Precursor Signatures Research Articles

Lean Blowout Proximity Sensing in a Low Emission Liquid-Fueled Combustor

ABSTRACT Advanced aircraft engine combustor designs, intended for achieving low NOx emissions, necessitate lean combustion with small operating margins above the LBO boundary, posing a high risk of exhibiting lean blowout (LBO) problems. Employing active LBO controllers receiving input from LBO proximity sensors can allow for narrower margins, thereby yielding multiple performance gains. Although several previous studies investigated LBO proximity sensing, they predominantly focused on premixed gas-fueled combustors. The application of proximity sensing approaches to liquid-fueled combustor designs, relevant to aircraft engines have not received adequate attention. Therefore, this study investigates LBO proximity sensing in a low emission lean direct injection (LDI) liquid-fueled combustor design developed by NASA. The combustor operates at atmospheric pressure with preheated air. The proximity sensing is examined by analyzing both OH* and CH* chemiluminescence signals, with a focus on assessing their relative performances. The signal analysis approaches include spectral, partial extinction event (LBO precursor) detection, signal RMS, and the CH*/OH* ratio, with an emphasis on the first two methods. Both steady-state and transient operating conditions have been examined. The combustor did not exhibit large-scale flame partial extinction and re-ignition events near LBO, as commonly observed in gas-fueled combustors. However, an increase in flame unsteadiness and partial extinction events with very subtle signatures in optical signals, have been observed. Low-pass filtering has been observed to considerably enhance the precursor signatures enabling their improved detection. With a reduction in LBO margin, an increase in signal low-frequency power, RMS, and precursor event occurrence rate have been observed, which were utilized for providing LBO proximity measures. A key finding from this study is that CH* signals provide significantly superior performance compared to OH* for the proximity sensing in all the approaches, and the potential reasons are discussed.

A Framework for Comparisons of Downburst Precursor Observations Using an All-Digital Phased-Array Weather Radar

Abstract Downbursts are rapidly evolving meteorological phenomena with numerous vertically oriented precursor signatures, and the temporal resolution and vertical sampling of the current NEXRAD system are too coarse to observe their evolution and precursor signatures properly. A future all-digital polarimetric phased-array weather radar (PAR) should be able to improve both temporal resolution and spatial sampling of the atmosphere to provide better observations of rapidly evolving hazards such as downbursts. Previous work has been focused on understanding the trade-offs associated with using various scanning techniques on stationary PARs; however, a rotating, polarimetric PAR (RPAR) is a more feasible and cost-effective candidate. Thus, understanding the trade-offs associated with using various scanning techniques on an RPAR is vital in learning how to best observe downbursts with such a system. This work develops a framework for analyzing the trade-offs associated with different scanning strategies in the observation of downbursts and their precursor signatures. A proof-of-concept analysis—which uses a Cloud Model 1 (CM1)-simulated downburst-producing thunderstorm—is also performed with both conventional and imaging scanning strategies in an adaptive scanning framework to show the potential value and feasibility of the framework. Preliminary results from the proof-of-concept analysis indicate that there is indeed a limit to the benefits of imaging as an update time speedup method. As imaging is used to achieve larger speedup factors, corresponding data degradation begins to hinder the observations of various precursor signatures.

Spatial and temporal behaviour of Ionospheric VTEC and Atmospheric parameters before New Zealand earthquake on 13th November 2016 (M 7.8)

In this paper, we present the results of the Ionospheric VTEC and atmospheric parameters such as Surface Latent Heat flux (SLHF), air temperature at 2 m from the surface (AT2m) and outgoing long-wave radiation (OLR) during New Zealand earthquake of M 7.8 on 13th Nov 2016 with a focal depth of 15.7 km. GPS data from 16 permanent IGS GPS stations from October 1 to November 19, 2016 are used for VTEC analysis. Global geomagnetic and solar parameters are also taken into account in the corresponding period. Both positive and negative anomalies in VTEC were observed using the Interquartile Sliding Moving Average method. Using the upper bound (UB) and lower bound (LB) of the VTEC time series, we observed a stronger enhancement of UB over the observed VTEC at the closer stations than at the far stations before New Zealand earthquake. We observed two VTEC anomalies 14 days and 2 days before this earthquake. By comparing the quiet days and the earthquake disturbed days, we observed significant deviations of the TEC on the earthquake disturbed days. The latitude variations of VTEC at each 30-min interval on November 13, 2016 clearly show the enhancement of the TEC signal just before the earthquake. TEC values appear to be normal between 00:00 and 04:30, peaking around 08:30 UT until the time of the earthquake (11:03 UT) in the New Zealand region. Atmospheric anomalies were calculated when the signal crossed the mean + 2*sigma; and with additional parameters such as the Excess Energy Flux Index (EEFI). SLHF parameters detected abnormal signal 33 and 18 days before the New Zealand earthquake. On October 18, 2016, the air temperature measured 286.25 °K at 2 m from the surface is 3.05 °K higher than the ten-year average and an “EEFI” of 2.18. The next day (October 19, 2016), the air temperature measured 2 m from the surface was 285.89 °K, while the ten-year mean air temperature at 2 m was 283.12 °K and the EEFI of 2.78. Two days after the second SLHF anomaly and four days before the earthquake (November 9, 2016), the anomalous fluctuations of AT2m for the current earthquake were observed for the second time. From the analysis of atmospheric parameters such as surface latent heat flux (SLHF), air temperature 2 m from the surface (AT2m) and outgoing long-wave radiation (OLR), it is observed that anomalous variations of these parameters were observed near the epicentral region before the New Zealand earthquake. VTEC together with atmospheric parameters (SLHF, AT2m and OLR) prove to be a promising tool for monitoring earthquake precursor signatures just before the New Zealand earthquake.

Cellular Plasticity As Mechanisms to Escape from NOTCH1-Inhibition in T-ALL

Cellular plasticity has recently emerged as an underlying mechanism for treatment refraction in cancer. Hence, characterizing cell states and the transcriptional changes required for state transitions is critical for the development of efficient targeted therapies. Acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic malignancy in children and adolescents that is associated with high rates of treatment failure and early relapse. T-ALL patients frequently harbor NOTCH1 activating mutations as the driving oncogene in this disease. Using T-ALL patient-derived xenograft (PDX) models carrying activating NOTCH1 mutations, we aim to u First, to determine how cell state diversity drives treatment refraction in T-ALL, we performed full-length single-cell transcriptome analysis on 3188 immune cells collected from 2 sensitive and 3 refractory PDX models. PDX models were treated with either with NOTCH inhibitor DBZ (Dipenzazepine; 10 μM/kg every other day intravenously) or vehicle. Profiled cells were collected at both a short (5 days) and a late time point (x-150 days) post-treatment to assess the effects of DBZ. Analysis of early hematopoietic and thymic precursor signatures demonstrate expression of immature hematopoietic signatures and acquisition of alternative lineage identities coexisting within the same cell, predominantly in refractory models. Analyses of pre-treatment samples indicated that disruption of the normal developmental hierarchy was associated with blockade at an early stage of T-cell commitment and can predict response to NOTCH inhibition in vivo. Upon treatment, cells underwent dramatic transcriptional reprogramming resulting in expansion of 2 distinct populations that greatly differ in both differentiation stage and developmental trajectory. One population expresses lymphoid differentiation programs, whereas the other population is enriched in genes associated with RNA processing and more immature hematopoietic signatures. Cell fate trajectories assessment using Monocle 2, revealed that consistent with their immature hematopoietic signature, refractory cells map at the start point of the differentiation trajectory, while sensitive cells clustered at the endpoint. We next sought to characterize the differentiation hierarchies that define the immature states. Developmental potential as assessed by CytoTRACE was higher in refractory cells when compared to their sensitive counterpart. To identify determinants of cell fate in a functionally relevant manner, we inferred gene regulatory network configurations using SCENIC and defined state specific regulon activity. Among the most prominently expressed regulons present in mature states, we identified transcriptional regulators involved in T-cell differentiation such as IKAROS, GATA3, and SOX5, while in immature states we observed high transcriptional regulon activity in transcription factors associated with renewal of hematopoietic progenitors such as ATF4, BCLAF1, and MYC in addition to the chromatin remodelers SMARCA4 and EZH2. To assess whether transcriptional rewiring in refractory cells results from greater chromatin accessibility, we performed single-cell ATAC sequencing (10x Genomics) on splenic cells from 1 sensitive and 1 refractory T-ALL PDX model treated with DBZ or vehicle. After integration with corresponding single-cell RNA-sequencing data, annotated ATAC profiles demonstrated greater chromatin accessibility, predominantly in active promotor and enhancer regions, in the refractory model compared to the sensitive model. Peak to gene linkage analysis revealed widespread alterations in cis-regulatory regions near genes associated with immature hematopoietic precursor signatures such as CD33. Furthermore, greater chromatin accessibility in refractory cells was associated with an increased number of enhancer loops per expressed gene as determined by H3K27ac HiChIP analysis. In conclusion, we demonstrated that presence of highly plastic cellular states defined by aberrant differentiation trajectories, distinct transcriptional circuitries, and remodeled chromatin architecture results in treatment escape in T-ALL.

Storm-Scale Polarimetric Radar Signatures Associated with Tornado Dissipation in Supercells

Abstract Polarimetric radar data from the WSR-88D network are used to examine the evolution of various polarimetric precursor signatures to tornado dissipation within a sample of 36 supercell storms. These signatures include an increase in bulk hook echo median raindrop size, a decrease in midlevel differential radar reflectivity factor (ZDR) column area, a decrease in the magnitude of the ZDR arc, an increase in the area of low-level large hail, and a decrease in the orientation angle of the vector separating low-level ZDR and specific differential phase (KDP) maxima. Only supercells that produced “long-duration” tornadoes (with at least four consecutive volumes of WSR-88D data) are investigated, so that signatures can be sufficiently tracked in time, and novel algorithms are used to isolate each storm-scale process. During the time leading up to tornado dissipation, we find that hook echo median drop size (D0) and median ZDR remain relatively constant, but hook echo median KDP and estimated number concentration (NT) increase. The ZDR arc maximum magnitude and ZDR–KDP separation orientation angles are observed to decrease in most dissipation cases. Neither the area of large hail nor the ZDR column area exhibit strong signals leading up to tornado dissipation. Finally, combinations of storm-scale behaviors and TVS behaviors occur most frequently just prior to tornado dissipation, but also are common 15–20 min prior to dissipation. The results from this study provide evidence that nowcasting tornado dissipation using dual-polarization radar may be possible when combined with TVS monitoring, subject to important caveats.

A statistical analysis of the relationship between Pc4 and Pc5 ULF waves, solar winds and geomagnetic storms for predicting earthquake precursor signatures in low latitude regions

Short-term earthquake forecasting is impossible due to the seismometer’s limited sensitivity in detecting the generation of micro-fractures prior to an earthquake. Therefore, there is a strong desire for a non-seismological approach, and one of the most established methods is geomagnetic disturbance observation. Previous research shows that disturbances in the ground geomagnetic field serves as a potential precursor for earthquake studies. It was discovered that electromagnetic waves (EM) in the Ultra-Low Frequency (ULF) range are a promising tool for studying the seismomagnetic effect of earthquake precursors. This study used a multiple regression approach to analyse the preliminary study on the relationship between Pc4 (6.7-22 mHz) and Pc5 (1.7-6.7 mHz) ULF magnetic pulsations, solar wind parameters and geomagnetic indices for predicting earthquake precursor signatures in low latitude regions. The ground geomagnetic field was collected from Davao station (7.00° N, 125.40° E), in the Philippines, which experiences nearby earthquake events (Magnitude <5.0, depth <100 km and epicentre distance from magnetometer station <100 km). The Pc5 ULF waves show the highest variance with four solar wind parameters, namely SWS, SWP, IMF-Bz, SIE and geomagnetic indices (SYM/H) prior to an earthquake event based on the regression model value of R2 = 0.1510. Furthermore, the IMF-Bz, SWS, SWP, SWE, and SYM/H were found to be significantly correlated with Pc5 ULF geomagnetic pulsation. This Pc5 ULF magnetic pulsation behaviour in solar winds and geomagnetic storms establishes the possibility of using Pc5 to predict earthquakes.

Interpretation of Stall Precursor Signatures

Abstract Unsteady aerodynamic phenomena appearing close to the stall boundary in axial fans and compressors have been the subject of extensive investigations. A particular phenomenon known as “rotating instabilities” typically occurs in the tip region at highly loaded conditions and is often linked to blade vibrations. During rig and engine testing, it is usually identified by the characteristic shape of its pressure spectra. In the 1990s, this shape has been explained as the result of a circumferentially propagating disturbance, which is unsteady in a frame of reference rotating with the disturbance. In this analysis, conclusions regarding its propagation speed and frequency have been made based on the analysis of spectral peaks, and this method is still often used to classify unsteady aerodynamic phenomena. However, in high subsonic and transonic machines, where aeroacoustic and aeroelastic phenomena interact with aerodynamic disturbances, the interpretation of measurements using spectra alone is challenging. The present article aims to demonstrate the difficulties and subtleties associated with the analysis of measurement signals, which need to be overcome to correctly interpret stall precursor signatures. At the example of a recent investigation on a composite fan, the consequences of sensor placement and postprocessing techniques are discussed with a focus on spectral averaging, isolation of non-synchronous phenomena, and multisensor cross correlation methods. It is seen that the interpretation of phenomena based solely on spectral peaks and their spacing can be misleading and that the characteristic features of a rotating instability spectrum do not require an unstable pulsating disturbance.

Early evolution of the solar accretion disk inferred from Cr-Ti-O isotopes in individual chondrules

Isotopic anomalies in chondrules hold important clues about the dynamics of mixing and transport processes in the solar accretion disk. The meaning of these anomalies is debated and they have been interpreted to indicate either disk-wide transport of chondrules or local heterogeneities of chondrule precursors. However, all previous studies relied on isotopic data for a single element (either Cr, Ti, or O), which does not allow distinguishing between source and precursor signatures as the cause of the chondrules' isotope anomalies. To overcome this problem, we obtained the first combined O, Ti, and Cr isotope data for individual chondrules from enstatite, ordinary, and carbonaceous chondrites. We find that chondrules from non-carbonaceous (NC) chondrites have relatively homogeneous Δ17O, ε50Ti, and ε54Cr, which are similar to the compositions of their host chondrites. By contrast, chondrules from carbonaceous chondrites (CC) have more variable compositions, some of which differ from the host chondrite compositions. Although the compositions of the analyzed CC and NC chondrules may overlap for either ε50Ti, ε54Cr, or Δ17O, in multi-isotope space, none of the CC chondrules plot in the compositional field of NC chondrites, and no NC chondrule plots within the field of CC chondrites. As such, our data reveal a fundamental isotopic difference between NC and CC chondrules, which is inconsistent with a disk-wide transport of chondrules across and between the NC and CC reservoirs. Instead, the isotopic variations among CC chondrules reflect local precursor heterogeneities, which most likely result from mixing between NC-like dust and a chemically diverse dust component that was isotopically similar to CAIs and AOAs. The same mixing processes, but on a larger, disk-wide scale, were likely responsible for establishing the distinct isotopic compositions of the NC and CC reservoirs, which represent in inner and outer disk, respectively.

Applying Deep Learning to Hail Detection: A Case Study

Deep learning is a subset of machine learning that uses deep neural networks (DNNs) capable of learning representations and extracting valuable information from vast data sets. Similarly, weather phenomena are often identified by patterns in data that serve as precursor signatures. Therefore, deep learning networks can be used to identify signatures of the weather phenomena, or possibly signatures not yet established by forecasters in addition to aiding forecasters in synthesizing the growing amount of meteorological observations. In this article, we demonstrate the value of deep learning for atmospheric science applications by providing a proof of concept, using deep learning for the detection of hail-bearing storms as a test case study. The deep learning network presented in this article obtains a higher precision when presented with multisource data and is able to identify a common feature associated with hail storms—decreased infrared brightness temperatures. This network and case study illustrate the capability of deep networks for the detection of weather phenomena and contribute to the growing awareness of deep learning among atmospheric scientists.

Radar Observations of Tornado-Warned Convection Associated with Tropical Cyclones over Florida

Abstract Statistical evaluations of tornado warnings issued during recent tropical cyclone events yielded an above-average false alarm ratio. This study analyzed tornado-warned convection associated with Tropical Storms Debby (2012) and Andrea (2013) using superresolution and dual-polarization data from Weather Surveillance Radar-1988 Doppler radars located throughout the Florida peninsula to identify precursor characteristics and signatures that would distinguish tornadic events prior to tornadogenesis. A series of radar-based interrogation guidance at varying ranges from radar is presented to help facilitate the reduction of the tornado-warning false alarm ratio without compromising the probability of detection. For convection within 74.1 km from the nearest radar, low-level velocity characteristics include a rotational velocity ≥ 10.3 m s−1 (20 kt), shear across the rotation ≥ 0.010 s−1, and a contracting rotation diameter. The convection should also exhibit supercell reflectivity signatures and at least a mesocyclone velocity enhancement signature or horizontal separation of greater ZDR and KDP values. Guidance at a range from 74.1 to 129.6 km is similar except for not requiring the presence of a supercell reflectivity signature and the change of the rotational velocity guidance to ≥7.7 m s−1 (15 kt) at the 0.5°-elevation angle. Convection at a range beyond 129.6 km only requires a rotational velocity ≥ 7.7 m s−1 (15 kt) at the 0.5°-elevation angle. Evaluation of the radar interrogation guidance for tornadic events and tornado-warned convection for six tropical cyclones reduced the number of false alarm events by 28.9% and reduced the false alarm ratio from 0.740 to 0.669.

Isotope signatures of N2O emitted from vegetable soil: Ammonia oxidation drives N2O production in NH4(+)-fertilized soil of North China.

Nitrous oxide (N2O) is a potent greenhouse gas. In North China, vegetable fields are amended with high levels of N fertilizer and irrigation water, which causes massive N2O flux. The aim of this study was to determine the contribution of microbial processes to N2O production and characterize isotopic signature effects on N2O source partitioning. We conducted a microcosm study that combined naturally abundant isotopologues and gas inhibitor techniques to analyze N2O flux and its isotopomer signatures [δ15Nbulk, δ18O, and SP (intramolecular 15N site preference)] that emitted from vegetable soil after the addition of NH4+ fertilizers. The results show that ammonia oxidation is the predominant process under high water content (70% water-filled pore space), and nitrifier denitrification contribution increases with increasing N content. δ15Nbulk and δ18O of N2O may not provide information about microbial processes due to great shifts in precursor signatures and atom exchange, especially for soil treated with NH4+ fertilizer. SP and associated two end-member mixing model are useful to distinguish N2O source and contribution. Further work is needed to explore isotopomer signature stability to improve N2O microbial process identification.

SLIPPING MAGNETIC RECONNECTION, CHROMOSPHERIC EVAPORATION, IMPLOSION, AND PRECURSORS IN THE 2014 SEPTEMBER 10 X1.6-CLASS SOLAR FLARE

ABSTRACT We investigate the occurrence of slipping magnetic reconnection, chromospheric evaporation, and coronal loop dynamics in the 2014 September 10 X-class flare. Slipping reconnection is found to be present throughout the flare from its early phase. Flare loops are seen to slip in opposite directions toward both ends of the ribbons. Velocities of 20–40 km s−1 are found within time windows where the slipping is well resolved. The warm coronal loops exhibit expanding and contracting motions that are interpreted as displacements due to the growing flux rope that subsequently erupts. This flux rope existed and erupted before the onset of apparent coronal implosion. This indicates that the energy release proceeds by slipping reconnection and not via coronal implosion. The slipping reconnection leads to changes in the geometry of the observed structures at the Interface Region Imaging Spectrograph slit position, from flare loop top to the footpoints in the ribbons. This results in variations of the observed velocities of chromospheric evaporation in the early flare phase. Finally, it is found that the precursor signatures, including localized EUV brightenings as well as nonthermal X-ray emission, are signatures of the flare itself, progressing from the early phase toward the impulsive phase, with the tether-cutting being provided by the slipping reconnection. The dynamics of both the flare and outlying coronal loops is found to be consistent with the predictions of the standard solar flare model in three dimensions.

DYNAMIC FLARING NON-POTENTIAL FIELDS ON QUIET SUN NETWORK SCALES

ABSTRACT We report on the identification of dynamic flaring non-potential structures on quiet Sun (QS) supergranular network scales. Data from the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory allow for the high spatial and temporal resolution of this diverse class of compact structures. The rapidly evolving non-potential events presented here, with lifetimes &lt;10 minutes, are on the order of 10″ in length. Thus, they contrast significantly with well-known active region (AR) non-potential structures such as high-temperature X-ray and EUV sigmoids (&gt;100″) and micro-sigmoids (&gt;10″) with lifetimes on the order of hours to days. The photospheric magnetic field environment derived from the Helioseismic and Magnetic Imager shows a lack of evidence for these flaring non-potential fields being associated with significant concentrations of bipolar magnetic elements. Of much interest to our events is the possibility of establishing them as precursor signatures of eruptive dynamics, similar to notions for AR sigmoids and micro-sigmoids, but associated with uneventful magnetic network regions. We suggest that the mixed network flux of QS-like magnetic environments, though unresolved, can provide sufficient free magnetic energy for flaring non-potential plasma structuring. The appearance of non-potential magnetic fields could be a fundamental process leading to self-organized criticality in the QS-like supergranular network and contribute to coronal heating, as these events undergo rapid helicial and vortical relaxations.

On new detailed ionogram signatures of Equatorial Plasma Bubbles from non-equatorial station during low solar activity

On new detailed ionogram signatures of Equatorial Plasma Bubbles from non-equatorial station during low solar activity

A Qualitative Analysis of NWS Forecasters’ Use of Phased-Array Radar Data during Severe Hail and Wind Events

Abstract The 2013 Phased Array Radar Innovative Sensing Experiment (PARISE) investigated the impacts of higher-temporal-resolution radar data on National Weather Service forecasters’ warning decision processes during severe hail and wind events. In total, 12 forecasters participated in the 2013 PARISE over a 6-week period during the summer of 2013. Participants were assigned to either a control [5-min phased-array radar (PAR) updates] or experimental (1-min PAR updates) group, and worked two cases in simulated real time. This paper focuses on the qualitative retrospective reports of participants’ warning decision processes that were collected using the recent case walk-through method. Timelines of participants’ warning decision process were created for both cases, which were then thematically coded according to a situational awareness framework. Coded themes included perception, comprehension, and projection. It was found that the experimental group perceived significantly more information during both cases than the control group (case 1 p = 0.045 and case 2 p = 0.041), which may have improved the quality of their comprehensions and projections. Analysis of timelines reveals that 1-min PAR updates were important to the experimental group’s more timely and accurate warning decisions. Not only did the 1-min PAR updates enable experimental participants to perceive precursor signatures earlier than control participants, but through monitoring trends in radar data, the experimental group was able to better detect storm motion, more accurately identify expected weather threats from severe thunderstorms, more easily observe strengthening and diminishing trends in storms, and make more correct tornado-related warning decisions.

A body-force based method to generate supersonic equilibrium turbulent boundary layer profiles

We further develop a simple counterflow body force-based approach to generate an equilibrium spatially developing turbulent boundary layer suitable for Direct Numerical Simulations (DNS) or Large Eddy Simulations (LES) of viscous–inviscid interactions. The force essentially induces a small separated region in an incoming specified laminar boundary layer. The resulting unstable shear layer then transitions and breaks down to yield the desired unsteady profile. The effects of wall thermal conditions are explored to demonstrate the capability of the method for both fixed wall and adiabatic wall conditions. We then describe an efficient method to select parameters that ensure transition by examining precursor signatures using generalized stability variables. These precursors are shown to be evident in a computational domain spanning only a small region around the trip and can also be detected using 2D simulations. Finally, the method is tested for different Mach numbers ranging from 1.7 to 2.9, with emphasis on flow field surveys, Reynolds stresses, and energy spectra. These results provide guidance on boundary conditions for desired boundary layer thickness at each Mach number. The consequences of using a much lower Reynolds number in computation relative to experiment are evident at the higher Mach number, where a self sustaining turbulent boundary layer is more difficult to obtain.

Novel AMKL Chimeric Transcription Factors Are Potent Inducers of Leukemia with Unique Mechanisms of Leukemogenesis

Acute megakaryoblastic leukemia (AMKL) accounts for ~10% of childhood AML. AMKL patients without Down syndrome have a poor outcome with a 3 year survival of less than 40%. To gain insight into the biology of this disease, we previously performed transcriptome sequencing on diagnostic blasts from a discovery cohort of 14 pediatric cases and validated our findings in a recurrency/validation cohort consisting of 34 pediatric and 28 adult samples. This analysis identified novel fusion transcripts restricted to pediatric AMKL including CBFA2T3-GLIS2,GATA2-HOXA9, MN1-FLI1, and NIPBL-HOXB9.To confirm their role in oncogenesis and gain insight into the mechanism whereby these fusions promote disease, we introduced each of them into murine hematopoietic cells and assessed their effect on in vitro colony replating as a surrogate measure of self-renewal. Hematopoietic cells transduced with a control retrovirus failed to form colonies after the second replating. By contrast, expression of each of the fusion genes resulted in a marked increase in self-renewal capacity, with colony formation persisting through 10 replatings. Immunophenotypic analysis revealed evidence of megakaryocytic differentiation in CBFA2T3-GLIS2 and MN1-FLI1 cohorts, whereas NIPBL-HOXB9 and GATA2-HOXA9 cells carried markers consistent with myeloid progenitors. Transplantation of fusion gene modified bone marrow cells into syngeneic recipients induced overt leukemia in all cohorts with the exception of CBFA2T3-GLIS2, suggesting an essential requirement for cooperative mutation(s) in cases expressing this chimeric gene. To assess self-renewal activity of the leukemia generated in our murine models, we conducted secondary transplants for all cohorts. In all cases, the leukemia was transplantable with a shorter latency than in the primary transplant setting.To characterize the tumors at the molecular level, 5 samples from each of the 3 fusions underwent array comparative genomic hybridization, transcriptome, and whole exome sequencing. Samples demonstrated a small number of cooperating mutations with 1.5 copy number alterations (range 0-6) and 6.4 single nucleotide variations (range 2-13) per case. Overall, cases carried an average of 7.9 mutations (range 2-14). Despite the low number of lesions, recurrently mutated genes were identified. These include activating mutations in Flt3, Kras, and cMet, as well as loss of function mutations in the tumor suppressors Phactr4, Wt1, and Tet2. A comparison between fusion subtypes did not reveal any statistically significant differences, although there was a trend towards a greater number of mutations in the GATA2-HOXA9 cohort. Transcriptome sequencing of cohorts, along with normal hematopoietic progenitor subsets, confirmed unique gene expression patterns between each of the fusions. Consistent with immunophenotyping, MN1-FLI1 demonstrated enrichment of the MEP signature while NIPBL-HOXB9 and GATA2-HOXA9 were enriched for CMP and monocyte precursor signatures respectively. ChIP-seq analysis of each of the fusions is underway to definitively identify the genomic targets whose expression is directly altered by their binding.A common characteristic between all fusions is the presence of protein interaction domains contributed by the N term partner, and DNA binding domains contributed by the C term partner. To determine if these fusions have a novel gain of function distinct from their independent counterparts, we introduced each partner gene into murine bone marrow cells for transplantation experiments. As previously described, introduction of MN1 into hematopoietic cells led to a highly penetrant leukemia. In contrast, HOXA9, HOXB9, and FLI1 all had >75% disease free survival with few myeloid leukemias resulting from their over expression, while GATA2 failed to induce any disease at all. NIPBL’s size precluded transplant assays. Therefore, to evaluate its contribution we introduced a point mutation previously shown to disrupt binding of NIPBL to the cohesion component MAU2. This alteration abrogated the ability of the fusion to induce leukemia in our transplant model, demonstrating the importance of this interaction in the pathogenesis of disease. In conclusion, our data confirms a pathogenic role for GATA2-HOXA9, MN1-FLI1, and NIPBL-HOXB9 in AMKL. Further studies delineating the cooperating mutations required for CBFA2T3-GLIS2 are indicated. DisclosuresNo relevant conflicts of interest to declare.

On the use of geomagnetic indices and ULF waves for earthquake precursor signatures

Ultralow frequency (ULF: 0.001–5 Hz) magnetic records have recently been used in the search for short‐term earthquake prediction methods. The separation of local and global effects in the magnetic records is the greatest challenge in this research area. Geomagnetic indices are often used to predict global ULF magnetic behavior where it is assumed that increases in a geomagnetic index correspond with an increase in ULF power. This paper examines the relationships between geomagnetic indices and ULF power, spectral polarization ratio, and the relationship between the spectral polarization ratio and solar wind parameters. The power in the ULF, Pc3‐5 bands (10–600 s), shows a linear correlation coefficient of 0.2 with the Kp magnetic activity index. The correlation varies with magnetic local time (MLT) and latitude. The correlation coefficient is inversely related to the integrated power in the ULF Pc3 band (10–45 s) over MLT and magnetic latitude. The ratio of spectral powers Z(ω)/G(ω) is discussed and shown to be a promising parameter in the search for earthquake precursor signals in ULF records.

On the origin of pressure and magnetic perturbations ahead of dipolarization fronts

Dipolarization fronts (DFs), earthward‐propagating structures in the Earth's magnetotail current sheet with sharp enhancements of the northward magnetic field Bz, are typically preceded by minor decreases in Bz. Other characteristic DF precursor signatures, including earthward flows and plasma density/pressure enhancements, have been explained in the context of ion acceleration and reflection at dipolarization fronts. In the same context here we simulate the spatial distribution of plasma pressure earthward of a convex DF. The resultant pressure distribution, which shows clear dawn‐dusk asymmetries with greater enhancements at the DF duskside, agrees with statistical observations. The simulation further reveals that the reflected ions can carry a secondary current earthward of the advancing DF, which explains the characteristic signature of the Bz dip immediately ahead of the DF.

Changes in Quasi-periodic Variations of Solar Photospheric Fields: Precursor to the Deep Solar Minimum in Cycle 23?

Possible precursor signatures in the quasi-periodic variations of solar photospheric fields were investigated in the build-up to one of the deepest solar minima experienced in the past 100 years. This unusual and deep solar minimum occurred between Solar Cycles 23 and 24. We used both wavelet and Fourier analysis to study the changes in the quasi-periodic variations of solar photospheric fields. Photospheric fields were derived using ground-based synoptic magnetograms spanning the period 1975.14 to 2009.86 and covering Solar Cycles 21, 22, and 23. A hemispheric asymmetry in the periodicities of the photospheric fields was seen only at latitudes above ± 45∘ when the data were divided into two parts based on a wavelet analysis: one prior to 1996 and the other after 1996. Furthermore, the hemispheric asymmetry was observed to be confined to the latitude range of 45∘ to 60∘. This can be attributed to the variations in polar surges that primarily depend on both the emergence of surface magnetic flux and varying solar-surface flows. The observed asymmetry along with the fact that both solar fields above ± 45∘ and micro-turbulence levels in the inner-heliosphere have been decreasing since the early- to mid-nineties (Janardhan et al. in Geophys. Res. Lett. 382, 20108, 2011) suggest that around this time active changes occurred in the solar dynamo that governs the underlying basic processes in the Sun. These changes in turn probably initiated the build-up to the very deep solar minimum at the end of Cycle 23. The decline in fields above ± 45∘, for well over a solar cycle, would imply that weak polar fields have been generated in the past two successive solar cycles, viz. Cycles 22 and 23. A continuation of this declining trend beyond 22 years, if it occurs, will have serious implications for our current understanding of the solar dynamo.