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The Single Field-of-view (SFOV) Sounder Atmospheric Product (SiFSAP) retrieval algorithm has been developed to address the need to retrieve high spatial resolution atmospheric data products from hyper-spectral sounders and ensure the radiometric consistency between the retrieved properties and measured spectral radiances. It is based on an integrated optimal estimation inversion scheme that processes data from the satellite based synergistic microwave (MW) and infrared (IR) spectral measurements from advanced sounders. The retrieval system utilizes the principal component radiative transfer model (PCRTM) which performs radiative transfer calculations monochromatically and includes accurate cloud scattering simulations. SiFSAP includes temperature, water vapor, surface skin temperature and emissivity, cloud height and microphysical properties, and concentrations of essential trace gases for each SFOV at a native instrument spatial resolution. Error estimations are provided based on a rigorous analysis for uncertainty propagation from the Top-Of-Atmosphere (TOA) spectral radiances to the retrieved geophysical properties. As a comparison, the spatial resolution for the traditional hyper-spectral sounder retrieval products is much coarser than the native resolution of the instruments due to common use of the ‘cloud clearing’ technique to compensate for the lack of cloud scattering simulation in the forward model. The degraded spatial resolution in traditional cloud-clearing sounder retrieval products limits their applications for capturing meteorological or climate signals at finer spatial scales. Moreover, rigorous uncertainty propagation estimation needed for long-term climate trend studies cannot be given due to the lack of direct radiative transfer relationships between the observed TOA radiances and the retrieved geophysical properties. With advantages of the higher spatial resolution, the simultaneous retrieval of atmospheric, cloud, and surface properties using all available spectral information, and the establishment of ‘radiance closure’ in the sounder spectral measurements, the SiFSAP provides additional information needed for various weather and climate studies and applications using sounding observations. This paper gives an overview of SiFSAP retrieval algorithm, and assessment of SiFSAP atmospheric temperature, water vapor, clouds, and surface products derived from the Cross-track Infrared Sounder (CrIS) and Advanced Technology Microwave Sounder (ATMS) data.

The ability of focal radiotherapy to promote priming of tumor-specific CD8+ T cells and increase responses to immunotherapy is dependent on infiltration of the tumor by Batf3-dependent conventional dendritic cell type 1 (cDC1) cells. Such infiltration is driven by radiotherapy-induced IFN type I (IFN-I). Other signals may also modulate cDC1 infiltration of irradiated tumors. Here we found increased expression of adenosine-generating enzymes CD38 and CD73 in irradiated mouse and human breast cancer cells and increased adenosine in mouse tumors following radiotherapy. CD73 blockade alone had no effect. CD73 blockade with radiotherapy restored radiotherapy-induced cDC1 infiltration of tumors in settings where radiotherapy induction of IFN-I was suboptimal. In the absence of radiotherapy-induced IFN-I, blockade of CD73 was required for rejection of the irradiated tumor and for systemic tumor control (abscopal effect) in the context of cytotoxic T-lymphocyte–associated protein 4 blockade. These results suggest that CD73 may be a radiation-induced checkpoint, and that CD73 blockade in combination with radiotherapy and immune checkpoint blockade might improve patient response to therapy.

Supplementary figures and tables

Breast white adipose tissue inflammation (BWATi) is associated with obesity and higher breast cancer risk among non-Hispanic white women. Obesity is prevalent in Hispanic/Latina patients with breast cancer, and the occurrence of BWATi in this population is not well-characterized. The association between BWATi and body mass index (BMI) was evaluated in Hispanic/Latina patients with breast cancer who underwent mastectomy. BWATi was defined as the presence of crown-like structures of the breast (CLS-B), detected by CD68 IHC in nontumor breast tissue. BWATi severity was quantified as number of CLS-B/cm2. Adipocyte diameter was measured using hematoxylin and eosin-stained breast tissue sections. Preoperative BMI (within 1 week prior to mastectomy) was categorized as normal (18.5–2), overweight (25.0–2), class I obesity (30.0–2), and class II–III obesity (35.0 kg/m2 or above). Patient charts were abstracted to record clinicopathologic features and liver function tests Ptrend 0.27 CLS-B/cm2) was associated with higher BMI (Ptrend = 0.046) and greater adipocyte diameter (P = 0.04). Adjusting for BMI, neoadjuvant chemotherapy, and elevated alanine aminotransferase were associated with severe BWATi, and current smoking was associated with mild BWATi (all P < 0.05). BWATi was associated with higher BMI in Hispanic/Latina patients with breast cancer, consistent with previously described associations in other populations.

Sup Fig 1

Clinicopathologic features stratified by treatment arm (RNA-seq analysis population).

Purpose: Both phosphatidylinositol 3-kinase/AKT and RAS/mitogen-activated protein kinase signal transduction pathways mediate 4E-BP1 phosphorylation, releasing 4E-BP1 from the mRNA cap and permitting translation initiation. Given the prevalence of PTEN and BRAF mutations in melanoma, we first examined translation initiation, as measured by phosphorylated 4E-BP1 (p-4E-BP1), in metastatic melanoma tissues and cell lines. We then tested the association between amounts of total and p-4E-BP1 and patient survival.Experimental Design: Seven human metastatic melanoma cells lines and 72 metastatic melanoma patients with accessible metastatic tumor tissues and extended follow-up information were studied. Expression of 4E-BP1 transcript, total 4E-BP1 protein, and p-4E-BP1 was examined. The relationship between 4E-BP1 transcript and protein expression was assessed in a subset of patient tumors (n = 41). The association between total and p-4E-BP1 levels and survival was examined in the larger cohort of patients (n = 72).Results: 4E-BP1 was hyperphosphorylated in 4 of 7 melanoma cell lines harboring both BRAF and PTEN mutations compared with untransformed melanocytes or RAS/RAF/PTEN wild-type melanoma cells. 4E-BP1 transcript correlated with 4E-BP1 total protein levels as measured by the semiquantitative reverse-phase protein array (P = 0.012). High levels of p-4E-BP1 were associated with worse overall and post-recurrence survival (P = 0.02 and 0.0003, respectively).Conclusion: Our data show that translation initiation is a common event in human metastatic melanoma and correlates with worse prognosis. Therefore, effective inhibition of the pathways responsible for 4E-BP1 phosphorylation should be considered to improve the treatment outcome of metastatic melanoma patients.

RNA structural switches are key regulators of gene expression in bacteria, yet their characterization in Metazoa remains limited. Here we present SwitchSeeker, a comprehensive computational and experimental approach for systematic identification of functional RNA structural switches. We applied SwitchSeeker to the human transcriptome and identified 245 putative RNA switches. To validate our approach, we characterized a previously unknown RNA switch in the 3’UTR of the RORC transcript.In vivoDMS-MaPseq, coupled with cryogenic electron microscopy, confirmed its existence as two alternative structural conformations. Furthermore, we used genome-scale CRISPR screens to identifytransfactors that regulate gene expression through this RNA structural switch. We found that nonsense-mediated mRNA decay acts on this element in a conformation-specific manner. SwitchSeeker provides an unbiased, experimentally-driven method for discovering RNA structural switches that shape the eukaryotic gene expression landscape.

We studied the 2018 outburst of the black hole transient H 1743 − 322 with a series of Insight-HXMT, NICER, and NuSTAR observations, covering the 1–120 keV band. With our broad-band X-ray spectral modelling, we confirm that the source remained in the low/hard state throughout the month-long outburst, although it became marginally softer at peak flux. We detected Type-C quasi-periodic oscillations (QPOs) and followed the evolution of their properties. The QPO frequency increased from ∼0.1 to ∼0.4 Hz during the rising phase of the outburst and decreased again in the decline. Continuum X-ray flux, power-law photon index, QPO frequency, and QPO root-mean-square amplitude were positively correlated. The QPO amplitude was slightly higher in the soft X-ray band (typical values of 12–16 per cent, compared with 8–10 per cent in the hard band). Our spectral-timing results shed light on the initial rising phase in the low/hard state, which has rarely been monitored with such high cadence, time resolution, and broad-band coverage. Combining spectral and timing properties, we find that ‘failed’ (hard state only) and ‘successful’ outbursts follow the same initial evolutionary track, although the former class of outburst never reaches the threshold for a transition to softer (thermally dominated) accretion regimes.

Background: The presence of white adipose tissue inflammation (WATi) in the breast has been associated with increased breast cancer risk and a worse clinical course. Elevated body mass index (BMI) and the post-menopausal state are both associated with breast WATi. Breast WATi has also been associated with increased expression of aromatase, the rate-limiting enzyme for estrogen biosynthesis. Currently, WATi is diagnosed in surgical samples of breast tissue by the identification of crown-like structures (CLS), which are comprised of a dead or dying adipocyte enveloped by macrophages. In contrast to surgical specimens, core biopsies have been shown to be inadequate for assessing WATi. Hence, there is an unmet need for strategies to non-invasively diagnose WATi. Here we used a novel lipidomics platform to identify potential non-invasive blood signatures of breast WATi. Methods: We conducted a cross-sectional study which included 100 patients who underwent mastectomy for breast cancer treatment or risk reduction. WATi was detected by CD68 immunohistochemistry to identify CLS. Breast aromatase expression levels were measured by qPCR. Clinicopathologic data were abstracted from electronic medical records. Lipidomic data were measured from blood plasma in collaboration with Waters Technologies Corporation. Lipid levels in association with breast WATi (presence/absence) and levels of aromatase expression (high/low) in non-tumorous breast tissue were examined using Welch’s t-test. P-values were adjusted for multiple comparisons by controlling the false discovery rate (FDR) using the Benjamini-Hochberg method. A logistic regression model was used to develop predictive models that evaluated potential lipid biomarkers of the presence of breast WATi and high breast aromatase expression levels. Stepwise regression was used for variable selection. AUC of the ROC curves was used to evaluate the performance of the predictive models. Results: Among 140 lipids analyzed, 13 were identified to be associated with breast WATi (P0.3). Specifically, 8 lipids had lower levels, and 6 lipids had higher levels in patients with breast WATi compared to those without. Levels of 7 lipids were significantly higher in patients with an increased level of aromatase (P0.3). After variable selection, LPE(22:6) (P=0.018), LPE(20:3) ES-(P=0.006), along with menopausal status and BMI provided an 86.0% (95% CI, 77.6%-94.5%) accuracy in predicting higher breast aromatase levels. Combining the effect of two lipids improved the accuracy by 10.4%(P=0.030) compared to the model only using menopausal status and BMI. A model with 5 lipids and menopausal status provided an 88.8%(95% CI, 81.9%-95.8%) accuracy for predicting breast WATi. The model performance improved by 9.2% (P=0.026) compared to the model only using menopausal status and BMI. Conclusions: Our study identified several lipid species that showed significant changes in association with breast WATi and levels of aromatase expression. Further validation of these blood signatures could provide non-invasive assessment of WATi and aromatase levels. The availability of such a diagnostic algorithm could help, in turn, to both identify women at elevated risk for breast cancer and for monitoring the efficacy of interventions aimed at reducing inflammation and aromatase levels. Citation Format: Xiao Cai, Siqi Wei, Zizhuo Xu, Xi K Zhou, Andrew Peck, Steven Lai, Giorgis Isaac, Hernando Olivos, Nayasha Munjoma, Suraj Dhungana, Rob Plumb, Andrew J Dannenberg, Neil M Iyengar. Plasma lipidomics analysis to identify potential non-invasive biomarkers for breast white adipose inflammation and aromatase expression levels [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-05.

Calcitonin gene–related peptide (CGRP) can bias the outcome of Ag presentation to responsive T cells in vitro away from Th1-type immunity and toward the Th2 and Th17 poles through actions on endothelial cells (ECs). To test the in vivo significance of this observation, we engineered a mouse lacking functional CGRP receptors on ECs (EC receptor activity modifying protein 1 [RAMP1] knockout mice). On percutaneous immunization to 1-fluoro-2,4-dinitrobenzene, stimulated CD4+ T cells from draining lymph nodes showed significantly reduced IL-17A expression with significantly increased IFN-γ, IL-4, and IL-22 expression at the protein and mRNA levels compared with control mice. Retinoic acid receptor-related orphan receptor γ t mRNA was significantly reduced, while mRNAs for T-box expressed in T cells and GATA binding protein 3 were significantly increased. In addition, EC RAMP1 knockout mice had significantly reduced contact hypersensitivity responses, and systemic administration of a CGRP receptor antagonist similarly inhibited contact hypersensitivity in wild-type mice. These observations provide compelling evidence that CGRP is a key regulator of cutaneous immunity through effects on ECs and suggest a novel pathway for potential therapeutic manipulation.

BackgroundOur near-real-time safety monitoring of 16 adverse events (AEs) following COVID-19 mRNA vaccination identified potential elevations in risk for six AEs following primary series and monovalent booster dose administration. The crude association with AEs does not imply causality. Accordingly, we conducted robust evaluations of the potential associations.MethodsWe conducted self-controlled case series studies of COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) in U.S. Medicare beneficiaries aged 65 years and older. Adjusted incidence rate ratio (IRRs) and 95% confidence intervals (CIs) were estimated following primary series doses for acute myocardial infarction (AMI), pulmonary embolism (PE), immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC); and following booster doses for AMI, PE, ITP, Bell ‘s Palsy (BP) and Myocarditis/Pericarditis (Myo/Peri).ResultsAmong 3,360,981 individuals who received 6,388,542 primary series doses and 6,156,100 individuals with monovalent booster doses of either BNT162b2 or mRNA-1273, AE counts were: AMI (3,653 primary series, 16,042 booster), inpatient PE (2,470 primary, 5,085 booster), ITP (1,085 primary, 88 booster), DIC (254 primary), BP (3,268 booster), and Myo/Peri (1,295 booster). The IRR for inpatient PE cases following BNT162b2 primary series and booster was 1.19 (95% CI: 1.03 to 1.38) and 0.86 (95% CI: 0.78 to 0.95), respectively; and for mRNA-1273 primary series and booster, 1.15 (95% CI: 0.94 to 1.41) and 0.87 (95% CI: 0.79 to 0.96), respectively. The IRR for BP following BNT162b2 and mRNA-1273 booster was 1.17 (95% CI: 1.06 to 1.29) and 1.16 (95% CI: 1.05 to 1.29), respectively.ConclusionIn these two studies of the U.S. elderly we did not find an increased risk for AMI, ITP, DIC, and Myo/Peri; the results were not consistent for PE; and there was a small elevated risk of BP after exposure to COVID-19 mRNA vaccines. These results support the favorable safety profile of COVID-19 mRNA vaccines administered in the elderly.HIGHLIGHTSThere was no increased risk for four of six outcomes following COVID-19 monovalent mRNA vaccines. There was a small elevated risk of Bell ‘s Palsy after exposure to COVID-19 monovalent mRNA vaccines. Risk of pulmonary embolism was not consistent after exposure to COVID-19 monovalent mRNA vaccines.

The Qinghai–Tibetan Plateau (QTP) played a crucial role in shaping the biodiversity in Asia during the Cenozoic. However, fossil records attributed to insects are still scarce from the QTP, which limits our understanding on the evolution of biodiversity in this large region. Fulgoridae (lanternfly) is a group of large planthopper in body size, which is found primarily in tropical regions. The majority of the Fulgoridae bear brilliant colors and elongated heads. The fossil records of Fulgoridae span from the Eocene to Miocene in the Northern Hemisphere, and only a few fossil species from Neogene deposits have been reported in Asia so far. Here, we report a new fossil record of Fulgoridae from the middle Eocene Lunpola Basin, central QTP. The specimen is in lateral compression, with complete abdomen, thorax, and part of the wings preserved, while most of the head is missing. It belongs to the “lower Fulgoroidea” judging by several strong lateral spines on the hind tibia and a row of teeth at the apex of the second metatarsomere. This fossil specimen is assigned to Fulgoridae by comparison with nine families of the “lower Fulgoroidea”. The specimen represents the earliest Fulgoridae fossil record in Asia and was considered a new morphotaxon based on the peculiar legs and wings. Based on the modern distribution of fulgorid and other paleontological evidence, we suggest a warm climate with relatively low elevation during the middle Eocene in the central QTP. Therefore, this new fossil record not only provides important information on insect diversity in the middle Eocene, but also gives new evidence on the paleoenvironment in the core area of the QTP from the perspective of an insect.

Funder: U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID), Funder: American Association for the Study of Liver Diseases (AASLD); doi: https://doi.org/10.13039/100005347, Vascular endothelial cells (ECs) play a central role in the pathophysiology of many diseases. The use of targeted nanoparticles (NPs) to deliver therapeutics to ECs could dramatically improve efficacy by providing elevated and sustained intracellular drug levels. However, achieving sufficient levels of NP targeting in human settings remains elusive. Here, we overcome this barrier by engineering a monobody adapter that presents antibodies on the NP surface in a manner that fully preserves their antigen-binding function. This system improves targeting efficacy in cultured ECs under flow by >1000-fold over conventional antibody immobilization using amine coupling and enables robust delivery of NPs to the ECs of human kidneys undergoing ex vivo perfusion, a clinical setting used for organ transplant. Our monobody adapter also enables a simple plug-and-play capacity that facilitates the evaluation of a diverse array of targeted NPs. This technology has the potential to simplify and possibly accelerate both the development and clinical translation of EC-targeted nanomedicines.

ImportanceSafety and effectiveness studies of COVID-19 vaccines are being conducted using clinical data, including administrative claims. However, claims data only partially capture administered COVID-19 vaccine doses for numerous reasons, such as vaccination at sites that do not generate claims for reimbursement.ObjectiveTo evaluate the extent to which Immunization Information Systems (IIS) data linked to claims data enhances claims-based COVID-19 vaccine capture for a commercially insured population and to estimate the magnitude of misclassification of vaccinated individuals as having unvaccinated status in the linked IIS and claims data.Design, Setting, and ParticipantsThis cohort study used claims data from a commercial health insurance database and obtained vaccination data from IIS repositories in 11 US states. Participants were individuals younger than 65 years who resided in 1 of 11 states of interest and who were insured in health plans from December 1, 2020, through December 31, 2021.Main Outcomes and MeasuresEstimated proportion of individuals with at least 1 dose of any COVID-19 vaccine and proportion of individuals with a completed vaccine series based on general population guidelines. Vaccination status estimates were calculated and compared using claims data alone and linked IIS and claims data. Remaining misclassification of vaccination status was assessed by comparing linked IIS and claims data estimates with estimates from external surveillance data sources (Centers for Disease Control and Prevention [CDC] and state Department of Health [DOH]) and capture-recapture analysis.ResultsThis cohort study included 5 112 722 individuals (mean [SD] age, 33.5 [17.6] years; 2 618 098 females [51.2%]) from 11 states. Characteristics of those who received at least 1 vaccine dose and those who completed a vaccine series were similar to the overall study population. The proportion with at least 1 vaccine dose increased from 32.8% using claims data alone to 48.1% when the data were supplemented with IIS vaccination records. Vaccination estimates using linked IIS and claims data varied widely by state. The percentage of individuals who completed a vaccine series increased from 24.4% to 41.9% after the addition of IIS vaccine records and varied across states. The percentages of underrecording using linked IIS and claims data were 12.1% to 47.1% lower than those using CDC data, 9.1% to 46.9% lower than the state DOH, and 9.2% to 50.9% lower than capture-recapture analysis.Conclusion and RelevanceResults of this study suggested that supplementing COVID-19 claims records with IIS vaccination records substantially increased the number of individuals who were identified as vaccinated, yet potential underrecording remained. Improvements in reporting vaccination data to IIS infrastructures could allow frequent updates of vaccination status for all individuals and all vaccines.

GRO J1008-57, as a Be/X-ray transient pulsar, is considered to have the highest magnetic field in known neutron star X-ray binary systems. Observational data of the X-ray outbursts in GRO J1008-57 from 2017 to 2020 were collected by the Insight-HXMT satellite. In this work, the spin period of the neutron star in GRO J1008-57 was determined to be about 93.28 seconds in August 2017, 93.22 seconds in February 2018, 93.25 seconds in June 2019 and 93.14 seconds in June 2020. GRO J1008-57 evolved in the spin-up process with a mean rate of − ( 2.10 ± 0.05 ) × 10−4 s/d from 2009 – 2018, and turned into a spin down process with a rate of ( 6.7 ± 0.6 ) × 10−5 s/d from Feb 2018 to June 2019. During the type II outburst of 2020, GRO J1008-57 had the spin-up torque again. During the torque reversals, the pulse profiles and continuum X-ray spectra did not change significantly, and the cyclotron resonant scattering feature around 80 keV was only detected during the outbursts in 2017 and 2020. Based on the observed mean spin-up rate, we estimated the inner accretion disk radius in GRO J1008-57 (about 1 - 2 times of the Alfven radius) by comparing different accretion torque models of magnetic neutron stars. During the spin-down process, the magnetic torque should dominate over the matter accreting inflow torque, and we constrained the surface dipole magnetic field B ≥ 6 × 10 12 G for the neutron star in GRO J1008-57, which is consistent with the magnetic field strength obtained by cyclotron line centroid energy.

BackgroundGeneral Practitioners (GPs) report high levels of burnout, job dissatisfaction, and turnover intention. The complexity of presenting problems to general practice makes diagnostic uncertainty a common occurrence that has been linked to burnout. The interrelationship between diagnostic uncertainty with other factors such as burnout, job satisfaction and turnover intention have not been previously examined.ObjectivesTo examine associations between diagnostic uncertainty, emotional exhaustion (EE), depersonalization (DP), job satisfaction, and turnover intention in GPs.MethodsSeventy general practices in England were randomly selected through the Oxford-Royal College of General Practitioners Research and Surveillance Centre (RCGP-RSC). A total of 348 GPs within 67 these practices completed a 10-item online questionnaire which included questions on GP characteristics, work-life balance, job satisfaction, sickness presenteeism, diagnostic uncertainty, turnover intention as well as EE and DP. Associations between diagnostic uncertainty and each of EE, DP, job satisfaction, and turnover intention were evaluated in multivariate mixed-effect ordinal logistic regressions whilst adjusting for covariates, to account for the correlation in the three outcomes of interest.ResultsAlmost one-third of GPs (n = 101; 29%) reported experiencing >10% of diagnostic uncertainty in their day-to-day practice over the past year. GPs reporting greater diagnostic uncertainty had higher levels of EE [OR = 3.90; 95% CI = (2.54, 5.99)], job dissatisfaction [OR = 2.01; 95% CI = (1.30, 3.13)] and turnover intention [OR = 4.51; 95% CI = (2.86, 7.11)]. GPs with no sickness presenteeism had lower levels of EE [OR = 0.53; 95% CI = (0.35, 0.82)], job dissatisfaction [OR = 0.56; 95% CI = (0.35, 0.88)], and turnover intention [OR = 0.61; 95% CI = (0.41, 0.91)].ConclusionDiagnostic uncertainty may not only negatively impact on the wellbeing of GPs, but could also have adverse implications on workforce retention in primary care.

We report on the Insight-HXMT observations of the new black hole X-ray binary MAXI J1820+070 during its 2018 outburst. Detailed spectral analysis via the continuum fitting method shows an evolution of the inferred spin during its high soft sate. Moreover, the hardness ratio, the non-thermal luminosity and the reflection fraction also undergo an evolution, exactly coincident to the period when the inferred spin transition takes place. The unphysical evolution of the spin is attributed to the evolution of the inner disc, which is caused by the collapse of a hot corona due to condensation mechanism or may be related to the deceleration of a jet-like corona. The studies of the inner disc radius and the relation between the disc luminosity and the inner disc radius suggest that, only at a particular epoch, did the inner edge of the disc reach the innermost stable circular orbit and the spin measurement is reliable. We then constrain the spin of MAXI J1820+070 to be a*=0.2^{+0.2}_{-0.3}. Such a slowly spinning black hole possessing a strong jet suggests that its jet activity is driven mainly by the accretion disc rather than by the black hole spin., Comment: 14 pages, 13 figures, 5 tables, accepted for publication in MNRAS

Fast radio bursts (FRBs) are short pulses observed in radio band from cosmological distances. One class of models invoke soft gamma-ray repeaters (SGRs), or magnetars, as the sources of FRBs. Some radio pulses have been observed from some magnetars, however, no FRB-like events had been detected in association any magnetar burst, including one giant flare. Recently, a pair of FRB-like bursts (FRB 200428 hereafter) separated by milliseconds (ms) were detected from the general direction of the Galactic magnetar SGR J1935+2154. Here we report the detection of a non-thermal X-ray burst in the 1-250 keV energy band with the Insight-HXMT satellite, which we identify as emitted from SGR J1935+2154. The burst showed two hard peaks with a separation of 34 ms, broadly consistent with that of the two bursts in FRB 200428. The delay time between the double radio and X-ray peaks is about 8.57 s, fully consistent with the dispersion delay of FRB 200428. We thus identify the non-thermal X-ray burst is associated with FRB 200428 whose high energy counterpart is the two hard peaks in X-ray. Our results suggest that the non-thermal X-ray burst and FRB 200428 share the same physical origin in an explosive event from SGR J1935+2154., 24 pages, 9 figures, 6 tables; initial submission to a journal on May 9th, 2020. Significant changes include updated localization and detailed spectral evolution of the X-ray burst, and better determination of the two narrow X-ray peaks corresponding to the two radio pulses. Conclusions are strengthened. Nature Astronomy online on Feb. 18, 2021

The new high strength, toughness and low density steel is a new generation of lightweight material with high protection, which is based on the theory of lattice dilution and lattice distortion and is manufactured by adding light elements to reduce its density. Furthermore, after impact process, the composite effects such as transformation induced plasticity (TRIP) effect, twinning induced plasticity (TWIP) effect, microbands induced plasticity (MBIP) effect and phase transformation precipitation occur in the microstructure. The specific strength and specific stiffness are better than those of aluminum, magnesium and titanium alloys, and the modulus is 3 times that of aluminum alloy and 2 times that of titanium alloy. Preliminary research shows that the application of low density steel in artillery system can greatly reduce the production cost. On the basis that all technical and tactical indexes meet the design requirements, it can realize lightweight, long-distance strategic delivery and battlefield real-time repair.

We report a search for a heavier partner of the recently observed state, denoted as , in the process , based on collision data collected at the center-of-mass energies of , 4.682 and 4.699 GeV with the BESIII detector. The is of interest as it is expected to be a candidate for a hidden-charm and open-strange tetraquark. A partial-reconstruction technique is used to isolate recoil-mass spectra, which are probed for a potential contribution from ( ). We find an excess of ( ) candidates with a significance of , after considering systematic uncertainties, at a mass of . As the data set is limited in size, the upper limits are evaluated at the 90% confidence level on the product of the Born cross sections ( ) and the branching fraction ( ) of , under different assumptions of the mass from 4.120 to 4.140 MeV and of the width from 10 to 50 MeV at the three center-of-mass energies. The upper limits of are found to be at the level of pb at each energy. Larger data samples are needed to confirm the state and clarify its nature in the coming years.

TPS400 Background: The objective of this randomized clinical trial is to demonstrate that 2 weeks (5 fractions) of real-time MRI-guided radiotherapy (RT) with an MR Linac does not significantly increase patient-reported GI and GU symptoms compared to 4 weeks (20 fractions) of RT 2 years after treatment completion. Methods: Key Eligibility Criteria: Inclusion Criteria 1. Men aged > 18 with histologically confirmed prostate cancer after prostatectomy with detectable PSA. 2. KPS > 70. 3. Patients with no evidence of distant metastatic disease on PET/CT/MRI/bone scan< 180 days prior to enrollment. 4. Ability to receive MRI-guided radiotherapy. 5. Ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Exclusion Criteria 1. Prior history of receiving pelvic RT. 2. Patient with history of IBD. 3. History of bladder neck or urethral stricture. Study Design/Endpoints: This is a randomized phase II non-inferiority trial comparing 5 fractions of ultrahypofractionated RT (32.5 Gy total with optional PSMA/MRI boost to 40 Gy) versus 20 fractions of hypofractionated RT (55 Gy total with optional PSMA/MRI boost to 60 Gy) in the post-operative setting for prostate cancer. Subjects will be stratified based on pre-specified stratification factors and randomized 1:1 to receive 5 or 20 fractions using permuted block randomization. The primary endpoint is the change in patient-reported GI and GU symptoms as measured by EPIC at 2 years from end of treatment. Secondary endpoints will include both the safety endpoints including change in GI and GU symptoms at 3, 6, 12 and 60 months from end of treatment, and multiple efficacy endpoints including time to progression, prostate cancer specific survival and overall survival. Sample Size: The sample size is calculated based on a non-inferiority design. The non-inferiority margins are set to be a change score of 6 points for the GI symptoms and 5 points for the GU symptoms. The standard deviations of the change scores are assumed to be 13.2 for the GI symptoms and 10.5 for the GU symptoms based on estimates generated in RTOG 0415 trial. This level of change in scores are deemed as clinically meaningful. For example, 6 points of change score for GI symptoms corresponds to two symptoms worsening by 1 level (i.e., loose stools and frequency of bowel movements change from “no problem” to “very small problem”) or one of the symptoms worsening by 2 levels (i.e., loose stool change from “no problem” to “small problem”). A sample size of 122 with 61 in each arm will ensure 80% power for GI endpoint and 83% power for GU endpoint to detect non-inferiority using a one-sided two-sample t-test at the significance level of 0.05. Adjusting for a projected 10% EPIC/non-compliance rate, 136 patients (68 per arm) will be randomized. Stratification Factors: Patients will be stratified according to baseline EPIC bowel and urinary domain scores and use of nodal treatment and ADT. Enrollment: 91 patients. Clinical trial information: NCT04422132 .

TPS399 Background: The objective of this randomized clinical trial is to demonstrate that 2 treatments of real-time MRI-guided radiotherapy (RT) does not significantly increase patient-reported GI and GU symptoms compared to 5 treatments of RT 2 years after treatment completion (24 months). Methods: Key Eligibility Criteria: Inclusion Criteria 1. Men aged > 18 with histologically confirmed low or intermediate risk prostate cancer per NCCN guidelines. 2. ECOG 0 – 1 3. IPSS < 18 4. Ability to receive MRI-guided radiotherapy. 5. Ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Exclusion Criteria 1. Prior history of receiving pelvic RT. 2. Patient with history of IBD. 3. Hip replacements. 4. History of bladder neck or urethral stricture. 5. TURP < 8 weeks prior to RT 6. Metastatic (pelvic nodal or distant) disease on CT, Bone, and/or PSMA PET scan. Study Design/Endpoints: This is a randomized phase II non-inferiority trial comparing 2 fractions of ultrahypofractionated RT (25 Gy total with optional PSMA/MRI boost to 28 Gy) versus 5 fractions of ultra-hypofractionated RT (37.5 Gy total with optional PSMA/MRI boost to 45 Gy) in the definitive setting for prostate cancer. Subjects will be stratified based on pre-specified stratification factors and randomized 1:1 to receive 2 or 5 fractions using permuted block randomization. The primary endpoint is the change in patient-reported GI and GU symptoms as measured by EPIC at 2 years from end of treatment. Secondary endpoints will include both the safety endpoints including change in GI and GU symptoms at 3, 6, 12 and 60 months from end of treatment, and multiple efficacy endpoints including time to progression, prostate cancer specific survival and overall survival. Sample Size: The sample size is calculated based on a non-inferiority design. The non-inferiority margins are set to be a change score of 6 points for the GI symptoms and 5 points for the GU symptoms. The standard deviations of the change scores are assumed to be 13.2 for the GI symptoms and 10.5 for the GU symptoms based on estimates generated in RTOG 0415 trial. This level of change in scores are deemed as clinically meaningful. For example, 6 points of change score for GI symptoms corresponds to two symptoms worsening by 1 level (i.e., loose stools and frequency of bowel movements change from “no problem” to “very small problem”) or one of the symptoms worsening by 2 levels (i.e., loose stool change from “no problem” to “small problem”). A sample size of 122 with 61 in each arm will ensure 80% power for GI endpoint and 83% power for GU endpoint to detect non-inferiority using a one-sided two-sample t-test at the significance level of 0.05. Adjusting for a projected 10% EPIC/non-compliance rate, 136 patients (68 per arm) will be randomized. Stratification Factors: Patients will be stratified according to baseline EPIC bowel and urinary domain scores and country of treatment. Enrollment: Eleven patients. Clinical trial information: NCT04984343 .

The rail grinding process generates a large amount of heat, which could lead to heat damage on the ground rails. But, the whole temperature field of rail ground by the grinding train has not been explored in detail. In the present study, finite element models of a rail and grinding wheel were established to simulate the rail grinding process. The temperature field and the thermo-mechanical coupling stress during rail grinding, and the residual stress after grinding were studied. Furthermore, through simplifying grinding wheels into heat sources, the temperature field of rail ground by a whole grinding train was investigated as well. The results indicated that the grinding temperature and the residual stress increased with the grinding depth and rotational speed, but decreased with the feed speed and radius of rail head. The thermo-mechanical coupling stress increased with the radius of rail head and grinding depth, and decreased with the rotational speed and feed speed. When ground by the whole grinding train, the increase in the number of grinding wheels at the same grinding angle and adjacent angles could lead to a rise in temperature on the rail surface. The speeds of grinding train and the rail head radius also have an influence on the temperature. The optimal feed speed of the grinding train should be below 12 km/h for R300, 16 km/h for R80, and 18 km/h for R13. The results could be used to optimize the grinding parameters and grinding pattern in the field.

The clusters InxO (x = 2, 3) and In4O0/—1 arestudied using density functional theory (B3PW91). The global minima contain linear di-coordinated, T-shape tri-coordinated, and planar tetra-coordinated oxygen atoms for In2O, In3O, and In4O, respectively. 18-valence electrons contribute to square structure of In4O. Excitingly, 19-valence electron in [In4O]– contains tetra-coordinated oxygen. Molecular orbitals analysis reveals that delocalized π-bonding and σ-bonding orbitals stabilize the planar tetra-coordinated bonding of oxygen. In addition, the stability becomes worse with a decrease in coordination number.

Chronic non-bacterial osteomyelitis (CNO) is a rare and difficult-to-diagnose disease, especially when limited to the jaws. We report the case of a 5-year-old girl with spontaneous jaw pain and a large pre-auricular facial swelling overlying the angle of the mandible that was non-responsive to previous antibiotic and non-steroidal anti-inflammatory treatment. The diagnosis was confirmed as CNO following evaluation and workup by a multidisciplinary team. The patient exhibited a favourable response to oral alendronate sodium plus vitamin D3 combination treatment. We believe that alendronate sodium is an effective second-line drug for CNO.

Significance CD8 T cell exhaustion is a key underlying factor limiting immunity in chronic infections and cancer. Persistent antigen exposure antagonizes formation of functional memory CD8 T cells that provide long-term protection and, instead, drives the development of exhausted CD8 T cells (T EX ). Improving T EX persistence and function is a major goal for reinvigorating immune responses against chronic infections and tumors. Here, we identify miR-29a as a molecule that attenuates exhaustion and enhances persistence and function of T EX . Enforced expression of miR-29a alters T EX transcriptome, resulting in robust changes in molecular pathways governed by fundamental transcription factors and epigenetic modulators. Thus, enforced miR-29a expression enhances T EX responses, attenuates exhaustion, and represents a target for improving the outcome of immunotherapy.

Recently, the system parameters of Cygnus X-1, i.e., the black hole mass M, the orbital inclination i and the source distance D, have been updated. As the input constraints of the continuum-fitting method, it is necessary to refine the spin with these new parameters. The Hard X-ray Modulation Telescope (HXMT, also named Insight) was successfully launched on June 15th, 2017 in China. In this work, we analyzed spectra obtained by the Insight-HXMT during 2017-2018 and re-estimated the spin via the continuum-fitting method. We first re-estimated the spin using old parameters and found the dimensionless spin parameter to be a ⁎ > 0.934 (3σ), which is consistent with previous measurements both from the continuum-fitting and iron-line fitting methods ( Gou et al. 2011 , Gou et al. 2014 ; Fabian et al. 2012 , Walton et al. 2016 , Tomsick et al. 2018 ). Then, when the new parameters were applied, we obtained an increased spin: a ⁎ > 0.967 (3σ), which is also consistent with the recent measurement (Zhao et al. 2020, submitted to ApJ) and also confirms an extreme Kerr black hole lying in this system.

A new black hole X-ray binary (BHXRB) MAXI J1535-571 was discovered by MAXI during its outburst in 2017. Using observations taken by the first Chinese X-ray satellite, the Hard X-ray Modulation Telescope (dubbed as Insight-HXMT), we perform a joint spectral analysis (2-150 keV) in both energy and time domains. The energy spectra provide the essential input for probing the intrinsic Quasi-Periodic Oscillation (QPO) fractional rms spectra (FRS). Our results show that during the intermediate state, the energy spectra are in general consistent with those reported by Swift/XRT and NuSTAR. However, the QPO FRS become harder and the FRS residuals may suggest the presence of either an additional power-law component in the energy spectrum or a turn-over in the intrinsic QPO FRS at high energies.

We study the 2018 outburst of Aql X-1 via the monitor of all sky X-ray image (MAXI) data. We show that the outburst starting in February 2018 is a member of short-low class in the frame of outburst duration and the peak count rate although the outburst morphology is slightly different from the other fast-rise-exponential-decay (FRED) type outbursts with a milder rising stage. We study the partial accretion in the weak propeller stage of Aql X-1 via the MAXI data of the 2018 outburst. We report on the spectral analysis of 3 observations of Aquila X-1 obtained by Insight – hard X-ray modulation telescope (Insight-HXMT) during the late decay stage of the 2018 outburst. We discuss that the data taken by Insight-HXMT is just after the transition to the weak propeller stage. Our analysis shows the necessity of a comptonization component to take into account the existence of an electron cloud resulting photons partly up-scattered.

We present a detailed timing study of the brightest persistent X-ray source Sco X-1 using the data collected by the Hard X-ray Modulation Telescope ( I n s i g h t -HXMT) from July 2017 to August 2018. A complete Z-track hardness-intensity diagram (HID) is obtained. The normal branch oscillations (NBOs) at ∼ 6 Hz in the lower part of the normal branch (NB) and the flare branch oscillations (FBOs) at ∼ 16 Hz in the beginning part of the flaring branch (FB) are found in observations with the Low Energy X-ray Telescope (LE) and the Medium Energy X-ray Telescope (ME) of I n s i g h t -HXMT, while the horizontal branch oscillations (HBOs) at ∼ 40 Hz and the kilohertz quasi-periodic oscillations (kHz QPOs) at ∼ 800 Hz are found simultaneously above 20 keV for the first time on the horizontal branch (HB) by the High Energy X-ray Telescope (HE) and ME. We find that for all types of the observed QPOs, the centroid frequencies are independent of energy, while the root mean square (rms) increases with energy; the centroid frequencies of both the HBOs and kHz QPOs increase along the Z-track from the top to the bottom of the HB; and the NBOs show soft phase lags increasing with energy. A continuous QPO transition from the FB to NB in ∼ 200 s are also detected. Our results indicate that the non-thermal emission is the origin of all types of QPOs, the innermost region of the accretion disk is non-thermal in nature, and the corona is nonhomogeneous geometrically.