On 5 May 2017, MMS observed a crater‐type flux rope on the dawnside tailward magnetopause with fluctuations. The boundary‐normal analysis shows that the fluctuations can be attributed to nonlinear ...Kelvin‐Helmholtz (KH) waves. Reconnection signatures such as flow reversals and Joule dissipation were identified at the leading and trailing edges of the flux rope. In particular, strong northward electron jets observed at the trailing edge indicated midlatitude reconnection associated with the 3‐D structure of the KH vortex. The scale size of the flux rope, together with reconnection signatures, strongly supports the interpretation that the flux rope was generated locally by KH vortex‐induced reconnection. The center of the flux rope also displayed signatures of guide‐field reconnection (out‐of‐plane electron jets, parallel electron heating, and Joule dissipation). These signatures indicate that an interface between two interlinked flux tubes was undergoing interaction, causing a local magnetic depression, resulting in an M‐shaped crater flux rope, as supported by reconstruction.
Plain Language Summary
Magnetic reconnection and Kelvin‐Helmholtz instability (KHI), two of the most fundamental physical processes occurring within the heliosphere and throughout the Universe, often occur simultaneously on the Earth's magnetopause. Previous studies indicate the importance of nonlinearly developed KH waves, which produce multiple kinetic layers facilitating reconnection both in and out of the velocity shear plane and resulting in the magnetic flux rope. However, these studies significantly lacked detailed in situ observations in quantity as well as appropriate 3‐D analyses of the structure of the KH vortex‐induced flux rope. In this paper, we use detailed observations by the MMS spacecraft to investigate both 2‐D and 3‐D structures of the flux rope developed along the KH waves. We found that two flux tubes interact through reconnection to form a single combined structure, which can explain the occurrence of M‐shaped crater flux rope.
Key Points
MMS observed a magnetic flux rope formed on the boundary of a nonlinear Kelvin‐Helmholtz (KH) wave
Both in‐plane and midlatitude reconnection associated with the 3‐D structure of the KH vortex‐inducedflux rope were identified
A current sheet at the flux rope center supported by reconstruction indicates two flux tubes interlinked to form a crater‐type flux rope
To establish the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) when screening externally validated cognition in Parkinson disease (PD), by comparison with a PD-focused test (Scales ...for Outcomes in Parkinson disease-Cognition SCOPA-COG) and the standardized Mini-Mental State Examination (S-MMSE) as benchmarks.
A convenience sample of 114 patients with idiopathic PD and 47 healthy controls was examined in a movement disorders center. The 21 patients with dementia (PD-D) were diagnosed using Movement Disorders Society criteria, externally validated by detailed independent functional and neuropsychological tests. The 21 patients with mild cognitive impairment (PD-MCI) scored 1.5 SD or more below normative data in at least 2 measures in 1 of 4 cognitive domains. Other patients had normal cognition (PD-N).
Primary outcomes using receiver operating characteristic (ROC) curve analyses showed that all 3 mental status tests produced excellent discrimination of PD-D from patients without dementia (area under the curve AUC, 87%-91%) and PD-MCI from PD-N patients (AUC, 78%-90%), but the MoCA was generally better suited across both assessments. The optimal MoCA screening cutoffs were <21/30 for PD-D (sensitivity 81%; specificity 95%; negative predictive value NPV 92%) and <26/30 for PD-MCI (sensitivity 90%; specificity 75%; NPV 95%). Further support that the MoCA is at least equivalent to the SCOPA-COG, and superior to the S-MMSE, came from the simultaneous classification of the 3 PD patient groups (volumes under a 3-dimensional ROC surface, chance = 17%: MoCA 79%, confidence interval CI 70%-89%; SCOPA-COG 74%, CI 62%-86%; MMSE-Sevens item 56%, CI 44%-68%; MMSE-World item 62%, CI 50%-73%).
The MoCA is a suitably accurate, brief test when screening all levels of cognition in PD.
Abstract
A critical challenge during volcanic emergencies is responding to rapid changes in eruptive behaviour. Actionable advice, essential in times of rising uncertainty, demands the rapid ...synthesis and communication of multiple datasets with prognoses. The 2020–2021 eruption of La Soufrière volcano exemplifies these challenges: a series of explosions from 9–22 April 2021 was preceded by three months of effusive activity, which commenced with a remarkably low level of detected unrest. Here we show how the development of an evolving conceptual model, and the expression of uncertainties via both elicitation and scenarios associated with this model, were key to anticipating this transition. This not only required input from multiple monitoring datasets but contextualisation via state-of-the-art hazard assessments, and evidence-based knowledge of critical decision-making timescales and community needs. In addition, we share strategies employed as a consequence of constraints on recognising and responding to eruptive transitions in a resource-constrained setting, which may guide similarly challenged volcano observatories worldwide.
Purpose
To validate three widely‐used acceleration methods in four‐dimensional (4D) flow cardiac MR; segmented 4D‐spoiled‐gradient‐echo (4D‐SPGR), 4D‐echo‐planar‐imaging (4D‐EPI), and 4D‐k‐t ...Broad‐use Linear Acquisition Speed‐up Technique (4D‐k‐t BLAST).
Materials and Methods
Acceleration methods were investigated in static/pulsatile phantoms and 25 volunteers on 1.5 Tesla MR systems. In phantoms, flow was quantified by 2D phase‐contrast (PC), the three 4D flow methods and the time‐beaker flow measurements. The later was used as the reference method. Peak velocity and flow assessment was done by means of all sequences. For peak velocity assessment 2D PC was used as the reference method. For flow assessment, consistency between mitral inflow and aortic outflow was investigated for all pulse‐sequences. Visual grading of image quality/artifacts was performed on a four‐point‐scale (0 = no artifacts; 3 = nonevaluable).
Results
For the pulsatile phantom experiments, the mean error for 2D PC = 1.0 ± 1.1%, 4D‐SPGR = 4.9 ± 1.3%, 4D‐EPI = 7.6 ± 1.3% and 4D‐k‐t BLAST = 4.4 ± 1.9%. In vivo, acquisition time was shortest for 4D‐EPI (4D‐EPI = 8 ± 2 min versus 4D‐SPGR = 9 ± 3 min, P < 0.05 and 4D‐k‐t BLAST = 9 ± 3 min, P = 0.29). 4D‐EPI and 4D‐k‐t BLAST had minimal artifacts, while for 4D‐SPGR, 40% of aortic valve/mitral valve (AV/MV) assessments scored 3 (nonevaluable). Peak velocity assessment using 4D‐EPI demonstrated best correlation to 2D PC (AV:r = 0.78, P < 0.001; MV:r = 0.71, P < 0.001). Coefficient of variability (CV) for net forward flow (NFF) volume was least for 4D‐EPI (7%) (2D PC:11%, 4D‐SPGR: 29%, 4D‐k‐t BLAST: 30%, respectively).
Conclusion
In phantom, all 4D flow techniques demonstrated mean error of less than 8%. 4D‐EPI demonstrated the least susceptibility to artifacts, good image quality, modest agreement with the current reference standard for peak intra‐cardiac velocities and the highest consistency of intra‐cardiac flow quantifications.
Level of Evidence: 1
Technical Efficacy: Stage 2
J. Magn. Reson. Imaging 2018;47:272–281.
The Magnetospheric Multiscale (MMS) mission was designed to make observations in the very small electron diffusion region (EDR), where magnetic reconnection takes place. From a data set of over 4500 ...magnetopause crossings obtained in the first phase of the mission, MMS had encounters near or within 12 EDRs. These 12 events and associated magnetopause crossings are considered as a group to determine if they span the widest possible range of external and internal conditions (i.e., in the solar wind and magnetosphere). In addition, observations from MMS are used to determine if there are multiple X‐lines present and also to provide information on X‐line location relative to the spacecraft. These 12 events represent nearly the widest possible range of conditions at the dayside magnetopause. They occur over a wide range of local times and magnetic shear angles between the magnetosheath and magnetospheric magnetic fields. Most show evidence for multiple reconnection sites.
Key Points
MMS X‐line events cover a wide range of external conditions
Almost all X‐line events are associated with multiple X‐lines at the magnetopause
Reconnection between the magnetosheath and an existing boundary layer is required for KH instability
Summary
Regulatory T cells (Tregs) are crucial in mediating immune homeostasis and promoting the establishment and maintenance of peripheral tolerance. However, in the context of cancer their role is ...more complex, and they are thought to contribute to the progress of many tumours. As cancer cells express both self‐ and tumour‐associated antigens, Tregs are key to dampening effector cell responses, and therefore represent one of the main obstacles to effective anti‐tumour responses. Suppression mechanisms employed by Tregs are thought to contribute significantly to the failure of current therapies that rely on induction or potentiation of anti‐tumour responses. This review will focus on the current evidence supporting the central role of Tregs in establishing tumour‐specific tolerance and promoting cancer escape. We outline the mechanisms underlying their suppressive function and discuss the potential routes of Tregs accumulation within the tumour, including enhanced recruitment, in‐situ or local proliferation, and de‐novo differentiation. In addition, we review some of the cancer treatment strategies that act, at least in part, to eliminate or interfere with the function of Tregs. The role of Tregs is being recognized increasingly in cancer, and controlling the function of these suppressive cells in the tumour microenvironment without compromising peripheral tolerance represents a significant challenge for cancer therapies.
The Life History of 21 Breast Cancers Nik-Zainal, Serena; Van Loo, Peter; Wedge, David C. ...
Cell,
05/2012, Letnik:
149, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Cancer evolves dynamically as clonal expansions supersede one another driven by shifting selective pressures, mutational processes, and disrupted cancer genes. These processes mark the genome, such ...that a cancer's life history is encrypted in the somatic mutations present. We developed algorithms to decipher this narrative and applied them to 21 breast cancers. Mutational processes evolve across a cancer's lifespan, with many emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, and most mutations are found in just a fraction of tumor cells. Every tumor has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent cell lineages capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis.
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► Genome-wide analyses of mutations emerging through time in 21 breast cancers ► Minimal expansion of subclones occurs until thousands of mutations have accumulated ► Cancer-specific signatures of point mutations and genomic instability emerge late ► ERBB2 amplification begins early but continues to evolve over long molecular time
Newly developed algorithms allow the reconstruction of the genomic history of different breast cancers, tracing the temporal evolution of each tumor and the emergence of the dominant subclones that will eventually trigger diagnosis.
Following the optical imaging of exoplanet candidate Fomalhaut b (Fom b), we present a numerical model of how Fomalhaut's debris disk is gravitationally shaped by a single interior planet. The model ...is simple, adaptable to other debris disks, and can be extended to accommodate multiple planets. If Fom b is the dominant perturber of the belt, then to produce the observed disk morphology it must have a mass M pl < 3M J, an orbital semimajor axis a pl > 101.5 AU, and an orbital eccentricity e pl = 0.11-0.13. These conclusions are independent of Fom b's photometry. To not disrupt the disk, a greater mass for Fom b demands a smaller orbit farther removed from the disk; thus, future astrometric measurement of Fom b's orbit, combined with our model of planet-disk interaction, can be used to determine the mass more precisely. The inner edge of the debris disk at a 133 AU lies at the periphery of Fom b's chaotic zone, and the mean disk eccentricity of e 0.11 is secularly forced by the planet, supporting predictions made prior to the discovery of Fom b. However, previous mass constraints based on disk morphology rely on several oversimplifications. We explain why our constraint is more reliable. It is based on a global model of the disk that is not restricted to the planet's chaotic zone boundary. Moreover, we screen disk parent bodies for dynamical stability over the system age of ~ 100 Myr, and model them separately from their dust grain progeny; the latter's orbits are strongly affected by radiation pressure and their lifetimes are limited to ~ 0.1 Myr by destructive grain-grain collisions. The single planet model predicts that planet and disk orbits be apsidally aligned. Fomalhaut b's nominal space velocity does not bear this out, but the astrometric uncertainties may be large. If the apsidal misalignment proves real, our calculated upper mass limit of 3M J still holds. If the orbits are aligned, our model predicts M pl = 0.5M J, a pl = 115 AU, and e pl = 0.12. Parent bodies are evacuated from mean-motion resonances with Fom b; these empty resonances are akin to the Kirkwood gaps opened by Jupiter. The belt contains at least 3M {circled plus} of solids that are grinding down to dust, their velocity dispersions stirred so strongly by Fom b that collisions are destructive. Such a large mass in solids is consistent with Fom b having formed in situ.
This paper reports on Magnetospheric Multiscale observations of whistler mode chorus and higher‐frequency electrostatic waves near and within a reconnection diffusion region on 23 November 2016. The ...diffusion region is bounded by crescent‐shaped electron distributions and associated dissipation just upstream of the X‐line and by magnetic field‐aligned currents and electric fields leading to dissipation near the electron stagnation point. Measurements were made southward of the X‐line as determined by southward directed ion and electron jets. We show that electrostatic wave generation is due to magnetosheath electron beams formed by the electron jets as they interact with a cold background plasma and more energetic population of magnetospheric electrons. On the magnetosphere side of the X‐line the electron beams are accompanied by a strong perpendicular electron temperature anisotropy, which is shown to be the source of an observed rising‐tone whistler mode chorus event. We show that the apex of the chorus event and the onset of electrostatic waves coincide with the opening of magnetic field lines at the electron stagnation point.
Key Points
Whistler mode chorus and higher‐frequency electrostatic waves were observed in the vicinity of a reconnection diffusion region at the dayside magnetopause
The location of the Earthward boundary of chorus and electrostatic waves coincides with the opening of magnetic field lines via reconnection
The causes of whistler mode chorus and electrostatic waves are shown to be electron temperature anisotropy and beam‐plasma interactions, respectively
Recently Assef et al. presented two catalogs of active galactic nucleus (AGN) candidates over 30,093 deg2 selected from the Wide-field Infrared Survey Explorer (WISE) observations. From their most ...reliable sample, Assef et al. identified 45 AGN candidates with the highest variability levels in the AllWISE catalog but that are not blazars. Here we present new spectroscopic observations of some of these targets to further constrain their nature. We also study their optical light curves using observations from the Catalina Real-Time Transient Survey (CRTS) and find that only seven show significant optical variability, and that five of those seven are spectroscopically classified as AGNs. In one of them, WISEA J094806.56+031801.7 (W0948+0318), we identify a transient event in the CRTS light curve. We present a detailed analysis of this transient and characterize it through its CRTS light curve and its multiwavelength spectral energy distribution obtained from GALEX, Pan-STARRS, and WISE observations. We find that the most likely source of the transient is a superluminous supernova (SLSN) in W0948+0318. We estimate the total radiated energy to be E = (1.6 0.3) × 1052 erg, making it one of the most energetic SLSNe observed. Based on the lack of change in mid-IR color throughout and after the transient event, we speculate that the location of the SLSN is within the torus of the AGN. We identify nine possible analogs to W0948+0318 based on their WISE light curves. None show optically detected transients and hence suggest significant dust obscuration. Finally, we estimate a rate of >2 × 10−7 yr−1 per AGN for these transients under the conservative assumption that none of the identified analogs have a common origin with the transient in W0948+0318.
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