Analytical modelling of hot-spot traffic in deterministically-routed k-ary n-cubes

Many research studies have proposed analytical models to evaluate the performance of k-ary n-cubes with deterministic wormhole routing. Such models however have so far been confined to uniform traffic distributions. There has been hardly any model proposed that deal with non-uniform traffic distributions that could arise due to, for instance, the presence of hot-spots in the network. This paper proposes the first analytical model to predict message latency in k-ary n-cubes with deterministic routing in the presence of hot-spots. The validity of the model is demonstrated by comparing analytical results with those obtained through extensive simulation experiments

Origins of the Ambient Solar Wind: Implications for Space Weather

The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

Molecular and functional variation in iPSC-derived sensory neurons

Induced pluripotent stem cells (iPSCs), and cells derived from them, have become key tools for modeling biological processes, particularly in cell types that are difficult to obtain from living donors. Here we present a map of regulatory variants in iPSC-derived neurons, based on 123 differentiations of iPSCs to a sensory neuronal fate. Gene expression was more variable across cultures than in primary dorsal root ganglion, particularly for genes related to nervous system development. Using single-cell RNA-sequencing, we found that the number of neuronal versus contaminating cells was influenced by iPSC culture conditions before differentiation. Despite high differentiation-induced variability, our allele-specific method detected thousands of quantitative trait loci (QTLs) that influenced gene expression, chromatin accessibility, and RNA splicing. On the basis of these detected QTLs, we estimate that recall-by-genotype studies that use iPSC-derived cells will require cells from at least 20-80 individuals to detect the effects of regulatory variants with moderately large effect sizes

Global solar wind variations over the last four centuries

The most recent “grand minimum” of solar activity, the Maunder minimum (MM, 1650–1710), is of great interest both for understanding the solar dynamo and providing insight into possible future heliospheric conditions. Here, we use nearly 30 years of output from a data-constrained magnetohydrodynamic model of the solar corona to calibrate heliospheric reconstructions based solely on sunspot observations. Using these empirical relations, we produce the first quantitative estimate of global solar wind variations over the last 400 years. Relative to the modern era, the MM shows a factor 2 reduction in near-Earth heliospheric magnetic field strength and solar wind speed, and up to a factor 4 increase in solar wind Mach number. Thus solar wind energy input into the Earth’s magnetosphere was reduced, resulting in a more Jupiter-like system, in agreement with the dearth of auroral reports from the time. The global heliosphere was both smaller and more symmetric under MM conditions, which has implications for the interpretation of cosmogenic radionuclide data and resulting total solar irradiance estimates during grand minima

Effect of high-pressure torsion on microstructure, mechanical properties and corrosion resistance of cast pure Mg

© 2018, The Author(s). High-pressure torsion (HPT) processing was applied to cast pure magnesium, and the effects of the deformation on the microstructure, hardness, tensile properties and corrosion resistance were evaluated. The microstructures of the processed samples were examined by electron backscatter diffraction, and the mechanical properties were determined by Vickers hardness and tensile testing. The corrosion resistance was studied using electrochemical impedance spectroscopy in a 3.5% NaCl solution. The results show that HPT processing effectively refines the grain size of Mg from millimeters in the cast structure to a few micrometers after processing and also creates a basal texture on the surface. It was found that one or five turns of HPT produced no significant difference in the grain size of the processed Mg and the hardness was a maximum after one turn due to recovery in some grains. Measurements showed that the yield strength of the cast Mg increased by about seven times whereas the corrosion resistance was not significantly affected by the HPT processing

Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia

In common with other chronic pain conditions, there is an unmet clinical need in the treatment of inherited erythromelalgia (IEM). TheSCN9Agene encoding the sodium channel Nav1.7 expressed in the peripheral nervous system plays a critical role in IEM. A gain-of-function mutation in this sodium channel leads to aberrant sensory neuronal activity and extreme pain, particularly in response to heat. Five patients with IEM were treated with a new potent and selective compound that blocked the Nav1.7 sodium channel resulting in a decrease in heat-induced pain in most of the patients. We derived induced pluripotent stem cell (iPSC) lines from four of five subjects and produced sensory neurons that emulated the clinical phenotype of hyperexcitability and aberrant responses to heat stimuli. When we compared the severity of the clinical phenotype with the hyperexcitability of the iPSC-derived sensory neurons, we saw a trend toward a correlation for individual mutations. The in vitro IEM phenotype was sensitive to Nav1.7 blockers, including the clinical test agent. Given the importance of peripherally expressed sodium channels in many pain conditions, our approach may have broader utility for a wide range of pain and sensory conditions

Pharmacologically Reversible, Loss of Function Mutations in the tm2 and tm4 Inner Pore Helices of Trek-1 k2p Channels

A better understanding of the gating of TREK two pore domain potassium (K2P) channels and their activation by compounds such as the negatively charged activator, flufenamic acid (FFA) is critical in the search for more potent and selective activators of these channels. Currents through wild-type and mutated human K2P channels expressed in tsA201 cells were measured using whole-cell patch-clamp recordings in the presence and absence of FFA. Mutation of the TM2.6 residue of TREK-1 to a phenylalanine (G171F) and a similar mutation of TM4.6 (A286F) substantially reduced current through TREK-1 channels. In complementary experiments, replacing the natural F residues at the equivalent position in TRESK channels, significantly enhanced current. Known, gain of function mutations of TREK-1 (G137I, Y284A) recovered current through these mutated channels. This reduction in current could be also be reversed pharmacologically, by FFA. However, an appropriate length MTS (MethaneThioSulfonate) cross-linking reagent (MTS14) restricted the activation of TREK-1_A286C channels by repeated application of FFA. This suggests that the cross-linker stabilises the channel in a conformation which blunts FFA activation. Pharmacologically reversible mutations of TREK channels will help to clarify the importance of these channels in pathophysiological conditions such as pain and depression