We study the evolution of the temporal properties of MAXI J1820+070 during the 2018 outburst in its hard state from MJD 58,190 to 58,289 with Insight-HXMT in a broad energy band 1-150 keV. We find ...different behaviors of the hardness ratio, the fractional rms and time lag before and after MJD 58,257, suggesting a transition occurred around this point. The observed time lags between the soft photons in the 1-5 keV band and the hard photons in higher energy bands, up to 150 keV, are frequency-dependent: the time lags in the low-frequency range, 2-10 mHz, are both soft and hard lags with a timescale of dozens of seconds but without a clear trend along the outburst; the time lags in the high-frequency range, 1-10 Hz, are only hard lags with a timescale of tens of milliseconds; they first increase until around MJD 58,257 and decrease after this date. The high-frequency time lags are significantly correlated to the photon index derived from the fit to the quasi-simultaneous NICER spectrum in the 1-10 keV band. This result is qualitatively consistent with a model in which the high-frequency time lags are produced by Comptonization in a jet.
Malnutrition is a common and critical problem that influences outcome in cancer patients. Body composition reflects a patient's metabolic profile and physiologic reserves, which might be the true ...determinant of prognosis. In the present study, which aimed to identify valuable new prognostic indicators, we investigated the association between computed tomography-quantified body composition and short-term outcomes after gastrectomy for gastric cancer.
Skeletal muscle index, mean muscle attenuation, and ratio of visceral-to-subcutaneous adipose tissue area (vsr) were calculated from preoperative computed tomography images. Low skeletal muscle index, low mean muscle attenuation, and high vsr were respectively termed "sarcopenia," "myosteatosis," and "visceral obesity." The association of body composition with postoperative complications and serum markers of nutrition and inflammation after radical gastrectomy were analyzed.
The overall complication rate was significantly higher in the sarcopenia (62.5% vs. 27.3%,
= 0.001) and myosteatosis groups (38.2% vs. 4%,
= 0.002). Patients with visceral obesity had a higher incidence of inflammatory complications (20.3% vs. 6.5%,
= 0.01). Multivariate logistic regression analysis demonstrated that sarcopenia (
= 0.013), myosteatosis (
= 0.017), and low serum retinol-binding protein (
= 0.019) were independent risk factors for overall complications. Compared with control subjects, patients with sarcopenia had lower postoperative levels of serum retinol-binding protein (
= 0.007), and patients with visceral obesity had higher levels of C-reactive protein (
= 0.026).
Sarcopenia, myosteatosis, and visceral obesity were significantly associated with increased rates of postoperative complications and affected the postoperative nutrition and inflammation status of patients with gastric cancer.
We are developing a transition edge sensor (TES) microcalorimeter array based on a Ti/Au superconducting bilayer, as a backup option for the X-IFU instrument on the Athena X-ray observatory. The ...array is read out by a frequency-division multiplexing readout system using a 1–5 MHz frequency band. Extensive research collaborations between NASA/Goddard and SRON have led to new design rules for microcalorimeters such as low resistivity of the superconductor bilayer, moderately high ohmic resistance of the TES by changing the aspect ratio and no extra metal strips. We have improved our detector fabrication process according to these design principles and produced TES arrays. Although single-pixel characterizations of these arrays are ongoing, the best energy resolution of 2.0 eV for 5.9 keV X-ray has been observed with a 120 × 20 μm
2
TES with a normal resistance of 150 mΩ, biased at 2.2 MHz frequency. This shows that our Ti/Au TES array has a potential to fulfill the detector requirements of the X-IFU instrument.
Elastic electron-proton scattering (e-p) and the spectroscopy of hydrogen atoms are the two methods traditionally used to determine the proton charge radius, r
. In 2010, a new method using muonic ...hydrogen atoms
found a substantial discrepancy compared with previous results
, which became known as the 'proton radius puzzle'. Despite experimental and theoretical efforts, the puzzle remains unresolved. In fact, there is a discrepancy between the two most recent spectroscopic measurements conducted on ordinary hydrogen
. Here we report on the proton charge radius experiment at Jefferson Laboratory (PRad), a high-precision e-p experiment that was established after the discrepancy was identified. We used a magnetic-spectrometer-free method along with a windowless hydrogen gas target, which overcame several limitations of previous e-p experiments and enabled measurements at very small forward-scattering angles. Our result, r
= 0.831 ± 0.007
± 0.012
femtometres, is smaller than the most recent high-precision e-p measurement
and 2.7 standard deviations smaller than the average of all e-p experimental results
. The smaller r
we have now measured supports the value found by two previous muonic hydrogen experiments
. In addition, our finding agrees with the revised value (announced in 2019) for the Rydberg constant
-one of the most accurately evaluated fundamental constants in physics.
Background
Although angiogenesis is an obvious pathological manifestation in the pathogenesis of syphilis, little is known about the underlying mechanisms of angiogenesis induced by reactions to ...Treponema pallidum antigens.
Objective
In this study, we sought to determine the role of recombinant T. pallidum Tp47 in promoting angiogenesis in endothelial cells and the related mechanism.
Methods
Evaluation of the pro‐angiogenic activity of recombinant T. pallidum Tp47 in human umbilical vein endothelial cells (HUVECs) was assessed, and the balance of matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) and the mechanisms underlying the involvement of Akt/mTOR/S6 pathways in this process were explored.
Results
Under stimulation by Tp47, HUVECs exhibited obvious proliferation, migration and tube formation. In addition, the apparent promotion of angiogenesis by Tp47 was observed using a zebrafish embryo model. During angiogenesis, the levels of MMP‐1 and MMP‐10 were significantly elevated, whereas those of TIMP‐1 and TIMP‐2 did not change. In addition, after transfection with siRNAMMP‐1 and siRNAMMP‐10, migration and tube formation were significantly inhibited. Akt/mTOR/S6 signalling was found to be involved in upregulating MMP‐1 and MMP‐10 expression, and the sequential blockade of steps in the pathways effectively prevented Tp47‐induced angiogenesis.
Conclusion
The results reveal the underlying mechanism of angiogenesis promoted by Tp47, namely, upregulating MMP‐1 and MMP‐10 expression to disrupt the MMP/TIMP balance through the Akt/mTOR/S6 pathway. These findings contribute to our understanding of the pathophysiology of syphilis.
•Aramid fiber surface was modified by PIVPGP of AA to improve wettability, adhesion.•Surface modification effect by PIVPGP of AA increased and then decreased with time.•Surface modification effect ...increased and then stayed unaltered with output power.•Ar plasma was the most effective in PIVPGP of AA on aramid fiber surface.•In studied range, optimum technology of PIVPGP of AA: Ar plasma, 15min, 300W.
Plasma induced vapor phase graft polymerization (PIVPGP) method was applied to modify aramid fiber surface. In this study, aramid fibers were pretreated under various plasma conditions such as different treatment times, output powers and working gases to see how these plasma processing parameters influenced the PIVPGP of acrylic acid (AA) on aramid fiber surface and its surface structure and properties. The analysis results of atomic force microscope (AFM) and X-ray photoelectron spectroscope (XPS) showed the increase of surface roughness and the introduction of OCOH, which confirmed that the PIVPGP of AA on aramid fiber surface was achieved. The contact angle and interfacial shear strength (IFSS) of the aramid fibers modified by PIVPGP of AA prominently decreased and increased, respectively, indicating the obvious improvements of surface wettability and adhesion between aramid fiber and matrix. The surface modification effects of aramid fiber by PIVPGP of AA firstly increased and then after 15min slightly decreased with the increasing plasma treatment time, and but firstly increased and then after 300W nearly remained unchanged with the increasing output power, respectively. Among different working gases, Ar plasma occupied first place, O2 plasma and N2 plasma came second and third in the aspect of PIVPGP of AA on aramid fiber surface, respectively. It could be concluded that the PIVPGP of AA on aramid fiber surface could effectively improve surface wettability and adhesion. Plasma conditions had signally influence on the efficiency of PIVPGP of AA on aramid fiber surface and its surface structure and properties with the primary sequence of plasma treatment time, output power and working gas. Therefore adequate plasma processing parameters should be carefully selected for the optimum surface modification of aramid fiber by PIVPGP of AA.
In this study, we apply a multidisciplinary approach to investigate falls in PD patients using clinical, demographic and neuroimaging data from two independent initiatives (University of Michigan and ...Tel Aviv Sourasky Medical Center). Using machine learning techniques, we construct predictive models to discriminate fallers and non-fallers. Through controlled feature selection, we identified the most salient predictors of patient falls including gait speed, Hoehn and Yahr stage, postural instability and gait difficulty-related measurements. The model-based and model-free analytical methods we employed included logistic regression, random forests, support vector machines, and XGboost. The reliability of the forecasts was assessed by internal statistical (5-fold) cross validation as well as by external out-of-bag validation. Four specific challenges were addressed in the study: Challenge 1, develop a protocol for harmonizing and aggregating complex, multisource, and multi-site Parkinson's disease data; Challenge 2, identify salient predictive features associated with specific clinical traits, e.g., patient falls; Challenge 3, forecast patient falls and evaluate the classification performance; and Challenge 4, predict tremor dominance (TD) vs. posture instability and gait difficulty (PIGD). Our findings suggest that, compared to other approaches, model-free machine learning based techniques provide a more reliable clinical outcome forecasting of falls in Parkinson's patients, for example, with a classification accuracy of about 70-80%.
Sulbactam is a class A β-lactamase inhibitor with intrinsic whole-cell activity against certain bacterial species, including Acinetobacter baumannii. The clinical use of sulbactam for A. baumannii ...infections is of interest due to increasing multidrug resistance in this pathogen. However, the molecular drivers of its antibacterial activity and resistance determinants have yet to be precisely defined. Here we show that the antibacterial activities of sulbactam vary widely across contemporary A. baumannii clinical isolates and are mediated through inhibition of the penicillin-binding proteins (PBPs) PBP1 and PBP3, with very low frequency of resistance; the rare pbp3 mutants with high levels of resistance to sulbactam are attenuated in fitness. These results support further investigation of the potential clinical utility of sulbactam.
The epithelium lining the airways of the adult human lung is composed of ciliated and secretory cells together with undifferentiated basal cells (BCs). The composition and organization of this ...epithelium is severely disrupted in many respiratory diseases. However, little is known about the mechanisms controlling airway homeostasis and repair after epithelial damage. Here, we exploit the mouse tracheobronchial epithelium, in which BCs function as resident stem cells, as a genetically tractable model of human small airways. Using a reporter allele we show that the low level of Notch signaling at steady state is greatly enhanced during repair and the generation of luminal progenitors. Loss-of-function experiments show that Notch signaling is required for the differentiation, but not self-renewal, of BCs. Moreover, sustained Notch activation in BCs promotes their luminal differentiation, primarily toward secretory lineages. We also provide evidence that this function of Notch signaling is conserved in BCs from human airways.
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► Notch signaling is active in steady-state airways and increased during repair ► Notch is required for differentiation, but not self-renewal, of airway basal cells ► Notch promotes luminal differentiation of mouse basal stem cells ► Functional evidence suggests that this mechanism is conserved in human basal cells
De-differentiation and activation of pro-inflammatory pathways are key transitions vascular smooth muscle cells (SMCs) make during atherogenesis. Here, we explored the upstream regulators of this ...'atherogenic transition'.
Genome-wide sequencing studies, including Assay for Transposase-Accessible Chromatin using sequencing and RNA-seq, were performed on cells isolated from both murine SMC-lineage-tracing models of atherosclerosis and human atherosclerotic lesions. At the bulk level, alterations in chromatin accessibility were associated with the atherogenic transitioning of lesional SMCs, especially in relation to genes that govern differentiation status and complement-dependent inflammation. Using computational biology, we observed that a transcription factor previously related to coronary artery disease, Activating transcription factor 3 (ATF3), was predicted to be an upstream regulator of genes altered during the transition. At the single-cell level, our results indicated that ATF3 is a key repressor of SMC transitioning towards the subset of cells that promote vascular inflammation by activating the complement cascade. The expression of ATF3 and complement component C3 was negatively correlated in SMCs from human atherosclerotic lesions, suggesting translational relevance. Phenome-wide association studies indicated that genetic variation that results in reduced expression of ATF3 is correlated with an increased risk for atherosclerosis, and the expression of ATF3 was significantly down-regulated in humans with advanced vascular disease.
Our study indicates that the plasticity of atherosclerotic SMCs may in part be explained by dynamic changes in their chromatin architecture, which in turn may contribute to their maladaptive response to inflammation-induced stress.
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