical properties, in particular under load (shear, pressure, external fields). Polarization and polarization analysis as well as the GISANS option are designed as potential modules to be implemented separately in the generic instrument layout. The instrument is highly flexible and offers a variety of different measurement modes. With respect to its mechanical components the instrument is exclusively based on current technology. Risks of failure for the chosen setup are minimum.Comment: Matched to the version submitted to Nuclear Instruments and Methods

Tri-snRNP-associated proteins interact with subunits of the TRAMP and nuclear exosome complexes, linking RNA decay and pre-mRNA splicing

Nuclear RNA decay factors are involved in many different pathways including rRNA processing, snRNA and snoRNA biogenesis, pre-mRNA processing, and the rapid decay of cryptic intergenic transcripts. In contrast to its yeast counterpart, the mammalian nuclear decay machinery is largely uncharacterized. Here we report interactions of several putative components of the human nuclear RNA decay machinery, including the TRAMP complex protein Mtr4 and the nuclear exosome constituents PM/Scl-100 and PM/Scl-75, with components of the U4/U6.U5 tri-snRNP complex required for pre-mRNA splicing. The tri-snRNP component Prp31 interacts indirectly with Mtr4 and PM/Scl-100 in a manner that is dependent on the phosphorylation sites in the middle of the protein, while Prp3 and Prp4 interact with the nuclear decay complex independent of Prp31. Together our results suggest recruitment of the nuclear decay machinery to the spliceosome to ensure production of properly spliced mRNA

On the Explanation of the Paramagnetic Meissner Effect in Superconductor/Ferromagnet Heterostructures

An increase of the magnetic moment in superconductor/ferromagnet (S/F) bilayers V(40nm)/F [F$=$Fe(1,3nm), Co(3nm), Ni(3nm)] was observed using SQUID magnetometry upon cooling below the superconducting transition temperature Tc in magnetic fields of 10 Oe to 50 Oe applied parallel to the sample surface. A similar increase, often called the paramagnetic Meissner effect (PME), was observed before in various superconductors and superconductor/ferromagnet systems. To explain the PME effect in the presented S/F bilayers a model based on a row of vortices located at the S/F interface is proposed. According to the model the magnetic moment induced below Tc consists of the paramagnetic contribution of the vortex cores and the diamagnetic contribution of the vortex-free region of the S layer. Since the thickness of the S layer is found to be 3-4 times less than the magnetic field penetration depth, this latter diamagnetic contribution is negligible. The model correctly accounts for the sign, the approximate magnitude and the field dependence of the paramagnetic and the Meissner contributions of the induced magnetic moment upon passing the superconducting transition of a ferromagnet/superconductor bilayer

Volume-rendered optical coherence tomography angiography during ocular interventions: Advocating for noninvasive intraoperative retinal perfusion monitoring.

We aimed to test for feasibility of volume-rendered optical coherence tomography angiography (OCTA) as a novel method for assessing/quantifying retinal vasculature during ocular procedures and to explore the potential for intraoperative use. Thirty patients undergoing periocular anaesthesia were enrolled, since published evidence suggests a reduction in ocular blood flow. Retinal perfusion was monitored based on planar OCTA image-derived data provided by a standard quantification algorithm and postprocessed/volume-rendered OCTA data using a custom software script. Overall, imaging procedures were successful, yet imaging artifacts occurred frequently. In interventional eyes, perfusion parameters decreased during anaesthesia. Planar image-derived and volume rendering-derived parameters were correlated. No correlation was found between perfusion parameters and a motion artifact score developed for this study, yet all perfusion parameters correlated with signal strength as displayed by the device. Concluding, volume-rendered OCTA allows for noninvasive three-dimensional retinal vasculature assessment/quantification in challenging surgical settings and appears generally feasible for intraoperative use

Structure and Function of a Mycobacterial NHEJ DNA Repair Polymerase

Non homologous end-joining (NHEJ)-mediated repair of DNA double-strand breaks in prokaryotes requires Ku and a specific multidomain DNA ligase (LigD). We present crystal structures of the primase/polymerisation domain (PolDom) of Mycobacterium tuberculosis LigD, alone and complexed with nucleotides. The PolDom structure combines the general fold of the archaeo-eukaryotic primase (AEP) superfamily with additional loops and domains that together form a deep cleft on the surface, likely used for DNA binding. Enzymatic analysis indicates that the PolDom of LigD, even in the absence of accessory domains and Ku proteins, has the potential to recognise DNA end-joining intermediates. Strikingly, one of the main signals for the specific and efficient binding of PolDom to DNA is the presence of a 5'-phosphate group, located at the single/double-stranded junction at both gapped and 3'-protruding DNA molecules. Although structurally unrelated, Pol lambda and Pol mu, the two eukaryotic DNA polymerases involved in NHEJ, are endowed with a similar capacity to bind a 5'-phosphate group. Other properties that are beneficial for NHEJ, such as the ability to generate template distortions and realignments of the primer, displayed by Pol lambda and Pol mu, are shared by the PolDom of bacterial LigD. In addition, PolDom can perform non-mutagenic translesion synthesis on termini containing modified bases. Significantly, ribonucleotide insertion appears to be a recurrent theme associated with NHEJ, maximised in this case by the deployment of a dedicated primase, although its in vivo relevance is unknown

The origin of life: chemical evolution of a metabolic system in a mineral honeycomb?

For the RNA-world hypothesis to be ecologically feasible, selection mechanisms acting on replicator communities need to be invoked and the corresponding scenarios of molecular evolution specified. Complementing our previous models of chemical evolution on mineral surfaces, in which selection was the consequence of the limited mobility of macromolecules attached to the surface, here we offer an alternative realization of prebiotic group-level selection: the physical encapsulation of local replicator communities into the pores of the mineral substrate. Based on cellular automaton simulations we argue that the effect of group selection in a mineral honeycomb could have been efficient enough to keep prebiotic ribozymes of different specificities and replication rates coexistent, and their metabolic cooperation protected from extensive molecular parasitism. We suggest that mutants of the mild parasites persistent in the metabolic system can acquire useful functions such as replicase activity or the production of membrane components, thus opening the way for the evolution of the first autonomous protocells on Earth

Worst case optimization for interfractional motion mitigation in carbon ion therapy of pancreatic cancer.

Introduction The efficacy of radiation therapy treatments for pancreatic cancer is compromised by abdominal motion which limits the spatial accuracy for dose delivery - especially for particles. In this work we investigate the potential of worst case optimization for interfractional offline motion mitigation in carbon ion treatments of pancreatic cancer.Methods We implement a worst case optimization algorithm that explicitly models the relative biological effectiveness of carbon ions during inverse planning. We perform a comparative treatment planning study for seven pancreatic cancer patients. Treatment plans that have been generated using worst case optimization are compared against (1) conventional intensity-modulated carbon ion therapy, (2) single field uniform dose carbon ion therapy, and (3) an ideal yet impractical scenario relying on daily re-planning. The dosimetric quality and robustness of the resulting treatment plans is evaluated using reconstructions of the daily delivered dose distributions on fractional control CTs.Results Idealized daily re-planning consistently gives the best dosimetric results with regard to both target coverage and organ at risk sparing. The absolute reduction of D 95 within the gross tumor volume during fractional dose reconstruction is most pronounced for conventional intensity-modulated carbon ion therapy. Single field uniform dose optimization exhibits no substantial reduction for six of seven patients and values for D 95 for worst case optimization fall in between. The treated volume (D>95 % prescription dose) outside of the gross tumor volume is reduced by a factor of two by worst case optimization compared to conventional optimization and single field uniform dose optimization. Single field uniform dose optimization comes at an increased radiation exposure of normal tissues, e.g. ≈2 Gy (RBE) in the mean dose in the kidneys compared to conventional and worst case optimization and ≈4 Gy (RBE) in D 1 in the spinal cord compared to worst case optimization.Conclusion Interfractional motion substantially deteriorates dose distributions for carbon ion treatments of pancreatic cancer patients. Single field uniform dose optimization mitigates the negative influence of motion on target coverage at an increased radiation exposure of normal tissue. Worst case optimization enables an exploration of the trade-off between robust target coverage and organ at risk sparing during inverse treatment planning beyond margin concepts