4,312 research outputs found

    Information for Successful Interaction with Autonomous Systems

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    Interaction in heterogeneous mission operations teams is not well matched to classical models of coordination with autonomous systems. We describe methods of loose coordination and information management in mission operations. We describe an information agent and information management tool suite for managing information from many sources, including autonomous agents. We present an integrated model of levels of complexity of agent and human behavior, which shows types of information processing and points of potential error in agent activities. We discuss the types of information needed for diagnosing problems and planning interactions with an autonomous system. We discuss types of coordination for which designs are needed for autonomous system functions

    Halogen Bonds Form the Basis for Selective P-TEFb Inhibition by DRB

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    SummaryCdk9, the kinase of the positive transcription elongation factor b, is required for processive transcription elongation by RNA polymerase II. Cdk9 inhibition contributes to the anticancer activity of many Cdk inhibitors under clinical investigation and hence there is interest in selective Cdk9 inhibitors. DRB (5,6-dichlorobenzimidazone-1-β-D-ribofuranoside) is a commonly used reagent for Cdk9 inhibition in cell biology studies. The crystal structures of Cdk9 and Cdk2 in complex with DRB reported here describe the molecular basis for the DRB selectivity toward Cdk9. The DRB chlorine atoms form halogen bonds that are specific for the Cdk9 kinase hinge region. Kinetic and thermodynamic experiments validate the structural findings and implicate the C-terminal residues of Cdk9 in contributing to the affinity for DRB. These results open the possibility to exploit halogen atoms in inhibitor design to specifically target Cdk9

    Item-specific proactive interference in olfactory working memory.

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    We examine item-specific olfactory proactive interference (PI) effects and undertake comparisons with verbal and non-verbal visual stimuli. Using a sequential recent-probes task, we show no evidence for PI with hard-to-name odours (Experiment 1). However, verbalisable odours do exhibit PI effects (Experiment 2). These findings occur despite above chance performance and similar serial position functions across both tasks. Experiments 3 and 4 apply words and faces, respectively, to our modified procedure, and show that methodological differences cannot explain the null finding in Experiment 1. The extent to which odours exhibit analogous PI effects to that of other modalities is, we argue, contingent on the characteristics of the odours employed

    Photochemistry of Nitrous Acid and Nitrite Ion

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    A study of the solution phase photochemistry of the nitrous acid/nitrite ion system in both water and non-aqueous solvents has been undertaken. Photolysis at 366nm of the aqueous system is known to form hydroxyl radical and nitric oxide. The relative contributions of the molecular and ionic forms to the photochemical production of radicals is unknown. Scavenging reactions of the hydroxyl radicals in aqueous and nonaqueous solution are used to determine the relative production of OH. formed by photolysis of HONO and N02-. Molecular nitrous acid is isolated from its conjugate base by extraction into benzene from water. The thermal decomposition of HONO in the extraction mixture was measured and it was found to be second order with respect to nitrous acid. The product of the photolysis of this benzene solution, PNP, indicates hydroxyl radical formation. Nitrite ion dissolves in aprotic solvents, such as DMF and DMSO, without the formation of nitrous acid. Photolysis of these solutions appears to result in the formation of phenol only. The quantum yield for the formation of phenol was determined to be 1.8 ± 0.3 x 10-2 mol/eins

    Targeting protein homeostasis with nelfinavir/salinomycin dual therapy effectively

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    Uncontrolled cell growth in Tuberous Sclerosis Complex occurs due to inappropriate activation of mechanistic (mammalian) target of rapamycin complex 1 (mTORC1). The current therapy, rapamycin, produced promising clinical trial results, but patient tumours regrow if treatment is discontinued, revealing rapamycin has cytostatic properties rather than a cytotoxic effect. Taking advantage of the enhanced levels of endoplasmic reticulum (ER) stress present in TSC2-null cells, we investigated drug combinations producing a cytotoxic response. We found a nelfinavir and salinomycin combination specifically killed TSC2-deficient, mTORC1 hyperactive cells. Cytotoxicity was rescued by reducing protein synthesis, either through mTORC1 inhibition or cycloheximide treatment. This indicates that the drug combination targets the cells by tipping the protein homeostasis balance of the already metabolically stressed TSC2-deficient cells in favour of cell death. Furthermore, this drug combination also inhibited tumour formation in TSC2-deficient cell models and caused tumour spheroid death in 3D culture. Importantly, the 3D assay could differentiate the cytostatic agent, rapamycin, from the cytotoxic nelfinavir/salinomycin combination. Sporadic cancer cell lines with hyperactive mTORC1 signalling were also susceptible to this nelfinavir/salinomycin drug combination. This work indicates that the protein homeostasis pathway is an attractive therapeutic target in both Tuberous Sclerosis Complex and mTORC1-driven sporadic cancers

    3DFeat-Net: Weakly Supervised Local 3D Features for Point Cloud Registration

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    In this paper, we propose the 3DFeat-Net which learns both 3D feature detector and descriptor for point cloud matching using weak supervision. Unlike many existing works, we do not require manual annotation of matching point clusters. Instead, we leverage on alignment and attention mechanisms to learn feature correspondences from GPS/INS tagged 3D point clouds without explicitly specifying them. We create training and benchmark outdoor Lidar datasets, and experiments show that 3DFeat-Net obtains state-of-the-art performance on these gravity-aligned datasets.Comment: 17 pages, 6 figures. Accepted in ECCV 201

    Embedding effective depression care: using theory for primary care organisational and systems change

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    Background: depression and related disorders represent a significant part of general practitioners (GPs) daily work. Implementing the evidence about what works for depression care into routine practice presents a challenge for researchers and service designers. The emerging consensus is that the transfer of efficacious interventions into routine practice is strongly linked to how well the interventions are based upon theory and take into account the contextual factors of the setting into which they are to be transferred. We set out to develop a conceptual framework to guide change and the implementation of best practice depression care in the primary care setting.Methods: we used a mixed method, observational approach to gather data about routine depression care in a range of primary care settings via: audit of electronic health records; observation of routine clinical care; and structured, facilitated whole of organisation meetings. Audit data were summarised using simple descriptive statistics. Observational data were collected using field notes. Organisational meetings were audio taped and transcribed. All the data sets were grouped, by organisation, and considered as a whole case. Normalisation Process Theory (NPT) was identified as an analytical theory to guide the conceptual framework development.Results: five privately owned primary care organisations (general practices) and one community health centre took part over the course of 18 months. We successfully developed a conceptual framework for implementing an effective model of depression care based on the four constructs of NPT: coherence, which proposes that depression work requires the conceptualisation of boundaries of who is depressed and who is not depressed and techniques for dealing with diffuseness; cognitive participation, which proposes that depression work requires engagement with a shared set of techniques that deal with depression as a health problem; collective action, which proposes that agreement is reached about how care is organised; and reflexive monitoring, which proposes that depression work requires agreement about how depression work will be monitored at the patient and practice level. We describe how these constructs can be used to guide the design and implementation of effective depression care in a way that can take account of contextual differences.Conclusions: ideas about what is required for an effective model and system of depression care in primary care need to be accompanied by theoretically informed frameworks that consider how these can be implemented. The conceptual framework we have presented can be used to guide organisational and system change to develop common language around each construct between policy makers, service users, professionals, and researchers. This shared understanding across groups is fundamental to the effective implementation of change in primary care for depressio

    Self-assessed proficiency and application of various skills learned during postgraduate pharmacy teaching skills development programs

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    The purpose of this study was to identify teaching skills commonly taught during the postgraduate pharmacy teaching skills development programs, to describe trainees\u27 perceived teaching proficiency, and the extent to which the learned teaching skills are applied in trainees\u27 current positions. An online survey was developed for pharmacists who completed postgraduate teaching skills development programs. The survey included demographic and program queries as well as questions on 23 teaching skills. Participants self-assessed their proficiency in and application of their learned teaching skills. The online survey resulted in 122 qualified responses. After training, the perceived proficiency in nearly all 23 teaching skills was high; however, the scores for application of teaching skills were significantly lower. A majority (91.7%) of survey respondents were engaged in experiential education. There is wide variability among the postgraduate pharmacy teaching skills development programs. Though the trainees perceived their proficiency in teaching skills to be high, the acquired teaching skills were underused
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