823 research outputs found

    Neural network based automatic limit prediction and avoidance system and method

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    A method for performance envelope boundary cueing for a vehicle control system comprises the steps of formulating a prediction system for a neural network and training the neural network to predict values of limited parameters as a function of current control positions and current vehicle operating conditions. The method further comprises the steps of applying the neural network to the control system of the vehicle, where the vehicle has capability for measuring current control positions and current vehicle operating conditions. The neural network generates a map of current control positions and vehicle operating conditions versus the limited parameters in a pre-determined vehicle operating condition. The method estimates critical control deflections from the current control positions required to drive the vehicle to a performance envelope boundary. Finally, the method comprises the steps of communicating the critical control deflection to the vehicle control system; and driving the vehicle control system to provide a tactile cue to an operator of the vehicle as the control positions approach the critical control deflections

    Performance of three- and five-stack achromatic half-wave plates at millimeter wavelengths

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    We study the performance of achromatic half-wave plates (AHWPs) as a function of the detection bandwidth of a power detector operating in the millimeter wave band and the spectral shape of the incident radiation. We focus particular attention on the extraction of the degree of incident polarization and its orientation angle from the intensity measured as a function of AHWP rotation angle, which we call the IVA (intensity versus angle). We describe the formalism to extract the two incident polarization parameters. We use this formalism to quantify the phase offset of the IVA and point to potential systematic errors in the extraction of this offset in cases where the incident spectrum is not sufficiently well known. We quantify the phase offset and modulation efficiency as a function of the relative angles between the plates in the stack and find that high modulation efficiency can be achieved with alignment accuracy of a few degrees. We present measurements of the spectral response of an AHWP made with five plates. The measurements predict a modulation efficiency that is higher than 98% for three bands centered at 150, 250, and 410 GHz

    Molecular Modulation of a-Subunit VISIT-DG Sequence Residue Asp-350 in the Catalytic sites of \u3cem\u3eEscherichia coli\u3c/em\u3e ATP Synthase.

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    ATP Synthase is the fundamental means of cellular energy production in animals, plants, and almost all microorganisms. In order to understand the mechanism of ATP catalysis, critical amino acid residues involved in Pi binding have to be identified. The αVISIT-DG sequence at the interface of α/β subunits that contains residues from 345-351 is highly conserved and αAsp-350 has been chosen because of its negative charge side chain and its close proximity (~2.8 Å) to the known phosphate binding residue αArg-376. The mutant\u27s αD350R, αD350Q, αD350A, αR376A/D, and αG351R/A/D were generated by site directed mutagenesis and several biochemical assays were performed on them to understand the role played by the amino acid residues in Pi binding. Biochemical results suggest that αD350 may be involved in catalysis of ATP synthase and play an important role in Pi binding, whereas αG351 may be involved only in the structural integrity

    Synthesis, in vitro, and in vivo evaluation of novel N-phenylindazolyl diarylureas as potential anti-cancer agents.

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    Novel N-phenylindazole based diarylureas have been designed, synthesized and evaluated as potential anticancer agents. In vitro cell viability studies of these derivatives illustrate good potency with IC50 values in the range of 0.4–50 μM in several cancer cell lines including murine metastatic breast cancer 4T1, murine glioblastoma GL261, human triple negative breast cancer MDA-MB-231, human pancreatic cancer MIAPaCa-2, and human colorectal cancer cell line WiDr. The ester group in the lead compound 8i was modified to incorporate amino-amides to increase solubility and stability while retaining biological activity. Further in vitro studies reveal that lead candidates inhibit tube length in HUVEC cells. In vivo systemic toxicity studies indicate that these candidate compounds are well tolerated in mice without any significant side effects. Anticancer efficacy studies in WiDr tumor xenograft and 4T1 tumor syngraft models demonstrate that the lead candidate 11 exhibits significant antitumor properties as a single agent in these tumor models

    Rosa26-GFP Direct Repeat (RaDR-GFP) Mice Reveal Tissue- and Age-Dependence of Homologous Recombination in Mammals In Vivo

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    Homologous recombination (HR) is critical for the repair of double strand breaks and broken replication forks. Although HR is mostly error free, inherent or environmental conditions that either suppress or induce HR cause genomic instability. Despite its importance in carcinogenesis, due to limitations in our ability to detect HR in vivo, little is known about HR in mammalian tissues. Here, we describe a mouse model in which a direct repeat HR substrate is targeted to the ubiquitously expressed Rosa26 locus. In the Rosa26 Direct Repeat-GFP (RaDR-GFP) mice, HR between two truncated EGFP expression cassettes can yield a fluorescent signal. In-house image analysis software provides a rapid method for quantifying recombination events within intact tissues, and the frequency of recombinant cells can be evaluated by flow cytometry. A comparison among 11 tissues shows that the frequency of recombinant cells varies by more than two orders of magnitude among tissues, wherein HR in the brain is the lowest. Additionally, de novo recombination events accumulate with age in the colon, showing that this mouse model can be used to study the impact of chronic exposures on genomic stability. Exposure to N-methyl-N-nitrosourea, an alkylating agent similar to the cancer chemotherapeutic temozolomide, shows that the colon, liver and pancreas are susceptible to DNA damage-induced HR. Finally, histological analysis of the underlying cell types reveals that pancreatic acinar cells and liver hepatocytes undergo HR and also that HR can be specifically detected in colonic somatic stem cells. Taken together, the RaDR-GFP mouse model provides new understanding of how tissue and age impact susceptibility to HR, and enables future studies of genetic, environmental and physiological factors that modulate HR in mammals.National Institutes of Health (U.S.) (Program Project Grant P01-CA026731)National Institutes of Health (U.S.) (R33-CA112151)National Institute of Environmental Health Sciences (P30-ES002109)Singapore-MIT Alliance for Research and Technology CenterNational Institutes of Health (U.S.) (P41-EB015871)National Cancer Institute (U.S.) (P30-CA014051

    Health Behaviors Predicting Risk of Obesity in US Adults: What Does a Healthy Lifestyle Look Like?

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    Objective The purpose of this study was to examine the association between lifestyle factors and body weight in a nationally representative sample of US adults and to evaluate the association between a novel “Healthy Habits Composite Score (HHCS)” and risk of obesity. Methods This cross-sectional study included data from 4870 adults who participated in the 2017–2018 National Health and Nutrition Examination Survey (NHANES). The HHCS was developed based on 4 factors: diet, physical activity, sedentary time, and sleep, all of which were measured during the NHANES. A “healthy lifestyle” was defined as meeting ≥3 of the 4 established criteria. Data analysis was conducted using SAS 9.4 and procedures to account for the complex survey design. All models were adjusted for age, sex, race, household income, and education. Results Adults with obesity had significantly lower dietary quality (48.8 ± 0.6 vs. 53.2 ± 0.9) and reported significantly more sedentary time (∼1 h more; 356.3 ± 7.0 vs. 301.4 ± 8.3 min) than lean adults, both p \u3c 0.001. Achieving a healthy lifestyle based on the HHCS was associated with nearly double the odds of having a healthy body weight (OR 1.9, p \u3c 0.001). Conclusions Following a lifestyle focused on healthy habits (diet quality, physical activity, limited sedentary time, and sleep) was strongly associated with a decreased risk of obesity: an individual who achieved three or more healthy habits had nearly twice the odds of having a healthy body weight. Therefore, comprehensive interventions that address and promote a wide range of healthy habits may be most effective for lowering obesity risk

    Information retrieval and text mining technologies for chemistry

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    Efficient access to chemical information contained in scientific literature, patents, technical reports, or the web is a pressing need shared by researchers and patent attorneys from different chemical disciplines. Retrieval of important chemical information in most cases starts with finding relevant documents for a particular chemical compound or family. Targeted retrieval of chemical documents is closely connected to the automatic recognition of chemical entities in the text, which commonly involves the extraction of the entire list of chemicals mentioned in a document, including any associated information. In this Review, we provide a comprehensive and in-depth description of fundamental concepts, technical implementations, and current technologies for meeting these information demands. A strong focus is placed on community challenges addressing systems performance, more particularly CHEMDNER and CHEMDNER patents tasks of BioCreative IV and V, respectively. Considering the growing interest in the construction of automatically annotated chemical knowledge bases that integrate chemical information and biological data, cheminformatics approaches for mapping the extracted chemical names into chemical structures and their subsequent annotation together with text mining applications for linking chemistry with biological information are also presented. Finally, future trends and current challenges are highlighted as a roadmap proposal for research in this emerging field.A.V. and M.K. acknowledge funding from the European Community’s Horizon 2020 Program (project reference: 654021 - OpenMinted). M.K. additionally acknowledges the Encomienda MINETAD-CNIO as part of the Plan for the Advancement of Language Technology. O.R. and J.O. thank the Foundation for Applied Medical Research (FIMA), University of Navarra (Pamplona, Spain). This work was partially funded by Consellería de Cultura, Educación e Ordenación Universitaria (Xunta de Galicia), and FEDER (European Union), and the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684). We thank Iñigo Garciá -Yoldi for useful feedback and discussions during the preparation of the manuscript.info:eu-repo/semantics/publishedVersio

    Text Mining the History of Medicine

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    Historical text archives constitute a rich and diverse source of information, which is becoming increasingly readily accessible, due to large-scale digitisation efforts. However, it can be difficult for researchers to explore and search such large volumes of data in an efficient manner. Text mining (TM) methods can help, through their ability to recognise various types of semantic information automatically, e.g., instances of concepts (places, medical conditions, drugs, etc.), synonyms/variant forms of concepts, and relationships holding between concepts (which drugs are used to treat which medical conditions, etc.). TM analysis allows search systems to incorporate functionality such as automatic suggestions of synonyms of user-entered query terms, exploration of different concepts mentioned within search results or isolation of documents in which concepts are related in specific ways. However, applying TM methods to historical text can be challenging, according to differences and evolutions in vocabulary, terminology, language structure and style, compared to more modern text. In this article, we present our efforts to overcome the various challenges faced in the semantic analysis of published historical medical text dating back to the mid 19th century. Firstly, we used evidence from diverse historical medical documents from different periods to develop new resources that provide accounts of the multiple, evolving ways in which concepts, their variants and relationships amongst them may be expressed. These resources were employed to support the development of a modular processing pipeline of TM tools for the robust detection of semantic information in historical medical documents with varying characteristics. We applied the pipeline to two large-scale medical document archives covering wide temporal ranges as the basis for the development of a publicly accessible semantically-oriented search system. The novel resources are available for research purposes, while the processing pipeline and its modules may be used and configured within the Argo TM platform
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