Nanoscale clusters in the high performance thermoelectric AgPbmSbTem+2

The local structure of the AgPbmSbTem+2 series of thermoelectric materials has been studied using the atomic pair distribution function (PDF) method. Three candidate-models were attempted for the structure of this class of materials using either a one-phase or a two-phase modeling procedure. Combining modeling the PDF with HRTEM data we show that AgPbmSbTem+2 contains nanoscale inclusions with composition close to AgPb3SbTe5 randomly embedded in a PbTe matrix.Comment: 7 pages, 5 figures, 2 tables, submitted to PR

Effectively Mapping Linguistic Abstractions for Message-passing Concurrency to Threads on the Java Virtual Machine

Efficient mapping of message passing concurrency (MPC) abstractions to Java Virtual Machine (JVM) threads is critical for performance, scalability, and CPU utilization; but tedious and time consuming to perform manually. In general, this mapping cannot be found in polynomial time, but we show that by exploiting the local characteristics of MPC abstractions and their communication patterns this mapping can be determined effectively. We describe our MPC abstraction to thread mapping technique, its realization in two frameworks (Panini and Akka), and its rigorous evaluation using several benchmarks from representative MPC frameworks. We also compare our technique against four default mapping techniques: thread-all, round-robin-task-all, random-task-all and work-stealing. Our evaluation shows that our mapping technique can improve the performance by 30%-60% over default mapping techniques. These improvements are due to a number of challenges addressed by our technique namely: i) balancing the computations across JVM threads, ii) reducing the communication overheads, iii) utilizing information about cache locality, and iv) mapping MPC abstractions to threads in a way that reduces the contention between JVM threads

Long-term field metal extraction by pelargonium:phytoextraction efficiency in relation to plant maturity

The long length of periods required for effective soil remediation via phytoextraction constitutes a weak point that reduces its industrial use. However, these calculated periods are mainly based on short-term and/or hydroponic controlled experiments. Moreover, only a few studies concern more than one metal, although soils are scarcely polluted by only one element.In this scientific context, the phytoextraction of metals and metalloids (Pb, Cd, Zn, Cu,and As) by Pelargonium was measured after a long-term field experiment. Both bulk and rhizosphere soils were analyzed in order to determine the mechanisms involved in soil-root transfer. First, a strong increase in lead phytoextraction was observed with plant maturity, significantly reducing the length of the period required for remediation. Rhizosphere Pb, Zn, Cu, Cd, and As accumulation was observed (compared to bulk soil), indicating metal mobilization by the plant, perhaps in relation to root activity. Moreover, metal phytoextraction and translocation were found to be a function of the metals’ nature. These results, taken altogether, suggest that Pelargonium could be used as a multi-metal hyperaccumulator under multi-metal soil contamination conditions, and they also provide an interesting insight for improving field phytoextraction remediation in terms of the length of time required, promoting this biological technique

Hydrazines as versatile chemical biology probes and drug-discovery tools for cofactor-dependent enzymes [preprint]

Known chemoproteomic probes generally use warheads that tag a single type of amino acid or modified form thereof to identify cases in which its hyper-reactivity underpins function. Much important biochemistry derives from electron-poor enzyme cofactors, transient intermediates and chemically-labile regulatory modifications, but probes for such species are underdeveloped. Here, we have innovated a versatile class of chemoproteomic probes for this less charted hemisphere of the proteome by using hydrazine as the common chemical warhead. Its electron-rich nature allows it to react by both polar and radicaloid mechanisms and to target multiple, pharmacologically important functional classes of enzymes bearing diverse organic and inorganic cofactors. Probe attachment can be blocked by active-site-directed inhibitors, and elaboration of the warhead supports connection of a target to a lead compound. The capacity of substituted hydrazines to profile, discover and inhibit diverse cofactor-dependent enzymes enables cell and tissue imaging and makes this platform useful for enzyme and drug discovery

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor

Processing Images from the Zwicky Transient Facility

The Zwicky Transient Facility is a new robotic-observing program, in which a newly engineered 600-MP digital camera with a pioneeringly large field of view, 47~square degrees, will be installed into the 48-inch Samuel Oschin Telescope at the Palomar Observatory. The camera will generate $\sim 1$~petabyte of raw image data over three years of operations. In parallel related work, new hardware and software systems are being developed to process these data in real time and build a long-term archive for the processed products. The first public release of archived products is planned for early 2019, which will include processed images and astronomical-source catalogs of the northern sky in the $g$ and $r$ bands. Source catalogs based on two different methods will be generated for the archive: aperture photometry and point-spread-function fitting.Comment: 6 pages, 4 figures, submitted to RTSRE Proceedings (www.rtsre.org

Identification of Neural Crest and Glial Enhancers at the Mouse Sox10 Locus through Transgenesis in Zebrafish

Sox10 is a dynamically regulated transcription factor gene that is essential for the development of neural crest–derived and oligodendroglial populations. Developmental genes often require multiple regulatory sequences that integrate discrete and overlapping functions to coordinate their expression. To identify Sox10 cis-regulatory elements, we integrated multiple model systems, including cell-based screens and transposon-mediated transgensis in zebrafish, to scrutinize mammalian conserved, noncoding genomic segments at the mouse Sox10 locus. We demonstrate that eight of 11 Sox10 genomic elements direct reporter gene expression in transgenic zebrafish similar to patterns observed in transgenic mice, despite an absence of observable sequence conservation between mice and zebrafish. Multiple segments direct expression in overlapping populations of neural crest derivatives and glial cells, ranging from pan-Sox10 and pan-neural crest regulatory control to the modulation of expression in subpopulations of Sox10-expressing cells, including developing melanocytes and Schwann cells. Several sequences demonstrate overlapping spatial control, yet direct expression in incompletely overlapping developmental intervals. We were able to partially explain neural crest expression patterns by the presence of head to head SoxE family binding sites within two of the elements. Moreover, we were able to use this transcription factor binding site signature to identify the corresponding zebrafish enhancers in the absence of overall sequence homology. We demonstrate the utility of zebrafish transgenesis as a high-fidelity surrogate in the dissection of mammalian gene regulation, especially those with dynamically controlled developmental expression

From Geometry to Numerics: interdisciplinary aspects in mathematical and numerical relativity

This article reviews some aspects in the current relationship between mathematical and numerical General Relativity. Focus is placed on the description of isolated systems, with a particular emphasis on recent developments in the study of black holes. Ideas concerning asymptotic flatness, the initial value problem, the constraint equations, evolution formalisms, geometric inequalities and quasi-local black hole horizons are discussed on the light of the interaction between numerical and mathematical relativists.Comment: Topical review commissioned by Classical and Quantum Gravity. Discussion inspired by the workshop "From Geometry to Numerics" (Paris, 20-24 November, 2006), part of the "General Relativity Trimester" at the Institut Henri Poincare (Fall 2006). Comments and references added. Typos corrected. Submitted to Classical and Quantum Gravit