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This paper introduces a novel anchor design to support anchor-based face detection for superior scale-invariant performance, especially on tiny faces. To achieve this, we explicitly address the problem that anchor-based detectors drop performance drastically on faces with tiny sizes, e.g. less than 16x16 pixels. In this paper, we investigate why this is the case. We discover that current anchor design cannot guarantee high overlaps between tiny faces and anchor boxes, which increases the difficulty of training. The new Expected Max Overlapping (EMO) score is proposed which can theoretically explain the low overlapping issue and inspire several effective strategies of new anchor design leading to higher face overlaps, including anchor stride reduction with new network architectures, extra shifted anchors, and stochastic face shifting. Comprehensive experiments show that our proposed method significantly outperforms the baseline anchor-based detector, while consistently achieving state-of-the-art results on challenging face detection datasets with competitive runtime speed., Comment: CVPR 2018

SUMMARY The histone variant H2A.Z is a hallmark of nucleosomes flanking promoters of protein-coding genes and is often found in nucleosomes that carry lysine 56-acetylated histone H3 (H3-K56Ac), a mark that promotes replication-independent nucleosome turnover. Here, we find that H3-K56Ac promotes RNA polymerase II occupancy at many protein-coding and noncoding loci, yet neither H3-K56Ac nor H2A.Z has a significant impact on steady-state mRNA levels in yeast. Instead, broad effects of H3-K56Ac or H2A.Z on RNA levels are revealed only in the absence of the nuclear RNA exosome. H2A.Z is also necessary for the expression of divergent, promoter-proximal non-coding RNAs (ncRNAs) in mouse embryonic stem cells. Finally, we show that H2A.Z functions with H3-K56Ac to facilitate formation of chromosome interaction domains (CIDs). Our study suggests that H2A.Z and H3-K56Ac work in concert with the RNA exosome to control mRNA and ncRNA expression, perhaps in part by regulating higher-order chromatin structures., Graphical Abstract

The paper describes the manufacturing process and the characterization of the tensile mechanical properties of treated and untreated palm dates long technical fibres. The fibres extracted from Fruit Bunch Branch of Palm Date (FBBPD) have been subjected to alkaline treatment with different NaOH concentrations at room temperature. The experimental results show that the chemical technical fibre treatments provide an increase of the mechanical properties (tensile strength and Young’s modulus) under quasi-static tensile loading. A specific treatment leads a threefold increase of the failure stress. An analysis of stress at failure has been performed over a population of 630 samples using Weibull statistics with two and three-parameters, together with a one-way analysis of variance (ANOVA). FBBPD technical fibres show stiffness and strength performance comparable to the ones of agave Americana L fibres, and higher failure at strength than okra fibres.

Widely transcribed compact genomes must cope with the major challenge of frequent overlapping or concurrent transcription events. Efficient and timely transcription termination is crucial to control pervasive transcription and prevent transcriptional interference. In yeast, transcription termination of RNA polymerase II (RNAPII) occurs via two possible pathways that both require recognition of termination signals on nascent RNA by specific factors. We describe here an additional mechanism of transcription termination for RNAPII and demonstrate its biological significance. We show that the transcriptional activator Reb1p bound to DNA is a roadblock for RNAPII, which pauses and is ubiquitinated, thus triggering termination. Reb1p-dependent termination generates a class of cryptic transcripts that are degraded in the nucleus by the exosome. We also observed transcriptional interference between neighboring genes in the absence of Reb1p. This work demonstrates the importance of roadblock termination for controlling pervasive transcription and preventing transcription through gene regulatory regions.

The paper describes from a statistical perspective the diameter-dependence tensile strength and Young’s modulus in 40 sisal fibres samples. The fibres tensile properties depend significantly upon their diameter, which has been determined using optical and SEM microscope techniques. Further characterisation of the sisal fibres has been carried out using FT-IR and DSC techniques. The fibres’ ultimate tensile strength and Young’s modulus have been evaluated using four different estimation methods from two and three-parameter Weibull distribution statistics. We show the significant sensitivity of the Weibull predictions versus the number of fibres samples used in the distributions, with the Weibull modulus m σ obtained from our results being 10% smaller compared to what is reported in open literature. The scatter of the mechanical properties of the sisal fibres shown in this work is also compared to analogous distributions present in other works.

Facial alignment involves finding a set of landmark points on an image with a known semantic meaning. However, this semantic meaning of landmark points is often lost in 2D approaches where landmarks are either moved to visible boundaries or ignored as the pose of the face changes. In order to extract consistent alignment points across large poses, the 3D structure of the face must be considered in the alignment step. However, extracting a 3D structure from a single 2D image usually requires alignment in the first place. We present our novel approach to simultaneously extract the 3D shape of the face and the semantically consistent 2D alignment through a 3D Spatial Transformer Network (3DSTN) to model both the camera projection matrix and the warping parameters of a 3D model. By utilizing a generic 3D model and a Thin Plate Spline (TPS) warping function, we are able to generate subject specific 3D shapes without the need for a large 3D shape basis. In addition, our proposed network can be trained in an end-to-end framework on entirely synthetic data from the 300W-LP dataset. Unlike other 3D methods, our approach only requires one pass through the network resulting in a faster than real-time alignment. Evaluations of our model on the Annotated Facial Landmarks in the Wild (AFLW) and AFLW2000-3D datasets show our method achieves state-of-the-art performance over other 3D approaches to alignment., Comment: International Conference on Computer Vision (ICCV) 2017

In this chapter we will discuss a one-step dissolution and fibre spinning method for chitin using ionic liquid 1-Ethyl-3-Methylimidazolium Acetate (EMImAc) as an environmentally benign solvent. A temperature-sensitive behaviour of chitin/EMImAc solution was observed during the fibre extrusion process. The regenerated chitin fibres were characterised through Fourier Transform Infrared Spectroscopy (FTIR), tensile testing, Scanning Electron Microscopy (SEM) and Wide Angle X-ray Diffraction (WAXD). Both molecular alignment and mechanical properties of chitin fibre increased as the draw ratio increased, confirmed by tensile testing results and the full width at half maximum (FWHM) of WAXD azimuthal scans. The regenerated chitin fibres with well controlled length, and good mechanical properties reported in this work could be potentially useful to explore the second most widely available polymer in nature for engineering and biomedical applications.

Robust hand detection and classification is one of the most crucial pre-processing steps to support human computer interaction, driver behavior monitoring, virtual reality, etc. This problem, however, is very challenging due to numerous variations of hand images in real-world scenarios. This work presents a novel approach named Multiple Scale Region-based Fully Convolutional Networks (MSRFCN) to robustly detect and classify human hand regions under various challenging conditions, e.g. occlusions, illumination, low-resolutions. In this approach, the whole image is passed through the proposed fully convolutional network to compute score maps. Those score maps with their position-sensitive properties can help to efficiently address a dilemma between translation-invariance in classification and detection. The method is evaluated on the challenging hand databases, i.e. the Vision for Intelligent Vehicles and Applications (VIVA) Challenge, Oxford hand dataset and compared against various recent hand detection methods. The experimental results show that our proposed MS-FRCN approach consistently achieves the state-of-the-art hand detection results, i.e. Average Precision (AP) / Average Recall (AR) of 95.1% / 94.5% at level 1 and 86.0% / 83.4% at level 2, on the VIVA challenge. In addition, the proposed method achieves the state-of-the-art results for left/right hand and driver/passenger classification tasks on the VIVA database with a significant improvement on AP/AR of ~7% and ~13% for both classification tasks, respectively. The hand detection performance of MS-RFCN reaches to 75.1% of AP and 77.8% of AR on Oxford database.

A regulatory Momordica charantia protein system was constructed allosterically by in vitro protein phosphorylation, in an attempt to evaluate antimycological pluripotency against dose-dependent susceptibilities in C. albicans. Fungal strain lineages susceptible to ketoconazole, econazole, miconazole, 5-flucytosine, nystatin and amphotericin B were prepared in laboratory, followed by identification via antifungal susceptibility testing. Protein phosphorylation was carried out in reactions with 5′-adenylic, guanidylic, cytidylic and uridylic acids and cyclic adenosine triphosphate, through catalysis of cyclin-dependent kinase 1, protein kinase A and protein kinase C respectively. Biochemical analysis of enzymatic reactions indicated the apparent Michaelis-Menten constants and maximal velocity values of 16.57–91.97 mM and 55.56–208.33 μM·min− 1, together with an approximate 1:1 reactant stoichiometric ratio. Three major protein phosphorylation sites were theoretically predicted at Thr255, Thr102 and Thr24 by a KinasePhos tool. Additionally, circular dichroism spectroscopy demonstrated that upon phosphorylation, protein folding structures were decreased in random coil, β6-sheet and α1-helix partial regions. McFarland equivalence standard testing yielded the concentration-dependent inhibition patterns, while fungus was grown in Sabouraud's dextrose agar. The minimal inhibitory concentrations of 0.16–0.51 μM (at 50% response) were obtained for free protein and phosphorylated counterparts. With respect to the 3-cycling susceptibility testing regimen, individuals of total protein forms were administrated in-turn at 0.14 μM/cycle. Relative inhibition ratios were retained to 66.13–81.04% of initial ones regarding the ketoconazole-susceptible C. albicans growth. An inhibitory protein system, with an advantage of decreasing antifungal susceptibilities to diverse antimycotics, was proposed because of regulatory pluripotency whereas little contribution to susceptibility in itself.

Splicing contributes to gene regulation and protein diversity, while abnormal splicing underlies both hereditary diseases and cancers. Various mutations that disrupt splicing factors, exonic or intronic splicing enhancers or silencers, as well as splice sites, could be responsible for abnormal splicing. Characterization of abnormal splicing events is not only helpful for understanding the molecular processes linking mutations to disease phenotypes, but also provides promising targets for targeted therapies. In addition, CRISPR/Cas9 editing could be benefited once more attention is given to potential abnormal splicing outcomes other than off-target effects at the DNA level. Although large-scale multiplexed genome editing has been demonstrated in yeast, and has also been attempted for particular exons or genes in other eukaryotic cells to achieve saturation, in practice it is much more difficult to measure splicing consequences with genome-wide saturation editing in human cells. Instead, massive somatic mutations accumulated in cancer cohorts provide invaluable opportunities to study somatic mutation-associated splicing events. Abnormal splicing is not necessarily limited to single genes. Transcript fusion is a special form of abnormal splicing that connects two or more genes due to splicing on a transcriptional level (rather than chromosomal translocations such as BCR-ABL in chronic myeloid leukemia). It could arise from conventional splicing on read-through transcripts when the two genes are next to each other and on the same strand, or from trans-splicing when two genes are on different chromosomes, strands or far away - a few cases had been reported. However, it was found that these fusions not only occurred in tumors but also in normal tissues; there was limited investigation regarding how the fusion could happen, whether it be due to mutations or not, and what the downstream perturbations were. Here, in an effort to characterize somatic mutation-associated abnormal splicing (especially in its simplest form, exon skipping events), we identified over one hundred such events in various tumors, including those in MET, PTEN and TP53. Surprisingly, we detected a recurrent, but previously undescribed, tumor-specific transcript fusion event between the cyclin-dependent kinase inhibitor CDKN1A and the RAS oncogene family gene RAB44. By creating genome-edited cell lines, we demonstrate a causal relationship between splice-site mutations in CDKN1A and the fusion to the RAB44 transcript. We further provide evidence that the fusion arises from a readthrough transcript that escapes exosome-mediated degradation when the splice-site mutation occurred, and we show that the presence of the fusion transcript correlates with TP53 inactivation and CDK activation. The strong tissue specificity of RAB44 and the relatively high prevalence of this transcript fusion in multiple types of cancers warrants further study which could inform subclassifications of these cancers and the development of targeted therapies.

Robust face detection in the wild is one of the ultimate components to support various facial related problems, i.e., unconstrained face recognition, facial periocular recognition, facial landmarking and pose estimation, facial expression recognition, 3D facial model construction, etc. Although the face detection problem has been intensely studied for decades with various commercial applications, it still meets problems in some real-world scenarios due to numerous challenges, e.g., heavy facial occlusions, extremely low resolutions, strong illumination, exceptional pose variations, image or video compression artifacts, etc. In this paper, we present a face detection approach named Contextual Multi-Scale Region-based Convolution Neural Network (CMS-RCNN) to robustly solve the problems mentioned above. Similar to the region-based CNNs, our proposed network consists of the region proposal component and the region-of-interest (RoI) detection component. However, far apart of that network, there are two main contributions in our proposed network that play a significant role to achieve the state-of-the-art performance in face detection. First, the multi-scale information is grouped both in region proposal and RoI detection to deal with tiny face regions. Second, our proposed network allows explicit body contextual reasoning in the network inspired from the intuition of human vision system. The proposed approach is benchmarked on two recent challenging face detection databases, i.e., the WIDER FACE Dataset which contains high degree of variability, as well as the Face Detection Dataset and Benchmark (FDDB). The experimental results show that our proposed approach trained on WIDER FACE Dataset outperforms strong baselines on WIDER FACE Dataset by a large margin, and consistently achieves competitive results on FDDB against the recent state-of-the-art face detection methods.

For a unicellular, non-motile organism like Saccharomyces cerevisiae, carbon sources act both as nutrients and as signaling molecules and consequently affect various fitness parameters including growth. It is therefore advantageous for yeast strains to adapt their growth to carbon source variation. The ability of a given genotype to manifest different phenotypes in varying environments is known as phenotypic plasticity. To identify quantitative trait loci (QTL) that drive plasticity in growth, two growth parameters (growth rate and biomass) were measured in a published dataset from meiotic recombinants of two genetically divergent yeast strains grown in different carbon sources. To identify QTL contributing to plasticity across pairs of environments, gene–environment interaction mapping was performed, which identified several QTL that have a differential effect across environments, some of which act antagonistically across pairs of environments. Multi-QTL analysis identified loci interacting with previously known growth affecting QTL as well as novel two-QTL interactions that affect growth. A QTL that had no significant independent effect was found to alter growth rate and biomass for several carbon sources through two-QTL interactions. Our study demonstrates that environment-specific epistatic interactions contribute to the growth plasticity in yeast. We propose that a targeted scan for epistatic interactions, such as the one described here, can help unravel mechanisms regulating phenotypic plasticity.

The problems of hand detection have been widely addressed in many areas, e.g. human computer interaction environment, driver behaviors monitoring, etc. However, the detection accuracy in recent hand detection systems are still far away from the demands in practice due to a number of challenges, e.g. hand variations, highly occlusions, low-resolution and strong lighting conditions. This paper presents the Multiple Scale Faster Region-based Convolutional Neural Network (MS-FRCNN) to handle the problems of hand detection in given digital images collected under challenging conditions. Our proposed method introduces a multiple scale deep feature extraction approach in order to handle the challenging factors to provide a robust hand detection algorithm. The method is evaluated on the challenging hand database, i.e. the Vision for Intelligent Vehicles and Applications (VIVA) Challenge, and compared against various recent hand detection methods. Our proposed method achieves the state-of-the-art results with 20% of the detection accuracy higher than the second best one in the VIVA challenge.

Overexpression of heat shock protein 27(HSP27) in gastric cancer is correlated with poor clinical prognosis. Melatonin, an endogenous hormone, shows promise in gastric cancer therapy. However, there is limited study on the biological activity of HSP27 in response to melatonin treatment. In this study, we show an anti-proliferative action of melatonin on human gastric cancer cell lines BGC-823 and MGC-803. Biochemically, the inhibitory effect of melatonin is accompanied by the upregulation of HSP27 phosphorylation level. Transfection of gastric cancer cells with HSP27-specific siRNA effectively reduces HSP27 phosphorylation and potentiated melatonin-induced inhibitory effect on cell proliferation. The reduction of cyclin D1 in melatonin-treated cells is also aggravated by HSP27 depletion. Moreover, melatonin stimulation increases p38 phosphorylation. Pretreatment with p38 inhibitor SB203580 not only remarkably suppresses melatonin-induced HSP27 phosphorylation, but also augment the inhibitory effect of melatonin on cyclin D1 expression as well as cell proliferation. Taken together, our study indicates the protective pathway of p38/HSP27 against melatonin-induced inhibitory effect on gastric cancer cell proliferation, suggesting that combined with p38/HSP27 pathway inhibitor, the therapeutic efficacy of melatonin on gastric cancer may be improved.

In this paper, we utilized dimethylhydrazine (DMH)-induced colorectal cancer (CC) model rats to explore the effects of casein glycomacropeptide (CGMP) on colorectal cancer. Rats with CC were orally administrated with 10, 50, or 100 mg/kg bw d CGMP, or the same volume of phosphate-buffered saline for 15 weeks. The total numbers of aberrant crypt foci (ACF) and crypts per focus in colon were scored using a light microscope at low magnification after the colon was stained with methylene blue solutions. The methylation level of DNA extracted from colon was detected using methylation-specific PCR. The expression of p16 and mucin 2 (MUC2) proteins were measured by immunohistochemistry. The results showed that although ACF were found in rats treated with CGMP, their number was significantly decreased compared to that of model rats. In addition, methylation and expression levels of p16 and MUC2 were also inhibited by CGMP, which were more obvious in rats treated with 50 mg/kg bw d CGMP. In conclusion, CGMP has potential application as nutritional therapy for preventing colorectal cancer.

This study investigates the anti-apoptotic function of casein glycomacropeptide (CGMP) against oxazolone-induced ulcerative colitis (UC) in a mouse model. We tested the effect of CGMP on the morphological and histological damages of colon in UC mice and examined the mRNA levels of FasL, TNF-α, p53, p65 and TGF-β1 in colon tissues. Our results show that CGMP treatments alleviated oxazolone-induced body weight loss as well as morphological and histological damages. In addition, CGMP attenuated FasL and p65 mRNA level in colon tissue, while having no significant effect on the expression of TNF-α and p53. This suggests that therapeutically, the anti-apoptotic effect of CGMP is mediated through the FasR/FasL pathway and the anti-inflammation affects the NF-κB/p65 pathway. This study furthers our understanding of UC and provides sound support for the development of milk-derived therapeutics.

Multifocus image fusion has emerged as a major topic in computer vision and image processing community since the optical lenses for most widely used imaging devices, such as auto-focus cameras, have a limiting focus range. Only objects at one particular depth will be truly in focus while out-of-focus objects will become blurry. The ability to create a single image where all scene areas appear sharp is desired not only in digital photography but also in various vision-related applications. We propose a novel image fusion scheme for combining two or multiple images with different focus points to generate an all-in-focus image. We formulate the problem of fusing multifocus images as choosing the most significant features from a sparse matrix obtained by a newly developed robust principal component analysis (RPCA) decomposition method to form a composite feature space. The local sparse features that represent salient information of the input images (i.e. sharp regions) are integrated to construct the resulting fused image. Experimental results have demonstrated that it is consistently superior to the other existing state-of-the-art fusion methods in terms of visual and quantitative evaluations.

H3K36 methylation by Set2 targets Rpd3S histone deacetylase to transcribed regions of mRNA genes, repressing internal cryptic promoters and slowing elongation. Here we explore the function of this pathway by analysing transcription in yeast undergoing a series of carbon source shifts. Approximately 80 mRNA genes show increased induction upon SET2 deletion. A majority of these promoters have overlapping lncRNA transcription that targets H3K36me3 and deacetylation by Rpd3S to the mRNA promoter. We previously reported a similar mechanism for H3K4me2-mediated repression via recruitment of the Set3C histone deacetylase. Here we show that the distance between an mRNA and overlapping lncRNA promoter determines whether Set2–Rpd3S or Set3C represses. This analysis also reveals many previously unreported cryptic ncRNAs induced by specific carbon sources, showing that cryptic promoters can be environmentally regulated. Therefore, in addition to repression of cryptic transcription and modulation of elongation, H3K36 methylation maintains optimal expression dynamics of many mRNAs and ncRNAs., H3K36 methylation by Set2 targets Rpd3S histone deacetylase to transcribed mRNA genes, repressing internal cryptic promoters and modulating elongation. Here, the authors provide evidence that the Set2-Rpd3S pathway also regulates dynamic expression of mRNAs and lncRNAs.

Robust face detection is one of the most important pre-processing steps to support facial expression analysis, facial landmarking, face recognition, pose estimation, building of 3D facial models, etc. Although this topic has been intensely studied for decades, it is still challenging due to numerous variants of face images in real-world scenarios. In this paper, we present a novel approach named Multiple Scale Faster Region-based Convolutional Neural Network (MS-FRCNN) to robustly detect human facial regions from images collected under various challenging conditions, e.g. large occlusions, extremely low resolutions, facial expressions, strong illumination variations, etc. The proposed approach is benchmarked on two challenging face detection databases, i.e. the Wider Face database and the Face Detection Dataset and Benchmark (FDDB), and compared against recent other face detection methods, e.g. Two-stage CNN, Multi-scale Cascade CNN, Faceness, Aggregate Chanel Features, HeadHunter, Multi-view Face Detection, Cascade CNN, etc. The experimental results show that our proposed approach consistently achieves highly competitive results with the state-of-the-art performance against other recent face detection methods., Accepted by BTAS 2016. arXiv admin note: substantial text overlap with arXiv:1606.05413

Weakly supervised methods have recently become one of the most popular machine learning methods since they are able to be used on large-scale datasets without the critical requirement of richly annotated data. In this paper, we present a novel, self-taught, discriminative facial feature analysis approach in the weakly supervised framework. Our method can find regions which are discriminative across classes yet consistent within a class and can solve many face related problems. The proposed method first trains a deep face model with high discriminative capability to extract facial features. The hypercolumn features are then used to give pixel level representation for better classification performance along with discriminative region detection. In addition, calibration approaches are proposed to enable the system to deal with multi-class and mixed-class problems. The system is also able to detect multiple discriminative regions from one image. Our uniform method is able to achieve competitive results in various face analysis applications, such as occlusion detection, face recognition, gender classification, twins verification and facial attractiveness analysis.

In this paper, we present an advanced deep learning based approach to automatically determine whether a driver is using a cell-phone as well as detect if his/her hands are on the steering wheel (i.e. counting the number of hands on the wheel). To robustly detect small objects such as hands, we propose Multiple Scale Faster-RCNN (MSFRCNN) approach that uses a standard Region Proposal Network (RPN) generation and incorporates feature maps from shallower convolution feature maps, i.e. conv3 and conv4, for ROI pooling. In our driver distraction detection framework, we first make use of the proposed MS-FRCNN to detect individual objects, namely, a hand, a cell-phone, and a steering wheel. Then, the geometric information is extracted to determine if a cell-phone is being used or how many hands are on the wheel. The proposed approach is demonstrated and evaluated on the Vision for Intelligent Vehicles and Applications (VIVA) Challenge database and the challenging Strategic Highway Research Program (SHRP-2) face view videos that was acquired to monitor drivers under naturalistic driving conditions. The experimental results show that our method archives better performance than Faster R-CNN on both hands on wheel detection and cell-phone usage detection while remaining at similar testing cost. Compare to the state-of-the-art cell-phone usage detection, our approach obtains higher accuracy, is less time consuming and is independent to landmarking. The groundtruth database will be publicly available.

Robust face detection and facial segmentation are crucial pre-processing steps to support facial recognition, expression analysis, pose estimation, building of 3D facial models, etc. In previous approaches, the process of face detection and facial segmentation are usually implemented as sequential, mostly separated modules. In these methods, face detection algorithms are usually first implemented so that facial regions can be located in given images. Segmentation algorithms are then carried out to find the facial boundaries and other facial features, such as the eyebrows, eyes, nose, mouth, etc. However, both of these tasks are challenging due to numerous variations of face images in the wild, e.g. facial expressions, illumination variations, occlusions, resolution, etc. In this chapter, we present a novel approach to detect human faces and segment facial features from given images simultaneously. Our proposed approach performs accurate facial feature segmentation and demonstrates its effectiveness on images from two challenging face databases, i.e. Multiple Biometric Grand Challenge (MBGC) and Labeled Faces in the Wild (LFW).

Yeast Npl3 is a highly abundant, nuclear-cytoplasmic shuttling, RNA-binding protein, related to metazoan SR proteins. Reported functions of Npl3 include transcription elongation, splicing and RNA 3’ end processing. We used UV crosslinking and analysis of cDNA (CRAC) to map precise RNA binding sites, and strand-specific tiling arrays to look at the effects of loss of Npl3 on all transcripts across the genome. We found that Npl3 binds diverse RNA species, both coding and non-coding, at sites indicative of roles in both early pre-mRNA processing and 3’ end formation. Tiling arrays and RNAPII mapping data revealed 3’ extended RNAPII-transcribed RNAs in the absence of Npl3, suggesting that defects in pre-mRNA packaging events result in termination readthrough. Transcription readthrough was widespread and frequently resulted in down-regulation of neighboring genes. We conclude that the absence of Npl3 results in widespread 3' extension of transcripts with pervasive effects on gene expression., Author Summary Npl3 is a yeast mRNA binding protein with many reported functions in RNA processing. We wanted to identify direct targets and therefore combined analyses of the transcriptome-wide effects of the loss of Npl3 on gene expression with UV crosslinking and bioinformatics to identify RNA-binding sites for Npl3. We found that Npl3 binds diverse sites on large numbers of transcripts, and that the loss of Npl3 results in transcriptional readthrough on many genes. One effect of this transcription readthrough is that the expression of numerous flanking genes is strongly down regulated. This underlines the importance of faithful termination for the correct regulation of gene expression. The effects of the loss of Npl3 are seen on both mRNAs and non-protein coding RNAs. These have distinct but overlapping termination mechanisms, with both classes requiring Npl3 for correct RNA packaging.

A high-sensitivity mechano-luminescent sensor was fabricated on the basis of piezoelectric/electroluminescent composites. The working principle of this mechano-luminescent sensor was elucidated by analyzing the relationship between the piezoelectric-induced charges and the electroluminescent effects. When a stress is applied on the piezoelectric layer, electrical charges will be induced at both the top and bottom sides of the piezoelectric layer. The induced electrical charges will lead to a light output from the electroluminescent layer, thus producing a mechano-luminescence effect. By increasing the vibration strength or frequency applied, the mechano-luminescence output can be obviously enhanced. Mechano-luminescence sensors have potential in smart stress-to-light devices, such as foot-stress-distribution-diagnosis systems and dynamic-load-monitors for bridge hanging cables.

Quality control of Chinese herbal tea remains a challenge due to our poor knowledge of their complex chemical profile. This study aims to investigate the chemical composition of one of the best-selling and famous brand of beverage in China, Wanglaoji Herbal Tea (WLJHT), via a full component quantitative analysis. In this paper, a total of thirty-two representative constituents were identified or tentatively characterized using ultra-high performance liquid chromatography coupled with quadrupole tandem time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Moreover, the quantitative analyses of fourteen constituents were performed by high performance liquid chromatography with a triple quadruple tandem mass spectrometry (HPLC-MS/MS) method and saccharide compositions of WLJHT were also quantitatively determined by high performance liquid chromatography (HPLC) with evaporative light scattering detector (ELSD) on a Hilic column, separately. Using multiple chromatographic techniques presented a good precision, sensitivity, repeatability and stability, and was successfully applied to analyze 16 batches of WLJHT samples. Therefore, it would be a reliable and useful approach for the quality control of WLJHT.

1057Background: Approximately eighty percent of breast cancer patients are estrogen receptor alpha (ER-α) positive. Although women initially respond well to endocrine therapies, resistance often em...

12101Background: Tumor mutation burden (TMB) is new clinical marker that predicts responses to immunotherapy, but the molecular basis of TMB is unknown. Understand the association between genomic l...

12108Background: Acquired EGFR mutations (C797, L792, G796) co-occurring with T790M were reported to lead the resistance to osimertinib. It was reported that for advanced NSCLC patients, exon 19 de...

There is a need to develop high-performance cellulose fibers as sustainable replacements for glass fibers, and as alternative precursors for carbon filaments. Traditional fiber spinning uses toxic solvents, but in this study, by using dimethyl sulfoxide (DMSO) as a co-solvent with an ionic liquid, a novel high-performance fiber with exceptional mechanical properties is produced. This involves a one-step dissolution, and cost-effective route to convert high concentrations of low molecular weight microcrystalline cellulose into high stiffness cellulose fibers. As the cellulose concentration increases from 20.8 to 23.6 wt%, strong optically anisotropic patterns appear for cellulose solutions, and the clearing temperature (T c) increases from ≈100 °C to above 105 °C. Highly aligned, stiff cellulose fibers are dry-jet wet spun from 20.8 and 23.6 wt% cellulose/1-ethyl-3-methylimidazolium diethyl phosphate/DMSO solutions, with a Young's modulus of up to ≈41 GPa. The significant alignment of cellulose chains along the fiber axis is confirmed by scanning electron microscopy, wide-angle X-ray diffraction, and powder X-ray diffraction. This process presents a new route to convert high concentrations of low molecular weight cellulose into high stiffness fibers, while significantly reducing the processing time and cost.

A liquid chromatography–tandem mass spectrometry (LC–MS–MS) method was developed for the simultaneous determination of paracetamol, pseudoephedrine and chlorpheniramine in human plasma. Diphenhydramine was used as the internal standard. Analytes were extracted from alkalized human plasma by liquid–liquid extraction (LLE) using ethyl acetate. After electrospray ionization positive ion fragments were detected in the selected reaction monitoring (SRM) mode with a triple quadrupole tandem mass spectrometer. The method was linear in the concentration range of 20.0–10000.0 ng mL−1 for paracetamol, 1.0–500.0 ng mL−1 for pseudoephedrine and 0.1–50.0 ng mL−1 for chlorpheniramine. The intra- and inter-day precisions were below 14.5% and the bias was between −7.3 and +2.8% for all analytes. The validated LC–MS–MS method was applied to a pharmacokinetic study in which each healthy Chinese volunteer received a tablet containing 300 mg benorylate, 30 mg pseudoephedrine hydrochloride and 2 mg chlorpheniramine maleate. This is the first assay method described for the simultaneous determination of paracetamol, pseudoephedrine and chlorpheniramine in human plasma samples.

A sensitive high-performance liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed and validated for the determination of clemastine in human plasma. After having been extracted from plasma samples by ethyl acetate, clemastine and internal standard, diphenhydramine, were separated on a C(18) column. Detection was performed on Thermo Finnigan TSQ Quantum triple quadrupole mass spectrometer by selected reaction monitoring (SRM) mode via electrospray ionization (ESI) source. The method was linear in the concentration range of 5.0-1000.0 pg/ml for clemastine. The intra- and inter-day precisions were within 13.4% and the deviations were between -1.1% and 5.6%. The fully validated LC/ESI-MS/MS method has been successfully applied to the preliminary pharmacokinetic study in healthy male Chinese volunteers.

Two new abietane diterpenoids, Gerardianin B (1) and Gerardianin C (2), one new lignan glycoside, Gerardianin D (3) and one new lupane-type triterpenoid, Gerardianol A (4), together with seven known abietane diterpenoids were isolated from the aerial parts of Rabdosia lophanthoides var. gerardianus. Their structures were determined by 1D and 2D NMR spectroscopic data. The cytotoxic activities of the nine diterpenoids were evaluated on human cancer cell lines. Compounds 6-11 exhibited significant cytotoxic activities against HepG2 cell lines with IC50 from 4.68 to 9.43μM and HCF-8 cell lines with IC50 from 9.12 to 13.53μM.

Kasugamycin, produced by Streptomyces kasugaensis and Streptomyces microaureus, is an important amino-glycoside family antibiotic and widely used for veterinary and agricultural applications. In the left flanking region of the previously reported kasugamycin gene cluster, four additional genes (two-component system kasW and kasX, MerR-family kasV, and isoprenylcysteine carboxyl methyltransferase kasS) were identified both in the low-yielding S. kasugaensis BCRC12349 and high-yielding S. microaureus XM301. Deletion of regulatory gene kasT abolished kasugamycin production, and its overexpression in BCRC12349 resulted in an increased titer by 186 %. Deletion of kasW, kasX, kasV, and kasS improved kasugamycin production by 12, 19, 194, and 22 %, respectively. qRT-PCR analysis demonstrated that the transcription of kas genes was significantly increased in all the four mutants. Similar gene inactivation was performed in the high-yielding strain S. microaureus XM301. As expected, the deletion of kasW/X resulted in a 58 % increase of the yield from 6 to 9.5 g/L. However, the deletion of kasV and over-expression of kasT had no obvious effect, and the disruption of kasS surprisingly decreased kasugamycin production. In addition, trans-complementation of the kasS mutant with a TTA codon-mutated kasS increased the kasugamycin yield by 20 %. A much higher transcription of kas genes was detected in the high-yielding XM301 than in the low-yielding BCRC12349, which may partially account for the discrepancy of gene inactivation effects between them. Our work not only generated engineered strains with improved kasugamycin yield, but also pointed out that different strategies on manipulating regulatory-related genes should be considered for low-yielding or high-yielding strains.

Shuanghuanglian injection (SHLI) has been widely used for administration with cephalosporin in China for long time. The objective of this study was to evaluate the pharmacological properties and biochemical changes of cefepime combined with SHLI. The SD rats included were received either an intravenous (iv. 4 mL/kg) dose of normal saline, or intravenous (iv. 0.74, 0.37, 0.185 g/kg, respectively) doses of SHLI once daily for 7 days. After last administration, cefepime (0.41 g/kg) was intravenous injected to the animals. The serum and urine samples were acquired and stored at 4 °C. They were used for quantitative determination of urea nitrogen (BUN), creatinine (CRE), urine protein, alkaline phosphatase (ALP) and N-acetyl-B-d-glucosaminidase (NAG). At different time points, the levels of cefepime in rat plasma were estimated for pharmacokinetic measures by HPLC. Aspirin was selected as internal standard (IS). The results showed that there were positive effects by increasing the total amount of CRE, BUN, NAG and urine protein (p 0.01 or0.05) and decreasing the levels of ALP (especially the high dose group of SHLI with cefepime) (p 0.01). Besides, the pharmacokinetic results indicated that cefepime was distributed as non-compartment model after intravenous administration. Compared with the corresponding values for the compounds given alone, the area under the blood drug concentration time curve (AUC0-t and AUC0-∞) was better increased in middle- and high-dose groups (pall 0.01), the mean residence time (MRT) of cefepime was larger (pall 0.01) and the total clearance (CL) was lower at different levels. The results mean that the duration and concentration of cefepime could be prolonged and the clearance reduced while in combination with SHLI. Furthermore, the cefepime in the three tested doses caused changes of renal tubular epithelial cells while the severity of changes mainly dependent on the specific doses. In conclusion, the results above-mentioned suggest a possible contribution of drug combination in the nephrotoxicity and biochemical alterations especially at high doses. Further, monitoring measures for the renal functions are warranted to evaluate during the combination of these two drugs.

Centralized integration of wind power causes challenges to the conventional dispatching method. This paper develops a three-level active power control system for a wind farm cluster(WFC) based on hierarchical principle, which includes the dispatching center, WFC main control station and wind farm execution stations. Besides the design scheme of the control interfaces between the main station and the execution stations, an active power control strategy towards the main station is also put forward, making it possible to determine active power control mode and fast calculate active power instruction values online. The proposed control strategy turns out to be effective in enhancing wind power penetration and reducing resource waste.

Background:Callicarpae Caulis et Folium (CCF) is a traditional Chinese medicine usually used for hemostasis in clinics. In this study, a novel LC–MS/MS method was developed and validated for the simultaneous quantification of three phenylethanoid glycosides in rat plasma (verbascoside, forsythoside B and poliumoside), which are the major bioactive compounds of CCF; MS was operated in negative mode. Results: This method was linear between 5.2 and 1010 ng/ml for poliumoside, 7.0 and 420 ng/ml for forsythoside B and 2.60 and 260.0 ng/ml for verbascoside. The MS/MS ion transitions monitored were m/z 769.4→160.5, m/z 755.3→593.3, m/z 623.1→160.5 and m/z 179.0→133.6 for poliumoside, forsythoside B, verbascoside and caffeic acid (IS), respectively. Linearity, accuracy, precision and extraction recovery of three analytes were all satisfactory. Conclusion: The method developed was sensitive, specific and rapid. It has been successfully applied in a PK study of three phenylethanoid glycosides after a single oral administration of CCF extract to rats.

The existing active power control methods which take single wind farm as a unit and regulate it independently cannot satisfy the complex control demand of large-scale wind power base. Therefore, wind farms are unitized as wind farm cluster (WFC) as a whole in this paper. An active power economic dispatch model of WFC considering short-term wind power prediction is proposed, which aims at maximizing the active power output of WFC while minimizing tie line power loss. As this dispatch model is a complicated integer programming problem with nonlinear constraints, it is transferred to the integer linear programming (ILP) problem and solved by commercial MILP solvers under the general algebraic modeling system (GAMS). Simulation results of an actual WFC in Northeast China proved the method to be effective and feasible.

Multifocus image fusion is an important research topic in the computer vision and image processing field. The optical lenses that are commonly used by imaging devices, such as auto-focus cameras, have a limiting focus range. Thus, only objects within the range of distances from the devices can be captured and recorded sharply while out-of-range objects become blur. In this paper, we present a novel image fusion scheme for combining two or multiple images with different focus points to generate an all-in-focus image. We formulate the problem of fusing multifocus images as choosing most significant features from a sparse matrix produced by a newly developed robust principal component analysis (RPCA) decomposition method to form a composite feature space. Thus, the salient features presented in sharp regions can be captured and integrated into a single representation. The sparse matrix is first divided into small blocks, and standard deviation is then calculated on each block as a selection criterion. To reduce blocking artifacts, a sliding window technique is utilized to smooth the transitions between blocks. The proposed fusion scheme has been demonstrated to successfully improve fusion quality in terms of visual and quantitative evaluations. The method is also able to effectively handle both grayscale and color images.

With the advent of big data and cloud computing era, scheduling and executing large-scale computing tasks effectively and allocating resources to tasks reasonably are becoming a quite challenging problem. And there is theoretical significance to research on efficient scheduling algorithm to improve resource utilization and task execution efficiency. We present a scheduling algorithm based on resource attribute selection RAS by sending a set of test tasks to an execution node to determine its resource attributes before a task is scheduled; and then selecting the optimal node to execute a task according to its resource requirements and the fitness between the resource node and the task, which also uses history task data if exists. We 1 give a formal definition of the resource attributes and 2 compute the fitness of the resource nodes and 3 store the information of node selection for next round. We integrate our algorithm into the Gearman scheduling framework, and through comparison with three other scheduling frameworks, we find out there is significant improvement in resource selection and resource utilization using RAS. The throughput of the RAS with work-stealing, WS is at least 30% higher than the other frameworks and the resource utilization of RAS WS reaches 0.94. The algorithm can make a good model for practical large scale application scheduling.

To study the conjugation reaction characteristics of caffeic acid micromolecule cistanoside F and bovine serum albumin.The interaction between bovine serum albumin (BSA) and cistanoside F that was separated from Callicarpa plant for the first time and abbreviated CF was detected by fluorescence (FS), UV-vis absorbance and circular dichroism (CD) under simulative physiological conditions.CF-BSA's static apparent binding constant (K(a)), number of binding sites (n), efficiency of energy transfer (E), spatial distance (r), thermodynamic parameters deltaG, deltaH and deltaS and changes in alpha-helical structure content in BSA before and after CF's effect were calculated to define the binding site of CF in BSA and analyze the impact of several common metal ions on the interaction of CF and BSA.Ground state compounds formed by CF and BSA could cause intrinsic fluorescence quenching. Their binding constant K(a) of cistanoside F with BSA was 4.36 x 10(4) L x mol at 25 degrees C, the number of binding site n was 1, and the spatial distance r was 3.09 nm. The results indicated that the hydrogen bond played a major role in cistanoside F-BSA association. The displacement experiments confirmed that cistanoside F can bind to site I of BSA. In addition, the binding constant of cistanoside F with BSA was enhanced after the addition of some common metal ions Mg2+, Fe3+, Cu2+ and Zn2+. The intrinsic fluorescence of BSA was quenched by cistanoside F via forming cistanoside F-BSA complex and non-radiation energy transfer. CD spectra showed that the binding of cistanoside F with BSA induced conformational changes in BSA.

Existing active power control methods mostly take one wind farm as unit and regulate its active power independently, which cannot effectively satisfy comprehensive active power control demands of large-scale wind power base. Therefore, this paper proposes an active power coordination control strategy for wind farm cluster (WFC). The corresponding control system is divided into four levels — wind energy management level, collector station regulation level, wind farm regulation level, wind turbine execution level — by using hierarchical principle. At the same time, in order to adapt to the complex and changeable operation situation of power system, five operational modes are proposed, which are Normal Operation mode, Peak-load Regulation mode, Frequency Regulation mode, Emergency Reduce mode and Communication Fault mode. The simulation results of a typical wind farm cluster of Jiuquan 10GW wind power base show that the coordination control strategy can not only guarantee the security and stability of power system but also make full use of wind energy to some extent.

To study the chemical constituents of Picrasma quassioides. The chemical constituents were isolated and purified by chromatographic methods over Sephadex LH-20 and silica gel column, and structurally elucidated by spectral analysis, including UV, IR, MS, 1H-NMR, 13C-NMR. Fourteen compounds were obtained and identified as trifolirhizin(1), maackiain(2), 3', 7-dihydroxy-4'-methoxylisoflavone(3), umbelliferone(4), emodin(5), nigakilactone F(6), picrasin B(7),picraqualide B (8),4-methoxy-5-hydroxycanthin-6-one(9), 4,5-dimethoxycanthin-6-one (10),5-methoxycanthin-6-one(11), 11-hydroxycanthin-6-one(12) , 1-methoxycarbonyl-beta-carboline(13), 1-hydroxymethyl-beta-carboline(14). Compounds 1-5 are reported from the first time for the genus Pricrasma.

Escherichia coli strains are used in secondary metabolism research for DNA cloning and transferring plasmids by intergeneric conjugation. Non-restricting strains are desirable for DNA cloning and non-methylating strains are beneficial for transferring DNA to methyl-restricting hosts, like Streptomyces coelicolor. We have constructed a non-methylating E. coli strain, JTU007, by deleting the DNA methylation genes dcm and dam from the widely used non-restricting cloning host DH10B. JTU007 was tested as donor for the conjugative transfer of a plasmid containing the 39 kb actinorhodin biosynthesis gene cluster to S. lividans and S. coelicolor. The Dcm− Dam− strain JTU007 transferred DNA into S. coelicolor A(3)2 derivatives at high frequency. To demonstrate the usefulness of E. coli JTU007 for gene cloning, we constructed a comprehensive S. toxytricini genomic cosmid library, and transferred it using high-throughput conjugation to the methyl-restricting S. coelicolor. One of the cosmid clones produced a brown pigment, and the clone was revealed to carry a tyrosinase operon. JTU007 is more useful than ET12567 because it does not restrict methylated DNA in primary cloning, and gives higher transformation and cosmid infection frequencies.

Two new triterpene glycosides named ilexpublesnin A (1) and ilexpublesnin B (2) were isolated from the root of Ilex pubescens. Their structures were determined as 3-O-(β- d -xylopyranosyl)-28-O-(β- d -glucopyranosyl)-3β, 19α-dihydroxyurs-23-oxo-12-en-28-oic acid (1) and 28-O-(β- d -xylopyranosyl-(2 → 1)-β- d -glucopyranosyl)-3β, 19α-dihydroxyurs-23-oxo-12-en-28-oic acid (2) on the basis of chemical and spectroscopic methods.

Aims of the study Fatty liver is the most common cause of abnormal liver function tests. We investigated the effect and its underlying mechanism of pomegranate flower (PGF), a traditional antidiabetic medicine, on fatty liver. Materials and methods At the endpoint of treatment of male Zucker diabetic fatty (ZDF) rats with PGF extract (500 mg/kg, p.o . × 6 weeks), liver weight index, hepatic lipid contents (enzymatic colorimetric methods) and droplet accumulation (Oil Red O staining) were determined. Gene profiles (RT-PCR) were analyzed in the liver of ZDF rats and in human liver-derived HepG2 cell line. Results PGF-treated ZDF rats showed reduced ratio of liver weight to tibia length, hepatic triglyceride contents and lipid droplets. These effects were accompanied by enhanced hepatic gene expression of peroxisome proliferator-activated receptor (PPAR)-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase (ACO), and reduced stearoyl-CoA desaturase-1. In contrast, PGF showed minimal effects on expression of genes responsible for synthesis, hydrolysis or uptake of fatty acid and triglycerides. PGF treatment also increased PPAR-alpha and ACO mRNA levels in HepG2 cells. Conclusion Our findings suggest that this Unani medicine ameliorates diabetes and obesity-associated fatty liver, at least in part, by activating hepatic expression of genes responsible for fatty acid oxidation.