PIKFYVE inhibition mitigates disease in models of diverse forms of ALS

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that results from many diverse genetic causes.Although therapeutics specifically targeting known causal mutations may rescue individual types of ALS, these approaches cannottreat most cases since they have unknown genetic etiology. Thus, there is a pressing need for therapeutic strategies that rescuemultiple forms of ALS. Here, we show that pharmacological inhibition of PIKFYVE kinase activates an unconventional proteinclearance mechanism involving exocytosis of aggregation-prone proteins. Reducing PIKFYVE activity ameliorates ALSpathology and extends survival of animal models and patient-derived motor neurons representing diverse forms of ALS includingC9ORF72, TARDBP, FUS, and sporadic. These findings highlight a potential approach for mitigating ALS pathogenesis that doesnot require stimulating macroautophagy or the ubiquitin-proteosome system.

Research on design methodology for railway freight service combination plans to meet diverse demands

Purpose–Facing the diverse needs of large-scale customers,based on available railway service resources and service capabilities,this paper aims to research the design method of railway freight service portfolio,select optimal service solutions and provide customers with comprehensive and customized freight services.Design/methodology/approach–Based on the characteristics of railway freight services throughout the entire process,the service system is decomposed into independent units of service functions,and a railway freight service combination model is constructed with the goal of minimizing response time,service cost and service time.A model solving algorithm based on adaptive genetic algorithm is proposed.Findings–Using the computational model,an empirical analysis was conducted on the entire process freight service plan for starch sold from Xi’an to Chengdu as an example.The results showed that the proposed optimization model and algorithm can effectively guide the design of freight plans and provide technical support for real-time response to customers’diversified entire process freight service needs.Originality/value–With the continuous optimization and upgrading of railway freight source structure,customer demands are becoming increasingly diverse and personalized.Studying and designing a reasonable railway freight service plan throughout the entire process is of great significance for timely response to customer needs,improving service efficiency and reducing design costs.

Morphophysiological Diversity and Haplotype Analysis of Saltol QTL Region in Diverse Rice Landraces for Salinity Tolerance

Rice is sensitive to salinity stress at both the seedling and reproductive stages.The present study used 145 rice genotypes comprising of 100 landraces and 45 advanced breeding lines collected from different regions of India.These genotypes were evaluated in hydroponics under control[electrical conductivity(ECe)~1.2 dS/m]and saline(ECe~10.0 dS/m)environments along with susceptible(IR29)and tolerant(FL478)checks.The stress susceptibility index for eight morphophysiological traits was estimated.Analysis of variance showed significant differences among the genotypes for all the parameters studied in control,stress and relative stress conditions.We identified 3 landraces(Kuttimanja,Tulasimog and IET-13713I)as tolerant and 14 lines as moderately tolerant to salt stress.Strong correlations in the morphological(root and shoot lengths)and physiological traits(shoot Na^(+),Ca^(2+)and Mg^(2+)contents,and Na^(+)/K^(+)ratio)were observed under all the conditions.The hierarchical cluster analysis grouped the genotypes into five clusters,among which cluster Ⅱ comprised salt-tolerant lines.Haplotyping of Saltol region using 11 simple sequence repeat markers on 17 saline tolerant and moderately tolerant lines was conducted.Markers AP3206F,RM10793 and RM3412b,located close to SKC1 gene(11.23‒12.55 Mb),displayed diverse allelic variations and they were not related to the FL478 type.In this region,tolerant lines like Kuttimanja,IET-13713I and Tulasimog have new alleles.As a result,these lines may be suitable candidates for novel genomic regions governing rice salinity tolerance.Salt-tolerance ability of Kuttimanja,Tulasimog and IET-13713I was validated in two years in three salinity stress environments.These promising lines can be used in breeding programs to broaden the genetic base of salinity tolerance in rice,and it may help to dissect key genomic regions responsible for salinity tolerance.

Diverse Deep Matrix Factorization With Hypergraph Regularization for Multi-View Data Representation

Deep matrix factorization(DMF)has been demonstrated to be a powerful tool to take in the complex hierarchical information of multi-view data(MDR).However,existing multiview DMF methods mainly explore the consistency of multi-view data,while neglecting the diversity among different views as well as the high-order relationships of data,resulting in the loss of valuable complementary information.In this paper,we design a hypergraph regularized diverse deep matrix factorization(HDDMF)model for multi-view data representation,to jointly utilize multi-view diversity and a high-order manifold in a multilayer factorization framework.A novel diversity enhancement term is designed to exploit the structural complementarity between different views of data.Hypergraph regularization is utilized to preserve the high-order geometry structure of data in each view.An efficient iterative optimization algorithm is developed to solve the proposed model with theoretical convergence analysis.Experimental results on five real-world data sets demonstrate that the proposed method significantly outperforms stateof-the-art multi-view learning approaches.

Genetic Diversity,Population Structure,and Genome-Wide Association Study of Seven Agronomic Traits in 273 Diverse Upload Cotton Accessions

Upland cotton(Gossypium hirsutum)is the most important plant producing natural fibers for the textile industry.In this study,we first investigated the phenotypic variation of seven agronomic traits of 273 diverse cotton accessions in the years 2017 and 2018,which were from 18 geographical regions.We found large variations among the traits in different geographical regions and only half of the traits in either years 2017 or 2018 followed a normal distribution.We then genotyped the collection with 81,612 high quality SNPs.Phylogenetic tree and population structure revealed a diverse genetic structure of the core collection,and geographical diversification was an important factor,but account for part of the variances of genetic diversification.We then performed genome-wide association study for the seven traits in the years 2017 and 2018,and the average values of each trait in the two years,respectively.We identified a total of 19 significant marker-trait associations and found that Pollen Ole e 1 allergen/extension could be the candidate gene associated with the fall-off cotton bolls from the last three branches.In addition,large variations were observed for the heritability of traits in the years 2017 and 2018.These results provide new potential candidate genes for further functional validation,which could be useful for genetic improvement and breeding of new cotton cultivars with better agronomic performances.

Screening for urinary markers predicting hematopoietic stem cell injury induced by busulfan using genetically diverse mice

Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of BU.Different susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary research.Methods:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in urine.The urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed proteins.Screening for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase pathways.Based on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU conditioning.Conclusions:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC injury.Using GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers.

基于Diverse AdaBoost改进SVM算法的无人机影像信息提取

无人机遥感影像具有像幅小、几何变形大、重叠不均等特殊性,给影像信息的提取提出了难题。该文提出基于Diverse AdaBoost改进SVM的分类方法,采用RBFSVM作为AdaBoost的弱分类器,达到自适应调整参数的目的,同时引入复杂度,解决弱分类器精确度与复杂度的平衡问题。最后,利用提出的改进算法分别对汉旺镇、林趴镇无人机遥感影像进行了道路、建筑物的提取,平均提取精度均达到95%以上,与采用SVM算法的提取结果进行比较,该方法能精确提取无人机影像信息。

A New Diverse Macrofossil Lagersttte from the Uppermost Ediacaran of Southwestern China

A new macrofossil Lagerstatte was discovered from the uppermost Ediacaran Jiucheng Member at Jinning and Jiangchuan of the eastern Yunnan, yielding numerous diverse well-preserved thallophyte macrofossils. These include the previously-known representatives of vendobionts, Vendotaenia and Tyrasotaenia, and the biggish multicellular benthos such as Chuaria-like and Tawuia- like fossiis, as well as Longfengshaniaceaens with diverse holdfast structures. There are still some other problematic macrofossils with peculiar configurations as well as uncertain relatives. The distinct dominance of the giant, unbranching thallophytes occasionally with holdfast structures distinguishes this assemblage from the other Ediacaran macrofossil Lagerstattes in the Doushantuo Formation at Miaohe, Wenghui and Lantian, and the contemporary assemblage in the Shibantan Member of Dengying Formation, Yangtze Gorges area. This paper outlines the characteristics of some of the multicellular macrofossils from the Jiucheng Member at Jiangchuan. They include some macrofossils with different types of holdfast structure, larger Chuaria-like and Tawuia-like morphology and questionable affinities as well. The discovery of greater diverse macrofossil assemblages from the Jiucheng Member of eastern Yunnan has further indicated that an important diversification and evolutionary radiation of metaphytes took place in the latest Ediacaran time. This radiation of largescale, benthic metaphyte along with phytoplankton was likely important contributors to the early Cambrian explosion of metazoans.

The Call of the Wild Is a Reflection of Jack London' s Diverse Philosophies

The Call of the Wild is one of the most famous novels written by Jack London.By borrowing vivid materials from his rich living experiences and diverse philosophies from different sources,he manages to make a dog named Buck the hero,an impressive image which at tracts broad attention of both readers and critics.The writer intends to explore the author' s diverse philosophies,from the perspectives of Marxism,Darwinism,Social Darwinism and the Superman Theory respectively.And the writer will also point out this is caused by the col lision of different social ideas at that time.

Simulation of methane adsorption in diverse organic pores in shale reservoirs with multi-period geological evolution

In shale reservoirs,the organic pores with various structures formed during the thermal evolution of organic matter are the main storage site for adsorbed methane.However,in the process of thermal evolution,the adsorption characteristics of methane in multi type and multi-scale organic matter pores have not been sufficiently studied.In this study,the molecular simulation method was used to study the adsorption characteristics of methane based on the geological conditions of Longmaxi Formation shale reservoir in Sichuan Basin,China.The results show that the characteristics of pore structure will affect the methane adsorption characteristics.The adsorption capacity of slit-pores for methane is much higher than that of cylindrical pores.The groove space inside the pore will change the density distribution of methane molecules in the pore,greatly improve the adsorption capacity of the pore,and increase the pressure sensitivity of the adsorption process.Although the variation of methane adsorption characteristics of different shapes is not consistent with pore size,all pores have the strongest methane adsorption capacity when the pore size is about 2 nm.In addition,the changes of temperature and pressure during the thermal evolution are also important factors to control the methane adsorption characteristics.The pore adsorption capacity first increases and then decreases with the increase of pressure,and increases with the increase of temperature.In the early stage of thermal evolution,pore adsorption capacity is strong and pressure sensitivity is weak;while in the late stage,it is on the contrary.

Clutter suppression for hypersonic vehicle-borne radar with frequency diverse array

The seriously range-ambiguous clutter is one of the main problems in clutter suppression for hypersonic vehicle-borne forward-looking radar. An approach based on the frequency diverse array (FDA) technique is proposed to mitigate the range ambiguous clutter. The frequency increment is designed to distinguish the clutter at ambiguous ranges and suppress the clutter by using a subspace projection algorithm. On the platform with high altitude or limited array antennas, the proposed method performs better for its independence of the elevation degrees-of-freedom (DOF). Finally, simulation results verify the effectiveness of the proposed method.

Gamma-aminobutyric acid A receptors in Alzheimer＇s disease： highly localized remodeling of a complex and diverse signaling pathway

Alzheimer＇s disease （AD）, the predominant form of dementia, is a chronic, incurable neurodegenerative disorder presenting with symptoms includ- ing progressive memory loss and disturbed emotional state. It has been estimated that dementia affects over 47 million people worldwide （Prince et al., 2015）, and with 60-80% of cases attributable to AD.

System Design and Signal Processing for Frequency Diverse Array Radar

Frequency diverse array(FDA)radar has been studied for more than 15 years and has attracted a lot of attention due to its potential advantages over the well-known phased array radar.The representative feature of FDA is range-angle-time-dependent transmit beampattern and its underlying properties are continuously revealed in the research.The formulation and exploitation of the transmit diversity with a frequency increment is the fundamental principle,which brings extra degrees-of-freedom(DOFs)in the transmit dimension.As the FDA radar carries additional information in range,it provides more flexibility in signal processing and also brings in new technical issues.This article overviews the state-of-the-art in FDA radar area and its applications,mainly based on the progress in our group.There are two main catalogs in FDA radar area,namely coherent FDA and FDA-MIMO(multiple-input multiple-output)radars.Potential applications including target parameter estimation,ambiguous clutter suppression,and deceptive jammer suppression are discussed.

Geometric interpretation of several classical iterative methods for linear system of equations and diverse relaxation parameter of the SOR method

Two kinds of iterative methods are designed to solve the linear system of equations, we obtain a new interpretation in terms of a geometric concept. Therefore, we have a better insight into the essence of the iterative methods and provide a reference for further study and design. Finally, a new iterative method is designed named as the diverse relaxation parameter of the SOR method which, in particular, demonstrates the geometric characteristics. Many examples prove that the method is quite effective.

Bayesian Reliability——Growth Analysis for Statistical of Diverse Population Based on Non-homogeneous Poisson Process

New armament systems are subjected to the method for dealing with multi-stage system reliability-growth statistical problems of diverse population in order to improve reliability before starting mass production. Aiming at the test process which is high expense and small sample-size in the development of complex system, the specific methods are studied on how to process the statistical information of Bayesian reliability growth regarding diverse populations. Firstly, according to the characteristics of reliability growth during product development, the Bayesian method is used to integrate the testing information of multi-stage and the order relations of distribution parameters. And then a Gamma-Beta prior distribution is proposed based on non-homogeneous Poisson process（NHPP） corresponding to the reliability growth process. The posterior distribution of reliability parameters is obtained regarding different stages of product, and the reliability parameters are evaluated based on the posterior distribution. Finally, Bayesian approach proposed in this paper for multi-stage reliability growth test is applied to the test process which is small sample-size in the astronautics filed. The results of a numerical example show that the presented model can make use of the diverse information synthetically, and pave the way for the application of the Bayesian model for multi-stage reliability growth test evaluation with small sample-size. The method is useful for evaluating multi-stage system reliability and making reliability growth plan rationally.

An Active Anti-Jamming Approach for Frequency Diverse Array Radar with Adaptive Weights

Due to the rapid development of electronic countermeasures(ECMs),the corresponding means of electronic counter countermeasures(ECCMs)are urgently needed.In this paper,an act-ive anti-jamming method based on frequency diverse array radar is proposed.By deriving the closed form of the phase center in a uniform line array FDA,we establish a model of the FDA signal based on adaptive weights and derive the effect of active anti-jamming in this regime.The pro-posed active anti-jamming method makes it difficult for jammers to detect or locate our radar.Fur-thermore,the effectiveness of the two frequency increment schemes in terms of anti-jamming is ana-lyzed by comparing the deviation of phase center.Finally,the simulation results verify the effective-ness and superiority of the proposed method.

Limitations for tungsten as plasma facing material in the diverse scenarios of the European inertial confinement fusion facility HiPER: Current status and new approaches

The high-power laser energy research(HiPER)project was a European project for demonstrating the feasibility of inertial fusion energy based on using direct-drive targets in a shock ignition scheme using a drywall evacuated chamber.HiPER was intended to drive the transition from a scientific proof of principle to a demonstration power plant in Europe.The project was divided into three realistic scenarios(Experimental,Prototype,and Demo)to help identify open problems and select appropriate technologies to solve them.One of the problems identified was the lack of appropriate plasma-facing materials(PFMs)for the reaction chamber.Therefore,a major challenge was to develop radiation-resistant materials able to withstand the large thermal loads and radiation in these reactors.In this paper,we describe the main threats that coarse-grained Wwould face in the diverse HiPER scenarios.Based on purely thermomechanical considerations,theWlifetimes for the HiPER Prototype and Demo scenarios are limited by fatigue to 14000 h and 28 h,respectively.The combined effects of thermal load and atomistic damage significantly reduce these lifetimes to just∼1000 shots for the Experimental scenario and a few minutes and seconds for the Prototype and Demo scenarios,respectively.Thus,coarse-grainedWis not an appropriatePFMfor the Prototype or Demo scenarios.Therefore,alternatives to this material need to be identified.Here,we review some of the different approaches that are being investigated,highlight the work done to characterize these new materials,and suggest further experiments.

Rapid and Reliable Method of High-Quality RNA Extraction from Diverse Plants

The isolation of high quality RNA is a crucial technique in plant molecular biology. The quality of RNA determines the reliability of downstream process like real time PCR. In this paper, we reported a high quality RNA extraction protocol for a variety of plant species. Our protocol is time effective than traditional RNA extraction methods. The method takes only an hour to complete the procedure. Spectral measurement and electrophoresis were used to demonstrate RNA quality and quantity. The extracted RNA was further used for cDNA synthesis, expression analysis and copy number determination through Real Time PCR. The results indicate that RNA was of good quality and fit for real time PCR. This high throughput plant RNA extraction protocol can be used to isolate high quality RNA from diverse plants for real time PCR and other downstream applications.

Demographic variation and habitat specialization of tree species in a diverse tropical forest of Cameroon

Background： Many tree species in tropical forests have distributions tracking local ridge-slope-valley topography. Previous work in a 50-ha plot in Korup National Park, Cameroon, demonstrated that 272 species, or 63% of those tested, were significantly associated with topography. Methods： We used two censuses of 329,000 trees ≥1 cm dbh to examine demographic variation at this site that would account for those observed habitat preferences. We tested two predictions. First, within a given topographic habitat, species specializing on that habitat （＇residents＇） should outperform species that are specialists of other habitats （＇foreigners＇）. Second, across different topographic habitats, species should perform best in the habitat on which they specialize （＇home＇） compared to other habitats （＇away＇）. Species＇ performance was estimated using growth and mortality rates. Results： In hierarchical models with species identity as a random effect, we found no evidence of a demographic advantage to resident species. Indeed, growth rates were most often higher for foreign species. Similarly, comparisons of species on their home vs. away habitats revealed no sign of a performance advantage on the home habitat. Conclusions＂ We reject the hypothesis that species distributions along a ridge-valley catena at Korup are caused by species differences in trees _〉1 cm dbh. Since there must be a demographic cause for habitat specialization, we offer three alternatives. First, the demographic advantage specialists have at home occurs at the reproductive or seedling stage, in sizes smaller than we census in the forest plot. Second, species may have higher performance on their preferred habitat when density is low, but when population builds up, there are negative density-dependent feedbacks that reduce performance. Third, demographic filtering may be produced by extreme environmental conditions that we did not observe during the census interval.

Can an evidence-based fall prevention program be translated for use in culturally diverse communities?

Older adult falls are a significant public health problem,but one that is amenable to preventive interventions.1,2 Despite the progress made in identifying risk factors,developing efficacious health-related interventions,and promoting evidencebased programs in the community,much work remains before these strategies are broadly available and effectively used to reduce fall-related injuries.3 As Newton and ScottFindlay4 have pointed out,the translation of basic scientific knowledge into clinical studies,and the transformation of clinical studies into improvements in health services and public health practices,remain major obstacles to widespread adoption.