Nucleophosmin (NPM1) is the most commonly mutated gene in acute myeloid leukemia (AML) resulting in aberrant cytoplasmic translocation of the encoded nucleolar protein (NPM1c
). NPM1c
maintains a ...unique leukemic gene expression program, characterized by activation of HOXA/B clusters and MEIS1 oncogene to facilitate leukemogenesis. However, the mechanisms by which NPM1c
controls such gene expression patterns to promote leukemogenesis remain largely unknown. Here, we show that the activation of HOXBLINC, a HOXB locus-associated long non-coding RNA (lncRNA), is a critical downstream mediator of NPM1c
-associated leukemic transcription program and leukemogenesis. HOXBLINC loss attenuates NPM1c
-driven leukemogenesis by rectifying the signature of NPM1c
leukemic transcription programs. Furthermore, overexpression of HoxBlinc (HoxBlincTg) in mice enhances HSC self-renewal and expands myelopoiesis, leading to the development of AML-like disease, reminiscent of the phenotypes seen in the Npm1 mutant knock-in (Npm1
) mice. HoxBlincTg and Npm1
HSPCs share significantly overlapped transcriptome and chromatin structure. Mechanistically, HoxBlinc binds to the promoter regions of NPM1c
signature genes to control their activation in HoxBlincTg HSPCs, via MLL1 recruitment and promoter H3K4me3 modification. Our study reveals that HOXBLINC lncRNA activation plays an essential oncogenic role in NPM1c
leukemia. HOXBLINC and its partner MLL1 are potential therapeutic targets for NPM1c
AML.
Electrochemically converting nitrate, a widespread water pollutant, back to valuable ammonia is a green and delocalized route for ammonia synthesis, and can be an appealing and supplementary ...alternative to the Haber-Bosch process. However, as there are other nitrate reduction pathways present, selectively guiding the reaction pathway towards ammonia is currently challenged by the lack of efficient catalysts. Here we report a selective and active nitrate reduction to ammonia on Fe single atom catalyst, with a maximal ammonia Faradaic efficiency of ~ 75% and a yield rate of up to ~ 20,000 μg h
mg
(0.46 mmol h
cm
). Our Fe single atom catalyst can effectively prevent the N-N coupling step required for N
due to the lack of neighboring metal sites, promoting ammonia product selectivity. Density functional theory calculations reveal the reaction mechanisms and the potential limiting steps for nitrate reduction on atomically dispersed Fe sites.
In this work, we study the transfer learning problem under high-dimensional generalized linear models (GLMs), which aim to improve the fit on target data by borrowing information from useful source ...data. Given which sources to transfer, we propose a transfer learning algorithm on GLM, and derive its
l
1
/
l
2
-estimation error bounds as well as a bound for a prediction error measure. The theoretical analysis shows that when the target and sources are sufficiently close to each other, these bounds could be improved over those of the classical penalized estimator using only target data under mild conditions. When we don't know which sources to transfer, an algorithm-free transferable source detection approach is introduced to detect informative sources. The detection consistency is proved under the high-dimensional GLM transfer learning setting. We also propose an algorithm to construct confidence intervals of each coefficient component, and the corresponding theories are provided. Extensive simulations and a real-data experiment verify the effectiveness of our algorithms. We implement the proposed GLM transfer learning algorithms in a new R package
glmtrans
, which is available on CRAN.
Supplementary materials
for this article are available online.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
WRKY transcription factors play a key role in the tolerance of biotic and abiotic stresses across various crop species, but the function of some WRKY genes, particularly in tomato, remains ...unexplored. Here, we characterize the roles of a previously unstudied WRKY gene, SlWRKY8, in the resistance to pathogen infection and the tolerance to drought and salt stresses. Expression of SlWRKY8 was up‐regulated upon Pseudomonas syringae pv. tomato DC3000 (Pst. DC3000), abiotic stresses such as drought, salt and cold, as well as ABA and SA treatments. The SlWRKY8 protein was localized to the nucleus with no transcription activation in yeast, but it could activate W‐box‐dependent transcription in plants. The overexpression of SlWRKY8 in tomato conferred a greater resistance to the pathogen Pst. DC3000 and resulted in the increased transcription levels of two pathogen‐related genes SlPR1a1 and SlPR7. Moreover, transgenic plants displayed the alleviated wilting or chlorosis phenotype under drought and salt stresses, with higher levels of stress‐induced osmotic substances like proline and higher transcript levels of the stress‐responsive genes SlAREB, SlDREB2A and SlRD29. Stomatal aperature was smaller under drought stress in transgenic plants, maintaining higher water content in leaves compared with wild‐type plants. The oxidative pressure, indicated by the concentration of hydrogen peroxide (H2O2) and malondialdehyde (MDA), was also reduced in transgenic plants, where we also observed higher levels of antioxidant enzyme activities under stress. Overall, our results suggest that SlWRKY8 functions as a positive regulator in plant immunity against pathogen infection as well as in plant responses to drought and salt stresses.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The electrochemical synthesis of chemicals and fuel feedstocks has been demonstrated to be a sustainable and “green” alternative to traditional chemical engineering, where oxygen evolution reaction ...(OER) plays a vital role in coupling with various cathodic reactions. While tremendous attention, involving both research and review topics, has been focused on pushing the limit of OER catalysts’ activity, the long-term stability of OER catalysts, which may play an even more important role in large-scale electrolysis industrialization, has been much less emphasized. Until this point, few systematic strategies for developing OER catalysts with industrially relevant durability have been reported. In this review, critical mechanisms that could influence OER stability are summarized, including surface reconstruction, lattice oxygen evolution, and the dissolution-redeposition process of catalysts. Moreover, to bridge the gap between lab-scale OER tests and large-scale electrocatalysis applications, stability considerations in electrolyzer design for long-term operation are also discussed in detail. This review provides catalyst and reactor design principles for overcoming OER stability challenges and will focus more attention from the field on the great importance of OER stability as well as future large-scale electrocatalysis applications.
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Recently, clean energy conversion through electrocatalysis is evolving rapidly as a promising alternative to fossil-fuel energy systems. However, electrolyzers have always suffered from long-term stability challenges, especially for the anodic oxygen evolution reaction catalysts. So far, other than high-cost noble-metal catalysts such as IrO2, no catalysts with industrially relevant stability for oxygen evolution process in acidic and neutral conditions have been demonstrated. Thus, mechanisms that lead to catalytic instability require further investigation and deep understanding to guide future catalyst design.
In order to explore both the origins of and solutions to the stability challenges, this review provides a comprehensive overview and analysis on mechanistic studies of OER catalytic stability. Surface reconstruction of catalysts under oxidation potential during oxygen evolution is one of the causes of catalyst degradation. In addition, lattice oxygen can sometimes participate in the reaction pathway and induce structural instability of catalysts. In addition, redeposition of dissolved ions onto the catalyst surface is a process that gains less attention but can greatly influence the catalytic stability. Besides the catalyst consideration, critical elements of electrolyzers are also discussed in this review to provide insights in electrolysis operation under more realistic conditions. Based on the studies summarized in this article, we also provide potential strategies to design stable OER catalysts. By appropriately tuning the components, structures, dissolution, and redeposition rates of catalysts, we believe that the development of catalysts with long-term stability for oxygen evolution reaction can be achieved in the near future.
Oxygen evolution reaction (OER) plays a vital role in clean energy conversion through electrochemical synthesis of chemicals and fuel feedstocks. However, OER catalysts have always suffered from long-term stability challenges. This review timely summarizes critical reaction mechanisms that could influence OER stability, discusses stability considerations for reactor designs, and proposes future perspectives and potential strategies for designing stable OER catalysts to overcome these challenges.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
7.
Traumatic brain injury in China Jiang, Ji-Yao; Gao, Guo-Yi; Feng, Jun-Feng ...
Lancet neurology,
March 2019, 2019-03-00, 20190301, Volume:
18, Issue:
3
Journal Article
Peer reviewed
China has more patients with traumatic brain injury (TBI) than most other countries in the world, making this condition a major public health concern. Population-based mortality of TBI in China is ...estimated to be approximately 13 cases per 100 000 people, which is similar to the rates reported in other countries. The implementation of various measures, such as safety legislation for road traffic, establishment of specialised neurosurgical intensive care units, and the development of evidence-based guidelines, have contributed to advancing prevention and care of patients with TBI in China. However, many challenges remain, which are augmented further by regional differences in TBI care. High-level care, such as intracranial pressure monitoring, is not universally available yet. In the past 30 years, the quality of TBI research in China has substantially improved, as evidenced by an increasing number of clinical trials done. The large number of patients with TBI and specialised trauma centres offer unique opportunities for TBI research in China. Furthermore, the formation and development of research collaborations between China and international groups are considered essential to advancing the quality of TBI care and research in China, and to improve quality of life in patients with this condition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective To evaluate whether very early treatment in our patients would result in better clinical outcomes and to compare these data with other infantile-onset Pompe disease (IOPD) cohort studies. ...Methods In this nationwide program, 669 797 newborns were screened for Pompe disease. We diagnosed IOPD in 14 of these newborns, and all were treated and followed in our hospital. Results After 2010, the mean age at first enzyme-replacement therapy (ERT) was 11.92 days. Our patients had better biological, physical, and developmental outcomes and lower anti-rh acid α-glucosidase antibodies after 2 years of treatment, even compared with one group that began ERT just 10 days later than our cohort. No patient had a hearing disorder or abnormal vision. The mean age for independent walking was 11.6 ± 1.3 months, the same age as normal children. Conclusions ERT for patients with IOPD should be initiated as early as possible before irreversible damage occurs. Our results indicate that early identification of patients with IOPD allows for the very early initiation of ERT. Starting ERT even a few days earlier may lead to better patient outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A variable screening procedure via correlation learning was proposed by Fan and Lv (2008) to reduce dimensionality in sparse ultra-high-dimensional models. Even when the true model is linear, the ...marginal regression can be highly nonlinear. To address this issue, we further extend the correlation learning to marginal nonparametric learning. Our nonparametric independence screening (NIS) is a specific type of sure independence screening. We propose several closely related variable screening procedures. We show that with general nonparametric models, under some mild technical conditions, the proposed independence screening methods have a sure screening property. The extent to which the dimensionality can be reduced by independence screening is also explicitly quantified. As a methodological extension, we also propose a data-driven thresholding and an iterative nonparametric independence screening (INIS) method to enhance the finite- sample performance for fitting sparse additive models. The simulation results and a real data analysis demonstrate that the proposed procedure works well with moderate sample size and large dimension and performs better than competing methods.
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BFBNIB, GIS, IJS, INZLJ, KISLJ, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK, ZRSKP
The Holomorphic Embedding Load-Flow Method (HELM) solves the power-flow problem to obtain the bus voltages as rational approximants, that is, a ratio of complex-valued polynomials of the embedding ...parameter. The proof of its claims (namely that: 1) it is guaranteed to find a solution if it exists; 2) it is guaranteed to find only a high-voltage (operable) solution; and 3) that it unequivocally signals if no solution exists) are rooted in complex analysis and the theory developed by Antonio Trias and Herbert Stahl. HELM is one variant of the holomorphic embedding method (HEM) for solving nonlinear equations, the details of which may differ from those available in its published patents. In this paper we show that the HEM represents a distinct class of nonlinear equation solvers that are recursive, rather than iterative. As such, for any given problem, there are an infinite number of HEM formulations, each with different numerical properties and precision demands. The objective of this paper is to provide an intuitive understanding of HEM and apply one variant to the power-flow problem. We introduce one possible PV bus model compatible with the HEM and examine some features of different holomorphic embeddings, giving step-by-step details of model building, germ calculation, and the recursive algorithm.
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