Alternating Projections and Douglas-Rachford for Sparse Affine Feasibility

The problem of finding a vector with the fewest nonzero elements that satisfies an underdetermined system of linear equations is an NP-complete problem that is typically solved numerically via convex heuristics or nicely-behaved nonconvex relaxations. In this work we consider elementary methods based on projections for solving a sparse feasibility problem without employing convex heuristics. In a recent paper Bauschke, Luke, Phan and Wang (2014) showed that, locally, the fundamental method of alternating projections must converge linearly to a solution to the sparse feasibility problem with an affine constraint. In this paper we apply different analytical tools that allow us to show global linear convergence of alternating projections under familiar constraint qualifications. These analytical tools can also be applied to other algorithms. This is demonstrated with the prominent Douglas-Rachford algorithm where we establish local linear convergence of this method applied to the sparse affine feasibility problem.Comment: 29 pages, 2 figures, 37 references. Much expanded version from last submission. Title changed to reflect new development

Hierarchical Losses and New Resources for Fine-grained Entity Typing and Linking

Extraction from raw text to a knowledge base of entities and fine-grained types is often cast as prediction into a flat set of entity and type labels, neglecting the rich hierarchies over types and entities contained in curated ontologies. Previous attempts to incorporate hierarchical structure have yielded little benefit and are restricted to shallow ontologies. This paper presents new methods using real and complex bilinear mappings for integrating hierarchical information, yielding substantial improvement over flat predictions in entity linking and fine-grained entity typing, and achieving new state-of-the-art results for end-to-end models on the benchmark FIGER dataset. We also present two new human-annotated datasets containing wide and deep hierarchies which we will release to the community to encourage further research in this direction: MedMentions, a collection of PubMed abstracts in which 246k mentions have been mapped to the massive UMLS ontology; and TypeNet, which aligns Freebase types with the WordNet hierarchy to obtain nearly 2k entity types. In experiments on all three datasets we show substantial gains from hierarchy-aware training.Comment: ACL 201

Nanoscale electrochemical movies and synchronous topographical mapping of electrocatalytic materials

Techniques in the scanning electrochemical probe microscopy (SEPM) family have shown great promise for resolving nanoscale structure–function (e.g., catalytic activity) at complex (electro)chemical interfaces, which is a long-term aspiration in (electro)materials science. In this work, we explore how a simple meniscus imaging probe, based on an easily-fabricated, single-channeled nanopipette (inner diameter ≈ 30 nm) can be deployed in the scanning electrochemical cell microscopy (SECCM) platform as a fast, versatile and robust method for the direct, synchronous electrochemical/topographical imaging of electrocatalytic materials at the nanoscale. Topographical and voltammetric data are acquired synchronously at a spatial resolution of 50 nm to construct maps that resolve particular surface features on the sub-10 nm scale and create electrochemical activity movies composed of hundreds of potential-resolved images on the minutes timescale. Using the hydrogen evolution reaction (HER) at molybdenite (MoS2) as an exemplar system, the experimental parameters critical to achieving a robust scanning protocol (e.g., approach voltage, reference potential calibration) with high resolution (e.g., hopping distance) and optimal scan times (e.g., voltammetric scan rate, approach rate etc.) are considered and discussed. Furthermore, sub-nanoentity reactivity mapping is demonstrated with glassy carbon (GC) supported single-crystalline {111}-oriented two-dimensional Au nanocrystals (AuNCs), which exhibit uniform catalytic activity at the single-entity and sub-single entity level. The approach outlined herein signposts a future in (electro)materials science in which the activity of electroactive nanomaterials can be viewed directly and related to structure through electrochemical movies, revealing active sites unambiguously

New developments in the treatment of metastatic melanoma – role of dabrafenib–trametinib combination therapy

Development of selective inhibitors of BRAF has improved the survival of patients with BRAF-mutant melanoma. The progression-free survival after treatment with a BRAF inhibitor is modest, however, and BRAF inhibitors induce cutaneous toxicity, likely due to paradoxical activation of the mitogen-activated protein kinase pathway. Combining selective BRAF and MEK inhibition, such as the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib, has been shown to improve the response rate and progression-free survival in patients with advanced melanoma while significantly alleviating the paradoxical activation of mitogen-activated protein kinase. This combination treatment results in a reduction in skin toxicity relative to that seen with a BRAF inhibitor alone; however, addition of the MEK inhibitor adds other toxicities, such as pyrexia and gastrointestinal or ocular toxicity. While combined BRAF–MEK inhibition appears primed to become a standard molecular approach for BRAF-mutant melanoma, the utility of the combination has to be considered in the rapidly changing landscape of immunotherapeutics, such as immune checkpoint blockade using anti-cytotoxic T lymphocyte antigen-4 and anti-programmed death-1/programmed death-L1 antibodies. Here we review the development of the dabrafenib plus trametinib combination, the characteristics of each drug and the combination, and the role of this combination in the management of patients with BRAF-mutant melanoma

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

Time-resolved detection of surface oxide formation at individual gold nanoparticles : role in electrocatalysis and new approach for sizing by electrochemical impacts

Nanoparticle (NP) impacts on electrode surfaces has become an important method for analyzing the properties and activity of individual NPs, by either: (i) electrocatalytic reactions; or (ii) volumetric (dissolution) analyses. Using Au NPs as an exemplar system, this contribution shows that it is possible to detect surface oxide formation at individual NPs, which occurs on a rapid timescale (ca. 500 µs). The charge associated with this ‘surface oxidation method’ can be used for sizing (with results that are comparable to TEM) despite charges of only fC being measured. This platform further allows the role of surface oxides in electrocatalysis to be elucidated, with the timescale of oxide formation being controllable (i.e., ‘tunable’) through the applied potential, as illustrated through studies of borohydride and hydrazine electro-oxidation. Finally, all of these studies are carried out on an oxide-covered gold substrate, which can be prepared and regenerated straightforwardly on a gold electrode, through the applied potential

Nanoscale surface structure–activity in electrochemistry and electrocatalysis

Nanostructured electrochemical interfaces (electrodes) are found in diverse applications ranging from electrocatalysis and energy storage to biomedical and environmental sensing. These functional materials, which possess compositional and structural heterogeneity over a wide range of length scales, are usually characterized by classical macroscopic or “bulk” electrochemical techniques that are not well-suited to analyzing the nonuniform fluxes that govern the electrochemical response at complex interfaces. In this Perspective, we highlight new directions to studying fundamental electrochemical and electrocatalytic phenomena, whereby nanoscale-resolved information on activity is related to electrode structure and properties colocated and at a commensurate scale by using complementary high-resolution microscopy techniques. This correlative electrochemical multimicroscopy strategy aims to unambiguously resolve structure and activity by identifying and characterizing the structural features that constitute an active surface, ultimately facilitating the rational design of functional electromaterials. The discussion encompasses high-resolution correlative structure–activity investigations at well-defined surfaces such as metal single crystals and layered materials, extended structurally/compositionally heterogeneous surfaces such as polycrystalline metals, and ensemble-type electrodes exemplified by nanoparticles on an electrode support surface. This Perspective provides a roadmap for next-generation studies in electrochemistry and electrocatalysis, advocating that complex electrode surfaces and interfaces be broken down and studied as a set of simpler “single entities” (e.g., steps, terraces, defects, crystal facets, grain boundaries, single particles), from which the resulting nanoscale understanding of reactivity can be used to create rational models, underpinned by theory and surface physics, that are self-consistent across broader length scales and time scales

The emplacement dynamics of pumice lobes ascertained from morphology and granulometry: Examples from the 1993 deposits at Lascar Volcano, Chile

The work presented here focuses on lobe shapes and clast populations within lobate termini of the 1993 pumice flow deposits at Lascar Volcano, Chile. A new method to analyze a coarse-tail grain size population with field photographs is presented. Using this method, > 33,000 (> 0.5 cm) clasts from the pumice lobes of the 1993 pumice flow deposits were measured at 36 sites, and the resultant grain size distributions were then related to lobe morphology. Lobe margins (i.e., levees, clefts, and snouts) were found to contain significantly larger pumice clasts and be more poorly sorted than lobe central channels (i.e., locations away from the margins). Previous laboratory experiments suggest lobe margins form by the floatation and deflection of larger clasts to the margins of an advancing flow lobe. Results here indicate that the same sorting process efficiently segregates clasts into two flow regimes: 1) a mobile central channel depleted in coarse clasts, and 2) friction-dominated margins enriched in clasts ≥ 15 cm. The lobe margins, 60% enriched in larger particles with matrix < 20%, slow and frictionally freeze from the base up and before the material in the central channel stops flowing. The advancing pumice lobes finally stop when the margins reach ~ 12 clasts thick and the central channel has insufficient mass flux or momentum to break through or over-top the static margins. These processes form a unique lobe and channel morphology deposit that is diagnostic of granular flow and typical of small to intermediate volume pumice flow emplacement