196 research outputs found

    Universality : exploring work value differences in the transitional economy of China

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    The universality issue of work value differences is explored in this research study which takes place in the transitional economy of China. Chinese organizations are searching for new methods of management to compete in the global market, as former state-run enterprises convert to performance-based organizations. In addition, their entry into The World Trade Organization in 2001 will accelerate opportunities for foreign trade and investment, both for China and other countries as well. This transitional status presents a myriad of opportunities for researchers to analyze the universality of their methods, models and theories on both a micro (individual) and macro (cultural) level, as well as in the organizational context. This research, which is set in Shanghai, examined work value differences on the micro (individual) and macro (cultural) level through a factor analysis and comparison with U. S. data. A MANOVA analyzed demographic variables (managerial level (supervisory v. task, work tenure, educational level, gender and age) assessing various groups\u27 traits in an organizational environment. Finally, using these findings, the universality of motivation models was conceptually developed. The Chinese work values were found to be of a collective nature with the concern of the group as an end goal. No significant differences were found in the demographic variables on the work values as the Confucian tradition and guanxi roles play an important part in the organization. Because of these findings, Western motivation models are unlikely to be an effective approach, as they are directed toward an individualist end goal

    A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.

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    Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (KD). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had KD values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018

    Extraction and inhibition of enzymatic activity of botulinum neurotoxins /B1, /B2, /B3, /B4, and /B5 by a panel of monoclonal anti-BoNT/B antibodies

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    <p>Abstract</p> <p>Background</p> <p>Botulism is caused by botulinum neurotoxins (BoNTs), extremely toxic proteins which can induce respiratory failure leading to long-term intensive care or death. Treatment for botulism includes administration of antitoxins, which must be administered early in the course of the intoxication; therefore, rapid determination of human exposure to BoNT is an important public health goal. In previous work, our laboratory reported on Endopep-MS, a mass spectrometry-based activity method for detecting and differentiating BoNT/A, /B, /E, and /F in clinical samples. We also demonstrated that antibody-capture is effective for purification and concentration of BoNTs from complex matrices such as clinical samples. However, some antibodies inhibit or neutralize the enzymatic activity of BoNT, so the choice of antibody for toxin extraction is critical.</p> <p>Results</p> <p>In this work, we evaluated 24 anti-BoNT/B monoclonal antibodies (mAbs) for their ability to inhibit the <it>in vitro </it>activity of BoNT/B1, /B2, /B3, /B4, and /B5 and to extract those toxins. Among the mAbs, there were significant differences in ability to extract BoNT/B subtypes and inhibitory effect on BoNT catalytic activity. Some of the mAbs tested enhanced the <it>in vitro </it>light chain activity of BoNT/B, suggesting that BoNT/B may undergo conformational change upon binding some mAbs.</p> <p>Conclusions</p> <p>In addition to determining <it>in vitro </it>inhibition abilities of a panel of mAbs against BoNT/B1-/B5, this work has determined B12.2 and 2B18.2 to be the best mAbs for sample preparation before Endopep-MS. These mAb characterizations also have the potential to assist with mechanistic studies of BoNT/B protection and treatment, which is important for studying alternative therapeutics for botulism.</p

    Double-Pionic Fusion of Nuclear Systems and the ABCEffect -- Aproaching a Puzzle by Exclusive and Kinematically Complete Measurements

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    The ABC effect - a puzzling low-mass enhancement in the ππ\pi\pi invariant mass spectrum - is well-known from inclusive measurements of two-pion production in nuclear fusion reactions. Here we report on first exclusive and kinematically complete measurements of the most basic double pionic fusion reaction pndπ0π0pn \to d \pi^0\pi^0 at 1.03 and 1.35 GeV. The measurements, which have been carried out at CELSIUS-WASA, reveal the ABC effect to be a (ππ)I=L=0(\pi\pi)_{I=L=0} channel phenomenon associated with both a resonance-like energy dependence in the integral cross section and the formation of a ΔΔ\Delta\Delta system in the intermediate state. A corresponding simple s-channel resonance ansatz provides a surprisingly good description of the data

    Extraction and Inhibition of Enzymatic Activity of Botulinum Neurotoxins/A1, /A2, and /A3 by a Panel of Monoclonal Anti-BoNT/A Antibodies

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    Botulinum neurotoxins (BoNTs) are extremely potent toxins that are capable of causing death or respiratory failure leading to long-term intensive care. Treatment includes serotype-specific antitoxins, which must be administered early in the course of the intoxication. Rapidly determining human exposure to BoNT is an important public health goal. In previous work, our laboratory focused on developing Endopep-MS, a mass spectrometry-based endopeptidase method for detecting and differentiating BoNT/A–G serotypes in buffer and BoNT/A, /B, /E, and /F in clinical samples. We have previously reported the effectiveness of antibody-capture to purify and concentrate BoNTs from complex matrices, such as clinical samples. Because some antibodies inhibit or neutralize the activity of BoNT, the choice of antibody with which to extract the toxin is critical. In this work, we evaluated a panel of 16 anti-BoNT/A monoclonal antibodies (mAbs) for their ability to inhibit the in vitro activity of BoNT/A1, /A2, and /A3 complex as well as the recombinant LC of A1. We also evaluated the same antibody panel for the ability to extract BoNT/A1, /A2, and /A3. Among the mAbs, there were significant differences in extraction efficiency, ability to extract BoNT/A subtypes, and inhibitory effect on BoNT catalytic activity. The mAbs binding the C-terminal portion of the BoNT/A heavy chain had optimal properties for use in the Endopep-MS assay
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