New aspects of a small GTPase RAB35 in brain development and function

In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or intermediates.These processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS superfamily.Dysfunction of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative diseases.Therefore,it is important to understand the physiological and pathological roles of RAB proteins in brain function.RAB35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell migration.RAB35 is also involved in neurite outgrowth and turnover of synaptic vesicles.We generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and function.These mice exhibited defects in anxiety-related behaviors and spatial memory.Strikingly,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal lamination.In contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex development.Recent studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's disease.In this review,we provide an overview of the current understanding of subcellular functions of RAB35.We also provide insights into the physiological role of RAB35 in mammalian brain development and function,and discuss the involvement of RAB35 dysfunction in neurodegenerative diseases.

Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

Postnatal development of rat retina:a continuous observation and comparison between the organotypic retinal explant model and in vivo development

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.

A causation mechanism for coal bursts during roadway development based on the major horizontal stress in coal:Very specific structural geology causing a localised loss of effective coal confinement and Newton’s second law

In 2017,one of the international authorities on coal bursts,Mark Christopher,published a paper entitled"Coal bursts that occur during development:A rock mechanics enigma",in which several relevant technical issues were identified.This paper outlines what is considered to be a credible,first-principles,mechanistic explanation for these three current development coal burst conundrums by reference to early published coal testing work examining the significance of a lack of"constraint"to coal stability and an understanding of how very specific structural geology and other geological features can logically cause this to occur in situ,albeit on a statistically very rare basis.This basic model is examined by reference to published information pertaining to the development coal-burst that occurred at the Austar Coal Mine in New South Wales,Australia,in 2014 and from the Sunnyside District in Utah,the United States.The"cause and effect"model for development of coal bursts presented also offers a meaningful explanation for the statistical improbability for what are nonetheless potentially highly-destructive events,being able to explain the statistical rarity being just as important to the credibility of the model as explaining the local conditions associated with burst events.The model could also form the basis for a robust,riskbased approach utilising a"hierarchy of controls",to the operational management of the development coal burst threat.Specifically,the use of pre-mining predictions for likely burst-prone and non-burstprone areas,the use of the mine layout to avoid or at least minimise mining within burst-prone areas if appropriate,and finally the development of an operational Trigger Action Response Plan(TARP)that reduces the likelihood of inadvertent roadway development into a burst-prone area without suitable safety controls already being in place.

Effects of Plant Secondary Metabolite Nicotine on Growth and Development of Frankliniella occidentalis

[Objective] The paper was to explore the chemical and molecular mechanisms of Frankliniella occidentalis, an important quarantine pest, against toxic substances. [Method] F. occidentalis were evaluated after continuous exposure to artificial diets containing nicotine from the 2^（nd） and the 3^（rd）instars for five generations, to determine the larval weight, pupal weight, and larval development duration. [Result] The larval development delayed and nicotine treatment significantly inhibited the weight gain of larvae. Compared to the control, the inhibition rates of larval weight and pupal weight were declined from 45% to 20% and from 25% to 4% respectively after feeding the 2^（nd）instars with nicotine for five generations.Nicotine delayed the larval growth and prolonged the generation duration of F. occidentalis. Nicotine showed more significant inhibitory effect on the lower instar larvae. With the increasing generations of secondary culture, the inhibitory effect of nicotine on larval weight and pupal weight was weakened. The developmental period of larvae was shortened, and the generation duration of F. occidentalis was shortened. [Conclusion] Nicotine affects the growth and development of F. occidentalis. F. occidentalis will gradually increase the adaptability to nicotine toxic substances after selfregulation for a few generations, and relieve the inhibitory effect of toxic substances.

Building Information Modeling-Based Secondary Development System for 3D Modeling of Underground Pipelines

Underground pipeline networks constitute a major component of urban infrastructure,and thus,it is imperative to have an efficient mechanism to manage them.This study introduces a secondary development system to efficiently model underground pipeline networks,using the building information modeling(BIM)-based software Revit.The system comprises separate pipe point and tubulation models.Using a Revit application programming interface(API),the spatial position and attribute data of the pipe points are extracted from a pipeline database,and the corresponding tubulation data are extracted from a tubulation database.Using the Family class in Revit API,the cluster in the self-built library of pipe point is inserted into the spatial location and the attribute data is added;in the same way,all pipeline instances in the pipeline system are created.The extension and localization of the model accelerated the modeling speed.The system was then used in a real construction project.The expansion of the model database and rapid modeling made the application of BIM technology in three-dimensional visualization of underground pipeline networks more convenient.Furthermore,it has applications in pipeline engineering construction and management.

The Second Development Method and Application Based on Ansys in Advanced Digital Manufacturing

The computer aided engineering is aiming at the numerical simulation-the important link in the advanced digital manufacturing.Its second development based on Ansys platform can be carried out often.In common,the Visual Basic and APDL are important development tools and are applied in the product design at the same time.In the paper,the secondary development flow and method based on Ansys is described.The parameter design and analysis process of the bridge girder erecting equipment is carried on with Ansys software and its secondary development tools—APDL and Visual Basics,including the interact between the mode of Ansys batch solving and Visual Basic.The method speeds up design and enhances the product the quality and the perfor- mance.

Simulation Analysis Module of High-speed Rail Bearings Based on Secondary Development in ADAMS

This paper develops a strong secondary development based on ADAMS feature which creates high-speed rail bearings for simulation analysis module. This thesis is in the case of non-circular pattern instructions of how to achieve rapid roller modeling, with analysis of functions and parameters required for the design of the simulation module of the high-speed rail bearing, as well as the design of dialog boxes, the environment and file structure. The specific modules is based on the secondary development language provided by ADAMS ! View. Through the menus, dialog boxes which input parameters, it can achieve high iron bearing automatic modeling, dynamic analysis and post-processing to simplify the analysis of high-speed rail bearing operations, as well as improving the high-speed rail bearing development efficiency.

Virtual Reality and Visual Simulation Technology in Platform Construction with Four Bucket Foundations Based on Secondary Development of Vega

The platform with bucket foundations can penetrate and migrate by underpressure/positive pressure technique caused by pumping water out/in the bucket. However, the construction process of bucket foundations cannot be clearly observed and effectively controlled due to the special nature of sea environment. By using an advanced simulation development tool of Multigen Creator, the visual construction simulation program for the platform with bucket foundations was developed to set up the virtual reality system with interaction control and observation in every view angle based on the secondary development technology of Vega platform. The application results show that the method is feasible and effective by simulating the whole construction process for the platform with four bucket foundations.

Second Language Development in an English-speaking Country

This study aims to report a learner＇s language exposure and language use, early experience in mainstream classroom, difficulties at different stages of learning, and attitudes towards bilingualism in an English speaking country. It is concluded that when a student studies a second language, he/she should develop both interpersonal communicative skills and cognitive/academic language proficiency.

基于Tv-SECOND的自动驾驶场景下的3D目标检测

针对自动驾驶场景中复杂环境下的3D目标检测任务,特别是远距离和遮挡条件下,为提高模型的检测准确率,在SECOND的基础上提出了Tv-SECOND两阶段算法。该算法提出一种基于Transformer架构的提案框特征提取模块,并在传统体素特征编码基础上提出可变形的体素特征编码模块。在KITTI数据集上进行测试,结果显示,所提出的算法相比SECOND在远距离和遮挡严重的情况下分别提高了7.49%、9.72%。同时与其他先进的两阶段方法相比,检测精度有不同程度的提升,证明了Tv-SECOND算法的有效性。新算法能够建立特征之间的依赖关系,聚合周边广域的上下文信息,增强模型的学习推理能力,有效提升了模型在远距离和遮挡的情况下的检测性能。

Teacher Professionalism and Professional Development of Chinese Secondary Teachers

The paper refers to some classic texts on professionalism/professionalization which offer a spectrum of different interpretations and shed light on the possible confusion of the terms,with critique on the classic functionalist claims and the emergence of new professionalism.The paper illustrates the history of Chinese secondary teachers over the last few decades,and tries to examine the implications of western conception of teacher professionalism and the professional development of Chinese secondary teachers.With the current trend toward globalization,Chinese teachers professionalism will take on a look of global professionalism(dominated by western professionalism),while with China's own context playing a role in its development.

THE 6TH INTERNATIONAL CONFERENCE ON RARE EARTH DEVELOPMENT AND APPLICATIONS ICRE'2010(The Second Circular)

Beijing / China August 2-6, 2010 Organized by The Chinese Society of Rare Earths (CSRE) Co-Organized by Peking University (PKU), Roskill Information Services Ltd., Metallurgical Council

GAMYB transcription factor LoMYB65 from lily plays a vital role in pollen development

Lily(Lilium spp.)is an important horticultural crop,but its use is limited due to serious pollen contamination problems.There are many studies on pollen development in model plants,but few on flower crops such as lilies.Gibberellin(GA)is a large class of hormones and plays an important role in plant vegetative growth and reproductive development.GAMYB is a group of the R2R3-MYB family upregulated by gibberellin,and plays an important role in anther development.Here,we isolated a novel GAMYB,named LoMYB65,from lily,which was closely related to the AtMYB65 and AtMYB33 in Arabidopsis.Fluorescence quantitative PCR results showed that LoMYB65 was mainly expressed in lily anthers.LoMYB65 could be activated by 288μmol·L^(-1)GA3treatment and the LoMYB65 protein was located in the nucleus and cytoplasm,and had transactivation in yeast and tobacco leaf cells.The conserved motif within 226 amino acids of the C-terminal of LoMYB65 contributed to its transactivation.Overexpression of LoMYB65 caused dwarf phenotype,unnormal tapetum development,less seeds of siliques in transgenic Arabidopsis plants,the transgenic plants showed partly male sterile.Simultaneously,silencing of LoMYB65 with VIGS(Virus Induced Gene Silencing)in lily anthers caused unnormal pollen development and reduced the pollen amount.Overexpression of LoMYB65 in Arabidopsis and silencing of LoMYB65 in lily resulted in decreased pollen counts,so we speculate that LoMYB65 may be dose-dependent.Overall,these findings suggest that LoMYB65 may play an important role in anther development and pollen formation in lily.LoMYB65 may provide a useful candidate gene for pollenless breeding of lily.

Development of mobile GIS system for forest resources second-class inventory

A special mobile GIS（Geographic Information System） system used for forest resources second-class inventory was developed on the basis of traditional forest resources inventory,remote sensing,GPS（Globe Positioning System） and embedded technology.Portable instrument,embedded development and the integration technology of RS（Remote Sensing）,GIS and GPS are all used in this special mobile GIS system.Further,the system composition,key techniques,and current situation of the practical application in China were analyzed in the study.The results are important for applying modern high-tech for the planning and design of digital forest resources to improve the precision and efficiency of inventory and reduce the labor cost and financial investment.

Development,characterization and solubility enhancement of comparative dissolution study of second generation of solid dispersions and microspheres for poorly water soluble drug

The poor dissolution characteristics of water-insoluble drugs are a major challenge for pharmaceutical scientists.Reduction of the particle size/increase in the surface area of the drug is a widely used and relatively simple method for increasing dissolution rates.The objective of this study was to improve solubility,release and comparability of dissolution of a poorly soluble drug using two different types of formulations(solid dispersions and microspheres).Hydrochlorothiazide was used as a model drug.The solid dispersions and microspheres were prepared by solvent evaporation method using ethyl cellulose,hydroxypropyl methylcellulose in different drug-to-carrier ratios(1:1,1:2 w:w).The prepared formulations were evaluated for interaction study by Fourier transform infrared spectroscopy,differential scanning calorimetry,percentage of practical yield,drug loading,surface morphology by scanning electron microscopy,optical microscopy and in-vitro release studies.The results showed no interaction between the drug and polymer,amorphous state of solid dispersions and microspheres,percentage yield of 42.53%to 78.10%,drug content of 99.60%to 99.64%,good spherical appearance in formulation VI and significant increase in the dissolution rate.

Conventional Geothermal Systems and Unconventional Geothermal Developments: An Overview

This paper provides an overview of conventional geothermal systems and unconventional geothermal developments as a common reference is needed for discussions between energy professionals. Conventional geothermal systems have the heat, permeability and fluid, requiring only drilling down to °C, normal heat flow or decaying radiogenic granite as heat sources, and used in district heating. Medium-temperature (MT) 100°C - 190°C, and high-temperature (HT) 190°C - 374°C resources are mostly at plate boundaries, with volcanic intrusive heat source, used mostly for electricity generation. Single well capacities are °C - 500°C) and a range of depths (1 m to 20 Km), but lack permeability or fluid, thus requiring stimulations for heat extraction by conduction. HVAC is 1 - 2 m deep and shallow geothermal down to 500 m in wells, both capturing °C, with °C are either advanced by geothermal developers at <7 Km depth (Enhanced Geothermal Systems (EGS), drilling below brittle-ductile transition zones and under geothermal fields), or by the Oil & Gas industry (Advanced Geothermal Systems, heat recovery from hydrocarbon wells or reservoirs, Superhot Rock Geothermal, and millimeter-wave drilling down to 20 Km). Their primary aim is electricity generation, relying on closed-loops, but EGS uses fractures for heat exchange with earthquake risks during fracking. Unconventional approaches could be everywhere, with shallow geothermal already functional. The deeper and hotter unconventional alternatives are still experimental, overcoming costs and technological challenges to become fully commercial. Meanwhile, the conventional geothermal resources remain the most proven opportunities for investments and development.

Development and technology status of energy storage in depleted gas reservoirs

Utilizing energy storage in depleted oil and gas reservoirs can improve productivity while reducing power costs and is one of the best ways to achieve synergistic development of"Carbon Peak–Carbon Neutral"and"Underground Resource Utiliza-tion".Starting from the development of Compressed Air Energy Storage(CAES)technology,the site selection of CAES in depleted gas and oil reservoirs,the evolution mechanism of reservoir dynamic sealing,and the high-flow CAES and injection technology are summarized.It focuses on analyzing the characteristics,key equipment,reservoir construction,application scenarios and cost analysis of CAES projects,and sorting out the technical key points and existing difficulties.The devel-opment trend of CAES technology is proposed,and the future development path is scrutinized to provide reference for the research of CAES projects in depleted oil and gas reservoirs.

BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.

Development of Tibet at New Historic Starting Point——People in Tibet greet Second Serfs Emancipation Day

March 28 of this year is the second Tibetan Serfs Emancipation Day. People of all nationalities in Tibet marked the day by hoisting the national flag and by singing and dancing. Smiles were on every face and a festive atmosphere pervaded the snowcovered plateau region.