Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or ...Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.展开更多
The wave/particle duality of particles in Physics is well known. Particles have properties that uniquely characterize them from one another, such as mass, charge and spin. Charged particles have associated Electric an...The wave/particle duality of particles in Physics is well known. Particles have properties that uniquely characterize them from one another, such as mass, charge and spin. Charged particles have associated Electric and Magnetic fields. Also, every moving particle has a De Broglie wavelength determined by its mass and velocity. This paper shows that all of these properties of a particle can be derived from a single wave function equation for that particle. Wave functions for the Electron and the Positron are presented and principles are provided that can be used to calculate the wave functions of all the fundamental particles in Physics. Fundamental particles such as electrons and positrons are considered to be point particles in the Standard Model of Physics and are not considered to have a structure. This paper demonstrates that they do indeed have structure and that this structure extends into the space around the particle’s center (in fact, they have infinite extent), but with rapidly diminishing energy density with the distance from that center. The particles are formed from Electromagnetic standing waves, which are stable solutions to the Schrödinger and Classical wave equations. This stable structure therefore accounts for both the wave and particle nature of these particles. In fact, all of their properties such as mass, spin and electric charge, can be accounted for from this structure. These particle properties appear to originate from a single point at the center of the wave function structure, in the same sort of way that the Shell theorem of gravity causes the gravity of a body to appear to all originate from a central point. This paper represents the first two fully characterized fundamental particles, with a complete description of their structure and properties, built up from the underlying Electromagnetic waves that comprise these and all fundamental particles.展开更多
The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates ...The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.展开更多
Chimeric antigen receptor natural killer(CAR-NK)cell therapy is an alternative immunotherapy that provides robust tumor-eliminating effects without inducing life-threatening toxicities and graft-versus-host disease.CA...Chimeric antigen receptor natural killer(CAR-NK)cell therapy is an alternative immunotherapy that provides robust tumor-eliminating effects without inducing life-threatening toxicities and graft-versus-host disease.CAR-NK cell therapy has enabled the development of“off-the-shelf”products that bypass the lengthy and expensive cell manufacturing process1.展开更多
Intervertebral disc degeneration is a leading cause of lower back pain and is characterized by pathological processes such as nucleus pulposus cell apoptosis,extracellular matrix imbalance,and annulus fibrosus rupture...Intervertebral disc degeneration is a leading cause of lower back pain and is characterized by pathological processes such as nucleus pulposus cell apoptosis,extracellular matrix imbalance,and annulus fibrosus rupture.These pathological changes result in disc height loss and functional decline,potentially leading to disc herniation.This comprehensive review aimed to address the current challenges in intervertebral disc degeneration treatment by evaluating the regenerative potential of stem cell-based therapies,with a particular focus on emerging technologies such as exosomes and gene vector systems.Through mechanisms such as differentiation,paracrine effects,and immunomodulation,stem cells facilitate extracellular matrix repair and reduce nucleus pulposus cell apoptosis.Despite recent advancements,clinical applications are hindered by challenges such as hypoxic disc environments and immune rejection.By analyzing recent preclinical and clinical findings,this review provided insights into optimizing stem cell therapy to overcome these obstacles and highlighted future directions in the field.展开更多
The transverse single-spin asymmetry forρ^(0) production in semi-inclusive deep inelastic scattering was recently reported by the COMPASS Collaboration.Using the Sivers function extracted from pion and kaon productio...The transverse single-spin asymmetry forρ^(0) production in semi-inclusive deep inelastic scattering was recently reported by the COMPASS Collaboration.Using the Sivers function extracted from pion and kaon productions,we perform a calculation of the Sivers asymmetry within the transverse momentum-dependent factorization.Our results are consistent with the COMPASS data,supporting the universality of the Sivers function in the semi-inclusive deep inelastic scattering process for different final-state hadrons within current experimental uncertainties.While different parametrizations of the Sivers function from global analyses allow describing the data equally well,we obtain very different predictions on the Sivers asymmetry ofρand K^(*)productions at electron-ion colliders,which therefore are expected to provide further constraints.展开更多
An effective power quality prediction for regional power grid can provide valuable references and contribute to the discovering and solving of power quality problems. So a predicting model for power quality steady sta...An effective power quality prediction for regional power grid can provide valuable references and contribute to the discovering and solving of power quality problems. So a predicting model for power quality steady state index based on chaotic theory and least squares support vector machine (LSSVM) is proposed in this paper. At first, the phase space reconstruction of original power quality data is performed to form a new data space containing the attractor. The new data space is used as training samples for the LSSVM. Then in order to predict power quality steady state index accurately, the particle swarm algorithm is adopted to optimize parameters of the LSSVM model. According to the simulation results based on power quality data measured in a certain distribution network, the model applies to several indexes with higher forecasting accuracy and strong practicability.展开更多
Nowadays, power quality issues are becoming a significant research topic because of the increasing inclusion of very sensitive devices and considerable renewable energy sources. In general, most of the previous power ...Nowadays, power quality issues are becoming a significant research topic because of the increasing inclusion of very sensitive devices and considerable renewable energy sources. In general, most of the previous power quality classification techniques focused on single power quality events and did not include an optimal feature selection process. This paper presents a classification system that employs Wavelet Transform and the RMS profile to extract the main features of the measured waveforms containing either single or complex disturbances. A data mining process is designed to select the optimal set of features that better describes each disturbance present in the waveform. Support Vector Machine binary classifiers organized in a “One Vs Rest” architecture are individually optimized to classify single and complex disturbances. The parameters that rule the performance of each binary classifier are also individually adjusted using a grid search algorithm that helps them achieve optimal performance. This specialized process significantly improves the total classification accuracy. Several single and complex disturbances were simulated in order to train and test the algorithm. The results show that the classifier is capable of identifying >99% of single disturbances and >97% of complex disturbances.展开更多
In the paper, a general framework for large scale modeling of macroeconomic and financial time series is introduced. The proposed approach is characterized by simplicity of implementation, performing well independentl...In the paper, a general framework for large scale modeling of macroeconomic and financial time series is introduced. The proposed approach is characterized by simplicity of implementation, performing well independently of persistence and heteroskedasticity properties, accounting for common deterministic and stochastic factors. Monte Carlo results strongly support the proposed methodology, validating its use also for relatively small cross-sectional and temporal samples.展开更多
Thrust-vectoring capability has become a critical feature for propulsion systems as space missions move from static to dynamic.Thrust-vectoring is a well-developed area of rocket engine science.For electric propulsion...Thrust-vectoring capability has become a critical feature for propulsion systems as space missions move from static to dynamic.Thrust-vectoring is a well-developed area of rocket engine science.For electric propulsion,however,it is an evolving field that has taken a new leap forward in recent years.A review and analysis of thrust-vectoring schemes for electric propulsion systems have been conducted.The scope of this review includes thrust-vectoring schemes that can be implemented for electrostatic,electromagnetic,and beam-driven thrusters.A classification of electric propulsion schemes that provide thrust-vectoring capability is developed.More attention is given to schemes implemented in laboratory prototypes and flight models.The final part is devoted to a discussion on the suitability of different electric propulsion systems with thrust-vectoring capability for modern space mission operations.The thrust-vectoring capability of electric propulsion is necessary for inner and outer space satellites,which are at a disadvantage with conventional unidirectional propulsion systems due to their limited maneuverability.展开更多
It is shown that such phenomena as quantum correlations (interaction of space-separated quantum entities), the action of magnetic vector potential on quantum entities in the absence of magnetic field, and near-field a...It is shown that such phenomena as quantum correlations (interaction of space-separated quantum entities), the action of magnetic vector potential on quantum entities in the absence of magnetic field, and near-field antenna effect (the existence of superluminally propagating electromagnetic fields) may be explained by action of spin supercurrents. In case of quantum correlations between quantum entities, spin supercurrent emerges between virtual particles pairs (virtual photons) created by those quantum entities. The explanation of magnetic vector potential and near-field antenna effect is based on contemporary principle of quantum mechanics: the physical vacuum is not an empty space but the ground state of the field consisting of quantum harmonic oscillators (QHOs) characterized by zero-point energy. Using the properties of the oscillators and spin supercurrent, it is proved that magnetic vector potential is proportional to the moment causing the orientation of spin of QHO along the direction of magnetic field. The near-field antenna effect is supposed to take place as a result of action of spin supercurrent causing secondary electromagnetic oscillations. In this way, the electromagnetic field may spread at the speed of spin supercurrent. As spin supercurrent is an inertia free process, its speed may be greater than that of light, which does not contradict postulates of special relativity that sets limits to the speed of inertial systems only.展开更多
Objective:To evaluate the Anaplasma phagocytophilum(A.phagocytophilum),Ehrlichia canis(E.canis,Dirofilaria immitis(D.immitis)(canine heartworm),Borrelia burgdorferi(B.burgdorferi)infections in countryside dogs from Yu...Objective:To evaluate the Anaplasma phagocytophilum(A.phagocytophilum),Ehrlichia canis(E.canis,Dirofilaria immitis(D.immitis)(canine heartworm),Borrelia burgdorferi(B.burgdorferi)infections in countryside dogs from Yunnan,Hainan and Anhui provinces.Methods:Serum samples were collected from 26 dogs in Yunnan.Hainan and Anhui provinces.The samples were tested using a commercial ELISA rapid diagnostic assay kit(SNAP^(?)4Dx^(?);IDEXX Laboratories,Inc.U.S.A.).Meaiiwliile,indirect immunofluorescence assay(IFA)recommended by WHO was conducted to delect IgG to A.phagocytophilum.Two methods were analyzed and compared.Results:The number of serologically positive dogs for IgG to A.phagocytophilum was only 2which was from Hainan province and none of the 26 dogs responded positive for E.canu.D.immitis(canine heartworm,and B.burgdorferi by ELISA rapid diagnostic method.The number of serologically positive dogs for IgG to A.phagocytophilum was 13(50%)by IFA method.Data of the two methods were analyzed by statistical software and the difference was statistically significant(P=0.002).Conclusions:It can be concluded that IFA method was more sensitive than ELISA rapid diagnostic method.However,we need conduct further and intensive epidemiology survey on tick-born diseases pathogens including.4.phagocytophilum,E.canis,D.immitis(canine heartworm),and B.burgdorferi which have public health significance.展开更多
Since its discovery in the 1980s,the insect cell-baculovirus expression vector system(IC-BEVS)has been widely used in biomedical applications,such as recombinant protein expression,drug screening,vaccine development,g...Since its discovery in the 1980s,the insect cell-baculovirus expression vector system(IC-BEVS)has been widely used in biomedical applications,such as recombinant protein expression,drug screening,vaccine development,gene therapy and so on[1].As a eukaryotic system,IC-BEVS has great development prospects due to its advantages such as high safety,simple operation,simultaneous expression of multi-subunit proteins,and suitability for large-scale cultivation[2].展开更多
Accurately estimating the State of Health(SOH)and Remaining Useful Life(RUL)of lithium-ion batteries(LIBs)is crucial for the continuous and stable operation of battery management systems.However,due to the complex int...Accurately estimating the State of Health(SOH)and Remaining Useful Life(RUL)of lithium-ion batteries(LIBs)is crucial for the continuous and stable operation of battery management systems.However,due to the complex internal chemical systems of LIBs and the nonlinear degradation of their performance,direct measurement of SOH and RUL is challenging.To address these issues,the Twin Support Vector Machine(TWSVM)method is proposed to predict SOH and RUL.Initially,the constant current charging time of the lithium battery is extracted as a health indicator(HI),decomposed using Variational Modal Decomposition(VMD),and feature correlations are computed using Importance of Random Forest Features(RF)to maximize the extraction of critical factors influencing battery performance degradation.Furthermore,to enhance the global search capability of the Convolution Optimization Algorithm(COA),improvements are made using Good Point Set theory and the Differential Evolution method.The Improved Convolution Optimization Algorithm(ICOA)is employed to optimize TWSVM parameters for constructing SOH and RUL prediction models.Finally,the proposed models are validated using NASA and CALCE lithium-ion battery datasets.Experimental results demonstrate that the proposed models achieve an RMSE not exceeding 0.007 and an MAPE not exceeding 0.0082 for SOH and RUL prediction,with a relative error in RUL prediction within the range of[-1.8%,2%].Compared to other models,the proposed model not only exhibits superior fitting capability but also demonstrates robust performance.展开更多
AIM: To kill CEA positive colorectal carcinoma cells specifically using the E coli cytosine deaminase (CD) suicide gene, a new replication-deficient recombinant adenoviral vector was constructed in which CD gene was c...AIM: To kill CEA positive colorectal carcinoma cells specifically using the E coli cytosine deaminase (CD) suicide gene, a new replication-deficient recombinant adenoviral vector was constructed in which CD gene was controlled under CEA promoter and its in vitro cytotoxic effects were evaluated. METHODS: Shuttle plasmid containing CD gene and regulatory sequence of the CEA gene was constructed and recombined with the right arm of adenovirus genome DNA in 293 cell strain. Dot blotting and PCR were used to identify positive plaques. The purification of adenovirus was performed with ultra-concentration in CsCl step gradients and the titration was measured with plaque formation assay. Cytotoxic effects were assayed with MTT method, The fifty percent inhibition concentration (IC(50)) of 5-FC was calculated using a curve-fitting parameter. The human colorectal carcinoma cell line, which was CEA-producing, and the CEA-nonproducing Hela cell line were applied in cytological tests. An established recombinant adenovirus vector AdCMVCD, in which the CD gene was controlled under CMV promoter, was used as virus control. Quantitative results were expressed as the mean +/- SD of the mean. Statistical analysis was performed using ANOVA test. RESULTS: The desired recombinant adenovirus vector was named AdCEACD. The results of dot blotting and PCR showed that the recombinant adenovirus contained CEA promoter and CD gene. Virus titer was about 5.0 X 10(14)pfu/L(-1) after purification. The CEA-producing Lovo cells were sensitive to 5-FC and had the same cytotoxic effect after infection with AdCEACD and AdCMVCD (The IC(50) values of 5-FC in parent Lovo cells, Lovo cells infected with 100 M.O.I AdCEACD and Lovo cells infected with 10 M.O.I AdCMVCD were 】15000, 216.5+/-38.1 and 128.8+/-25.4 micromol.L(-1), P【0.001, respectively), and the cytotoxicity of 5-FC increased accordingly when the m.o.i of adenoviruses were enhanced (The value of IC(50) of 5-FC was reduced to 27.9+/-4.2 micromol.L(-1) in 1000 M.O.I AdCEACD infected Lovo cells and 24.8+/-7.1 micromol.L(-1) in 100 M.O.I AdCMVCD infected Lovo cells, P【0.05, P【0.01, respectively). The CEA-nonproducing Hela cells had no effect after infection with AdCEACD, but Hela cells had the cytotoxic sensitivity to 5-FC after infection with AdCMVCD (The IC(50) of 5-FC in parent Hele cells and Hela cells infected with AdCMVCD at 10 M.O.I was 】15000 and 214.5+/-31.3 micromol.L(-1), P【0.001). AdCEACD/5-FC system also had bystander effect, and the viability was about 30 percent when the proportion of transfected cells was only 10 percent. CONCLUSION: The recombinant adenovirus vector AdCEACD has the character of cell type-specific gene delivery. The AdCEACD/5-FC system may become a new, potent and specific approach for the gene therapy of CEA-positive neoplasms, especially colon carcinoma.展开更多
In this work, a total of 322 tests were taken on young volunteers by performing 10 different falls, 6 different Activities of Daily Living (ADL) and 7 Dynamic Gait Index (DGI) tests using a custom-designed Wireless Ga...In this work, a total of 322 tests were taken on young volunteers by performing 10 different falls, 6 different Activities of Daily Living (ADL) and 7 Dynamic Gait Index (DGI) tests using a custom-designed Wireless Gait Analysis Sensor (WGAS). In order to perform automatic fall detection, we used Back Propagation Artificial Neural Network (BP-ANN) and Support Vector Machine (SVM) based on the 6 features extracted from the raw data. The WGAS, which includes a tri-axial accelerometer, 2 gyroscopes, and a MSP430 microcontroller, is worn by the subjects at either T4 (at back) or as a belt-clip in front of the waist during the various tests. The raw data is wirelessly transmitted from the WGAS to a near-by PC for real-time fall classification. The BP ANN is optimized by varying the training, testing and validation data sets and training the network with different learning schemes. SVM is optimized by using three different kernels and selecting the kernel for best classification rate. The overall accuracy of BP ANN is obtained as 98.20% with LM and RPROP training from the T4 data, while from the data taken at the belt, we achieved 98.70% with LM and SCG learning. The overall accuracy using SVM was 98.80% and 98.71% with RBF kernel from the T4 and belt position data, respectively.展开更多
Objective:To evaluate the larvicidal and pupicidal potential of the methanolic extracts from Moringa oleifera(M.oleifera) plant seeds against malarial vector Anopheles stephensi(A.stephensi) mosquitoes at different co...Objective:To evaluate the larvicidal and pupicidal potential of the methanolic extracts from Moringa oleifera(M.oleifera) plant seeds against malarial vector Anopheles stephensi(A.stephensi) mosquitoes at different concentrations(20,40,60,80 and 100 ppm).Methods:M.oleifera was collected from the area of around Bharathiar University,Coimbatore.The dried plant materials were powdered by an electrical blender.From each sample,100 g of the plant material were extracted with 300 mL of methanol for 8 h in a Soxhlet apparatus.The extracts were evaporated to dryness in rotary vacuum evaporator to yield 122 mg and 110 mg of dark greenish material(residue) from Arcang amara and Ocimum basilicum,respectively.One gram of the each plant residue was dissolved separately in 100 mL of acetone(stock solution) from which different concentrations, i.e.,20,40,60,80 and 100 ppm were prepared.Results:Larvicidal activity of M.oleifera exhibited in the first to fourth instar larvae of the A.stephensi,and the LC_(50) and LC_(90) values were 57.79 ppm and 125.93 ppm for the first instar,63.90 ppm and 133.07 ppm for the second inslar,72.45 ppm and 139.82 ppm for the third instar,78.93 ppm and 143.20 ppm for the fourth instar,respectively. During the pupal stage the methanolic extract of M.oleifera showed that the LC_(50),and LC_(90) values were 67.77 ppm and 141.00 ppm,respectively.Conclusions:The present study indicates that the phytochemicals derived from M.oleifera seeds extracts are effective mosquito vector control agents and the plant extracts may be used for further integrated pest management programs.展开更多
Accurate vector extraction from design drawings is required first to automatically create 3D models from pixel-level engineering design drawings. However, this task faces the challenges of complicated design shapes as...Accurate vector extraction from design drawings is required first to automatically create 3D models from pixel-level engineering design drawings. However, this task faces the challenges of complicated design shapes as well as cumbersome and cluttered annotations on drawings, which interfere with the vector extraction heavily. In this article, the transmission tower containing the most complex structure is taken as the research object, and a semantic segmentation network is constructed to first segment the shape masks from the pixel-level drawings. Preprocessing and postprocessing are also proposed to ensure the stability and accuracy of the shape mask segmentation. Then, based on the obtained shape masks, a vector extraction network guided by heatmaps is designed to extract structural vectors by fusing the features from node heatmap and skeleton heatmap, respectively. Compared with the state-of-the-art methods, experiment results illustrate that the proposed semantic segmentation method can effectively eliminate the interference of many elements on drawings to segment the shape masks effectively, meanwhile, the model trained by the proposed vector extraction network can accurately extract the vectors such as nodes and line connections, avoiding redundant vector detection. The proposed method lays a solid foundation for automatic 3D model reconstruction and contributes to technological advancements in relevant fields.展开更多
We demonstrate an effective and optimal strategy for generating spatially resolved longitudinal spin angular momentum(LSAM)in optical tweezers by tightly focusing the first-order spirally polarized vector(SPV)beams wi...We demonstrate an effective and optimal strategy for generating spatially resolved longitudinal spin angular momentum(LSAM)in optical tweezers by tightly focusing the first-order spirally polarized vector(SPV)beams with zero intrinsic angular momentum into a refractive index stratified medium.The stratified medium gives rise to a spherically aberrated intensity profile near the focal region of the optical tweezers,with off-axis intensity lobes in the radial direction possessing opposite LSAM(helicities corresponding toσ=+1 and−1)compared to the beam center.We trap mesoscopic birefringent particles in an off-axis intensity lobe as well as at the beam center by modifying the trapping plane and observe particles spinning in opposite directions depending on their location.The direction of rotation depends on the particle size with larger particles spinning either clockwise or anticlockwise depending on the direction of spirality of the polarization of the SPV beam after tight focusing,while smaller particles spin in both directions depending on their spatial locations.Numerical simulations support our experimental observations.Our results introduce new avenues in spin-orbit optomechanics to facilitate novel yet straightforward avenues for exotic and complex particle manipulation in optical tweezers.展开更多
文摘Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.
文摘The wave/particle duality of particles in Physics is well known. Particles have properties that uniquely characterize them from one another, such as mass, charge and spin. Charged particles have associated Electric and Magnetic fields. Also, every moving particle has a De Broglie wavelength determined by its mass and velocity. This paper shows that all of these properties of a particle can be derived from a single wave function equation for that particle. Wave functions for the Electron and the Positron are presented and principles are provided that can be used to calculate the wave functions of all the fundamental particles in Physics. Fundamental particles such as electrons and positrons are considered to be point particles in the Standard Model of Physics and are not considered to have a structure. This paper demonstrates that they do indeed have structure and that this structure extends into the space around the particle’s center (in fact, they have infinite extent), but with rapidly diminishing energy density with the distance from that center. The particles are formed from Electromagnetic standing waves, which are stable solutions to the Schrödinger and Classical wave equations. This stable structure therefore accounts for both the wave and particle nature of these particles. In fact, all of their properties such as mass, spin and electric charge, can be accounted for from this structure. These particle properties appear to originate from a single point at the center of the wave function structure, in the same sort of way that the Shell theorem of gravity causes the gravity of a body to appear to all originate from a central point. This paper represents the first two fully characterized fundamental particles, with a complete description of their structure and properties, built up from the underlying Electromagnetic waves that comprise these and all fundamental particles.
基金supported by grants PID2020-120308RB-I00 and PID2023-147802OB-I00 funded by MICIU/AEI/10.13039/501100011033FEDER,UE,by Aligning Science Across Parkinson’s(ref.ASAP-020505)through the Michael J.Fox Foundation for Parkinson’s Research+1 种基金by CiberNed Intramural Collaborative Projects(ref.PI2020/09)by the Spanish Fundación Mutua Madrile?a de Investigación Médica(to JLL)。
文摘The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.
基金supported by grants from the Noncommunicable Chronic Diseases-National Science and Technology Major Project(Grant No.2023ZD0501300)Science Technology Department of Zhejiang Province(Grant No.2021C03117)+2 种基金National Natural Science Foundation of China(Grant No.82350104 and 82170219)Natural Science Foundation of Zhejiang Province,China(Grant No.LY23H080004 and LY24H080001)Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(Grant No.2021KY199)。
文摘Chimeric antigen receptor natural killer(CAR-NK)cell therapy is an alternative immunotherapy that provides robust tumor-eliminating effects without inducing life-threatening toxicities and graft-versus-host disease.CAR-NK cell therapy has enabled the development of“off-the-shelf”products that bypass the lengthy and expensive cell manufacturing process1.
基金Supported by Henan Province Key Research and Development Program,No.231111311000Henan Provincial Science and Technology Research Project,No.232102310411+2 种基金Henan Province Medical Science and Technology Key Project,No.LHGJ20220566 and No.LHGJ20240365Henan Province Medical Education Research Project,No.WJLX2023079Zhengzhou Medical and Health Technology Innovation Guidance Program,No.2024YLZDJH022.
文摘Intervertebral disc degeneration is a leading cause of lower back pain and is characterized by pathological processes such as nucleus pulposus cell apoptosis,extracellular matrix imbalance,and annulus fibrosus rupture.These pathological changes result in disc height loss and functional decline,potentially leading to disc herniation.This comprehensive review aimed to address the current challenges in intervertebral disc degeneration treatment by evaluating the regenerative potential of stem cell-based therapies,with a particular focus on emerging technologies such as exosomes and gene vector systems.Through mechanisms such as differentiation,paracrine effects,and immunomodulation,stem cells facilitate extracellular matrix repair and reduce nucleus pulposus cell apoptosis.Despite recent advancements,clinical applications are hindered by challenges such as hypoxic disc environments and immune rejection.By analyzing recent preclinical and clinical findings,this review provided insights into optimizing stem cell therapy to overcome these obstacles and highlighted future directions in the field.
基金supported by the National Key R&D Program of China(Grant No.2024YFA1611004)the National Natural Science Foundation of China(Grant Nos.12175117,12475084,and 12321005)the Shandong Province Natural Science Foundation(Grant Nos.ZFJH202303 and ZR2024MA012)。
文摘The transverse single-spin asymmetry forρ^(0) production in semi-inclusive deep inelastic scattering was recently reported by the COMPASS Collaboration.Using the Sivers function extracted from pion and kaon productions,we perform a calculation of the Sivers asymmetry within the transverse momentum-dependent factorization.Our results are consistent with the COMPASS data,supporting the universality of the Sivers function in the semi-inclusive deep inelastic scattering process for different final-state hadrons within current experimental uncertainties.While different parametrizations of the Sivers function from global analyses allow describing the data equally well,we obtain very different predictions on the Sivers asymmetry ofρand K^(*)productions at electron-ion colliders,which therefore are expected to provide further constraints.
文摘An effective power quality prediction for regional power grid can provide valuable references and contribute to the discovering and solving of power quality problems. So a predicting model for power quality steady state index based on chaotic theory and least squares support vector machine (LSSVM) is proposed in this paper. At first, the phase space reconstruction of original power quality data is performed to form a new data space containing the attractor. The new data space is used as training samples for the LSSVM. Then in order to predict power quality steady state index accurately, the particle swarm algorithm is adopted to optimize parameters of the LSSVM model. According to the simulation results based on power quality data measured in a certain distribution network, the model applies to several indexes with higher forecasting accuracy and strong practicability.
文摘Nowadays, power quality issues are becoming a significant research topic because of the increasing inclusion of very sensitive devices and considerable renewable energy sources. In general, most of the previous power quality classification techniques focused on single power quality events and did not include an optimal feature selection process. This paper presents a classification system that employs Wavelet Transform and the RMS profile to extract the main features of the measured waveforms containing either single or complex disturbances. A data mining process is designed to select the optimal set of features that better describes each disturbance present in the waveform. Support Vector Machine binary classifiers organized in a “One Vs Rest” architecture are individually optimized to classify single and complex disturbances. The parameters that rule the performance of each binary classifier are also individually adjusted using a grid search algorithm that helps them achieve optimal performance. This specialized process significantly improves the total classification accuracy. Several single and complex disturbances were simulated in order to train and test the algorithm. The results show that the classifier is capable of identifying >99% of single disturbances and >97% of complex disturbances.
文摘In the paper, a general framework for large scale modeling of macroeconomic and financial time series is introduced. The proposed approach is characterized by simplicity of implementation, performing well independently of persistence and heteroskedasticity properties, accounting for common deterministic and stochastic factors. Monte Carlo results strongly support the proposed methodology, validating its use also for relatively small cross-sectional and temporal samples.
基金performed at large-scale research facility"Beam-M"of Bauman Moscow State Technical University following the government task by the Ministry of Science and Higher Education of the Russian Federation(No.FSFN-2024-0007).
文摘Thrust-vectoring capability has become a critical feature for propulsion systems as space missions move from static to dynamic.Thrust-vectoring is a well-developed area of rocket engine science.For electric propulsion,however,it is an evolving field that has taken a new leap forward in recent years.A review and analysis of thrust-vectoring schemes for electric propulsion systems have been conducted.The scope of this review includes thrust-vectoring schemes that can be implemented for electrostatic,electromagnetic,and beam-driven thrusters.A classification of electric propulsion schemes that provide thrust-vectoring capability is developed.More attention is given to schemes implemented in laboratory prototypes and flight models.The final part is devoted to a discussion on the suitability of different electric propulsion systems with thrust-vectoring capability for modern space mission operations.The thrust-vectoring capability of electric propulsion is necessary for inner and outer space satellites,which are at a disadvantage with conventional unidirectional propulsion systems due to their limited maneuverability.
文摘It is shown that such phenomena as quantum correlations (interaction of space-separated quantum entities), the action of magnetic vector potential on quantum entities in the absence of magnetic field, and near-field antenna effect (the existence of superluminally propagating electromagnetic fields) may be explained by action of spin supercurrents. In case of quantum correlations between quantum entities, spin supercurrent emerges between virtual particles pairs (virtual photons) created by those quantum entities. The explanation of magnetic vector potential and near-field antenna effect is based on contemporary principle of quantum mechanics: the physical vacuum is not an empty space but the ground state of the field consisting of quantum harmonic oscillators (QHOs) characterized by zero-point energy. Using the properties of the oscillators and spin supercurrent, it is proved that magnetic vector potential is proportional to the moment causing the orientation of spin of QHO along the direction of magnetic field. The near-field antenna effect is supposed to take place as a result of action of spin supercurrent causing secondary electromagnetic oscillations. In this way, the electromagnetic field may spread at the speed of spin supercurrent. As spin supercurrent is an inertia free process, its speed may be greater than that of light, which does not contradict postulates of special relativity that sets limits to the speed of inertial systems only.
基金supported by the National Basic Research Program of China(973 Program)2010CB530200(2010CB530206)the China-US Collaborative Program on Emerging and Re-emerging Infectious Disease(No.1U2GGH000018-01)
文摘Objective:To evaluate the Anaplasma phagocytophilum(A.phagocytophilum),Ehrlichia canis(E.canis,Dirofilaria immitis(D.immitis)(canine heartworm),Borrelia burgdorferi(B.burgdorferi)infections in countryside dogs from Yunnan,Hainan and Anhui provinces.Methods:Serum samples were collected from 26 dogs in Yunnan.Hainan and Anhui provinces.The samples were tested using a commercial ELISA rapid diagnostic assay kit(SNAP^(?)4Dx^(?);IDEXX Laboratories,Inc.U.S.A.).Meaiiwliile,indirect immunofluorescence assay(IFA)recommended by WHO was conducted to delect IgG to A.phagocytophilum.Two methods were analyzed and compared.Results:The number of serologically positive dogs for IgG to A.phagocytophilum was only 2which was from Hainan province and none of the 26 dogs responded positive for E.canu.D.immitis(canine heartworm,and B.burgdorferi by ELISA rapid diagnostic method.The number of serologically positive dogs for IgG to A.phagocytophilum was 13(50%)by IFA method.Data of the two methods were analyzed by statistical software and the difference was statistically significant(P=0.002).Conclusions:It can be concluded that IFA method was more sensitive than ELISA rapid diagnostic method.However,we need conduct further and intensive epidemiology survey on tick-born diseases pathogens including.4.phagocytophilum,E.canis,D.immitis(canine heartworm),and B.burgdorferi which have public health significance.
文摘Since its discovery in the 1980s,the insect cell-baculovirus expression vector system(IC-BEVS)has been widely used in biomedical applications,such as recombinant protein expression,drug screening,vaccine development,gene therapy and so on[1].As a eukaryotic system,IC-BEVS has great development prospects due to its advantages such as high safety,simple operation,simultaneous expression of multi-subunit proteins,and suitability for large-scale cultivation[2].
基金funded by the Pyramid Talent Training Project of Beijing University of Civil Engineering and Architecture under Grant GJZJ20220802。
文摘Accurately estimating the State of Health(SOH)and Remaining Useful Life(RUL)of lithium-ion batteries(LIBs)is crucial for the continuous and stable operation of battery management systems.However,due to the complex internal chemical systems of LIBs and the nonlinear degradation of their performance,direct measurement of SOH and RUL is challenging.To address these issues,the Twin Support Vector Machine(TWSVM)method is proposed to predict SOH and RUL.Initially,the constant current charging time of the lithium battery is extracted as a health indicator(HI),decomposed using Variational Modal Decomposition(VMD),and feature correlations are computed using Importance of Random Forest Features(RF)to maximize the extraction of critical factors influencing battery performance degradation.Furthermore,to enhance the global search capability of the Convolution Optimization Algorithm(COA),improvements are made using Good Point Set theory and the Differential Evolution method.The Improved Convolution Optimization Algorithm(ICOA)is employed to optimize TWSVM parameters for constructing SOH and RUL prediction models.Finally,the proposed models are validated using NASA and CALCE lithium-ion battery datasets.Experimental results demonstrate that the proposed models achieve an RMSE not exceeding 0.007 and an MAPE not exceeding 0.0082 for SOH and RUL prediction,with a relative error in RUL prediction within the range of[-1.8%,2%].Compared to other models,the proposed model not only exhibits superior fitting capability but also demonstrates robust performance.
基金the Creation Foundation of Nanjing Medical University,No.Cx9905
文摘AIM: To kill CEA positive colorectal carcinoma cells specifically using the E coli cytosine deaminase (CD) suicide gene, a new replication-deficient recombinant adenoviral vector was constructed in which CD gene was controlled under CEA promoter and its in vitro cytotoxic effects were evaluated. METHODS: Shuttle plasmid containing CD gene and regulatory sequence of the CEA gene was constructed and recombined with the right arm of adenovirus genome DNA in 293 cell strain. Dot blotting and PCR were used to identify positive plaques. The purification of adenovirus was performed with ultra-concentration in CsCl step gradients and the titration was measured with plaque formation assay. Cytotoxic effects were assayed with MTT method, The fifty percent inhibition concentration (IC(50)) of 5-FC was calculated using a curve-fitting parameter. The human colorectal carcinoma cell line, which was CEA-producing, and the CEA-nonproducing Hela cell line were applied in cytological tests. An established recombinant adenovirus vector AdCMVCD, in which the CD gene was controlled under CMV promoter, was used as virus control. Quantitative results were expressed as the mean +/- SD of the mean. Statistical analysis was performed using ANOVA test. RESULTS: The desired recombinant adenovirus vector was named AdCEACD. The results of dot blotting and PCR showed that the recombinant adenovirus contained CEA promoter and CD gene. Virus titer was about 5.0 X 10(14)pfu/L(-1) after purification. The CEA-producing Lovo cells were sensitive to 5-FC and had the same cytotoxic effect after infection with AdCEACD and AdCMVCD (The IC(50) values of 5-FC in parent Lovo cells, Lovo cells infected with 100 M.O.I AdCEACD and Lovo cells infected with 10 M.O.I AdCMVCD were 】15000, 216.5+/-38.1 and 128.8+/-25.4 micromol.L(-1), P【0.001, respectively), and the cytotoxicity of 5-FC increased accordingly when the m.o.i of adenoviruses were enhanced (The value of IC(50) of 5-FC was reduced to 27.9+/-4.2 micromol.L(-1) in 1000 M.O.I AdCEACD infected Lovo cells and 24.8+/-7.1 micromol.L(-1) in 100 M.O.I AdCMVCD infected Lovo cells, P【0.05, P【0.01, respectively). The CEA-nonproducing Hela cells had no effect after infection with AdCEACD, but Hela cells had the cytotoxic sensitivity to 5-FC after infection with AdCMVCD (The IC(50) of 5-FC in parent Hele cells and Hela cells infected with AdCMVCD at 10 M.O.I was 】15000 and 214.5+/-31.3 micromol.L(-1), P【0.001). AdCEACD/5-FC system also had bystander effect, and the viability was about 30 percent when the proportion of transfected cells was only 10 percent. CONCLUSION: The recombinant adenovirus vector AdCEACD has the character of cell type-specific gene delivery. The AdCEACD/5-FC system may become a new, potent and specific approach for the gene therapy of CEA-positive neoplasms, especially colon carcinoma.
文摘In this work, a total of 322 tests were taken on young volunteers by performing 10 different falls, 6 different Activities of Daily Living (ADL) and 7 Dynamic Gait Index (DGI) tests using a custom-designed Wireless Gait Analysis Sensor (WGAS). In order to perform automatic fall detection, we used Back Propagation Artificial Neural Network (BP-ANN) and Support Vector Machine (SVM) based on the 6 features extracted from the raw data. The WGAS, which includes a tri-axial accelerometer, 2 gyroscopes, and a MSP430 microcontroller, is worn by the subjects at either T4 (at back) or as a belt-clip in front of the waist during the various tests. The raw data is wirelessly transmitted from the WGAS to a near-by PC for real-time fall classification. The BP ANN is optimized by varying the training, testing and validation data sets and training the network with different learning schemes. SVM is optimized by using three different kernels and selecting the kernel for best classification rate. The overall accuracy of BP ANN is obtained as 98.20% with LM and RPROP training from the T4 data, while from the data taken at the belt, we achieved 98.70% with LM and SCG learning. The overall accuracy using SVM was 98.80% and 98.71% with RBF kernel from the T4 and belt position data, respectively.
文摘Objective:To evaluate the larvicidal and pupicidal potential of the methanolic extracts from Moringa oleifera(M.oleifera) plant seeds against malarial vector Anopheles stephensi(A.stephensi) mosquitoes at different concentrations(20,40,60,80 and 100 ppm).Methods:M.oleifera was collected from the area of around Bharathiar University,Coimbatore.The dried plant materials were powdered by an electrical blender.From each sample,100 g of the plant material were extracted with 300 mL of methanol for 8 h in a Soxhlet apparatus.The extracts were evaporated to dryness in rotary vacuum evaporator to yield 122 mg and 110 mg of dark greenish material(residue) from Arcang amara and Ocimum basilicum,respectively.One gram of the each plant residue was dissolved separately in 100 mL of acetone(stock solution) from which different concentrations, i.e.,20,40,60,80 and 100 ppm were prepared.Results:Larvicidal activity of M.oleifera exhibited in the first to fourth instar larvae of the A.stephensi,and the LC_(50) and LC_(90) values were 57.79 ppm and 125.93 ppm for the first instar,63.90 ppm and 133.07 ppm for the second inslar,72.45 ppm and 139.82 ppm for the third instar,78.93 ppm and 143.20 ppm for the fourth instar,respectively. During the pupal stage the methanolic extract of M.oleifera showed that the LC_(50),and LC_(90) values were 67.77 ppm and 141.00 ppm,respectively.Conclusions:The present study indicates that the phytochemicals derived from M.oleifera seeds extracts are effective mosquito vector control agents and the plant extracts may be used for further integrated pest management programs.
基金funded by the Chinese State Grid Jiangsu Electric Power Co.,Ltd.Science and Technology Project Funding,Grant Number J2023031.
文摘Accurate vector extraction from design drawings is required first to automatically create 3D models from pixel-level engineering design drawings. However, this task faces the challenges of complicated design shapes as well as cumbersome and cluttered annotations on drawings, which interfere with the vector extraction heavily. In this article, the transmission tower containing the most complex structure is taken as the research object, and a semantic segmentation network is constructed to first segment the shape masks from the pixel-level drawings. Preprocessing and postprocessing are also proposed to ensure the stability and accuracy of the shape mask segmentation. Then, based on the obtained shape masks, a vector extraction network guided by heatmaps is designed to extract structural vectors by fusing the features from node heatmap and skeleton heatmap, respectively. Compared with the state-of-the-art methods, experiment results illustrate that the proposed semantic segmentation method can effectively eliminate the interference of many elements on drawings to segment the shape masks effectively, meanwhile, the model trained by the proposed vector extraction network can accurately extract the vectors such as nodes and line connections, avoiding redundant vector detection. The proposed method lays a solid foundation for automatic 3D model reconstruction and contributes to technological advancements in relevant fields.
基金the SERB,Department of Science and Technology,Government of India(Project No.EMR/2017/001456)aIISER Kolkata IPh.D fellowship for research.
文摘We demonstrate an effective and optimal strategy for generating spatially resolved longitudinal spin angular momentum(LSAM)in optical tweezers by tightly focusing the first-order spirally polarized vector(SPV)beams with zero intrinsic angular momentum into a refractive index stratified medium.The stratified medium gives rise to a spherically aberrated intensity profile near the focal region of the optical tweezers,with off-axis intensity lobes in the radial direction possessing opposite LSAM(helicities corresponding toσ=+1 and−1)compared to the beam center.We trap mesoscopic birefringent particles in an off-axis intensity lobe as well as at the beam center by modifying the trapping plane and observe particles spinning in opposite directions depending on their location.The direction of rotation depends on the particle size with larger particles spinning either clockwise or anticlockwise depending on the direction of spirality of the polarization of the SPV beam after tight focusing,while smaller particles spin in both directions depending on their spatial locations.Numerical simulations support our experimental observations.Our results introduce new avenues in spin-orbit optomechanics to facilitate novel yet straightforward avenues for exotic and complex particle manipulation in optical tweezers.
