Characterizing the transcriptome of individual cells is fundamental to understanding complex biological systems. We describe a droplet-based system that enables 3' mRNA counting of tens of thousands ...of single cells per sample. Cell encapsulation, of up to 8 samples at a time, takes place in ∼6 min, with ∼50% cell capture efficiency. To demonstrate the system's technical performance, we collected transcriptome data from ∼250k single cells across 29 samples. We validated the sensitivity of the system and its ability to detect rare populations using cell lines and synthetic RNAs. We profiled 68k peripheral blood mononuclear cells to demonstrate the system's ability to characterize large immune populations. Finally, we used sequence variation in the transcriptome data to determine host and donor chimerism at single-cell resolution from bone marrow mononuclear cells isolated from transplant patients.
We assessed the non-inferiority of accelerated fractionation (AF) (2.4Gy/fraction) compared with standard fractionation (SF) (2Gy/fraction) regarding progression-free survival (PFS) in patients with ...T1-2N0M0 glottic cancer (GC).
In this multi-institutional, randomized, phase III trial, patients were enrolled from 32 Japanese institutions. Key inclusion criteria were GC T1-2N0M0, age 20–80, Eastern Cooperative Oncology Group performance status of 0–1, and adequate organ function. Patients were randomly assigned to receive either SF of 66–70Gy (33–35 fractions), or AF of 60–64.8Gy (25–27 fractions). The primary end point was the proportion of 3-year PFS. The planned sample size was 360 with a non-inferiority margin of 5%.
Between 2007 and 2013, 370 patients were randomized (184/186 to SF/AF). Three-year PFS was 79.9%(95% confidence interval CI 73.4–85.4) for SF and 81.7% (95% CI 75.4–87.0) for AF (difference 1.8%, 91% CI−5.1% to 8.8%; one-sided P=0.047>0.045). The cumulative incidences of local failure at 3years for SF/AF were 15.9%/10.3%. No significant difference was observed in 3-year overall survival (OS) between SF and AF. Grade 3 or 4 acute and late toxicities developed in 22 (12.4%)/21 (11.5%) and 2 (1.1%)/1 (0.5%) in the SF/AF arms.
Although the non-inferiority of AF was not confirmed statistically, the similar efficacy and toxicity of AF compared with SF, as well as the practical convenience of its fewer treatment sessions, suggest the potential of AF as a treatment option for early GC.
UMIN Clinical Trial Registry, number UMIN000000819.
One of the recent developments in ionospheric research was the introduction of a subauroral spectacle called STEVE (Strong Thermal Emission Velocity Enhancement). Although STEVE has been documented ...by amateur night sky watchers for decades, it is an exciting new upper atmospheric phenomenon for the scientific community. Observed first by amateur auroral photographers, STEVE appeared as a narrow luminous structure across the night sky. Currently, only one scientific study has focused on STEVE, revealing that it corresponds to a narrow (tens of kilometers in north‐south extent) and long (thousands of kilometers in east‐west direction) structure located in the subauroral region. An important and fundamental question that arises from this study is the origin of STEVE; more specifically, does STEVE correspond to a new ionospheric phenomenon or is it due to particle precipitation? In this letter, we analyze a STEVE event on 28 March 2008 observed by Time History of Events and Macroscale Interactions during Substorms (THEMIS) ground‐based All‐Sky Imagers and a Polar Orbiting Environmental Satellite (POES). The POES‐17 satellite crossed STEVE at the center of the All‐Sky Imager field‐of‐view, allowing us to collect particle data simultaneously. These concurrent measurements show that STEVE might not be associated with particle precipitation (electrons or ions). Therefore, this event suggests that STEVE's skyglow (which we defined to be unrelated to aurora or airglow) could be generated in the ionosphere.
Plain Language Summary
Recently, the scientific community stumbled upon a rare atmospheric phenomenon called Strong Thermal Emission Velocity Enhancement (STEVE) that has been well documented by amateur auroral photographers for decades. STEVE appears across the night sky as an extremely narrow ribbon of vibrant purple and white hues. In this letter, we address an important fundamental question: Is STEVE caused by particle precipitation like aurora or is it produced by a new ionospheric phenomenon? We analyzed a STEVE event using a network of ground‐based All‐Sky Imagers across Canada and energetic particle detectors on one of National Oceanic and Atmospheric Administration's Polar Orbiting Environmental Satellites. Our results verify that this STEVE event is clearly distinct from the aurora since it is characterized by the absence of particle precipitation. Interestingly, its skyglow could be generated by a new and fundamentally different mechanism in the ionosphere.
Key Points
First study of STEVE event in conjunction with POES satellite suggests ionospheric origin of STEVE
This STEVE event is not aurora. Particle precipitation is not observed for this event
STEVE's skyglow could be associated with protons below 50 eV or generated by a fundamentally different mechanism in the ionosphere
We present three STEVE (strong thermal emission velocity enhancement) events in conjunction with Time History of Events and Macroscale Interactions (THEMIS) in the magnetosphere and Defense ...Meteorological Satellite Program (DMSP) and Swarm in the ionosphere, for determining equatorial and interhemispheric signatures of the STEVE purple/mauve arc and picket fence. Both types of STEVE emissions are associated with subauroral ion drifts (SAID), electron heating, and plasma waves. The magnetosphere observations show structured electrons and flows and waves (likely kinetic Alfven, magnetosonic, or lower‐hybrid waves) just outside the plasmasphere. Interestingly, the event with the picket fence had a >~1 keV electron structure detached from the electron plasma sheet, upward field‐aligned currents (FACs), and ultraviolet emissions in the conjugate hemisphere, while the event with only the mauve arc did not have precipitation or ultraviolet emission. We suggest that the electron precipitation drives the picket fence, and heating drives the mauve as thermal emission.
Plain Language Summary
STEVE (strong thermal emission velocity enhancement) has become increasingly popular among citizen scientists due to its distinct colors and structures of emission in the night sky and its occurrence over more populated areas than for typical aurora in the auroral oval. This study addresses two major questions of STEVE: What is the energy source of the STEVE purple or mauve colored arc and green picket fence up in space? and Does STEVE occur in the Northern and Southern Hemispheres at the same time? Using a set of imaging and satellite observations, this study found that STEVE is connected to fast plasma flows, sharp plasma boundaries, and intense waves 25,000 km (15,000 miles) up in space. Photographs taken by citizen scientists have played a key role in finding STEVE and its morphology. Plasma heating due to the fast flows and waves is suggested to drive the mauve colored arc. But this mechanism does not explain the picket fence. We found that energetic particle precipitation drives the picket fence. The picket fence is found to occur in both hemispheres at the same time, supporting that the energy source far up in space feeds energy to both hemispheres.
Key Points
Magnetosphere observations show that STEVE corresponds to SAID, plasmapause, structured plasma boundaries, and waves in the magnetosphere
The picket fence is driven by electron precipitation; the red arc is driven by heat flux or frictional heating
Simultaneous conjugate observations show that part of STEVE has interhemispheric conjugacy
Epidemiological studies suggest that the severity of periodontitis is higher in people with diabetes than in healthy individuals. Insulin resistance might play a crucial role in the pathogenesis of ...multiple diabetic complications and is reportedly induced in the gingiva of rodents with type 2 diabetes; however, the molecular mechanisms underlying the pathogenesis of diabetes-related periodontitis remain unclear. Therefore, we aimed to investigate whether endothelial insulin resistance in the gingiva may contribute to the pathogenesis of periodontitis as well as elucidate its underlying molecular mechanisms. We demonstrated that insulin treatment downregulated lipopolysaccharide (LPS)–induced or tumor necrosis factor α (TNFα)–induced VCAM1 expression in endothelial cells (ECs) via the PI3K/Akt activating pathway, resulting in reduced cellular adhesion between ECs and leukocytes. Hyperglycemia-induced selective insulin resistance in ECs diminished the effect of insulin on LPS- or TNFα-stimulated VCAM1 expression. Vascular endothelial cell–specific insulin receptor knockout (VEIRKO) mice exhibited selective inhibition of the PI3K/Akt pathway in the gingiva and advanced experimental periodontitis-induced alveolar bone loss via upregulation of Vcam1, Tnfα, Mcp-1, Rankl, and neutrophil migration into the gingiva compared with that in the wild-type (WT) mice despite being free from diabetes. We also observed that insulin-mediated activation of FoxO1, a downstream target of Akt, was suppressed in the gingiva of VEIRKO and high-fat diet (HFD)–fed mice, hyperglycemia-treated ECs, and primary ECs from VEIRKO. Further analysis using ECs transfected with intact and mutated FoxO1, with mutations at 3 insulin-mediated phosphorylation sites (T24A, S256D, S316A), suggested that insulin-mediated regulation of VCAM1 expression and cellular adhesion of ECs with leukocytes was attenuated by mutated FoxO1 overexpression. These results suggest that insulin resistance in ECs may contribute to the progression of periodontitis via dysregulated VCAM1 expression and cellular adhesion with leukocytes, resulting from reduced activation of the PI3K/Akt/FoxO1 axis.
The possibility that the dipolarization fronts (DFs) observed in the plasma sheet could be produced by the ballooning/interchange instability is explored using three‐dimensional electromagnetic ...particle‐in‐cell simulations. The localized interchange heads produced in the nonlinear stage of the instability exhibit the main near‐equatorial properties of a DF: the cross‐tail extent is on the order of 1 RE, the ramp‐ups in Bz and the magnitude of Ey as well as the sharp density decrease all occur on the ion inertial scale, while there is a more gradual increase in the bulk flow. The field‐aligned currents associated with the breakup of the head should produce a structuring of the corresponding auroral streamer in the ionosphere, a result that is confirmed by Time History of Events and Macroscale Interactions during Substorms (THEMIS) all‐sky imager data. The dissipation associated with the head occurs in electron‐scale regions in the center of the plasma sheet. Away from the center, the head is strongly modulated by waves with frequency on the order of the ion gyrofrequency. The strength of the accompanying Ey oscillations is in the range of 30–50 mV/m, and the δE/δB ratio is 3–4 times the local Alfvén speed. The waves appear to be produced by the electromagnetic current‐driven ion cyclotron instability.
Key Points
BICI mode reproduces key features of dipolarization fronts
Breakup of BICI leads to structuring of auroral streamers
Off axis a DF exhibits strong electromagnetic ion cyclotron waves
A critical, long‐standing problem in substorm research is identification of the sequence of events leading to substorm auroral onset. Based on event and statistical analysis of THEMIS all‐sky imager ...data, we show that there is a distinct and repeatable sequence of events leading to onset, the sequence having similarities to and important differences from previous ideas. The sequence is initiated by a poleward boundary intensification (PBI) and followed by a north‐south (N‐S) arc moving equatorward toward the onset latitude. Because of the linkage of fast magnetotail flows to PBIs and to N‐S auroras, the results indicate that onset is preceded by enhanced earthward plasma flows associated with enhanced reconnection near the pre‐existing open‐closed field line boundary. The flows carry new plasma from the open field line region to the plasma sheet. The auroral observations indicate that Earthward‐transport of the new plasma leads to a near‐Earth instability and auroral breakup ∼5.5 min after PBI formation. Our observations also indicate the importance of region 2 magnetosphere‐ionosphere electrodynamic coupling, which may play an important role in the motion of pre‐onset auroral forms and determining the local times of onsets. Furthermore, we find motion of the pre‐onset auroral forms around the Harang reversal and along the growth phase arc, reflecting a well‐developed region 2 current system within the duskside convection cell, and also a high probability of diffuse‐appearing aurora occurrence near the onset latitude, indicating high plasma pressure along these inner plasma sheet field lines, which would drive large region 2 currents.
We present the first observations of ionospheric phenomena using the newly deployed Transition Region Explorer (TREx) Spectrograph. On the night of 10 April 2018, STEVE (Strong Thermal Emission ...Velocity Enhancement) and the Picket Fence optical structures were observed by the spectrograph in Lucky Lake, Saskatchewan. STEVE contains an enhancement of the OI red‐line (630‐nm) emission and a continuum which spans the visible wavelengths. Based upon its spectrum, we assert that the characteristic mauve color of STEVE is a result of this continuum. The spectrum of the Picket Fence contains a strong OI green‐line (557.7‐nm) emission similar to that produced in typical auroral structures. From their spectra, we assert that the Picket Fence is caused by particle precipitation and thus that the Picket Fence is a form of aurora, while STEVE's spectrum confirms that it is not aurora.
Key Points
The Picket Fence spectrum is similar to aurora
The STEVE spectrum contains a continuum similar to NO airglow
STEVE is unlikely to be aurora
Recent ionospheric measurements suggest polar cap flow channels often trigger nightside auroral brightening. However, measurements were limited to the ionosphere, and it was not understood if such ...flow channels can exist in the lobe and can trigger magnetotail reconnection in a localized cross‐tail extent. We examined if localized flow channels can form self‐consistently in a global MHD regime, and if so, how such flow channels originate and relate to localized magnetotail reconnection. We show that lobe convection became nonuniform with azimuthally narrow flow channels (enhanced dawn‐dusk electric fields) of ~3 RE cross‐tail width. The flow channels propagated from the dayside toward the plasma sheet as an interplanetary magnetic field (IMF) discontinuity swept tailward. The plasma sheet around the lobe flow channels became thinner with a similar cross‐tail extent and then localized reconnection occurred. These results suggest that localized flow channels can propagate tailward across the lobe and drive localized magnetotail reconnection, that the cross‐tail width of reconnection and resulting plasma sheet flow channels and dipolarization fronts are related to the width of inflow from the lobe, and that IMF discontinuities drive lobe flow channels.
Key Points
Lobe convection became nonuniform with azimuthally narrow flow channels
Lobe flow channels propagate tailward and drive localized magnetotail reconnection
The cross‐tail width of reconnection and BBFs is related to the width of inflow from the lobe
We have used all‐sky imaging to relate different types of auroral oval disturbances to large‐scale traveling ionospheric disturbances (LSTIDs). We selected eight nights with good all‐sky imaging and ...Global Positioning System total electron content coverage, including five non–storm time periods with isolated initiations of geomagnetic activity and three storm main phase periods with continuous activity. Periods with LSTIDs generally started and stopped with initiation and cessation of activity. We found evidence that individual LSTIDs often show 1‐1 correspondence with identifiable auroral disturbances, disturbances either being related to a substorm onset or to auroral streamers without a substorm. Since substorm ground magnetic depressions are directly related to the electric fields and electron precipitation of auroral streamers, we hypothesize that streamers may be the primary drivers of individual nightside LSTIDs with or without a substorm. Additionally, we found evidence that (1) LSTIDs detection is more likely near the longitude range of the initiating disturbance than further away, (2) the orientation of LSTID phase fronts depends on location relative to disturbance longitude, and (3) disturbance ionospheric current and magnetic latitude may influence whether a given disturbance leads to a detectable LSTID. Numerous LSTIDs (10 to 12 over 7‐ to 8‐hr periods) were detected during southward interplanetary magnetic field periods of coronal mass ejection storm main phases, the vast majority reflecting streamers in the absence of substorms. Less LSTIDs were seen during the one examined high‐speed‐stream storm. We have also found evidence that omega band disturbances may drive interesting TIDs that are distinct from the LSTIDs driven by the substorm and streamer disturbances.
Key Points
All‐sky imaging was used to relate auroral oval disturbances to large‐scale traveling ionospheric disturbances (LSTIDs)
Streamers may be the primary drivers of individual nightside LSTIDs, with or without a substorm
Possible LSTID longitude, orientation, and strength connections suggested
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