Changes in P2Y purinoreceptor-mediated intracellular calcium signal pathways results in inositol-1, 4, 5-triphosphate-sensitive calcium stores in rat small trigeminal ganglion neurons

BACKGROUND: Most of the currently available information on purinergic receptors (P2Rs) involved in pain transmission is based on results obtained in dorsal root ganglion or the spinal cord. However, the mechanism of P2Rs in trigeminal neuralgia remains unclear. OBJECTIVE: To investigate changes in the P2R-mediated calcium signaling pathway in nociceptive trigeminal ganglion neurons. DESIGN, TIME AND SETTING: In vitro experiments were conducted at the Patch-Clamp Laboratory of Comprehensive Experiment Center of Anhui Medical University, China from September 2008 to June 2009. MATERIALS: Thapsigargin, caffeine, suramin, and adenosine 5’-triphosphate were purchased from Sigma, USA. METHODS: Using Fura-2-based microfluorimetry, intracellular calcium concentration ([Ca2+]i) was measured in freshly isolated adult rat small trigeminal ganglion neurons before and after drug application. MAIN OUTCOME MEASURES: Fluorescent intensities were expressed as the ratio F340/F380 to observe [Ca2+]i changes. RESULTS: In normal extracellular solution and Ca2+-free solution, application of thapsigargin (1 μmol/L), a sarcoplasmic reticulum Ca2+ pump adenosine 5’-triphosphate inhibitor, as well as caffeine (20 mmol/L), a ryanodine receptor agonist, triggered [Ca2+]i increase in small trigeminal ganglion neurons. A similar response was induced by application of adenosine 5’-triphosphate (100 μmol/L). In Ca2+-free conditions, adenosine 5’-triphosphate-induced [Ca2+]i transients in small trigeminal ganglion neurons were inhibited in cells pre-treated with thapsigargin (P < 0.01), but not by caffeine (P > 0.05). In normal, extracellular solution, adenosine 5’-triphosphate-induced [Ca2+]i transients in small trigeminal ganglion neurons were partly inhibited in cells pre-treated with thapsigargin (P < 0.05). CONCLUSION: Inositol-1, 4, 5-triphosphate (IP3)- and ryanodine-sensitive Ca2+ stores exist in rat nociceptive trigeminal ganglion neurons. Two pathways are involved in the purinoreceptor-mediated [Ca2+]i rise observed in nociceptive trigeminal ganglion neurons. One pathway involves the metabotropic P2Y receptors, which are associated with the IP3 sensitive Ca2+store, and the second pathway is coupled to ionotropic P2X receptors that induce the Ca2+ influx.

A Stochastic Programming Strategy in Microgrid Cyber Physical Energy System for Energy Optimal Operation

This paper focuses on the energy optimal operation problem of microgrids(MGs) under stochastic environment.The deterministic method of MGs operation is often uneconomical because it fails to consider the high randomness of unconventional energy resources.Therefore,it is necessary to develop a novel operation approach combining the uncertainty in the physical world with modeling strategy in the cyber system.This paper proposes an energy scheduling optimization strategy based on stochastic programming model by considering the uncertainty in MGs.The goal is to minimize the expected operation cost of MGs.The uncertainties are modeled based on autoregressive moving average(ARMA) model to expose the effects of physical world on cyber world.Through the comparison of the simulation results with deterministic method,it is shown that the effectiveness and robustness of proposed stochastic energy scheduling optimization strategy for MGs are valid.

MAS Based Distributed Automatic Generation Control for Cyber-Physical Microgrid System

The microgrid is a typical cyber-physical microgrid system(CPMS). The physical unconventional distributed generators(DGs) are intermittent and inverter-interfaced which makes them very different to control. The cyber components,such as the embedded computer and communication network,are equipped with DGs, to process and transmit the necessary information for the controllers. In order to ensure system-wide observability, controllability and stabilization for the microgrid,the cyber and physical component need to be integrated. For the physical component of CPMS, the droop-control method is popular as it can be applied in both modes of operation to improve the grid transient performance. Traditional droop control methods have the drawback of the inherent trade-off between power sharing and voltage and frequency regulation. In this paper, the global information(such as the average voltage and the output active power of the microgrid and so on) are acquired distributedly based on multi-agent system(MAS). Based on the global information from cyber components of CPMS, automatic generation control(AGC) and automatic voltage control(AVC)are proposed to deal with the drawback of traditional droop control. Simulation studies in PSCAD demonstrate the effectiveness of the proposed control methods.

Ultrafast electron microscopy in material science

Recent advances in the ultrafast transmission electron microscope(UTEM), with combined spatial and temporal resolutions, have made it possible to directly visualize the atomic, electronic, and magnetic structural dynamics of materials.In this review, we highlight the recent progress of UTEM techniques and their applications to a variety of material systems.It is emphasized that numerous significant ultrafast dynamic issues in material science can be solved by the integration of the pump–probe approach with the well-developed conventional transmission electron microscopy(TEM) techniques. For instance, UTEM diffraction experiments can be performed to investigate photoinduced atomic-scale dynamics, including the chemical reactions, non-equilibrium phase transition/melting, and lattice phonon coupling. UTEM imaging methods are invaluable for studying, in real space, the elementary processes of structural and morphological changes, as well as magnetic-domain evolution in the Lorentz TEM mode, at a high magnification. UTEM electron energy-loss spectroscopic techniques allow the examination of the ultrafast valence states and electronic structure dynamics, while photoinduced near-field electron microscopy extends the capability of the UTEM to the regime of electromagnetic-field imaging with a high real space resolution.

Expert recommendation on collection,storage,annotation,and management of data related to medical artificial intelligence

Medical artificial intelligence(AI)and big data technology have rapidly advanced in recent years,and they are now routinely used for image-based diagnosis.China has a massive amount of medical data.However,a uniform criteria for medical data quality have yet to be established.Therefore,this review aimed to develop a standardized and detailed set of quality criteria for medical data collection,storage,annotation,and management related to medical AI.This would greatly improve the process of medical data resource sharing and the use of AI in clinical medicine.

The effect of clinical-grade retinal pigment epithelium derived from human embryonic stem cells using different transplantation strategies

Dear Editor, Many forms of sight-threatening diseases, including retinitis pigmentosa (RP) and age-related macular degeneration (AMD), are caused by the dysfunction, degeneration and loss of the retinal pigment epithelium (RPE)(Strauss, 2005). RPE cell transplantation may potentially recover or halt disease progression, in which human embryonic stem cells (hESCs) could serve as an unlimited donor source for RPE differentiation, and a few clinical trials have shown the safety and effective of transplantation of hESCs-derived RPE (hESC-RPE) for AMD patients (Schwartz et al., 2012;Schwartz etal., 2015;Song etal., 2015;da Cruz et al., 2018;Kashani et al., 2018;Liu et al., 2018).

Regulations in the United States for cell transplantation clinical trials in neurological diseases

Objective: This study aimed to use a systematic approach to evaluate the current utilization, safety, and effectiveness of cell therapies for neurological diseases in human. And review the present regulations, considering United States(US) as a representative country, for cell transplantation in neurological disease and discuss the challenges facing the field of neurology in the coming decades. Methods: A detailed search was performed in systematic literature reviews of cellular‐based therapies in neurological diseases, using Pub Med, web of science, and clinical trials. Regulations of cell therapy products used for clinical trials were searched from the Food and Drug Administration(FDA) and the National Institutes of Health(NIH).Results: Seven most common types of cell therapies for neurological diseases have been reported to be relatively safe with varying degrees of neurological recovery.And a series of regulations in US for cellular therapy was summarized including preclinical evaluations, sourcing material, stem cell manufacturing and characterization,cell therapy product, and clinical trials. Conclusions: Stem cell‐based therapy holds great promise for a cure of such diseases and will value a growing population of patients. However, regulatory permitting activity of the US in the sphere of stem cells, technologies of regenerative medicine and substitutive cell therapy are selective, theoretical and does not fit the existing norm and rules. Compiled well‐defined regulations to guide the application of stem cell products for clinical trials should be formulated.

Immunity-and-matrix-regulatory cells enhance cartilage regeneration for meniscus injuries: a phase I dose-escalation trial

Immunity-and-matrix-regulatory cells(IMRCs)derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix,which could be mass-produced with stable biological properties.Despite resemblance to mesenchymal stem cells(MSCs)in terms of self-renew and tri-lineage differentiation,the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined.Here,we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury.Following injection into the knees of rabbits with meniscal injury,IMRCs enhanced endogenous fibrocartilage regeneration.In the dose-escalating phase I clinical trial(NCT03839238)with eighteen patients recruited,we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting.Furthermore,the effective results of magnetic resonance imaging(MRI)of meniscus repair and knee functional scores suggested that 5×107 cells are optimal for meniscus injury treatment.In summary,we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury.Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.

Analysis of multi-center topological domain states in BiFeO_(3)nanodot arrays

High-density ferroelectric BiFeO_(3)(BFO)nanodot arrays were developed through template-assisted tailoring of epitaxial thin films.By combining piezoresponse force microscopy(PFM)and Kelvin probe force microscopy(KPFM)imaging techniques,we found that oxygen vacancies in nanodot arrays can be transported in the presence of an electric field.Besides triple-center domains,quadruple-center domains with different vertical polarizations were also identified.This was confirmed by combining the measurements of the domain switching and polarization vector distribution.The competition between the accumulation of mobile charges,such as oxygen vacancies,on the interface and the geometric constraints of nanodots led to the formation of these topological domain states.These abnormal multi-center topological defect states pave the way for improving the storage density of ferroelectric memory devices.

Distributed Event-triggered Secondary Control for Average Bus Voltage Regulation and Proportional Load Sharing of DC Microgrid

This paper proposes a novel distributed event-triggered secondary control method to overcome the drawbacks of primary control for direct current(DC)microgrids.With eventtriggered distributed communication,the proposed control method can achieve system-wide control of parallel distrubted generators(DGs)with two main control objectives:①estimate the average bus voltage and regulate it at the nominal value;②achieve accurate current sharing among the DGs in proportion to their power output ratings.Furthermore,the proposed control strategy can be implemented in a distributed way that shares the required tasks among the DGs.Thus,it shows the advantages of being flexible and scalable.Furthermore,this paper proposes a simple event-triggered condition that does not need extra state estimator.Thus,limited communication among neighbors is required only when the event-triggered condition is satisfied,which significantly reduces the communication burden at the cyber layer.