Electron beam-induced current imaging with two-angstrom resolution.

An electron microscope's primary beam simultaneously ejects secondary electrons (SEs) from the sample and generates electron beam-induced currents (EBICs) in the sample. Both signals can be captured and digitized to produce images. The off-sample Everhart-Thornley detectors that are common in scanning electron microscopes (SEMs) can detect SEs with low noise and high bandwidth. However, the transimpedance amplifiers appropriate for detecting EBICs do not have such good performance, which makes accessing the benefits of EBIC imaging at high-resolution relatively more challenging. Here we report lattice-resolution imaging via detection of the EBIC produced by SE emission (SEEBIC). We use an aberration-corrected scanning transmission electron microscope (STEM), and image both microfabricated devices and standard calibration grids

Irreversibility at macromolecular scales in the flake graphite of the lithium-ion battery anode.

Charging a commercial lithium-ion battery intercalates lithium into the graphite-based anode, creating various lithium carbide structures. Despite their economic importance, these structures and the dynamics of their charging-discharging transitions are not well-understood. We have videoed single microcrystals of high-quality, natural graphite undergoing multiple lithiation-delithiation cycles. Because the equilibrium lithium-carbide compounds corresponding to full, half, and one-third charge are gold, red, and blue respectively, video observations give direct insight into both the macromolecular structures and the kinematics of charging and discharging. We find that the transport during the first lithiation is slow and orderly, and follows the core-shell or shrinking annuli model with phase boundaries moving at constant velocities (i.e. non-diffusively). Subsequent lithiations are markedly different, showing transport that is both faster and disorderly, which indicates that the initially pristine graphite is irreversibly and considerably altered during the first cycle. In all cases deintercalation is not the time-reverse of intercalation. These findings both illustrate how lithium enters nearly defect-free host material, and highlight the differences between the idealized case and an actual, cycling graphite anode

Plasma microRNA levels following resection of metastatic melanoma

Melanoma remains the leading cause of skin cancer–related deaths. Surgical resection and adjuvant therapies can result in disease-free intervals for stage III and stage IV disease; however, recurrence is common. Understanding microRNA (miR) dynamics following surgical resection of melanomas is critical to accurately interpret miR changes suggestive of melanoma recurrence. Plasma of 6 patients with stage III (n = 2) and stage IV (n = 4) melanoma was evaluated using the NanoString platform to determine pre- and postsurgical miR expression profiles, enabling analysis of more than 800 miRs simultaneously in 12 samples. Principal component analysis detected underlying patterns of miR expression between pre- vs postsurgical patients. Group A contained 3 of 4 patients with stage IV disease (pre- and postsurgical samples) and 2 patients with stage III disease (postsurgical samples only). The corresponding preoperative samples to both individuals with stage III disease were contained in group B along with 1 individual with stage IV disease (pre- and postsurgical samples). Group A was distinguished from group B by statistically significant analysis of variance changes in miR expression ( P < .0001). This analysis revealed that group A vs group B had downregulation of let-7b-5p, miR-520f, miR-720, miR-4454, miR-21-5p, miR-22-3p, miR-151a-3p, miR-378e, and miR-1283 and upregulation of miR-126-3p, miR-223-3p, miR-451a, let-7a-5p, let-7g-5p, miR-15b-5p, miR-16-5p, miR-20a-5p, miR-20b-5p, miR-23a-3p, miR-26a-5p, miR-106a-5p, miR-17-5p, miR-130a-3p, miR-142-3p, miR-150-5p, miR-191-5p, miR-199a-3p, miR-199b-3p, and miR-1976. Changes in miR expression were not readily evident in individuals with distant metastatic disease (stage IV) as these individuals may have prolonged inflammatory responses. Thus, inflammatory-driven miRs coinciding with tumor-derived miRs can blunt anticipated changes in expression profiles following surgical resection

Exploring Mechanisms for Model‐Dependency of the Stratospheric Response to Arctic Warming

The Arctic is estimated to have warmed up to four times faster than the rest of the globe since the 1980s. There is significant interest in understanding the mechanisms by which such warming may impact weather and climate at lower latitudes. One such mechanism is the “stratospheric pathway”; Arctic warming is proposed to induce a wave‐driven weakening of the stratospheric polar vortex, which may subsequently impact large‐scale tropospheric circulation. However, recent comprehensive model studies have found systematic differences in both the magnitude and sign of the stratospheric response to Arctic warming. Using a series of idealized model simulations, we show that this response is sensitive to characteristics of the warming and mean polar vortex strength. In all simulations, imposed polar warming amplifies upward wave propagation from the troposphere, consistent with comprehensive models. However, as polar warming strength and depth increases, the region through which waves can propagate is narrowed, inducing wave breaking and deceleration of the flow in the lower stratosphere. Thus, the mid‐stratosphere is less affected, with reduced sudden stratospheric warming frequency for stronger and deeper warming compared to weaker and shallower warming. We also find that the sign of the stratospheric response depends on the mean strength of the vortex, and that the stratospheric response in turn plays a role in the magnitude of the tropospheric jet response. Our results help explain the spread across multimodel ensembles of comprehensive climate models

Differential electron yield imaging with STXM

Total electron yield (TEY) imaging is an established scanning transmission X-ray microscopy (STXM) technique that gives varying contrast based on a sample's geometry, elemental composition, and electrical conductivity. However, the TEY-STXM signal is determined solely by the electrons that the beam ejects from the sample. A related technique, X-ray beam-induced current (XBIC) imaging, is sensitive to electrons and holes independently, but requires electric fields in the sample. Here we report that multi-electrode devices can be wired to produce differential electron yield (DEY) contrast, which is also independently sensitive to electrons and holes, but does not require an electric field. Depending on whether the region illuminated by the focused STXM beam is better connected to one electrode or another, the DEY-STXM contrast changes sign. DEY-STXM images thus provide a vivid map of a device's connectivity landscape, which can be key to understanding device function and failure. To demonstrate an application in the area of failure analysis, we image a 100~nm, lithographically-defined aluminum nanowire that has failed after being stressed with a large current density.Comment: 8 pages, 6 figure

Dark-field transmission electron microscopy and the Debye-Waller factor of graphene

Graphene's structure bears on both the material's electronic properties and fundamental questions about long range order in two-dimensional crystals. We present an analytic calculation of selected area electron diffraction from multi-layer graphene and compare it with data from samples prepared by chemical vapor deposition and mechanical exfoliation. A single layer scatters only 0.5% of the incident electrons, so this kinematical calculation can be considered reliable for five or fewer layers. Dark-field transmission electron micrographs of multi-layer graphene illustrate how knowledge of the diffraction peak intensities can be applied for rapid mapping of thickness, stacking, and grain boundaries. The diffraction peak intensities also depend on the mean-square displacement of atoms from their ideal lattice locations, which is parameterized by a Debye-Waller factor. We measure the Debye-Waller factor of a suspended monolayer of exfoliated graphene and find a result consistent with an estimate based on the Debye model. For laboratory-scale graphene samples, finite size effects are sufficient to stabilize the graphene lattice against melting, indicating that ripples in the third dimension are not necessary.Comment: 10 pages, 4 figure

Analysis of the 10q11 Cancer Risk Locus Implicates MSMB and NCOA4 in Human Prostate Tumorigenesis

Genome-wide association studies (GWAS) have established a variant, rs10993994, on chromosome 10q11 as being associated with prostate cancer risk. Since the variant is located outside of a protein-coding region, the target genes driving tumorigenesis are not readily apparent. Two genes nearest to this variant, MSMB and NCOA4, are strong candidates for mediating the effects of rs109939934. In a cohort of 180 individuals, we demonstrate that the rs10993994 risk allele is associated with decreased expression of two MSMB isoforms in histologically normal and malignant prostate tissue. In addition, the risk allele is associated with increased expression of five NCOA4 isoforms in histologically normal prostate tissue only. No consistent association with either gene is observed in breast or colon tissue. In conjunction with these findings, suppression of MSMB expression or NCOA4 overexpression promotes anchorage-independent growth of prostate epithelial cells, but not growth of breast epithelial cells. These data suggest that germline variation at chromosome 10q11 contributes to prostate cancer risk by influencing expression of at least two genes. More broadly, the findings demonstrate that disease risk alleles may influence multiple genes, and associations between genotype and expression may only be observed in the context of specific tissue and disease states