75 research outputs found

    Hybrid Planning and Control for Multiple Fixed-Wing Aircraft under Input Constraints

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    This paper presents a novel hybrid control protocol for de-conflicting multiple vehicles with constraints on control inputs. We consider turning rate and linear speed constraints to represent fixed-wing or car-like vehicles. A set of state-feedback controllers along with a state-dependent switching logic are synthesized in a hybrid system to generate collision-free trajectories that converge to the desired destinations of the vehicles. The switching law is designed so that the safety can be guaranteed while no Zeno behavior can occur. A novel temporary goal assignment technique is also designed to guarantee convergence. We analyze the individual modes for safety and the closed-loop hybrid system for convergence. The theoretical developments are demonstrated via simulation results.Comment: Best Student Paper Finalist, AIAA-SciTech GNC Conference, 201

    Fusing R features and local features with context-aware kernels for action recognition

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    The performance of action recognition in video sequences depends significantly on the representation of actions and the similarity measurement between the representations. In this paper, we combine two kinds of features extracted from the spatio-temporal interest points with context-aware kernels for action recognition. For the action representation, local cuboid features extracted around interest points are very popular using a Bag of Visual Words (BOVW) model. Such representations, however, ignore potentially valuable information about the global spatio-temporal distribution of interest points. We propose a new global feature to capture the detailed geometrical distribution of interest points. It is calculated by using the 3D R transform which is defined as an extended 3D discrete Radon transform, followed by the application of a two-directional two-dimensional principal component analysis. For the similarity measurement, we model a video set as an optimized probabilistic hypergraph and propose a context-aware kernel to measure high order relationships among videos. The context-aware kernel is more robust to the noise and outliers in the data than the traditional context-free kernel which just considers the pairwise relationships between videos. The hyperedges of the hypergraph are constructed based on a learnt Mahalanobis distance metric. Any disturbing information from other classes is excluded from each hyperedge. Finally, a multiple kernel learning algorithm is designed by integrating the l2 norm regularization into a linear SVM classifier to fuse the R feature and the BOVW representation for action recognition. Experimental results on several datasets demonstrate the effectiveness of the proposed approach for action recognition

    Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS

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    We hereby provide the initial portrait of lincNORS, a spliced lincRNA generated by the MIR193BHG locus, entirely distinct from the previously described miR-193b-365a tandem. While inducible by low O2 in a variety of cells and associated with hypoxia in vivo, our studies show that lincNORS is subject to multiple regulatory inputs, including estrogen signals. Biochemically, this lincRNA fine-tunes cellular sterol/steroid biosynthesis by repressing the expression of multiple pathway components. Mechanistically, the function of lincNORS requires the presence of RALY, an RNA-binding protein recently found to be implicated in cholesterol homeostasis. We also noticed the proximity between this locus and naturally occurring genetic variations highly significant for sterol/steroid-related phenotypes, in particular the age of sexual maturation. An integrative analysis of these variants provided a more formal link between these phenotypes and lincNORS, further strengthening the case for its biological relevance

    Adult Cardiac Progenitor Cell Aggregates Exhibit Survival Benefit Both In Vitro and In Vivo

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    Background: A major hurdle in the use of exogenous stems cells for therapeutic regeneration of injured myocardium remains the poor survival of implanted cells. To date, the delivery of stem cells into myocardium has largely focused on implantation of cell suspensions. Methodology and Principal Findings: We hypothesize that delivering progenitor cells in an aggregate form would serve to mimic the endogenous state with proper cell-cell contact, and may aid the survival of implanted cells. Microwell methodologies allow for the culture of homogenous 3D cell aggregates, thereby allowing cell-cell contact. In this study, we find that the culture of cardiac progenitor cells in a 3D cell aggregate augments cell survival and protects against cellular toxins and stressors, including hydrogen peroxide and anoxia/reoxygenation induced cell death. Moreover, using a murine model of cardiac ischemia-reperfusion injury, we find that delivery of cardiac progenitor cells in the form of 3D aggregates improved in vivo survival of implanted cells. Conclusion: Collectively, our data support the notion that growth in 3D cellular systems and maintenance of cell-cell contact improves exogenous cell survival following delivery into myocardium. These approaches may serve as a strategy to improve cardiovascular cell-based therapies

    Deleterious ABCA7 mutations and transcript rescue mechanisms in early onset Alzheimer’s disease

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    Abstract: Premature termination codon (PTC) mutations in the ATP-Binding Cassette, Sub-Family A, Member 7 gene (ABCA7) have recently been identified as intermediate-to-high penetrant risk factor for late-onset Alzheimer's disease (LOAD). High variability, however, is observed in downstream ABCA7 mRNA and protein expression, disease penetrance, and onset age, indicative of unknown modifying factors. Here, we investigated the prevalence and disease penetrance of ABCA7 PTC mutations in a large early onset AD (EOAD)-control cohort, and examined the effect on transcript level with comprehensive third-generation long-read sequencing. We characterized the ABCA7 coding sequence with next-generation sequencing in 928 EOAD patients and 980 matched control individuals. With MetaSKAT rare variant association analysis, we observed a fivefold enrichment (p = 0.0004) of PTC mutations in EOAD patients (3%) versus controls (0.6%). Ten novel PTC mutations were only observed in patients, and PTC mutation carriers in general had an increased familial AD load. In addition, we observed nominal risk reducing trends for three common coding variants. Seven PTC mutations were further analyzed using targeted long-read cDNA sequencing on an Oxford Nanopore MinION platform. PTC-containing transcripts for each investigated PTC mutation were observed at varying proportion (5-41% of the total read count), implying incomplete nonsense-mediated mRNA decay (NMD). Furthermore, we distinguished and phased several previously unknown alternative splicing events (up to 30% of transcripts). In conjunction with PTC mutations, several of these novel ABCA7 isoforms have the potential to rescue deleterious PTC effects. In conclusion, ABCA7 PTC mutations play a substantial role in EOAD, warranting genetic screening of ABCA7 in genetically unexplained patients. Long-read cDNA sequencing revealed both varying degrees of NMD and transcript-modifying events, which may influence ABCA7 dosage, disease severity, and may create opportunities for therapeutic interventions in AD

    Predictive factors of antiproliferative activity of octreotide LAR as first-line therapy for advanced neuroendocrine tumours

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    background: The antiproliferative activity of octreotide LAR in neuroendocrine tumours (NETs) has been demonstrated by small retrospective studies and confirmed by a prospective phase III trial (PROMID). However, there are limited data about the duration and predictors of response. The aim of our retrospective study was to determine the time to radiological progression (TTRP) of disease and the factors that were associated with better response. methods: A total of 254 treatment naïve patients with advanced NETs and positive somatostatin receptor scintigraphy were included. Mean follow-up period was 42 months. results: The location of primary was in the small bowel in 204, pancreas in 22, lungs in 14, rectum in 7 and unknown in 7 patients. Most tumours were well-differentiated, G1 (58%) and G2 (23%). The majority of patients commenced octreotide LAR due to functional symptoms (57%), radiological progression (10%) or in the presence of asymptomatic and stable disease on the basis of data from the PROMID trial (18.5%). Partial response occurred in 5%. For all patients, the median TTRP was 37 months (95% confidence interval, CI: 32–52 months). There was a statistically significant shorter TTRP in patients with pancreatic tumours, liver metastases and intermediate grade tumours. Extremely raised (>10 times the upper limit of normal) baseline chromogranin A levels were associated with an unfavourable outcome. In contrast, male sex, carcinoid heart disease and initiation of treatment in the presence of stable disease were predictive of a better response. Age, extra-hepatic metastases, presence of mesenteric desmoplasia, previous resection and functional status of the primary tumour did not affect response. conclusions: The duration of the antiproliferative effect of octreotide LAR seems to be longer than previously reported. This study has identified several predictors of response in a large cohort of patients with NETs on somatostatin analogue therapy

    Venous Blood Derivatives as FBS-Substitutes for Mesenchymal Stem Cells: A Systematic Scoping Review

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    Binary Rejuvenation: Applications and Challenges

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    Software engineers have long performed source code rejuvenation, or rewriting of obsolete or outdated programming idioms to modern counterparts. Inspired by this practice, the authors propose binary rejuvenation by updating selected binary files
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