To realize graphene-based electronics, various types of graphene are required; thus, modulation of its electrical properties is of great importance. Theoretic studies show that intentional doping is a promising route for this goal, and the doped graphene might promise fascinating properties and widespread applications. However, there is no experimental example and electrical testing of the substitutionally doped graphene up to date. Here, we synthesize the N-doped graphene by a chemical vapor deposition (CVD) method. We find that most of them are few-layer graphene, although single-layer graphene can be occasionally detected. As doping accompanies with the recombination of carbon atoms into graphene in the CVD process, N atoms can be substitutionally doped into the graphene lattice, which is hard to realize by other synthetic methods. Electrical measurements show that the N-doped graphene exhibits an n-type behavior, indicating substitutional doping can effectively modulate the electrical properties of graphene. Our finding provides a new experimental instance of graphene and would promote the research and applications of graphene.

DNA topoisomerases are the targets of important anticancer and antibacterial drugs. Camptothecins and novel noncamptothecins in clinical development (indenoisoquinolines and ARC-111) target eukaryotic type IB topoisomerases (Top1), whereas human type IIA topoisomerases (Top2alpha and Top2beta) are the targets of the widely used anticancer agents etoposide, anthracyclines (doxorubicin, daunorubicin), and mitoxantrone. Bacterial type II topoisomerases (gyrase and Topo IV) are the targets of quinolones and aminocoumarin antibiotics. This review focuses on the molecular and biochemical characteristics of topoisomerases and their inhibitors. We also discuss the common mechanism of action of topoisomerase poisons by interfacial inhibition and trapping of topoisomerase cleavage complexes.

The effectiveness and cost are always top factors for policy-makers to decide control measures and most measures had no pre-test before implementation. Due to the COVID-19 pandemic, human activities are largely restricted in many regions in India since mid-March of 2020, and it is a progressing experiment to testify effectiveness of restricted emissions. In this study, concentrations of six criteria pollutants, PM 10 , PM 2.5 , CO, NO 2 , ozone and SO 2 during March 16th to April 14th from 2017 to 2020 in 22 cities covering different regions of India were analysed. Overall, around 43, 31, 10, and 18% decreases in PM 2.5 , PM 10 , CO, and NO 2 in India were observed during lockdown period compared to previous years. While, there were 17% increase in O 3 and negligible changes in SO 2 . The air quality index (AQI) reduced by 44, 33, 29, 15 and 32% in north, south, east, central and western India, respectively. Correlation between cities especially in northern and eastern regions improved in 2020 compared to previous years, indicating more significant regional transport than previous years. The mean excessive risks of PM reduced by~52% nationwide due to restricted activities in lockdown period. To eliminate the effects of possible favourable meteorology, the WRF-AERMOD model system was also applied in Delhi-NCR with actual meteorology during the lockdown period and an un-favourable event in early November of 2019 and results show that predicted PM 2.5 could increase by only 33% in unfavourable meteorology. This study gives confidence to the regulatory bodies that even during unfavourable meteorology, a significant improvement in air quality could be expected if strict execution of air quality control plans is implemented.

SUMMARY In this study, we show that evolutionarily conserved chromosome loop anchors bound by CTCF and cohesin are vulnerable to DNA double strand breaks (DSBs) mediated by topoisomerase 2B (TOP2B). Polymorphisms in the genome that redistribute CTCF/cohesin occupancy rewire DNA cleavage sites to novel loop anchors. While transcription- and replication-coupled genomic rearrangements have been well documented, we demonstrate that DSBs formed at loop anchors are largely transcription-, replication-, and cell type- independent. DSBs are continuously formed throughout interphase, are enriched on both sides of strong topological domain borders, and frequently occur at breakpoint clusters commonly translocated in cancer. Thus, loop anchors serve as fragile sites that generate DSBs and chromosomal rearrangements.

The Visual Object Tracking challenge 2015, VOT2015, aims at comparing short-term single-object visual trackers that do not apply pre-learned models of object appearance. Results of 62 trackers are presented. The number of tested trackers makes VOT 2015 the largest benchmark on shortterm tracking to date. For each participating tracker, a short description is provided in the appendix. Features of the VOT2015 challenge that go beyond its VOT2014 predecessor are: (i) a new VOT2015 dataset twice as large as in VOT2014 with full annotation of targets by rotated bounding boxes and per-frame attribute, (ii) extensions of the VOT2014 evaluation methodology by introduction of a new performance measure. The dataset, the evaluation kit as well as the results are publicly available at the challenge website 1 .

Topoisomerase I (Top1) is an abundant and essential enzyme. Top1 is the selective target of camptothecins, which are effective anticancer agents. Top1-DNA cleavage complexes can also be trapped by various endogenous and exogenous DNA lesions including mismatches, abasic sites and carcinogenic adducts. Tyrosyl-DNA phosphodiesterase (Tdp1) is one of the repair enzymes for Top1-DNA covalent complexes. Tdp1 forms a multiprotein complex that includes poly(ADP) ribose polymerase (PARP). PARP-deficient cells are hypersensitive to camptothecins and functionally deficient for Tdp1. We will review recent developments in several pathways involved in the repair of Top1 cleavage complexes and the role of Chk1 and Chk2 checkpoint kinases in the cellular responses to Top1 inhibitors. The genes conferring camptothecin hypersensitivity are compiled for humans, budding yeast and fission yeast. A. Introduction: Mammalian Topoisomerase Families, Top1 Functions and Catalytic MechanismsSeven topoisomerase genes are encoded in the human nuclear genome [1]. The enzymes (abbreviated Topo or Top) have been numbered in the order of their discovery except for the most recent enzyme, mitochondrial topoisomerase I (Top1mt) [2,3]. Vertebrate cells contain two Top1 (Top1 for the nuclear genome and Top1mt for the mitochondrial genome), two Top2 (Top2α and β) and two Top3 (Top3α and β). The seventh topoisomerase is Spo11, whose expression is restricted to germ cells. Top3α forms heterodimers with BLM (the gene product deficient in Bloom syndrome) and is functionally related to the resolution of post-replicative hemicatenanes and recombination intermediates [4,5]. Top1 proteins belong to the family of the tyrosine recombinases (which includes λ-integrase, Flip and Cre recombinases), and Top2 is related to bacterial gyrase and Topo IV, which are the targets of quinolone antibiotics.Topoisomerases and tyrosine recombinases nick and religate DNA by forming a covalent enzyme-DNA intermediate between an enzyme catalytic tyrosine residue and the end of the broken DNA (Fig. 1). These covalent intermediates are generally referred to as "cleavage (or cleavable) complexes" (Fig. 2). Topoisomerases have also been classified in two groups depending whether they cleave and religate one strand (type I) or both strands (type II) of the DNA duplex. Type I enzymes include Top1 (nuclear), Top1mt, Top3α and β and type II enzymes include Top2α and β and Spo11.Top1 is essential in vertebrates and flies but not in yeast. Knocking out the TOP1 gene results in early embryonic lethality in mouse [6] and fly [7]. By contrast, yeast survives in the absence *To whom reprint requests should be addressed, Bldg. 37, Rm. 5068, NIH, Bethesda, MD 20892-4255 [8]. Top1 is expressed constitutively throughout the cell cycle [9] and is concentrated in the nucleolus [10,11]. Its main function is to relieve both positive and negative DNA supercoiling generated by transcription and replication, and possibly DNA repair and chromatin remodeling [1,[12][13][14]. The mechanistic sim...

Replication protein A (RPA) is a DNA single‐strand binding protein essential for DNA replication, recombination and repair. In human cells treated with the topoisomerase inhibitors camptothecin or etoposide (VP‐16), we find that RPA2, the middle‐sized subunit of RPA, becomes rapidly phosphorylated. This response appears to be due to DNA‐dependent protein kinase (DNA‐PK) and to be independent of p53 or the ataxia telangiectasia mutated (ATM) protein. RPA2 phosphorylation in response to camptothecin required ongoing DNA replication. Camptothecin itself partially inhibited DNA synthesis, and this inhibition followed the same kinetics as DNA‐PK activation and RPA2 phosphorylation. DNA‐PK activation and RPA2 phosphorylation were prevented by the cell‐cycle checkpoint abrogator 7‐hydroxystaurosporine (UCN‐01), which markedly potentiates camptothecin cytotoxicity. The DNA‐PK catalytic subunit (DNA‐PKcs) was found to bind RPA which was replaced by the Ku autoantigen upon camptothecin treatment. DNA‐PKcs interacted directly with RPA1 in vitro. We propose that the encounter of a replication fork with a topoisomerase–DNA cleavage complex could lead to a juxtaposition of replication fork‐associated RPA and DNA double‐strand end‐associated DNA‐PK, leading to RPA2 phosphorylation which may signal the presence of DNA damage to an S‐phase checkpoint mechanism. Keywords: camptothecin/DNA damage/DNA‐dependent protein kinase/RPA2 phosphorylation

SUMMARY We report a mechanism through which the transcription machinery directly controls topoisomerase 1 (TOP1) activity to adjust DNA topology throughout the transcription cycle. By comparing TOP1 occupancy using ChIP-Seq, versus TOP1 activity using TOP1-Seq, a method reported here to map catalytically engaged TOP1, TOP1 bound at promoters was discovered to become fully active only after pause-release. This transition coupled the phosphorylation of the carboxyl-terminal-domain (CTD) of RNA polymerase II (RNAPII) with stimulation of TOP1 above its basal rate, enhancing its processivity. TOP1 stimulation is strongly dependent on the kinase activity of BRD4, a protein that phosphorylates Ser2-CTD and regulates RNAPII pause-release. Thus the coordinated action of BRD4 and TOP1 overcame the torsional stress opposing transcription as RNAPII commenced elongation, but preserved negative supercoiling that assists promoter melting at start sites. This nexus between transcription and DNA topology promises to elicit new strategies to intercept pathological gene expression.