154 research outputs found

    Quasi-linearization approach for the under-actuated robots

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    A novel technique to reduce energy consumption for industrial robots by using redundancy and under-actuated configurations is introduced in this paper. The study concentrates on kinematics including a passive axis which causes a highly nonlinear coupling of the Coriolis and centrifugal forces and high inertia coupling. The challenge of meeting the requirements of position accuracy, precision, and repeatability combined with the requirements for the speed, acceleration, and torque is coped with by solving a sequence of linear two point boundary value problems for controlling the movement of the end effector between two points. The advantages of this method are the ability of reducing the computation time dramatically, computer storage, and linearizing the nonlinear model. Furthermore the optimal trajectories are identified with minimizing energy consumption and enabling high speed capability. Numerical simulations are conducted to validate the theoretical analysis

    Molecular Structure of Pyrazinamide: A Critical Assessment of Modern Gas Electron Diffraction Data from Three Laboratories

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    Otlyotov AA, Girichev, Georgiy V, Rykov AN, Glodde T, Vishnevskiy Y. Molecular Structure of Pyrazinamide: A Critical Assessment of Modern Gas Electron Diffraction Data from Three Laboratories. JOURNAL OF PHYSICAL CHEMISTRY A. 2020;124(25):5204-5211.Accuracy and precision of molecular parameters determined by modern gas electron diffraction have been investigated. Diffraction patterns of gaseous pyrazinamide have been measured independently in three laboratories, in Bielefeld (Germany), Ivanovo (Russia), and Moscow (Russia). All data sets have been analyzed in equal manner using a highly controlled background elimination procedure and flexible restraints in molecular structure refinement. In detailed examination and comparison of the obtained results we have determined the average experimental precision of 0.004 angstrom for bond lengths and 0.2 degrees for angles. The corresponding average deviations of the refined parameters from the ae-CCSD(T)/cc-pwCVTZ theoretical values were 0.003 angstrom and 0.2 degrees. The average precision for refined amplitudes of interatomic vibrations was determined to be 0.005 angstrom. It is recommended to take into account these values in calculations of total errors for refined parameters of other molecules with comparable complexity

    Emotional bias training as a treatment for anxiety and depression: evidence from experimental medicine studies in healthy and medicated samples.

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    BACKGROUND: Anxiety and depression are leading causes of disability worldwide, yet individuals are often unable to access appropriate treatment. There is a need to develop effective interventions that can be delivered remotely. Previous research has suggested that emotional processing biases are a potential target for intervention, and these may be altered through brief training programs. METHODS: We report two experimental medicine studies of emotional bias training in two samples: individuals from the general population (n = 522) and individuals currently taking antidepressants to treat anxiety or depression (n = 212). Participants, recruited online, completed four sessions of EBT from their own home. Mental health and cognitive functioning outcomes were assessed at baseline, immediately post-training, and at 2-week follow-up. RESULTS: In both studies, our intervention successfully trained participants to perceive ambiguous social information more positively. This persisted at a 2-week follow-up. There was no clear evidence that this change in emotional processing transferred to improvements in symptoms in the primary analyses. However, in both studies, there was weak evidence for improved quality of life following EBT amongst individuals with more depressive symptoms at baseline. No clear evidence of transfer effects was observed for self-reported daily stress, anhedonia or depressive symptoms. Exploratory analyses suggested that younger participants reported greater treatment gains. CONCLUSIONS: These studies demonstrate the effectiveness of delivering a multi-session online training program to promote lasting cognitive changes. Given the inconsistent evidence for transfer effects, EBT requires further development before it can be considered as a treatment for anxiety and depression

    Isolation of singlet carbene derived 2-phospha-1,3-butadienes and their sequential one-electron oxidation to radical cations and dications

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    A synthetic strategy for the 2-phospha-1,3-butadiene derivatives [{(IPr)C(Ph)}P(cAACMe^{Me})] (3a) and [{(IPr)C(Ph)}P(cAACCy^{Cy})] (3b) (IPr = C{(NDipp)CH}2_{2}, Dipp = 2,6-iPr2_{2}C6_{6}H3_{3}; cAACMe^{Me} = C{(NDipp)CMe2_{2}CH2_{2}CMe2_{2}}; cAACCy^{Cy} = C{(NDipp)CMe2_{2}CH2_{2}C(Cy)}, Cy = cyclohexyl) containing a C=C–P=C framework has been established. Compounds 3a and 3b have a remarkably small HOMO–LUMO energy gap (3a: 5.09; 3b: 5.05 eV) with a very high-lying HOMO (-4.95 eV for each). Consequently, 3a and 3b readily undergo one-electron oxidation with the mild oxidizing agent GaCl3_{3} to afford radical cations [{(IPr)C(Ph)}P(cAACR^{R})]GaCl4_{4} (R = Me 4a, Cy 4b) as crystalline solids. The main UV-vis absorption band for 4a and 4b is red-shifted with respect to that of 3a and 3b, which is associated with the SOMO related transitions. The EPR spectra of compounds 4a and 4b each exhibit a doublet due to coupling of the unpaired electron with the 31^{31}P nucleus. Further oneelectron removal from the radical cations 4a and 4b is also feasible with GaCl3_{3}, affording the dications [{(IPr)C(Ph)}P(cAACR^{R})](GaCl4_{4})2_{2} (R = Me 5a, Cy 5b) as yellow crystals. The molecular structures of compounds 3–5 have been determined by X-ray diffraction and analyzed by DFT calculations

    Emotional bias training as a treatment for anxiety and depression:evidence from experimental medicine studies in healthy and medicated samples

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    BACKGROUND: Anxiety and depression are leading causes of disability worldwide, yet individuals are often unable to access appropriate treatment. There is a need to develop effective interventions that can be delivered remotely. Previous research has suggested that emotional processing biases are a potential target for intervention, and these may be altered through brief training programs. METHODS: We report two experimental medicine studies of emotional bias training in two samples: individuals from the general population (n = 522) and individuals currently taking antidepressants to treat anxiety or depression (n = 212). Participants, recruited online, completed four sessions of EBT from their own home. Mental health and cognitive functioning outcomes were assessed at baseline, immediately post-training, and at 2-week follow-up. RESULTS: In both studies, our intervention successfully trained participants to perceive ambiguous social information more positively. This persisted at a 2-week follow-up. There was no clear evidence that this change in emotional processing transferred to improvements in symptoms in the primary analyses. However, in both studies, there was weak evidence for improved quality of life following EBT amongst individuals with more depressive symptoms at baseline. No clear evidence of transfer effects was observed for self-reported daily stress, anhedonia or depressive symptoms. Exploratory analyses suggested that younger participants reported greater treatment gains. CONCLUSIONS: These studies demonstrate the effectiveness of delivering a multi-session online training program to promote lasting cognitive changes. Given the inconsistent evidence for transfer effects, EBT requires further development before it can be considered as a treatment for anxiety and depression

    Infections with Avian Pathogenic and Fecal Escherichia coli Strains Display Similar Lung Histopathology and Macrophage Apoptosis

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    The purpose of this study was to compare histopathological changes in the lungs of chickens infected with avian pathogenic (APEC) and avian fecal (Afecal) Escherichia coli strains, and to analyze how the interaction of the bacteria with avian macrophages relates to the outcome of the infection. Chickens were infected intratracheally with three APEC strains, MT78, IMT5155, and UEL17, and one non-pathogenic Afecal strain, IMT5104. The pathogenicity of the strains was assessed by isolating bacteria from lungs, kidneys, and spleens at 24 h post-infection (p.i.). Lungs were examined for histopathological changes at 12, 18, and 24 h p.i. Serial lung sections were stained with hematoxylin and eosin (HE), terminal deoxynucleotidyl dUTP nick end labeling (TUNEL) for detection of apoptotic cells, and an anti-O2 antibody for detection of MT78 and IMT5155. UEL17 and IMT5104 did not cause systemic infections and the extents of lung colonization were two orders of magnitude lower than for the septicemic strains MT78 and IMT5155, yet all four strains caused the same extent of inflammation in the lungs. The inflammation was localized; there were some congested areas next to unaffected areas. Only the inflamed regions became labeled with anti-O2 antibody. TUNEL labeling revealed the presence of apoptotic cells at 12 h p.i in the inflamed regions only, and before any necrotic foci could be seen. The TUNEL-positive cells were very likely dying heterophils, as evidenced by the purulent inflammation. Some of the dying cells observed in avian lungs in situ may also be macrophages, since all four avian E. coli induced caspase 3/7 activation in monolayers of HD11 avian macrophages. In summary, both pathogenic and non-pathogenic fecal strains of avian E. coli produce focal infections in the avian lung, and these are accompanied by inflammation and cell death in the infected areas

    Physicochemical and Biological Evaluation of siRNA Polyplexes Based on PEGylated Poly(amido amine)s

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    PURPOSE: Use of RNA interference as novel therapeutic strategy is hampered by inefficient delivery of its mediator, siRNA, to target cells. Cationic polymers have been thoroughly investigated for this purpose but often display unfavorable characteristics for systemic administration, such as interactions with serum and/or toxicity. METHODS: We report the synthesis of a new PEGylated polymer based on biodegradable poly(amido amine)s with disulfide linkages in the backbone. Various amounts of PEGylated polymers were mixed with their unPEGylated counterparts prior to polyplex formation to alter PEG content in the final complex. RESULTS: PEGylation effectively decreased polyplex surface charge, salt- or serum-induced aggregation and interaction with erythrocytes. Increasing amount of PEG in formulation also reduced its stability against heparin displacement, cellular uptake and subsequent silencing efficiency. Yet, for polyplexes with high PEG content, significant gene silencing efficacy was found, which was combined with almost no toxicity. CONCLUSIONS: PEGylated poly(amido amine)s are promising carriers for systemic siRNA delivery in vivo

    Chitosan-Graft-Branched Polyethylenimine Copolymers: Influence of Degree of Grafting on Transfection Behavior

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    BACKGROUND: Successful non-viral gene delivery currently requires compromises to achieve useful transfection levels while minimizing toxicity. Despite high molecular weight (MW) branched polyethylenimine (bPEI) is considered the gold standard polymeric transfectant, it suffers from high cytotoxicity. Inversely, its low MW counterpart is less toxic and effective in transfection. Moreover, chitosan is a highly biocompatible and biodegradable polymer but characterized by very low transfection efficiency. In this scenario, a straightforward approach widely exploited to develop effective transfectants relies on the synthesis of chitosan-graft-low MW bPEIs (Chi-g-bPEI(x)) but, despite the vast amount of work that has been done in developing promising polymeric assemblies, the possible influence of the degree of grafting on the overall behavior of copolymers for gene delivery has been largely overlooked. METHODOLOGY/PRINCIPAL FINDINGS: With the aim of providing a comprehensive evaluation of the pivotal role of the degree of grafting in modulating the overall transfection effectiveness of copolymeric vectors, we have synthesized seven Chi-g-bPEI(x) derivatives with a variable amount of bPEI grafts (minimum: 0.6%; maximum: 8.8%). Along the Chi-g-bPEI(x) series, the higher the degree of grafting, the greater the ζ-potential and the cytotoxicity of the resulting polyplexes. Most important, in all cell lines tested the intermediate degree of grafting of 2.7% conferred low cytotoxicity and higher transfection efficiency compared to other Chi-g-bPEI(x) copolymers. We emphasize that, in transfection experiments carried out in primary articular chondrocytes, Chi-g-bPEI(2.7%) was as effective as and less cytotoxic than the gold standard 25 kDa bPEI. CONCLUSIONS/SIGNIFICANCE: This work underlines for the first time the pivotal role of the degree of grafting in modulating the overall transfection effectiveness of Chi-g-bPEI(x) copolymers. Crucially, we have demonstrated that, along the copolymer series, the fine tuning of the degree of grafting directly affected the overall charge of polyplexes and, altogether, had a direct effect on cytotoxicity
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