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The Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction is used as a ligation tool throughout chemical and biological sciences. Despite the pervasiveness of CuAAC, there is a need to develop more efficient methods to form 1,4-triazole ligated products with low loadings of Cu. In this paper, we disclose a mechanistic model for the ynamine-azide (3 + 2) cycloadditions catalyzed by copper(II) acetate. Using multinuclear nuclear magnetic resonance spectroscopy, electron paramagnetic resonance spectroscopy, and high-performance liquid chromatography analyses, a dual catalytic cycle is identified. First, the formation of a diyne species via Glaser–Hay coupling of a terminal ynamine forms a Cu(I) species competent to catalyze an ynamine-azide (3 + 2) cycloaddition. Second, the benzimidazole unit of the ynamine structure has multiple roles: assisting C–H activation, Cu coordination, and the formation of a postreaction resting state Cu complex after completion of the (3 + 2) cycloaddition. Finally, reactivation of the Cu resting state complex is shown by the addition of isotopically labeled ynamine and azide substrates to form a labeled 1,4-triazole product. This work provides a mechanistic basis for the use of mixed valency binuclear catalytic Cu species in conjunction with Cu-coordinating alkynes to afford superior reactivity in CuAAC reactions. Additionally, these data show how the CuAAC reaction kinetics can be modulated by changes to the alkyne substrate, which then has a predictable effect on the reaction mechanism.

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P< 5 × 10−8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.

Reverse shoulder arthroplasty is a common procedure performed for a variety of shoulder pathologies.

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Virus infections of the central nervous system (CNS) cause important diseases of humans and animals. As in other tissues, innate antiviral responses mediated by type I interferons (IFNs) are crucially important in controlling CNS virus infections. The maturity of neuronal populations is an established critical factor determining the outcome of CNS virus infection. Using primary cultures of mouse cortical neurons, we investigated the relationships between neuronal maturation, type I IFN responses, and the outcome of Semliki Forest virus infection. The virus replicated better, infected more cells, and produced higher titres of infectious viruses in immature neurons. Complete transcriptome analysis demonstrated that resting immature neurons have low transcriptional competence to mount antiviral responses. They had no detectable transcription of the genes Ddx58and Ifih1, which encode key RNA virus cytoplasmic sensors RIG-I and MDA5, and very low expression of genes encoding key regulators of associated signalling pathways. Upon infection, immature neurons failed to mount an antiviral response as evidenced by their failure to produce chemokines, IFNs, and other cytokines. Treatment of immature neurons with exogenous IFNβ prior to infection resulted in antiviral responses and lower levels of virus replication and infectious virus production. In contrast, resting mature neurons generated a robust antiviral response. This was augmented by pretreatment with IFNβ. Infection of mature neurons derived from IFNAR−/− mice did not make an antiviral response and replicated virus to high levels.

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Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding.

We examine a Dipolarization Front (DF) event with an embedded electron diffusion region (EDR), observed by the Magnetospheric Multiscale (MMS) spacecraft on 08 September 2018 at 14:51:30 UT in the Earth's magnetotail by applying multi‐scale multipoint analysis methods. In order to study the large‐scale context of this DF, we use conjunction observations of the Cluster spacecraft together with MMS. A polynomial magnetic field reconstruction technique is applied to MMS data to characterize the embedded electron current sheet including its velocity and the X‐line exhaust opening angle. Our results show that the MMS and Cluster spacecraft were located in two counter‐rotating vortex flows, and such flows may distort a flux tube in a way that the local magnetic shear angle is increased and localized magnetic reconnection may be triggered. Using multi‐point data from MMS we further show that the local normalized reconnection rate is in the range of R∼ 0.16 to 0.18. We find a highly asymmetric electron in‐ and outflow structure, consistent with previous simulations on strong guide‐field reconnection events. This study shows that magnetic reconnection may not only take place at large‐scale stable magnetopause or magnetotail current sheets but also in transient localized current sheets, produced as a consequence of the interaction between the fast Earthward flows and the Earth's dipole field. Magnetic Reconnection is a key energy conversion process, where magnetic energy is converted into kinetic energy of plasma particles. During this process the magnetic field topology changes and the plasma particles decouple from the magnetic field in the so‐called diffusion region and get accelerated, forming a fast outflow jet. Over the last decades, hints arise that reconnection can take place at many different places in the magnetosphere and also very locally and intermittently. Fast plasma flows in the Magnetotail, moving toward the Earth, are assumed to be a consequence of magnetic reconnection, and are often accompanied by dipolar‐shaped magnetic flux bundles, embedded into them. The leading edges of such flux bundles are called dipolarization fronts (DF). In this work, we investigate a DF event, which hosts a diffusion region. First, we study the large‐scale characteristics of the DF, by utilizing data from both the Magnetospheric Multiscale (MMS) and the Cluster mission, that observe different regions of the event almost simultaneously. Second, we performed a 3D magnetic field reconstruction technique and compared the results to MMS data, to investigate the event on small scales. A thin current sheet inside a dipolarization front, embedded in a diverging flow is analyzed using a polynomial reconstruction techniqueTransient reconnection event is detected in a high magnetic shear region, where the magnetic field is deflected due to duskward fast plasma flowThe reconstructed current sheet has a guide field of ∼1.8 the reconnecting component with normalized reconnection rate between 0.16 and 0.18 A thin current sheet inside a dipolarization front, embedded in a diverging flow is analyzed using a polynomial reconstruction technique Transient reconnection event is detected in a high magnetic shear region, where the magnetic field is deflected due to duskward fast plasma flow The reconstructed current sheet has a guide field of ∼1.8 the reconnecting component with normalized reconnection rate between 0.16 and 0.18

Insulin resistance is a major risk factor for numerous diseases, including type 2 diabetes and cardiovascular disease. These disorders have dramatically increased in incidence with modern life, suggesting that excess nutrients and obesity are major causes of “common” insulin resistance. Despite considerable effort, the mechanisms that contribute to common insulin resistance are not resolved. There is universal agreement that extracellular perturbations, such as nutrient excess, hyperinsulinemia, glucocorticoids, or inflammation, trigger intracellular stress in key metabolic target tissues, such as muscle and adipose tissue, and this impairs the ability of insulin to initiate its normal metabolic actions in these cells. Here, we present evidence that the impairment in insulin action is independent of proximal elements of the insulin signaling pathway and is likely specific to the glucoregulatory branch of insulin signaling. We propose that many intracellular stress pathways act in concert to increase mitochondrial reactive oxygen species to trigger insulin resistance. We speculate that this may be a physiological pathway to conserve glucose during specific states, such as fasting, and that, in the presence of chronic nutrient excess, this pathway ultimately leads to disease. This review highlights key points in this pathway that require further research effort.

The rapid changes of magnetic fields associated with nighttime magnetic perturbations with amplitudes |ΔB| of hundreds of nanoteslas and 5‐ to 10‐min periods can induce bursts of geomagnetically induced currents that can harm technological systems. This paper presents three cases of intervals of intense and complex nighttime magnetic perturbations in eastern Arctic Canada in 2015, augmented by observations from auroral imagers and high‐altitude spacecraft in the nightside magnetosphere. Each case occurred within 1 hr after substorm onsets. None occurred during the main phase of a geomagnetic storm, and only the first during the early recovery phase (of a moderate storm). The cases were similar in that two or three intervals occurred in this region over a span of ~1 hr; these showed a spatial progression, in that successive intervals occurred later at more western and northern stations. During several intervals, individual peak Bximpulses occurred nearly simultaneously (within 1–2 min) at several stations, while during others the impulses occurred later at more western and northern stations, and during one interval they occurred later at southern stations. During both of the cases for which auroral images were available, a westward traveling surge and a poleward auroral expansion and/or poleward boundary intensification occurred, and during two events auroral streamers coincided in time and location with magnetic perturbations. These observations appear to be consistent with several earlier studies connecting nighttime magnetic perturbation events to localized auroral structures and to dipolarizing flux bundles and bursty bulk flows in the magnetotail. In each case study, two or three perturbation intervals occurred within a span of less than 1 hr; later intervals appeared to the north and westIndividual perturbation events typically had a horizontal radius (center to half maximum amplitude) of ~275 kmEvents were closely associated with auroral streamers and less closely associated with substorm onsets and magnetotail dipolarizations

AimsWe present our experience of using a metal-backed prosthesis and autologous bone graft to treat gross glenoid bone deficiency.Patients and MethodsA prospective cohort study of the first 45 shoulder arthroplasties using the SMR Axioma Trabecular Titanium (TT) metal-backed glenoid with autologous bone graft. Between May 2013 and December 2014, 45 shoulder arthroplasties were carried out in 44 patients with a mean age of 64 years (35 to 89). The indications were 23 complex primary arthroplasties, 12 to revise a hemiarthroplasty or resurfacing, five for aseptic loosening of the glenoid, and five for infection.ResultsOf the 45 patients, 16 had anatomical shoulder arthroplasties (ASA) and 29 had reverse shoulder arthroplasties (RSA). Postoperatively, 43/45 patients had a CT scan. In 41 of 43 patients (95%), the glenoid peg achieved > 50% integration. In 40 of 43 cases (93%), the graft was fully or partially integrated. There were seven revisions (16%) but only four (9%) required a change of baseplate. Four (25%) of the 16 ASAs were revised for instability or cuff failure. At two-year radiological follow-up, five of the 41 cases (11%) showed some evidence of lucent lines.ConclusionThe use of a metal baseplate with a trabecular titanium surface in conjunction with autologous bone graft is a reliable method of addressing glenoid bone defects in primary and revision RSA setting in the short term. ASAs have a higher rate of complications with this technique.

In recent decades, counter-monuments have emerged as a new, critical mode of commemorative practice. Even as such practice defines itself by its opposition to traditional monumentality, it has helped to reinvigorate public and professional interest in commemorative activities and landscapes and has developed its own, new conventions. Terminology and analysis in scholarship on counter-monuments have remained relatively imprecise with writers in English and German employing the term ‘counter-monument’ or Gegendenkmalin different and sometimes confusing ways. In this paper we draw together literature published in English and German to clarify and to map various conceptions and categorisations. To do so we distinguish between two kinds of projects that have been called counter-monuments: those that adopt anti-monumental strategies, counter to traditional monument principles, and those that are designed to counter a specific existing monument and the values it represents.

Trafficking regulator of GLUT4 1 (TRARG1) was recently identified to localize to glucose transporter type 4 (GLUT4) storage vesicles (GSVs) and to positively regulate GLUT4 trafficking. Our knowledge of TRARG1 structure and membrane topology is limited to predictive models, hampering efforts to further our mechanistic understanding of how it carries out its functions. Here, we use a combination of bioinformatics prediction tools and biochemical assays to define the membrane topology of the 173-amino acid mouse TRARG1. These analyses revealed that, contrary to the consensus prediction, the N-terminus is cytosolic and that a short segment at the C-terminus resides in the luminal/extracellular space. Based on our biochemical analyses including membrane association and antibody accessibility assays, we conclude that TRARG1 has one transmembrane domain (TMD) (145–172) and a re-entrant loop between residues 101 and 127.

Kelvin‐Helmholtz waves (KHWs), which have been widely observed at the magnetopause in the region near the Earth, play an essential role in the transport of solar wind plasma and energy into the magnetosphere under dominantly northward interplanetary magnetic field (IMF) conditions. In this study, we present simultaneous observations of KHWs under the northward IMF observed by both the Acceleration, Reconnection, Turbulence, and Electrodynamics of Moon's Interaction with the Sun (ARTEMIS) spacecraft in the Earth's magnetotail around the lunar orbit (at X~ −50RE, Y~ 30RE, dusk side) and the Geotail in the near‐Earth space (at X~ −5RE, Y~ −10RE, dawn side). The KHWs are quantitatively characterized by their dominant period, phase velocity, and wavelength, utilizing wavelet analysis and an approximation of their center‐of‐mass velocity. Our results suggest that the phase velocity and spatial scale of KHWs may increase as they propagate along the boundary layer toward the tail. Alternatively, the differences between the ARTEMIS and Geotail observations may indicate the possibility of dawn‐dusk asymmetry in the excited KHWs in this study. Our results strongly evidence the existence of the development of KHWs in terms of their wave frequency and scale size in the magnetotail and provide insight to the time evolution of KHWs along the magnetopause. Simultaneous observations of KHWs in the midtail and the near‐Earth spaceKHWs possibly increase their sizes toward the tailPotential evidence of dawn‐dusk asymmetry in the KHWs

The influence of the interplanetary magnetic field (IMF) cone angle θ(the angle between the IMF direction and the Sun‐Earth line) on the invariant latitudes of the footprints of the field‐aligned currents (FACs) in the magnetotail has been investigated. We performed a statistical study of 542 FAC cases observed by the four Cluster spacecraft in the Northern Hemisphere. The results show that there are almost no FACs when the IMF cone angle is less than 10°, and there are indications of the FACs in the plasma sheet boundary layers being weak under the radial IMF conditions. The footprints of the large FAC (>10 nA/m2) cases are within invariant latitudes <71° and mainly within IMF cone angles θ> 60°, which implies that the footprints of the large FACs mainly expand equatorward with large IMF cone angle. The equatorward boundary of the FAC footprints in the polar region decreases with increasing IMF cone angle (and has a better correlation for northward IMF), which shows that the IMF cone angle plays an important controlling role in FAC distributions in the magnetosphere‐ionosphere coupling system. There is almost no correlation between the poleward boundary and the IMF cone angle for both northward and southward IMF. This is because the poleward boundary movement is limited by an enhanced lobe magnetic flux. This is the first time a correlation between FAC footprints in the polar region and IMF cone angles has been determined. Only the equatorward boundary of polar region footprints of FACs in the magnetotail lowers with increasing IMF cone angleThe footprints of FACs (with large density) are located at ILAT < 71° and mainly correspond to large IMF cone angles (theta > 60°)The relationship between polar region footprints of FACs in the PSBL and the IMF cone angle is determined for the first time

The Electron Spectrometer (ELS) of the Cassini Plasma Spectrometer has observed photoelectrons produced in the plume of Enceladus. These photoelectrons are observed during Enceladus encounters in the energetic particle shadow where the spacecraft is largely shielded from penetrating radiation by the moon. We present a complex electron spectrum at Enceladus including evidence of two previously unidentified electron populations at 6–10 eV and 10–16 eV. We estimate that the proportion of “hot” (>15 eV) to “cold” (<15 eV) electrons during the Enceladus flybys is ≈ 0.1–0.5%. We have constructed a model of photoelectron production in the plume and compared it with ELS Enceladus flyby data by scaling and energy shifting according to spacecraft potential. We suggest that the complex structure of the electron spectrum observed can be explained entirely by photoelectron production in the plume ionosphere. Plume photoelectron production can be modeled using the solar spectrum, photoionization interaction cross sections and plume neutral densitiesBackground subtraction reveals a complex structure at low energies, including two previously unidentified photoelectron peaksWe show qualitatively that the observed photoelectron spectrum near Enceladus can be explained entirely by plume photoelectrons

We investigate a 15‐day period in October 2011. Auroral observations by the Special Sensor Ultraviolet Spectrographic Imager instrument onboard the Defense Meteorological Satellite Program F16, F17, and F18 spacecraft indicate that the polar regions were covered by weak cusp‐aligned arc (CAA) emissions whenever the interplanetary magnetic field (IMF) clock angle was small, |θ| < 45°, which amounted to 30% of the time. Simultaneous observations of ions and electrons in the tail by the Cluster C4 and Geotail spacecraft showed that during these intervals dense (≈1 cm−3) plasma was observed, even as far from the equatorial plane of the tail as |ZGSE| ≈ 13 RE. The ions had a pitch angle distribution peaking parallel and antiparallel to the magnetic field and the electrons had pitch angles that peaked perpendicular to the field. We interpret the counter‐streaming ions and double loss‐cone electrons as evidence that the plasma was trapped on closed field lines, and acted as a source for the CAA emission across the polar regions. This suggests that the magnetosphere was almost entirely closed during these periods. We further argue that the closure occurred as a consequence of dual‐lobe reconnection. Our finding forces a significant re‐evaluation of the magnetic topology of the magnetosphere during periods of northwards IMF. The magnetosphere is usually assumed to contain both open and closed magnetic flux. Closed magnetic field lines have both ends connected to the Earth; open field lines connect to the Earth at one end and into the interplanetary medium at the other. There tends to be little plasma on open field lines as the particles escape down the magnetotail, whereas plasma on closed field lines is trapped. Open flux near the poles naturally explains the oval configuration of Earth's auroras, with a lack of auroras at very high latitudes where there is no plasma to cause emissions. Somewhat unexpectedly, we show that auroral emission near the poles is common and that at these times there is significant plasma in the magnetotail, indicating that the magnetosphere contains only closed flux. We propose that this magnetic configuration is formed by a process known as dual‐lobe magnetic reconnection which occurs when the interplanetary magnetic field (IMF) within the solar wind points northwards. We must re‐evaluate the standard picture of magnetospheric structure during these periods of northwards IMF. Cusp‐aligned arcs (CAAs) observed by the Defense Meteorological Satellite Program spacecraft occur frequently for northward interplanetary magnetic fieldCluster and Geotail observations show that the arcs are accompanied by trapped plasma at high latitudes in the magnetotailWe interpret CAAs as a signature of a magnetosphere almost entirely closed by dual‐lobe reconnection Cusp‐aligned arcs (CAAs) observed by the Defense Meteorological Satellite Program spacecraft occur frequently for northward interplanetary magnetic field Cluster and Geotail observations show that the arcs are accompanied by trapped plasma at high latitudes in the magnetotail We interpret CAAs as a signature of a magnetosphere almost entirely closed by dual‐lobe reconnection

Insulin triggers an extensive signaling cascade to coordinate adipocyte glucose metabolism. It is considered that the major role of insulin is to provide anabolic substrates by activating GLUT4-dependent glucose uptake. However, insulin stimulates phosphorylation of many metabolic proteins. To examine the implications of this on glucose metabolism, we performed dynamic tracer metabolomics in cultured adipocytes treated with insulin. Temporal analysis of metabolite concentrations and tracer labeling revealed rapid and distinct changes in glucose metabolism, favoring specific glycolytic branch points and pyruvate anaplerosis. Integrating dynamic metabolomics and phosphoproteomics data revealed that insulin-dependent phosphorylation of anabolic enzymes occurred prior to substrate accumulation. Indeed, glycogen synthesis was activated independently of glucose supply. We refer to this phenomenon as metabolic priming, whereby insulin signaling creates a demand-driven system to “pull” glucose into specific anabolic pathways. This complements the supply-driven regulation of anabolism by substrate accumulation and highlights an additional role for insulin action in adipocyte glucose metabolism.

Teucrium yemense(Defl), locally known as Reehal Fatima, is a medicinal plant commonly grown in Saudi Arabia and Yemen. Phytochemical investigation of the aerial parts of T. yemenseyielded six new neoclerodane diterpenoids, namely fatimanol A–E (1, 2, 3, 5, and 6) and fatimanone (4), and the known teulepicephin (7). As both the Teucriumgenus and the related Lamiaceaefamily have previously been widely reported to possess anthelmintic and antimicrobial activities, the structural and biological characterization of the seven diterpenoids was pursued. The structures of the new compounds were elucidated from their 2D NMR and MS profiles and by comparison to related compounds. The structure of fatimanol D (5) was confirmed by X-ray crystallographic analysis. The new structures contribute to the breadth of knowledge of secondary metabolites in this genus.

Energy conversion on the dipolarization fronts (DFs) has attracted much research attention through the suggestion that intense current densities associated with DFs can modify the more global magnetotail current system. The current structures associated with a DF are at the scale of one to a few ion gyroradii, and their duration is comparable to a spacecraft's spin period. Hence, it is crucial to understand the physical mechanisms of DFs with measurements at a timescale shorter than a spin period. We present a case study whereby we use measurements from the Magnetospheric Multiscale (MMS) Mission, which provides full 3‐D particle distributions with a cadence much shorter than a spin period. We provide a cross validation amongst the current density calculations and examine the assumptions that have been adopted in previous literature using the advantages of MMS mission (i.e., small‐scale tetrahedron and high temporal resolution). We also provide a cross validation on the terms in the generalized Ohm's law using these advantageous measurements. Our results clearly show that the majority of the currents on the DF are contributed by both ion and electron diamagnetic drifts. Our analysis also implies that the ion frozen‐in condition does not hold on the DF, while electron frozen‐in condition likely holds. The new experimental capabilities allow us to accurately calculate Joule heating within the DF, which shows that plasma energy is being converted to magnetic energy in our event. We reveal that electrons and ions carry comparable currents on a DFWe compared three calculations of current density and show very consistent resultsHall MHD is not suitable for DF study, while the electron MHD is likely suitable

Paediatric Monteggia-type injuries are complicated by treatment failure and posterior interosseous nerve palsy, without reliable predictive indicators. Outcome is considered to be good, with little patient-reported evidence. We propose novel radiographic parameters. A total of 33 Monteggia-type injuries were analysed. Posterior interosseous nerve palsy was strongly predicted by the Radial Head Displacement Index. The presence of two or more of three novel instability markers was associated strongly with treatment failure. Patient-reported outcome measures were almost uniformly excellent. We advocate the use of a new, inclusive, stability-based classification of Monteggia-type injuries to predict patients who require accurate internal fixation.

FGF21 improves the metabolic profile of obese animals through its actions on adipocytes. To elucidate the signaling network responsible for mediating these effects, we quantified dynamic changes in the adipocyte phosphoproteome following acute exposure to FGF21. FGF21 regulated a network of 821 phosphosites on 542 proteins. A major FGF21-regulated signaling node was mTORC1/S6K. In contrast to insulin, FGF21 activated mTORC1 via MAPK rather than through the canonical PI3K/AKT pathway. Activation of mTORC1/S6K by FGF21 was surprising because this is thought to contribute to deleterious metabolic effects such as obesity and insulin resistance. Rather, mTORC1 mediated many of the beneficial actions of FGF21 in vitro, including UCP1and FGF21induction, increased adiponectin secretion, and enhanced glucose uptake without any adverse effects on insulin action. This study provides a global view of FGF21 signaling and suggests that mTORC1 may act to facilitate FGF21-mediated health benefits in vivo.

Flux transfer events (FTEs) are magnetic structures generated by time‐varying reconnection at the dayside magnetopause. Understanding their generation mechanism is important, because it is necessary in order to understand the global contribution of FTEs to the convection process. We present observations of several FTEs sequentially observed by Cluster at the subsolar magnetopause. Cluster detected also several reconnection jets, which seem to be systematically associated with the trailing edge of the FTEs. This association is expected only in the FTEs formed by single X line reconnection but could be compatible also with the multiple X line model, when reconnection at one X line is dominant. Instead, it does not seem compatible with original mechanism proposed by Russell and Elphic (1978). For a large FTE, not associated with any reconnection jet, the Grad‐Shafranov reconstruction obtained from Cluster 1 data recovers a flux rope, indicative of multiple X line reconnection. This same FTE was detected also by Cluster 3, which observed an asymmetric signature in the magnetic field component normal to the magnetopause. We show that this asymmetric signature was caused by an outward motion of the magnetopause. The orientation of the other FTEs, obtained from a Grad‐Shafranov optimization, shows considerable spread, despite the relatively steady conditions. Our interpretation is that a combination of single and multiple X line reconnection generated these FTEs. The FTEs in the first part of the crossing, associated with reconnection jets, are generated by the single X line model and may therefore not satisfy the Grad‐Shafranov assumptions so well. Instead, the last FTE, slower, bigger, and well separated from the previous ones, may be formed by multiple X line reconnection. Reconnection jets are systematically associated with the trailing edge of these FTEs; this suggests the single X line generation mechanismThe FTEs observed during this event are potentially generated by different generation mechanisms: single X line and multiple X linesThe asymmetric Bn signature observed during one FTE is probably explained by an outward motion of the magnetopause

The dipolarization front (DF), usually observed near the leading edge of a bursty bulk flow (BBF), is thought to carry an intense current sufficient to modify the large-scale near-Earth magnetotail current system. However, the physical mechanism of the current generation associated with DFs is poorly understood. This is primarily due to the limitations of conventional plasma instruments which are unable to provide a sufficient number of unaliased 3-D distribution functions on the timescale of the DF, which usually travels past a spacecraft in only a few seconds. It is thus almost impossible to unambiguously determine the detailed plasma structure of the DF at the usual temporal resolution of such instruments. Here we present detailed plasma measurements using the Cluster Plasma Electron and Current Experiment and Cluster Ion Spectrometry-Composition and Distribution Function ion data for an event during which it was possible to observe the full pitch angle distribution at a cadence of 1/4 s. The observations clearly show details of plasma substructure within the DF, including the presence of field-aligned electron beams. In this event, the current density carried by the electron beam is much larger than the current obtained from the curlometer method. We also suggest that the field-aligned current around the DF obtained from the curlometer method may have been misinterpreted in previous studies. Our results imply that the nature of the DF current system needs to be revisited using high-resolution particle measurements, such as those observations shortly to be available from the Magnetospheric Multiscale mission. Substructure electron beam on the DF is reported for the first timeThe electron beam carried current is much higher than the field-aligned current previously reportedThe parallel electron beams on the DF at energies of a few hundreds eV

We modeled Cluster spacecraft observations of slow electrostatic solitary waves (SESWs) in the Earth's northern plasma sheet boundary layer (PSBL) region on the basis of nonlinear fluid theory and fluid simulation. Various plasma parameters observed by the Cluster satellite at the time of the SESWs were examined to investigate the generation process of the SESWs. The nonlinear fluid model shows the coexistence of slow and fast ion acoustic waves and the presence of electron acoustic waves in the PSBL region. The fluid simulations, performed to examine the evolution of these waves in the PSBL region, showed the presence of an extra mode along with the waves supported by the nonlinear fluid theory. This extra mode is identified as the Buneman mode, which is generated by relative drifts of ions and electrons. A detailed investigation of the characteristics of the SESWs reveals that the SESWs are slow ion acoustic solitary waves. Slow electrostatic solitary waves observed by Cluster in the plasma sheet boundary layerThe wave observations modeled by nonlinear fluid theory and fluid simulationThe study suggest that the slow solitary waves can be explained by slow ion acoustic solitary waves

Theory predicts that the first adiabatic invariant of a charged particle may be violated in a region of highly curved field lines, leading to significant pitch angle scattering for particles whose gyroradius are comparable to the radius of the magnetic field line curvature. This scattering generates more isotropic particle distribution functions, with important impacts on the presence or absence of plasma instabilities. Using magnetic curvature analysis based on multipoint Cluster spacecraft observations, we present the first investigation of magnetic curvature in the vicinity of an ion diffusion region where reconnected field lines are highly curved. Electrons at energies > 8 keV show a clear pitch angle ordering between bidirectional and trapped distribution in surrounding regions, while we show that in the more central part of the ion diffusion region electrons above such energies become isotropic. By contrast, colder electrons (~1 keV) retain their bidirectional character throughout the diffusion regions. The calculated adiabatic parameter K2for these electrons is in agreement with theory. This study provides the first observational evidence for particle pitch angle scattering due to magnetic field lines with well characterized curvature in a space plasma. First multispacecraft analysis of magnetic field curvature in the ion diffusion regionElectron dynamics is analyzed as a function of magnetic field curvatureObservational evidence for magnetic curvature‐induced electron pitch angle scattering

Although the particle carriers of field‐aligned currents (FACs) in the Earth's magnetotail play an important role in the transfer of momentum and energy between the solar wind, magnetosphere, and ionosphere, the characteristics of the FAC carriers have been poorly understood. Taking advantage of multiinstrument magnetic field and plasma data collected by the four spacecraft of the Cluster constellation as they traversed the northern plasma sheet boundary layer in the magnetotail on 14 September 2004, we identified the species type and energy range of the FAC carriers for the first time. The results indicate that part of tailward FACs is carried by energetic keV ions, which are probably originated from the ionosphere through outflow, and they are not too small (~2 nA/m2) to be ignored. The earthward (tailward) FACs are mainly carried by the dominant tailward (earthward) motion of electrons, and higher‐energy electrons (from ~0.5 to 26 keV) are the main carriers. The FAC in the PSBLs studied by both Mfield and its carriers in a substorm timeThe species type and energy range of the FAC carriers are identified for the first timeNot only electrons but also ions can be significant to carry the FACs in the magnetotail

The magnetospheric cusps are important sites of the coupling of a magnetosphere with the solar wind. The combination of both ground‐ and space‐based observations at Earth has enabled considerable progress to be made in understanding the terrestrial cusp and its role in the coupling of the magnetosphere to the solar wind via the polar magnetosphere. Voyager 2 fully explored Neptune's cusp in 1989, but highly inclined orbits of the Cassini spacecraft at Saturn present the most recent opportunity to repeatedly study the polar magnetosphere of a rapidly rotating planet. In this paper we discuss observations made by Cassini during two passes through Saturn's southern polar magnetosphere. Our main findings are that (i) Cassini directly encounters the southern polar cusp with evidence for the entry of magnetosheath plasma into the cusp via magnetopause reconnection, (ii) magnetopause reconnection and entry of plasma into the cusp can occur over a range of solar wind conditions, and (iii) double cusp morphologies are consistent with the position of the cusp oscillating in phase with Saturn's global magnetospheric periodicities. Saturn's southern polar cusp is active under a range of solar wind conditionsEvidence for injection of magnetosheath plasma into the cusp via dayside magnetopause reconnectionThe position of Saturn's southern polar cusp oscillates in with global magnetospheric periodicities

Insulin resistance (IR) is a complex pathophysiological state that arises from both environmental and genetic perturbations and leads to a variety of diseases, including type-2 diabetes (T2D). Obesity is associated with enhanced adipose tissue inflammation, which may play a role in disease progression. Inflammation modulates protein glycosylation in a variety of cell types, and this has been associated with biological dysregulation. Here, we have examined the effects of an inflammatory insult on protein glycosylation in adipocytes. We performed quantitative N-glycome profiling of membrane proteins derived from mouse 3T3-L1 adipocytes that had been incubated with or without the proinflammatory cytokine TNF-alpha to induce IR. We identified the regulation of specific terminal N-glycan epitopes, including an increase in terminal di-galactose- and a decrease in biantennary alpha-2,3-sialoglycans. The altered N-glycosylation of TNF-alpha-treated adipocytes correlated with the regulation of specific glycosyltransferases, including the up-regulation of B4GalT5 and Ggta1 galactosyltransferases and down-regulation of ST3Gal6 sialyltransferase. Knockdown of B4GalT5 down-regulated the terminal di-galactose N-glycans, confirming the involvement of this enzyme in the TNF-alpha-regulated N-glycome. SILAC-based quantitative glycoproteomics of enriched N-glycopeptides with and without deglycosylation were used to identify the protein and glycosylation sites modified with these regulated N-glycans. The combined proteome and glycoproteome workflow provided a relative quantification of changes in protein abundance versus N-glycosylation occupancy versussite-specific N-glycans on a proteome-wide level. This revealed the modulation of N-glycosylation on specific proteins in IR, including those previously associated with insulin-stimulated GLUT4 trafficking to the plasma membrane.

Research into cellular metabolism has become more high-throughput, with typical cell-culture experiments being performed in multiwell plates (microplates). This format presents a challenge when trying to collect gaseous products, such as carbon dioxide (CO2), which requires a sealed environment and a vessel separate from the biological sample. To address this limitation, we developed a gas trapping protocol using perforated plastic lids in sealed cell-culture multiwell plates. We used this trap design to measure CO2production from glucose and fatty acid metabolism, as well as hydrogen sulfide production from cysteine-treated cells. Our data clearly show that this gas trap can be applied to liquid and solid gas-collection media and can be used to study gaseous product generation by both adherent cells and cells in suspension. Since our gas traps can be adapted to multiwell plates of various sizes, they present a convenient, cost-effective solution that can accommodate the trend toward high-throughput measurements in metabolic research.

During substorm growth phases, magnetic reconnection at the magnetopause extracts ~1015J from the solar wind which is then stored in the magnetotail lobes. Plasma sheet pressure increases to balance magnetic flux density increases in the lobes. Here we examine plasma sheet pressure, density, and temperature during substorm growth phases using 9 years of Cluster data (>316,000 data points). We show that plasma sheet pressure and temperature are higher during growth phases with higher solar wind driving, whereas the density is approximately constant. We also show a weak correlation between plasma sheet temperature before onset and the minimum SuperMAG AL (SML) auroral index in the subsequent substorm. We discuss how energization of the plasma sheet before onset may result from thermodynamically adiabatic processes; how hotter plasma sheets may result in magnetotail instabilities, and how this relates to the onset and size of the subsequent substorm expansion phase. Growth phase plasma sheet temperature varies with solar wind drivingHigher temperatures observed in intervals of higher drivingPlasma sheet temperature can influence substorm onset and size

Arthropod vectors, such as mosquitoes, ticks, biting midges and sand flies, transmit many viruses that can cause outbreaks of disease in humans and animals around the world. Arthropod vector species are invading new areas due to globalisation and environmental changes, and contact between exotic animal species, humans and arthropod vectors is increasing, bringing with it the regular emergence of new arboviruses. For future strategies to control arbovirus transmission, it is important to improve our understanding of virus-vector interactions. In the last decade knowledge of arthropod antiviral immunity has increased rapidly. RNAi has been proposed as the most important antiviral response in mosquitoes and it is likely to be the most important antiviral response in all arthropods. However, other newly-discovered antiviral strategies such as melanisation and the link between RNAi and the JAK/STAT pathway via the cytokine Vago have been characterised in the last few years. This review aims to summarise the most important and most recent advances made in arthropod antiviral immunity.

Measurements from the closely spaced Cluster spacecraft are used to study the structure of the magnetic and electric fields within the magnetic ramp of dipolarization fronts (DF) observed close to the neutral sheet and the midnight meridian (YGSM<3RE). The spacecraft separation was small enough (<300 km) to treat the magnetic ramp of the DF front as a planar structure as indicated from variance analysis. The finite value of the magnetic field along the minimum variance direction for the events studied indicates that the dipolarization front structure was distinct from a tangential discontinuity. In addition to the main increase of the magnetic field in the maximum variance component, strong oscillations were observed in the intermediate component. The presence of this oscillatory structure results in an expansion of the region in which a change of magnetic pressure occurs, the size of which is typically an ion Larmor radius or greater. This widening is important in maintaining the pressure balance at the edge of the DF. This phenomenon resembles observations of intense current sheets in the magnetotail and also laboratory experiments of current sheet formation, in which a similar widening of the ramp region has been observed. In this paper we argue against the idea that an electron temperature anisotropy, resulting in electron curvature currents, can explain the formation of the oscillatory structures observed at DFs. These oscillations can be explained as eigenmode waves of the plasma that propagate away from the disturbance (DF) that is moving at subsonic speeds. Oscillations observed within the magnetic ramp indicate field‐aligned currents that are expected to be associated with DF. The fine structure of the dipolarization front is describedIdentification of oscillations within the dipolarization front are presentedThe bipolar structure of the electric field within dipolarization front is shown

Using the Cluster multispacecraft observations, we analyze a long‐duration field‐aligned high‐flux electron disturbance in the cusp region on 30 September 2001. All four Cluster spacecraft observed the same disturbance in which both the upward and downward electrons are observed and the electron flux was 1 order of magnitude higher than usual in the cusp. The temporal scale of the field‐aligned electron disturbance was at least 50 min. The spatial scale was about 540 km in the direction along the orbit and at least 1800 km in local time extent in the midaltitude cusp region. It was the longest duration and the largest spatial scale of any field‐aligned electron disturbance observed in the polar region up to date, and its observation would not have been possible with a single satellite. Both upward and downward electrons are the main contributors to the field‐aligned currents in the electron disturbance. During this electron disturbance, the solar wind dynamic pressure increased, and the interplanetary magnetic field (IMF) kept being southward. It is likely that the field‐aligned high‐flux electron disturbance with its long temporal and large spatial scales was caused by high dynamic pressure of the solar wind during a permanently southward IMF. This enables us to learn more about electron disturbances in the cusp and is important to understand the physical mechanism, especially for the solar wind‐magnetosphere‐ionosphere coupling. Cusp electron disturbance lasted 50 min with spatial scale of 540 km and 1800 kmThe longest and largest electron disturbance in polar region up to dateCaused by high solar wind dynamic pressure and permanent southward IMF

Ticks transmit various human and animal microbial pathogens and may harbour more than one pathogen simultaneously. Both viruses and bacteria can trigger, and may subsequently suppress, vertebrate host and arthropod vector anti-microbial responses. Microbial coinfection of ticks could lead to an advantage or disadvantage for one or more of the microorganisms. In this preliminary study, cell lines derived from the ticks Ixodes scapularisand Ixodes ricinuswere infected sequentially with 2 arthropod-borne pathogens, Borrelia burgdorferis.s., Ehrlichia ruminantium, or Semliki Forest virus (SFV), and the effect of coinfection on the replication of these pathogens was measured. Prior infection of tick cell cultures with the spirochaete B. burgdorferienhanced subsequent replication of the rickettsial pathogen E. ruminantiumwhereas addition of spirochaetes to cells infected with E. ruminantiumhad no effect on growth of the latter. Both prior and subsequent presence of B. burgdorferialso had a positive effect on SFV replication. Presence of E. ruminantiumor SFV had no measurable effect on B. burgdorferigrowth. In tick cells infected first with E. ruminantiumand then with SFV, virus replication was significantly higher across all time points measured (24, 48, 72h post infection), while presence of the virus had no detectable effect on bacterial growth. When cells were infected first with SFV and then with E. ruminantium, there was no effect on replication of either pathogen. The results of this preliminary study indicate that interplay does occur between different pathogens during infection of tick cells. Further study is needed to determine if this results from direct pathogen–pathogen interaction or from effects on host cell defences, and to determine if these observations also apply in vivo in ticks. If presence of one pathogen in the tick vector results in increased replication of another, this could have implications for disease transmission and incidence.

Magnetic reconnection is an efficient way to convert magnetic energy into particle energy. In this paper, we use Cluster thermal electron and ion measurements in the vicinity of a reconnection X line to delineate the structure of the reconnection current sheet. Multispacecraft observations made by Cluster on 18 August 2002 indicate that an X line drifted close to the spacecraft, about 3.4 REearthward of the position where another X line had been observed earlier. Comparison of the Hall magnetic and electric field geometry and the observed properties of energetic electron beams streaming along the separatrix between the Cluster spacecraft indicates that the second X line formed within 20 s of the observation of the first X line. Repeated flow reversals and Hall field geometry together with the presence of a magnetic island embedded in the outflow region downstream of the first X line suggest that the initial current sheet was unstable, perhaps to the tearing mode. We identify a region with a thickness of 0.72 ion inertial lengths (29 electron inertial lengths, de) of super‐Alfvénic electron outflow (greater than the ion in‐flow Alfvén speed) during the period when the spacecraft was in the vicinity of the neutral sheet. Slightly below the neutral sheet, Cluster observed asymmetric counter‐streaming electrons with a loss of axisymmetry in the electron (V⟂1,V⟂2) distribution functions over a thin boundary with a thickness of several de. This electron‐scale transition layer was embedded in a much wider region where both the ion and electron Walén tests failed, and the electron super‐Alfvénic bulk outflow jets with high‐energy electron beams were detected. Those phenomena provide details of the substructure of the reconnection current sheet and suggest that the spacecraft traversed or skimmed the tailward edge of an elongated electron current layer. We also note that this event differs from a previously reported reconnection event in that strong electron temperature anisotropy (T∥>T⟂) is observed both in the inflow region and in the exhaust, where the anisotropy appears to be associated with the elongated electron outflow jets. In‐situ observations of multiple X‐line structuresThe substructure of the reconnection current sheet in Earth's magnetotailSuper‐Alfvenic electron jets and a loss of axisymmetry in electron distribution

In recent decades, counter-monuments have emerged as a new, critical mode of commemorative practice. Even as such practice defines itself by its opposition to traditional monumentality, it has helped to reinvigorate public and professional interest in commemorative activities and landscapes and has developed its own, new conventions. Terminology and analysis in scholarship on counter-monuments have remained relatively imprecise with writers in English and German employing the term ‘counter-monument’ or Gegendenkmalin different and sometimes confusing ways. In this paper we draw together literature published in English and German to clarify and to map various conceptions and categorisations. To do so we distinguish between two kinds of projects that have been called counter-monuments: those that adopt anti-monumental strategies, counter to traditional monument principles, and those that are designed to counter a specific existing monument and the values it represents.

As well as being vectors of many viral, bacterial, and protozoan pathogens of medical and veterinary importance, ticks harbour a variety of microorganisms which are not known to be pathogenic for vertebrate hosts. Continuous cell lines established from ixodid and argasid ticks could be infected with such endosymbiotic bacteria and endogenous viruses, but to date very few cell lines have been examined for their presence. DNA and RNA extracted from over 50 tick cell lines deposited in the Roslin Wellcome Trust Tick Cell Biobank (http://tickcells.roslin.ac.uk) were screened for presence of bacteria and RNA viruses, respectively. Sequencing of PCR products amplified using pan-16S rRNA primers revealed the presence of DNA sequences from bacterial endosymbionts in several cell lines derived from Amblyommaand Dermacentorspp. ticks. Identification to species level was attempted using Rickettsia- and Francisella-specific primers. Pan-Nairovirus primers amplified PCR products of uncertain specificity in cell lines derived from Rhipicephalus, Hyalomma, Ixodes, Carios, and Ornithodorosspp. ticks. Further characterisation attempted with primers specific for Crimean-Congo haemorrhagic fever virus segments confirmed the absence of this arbovirus in the cells. A set of pan-Flavivirus primers did not detect endogenous viruses in any of the cell lines. Transmission electron microscopy revealed the presence of endogenous reovirus-like viruses in many of the cell lines; only 4 of these lines gave positive results with primers specific for the tick Orbivirus St Croix River virus, indicating that there may be additional, as yet undescribed ‘tick-only’ viruses inhabiting tick cell lines.

AXIOM (Advanced X‐ray Imaging Of the Magnetosphere) is a concept mission which aims to explain how the Earth's magnetosphere responds to the changing impact of the solar wind using a unique method never attempted before; performing wide‐field soft X‐ray imaging and spectroscopy of the magnetosheath, magnetopause and bow shock at high spatial and temporal resolution. Global imaging of these regions is possible because of the solar wind charge exchange (SWCX) process which produces elevated soft X‐ray emission from the interaction of high charge‐state solar wind ions with primarily neutral hydrogen in the Earth's exosphere and near‐interplanetary space (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

This paper reflects on the importance of study groups in contributing to a positive postgraduate experience and explores specific concepts, such as 'disappearing behaviours' in contrasting the 'official' languages of universities with the beneficial behaviours found through study groups. Additionally the paper advocates the systematic inclusion of strategies such as study groups in the postgraduate experience. Funding arrangements and research frameworks for higher education in Australia focus on student progress and completion, as well as comparison of research quality within and between universities. As a result, there is a significant emphasis on timely completion of postgraduate degrees. This paper posits that there is an apparent contradiction between the indicators of success in this area, such as completion rates and annual progress reports and the positive contribution that study groups can make to the doctoral student experience.

An X3.4 solar flare and a fast halo coronal mass ejection (CME) occurred on 2006 December 13, accompanied by a high flux of energetic particles recorded both in near-Earth space and at ground level. Our purpose is to provide evidence of flare acceleration in a major solar energetic particle (SEP) event. We first present observations from ACE/EPAM, GOES, and the Apatity neutron monitor. It is found that the initial particle release time coincides with the flare emission and that the spectrum becomes softer and the anisotropy becomes weaker during particle injection, indicating that the acceleration source changes from a confined coronal site to a widespread interplanetary CME-driven shock. We then describe a comprehensive study of the associated flare active region. By use of imaging data from HINODE/SOT and SOHO/MDI magnetogram, we infer the flare magnetic reconnection rate in the form of the magnetic flux change rate. This correlates in time with the microwave emission, indicating a physical link between the flare magnetic reconnection and the acceleration of nonthermal particles. Combining radio spectrograph data from Huairou/NOAC, Culgoora/IPS, Learmonth/RSTN, and WAVES/WIND leads to a continuous and longlasting radio burst extending from a few GHz down to several?kHz. Based on the photospheric vector magnetogram from Huairou/NOAC and the nonlinear force free field (NFFF) reconstruction method, we derive the 3D magnetic field configuration shortly after the eruption. Furthermore, we also compute coronal field lines extending to a few solar radii using a potential-field source-surface (PFSS) model. Both the so-called type III-l burst and the magnetic field configuration suggest that open-field lines extend from the flare active region into interplanetary space, allowing the accelerated and charged particles escape.

The article offers tips on traveling to Calvados, France. According to the article, the region was the site for the last successful conquest of Great Britain and the target of the largest seaborne invasion in history. The Cote Fleurie at Calvados' eastern end is home to the seaside towns of Honfleur and Deauville.

The article provides tips on traveling along the German Alpine Road in Bavaria, Germany. The 250-mile road covers the edge of Lake Bodensee in the west to the Konigssee in the east. One option for traveling along the road is to choose a base and explore its surrounds in detail. Other Bavarian driving routes of interest to tourists include the Castle Road and the Romantic Road.

The article describes the travel destination to the islands of Great Britain. The concrete bunkers in the Channel Islands are a reminder of the suffering during the time of the German occupation. Big beaches line the coast of Guernsey. Among the island’s top attractions is the Sausmarez Manor with its sculpture trail. The island of Sark is famous for its landscapes of fields and forests. INSET: FERRY CROSSINGS..

The article features several tourist attractions in Slovenia. The author enumerates some of its attractions that include castles, spectacular view of the Alps, lakes and caves. He encourages tourists to visit the Triglav National Park, which encompasses most of the Julian Alps. Lake Bled, on the other hand, boasts a church tower and cliff-top castle, considered to be the country's most iconic image. INSET: Essential Slovenia..

The article features famous sites which could be found in Kraków, capital of Poland. Among the sites featured are the Market Square, Museum of Pharmacy or Jan Matejko's House, and the Oskar Schindler's Factory. Information about each site is offered in this article. It also provides data about Kraków's good places to eat, as well as the day-to-day costs for travelers.