Hard Real Time Quick Exafs Data Acquisition With All Open Source Software on a Commodity Personal Computer.

We describe here the data acquisition subsystem of the Quick EXAFS (QEXAFS) experiment at the National Synchrotron Light Source of Brookhaven National Laboratory. For ease of future growth and flexibility, almost all software components are open source with very active maintainers. Among them, Linux running on x86 desktop computer, RTAI for real-time response, COMEDI driver for the data acquisition hardware, Qt and PyQt for graphical user interface, PyQwt for plotting, and Python for scripting. The signal (A/D) and energy-reading (IK220 encoder) devices in the PCI computer are also EPICS enabled. The control system scans the monochromator energy through a networked EPICS motor. With the real-time kernel, the system is capable of deterministic data-sampling period of tens of micro-seconds with typical timing-jitter of several micro-seconds. At the same time, Linux is running in other non-real-time processes handling the user-interface. A modern Qt-based controls-front end enhances productivity. The fast plotting and zooming of data in time or energy coordinates let the experimenters verify the quality of the data before detailed analysis. Python scripting is built-in for automation. The typical data-rate for continuous runs are around ten mega-bytes per minute

The Complexity of Flat Freeze LTL

We consider the model-checking problem for freeze LTL on one-counter automata (OCAs). Freeze LTL extends LTL with the freeze quantifier, which allows one to store different counter values of a run in registers so that they can be compared with one another. As the model-checking problem is undecidable in general, we focus on the flat fragment of freeze LTL, in which the usage of the freeze quantifier is restricted. Recently, Lechner et al. showed that model checking for flat freeze LTL on OCAs with binary encoding of counter updates is decidable and in 2NEXPTIME. In this paper, we prove that the problem is, in fact, NEXPTIME-complete no matter whether counter updates are encoded in unary or binary. Like Lechner et al., we rely on a reduction to the reachability problem in OCAs with parameterized tests (OCAPs). The new aspect is that we simulate OCAPs by alternating two-way automata over words. This implies an exponential upper bound on the parameter values that we exploit towards an NP algorithm for reachability in OCAPs with unary updates. We obtain our main result as a corollary

Synechocystis sp. PCC 6803 Requires the Bidirectional Hydrogenase to Metabolize Glucose and Arginine Under Oxic Conditions

The cyanobacterium Synechocystis sp.PCC 6803 possesses a bidirectional NiFe-hydrogenase, HoxEFUYH. It functions to produce hydrogen under dark, fermentative conditions and photoproduces hydrogen when dark-adapted cells are illuminated. Unexpectedly, we found that the deletion of the large subunit of the hydrogenase (HoxH) in Synechocystis leads to an inability to grow on arginine and glucose under continuous light in the presence of oxygen. This is surprising, as the hydrogenase is an oxygen-sensitive enzyme. In wild-type (WT) cells, thylakoid membranes largely disappeared, cyanophycin accumulated, and the plastoquinone (PQ) pool was highly reduced, whereas ΔhoxH cells entered a dormant-like state and neither consumed glucose nor arginine at comparable rates to the WT. Hydrogen production was not traceable in the WT under these conditions. We tested and could show that the hydrogenase does not work as an oxidase on arginine and glucose but has an impact on the redox states of photosynthetic complexes in the presence of oxygen. It acts as an electron valve as an immediate response to the supply of arginine and glucose but supports the input of electrons from arginine and glucose oxidation into the photosynthetic electron chain in the long run, possibly via the NDH-1 complex. Despite the data presented in this study, the latter scenario requires further proof. The exact role of the hydrogenase in the presence of arginine and glucose remains unresolved. In addition, a unique feature of the hydrogenase is its ability to shift electrons between NAD(H), NADP(H), ferredoxin, and flavodoxin, which was recently shown in vitro and might be required for fine-tuning. Taken together, our data show that Synechocystis depends on the hydrogenase to metabolize organic carbon and nitrogen in the presence of oxygen, which might be an explanation for its prevalence in aerobic cyanobacteria

Inelastic x-ray scattering at the National Synchrotron Light

The research program at the inelastic x-ray scattering beamline at the National Synchrotron Light Source is focused on the study of elementary excitations in condensed matter with total energy resolution on the order of 0.1 eV to 1.0 eV. Results from selected experiments are reported to demonstrate the capability of the beamline as well as the information can be obtained from inelastic x- ray scattering experiments

Application of numerical methods in the study operational characteristics of the combustion chamber (pumping unit GPA-16U) at different loads

We report on X-ray resonance exchange and neutron scattering of metallic GdS. At the LII and LIII absorption edges of Gd, resonance enhancements of more than two orders of magnitude over the non-resonant magnetic scattering are observed. Polarisation analysis proves that these enhancements are due to dipolar transitions from the 2p to the 5d states. The branching ratio between the LII and LIII edges of 2.5 suggests a polarisation of the 5d electrons in the ground state. The antiferromagnetic order is of type II in the fcc lattice. Single crystal diffraction of hot neutrons suggests that the spin direction lies within the (111) planes with a value for the sublattice magnetisation of 6.51(3) $\mu_{\rm B}$. The critical exponent for the sublattice magnetisation has a value of $\beta = 0.38(2)$ in agreement with a pure Heisenberg model. Above TN, a sharp component persists in the critical diffuse scattering. Lattice distortions give indications for two additional low-temperature phase transitions at about 49 K and 32 K. We argue that these transitions are not connected to spin reorientations and discuss the possible influence of fourth-order exchange interactions

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Identifying Human Disease Genes through Cross-Species Gene Mapping of Evolutionary Conserved Processes

Understanding complex networks that modulate development in humans is hampered by genetic and phenotypic heterogeneity within and between populations. Here we present a method that exploits natural variation in highly diverse mouse genetic reference panels in which genetic and environmental factors can be tightly controlled. The aim of our study is to test a cross-species genetic mapping strategy, which compares data of gene mapping in human patients with functional data obtained by QTL mapping in recombinant inbred mouse strains in order to prioritize human disease candidate genes.We exploit evolutionary conservation of developmental phenotypes to discover gene variants that influence brain development in humans. We studied corpus callosum volume in a recombinant inbred mouse panel (C57BL/6J×DBA/2J, BXD strains) using high-field strength MRI technology. We aligned mouse mapping results for this neuro-anatomical phenotype with genetic data from patients with abnormal corpus callosum (ACC) development.).This approach that exploits highly diverse mouse strains provides an efficient and effective translational bridge to study the etiology of human developmental disorders, such as autism and schizophrenia

CTCF variants in 39 individuals with a variable neurodevelopmental disorder broaden the mutational and clinical spectrum

Purpose: Pathogenic variants in the chromatin organizer CTCF were previously reported in seven individuals with a neurodevelopmental disorder (NDD). Methods: Through international collaboration we collected data from 39 subjects with variants in CTCF. We performed transcriptome analysis on RNA from blood samples and utilized Drosophila melanogaster to investigate the impact of Ctcf dosage alteration on nervous system development and function. Results: The individuals in our cohort carried 2 deletions, 8 likely gene-disruptive, 2 splice-site, and 20 different missense variants, most of them de novo. Two cases were familial. The associated phenotype was of variable severity extending from mild developmental delay or normal IQ to severe intellectual disability. Feeding difficulties and behavioral abnormalities were common, and variable other findings including growth restriction and cardiac defects were observed. RNA-sequencing in five individuals identified 3828 deregulated genes enriched for known NDD genes and biological processes such as transcriptional regulation. Ctcf dosage alteration in Drosophila resulted in impaired gross neurological functioning and learning and memory deficits. Conclusion: We significantly broaden the mutational and clinical spectrum of CTCF-associated NDDs. Our data shed light onto the functional role of CTCF by identifying deregulated genes and show that Ctcf alterations result in nervous system defects in Drosophila.Peer reviewe