No abstract

Graphene liquid cell electron microscopy has the necessary temporal and spatial resolution to enable the in situ observation of nanoscale dynamics in solution. However, the chemistry of the solution in the liquid cell during imaging is as yet poorly understood due to the generation of a complex mixture of radiolysis products by the electron beam. In this work, the etching trajectories of nanocrystals were used as a probe to determine the effect of the electron beam dose rate and preloaded etchant, FeCl 3 , on the chemistry of the liquid cell. Initially, illuminating the sample at a low electron beam dose rate generates hydrogen bubbles, providing a reservoir of sacrificial reductant. Increasing the electron beam dose rate leads to a constant etching rate that varies linearly with the electron beam dose rate. Comparing these results with the oxidation potentials of the species in solution, the electron beam likely controls the total concentration of oxidative species in solution and FeCl 3 likely controls the relative ratio of oxidative species, independently determining the etching rate and chemical potential of the reaction, respectively. Correlating these liquid cell etching results with the ex situ oxidative etching of gold nanocrystals using FeCl 3 provides further insight into the liquid cell chemistry while corroborating the liquid cell dynamics with ex situ synthetic behavior. This understanding of the chemistry in the liquid cell will allow researchers to better control the liquid cell electron microscopy environment, allowing new nanoscale materials science experiments to be conducted systematically in a reproducible manner.

Secreted proteins in the Wnt family regulate gene expression in target cells by causing the accumulation of the transcriptional activator beta-catenin. In the absence of Wnt, a protein complex assembled around the scaffold protein Axin targets beta-catenin for destruction, thereby preventing it from transducing inappropriate signals. Loss of Axin or its binding partners APC and GSK3 results in aberrant activation of the Wnt signaling response. We have analyzed the effects of mutant forms of Drosophila Axin with large internal deletions when expressed at physiological levels in vivo, either in the presence or absence of wild type Axin. Surprisingly, even deletions that completely remove the binding sites for fly APC, GSK3 or beta-catenin, though they fail to rescue to viability, these mutant forms of Axin cause only mild developmental defects, indicating largely retained Axin function. Furthermore, two lethal Axin deletion constructs, AxinDeltaRGS and AxinDeltabeta cat(DeltaArm), can complement each other and restore viability. Our findings support a model in which the Axin complex is assembled through cooperative tripartite interactions among the binding partners, making the assembly of functional complexes surprisingly robust.

Hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT). Recent data suggest that body composition features strongly affect post-LT mortality. We examined the impact of body composition on post-LT mortality in patients with HCC. Methods: Data on adult LT recipients who received MELD exception for HCC between 2/29/02-12/31/13 and had CT scan anytime 6 months prior to LT were reviewed (N=118). All available CT scan DICOM (Digital Imaging and Communications in Medicine) files were analyzed using a semiautomated high throughput methodology with algorithms programmed in MATLAB®. Analytic morphomics measurements including dorsal muscle group (DMG) area, visceral and subcutaneous fat and bone mineral density (BMD) were taken at the bottom of the 11th thoracic vertebral level. Results: Thirty-two patients (28%) died during the median follow up of 4.4 years. Number of HCC lesions (HR=2.72; P<0.001), BMD (HR=0.90/HU; P=0.03), pre-LT loco-regional therapy (HR=0.34; P<0.001) and donor age (HR=1.05; P<0.001) were the independent predictors of post-LT mortality. DMG area did not affect post-LT survival. Conclusion: In addition to number of HCC lesions and pre-LT loco-regional therapy, low BMD, a surrogate for bone loss rather than DMG area, was independently associated with post-LT mortality in HCC patients. Bone loss may be an early marker of deconditioning that precedes sarcopenia and may affect transplant outcomes.

Background Vascular pathologies constitute a major cause of graft rejection following organ transplantation. Recent studies have documented an improvement in transplant outcome when organs are preserved through pulsatile perfusion, however, the underlying mechanisms of these observations are poorly characterized. We hypothesized that the temporary absence of flow occurring in the context of organ cold storage conditions disrupts endothelial vasoprotective programs, and that this consequence of stasis may be a target for pharmacological modulation. Methods The expression of the transcription factor KLF2 and its vasoprotective target genes were assessed during cold storage conditions in cultured human endothelial cells and murine aortic segments. In addition, we evaluated the effect of simvastatin use as a supplement in a cold preservation solution on the expression of vasoprotective genes, and on endothelial activation and apoptosis. Results The expression of endothelial KLF2 and its vasoprotective transcriptional targets were rapidly lost during cold preservation in vitro and ex vivo. Importantly, simvastatin treatment blocked the decay of KLF2, sustaining a vasoprotective phenotype, and preventing endothelial activation and apoptosis. Conclusions Flow stasis leads to acute endothelial dysfunction and apoptosis in the context of cold storage conditions. Supplementation of organ preservation solutions with pharmacologic agents that restore endothelial vasoprotective programs via KLF2 upregulation may represent a significant advancement of current organ preservation techniques.

We probe electric-field noise near the metal surface of an ion trap chip in a previously unexplored high-temperature regime. We observe a non-trivial temperature dependence with the noise amplitude at 1-MHz frequency saturating around 500 K. Measurements of the noise spectrum reveal a 1/f α≈1 -dependence and a small decrease in α between low and high temperatures. This behavior can be explained by considering noise from a distribution of thermally-activated two-level fluctuators with activation energies between 0.35 eV and 0.65 eV. Processes in this energy range may be relevant to understanding electric-field noise in ion traps; for example defect motion in the solid state and surface adsorbate binding energies. Studying these processes may aid in identifying the origin of excess electric-field noise in ion traps -a major source of ion motional decoherence limiting the performance of surface traps as quantum devices.

No abstract

Background & Aims: Use of direct-acting oral anticoagulants (DOACs) is increasing, but little is known about the associated risks in patients undergoing colonoscopy with polypectomy. We aimed to determine the risk of post-polypectomy complications in patients prescribed DOACs. Methods: We performed a retrospective analysis using the Clinformatics Data Mart Database (a de-identified administrative database from a large national insurance provider) to identify adults who underwent colonoscopy with polypectomy or endoscopic mucosal resection (EMR) from January 1, 2011, through December 31, 2015. We collected data from 11,504 patients prescribed antithrombotic agents (1590 DOAC, 3471 warfarin, and 6443 clopidogrel) and 599,983 patients not prescribed antithrombotics of interest (controls). We compared 30-day post-polypectomy complications, including gastrointestinal bleeding (GIB), cerebrovascular accident (CVA), myocardial infarction (MI), and hospital admissions, of patients prescribed DOACs, warfarin, or clopidogrel vs controls. Results: Post-polypectomy complications were uncommon but occurred in a significantly higher proportion of patients receiving any antithrombotic vs controls (P<0.001). The percentage of patients in the DOAC group with GIB was 0.63% (95% CI, 0.3%-1.2%) vs 0.2% (95% CI, 0.2%-0.3%) in controls. The percentage of patients with CVA in the DOAC group was 0.06% (95% CI, 0.01%-0.35%) vs 0.04% (95% CI, 0.04%-0.05%) in controls. After we adjusted for bridge anticoagulation, EMR, Charlson comorbidity index (CCI), and CHADS 2 (congestive heart failure, hypertension, age over 75, diabetes, stroke [double weight]) score, patients prescribed DOACs no longer had a