New electron source concept for single-shot sub-100 fs electron diffraction in the 100 keV range

We present a method for producing sub-100 fs electron bunches that are suitable for single-shot ultrafast electron diffraction experiments in the 100 keV energy range. A combination of analytical results and state-of-the-art numerical simulations show that it is possible to create 100 keV, 0.1 pC, 20 fs electron bunches with a spotsize smaller than 500 micron and a transverse coherence length of 3 nm, using established technologies in a table-top set-up. The system operates in the space-charge dominated regime to produce energy-correlated bunches that are recompressed by established radio-frequency techniques. With this approach we overcome the Coulomb expansion of the bunch, providing an entirely new ultrafast electron diffraction source concept

Compression of sub-relativistic space-charge-dominated electron bunches for single-shot femtosecond electron diffraction

We demonstrate compression of 95 keV, space-charge-dominated electron bunches to sub-100 fs durations. These bunches have sufficient charge (200 fC) and are of sufficient quality to capture a diffraction pattern with a single shot, which we demonstrate by a diffraction experiment on a polycrystalline gold foil. Compression is realized by means of velocity bunching as a result of a velocity chirp, induced by the oscillatory longitudinal electric field of a 3 GHz radio-frequency cavity. The arrival time jitter is measured to be 80 fs

Large-scale groundwater modeling using global datasets: a test case for the Rhine-Meuse basin

The current generation of large-scale hydrological models does not include a groundwater flow component. Large-scale groundwater models, involving aquifers and basins of multiple countries, are still rare mainly due to a lack of hydro-geological data which are usually only available in developed countries. In this study, we propose a novel approach to construct large-scale groundwater models by using global datasets that are readily available. As the test-bed, we use the combined Rhine-Meuse basin that contains groundwater head data used to verify the model output. We start by building a distributed land surface model (30 arc-second resolution) to estimate groundwater recharge and river discharge. Subsequently, a MODFLOW transient groundwater model is built and forced by the recharge and surface water levels calculated by the land surface model. Results are promising despite the fact that we still use an offline procedure to couple the land surface and MODFLOW groundwater models (i.e. the simulations of both models are separately performed). The simulated river discharges compare well to the observations. Moreover, based on our sensitivity analysis, in which we run several groundwater model scenarios with various hydro-geological parameter settings, we observe that the model can reasonably well reproduce the observed groundwater head time series. However, we note that there are still some limitations in the current approach, specifically because the offline-coupling technique simplifies the dynamic feedbacks between surface water levels and groundwater heads, and between soil moisture states and groundwater heads. Also the current sensitivity analysis ignores the uncertainty of the land surface model output. Despite these limitations, we argue that the results of the current model show a promise for large-scale groundwater modeling practices, including for data-poor environments and at the global scale

Influence of Deep Margin Elevation and preparation design on the fracture strength of indirectly restored molars

The objectives of this in-vitro study were to investigate the influence of Deep Margin Elevation (DME) and the preparation design (cusp coverage) on the fracture strength and repairability of CAD/CAM manufactured lithium disilicate (LS2) restorations on molars. Sound extracted human molars (n = 60) were randomly divided into 4 groups (n = 15) (inlay without DME (InoD); inlay with DME (IWD); onlay without DME (OnoD); onlay with DME (OnWD)). All samples were aged (1.2 × 106 cycles of 50N, 8000 cycles of 5–55 °C) followed by oblique static loading until fracture. Fracture strength was measured in Newton and the fracture analysis was performed using a (scanning electron) microscope. Data was statistically analyzed using two-way ANOVA and contingency tables. DME did not affect the fracture strength of LS2 restorations to a statistically significant level (p =.15). Onlays were stronger compared to inlays (p =.00). DME and preparation design did not interact (p =.97). However, onlays with DME were significantly stronger than inlays without DME (p =.00). More repairable fractures were observed among inlays (p =.00). Catastrophic, crown-root fractures were more prevalent in onlays (p =.00). DME did not influence repairability of fractures or fracture types to a statistically significant level (p &gt;.05). Within the limitations of this in-vitro study, DME did not statistical significantly affect the fracture strength, nor the fracture type or repairability of LS2 restorations in molars. Cusp coverage did increase the fracture strength. However, oblique forces necessary to fracture both inlays and onlays, either with or without DME, by far exceeded the bite forces that can be expected under physiological clinical conditions. Hence, both inlays and onlays are likely to be fracture resistant during clinical service.</p

Identifying somatic changes in drug transporters using whole genome and transcriptome sequencing data of advanced tumors

Drug resistance is a perpetual problem in cancer therapy with many underlying mechanisms. Alterations in drug transport over the cancer cell membrane can severely alter intratumoral drug exposure, contributing to resistance. Here, we present the somatic mutational landscape of 48 ATP-binding cassette and 416 solute carrier transporter genes in a cohort (CPCT-02; NCT01855477) of 3290 patients with different types of advanced and metastasized cancer through analysis of whole genome and transcriptome sequencing. In order to identify potential stressor mechanisms, we stratified patients based on previous systemic therapies and subsequently investigated the enrichment of mutations and copy-number alterations of transporter genes. In tumors from patients pretreated with protein kinase inhibitors (PKIs), genes encoding for specific copper (SLC31A1 and SLC31A2, χ2-test adjusted p-values: 6.9e-09 and 2.5e-09) and nucleoside transporters (SLC28A2 and SLC28A3, χ2-test adjusted p-values: 3.5e-06 and 6.8e-07) were deleted significantly more frequently than in patients pretreated with chemotherapy. Moreover, we detected 16 transporters that were differentially expressed at RNA level between these treatment groups. These findings contradict mechanisms of selective pressure, as they would be expected to originate during treatment with chemotherapy rather than with PKIs. Hence, they might constitute primary drug resistance mechanisms and, therefore, warrant further study.</p

Statistical M-Estimation and Consistency in Large Deformable Models for Image Warping

The problem of defining appropriate distances between shapes or images and modeling the variability of natural images by group transformations is at the heart of modern image analysis. A current trend is the study of probabilistic and statistical aspects of deformation models, and the development of consistent statistical procedure for the estimation of template images. In this paper, we consider a set of images randomly warped from a mean template which has to be recovered. For this, we define an appropriate statistical parametric model to generate random diffeomorphic deformations in two-dimensions. Then, we focus on the problem of estimating the mean pattern when the images are observed with noise. This problem is challenging both from a theoretical and a practical point of view. M-estimation theory enables us to build an estimator defined as a minimizer of a well-tailored empirical criterion. We prove the convergence of this estimator and propose a gradient descent algorithm to compute this M-estimator in practice. Simulations of template extraction and an application to image clustering and classification are also provided