Navigating the pathways:TAR-DNA-binding-protein-43 aggregation,axonal transport,and local synthesis in amyotrophic lateral sclerosis pathology

Neurons are highly polarized cells with axons reaching over a meter long in adult humans.To survive and maintain their proper function,neurons depend on specific mechanisms that regulate spatiotemporal signaling and metabolic events,which need to be carried out at the right place,time,and intensity.Such mechanisms include axonal transport,local synthesis,and liquid-liquid phase separations.Alterations and malfunctions in these processes are correlated to neurodegenerative diseases such as amyotrophic lateral sclerosis(ALS).

Understanding the local structure and thermophysical behavior of Mg-La liquid alloys via machine learning potential

The local structure and thermophysical behavior of Mg-La liquid alloys were in-depth understood using deep potential molecular dynamic(DPMD) simulation driven via machine learning to promote the development of Mg-La alloys. The robustness of the trained deep potential(DP) model was thoroughly evaluated through several aspects, including root-mean-square errors(RMSEs), energy and force data, and structural information comparison results;the results indicate the carefully trained DP model is reliable. The component and temperature dependence of the local structure in the Mg-La liquid alloy was analyzed. The effect of Mg content in the system on the first coordination shell of the atomic pairs is the same as that of temperature. The pre-peak demonstrated in the structure factor indicates the presence of a medium-range ordered structure in the Mg-La liquid alloy, which is particularly pronounced in the 80at% Mg system and disappears at elevated temperatures. The density, self-diffusion coefficient, and shear viscosity for the Mg-La liquid alloy were predicted via DPMD simulation, the evolution patterns with Mg content and temperature were subsequently discussed, and a database was established accordingly. Finally, the mixing enthalpy and elemental activity of the Mg-La liquid alloy at 1200 K were reliably evaluated,which provides new guidance for related studies.

The impact of spatial scale on local Moran's I clustering of annual fishing effort for Dosidicus gigas offshore Peru

The spatial scale(?shing grid) of ?sheries research af fects the observed spatial patterns of?sheries resources such as catch-per-unit-ef fort(CPUE) and ?shing ef fort. We examined the scale impact of high value(HH) clusters of the annual ?shing ef fort for Dosidicus gigas of fshore Peru from 2009 to 2012.For a multi-scale analysis, the original commercial ?shery data were tessellated to twelve spatial scales from 6′ to 72′ with an interval of 6′. Under these spatial scales, D. gigas clusters were identi?ed using the Anselin Local Moran's I. Statistics including the number of points, mean CPUE, standard deviation(SD),skewness, kurtosis, area and centroid were calculated for these HH clusters. We found that the z-score of global Moran's I and the number of points for HH clusters follow a power law scaling relationship from2009 to 2012. The mean ef fort and its SD also follow a power law scaling relationship from 2009 to 2012.The skewness follows a linear scaling relationship in 2010 and 2011 but ?uctuates with spatial scale in2009 and 2012; kurtosis follows a logarithmic scale relationship in 2009, 2011 and 2012 but a linear scale relationship in 2010. Cluster area follows a power law scaling relationship in 2010 and 2012, a linear scaling relationship in 2009, and a quadratic scaling relationship in 2011. Based on the peaks of Moran's I indices and the multi-scale analysis, we conclude that the optimum scales are 12′ in 2009 ? 2011 and 6′ in 2012, while the coarsest allowable scales are 48′ in 2009, 2010 and 2012, and 60′ in 2011. Our research provides the best spatial scales for conducting spatial analysis of this pelagic species, and provides a better understanding of scaling behavior for the ?shing ef fort of D. gigas in the of fshore Peruvian waters.

一类d-维齐次Moran集的分形维数

该文研究了一类特殊的d-维齐次Moran集:{m_(k)^(d)}型齐次Moran集,利用质量分布原理、乘积集的分形维数不等式以及关于一维齐次Moran集上盒维数的重要引理,结合{m_(k)^(d)}型齐次Moran集的自身结构,得到了{m_(k)^(d)}型齐次Moran集在特定条件下的Hausdorff维数与上盒维数的表达式.

一类平面Moran测度的谱性研究

谱测度的研究是经典傅里叶分析在一般测度上的推广,它对分形几何、调和分析和小波分析等领域的研究都有重要意义.文章主要研究由扩张整矩阵序列和四元标准数字集序列生成的一类平面Moran测度的谱性.通过研究测度的傅里叶变换的零点与正交集之间的关系,进一步刻画该Moran测度的谱结构.最后,给出该Moran测度成为谱测度的必要条件.

一类高维齐次Moran集的Hausdorff维数与上盒维数

本文构造一类特殊的高维齐次Moran集:{m^(d)_(k)}型齐次Moran集,并得到了满足一定条件的这类集合的Hausdorff维数与上盒维数的表达式.

A study of the effect of local scour on the flow field near the spur dike

The flow field near a spur dike such as down flow and horseshoe vortex system(HVS)are susceptible to the topographic changes in the local scouring process,resulting in variation of the sediment transport with time.In this study,large eddy simulations with fixed-bed at different scouring stages were conducted to investigate the changes in flow field.The results imply that the bed deformation leads to an increase in flow rate per unit area,which represent the capability of sediment transportation by water,in the scour hole.Moreover,the intensity of turbulent kinetic energy and bimodal motion near the sand bed induced by the HVS were also varied.However,the peak moments between the two sediment transport mechanisms were different.Hence,understanding the complex feedback mechanism between topography and flow field is essential for the local scour problem.

Genome-wide investigation to assess copy number variants in the Italian local chicken population

Background Copy number variants(CNV)hold significant functional and evolutionary importance.Numerous ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure of livestock.High-density chips have enabled the detection of CNV with increased resolution,leading to the identification of even small CNV.This study aimed to identify CNV in local Italian chicken breeds and investigate their distribution across the genome.Results Copy number variants were mainly distributed across the first six chromosomes and primarily associated with loss type CNV.The majority of CNV in the investigated breeds were of types 0 and 1,and the minimum length of CNV was significantly larger than that reported in previous studies.Interestingly,a high proportion of the length of chromosome 16 was covered by copy number variation regions(CNVR),with the major histocompatibility complex being the likely cause.Among the genes identified within CNVR,only those present in at least five animals across breeds(n=95)were discussed to reduce the focus on redundant CNV.Some of these genes have been associated to functional traits in chickens.Notably,several CNVR on different chromosomes harbor genes related to muscle development,tissue-specific biological processes,heat stress resistance,and immune response.Quantitative trait loci(QTL)were also analyzed to investigate potential overlapping with the identified CNVR:54 out of the 95 gene-containing regions overlapped with 428 QTL associated to body weight and size,carcass characteristics,egg production,egg components,fat deposition,and feed intake.Conclusions The genomic phenomena reported in this study that can cause changes in the distribution of CNV within the genome over time and the comparison of these differences in CNVR of the local chicken breeds could help in preserving these genetic resources.

Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy

Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.

Scheme Based on Multi-Level Patch Attention and Lesion Localization for Diabetic Retinopathy Grading

Early screening of diabetes retinopathy(DR)plays an important role in preventing irreversible blindness.Existing research has failed to fully explore effective DR lesion information in fundus maps.Besides,traditional attention schemes have not considered the impact of lesion type differences on grading,resulting in unreasonable extraction of important lesion features.Therefore,this paper proposes a DR diagnosis scheme that integrates a multi-level patch attention generator(MPAG)and a lesion localization module(LLM).Firstly,MPAGis used to predict patches of different sizes and generate a weighted attention map based on the prediction score and the types of lesions contained in the patches,fully considering the impact of lesion type differences on grading,solving the problem that the attention maps of lesions cannot be further refined and then adapted to the final DR diagnosis task.Secondly,the LLM generates a global attention map based on localization.Finally,the weighted attention map and global attention map are weighted with the fundus map to fully explore effective DR lesion information and increase the attention of the classification network to lesion details.This paper demonstrates the effectiveness of the proposed method through extensive experiments on the public DDR dataset,obtaining an accuracy of 0.8064.

Deep brain implantable microelectrode arrays for detection and functional localization of the subthalamic nucleus in rats with Parkinson’s disease

The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.

Cooperative Anti-Jamming and Interference Mitigation for UAV Networks: A Local Altruistic Game Approach

To improve the anti-jamming and interference mitigation ability of the UAV-aided communication systems, this paper investigates the channel selection optimization problem in face of both internal mutual interference and external malicious jamming. A cooperative anti-jamming and interference mitigation method based on local altruistic is proposed to optimize UAVs’ channel selection. Specifically, a Stackelberg game is modeled to formulate the confrontation relationship between UAVs and the jammer. A local altruistic game is modeled with each UAV considering the utilities of both itself and other UAVs. A distributed cooperative anti-jamming and interference mitigation algorithm is proposed to obtain the Stackelberg equilibrium. Finally, the convergence of the proposed algorithm and the impact of the transmission power on the system loss value are analyzed, and the anti-jamming performance of the proposed algorithm can be improved by around 64% compared with the existing algorithms.

Numerical study on local scour characteristics around submarine pipelines in the Yellow River Delta silty sandy soil under waves and currents

Due to their high reliability and cost-efficiency,submarine pipelines are widely used in offshore oil and gas resource engineering.Due to the interaction of waves,currents,seabed,and pipeline structures,the soil around submarine pipelines is prone to local scour,severely affecting their operational safety.With the Yellow River Delta as the research area and based on the renormalized group(RNG)k-εturbulence model and Stokes fifth-order wave theory,this study solves the Navier-Stokes(N-S)equation using the finite difference method.The volume of fluid(VOF)method is used to describe the fluid-free surface,and a threedimensional numerical model of currents and waves-submarine pipeline-silty sandy seabed is established.The rationality of the numerical model is verified using a self-built waveflow flume.On this basis,in this study,the local scour development and characteristics of submarine pipelines in the Yellow River Delta silty sandy seabed in the prototype environment are explored and the influence of the presence of pipelines on hydrodynamic features such as surrounding flow field,shear stress,and turbulence intensity is analyzed.The results indicate that(1)local scour around submarine pipelines can be divided into three stages:rapid scour,slow scour,and stable scour.The maximum scour depth occurs directly below the pipeline,and the shape of the scour pits is asymmetric.(2)As the water depth decreases and the pipeline suspension height increases,the scour becomes more intense.(3)When currents go through a pipeline,a clear stagnation point is formed in front of the pipeline,and the flow velocity is positively correlated with the depth of scour.This study can provide a valuable reference for the protection of submarine pipelines in this area.

Life cycle assessment as a prospective tool for sustainable agriculture and food planning at a local level

Owing to the far-reaching environmental consequences of agriculture and food systems,such as their contribution to climate change,there is an urgent need to reduce their impact.International and national governments set sustainability targets and implement corresponding measures.Nevertheless,critics of the globalized system claim that a territorial administrative scale is better suited to address sustainability issues.Yet,at the subnational level,local authorities rarely apply a systemic environmental assessment to enhance their action plans.This paper employs a territorial life cycle assessment methodology to improve local environmental agri-food planning.The objective is to identify significant direct and indirect environmental hotspots,their origins,and formulate effective mitigation strategies.The methodology is applied to the administrative department of Finistere,a strategic agricultural region in North-Western France.Multiple environmental criteria including climate change,fossil resource scarcity,toxicity,and land use are modeled.The findings reveal that the primary environmental hotspots of the studied local food system arise from indirect sources,such as livestock feed or diesel consumption.Livestock reduction and organic farming conversion emerge as the most environmentally efficient strategies,resulting in a 25%decrease in the climate change indicator.However,the overall modeled impact reduction is insufficient following national objectives and remains limited for the land use indicator.These results highlight the innovative application of life cycle assessment led at a local level,offering insights for the further advancement of systematic and prospective local agri-food assessment.Additionally,they provide guidance for local authorities to enhance the sustainability of planning strategies.

基于Moran’s I的多变量空间自相关研究与应用

针对传统空间Moran’s I只适用于分析单一变量的局限性,提出基于Moran’s I的多变量空间自相关性分析理论.首先,借助传统空间Moran’s I的向量定义,推导出适用于分析多变量空间自相关性的Moran’s I矩阵,并通过蒙特卡洛法模拟研究Moran’s I矩阵中元素的分布情况,结果显示:在样本量较小时,只有非主对角线上的元素服从正态分布,在样本量较大时,任一元素都服从正态分布.基于上述分布结论,可对Moran’s I矩阵中元素进行显著性检验.其次,当空间权重矩阵为正定矩阵时,证明Moran’s I矩阵服从Wishart分布.然后,根据Moran’s I矩阵的代数意义提出适用于多变量空间自相关理论的若干综合评价指标.最后,结合多维空气污染数据进行空间自相关分析.

Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.

Integrated multi-scale approach combining global homogenization and local refinement for multi-field analysis of high-temperature superconducting composite magnets

Second-generation high-temperature superconducting(HTS)conductors,specifically rare earth-barium-copper-oxide(REBCO)coated conductor(CC)tapes,are promising candidates for high-energy and high-field superconducting applications.With respect to epoxy-impregnated REBCO composite magnets that comprise multilayer components,the thermomechanical characteristics of each component differ considerably under extremely low temperatures and strong electromagnetic fields.Traditional numerical models include homogenized orthotropic models,which simplify overall field calculation but miss detailed multi-physics aspects,and full refinement(FR)ones that are thorough but computationally demanding.Herein,we propose an extended multi-scale approach for analyzing the multi-field characteristics of an epoxy-impregnated composite magnet assembled by HTS pancake coils.This approach combines a global homogenization(GH)scheme based on the homogenized electromagnetic T-A model,a method for solving Maxwell's equations for superconducting materials based on the current vector potential T and the magnetic field vector potential A,and a homogenized orthotropic thermoelastic model to assess the electromagnetic and thermoelastic properties at the macroscopic scale.We then identify“dangerous regions”at the macroscopic scale and obtain finer details using a local refinement(LR)scheme to capture the responses of each component material in the HTS composite tapes at the mesoscopic scale.The results of the present GH-LR multi-scale approach agree well with those of the FR scheme and the experimental data in the literature,indicating that the present approach is accurate and efficient.The proposed GH-LR multi-scale approach can serve as a valuable tool for evaluating the risk of failure in large-scale HTS composite magnets.

Assessment of earthquake location uncertainties for the design of local seismic networks

The ability to estimate earthquake source locations,along with the appraisal of relevant uncertainties,is paramount in monitoring both natural and human-induced micro-seismicity.For this purpose,a monitoring network must be designed to minimize the location errors introduced by geometrically unbalanced networks.In this study,we first review different sources of errors relevant to the localization of seismic events,how they propagate through localization algorithms,and their impact on outcomes.We then propose a quantitative method,based on a Monte Carlo approach,to estimate the uncertainty in earthquake locations that is suited to the design,optimization,and assessment of the performance of a local seismic monitoring network.To illustrate the performance of the proposed approach,we analyzed the distribution of the localization uncertainties and their related dispersion for a highly dense grid of theoretical hypocenters in both the horizontal and vertical directions using an actual monitoring network layout.The results expand,quantitatively,the qualitative indications derived from purely geometrical parameters(azimuthal gap(AG))and classical detectability maps.The proposed method enables the systematic design,optimization,and evaluation of local seismic monitoring networks,enhancing monitoring accuracy in areas proximal to hydrocarbon production,geothermal fields,underground natural gas storage,and other subsurface activities.This approach aids in the accurate estimation of earthquake source locations and their associated uncertainties,which are crucial for assessing and mitigating seismic risks,thereby enabling the implementation of proactive measures to minimize potential hazards.From an operational perspective,reliably estimating location accuracy is crucial for evaluating the position of seismogenic sources and assessing possible links between well activities and the onset of seismicity.

SNR and RSSI Based an Optimized Machine Learning Based Indoor Localization Approach:Multistory Round Building Scenario over LoRa Network

In situations when the precise position of a machine is unknown,localization becomes crucial.This research focuses on improving the position prediction accuracy over long-range(LoRa)network using an optimized machine learning-based technique.In order to increase the prediction accuracy of the reference point position on the data collected using the fingerprinting method over LoRa technology,this study proposed an optimized machine learning(ML)based algorithm.Received signal strength indicator(RSSI)data from the sensors at different positions was first gathered via an experiment through the LoRa network in a multistory round layout building.The noise factor is also taken into account,and the signal-to-noise ratio(SNR)value is recorded for every RSSI measurement.This study concludes the examination of reference point accuracy with the modified KNN method(MKNN).MKNN was created to more precisely anticipate the position of the reference point.The findings showed that MKNN outperformed other algorithms in terms of accuracy and complexity.

Survey of Indoor Localization Based on Deep Learning

This study comprehensively examines the current state of deep learning (DL) usage in indoor positioning.It emphasizes the significance and efficiency of convolutional neural networks (CNNs) and recurrent neuralnetworks (RNNs). Unlike prior studies focused on single sensor modalities like Wi-Fi or Bluetooth, this researchexplores the integration of multiple sensor modalities (e.g.,Wi-Fi, Bluetooth, Ultra-Wideband, ZigBee) to expandindoor localization methods, particularly in obstructed environments. It addresses the challenge of precise objectlocalization, introducing a novel hybrid DL approach using received signal information (RSI), Received SignalStrength (RSS), and Channel State Information (CSI) data to enhance accuracy and stability. Moreover, thestudy introduces a device-free indoor localization algorithm, offering a significant advancement with potentialobject or individual tracking applications. It recognizes the increasing importance of indoor positioning forlocation-based services. It anticipates future developments while acknowledging challenges such as multipathinterference, noise, data standardization, and scarcity of labeled data. This research contributes significantly toindoor localization technology, offering adaptability, device independence, and multifaceted DL-based solutionsfor real-world challenges and future advancements. Thus, the proposed work addresses challenges in objectlocalization precision and introduces a novel hybrid deep learning approach, contributing to advancing locationcentricservices.While deep learning-based indoor localization techniques have improved accuracy, challenges likedata noise, standardization, and availability of training data persist. However, ongoing developments are expectedto enhance indoor positioning systems to meet real-world demands.