Correction of Optical Aberrations in Elliptic Neutron Guides

Modern, nonlinear ballistic neutron guides are an attractive concept in neutron beam delivery and instrumentation, because they offer increased performance over straight or linearly tapered guides. However, like other ballistic geometries they have the potential to create significantly non-trivial instrumental resolution functions. We address the source of the most prominent optical aberration, namely coma, and we show that for extended sources the off-axis rays have a different focal length from on-axis rays, leading to multiple reflections in the guide system. We illustrate how the interplay between coma, sources of finite size, and mirrors with non-perfect reflectivity can therefore conspire to produce uneven distributions in the neutron beam divergence, the source of complicated resolution functions. To solve these problems, we propose a hybrid elliptic-parabolic guide geometry. Using this new kind of neutron guide shape, it is possible to condition the neutron beam and remove almost all of the aberrations, whilst providing the same performance in beam current as a standard elliptic neutron guide. We highlight the positive implications for a number of neutron scattering instrument types that this new shape can bring.Comment: Presented at NOP2010 Conference in Alpe d'Huez, France, in March 201

Stability and placement of Ag/AgCl quasi-reference counter electrodes in confined electrochemical cells

Nanoelectrochemistry is an important and growing branch of electrochemistry that encompasses a number of key research areas, including (electro)catalysis, energy storage, biomedical/environmental sensing, and electrochemical imaging. Nanoscale electrochemical measurements are often performed in confined environments over prolonged experimental time scales with nonisolated quasi-reference counter electrodes (QRCEs) in a simplified two-electrode format. Herein, we consider the stability of commonly used Ag/AgCl QRCEs, comprising an AgCl-coated wire, in a nanopipet configuration, which simulates the confined electrochemical cell arrangement commonly encountered in nanoelectrochemical systems. Ag/AgCl QRCEs possess a very stable reference potential even when used immediately after preparation and, when deployed in Cl– free electrolyte media (e.g., 0.1 M HClO4) in the scanning ion conductance microscopy (SICM) format, drift by only ca. 1 mV h–1 on the several hours time scale. Furthermore, contrary to some previous reports, when employed in a scanning electrochemical cell microscopy (SECCM) format (meniscus contact with a working electrode surface), Ag/AgCl QRCEs do not cause fouling of the surface (i.e., with soluble redox byproducts, such as Ag+) on at least the 6 h time scale, as long as suitable precautions with respect to electrode handling and placement within the nanopipet are observed. These experimental observations are validated through finite element method (FEM) simulations, which consider Ag+ transport within a nanopipet probe in the SECCM and SICM configurations. These results confirm that Ag/AgCl is a stable and robust QRCE in confined electrochemical environments, such as in nanopipets used in SICM, for nanopore measurements, for printing and patterning, and in SECCM, justifying the widespread use of this electrode in the field of nanoelectrochemistry and beyond

Development of a single-session, transdiagnostic preventive intervention for young adults at risk for emotional disorders

Cognitive-behavioral prevention programs have demonstrated efficacy in reducing subclinical symptoms of anxiety and depression, and there is some evidence to suggest that they can lower the risk of future disorder onset. However, existing interventions tend to be relatively lengthy and target specific disorders or problem areas, both of which limit their potential for widespread dissemination. To address these limitations, we aimed to develop a single-session, transdiagnostic preventive intervention based on the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders for young adults at risk for developing anxiety and/or depressive disorders within a college setting. Results from this proof-of-concept study indicated that the intervention was viewed as highly satisfactory and acceptable. The intervention also was successful at delivering adaptive emotion management skills in its 2-hr workshop format. Future studies evaluating the efficacy of this novel transdiagnostic, emotion-focused prevention program are warranted.Accepted manuscrip

Nanoscale electrochemical mapping

Surfaces and interfaces, of both practical and fundamental interest, have long been recognized to be complex, yet while there are many microscopy and spectroscopy methods for imaging structure, topography and surface chemical composition at high spatial resolution, there are relatively few techniques for mapping associated chemical fluxes in the near-interface region. In this regard, scanning electrochemical probe microscopy (SEPM), which utilizes a small scale electrode probe as an imaging device, has had a unique place in the scanning probe microscopy (SPM) family of techniques, in being able to map chemical fluxes and interfacial reactivity. For a long time, techniques such as scanning electrochemical microscopy (SECM) were largely stuck at the micron –or larger –scale in terms of spatial resolution, but recent years have seen spectacular progress, such that a variety of different types of SEPM technique are now available and 10sof nm spatial resolution is becoming increasingly accessible. This step-change in capability is opening many new opportunities for the characterization of flux processes and interfacial activity in a whole raft of systems, including electrode surfaces, electromaterials, soft matter, living cells and tissues

Simultaneous topography and reaction flux mapping at and around electrocatalytic nanoparticles

The characterization of electrocatalytic reactions at individual nanoparticles (NPs) is presently of considerable interest but very challenging. Herein, we demonstrate how simple-to-fabricate nanopipette probes with diameters of approximately 30 nm can be deployed in a scanning ion conductance microscopy (SICM) platform to simultaneously visualize electrochemical reactivity and topography with high spatial resolution at electrochemical interfaces. By employing a self-referencing hopping mode protocol, whereby the probe is brought from bulk solution to the near-surface at each pixel, and with potential-time control applied at the substrate, current measurements at the nanopipette can be made with high precision and resolution (30 nm resolution, 2600 pixels μm–2, <0.3 s pixel−1) to reveal a wealth of information on the substrate physicochemical properties. This methodology has been applied to image the electrocatalytic oxidation of borohydride at ensembles of AuNPs on a carbon fiber support in alkaline media, whereby the depletion of hydroxide ions and release of water during the reaction results in a detectable change in the ionic composition around the NPs. Through the use of finite element method simulations, these observations are validated and analyzed to reveal important information on heterogeneities in ion flux between the top of a NP and the gap at the NP-support contact, diffusional overlap and competition for reactant between neighboring NPs, and differences in NP activity. These studies highlight key issues that influence the behavior of NP assemblies at the single NP level and provide a platform for the use of SICM as an important tool for electrocatalysis studies

The unified protocol for transdiagnostic treatment of emotional disorders compared with diagnosis-specific protocols for anxiety disorders a randomized clinical trial

IMPORTANCE: Transdiagnostic interventions have been developed to address barriers to the dissemination of evidence-based psychological treatments, but only a few preliminary studies have compared these approaches with existing evidence-based psychological treatments. OBJECTIVE: To determine whether the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) is at least as efficacious as single-disorder protocols (SDPs) in the treatment of anxiety disorders. DESIGN, SETTING, AND PARTICIPANTS: From June 23, 2011, to March 5, 2015, a total of 223 patients at an outpatient treatment center with a principal diagnosis of panic disorder with or without agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, or social anxiety disorder were randomly assigned by principal diagnosis to the UP, an SDP, or a waitlist control condition. Patients received up to 16 sessions of the UP or an SDP for 16 to 21 weeks. Outcomes were assessed at baseline, after treatment, and at 6-month follow-up. Analysis in this equivalence trial was based on intention to treat. INTERVENTIONS: The UP or SDPs. MAIN OUTCOMES AND MEASURES: Blinded evaluations of principal diagnosis clinical severity rating were used to evaluate an a priori hypothesis of equivalence between the UP and SDPs. RESULTS: Among the 223 patients (124 women and 99 men; mean [SD] age, 31.1 [11.0] years), 88 were randomized to receive the UP, 91 to receive an SDP, and 44 to the waitlist control condition. Patients were more likely to complete treatment with the UP than with SDPs (odds ratio, 3.11; 95% CI, 1.44-6.74). Both the UP (Cohen d, −0.93; 95% CI, −1.29 to −0.57) and SDPs (Cohen d, −1.08; 95% CI, −1.43 to −0.73) were superior to the waitlist control condition at acute outcome. Reductions in clinical severity rating from baseline to the end of treatment (β, 0.25; 95% CI, −0.26 to 0.75) and from baseline to the 6-month follow-up (β, 0.16; 95% CI, −0.39 to 0.70) indicated statistical equivalence between the UP and SDPs. CONCLUSIONS AND RELEVANCE: The UP produces symptom reduction equivalent to criterion standard evidence-based psychological treatments for anxiety disorders with less attrition. Thus, it may be possible to use 1 protocol instead of multiple SDPs to more efficiently treat the most commonly occurring anxiety and depressive disorders.This study was funded by grant R01 MH090053 from the National Institute of Mental Health. (R01 MH090053 - National Institute of Mental Health)First author draf

Hepatitis C Virus Indirectly Disrupts DNA Damage-Induced p53 Responses by Activating Protein Kinase R

ABSTRACT Many DNA tumor viruses promote cellular transformation by inactivating the critically important tumor suppressor protein p53. In contrast, it is not known whether p53 function is disrupted by hepatitis C virus (HCV), a unique, oncogenic RNA virus that is the leading infectious cause of liver cancer in many regions of the world. Here we show that HCV-permissive, liver-derived HepG2 cells engineered to constitutively express microRNA-122 (HepG2/miR-122 cells) have normal p53-mediated responses to DNA damage and that HCV replication in these cells potently suppresses p53 responses to etoposide, an inducer of DNA damage, or nutlin-3, an inhibitor of p53 degradation pathways. Upregulation of p53-dependent targets is consequently repressed within HCV-infected cells, with potential consequences for cell survival. Despite this, p53 function is not disrupted by overexpression of the complete HCV polyprotein, suggesting that altered p53 function may result from the host response to viral RNA replication intermediates. Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated ablation of double-stranded RNA (dsRNA)-activated protein kinase R (PKR) restored p53 responses while boosting HCV replication, showing that p53 inhibition results directly from viral activation of PKR. The hepatocellular abundance of phosphorylated PKR is elevated in HCV-infected chimpanzees, suggesting that PKR activation and consequent p53 inhibition accompany HCV infection in vivo . These findings reveal a feature of the host response to HCV infection that may contribute to hepatocellular carcinogenesis. IMPORTANCE Chronic infection with hepatitis C virus (HCV) is the leading cause of liver cancer in most developed nations. However, the mechanisms whereby HCV infection promotes carcinogenesis remain unclear. Here, we demonstrate that HCV infection inhibits the activation of p53 following DNA damage. Contrary to previous reports, HCV protein expression is insufficient to inhibit p53. Rather, p53 inhibition is mediated by cellular protein kinase R (PKR), which is activated by HCV RNA replication and subsequently suppresses global protein synthesis. These results redefine our understanding of how HCV infection influences p53 function. We speculate that persistent disruption of p53-mediated DNA damage responses may contribute to hepatocellular carcinogenesis in chronically infected individuals

Improving Sparse Representation-Based Classification Using Local Principal Component Analysis

Sparse representation-based classification (SRC), proposed by Wright et al., seeks the sparsest decomposition of a test sample over the dictionary of training samples, with classification to the most-contributing class. Because it assumes test samples can be written as linear combinations of their same-class training samples, the success of SRC depends on the size and representativeness of the training set. Our proposed classification algorithm enlarges the training set by using local principal component analysis to approximate the basis vectors of the tangent hyperplane of the class manifold at each training sample. The dictionary in SRC is replaced by a local dictionary that adapts to the test sample and includes training samples and their corresponding tangent basis vectors. We use a synthetic data set and three face databases to demonstrate that this method can achieve higher classification accuracy than SRC in cases of sparse sampling, nonlinear class manifolds, and stringent dimension reduction.Comment: Published in "Computational Intelligence for Pattern Recognition," editors Shyi-Ming Chen and Witold Pedrycz. The original publication is available at http://www.springerlink.co