Myeloproliferative neoplasms (MPNs) feature a malignant clone containing the JAK2 V617F mutation, or another mutation causing dysregulated JAK2 kinase activity. The multiple disease phenotypes of ...MPNs, and their tendency to transform phenotypically, suggest pathophysiologic heterogeneities beyond a common phenomenon of JAK2 hyperactivation. JAK2 has the potential to activate multiple other signaling molecules, either directly through downstream effectors, or indirectly through induction of target gene expression. We have interrogated myeloproliferative signaling in myelofibrosis (MF) and secondary acute myeloid leukemia (sAML) patient samples using mass cytometry, which allows the quantitative measurement of multiple signaling molecules simultaneously at the single-cell level, in cell populations representing a nearly complete spectrum of hematopoiesis. MF and sAML malignant cells demonstrated a high prevalence of hyperactivation of the JAK-STAT, MAP kinase, PI3 kinase and NFκB signaling pathways. Constitutive NFκB signaling was evident across MF and sAML patients. A supporting gene set enrichment analysis (GSEA) of MF showed many NFκB target genes to be expressed above normal levels in MF patient CD34+ cells. NFκB inhibition suppressed colony formation from MF CD34+ cells. This study indicates that NFκB signaling contributes to human myeloproliferative disease and is abnormally activated in MF and sAML.
We have searched for short periodicities in the light curves of stars with Teff cooler than 4000 K made from 2-minute cadence data obtained in Transiting Exoplanet Survey Satellite sectors 1 and 2. ...Herein we report the discovery of 10 rapidly rotating M dwarfs with highly structured rotational modulation patterns among 371 M dwarfs found to have rotation periods less than 1 day. Starspot models cannot explain the highly structured periodic variations that typically exhibit between 10 and 40 Fourier harmonics. A similar set of objects was previously reported following K2 observations of the Upper Scorpius association. We examine the possibility that the unusual structured light curves could stem from absorption by charged dust particles that are trapped in or near the stellar magnetosphere. We also briefly explore the possibilities that the sharp structured features in the light curves are produced by extinction by coronal gas, by beaming of the radiation emitted from the stellar surface, or by occultations of spots by a dusty ring that surrounds the star. The last is perhaps the most promising of these scenarios. Most of the structured rotators display flaring activity, and we investigate changes in the modulation pattern following the largest flares. As part of this study, we also report the discovery of 17 rapidly rotating M dwarfs with rotational periods below 4 hr, of which the shortest period is 1.63 hr.
ABSTRACT
Many scientific investigations of photometric galaxy surveys require redshift estimates, whose uncertainty properties are best encapsulated by photometric redshift (photo-z) posterior ...probability density functions (PDFs). A plethora of photo-z PDF estimation methodologies abound, producing discrepant results with no consensus on a preferred approach. We present the results of a comprehensive experiment comparing 12 photo-z algorithms applied to mock data produced for The Rubin Observatory Legacy Survey of Space and Time Dark Energy Science Collaboration. By supplying perfect prior information, in the form of the complete template library and a representative training set as inputs to each code, we demonstrate the impact of the assumptions underlying each technique on the output photo-z PDFs. In the absence of a notion of true, unbiased photo-z PDFs, we evaluate and interpret multiple metrics of the ensemble properties of the derived photo-z PDFs as well as traditional reductions to photo-z point estimates. We report systematic biases and overall over/underbreadth of the photo-z PDFs of many popular codes, which may indicate avenues for improvement in the algorithms or implementations. Furthermore, we raise attention to the limitations of established metrics for assessing photo-z PDF accuracy; though we identify the conditional density estimate loss as a promising metric of photo-z PDF performance in the case where true redshifts are available but true photo-z PDFs are not, we emphasize the need for science-specific performance metrics.
Recovering fluoride from wastewater has large economic and environmental significance within the fluorine industry. A novel crystallization process was proposed for the recovery and the removal of ...fluorine-containing industrial wastewater by steps. A pilot-scale reaction-separation integrated reactor was used to recover the sandy cryolite via crystallization. A pilot-scale fluidized bed reactor was used to recover the sandy calcium fluoride via crystallization. The results showed that the recovery rate of cryolite was greater than 70%, with a purity of more than 89%. The qualities of cryolite products could meet the national standard for synthetic cryolite in China. The purity of the calcium fluoride was greater than 71%, with a particle size of 153.1 μm, and a water content of 27%. The qualities of calcium fluoride products could meet the national standard of comminuted fluorspar in China. Both the cryolite products and the calcium fluoride products could be reused as raw materials. The fluoride concentration of the wastewater was less than 10 mg/L, which met the national discharge standard in China.
We report the detection of a transiting super-Earth-sized planet (
R
= 1.39 ± 0.09
R
⊕
) in a 1.4-day orbit around L 168-9 (TOI-134), a bright M1V dwarf (
V
= 11,
K
= 7.1) located at 25.15 ± 0.02 pc. ...The host star was observed in the first sector of the Transiting Exoplanet Survey Satellite (TESS) mission. For confirmation and planet mass measurement purposes, this was followed up with ground-based photometry, seeing-limited and high-resolution imaging, and precise radial velocity (PRV) observations using the HARPS and
Magellan
/PFS spectrographs. By combining the TESS data and PRV observations, we find the mass of L 168-9 b to be 4.60 ± 0.56
M
⊕
and thus the bulk density to be 1.74
−0.33
+0.44
times higher than that of the Earth. The orbital eccentricity is smaller than 0.21 (95% confidence). This planet is a level one candidate for the TESS mission’s scientific objective of measuring the masses of 50 small planets, and it is one of the most observationally accessible terrestrial planets for future atmospheric characterization.
Background
The epidemiology of multiple drug intolerance syndrome (MDIS) and multiple drug allergy syndrome (MDAS) is poorly characterized. We used electronic health record (EHR) data to describe ...prevalences of MDIS and MDAS and to examine associations with anxiety and depression.
Methods
Patients with ≥3 outpatient encounters at Partners HealthCare System from 2008 to 2015 were included. Patients with MDIS had intolerances to ≥3 drug classes, and patients with MDAS had hypersensitivities to ≥2 drug classes. Psychiatric conditions and comorbidities were defined from the EHR and used in multivariable logistic regression models to assess the relation between anxiety/depression and MDIS/MDAS.
Results
Of 746 888 patients, 47 634 (6.4%) had MDIS and 8615 (1.2%) had MDAS; 3171 (0.4%) had both. Anxiety (adjusted odds ratio aOR 1.72 1.65, 1.80), depression (aOR 1.46 1.41, 1.52), and both anxiety and depression (aOR 1.97 1.86, 2.08) were associated with increased odds of MDIS. Depression was associated with increased odds of MDAS (aOR 1.41 1.28, 1.56), but there were no clear associations with anxiety (aOR 1.13 0.99, 1.30) nor both depression and anxiety (aOR 1.13 0.92, 1.38).
Conclusion
While 6% of patients had MDIS, only 1% had MDAS. MDIS was associated with both anxiety and depression; patients with both anxiety and depression had an almost twofold increased odds of MDIS. MDAS was associated with a 40% increased odds of depression, but there was no significant association with anxiety. Psychological assessments may be useful in the evaluation and treatment of patients with MDIS and MDAS; physiologic causes for MDAS warrant further investigation.
In this study, we used electronic health record data from 746 888 patients in a large US healthcare system to determine the prevalence of multiple drug intolerance syndrome (MDIS, 6%) and multiple drug allergy syndrome (MDAS, 1%). Patients with both MDIS and MDAS comprised 0.4% of the population (upper left). Common drug classes for MDIS and MDAS were penicillins, opiates, sulfonamides, and nonsteroidal antiinflammatory drugs (upper right). We assessed the association between MDIS and MDAS and anxiety and depression while adjusting for confounding variables (bottom right). MDIS was associated with both depression and anxiety; patients with both depression and anxiety had a twofold increased odds of MDIS. MDAS was associated with a 40% increased odds of depression, but there was no consistent relationship with anxiety.
Objective
Deficiency of adenosine deaminase 2 (DADA2) is a potentially fatal monogenic syndrome characterized by variable manifestations of systemic vasculitis, bone marrow failure, and ...immunodeficiency. Most cases are diagnosed by pediatric care providers, given the typical early age of disease onset. This study was undertaken to describe the clinical phenotypes and treatment response both in adults and in children with DADA2 in India.
Methods
A retrospective analysis of pediatric and adult patients with DADA2 diagnosed at various rheumatology centers across India was conducted. Clinical characteristics, diagnostic findings, and treatment responses were analyzed in all subjects.
Results
In total, 33 cases of DADA2 were confirmed in this cohort between April 2017 and March 2020. Unlike previous studies, nearly one‐half of the confirmed cases presented during adulthood. All symptomatic patients exhibited features of vasculitis, whereas constitutional symptoms and anemia were more common in pediatric patients. Cutaneous and neurologic involvement were common, and 18 subjects had experienced at least one stroke. In addition, the clinical spectrum of DADA2 was expanded by recognition of novel features in these patients, including pancreatic infarction, focal myocarditis, and diffuse alveolar hemorrhage. Treatment with tumor necrosis factor inhibitors (TNFi) was initiated in 25 patients. All of the identified disease manifestations showed marked improvement after initiation of TNFi, and disease remission was achieved in 19 patients. Two cases were complicated by tuberculosis infection, and 2 deaths were reported.
Conclusion
This report presents the first case series of patients with DADA2 from India, diagnosed by adult and pediatric care providers. The findings raise awareness of this syndrome, particularly with regard to its presentation in adults.
This study presents a statistical investigation of the force balance and structures in the flux ropes in Mercury's magnetotail plasma sheet by using the measurements of MErcury Surface, Space ...ENviroment, GEochemistry, and Ranging (MESSENGER). One hundred sixty‐eight flux ropes were identified from the 14 hot seasons of MESSENGER from 11 March 2011 to 30 April 2015, and 143 of them show clear magnetic field enhancements with the core field being ≥20% higher than the background magnetic field. The investigation on the force balance of these 143 flux ropes shows that magnetic pressure gradient force cannot be solely balanced by magnetic tension force, implying that thermal plasma pressure gradient force cannot be neglected in the flux ropes. We employ a non‐force‐free model considering the contribution of thermal pressure to resolve the physical properties of flux ropes in Mercury's magnetotail. Twenty‐eight flux ropes are obtained through the fitting to the non‐force‐free model. The flux ropes are found to be consistent with the flattened structures, in which the mean semimajor is ∼851 km and semiminor is ∼333 km, both are several times the local proton inertial length. The average core field is estimated to be ∼57.5 nT, and flux content is ∼0.019 MWb, much larger than the previous results obtained from force‐free flux rope model. The importance of thermal pressure gradient in the force balance of the flux ropes and the flattened structure indicates that the flux ropes in Mercury's magnetotail plasma sheet are mostly in early stage of the evolution, and still contain enough plasma to affect their magnetic structures.
Key Points
Thermal pressure gradient is significant for the flux ropes in Mercury's magnetotail
Non‐force‐free modeling reveals the flatten structure and much higher magnetic flux of the flux ropes different from the previous studies
Flux ropes in this study should be in their early stage of evolution and could be strongly affected by thermal pressure
Reversible control over the microparticle motion using light excites interesting applications in optofluidics, microswimmers, artificial optical matter, and biomedical engineering. The dielectric ...microspheres swim towards the near infrared pulsed laser in response to the backaction force mediated by photonic nanojet. Hereby, we report that the backaction force exhibits hysteretic behaviour owing to the distinguishable responses of the temperature rise inside the nanojet and the temperature rise of the liquid ensemble. Accordingly, the magnitude of backaction force at the same laser power varies between power increase and decrease stages. In order to develop multidimensional manipulation tool, we studied the possibility of using lasers with different spatiotemporal profiles to mediate the backaction force, and developed the counterpropagating beam scheme for reversible control of the particle motion directions. We further harness the hysteresis to reverse the direction of backaction force on dielectric particles in presence of a constant force from a counter-propagating beam with broadband supercontinuum spectrum. In contrast to the microsphere caught in the single beam gradient trap, the microsphere encounters augmented Brownian motion at higher balanced power level. The microsphere would eventually escape from the common region of the paired beams, enabling high throughput morphology analysis for cancer cell classification, biopsy, and diagnosis.
We elucidate here the significance of microstructure, in particular, martensite–austenite constituent, in influencing impact toughness and yield-to-tensile strength ratio in a low carbon low-alloyed ...steel processed via combination of thermo-mechanical controlled processing and tempering. The objective of the study described here is to explore the impact of tempering temperature on the stability of bainite in the attempt to obtain high strength steel with yield strength greater than 600MPa and yield ratio less than 0.85, together with superior impact toughness. An accompanying objective is to study the striking variation in toughness with tempering temperature, while the strength exhibited insignificant change. The microstructure of the studied steel primarily comprised of fine lath and granular bainite, small fraction of ferrite, together with some martensite–austenite constituent. The morphology of martensite–austenite constituent was granular and stringer-type, and was located between laths or at the bainite/ferrite boundary. With the increase in tempering temperature, the microstructure became coarse and martensite–austenite constituent was decomposed, leading to decrease in tensile strength and impact toughness, while the yield strength continued to remain stable. High strength, good toughness, and low yield ratio was obtained at lower tempering temperature and is attributed to the fine lath-type microstructure and stable martensite–austenite constituent.
PDF
