Compared with conventional well, herringbone-like laterals wells can increase the area of oil release, and can reduce the number of wellhead slots of platforms,?and?also can greatly improve the development efficiency....Compared with conventional well, herringbone-like laterals wells can increase the area of oil release, and can reduce the number of wellhead slots of platforms,?and?also can greatly improve the development efficiency. Based on threshold pressure gradient in heavy oil reservoir,?and?the applied principle of mirror reflection and superposition, the pressure distribution equation of herringbone-like laterals wells is obtained in heavy oil reservoir. Productivity model of herringbone-like laterals wells is proposed by reservoir-wellbore steady seepage. The example shows that the productivity model is great accuracy?to?predict the productivity of herringbone-like laterals wells. The model is used to analyze the branching length, branching angle, branching symmetry, branching position and spacing and their effects on productivity of herringbone-like laterals wells. The principle of optimizing the well shape of herringbone-like laterals wells is proposed.展开更多
An analytical approach was developed to design a single uniformly sloping lateral in the micro-irrigation systems.Emission uniformity was used as the water application uniformity criterion.Energy relations based on th...An analytical approach was developed to design a single uniformly sloping lateral in the micro-irrigation systems.Emission uniformity was used as the water application uniformity criterion.Energy relations based on the energy-gradient-line approach were revamped to account for the spatial variance of emitter outflow and the emitter connections local energy losses.Four pressure head grade line profiles were distinguished:uphill,horizontal,gentle downhill and steep downhill.Analytical expressions of emission uniformity by hydraulic variation for each pressure profile were developed based on the design variables:length and diameter of lateral,emitter spacing,emitter flow equation parameters,equivalent length characterizing local losses and ground slope.The design conditions for selecting emitter type,the number of emitters per plant and designing the diameter of the uphill and steep downhill laterals were also developed.The nonlinear equations for determining lateral diameter and lateral length were solved iteratively by using the built-in root-finding function of(Tools>Goal Seek…)in the calculation spreadsheet of Microsoft Excel.The procedures also provide the options to fix the design lateral diameter with the commercial standard size or fix the design lateral length based on the field size.The operating inlet pressure and maximum amplitude of the pressure head throughout the lateral could also be determined easily by the procedure.Two numerical applications with various slope combinations indicate that the proposed analytical approach produces results close to the accurate stepwise numerical solutions.In comparison with Keller method,the proposed approach could produce more appropriate designs.展开更多
Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect ...Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.展开更多
Mitochondria are critical cellular energy resources and are central to the life of the neuron.Mitophagy selectively clears damaged or dysfunctional mitochondria through autophagic machinery to maintain mitochondrial q...Mitochondria are critical cellular energy resources and are central to the life of the neuron.Mitophagy selectively clears damaged or dysfunctional mitochondria through autophagic machinery to maintain mitochondrial quality control and homeostasis.Mature neurons are postmitotic and consume substantial energy,thus require highly efficient mitophagy pathways to turn over damaged or dysfunctional mitochondria.Recent evidence indicates that mitophagy is pivotal to the pathogenesis of neurological diseases.However,more work is needed to study mitophagy pathway components as potential therapeutic targets.In this review,we briefly discuss the characteristics of nonselective autophagy and selective autophagy,including ERphagy,aggrephagy,and mitophagy.We then introduce the mechanisms of Parkin-dependent and Parkin-independent mitophagy pathways under physiological conditions.Next,we summarize the diverse repertoire of mitochondrial membrane receptors and phospholipids that mediate mitophagy.Importantly,we review the critical role of mitophagy in the pathogenesis of neurodegenerative diseases including Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.Last,we discuss recent studies considering mitophagy as a potential therapeutic target for treating neurodegenerative diseases.Together,our review may provide novel views to better understand the roles of mitophagy in neurodegenerative disease pathogenesis.展开更多
Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exoso...Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.展开更多
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 t...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).展开更多
BACKGROUND Ultrasound guide technology,which can provide real-time visualization of the needle tip and tissues and avoid many adverse events,is widely used in mini-mally invasive therapy.However,the studies on ultraso...BACKGROUND Ultrasound guide technology,which can provide real-time visualization of the needle tip and tissues and avoid many adverse events,is widely used in mini-mally invasive therapy.However,the studies on ultrasound-guided Lateral recess block(LRB)are limited,this is probably because there is no recognized standard method for ultrasound scanning.This study aimed to evaluate the effect of ultrasound-guided LRB in patients with lateral recess stenosis(LRS).CASE SUMMARY A 65-year-old patient complained of low back pain accompanied occasionally by pain and numbness in the left lower limb.Physical examination showed ten-derness on the spinous process and paraspinal muscles from L1 to S1,extensor hallucis longus and tibialis anterior weakness(muscle strength:4-),and a positive straight leg raising test in the left lower limb(60°).Magnetic resonance imaging showed L4–L5 disc degeneration with left LRS and nerve root entrapment.Subsequently,the patient was diagnosed with LRS.This patient was treated with a novel ultrasound-guided LRB approach.The patient’s symptoms significantly improved without any complications at 1 wk postoperatively and at the 3-month follow-up.CONCLUSION This is the first report on the LRS treatment with ultrasound-guided LRB from the contralateral spinous process along the inner side of the articular process by out-plane technique.Further studies are expected to investigate the efficacy and safety of ultrasound-guided LRB for patients with LRS.展开更多
Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of sufferin...Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of suffering.The lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption.However,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear.In this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such reactions.Notably,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats.Lastly,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions.Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.展开更多
The prediction of liquefaction-induced lateral spreading/displacement(Dh)is a challenging task for civil/geotechnical engineers.In this study,a new approach is proposed to predict Dh using gene expression programming(...The prediction of liquefaction-induced lateral spreading/displacement(Dh)is a challenging task for civil/geotechnical engineers.In this study,a new approach is proposed to predict Dh using gene expression programming(GEP).Based on statistical reasoning,individual models were developed for two topographies:free-face and gently sloping ground.Along with a comparison with conventional approaches for predicting the Dh,four additional regression-based soft computing models,i.e.Gaussian process regression(GPR),relevance vector machine(RVM),sequential minimal optimization regression(SMOR),and M5-tree,were developed and compared with the GEP model.The results indicate that the GEP models predict Dh with less bias,as evidenced by the root mean square error(RMSE)and mean absolute error(MAE)for training(i.e.1.092 and 0.815;and 0.643 and 0.526)and for testing(i.e.0.89 and 0.705;and 0.773 and 0.573)in free-face and gently sloping ground topographies,respectively.The overall performance for the free-face topology was ranked as follows:GEP>RVM>M5-tree>GPR>SMOR,with a total score of 40,32,24,15,and 10,respectively.For the gently sloping condition,the performance was ranked as follows:GEP>RVM>GPR>M5-tree>SMOR with a total score of 40,32,21,19,and 8,respectively.Finally,the results of the sensitivity analysis showed that for both free-face and gently sloping ground,the liquefiable layer thickness(T_(15))was the major parameter with percentage deterioration(%D)value of 99.15 and 90.72,respectively.展开更多
Existing studies have focused on the behavior of the retaining wall equipped with expanded polystyrene(EPS)geofoam inclusions under semi-infinite surcharge loading rather than limited surcharge loading.In this paper,t...Existing studies have focused on the behavior of the retaining wall equipped with expanded polystyrene(EPS)geofoam inclusions under semi-infinite surcharge loading rather than limited surcharge loading.In this paper,the failure mode and the earth pressure acting on the rigid retaining wall with EPS geofoam inclusions and granular backfills(henceforth referred to as EPS-wall),under limited surcharge loading are investigated through two-and three-dimensional model tests.The testing results show that different from the sliding of almost all the backfill in the EPS-wall under semi-infinite surcharge loading,only an approximately triangular backfill slides in the wall under limited surcharge loading.The distribution of the lateral earth pressure on the EPS-wall under limited surcharge loading is non-linear,and the distribution changes from the increase of the wall depth to the decrease with the increase of the limited surcharge loading.An approach based on the force equilibrium of a differential element is developed to predict the lateral earth pressure behind the EPS-wall subjected to limited surcharge loading,and its performance was fully validated by the three-dimensional model tests.展开更多
Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system.Currently,there is no cure for neurodegenerative diseases and th...Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system.Currently,there is no cure for neurodegenerative diseases and this means a heavy burden for patients and the health system worldwide.Therefore,it is necessary to find new therapeutic approaches,and antisense therapies offer this possibility,having the great advantage of not modifying cellular genome and potentially being safer.Many preclinical and clinical studies aim to test the safety and effectiveness of antisense therapies in the treatment of neurodegenerative diseases.The objective of this review is to summarize the recent advances in the development of these new technologies to treat the most common neurodegenerative diseases,with a focus on those antisense therapies that have already received the approval of the U.S.Food and Drug Administration.展开更多
Neurodegenerative diseases are often misdiagnosed,especially when the diagnosis is based solely on clinical symptoms.The p75 neurotrophic receptor(p75^(NTR))has been studied as an index of sensory and motor nerve deve...Neurodegenerative diseases are often misdiagnosed,especially when the diagnosis is based solely on clinical symptoms.The p75 neurotrophic receptor(p75^(NTR))has been studied as an index of sensory and motor nerve development and maturation.Its cleavable extracellular domain(ECD)is readily detectable in various biological fluids including plasma,serum and urine.There is evidence for increased p75NTR ECD levels in neurodegenerative diseases such as Alzheimer’s disease,amyotrophic lateral sclerosis,age-related dementia,schizophrenia,and diabetic neuropathy.Whether p75^(NTR) ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders,and whether it could potentially lead to the development of targeted therapies,remains an open question.In this review,we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative diseases.We also highlight areas that require further investigation to better understand the role of p75^(NTR) ECD in the clinical diagnosis and management of neurodegenerative disorders.展开更多
Traditional transgenic detection methods require high test conditions and struggle to be both sensitive and efficient.In this study,a one-tube dual recombinase polymerase amplification(RPA)reaction system for CP4-EPSP...Traditional transgenic detection methods require high test conditions and struggle to be both sensitive and efficient.In this study,a one-tube dual recombinase polymerase amplification(RPA)reaction system for CP4-EPSPS and Cry1Ab/Ac was proposed and combined with a lateral flow immunochromatographic assay,named“Dual-RPA-LFD”,to visualize the dual detection of genetically modified(GM)crops.In which,the herbicide tolerance gene CP4-EPSPS and the insect resistance gene Cry1Ab/Ac were selected as targets taking into account the current status of the most widespread application of insect resistance and herbicide tolerance traits and their stacked traits.Gradient diluted plasmids,transgenic standards,and actual samples were used as templates to conduct sensitivity,specificity,and practicality assays,respectively.The constructed method achieved the visual detection of plasmid at levels as low as 100 copies,demonstrating its high sensitivity.In addition,good applicability to transgenic samples was observed,with no cross-interference between two test lines and no influence from other genes.In conclusion,this strategy achieved the expected purpose of simultaneous detection of the two popular targets in GM crops within 20 min at 37°C in a rapid,equipmentfree field manner,providing a new alternative for rapid screening for transgenic assays in the field.展开更多
Fracture of the lateral process of the talus(FLPT)is uncommon in clinical practice and can be easily missed or misdiagnosed.In recent years,as researchers from all over the world have further deepened their research o...Fracture of the lateral process of the talus(FLPT)is uncommon in clinical practice and can be easily missed or misdiagnosed.In recent years,as researchers from all over the world have further deepened their research on FLPT,there has been a breakthrough in the classification,and the methods and principles of clinical management have changed accordingly;however,there is still no standardized guideline for the diagnosis and management of FLPT,and there have been few relevant literature review articles related to this kind of fracture in the past at least 5 years.In this article,we review the clinical classification,classification-based therapeutic recommendations,and prognosis of FLPT,with the aim of providing a reference for the clinical diagnosis and management of this infrequent fracture.展开更多
Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of research.Thus,the journey to understanding or treating amy...Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of research.Thus,the journey to understanding or treating amyotrophic lateral sclerosis is still a long one.According to current research,amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic pathways.The progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral sclerosis.Here,we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis,as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral sclerosis.In addition,we discuss current emerging strategies for the treatment of amyotrophic lateral sclerosis.Studying the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.展开更多
The safe and efficient development of natural gas hydrate requires a deep understanding of the deformation behaviors of reservoirs.In this study,a series of triaxial shearing tests are carried out to investigate the d...The safe and efficient development of natural gas hydrate requires a deep understanding of the deformation behaviors of reservoirs.In this study,a series of triaxial shearing tests are carried out to investigate the deformation properties of hydrate-bearing sediments.Variations of volumetric and lateral strains versus hydrate saturation are analyzed comprehensively.Results indicate that the sediments with high hydrate saturation show dilative behaviors,which lead to strain-softening characteristics during shearing.The volumetric strain curves have a tendency to transform gradually from dilatation to compression with the increase in effective confining pressure.An easy prediction model is proposed to describe the relationship between volumetric and axial strains.The model coefficientβis the key dominating factor for the shape of volumetric strain curves and can be determined by the hydrate saturation and stress state.Moreover,a modified model is established for the calculation of lateral strain.The corresponding determination method is provided for the easy estimation of model coefficients for medium sand sediments containing hydrate.This study provides a theoretical and experimental reference for deformation estimation in natural gas hydrate development.展开更多
Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann c...Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend.A more sensitive in-house assay suggested possible inflammasome activation during the disease course.A trend for clinical stabilization was observed during the infusion period.Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles.Initial findings suggest that this approach is safe.展开更多
Regarding the lane keeping system,path tracking accuracy and lateral stability at high speeds need to be taken into account especially for commercial vehicles due to the characteristics of larger mass,longer wheelbase...Regarding the lane keeping system,path tracking accuracy and lateral stability at high speeds need to be taken into account especially for commercial vehicles due to the characteristics of larger mass,longer wheelbase and higher mass center.To improve the performance mentioned above comprehensively,the control strategy based on improved artificial potential field(APF)algorithm is proposed.In the paper,time to lane crossing(TLC)is introduced into the potential field function to enhance the accuracy of path tracking,meanwhile the vehicle dynamics parameters including yaw rate and lateral acceleration are chosen as the repulsive force field source.The lane keeping controller based on improved APF algorithm is designed and the stability of the control system is proved based on Lyapunov theory.In addition,adaptive inertial weight particle swarm optimization algorithm(AIWPSO)is applied to optimize the gain of each potential field function.The co-simulation results indicate that the comprehensive evaluation index respecting lane tracking accuracy and lateral stability is reduced remarkably.Finally,the proposed control strategy is verified by the HiL test.It provides a beneficial reference for dynamics control of commercial vehicles and enriches the theoretical development and practical application of artificial potential field method in the field of intelligent driving.展开更多
This paper presents experimental studies on a compacted expansive soil,from Nanyang,China for investigating the at-rest lateral earth pressureσL of expansive soils.The key studies include(i)relationships between the...This paper presents experimental studies on a compacted expansive soil,from Nanyang,China for investigating the at-rest lateral earth pressureσL of expansive soils.The key studies include(i)relationships between theσL and the vertical stressσV during soaking and consolidation,(ii)the influences of initial dry densityρd0 and moisture content w 0 on the vertical and lateral swelling pressures at no swelling strain(i.e.σV0 andσL0),and(iii)evolution of theσL during five long-term wetting-drying cycles.Experimental results demonstrated that the post-soakingσL-σV relationships are piecewise linear and their slopes in the passive state(σL>σV)and active state(σL<σV)are similar to that of the consolidationσL-σV relationships in the normal-and over-consolidated states,respectively.The soakingσL-σV relationships converge to the consolidationσL-σV relationships at a thresholdσV where the interparticle swelling is restrained.TheσL0 andσV0 increase monotonically withρd0;however,they show increasing-then-decreasing trends with the w 0.The extent of compaction-induced swelling anisotropy,which is evaluated byσL0/σV0,reduces with an increase in the compaction energy and molding water content.TheσL reduces over moisture cycles and the stress relaxation in theσL during soaking is observed.An approach was developed to predict the at-rest soakingσL-σV relationships,which requires conventional consolidation and shear strength properties and one measurement of theσL-σV relationships during soaking.The proposed approach was validated using the results of three different expansive soils available in the literature.展开更多
文摘Compared with conventional well, herringbone-like laterals wells can increase the area of oil release, and can reduce the number of wellhead slots of platforms,?and?also can greatly improve the development efficiency. Based on threshold pressure gradient in heavy oil reservoir,?and?the applied principle of mirror reflection and superposition, the pressure distribution equation of herringbone-like laterals wells is obtained in heavy oil reservoir. Productivity model of herringbone-like laterals wells is proposed by reservoir-wellbore steady seepage. The example shows that the productivity model is great accuracy?to?predict the productivity of herringbone-like laterals wells. The model is used to analyze the branching length, branching angle, branching symmetry, branching position and spacing and their effects on productivity of herringbone-like laterals wells. The principle of optimizing the well shape of herringbone-like laterals wells is proposed.
基金supported by the Special Foundation of National Science & Technology Supporting Plan( 2011BAD29B02)the "111" Project (B12007)
文摘An analytical approach was developed to design a single uniformly sloping lateral in the micro-irrigation systems.Emission uniformity was used as the water application uniformity criterion.Energy relations based on the energy-gradient-line approach were revamped to account for the spatial variance of emitter outflow and the emitter connections local energy losses.Four pressure head grade line profiles were distinguished:uphill,horizontal,gentle downhill and steep downhill.Analytical expressions of emission uniformity by hydraulic variation for each pressure profile were developed based on the design variables:length and diameter of lateral,emitter spacing,emitter flow equation parameters,equivalent length characterizing local losses and ground slope.The design conditions for selecting emitter type,the number of emitters per plant and designing the diameter of the uphill and steep downhill laterals were also developed.The nonlinear equations for determining lateral diameter and lateral length were solved iteratively by using the built-in root-finding function of(Tools>Goal Seek…)in the calculation spreadsheet of Microsoft Excel.The procedures also provide the options to fix the design lateral diameter with the commercial standard size or fix the design lateral length based on the field size.The operating inlet pressure and maximum amplitude of the pressure head throughout the lateral could also be determined easily by the procedure.Two numerical applications with various slope combinations indicate that the proposed analytical approach produces results close to the accurate stepwise numerical solutions.In comparison with Keller method,the proposed approach could produce more appropriate designs.
基金supported by the grants from Shanghai Shuguang Plan Project,No.18SG15(to SC)Shanghai Outstanding Young Scholars Project+2 种基金Shanghai Talent Development Project,No.2019044(to SC)Medical-engineering cross fund of Shanghai Jiao Tong University,No.YG2022QN009(to QZ)the National Natural Science Foundation of China,No.82201558(to QZ)。
文摘Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.
基金supported by the National Natural Science Foundation of China,Nos.82001211(to KY),82101241(to SW),and 82125032(to FL).
文摘Mitochondria are critical cellular energy resources and are central to the life of the neuron.Mitophagy selectively clears damaged or dysfunctional mitochondria through autophagic machinery to maintain mitochondrial quality control and homeostasis.Mature neurons are postmitotic and consume substantial energy,thus require highly efficient mitophagy pathways to turn over damaged or dysfunctional mitochondria.Recent evidence indicates that mitophagy is pivotal to the pathogenesis of neurological diseases.However,more work is needed to study mitophagy pathway components as potential therapeutic targets.In this review,we briefly discuss the characteristics of nonselective autophagy and selective autophagy,including ERphagy,aggrephagy,and mitophagy.We then introduce the mechanisms of Parkin-dependent and Parkin-independent mitophagy pathways under physiological conditions.Next,we summarize the diverse repertoire of mitochondrial membrane receptors and phospholipids that mediate mitophagy.Importantly,we review the critical role of mitophagy in the pathogenesis of neurodegenerative diseases including Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.Last,we discuss recent studies considering mitophagy as a potential therapeutic target for treating neurodegenerative diseases.Together,our review may provide novel views to better understand the roles of mitophagy in neurodegenerative disease pathogenesis.
基金supported by grants from the Department of Science and Technology of Sichuan Province,Nos.2021ZYD0093(to LY),2022YFS0597(to LY),2021YJ0480(to YT),and 2022ZYD0076(to JY)。
文摘Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.
基金in part supported by the National Natural Science Foundation of China,Nos.30560042,81160161,81360198,and 82160255Education Department of Jiangxi Province,Nos.GJJ13198 and GJJ170021+1 种基金Jiangxi Provincial Department of Science and Technology,No.20192BAB205043Health and Family Planning Commission of Jiangxi Province,Nos.20181019 and 202210002(all to RX)。
文摘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).
基金Supported by the National Natural Science Foundation of China,No.82305380The Postdoctoral Research Program,West China Hospital,Sichuan University,No.2020HXBH018.
文摘BACKGROUND Ultrasound guide technology,which can provide real-time visualization of the needle tip and tissues and avoid many adverse events,is widely used in mini-mally invasive therapy.However,the studies on ultrasound-guided Lateral recess block(LRB)are limited,this is probably because there is no recognized standard method for ultrasound scanning.This study aimed to evaluate the effect of ultrasound-guided LRB in patients with lateral recess stenosis(LRS).CASE SUMMARY A 65-year-old patient complained of low back pain accompanied occasionally by pain and numbness in the left lower limb.Physical examination showed ten-derness on the spinous process and paraspinal muscles from L1 to S1,extensor hallucis longus and tibialis anterior weakness(muscle strength:4-),and a positive straight leg raising test in the left lower limb(60°).Magnetic resonance imaging showed L4–L5 disc degeneration with left LRS and nerve root entrapment.Subsequently,the patient was diagnosed with LRS.This patient was treated with a novel ultrasound-guided LRB approach.The patient’s symptoms significantly improved without any complications at 1 wk postoperatively and at the 3-month follow-up.CONCLUSION This is the first report on the LRS treatment with ultrasound-guided LRB from the contralateral spinous process along the inner side of the articular process by out-plane technique.Further studies are expected to investigate the efficacy and safety of ultrasound-guided LRB for patients with LRS.
基金supported by the Shenzhen Key Laboratory of Drug Addiction (ZDSYS20190902093601675)CAS Key Laboratory of Brain Connectome and Manipulation (2019DP173024)+2 种基金National Natural Science Foundation of China (82274358)Shenzhen-Hong Kong Institute of Brain ScienceGuangdong Basic and Applied Basic Research Foundation (2023B1515040009)
文摘Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of suffering.The lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption.However,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear.In this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such reactions.Notably,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats.Lastly,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions.Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.
文摘The prediction of liquefaction-induced lateral spreading/displacement(Dh)is a challenging task for civil/geotechnical engineers.In this study,a new approach is proposed to predict Dh using gene expression programming(GEP).Based on statistical reasoning,individual models were developed for two topographies:free-face and gently sloping ground.Along with a comparison with conventional approaches for predicting the Dh,four additional regression-based soft computing models,i.e.Gaussian process regression(GPR),relevance vector machine(RVM),sequential minimal optimization regression(SMOR),and M5-tree,were developed and compared with the GEP model.The results indicate that the GEP models predict Dh with less bias,as evidenced by the root mean square error(RMSE)and mean absolute error(MAE)for training(i.e.1.092 and 0.815;and 0.643 and 0.526)and for testing(i.e.0.89 and 0.705;and 0.773 and 0.573)in free-face and gently sloping ground topographies,respectively.The overall performance for the free-face topology was ranked as follows:GEP>RVM>M5-tree>GPR>SMOR,with a total score of 40,32,24,15,and 10,respectively.For the gently sloping condition,the performance was ranked as follows:GEP>RVM>GPR>M5-tree>SMOR with a total score of 40,32,21,19,and 8,respectively.Finally,the results of the sensitivity analysis showed that for both free-face and gently sloping ground,the liquefiable layer thickness(T_(15))was the major parameter with percentage deterioration(%D)value of 99.15 and 90.72,respectively.
基金funding support from National Natural Science Foundation of China(Grant No.52179109)Jiangsu Provincial Natural Science Foundation(Grant No.BK20230967)Open Research Fund of State Key Laboratory of Mechanical Behavior and System Safety of Traffic Engineering Structures,Shijiazhuang Tiedao University(Grant No.KF2022-02).
文摘Existing studies have focused on the behavior of the retaining wall equipped with expanded polystyrene(EPS)geofoam inclusions under semi-infinite surcharge loading rather than limited surcharge loading.In this paper,the failure mode and the earth pressure acting on the rigid retaining wall with EPS geofoam inclusions and granular backfills(henceforth referred to as EPS-wall),under limited surcharge loading are investigated through two-and three-dimensional model tests.The testing results show that different from the sliding of almost all the backfill in the EPS-wall under semi-infinite surcharge loading,only an approximately triangular backfill slides in the wall under limited surcharge loading.The distribution of the lateral earth pressure on the EPS-wall under limited surcharge loading is non-linear,and the distribution changes from the increase of the wall depth to the decrease with the increase of the limited surcharge loading.An approach based on the force equilibrium of a differential element is developed to predict the lateral earth pressure behind the EPS-wall subjected to limited surcharge loading,and its performance was fully validated by the three-dimensional model tests.
基金supported by Association 2HE(Center for Human Health and Environment)by Regione Puglia-Grant Malattie Rare DUP n.246 of 2019(to CB).
文摘Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system.Currently,there is no cure for neurodegenerative diseases and this means a heavy burden for patients and the health system worldwide.Therefore,it is necessary to find new therapeutic approaches,and antisense therapies offer this possibility,having the great advantage of not modifying cellular genome and potentially being safer.Many preclinical and clinical studies aim to test the safety and effectiveness of antisense therapies in the treatment of neurodegenerative diseases.The objective of this review is to summarize the recent advances in the development of these new technologies to treat the most common neurodegenerative diseases,with a focus on those antisense therapies that have already received the approval of the U.S.Food and Drug Administration.
文摘Neurodegenerative diseases are often misdiagnosed,especially when the diagnosis is based solely on clinical symptoms.The p75 neurotrophic receptor(p75^(NTR))has been studied as an index of sensory and motor nerve development and maturation.Its cleavable extracellular domain(ECD)is readily detectable in various biological fluids including plasma,serum and urine.There is evidence for increased p75NTR ECD levels in neurodegenerative diseases such as Alzheimer’s disease,amyotrophic lateral sclerosis,age-related dementia,schizophrenia,and diabetic neuropathy.Whether p75^(NTR) ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders,and whether it could potentially lead to the development of targeted therapies,remains an open question.In this review,we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative diseases.We also highlight areas that require further investigation to better understand the role of p75^(NTR) ECD in the clinical diagnosis and management of neurodegenerative disorders.
基金supported by the Scientific and Innovative Action Plan of Shanghai(21N31900800)Shanghai Rising-Star Program(23QB1403500)+4 种基金the Shanghai Sailing Program(20YF1443000)Shanghai Science and Technology Commission,the Belt and Road Project(20310750500)Talent Project of SAAS(2023-2025)Runup Plan of SAAS(ZP22211)the SAAS Program for Excellent Research Team(2022(B-16))。
文摘Traditional transgenic detection methods require high test conditions and struggle to be both sensitive and efficient.In this study,a one-tube dual recombinase polymerase amplification(RPA)reaction system for CP4-EPSPS and Cry1Ab/Ac was proposed and combined with a lateral flow immunochromatographic assay,named“Dual-RPA-LFD”,to visualize the dual detection of genetically modified(GM)crops.In which,the herbicide tolerance gene CP4-EPSPS and the insect resistance gene Cry1Ab/Ac were selected as targets taking into account the current status of the most widespread application of insect resistance and herbicide tolerance traits and their stacked traits.Gradient diluted plasmids,transgenic standards,and actual samples were used as templates to conduct sensitivity,specificity,and practicality assays,respectively.The constructed method achieved the visual detection of plasmid at levels as low as 100 copies,demonstrating its high sensitivity.In addition,good applicability to transgenic samples was observed,with no cross-interference between two test lines and no influence from other genes.In conclusion,this strategy achieved the expected purpose of simultaneous detection of the two popular targets in GM crops within 20 min at 37°C in a rapid,equipmentfree field manner,providing a new alternative for rapid screening for transgenic assays in the field.
基金Supported by The China Scholarship Council,No.202308420035.
文摘Fracture of the lateral process of the talus(FLPT)is uncommon in clinical practice and can be easily missed or misdiagnosed.In recent years,as researchers from all over the world have further deepened their research on FLPT,there has been a breakthrough in the classification,and the methods and principles of clinical management have changed accordingly;however,there is still no standardized guideline for the diagnosis and management of FLPT,and there have been few relevant literature review articles related to this kind of fracture in the past at least 5 years.In this article,we review the clinical classification,classification-based therapeutic recommendations,and prognosis of FLPT,with the aim of providing a reference for the clinical diagnosis and management of this infrequent fracture.
基金supported by the National Natural Science Foundation of China,Nos.30560042,81160161,81360198,and 82160255Education Department of Jiangxi Province,Nos.GJJ13198 and GJJ170021+1 种基金Jiangxi Provincial Department of Science and Technology,No.20192BAB205043Health and Family Planning Commission of Jiangxi Province,Nos.20181019 and 202210002(all to RX).
文摘Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of research.Thus,the journey to understanding or treating amyotrophic lateral sclerosis is still a long one.According to current research,amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic pathways.The progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral sclerosis.Here,we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis,as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral sclerosis.In addition,we discuss current emerging strategies for the treatment of amyotrophic lateral sclerosis.Studying the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.
基金supported by the Qingdao Natural Science Foundation(No.23-2-1-54-zyyd-jch)the National Natural Science Foundation of China(Nos.42076217,41976074)+1 种基金the Laoshan Laboratory(No.LSKJ202203506)the Key Laboratory of Geotechnical and Underground Engineering of Ministry of Education,Tongji University(No.KLE-TJGE-G2202).
文摘The safe and efficient development of natural gas hydrate requires a deep understanding of the deformation behaviors of reservoirs.In this study,a series of triaxial shearing tests are carried out to investigate the deformation properties of hydrate-bearing sediments.Variations of volumetric and lateral strains versus hydrate saturation are analyzed comprehensively.Results indicate that the sediments with high hydrate saturation show dilative behaviors,which lead to strain-softening characteristics during shearing.The volumetric strain curves have a tendency to transform gradually from dilatation to compression with the increase in effective confining pressure.An easy prediction model is proposed to describe the relationship between volumetric and axial strains.The model coefficientβis the key dominating factor for the shape of volumetric strain curves and can be determined by the hydrate saturation and stress state.Moreover,a modified model is established for the calculation of lateral strain.The corresponding determination method is provided for the easy estimation of model coefficients for medium sand sediments containing hydrate.This study provides a theoretical and experimental reference for deformation estimation in natural gas hydrate development.
基金support from the Miami Project to Cure Paralysis,the Buoniconti Fund,and the Interdisciplinary Stem Cell Institute(to AK,WDD,JDG,and ADL)the unconditional support of Dean Henri Ford of the Leonard M.Miller School of Medicine at the University of Miami.
文摘Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend.A more sensitive in-house assay suggested possible inflammasome activation during the disease course.A trend for clinical stabilization was observed during the infusion period.Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles.Initial findings suggest that this approach is safe.
基金Supported by National Natural Science Foundation of China(Grant Nos.51605199,U20A20333,52225212)Six Talent Peak Funding Projects in Jiangsu Province of China(Grant No.2019-GDZB-084)Key Science and Technology Support Program in Taizhou City of China(Grant No.TG202307).
文摘Regarding the lane keeping system,path tracking accuracy and lateral stability at high speeds need to be taken into account especially for commercial vehicles due to the characteristics of larger mass,longer wheelbase and higher mass center.To improve the performance mentioned above comprehensively,the control strategy based on improved artificial potential field(APF)algorithm is proposed.In the paper,time to lane crossing(TLC)is introduced into the potential field function to enhance the accuracy of path tracking,meanwhile the vehicle dynamics parameters including yaw rate and lateral acceleration are chosen as the repulsive force field source.The lane keeping controller based on improved APF algorithm is designed and the stability of the control system is proved based on Lyapunov theory.In addition,adaptive inertial weight particle swarm optimization algorithm(AIWPSO)is applied to optimize the gain of each potential field function.The co-simulation results indicate that the comprehensive evaluation index respecting lane tracking accuracy and lateral stability is reduced remarkably.Finally,the proposed control strategy is verified by the HiL test.It provides a beneficial reference for dynamics control of commercial vehicles and enriches the theoretical development and practical application of artificial potential field method in the field of intelligent driving.
基金sponsored by the National Natural Science Foundation of China(Grant Nos.52378365 and 52179109)Jiangsu Province Excellent Postdoctoral Program(Grant No.2023)China Scholarship Council-University of Ottawa Joint Scholarship.
文摘This paper presents experimental studies on a compacted expansive soil,from Nanyang,China for investigating the at-rest lateral earth pressureσL of expansive soils.The key studies include(i)relationships between theσL and the vertical stressσV during soaking and consolidation,(ii)the influences of initial dry densityρd0 and moisture content w 0 on the vertical and lateral swelling pressures at no swelling strain(i.e.σV0 andσL0),and(iii)evolution of theσL during five long-term wetting-drying cycles.Experimental results demonstrated that the post-soakingσL-σV relationships are piecewise linear and their slopes in the passive state(σL>σV)and active state(σL<σV)are similar to that of the consolidationσL-σV relationships in the normal-and over-consolidated states,respectively.The soakingσL-σV relationships converge to the consolidationσL-σV relationships at a thresholdσV where the interparticle swelling is restrained.TheσL0 andσV0 increase monotonically withρd0;however,they show increasing-then-decreasing trends with the w 0.The extent of compaction-induced swelling anisotropy,which is evaluated byσL0/σV0,reduces with an increase in the compaction energy and molding water content.TheσL reduces over moisture cycles and the stress relaxation in theσL during soaking is observed.An approach was developed to predict the at-rest soakingσL-σV relationships,which requires conventional consolidation and shear strength properties and one measurement of theσL-σV relationships during soaking.The proposed approach was validated using the results of three different expansive soils available in the literature.