68 research outputs found

    Gesture Detection Towards Real-Time Ergonomic Analysis for Intelligent Automation Assistance

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    Manual handling involves transporting of load by hand through lifting or lowering and operators on the manufacturing shop floor are daily faced with constant lifting and lowering operations which leads to Work-Related Musculoskeletal Disorders. The trend in data collection on the Shop floor for ergonomic evaluation during manual handling activities has revealed a gap in gesture detection as gesture triggered data collection could facilitate more accurate ergonomic data capture and analysis. This paper presents an application developed to detect gestures towards triggering real-time human motion data capture on the shop floor for ergonomic evaluations and risk assessment using the Microsoft Kinect. The machine learning technology known as the discrete indicator—precisely the AdaBoost Trigger indicator was employed to train the gestures. Our results show that the Kinect can be trained to detect gestures towards real-time ergonomic analysis and possibly offering intelligent automation assistance during human posture detrimental tasks

    The development and characterization of a 60K SNP chip for chicken

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    <p>Abstract</p> <p>Background</p> <p>In livestock species like the chicken, high throughput single nucleotide polymorphism (SNP) genotyping assays are increasingly being used for whole genome association studies and as a tool in breeding (referred to as genomic selection). To be of value in a wide variety of breeds and populations, the success rate of the SNP genotyping assay, the distribution of the SNP across the genome and the minor allele frequencies (MAF) of the SNPs used are extremely important.</p> <p>Results</p> <p>We describe the design of a moderate density (60k) Illumina SNP BeadChip in chicken consisting of SNPs known to be segregating at high to medium minor allele frequencies (MAF) in the two major types of commercial chicken (broilers and layers). This was achieved by the identification of 352,303 SNPs with moderate to high MAF in 2 broilers and 2 layer lines using Illumina sequencing on reduced representation libraries. To further increase the utility of the chip, we also identified SNPs on sequences currently not covered by the chicken genome assembly (Gallus_gallus-2.1). This was achieved by 454 sequencing of the chicken genome at a depth of 12x and the identification of SNPs on 454-derived contigs not covered by the current chicken genome assembly. In total we added 790 SNPs that mapped to 454-derived contigs as well as 421 SNPs with a position on Chr_random of the current assembly. The SNP chip contains 57,636 SNPs of which 54,293 could be genotyped and were shown to be segregating in chicken populations. Our SNP identification procedure appeared to be highly reliable and the overall validation rate of the SNPs on the chip was 94%. We were able to map 328 SNPs derived from the 454 sequence contigs on the chicken genome. The majority of these SNPs map to chromosomes that are already represented in genome build Gallus_gallus-2.1.0. Twenty-eight SNPs were used to construct two new linkage groups most likely representing two micro-chromosomes not covered by the current genome assembly.</p> <p>Conclusions</p> <p>The high success rate of the SNPs on the Illumina chicken 60K Beadchip emphasizes the power of Next generation sequence (NGS) technology for the SNP identification and selection step. The identification of SNPs from sequence contigs derived from NGS sequencing resulted in improved coverage of the chicken genome and the construction of two new linkage groups most likely representing two chicken micro-chromosomes.</p

    Exome-wide somatic mutation characterization of small bowel adenocarcinoma

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    Small bowel adenocarcinoma (SBA) is an aggressive disease with limited treatment options. Despite previous studies, its molecular genetic background has remained somewhat elusive. To comprehensively characterize the mutational landscape of this tumor type, and to identify possible targets of treatment, we conducted the first large exome sequencing study on a population-based set of SBA samples from all three small bowel segments. Archival tissue from 106 primary tumors with appropriate clinical information were available for exome sequencing from a patient series consisting of a majority of confirmed SBA cases diagnosed in Finland between the years 2003-2011. Paired-end exome sequencing was performed using Illumina HiSeq 4000, and OncodriveFML was used to identify driver genes from the exome data. We also defined frequently affected cancer signalling pathways and performed the first extensive allelic imbalance (Al) analysis in SBA. Exome data analysis revealed significantly mutated genes previously linked to SBA (TP53, KRAS, APC, SMAD4, and BRAF), recently reported potential driver genes (SOX9, ATM, and ARID2), as well as novel candidate driver genes, such as ACVR2A, ACVR1B, BRCA2, and SMARCA4. We also identified clear mutation hotspot patterns in ERBB2 and BRAF. No BRAF V600E mutations were observed. Additionally, we present a comprehensive mutation signature analysis of SBA, highlighting established signatures 1A, 6, and 17, as well as U2 which is a previously unvalidated signature. Finally, comparison of the three small bowel segments revealed differences in tumor characteristics. This comprehensive work unveils the mutational landscape and most frequently affected genes and pathways in SBA, providing potential therapeutic targets, and novel and more thorough insights into the genetic background of this tumor type.Peer reviewe

    Clear Genetic Distinctiveness between Human- and Pig-Derived Trichuris Based on Analyses of Mitochondrial Datasets

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    The whipworm, Trichuris trichiura, causes trichuriasis in ∼600 million people worldwide, mainly in developing countries. Whipworms also infect other animal hosts, including pigs (T. suis), dogs (T. vulpis) and non-human primates, and cause disease in these hosts, which is similar to trichuriasis of humans. Although Trichuris species are considered to be host specific, there has been considerable controversy, over the years, as to whether T. trichiura and T. suis are the same or distinct species. Here, we characterised the entire mitochondrial genomes of human-derived Trichuris and pig-derived Trichuris, compared them and then tested the hypothesis that the parasites from these two host species are genetically distinct in a phylogenetic analysis of the sequence data. Taken together, the findings support the proposal that T. trichiura and T. suis are separate species, consistent with previous data for nuclear ribosomal DNA. Using molecular analytical tools, employing genetic markers defined herein, future work should conduct large-scale studies to establish whether T. trichiura is found in pigs and T. suis in humans in endemic regions

    Binding Modes of Peptidomimetics Designed to Inhibit STAT3

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    STAT3 is a transcription factor that has been found to be constitutively activated in a number of human cancers. Dimerization of STAT3 via its SH2 domain and the subsequent translocation of the dimer to the nucleus leads to transcription of anti-apoptotic genes. Prevention of the dimerization is thus an attractive strategy for inhibiting the activity of STAT3. Phosphotyrosine-based peptidomimetic inhibitors, which mimic pTyr-Xaa-Yaa-Gln motif and have strong to weak binding affinities, have been previously investigated. It is well-known that structures of protein-inhibitor complexes are important for understanding the binding interactions and designing stronger inhibitors. Experimental structures of inhibitors bound to the SH2 domain of STAT3 are, however, unavailable. In this paper we describe a computational study that combined molecular docking and molecular dynamics to model structures of 12 peptidomimetic inhibitors bound to the SH2 domain of STAT3. A detailed analysis of the modeled structures was performed to evaluate the characteristics of the binding interactions. We also estimated the binding affinities of the inhibitors by combining MMPB/GBSA-based energies and entropic cost of binding. The estimated affinities correlate strongly with the experimentally obtained affinities. Modeling results show binding modes that are consistent with limited previous modeling studies on binding interactions involving the SH2 domain and phosphotyrosine(pTyr)-based inhibitors. We also discovered a stable novel binding mode that involves deformation of two loops of the SH2 domain that subsequently bury the C-terminal end of one of the stronger inhibitors. The novel binding mode could prove useful for developing more potent inhibitors aimed at preventing dimerization of cancer target protein STAT3

    The Fragmented Mitochondrial Ribosomal RNAs of Plasmodium falciparum

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    The mitochondrial genome in the human malaria parasite Plasmodium falciparum is most unusual. Over half the genome is composed of the genes for three classic mitochondrial proteins: cytochrome oxidase subunits I and III and apocytochrome b. The remainder encodes numerous small RNAs, ranging in size from 23 to 190 nt. Previous analysis revealed that some of these transcripts have significant sequence identity with highly conserved regions of large and small subunit rRNAs, and can form the expected secondary structures. However, these rRNA fragments are not encoded in linear order; instead, they are intermixed with one another and the protein coding genes, and are coded on both strands of the genome. This unorthodox arrangement hindered the identification of transcripts corresponding to other regions of rRNA that are highly conserved and/or are known to participate directly in protein synthesis.The identification of 14 additional small mitochondrial transcripts from P. falciparum and the assignment of 27 small RNAs (12 SSU RNAs totaling 804 nt, 15 LSU RNAs totaling 1233 nt) to specific regions of rRNA are supported by multiple lines of evidence. The regions now represented are highly similar to those of the small but contiguous mitochondrial rRNAs of Caenorhabditis elegans. The P. falciparum rRNA fragments cluster on the interfaces of the two ribosomal subunits in the three-dimensional structure of the ribosome.All of the rRNA fragments are now presumed to have been identified with experimental methods, and nearly all of these have been mapped onto the SSU and LSU rRNAs. Conversely, all regions of the rRNAs that are known to be directly associated with protein synthesis have been identified in the P. falciparum mitochondrial genome and RNA transcripts. The fragmentation of the rRNA in the P. falciparum mitochondrion is the most extreme example of any rRNA fragmentation discovered

    Phylogenetic evidence for the invasion of a commercialized European Phasmarhabditis hermaphrodita lineage into North America and New Zealand

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    Biological control (biocontrol) as a component of pest management strategies reduces reliance on synthetic chemicals, and seemingly offers a natural approach that minimizes environmental impact. However, introducing a new organism to new environments as a classical biocontrol agent can have broad and unanticipated biodiversity effects and conservation consequences. Nematodes are currently used in a variety of commercial biocontrol applications, including the use of Phasmarhabditis hermaphrodita as an agent targeting pest slug and snail species. This species was originally discovered in Germany, and is generally thought to have European origins. P. hermaphrodita is sold under the trade name Nemaslug®, and is available only in European markets. However, this nematode species was discovered in New Zealand and the western United States, though its specific origins remained unclear. In this study, we analyzed 45 nematode strains representing eight different Phasmarhabditis species, collected from nine countries around the world. A segment of nematode mitochondrial DNA (mtDNA) was sequenced and subjected to phylogenetic analyses. Our mtDNA phylogenies were overall consistent with previous analyses based on nuclear ribosomal RNA (rRNA) loci. The recently discovered P. hermaphrodita strains in New Zealand and the United States had mtDNA haplotypes nearly identical to that of Nemaslug®, and these were placed together in an intraspecific monophyletic clade with high support in maximum likelihood and Bayesian analyses. We also examined bacteria that co-cultured with the nematode strains isolated in Oregon, USA, by analyzing 16S rRNA sequences. Eight different bacterial genera were found to associate with these nematodes, though Moraxella osloensis, the bacteria species used in the Nemaslug® formulation, was not detected. This study provided evidence that nematodes deriving from the Nemaslug® biocontrol product have invaded countries where its use is prohibited by regulatory agencies and not commercially available

    AXL receptor tyrosine kinase as a therapeutic target in NSCLC

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    Ross A Okimoto,1 Trever G Bivona1,2 1Division of Hematology and Medical Oncology, University of California San Francisco, San Francisco, CA, USA; 2Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA Abstract: The AXL receptor tyrosine kinase and its ligand, Gas6, regulate key processes in lung cancer growth, metastasis, and epithelial&ndash;mesenchymal transition-associated drug resistance. Gas6 and AXL expression have been correlated with poor prognosis and advanced clinical stage in patients with lung cancer, and targeting the Gas6/AXL pathway demonstrates antitumor activity, decreases cellular invasion, and restores sensitivity in de novo and acquired drug resistance models. These findings implicate AXL as a promising therapeutic target in lung cancer. In this review, we explore the role of AXL in lung cancer progression, from tumor development to disseminated disease, and highlight the current clinical landscape of anti-AXL therapeutics. Keywords: Gas6, lung cancer, targeted therapy, drug resistance&nbsp
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