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The EROC curves produced by the proposed method are compared to those produced by the MCMC approach or analytical computation when feasible. The proposed method provides a new approach for approximating the IO and may advance the application of EROC analysis for optimizing imaging systems.Deep neural networks, in particular convolutional networks, have rapidly become a popular choice for analyzing histopathology images. However, training these models relies heavily on a large number of samples manually annotated by experts, which is cumbersome and expensive. In addition, it is difficult to obtain a perfect set of labels due to the variability between expert annotations. This paper presents a novel active learning (AL) framework for histopathology image analysis, named PathAL. To reduce the required number of expert annotations, PathAL selects two groups of unlabeled data in each training iteration one "informative" sample that requires additional expert annotation, and one "confident predictive" sample that is automatically added to the training set using the model's pseudo-labels. To reduce the impact of the noisy-labeled samples in the training set, PathAL systematically identifies noisy samples and excludes them to improve the generalization of the model. Our model advances the existing AL ithm.Childhood obesity is a growing concern as it can lead to lifelong health problems that carry over into adulthood. A substantial contributing factor to obesity is the physical activity (PA) habits that are formed in early childhood, as these habits tend to sustain throughout adulthood. To aid children in forming healthy PA habits, we designed a mixed reality system called the Virtual Fitness Buddy ecosystem, in which children can interact with a virtual pet agent. As a child exercises, their pet becomes slimmer, faster, and able to play more games with them. Our initial deployment of this project showed promise but was only designed for a short-term intervention lasting three days. More recently, we have scaled it from a pilot grade study to a 9-month intervention comprised of 422 children. Ultimately, our goal is to scale this project to be a nationwide primary prevention program to encourage moderate to vigorous PA in children. This article explores the challenges and lessons learned during the design and deployment of this system at scale in the field.The high computational cost of neural networks has prevented recent successes in RGB-D salient object detection (SOD) from benefiting real-world applications. Hence, this paper introduces a novel network, MobileSal, which focuses on efficient RGB-D SOD using mobile networks for deep feature extraction. However, mobile networks are less powerful in feature representation than cumbersome networks. To this end, we observe that the depth information of color images can strengthen the feature representation related to SOD if leveraged properly. Therefore, we propose an implicit depth restoration (IDR) technique to strengthen the mobile networks' feature representation capability for RGB-D SOD. IDR is only adopted in the training phase and is omitted during testing, so it is computationally free. Besides, we propose compact pyramid refinement (CPR) for efficient multi-level feature aggregation to derive salient objects with clear boundaries. With IDR and CPR incorporated, MobileSal performs favorably against state-of-the-art methods on six challenging RGB-D SOD datasets with much faster speed (450fps for the input size of 320320) and fewer parameters (6.5M). The code will be released at https//github.com/yuhuan-wu/mobilesal.A dynamically weighted directed network (DWDN) is frequently encountered in various big data-related applications like a terminal interaction pattern analysis system (TIPAS) concerned in this study. It consists of large-scale dynamic interactions among numerous nodes. As the involved nodes increase drastically, it becomes impossible to observe their full interactions at each time slot, making a resultant DWDN High Dimensional and Incomplete (HDI). An HDI DWDN, in spite of its incompleteness, contains rich knowledge regarding involved nodes various behavior patterns. To extract such knowledge from an HDI DWDN, this paper proposes a novel Alternating direction method of multipliers (ADMM)-based Nonnegative Latent-factorization of Tensors (ANLT) model. It adopts three-fold ideas a) building a data density-oriented augmented Lagrangian function for efficiently handling an HDI tensors incompleteness and nonnegativity; b) splitting the optimization task in each iteration into an elaborately designed subtask series where each one is solved based on the previously solved ones following the ADMM principle to achieve fast convergence; and c) theoretically proving that its convergence is guaranteed with its efficient learning scheme. Experimental results on six DWDNs from real applications demonstrate that the proposed ANLT outperforms state-of-the-art models significantly in both computational efficiency and prediction accuracy.Precision CRISPR gene editing relies on the cellular homology-directed DNA repair (HDR) to introduce custom DNA sequences to target sites. The HDR editing efficiency varies between cell types and genomic sites, and the sources of this variation are incompletely understood. Here, we have studied the effect of 450 DNA repair protein-Cas9 fusions on CRISPR genome editing outcomes. We find the majority of fusions to improve precision genome editing only modestly in a locus- and cell-type specific manner. GW806742X We identify Cas9-POLD3 fusion that enhances editing by speeding up the initiation of DNA repair. We conclude that while DNA repair protein fusions to Cas9 can improve HDR CRISPR editing, most need to be optimized to the cell type and genomic site, highlighting the diversity of factors contributing to locus-specific genome editing outcomes.When compulsions and obsessive thoughts took over her world, a graduate student found strength in her identity as a scientist.Nature has evolved many supramolecular proteins assembled in certain, sometimes even seemingly oversophisticated, morphological manners. The rationale behind such evolutionary efforts is often poorly understood. Here, we provide atomic-resolution insights into how the dynamic building of a structurally complex enzyme with higher order symmetry offers amenability to intricate regulation. We have established the functional coupling between enzymatic activity and protein morphological states of glutamine synthetase (GS), an old multi-subunit enzyme essential for cellular nitrogen metabolism. Cryo-EM structure determination of GS in both the catalytically active and inactive assembly states allows us to reveal an unanticipated self-assembly-induced disorder-order transition paradigm, in which the remote interactions between two subcomplex entities significantly rigidify the otherwise structurally fluctuating active sites, thereby regulating activity. We further show in vivo evidences that how the enzyme morphology transitions could be modulated by cellular factors on demand. Collectively, our data present an example of how assembly status transition offers an avenue for activity modulation, and sharpens our mechanistic understanding of the complex functional and regulatory properties of supramolecular enzymes.Photosynthesis in wheat (Triticum aestivum L.) pericarps may contribute appreciably to wheat grain yield. Consequently, we investigated the temporal variation of traits related to photosynthesis and sucrose metabolism in the pericarps and flag leaves of three wheat genotypes, Huandoy, Amurskaja 75 and Greece 25, which are reported to differ in expression of genes related to the C4 pathway in wheat grain. Significant site-specific, genotypic and temporal variation in the maximum carboxylation rate (Vc max ) and maximum rates of electron transport (J max ) (biological capacity of carbon assimilation) were observed early in ontogeny that dissipated by late grain filling. Although the transcript abundance of rbcS and rbcL in flag leaves was significantly higher than in the pericarps, in line with their photosynthetic prominence, both organ types displayed similar expression patterns among growth stages. The higher N concentrations in the pericarps during grain enlargement suggest increased Rubisco; however, expression of rbcS and rbcL indicated the contrary. From heading to 14days post-anthesis, wheat pericarps exhibited a strong, positive correlation between biological capacity for carbon assimilation and expression of key genes related to sucrose metabolism (SPS1 , SUS1 and SPP1 ). The strong correlation between spike dry weight and the biological capacity for carbon assimilation along with other findings of this study suggest that metabolic processes in wheat spikes may play a major role in grain filling, total yield and quality.This study provides an update on invasive Haemophilus influenzae disease in Bellvitge University Hospital (2014-2019), reporting its evolution from a previous period (2008-2013) and analysing the non-typeable H. influenzae (NTHi) population structure using a clade-related classification. Clinical data, antimicrobial susceptibility and serotyping were studied and compared with those of the previous period. Population structure was assessed by multilocus sequence typing (MLST), SNP-based phylogenetic analysis and clade-related classification. The incidence of invasive H. influenzae disease remained constant between the two periods (average 2.07 cases per 100 000 population), while the 30 day mortality rate decreased (20.7-14.7 %, respectively). Immunosuppressive therapy (40 %) and malignancy (36 %) were the most frequent comorbidities. Ampicillin and fluoroquinolone resistance rates had increased between the two periods (10-17.6 % and 0-4.4 %, respectively). NTHi was the main cause of invasive disease in both periods (84.3 and 85.3 %), followed by serotype f (12.9 and 8.8 %). NTHi displayed high genetic diversity. However, two clusters of 13 (n=20) and 5 sequence types (STs) (n=10) associated with clade V included NTHi strains of the most prevalent STs (ST3 and ST103), many of which showed increased frequency over time. Moreover, ST103 and ST160 from clade V were associated with β-lactam resistance. Invasive H. influenzae disease is uncommon, but can be severe, especially in the elderly with comorbidities. NTHi remains the main cause of invasive disease, with ST103 and ST160 (clade V) responsible for increasing β-lactam resistance over time.The economically important plant pathogen Xylella fastidiosa has been reported in multiple regions of the globe during the last two decades, threatening a growing list of plants. Particularly, X. fastidiosa subspecies fastidiosa causes Pierce's disease (PD) of grapevines, which is a problem in the USA, Spain, and Taiwan. In this work, we studied PD-causing subsp. fastidiosa populations and compared the genome sequences of 33 isolates found in Central Taiwan with 171 isolates from the USA and two from Spain. Phylogenetic relationships, haplotype networks, and genetic diversity analyses confirmed that subsp. fastidiosa was recently introduced into Taiwan from the Southeast USA (i.e. the PD-I lineage). Recent core-genome recombination events were detected among introduced subsp. fastidiosa isolates in Taiwan and contributed to the development of genetic diversity. The genetic diversity observed includes contributions through recombination from unknown donors, suggesting that higher genetic diversity exists in the region.
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