Owing to the integration of energy digitization and artificial intelligence technology,smart energy grids can realize the stable,efficient and clean operation of power systems.However,the emergence of cyber-physical a...Owing to the integration of energy digitization and artificial intelligence technology,smart energy grids can realize the stable,efficient and clean operation of power systems.However,the emergence of cyber-physical attacks,such as dynamic load-altering attacks(DLAAs)has introduced great challenges to the security of smart energy grids.Thus,this study developed a novel cyber-physical collaborative security framework for DLAAs in smart energy grids.The proposed framework integrates attack prediction in the cyber layer with the detection and localization of attacks in the physical layer.First,a data-driven method was proposed to predict the DLAA sequence in the cyber layer.By designing a double radial basis function network,the influence of disturbances on attack prediction can be eliminated.Based on the prediction results,an unknown input observer-based detection and localization method was further developed for the physical layer.In addition,an adaptive threshold was designed to replace the traditional precomputed threshold and improve the detection performance of the DLAAs.Consequently,through the collaborative work of the cyber-physics layer,injected DLAAs were effectively detected and located.Compared with existing methodologies,the simulation results on IEEE 14-bus and 118-bus power systems verified the superiority of the proposed cyber-physical collaborative detection and localization against DLAAs.展开更多
The Blade Altering Toolbox(BAT)described in this paper is a tool designed for fast reconstruction of an altered blade geometry for design optimization purposes.The BAT algorithm is capable of twisting a given rotor’s...The Blade Altering Toolbox(BAT)described in this paper is a tool designed for fast reconstruction of an altered blade geometry for design optimization purposes.The BAT algorithm is capable of twisting a given rotor’s angle of attack and stretching the chord length along the span of the rotor.Several test cases were run using the BAT’s algorithm.The BAT code’s twisting,stretching,and mesh reconstruction capabilities proved to be able to handle reasonably large geometric alterations to a provided input rotor geometry.The test examples showed that the toolbox’s algorithm could handle any stretching of the blade’s chord as long as the blade remained within the original bounds of the unaltered mesh.The algorithm appears to fail when the net twist angle applied the geometry exceeds approximately 30 degrees,however this limitation is dependent on the initial geometry and other input parameters.Overall,the algorithm is a very powerful tool for automating a design optimization procedure.展开更多
We establish fixed point theorems in complete fuzzy metric space by using notion of altering distance, initiated by Khan et al. [Bull. Austral. Math. Soc. 30 (1984), 1-9]. Also, we find an affirmative answer in fuzzy ...We establish fixed point theorems in complete fuzzy metric space by using notion of altering distance, initiated by Khan et al. [Bull. Austral. Math. Soc. 30 (1984), 1-9]. Also, we find an affirmative answer in fuzzy metric space to the problem of Sastry [TamkangJ. Math., 31(3) (2000), 243-250].展开更多
Some common fixed point results for mappings satisfying a quasi-contractive condition which involves altering distance functions are obtained in partially ordered complete cone metric spaces. A sufficient condition fo...Some common fixed point results for mappings satisfying a quasi-contractive condition which involves altering distance functions are obtained in partially ordered complete cone metric spaces. A sufficient condition for the uniqueness of common fixed point is proved. Also, an example is given to support our results.展开更多
The condition and physical sense of actual dynamic user optimum are explained by analyzing a simple road network route choice. To match the practical application requirements, assignment network and simulation network...The condition and physical sense of actual dynamic user optimum are explained by analyzing a simple road network route choice. To match the practical application requirements, assignment network and simulation network are classified account for varying flowing loading. Instantaneous dynamic user optimum model should be applied to the former and actual dynamic user optimum model the latter respectively. The two model’s feasibility is studied as well. Considering the application in ATMS, the model is mainly used to analyze the altering OD problem. Moreover, it adds the method of route adapting into the object function selection to appraise elastic trip strategy and set up real means of route inducement.展开更多
In the present paper, we prove two theorems. In first theorem, we prove fixed point result for self-maps in the metric space under contractive condition of integral type by altering distance. In second result, we prov...In the present paper, we prove two theorems. In first theorem, we prove fixed point result for self-maps in the metric space under contractive condition of integral type by altering distance. In second result, we prove a unique common fixed point theorem by considering four sub compatible maps under a contractive condition of integral type.展开更多
Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and...Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.展开更多
Spinal cord injury(SCI)involves an initial traumatic phase,followed by secondary events such as ischemia,increased blood-spinal cord barrier permeability,ionic disruption,glutamate excitotoxicity,and metabolic alterat...Spinal cord injury(SCI)involves an initial traumatic phase,followed by secondary events such as ischemia,increased blood-spinal cord barrier permeability,ionic disruption,glutamate excitotoxicity,and metabolic alterations.A pe rsistent and exagge rated inflammato ry response within the spinal cord accompanies these events(Lima et al.,2022).The complexity and interplay of these mechanisms exacerbate the initial injury,leading to a degenerative process at the injury site.While the initial trauma is unavoidable,the secondary injury begins within minutes and can last for months,creating an optimal window for therapeutic intervention.展开更多
Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histo...Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histological alterations including amyloid-beta (AB) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.展开更多
Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental...Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult life.To maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.展开更多
A new approach for treating the mesh with Lagrangian scheme of finite volume method is presented. It has been proved that classical Lagrangian method is difficult to cope with large deformation in tracking material pa...A new approach for treating the mesh with Lagrangian scheme of finite volume method is presented. It has been proved that classical Lagrangian method is difficult to cope with large deformation in tracking material particles due to severe distortion of cells, and the changing connectivity of the mesh seems especially attractive for solving such issues. The mesh with large deformation based on computational geometry is optimized by using new method. This paper develops a processing system for arbitrary polygonal unstructured grid,the intelligent variable grid neighborhood technologies is utilized to improve the quality of mesh in calculation process, and arbitrary polygonal mesh is used in the Lagrangian finite volume scheme. The performance of the new method is demonstrated through series of numerical examples, and the simulation capability is efficiently presented in coping with the systems with large deformations.展开更多
The phytohormones gibberellic acid (GA) and abscisic acid (ABA) antagonistically control seed germina- tion. High levels of GA favor seed germination, whereas high levels of ABA hinder this process. The direct rel...The phytohormones gibberellic acid (GA) and abscisic acid (ABA) antagonistically control seed germina- tion. High levels of GA favor seed germination, whereas high levels of ABA hinder this process. The direct relationship between GA biosynthesis and seed germina- tion ability need further investigation. Here, we identified the ABA-insensitive gain-of-function mutant germination insensitive to ABA mutant 2 (gim2) by screening a population of XVE T-DNA-tagged mutant lines. Based on two loss-of-function gim2-ko mutant lines, the disruption of GIM2 function caused a delay in seed germination. By contrast, upregulation of GIM2 accelerated seed germina- tion, as observed in transgenic lines overexpressing GIM2 (OE). We detected a reduction in endogenous bioactive GA levels and an increase in endogenous ABA levels in the gim2-ko mutants compared to wild type. Conversely, the OE lines had increased endogenous bioactive GA levels and decreased endogenous ABA levels. The expression levels of a set of GA- and]or ABA-related genes were altered in both the gim2-ko mutants and the OE lines. We confirmed that GIM2 has dioxygenase activity using an in vitro enzyme assay, observing that GIM2 can oxidize GA^2. Hence, our characterization of GIM2 demonstrates that it plays a role in seed germination by affecting the GA metabolic pathway in Arabidopsis.展开更多
BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in the...BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.展开更多
Over the last 30 years,a new actor in the area of ecology and evolution has emerged:niche construction theory(NCT).The fundamental premise of NCT is that organisms may actively influence evolutionary processes by modi...Over the last 30 years,a new actor in the area of ecology and evolution has emerged:niche construction theory(NCT).The fundamental premise of NCT is that organisms may actively influence evolutionary processes by modifying their circumstances[1].According to Trappes et al.,[2]the concept of niche construction should only be applied to species that alter their environment,which they believe to be its intuitive scope.They add two more terms to describe the ways that organisms engage with their surroundings and so influence their niches:when organisms choose their environment,this is known as niche choice,and when they adapt their phenotype to fit their environment,this is known as niche conformance.These three concepts are often referred to as niche-altering mechanisms,or NC3 mechanisms:niche conformance,niche construction,and niche choice.This is in line with definitions of mechanisms developed in scientific philosophy[2].展开更多
It iS general practice in China for coupsactively to alter a charge.There are threeimportant reasons for this that people tendto overlook.They can be detailed as thefollowing:(1)The bill ofcomplaint separatesof charge...It iS general practice in China for coupsactively to alter a charge.There are threeimportant reasons for this that people tendto overlook.They can be detailed as thefollowing:(1)The bill ofcomplaint separatesof charge facts from legal comments.insteadof integrating them.(2)It is common展开更多
Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness an...Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.展开更多
Liver cancer,primarily hepatocellular carcinoma,remains a global health challenge with rising incidence and limited therapeutic options.Genetic factors play a pivotal role in the development and progression of liver c...Liver cancer,primarily hepatocellular carcinoma,remains a global health challenge with rising incidence and limited therapeutic options.Genetic factors play a pivotal role in the development and progression of liver cancer.This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer.We discuss the genetic underpinnings of liver cancer,emphasizing the critical role of risk-associated genetic variants,somatic mutations,and epigenetic alterations.We also explore the intricate interplay between environmental factors and genetics,highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy,and advancements in high-throughput sequencing technologies.By synthesizing the latest research findings,we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer,shedding light on their potential to revolutionize early detection,risk assessment,and targeted therapies in the fight against this devastating disease.展开更多
The studies on hydrothermal alteration-induced eff ects in surface and subsurface rocks provide useful information in the characterization and exploitation of a geothermal reservoir.Generally,these studies are based o...The studies on hydrothermal alteration-induced eff ects in surface and subsurface rocks provide useful information in the characterization and exploitation of a geothermal reservoir.Generally,these studies are based on traditional,and reliable methods like petrography(primary and secondary minerals,and grade of alteration),and geochemistry(mobility of elements,changes in mass and concentration of elements,and fluid inclusions).Recently,apart from these established methods,some methods based on the geochemical(Chemical Index of Alteration,CIA;Weathering Index of Parkar,WIP;Loss on Ignition,LOI;and Sulfur,S)and rock magnetic properties(magnetic susceptibility,χlf;and percentage frequency-dependent susceptibility,χfd%)are also being applied in the identification of whether a rock is an altered or a fresh one.The Acoculco Geothermal Field(AGF),Mexico,is characterized by high temperature and very low permeability,and it is considered a promissory Enhanced Geothermal System.The following changes are observed in the rocks as a result of an increase in hydrothermal alteration:(1)an increase in CIA,LOI,and S values,and a decrease in WIP;(2)an increase in quartz and quartz polymorph minerals(silicification),and clay minerals(argillization);and(3)decrease inχlf values.At AGF,the most altered surface acid rocks are characterized by entirely quartz and its polymorphs,and clay minerals.The present study also indicates the applicability of the binary plots of major elements(felsic vs mafic component)and rock magnetic parameters(χlf vs.χfd%).The rock withχfd%value of 2-10 andχlf value<0.5×10^(-6)m^(3) kg^(-1)indicate the presence of single domain and stable single domain grains,which in turn suggests that it is an altered rock.These methods are simple to apply,rapid,reliable,and have the potential to become eff ective tools for the identifi cation of hydrothermally altered rocks during the initial stage of geothermal exploration.展开更多
Hydrous Cr-bearing uvarovite garnets are rare in natural occurrences and belong to the ugrandite series and exist in binary solid solutions with grossular and andradite garnets. Here, we report the occurrence of hydro...Hydrous Cr-bearing uvarovite garnets are rare in natural occurrences and belong to the ugrandite series and exist in binary solid solutions with grossular and andradite garnets. Here, we report the occurrence of hydrous uvarovite garnet having Cr_(2)O_(3) upto 19.66 wt% and CaO of 32.12–35.14 wt% in the serpentinized mantle peridotites of Naga Hills Ophiolite(NHO), India. They occur in association with low-Cr diopsides. They are enriched in LILE(Ba, Sr), LREEs, with fractionating LREE-MREE [avg.(La/Sm)_(N) = 2.16] with flat MREE/HREE patterns [avg.(Sm/Yb)_(N) = 0.95]. Raman spectra indicate the presence of hydroxyl(OH^(–)) peaks from 3500 to 3700 cm^(-1). Relative abundances in fluid mobile elements and their close association with clinopyroxenes are suggestive of the formation of uvarovite garnets through low temperature metasomatic alteration of low-Cr diopsides by hydrothermal slab fluids. The high LREE concentration and absence of Eu anomaly in the garnet further attest to alkaline nature of the transporting slab dehydrated fluid rather the involvement of low-p H solution. The chemical characteristics of the hydroxyl bearing uvarovite hosted by the mantle peridotite of NHO deviate from the classical features of uvarovite garnet, and their origin is attributed to the fluid-induced metasomatism of the sub arc mantle wedge in a suprasubduction zone regime.展开更多
The Koyna-Warna seismogenic region overlying the Deccan volcanic province of Western India has been experiencing the recurrence of earthquakes since 1967 soon after the impoundment of the Koyna Dam.A large number of s...The Koyna-Warna seismogenic region overlying the Deccan volcanic province of Western India has been experiencing the recurrence of earthquakes since 1967 soon after the impoundment of the Koyna Dam.A large number of small to medium-magnitude shallow focus earthquakes(>100,000)have been detected in this intraplate region during the last six decades.In the present study,the core samples recovered from the borehole‘KBH3’drilled upto 1134 m depth in the pre-Deccan granitoids basement rocks of this region have been subjected to mineralogical and geochemical studies.展开更多
基金supported by the National Nature Science Foundation of China under 62203376the Science and Technology Plan of Hebei Education Department under QN2021139+1 种基金the Nature Science Foundation of Hebei Province under F2021203043the Open Research Fund of Jiangsu Collaborative Innovation Center for Smart Distribution Network,Nanjing Institute of Technology under No.XTCX202203.
文摘Owing to the integration of energy digitization and artificial intelligence technology,smart energy grids can realize the stable,efficient and clean operation of power systems.However,the emergence of cyber-physical attacks,such as dynamic load-altering attacks(DLAAs)has introduced great challenges to the security of smart energy grids.Thus,this study developed a novel cyber-physical collaborative security framework for DLAAs in smart energy grids.The proposed framework integrates attack prediction in the cyber layer with the detection and localization of attacks in the physical layer.First,a data-driven method was proposed to predict the DLAA sequence in the cyber layer.By designing a double radial basis function network,the influence of disturbances on attack prediction can be eliminated.Based on the prediction results,an unknown input observer-based detection and localization method was further developed for the physical layer.In addition,an adaptive threshold was designed to replace the traditional precomputed threshold and improve the detection performance of the DLAAs.Consequently,through the collaborative work of the cyber-physics layer,injected DLAAs were effectively detected and located.Compared with existing methodologies,the simulation results on IEEE 14-bus and 118-bus power systems verified the superiority of the proposed cyber-physical collaborative detection and localization against DLAAs.
基金NASA Glenn Research Center,Award Number,GRT00060658NSF IUCRC Smart Vehicle Concept Research Seed Program,No Award Number Provided.
文摘The Blade Altering Toolbox(BAT)described in this paper is a tool designed for fast reconstruction of an altered blade geometry for design optimization purposes.The BAT algorithm is capable of twisting a given rotor’s angle of attack and stretching the chord length along the span of the rotor.Several test cases were run using the BAT’s algorithm.The BAT code’s twisting,stretching,and mesh reconstruction capabilities proved to be able to handle reasonably large geometric alterations to a provided input rotor geometry.The test examples showed that the toolbox’s algorithm could handle any stretching of the blade’s chord as long as the blade remained within the original bounds of the unaltered mesh.The algorithm appears to fail when the net twist angle applied the geometry exceeds approximately 30 degrees,however this limitation is dependent on the initial geometry and other input parameters.Overall,the algorithm is a very powerful tool for automating a design optimization procedure.
文摘We establish fixed point theorems in complete fuzzy metric space by using notion of altering distance, initiated by Khan et al. [Bull. Austral. Math. Soc. 30 (1984), 1-9]. Also, we find an affirmative answer in fuzzy metric space to the problem of Sastry [TamkangJ. Math., 31(3) (2000), 243-250].
基金Supported by the National Natural Science Foundation of China(11271293)
文摘Some common fixed point results for mappings satisfying a quasi-contractive condition which involves altering distance functions are obtained in partially ordered complete cone metric spaces. A sufficient condition for the uniqueness of common fixed point is proved. Also, an example is given to support our results.
文摘The condition and physical sense of actual dynamic user optimum are explained by analyzing a simple road network route choice. To match the practical application requirements, assignment network and simulation network are classified account for varying flowing loading. Instantaneous dynamic user optimum model should be applied to the former and actual dynamic user optimum model the latter respectively. The two model’s feasibility is studied as well. Considering the application in ATMS, the model is mainly used to analyze the altering OD problem. Moreover, it adds the method of route adapting into the object function selection to appraise elastic trip strategy and set up real means of route inducement.
文摘In the present paper, we prove two theorems. In first theorem, we prove fixed point result for self-maps in the metric space under contractive condition of integral type by altering distance. In second result, we prove a unique common fixed point theorem by considering four sub compatible maps under a contractive condition of integral type.
基金supported by NIH funding(RF1NS110637,2RF1NS094527,R01NS110635)to JW.
文摘Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.
基金funded by national funds,through the Foundation for Science and Technology(FCT)-project UIDB/50026/2020,UIDP/50026/2020(to NAS),EXPL/MEDPAT/0931/2021(to SM)Financial support was provided by Prémios Santa Casa Neurociências-Prize Melo e Castro for Spinal Cord Injury Research(MC-18-2021)+2 种基金Wings For Life Spinal Cord Research Foundation(WFL-PT-14/23)"la Caixa"Foundation(HR23-00484)(to NAS)the FCT for the Scientific Employment Stimulus to NAS and SM(CEECIND/04794/2017 and CEECIND/01902/2017)。
文摘Spinal cord injury(SCI)involves an initial traumatic phase,followed by secondary events such as ischemia,increased blood-spinal cord barrier permeability,ionic disruption,glutamate excitotoxicity,and metabolic alterations.A pe rsistent and exagge rated inflammato ry response within the spinal cord accompanies these events(Lima et al.,2022).The complexity and interplay of these mechanisms exacerbate the initial injury,leading to a degenerative process at the injury site.While the initial trauma is unavoidable,the secondary injury begins within minutes and can last for months,creating an optimal window for therapeutic intervention.
基金supported by an under-40 grant from the Italian Association for Alzheimer’s Research [AIRALZH AGYR2021]the Strategic University Projects–Young Researcher Independence grant [YRG2021] from the Università Campus Bio-Medico di Roma (Rome, Italy)(to LLB)+1 种基金Italian Ministry of Health [Research Grant:GR-2019-12370446]the American Alzheimer’s Association [AARG-22-922961](to PK)。
文摘Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histological alterations including amyloid-beta (AB) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.
基金supported by funds from the Italian Ministry of Health,Ricerca Finalizzata,(Grant N.GR-2013-02355882 and GR-2021-12373946 to AL)5x1000 Project of the Istituto Superiore di Sanità(Project code:ISS5x1000_21-949432e8c9be to AL)the European Union–NextGeneration EU through the Italian Ministry of University and Research under PNRR-M4C2-I1.3 Project PE_00000019“HEAL ITALIA”to EA(CUP I83C22001830006)。
文摘Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult life.To maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.
基金supported in part by the National Natural Science Foundation of China under Grant 11372051,Grant 11475029part by the Fund of the China Academy of Engineering Physics under Grant 20150202045
文摘A new approach for treating the mesh with Lagrangian scheme of finite volume method is presented. It has been proved that classical Lagrangian method is difficult to cope with large deformation in tracking material particles due to severe distortion of cells, and the changing connectivity of the mesh seems especially attractive for solving such issues. The mesh with large deformation based on computational geometry is optimized by using new method. This paper develops a processing system for arbitrary polygonal unstructured grid,the intelligent variable grid neighborhood technologies is utilized to improve the quality of mesh in calculation process, and arbitrary polygonal mesh is used in the Lagrangian finite volume scheme. The performance of the new method is demonstrated through series of numerical examples, and the simulation capability is efficiently presented in coping with the systems with large deformations.
基金the ‘Large-scale Instrument and Equipment Sharing Foundation of Wuhan University’ for supporting the use of the instruments in the College of Life Sciences in Wuhan Universitysupported by grants to Y.W. from Nation Natural Science Foundation of China (31270333 and 90817013)the Major State Basic Research Program from the Ministry of Science and Technology of China (2013CB126900)
文摘The phytohormones gibberellic acid (GA) and abscisic acid (ABA) antagonistically control seed germina- tion. High levels of GA favor seed germination, whereas high levels of ABA hinder this process. The direct relationship between GA biosynthesis and seed germina- tion ability need further investigation. Here, we identified the ABA-insensitive gain-of-function mutant germination insensitive to ABA mutant 2 (gim2) by screening a population of XVE T-DNA-tagged mutant lines. Based on two loss-of-function gim2-ko mutant lines, the disruption of GIM2 function caused a delay in seed germination. By contrast, upregulation of GIM2 accelerated seed germina- tion, as observed in transgenic lines overexpressing GIM2 (OE). We detected a reduction in endogenous bioactive GA levels and an increase in endogenous ABA levels in the gim2-ko mutants compared to wild type. Conversely, the OE lines had increased endogenous bioactive GA levels and decreased endogenous ABA levels. The expression levels of a set of GA- and]or ABA-related genes were altered in both the gim2-ko mutants and the OE lines. We confirmed that GIM2 has dioxygenase activity using an in vitro enzyme assay, observing that GIM2 can oxidize GA^2. Hence, our characterization of GIM2 demonstrates that it plays a role in seed germination by affecting the GA metabolic pathway in Arabidopsis.
文摘BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.
文摘Over the last 30 years,a new actor in the area of ecology and evolution has emerged:niche construction theory(NCT).The fundamental premise of NCT is that organisms may actively influence evolutionary processes by modifying their circumstances[1].According to Trappes et al.,[2]the concept of niche construction should only be applied to species that alter their environment,which they believe to be its intuitive scope.They add two more terms to describe the ways that organisms engage with their surroundings and so influence their niches:when organisms choose their environment,this is known as niche choice,and when they adapt their phenotype to fit their environment,this is known as niche conformance.These three concepts are often referred to as niche-altering mechanisms,or NC3 mechanisms:niche conformance,niche construction,and niche choice.This is in line with definitions of mechanisms developed in scientific philosophy[2].
文摘It iS general practice in China for coupsactively to alter a charge.There are threeimportant reasons for this that people tendto overlook.They can be detailed as thefollowing:(1)The bill ofcomplaint separatesof charge facts from legal comments.insteadof integrating them.(2)It is common
基金supported by the Project on InterGovernmental International Scientific and Technological Innovation Cooperation in National Key Projects of Research and Development Plan (No. 2019YFE0106400)the National Natural Science Foundation of China (No. 81771875)。
文摘Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.
基金European Union-Next Generation EU,Through the National Recovery and Resilience Plan of the Republic of Bulgaria Project,No.BG-RRP-2.004-0008.
文摘Liver cancer,primarily hepatocellular carcinoma,remains a global health challenge with rising incidence and limited therapeutic options.Genetic factors play a pivotal role in the development and progression of liver cancer.This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer.We discuss the genetic underpinnings of liver cancer,emphasizing the critical role of risk-associated genetic variants,somatic mutations,and epigenetic alterations.We also explore the intricate interplay between environmental factors and genetics,highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy,and advancements in high-throughput sequencing technologies.By synthesizing the latest research findings,we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer,shedding light on their potential to revolutionize early detection,risk assessment,and targeted therapies in the fight against this devastating disease.
基金Rock magnetic instruments used in this work are procured with the funding from CEMIE Geo project 207032(Fondo de Sustentabilidad Energética de CONACy T-SENER,Government of Mexico)。
文摘The studies on hydrothermal alteration-induced eff ects in surface and subsurface rocks provide useful information in the characterization and exploitation of a geothermal reservoir.Generally,these studies are based on traditional,and reliable methods like petrography(primary and secondary minerals,and grade of alteration),and geochemistry(mobility of elements,changes in mass and concentration of elements,and fluid inclusions).Recently,apart from these established methods,some methods based on the geochemical(Chemical Index of Alteration,CIA;Weathering Index of Parkar,WIP;Loss on Ignition,LOI;and Sulfur,S)and rock magnetic properties(magnetic susceptibility,χlf;and percentage frequency-dependent susceptibility,χfd%)are also being applied in the identification of whether a rock is an altered or a fresh one.The Acoculco Geothermal Field(AGF),Mexico,is characterized by high temperature and very low permeability,and it is considered a promissory Enhanced Geothermal System.The following changes are observed in the rocks as a result of an increase in hydrothermal alteration:(1)an increase in CIA,LOI,and S values,and a decrease in WIP;(2)an increase in quartz and quartz polymorph minerals(silicification),and clay minerals(argillization);and(3)decrease inχlf values.At AGF,the most altered surface acid rocks are characterized by entirely quartz and its polymorphs,and clay minerals.The present study also indicates the applicability of the binary plots of major elements(felsic vs mafic component)and rock magnetic parameters(χlf vs.χfd%).The rock withχfd%value of 2-10 andχlf value<0.5×10^(-6)m^(3) kg^(-1)indicate the presence of single domain and stable single domain grains,which in turn suggests that it is an altered rock.These methods are simple to apply,rapid,reliable,and have the potential to become eff ective tools for the identifi cation of hydrothermally altered rocks during the initial stage of geothermal exploration.
基金the funding received from the Science and Engineering Research Board (SERB), Govt. of India under GAP 3291funded by Ministry of Earth Science (MoES) with project reference number Mo ES/ P.O. (Seismic) 8 (09)-Geochron/2012。
文摘Hydrous Cr-bearing uvarovite garnets are rare in natural occurrences and belong to the ugrandite series and exist in binary solid solutions with grossular and andradite garnets. Here, we report the occurrence of hydrous uvarovite garnet having Cr_(2)O_(3) upto 19.66 wt% and CaO of 32.12–35.14 wt% in the serpentinized mantle peridotites of Naga Hills Ophiolite(NHO), India. They occur in association with low-Cr diopsides. They are enriched in LILE(Ba, Sr), LREEs, with fractionating LREE-MREE [avg.(La/Sm)_(N) = 2.16] with flat MREE/HREE patterns [avg.(Sm/Yb)_(N) = 0.95]. Raman spectra indicate the presence of hydroxyl(OH^(–)) peaks from 3500 to 3700 cm^(-1). Relative abundances in fluid mobile elements and their close association with clinopyroxenes are suggestive of the formation of uvarovite garnets through low temperature metasomatic alteration of low-Cr diopsides by hydrothermal slab fluids. The high LREE concentration and absence of Eu anomaly in the garnet further attest to alkaline nature of the transporting slab dehydrated fluid rather the involvement of low-p H solution. The chemical characteristics of the hydroxyl bearing uvarovite hosted by the mantle peridotite of NHO deviate from the classical features of uvarovite garnet, and their origin is attributed to the fluid-induced metasomatism of the sub arc mantle wedge in a suprasubduction zone regime.
基金the Ministry of Earth Sciences,Govt of India,for the financial support[MoES/P.O.(Seismo)/1(374)/2019]and Dr.Sukanta Roy,Project Director,MoES-BGRL,Karad,for providing samples.
文摘The Koyna-Warna seismogenic region overlying the Deccan volcanic province of Western India has been experiencing the recurrence of earthquakes since 1967 soon after the impoundment of the Koyna Dam.A large number of small to medium-magnitude shallow focus earthquakes(>100,000)have been detected in this intraplate region during the last six decades.In the present study,the core samples recovered from the borehole‘KBH3’drilled upto 1134 m depth in the pre-Deccan granitoids basement rocks of this region have been subjected to mineralogical and geochemical studies.