Is serine racemase(SRR) a second hit target for LRRK2-G2019S induced Parkinson's disease?

To date,at least 7 million people are suffering from Parkinson's disease(PD)worldwide,which is the second most prevalent,age-associated,and progressive neurodegenerative disorder(Tysnes and Storstein,2017).Given the accelerated global pace of aging,it becomes of fundamental importance that we start understanding the origins of neurodegeneration in order to develop effective disease modifying treatments.Most PD patients suffer from a combination of motor and nonmotor disabilities.

Modulation of Tropical Cyclogenesis in the Western North Pacific by the Quasi-Biweekly Oscillation

The quasi-biweekly oscillation （QBWO） is the second most dominant intraseasonal mode over the westem North Pacific （WNP） during boreal summer. In this study, the modulation of WNP tropical cyclogenesis （TCG） by the QBWO and its association with large-scale patterns are investigated. A strong modulation of WNP TCG events by the QBWO is found. More TCG events occur during the QBWO＇s convectively active phase. Based on the genesis potential index （GPI）, we further evaluate the role of environmental factors in affecting WNP TCG. The positive GPI anomalies associated with the QBWO correspond well with TCG counts and locations. A large positive GPI anomaly is spatially correlated with WNP TCG events during a life cycle of the QBWO. The low-level relative vorticity and mid-level relative humidity appear to be two dominant contributors to the QBWO-composited GPI anomalies during the QBWO＇s active phase, followed by the nonlinear and potential intensity terms. These positive contributions to the GPI anomalies are partly offset by the negative contribution from the vertical wind shear. During the QBWO＇s inactive phase, the mid-level relative humidity appears to be the largest contributor, while weak contributions are also made by the nonlinear and low-level relative vorticity terms. Meanwhile, these positive contributions are partly cancelled out by the negative contribution from the potential intensity. The contributions of these environmental factors to the GPI anomalies associated with the QBWO are similar in all five flow patterns--the monsoon shear line, monsoon confluence region, monsoon gyre, easterly wave, and Rossby wave energy dispersion associated with a preexisting TC. Further analyses show that the QBWO strongly modulates the synoptic-scale wave trains （SSWs） over the WNP, with larger amplitude SSWs during the QBWO＇s active phase. This implies a possible enhanced （weakened） relationship between TCG and SSWs during the active （inactive） phase. This study improves our understanding of the modulation of WNP TCG by the QBWO and thus helps with efforts to improve the intraseasonal prediction of WNP TCG.

不同大气稳定度下绿化街谷流动的大涡模拟

耦合大涡模拟与植被阻力、热源项模型,提出了城市灌木绿化街谷内风场和污染物浓度分布的热、动力数学模型.首先利用均匀植被层边界层湍流算例考核了模型的合理性以及程序的稳定性,表明本文模型能较好模拟植被层内部速度分布,并能对温度变化做出正确响应.对形状因子为0.5的理想绿化街谷,研究了街谷大气不同稳定度对街谷内风场和污染物浓度分布的影响.结果表明,相比于裸露街谷,植被层的引入减弱了街谷内环流风场强度,同时减小了街谷顶部污染物置换速率(pollutant exchange rate,PER),导致绿化街谷地面、背风面和迎风面附近污染物浓度增加.对于街谷大气稳定度对绿化街谷内风场和污染物浓度分布的影响,街谷大气强不稳定情形下,街谷顶部、地面、背风面和迎风面附近,风速比街谷大气中性层结时明显降低,污染物浓度相应增加;街谷大气弱不稳定情形下,街谷顶部和迎风面附近,风速有轻微减弱,同时,街谷地面和背风面附近,风速有加强趋势,导致绿化街谷内污染物浓度在迎风面和背风面比中性层结时减小,而在两排植被层之间有所加强.关于街谷大气稳定度对街谷顶部PER的影响,街谷大气弱不稳定情形街谷顶部PER要比街谷大气中性层结时小,而街谷大气强不稳定情形街谷顶部PER最小.

Solution of N-S equations based on the quadtree cut cell method

With the characteristic of the quadtree data structure, a new mesh generation method, which adopts square meshes to decompose a background domain and a cut cell approach to express arbitrary boundaries, is proposed to keep the grids generated with a good orthogonality easily. The solution of N-S equations via finite volume method for this kind of unstructured meshes is derived. The mesh generator and N-S solver are implemented to study two benchmark cases, i.e. a lid driven flow within an inclined square and a natural convection heat transfer flow in a square duct with an inner hot circular face. The simulation results are in agreement with the benchmark values, verifying that the present methodology is valid and will be a strong tool for two-dimensional flow and heat transfer simulations, especially in the case of complex boundaries.

A High-Throughput Screening System for Arabidopsis Transcription Factors and Its Application to Med25-Dependent Transcriptional Regulation

The activities of transcription factors （TFs） require interactions with specific DNA sequences and other reg- ulatory proteins. To detect such interactions in Arabidopsis, we developed a high-throughput screening system with a Gateway-compatible Gal4-AD-TF library of 1589 Arabidopsis TFs, which can be easily screened by mating-based yeast-one-hybrid （YIH） and yeast-two-hybrid （Y2H） methods. The efficiency of the system was validated by examining two well-characterized TF-DNA and TF-protein interactions： the CHE-CCA1 promoter interaction by YIH and NPR1-TGAs interactions by Y2H. We used this system to identify eight TFs that interact with a Mediator subunit, Med25, a key reg- ulator in JA signaling. We identified five TFs that interacted with the GCC-box cis-element in the promoter of PDF1.2, a downstream gene of Med25. We found that three of these TFs, all from the AP2-EREBP family, interact directly both with Med25 and the GCC-box of PDF1.2, suggesting that Med25 regulates PDF1.2 expression through these three TFs. These results demonstrate that this high-throughput Y1H/Y2H screening system is an efficient tool for studying transcrip- tional regulation networks in Arabidopsis. This system will be available for other Arabidopsis researchers, and thus it provides a vital resource for the Arabidopsis community.

HsfAld, a Protein Identified via FOX Hunting Using Thellungiella salsuginea cDNAs Improves Heat Tolerance by Regulating Heat-Stress-Responsive Gene Expression

Thellungiella salsuginea （formerly T. halophila）, a species closely related to Arabidopsis （Arabidopsis thali-ana）, is tolerant not only to high salt levels, but also to chilling, freezing, and ozone. Here, we report that T. salsuginea also shows greater heat tolerance than Arabidopsis. We identified T. salsuginea HsfAld （TsHsfAld） as a gene that can confer marked heat tolerance on Arabidopsis. TsHsfAld was identified via Full-length cDNA Over-eXpressing gene （FOX） hunt-ing from among a collection of heat-stress-related T. salsuginea cDNAs. Transgenic Arabidopsis overexpressing TsHsfAld showed constitutive up-regulation of many genes in the Arabidopsis AtHsfA1 regulon under normal growth tempera-ture. in Arabidopsis mesophyll protoplasts, TsHsfAld was localized in both the nucleus and the cytoplasm. TsHsfAld also interacted with AtHSP90, which negatively regulates AtHsfAls by forming HsfA1-HSP90 complexes in the cytoplasm. It is likely that the partial nuclear localization of TsHsfAld induced the expression of the AtHsfAld regulon in the transgenic plants at normal temperature. We also discovered that transgenic Arabidopsis plants overexpressing AtHsfAldwere more heat-tolerant than wild-type plants and up-regulated the expression of the HsfAld regulon, as was observed in TsHsfAld-overexpressing plants. We propose that the products of both TsHsfAld and AtHsfAld function as positive regulators of Arabidopsis heat-stress response and would be useful for the improvement of heat-stress tolerance in other plants.

Development of CMAQ for East Asia CO_2 data assimilation under an EnKF framework: a first result

Under an Ensemble Kalman Filter(EnKF)framework,Regional Atmospheric Modeling System and Models-3 Community Multi-scale Air Quality(RAMS–CMAQ)modeling system is developed to be a CO2data assimilation system EnKF–CMAQ,and the EnKF–CMAQ system is then applied to East Asia for validation with real continuous surface CO2concentration observations available in the study domain instead of using an observation simulation system experiment.Experiments with an experimental period of January 23 to February 7,2007 are conducted,and the experimental results of the EnKF–CMAQ system and the RAMS–CMAQ model are compared against continuous surface CO2observations from assimilation sites and independent reference sites.Distributions of daily mean CO2concentration increments show that the EnKF–CMAQ system confines the update of daily mean CO2within areas nearby and downwind of the assimilation sites.Both the CO2concentration ensemble spreads and background error covariances show flow-dependent patterns.The results indicate the crucial role of wind transport in the CO2data assimilation,which agrees with the previous studies.The average bias and the average root-mean-square error(RMSE)of daily mean CO2concentration at the assimilation sites are reduced by 1.00 and1.83 ppm,respectively,and those at the reference sites are reduced by 0.24 and 0.22 ppm,respectively.The results demonstrate the EnKF–CMAQ system is capable of assimilating the continuous surface CO2concentration observations to improve the simulation accuracy of the atmospheric CO2synoptic variation.Since growing CO2observations over East Asia are being available nowadays,this work is our first step to generate consistent spatial and temporal atmospheric CO2concentration fields over East Asia,particularly over China,using both in situ and satellite observations.

Numerical simulation of nanoparticle pattern fabricated by electrostatic spray deposition

Electrospray deposition （ESD） as a patterning method of nanoparticles deposited on a substrate has attracted much attention due to several advantages over other methods. However, obtaining an optimum ESD processing condition for nanoparticle pattern relies much on trial experiments because of the lack of reliable numerical simulation. In this study, the deposition characteristics of nanoparticle generated by electrospray were investigated by using a three-dimensional Lagrangian model. Three important process parameters, including solution dielectric constant, applied voltage and surface charge density on mask were considered by fixing the geometrical parameters of the ESD device. Simulation result showed that under the condition of without a mask, the spray diameter increases with increasing solvent dielectric constant, and higher applied voltage makes the spray area wider. Controllability of focusing by changing surface charge density on the mask was confirmed： higher surface charge density on the mask results in more focused deposition. Validity of the numerical simulation developed in this study was verified by comnarison with exoerimental data.

Viscous Micropump Simulation by Particle/Continuum Methods

A novel viscous micropump consisting of a cylindrical rotor eccentrically placed inside a microchannel is simulated by the two Volume-CAD(V-CAD)framework-based flow solvers,i.e.,the direct simulation Monte Carlo(DSMC)package(named as V-DSMC)and the Navier-Stoke solver(named as V-Flow).V-DSMC is used in the case of the pump applied to gas,while V-Flow is applied to model the pump in the case of liquid working medium.The pumping performance curves under different liquid media with the variation of Reynolds number,as well as under different eccentricity factors are obtained.The performance and the flow filed characteristics are very sensitive to the tangential momentum accommodation coefficient in the case of gas medium.Three recirculations exist in the flow field,and the sizes of recirculation are different at the different operating points in a performance curve.

SD3, an Arabidopsis thaliana Homolog of TIM21, Affects Intracellular ATP Levels and Seedling Development

It is poorly understood how plants control their growth by cell division, elongation, and differentiation. We have characterized a seedling-lethal mutant segregation distortion 3 （sd3） that showed a very dwarf phenotype when grown in the light and, in the dark, had short hypocotyls with reduced ploidy levels. The corresponding gene of SD3 encodes a protein with high similarity to yeast translocase on the inner mitochondrial membrane 21 （TIM21）, which is a component of the TIM23 complex. Indeed, SD3 protein fused to GFP localized in the mitochondria. SD3 overexpression increased cotyledon size in the light and hypocotyl thickness in the dark. The expression of genes for several subunits of the respiratory-chain complexes III and IV was up-regulated in SD3-overexpressing plants. Furthermore, these plants showed high levels of ATP whereas those of sd3 were low. These results suggested that SD3 induced an increase in cell size by raising the expression of the respiratory-chain subunit genes and hence increased the intracellular ATP levels, We propose that intracellular ATP levels regulated by mitochondria control plant organ size.

Data I/O management approach for the post-hoc visualization of big simulation data results

Leading-edge supercomputers,such as the K computer,have generated a vast amount of simulation results,and most of these datasets were stored on the file system for the post-hoc analysis such as visualization.In this work,we first investigated the data generation trends of the K computer by analyzing some operational log data files.We verified a tendency of generating large amounts of distributed files as simulation outputs,and in most cases,the number of files has been proportional to the number of utilized computational nodes,that is,each computational node producing one or more files.Considering that the computational cost of visualization tasks is usually much smaller than that required for large-scale numerical simulations,a flexible data input/output(I/O)management mechanism becomes highly useful for the post-hoc visualization and analysis.In this work,we focused on the xDMlib data management library,and its flexible data I/O mechanism in order to enable flexible data loading of big computational climate simulation results.In the proposed approach,a pre-processing is executed on the target distributed files for generating a light-weight metadata necessary for the elaboration of the data assignment mapping used in the subsequent data loading process.We evaluated the proposed approach by using a 32-node visualization cluster,and the K computer.Besides the inevitable performance penalty associated with longer data loading time,when using smaller number of processes,there is a benefit for avoiding any data replication via copy,conversion,or extraction.In addition,users will be able to freely select any number of nodes,without caring about the number of distributed files,for the post-hoc visualization and analysis purposes.

Contribution of Genomics to Gene Discovery in Plant Abiotic Stress Responses

Sustaining agricultural production under adverse environ- mental conditions, such as drought and high salinity, rep- resents a major challenge. The discovery of key genes and signal transduction pathways underlying plant responses to environmental stress will play an important role in devel- oping strategies for the genetic improvement of crops to address this challenge. Crop functional genomics has greatly contributed to the identification of abiotic stress-related genes. Current advances in genomic technologies now pro- vide effective and high-throughput methods for identifying stress-related genes at a genome-wide level, especially with the availability of the complete genomic sequence of several model and crop plant species. The development of genetic database resources has allowed bioinformatic approaches to identify stress-tolerant gene families across species based on homology and synteny. Additionally, genome-wide associa- tion studies （GWAS） for complex trait loci in crops have facili- tated the discovery of critical stress-related genes and their favorable alleles.

Is germinal center selection required for influenza vaccination?

It has long been believed that the generation of high-affinity neutralizing antibodies is critical for antiviral humoral immunity.The production of high-affinity antibodies depends on the formation of germinal centers(GC)in lymph nodes and a subset of T cells called follicular helper T(T_(FH))cells in GCs.

SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism

The SARS-CoV-2 infection causes severe immune disruption.However,it is unclear if disrupted immune regulation still exists and pertains in recovered COVID-19 patients.In our study,we have characterized the immunephe no type of B cells from 15 recovered COVID-19 patients,and found that healthy controls and recovered patients had similar B-cell populations before and after BCR stimulation,but the frequencies of PBC in patients were significantly increased when compared to healthy controls before stimulation.However,the percentage of unswitched memory B cells was decreased in recovered patients but not changed in healthy controls upon BCR stimulation.Interestingly,we found that CD19 expression was significantly reduced in almost all the B-cell subsets in recovered patients.Moreover,the BCR signaling and early B-cell response were disrupted upon BCR stimulation.Mechanistically,we found that the reduced CD19 expression was caused by the dysregulation of cell metabolism.In conclusion,we found that SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhandng B-cell metabolism,which may provide a new intervention target to cure COVID-19.