To date, it is unknown whether it is possible to construct a complete graph invariant in polynomial time, so fast algorithms for checking non-isomorphism are important, including heuristic algorithms, and for successf...To date, it is unknown whether it is possible to construct a complete graph invariant in polynomial time, so fast algorithms for checking non-isomorphism are important, including heuristic algorithms, and for successful implementations of such heuristics, both the tasks of some modification of previously described graph invariants and the description of new invariants remain relevant. Many of the described invariants make it possible to distinguish a larger number of graphs in the real time of a computer program. In this paper, we propose an invariant for a special kind of directed graphs, namely, for tournaments. The last ones, from our point of view, are interesting because when fixing the order of vertices, the number of different tournaments is exactly equal to the number of undirected graphs, also with fixing the order of vertices. In the invariant we are considering, all possible tournaments consisting of a subset of vertices of a given digraph with the same set of arcs are iterated over. For such subset tournaments, the places are calculated in the usual way, which are summed up to obtain the final values of the points of the vertices;these points form the proposed invariant. As we expected, calculations of the new invariant showed that it does not coincide with the most natural invariant for tournaments, in which the number of points is calculated for each participant. So far, we have conducted a small number of computational experiments, and the minimum value of the pair correlation between the sequences representing these two invariants that we found is for dimension 15.展开更多
The paper describes some implementation aspects of an algorithm for approximate solution of the traveling salesman problem based on the construction of convex closed contours on the initial set of points (“cities”) ...The paper describes some implementation aspects of an algorithm for approximate solution of the traveling salesman problem based on the construction of convex closed contours on the initial set of points (“cities”) and their subsequent combination into a closed path (the so-called contour algorithm or “onion husk” algorithm). A number of heuristics related to the different stages of the algorithm are considered, and various variants of the algorithm based on these heuristics are analyzed. Sets of randomly generated points of different sizes (from 4 to 90 and from 500 to 10,000) were used to test the algorithms. The numerical results obtained are compared with the results of two well-known combinatorial optimization algorithms, namely the algorithm based on the branch and bound method and the simulated annealing algorithm. .展开更多
We investigate decomposition of codes and finite languages. A prime decomposition is a decomposition of a code or languages into a concatenation of nontrivial prime codes or languages. A code is prime if it cannot be ...We investigate decomposition of codes and finite languages. A prime decomposition is a decomposition of a code or languages into a concatenation of nontrivial prime codes or languages. A code is prime if it cannot be decomposed into at least two nontrivial codes as the same for the languages. In the paper, a linear time algorithm is designed, which finds the prime decomposition. If codes or finite languages are presented as given by its minimal deterministic automaton, then from the point of view of abstract algebra and graph theory, this automaton has special properties. The study was conducted using system for computational Discrete Algebra GAP. .展开更多
This paper presents the past,present and future status of the Russian VLBI network "Quasar".This network has been developed for at least 20 years by the Institute of Applied Astronomy of the Russian Academy ...This paper presents the past,present and future status of the Russian VLBI network "Quasar".This network has been developed for at least 20 years by the Institute of Applied Astronomy of the Russian Academy of Sciences(IAA RAS). The equipment installed currently at each "Quasar" station and the facilities for processing observational data are described briefly. The latest results are presented, including the Earth orientation parameters(EOP) determined from the "Quasar" VLBI data and comparison with those from other processing centers. Our future plans to extend the "Quasar" VLB I network to the east and to the west will be carried out by establishing the Ussurijsk station in the Far East and the RussianCuban station in the west. They are considered in the context of the Russian section activity in the GGOS project. The expected improvement of the EOP determination accuracy can be obtained within the future configuration of the "Quasar" network,which is proved by simulation.展开更多
Rapid urbanization has led to changes in the urban land surface thermal environment.However,there are still much unknown about the urban land surface thermal conditions in permafrost regions.Permafrost is a unique geo...Rapid urbanization has led to changes in the urban land surface thermal environment.However,there are still much unknown about the urban land surface thermal conditions in permafrost regions.Permafrost is a unique geological environment,changes in the urban land surface thermal environment may trigger geological disasters caused by permafrost degradation.This study utilized remote sensing data and geographic de-tectors to identify the dynamic changes in land surface temperature(LST)and land use/land cover(LU/LC)in Yakutsk,as well as the potential factors contributing to LST variations.Between 1992 and 2020,the built-up area in Yakutsk increased by 36%,and the annual average LST in Yakutsk has risen by 6.67℃,accompanied by an expansion of high-temperature areas.Despite ongoing greening efforts,rapid urbanization poses a threat to these green spaces.Changes in the normalized difference built-up index(NDBI)and land use transfer(LDT)were identified as the primary drivers of urban LST changes.By integrating geographic detector technology and artificial neural network models,we optimized the selection of input factors in the prediction model and used it to explore the future changes in LST in Yakutsk.The average LST in Yakutsk is expected to reach 23.4℃ and 25.1℃ in 2030 and 2040,respectively,with a further increase in high-temperature areas.This study provides a reference for ecological,hydrological,and geological assessments of cities in permafrost regions.展开更多
The aim is to study the set of subsets of grids of the Waterloo language from the point of view of abstract algebra and graph theory. The study was conducted using the library for working with transition graphs of non...The aim is to study the set of subsets of grids of the Waterloo language from the point of view of abstract algebra and graph theory. The study was conducted using the library for working with transition graphs of nondeterministic finite automata NFALib implemented by one of the authors in C#, as well as statistical methods for analyzing algorithms. The results are regularities obtained when considering semilattices on a set of subsets of grids of the Waterloo language. It follows from the results obtained that the minimum covering automaton equivalent to the Waterloo automaton can be obtained by adding one additional to the minimum covering set of grids. .展开更多
Based on the standard definition of the product (concatenation), the natural non-negative degree of the language is introduced. Root extraction is the reverse operation to it, and it can be defined in several differen...Based on the standard definition of the product (concatenation), the natural non-negative degree of the language is introduced. Root extraction is the reverse operation to it, and it can be defined in several different ways. Despite the simplicity of the formulation of the problem of extracting the root, the authors could not find any description of it in the literature (as well as on the Internet), including even its formulation. Most of the material in this article is devoted to the simplest version of the formulation: the root of the 2<sup>nd</sup> degree for the 1-letter alphabet, but many of the provisions of the article are generalized to more complex cases. Apparently, for a possible future description of a polynomial algorithm for solving at least one of the described statements of root extraction problems, it is first necessary to really analyze in detail such a special case, that is: either describe the necessary polynomial algorithm, or, conversely, show that the problem belongs to the class of NP-complete problems. Thus, in this article, we do not propose a polynomial algorithm for the problems under consideration;however, the models described here should help in constructing appropriate heuristic algorithms for their solution. A detailed description of the possible further application of such heuristic algorithms is beyond the scope of this article. .展开更多
We continue to consider one of the cybernetic methods in biology related to the study of DNA chains. Exactly, we are considering the problem of reconstructing the distance matrix for DNA chains. Such a matrix is forme...We continue to consider one of the cybernetic methods in biology related to the study of DNA chains. Exactly, we are considering the problem of reconstructing the distance matrix for DNA chains. Such a matrix is formed on the basis of any of the possible algorithms for determining the distances between DNA chains, as well as any specific object of study. At the same time, for example, the practical programming results show that on an average modern computer, it takes about a day to build such a 30 × 30 matrix for mnDNAs using the Needleman-Wunsch algorithm;therefore, for such a 300 × 300 matrix, about 3 months of continuous computer operation is expected. Thus, even for a relatively small number of species, calculating the distance matrix on conventional computers is hardly feasible and the supercomputers are usually not available. Therefore, we started publishing our variants of the algorithms for calculating the distance between two DNA chains, then we publish algorithms for restoring partially filled matrices, i.e., the inverse problem of matrix processing. Previously, we used the method of branches and boundaries, but in this paper we propose to use another new algorithm for restoring the distance matrix for DNA chains. Our recent work has shown that even greater improvement in the quality of the algorithm can often be achieved without improving the auxiliary heuristics of the branches and boundaries method. Thus, we are improving the algorithms that formulate the greedy function of this method only. .展开更多
High seismic activity, difficult permafrost and hydrogeological conditions of South Yakutia(Russia) complicate building and exploitation of engineering construction and require additional detailed and complex research...High seismic activity, difficult permafrost and hydrogeological conditions of South Yakutia(Russia) complicate building and exploitation of engineering construction and require additional detailed and complex research. These conditions are evident within two sites. The first site is located in the middle reach of the Duray River, where it is crossed by the highway Lena. The second site is located on the right side of the Chulmakan River Valley, 400 meters to the east of the ESPO oil pipeline route. Seismic events, occurring four years ago, led to landslides in the mentioned sites. Formation of joint fissures on slopes assisted drainage of aquifers of free water exchange zone. It is worth noting that at the Duray River site, 59 cm of active soil slumping movement towards the roadbed has occurred within two summer months. Such a process is complicated by cryogenic disintegration of rocks in the base of the landslide body due to groundwater discharge and icing formation in winter.展开更多
Background:Lung hypoplasia,pulmonary persistent hypertension of the newborn and its morphological changes are the main features in congenital diaphragmatic hernia(CDH).This study was undertaken to investigate if anten...Background:Lung hypoplasia,pulmonary persistent hypertension of the newborn and its morphological changes are the main features in congenital diaphragmatic hernia(CDH).This study was undertaken to investigate if antenatal use of sildenafil and/or bosentan attenuates vascular remodeling,promotes branching,and improves alveolarization in experimental nitrofeninduced CDH.Methods:Nitrofen(100 mg)was gavage-fed to pregnant rats at post conception day(PCD)9 to induce CDH.The rats were randomized to 5 groups:1)control;2)nitrofen;3)nitrofen+sildenafil 100 mg/kg per day at PCD 16-20;4)nitrofen+bosentan 30 mg/kg per day,at PCD 16-20,and 5)nitrofen+bosentan+sildenafil,same doses and administration days.After cesarean delivery,the offsprings were sacrifi ced.The diaphragmatic defect and pulmonary hypoplasia were identified,and the lungs were dissected.Arterial wall thickness,bronchiolar density and alveolarization were assessed.Results:The offsprings with CDH were characterized by severe pulmonary hypoplasia(lung weight-to-body weight ratio:0.0263[95%confidence interval(CI)0.0242-0.0278)]in the nitrofen group versus 0.0385(95%CI 0.0355-0.0424)in the control group(P=0.0001).Pulmonary arterial wall thickness was decreased to 3.0(95%CI 2.8-3.7)μm in the nitrofen+sildenafil group versus 5.0(95%CI 4.1-4.9)μm in the nitrofen group(P=0.02).Terminal bronchioles increased to 13.7(95%CI 10.7-15.2)μm in the nitrofen+bosentan group in contrast to 8.7(95%CI 7.2-9.4)μm in the nitrofen group(P=0.002).More significant differences(P=0.0001)were seen in terminal bronchioles in the nitrofen+sildenafil+bosentan group than in the nitrofen group[14.0(95%CI 12.5-15.4)μm versus 8.5(95%CI 7.1-9.3)μm].Pulmonary arterial wall thickness was also decreased in the former group.Conclusions:In this rat model,antenatal treatment with sildenafil attenuates vascular remodeling.Bosentan promotes the development of terminal bronchioles in nitrofen-induced CDH.展开更多
BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cell...BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cells and the need of adequate animal models for preclinical testing.Direct reprogramming of somatic cells into neuronal and glial precursors might be a promising solution to the first challenge.The use of non-human primates for preclinical studies exploring new treatment paradigms in SCI results in data with more translational relevance to human SCI.AIM To investigate the safety and efficacy of intraspinal transplantation of directly reprogrammed neural precursor cells(drNPCs).METHODS Seven non-human primates with verified complete thoracic SCI were divided into two groups:drNPC group(n=4)was subjected to intraspinal transplantation of 5 million drNPCs rostral and caudal to the lesion site 2 wk post injury,and lesion control(n=3)was injected identically with the equivalent volume of vehicle.RESULTS Follow-up for 12 wk revealed that animals in the drNPC group demonstrated a significant recovery of the paralyzed hindlimb as well as recovery of somatosensory evoked potential and motor evoked potential of injured pathways.Magnetic resonance diffusion tensor imaging data confirmed the intraspinal transplantation of drNPCs did not adversely affect the morphology of the central nervous system or cerebrospinal fluid circulation.Subsequent immunohistochemical analysis showed that drNPCs maintained SOX2 expression characteristic of multipotency in the transplanted spinal cord for at least 12 wk,migrating to areas of axon growth cones.CONCLUSION Our data demonstrated that drNPC transplantation was safe and contributed to improvement of spinal cord function after acute SCI,based on neurological status assessment and neurophysiological recovery within 12 wk after transplantation.The functional improvement described was not associated with neuronal differentiation of the allogeneic drNPCs.Instead,directed drNPCs migr展开更多
In contrast to the cognate Laplace equation, for which a vast number of Green's functions is available, the field is not that developed for the static Klein-Gordon equation. The latter represents, nonetheless, a natu...In contrast to the cognate Laplace equation, for which a vast number of Green's functions is available, the field is not that developed for the static Klein-Gordon equation. The latter represents, nonetheless, a natural area for application of some of the methods that are proven productive for the Laplace equation. The perspective looks especially attractive for the methods of images and eigenfunction expansion. This study is based on our experience recently gained on the construction of Green's functions for elliptic partial differential equations. An extensive list of boundary-value problems formulated for the static Klein-Gordon equation is considered. Computerfriendly representations of their Green's functions are obtained, most of which have never been published before.展开更多
基金国家自然科学基金项目(41771078)国家自然科学基金委员会(NSFC)与俄罗斯基础研究基金会(RFBR)合作交流项目(42011530083)+1 种基金Russian Foundation for Basic Research-RFBR(20-55-53006)雅砻江流域水电开发有限公司科学技术项目(LHKA-G201906)资助。
文摘To date, it is unknown whether it is possible to construct a complete graph invariant in polynomial time, so fast algorithms for checking non-isomorphism are important, including heuristic algorithms, and for successful implementations of such heuristics, both the tasks of some modification of previously described graph invariants and the description of new invariants remain relevant. Many of the described invariants make it possible to distinguish a larger number of graphs in the real time of a computer program. In this paper, we propose an invariant for a special kind of directed graphs, namely, for tournaments. The last ones, from our point of view, are interesting because when fixing the order of vertices, the number of different tournaments is exactly equal to the number of undirected graphs, also with fixing the order of vertices. In the invariant we are considering, all possible tournaments consisting of a subset of vertices of a given digraph with the same set of arcs are iterated over. For such subset tournaments, the places are calculated in the usual way, which are summed up to obtain the final values of the points of the vertices;these points form the proposed invariant. As we expected, calculations of the new invariant showed that it does not coincide with the most natural invariant for tournaments, in which the number of points is calculated for each participant. So far, we have conducted a small number of computational experiments, and the minimum value of the pair correlation between the sequences representing these two invariants that we found is for dimension 15.
文摘The paper describes some implementation aspects of an algorithm for approximate solution of the traveling salesman problem based on the construction of convex closed contours on the initial set of points (“cities”) and their subsequent combination into a closed path (the so-called contour algorithm or “onion husk” algorithm). A number of heuristics related to the different stages of the algorithm are considered, and various variants of the algorithm based on these heuristics are analyzed. Sets of randomly generated points of different sizes (from 4 to 90 and from 500 to 10,000) were used to test the algorithms. The numerical results obtained are compared with the results of two well-known combinatorial optimization algorithms, namely the algorithm based on the branch and bound method and the simulated annealing algorithm. .
文摘We investigate decomposition of codes and finite languages. A prime decomposition is a decomposition of a code or languages into a concatenation of nontrivial prime codes or languages. A code is prime if it cannot be decomposed into at least two nontrivial codes as the same for the languages. In the paper, a linear time algorithm is designed, which finds the prime decomposition. If codes or finite languages are presented as given by its minimal deterministic automaton, then from the point of view of abstract algebra and graph theory, this automaton has special properties. The study was conducted using system for computational Discrete Algebra GAP. .
文摘This paper presents the past,present and future status of the Russian VLBI network "Quasar".This network has been developed for at least 20 years by the Institute of Applied Astronomy of the Russian Academy of Sciences(IAA RAS). The equipment installed currently at each "Quasar" station and the facilities for processing observational data are described briefly. The latest results are presented, including the Earth orientation parameters(EOP) determined from the "Quasar" VLBI data and comparison with those from other processing centers. Our future plans to extend the "Quasar" VLB I network to the east and to the west will be carried out by establishing the Ussurijsk station in the Far East and the RussianCuban station in the west. They are considered in the context of the Russian section activity in the GGOS project. The expected improvement of the EOP determination accuracy can be obtained within the future configuration of the "Quasar" network,which is proved by simulation.
基金support of the following research grants,the National Natural Science Foundation of China (NSFC) (42011530083)Scientific and technological Research and Development Project of Qinghai-Tibet Group (QZ2022-G02)+3 种基金Heilongjiang Transportation Investment Group Co.,Ltd (JT-100000-ZC-FW-2021-0129)special project for the investigation of basic science and technology resources (2022FY100702)Key Research and Development Program guidancee project of Heilongjiang province (GZ20220095,GZ20220052)the Fundamental Research Funds for the Central Universities (2572022AW58).
文摘Rapid urbanization has led to changes in the urban land surface thermal environment.However,there are still much unknown about the urban land surface thermal conditions in permafrost regions.Permafrost is a unique geological environment,changes in the urban land surface thermal environment may trigger geological disasters caused by permafrost degradation.This study utilized remote sensing data and geographic de-tectors to identify the dynamic changes in land surface temperature(LST)and land use/land cover(LU/LC)in Yakutsk,as well as the potential factors contributing to LST variations.Between 1992 and 2020,the built-up area in Yakutsk increased by 36%,and the annual average LST in Yakutsk has risen by 6.67℃,accompanied by an expansion of high-temperature areas.Despite ongoing greening efforts,rapid urbanization poses a threat to these green spaces.Changes in the normalized difference built-up index(NDBI)and land use transfer(LDT)were identified as the primary drivers of urban LST changes.By integrating geographic detector technology and artificial neural network models,we optimized the selection of input factors in the prediction model and used it to explore the future changes in LST in Yakutsk.The average LST in Yakutsk is expected to reach 23.4℃ and 25.1℃ in 2030 and 2040,respectively,with a further increase in high-temperature areas.This study provides a reference for ecological,hydrological,and geological assessments of cities in permafrost regions.
基金国家自然科学基金项目(41771078,41971085)国家自然科学基金中俄交流项目(4191101321)+1 种基金中国科学院国际合作局对外合作重点项目(131B62KYSB20170012)Russian Foundation for Basic Research(20-55-53006)资助。
文摘The aim is to study the set of subsets of grids of the Waterloo language from the point of view of abstract algebra and graph theory. The study was conducted using the library for working with transition graphs of nondeterministic finite automata NFALib implemented by one of the authors in C#, as well as statistical methods for analyzing algorithms. The results are regularities obtained when considering semilattices on a set of subsets of grids of the Waterloo language. It follows from the results obtained that the minimum covering automaton equivalent to the Waterloo automaton can be obtained by adding one additional to the minimum covering set of grids. .
文摘Based on the standard definition of the product (concatenation), the natural non-negative degree of the language is introduced. Root extraction is the reverse operation to it, and it can be defined in several different ways. Despite the simplicity of the formulation of the problem of extracting the root, the authors could not find any description of it in the literature (as well as on the Internet), including even its formulation. Most of the material in this article is devoted to the simplest version of the formulation: the root of the 2<sup>nd</sup> degree for the 1-letter alphabet, but many of the provisions of the article are generalized to more complex cases. Apparently, for a possible future description of a polynomial algorithm for solving at least one of the described statements of root extraction problems, it is first necessary to really analyze in detail such a special case, that is: either describe the necessary polynomial algorithm, or, conversely, show that the problem belongs to the class of NP-complete problems. Thus, in this article, we do not propose a polynomial algorithm for the problems under consideration;however, the models described here should help in constructing appropriate heuristic algorithms for their solution. A detailed description of the possible further application of such heuristic algorithms is beyond the scope of this article. .
文摘We continue to consider one of the cybernetic methods in biology related to the study of DNA chains. Exactly, we are considering the problem of reconstructing the distance matrix for DNA chains. Such a matrix is formed on the basis of any of the possible algorithms for determining the distances between DNA chains, as well as any specific object of study. At the same time, for example, the practical programming results show that on an average modern computer, it takes about a day to build such a 30 × 30 matrix for mnDNAs using the Needleman-Wunsch algorithm;therefore, for such a 300 × 300 matrix, about 3 months of continuous computer operation is expected. Thus, even for a relatively small number of species, calculating the distance matrix on conventional computers is hardly feasible and the supercomputers are usually not available. Therefore, we started publishing our variants of the algorithms for calculating the distance between two DNA chains, then we publish algorithms for restoring partially filled matrices, i.e., the inverse problem of matrix processing. Previously, we used the method of branches and boundaries, but in this paper we propose to use another new algorithm for restoring the distance matrix for DNA chains. Our recent work has shown that even greater improvement in the quality of the algorithm can often be achieved without improving the auxiliary heuristics of the branches and boundaries method. Thus, we are improving the algorithms that formulate the greedy function of this method only. .
基金supported by Russian Foundation for Basic Research (RFBR, Nos. 16-35-60027, 16-35-60028)
文摘High seismic activity, difficult permafrost and hydrogeological conditions of South Yakutia(Russia) complicate building and exploitation of engineering construction and require additional detailed and complex research. These conditions are evident within two sites. The first site is located in the middle reach of the Duray River, where it is crossed by the highway Lena. The second site is located on the right side of the Chulmakan River Valley, 400 meters to the east of the ESPO oil pipeline route. Seismic events, occurring four years ago, led to landslides in the mentioned sites. Formation of joint fissures on slopes assisted drainage of aquifers of free water exchange zone. It is worth noting that at the Duray River site, 59 cm of active soil slumping movement towards the roadbed has occurred within two summer months. Such a process is complicated by cryogenic disintegration of rocks in the base of the landslide body due to groundwater discharge and icing formation in winter.
基金supported by grants from the Fondo de Fomento a la Investigación,Instituto Mexicano del Seguro Social(FOFOI-FIS,IMSS,2006/1A/I/031-FIS/IMSS/PROT/205)by Miami Children's Hospital&Sheridan Health Corporation.
文摘Background:Lung hypoplasia,pulmonary persistent hypertension of the newborn and its morphological changes are the main features in congenital diaphragmatic hernia(CDH).This study was undertaken to investigate if antenatal use of sildenafil and/or bosentan attenuates vascular remodeling,promotes branching,and improves alveolarization in experimental nitrofeninduced CDH.Methods:Nitrofen(100 mg)was gavage-fed to pregnant rats at post conception day(PCD)9 to induce CDH.The rats were randomized to 5 groups:1)control;2)nitrofen;3)nitrofen+sildenafil 100 mg/kg per day at PCD 16-20;4)nitrofen+bosentan 30 mg/kg per day,at PCD 16-20,and 5)nitrofen+bosentan+sildenafil,same doses and administration days.After cesarean delivery,the offsprings were sacrifi ced.The diaphragmatic defect and pulmonary hypoplasia were identified,and the lungs were dissected.Arterial wall thickness,bronchiolar density and alveolarization were assessed.Results:The offsprings with CDH were characterized by severe pulmonary hypoplasia(lung weight-to-body weight ratio:0.0263[95%confidence interval(CI)0.0242-0.0278)]in the nitrofen group versus 0.0385(95%CI 0.0355-0.0424)in the control group(P=0.0001).Pulmonary arterial wall thickness was decreased to 3.0(95%CI 2.8-3.7)μm in the nitrofen+sildenafil group versus 5.0(95%CI 4.1-4.9)μm in the nitrofen group(P=0.02).Terminal bronchioles increased to 13.7(95%CI 10.7-15.2)μm in the nitrofen+bosentan group in contrast to 8.7(95%CI 7.2-9.4)μm in the nitrofen group(P=0.002).More significant differences(P=0.0001)were seen in terminal bronchioles in the nitrofen+sildenafil+bosentan group than in the nitrofen group[14.0(95%CI 12.5-15.4)μm versus 8.5(95%CI 7.1-9.3)μm].Pulmonary arterial wall thickness was also decreased in the former group.Conclusions:In this rat model,antenatal treatment with sildenafil attenuates vascular remodeling.Bosentan promotes the development of terminal bronchioles in nitrofen-induced CDH.
基金Supported by Russian Science Foundation,No.16-15-10432。
文摘BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cells and the need of adequate animal models for preclinical testing.Direct reprogramming of somatic cells into neuronal and glial precursors might be a promising solution to the first challenge.The use of non-human primates for preclinical studies exploring new treatment paradigms in SCI results in data with more translational relevance to human SCI.AIM To investigate the safety and efficacy of intraspinal transplantation of directly reprogrammed neural precursor cells(drNPCs).METHODS Seven non-human primates with verified complete thoracic SCI were divided into two groups:drNPC group(n=4)was subjected to intraspinal transplantation of 5 million drNPCs rostral and caudal to the lesion site 2 wk post injury,and lesion control(n=3)was injected identically with the equivalent volume of vehicle.RESULTS Follow-up for 12 wk revealed that animals in the drNPC group demonstrated a significant recovery of the paralyzed hindlimb as well as recovery of somatosensory evoked potential and motor evoked potential of injured pathways.Magnetic resonance diffusion tensor imaging data confirmed the intraspinal transplantation of drNPCs did not adversely affect the morphology of the central nervous system or cerebrospinal fluid circulation.Subsequent immunohistochemical analysis showed that drNPCs maintained SOX2 expression characteristic of multipotency in the transplanted spinal cord for at least 12 wk,migrating to areas of axon growth cones.CONCLUSION Our data demonstrated that drNPC transplantation was safe and contributed to improvement of spinal cord function after acute SCI,based on neurological status assessment and neurophysiological recovery within 12 wk after transplantation.The functional improvement described was not associated with neuronal differentiation of the allogeneic drNPCs.Instead,directed drNPCs migr
文摘In contrast to the cognate Laplace equation, for which a vast number of Green's functions is available, the field is not that developed for the static Klein-Gordon equation. The latter represents, nonetheless, a natural area for application of some of the methods that are proven productive for the Laplace equation. The perspective looks especially attractive for the methods of images and eigenfunction expansion. This study is based on our experience recently gained on the construction of Green's functions for elliptic partial differential equations. An extensive list of boundary-value problems formulated for the static Klein-Gordon equation is considered. Computerfriendly representations of their Green's functions are obtained, most of which have never been published before.