We introduce a new dataset, Human3.6M, of 3.6 Million accurate 3D Human poses, acquired by recording the performance of 5 female and 6 male subjects, under 4 different viewpoints, for training ...realistic human sensing systems and for evaluating the next generation of human pose estimation models and algorithms. Besides increasing the size of the datasets in the current state-of-the-art by several orders of magnitude, we also aim to complement such datasets with a diverse set of motions and poses encountered as part of typical human activities (taking photos, talking on the phone, posing, greeting, eating, etc.), with additional synchronized image, human motion capture, and time of flight (depth) data, and with accurate 3D body scans of all the subject actors involved. We also provide controlled mixed reality evaluation scenarios where 3D human models are animated using motion capture and inserted using correct 3D geometry, in complex real environments, viewed with moving cameras, and under occlusion. Finally, we provide a set of large-scale statistical models and detailed evaluation baselines for the dataset illustrating its diversity and the scope for improvement by future work in the research community. Our experiments show that our best large-scale model can leverage our full training set to obtain a 20% improvement in performance compared to a training set of the scale of the largest existing public dataset for this problem. Yet the potential for improvement by leveraging higher capacity, more complex models with our large dataset, is substantially vaster and should stimulate future research. The dataset together with code for the associated large-scale learning models, features, visualization tools, as well as the evaluation server, is available online at http://vision.imar.ro/human3.6m.
The importance of medical imaging in the diagnosis and monitoring of cancer cannot be overstated. As personalized cancer treatments are gaining popularity, a need for more advanced imaging techniques ...has grown significantly. Nanoparticles are uniquely suited to fill this void, not only as imaging contrast agents but also as companion diagnostics. This review provides an overview of many ways nanoparticle imaging agents have contributed to cancer imaging, both preclinically and in the clinic, as well as charting future directions in companion diagnostics. We conclude that, while nanoparticle-based imaging agents are not without considerable scientific and developmental challenges, they enable enhanced imaging in nearly every modality, hold potential as in vivo companion diagnostics, and offer precise cancer treatment and maximize intervention efficacy.
The molecular mechanisms specifying the dendritic morphology of different neuronal subtypes are poorly understood. Here we demonstrate that the bHLH transcription factor Neurogenin2 (Ngn2) is both ...necessary and sufficient for specifying the dendritic morphology of pyramidal neurons in vivo by specifying the polarity of its leading process during the initiation of radial migration. The ability of Ngn2 to promote a polarized leading process outgrowth requires the phosphorylation of a single tyrosine residue at position 241, an event that is neither involved in Ngn2 direct transactivation properties nor its proneural function. Interestingly, the migration defect observed in the Ngn2 knockout mouse and in progenitors expressing the Ngn2Y241F mutation can be rescued by inhibiting the activity of the small-GTPase RhoA in cortical progenitors. Our results demonstrate that Ngn2 coordinates the acquisition of the radial migration properties and the unipolar dendritic morphology characterizing pyramidal neurons through molecular mechanisms distinct from those mediating its proneural activity.
Abstract Transposable elements (TEs) are found in virtually every eukaryotic genome and are important for generating de novo genetic variation. However, outside of costly and time-consuming ...whole-genome sequencing approaches, the set of available methods to study TE polymorphisms in non-model species is very limited. The Transposon Display (TD) is a simple yet effective technique to characterize polymorphisms across samples by identifying amplified fragment length polymorphisms using primers targeting specific TE families. So far, this technique has almost exclusively been used in plants. Here, we present an optimized TD protocol for insect species with small genomes such as ants (ca. 200-600 Mb). We characterized TE polymorphisms between two distinct genetic lineages of the invasive ant Cardiocondyla obscurior, as well as between neighboring populations of the New World lineage. We found active LTR/Ty3 retrotransposons, that contributed to the genetic diversification of populations in this species.
Many methods have been used to determine differential gene expression from single-cell RNA (scRNA)-seq data. We evaluated 36 approaches using experimental and synthetic data and found considerable ...differences in the number and characteristics of the genes that are called differentially expressed. Prefiltering of lowly expressed genes has important effects, particularly for some of the methods developed for bulk RNA-seq data analysis. However, we found that bulk RNA-seq analysis methods do not generally perform worse than those developed specifically for scRNA-seq. We also present conquer, a repository of consistently processed, analysis-ready public scRNA-seq data sets that is aimed at simplifying method evaluation and reanalysis of published results. Each data set provides abundance estimates for both genes and transcripts, as well as quality control and exploratory analysis reports.
Organism-level systems biology aims to identify, analyze, control and design cellular circuits in organisms. Many experimental and computational approaches have been developed over the years to allow ...us to conduct these studies. Some of the most powerful methods are based on using optical imaging in combination with fluorescent labeling, and for those one of the long-standing stumbling blocks has been tissue opacity. Recently, the solutions to this problem have started to emerge based on whole-body and whole-organ clearing techniques that employ innovative tissue-clearing chemistry. Here, we review these advancements and discuss how combining new clearing techniques with high-performing fluorescent proteins or small molecule tags, rapid volume imaging and efficient image informatics is resulting in comprehensive and quantitative organ-wide, single-cell resolution experimental data. These technologies are starting to yield information on connectivity and dynamics in cellular circuits at unprecedented resolution, and bring us closer to system-level understanding of physiology and diseases of complex mammalian systems.
Some of the most powerful methods to obtain organism-level systems biology information are based on using optical probes and methods to peer into organs, tissues, and organisms. Susaki and Ueda review the state of the art in the field, focusing on chemistry-based whole-body and whole-organ clearing techniques.
Surgical resection is the primary and most effective treatment for most patients with solid tumors. However, patients suffer from postoperative recurrence and metastasis. In the past years, emerging ...nanotechnology has led the way to minimally invasive, precision and intelligent oncological surgery after the rapid development of minimally invasive surgical technology. Advanced nanotechnology in the construction of nanomaterials (NMs) for precision imaging‐guided surgery (IGS) as well as surgery‐assisted synergistic therapy is summarized, thereby unlocking the advantages of nanotechnology in multimodal IGS‐assisted precision synergistic cancer therapy. First, mechanisms and principles of NMs to surgical targets are briefly introduced. Multimodal imaging based on molecular imaging technologies provides a practical method to achieve intraoperative visualization with high resolution and deep tissue penetration. Moreover, multifunctional NMs synergize surgery with adjuvant therapy (e.g., chemotherapy, immunotherapy, phototherapy) to eliminate residual lesions. Finally, key issues in the development of ideal theranostic NMs associated with surgical applications and challenges of clinical transformation are discussed to push forward further development of NMs for multimodal IGS‐assisted precision synergistic cancer therapy.
State‐of‐the‐art advances in advanced nanotechnology for precision surgery are presented, with emphasis on multimodal imaging‐guided precision surgery for intraoperative visualization and synergistic surgical therapy for the elimination of residual lesions. These are of great value to push forward the development of nanomaterials in oncological surgery and clinical translation.
The Illumina DNA sequencing platform generates accurate but short reads, which can be used to produce accurate but fragmented genome assemblies. Pacific Biosciences and Oxford Nanopore Technologies ...DNA sequencing platforms generate long reads that can produce complete genome assemblies, but the sequencing is more expensive and error-prone. There is significant interest in combining data from these complementary sequencing technologies to generate more accurate "hybrid" assemblies. However, few tools exist that truly leverage the benefits of both types of data, namely the accuracy of short reads and the structural resolving power of long reads. Here we present Unicycler, a new tool for assembling bacterial genomes from a combination of short and long reads, which produces assemblies that are accurate, complete and cost-effective. Unicycler builds an initial assembly graph from short reads using the de novo assembler SPAdes and then simplifies the graph using information from short and long reads. Unicycler uses a novel semi-global aligner to align long reads to the assembly graph. Tests on both synthetic and real reads show Unicycler can assemble larger contigs with fewer misassemblies than other hybrid assemblers, even when long-read depth and accuracy are low. Unicycler is open source (GPLv3) and available at github.com/rrwick/Unicycler.
High-throughput RNA sequencing is an increasingly accessible method for studying gene structure and activity on a genome-wide scale. A critical step in RNA-seq data analysis is the alignment of ...partial transcript reads to a reference genome sequence. To assess the performance of current mapping software, we invited developers of RNA-seq aligners to process four large human and mouse RNA-seq data sets. In total, we compared 26 mapping protocols based on 11 programs and pipelines and found major performance differences between methods on numerous benchmarks, including alignment yield, basewise accuracy, mismatch and gap placement, exon junction discovery and suitability of alignments for transcript reconstruction. We observed concordant results on real and simulated RNA-seq data, confirming the relevance of the metrics employed. Future developments in RNA-seq alignment methods would benefit from improved placement of multimapped reads, balanced utilization of existing gene annotation and a reduced false discovery rate for splice junctions.
PDF
