The pathogenic mechanism of TAR DNA-binding protein 43(TDP-43)in amyotrophic lateral sclerosis

The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).

B-COPNA resin formation from ethylene tar light fractions:Process development and mechanical exploration by molecular simulation

An efficient utilization strategy of ethylene tar(ET),the main by-product of the ethylene cracking unit,is urgently required to meet demands for modern petrochemical industry.On the other hand,condensed polynuclear aromatic resin of moderate condensation degree(B-COPNA)is a widely used carbon material due to its superb processability,the production of which is,however,seriously limited by the high cost of raw materials.Under such context,an interesting strategy was proposed in this study for producing B-COPNA resin using crosslinked light fractions of ethylene tar(ETLF,boiling point<260℃)facilitated by molecular simulation.1,4-Benzenedimethanol(PXG)was first selected as the crosslinking agent according to the findings of molecular simulation.The effects of operating conditions,including reactions temperature,crosslinking agent,and catalyst content on the softening point and yield of B-COPNA resin products were then investigated to optimize the process.The reaction mechanism of resin production was studied by analyzing the molecular structure and transition state of ETLF and crosslinking agents.It was shown that PXG exhibited a superior capacity of withdrawing electrons and a higher electrophilic reactivity than other crosslinking agents.In addition to the highest yield and greatest heat properties,PXG-prepared resin contained the most condensed aromatics.The corresponding optimized conditions of resin preparation were 180℃,1:1.9(PXG:ETLF),and 3%(mass)of catalyst content with a resin yield of 78.57%.It was the electrophilic substitution reaction that occurred between the ETLF and crosslinking agent molecules that were responsible for the resin formation,according to the experimental characterization and molecular simulation.Hence,it was confirmed that the proposed strategy and demonstrated process can achieve a clean and high value-added utilization of ETLF via B-COPNA resin preparation,bringing huge economic value to the current petrochemical industry.

Comparison of Combustion Characteristics of Tars Produced with Tobacco Stem Biomass Gasification

In order to study the combustion characteristics of tar in biomass gasifier inner wall and gasification gas,“tobacco stem semi-tar inside furnace”,“tobacco stem tar inside furnace”and“tobacco stem tar out-of-furnace”were subjected to thermogravimetric experiments,and the combustion characteristics and kinetic characteristics were analyzed.The result shows that“tobacco stem semi-tar inside furnace”has the highest value and“tobacco stem tar out-of-furnace”is has the lowest value on ignition characteristics,combustion characteristics and combustible stability;“tobacco stem semi-tar inside furnace”has the lowest value and“tobacco stem tar outside furnace”has the highest value on burnout characteristics;“tobacco stem tar outside furnace”has the highest value and“tobacco stem tar inside furnace”has the lowest value on integrated combustion characteristics.

Optimization of Hydrocracking Process for Enhanced BTX Production from Coal Tar-Derived Hydrorefined Products

Hydroconversion of coal tar to produce aromatic hydrocarbons(BTX)represents a crucial strategy for the highvalue hierarchical utilization of coal.This study focused on the hydrocracking of hydrorefined products derived from coal tar to enhance the production of benzene,toluene,and xylene(BTX).Various reaction conditions,including reaction temperature,hydrogen pressure,space velocity,and hydrogen-to-oil volume ratio,were systematically explored to optimize BTX yields while also considering the process’s economic feasibility.The results indicate that increasing the reaction temperature from 360℃ to 390℃ significantly favors the production of BTX,with yields increasing from 21.42%to 41.14%.Similarly,an increase in hydrogen pressure from 4 MPa to 6 MPa boosts BTX production,with yields rising from 36.31%to 41.14%.Reducing the space velocity from 2 h^(-1) to 0.5 h^(-1) also favors the BTX production process,with yields increasing from 37.96%to 45.13%.Furthermore,raising the hydrogen-to-oil volume ratio from 750 to 1500 improves BTX yields from 41.61%to 45.44%.Through economic analysis,the optimal conditions for BTX production were identified as a reaction temperature of 390℃,hydrogen pressure of 5-6 MPa,space velocity of 1 h^(-1),and hydrogen-to-oil volume ratio of 1000,achieving a BTX yield of 43.73%.This investigation highlights the importance of a holistic evaluation of hydrocracking conditions to optimize BTX production.Furthermore,the findings offer valuable insights for the design and operation of industrial hydrocracking processes aimed at efficiently converting coal tar-derived hydrorefined feedstock into BTX.

Asymptotic normality of error density estimator in stationary and explosive autoregressive models

In this paper,we consider the limit distribution of the error density function estima-tor in the rst-order autoregressive models with negatively associated and positively associated random errors.Under mild regularity assumptions,some asymptotic normality results of the residual density estimator are obtained when the autoregressive models are stationary process and explosive process.In order to illustrate these results,some simulations such as con dence intervals and mean integrated square errors are provided in this paper.It shows that the residual density estimator can replace the density\estimator"which contains errors.

Pittsburgh Guitars成立45周年,延续关于爱的故事

“Rocking the 'Burgh”,Pittsburgh Guitars于2024年庆祝成立45周年纪念。MMR杂志决定与曾经的忠实客户、现在的商店所有者John Bechtold坐下来,细致地了解一下这家商店的历史过往。Pittsburgh Guitars由Carl Grefenstette创立于1979年,现已成为当地音乐家和全球巨星们的打卡地。著名的大牌客户包括The Cult、Cheap Trick、Social Distortion、The Who、Nirvana、The Replacements等乐队的成员,不胜枚举。

Modified switched IMM estimator based on autoregressive extended Viterbi method for maneuvering target tracking

In this paper, a new approach of maneuvering target tracking algorithm based on the autoregressive extended Viterbi(AREV) model is proposed. In contrast to weakness of traditional constant velocity(CV) and constant acceleration(CA) models to noise effect reduction, the autoregressive(AR) part of the new model which changes the structure of state space equations is proposed. Also using a dynamic form of the state transition matrix leads to improving the rate of convergence and decreasing the noise effects. Since AR will impose the load of overmodeling to the computations, the extended Viterbi(EV) method is incorporated to AR in two cases of EV1 and EV2. According to most probable paths in the interacting multiple model(IMM) during nonmaneuvering and maneuvering parts of estimation, EV1 and EV2 respectively can decrease load of overmodeling computations and improve the AR performance. This new method is coupled with proposed detection schemes for maneuver occurrence and termination as well as for switching initializations. Appropriate design parameter values are derived for the detection schemes of maneuver occurrences and terminations. Finally, simulations demonstrate that the performance of the proposed model is better than the other older linear and also nonlinear algorithms in constant velocity motions and also in various types of maneuvers.

Preparation of pitch precursor with excellent spinnability for general-purpose carbon fibre using coal tar pitch as raw material

Tetrahydrofuran(THF) extract of coal tar pitch(CTP) was used instead of blending CTP with pretreated pyrolysis fuel oil to prepare an isotropic pitch precursor with excellent spinnability for general-purpose carbon fibre through bromination-dehydrobromination. The feasibility and effectiveness of synthesising an isotropic pitch precursor derived from THF-soluble(CTP-THFs) is demonstrated in this study.The results show that CTP-THFs contains more light components than CTP;CTP-THFs and CTP monomer proportions were 62.52% and 45.32%, respectively. However, based on comparisons of CTP-THFsBr0 and CTPBr0 characterisations, CTP-THFs exhibits better polycondensation than CTP. Bromination-dehydrobro mination promotes polycondensation of pitch precursors, leading to greater carbon aromaticity in CTP-THFsBr5, CTP-THFsBr10, and CTP-THFsBr15 than that in CTP-THFsBr0 and CTPBr0. CTP-THFsBr5 and CTP-THFsBr10 have excellent spinnability even with softening points as high as 230 ℃. The pericondensed carbon and carbon aromaticity of CTP-THFsBr5 and CTP-THFsBr10 are high owing to the higher degree of polycondensation;however, they still possess a more linear molecular structure. The as-prepared carbon fibre exhibits homogeneity and uniformity, and the mechanical performance is comparable with that of commercial general-purpose carbon fibre products.

5-Hydroxytryptamine:a potential therapeutic target in amyotrophic lateral sclerosis

Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis(ALS) is closely linked to 5-hydroxytryptamine(5-HT).To investigate this further,we administered 5-HT receptor antagonists to SOD1*G93A transgenic(ALS mouse model) and wide-type mice.This involved intraperitoneal injections of either granisetron,piboserod,or ritanserin,which inhibit the 5-HT3,5-HT4,and 5-HT2 receptors,respectively.The transgenic mice were found to have fewer5-HT-positive cells in the spinal cord compared with wide-type mice.We found that the administration of granisetron reduced the body weight of the transgenic mice,while piboserod and ritanserin worsened the motor functioning,as assessed using a hanging wire test.However,none of the 5-HT receptor antagonists affected the disease progression.We analyzed the distribution and/or expression of TAR DNA binding protein 43(TDP-43) and superoxide dismutase 1 G93A(SOD1-G93A),which fo rm abnormal aggregates in ALS.We found that the expression of these proteins increased following the administration of all three 5-HT receptor antagonists.In addition,the disease-related mislocalization of TD P-43 to the cytoplasm increased markedly for all three drugs.In ce rtain anatomical regions,the 5-HT receptor antagonists also led to a marked increase in the number of astrocytes and microglia and a decrease in the number of neurons.These results indicate that 5-HT deficiency may play a role in the pathogenesis of amyotrophic lateral sclerosis by inducing the abnormal expression and/or distribution of TDP-43 and SOD1-G93A and by activating glial cells.5-HT co uld therefore be a potential therapeutic target for amyotrophic lateral sclerosis.

基于XOR的TAR-CAU数据更新方法

在基于纠删码的云存储系统中,数据更新的性能往往受到网络带宽的限制。鉴于此,提出了基于异或(XOR)的TAR-CAU数据更新算法,该算法基于以下设计原则:1)利用数据更新量普遍较小的特点,将多条带的数据更新打包处理,减少网络往返次数,加快数据传输效率;2)采用基于XOR的更新,提高编解码效率。仿真实验和本地集群实验结果表明,相比于CAU算法,在数据更新量较小时,TAR-CAU算法能够提高至少44%的数据更新吞吐量。

Time series analysis-based seasonal autoregressive fractionally integrated moving average to estimate hepatitis B and C epidemics in China

BACKGROUND Hepatitis B(HB)and hepatitis C(HC)place the largest burden in China,and a goal of eliminating them as a major public health threat by 2030 has been set.Making more informed and accurate forecasts of their spread is essential for developing effective strategies,heightening the requirement for early warning to deal with such a major public health threat.AIM To monitor HB and HC epidemics by the design of a paradigmatic seasonal autoregressive fractionally integrated moving average(SARFIMA)for projections into 2030,and to compare the effectiveness with the seasonal autoregressive integrated moving average(SARIMA).METHODS Monthly HB and HC incidence cases in China were obtained from January 2004 to June 2023.Descriptive analysis and the Hodrick-Prescott method were employed to identify trends and seasonality.Two periods(from January 2004 to June 2022 and from January 2004 to December 2015,respectively)were used as the training sets to develop both models,while the remaining periods served as the test sets to evaluate the forecasting accuracy.RESULTS There were incidents of 23400874 HB cases and 3590867 HC cases from January 2004 to June 2023.Overall,HB remained steady[average annual percentage change(AAPC)=0.44,95%confidence interval(95%CI):-0.94-1.84]while HC was increasing(AAPC=8.91,95%CI:6.98-10.88),and both had a peak in March and a trough in February.In the 12-step-ahead HB forecast,the mean absolute deviation(15211.94),root mean square error(18762.94),mean absolute percentage error(0.17),mean error rate(0.15),and root mean square percentage error(0.25)under the best SARFIMA(3,0,0)(0,0.449,2)12 were smaller than those under the best SARIMA(3,0,0)(0,1,2)12(16867.71,20775.12,0.19,0.17,and 0.27,respectively).Similar results were also observed for the 90-step-ahead HB,12-step-ahead HC,and 90-step-ahead HC forecasts.The predicted HB incidents totaled 9865400(95%CI:7508093-12222709)cases and HC totaled 1659485(95%CI:856681-2462290)cases during 2023-2030.CONCLUSION Under current interventions,China faces enormous challenges to eliminate HB and HC epidemics by 2030,and effective strategies must be reinforced.The integration of SARFIMA into public health for the management of HB and HC epidemics can potentially result in more informed and efficient interventions,surpassing the capabilities of SARIMA.

Effects of Ethylene Tar-Based Pitch Coatings on the Electrochemical Properties of Graphite Anode Materials

To improve the electrochemical performance of graphite anode materials,pitches with various softening points(150℃,180℃,200℃,and 250℃)were prepared from ethylene tar and used to coat graphite through a liquid coating process.The effects of the softening point of the pitch and the coating amount on the microstructure and electrochemical properties of graphite were studied by methods including thermogravimetric analysis,X-ray diffraction,Raman spectroscopy,surface area analysis,scanning electron microscopy,transmission electron microscopy,and electrochemical testing.The graphite particles were coated uniformly by the pyrolytic carbon in the pitch.The coating changed the degree of graphitization,decreased the average specific surface area,and improved the electrochemical performance significantly.The best battery anode performance was obtained when the mass ratio of pitch to graphite was 10%,the heat treatment temperature was 1100℃,and the softening point of the pitch was 250℃.Under the optimum conditions,the irreversible capacity loss in the first cycle at 0.1 C was only 23 mAh/g,and the first Coulombic efficiency reached 94.2%.The capacity retention rate was 98.3%after 100 charge-discharge cycles at 0.1 C.

Constructing Confidence Regions for Autoregressive-Model Parameters

We discuss formulas and techniques for finding maximum-likelihood estimators of parameters of autoregressive (with particular emphasis on Markov and Yule) models, computing their asymptotic variance-covariance matrix and displaying the resulting confidence regions;Monte Carlo simulation is then used to establish the accuracy of the corresponding level of confidence. The results indicate that a direct application of the Central Limit Theorem yields errors too large to be acceptable;instead, we recommend using a technique based directly on the natural logarithm of the likelihood function, verifying its substantially higher accuracy. Our study is then extended to the case of estimating only a subset of a model’s parameters, when the remaining ones (called nuisance) are of no interest to us.

Ultra-deep Removal of Metal Ions from Coal Tar by Complexation:Experimental Studies and Density Functional Theory Simulations

As one of the important aspects of upgrading coal tar,the ultra-deep removal of metal ions via the complexation method was investigated by screening four complexing agents and performing density functional theory(DFT)simulations.Analysis of the compositions and contents of the metallic compounds in the coal tar revealed that the main components were iron and calcium naphthenates.Direct filtration reduced the mechanical impurity content from 0.24%to 0.0752%,indicating that most of the large particles could be easily removed.Among the four complexing agents,namely,acetic acid,oxalic acid,citric acid,and ethylenediaminetetraacetic acid,oxalic acid exhibited the best demetallization performance.The DFT simulations suggested that the high performance of oxalic acid originated from its 1:1 coordination mode,rigid dicarboxyl structure,and greater binding energy.

Feasibility Investigation of Bitumen Properties by Blending of Coal Tar Pitch

There are numerous methods and additives available to improve the durability and quality of road bitumen. A coal tar obtained by coal coking was distilled in a laboratory into fractions of initial boiling point IBP-180℃ (gasoline-like fuel), 180℃ - 360℃ (diesel-like fuel), and >360℃ (residue or coal tar pitch). The coal tar pitch was added into road bitumen by up to 1 - 5 wt% and investigated the alteration of physical and chemical properties. The physico-mechanical properties of coal tar pitch and bitumen blends, as well as the chemical group composition, were determined using standard techniques (MNS) and the SARA method, respectively. Results of 3% coal tar pitch addition into bitumen enhanced ductility by 12.4% and softening point by 1.6℃. We found that blending with bitumen coal tar pitch as a modifier could improve bitumen properties.

Peer Pressure and Harmful Use of Alcohol in Thailand: A Spatial Autoregressive Model Application

Due to peer pressure playing a crucial role in the decision to drink,people who have a more fragile temperament might be expected to be at higher risk.Moreover,many studies have investigated the influence of peer pressure on alcohol consumption,but few have examined the relationship between heavy drinking and peer pressure via a spatial autoregressive model(SAR)in low/middle-income countries,such as Thailand.This paper investigated the connection between heavy drinkers over the age of 15 years who drink more than or equal to 60 grams of unmixed alcohol at least once per month based on the Thai Survey of Cigarette Smoking and Alcoholic Drinking Behavior,2014.Further,the drinkers were assumed to socialize with two peer groups:immediate family and close friends.Our paper considered a SAR model because SAR can overcome the reflection problem encountered using a linear-in-means model and the correlated effect problem found with hierarchical models.The mainfinding was the discovery of a significant and positive peer effect on alcohol consumption among heavy drinkers.In addition,there was evidence of education having an effect,but no evidence of income affecting on alcohol consumption.Specifically,a higher level of education was linked with lower levels of alcohol consumption.The results not only help us to understand the peer effect and alcohol consumption behavior,but policymakers can also apply peer effect-based strategies to formulate effective policies to decrease the alcohol consumption rate in Thailand.

Partial Time-Varying Coefficient Regression and Autoregressive Mixed Model

Regression and autoregressive mixed models are classical models used to analyze the relationship between time series response variable and other covariates. The coefficients in traditional regression and autoregressive mixed models are constants. However, for complicated data, the coefficients of covariates may change with time. In this article, we propose a kind of partial time-varying coefficient regression and autoregressive mixed model and obtain the local weighted least-square estimators of coefficient functions by the local polynomial technique. The asymptotic normality properties of estimators are derived under regularity conditions, and simulation studies are conducted to empirically examine the finite-sample performances of the proposed estimators. Finally, we use real data about Lake Shasta inflow to illustrate the application of the proposed model.

Partial Time-Varying Coefficient Regression and Autoregressive Mixed Model

Regression and autoregressive mixed models are classical models used to analyze the relationship between time series response variable and other covariates. The coefficients in traditional regression and autoregressive mixed models are constants. However, for complicated data, the coefficients of covariates may change with time. In this article, we propose a kind of partial time-varying coefficient regression and autoregressive mixed model and obtain the local weighted least-square estimators of coefficient functions by the local polynomial technique. The asymptotic normality properties of estimators are derived under regularity conditions, and simulation studies are conducted to empirically examine the finite-sample performances of the proposed estimators. Finally, we use real data about Lake Shasta inflow to illustrate the application of the proposed model.

Trend Autoregressive Model Exact Run Length Evaluation on a Two-Sided Extended EWMA Chart

The Extended Exponentially Weighted Moving Average(extended EWMA)control chart is one of the control charts and can be used to quickly detect a small shift.The performance of control charts can be evaluated with the average run length(ARL).Due to the deriving explicit formulas for the ARL on a two-sided extended EWMA control chart for trend autoregressive or trend AR(p)model has not been reported previously.The aim of this study is to derive the explicit formulas for the ARL on a two-sided extended EWMA con-trol chart for the trend AR(p)model as well as the trend AR(1)and trend AR(2)models with exponential white noise.The analytical solution accuracy was obtained with the extended EWMA control chart and was compared to the numer-ical integral equation(NIE)method.The results show that the ARL obtained by the explicit formula and the NIE method is hardly different,but the explicit for-mula can help decrease the computational(CPU)time.Furthermore,this is also expanded to comparative performance with the Exponentially Weighted Moving Average(EWMA)control chart.The performance of the extended EWMA control chart is better than the EWMA control chart for all situations,both the trend AR(1)and trend AR(2)models.Finally,the analytical solution of ARL is applied to real-world data in the healthfield,such as COVID-19 data in the United Kingdom and Sweden,to demonstrate the efficacy of the proposed method.

Separation and analysis of six fractions in low temperature coal tar by column chromatography

The low temperature coal tar(CT)is taken as the raw material,and the extraction and column chromatography are used for detailed and accurate characterization in this paper.The n-heptane soluble fraction(CT-HS)and insoluble fraction(CT-HI)were obtained by n-heptane Soxhlet extraction.The extraction rate of CT-HS reached 92.79%(mass),which indicated that there are few heavy compounds in it.Further,different solvents(methylbenzene,benzene,ethyl acetate,methylbenzene-ethanol)were used to elute CT-HS by chromatographic column to obtain five fractions(saturates,aromatics,heteroatoms,phenolics and resins,named CT-SA,CT-AR,CT-HE,CT-PH,CT-RE,respectively).The yields of CTSA,CT-AR,CT-HE,CT-PH,CT-RE are 42.12%,10.43%,2.19%,9.50%and 6.63%(mass),respectively.Gas chromatography-mass spectrometry analysis of eluting components show that alkanes are the main components in CT,followed by polycyclic aromatics,and the corresponding fractions are CT-SA and CT-AR,respectively.The relative content of aliphatics in CT-SA is 76.93%,and the relative content of aromatics in CT-AR is 75.05%.This separation technology effectively separates and enriches different components in CT,and the activation energy required for the pyrolysis process of a single eluting fraction is lower than that of CT,which is expected to provide an important reference for the separation,analysis and conversion of complex oil products such as coal-oil co-processing products,coal tar and other complex heavy carbon oil products.