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In order to improve the accuracy of the teaching effect evaluation, a teaching effect evaluation model based on the intelligent fuzzy system is designed. The evaluation index are selected based on the teaching situation of physical education courses, relevant national policy documents, subject textbooks, intelligent fuzzy system to modify the index system through expert interview, determine the weight coefficient of each index by hierarchical analysis method (AHP), and calculate the single layer and total ranking of the index matrix to realize the evaluation of physical education courses. The test results show that the fuzzy evaluation accuracy of the proposed model is above 95.63%, with high evaluation performance and strong utility.

Patients with coronavirus disease 2019 (COVID-19) commonly have manifestations of heart disease. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome encodes 27 proteins. Currently, SARS-CoV-2 gene-induced abnormalities of human heart muscle cells remain elusive. Here, we comprehensively characterized the detrimental effects of a SARS-CoV-2 gene, Orf9c, on human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) by preforming multi-omic analyses. Transcriptomic analyses of hPSC-CMs infected by SARS-CoV-2 with Orf9c overexpression (Orf9c

MXenes are an emerging family of transition-metal carbides, nitrides, and carbonitrides that are promising for a variety of applications, including energy storage, gas sensors, and electromagnetic interference shielding. A recent report on a very high breakdown current density of ∼1.2 × 108 A cm–2 in Ti3C2Tx further extended the list of potential applications of MXenes to miniaturized on-chip interconnects. In this study, we investigated another promising member of the MXene family, Nb4C3Tx, and found that it also has a very high breakdown current density of ∼1.1 × 108 A cm–2, which is comparable to that of Ti3C2Tx and other highly conductive two-dimensional materials, such as graphene. The measurements were performed on electronic devices based on individual monolayer flakes of Nb4C3Tx, which were tested at gradually increasing voltages until the electrical breakdown was observed. The morphology of Nb4C3Tx devices after the breakdown was studied by microscopic techniques. The high breakdown current densities of Ti3C2Tx and Nb4C3Tx suggest that other members of the large MXene family likely possess this property and could be employed in applications utilizing their high current-carrying capacity.

An experimental research on the condensation heat transfer characteristic of surface chromium-plated tube was put forwards with non condensation gas. The experimental result suggests that the factors of pressure, air mass fraction and wall subcooling affect the condensation heat transfer process of surface chromium-plated tube, which is similar to that of stainless steel tube. In addition, by comparing with the stainless steel tube, the chromium-plated tube condensation heat transfer capacity changes more obviously with the variation of air mass fraction. That is to say, under the low air mass fraction condition, due to the existence of non condensation gas layer, the difference between those two tube-types is little; but under the high air mass fraction condition, the condensation heat transfer capacity of surface chromium-plated tube is higher than stainless steel tubes lightly. At last, by fitting the experimental data, the empirical formula of condensation heat transfer of surface chrome-plated tube under the condition of non condensing gas is obtained. The deviation is less than 20%.

Natural circulation is widely used in the many industries owing to inherent safety. A typical case is Passive Containment Cooling System in the Chinese third-generation nuclear plant HPR1000. It uses an open natural circulation structure and contains an inner-containment heat exchanger, an outer-containment altitude water tank and connecting pipes. The altitude water tank connects with atmosphere, making its operation pressure is atmospheric pressure. For designing such an open natural circulation system, the steady-state flow behavior of of which is an important evaluate indicator, because it can directly reflect the flow capacity and heat transfer capacity of the PCS system. Considering that the long-term stable operating condition of the PCS system is the boiling-driven open natural circulation flow. Therefore, it is of significance to study the steady-state flow characteristics of the boiling-driven open natural circulation system. In this paper, a theoretical formula to determine the steady-state flow behavior of a open boiling-driven natural circulation. Due to the lack of condensation process of two-phase circulation fluid, the integral result of steady momentum equation is not equal to zero. A special formula processing of accelerated pressure drop integral result is taken in this paper during the formula derivation process. The theoretical analysis results of which were validated by the experimental data. This paper aims at providing technical support for the design of open natural circulation systems.

Allelic series are extremely valuable genetic tools to study gene function and identify essential structural features of gene products. In mice, allelic series have been engineered using conventional gene targeting in embryonic stem cells or chemical mutagenesis. While these approaches have provided valuable information about the function of genes, they remain cumbersome. Modern approaches such as CRISPR-Cas9 technologies now allow for the precise and cost-effective generation of mouse models with specific mutations, facilitating the development of allelic series. Here, we describe procedures for the generation of three types of mutations used to dissect protein function in vivo using CRISPR-Cas9 technology. This step-by-step protocol describes the generation of missense mutations, large in-frame deletions, and insertions of genetic material using SCY1-like 1 (Scyl1) as a model gene.

Complex oxide heterointerfaces and van der Waals heterostructures present two versatile but intrinsically different platforms for exploring emergent quantum phenomena and designing new functionalities. The rich opportunity offered by the synergy between these two classes of materials, however, is yet to be charted. Here, we report an unconventional nonlinear optical filtering effect resulting from the interfacial polar alignment between monolayer MoS$_2$ and a neighboring ferroelectric oxide thin film. The second harmonic generation response at the heterointerface is either substantially enhanced or almost entirely quenched by an underlying ferroelectric domain wall depending on its chirality, and can be further tailored by the polar domains. Unlike the extensively studied coupling mechanisms driven by charge, spin, and lattice, the interfacial tailoring effect is solely mediated by the polar symmetry, as well explained via our density functional theory calculations, pointing to a new material strategy for the functional design of nanoscale reconfigurable optical applications., 22 pages, 4 figures

Internet of things technology can not only improve people’s lives, but also bring great changes and innovations to the industry and promote the rapid development of economy. The future communication system will be a system of everything connected with IoT. There will be various types of user equipment in the system. The standards adopted by different types of equipment are different, and the required business levels are also different. This will bring great challenges to the resource allocation of the system. Artificial intelligence algorithms provide technical support for future intelligent wireless systems. The system can select appropriate artificial intelligence algorithms according to different application scenarios and establish more accurate mathematical models to serve the network. According to the business priority analysis of user equipment under the wide area Internet of things, considering the user scheduling as the constraint condition, a high-altitude platform user equipment scheduling model based on artificial intelligence k-means algorithm under the user scheduling constraint condition is established. Based on the user equipment scheduling model of high-altitude platform based on artificial intelligence k-means algorithm, a two-stage K-means improved algorithm is proposed to cluster the user equipment of wide area Internet of things, which is divided into preprocessing training stage and K-means algorithm clustering stage. The initial center value is not randomly selected. In the preprocessing training stage, the scheduling priority of each user is obtained according to the channel environment and packet length of the user equipment. The first k user equipment with the same scheduling priority is used as the initial clustering points to complete the preprocessing training. Then, K-means algorithm is used to cluster the new user equipment to be scheduled until convergence. The intelligent scheduling of user equipment under the wide area Internet of things is realized.

We report the effect of remote surface optical (RSO) phonon scattering on carrier mobility in monolayer graphene gated by ferroelectric oxide. We fabricate monolayer graphene transistors back-gated by epitaxial (001) Ba0.6Sr0.4TiO3 films, with field effect mobility up to 23 000 cm2 V−1 s−1 achieved. Switching ferroelectric polarization induces nonvolatile modulation of resistance and quantum Hall effect in graphene at low temperatures. Ellipsometry spectroscopy studies reveal four pairs of optical phonon modes in Ba0.6Sr0.4TiO3, from which we extract RSO phonon frequencies. The temperature dependence of resistivity in graphene can be well accounted for by considering the scattering from the intrinsic longitudinal acoustic phonon and the RSO phonon, with the latter dominated by the mode at 35.8 meV. Our study reveals the room temperature mobility limit of ferroelectric-gated graphene transistors imposed by RSO phonon scattering.

Background & Aims: Liver fibrosis is a pathological healing process resulting from hepatic stellate cell (HSC) activation and the generation of myofibroblasts from activated HSCs. The precise underlying mechanisms of liver fibrogenesis are still largely vague due to lack of understanding the functional heterogeneity of activated HSCs during liver injury. Approach and Results: In this study, to define the mechanism of HSC activation, we performed the transcriptomic analysis at single-cell resolution (scRNA-seq) on HSCs in mice treated with carbon tetrachloride (CCl4). By employing LRAT-Cre:Rosa26mT/mG mice, we were able to isolate an activated GFP-positive HSC lineage derived cell population by fluorescence-activated cell sorter (FACS). A total of 8 HSC subpopulations were identified based on an unsupervised analysis. Each HSC cluster displayed a unique transcriptomic profile, despite all clusters expressing common mouse HSC marker genes. We demonstrated that one of the HSC subpopulations expressed high levels of mitosis regulatory genes, velocity, and monocle analysis indicated that these HSCs are at transitioning and proliferating phases at the beginning of HSCs activation and will eventually give rise to several other HSC subtypes. We also demonstrated cell clusters representing HSC-derived mature myofibroblast populations that express myofibroblasts hallmark genes with unique contractile properties. Most importantly, we found a novel HSC cluster that is likely to be critical in liver regeneration, immune reaction, and vascular remodeling, in which the unique profiles of genes such as Rgs5, Angptl6, and Meg3 are highly expressed. Lastly, we demonstrated that the heterogeneity of HSCs in the injured mouse livers is closely similar to that of cirrhotic human livers. Conclusions: Collectively, our scRNA-seq data provided insight into the landscape of activated HSC populations and the dynamic transitional pathway from HSC to myofibroblasts in response to liver injury.

Ventricular trabeculation and compaction are two essential morphogenetic events for generating a functionally competent ventricular wall. A significant reduction in trabeculation is usually associated with hypoplastic wall and ventricular compact zone deficiencies, which commonly leads to embryonic heart failure and early embryonic lethality. In contrast, the arrest of ventricular wall compaction (noncompaction) is believed to be causative to the left ventricular noncompaction (LVNC), a genetically heterogeneous disorder and the third most common cardiomyopathy among pediatric patients. After critically reviewing recent findings from genetically engineered mouse models, we suggest a model which proposes that defects in myofibrillogenesis and polarization in trabecular cardiomyocytes underlies the common pathogenic mechanism for ventricular noncompaction.

Natural circulation design is widely used in the passive safety systems of advanced nuclear power reactors. The irregular and chaotic flow oscillations are often observed in boiling natural circulation systems so it is difficult for operators to monitor and predict the condition of these systems. An online condition forecasting method for natural circulation system is proposed in this study as an assisting technique for plant operators. The proposed prediction approach was developed based on Ensemble of Online Sequential Extreme Learning Machine (EOS-ELM) and phase space reconstruction. Online Sequential Extreme Learning Machine (OS-ELM) is an online sequential learning neural network algorithm and EOS-ELM is the ensemble method of it. The proposed condition prediction method can be initiated by a small chunk of monitoring data and it can be updated by newly arrived data at very fast speed during the online prediction. Simulation experiments were conducted on the data of two natural circulation loops to validate the performance of the proposed method. The simulation results show that the proposed predication model can successfully recognize different types of flow oscillations and accurately forecast the trend of monitored plant variables. The influence of the number of hidden nodes and neural network inputs on prediction performance was studied and the proposed model can achieve good accuracy in a wide parameter range. Moreover, the comparison results show that the proposed condition prediction method has much faster online learning speed and better prediction accuracy than conventional neural network model.

Bone morphogenetic protein 10 (BMP10) is a cardiac peptide growth factor belonging to the transforming growth factor β superfamily that critically controls cardiovascular development, growth, and maturation. It has been shown that BMP10 elicits its intracellular signaling through a receptor complex of activin receptor-like kinase 1 with morphogenetic protein receptor type II or activin receptor type 2A. Previously, we generated and characterized a transgenic mouse line expressing BMP10 from the α-myosin heavy chain gene promoter and found that these mice have normal cardiac hypertrophic responses to both physiological and pathological stimuli. In this study, we report that these transgenic mice exhibit significantly reduced levels of cardiomyocyte apoptosis and cardiac fibrosis in response to a prolonged administration of the β-adrenoreceptor agonist isoproterenol. We further confirmed this cardioprotective function with a newly generated conditional Bmp10 transgenic mouse line, in which Bmp10 was activated in adult hearts by tamoxifen. Moreover, the intraperitoneal administration of recombinant human BMP10 was found to effectively protect hearts from injury, suggesting potential therapeutic utility of using BMP10 to prevent heart failure. Gene profiling and biochemical analyses indicated that BMP10 activates the SMAD-mediated canonical pathway and, unexpectedly, also the signal transducer and activator of transcription 3 (STAT3)–mediated signaling pathway both in vivo and in vitro. Additional findings further supported the notion that BMP10's cardioprotective function likely is due to its dual activation of SMAD- and STAT3-regulated signaling pathways, promoting cardiomyocyte survival and suppressing cardiac fibrosis.

Complex oxide heterointerfaces and van der Waals heterostructures present two versatile but intrinsically different platforms for exploring emergent quantum phenomena and designing new functionalities. The rich opportunity offered by the synergy between these two classes of materials, however, is yet to be charted. Here, we report an unconventional nonlinear optical filtering effect resulting from the interfacial polar alignment between monolayer MoS2 and a neighboring ferroelectric oxide thin film. The second harmonic generation response at the heterointerface is either substantially enhanced or almost entirely quenched by an underlying ferroelectric domain wall depending on its chirality, and can be further tailored by the polar domains. Unlike the extensively studied coupling mechanisms driven by charge, spin, and lattice, the interfacial tailoring effect is solely mediated by the polar symmetry, as well explained via our density functional theory calculations, pointing to a new material strategy for the functional design of nanoscale reconfigurable optical applications., The heterointerface between complex oxides and van der Waals materials presents a versatile platform for exploring new functionalities. Here, the authors report an unconventional nonlinear optical filtering effect resulting from the interfacial polar alignment between monolayer MoS2 and a ferroelectric oxide thin film.

Background CRISPR-Cas9 gene-editing technology has facilitated the generation of knockout mice, providing an alternative to cumbersome and time-consuming traditional embryonic stem cell-based methods. An earlier study reported up to 16% efficiency in generating conditional knockout (cKO or floxed) alleles by microinjection of 2 single guide RNAs (sgRNA) and 2 single-stranded oligonucleotides as donors (referred herein as “two-donor floxing” method). Results We re-evaluate the two-donor method from a consortium of 20 laboratories across the world. The dataset constitutes 56 genetic loci, 17,887 zygotes, and 1718 live-born mice, of which only 15 (0.87%) mice contain cKO alleles. We subject the dataset to statistical analyses and a machine learning algorithm, which reveals that none of the factors analyzed was predictive for the success of this method. We test some of the newer methods that use one-donor DNA on 18 loci for which the two-donor approach failed to produce cKO alleles. We find that the one-donor methods are 10- to 20-fold more efficient than the two-donor approach. Conclusion We propose that the two-donor method lacks efficiency because it relies on two simultaneous recombination events in cis, an outcome that is dwarfed by pervasive accompanying undesired editing events. The methods that use one-donor DNA are fairly efficient as they rely on only one recombination event, and the probability of correct insertion of the donor cassette without unanticipated mutational events is much higher. Therefore, one-donor methods offer higher efficiencies for the routine generation of cKO animal models.

Cardiomyocyte-restricted overexpression of FK506-binding protein 12 transgenic (αMyHC-FKBP12) mice develop spontaneous atrial fibrillation (AF). The aim of the present study is to explore the mechanisms underlying the occurrence of AF in αMyHC-FKBP12 mice. Spontaneous AF was documented by telemetry in vivo and Langendorff-perfused hearts of αMyHC-FKBP12 and littermate control mice in vitro. Atrial conduction velocity was evaluated by optical mapping. The patch-clamp technique was applied to determine the potentially altered electrophysiology in atrial myocytes. Channel protein expression levels were evaluated by Western blot analyses. Spontaneous AF was recorded in four of seven αMyHC-FKBP12 mice but in none of eight nontransgenic (NTG) controls. Atrial conduction velocity was significantly reduced in αMyHC-FKBP12 hearts compared with NTG hearts. Interestingly, the mean action potential duration at 50% but not 90% was significantly prolonged in αMyHC-FKBP12 atrial myocytes compared with their NTG counterparts. Consistent with decreased conduction velocity, average peak Na+ current ( INa) density was dramatically reduced and the INa inactivation curve was shifted by approximately +7 mV in αMyHC-FKBP12 atrial myocytes, whereas the activation and recovery curves were unaltered. The Nav1.5 expression level was significantly reduced in αMyHC-FKBP12 atria. Furthermore, we found increases in atrial Cav1.2 protein levels and peak L-type Ca2+ current density and increased levels of fibrosis in αMyHC-FKBP12 atria. In summary, cardiomyocyte-restricted overexpression of FKBP12 reduces the atrial Nav1.5 expression level and mean peak INa, which is associated with increased peak L-type Ca2+ current and interstitial fibrosis in atria. The combined electrophysiological and structural changes facilitated the development of local conduction block and altered action potential duration and spontaneous AF. NEW & NOTEWORTHY This study addresses a long-standing riddle regarding the role of FK506-binding protein 12 in cardiac physiology. The work provides further evidence that FK506-binding protein 12 is a critical component for regulating voltage-gated sodium current and in so doing has an important role in arrhythmogenic physiology, such as atrial fibrillation.

Protein phosphatase 5 (PP5), a serine/threonine phosphatase, has a wide range of biological functions and exhibits elevated expression in tumor cells. We previously reported that pp5-deficient mice have altered ataxia-telangiectasia mutated (ATM)-mediated signaling and function. However, this regulation was likely indirect, as ATM is not a known PP5 substrate. In the current study, we found that pp5-deficient mice are hypersensitive to genotoxic stress. This hypersensitivity was associated with the marked up-regulation of the tumor suppressor tumor protein p53 and its downstream targets cyclin-dependent kinase inhibitor 1A (p21), MDM2 proto-oncogene (MDM2), and phosphatase and tensin homolog (PTEN) in pp5-deficient tissues and cells. These observations suggested that PP5 plays a role in regulating p53 stability and function. Experiments conducted with p53(+/−)pp5(+/−) or p53(+/−)pp5(−/−) mice revealed that complete loss of PP5 reduces tumorigenesis in the p53(+/−) mice. Biochemical analyses further revealed that PP5 directly interacts with and dephosphorylates p53 at multiple serine/threonine residues, resulting in inhibition of p53-mediated transcriptional activity. Interestingly, PP5 expression was significantly up-regulated in p53-deficient cells, and further analysis of pp5 promoter activity revealed that p53 strongly represses PP5 transcription. Our results suggest a reciprocal regulatory interplay between PP5 and p53, providing an important feedback mechanism for the cellular response to genotoxic stress.

In vertebrate hearts, the ventricular trabecular myocardium develops as a sponge-like network of cardiomyocytes that is critical for contraction and conduction, ventricular septation, papillary muscle formation and wall thickening through the process of compaction1. Defective trabeculation leads to embryonic lethality2–4 or non-compaction cardiomyopathy (NCC)5. There are divergent views on when and how trabeculation is initiated in different species. In zebrafish, trabecular cardiomyocytes extrude from compact myocardium6, whereas in chicks, chamber wall thickening occurs before overt trabeculation7. In mice, the onset of trabeculation has not been described, but is proposed to begin at embryonic day 9.0, when cardiomyocytes form radially oriented ribs2. Endocardium–myocardium communication is essential for trabeculation, and numerous signalling pathways have been identified, including Notch2,8 and Neuregulin (NRG)4. Late disruption of the Notch pathway causes NCC5. Whereas it has been shown that mutations in the extracellular matrix (ECM) genes Has2 and Vcan prevent the formation of trabeculae in mice9,10 and the matrix metalloprotease ADAMTS1 promotes trabecular termination3, the pathways involved in ECM dynamics and the molecular regulation of trabeculation during its early phases remain unexplored. Here we present a model of trabeculation in mice that integrates dynamic endocardial and myocardial cell behaviours and ECM remodelling, and reveal new epistatic relationships between the involved signalling pathways. NOTCH1 signalling promotes ECM degradation during the formation of endocardial projections that are critical for individualization of trabecular units, whereas NRG1 promotes myocardial ECM synthesis, which is necessary for trabecular rearrangement and growth. These systems interconnect through NRG1 control of Vegfa, but act antagonistically to establish trabecular architecture. These insights enabled the prediction of persistent ECM and cardiomyocyte growth in a mouse NCC model, providing new insights into the pathophysiology of congenital heart disease. A new model of cardiac trabeculation in mice is presented in which NOTCH1 and NRG1 have opposing roles in extracellular matrix degradation and synthesis that are essential for defining trabecular architecture.

A mathematical separated flow model has been developed that is applicable to the annular two-phase flow in the rectangular narrow channels with peripheral heating. The theoretical annular flow model is based on the fundamental conservation principles: the mass, momentum and energy conservation equations of liquid film, and the momentum conservation equation of the vapor core. Through numerically solving the closed equations, boiling heat transfer coefficient, axial pressure gradient, liquid film thickness and velocity profiles in the liquid film are obtained. A good agreement has been found through comparing the experimental data and theoretically predicted results. The liquid film thickness will decrease with the increase of heat flux and channel width, while increases with increasing flow rate and channel height. The velocity profile in the liquid film is not linear when the thickness of the liquid film is not very thin and it increases with increasing heat flux, while decreases with the increase of mass flow rate and channel size. The effects of heat flux and channel width on velocity in the liquid film are larger than that of mass flow rate. The velocity in liquid film tends towards linear, when the liquid film is mainly in the laminar boundary layer.

The incidence of asthma is more common in boys than in girls during the childhood, and more common in premenopausal female than age-matched males. Our previous study demonstrated a gender difference in histamine-mediated neuroexcitability in nodose ganglia neurons (NGNs), highlighting a possibility of histamine-mediated gender difference in asthma via visceral afferent function. In the present study, we aimed to explore the gender difference in expression profiles of histamine receptors (HRs) in nodose ganglia (NG) and individual identified NGNs to provide deeper insights into the mechanisms involved in sexual dimorphism of asthma. Western-blot and SYBR green RT-PCR showed that H2R and H3R were highly expressed in NG of females compared with males and downregulated in ovariectomized females. H1R was equally expressed in NG of both sexes and not altered by ovariectomy. Furthermore, this highly expressive H2R and H3R were distributed in both myelinated and unmyelinated NGNs isolated from adult female rats by immunofluorescence and single-cell RT-PCR. H3R widely distributed in all tested neuron subtypes and its expression did not show significant difference among neuron subtypes. H2R was widely and highly expressed in low-threshold and sex-specific subpopulation of myelinated Ah-types compared with myelinated A- and unmyelinated C-type NGNs. Unexpectedly, weak expression of H1R was detected in both myelinated and unmyelinated NGNs by immunofluorescence, which was further confirmed by single-cell RT-PCR. Our results suggest that the sexual dimorphism in the expression of H2R and H3R in vagal afferents very likely contributes, at least partially, to the gender difference in prevalence and severity of asthma.

In order to research the characteristics of boiling flows in a vertical rectangular narrow channel, a series of convective boiling heat transfer experiments are performed. The test section is made of stainless steel with an inner diameter of 2 × 40 mm and heated length of 1100 mm. The 3194 experimental data points are obtained for a heat flux range of 10–700 kW/m 2 , a mass flux range of 200–2400 kg/m 2 s, a system pressure range of 0.1–2.5 MPa, and a quality range of 0–0.8. Eighteen prediction models are used to predict the flow boiling heat transfer coefficient of the rectangular narrow channel and the predicted value is compared against the database including 3194 data points, the results show that Chen type correlations and Lazarek and Black type correlations are not suitable for the rectangular channel very much. The Kim and Mudawar correlation is the best one among the 18 models. A new correlation is developed based on the superposition concept of nucleate boiling and convective boiling. the new correlation is shown to provide a good prediction against the database, evidenced by an overall MAE of 14.4%, with 95.2% and 98.6% of the data falling within ±30% and ±35% error bands, respectively.

// Zhen-Yu Yan 1, 2 , Tao Ban 1, 3 , Yao Fan 1 , Wei-Ran Chen 1 , Hong-Li Sun 4 , Hanying Chen 4 , Quo-Fen Qiao 1, 3 , Bai-Yan Li 1 1 Department of Pharmacology, Harbin Medical University, Harbin, China 2 Riley Heart Research Center, Division of Pediatric Cardiology, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, USA 3 Key Laboratory of Cardiovascular Medicine Research, Harbin Medical University, Harbin, China 4 Department of Pharmacology, Da-Qing Campus of Harbin Medical University, Da-Qing, China Correspondence to: Bai-Yan Li, e-mail: liby@ems.hrbmu.edu.cn Keywords: Pathology Section, reverse mode of Na+-Ca2+ exchanger, dobutamine, action potential, voltage-gated ion channel, ventricular cardiomyocyte Abbreviations: NCX, Na + /Ca 2+ exchanger Received: June 15, 2015 Accepted: July 24, 2015 Published: August 06, 2015 ABSTRACT Background: Dobutamine is commonly used for clinical management of heart failure and its pharmacological effects have long been investigated as inotropics via β–receptor activation. However, there is no electrophysiological evidence if dobutamine contributes inotropic action due at least partially to the reverse mode of Na + -Ca 2+ exchanger (NCX) activation. Methods: Action potential (AP), voltage-gated Na + ( I Na ), Ca 2+ ( I Ca ), and K + ( I to and I K1 ) currents were observed using whole-cell patch technique before and after dobutamine in ventricular cardiomyocytes isolated from adult mouse hearts. Another sets of observation were also performed with Kb-r7943 or in the solution without [Ca 2+ ] o . Results: Dobutamine (0.1–1.0 μM) significantly enhanced the AP depolarization with prolongation of AP duration (APD) in a concentration-dependent fashion. The density of I Na was also increased concentration-dependently without alternation of voltage-dependent steady-status of activation and inactivation, reactivation as well. Whereas, the activities for I Ca , I to , and I K1 were not changed by dobutamine. Intriguingly, the dobutamine-mediated changes in AP repolarization were abolished by 3 μM Kb-r7943 pretreatment or by simply removing [Ca 2+ ] o without affecting accelerated depolarization. Additionally, the ratio of APD 50 /APD 90 was not significantly altered in the presence of dobutamine, implying that effective refractory period was remain unchanged. Conclusion: This novel finding provides evidence that dobutamine upregulates of voltage-gated Na + channel function and Na + influx-induced activation of the reverse mode of NCX, suggesting that dobutamine may not only accelerate ventricular contraction via fast depolarization but also cause Ca 2+ influx, which contributes its positive inotropic effect synergistically with β-receptor activation without increasing the arrhythmogenetic risk.

More and more attentions have been paid to the impact of the earthquake on the reactor thermal hydraulics after the Fukushima accident. In order to figure out the seismic effect on the flow in primary loop, the natural circulation in primary loop of CPR1000 influenced by earthquake is modeled by learning from the study on natural circulation under ocean conditions. Natural circulation ability at earthquake, which includes longitudinal earthquake and transversal earthquake, is dynamically simulated by a program written with MATLAB, respectively. Besides, the safety of the system is discussed based on the calculated results. The research results show that, once the longitudinal earthquake occurs, in the earlier stage of earthquake, the peak and valley values of the coolant mass flow rate decrease gradually and the amplitude will be a constant as time goes on because of flow fluctuation in seismic condition. On the contrary, as for transversal earthquake, the peak and valley values of the coolant mass flow rate increase gradually in the earlier stage of earthquake. However, the amplitude will be a constant as time goes on, just like that in the longitudinal earthquake. For both of the two conditions, they have the same characteristics. The constant mentioned above grows up with the increase of the earthquake acceleration peak value and the period; the fluctuation period of mass flow rate is generally the same as the period of earthquake acceleration and the mass flow rate changes steadily; the average mass flow rate decreases slightly with the increase of the earthquake acceleration peak value and the period. Both of the vibration period and the peak of seismic wave have disturbing effect on reactor coolant system natural circulation. And the increase of the peak of the earthquake acceleration as well as the period of the earthquake acceleration will reduce the natural circulation ability. In the range of research parameters, the system is considered to be safe according to the calculation results of core coolant temperature.

Contains fulltext : 169834.pdf (Publisher’s version ) (Open Access) Contains fulltext : 169834pos.pdf (Author’s version postprint ) (Open Access) BACKGROUND: Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis. METHODS: In this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0.0156. FINDINGS: Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohen's d=-0.15), amygdala (d=-0.19), caudate (d=-0.11), hippocampus (d=-0.11), putamen (d=-0.14), and intracranial volume (d=-0.10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0.95) and thalamus (p=0.39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (21 years): in the accumbens (Cohen's d=-0.19 vs -0.10), amygdala (d=-0.18 vs -0.14), caudate (d=-0.13 vs -0.07), hippocampus (d=-0.12 vs -0.06), putamen (d=-0.18 vs -0.08), and intracranial volume (d=-0.14 vs 0.01). There was no difference between children and adults for the pallidum (p=0.79) or thalamus (p=0.89). Case-control differences in adults were non-significant (all p>0.03). Psychostimulant medication use (all p>0.15) or symptom scores (all p>0.02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0.5). INTERPRETATION: With the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes. FUNDING: National Institutes of Health. 10 p.