Entanglement in quantum theory is a peculiar concept to scientists. With this concept we are forced to re-consider the cluster property which means that one event is irrelevant to another event when they are fully far...Entanglement in quantum theory is a peculiar concept to scientists. With this concept we are forced to re-consider the cluster property which means that one event is irrelevant to another event when they are fully far away. In the recent works we showed that the quasi-degenerate states induce the violation of cluster property in antiferromagnets when the continuous symmetry breaks spontaneously. We expect that the violation of cluster property will be observed in other materials too, because the spontaneous symmetry breaking is found in many systems such as the high temperature superconductors and the superfluidity. In order to examine the cluster property for these materials, we studied a quantum nonlinear sigma model with U(1) symmetry in the previous work. There we showed that the model does have quasi-degenerate states. In this paper we study the quantum nonlinear sigma model with SU(2) symmetry. In our approach we first define the quantum system on the lattice and then adopt the representation where the kinetic term is diagonalized. Since we have no definition on the conjugate variable to the angle variable, we use the angular momentum operators instead for the kinetic term. In this representation we introduce the states with the fixed quantum numbers and carry out numerical calculations using quantum Monte Carlo methods and other methods. Through analytical and numerical studies, we conclude that the energy of the quasi-degenerate state is proportional to the squared total angular momentum as well as to the inverse of the lattice size.展开更多
A macroscopic based multi-mechanism constitutive model is constructed in the framework of irreversible thermodynamics to describe the degeneration of shape memory effect occurring in the thermo-mechanical cyclic defor...A macroscopic based multi-mechanism constitutive model is constructed in the framework of irreversible thermodynamics to describe the degeneration of shape memory effect occurring in the thermo-mechanical cyclic deformation of NiTi shape memory alloys (SMAs). Three phases, austenite A, twinned martensite and detwinned martensite , as well as the phase transitions occurring between each pair of phases (, , , , and are considered in the proposed model. Meanwhile, two kinds of inelastic deformation mechanisms, martensite transformation-induced plasticity and reorientation-induced plasticity, are used to explain the degeneration of shape memory effects of NiTi SMAs. The evolution equations of internal variables are proposed by attributing the degeneration of shape memory effect to the interaction between the three phases (A, , and and plastic deformation. Finally, the capability of the proposed model is verified by comparing the predictions with the experimental results of NiTi SMAs. It is shown that the degeneration of shape memory effect and its dependence on the loading level can be reasonably described by the proposed model.展开更多
Background:A new rat tail intervertebral disc degeneration model was established to observe the morphologic and biologic changes of static bending and compression applied to the discs.Methods:In total,20 Sprague-Dawle...Background:A new rat tail intervertebral disc degeneration model was established to observe the morphologic and biologic changes of static bending and compression applied to the discs.Methods:In total,20 Sprague-Dawley rats with similar weight were randomly di-vided into 4 groups.Group 1 served as a control group for a baseline assessment of normal discs.Group 2 underwent a sham surgery,using an external device to bend the vertebrae of coccygeal 8-10.Groups 3 and 4 were the loaded groups,and exter-nal devices were instrumented to bend the spine with a compression level of 1.8 N and 4.5 N,respectively.Magnetic resonance imaging(MRI),histological,and quanti-tative real-time PCR(qRT-PCR)analysis were performed on all animals on day 14 of the experiment.Results:Magnetic resonance imaging and histological results showed that the changes of intervertebral disc degeneration increased with the size of compression load.Some architecture disorganizations in nucleus pulposus and annulus fibro-sus were found on both of the convex and concave side in the groups of 1.8 N and 4.5 N.An upregulation of MM-3,MM-13,and collagen 1-α1 mRNA expression and a downregulation of collagen 2-α1 and aggrecan mRNA expression were observed in the sham and loading groups.Significant changes were found between the loading groups,whereas the sham group showed similar results to the control group.Conclusions:Static bending and compression could induce progressive disc degen-eration,which could be used for biologic study on disc degeneration promoted by static complex loading.展开更多
The G93A-SOD1 mice model and MRI diffusion as a preclinical tool to study amyotrophic lateral sclerosis （ALS）： ALS is a progressive neurological disease characterized primarily by the development of limb paralysis,...The G93A-SOD1 mice model and MRI diffusion as a preclinical tool to study amyotrophic lateral sclerosis （ALS）： ALS is a progressive neurological disease characterized primarily by the development of limb paralysis, which eventually leads to lack of control on muscles under voluntary control and death within 3–5 years. Genetic heterogeneity and environmental factors play a critical role in the rate of disease progression and patients display faster declines once the symptoms have manifested. Since its original discovery, ALS has been associated with pathological alterations in motor neurons located in the spinal cord （SC）, where neuronal loss by a mutation in the protein superoxide dismutase in parenthesis （mSOD1） and impairment in axonal connectivity, have been linked to early functional impairments. In addition,mechanisms of neuroinflammation, apoptosis, necroptosis and autophagy have been also implicated in the development of this disease. Among different animal models developed to study ALS, the transgenic G93A-SOD1 mouse has become recognized as a benchmark model for preclinical screening of ALS therapies. Furthermore, the progressive alterations in the locomotor phenotype expressed in this model closely resemble the progressive lower limb dysfunction of ALS patients. Among other imaging tools, MR diffusion tensor imaging （DTI） has emerged as a crucial, noninvasive and real time neuroimaging tool to gather information in ALS. One of the current concerns with the use of DTI is the lack of biological validation of the microstructural information given by this technique. Although clinical studies using DTI can provide a remarkable insight on the targets of neurodegeneration and disease course,they lack histological correlations. To address these shortcomings, preclinical models can be designed to validate the microstructural information unveiled by this particular MRI technique. Thus, the scope of this review is to describe how MRI diffusion and optical microscopy evaluate axonal structural changes at early stages of the disease in a preclinical model of ALS.展开更多
Objectives： To develop a rabbit model of intervertebral disc degeneration that more exactly simulates the pathological changes of human intervertebral disc degeneration. Methods： Twelve New Zealand white rabbits wer...Objectives： To develop a rabbit model of intervertebral disc degeneration that more exactly simulates the pathological changes of human intervertebral disc degeneration. Methods： Twelve New Zealand white rabbits were utilized to establish three different disc injury models according to the following protocol; group A： anulus punctures were done with a 18-gauge needle at L2-L3 and L5-L6; Group B： intradiscal injection of interleukin-1 IL-1β with a 23-gauge needle at L3-L4; and Group C： intradiscal injection of phosphate buffer saline（PBS） with a 23-gauge needle at L4-LS. The L1-L2 level was used as a control. Rabbits were killed after 24 weeks. The intervertebral disc height was measured by lateral plain radiographs. After the radiographic measurements were obtained, the intervertebral discs were removed and analyzed for DNA, sulfated glycosaminoglycan（s-GAG） and water contents of nucleus pulposus. Results： The intervertebral disc height, s-GAG, and water contents in anulus needle punctures were significantly decreased in Group A, but the DNA content in the nucleus pulposus was significantly increased when compared to the control. The significant decrease of disc height and water contents were demonstrated, only the s-GAG and DNA contents did not show a significant difference in Group B when compared to the control. The significant decrease of disc height, s-GAG, water, and DNA contents did not show in Group C when compared to the control. Conclusion： The 18-gauge puncture models produced the most consistent disc degeneration in the rabbit lumbar spine.展开更多
Parkinson’s disease (PD) is a common neurodegenerative disease with unclear pathogenesis. Currently, there are no disease-modifying neuron-protecting drugs to slow down the neuronal degeneration. Mutations in the leu...Parkinson’s disease (PD) is a common neurodegenerative disease with unclear pathogenesis. Currently, there are no disease-modifying neuron-protecting drugs to slow down the neuronal degeneration. Mutations in the leucine-rich repeat kinase 2 (LRRK2) cause genetic forms of PD and contribute to sporadic PD as well. Disruption of LRRK2 kinase functions has become one of the potential mechanisms underlying disease-linked mutation-induced neuronal degeneration. To further characterize the pharmacological effects of a reported LRRK2 kinase inhibitor, LDN-73794, in vitro cell models and a LRRK2 Drosophila PD model were used. LDN-73794 reduced LRRK2 kinase activity in vitro and in vivo. Moreover, LDN-73794 increased survival, improved locomotor activity, and suppressed DA neuron loss in LRRK2 transgenic flies. These results suggest that inhibition of LRRK2 kinase activity can be a potential therapeutic strategy for PD intervention and LDN-73794 could be a potential lead compound for developing neuroprotective therapeutics.展开更多
Entanglement in quantum theory is a concept that has confused many scientists. This concept implies that the cluster property, which means no relations between sufficiently separated two events, is non-trivial. In the...Entanglement in quantum theory is a concept that has confused many scientists. This concept implies that the cluster property, which means no relations between sufficiently separated two events, is non-trivial. In the works for some quantum spin systems, which have been recently published by the author, extensive and quantitative examinations were made about the violation of cluster property in the correlation function of the spin operator. The previous study of these quantum antiferromagnets showed that this violation is induced by the degenerate states in the systems where the continuous symmetry spontaneously breaks. Since this breaking is found in many materials such as the high temperature superconductors and the superfluidity, it is an important question whether we can observe the violation of the cluster property in them. As a step to answer this question we study a quantum nonlinear sigma model with U(1) symmetry in this paper. It is well known that this model, which has been derived as an effective model of the quantum spin systems, can also be applied to investigations of many materials. Notifying that the existence of the degenerate states is essential for the violation, we made numerical calculations in addition to theoretical arguments to find these states in the nonlinear sigma model. Then, successfully finding the degenerate states in the model, we came to a conclusion that there is a chance to observe the violation of cluster property in many materials to which the nonlinear sigma model applies.展开更多
To describe the current aging population in China and globally,especially as it applies to age-related macular degeneration(AMD).To review the current standards of care for treating both wet(exudative)eAMD and dry(atr...To describe the current aging population in China and globally,especially as it applies to age-related macular degeneration(AMD).To review the current standards of care for treating both wet(exudative)eAMD and dry(atrophic)aAMD.And to introduce a model for experimentation that is based on the Age-Related Eye Disease Study(AREDS)using eye bank tissue.A literature search that outlines current aging populations,standards of clinical treatment as defined by large,multicenter,randomized clinical trials that present level-I data with a low risk for bias.An experimental model system of AMD is presented that enables scientific analysis of AMD pathogenesis by applying grading criteria from the AREDS to human eye bank eyes.Analysis includes proteomic,cellular,and functional genomics.The standard of care for the treatment of eAMD is currently defined by the use of several anti-vascular endothelial growth(anti-VEGF)agents alone or in combination with photodynamic therapy.Monotherapy treatment intervals may be monthly,as needed,or by using a treat-and-extend(TAE)protocol.There are no proven therapies for aAMD.AMD that is phenotypically defined at AREDS level 3,should be managed with the use of anti-oxidant vitamins,lutein/zeaxanthin and zinc(AREDS-2 formulation).By understanding the multiple etiologies in the pathogenesis of AMD(i.e.,oxidative stress,inflammation,and genetics),the use of human eye bank tissues graded according to the Minnesota Grading System(MGS)will enable future insights into the pathogenesis of AMD.Initial AMD management is with lifestyle modification such as avoiding smoking,eating a healthy diet and using appropriate vitamin supplements(AREDS-2).For eAMD,anti-VEGF therapies using either pro re nata(PRN)or TAE protocols are recommended,with photodynamic therapy in appropriate cases.New cellular information will direct future,potential therapies and these will originate from experimental models,such as the proposed eye bank model using the MGS,that leverages the prospective AREDS database.展开更多
文摘Entanglement in quantum theory is a peculiar concept to scientists. With this concept we are forced to re-consider the cluster property which means that one event is irrelevant to another event when they are fully far away. In the recent works we showed that the quasi-degenerate states induce the violation of cluster property in antiferromagnets when the continuous symmetry breaks spontaneously. We expect that the violation of cluster property will be observed in other materials too, because the spontaneous symmetry breaking is found in many systems such as the high temperature superconductors and the superfluidity. In order to examine the cluster property for these materials, we studied a quantum nonlinear sigma model with U(1) symmetry in the previous work. There we showed that the model does have quasi-degenerate states. In this paper we study the quantum nonlinear sigma model with SU(2) symmetry. In our approach we first define the quantum system on the lattice and then adopt the representation where the kinetic term is diagonalized. Since we have no definition on the conjugate variable to the angle variable, we use the angular momentum operators instead for the kinetic term. In this representation we introduce the states with the fixed quantum numbers and carry out numerical calculations using quantum Monte Carlo methods and other methods. Through analytical and numerical studies, we conclude that the energy of the quasi-degenerate state is proportional to the squared total angular momentum as well as to the inverse of the lattice size.
基金Financial supports by the National Natural Science Foundation of China (Grant 11532010)the project for Sichuan Provincial Youth Science and Technology Innovation Team, China (Grant 2013TD0004)
文摘A macroscopic based multi-mechanism constitutive model is constructed in the framework of irreversible thermodynamics to describe the degeneration of shape memory effect occurring in the thermo-mechanical cyclic deformation of NiTi shape memory alloys (SMAs). Three phases, austenite A, twinned martensite and detwinned martensite , as well as the phase transitions occurring between each pair of phases (, , , , and are considered in the proposed model. Meanwhile, two kinds of inelastic deformation mechanisms, martensite transformation-induced plasticity and reorientation-induced plasticity, are used to explain the degeneration of shape memory effects of NiTi SMAs. The evolution equations of internal variables are proposed by attributing the degeneration of shape memory effect to the interaction between the three phases (A, , and and plastic deformation. Finally, the capability of the proposed model is verified by comparing the predictions with the experimental results of NiTi SMAs. It is shown that the degeneration of shape memory effect and its dependence on the loading level can be reasonably described by the proposed model.
文摘Background:A new rat tail intervertebral disc degeneration model was established to observe the morphologic and biologic changes of static bending and compression applied to the discs.Methods:In total,20 Sprague-Dawley rats with similar weight were randomly di-vided into 4 groups.Group 1 served as a control group for a baseline assessment of normal discs.Group 2 underwent a sham surgery,using an external device to bend the vertebrae of coccygeal 8-10.Groups 3 and 4 were the loaded groups,and exter-nal devices were instrumented to bend the spine with a compression level of 1.8 N and 4.5 N,respectively.Magnetic resonance imaging(MRI),histological,and quanti-tative real-time PCR(qRT-PCR)analysis were performed on all animals on day 14 of the experiment.Results:Magnetic resonance imaging and histological results showed that the changes of intervertebral disc degeneration increased with the size of compression load.Some architecture disorganizations in nucleus pulposus and annulus fibro-sus were found on both of the convex and concave side in the groups of 1.8 N and 4.5 N.An upregulation of MM-3,MM-13,and collagen 1-α1 mRNA expression and a downregulation of collagen 2-α1 and aggrecan mRNA expression were observed in the sham and loading groups.Significant changes were found between the loading groups,whereas the sham group showed similar results to the control group.Conclusions:Static bending and compression could induce progressive disc degen-eration,which could be used for biologic study on disc degeneration promoted by static complex loading.
基金provided by the Chicago Biomedical Consortium’s Postdoctoral Research Award,No.085740
文摘The G93A-SOD1 mice model and MRI diffusion as a preclinical tool to study amyotrophic lateral sclerosis （ALS）： ALS is a progressive neurological disease characterized primarily by the development of limb paralysis, which eventually leads to lack of control on muscles under voluntary control and death within 3–5 years. Genetic heterogeneity and environmental factors play a critical role in the rate of disease progression and patients display faster declines once the symptoms have manifested. Since its original discovery, ALS has been associated with pathological alterations in motor neurons located in the spinal cord （SC）, where neuronal loss by a mutation in the protein superoxide dismutase in parenthesis （mSOD1） and impairment in axonal connectivity, have been linked to early functional impairments. In addition,mechanisms of neuroinflammation, apoptosis, necroptosis and autophagy have been also implicated in the development of this disease. Among different animal models developed to study ALS, the transgenic G93A-SOD1 mouse has become recognized as a benchmark model for preclinical screening of ALS therapies. Furthermore, the progressive alterations in the locomotor phenotype expressed in this model closely resemble the progressive lower limb dysfunction of ALS patients. Among other imaging tools, MR diffusion tensor imaging （DTI） has emerged as a crucial, noninvasive and real time neuroimaging tool to gather information in ALS. One of the current concerns with the use of DTI is the lack of biological validation of the microstructural information given by this technique. Although clinical studies using DTI can provide a remarkable insight on the targets of neurodegeneration and disease course,they lack histological correlations. To address these shortcomings, preclinical models can be designed to validate the microstructural information unveiled by this particular MRI technique. Thus, the scope of this review is to describe how MRI diffusion and optical microscopy evaluate axonal structural changes at early stages of the disease in a preclinical model of ALS.
基金National Natural Science Foundation ofChina(30400163)
文摘Objectives： To develop a rabbit model of intervertebral disc degeneration that more exactly simulates the pathological changes of human intervertebral disc degeneration. Methods： Twelve New Zealand white rabbits were utilized to establish three different disc injury models according to the following protocol; group A： anulus punctures were done with a 18-gauge needle at L2-L3 and L5-L6; Group B： intradiscal injection of interleukin-1 IL-1β with a 23-gauge needle at L3-L4; and Group C： intradiscal injection of phosphate buffer saline（PBS） with a 23-gauge needle at L4-LS. The L1-L2 level was used as a control. Rabbits were killed after 24 weeks. The intervertebral disc height was measured by lateral plain radiographs. After the radiographic measurements were obtained, the intervertebral discs were removed and analyzed for DNA, sulfated glycosaminoglycan（s-GAG） and water contents of nucleus pulposus. Results： The intervertebral disc height, s-GAG, and water contents in anulus needle punctures were significantly decreased in Group A, but the DNA content in the nucleus pulposus was significantly increased when compared to the control. The significant decrease of disc height and water contents were demonstrated, only the s-GAG and DNA contents did not show a significant difference in Group B when compared to the control. The significant decrease of disc height, s-GAG, water, and DNA contents did not show in Group C when compared to the control. Conclusion： The 18-gauge puncture models produced the most consistent disc degeneration in the rabbit lumbar spine.
文摘Parkinson’s disease (PD) is a common neurodegenerative disease with unclear pathogenesis. Currently, there are no disease-modifying neuron-protecting drugs to slow down the neuronal degeneration. Mutations in the leucine-rich repeat kinase 2 (LRRK2) cause genetic forms of PD and contribute to sporadic PD as well. Disruption of LRRK2 kinase functions has become one of the potential mechanisms underlying disease-linked mutation-induced neuronal degeneration. To further characterize the pharmacological effects of a reported LRRK2 kinase inhibitor, LDN-73794, in vitro cell models and a LRRK2 Drosophila PD model were used. LDN-73794 reduced LRRK2 kinase activity in vitro and in vivo. Moreover, LDN-73794 increased survival, improved locomotor activity, and suppressed DA neuron loss in LRRK2 transgenic flies. These results suggest that inhibition of LRRK2 kinase activity can be a potential therapeutic strategy for PD intervention and LDN-73794 could be a potential lead compound for developing neuroprotective therapeutics.
文摘Entanglement in quantum theory is a concept that has confused many scientists. This concept implies that the cluster property, which means no relations between sufficiently separated two events, is non-trivial. In the works for some quantum spin systems, which have been recently published by the author, extensive and quantitative examinations were made about the violation of cluster property in the correlation function of the spin operator. The previous study of these quantum antiferromagnets showed that this violation is induced by the degenerate states in the systems where the continuous symmetry spontaneously breaks. Since this breaking is found in many materials such as the high temperature superconductors and the superfluidity, it is an important question whether we can observe the violation of the cluster property in them. As a step to answer this question we study a quantum nonlinear sigma model with U(1) symmetry in this paper. It is well known that this model, which has been derived as an effective model of the quantum spin systems, can also be applied to investigations of many materials. Notifying that the existence of the degenerate states is essential for the violation, we made numerical calculations in addition to theoretical arguments to find these states in the nonlinear sigma model. Then, successfully finding the degenerate states in the model, we came to a conclusion that there is a chance to observe the violation of cluster property in many materials to which the nonlinear sigma model applies.
基金This work was supported in part by NIH/NIA RO1 AG025392 NIH/NEI:RO1 EY022097,JoAnne Smith and Delta Airlines Charitable Donation,and an unrestricted grant from Research to Prevent Blindness to the Mayo Clinic,Department of Ophthalmology,Rochester,MN,USA.
文摘To describe the current aging population in China and globally,especially as it applies to age-related macular degeneration(AMD).To review the current standards of care for treating both wet(exudative)eAMD and dry(atrophic)aAMD.And to introduce a model for experimentation that is based on the Age-Related Eye Disease Study(AREDS)using eye bank tissue.A literature search that outlines current aging populations,standards of clinical treatment as defined by large,multicenter,randomized clinical trials that present level-I data with a low risk for bias.An experimental model system of AMD is presented that enables scientific analysis of AMD pathogenesis by applying grading criteria from the AREDS to human eye bank eyes.Analysis includes proteomic,cellular,and functional genomics.The standard of care for the treatment of eAMD is currently defined by the use of several anti-vascular endothelial growth(anti-VEGF)agents alone or in combination with photodynamic therapy.Monotherapy treatment intervals may be monthly,as needed,or by using a treat-and-extend(TAE)protocol.There are no proven therapies for aAMD.AMD that is phenotypically defined at AREDS level 3,should be managed with the use of anti-oxidant vitamins,lutein/zeaxanthin and zinc(AREDS-2 formulation).By understanding the multiple etiologies in the pathogenesis of AMD(i.e.,oxidative stress,inflammation,and genetics),the use of human eye bank tissues graded according to the Minnesota Grading System(MGS)will enable future insights into the pathogenesis of AMD.Initial AMD management is with lifestyle modification such as avoiding smoking,eating a healthy diet and using appropriate vitamin supplements(AREDS-2).For eAMD,anti-VEGF therapies using either pro re nata(PRN)or TAE protocols are recommended,with photodynamic therapy in appropriate cases.New cellular information will direct future,potential therapies and these will originate from experimental models,such as the proposed eye bank model using the MGS,that leverages the prospective AREDS database.
