In this paper, we aim to design an autonomous tracking system for a swarm of unmanned aerial vehicles (UAVs) to localize a radio frequency (RF) mobile target. In the system, UAVs equipped with ...omnidirectional received signal strength (RSS) sensors can cooperatively search the target with a specified tracking accuracy. To achieve fast localization and tracking in the highly dynamic channel environment (e.g., time-varying transmit power and intermittent signal), we formulate a flight decision problem as a constrained Markov decision process (CMDP) with the main objective of avoiding redundant UAV flight path. Then, we propose an enhanced multi-agent reinforcement learning to coordinate multiple UAVs performing real-time target tracking. The core of the proposed scheme is a feedback control system that takes into account the uncertainty of the channel estimate. We prove that the proposed algorithm can converge to the optimal decision. Our simulation results show that the proposed scheme outperforms standard Q-learning and multi-agent Q-learning algorithms in terms of searching time and successful localization probability.
Peroxisomes account for ~35% of total H2O2 generation in mammalian tissues. Peroxisomal ACOX1 (acyl‐CoA oxidase 1) is the first and rate‐limiting enzyme in fatty acid β‐oxidation and a major producer ...of H2O2. ACOX1 dysfunction is linked to peroxisomal disorders and hepatocarcinogenesis. Here, we show that the deacetylase sirtuin 5 (SIRT5) is present in peroxisomes and that ACOX1 is a physiological substrate of SIRT5. Mechanistically, SIRT5‐mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation in both cultured cells and mouse livers. Deletion of SIRT5 increases H2O2 production and oxidative DNA damage, which can be alleviated by ACOX1 knockdown. We show that SIRT5 downregulation is associated with increased succinylation and activity of ACOX1 and oxidative DNA damage response in hepatocellular carcinoma (HCC). Our study reveals a novel role of SIRT5 in inhibiting peroxisome‐induced oxidative stress, in liver protection, and in suppressing HCC development.
Synopsis
This study reveals a role for SIRT5 in regulating peroxisomal H2O2 and ROS homeostasis and indicates its potential function in liver protection and hepatocellular carcinoma suppression.
SIRT5 is localized in peroxisomes where it controls H2O2 metabolism.
SIRT5‐mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation.
SIRT5 downregulation increases ACOX1 activity and oxidative DNA damage response in HCC.
This study reveals a role for SIRT5 in regulating peroxisomal H2O2 and ROS homeostasis and indicates its potential function in liver protection and hepatocellular carcinoma suppression.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Nascent RNA may form a three-stranded structure with DNA, called an R-loop, which has been linked to fundamental biological processes such as transcription, replication and genome instability. Here, ...we provide a detailed protocol for a newly developed strategy, named R-ChIP, for robust capture of R-loops genome-wide. Distinct from R-loop-mapping methods based on the monoclonal antibody S9.6, which recognizes RNA-DNA hybrid structures, R-ChIP involves expression of an exogenous catalytically inactive RNASEH1 in cells to bind RNA-DNA hybrids but not resolve them. This is followed by chromatin immunoprecipitation (ChIP) of the tagged RNASEH1 and construction of a strand-specific library for deep sequencing. It takes ~3 weeks to establish a stable cell line expressing the mutant enzyme and 5 more days to proceed with the R-ChIP protocol. In principle, R-ChIP is applicable to both cell lines and animals, as long as the catalytically inactive RNASEH1 can be expressed to study the dynamics of R-loop formation and resolution, as well as its impact on the functionality of the genome. In our recent studies with R-ChIP, we showed an intimate spatiotemporal relationship between R-loops and RNA polymerase II pausing/pause release, as well as linking augmented R-loop formation to DNA damage response induced by driver mutations of key splicing factors associated with myelodysplastic syndrome (MDS).
Mutations in several general pre-mRNA splicing factors have been linked to myelodysplastic syndromes (MDSs) and solid tumors. These mutations have generally been assumed to cause disease by the ...resultant splicing defects, but different mutations appear to induce distinct splicing defects, raising the possibility that an alternative common mechanism is involved. Here we report a chain of events triggered by multiple splicing factor mutations, especially high-risk alleles in SRSF2 and U2AF1, including elevated R-loops, replication stress, and activation of the ataxia telangiectasia and Rad3-related protein (ATR)-Chk1 pathway. We further demonstrate that enhanced R-loops, opposite to the expectation from gained RNA binding with mutant SRSF2, result from impaired transcription pause release because the mutant protein loses its ability to extract the RNA polymerase II (Pol II) C-terminal domain (CTD) kinase—the positive transcription elongation factor complex (P-TEFb)—from the 7SK complex. Enhanced R-loops are linked to compromised proliferation of bone-marrow-derived blood progenitors, which can be partially rescued by RNase H overexpression, suggesting a direct contribution of augmented R-loops to the MDS phenotype.
Display omitted
•Mutations in splicing factors cause cell cycle arrest but distinct splicing defects•Causal mutations in SRSF2 and U2AF1 activate the ATR, but not ATM, pathway•R-loops are augmented genome-wide in SRSF2 and U2AF1 mutants•Overexpressed RNase H partially corrects growth defect of hematopoietic progenitors
Chen et al. report that myelodysplastic syndrome-associated mutations in splicing factors, including SRSF2 and U2AF1, cause cell growth defects through elevated R-loops, replication stress, and ATR-Chk1 activation. Mutant SRSF2 induces transcription pausing and, thus, R-loops, possibly because of its compromised ability in extracting p-TEFb from the 7SK complex at TSSs.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mobile relaying is envisioned as a promising technology to alleviate the masking effect in satellite links. Nevertheless, due to the mobility and limited communication range, the network topology in ...mobile relay networks becomes highly dynamic and time-varying, resulting in increased difficulty of network optimization. This letter investigates unmanned aerial vehicles (UAVs) aided hybrid satellite-terrestrial network, where UAVs are served as mobile relay base stations to assist the communication between the satellite and ground users. We aim to maximize the number of served users by optimizing UAV trajectory and user link selection. To solve the formulated mixed-integer and non-convex optimization problem, we first find the optimal link selection via a designed graph neural network (GNN), and then adjust the UAV locations by using model-free reinforcement learning (RL), alternately. Numerical results demonstrate that our proposed scheme is superior to the state-of-the-art RL algorithms.
For any n\in \mathbb {N}=\{0,1,2,\ldots \} and b,c\in \mathbb {Z}, the generalized central trinomial coefficient T_n(b,c) denotes the coefficient of x^n in the expansion of (x^2+bx+c)^n. Let p be an ...odd prime. In this paper, we determine the summations \sum _{k=0}^{p-1}T_k(b,c)^2/m^k modulo p^2 for integers m with certain restrictions. As applications, we confirm some conjectural congruences of Sun Sci. China Math. 57 (2014), pp. 1375–1400.
Hydrogen is regarded as an attractive alternative energy carrier due to its high gravimetric energy density and only water production upon combustion. However, due to its low volumetric energy ...density, there are still some challenges in practical hydrogen storage and transportation. In the past decade, using chemical bonds of liquid organic molecules as hydrogen carriers to generate hydrogen in situ provided a feasible method to potentially solve this problem. Research efforts on liquid organic hydrogen carriers (LOHCs) seek practical carrier systems and advanced catalytic materials that have the potential to reduce costs, increase reaction rate, and provide a more efficient catalytic hydrogen generation/storage process. In this work, we used methanol as a hydrogen carrier to release hydrogen in situ with the single-site Pt1/CeO2 catalyst. Moreover, in this reaction, compared with traditional nanoparticle catalysts, the single site catalyst displays excellent hydrogen generation efficiency, 40 times higher than 2.5 nm Pt/CeO2 sample, and 800 times higher compared to 7.0 nm Pt/CeO2 sample. This in-depth study highlights the benefits of single-site catalysts and paves the way for further rational design of highly efficient catalysts for sustainable energy storage applications.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Free carbene readily causes multiple side reactions due to its high energy, thus its asymmetric transformation is very difficult. We present here our findings of high‐pKa Brønsted acid catalysts that ...enable free carbene insertion into N−H bonds of amines to prepare chiral α‐amino acid derivatives with high enantioselectivity. Under irradiation with visible light, diazo compounds produce high‐energy free carbenes that are captured by amines to form free ylide intermediates, and then the newly designed high‐pKa Brønsted acids, chiral spiro phosphamides, promote the proton transfer of ylides to afford the products. Computational and kinetic studies uncover the principle for the rational design of proton‐transfer catalysts and explain how the catalysts accelerate this transformation and provide stereocontrol.
A highly enantioselective free carbene insertion into the N−H bond of amines has been achieved. Newly designed high‐pKa Brønsted acid catalysts, chiral spiro phosphamides, were found to be key and promote the proton transfer of the ylide intermediates and control the enantioselectivity of the reaction. The reaction provides a new approach to amino acid derivatives.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This paper investigates a dynamic 3D trajectory design of multiple cache-enabled unmanned aerial vehicles (UAVs) in a wireless device-to-device (D2D) caching network with the goal of maximizing the ...long-term network throughput. By storing popular content at the nearby mobile user devices, D2D caching is an efficient method to improve network throughput and alleviate backhaul burden. With the attractive features of high mobility and flexible deployment, UAVs have recently attracted significant attention as cache-enabled flying base stations. The use of cache-enabled UAVs opens up the possibility of tracking the mobility pattern of the corresponding users and serving them under limited cache storage capacity. However, it is challenging to determine the optimal UAV trajectory due to the dynamic environment with frequently changing network topology and the coexistence of aerial and terrestrial caching nodes. In response, we propose a novel multi-agent reinforcement learning based framework to determine the optimal 3D trajectory of each UAV in a distributed manner without a central coordinator. In the proposed method, multiple UAVs can cooperatively make flight decisions by sharing the gained experiences within a certain proximity to each other. Simulation results reveal that our algorithm outperforms the traditional single- and multi-agent Q-learning algorithms. This work confirms the feasibility and effectiveness of cache-enabled UAVs which serve as an important complement to terrestrial D2D caching nodes.
Splicing factors are vital for the regulation of RNA splicing, but some have also been implicated in regulating transcription. The underlying molecular mechanisms of their involvement in ...transcriptional processes remain poorly understood.
Here, we describe a direct role of splicing factor RBM22 in coordinating multiple steps of RNA Polymerase II (RNAPII) transcription in human cells. The RBM22 protein widely occupies the RNAPII-transcribed gene locus in the nucleus. Loss of RBM22 promotes RNAPII pause release, reduces elongation velocity, and provokes transcriptional readthrough genome-wide, coupled with production of transcripts containing sequences from downstream of the gene. RBM22 preferentially binds to the hyperphosphorylated, transcriptionally engaged RNAPII and coordinates its dynamics by regulating the homeostasis of the 7SK-P-TEFb complex and the association between RNAPII and SPT5 at the chromatin level.
Our results uncover the multifaceted role of RBM22 in orchestrating the transcriptional program of RNAPII and provide evidence implicating a splicing factor in both RNAPII elongation kinetics and termination control.
PDF
