Neurotransmission at dopaminergic synapses has been studied with techniques that provide high temporal resolution but cannot resolve individual synapses. To elucidate the spatial dynamics and heterogeneity of individual dopamine boutons, we developed fluorescent false neurotransmitter 200 (FFN200), a vesicular monoamine transporter 2 (VMAT2) substrate that is the first probe to selectively trace monoamine exocytosis in both neuronal cell culture and brain tissue. By monitoring electrically-evoked Ca2+ transients with GCaMP3 and FFN200 release simultaneously, we find that only a small fraction of dopamine boutons that exhibit Ca2+ influx engage in exocytosis, a result confirmed with activity-dependent loading of the endocytic probe FM 1-43. Thus, only a low fraction of striatal dopamine axonal sites with uptake-competent VMAT2 vesicles are capable of transmitter release. This is consistent with the presence of functionally “silent” dopamine vesicle clusters and represents a first report suggestive of presynaptically silent neuromodulatory synapses.
Previous studies on how framing differentially affects consumer perceptions of value from equivalent deals indicate that perceptions of deal value from price-saving versus extra-product promotions are moderated by the stock-up characteristic of the category. In this study, the authors explored the relationship between stock-up characteristic and frame preference and the influence of the consumable nature of goods on frame preference. An experiment involving 223 student participants showed that consumable nature, but not stock-up characteristic, affected frame preference. The authors discuss the implications of this finding for the study of information framing and how it impacts consumer judgment and decision making.
In recent years, with the development of mobile devices, the location based services (LBSs) have become more and more prevailing and most applications installed on these devices call for location information. Yet, the untrusted LBS provider can collect these location information, which may potentially threaten users' location privacy. In view of this challenge, we propose a two-tier schema for the privacy preservation based on k−anonymity principle meanwhile reduce the cost for privacy protection. Concretely, we divide the users into groups in order to maximize the privacy level and in each group one proxy is selected to generate dummy locations and share the returned results from LBS provider; then, on each group, an auction mechanism is proposed to determine the payment of each user to the proxy as the compensation, which satisfies budget balance and incentive compatibility. To evalue the performance of the proposed schema, a simulated experiment is conducted.
AIMTo systematically evaluate the prognostic-predictive capability of Bcl-2 in colorectal cancer (CRC).METHODSA systematic literature search was conducted using PubMed, Web of Science and EMBASE databases. Any eligible study must meet the following criteria: (1) bcl-2 expression was evaluated in human CRC tissues by immunohistochemistry; (2) assessment of the relationships between bcl-2 expression and overall survival (OS), disease free survival (DFS), recurrent free survival (RFS) or clinic-pathological characteristics of CRC was included; (3) sufficient information was provided to estimate the hazard ratio (HR) or odds ratio and their 95% confidence intervals (CIs); and (4) the study was published in English. The impact of Bcl-2 expression on survival of CRC patients were evaluated through this meta-analysis.RESULTSA total of 40 eligible articles involving 7658 patients were enrolled in our final analysis. We drew the conclusion that Bcl-2 high expression was significantly correlated with favorable OS (pooled HR = 0.69, 95%CI: 0.55-0.87, P = 0.002) and better DFS/RFS (pooled HR = 0.65, 95%CI: 0.50-0.85, P = 0.001). Additionally, the subgroup analysis suggested that Bcl-2 overexpression was significantly associated with prognosis (OS) especially in patients came from Europe and America but not Asian and patients who did not receive any adjuvant therapy before surgery. Finally, our present results indicated that expression of bcl-2 protein was associated with high differentiation grade and A/B Ducks’ stage.CONCLUSIONBcl-2 high expression was significantly correlated with favorable OS and better DFS/RFS. Hence, we propose that Bcl-2 may be a valuable prognostic-predictive marker in CRC.
In this paper, an optimal control algorithm is designed for uncertain nonlinear systems in discrete-time, which are in nonaffine form and with unknown dead-zone. The main contributions of this paper are that an optimal control algorithm is for the first time framed in this paper for nonlinear systems with nonaffine dead-zone, and the adaptive parameter law for dead-zone is calculated by using the gradient rules. The mean value theory is employed to deal with the nonaffine dead-zone input and the implicit function theory based on reinforcement learning is appropriately introduced to find an unknown ideal controller which is approximated by using the action network. Other neural networks are taken as the critic networks to approximate the strategic utility functions. Based on the Lyapunov stability analysis theory, we can prove the stability of systems, i.e., the optimal control laws can guarantee that all the signals in the closed-loop system are bounded and the tracking errors are converged to a small compact set. Finally, two simulation examples demonstrate the effectiveness of the design algorithm.
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