Hepatocellular carcinoma(HCC) is the fourth cause of cancer related mortality, and its incidence is rapidly increasing. Viral hepatitis, alcohol abuse, and exposure to hepatotoxins are major risk factors, but nonalcoh...Hepatocellular carcinoma(HCC) is the fourth cause of cancer related mortality, and its incidence is rapidly increasing. Viral hepatitis, alcohol abuse, and exposure to hepatotoxins are major risk factors, but nonalcoholic fatty liver disease(NAFLD) associated with obesity, insulin resistance, and type 2 diabetes, is an increasingly recognized trigger, especially in developed countries. Older age, severity of insulin resistance and diabetes, and iron overload have been reported to predispose to HCC in this context. Remarkably, HCCs have been reported in non-cirrhotic livers in a higher proportion of cases in NAFLD patients than in other etiologies. Inherited factors have also been implicated to explain the different individual susceptibility to develop HCC, and their role seems magnified in fatty liver, where only a minority of affected subjects progresses to cancer. In particular, the common I148 M variant of the PNPLA3 gene influencing hepatic lipid metabolism influences HCC risk independently of its effect on the progression of liver fibrosis. Recently, rare loss-of-function mutations in Apolipoprotein B resulting in very low density lipoproteins hepatic retention and in Telomerase reverse transcriptase influencing cellular senescence have also been linked to HCC in NAFLD. Indeed, hepatic stellate cells senescence has been suggested to bridge tissue aging with alterations of the intestinal microbiota in the pathogenesis of obesity-related HCC. A deeper understanding of the mechanisms mediating hepatic carcinogenesis during insulin resistance, and the identification of its genetic determinants will hopefully provide new diagnostic and therapeutic tools.展开更多
The corona-generated audible noise(AN)factor is an important consideration in the design and operation of ultrahigh voltage direct current(DC)and alternate current(AC)transmission lines.Due to the differences in disch...The corona-generated audible noise(AN)factor is an important consideration in the design and operation of ultrahigh voltage direct current(DC)and alternate current(AC)transmission lines.Due to the differences in discharge process and corona-generated space charges between the DC and AC corona discharge,the audible noise from DC and AC corona has different characteristics.This paper conducts a series of experiments by measuring the time-domain waveforms of the audible noise from a single corona source under DC and AC voltage.Sound pressure pulses are extracted from a correlation analysis,and then a detailed comparison of the basic characteristics of DC and AC corona-generated AN in time-domain and frequency spectrum is given.Results from this paper stand to contribute to an explanation of existing results in AN measurement and analysis from DC and AC transmission lines.展开更多
In the past decade,ferroelectric materials have been intensively explored as promising photocatalysts.An intriguing ability of ferroelectrics is to directly sperate the photogenerated electrons and holes,which is beli...In the past decade,ferroelectric materials have been intensively explored as promising photocatalysts.An intriguing ability of ferroelectrics is to directly sperate the photogenerated electrons and holes,which is believed to arise from a spontaneous polarization.Understanding how polarization affects the photocatalytic performance is vital to design high-efficiency photocatalysts.In this work,we report a size effect of ferroelectric polarization on regulating the photocatalytic overall water splitting of SrTiO_(3)/PbTiO_(3)nanoplate heterostructures for the first time.This was realized hydrothermally by controlling the thickness and thus spontaneous polarization strength of single-crystal and single-domain PbTiO_(3)nanoplates,which served as the substrate for selective heteroepitaxial growth of SrTiO_(3).An enhancement of 22 times in the photocatalytic overall water splitting performance of the heterostructures has been achieved when the average thickness of the nanoplate increases from 30 to 107 nm.A combined experimental investigation revealed that the incompletely compensated depolarization filed is the dominated driving force for the photogenerated carrier separation within heterostructures,and its increase with the thickness of the nanoplates accounts for the enhancement of photocatalytic activity.Moreover,the concentration of oxygen vacancies for negative polarization compensation has been found to grow as the thickness of the nanoplates increases,which promotes oxygen evolution reaction and reduces the stoichiometric ratio of H_(2)/O_(2).These findings may provide the opportunity to design and develop high-efficiency ferroelectric photocatalysts.展开更多
Single-domain antibodies(sdAbs),initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs,have emerged as a promising alternative to conventional therapeutic antibodies.These sdAbs hav...Single-domain antibodies(sdAbs),initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs,have emerged as a promising alternative to conventional therapeutic antibodies.These sdAbs have many superior physicochemical and pharmacological properties,including small size,good solubility and thermostability,easier accessible epitopes,and strong tissue penetration.However,the inherent challenges associated with the animal origin of sdAbs limit their clinical use.In recent years,various innovative humanization technologies,including complementarity-determining region(CDR)grafting or complete engineering of fully human sdAbs,have been developed to mitigate potential immunogenicity issues and enhance their compatibility.This review provides a comprehensive exploration of sdAbs,emphasizing their distinctive features and the progress in humanization methodologies.In addition,we provide an overview of the recent progress in developing drugs and therapeutic strategies based on sdAbs and their potential in solid tumor treatment,such as sdAbedrug conjugates,multispecific sdAbs,sdAb-based delivery systems,and sdAb-based cell therapy.展开更多
Despite the huge accumulation of scientific literature,it is inefficient and laborious to manually search it for useful information to investigate structure-activity relationships.Here,we propose an efficient text-min...Despite the huge accumulation of scientific literature,it is inefficient and laborious to manually search it for useful information to investigate structure-activity relationships.Here,we propose an efficient text-mining framework for the discovery of credible and valuable domain knowledge from abstracts of scientific literature focusing on Nickel-based single crystal superalloys.Firstly,the credibility of abstracts is quantified in terms of source timeliness,publication authority and author’s academic standing.Next,eight entity types and domain dictionaries describing Nickel-based single crystal superalloys are predefined to realize the named entity recognition from the abstracts,achieving an accuracy of 85.10%.Thirdly,by formulating 12 naming rules for the alloy brands derived from the recognized entities,we extract the target entities and refine them as domain knowledge through the credibility analysis.Following this,we also map out the academic cooperative“Author-Literature-Institute”network,characterize the generations of Nickel-based single crystal superalloys,as well as obtain the fractions of the most important chemical elements in superalloys.The extracted rich and diverse knowledge of Nickel-based single crystal superalloys provides important insights toward understanding the structure-activity relationships for Nickel-based single crystal superalloys and is expected to accelerate the design and discovery of novel superalloys.展开更多
It was reported a facile strategy to fabricate magnetite(Fe3O4)single-crystal particles with critical single-domain size by employing graphene oxide(GO)sheets as template.In this method,the small-sized Fe2 O3 nanopart...It was reported a facile strategy to fabricate magnetite(Fe3O4)single-crystal particles with critical single-domain size by employing graphene oxide(GO)sheets as template.In this method,the small-sized Fe2 O3 nanoparticles were first synthesized,and then low-temperature annealing under H2 would convert them into large-sized Fe3 O4 single-crystal particles.The synthetic particles with an average size of 100 nm exhibit high saturation magnetization(Ms)of 0.085 A·m^2·g^-1,which is very close to theoretical value,being among the highest values in ever reported for Fe3O4 made from chemical methods.On this basis,the small-sized Fe3 O4 particles(average size of 30 nm)were also fabricated by coating with Na2 CO3 shell.展开更多
We focus on the single layer formulation which provides an integral equation of the first kind that is very badly conditioned. The condition number of the unpreconditioned system increases exponentially with the multi...We focus on the single layer formulation which provides an integral equation of the first kind that is very badly conditioned. The condition number of the unpreconditioned system increases exponentially with the multiscale levels. A remedy utilizing overlapping domain decompositions applied to the Boundary Element Method by means of wavelets is examined. The width of the overlapping of the subdomains plays an important role in the estimation of the eigenvalues as well as the condition number of the additive domain decomposition operator. We examine the convergence analysis of the domain decomposition method which depends on the wavelet levels and on the size of the subdomain overlaps. Our theoretical results related to the additive Schwarz method are corroborated by numerical outputs.展开更多
Type IV collagenase plays a pivotal role in invasion, metastasis and angiogenesis of tumor. Single domain antibodies are attractive as tumor-targeting vehicle because of their much smaller size com-pared with antibody...Type IV collagenase plays a pivotal role in invasion, metastasis and angiogenesis of tumor. Single domain antibodies are attractive as tumor-targeting vehicle because of their much smaller size com-pared with antibody molecules produced by conventional methods. Lidamycin (LDM) is a potent enediyne-containing antitumor antibiotic. In this study an engineered and energized fusion protein VL-LDP-AE composed of lidamycin and VL domain of mAb 3G11 directed against type IV collagenase was prepared using a novel two-step method. First a VL-LDP fusion protein was constructed by DNA recombination. Secondly VL-LDP-AE was obtained by molecular reconstitution. In MTT assay, VL-LDP-AE showed potent cytotoxicity to HT-1080 cells and KB cells with IC50 values of 8.55×10-12 and 1.70×10-11 mol/L, respectively. VL-LDP-AE showed antiangiogenic activity in chick chrorioallantoic membrane (CAM) assay and tube formation assay. In in vivo experiments, VL-LDP-AE was proved to be more effective than free LDM against the growth of subcutaneously transplanted hepatoma 22 in mice. Drugs were given intravenously on day 3 and 10 after tumor transplantation. Compared in terms of maximal tolerated doses, VL-LDP-AE at 0.25 mg/kg suppressed the tumor growth by 89.5%, LDM at 0.05 mg/kg by 69.9%, and mitomycin at 1 mg/kg by 35%. Having a molecular weight of 25.2 kDa, VL-LDP-AE was much smaller than other reported antibody-based drugs. The results suggested that VL-LDP-AE would be a promising candidate for tumor targeting therapy. And the 2-step approach could serve as a new technology platform for making a series of highly potent engineered antibody-based drugs for a variety of cancers.展开更多
I. INTRODUCTIONThe outstanding magnetic properties of Nd-Fe-B permanent alloy with very high coercive force and maximum magnetic energy product have attracted scientists’ attention greatly and extensive investigation...I. INTRODUCTIONThe outstanding magnetic properties of Nd-Fe-B permanent alloy with very high coercive force and maximum magnetic energy product have attracted scientists’ attention greatly and extensive investigation has been made on its structure and mag-展开更多
To study the influence of thickness on the magnetic properties of ReBCO(Re = Y, Gd, Sm, Nd, etc.) bulk superconductors, a single domain gadolinium barium copper oxide(GdBCO) bulk superconductor fabricated by the Re + ...To study the influence of thickness on the magnetic properties of ReBCO(Re = Y, Gd, Sm, Nd, etc.) bulk superconductors, a single domain gadolinium barium copper oxide(GdBCO) bulk superconductor fabricated by the Re + 011 top seeded infiltration growth(Re + 011 TSIG) method was continuously sliced along the bottom to obtain samples of different thickness. The levitation force and attractive force of these samples were tested at 77 K in the zero-field-cooled(ZFC)state. It is found that as the sample thickness decreases, the levitation force decreases gradually whereas the attractive force increases. This is related to the varied ability to resist the penetration of magnetic field occasioned by varying sample thickness, which are deeply revealed by combining with the characteristics of the non-ideal type-II superconductor. Further,the levitation force exhibits a trend of slow initial change followed by rapid change, which may be attributed to the growth of the sample. Measurement of the trapped field shows that a similar distribution of trapped field at the top and bottom surfaces can be achieved by removing some materials from the bottom of the bulk. These results provide a reference for meeting the actual requirements of ReBCO bulks of different thicknesses and greatly contribute to practical designs and applications.展开更多
Single receiver positioning has been widely used as a standard and standalone positioning technique for about 25 years.To detect the slowly growing faults caused by satellite and receiver clocks in single receiver pos...Single receiver positioning has been widely used as a standard and standalone positioning technique for about 25 years.To detect the slowly growing faults caused by satellite and receiver clocks in single receiver positioning,the Autonomous Integrity Monitoring with an Extrapolation method(AIME)was proposed based on the Kalman filter measurement domain.However,AIME was designed with the assumption of there is the same number of visible satellites at each epoch,which limits its application.To address this issue,this paper proposes a state-domain Robust Autonomous Integrity Monitoring with the Extrapolation Method(SRAIME).The slowly growing fault detection statistics is established based on the difference between the estimates of the state propagator and the posterior state estimation in Kalman filtering.Meanwhile,singular value decomposition is adopted to factor the covariance matrix of the difference to increase computational robustness.Besides,the relevant formulas of the proposed method are theoretically derived,and it is proven that the proposed method is suitable for any positioning model based on the Kalman filter.Additionally,the results of two experiments indicate that SRAIME can detect slowly growing faults in single receiver positioning earlier than AIME.展开更多
文摘Hepatocellular carcinoma(HCC) is the fourth cause of cancer related mortality, and its incidence is rapidly increasing. Viral hepatitis, alcohol abuse, and exposure to hepatotoxins are major risk factors, but nonalcoholic fatty liver disease(NAFLD) associated with obesity, insulin resistance, and type 2 diabetes, is an increasingly recognized trigger, especially in developed countries. Older age, severity of insulin resistance and diabetes, and iron overload have been reported to predispose to HCC in this context. Remarkably, HCCs have been reported in non-cirrhotic livers in a higher proportion of cases in NAFLD patients than in other etiologies. Inherited factors have also been implicated to explain the different individual susceptibility to develop HCC, and their role seems magnified in fatty liver, where only a minority of affected subjects progresses to cancer. In particular, the common I148 M variant of the PNPLA3 gene influencing hepatic lipid metabolism influences HCC risk independently of its effect on the progression of liver fibrosis. Recently, rare loss-of-function mutations in Apolipoprotein B resulting in very low density lipoproteins hepatic retention and in Telomerase reverse transcriptase influencing cellular senescence have also been linked to HCC in NAFLD. Indeed, hepatic stellate cells senescence has been suggested to bridge tissue aging with alterations of the intestinal microbiota in the pathogenesis of obesity-related HCC. A deeper understanding of the mechanisms mediating hepatic carcinogenesis during insulin resistance, and the identification of its genetic determinants will hopefully provide new diagnostic and therapeutic tools.
基金supported by National Basic Research Program of China(973 Program)under Grant 2011CB209402.
文摘The corona-generated audible noise(AN)factor is an important consideration in the design and operation of ultrahigh voltage direct current(DC)and alternate current(AC)transmission lines.Due to the differences in discharge process and corona-generated space charges between the DC and AC corona discharge,the audible noise from DC and AC corona has different characteristics.This paper conducts a series of experiments by measuring the time-domain waveforms of the audible noise from a single corona source under DC and AC voltage.Sound pressure pulses are extracted from a correlation analysis,and then a detailed comparison of the basic characteristics of DC and AC corona-generated AN in time-domain and frequency spectrum is given.Results from this paper stand to contribute to an explanation of existing results in AN measurement and analysis from DC and AC transmission lines.
基金supported by the National Key R&D Program of China(No.2021YFA1500800)the National Natural Science Foundation of China(Nos.52425201,52272129,and 12125407)+2 种基金the Natural Science Foundation of Zhejiang Province,China(No.LR21E020004)the ShanxiZheda Institute of Advanced Materials and Chemical Engineering(No.2021SX-FR007)the Joint Funds of the National Natural Science Foundation of China(No.U21A2067).
文摘In the past decade,ferroelectric materials have been intensively explored as promising photocatalysts.An intriguing ability of ferroelectrics is to directly sperate the photogenerated electrons and holes,which is believed to arise from a spontaneous polarization.Understanding how polarization affects the photocatalytic performance is vital to design high-efficiency photocatalysts.In this work,we report a size effect of ferroelectric polarization on regulating the photocatalytic overall water splitting of SrTiO_(3)/PbTiO_(3)nanoplate heterostructures for the first time.This was realized hydrothermally by controlling the thickness and thus spontaneous polarization strength of single-crystal and single-domain PbTiO_(3)nanoplates,which served as the substrate for selective heteroepitaxial growth of SrTiO_(3).An enhancement of 22 times in the photocatalytic overall water splitting performance of the heterostructures has been achieved when the average thickness of the nanoplate increases from 30 to 107 nm.A combined experimental investigation revealed that the incompletely compensated depolarization filed is the dominated driving force for the photogenerated carrier separation within heterostructures,and its increase with the thickness of the nanoplates accounts for the enhancement of photocatalytic activity.Moreover,the concentration of oxygen vacancies for negative polarization compensation has been found to grow as the thickness of the nanoplates increases,which promotes oxygen evolution reaction and reduces the stoichiometric ratio of H_(2)/O_(2).These findings may provide the opportunity to design and develop high-efficiency ferroelectric photocatalysts.
基金supported by grants from the National Key R&D Program of China(2019YFA0904400)National Natural Science Foundation of China(32270984)+1 种基金Science and Technology Commission of Shanghai Municipality(23XD1400800,China)Shanghai Municipal Health Commission(GWVI-11.2-YQ46,China).
文摘Single-domain antibodies(sdAbs),initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs,have emerged as a promising alternative to conventional therapeutic antibodies.These sdAbs have many superior physicochemical and pharmacological properties,including small size,good solubility and thermostability,easier accessible epitopes,and strong tissue penetration.However,the inherent challenges associated with the animal origin of sdAbs limit their clinical use.In recent years,various innovative humanization technologies,including complementarity-determining region(CDR)grafting or complete engineering of fully human sdAbs,have been developed to mitigate potential immunogenicity issues and enhance their compatibility.This review provides a comprehensive exploration of sdAbs,emphasizing their distinctive features and the progress in humanization methodologies.In addition,we provide an overview of the recent progress in developing drugs and therapeutic strategies based on sdAbs and their potential in solid tumor treatment,such as sdAbedrug conjugates,multispecific sdAbs,sdAb-based delivery systems,and sdAb-based cell therapy.
基金supported by the National Natural Science Foundation of China(Grant No.52073169)the National Key Research and Development Program of China(Grant No.2021YFB3802101)the Key Research Project of Zhejiang Laboratory(Grant No.2021PE0AC02)。
文摘Despite the huge accumulation of scientific literature,it is inefficient and laborious to manually search it for useful information to investigate structure-activity relationships.Here,we propose an efficient text-mining framework for the discovery of credible and valuable domain knowledge from abstracts of scientific literature focusing on Nickel-based single crystal superalloys.Firstly,the credibility of abstracts is quantified in terms of source timeliness,publication authority and author’s academic standing.Next,eight entity types and domain dictionaries describing Nickel-based single crystal superalloys are predefined to realize the named entity recognition from the abstracts,achieving an accuracy of 85.10%.Thirdly,by formulating 12 naming rules for the alloy brands derived from the recognized entities,we extract the target entities and refine them as domain knowledge through the credibility analysis.Following this,we also map out the academic cooperative“Author-Literature-Institute”network,characterize the generations of Nickel-based single crystal superalloys,as well as obtain the fractions of the most important chemical elements in superalloys.The extracted rich and diverse knowledge of Nickel-based single crystal superalloys provides important insights toward understanding the structure-activity relationships for Nickel-based single crystal superalloys and is expected to accelerate the design and discovery of novel superalloys.
基金financially supported by the National Natural Science Foundation of China(No.51701109)
文摘It was reported a facile strategy to fabricate magnetite(Fe3O4)single-crystal particles with critical single-domain size by employing graphene oxide(GO)sheets as template.In this method,the small-sized Fe2 O3 nanoparticles were first synthesized,and then low-temperature annealing under H2 would convert them into large-sized Fe3 O4 single-crystal particles.The synthetic particles with an average size of 100 nm exhibit high saturation magnetization(Ms)of 0.085 A·m^2·g^-1,which is very close to theoretical value,being among the highest values in ever reported for Fe3O4 made from chemical methods.On this basis,the small-sized Fe3 O4 particles(average size of 30 nm)were also fabricated by coating with Na2 CO3 shell.
文摘We focus on the single layer formulation which provides an integral equation of the first kind that is very badly conditioned. The condition number of the unpreconditioned system increases exponentially with the multiscale levels. A remedy utilizing overlapping domain decompositions applied to the Boundary Element Method by means of wavelets is examined. The width of the overlapping of the subdomains plays an important role in the estimation of the eigenvalues as well as the condition number of the additive domain decomposition operator. We examine the convergence analysis of the domain decomposition method which depends on the wavelet levels and on the size of the subdomain overlaps. Our theoretical results related to the additive Schwarz method are corroborated by numerical outputs.
基金Supported by the National High Technology Research and Development Program of China (863 Program)(Grant No. 2006AA02A255)
文摘Type IV collagenase plays a pivotal role in invasion, metastasis and angiogenesis of tumor. Single domain antibodies are attractive as tumor-targeting vehicle because of their much smaller size com-pared with antibody molecules produced by conventional methods. Lidamycin (LDM) is a potent enediyne-containing antitumor antibiotic. In this study an engineered and energized fusion protein VL-LDP-AE composed of lidamycin and VL domain of mAb 3G11 directed against type IV collagenase was prepared using a novel two-step method. First a VL-LDP fusion protein was constructed by DNA recombination. Secondly VL-LDP-AE was obtained by molecular reconstitution. In MTT assay, VL-LDP-AE showed potent cytotoxicity to HT-1080 cells and KB cells with IC50 values of 8.55×10-12 and 1.70×10-11 mol/L, respectively. VL-LDP-AE showed antiangiogenic activity in chick chrorioallantoic membrane (CAM) assay and tube formation assay. In in vivo experiments, VL-LDP-AE was proved to be more effective than free LDM against the growth of subcutaneously transplanted hepatoma 22 in mice. Drugs were given intravenously on day 3 and 10 after tumor transplantation. Compared in terms of maximal tolerated doses, VL-LDP-AE at 0.25 mg/kg suppressed the tumor growth by 89.5%, LDM at 0.05 mg/kg by 69.9%, and mitomycin at 1 mg/kg by 35%. Having a molecular weight of 25.2 kDa, VL-LDP-AE was much smaller than other reported antibody-based drugs. The results suggested that VL-LDP-AE would be a promising candidate for tumor targeting therapy. And the 2-step approach could serve as a new technology platform for making a series of highly potent engineered antibody-based drugs for a variety of cancers.
文摘I. INTRODUCTIONThe outstanding magnetic properties of Nd-Fe-B permanent alloy with very high coercive force and maximum magnetic energy product have attracted scientists’ attention greatly and extensive investigation has been made on its structure and mag-
基金supported by the National Natural Science Foundation of China (Grant No. 52072229)the Key-grant Project of the Ministry of Education of China (Grant No. 311033)+1 种基金the Fundamental Research Funds for the Central Universities (Grant No. GK201706001)the Teaching Reform and Innovation Project of Higher Education in Shanxi Province, China (Grant No. J2021719)。
文摘To study the influence of thickness on the magnetic properties of ReBCO(Re = Y, Gd, Sm, Nd, etc.) bulk superconductors, a single domain gadolinium barium copper oxide(GdBCO) bulk superconductor fabricated by the Re + 011 top seeded infiltration growth(Re + 011 TSIG) method was continuously sliced along the bottom to obtain samples of different thickness. The levitation force and attractive force of these samples were tested at 77 K in the zero-field-cooled(ZFC)state. It is found that as the sample thickness decreases, the levitation force decreases gradually whereas the attractive force increases. This is related to the varied ability to resist the penetration of magnetic field occasioned by varying sample thickness, which are deeply revealed by combining with the characteristics of the non-ideal type-II superconductor. Further,the levitation force exhibits a trend of slow initial change followed by rapid change, which may be attributed to the growth of the sample. Measurement of the trapped field shows that a similar distribution of trapped field at the top and bottom surfaces can be achieved by removing some materials from the bottom of the bulk. These results provide a reference for meeting the actual requirements of ReBCO bulks of different thicknesses and greatly contribute to practical designs and applications.
基金This work was supported by the Fundamental Research Funds for the Central Universities(No.2019XKQYMS52)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Single receiver positioning has been widely used as a standard and standalone positioning technique for about 25 years.To detect the slowly growing faults caused by satellite and receiver clocks in single receiver positioning,the Autonomous Integrity Monitoring with an Extrapolation method(AIME)was proposed based on the Kalman filter measurement domain.However,AIME was designed with the assumption of there is the same number of visible satellites at each epoch,which limits its application.To address this issue,this paper proposes a state-domain Robust Autonomous Integrity Monitoring with the Extrapolation Method(SRAIME).The slowly growing fault detection statistics is established based on the difference between the estimates of the state propagator and the posterior state estimation in Kalman filtering.Meanwhile,singular value decomposition is adopted to factor the covariance matrix of the difference to increase computational robustness.Besides,the relevant formulas of the proposed method are theoretically derived,and it is proven that the proposed method is suitable for any positioning model based on the Kalman filter.Additionally,the results of two experiments indicate that SRAIME can detect slowly growing faults in single receiver positioning earlier than AIME.