Ultra-small-angle X-ray photon correlation spectroscopy using the Eiger detector.

Successful implementation of the single-photon-counting Eiger 500k pixel array detector for sub-millisecond X-ray photon correlation spectroscopy (XPCS) measurements in the ultra-small-angle scattering region is reported. The performance is demonstrated by measuring the dynamics of dilute silica colloids in aqueous solvents when the detector is operated at different counter depths, 4, 8 and 12 bit. In the fastest mode involving 4 bit parallel readout, a stable frame rate of 22 kHz is obtained that enabled measurement of intensity-intensity autocorrelation functions with good statistics down to the 50 µs range for a sample with sufficient scattering power. The high frame rate and spatial resolution together with large number of pixels of the detector facilitate the investigation of sub-millisecond dynamics over a broad length scale by multispeckle XPCS. This is illustrated by an example involving phoretic motion of colloids during the phase separation of the solvent.

Genetic and epigenetic methylation defects and implication of the ERMN gene in autism spectrum disorders.

Autism spectrum disorders (ASD) are highly heritable and genetically complex conditions. Although highly penetrant mutations in multiple genes have been identified, they account for the etiology of <1/3 of cases. There is also strong evidence for environmental contribution to ASD, which can be mediated by still poorly explored epigenetic modifications. We searched for methylation changes on blood DNA of 53 male ASD patients and 757 healthy controls using a methylomic array (450K Illumina), correlated the variants with transcriptional alterations in blood RNAseq data, and performed a case-control association study of the relevant findings in a larger cohort (394 cases and 500 controls). We found 700 differentially methylated CpGs, most of them hypomethylated in the ASD group (83.9%), with cis-acting expression changes at 7.6% of locations. Relevant findings included: (1) hypomethylation caused by rare genetic variants (meSNVs) at six loci (ERMN, USP24, METTL21C, PDE10A, STX16 and DBT) significantly associated with ASD (q-value <0.05); and (2) clustered epimutations associated to transcriptional changes in single-ASD patients (n=4). All meSNVs and clustered epimutations were inherited from unaffected parents. Resequencing of the top candidate genes also revealed a significant load of deleterious mutations affecting ERMN in ASD compared with controls. Our data indicate that inherited methylation alterations detectable in blood DNA, due to either genetic or epigenetic defects, can affect gene expression and contribute to ASD susceptibility most likely in an additive manner, and implicate ERMN as a novel ASD gene.

New cryogenic environment for beamline ID22 at the European Synchrotron Radiation Facility.

A compact minicryostat has been well adapted on the hard x-ray microprobe ID22 of the European Synchrotron Radiation Facility. For variable low-temperature investigations, its special technical design provides precise scanning microscopy and allows easy access for multiple detection modes. Based on x-ray excited optical luminescence technique on the micrometer scale, details of the equipment, its temperature calibration, and typical results are described. Data collections from InAs quantum heterostructures support the excellent thermal performance of the novel cryogenic device.

Analysis of forced wheezes in asthma patients.

BACKGROUND: Spirometric parameters can be normal in many stable asthma patients, making a diagnosis difficult at certain times in the course of disease. OBJECTIVES: The present study aims to find differences and similarities in the acoustic characteristics of forced wheezes among asthma patients with and without normal spirometric values. METHODS: Eleven chronic asthma patients (8 men/3 women) with moderate-to-severe airway obstruction (FEV1 48.4%), 9 stable asthma patients (6 males/3 females) with normal spirometry (FEV1 84.0%) and a positive methacholine test and 14 healthy subjects (8/6) were enrolled in the study. A contact sensor was placed on the trachea, and wheezes were detected by a modified Shabtai-Musih algorithm in a time-frequency representation. RESULTS: More wheezes were recorded in obstructive asthma patients than in stable asthma and control subjects: nonstable asthma 13.6 (13.3), stable asthma 3.5 (3.0) and control subjects 2.5 (2.1). The mean frequency of all wheezes detected was higher in control subjects than in either stable or non-stable asthma patients. The change in the total number of wheezes after terbutaline inhalation was more pronounced in nonstable asthma patients than in stable asthmatics and control subjects. CONCLUSIONS: This study confirms that wheeze recording during forced expiratory maneuvers can be a complementary measure to spirometry to identify asthma patients.

ID22: a multitechnique hard X-ray microprobe beamline at the European Synchrotron Radiation Facility.

The ID22 beamline is dedicated to hard X-ray microanalysis allowing the combination of fluorescence, spectroscopy, diffraction and tomography techniques in a wide energy range from 6 to 70 keV. The recent installation of an in-vacuum undulator, a new sample stage and the adaptation of various focusing optics has contributed to a great improvement in the capabilities of the beamline, which is now accessed by a wide user community issued from medical, earth and environmental science, archaeology and material science. Many applications requiring low detection limits for localization/speciation of trace elements together with structural analysis have been developed at the beamline on the (sub)micrometer scale. The possibility of combining simultaneously different analytical probes offers the opportunity of a thorough study of a given sample or scientific problem. This paper presents a review of the recent developments of the beamline and a detailed description of its capabilities through examples from different fields of applications.