254 research outputs found

    Pseudorehearsal in value function approximation

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    Catastrophic forgetting is of special importance in reinforcement learning, as the data distribution is generally non-stationary over time. We study and compare several pseudorehearsal approaches for Q-learning with function approximation in a pole balancing task. We have found that pseudorehearsal seems to assist learning even in such very simple problems, given proper initialization of the rehearsal parameters

    Mapping Proprioception across a 2D Horizontal Workspace

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    Relatively few studies have been reported that document how proprioception varies across the workspace of the human arm. Here we examined proprioceptive function across a horizontal planar workspace, using a new method that avoids active movement and interactions with other sensory modalities. We systematically mapped both proprioceptive acuity (sensitivity to hand position change) and bias (perceived location of the hand), across a horizontal-plane 2D workspace. Proprioception of both the left and right arms was tested at nine workspace locations and in 2 orthogonal directions (left-right and forwards-backwards). Subjects made repeated judgments about the position of their hand with respect to a remembered proprioceptive reference position, while grasping the handle of a robotic linkage that passively moved their hand to each judgement location. To rule out the possibility that the memory component of the proprioceptive testing procedure may have influenced our results, we repeated the procedure in a second experiment using a persistent visual reference position. Both methods resulted in qualitatively similar findings. Proprioception is not uniform across the workspace. Acuity was greater for limb configurations in which the hand was closer to the body, and was greater in a forward-backward direction than in a left-right direction. A robust difference in proprioceptive bias was observed across both experiments. At all workspace locations, the left hand was perceived to be to the left of its actual position, and the right hand was perceived to be to the right of its actual position. Finally, bias was smaller for hand positions closer to the body. The results of this study provide a systematic map of proprioceptive acuity and bias across the workspace of the limb that may be used to augment computational models of sensory-motor control, and to inform clinical assessment of sensory function in patients with sensory-motor deficits

    DCE-MRI perfusion and permeability parameters as predictors of tumor response to CCRT in patients with locally advanced NSCLC

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    In this prospective study, 36 patients with stage III non-small cell lung cancers (NSCLC), who underwent dynamic contrast-enhanced MRI (DCE-MRI) before concurrent chemo-radiotherapy (CCRT) were enrolled. Pharmacokinetic analysis was carried out after non-rigid motion registration. The perfusion parameters including Blood Flow (BF), Blood Volume (BV), Mean Transit Time (MTT) and permeability parameters including endothelial transfer constant (Ktrans), reflux rate (Kep), fractional extravascular extracellular space volume (Ve), fractional plasma volume (Vp) were calculated, and their relationship with tumor regression was evaluated. The value of these parameters on predicting responders were calculated by receiver operating characteristic (ROC) curve. Multivariate logistic regression analysis was conducted to find the independent variables. Tumor regression rate is negatively correlated with V e and its standard variation V e-SD and positively correlated with K trans and Kep. Significant differences between responders and non-responders existed in Ktrans, Kep, Ve, Ve-SD, MTT, BV-SD and MTT-SD (P < 0.05). ROC indicated that Ve < 0.24 gave the largest area under curve of 0.865 to predict responders. Multivariate logistic regression analysis also showed Ve was a significant predictor. Baseline perfusion and permeability parameters calculated from DCE-MRI were seen to be a viable tool for predicting the early treatment response after CCRT of NSCLC. © 2016 The Author(s)

    Neurogenic mechanisms in bladder and bowel ageing

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    The prevalence of both urinary and faecal incontinence, and also chronic constipation, increases with ageing and these conditions have a major impact on the quality of life of the elderly. Management of bladder and bowel dysfunction in the elderly is currently far from ideal and also carries a significant financial burden. Understanding how these changes occur is thus a major priority in biogerontology. The functions of the bladder and terminal bowel are regulated by complex neuronal networks. In particular neurons of the spinal cord and peripheral ganglia play a key role in regulating micturition and defaecation reflexes as well as promoting continence. In this review we discuss the evidence for ageing-induced neuronal dysfunction that might predispose to neurogenic forms of incontinence in the elderly

    P2X7 receptors induce degranulation in human mast cells.

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    Mast cells play important roles in host defence against pathogens, as well as being a key effector cell in diseases with an allergic basis such as asthma and an increasing list of other chronic inflammatory conditions. Mast cells initiate immune responses through the release of newly synthesised eicosanoids and the secretion of pre-formed mediators such as histamine which they store in specialised granules. Calcium plays a key role in regulating both the synthesis and secretion of mast-cell-derived mediators, with influx across the membrane, in particular, being necessary for degranulation. This raises the possibility that calcium influx through P2X receptors may lead to antigen-independent secretion of histamine and other granule-derived mediators from human mast cells. Here we show that activation of P2X7 receptors with both ATP and BzATP induces robust calcium rises in human mast cells and triggers their degranulation; both effects are blocked by the P2X7 antagonist AZ11645373, or the removal of calcium from the extracellular medium. Activation of P2X1 receptors with αβmeATP also induces calcium influx in human mast cells, which is significantly reduced by both PPADS and NF 449. P2X1 receptor activation, however, does not trigger degranulation. The results indicate that P2X7 receptors may play a significant role in contributing to the unwanted activation of mast cells in chronic inflammatory conditions where extracellular ATP levels are elevated

    Biogenic and Synthetic Polyamines Bind Cationic Dendrimers

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    Biogenic polyamines are essential for cell growth and differentiation, while polyamine analogues exert antitumor activity in multiple experimental model systems, including breast and lung cancer. Dendrimers are widely used for drug delivery in vitro and in vivo. We report the bindings of biogenic polyamines, spermine (spm), and spermidine (spmd), and their synthetic analogues, 3,7,11,15-tetrazaheptadecane.4HCl (BE-333) and 3,7,11,15,19-pentazahenicosane.5HCl (BE-3333) to dendrimers of different compositions, mPEG-PAMAM (G3), mPEG-PAMAM (G4) and PAMAM (G4). FTIR and UV-visible spectroscopic methods as well as molecular modeling were used to analyze polyamine binding mode, the binding constant and the effects of polyamine complexation on dendrimer stability and conformation. Structural analysis showed that polyamines bound dendrimers through both hydrophobic and hydrophilic contacts with overall binding constants of Kspm-mPEG-G3 = 7.6×104 M−1, Kspm-mPEG-PAMAM-G4 = 4.6×104 M−1, Kspm-PAMAM-G4 = 6.6×104 M−1, Kspmd-mPEG-G3 = 1.0×105 M−1, Kspmd-mPEG-PAMAM-G4 = 5.5×104 M−1, Kspmd-PAMAM-G4 = 9.2×104 M−1, KBE-333-mPEG-G3 = 4.2×104 M−1, KBe-333-mPEG-PAMAM-G4 = 3.2×104 M−1, KBE-333-PAMAM-G4 = 3.6×104 M−1, KBE-3333-mPEG-G3 = 2.2×104 M−1, KBe-3333-mPEG-PAMAM-G4 = 2.4×104 M−1, KBE-3333-PAMAM-G4 = 2.3×104 M−1. Biogenic polyamines showed stronger affinity toward dendrimers than those of synthetic polyamines, while weaker interaction was observed as polyamine cationic charges increased. The free binding energies calculated from docking studies were: −3.2 (spermine), −3.5 (spermidine) and −3.03 (BE-3333) kcal/mol, with the following order of binding affinity: spermidine-PAMAM-G-4>spermine-PAMMAM-G4>BE-3333-PAMAM-G4 consistent with spectroscopic data. Our results suggest that dendrimers can act as carrier vehicles for delivering antitumor polyamine analogues to target tissues

    An Information Theory Approach to Hypothesis Testing in Criminological Research

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    Background: This research demonstrates how the Akaike information criterion (AIC) can be an alternative to null hypothesis significance testing in selecting best fitting models. It presents an example to illustrate how AIC can be used in this way. Methods: Using data from Milwaukee, Wisconsin, we test models of place-based predictor variables on street robbery and commercial robbery. We build models to balance explanatory power and parsimony. Measures include the presence of different kinds of businesses, together with selected age groups and social disadvantage. Results: Models including place-based measures of land use emerged as the best models among the set of tested models. These were superior to models that included measures of age and socioeconomic status. The best models for commercial and street robbery include three measures of ordinary businesses, liquor stores, and spatial lag. Conclusions: Models based on information theory offer a useful alternative to significance testing when a strong theoretical framework guides the selection of model sets. Theoretically relevant ‘ordinary businesses’ have a greater influence on robbery than socioeconomic variables and most measures of discretionary businesses

    Microabrasion in tooth enamel discoloration defects: three cases with long-term follow-ups

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    Superficial irregularities and certain intrinsic stains on the dental enamel surfaces can be resolved by enamel microabrasion, however, treatment for such defects need to be confined to the outermost regions of the enamel surface. Dental bleaching and resin-based composite repair are also often useful for certain situations for tooth color corrections. This article presented and discussed the indications and limitations of enamel microabrasion treatment. Three case reports treated by enamel microabrasion were also presented after 11, 20 and 23 years of follow-ups
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