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BACKGROUND: X-ray grating interferometry normally requires multiple steps and exposures, causing a prolonged imaging time. There is motivation to use fewer steps to reduce scanning time and complexity, while keeping fidelity of the retrieved signals. OBJECTIVE: We propose an iterative signal retrieval method, extracting attenuation, dark field contrast (DFC), and differential phase contrast (DPC) signals from two X-ray exposures. METHODS: Two shots were captured at G2 grating positions with difference of 1/4 grating period. The algorithm consists of two stages. At the first stage, amplitude of sample phase stepping curve retrieved by virtual phase stepping (VPS) method, visibility and local phase of background phase stepping curve are used to limit the results to the proximity of the ground truth. After the second stage, three high-quality parameters, amplitude, visibility, and local phase, are retrieved through finetuning, and three signals are calculated. Simulated and real-sample experiments were conducted to validate this method. RESULTS: We used standard phase stepping result as benchmark and calculated structural similarity (SSIM) and peak signal-to-noise ratio (PSNR) between benchmark and parameters retrieved by our dual-shot method and virtual phase stepping (VPS) method. For both simulated and real-sample experiments, the SSIM and PSNR value of dual-shot method are higher than those of VPS method. For real-sample method, we also conducted a three-step PS, and the SSIM and PSNR value of dual-shot method are slightly lower than those of three-step PS. CONCLUSION: Using our dual-shot method demonstrates higher performance than other single-shot method in retrieving high-quality signals, and it also reduces radiation dose and time.

Purpose Breast cancer is the most common malignancy in women. Unfortunately, current breast imaging techniques all suffer from certain limitations: they are either not fully three dimensional, have an insufficient resolution or low soft-tissue contrast. Grating interferometry breast computed tomography (GI-BCT) is a promising X-ray phase contrast modality that could overcome these limitations by offering high soft-tissue contrast and excellent three-dimensional resolution. To enable the transition of this technology to clinical practice, dedicated data-processing algorithms must be developed in order to effectively retrieve the signals of interest from the measured raw data. Methods This article proposes a novel denoising algorithm that can cope with the high-noise amplitudes and heteroscedasticity which arise in GI-BCT when operated in a low-dose regime to effectively regularize the ill-conditioned GI-BCT inverse problem. We present a data-driven algorithm called INSIDEnet, which combines different ideas such as multiscale image processing, transform-domain filtering, transform learning, and explicit orthogonality to build an Interpretable NonexpanSIve Data-Efficient network (INSIDEnet). Results We apply the method to simulated breast phantom datasets and to real data acquired on a GI-BCT prototype and show that the proposed algorithm outperforms traditional state-of-the-art filters and is competitive with deep neural networks. The strong inductive bias given by the proposed model's architecture allows to reliably train the algorithm with very limited data while providing high model interpretability, thus offering a great advantage over classical convolutional neural networks (CNNs). Conclusions The proposed INSIDEnet is highly data-efficient, interpretable, and outperforms state-of-the-art CNNs when trained on very limited training data. We expect the proposed method to become an important tool as part of a dedicated plug-and-play GI-BCT reconstruction framework, needed to translate this promising technology to the clinics., Medical Physics, 49 (6), ISSN:0094-2405, ISSN:2473-4209, ISSN:1522-8541

Purpose Grating-based x-ray phase-contrast imaging (GPCI) is a promising technique for clinical applications as it can provide two newly emerging imaging modalities (differential phase-contrast and dark-field contrast) in addition to the conventional absorption contrast. As far, phase-stepping strategy is the most commonly used approach in GPCI to indirectly acquire differential phase-contrast and dark-field contrast. It is known that the obtained phase-stepping curves (PSCs) have the cosine property and the convolution property, leading to two types of information retrieval approaches in literature: the Fourier component analysis and the multi-order moment analysis. The purpose of this paper is to derive a new property of PSCs and apply the property to noise optimization for information retrieval. Methods Based on the cosine expression of the flat PSC without the sample and the well-established convolution relationship between the flat PSC and the sample PSC, we reveal an important integral property of PSCs: the inner product of PSCs and an arbitrary function contains only zero-order and first-order components in the Fourier series. Furthermore, we apply the property to the direct multi-order moment analysis and propose a set of generalized forms including an optimal one in the presence of noise. Results To validate the effectiveness of our analysis, we compared the simulated and real experiment results retrieved by the original direct multi-order moment analysis with the ones retrieved by our proposed noise-optimal form. A significant improvement of noise performance by our method is observed and the improvement ratio in differential phase-contrast is consistent with our theoretical calculation (39.2%). Conclusions In this paper, we reveal a new integral property of the acquired PSCs with and without samples in GPCI, which can be applied to information retrieval approaches like the direct multi-order moment analysis. Then we optimize these approaches to improve the noise performance, offering great potentials of dose reduction in practical applications.

In a piloted jet flame, the pilot flame has an effect of stabilizing the main flame. Detailed mechanisms of pilot flame/main flame interaction are however not well studied. It is expected that the pilot flame affects the main flame through the following mechanisms: (a) the pilot flame provides the heat and radicals to the reaction zone of the main flame, (b) the pilot flame prevents the cold ambient air from being entrained into the main flame, and (c) the pilot flame modifies the stretch rate of the main flame. In this paper, detailed numerical simulations of piloted laminar methane/air jet flames are carried out to elucidate the effect of pilot flame on the structure and burning velocity of the main jet flame. One-dimensional (1D) freely propagating flame is also simulated to investigate the effect of hot gas mixing with the unburned fuel/air mixture, and 1D counter-flow flame is simulated to study the diffusion of the hot gas from the pilot flame to the reaction zone of the main flame and the effect of flame stretch. The results showed that heat transfer from the pilot flame to the main flame has a more significant effect on the structures and propagation of the main flame than the mass transfer from the pilot flame to the main flame. The heat and mass transfer from the pilot flame affects the local equivalence ratio and temperature of the unburned mixture, which gives rise to a significant enhancement of burning velocity. When the hot gas from the pilot flame is at sufficiently high temperatures, an ultra-lean fuel/air mixture can burn at equivalence ratio below the flammability limit. The reaction rate and burning velocity of ultra fuel-lean flames are enhanced by the strain rate, whereas for a main flame with the equivalence ratio closer to that of pilot flame, the reactivity and burning velocity of the main flame decrease with increasing strain rate. (Less)

We present a method to produce small pitch gratings for X-ray interferometric imaging applications, allowing the phase sensitivity to be increased and/or the length of the laboratory setup to be minimized. The method is based on fabrication of high aspect ratio silicon microstructures using deep reactive ion etching (Bosch technique) of dense grating arrays and followed by conformal electroplating of Au. We demonstrated that low resistivity Si substrates (, Micromachines, 12 (5), ISSN:2072-666X

Objectives Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, as several research works have demonstrated in a pre-clinical setting, since it is able to provide attenuation, differential phase contrast, and scattering images simultaneously. In order to translate this technique to the clinics, it has to be adapted to cover a large field-of-view within a clinically acceptable exposure time and radiation dose. Methods We set up a grating interferometer that fits into a standard mammography system and fulfilled the aforementioned conditions. Here, we present the first mastectomy images acquired with this experimental device. Results and conclusion Our system performs at a mean glandular dose of 1.6 mGy for a 5-cm-thick, 18%-dense breast, and a field-of-view of 26 × 21 cm2. It seems to be well-suited as basis for a clinical-environment device. Further, dark-field signals seem to support an improved lesion visualization. Evidently, the effective impact of such indications must be evaluated and quantified within the context of a proper reader study. Key Points • Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, since it is sensitive to refraction and scattering and thus provides additional tissue information. • The most straightforward way to do grating-interferometry in the clinics is to modify a standard mammography device. • In a first approximation, the doses given with this technique seem to be similar to those of conventional mammography.

High quality gratings are among the key elements for successful imaging with X-ray grating interferometry. Grating fabrication, specifically of absorption gratings, with high aspect ratio and large area, is a great challenge from a microfabrication point of view. In this paper the fabrication of absorption gratings by seedless electroplating of gold in high aspect ratio silicon moulds that are fabricated by deep reactive ion etching (Bosch process) is presented. We report on our latest results and discuss the possibility of reducing the grating period down to 1.3 μ m . In addition, the quality of the gratings is assessed by performing visibility measurements and imaging various samples on a compact in house X-ray grating interferometer.

Objective To evaluate the accuracy of semiautomated segmentation of urinary stone size in computed tomography (CT) compared with manual measurement. Materials and Methods A total of 103 patients (32f, 71m ; mean age 52 years±18 that were diagnosed with urolithiasis and collected stones received standardized ex vivo CT-scans and radiography of the stones. Stone size was segmented semiautomatically using commercial software (syngo.via, Siemens, Germany) and compared with manual caliper measurement on digital radiography. Results Mean size was 4.4 mm in CT and 4.6 mm in radiography. Depending on number of stones analyzed per patient, estimation of stone size showed moderate to excellent correlation for both methods. There was no significant difference in overall size measurement. Conclusion Semiautomatic segmentation of urinary stone size in CT is possible and reduces measurement errors, allowing more precise estimation especially for smaller concrements. Neighboring stones may hamper segmentation of stone size.

The well-established functions of UHRF1 converge to DNA biological processes, as exemplified by DNA methylation maintenance and DNA damage repair during cell cycles. However, the potential effect of UHRF1 on RNA metabolism is largely unexplored. Here, we revealed that UHRF1 serves as a novel alternative RNA splicing regulator. The protein interactome of UHRF1 identified various splicing factors. Among them, SF3B3 could interact with UHRF1 directly and participate in UHRF1-regulated alternative splicing events. Furthermore, we interrogated the RNA interactome of UHRF1, and surprisingly, we identified U snRNAs, the canonical spliceosome components, in the purified UHRF1 complex. Unexpectedly, we found H3R2 methylation status determines the binding preference of U snRNAs, especially U2 snRNAs. The involvement of U snRNAs in UHRF1-containing complex and their binding preference to specific chromatin configuration imply a finely orchestrated mechanism at play. Our results provided the resources and pinpointed the molecular basis of UHRF1-mediated alternative RNA splicing, which will help us better our understanding of the physiological and pathological roles of UHRF1 in disease development.

Phase-contrast imaging is an emerging technology that may increase the signal-difference-to-noise ratio in medical imaging. One of the most promising phase-contrast techniques is Talbot interferometry, which, combined with energy-sensitive photon-counting detectors, enables spectral differential phase-contrast mammography. We have evaluated a realistic system based on this technique by cascaded-systems analysis and with a task-dependent ideal-observer detectability index as a figure-of-merit. Beam-propagation simulations were used for validation and illustration of the analytical framework. Differential phase contrast improved detectability compared to absorption contrast, in particular for fine tumor structures. This result was supported by images of human mastectomy samples that were acquired with a conventional detector. The optimal incident energy was higher in differential phase contrast than in absorption contrast when disregarding the setup design energy. Further, optimal weighting of the transmitted spectrum was found to have a weaker energy dependence than for absorption contrast. Taking the design energy into account yielded a superimposed maximum on both detectability as a function of incident energy, and on optimal weighting. Spectral material decomposition was not facilitated by phase contrast, but phase information may be used instead of spectral information. QC 20120731

X-ray grating interferometry (XGI) can provide access to unresolved sub-pixel information by utilizing the so-called dark-field or visibility reduction contrast. A recently developed variant of conventional XGI named dual-phase grating interferometer, based only on phase-shifting structures, has allowed for straightforward micro-structural investigations over multiple length scales with conventional X-ray sources. Nonetheless, the theoretical framework of the image formation for the dark-field signal has not been fully developed yet, thus hindering the quantification of unresolved micro-structures. In this work, we expand the current theoretical formulation of dual-phase grating interferometers taking into account polychromatic sources and beam hardening effects. We propose a model that considers the contribution of beam hardening to the visibility reduction and accounts for it. Finally, the method is applied to previously acquired and new experimental data showing that discrimination between actual micro-structures and beam hardening effects can be achieved.

Summary Molecular mechanisms underlying adaptive targeted therapy resistance in pancreatic ductal adenocarcinoma (PDAC) are poorly understood. Here, we identify SETD5 as a major driver of PDAC resistance to MEK1/2 inhibition (MEKi). SETD5 is induced by MEKi resistance and its deletion restores refractory PDAC vulnerability to MEKi therapy in mouse models and patient-derived xenografts. SETD5 lacks histone methyltransferase activity but scaffolds a co-repressor complex, including HDAC3 and G9a. Gene silencing by the SETD5 complex regulates known drug resistance pathways to reprogram cellular responses to MEKi. Pharmacological co-targeting of MEK1/2, HDAC3, and G9a sustains PDAC tumor growth inhibition in vivo. Our work uncovers SETD5 as a key mediator of acquired MEKi therapy resistance in PDAC and suggests a context for advancing MEKi use in the clinic.

Within neutron imaging, different methods have been developed with the aim to go beyond the conventional contrast modalities, such as grating interferometry. Existing grating interferometers are sensitive to scattering in a single direction only, and thus investigations of anisotropic scattering structures imply the need for a circular scan of either the sample or the gratings. Here we propose an approach that allows assessment of anisotropic scattering in a single acquisition mode and to broaden the range of the investigation with respect to the probed correlation lengths. This is achieved by a far-field grating interferometer with a tailored 2D-design. The combination of a directional neutron dark-field imaging approach with a scan of the sample to detector distance yields to the characterization of the local 2D real-space correlation functions of a strongly oriented sample analogous to conventional small-angle scattering. Our results usher in quantitative and spatially resolved investigations of anisotropic and strongly oriented systems beyond current capabilities., Communications Physics, 3 (1)

The retina is one of the most tiny and sophisticated tissues of the body. Three dimensional (3D) visualization of the whole retina is valuable both in clinical and research arenas. The tissue has been predominantly assessed by time-consuming histopathology and optical coherence tomography (OCT) in research and clinical arenas. However, none of the two methods can provide 3D imaging of the retina. The purpose of this study is to give a volumetric visualization of rat retina at submicron resolution, using an emerging imaging technique-phase-contrast X-ray CT. A Sprague-Dawley (SD) rat eye specimen was scanned with X-ray differential phase contrast tomographic microscopy (DPC-microCT) equipped at the Swiss Light Source synchrotron. After scanning, the specimen was subjected to routine histology procedures and severed as a reference. The morphological characteristics and signal features of the retina in the DPC-microCT images were evaluated. The total retina and its sublayers thicknesses were measured on the DPC-microCT images and compared with those obtained from the histological sections. The retina structures revealed by DPC-microCT were highly consistent with the histological section. In this study, we achieved nondestructive 3D visualization of SD rat retina. In addition to detailed anatomical structures, the objective parameters provided by DPC-microCT make it a useful tool for retinal research and disease diagnosis in the early stage.

MÖNCH is a 25 µm-pitch charge-integrating detector aimed at exploring the limits of current hybrid silicon detector technology. The small pixel size makes it ideal for high-resolution imaging. With an electronic noise of about 110 eV r.m.s., it opens new perspectives for many synchrotron applications where currently the detector is the limiting factor, e.g. inelastic X-ray scattering, Laue diffraction and soft X-ray or high-resolution color imaging. Due to the small pixel pitch, the charge cloud generated by absorbed X-rays is shared between neighboring pixels for most of the photons. Therefore, at low photon fluxes, interpolation algorithms can be applied to determine the absorption position of each photon with a resolution of the order of 1 µm. In this work, the characterization results of one of the MÖNCH prototypes are presented under low-flux conditions. A custom interpolation algorithm is described and applied to the data to obtain high-resolution images. Images obtained in grating interferometry experiments without the use of the absorption grating G2 are shown and discussed. Perspectives for the future developments of the MÖNCH detector are also presented., Journal of Synchrotron Radiation, 23 (6), ISSN:0909-0495, ISSN:1600-5775

SummaryNono is a component of the para-speckle, which stores and processes RNA. Mouse embryonic stem cells (mESCs) lack para-speckles, leaving the function of Nono in mESCs unclear. Here, we find that Nono functions as a chromatin regulator cooperating with Erk to regulate mESC pluripotency. We report that Nono loss results in robust self-renewing mESCs with epigenomic and transcriptomic features resembling the 2i (GSK and Erk inhibitors)-induced “ground state.” Erk interacts with and is required for Nono localization to a subset of bivalent genes that have high levels of poised RNA polymerase. Nono loss compromises Erk activation and RNA polymerase poising at its target bivalent genes in undifferentiated mESCs, thus disrupting target gene activation and differentiation. These findings argue that Nono collaborates with Erk signaling to regulate the integrity of bivalent domains and mESC pluripotency.

Insights into the micro- and nano-architecture of materials is crucial for understanding and predicting their macroscopic behaviour. In particular, for emerging applications such as meta-materials, the micrometer scale becomes highly relevant. The micro-architecture of such materials can be tailored to exhibit specific mechanical, optical or electromagnetic behaviours. Consequently, quality control at micrometer scale must be guaranteed over extended areas. Mesoscale investigations over millimetre sized areas can be performed by scanning small angle X-ray scattering methods (SAXS). However, due to their long measurement times, real time or operando investigations are hindered. Here we present a method based on X-ray diffractive optics that enables the acquisition of SAXS signals in a single shot (few milliseconds) over extended areas. This method is applicable to a wide range of X-ray sources with varying levels of spatial coherence and monochromaticity, as demonstrated from the experimental results. This enables a scalable solution of spatially resolved SAXS., Nature Communications, 10, ISSN:2041-1723

Despite the fact that the resolution of conventional contact/proximity lithography can reach feature sizes down to ~0.5-0.6 micrometers, the accurate control of the linewidth and uniformity becomes already very challenging for gratings with periods in the range of 1-2 {\mu}m. This is particularly relevant for the exposure of large areas and wafers thinner than 300{\mu}m. If the wafer or mask surface is not fully flat due to any kind of defects, such as bowing/warpage or remaining topography of the surface in case of overlay exposures, noticeable linewidth variations or complete failure of lithography step will occur. We utilized the newly developed Displacement Talbot lithography to pattern gratings with equal lines and spaces and periods in the range of 1.0 to 2.4 {\mu}m. The exposures in this lithography process do not require contact between the mask and the wafer, which makes it essentially insensitive to surface planarity and enables exposures with very high linewidth uniformity on thin and even slightly deformed wafers. We demonstrated pattern transfer of such exposures into Si substrates by reactive ion etching using the Bosch process. An etching depth of 30 {\mu}m or more for the whole range of periods was achieved, which corresponds to very high aspect ratios up to 60:1. The application of the fabricated gratings in phase contrast x-ray imaging is presented.

Grating interferometry mammography (GIM) is an experimental breast imaging method at the edge of being clinically implemented. Besides attenuation, GIM can measure the refraction and scattering of x-rays resulting in differential phase contrast (DPC) and dark-field (DF) images. In this exploratory study, we assessed the feasibility of using microbubbles as a contrast agent in GIM. Two millilitres of microbubbles and iodine were respectively injected into ex vivo breast phantoms, consisting of fresh chicken breasts. Native and postcontrast images were acquired with a clinically compatible GIM setup, operated at 38 kVp, 14-s acquisition time, and with a dose of 1.3 mGy. The visibility of the contrast agents was analysed in a side-by-side comparison by three radiologists. The contrast-to-noise-ratio (CNR) was calculated for each contrast agent. We found that both contrast agents were judged to be visible by the readers. The mean CNR was 3.1 ± 1.9 for microbubbles in DF and 24.2 ± 6.5 for iodine in attenuation. In conclusion, this is a first proof-of-mechanism study that microbubbles could be used as a contrast agent in clinically compatible GIM, due to their scattering properties, which implies the potential use of a contrast agent with a high safety profile in x-ray-based breast imaging. ISSN:2509-9280

In most cases, the analysis of small-angle and wide-angle X-ray scattering (SAXS and WAXS, respectively) requires a theoretical model to describe the sample's scattering, complicating the interpretation of the scattering resulting from complex heterogeneous samples. This is the reason why, in general, the analysis of a large number of scattering patterns, such as are generated by time-resolved and scanning methods, remains challenging. Here, a model-free classification method to separate SAXS/WAXS signals on the basis of their inflection points is introduced and demonstrated. This article focuses on the segmentation of scanning SAXS/WAXS maps for which each pixel corresponds to an azimuthally integrated scattering curve. In such a way, the sample composition distribution can be segmented through signal classification without applying a model or previous sample knowledge. Dimensionality reduction and clustering algorithms are employed to classify SAXS/WAXS signals according to their similarity. The number of clusters, i.e. the main sample regions detected by SAXS/WAXS signal similarity, is automatically estimated. From each cluster, a main representative SAXS/WAXS signal is extracted to uncover the spatial distribution of the mixtures of phases that form the sample. As examples of applications, a mudrock sample and two breast tissue lesions are segmented., Journal of Applied Crystallography, 51, ISSN:0021-8898, ISSN:1600-5767

X-ray phase contrast imaging is a powerful analysis technique for materials science and biomedicine. Here, we report on laboratory grating-based X-ray interferometry employing a microfocus X-ray source and a high Talbot order (35th) asymmetric geometry to achieve high angular sensitivity and high spatial resolution X-ray phase contrast imaging in a compact system (total length µm) and a single-photon counting X-ray detector (75 µm pixel size). The performance of the X-ray interferometer was fully characterized in terms of angular sensitivity and spatial resolution. Finally, the potential of laboratory X-ray phase contrast for biomedical imaging is demonstrated by obtaining high resolution X-ray phase tomographies of a mouse embryo embedded in solid paraffin and a formalin-fixed full-thickness sample of human left ventricle in water with a spatial resolution of 21.5 µm.

Regulation of enhancer activity is important for controlling gene expression programs. Here we report that a biochemical complex that contains a potential chromatin reader, RACK7 and the histone lysine 4 tri-methyl (H3K4me3)-specific demethylase KDM5C occupies many active enhancers, including almost all super-enhancers. Loss of RACK7 or KDM5C results in overactivation of enhancers, characterized by the deposition of H3K4me3 and H3K27Ac, together with increased transcription of eRNAs and nearby genes. Furthermore, loss of RACK7 or KDM5C leads to de-repression of S100A oncogenes and various cancer-related phenotypes. Our findings reveal a RACK7/KDM5C-regulated, dynamic interchange between histone H3K4me1 and H3K4me3 at active enhancers, representing an additional layer of regulation of enhancer activity. We propose that RACK7/KDM5C functions as an enhancer “brake” to ensure appropriate enhancer activity, which, when compromised, could contribute to tumorigenesis.

Purpose In addition to absorption imaging, grating interferometry-based mammography (GIM) is capable of detecting differential-phase and scattering signals. In particular, the scattering signal can enable a quantifiable characterization of breast lesions. The purpose of this study was to determine if suspicious microcalcifications associated with benign or malignant lesions can be discriminated based on their absorption and scattering properties. Materials and Methods In this prospective, ethically approved study, 62 patients (mean age 60 y, range 39–89) with suspicious microcalcifications, who underwent stereotactic biopsies, were included. Biopsies were measured with an experimental GIM device and the ratios of the scattering and absorption signal (R-value) for microcalcifications were calculated. The mean R-values for benign and malignant lesions associated with microcalcifications were compared with the final histopathological diagnosis using a t-test. Results Twenty of the 62 participants had microcalcifications associated with malignancy. Comparing the two largest histopathological sub-groups of fibrosis (n = 23) vs. ductal carcinoma in situ (n = 15) resulted in an average R-value of 4.08 for benign and 2.80 for malignant lesions; p = 0.07. All microcalcifications associated with malignancy had an R-value below 4.71. Excluding microcalcifications with an R-value above this threshold would result in an 11 % reduction of false positives. Conclusion The novel GIM modality has the potential to non-invasively characterize microcalcifications and might aid in the discrimination of benign from malignant lesions in fresh biopsy samples.

Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, as several research works have demonstrated in a pre-clinical setting, since it is able to provide attenuation, differential phase contrast, and scattering images simultaneously. In order to translate this technique to the clinics, it has to be adapted to cover a large field-of-view within a clinically acceptable exposure time and radiation dose.We set up a grating interferometer that fits into a standard mammography system and fulfilled the aforementioned conditions. Here, we present the first mastectomy images acquired with this experimental device.Our system performs at a mean glandular dose of 1.6 mGy for a 5-cm-thick, 18%-dense breast, and a field-of-view of 26 × 21 cm2. It seems to be well-suited as basis for a clinical-environment device. Further, dark-field signals seem to support an improved lesion visualization. Evidently, the effective impact of such indications must be evaluated and quantified within the context of a proper reader study.• Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, since it is sensitive to refraction and scattering and thus provides additional tissue information. • The most straightforward way to do grating-interferometry in the clinics is to modify a standard mammography device. • In a first approximation, the doses given with this technique seem to be similar to those of conventional mammography.

Lysine methylation is a prevalent post-translational modification (PTM) used by the cell to reversibly regulate protein function. Although it has been extensively studied in the context of histones and the associated chromatin, the remaining methyllysine proteome remains largely unexplored. This SnapShot provides an overview of the current state of lysine methylation research and its emergence as a dynamic PTM occurring on histone and non-histone proteins. Lysine methylation is a prevalent post-translational modification (PTM) used by the cell to reversibly regulate protein function. Although it has been extensively studied in the context of histones and the associated chromatin, the remaining methyllysine proteome remains largely unexplored. This SnapShot provides an overview of the current state of lysine methylation research and its emergence as a dynamic PTM occurring on histone and non-histone proteins.

BS69 (aka ZMYND11) contains tandemly arranged PHD, BROMO and PWWP domains, which are chromatin recognition modalities. Here we show that BS69 selectively recognizes histone variant H3.3 lysine 36 trimethylation (H3.3K36me3) via its chromatin-binding domains. We further identify BS69 association with RNA splicing regulators including the U5 snRNP components of the spliceosome such as EFTUD2. Remarkably, RNA-seq shows that BS69 mainly regulates intron retention (IR), which is the least well-understood RNA alternative splicing event in mammalian cells. Biochemical and genetic experiments demonstrate that BS69 promotes IR by antagonizing EFTUD2 through physical interactions. We further show that regulation of IR by BS69 also depends on its binding to H3K36me3-decorated chromatin. Taken together, our study identifies an H3.3K36me3-specific reader and a regulator of IR, and reveals a novel and unexpected role of BS69 in connecting histone H3.3K36me3 to regulated RNA splicing, providing significant new insights into chromatin regulation of pre-mRNA processing.

Grating-based phase contrast mammography can help facilitate breast cancer diagnosis, as several research works have demonstrated. To translate this technique to the clinics, it has to be adapted to cover a large field of view within a limited exposure time and with a clinically acceptable radiation dose. This indicates that a straightforward approach would be to install a grating interferometer (GI) into a commercial mammography device. We developed a wave propagation based optimization method to select the most convenient GI designs in terms of phase and dark-field sensitivities for the Philips Microdose Mammography (PMM) setup. The phase sensitivity was defined as the minimum detectable breast tissue electron density gradient, whereas the dark-field sensitivity was defined as its corresponding signal-to-noise Ratio (SNR). To be able to derive sample-dependent sensitivity metrics, a visibility reduction model for breast tissue was formulated, based on previous research works on the dark-field signal and utilizing available Ultra-Small-Angle X-ray Scattering (USAXS) data and the outcomes of measurements on formalin-fixed breast tissue specimens carried out in tube-based grating interferometers. The results of this optimization indicate the optimal scenarios for each metric are different and fundamentally depend on the noise behavior of the signals and the visibility reduction trend with respect to the system autocorrelation length. In addition, since the inter-grating distance is constrained by the space available between the breast support and the detector, the best way we have to improve sensitivity is to count on a small G2 pitch.

An X-ray grating interferometer (GI) suitable for clinical mammography must comply with quite strict dose, scanning time and geometry limitations, while being able to detect tumors, microcalcifications and other abnormalities. Such a design task is not straightforward, since obtaining optimal phase-contrast and dark-field signals with clinically compatible doses and geometrical constraints is remarkably challenging. In this work, we present a wave propagation based optimization that uses the phase and dark-field sensitivities as figures of merit. This method was used to calculate the optimal interferometer designs for a commercial mammography setup. Its accuracy was validated by measuring the visibility of polycarbonate samples of different thicknesses on a Talbot-Lau interferometer installed on this device and considering some of the most common grating imperfections to be able to reproduce the experimental values. The optimization method outcomes indicate that small grating pitches are required to boost sensitivity in such a constrained setup and that there is a different optimal scenario for each signal type.

Scanning small-angle x-ray scattering (SAXS) measurements were performed on 36 formalin-fixed breast tissue biopsies obtained from two patients. All samples contained microcalcifications of type II, i.e. formed by hydroxyapatite. We demonstrate the feasibility of classifying breast lesions by scanning SAXS of tissues containing microcalcifications with a resolution of 35 mu m x 30 mu m We report a characteristic Bragg peak found around q = 1.725 nm(-1) that occurs primarily for malignant lesions. Such a clear SAXS fingerprint is potentially linked to structural changes of breast tissue and corresponds to dimensions of about 3.7 nm. This material property could be used as an early indicator of malignancy development, as it is readily assessed by SAXS. If this fingerprint is combined with other known SAXS features, which also indicate the level of malignancy, such as lipid spacing and collagen periodicity, it could complement traditional pathology-based analyses. To confirm the SAXS-based classification, a histopathological workup and a gold standard histopathological diagnosis were conducted to determine the malignancy level of the lesions. Our aim is to report this SAXS fingerprint, which is clearly related to malignant breast lesions. However, any further conclusion based on our dataset is limited by the low number of patients and samples. Running a broad study to increase the number of samples and patients is of great importance and relevance for the breast-imaging community.

X-ray grating-based mammography can potentially revolutionize the radiologic approach to breast imaging, because it works well with conventional X-ray tube and can retrieve attenuation, differential phase and dark-field information in a single scanning. However, images, especially the differential phase and dark-field images, are contaminated by noises, which would cause deterioration of the image quality and make the image denoising essential. In this paper, noise-analysis-based non-local means (NANLM) denoising method is proposed for X-ray grating-based mammography based on the previous work on noise analysis. Since pixelwise noise variances can be estimated by noise analysis, NANLM makes use of the self-similarity and sparseness in noise variances to estimate pixel intensities as a similarity-weighted average. Furthermore, in order to estimate noise variances more accurately for better image quality, a two-step NLM-NANLM method is proposed. Numerical simulation, sample model and mammography results all validate the effectiveness of the proposed method.

This paper presents a novel approach towards showing how contractor in agent-based simulation for complex warfare system such as multi-sensor battlefield reconnaissance system can be selected in Contract Net Protocol (CNP) with high efficiency. We first analyze agent and agent-based simulation framework, CNP and collaborators, and present agents interaction chain used to actualize CNP and establish agents trust network. We then obtain contractor's importance weight and dynamic trust by presenting fuzzy similarity-based algorithm and trust modifying algorithm, thus we propose contractor selecting approach based on maximum dynamic integrative trust. We validate the feasibility and capability of this approach by implementing simulation, analyzing compared results and checking the model.

In X-ray grating interferometry, dark-field contrast arises due to partial extinction of the detected interference fringes. This is also called visibility reduction and is attributed to small-angle scattering from unresolved structures in the imaged object. In recent years, analytical quantitative frameworks of dark-field contrast have been developed for highly diluted monodisperse microsphere suspensions with maximum 6% volume fraction. These frameworks assume that scattering particles are separated by large enough distances, which make any interparticle scattering interference negligible. In this paper, we start from the small-angle scattering intensity equation and, by linking Fourier and real-space, we introduce the structure factor and thus extend the analytical and experimental quantitative interpretation of dark-field contrast, for a range of suspensions with volume fractions reaching 40%. The structure factor accounts for interparticle scattering interference. Without introducing any additional fitting parameters, we successfully predict the experimental values measured at the TOMCAT beamline, Swiss Light Source. Finally, we apply this theoretical framework to an experiment probing a range of system correlation lengths by acquiring dark-field images at different energies. This proposed method has the potential to be applied in single-shot-mode using a polychromatic X-ray tube setup and a single-photon-counting energy-resolving detector., Scientific Reports, 6, ISSN:2045-2322

Nature Communications, 7, ISSN:2041-1723

X-ray scattering imaging can provide complementary information to conventional absorption based radiographic imaging about the unresolved microstructures of a sample. The scattering signal can be accessed with various methods based on coherent illumination, which span from self-imaging to speckle scanning. The directional sensitivity of the existing real space imaging methods is limited to a few directions on the imaging plane and requires scanning of the optical components, or the rotation of either the sample or the imaging setup, in order to cover the full range of possible scattering directions. In this Letter the authors propose a new method that allows the simultaneous acquisition of scattering images in all possible directions in a single shot. This is achieved by a specialized phase grating and a detector with sufficient spatial resolution to record the generated interference fringe. The structural length scale sensitivity of the system can be tuned by varying its geometry for a fixed grating design. Taking into account ongoing developments in the field of compact x-ray sources that allow high brightness and sufficient spatial coherence, the applicability of omnidirectional scattering imaging in industrial and medical settings is boosted significantly.