Differential phase contrast images in scanning transmission electron microscopy can be directly and quantitatively related to the gradient of the projected specimen potential provided that (a) the ...specimen can be treated as a phase object and (b) full 2D diffraction patterns as a function of probe position can be obtained. Both are challenging to achieve in atomic resolution imaging. The former is fundamentally limited by probe spreading and dynamical electron scattering, and we explore its validity domain in the context of atomic resolution differential phase contrast imaging. The latter, for which proof-of-principle experimental data sets exist, is not yet routine. We explore the extent to which more established segmented detector geometries can instead be used to reconstruct a quantitatively good approximation to the projected specimen potential.
•Atomic-resolution differential phase contrast (DPC) imaging explored via simulation.•Phase-object approximation limits quantification to specimens a few nanometers thick.•Segmented detectors give good estimates of the diffraction pattern's first moment.
We explore the dynamics of image formation in the so-called annular bright field mode in scanning transmission electron microscopy, whereby an annular detector is used with detector collection range ...lying within the cone of illumination, i.e. the bright field region. We show that this imaging mode allows us to reliably image both light and heavy columns over a range of thickness and defocus values, and we explain the contrast mechanisms involved. The role of probe and detector aperture sizes is considered, as is the sensitivity of the method to intercolumn spacing and local disorder.
Activating mutation of KRAS and BRAF are focused on as potential prognostic and predictive biomarkers in patients with colorectal cancer (CRC) treated with anti-EGFR therapies. This study ...investigated the clinicopathological features and prognostic impact of KRAS/BRAF mutation in advanced and recurrent CRC patients.
Patients with advanced and recurrent CRC treated with systemic chemotherapy (n=229) were analysed for KRAS/BRAF genotypes by cycleave PCR. Prognostic factors associated with survival were identified by univariate and multivariate analyses using the Cox proportional hazards model.
KRAS and BRAF mutations were present in 34.5% and 6.5% of patients, respectively. BRAF mutated tumours were more likely to develop on the right of the colon, and to be of the poorly differentiated adenocarcinoma or mucinous carcinoma, and peritoneal metastasis. The median overall survival (OS) for BRAF mutation-positive and KRAS 13 mutation-positive patients was 11.0 and 27.7 months, respectively, which was significantly worse than that for patients with wild-type (wt) KRAS and BRAF (40.6 months) (BRAF; HR=4.25, P<0.001, KRAS13; HR=2.03, P=0.024). After adjustment for significant features by multivariate Cox regression analysis, BRAF mutation was associated with poor OS (HR=4.23, P=0.019).
Presence of mutated BRAF is one of the most powerful prognostic factors for advanced and recurrent CRC. The KRAS13 mutation showed a trend towards poor OS in patients with advanced and recurrent CRC.
When the motion of electrons is restricted to a plane under a perpendicular magnetic field, a variety of quantum phases emerge at low temperatures, the properties of which are dictated by the Coulomb ...interaction and its interplay with disorder. At very strong magnetic field, the sequence of fractional quantum Hall liquid phases1 terminates in an insulating phase, which is widely believed to be due to the solidification of electrons into domains possessing Wigner crystal2 order3, 4, 5, 6, 7, 8, 9, 10, 11. The existence of such Wigner crystal domains is signalled by the emergence of microwave pinning-mode resonances10, 11, which reflect the mechanical properties characteristic of a solid. However, the most direct manifestation of the broken translational symmetry accompanying the solidification--the spatial modulation of particles' probability amplitudes--has not been observed yet. Here, we demonstrate that nuclear magnetic resonance provides a direct probe of the density topography of electron solids in the integer and fractional quantum Hall regimes. The data uncover quantum and thermal fluctuations of lattice electrons resolved on the nanometre scale. Our results pave the way to studies of other exotic phases with non-trivial spatial spin/charge order.
•The selective recovery of indium was achieved in CCFS from sulfuric acid solution.•Anionic organophosphate surfactant was selected as the selective metal collector.•The screening tests on ...anionic/nonionic surfactants on the market were carried out.
Continuous counter-current foam separation (CCFS) with simultaneous injections of metal and surfactant solutions respectively into rising foam bed was applied to In(III) recovery from sulfuric acid solutions containing ternary metal ions of In/Cu/Zn. Through the screening tests of the surfactants in both conventional batch foam separation and CCFS, anionic organophosphate surfactant which has similar structure to phosphoric acid extractant (D2EHPA) was selected as the metal collector, with an addition of a nonionic co-surfactant as the foam stabilizer. The optimized surfactant combination was shown anionic A219B/nonionic POOE20 in this study; the complete recovery of In(III) was attained with the enrichment ratio of 5.5, whereas those of the other metals were suppressed in trace level, resulting in the excellent selective recovery. Moreover, metal solutions of quaternary In/Fe/Cu/Zn were also examined, and a dose of reductant for interfering Fe(III) into the metal solution was executed for improving the separation efficiency; the dose of ascorbic acid could invert the affinity order of A219B from Fe > In to In > Fe. The percent recovery and enrichment ratio of In(III) were 97% and 5.5, while the separation factors of In/Fe, In/Cu and In/Zn were 93, 1300 and 1300 respectively. This is our first favorable case for expanding the choice range of target metal ions in CCFS using anionic surfactants.
Atomic-resolution electron microscopes utilize high-power magnetic lenses to produce magnified images of the atomic details of matter. Doing so involves placing samples inside the magnetic objective ...lens, where magnetic fields of up to a few tesla are always exerted. This can largely alter, or even destroy, the magnetic and physical structures of interest. Here, we describe a newly developed magnetic objective lens system that realizes a magnetic field free environment at the sample position. Combined with a higher-order aberration corrector, we achieve direct, atom-resolved imaging with sub-Å spatial resolution with a residual magnetic field of less than 0.2 mT at the sample position. This capability enables direct atom-resolved imaging of magnetic materials such as silicon steels. Removing the need to subject samples to high magnetic field environments enables a new stage in atomic resolution electron microscopy that realizes direct, atomic-level observation of samples without unwanted high magnetic field effects.
The selective degradation of target proteins with small molecules is a novel approach to the treatment of various diseases, including cancer. We have developed a protein knockdown system with a ...series of hybrid small compounds that induce the selective degradation of target proteins via the ubiquitin-proteasome pathway. In this study, we designed and synthesized novel small molecules called SNIPER(TACC3)s, which target the spindle regulatory protein transforming acidic coiled-coil-3 (TACC3). SNIPER(TACC3)s induce poly-ubiquitylation and proteasomal degradation of TACC3 and reduce the TACC3 protein level in cells. Mechanistic analysis indicated that the ubiquitin ligase APC/C(CDH1) mediates the SNIPER(TACC3)-induced degradation of TACC3. Intriguingly, SNIPER(TACC3) selectively induced cell death in cancer cells expressing a larger amount of TACC3 protein than normal cells. These results suggest that protein knockdown of TACC3 by SNIPER(TACC3) is a potential strategy for treating cancers overexpressing the TACC3 protein.
Impurity doping often alters or improves the properties of materials. In alumina, grain boundaries play a key role in deformation mechanisms, particularly in the phenomenon of grain boundary sliding ...during creep at high temperatures. We elucidated the atomic-scale structure in alumina grain boundaries and its relationship to the suppression of creep upon doping with yttrium by using atomic resolution microscopy and high-precision calculations. We find that the yttrium segregates to very localized regions along the grain boundary and alters the local bonding environment, thereby strengthening the boundary against mechanical creep.
Chemical mapping using energy dispersive X-ray spectroscopy (EDS) in scanning transmission electron microscopy (STEM) has recently shown to be a powerful technique in analyzing the elemental identity ...and location of atomic columns in materials at atomic resolution. However, most applications of EDS STEM have been used only to qualitatively map whether elements are present at specific sites. Obtaining calibrated EDS STEM maps so that they are on an absolute scale is a difficult task and even if one achieves this, extracting quantitative information about the specimen – such as the number or density of atoms under the probe – adds yet another layer of complexity to the analysis due to the multiple elastic and inelastic scattering of the electron probe. Quantitative information may be obtained by comparing calibrated EDS STEM with theoretical simulations, but in this case a model of the structure must be assumed a priori. Here we first theoretically explore how exactly elastic and thermal scattering of the probe confounds the quantitative information one is able to extract about the specimen from an EDS STEM map. We then show using simulation how tilting the specimen (or incident probe) can reduce the effects of scattering and how it can provide quantitative information about the specimen. We then discuss drawbacks of this method – such as the loss of atomic resolution along the tilt direction – but follow this with a possible remedy: precession averaged EDS STEM mapping.
•Signal obtained in EDS STEM maps (of STO) compared to non-channelling signal.•Deviation from non-channelling signal occurs in on-axis experiments.•Tilting specimen: signal close to non-channelling case but atomic resolution is lost.•Tilt-precession series: non-channelling signal and atomic-resolution features obtained.•Associated issues are discussed.
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