Water soluble ferrocene (Fc) derivatives are promising cathode materials for aqueous organic redox flow batteries (AORFBs) towards scalable energy storage. However, their structure-performance ...relationship and degradation mechanism in aqueous electrolytes remain unclear. Herein, physicochemical and electrochemical properties, battery performance, and degradation mechanisms of three Fc catholytes, (ferrocenylmethyl)trimethylammonium chloride (
C
1
-FcNCl
), (2-ferrocenyl-ethyl)trimethylammonium chloride (
C
2
-FcNCl
), and (3-ferrocenyl-propyl)trimethylammonium chloride (
C
3
-FcNCl
) in pH neutral aqueous electrolytes were systemically investigated. UV-Vis and gas chromatography (GC) studies confirmed the thermal and photolytic
C
x
-Cp
−
ligand dissociation decomposition pathways of both discharged and charged states of
C
1
-FcNCl
and
C
2
-FcNCl
catholytes. In contrast, in the case of the
C
3
-FcNCl
catholyte, the electron-donating 3-(trimethylammonium)propyl group strengthens the coordination between the
C
3
-Cp
−
ligand and the Fe
3+
or Fe
2+
center and thus mitigates the ligand-dissociation degradation. Consistently, the Fc electrolytes displayed cycling stability in both half-cell and full-cell flow batteries in the order of
C
1
-FcNCl
<
C
2
-FcNCl
<
C
3
-FcNCl
.
Thermal and photolytic degradation pathways for water soluble ferrocene cathode electrolytes are elucidated in aqueous redox flow batteries. Design principles are presented to develop advanced coordination complex redox active electrolytes for energy storage.
Histone modifications are key regulators of chromatin function. However, little is known to what extent histone modifications can directly impact on chromatin. Here, we address how a modification ...within the globular domain of histones regulates chromatin function. We demonstrate that H3K122ac can be sufficient to stimulate transcription and that mutation of H3K122 impairs transcriptional activation, which we attribute to a direct effect of H3K122ac on histone-DNA binding. In line with this, we find that H3K122ac defines genome-wide genetic elements and chromatin features associated with active transcription. Furthermore, H3K122ac is catalyzed by the coactivators p300/CBP and can be induced by nuclear hormone receptor signaling. Collectively, this suggests that transcriptional regulators elicit their effects not only via signaling to histone tails but also via direct structural perturbation of nucleosomes by directing acetylation to their lateral surface.
Display omitted
► H3K122ac is a conserved modification on the lateral surface of the histone octamer ► Enrichment of H3K122ac at gene promoters correlates with transcriptional output ► H3K122ac stimulates histone eviction from and transcription of chromatin ► High levels of H3K122ac are a signature of active gene enhancers
Acetylation of histone H3 at lysine 122 (H3K122ac) is found to be catalyzed by p300/CBP and to mark transcriptionally active chromatin genome wide. H3K122ac likely promotes transcription directly by weakening histone-DNA interactions rather than indirectly by recruiting an effector.
Tanking up energy through atypical charging Hu, Bo; Liu, T Leo
Science (American Association for the Advancement of Science),
2021-May-21, 2021-05-21, 20210521, Volume:
372, Issue:
6544
Journal Article
Peer reviewed
Designed ketone molecules can undergo two-electron charge storage in aqueous solutions
Aqueous redox flow batteries could provide viable grid-scale electrochemical energy storage for renewable energy ...because of their high-power performance, scalability, and safe operation (
1
,
2
). Redox-active organic molecules serve as the energy storage materials (
2
,
3
), but only very few organic molecules, such as viologen (
4
,
5
) and anthraquinone molecules (
6
), have demonstrated promising energy storage performance (
2
). Efforts continue to develop other families of organic molecules for flow battery applications that would have dense charge capacities and be chemically robust. On page 836 of this issue, Feng
et al.
(
7
) report a class of ingeniously designed 9-fluorenone (FL) molecules as high-performance, potentially low-cost organic anode electrolytes (anolytes) in aqueous organic redox flow batteries (see the figure, top). These FL anolytes not only display exceptional energy storage performance but also exhibit an unprecedented two-electron storage mechanism.
In resting-state functional magnetic resonance imaging (fMRI), functional connectivity measures can be influenced by the presence of a strong global component. A widely used pre-processing method for ...reducing the contribution of this component is global signal regression, in which a global mean time series signal is projected out of the fMRI time series data prior to the computation of connectivity measures. However, the use of global signal regression is controversial because the method can bias the correlation values to have an approximately zero mean and may in some instances create artifactual negative correlations. In addition, while many studies treat the global signal as a non-neural confound that needs to be removed, evidence from electrophysiological and fMRI measures in primates suggests that the global signal may contain significant neural correlates. In this study, we used simultaneously acquired fMRI and electroencephalographic (EEG) measures of resting-state activity to assess the relation between the fMRI global signal and EEG measures of vigilance in humans. We found that the amplitude of the global signal (defined as the standard deviation of the global signal) exhibited a significant negative correlation with EEG vigilance across subjects studied in the eyes-closed condition. In addition, increases in EEG vigilance due to the ingestion of caffeine were significantly associated with both a decrease in global signal amplitude and an increase in the average level of anti-correlation between the default mode network and the task-positive network.
•Global signal amplitude (GSamp) is negatively correlated with EEG vigilance.•Caffeine-induced decreases in GSamp are related to increases in EEG vigilance.•Increases in EEG vigilance are related to increases in DMN-TPN anti-correlation.
Deep learning based retinal OCT segmentation Pekala, M.; Joshi, N.; Liu, T.Y. Alvin ...
Computers in biology and medicine,
November 2019, 2019-11-00, 20191101, Volume:
114
Journal Article
Peer reviewed
We look at the recent application of deep learning (DL) methods in automated fine-grained segmentation of spectral domain optical coherence tomography (OCT) images of the retina. We describe a new ...method combining fully convolutional networks (FCN) with Gaussian Processes for post processing. We report performance comparisons between the proposed approach, human clinicians, and other machine learning (ML) such as graph based approaches. The approach is demonstrated on an OCT dataset consisting of mild non-proliferative diabetic retinopathy from the University of Miami. The method is shown to have performance on par with humans, also compares favorably with the other ML methods, and appears to have as small or smaller mean unsigned error (equal to 1.06), versus errors ranging from 1.17 to 1.81 for other methods, and compared with human error of 1.10.
Abstract
Nanoparticle strengthening provides a crucial basis for developing high-performance structural materials with potentially superb mechanical properties for structural applications. However, ...the general wisdom often fails to work well due to the poor thermal stability of nanoparticles, and the rapid coarsening of these particles will lead to the accelerated failures of these materials especially at elevated temperatures. Here, we demonstrate a strategy to achieve ultra-stable nanoparticles at 800~1000 °C in a Ni
59.9-
x
Co
x
Fe
13
Cr
15
Al
6
Ti
6
B
0.1
(at.%) chemically complex alloy, resulting from the controllable sluggish lattice diffusion (SLD) effect. Our diffusion kinetic simulations reveal that the Co element leads to a significant reduction in the interdiffusion coefficients of all the main elements, especially for the Al element, with a maximum of up to 5 orders of magnitude. Utilizing first-principles calculations, we further unveil the incompressibility of Al induced by the increased concentration of Co plays a critical role in controlling the SLD effect. These findings are useful for providing advances in the design of novel structural alloys with extraordinary property-microstructure stability combinations for structural applications.
Diabetic retinopathy (DR) is a leading cause of vision loss worldwide. Screening for DR is recommended in children and adolescents, but adherence is poor. Recently, autonomous artificial intelligence ...(AI) systems have been developed for early detection of DR and have been included in the American Diabetes Association's guidelines for screening in adults. We sought to determine the diagnostic efficacy of autonomous AI for the diabetic eye exam in youth with diabetes.
In this prospective study, point-of-care diabetic eye exam was implemented using a nonmydriatic fundus camera with an autonomous AI system for detection of DR in a multidisciplinary pediatric diabetes center. Sensitivity, specificity, and diagnosability of AI was compared with consensus grading by retinal specialists, who were masked to AI output. Adherence to screening guidelines was measured before and after AI implementation.
Three hundred ten youth with diabetes aged 5-21 years were included, of whom 4.2% had DR. Diagnosability of AI was 97.5% (302 of 310). The sensitivity and specificity of AI to detect more-than-mild DR was 85.7% (95% CI 42.1-99.6%) and 79.3% (74.3-83.8%), respectively, compared with the reference standard as defined by retina specialists. Adherence improved from 49% to 95% after AI implementation.
Use of a nonmydriatic fundus camera with autonomous AI was safe and effective for the diabetic eye exam in youth in our study. Adherence to screening guidelines improved with AI implementation. As the prevalence of diabetes increases in youth and adherence to screening guidelines remains suboptimal, effective strategies for diabetic eye exams in this population are needed.
The epithelial-mesenchymal transition (EMT) is crucial to cancer progression and metastasis. Although multiple cellular miRNAs have been identified to regulate the EMT and metastasis in cancers, the ...role of viral miRNAs in cancer progression remains largely unknown. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy typically characterized by its early metastasis. In the present study, we have discovered the involvement of a viral miRNA, EBV-miR-BART7-3p, in the EMT and metastasis of NPC cells. Initially, we observed that EBV-miR-BART7-3p was highly expressed in NPC and positively correlated with lymph node metastasis and clinical stage of NPC. Subsequently, we demonstrated that EBV-miR-BART7-3p enhanced cell migration/invasion in vitro, cancer metastasis in vivo, and particularly the EMT characterized by loss of epithelial markers and gain of mesenchymal features in NPC cells. Furthermore, mechanistic studies disclosed that EBV-miR-BART7-3p targeted a major human tumor suppressor PTEN, modulating PI3K/Akt/GSK-3β signaling and eventually leading to the high expression and nuclear accumulation of Snail and β-catenin, which favor EMT. Knockdown of PTEN could phenocopy the effect of EBV-miR-BART7-3p, whereas re-expression of PTEN resulted in a phenotypic reversion. Moreover, these findings were supported by an observation of an EBV-positive cell model in which silencing of endogenous EBV-miR-BART7-3p partially attenuated cell migration/invasion and altered EMT protein expression pattern via reverting PI3K/Akt, Snail and β-catenin expression. Thus, this study suggests a novel mechanism by which EBV-miR-BART7-3p modulates the EMT and metastasis of NPC cells, and a clinical implication of EBV-miR-BART7-3p as a potential biomarker or therapeutic target.
The phase III ALEX study in patients with treatment-naive advanced anaplastic lymphoma kinase mutation-positive (ALK+) non-small-cell lung cancer (NSCLC) met its primary end point of improved ...progression-free survival (PFS) with alectinib versus crizotinib. Here, we present detailed central nervous system (CNS) efficacy data from ALEX.
Overall, 303 patients aged ≥18 years underwent 1:1 randomization to receive twice-daily doses of alectinib 600 mg or crizotinib 250 mg. Brain imaging was conducted in all patients at baseline and every subsequent 8 weeks. End points (analyzed by subgroup: patients with/without baseline CNS metastases; patients with/without prior radiotherapy) included PFS, CNS objective response rate (ORR), and time to CNS progression.
In total, 122 patients had Independent Review Committee-assessed baseline CNS metastases (alectinib,n = 64; crizotinib,n = 58), 43 had measurable lesions (alectinib,n = 21; crizotinib,n = 22), and 46 had received prior radiotherapy (alectinib,n = 25; crizotinib,n = 21). Investigator-assessed PFS with alectinib was consistent between patients with baseline CNS metastases hazard ratio (HR) 0.40, 95% confidence interval (CI): 0.25–0.64 and those without (HR 0.51, 95% CI: 0.33–0.80,P interaction = 0.36). Similar results were seen in patients regardless of prior radiotherapy. Time to CNS progression was significantly longer with alectinib versus crizotinib and comparable between patients with and without baseline CNS metastases (P < 0.0001). CNS ORR was 85.7% with alectinib versus 71.4% with crizotinib in patients who received prior radiotherapy and 78.6% versus 40.0%, respectively, in those who had not.
Alectinib demonstrated superior CNS activity and significantly delayed CNS progression versus crizotinib in patients with previously untreated, advancedALK+ NSCLC, irrespective of prior CNS disease or radiotherapy.
ClinicalTrials.gov NCT02075840
PDF
