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Conductive hydrogels have attracted extensive interest owing to its potential in soft robotics, electronic skin, and human monitoring. However, insufficient mechanical properties, lower adhesivity, and unsatisfactory conductivity seriously hinder potential applications in this emerging field. Herein, a highly elastic conductive hydrogel with a combination of favorable mechanical properties, self-adhesiveness, and excellent electrical performance was achieved by the synergistic effect of aminated lignin (AL), polydopamine (PDA), polyacrylamide (PAM) chains, and biomass carbon aerogel (C-SPF). In detail, AL was applied to induce slow oxidative polymerization of DA for preparing the sticky hydrogel containing PDA. Then, C-SPF carbon aerogel was used as a matrix to construct a dual-network structured composite hydrogel by combining with the hydrogels derived from PDA, AL, and PAM. The as-prepared conductive hydrogel displayed excellent mechanical performance, strong adhesive strength, and repeatable adhesivity. The prepared hydrogel-based pressure sensor possessed fast response (0.6 s loading and 0.8 s unloading stress time), high response (maximum RCR = 1.8 × 10

MoO2 is a promising anode material for lithium-ion batteries, however, the lithiation of bulk MoO2 is usually limited to addition-type reaction at room temperature, and the conversion reaction is hindered because of the sluggish kinetics. Herein, a nanocomposite of MoO2 embedded in nitrogen-doped carbon (MoO2/NC) is synthesized through the in situ thermolysis of an organic molybdenum complex MoO2(acac)(phen) (acac = acetylacetone, phen = 1,10-Phenanthroline). Owing to the fact that [MoO2]2+ can be strongly chelated by phen, the molybdenum source in the MoO2(acac)(phen) precursor is highly dispersed, leading to the formation of ultra-small MoO2 nanoparticles in the nanocomposite, which can facilitate the conversion reaction. Moreover, the NC matrix can guarantee a high electrical conductivity and effectively accommodate the volume changes triggered by the conversion reaction. Consequently, the MoO2/NC nanocomposite exhibits outstanding electrochemical properties, including large reversible capacity of 950 mA h g−1 at 0.1 A g−1, high-rate capability of 605 mA h g−1 at 2 A g−1, and excellent cycling stability over 500 cycles as an anode material for lithium-ion batteries.

To systematically explore the critical contributions of both molecular weights and crystallization temperature and chain length and molar ratios to the formation of stereocomplexes (SCs), our group quantitatively prepared a wide MW range of symmetric and asymmetric poly(lactic acid) (PLA) racemic blends, which contains L-MW PLLA with

Shaddock peel, a crop by-product mainly composed of cellulose, hemicellulose, lignin, and pectin, was developed as a flexible sensitive material for detecting environmental external pressure. Firstly, a natural carbon framework (C-SPF) with high conductivity was prepared using hydrothermal treatment followed by carbonization. Then, the PDMS elastomer was coated on the C-SPF instead of dense filling to convert the brittle C-SPF into elastic porous materials (M-SPF). Benefiting from the large deformation space of the porous framework and the stable interactions between PDMS and C-SPF, M-SPF exhibited ultrahigh coercibility (up to 99.0% strain) and high elasticity (99.4% height retention for 10 000 cycles at 50.0% strain). The M-SPF-based pressure sensor also exhibited a quick response (loading and unloading times were 20 ms and 30 ms), high sensitivity (63.4 kPa−1), wide working range (from 0 to 800 kPa), and stable stress-electric current response (10 000 cycles). These advantages open a door to a variety of applications, such as flexible wearable devices, which demonstrated human physiological signal monitoring. The low cost, simple design and portable use of piezoresistive sensors highlight the potential application of the crop by-product shaddock peel as a high-value material.

Background Few reliable methods to simulate and evaluate the intersegmental plane have been reported. We introduce intersegmental plane simulation based on the bronchus-vein-artery triad in three-dimensionally reconstructed images from patients who underwent segmentectomy for early lung cancer. Methods We collected clinical data of consecutive patients with early-stage lung cancer who underwent three-dimensional imaging-guided single-port thoracoscopic segmentectomy at Department No. 1 of Thoracic Surgery at Fujian Medical University Fujian Union Hospital from January 2019 to July 2019. Patients were divided into two groups according to the application of intersegmental plane simulation and nodule analysis: the intersegmental plane group and the non-intersegmental plane group. General clinical characteristics, operation status, and postoperative recovery were compared between groups. The three-dimensional reconstruction results in the intersegmental plane group were analyzed and summarized. Results A total of 120 patients were included (61 in the intersegmental plane group and 59 in the non-intersegmental plane group). There were no significant differences between the two groups in general characteristics (all P>0.05). All target lesions were resected in both groups. There were no significant differences between groups in operation characteristics or postoperative recovery, with the exception of the duration of chest drainage and the rate of gross margin insufficiency. There were five cases of gross margin insufficiency in the non-intersegmental plane group. With three-dimensional imaging reconstruction, a total of 131 intersegmental veins could be used to evaluate the simulated intersegmental plane in 61 patients, with an average of 2.1±0.5 veins per patient. Two patients (3.3%) had one vein that could be used to evaluate the intersegmental plane, 50 patients (82.3%) had two, seven patients (11.3%) had three, and two patients (3.3%) had four. The total number of intersegmental veins located on the simulated intersegmental plane was 124 (94.7%), with an average of 2.0±0.6 veins per patient. The accuracy of intersegmental plane simulation was 91.8% (56/61). Conclusions The bronchus-vein-artery triad in intersegmental plane simulation can assist surgeons in preoperative planning and can facilitate complete resection of early lung cancer with sufficient surgical margins.

Chromatin-associated RNA (caRNA) has been proposed as a type of epigenomic modifier. Here, we test whether environmental stress can induce cellular dysfunction through modulating RNA-chromatin interactions. We induce endothelial cell (EC) dysfunction with high glucose and TNFα (H + T), that mimic the common stress in diabetes mellitus. We characterize the H + T-induced changes in gene expression by single cell (sc)RNA-seq, DNA interactions by Hi-C, and RNA-chromatin interactions by iMARGI. H + T induce inter-chromosomal RNA-chromatin interactions, particularly among the super enhancers. To test the causal relationship between H + T-induced RNA-chromatin interactions and the expression of EC dysfunction-related genes, we suppress the LINC00607 RNA. This suppression attenuates the expression of SERPINE1, a critical pro-inflammatory and pro-fibrotic gene. Furthermore, the changes of the co-expression gene network between diabetic and healthy donor-derived ECs corroborate the H + T-induced RNA-chromatin interactions. Taken together, caRNA-mediated dysregulation of gene expression modulates EC dysfunction, a crucial mechanism underlying numerous diseases., Global interaction of chromatin-associated RNAs and DNA can be identified in situ. Here the authors report the genome-wide increase of interchromosomal RNA-DNA interactions and demonstrate the importance of such RNA-DNA contacts exemplified by LINC00607 RNA and SERPINE1 gene’s super enhancer in dysfunctional endothelial cell models.

RNA–chromatin interactions represent an important aspect of the transcriptional regulation of genes and transposable elements. However, analyses of chromatin-associated RNAs (caRNAs) are often limited to one caRNA at a time. Here, we describe the iMARGI (in situ mapping of RNA–genome interactome) technique, which is used to discover caRNAs and reveal their respective genomic interaction loci. iMARGI starts with in situ crosslinking and genome fragmentation, followed by converting each proximal RNA–DNA pair into an RNA–linker–DNA chimeric sequence. These chimeric sequences are subsequently converted into a sequencing library suitable for paired-end sequencing. A standardized bioinformatic software package, iMARGI-Docker, is provided to decode the paired-end sequencing data into caRNA–DNA interactions. Compared to its predecessor MARGI (mapping RNA–genome interactions), the number of input cells for iMARGI is 3–5 million (a 100-fold reduction), experimental time is reduced, and clear checkpoints have been established. It takes a few hours a day and a total of 8 d to complete the construction of an iMARGI sequencing library and 1 d to carry out data processing with iMARGI-Docker. iMARGI (in situ mapping of RNA–genome interactome) is a proximity ligation method for global profiling of chromatin-associated RNAs. A linker sequence bridges DNA and RNA in physical proximity, permitting sequencing library preparation and mapping of DNA–RNA contacts.

The aim of this paper is to study the periodic traveling wave solutions in a nonautonomous reaction-diffusion susceptible-infected-removed epidemic model with general nonlinear incidence and time-periodic environment. The basic reproduction number [Formula: see text] and the critical wave speed c* are defined. By the fixed-point theorem and upper–lower solutions, the sufficient conditions for the existence of traveling waves satisfying some asymptotic boundary conditions are deduced, and the nonexistence of periodic traveling waves is also obtained. Numerical simulations are carried out to support the theoretical results.

In this paper, for a class of nonlocal dispersal SIR epidemic models with nonlinear incidence, we study the existence of traveling waves connecting the disease-free equilibrium with endemic equilibrium. We obtain that the existence of traveling waves depends on the minimal wave speed $c^{*}$ and basic reproduction number $\mathcal{R}_{0}$ . That is, if $\mathcal{R}_{0}>1$ and $c> c^{*}$ then the model has a traveling wave connecting the disease-free equilibrium with endemic equilibrium. Otherwise, if $\mathcal{R}_{0}>1$ and $0< c< c^{*}$ , then there does not exist the traveling wave connecting the disease-free equilibrium with endemic equilibrium. The numerical simulations verify the theoretical results. Our results improve and generalize some known results.

Chromatin-associated RNA (caRNA) is a vital component of the interphase nucleus; yet its distribution and role in the three-dimensional (3D) genome organization and function remain poorly understood. Here, we map caRNA’s spatial distribution on the 3D genome in human embryonic stem cells, fibroblasts, and myelogenous leukemia cells. We find that the relative abundance of trans-acting caRNA reflects the functional nuclear compartmentalization of the 3D genome, and the caRNA’s sequence features are predictive of its spatial localization. We observe extensive caRNA-genome interactions that span several hundred kilobases to several megabases. These caRNA domains correlate with chromatin loops and enhancer-promoter interactions. We report a tradeoff of caRNA’s promotive and suppressive roles to chromatin interactions. As a result, caRNA promotes chromatin interactions outside the anchors of chromatin loops, whereas caRNA exhibits an overall suppressive impact to chromatin interactions between loop anchors. Furthermore, caRNA suppresses chromatin loops’ number and strengths genome-wide, and this suppression depends on electric charge-mediated RNA interactions. These results reveal caRNA’s multifaced role in regulating 3D chromatin organization and highlight caRNA’s ability to modulate chromatin looping.

Porcine reproductive and respiratory syndrome virus (PRRSV) is economically important and characterized by its extensive variation. The codon usage patterns and their influence on viral evolution and host adaptation among different PRRSV strains remain largely unknown. Here, the codon usage of ORF5 genes from lineages 1, 3, 5, and 8, and MLV strains of type 2 PRRSV in China was analyzed. A compositional property analysis of ORF5 genes revealed that nucleotide C is most frequently used at the third position of codons, accompanied by rich GC3s. The effective number of codon (ENC) and codon pair bias (CPB) values indicate that all ORF5 genes have low codon bias and the differences in CPB scores among four lineages are almost not significant. When compared with host codon usage patterns, lineage 1 strains show higher CAI and SiD values, with a high similarity to pig, which might relate to its predominant epidemic propensity in the field. The CAI, RCDI, and SiD values of ORF5 genes from different passages of MLV JXA1R indicate no relation between attenuation and CPB or codon adaptation decrease during serial passage on non-host cells. These findings provide a novel way of understanding the PRRSV’s evolution, related to viral survival, host adaptation, and virulence.

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BACKGROUND The aim of this study was to construct a nomogram to predict the prognosis of patients with gastrointestinal stromal tumor (GIST). MATERIAL AND METHODS We enrolled 4086 GIST patients listed in the SEER database from 1998 to 2015. They were separated to 2 groups: an experimental group (n=2862) and a verification group (n=1224). A nomogram was constructed by using statistically significant prognostic factors. RESULTS A nomogram that included age, sex, marital status, tumor location, grade, SEER stage, tumor size, and surgical management was developed. It can be used to predict overall survival (OS), while adding AJCC 7th TNM stage can predict cancer-specific survival (CSS). The C-index used to forecast OS and CSS nomograms was 0.778 (95% CI, 0.76-0.79) and 0.818 (95% CI, 0.80-0.84), respectively. CONCLUSIONS The nomogram can effectively predict 3- and 5-year CSS in patients with GIST, and its use can improve clinical practice.

Magnetic induction field (MIF) of the magnetite particles with five Johnson solid shapes was analyzed using the finite-element method. A new method is proposed to calculate the MIF of irregular magnetite particles by studying their magnetic flux density, and the results show that sphericity is a key factor affecting the MIF of a regular-shaped particle. Moreover, the calculation value of the MIF using particle volume radius ( $r$ ) is more accurate with the higher sphericity. In addition, the relative position is another important factor affecting the accuracy of MIF calculation. The further the distance from the particle center, the more accurate is the MIF. More specifically, when the distance is $4r$ , the average value of the relative difference drops to less than 5.0% with the sphericity of 0.91, 0.92, and 0.93, respectively. Therefore, we suggest that it is feasible to use a sphere MIF instead of an irregular particle MIF to simulate the interaction and motion of massive magnetite particles.

Human T-cell leukemia virus type 1 (HTLV-1) is the first retrovirus that has conclusively been shown to cause human diseases. In HIV-1, specific interactions between the nucleocapsid (NC) domain of the Gag protein and genomic RNA (gRNA) mediate gRNA dimerization and selective packaging; however, the mechanism for gRNA packaging in HTLV-1, a deltaretrovirus, is unclear. In other deltaretroviruses, the matrix (MA) and NC domains of Gag are both involved in gRNA packaging, but MA binds nucleic acids with higher affinity and has more robust chaperone activity, suggesting that this domain may play a primary role. Here, we show that the MA domain of HTLV-1, but not the NC domain, binds short hairpin RNAs derived from the putative gRNA packaging signal. RNA probing of the HTLV-1 5′ leader and cross-linking studies revealed that the primer-binding site and a region within the putative packaging signal form stable hairpins that interact with MA. In addition to a previously identified palindromic dimerization initiation site (DIS), we identified a new DIS in HTLV-1 gRNA and found that both palindromic sequences bind specifically the NC domain. Surprisingly, a mutant partially defective in dimer formation in vitro exhibited a significant increase in RNA packaging into HTLV-1–like particles, suggesting that efficient RNA dimerization may not be strictly required for RNA packaging in HTLV-1. Moreover, the lifecycle of HTLV-1 and other deltaretroviruses may be characterized by NC and MA functions that are distinct from those of the corresponding HIV-1 proteins, but together provide the functions required for viral replication.

The accurate detection of cancer-associated venous thromboembolism (VTE) can avoid unnecessary diagnostic imaging or laboratory tests.We sought to determine clinical and cancer-related risk factors of VTE that can be used as predictors for oncology patients presenting to the emergency department (ED) with suspected VTE.We retrospectively analyzed all consecutive patients who presented with suspicion of VTE to The University of Texas MD Anderson Cancer Center ED between January 1, 2009, and January 1, 2013. Logistic regression models were used to identify risk factors that were associated with VTE. The ability of these factors to predict VTE was externally validated using a second cohort of patients who presented to King Hussein Cancer Center ED between January 1, 2009, and January 1, 2016.Cancer-related covariates associated with the occurrence of VTE were high-risk cancer type (odds ratio [OR] 3.64 [95% confidence interval {CI} 2.37-5.60], p 0.001), presentation within 6 months of the cancer diagnosis (OR 1.92 [95% CI 1.62-2.28], p 0.001), active cancer (OR 1.35 [95% CI 1.10-1.65], p = 0.003), advanced stage (OR 1.40 [95% CI 1.01-1.94], p = 0.044), and the presence of brain metastasis (OR 1.73 [95% CI 1.32-2.27], p 0.001). When combined, these factors along with other clinical factors showed high prediction performance for VTE in the external validation cohort.Cancer risk group, presentation within 6 months of cancer diagnosis, active and advanced cancer, and the presence of brain metastases along with other related clinical factors can be used to predict VTE in patients with cancer presenting to the ED.

Chromatins are pervasively attached by RNAs. Here, we asked whether global RNA-chromatin contacts are altered in a given cell type in a disease context, and whether these alterations impact gene expression and cell function. In endothelial cells (ECs) treated by high-glucose and TNFα, we employed single-cell RNA-sequencing and in situ mapping of RNA-genome interaction (iMARGI) assay to delineate temporal changes in transcriptome and RNA-chromatin interactome. ECs displayed dramatic and heterogeneous changes in single cell transcriptome, accompanied by a dynamic and strong increase in inter-chromosomal RNA-DNA interactions, particularly among super enhancers (SEs). These SEs overlap with genes contributing to inflammatory response and endothelial mesenchymal transition (EndoMT), two key aspects of endothelial dysfunction. Perturbation of a high-glucose and TNFα-activated interaction involving SEs overlapping LINC00607 and SERPINE1 attenuated the pro-inflammatory and pro-EndoMT gene induction and EC dysfunction. Our findings highlight RNA-chromatin contacts as a crucial regulatory feature in biological and disease processes, exemplified by endothelial dysfunction, a major mediator of numerous diseases.

Real-time hand gesture recognition in complex environments has many challenges, such as poor real-time performances and robustness to environmental changes. This paper takes the hand gesture control of the unmanned vehicle as the application background, and focuses on the gesture detection and recognition of video streams based on deep learning in the complex environment. In this paper, we detect the hand in a complex environment by training the ssd_mobilenet model, and initialize the tracking with kalman filter. Then, we detect the hand keypoints by following the architecture of Convolutional Pose Machines (CPMs), in order to obtain the belief maps for all keypoints that are used as the train sets of Convolutional Neural Networks (CNNs). Finally, based on the results obtained by our classification, this paper proposes a method of multi-frame recursion to minimize the influences of redundant frames and error frames. In this paper, eight kinds of gestures for controlling vehicle are identified. The experimental results show that our method can successfully realize real-time hand gesture recognition in the video streams. The recognition accuracy can reach 96.7%, and the average recognition speed reaches 12 fps, which basically meets the real-time requirements and successfully applys to mobile terminals such as TX2 for engineering practice.

RNA-chromatin interactions represent an important aspect of transcriptional regulation of genes and transposable elements. However, analyses of chromatin-associated RNAs (caRNA) are often limited to one caRNA at a time. Here, we describe the iMARGI (in situ Mapping of RNA-Genome Interactome) technique used to discover caRNAs and reveal their respective genomic interaction loci. iMARGI starts with in situ crosslinking and genome fragmentation, followed by converting each proximal RNA-DNA pair into an RNA-linker-DNA chimeric sequence. These chimeric sequences are subsequently converted into a sequencing library suitable for paired-end sequencing. A standardized bioinformatic software package called iMARGI-Dockeris provided to decode the pairedend sequencing data into caRNA-DNA interactions. Compared to its predecessor MARGI, in iMARGI the number of input cells is 3-5 million, which is reduced by 100-fold, experimental time is reduced, clear checkpoints have been established. It takes a few hours a day and a total of 8 days to complete the construction of an iMARGI sequencing library and one day to carry out data processing with iMARGI-Docker.

Chemical and enzymatic probing of RNA secondary structure and RNA/protein interactions provides the basis for understanding the functions of structured RNAs. However, the ability to rapidly perform such experiments using capillary electrophoresis has been hampered by relatively labor-intensive data analysis software. While these computationally robust programs have been shown to calculate residue-specific reactivities to a high degree of accuracy, they often require time-consuming manual intervention and lack the ability to be easily modified by users. To alleviate these issues, RiboCAT (Ribonucleic acid capillary-electrophoresis analysis tool) was developed as a user-friendly, Microsoft Excel–based tool that reduces the need for manual intervention, thereby significantly shortening the time required for data analysis. Features of this tool include (i) the use of an Excel platform, (ii) a method of intercapillary signal alignment using internal size standards, (iii) a peak-sharpening algorithm to more accurately identify peaks, and (iv) an open architecture allowing for simple user intervention. Furthermore, a complementary tool, RiboDOG (RiboCAT data output generator) was designed to facilitate the comparison of multiple data sets, highlighting potential inconsistencies and inaccuracies that may have occurred during analysis. Using these new tools, the secondary structure of the HIV-1 5′ untranslated region (5′UTR) was determined using selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE), matching the results of previous work.

In this paper, a reaction-diffusion SIR epidemic model is proposed. It takes into account the individuals mobility, the time periodicity of the infection rate and recovery rate, and the general nonlinear incidence function, which contains a number of classical incidence functions. In our model, due to the introduction of the general nonlinear incidence function, the boundedness of the infected individuals can not be obtained, so we study the existence and nonexistence of periodic traveling wave solutions of original system with the aid of auxiliary system. The basic reproduction number R 0 and the critical wave speed c * are given. We obtained the existence and uniqueness of periodic traveling waves for each wave speed c > c * using the Schauder’s fixed points theorem when R 0 > 1 . The nonexistence of periodic traveling waves for two cases (i) R 0 > 1 and 0 c c * , (ii) R 0 ≤ 1 and c ≥ 0 are also obtained. These results generalize and improve the existing conclusions. Finally, the numerical experiments support the theoretical results. The differences of traveling wave solution between periodic system and general aperiodic coefficient system are analyzed by numerical simulations.

Background: Microsatellite instability (MSI) is often associated with poor cancer prognosis and is considered a hallmark in certain types of cancer such as Lynch Syndrome. MSI status has been approved by the FDA as a pan-cancer biomarker to stratify patients who exhibit clinical response to immune checkpoint inhibitor therapy. Circulating tumor DNA (ctDNA) is a novel, non-invasive and real-time approach to study various types of cancers including those that have tissue availability limitations. However, overwhelming majority of circulating cell-free DNA (cfDNA) is from healthy tissues, with a low ctDNA fraction. Another complicating factor is the generally elevated sequencing error rate in repeat regions where microsatellites (MS) are observed compared to non-repeat regions. Hence, MSI status inferred from ctDNA tends to be more error prone. Thus, it is important to differentiate signal from noise by error profiling to obtain accurate MSI status. Methodology: Here we present patterns in error rate that we observed in repeat sites and a method that leverages these observations to detect MSI status in ctDNA samples. We used 202 healthy cfDNA samples generated via TruSightTM Oncology 500 ctDNA, a research use assay (Illumina, Inc. San Diego CA), and evaluated more than 112000 repeat sites in an exploratory analysis. UMI collapsed reads were used to generate the read distribution at specific sites; the error rate is the fraction of reads with non-reference repeat counts. Based on this analysis, we developed an algorithm that generates the repeat length distribution for each MS site using duplex reads and then uses an information theoretic approach to determine the stability status of a specific locus. Final MSI score for a particular tumor sample was defined as the sum of distance between repeat length distribution of MS sites in a cohort of normal samples and the tumor sample. To assess the performance of our method, we applied it to cfDNA samples with known MSI status and titrated MSI-H cell lines with varying tumor fractions to obtain the MSI status. Results: The exploratory analysis revealed that error rates differed by 10 fold based on the read support in duplex sequencing; error rates increased as the repeat unit size of an MS site increased; for MS sites with the same repeat length, the error rate declined with higher repeat shift; the error rate in dinucleotide repeat sites was around 10 fold higher than mono nucleotide sites. We achieved 100% overall agreement in MSI status between 136 matched FFPE and cfDNA samples. For titrated MSI-H samples with low tumor fraction, our method attained 100% sensitivity at 0.625% MSI-H content titration into a microsatellite stable (MSS) background. Conclusion: Our analysis demonstrates that utilizing read characteristics from sequencing data leads to better prediction of MSI status and using this information our algorithm accurately predicts MSI status in cfDNA samples with wide ranging tumor content. Citation Format: Divy S. Kangeyan, Shile Zhang, Sigrid Katz, Brian Crain, Janel Lee, Alex G. Mentzer, Charlene Echegaray, Jennifer Silhavy, Weixin Wu, Tingting Jiang, Chen Zhao, Sven Bilke. Microsatellite instability error correction in cell-free DNA sequencing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 839.

This paper investigates the traveling wave in a nonlocal dispersal susceptible-infected-removed epidemic model with general nonlinear incidence and nonlocal delayed effects. It is shown that the existence and nonexistence of nontrivial traveling waves are fully determined by the basic reproduction number R0 and critical wave speed c*. When R0>1 and c > c*, the existence of traveling waves is obtained by means of an auxiliary system, the methods of upper-lower solutions, Schauder’s fixed point theorem, and some limiting techniques. When R0>1 and 0 < c < c*, the nonexistence of traveling waves is established by the reduction to absurdity and the theory of asymptotic spreading.

Significance It remains formidable to predict what unreported RNA pairs can form new fusion transcripts. By systematic mapping of chromatin-associated RNAs and their respective genomic interaction loci, we obtained genome-wide RNA–DNA interaction maps from two noncancerous cell types. The gene pairs involved in RNA–DNA interactions in these normal cells exhibited strong overlap with those with cancer-derived fusion transcripts. These data suggest an RNA-poise model, where the spatial proximity of one gene’s transcripts and the other gene’s genomic sequence poises for the creation of fusion transcripts. We validated this model with 96 additional lung cancer samples. One of these additional samples exhibited fusion transcripts without a corresponding fusion gene, suggesting that genome recombination is not a required step of the RNA-poise model., Fusion transcripts are used as biomarkers in companion diagnoses. Although more than 15,000 fusion RNAs have been identified from diverse cancer types, few common features have been reported. Here, we compared 16,410 fusion transcripts detected in cancer (from a published cohort of 9,966 tumor samples of 33 cancer types) with genome-wide RNA–DNA interactions mapped in two normal, noncancerous cell types [using iMARGI, an enhanced version of the mapping of RNA–genome interactions (MARGI) assay]. Among the top 10 most significant RNA–DNA interactions in normal cells, 5 colocalized with the gene pairs that formed fusion RNAs in cancer. Furthermore, throughout the genome, the frequency of a gene pair to exhibit RNA–DNA interactions is positively correlated with the probability of this gene pair to present documented fusion transcripts in cancer. To test whether RNA–DNA interactions in normal cells are predictive of fusion RNAs, we analyzed these in a validation cohort of 96 lung cancer samples using RNA sequencing (RNA-seq). Thirty-seven of 42 fusion transcripts in the validation cohort were found to exhibit RNA–DNA interactions in normal cells. Finally, by combining RNA-seq, single-molecule RNA FISH, and DNA FISH, we detected a cancer sample with EML4-ALK fusion RNA without forming the EML4-ALK fusion gene. Collectively, these data suggest an RNA-poise model, where spatial proximity of RNA and DNA could poise for the creation of fusion transcripts.

In situ mapping of RNA-Genome Interactome (iMARGI) is a technique that globally maps native RNA-genome interactions from unperturbed cells. It is an improved version of traditional MARGI published in 2017. Compared to traditional MARGI, this technique performs RNA-DNA proximity ligation in situ inside intact nucleus instead of in solution to reduce random ligation. It also reduces the number of cell input by 100-fold and shortens experimental processing time. In this protocol, cells are crosslinked with formaldehyde. Intact nuclei are collected from fixed cells and permeabilized with SDS. A restriction enzyme AluI is used to digest chromatin into DNA fragments and RNase I is used to fragment RNA. A specially designed biotinylated linker is introduced to ligate to 3´-end of RNA first and then this RNA-ligated linker is ligated to DNA. These ligation steps are controlled by the configuration of the linker and by sequential applications of different end modifications and ligation enzymes. Nuclei are lysed, and successfully ligated products, in the form of RNA-linker-DNA are selected with streptavidin beads, followed by converting the RNA part of chimera into cDNA on beads. cDNA-linker-DNA is circularized and then cut in the middle, producing DNAs with the configuration left.half.Linker-RNA-DNA-right.half.Linker, which are subjected to library amplification and paired-end sequencing.

Fusion transcripts are used as biomarkers in companion diagnoses. Although more than 15,000 fusion RNAs have been identified from diverse cancer types, few common features have been reported. Here, we compared 16,410 fusion transcripts detected in cancer (from a published cohort of 9,966 tumor samples of 33 cancer types) with genome-wide RNA-DNA interactions mapped in two normal, non-cancerous cell types (using iMARGI, an enhanced version of the MARGI [Mapping RNA-Genome Interactions assay]). Among the top 10 most significant RNA-DNA interactions in normal cells, 5 co-localized with the gene pairs that formed fusion RNAs in cancer. Furthermore, throughout the genome, the frequency of a gene pair to exhibit RNA-DNA interactions is positively correlated with the probability of this gene pair to present documented fusion transcripts in cancer. To test whether RNA-DNA interactions in normal cells are predictive of fusion RNAs, we analyzed these in a validation cohort of 96 lung cancer samples using RNA-seq. 37 out of 42 fusion transcripts in the validation cohort were found to exhibit RNA-DNA interactions in normal cells. Finally, by combining RNA-seq, single-molecule RNA FISH, and DNA FISH, we detected a cancer sample with EML4-ALK fusion RNA without forming the EML4-ALK fusion gene. Collectively, these data suggest a novel RNA-poise model, where spatial proximity of RNA and DNA could poise for the creation of fusion transcripts.

The three lowest energy conformations of the title compound have been investigated using quantum chemical calculations and the lowest energy conformer has been observed using pure rotational spectroscopy. The lowest energy conformer possesses C 2 symmetry, a helical CF2 backbone, with the hydrogens nearly eclipsing one another when looking down the long axis of the molecule. The technique of Fourier transform microwave spectroscopy in conjunction with quantum chemical calculations is demonstrated as a complimentary method to X-ray diffraction for structural determinations of small oligomers for which the location of hydrogen atoms may be important.

The loss of open-circuit voltage is a major obstacle for approaching the theoretical value of the power conversion efficiency in hybrid perovskite solar cells. In this study, a feasible and effective strategy for modifying the interface between the perovskite and the mesoporous TiO2 layer is proposed and implemented for the first time using 2-methylimidazole as a coating layer. As a result, the open-circuit voltage in the perovskite solar cells is significantly improved by 80 mV. The electronic impedance spectroscopy and photoluminescence spectroscopy results demonstrate that the modification of 2-methylimidazole as an interfacial insulating layer suppresses the electron transfer back from the anode electrode to the perovskite active layer, thereby inhibiting the recombination of the carriers at the interfaces, which results in an enhancement of the open-circuit voltage in the device. The cell modified with 2-methylimidazole shows increases in the open-circuit voltage from 1.05 to 1.13 V and in the power conversion efficiency from 17.48% to 19.45%. The optimal device with an area of 1 cm2 also exhibits an impressive efficiency of 16.38%.

G-Quadruplexes formed by G-rich DNA are of broad interest due to their involvement in telomere function, gene transcription and recombination. Small ligands that interact strongly with G-quadruplexes have been considered to further influence telomeric function and gene transcription. Because most G-rich sequences are trapped in duplex structures in gene promoters, ligands that can stabilize G-quadruplexes in the presence of their complimentary strands would likely have strong effects on gene transcription. Here, we report a novel simple small molecule (pyridyl carboxamide), consisting of three pyridine rings and four amide bonds. Comparing with some reported G-quadruplex ligands, this molecule not only selectively stabilizes G-quadruplexes rather than duplexes, but also maintains a G-quadruplex structure even if the G-rich region was trapped in long double-stranded DNA (dsDNA). It is widely believed that the dissociation of duplexes is involved in gene transcription and that the formation of the G-quadruplex influences some oncogene expression. Py-Am exhibited strong G-quadruplex-forming ability within a long dsDNA sequence, suggesting it would have potent effects on the G-quadruplex-forming sequences involved in gene transcription.

To determine the efficacy and safety of telbivudine for blocking intrauterine transmission of hepatitis B virus (HBV) in pregnant women with high-load HBV DNA.Women in general good health and pragnant were enrolled for study between the ages of 20 to 40 year-old, with a diagnosis of HBV infection with high-load HBV DNA level (≥1*10(6) IU/ml). According to each participant's willingness, the women were divided into a telbivudine treatment group (82 women) and an untreated control group (75 women). The telbivudine treatment was initiated at gestation week 26 as oral dosing of 600 mg/d and continued until 1 month after the birth.Women in the control group had not gotten any antiviral drug treatment. All of the women delivered by cesarean section, and all of the neonates were administered the standard passive immunization therapy, which consisted of a hepatitis B immunoglobulin (200 IU) injection given within 12 hours of birth and an injection of hepatitis B vaccine (20 µg) at birth and at postnatal month 1 and 6. None of the mother's performed breastfeeding.The telbivudine-treated women showed a significant decrease in HBV DNA levels prior to delivery, as well as significantly decreased prenatal HBV DNA levels (2 logl0). Efficiency of the telbivudine treatment was 100%. Immediately prior to delivery, 16 (19.5%) of the women in the telbivudine treatment group showed negative HBV DNA status, as opposed to the untreated control group in which no women showed negative status. The telbivudine treatment group had no case of maternal or fetal adverse reaction or of congenital malformation.Use of telbivudine antiviral therapy during late pregnancy in women with high-load HBV DNA can significantly reduce level of HBV DNA in maternal peripheral blood, block HBV intrauterine transmission, and provide good short-term efficacy, with good tolerability and safety.

Adrenocortical carcinoma is a rare malignancy with poor prognosis and limited response to chemotherapy. Hepatocyte growth factor (HGF) and its receptor cMET augment cancer growth and resistance to chemotherapy, but their role in adrenocortical carcinoma has not been examined. In this study, we investigated the association between HGF/cMET expression and cancer hallmarks of adrenocortical carcinoma. Transcriptomic and immunohistochemical analyses indicated that increased HGF/cMET expression in human adrenocortical carcinoma samples was positively associated with cancer-related biologic processes, including proliferation and angiogenesis, and negatively correlated with apoptosis. Accordingly, treatment of adrenocortical carcinoma cells with exogenous HGF resulted in increased cell proliferation in vitro and in vivo while short hairpin RNA–mediated knockdown or pharmacologic inhibition of cMET suppressed cell proliferation and tumor growth. Moreover, exposure of cells to mitotane, cisplatin, or radiation rapidly induced pro-cMET expression and was associated with an enrichment of genes (e.g., CYP450 family) related to therapy resistance, further implicating cMET in the anticancer drug response. Together, these data suggest an important role for HGF/cMET signaling in adrenocortical carcinoma growth and resistance to commonly used treatments. Targeting cMET, alone or in combination with other drugs, could provide a breakthrough in the management of this aggressive cancer. Cancer Res; 75(19); 4131–42. ©2015 AACR.

A toxin producing phytoplankton-zooplankton model with inhibitory exponential substrate and time delay has been formulated and analyzed. Since the liberation of toxic substances by phytoplankton species is not an instantaneous process but is mediated by some time lag required for maturity of the species and the zooplankton mortality due to the toxic phytoplankton bloom occurs after some time laps of the bloom of toxic phytoplankton, we induced a discrete time delay to both of the consume response function and distribution of toxic substance term. Furthermore, based on the fact that the predation rate decreases at large toxic-phytoplankton density, the system is modelled via a Tissiet type functional response. We study the dynamical behaviour and investigate the conditions to guarantee the coexistence of two species. Analytical methods and numerical simulations are used to obtain information about the qualitative behaviour of the models.

Most clinical studies of heparin-induced thrombocytopenia have not included cancer patients who have high risk of thromboembolism, frequent exposure to heparin, and many potential causes of thrombocytopenia other than heparin-induced thrombocytopenia. To estimate the incidence and prevalence of heparin-induced thrombocytopenia in cancer patients, we identified cases based on diagnostic codes, anti-heparin antibody testing, and clinical characteristics (4T score) at a comprehensive cancer center between 1 October 2008 and 31 December 2011. We estimated that the prevalence of heparin-induced thrombocytopenia to be 0.02% among all cancer patients and 0.24% among cancer patients exposed to heparin. The annual incidence of heparin-induced thrombocytopenia was 0.57 cases per 1000 cancer patients exposed to heparin. Of the 40 cancer patients with the International Classification of Diseases (Ninth Revision; ICD-9) code for heparin-induced thrombocytopenia, positive anti-heparin antibody, and 4T score ≥4, 5 (12.5%) died of related thromboembolic or hemorrhagic complications. In a multivariate logistic regression model, male gender was a significant ( p = 0.035) factor, and non-hematological malignancy was a significant ( p = 0.017) factor associated with anti-heparin antibody positivity. Future studies may further examine the risk factors associated with heparin-induced thrombocytopenia in larger cohorts.

Genome-wide association studies have identified polymorphisms at chromosome 9q22.23 as a new thyroid cancer (TC) susceptibility locus in populations of European descent. Since then, the relationship between three common variations (rs965513, rs1867277, and rs71369530) of FOXE1 and TC has been reported in various ethnic groups; however, the results have been inconclusive. To derive a more precise estimation of the relationship as well as to quantify the between-study heterogeneity and potential bias, a meta-analysis including 120,258 individuals from 16 studies was performed. An overall random-effect per-allele odds ratio (OR) of 1.74 (95 % confidence interval (95 % CI), 1.62–1.86, P