Underhand cut-and-fill mining has been widely used in underground mining operations,especially when the rock mass or orebody is of poor quality or prone to rockburst due to high stress.In such cases,mining workers sho...Underhand cut-and-fill mining has been widely used in underground mining operations,especially when the rock mass or orebody is of poor quality or prone to rockburst due to high stress.In such cases,mining workers should carry out all production activities under the cemented backfill roof or sill mat instead of a highly fractured and unstable rock roof or a strong rock roof with a high potential of rockburst.Therefore,the stability and required strength of the sill mat are critical issues for mining engineers.In 1991,Mitchell considered that sill mat could fail by caving,sliding,rotation,and flexure.Mitchell also proposed an analytical solution to determine the minimum required strength of the sill mat for each type of failure based on two stiff or immobile rock walls.However,recent publications using numerical modeling and field measurements indicate that the compressive stresses in the sill mat induced by rock wall closure due to a stope excavation beneath the sill mat can be significant.It is thus highly necessary to investigate the required strength of the sill mat by considering rock wall closure.In this study,the crushing failure of sill mat due to rock wall closure generated by underground excavation and a new failure mode called"crushing and caving”is revealed by numerical modeling.An analytical solution corresponding to each failure mode is then developed to estimate the minimum required cohesion(cmin)of the sill mat.A criterion is also proposed to determine if the sill mat fails by crushing or crushing-and-caving failure.The proposed analytical solution does not involve any correction coefficients.The validity of the proposed analytical solution is demonstrated by numerical modeling.The proposed analytical solution can thus be employed to predict the cmin of sill mat subjected to wall closure generated by underlying stope excavation.展开更多
Through the Economic-Value-Added(EVA)valuation model,the expected market value of equity can be determined by adding the book value of equity with the present value of expected EVAs under the assumption of constant re...Through the Economic-Value-Added(EVA)valuation model,the expected market value of equity can be determined by adding the book value of equity with the present value of expected EVAs under the assumption of constant required return and constant return on equity.The equation of EVA valuation model has taken its shape under the assumption of constant required return and constant return on equity.However,a large body of empirical evidence indicates that required rate of return never remain constant.The EVA-valuation model formulated under constant required return cannot be implemented under the scenario of changing required return.In this study,we explored whether the EVA valuation model could be implemented under changing required return by making any changes in the model and found that it could be implemented under the scenario of changing required return by replacing the book value of the equity of the existing model with the present value of required earnings or normal market earnings.We further examined whether the explanatory ability of the EVA valuation model under the assumption of changing required return is better than that of the valuation model under the assumption of constant required return.Relative information content analyses were conducted by considering sample of the intrinsic value of equities determined by valuation models and the market value of equities of 69 large-cap,88 mid-cap,and 79 small-cap companies.The results showed that the EVA-based valuation model with changing normal market return outperformed the EVA-based valuation model with constant required return.展开更多
To evaluate the differences in outcomes of treatment with denosumab alone or denosumab combined with vitamin D and calcium supplementation in patients with primary osteoporosis. Patients were split into a denosumab mo...To evaluate the differences in outcomes of treatment with denosumab alone or denosumab combined with vitamin D and calcium supplementation in patients with primary osteoporosis. Patients were split into a denosumab monotherapy group （18 cases） or a denosumab plus vitamin D supplementation group （combination group; 23 cases）. We measured serum bone alkaline phosphatase （BAP）, tartrate-resistant acid phosphatase （TRACP）-5b and urinary N-terminal telopeptide of type-I collagen （NTX） at baseline, 1 week, as well as at I month and 2, 4, 8 and 12 months. We also measured bone mineral density （BMD） of L1-4 lumbar vertebrae （L）-BMD and bilateral hips （H）-BMD at baseline and at 4, 8 and 12 months. There was no significant difference in patient background. TRACP-5b and urinary NTX were significantly suppressed in both groups from I week to 12 months （except at 12 months for NTX）. In the combination group, TRACP-5b was significantly decreased compared with the denosumab monotherapy group at 2 and 4 months （P 〈 0.05）. BAP was significantly suppressed in both groups at 2-12 months. L-BMD significantly increased at 8 and 12 months （8.9%） in the combination group and at 4, 8 and 12 months （6.0%） in the denosumab monotherapy group, compared with those before treatment. H-BMD was significantly increased in the combination group （3.6%） compared with the denosumab group （1.2%） at 12 months （P 〈 0.05）. Compared with denosumab monotherapy, combination therapy of denosumab with vitamin D and calcium stopped the decrease in calcium caused by denosumab, inhibited bone metabolism to a greater extent, and increased BMD （especially at the hips）.展开更多
Vibrio parahaemolyticus, the leading cause of seafood-borne gastroenteritis, has the ability to form biofilms on biotic and abiotic surfaces. Biofilm formation is a complicated process involving many specific structur...Vibrio parahaemolyticus, the leading cause of seafood-borne gastroenteritis, has the ability to form biofilms on biotic and abiotic surfaces. Biofilm formation is a complicated process involving many specific structures and regulatory processes. The most significant of the structures and processes include polar and lateral flagella, mannose-sensitive hemagglutinin typeⅣpili, chitin-regulated pili,capsular polysaccharide (CPS), exopolysaccharide展开更多
Mesenchymal stem cell （MSC）-based treatments have shown promise for improving tendon healing and repair. MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical st...Mesenchymal stem cell （MSC）-based treatments have shown promise for improving tendon healing and repair. MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical stimuli, including into tenocytes. Cell elongation and cytoskeletal tension have been shown to be instrumental to the process of MSC differentiation. Previous studies have shown that inhibition of stress fiber formation leads MSCs to default toward an adipogenic lineage, which suggests that stress fibers are required for MSCs to sense the environmental factors that can induce differentiation into tenocytes. As the Rho/ROCK signal transduction pathway plays a critical role in both stress fiber formation and in cell sensation, we examined whether the activation of this pathway was required when inducing MSC tendon differentiation using rope-like silk scaffolds. To accomplish this, we employed a loss-of-function approach by knocking out ROCK, actin and myosin （two other components of the pathway） using the specific inhibitors Y-27632, Latrunculin A and blebbistatin, respectively. We demonstrated that independently disrupting the cytoskeleton and the Rho/ ROCK pathway abolished the expression of tendon differentiation markers and led to a loss of spindle morphology. Together, these studies suggest that the tension that is generated by MSC elongation is essential for MSC teno-differentiation and that the Rho/ROCK pathway is a critical mediator of tendon differentiation on rope-like silk scaffolds.展开更多
Lipoprotein receptor-related protein 6 （LRP6） plays a critical role in skeletal development and homeostasis in adults. However, the role of LRP6 in mesenchymal stem cells （MSCs）, skeletal stem cells that give rise...Lipoprotein receptor-related protein 6 （LRP6） plays a critical role in skeletal development and homeostasis in adults. However, the role of LRP6 in mesenchymal stem cells （MSCs）, skeletal stem cells that give rise to osteoblastic lineage, is unknown. In this study, we generated mice lacking LRP6 expression specifically in nestin＋ MSCs by crossing nestin-Cre mice with LRP6 flox mice and investigated the functional changes of bone marrow MSCs and skeletal alterations. Mice with LRP6 deletion in nestin＋ cells demonstrated reductions in body weight and body length at I and 3 months of age. Bone architecture measured by microCT （uCT） showed a significant reduction in bone mass in both trabecular and cortical bone of homozygous and heterozygous LRP6 mutant mice. A dramatic reduction in the numbers of osteoblasts but much less significant reduction in the numbers of osteoclasts was observed in the mutant mice. Osterix＋ osteoprogenitors and osteocalcin＋ osteoblasts significantly reduced at the secondary spongiosa area, but only moderately decreased at the primary spongiosa area in mutant mice. Bone marrow MSCs from the mutant mice showed decreased colony forming, cell viability and cell proliferation. Thus, LRP6 in bone marrow MSCs is essential for their survival and proliferation, and therefore, is a key positive regulator for bone formation during skeletal growth and remodeling.展开更多
Backfill is increasingly used in underground mines to reduce the surface impact from the wastes produced by the mining operations. But the main objectives of backfilling are to improve ground stability and reduce ore ...Backfill is increasingly used in underground mines to reduce the surface impact from the wastes produced by the mining operations. But the main objectives of backfilling are to improve ground stability and reduce ore dilution. To this end, the backfill in a stope must possess a minimum strength to remain self-standing during mining of an adjacent stope. This required strength is often estimated using a solution proposed by Mitchell and co-workers, which was based on a limit equilibrium analysis of a wedge exposed by the open face. In this paper, three dimensional numerical simulations have been performed to assess the behavior of the wedge model. A new limit equilibrium solution is proposed, based on the backfill displacements obtained from the simulations. Comparisons are made between the proposed solution and experimental and numerical modeling results. Compared with the previous solution, a better agreement is obtained between the new solution and experimental results for the required cohesion and factor of safety. For large scale(field) conditions, the results also show that the required strength obtained from the proposed solution corresponds quite well to the simulated backfill response.展开更多
Methods to remove dust deposits by high-speed airflow have significant potential applications,with optimal design of flow velocity being the core technology.In this paper,we discuss the wind speed required for particl...Methods to remove dust deposits by high-speed airflow have significant potential applications,with optimal design of flow velocity being the core technology.In this paper,we discuss the wind speed required for particle removal from photovoltaic(PV)panels by compressed air by analyzing the force exerted on the dust deposited on inclined photovoltaic panels,which also included different electrification mechanisms of dust while it is in contact with the PV panel.The results show that the effect of the particle charging mechanism in the electric field generated by the PV panel is greatly smaller than the effect of the Van der Waals force and gravity,but the effect of the particle charged by the contact electrification mechanism in the electrostatic field is very pronounced.The wind speed required for dust removal from the PV panel increases linearly with the PV panel electric field,so we suggest that the nighttime,when the PV electric field is relatively small,would be more appropriate time for dust removal.The above results are of great scientific importance for accurately grasping the dust distribution law and for achieving scientific removal of dust on PV panels.展开更多
A large body of literature suggests that bone metabolism is susceptible to the ill effects of reactive species that accumulate in the body and cause cellular dysfunction. One of the body＇s front lines in defense agai...A large body of literature suggests that bone metabolism is susceptible to the ill effects of reactive species that accumulate in the body and cause cellular dysfunction. One of the body＇s front lines in defense against such damage is the transcription factor, Nrf2. This transcription factor regulates a plethora of antioxidant and cellular defense pathways to protect cells from such damage. Despite the breadth of knowledge of both the function of Nrf2 and the effects of reactive species in bone metabolism, the direct role of Nrf2 in skeletal biology has yet to be thoroughly examined. Thus, in the current study, we have examined the role of Nrf2 in postnatal bone metabolism in mice. Mice lacking Nrf2 （Nrf2-/-） exhibited a marked deficit in postnatal bone acquisition, which was most severe at 3 weeks of age when osteoblast numbers were 12-fold less than observed in control animals. While primary osteoblasts from Nrf2-/- mice functioned normally in vitro, the colony forming capacity of bone marrow stromal cells （BMSCs） from these mice was significantly reduced compared to controls. This defect could be rescued through treatment with the radical scavenger N-acetyl cysteine （NAC）, suggesting that increased reactive species stress might impair early osteoblastogenesis in BMSCs and lead to the failure of bone acquisition observed in Nrf2-/- animals. Taken together, these studies suggest Nrf2 represents a key pathway in regulating bone metabolism, which may provide future therapeutic targets to treat osteoporosis.展开更多
Precise regulation of stem cell self-renewal versus differentiation is important for the maintenance of tissue ho- meostasis. Early loss of stem cell activity results in premature ageing, while excess stem cell activi...Precise regulation of stem cell self-renewal versus differentiation is important for the maintenance of tissue ho- meostasis. Early loss of stem cell activity results in premature ageing, while excess stem cell activity leads to over- proliferation and cancer initiation （Fuchs et al., 2004; Scadden, 2006; Jones and Wagers, 2008; Morrison and Spradling, 2008）. Thus, understanding the mechanism con- trolling stem cell self-renewal and differentiation is critical for development of potential clinic therapy in the future.展开更多
Human immunodeficiency virus-1(HIV-1)encodes simply 15 proteins and thus depends on multiple host cellular factors for virus reproduction.Spastin,a microtubule severing protein,is an identified HIV-1 dependency factor...Human immunodeficiency virus-1(HIV-1)encodes simply 15 proteins and thus depends on multiple host cellular factors for virus reproduction.Spastin,a microtubule severing protein,is an identified HIV-1 dependency factor,but the mechanism regulating HIV-1 is unclear.Here,the study showed that knockdown of spastin inhibited the production of the intracellular HIV-1 Gag protein and new virions through enhancing Gag lysosomal degradation.Further investigation showed that increased sodium tolerance 1(IST1),the subunit of endosomal sorting complex required for transport(ESCRT),could interact with the MIT domain of spastin to regulate the intracellular Gag production.In summary,spastin is required for HIV-1 replication,while spastin-IST1 interaction facilitates virus production by regulating HIV-1 Gag intracellular trafficking and degradation.Spastin may serve as new target for HIV-1 prophylactic and therapy.展开更多
Myelin plays important roles in vertebrates,ensuring the rapid propagation of action potentials and the long-term integrity of axons,but the molecular mechanisms of myelin formation remain poorly understood.Recent stu...Myelin plays important roles in vertebrates,ensuring the rapid propagation of action potentials and the long-term integrity of axons,but the molecular mechanisms of myelin formation remain poorly understood.Recent studies have demonstrated that myelination is regulated by the TYRO3,AXL（also known as UFO）and MERTK.展开更多
In required navigation performance（RNP）, total system error（TSE） is estimated to provide a timely warning in the presence of an excessive error. In this paper, by analyzing the underlying formation mechanism, the ...In required navigation performance（RNP）, total system error（TSE） is estimated to provide a timely warning in the presence of an excessive error. In this paper, by analyzing the underlying formation mechanism, the TSE estimation is modeled as the estimation fusion of a fixed bias and a Gaussian random variable. To address the challenge of high computational load induced by the accurate numerical method, two efficient methods are proposed for real-time application, which are called the circle tangent ellipse method（CTEM） and the line tangent ellipse method（LTEM）,respectively. Compared with the accurate numerical method and the traditional scalar quantity summation method（SQSM）, the computational load and accuracy of these four methods are extensively analyzed. The theoretical and experimental results both show that the computing time of the LTEM is approximately equal to that of the SQSM, while it is only about 1/30 and 1/6 of that of the numerical method and the CTEM. Moreover, the estimation result of the LTEM is parallel with that of the numerical method, but is more accurate than those of the SQSM and the CTEM. It is illustrated that the LTEM is quite appropriate for real-time TSE estimation in RNP application.展开更多
Animal behaviors and higher-order functions rely on complex neural circuits built by synaptic connections （synapses） to deliver messages among different brain cells. As the major mediator in the nervous system, neur...Animal behaviors and higher-order functions rely on complex neural circuits built by synaptic connections （synapses） to deliver messages among different brain cells. As the major mediator in the nervous system, neurons communicate via synapses, which undergo constant structural remodeling with strict regulation.展开更多
Selenocysteine, a selenium-containing analog of cysteine, is found in the prokaryotic and eukaryotic kingdoms in active sites of enzymes involved in oxidation-reduction reactions. This aminoacid is cotranslationally i...Selenocysteine, a selenium-containing analog of cysteine, is found in the prokaryotic and eukaryotic kingdoms in active sites of enzymes involved in oxidation-reduction reactions. This aminoacid is cotranslationally incorporated at UGA codons which usually act as translation stop codons. In eukaryotes, decoding of selenocysteine necessitates the participation of the selenocysteine insertion sequence (SECIS), an element lying in the 3' -untranslated region of selenoprotein mRNAs. A detailed experimental study of the secondary structures of the SECIS elements of rat and human type 1 iodothyronine deiodinases and rat glutathione peroxidase was performed. Enzymatic and chemical structure probing led us to propose a secondary structure model, supported by sequence comparison of 23 SECIS mRNAs. The secondary structure model revealed the existence of a novel type of RNA motif composed of four consecutive non-Watson-Crick base-pairs. Using gel shift experiments, we identified in several mammalian cell type extracts the protein SBP,for SECIS-binding protein, that specifically recognizes the iodothyronine deiodinases and glutathione peroxidase SECIS elements. The structural model that we derived for the SECIS RNAs discloses RNA features possibly implicated in the binding of SBP and/or SECIS function展开更多
Nedd1 (neural precursor cell expressed, developmentally down-regulated gene 1) is an evolutionarily conserved protein that has previously been characterized as a new member
It is well known that there is abundant water resources in basin of the Yangtze River, the first largest river in China, which is mainly located in Southern China. However, water resources is very scarce in the basin ...It is well known that there is abundant water resources in basin of the Yangtze River, the first largest river in China, which is mainly located in Southern China. However, water resources is very scarce in the basin of the Yellow River, which is mainly located in Northern China. So the western route project of south-north water transfer scheme （WRP-SNWTS） aims to transfer water from the Yangtze River to the Yellow River. The area of WRP-SNWT, located in the upper reaches of the Yangtze River and the main areas of Sichuan and the marginal areas of the Qinghai-Tibet Plateau, has sufficient water resources but fragile ecology and environment. Therefore, it is necessary for WRP-SNWT to analyze the ecology water required. Based on the planning principles of from low elevation to high elevation, from small to large, from short to long and from easy to difficulty, the WRP-SNWT will be constructed through three stage projects. The western route first stage project of the south-north water transfer scheme （WRFST-SNWTS） is planned to transfer 4×10^9m^3/a from six tributaries of the Yalong river and from Dadu river to Jiaqu of Yellow River.. Daqu river and Niqu river are the branches of Xianshui river. Sequ river, Duke river, Make river and Ake river are the branches of Dadu river, which account for 65-70% of the total river run-off. It need more research and the rest run-off can satisfy channel ecology water required. According to analysis ecological water required which mainly satisfy for aquicolous biology in water-exporting region, such as low air temperature. Fish and aquicolous biology main living from May to August, and rivers are iced up from December to March of next year, ecology water required mainly for fish and aquicolous biology. The flow criterion of Tennant method is modified. The ecology water required of WRFSP-SNWTS is estimated by the flow data of Zhuwo gauging station, Zhuba gauging station, Chuosijia gauging station and Zumuzu gauging station. The result show that the ecology water required calculated by modified Tennant less 1 l percent than that of Tennant. This estimating result can supply more water resources for transferring to Yellow River. Meanwhile, this can supply gist for research transferring water of WRFSP-SNWTS.展开更多
In order to build a high-quality team of teachers in vocational higher education institutions, and investigate the current situation of teachers of common required courses in vocational higher education institutions o...In order to build a high-quality team of teachers in vocational higher education institutions, and investigate the current situation of teachers of common required courses in vocational higher education institutions of Hainan Province, an empirical research is conducted. A questionnaire survey was carried out in aspects of satisfaction of teaching and scientific research, professional quality, work saturation and teacher’s job satisfaction. The research results shows that the professional quality of teachers of common required courses cannot significantly influence the satisfaction of teaching and scientific research;Job saturation can positively influence teaching and research satisfaction;teaching and research satisfaction can positively influence teachers’ job satisfaction.展开更多
We apply the method of guidance by a required velocity for solving the optimal control problem over spacecraft’s reorientation from known initial attitude into a required final attitude.We suppose that attitude contr...We apply the method of guidance by a required velocity for solving the optimal control problem over spacecraft’s reorientation from known initial attitude into a required final attitude.We suppose that attitude control is carried out by impulse jet engines.For optimization of fuel consumption,the controlling moments are calculated and formed according to the method of free trajectories together with principle of iterative control using the quaternions for generating commands to actuators.Optimal solution corresponds to the principle“acceleration-free rotation-separate corrections-free rotation-braking”.Rotation along a hitting trajectory is supported by insignificant correction of the uncontrolled motion at discrete instants between segments of acceleration and braking.Various strategies of forming the correction impulses during stage of free motion are suggested.Improving accuracy of achievement of spacecraft's final position is reached by terminal control using information about current attitude and angular velocity measurements for determining an instant of beginning of braking(condition for start of braking based on actual motion parameters is formulated in analytical form).The described method is universal and invariant relative to moments of inertia.Developed laws of attitude control concern the algorithms with prognostic model,the synthesized control modes are invariant with respect to both external perturbations and parametric errors.Results of mathematical modeling are presented that demonstrate practical feasibility and high efficiency of designed algorithms.展开更多
Chinese enterprises in Africa need to understand local conditions to succed LIKe all local officials in Africa, Veueza Kasiringua from Namibia hopes she can provide momentum for local economic development and the impr...Chinese enterprises in Africa need to understand local conditions to succed LIKe all local officials in Africa, Veueza Kasiringua from Namibia hopes she can provide momentum for local economic development and the improvement of people＇s livelihood during her tenure. ＂China has more than 30 years＇ experience in this regard that could be shared with Africa,＂ Veueza Kasiringua, Chairperson of the Management Committee of Tsumeb Municipality in Namib-展开更多
基金financial support from the Young Scientist Project of the National Key Research and Development Program of China(Grant No.2021YFC2900600)Beijing Nova Program(Grant No.20220484057)+1 种基金The authors acknowledge the financial support from the Natural Sciences and Engineering Research Council of Canada(Grant No.RGPIN-2018-06902)industrial partners of the Research Institute on Mines and the Environment(RIME UQAT-Polytechnique:https://irme.ca/en/).
文摘Underhand cut-and-fill mining has been widely used in underground mining operations,especially when the rock mass or orebody is of poor quality or prone to rockburst due to high stress.In such cases,mining workers should carry out all production activities under the cemented backfill roof or sill mat instead of a highly fractured and unstable rock roof or a strong rock roof with a high potential of rockburst.Therefore,the stability and required strength of the sill mat are critical issues for mining engineers.In 1991,Mitchell considered that sill mat could fail by caving,sliding,rotation,and flexure.Mitchell also proposed an analytical solution to determine the minimum required strength of the sill mat for each type of failure based on two stiff or immobile rock walls.However,recent publications using numerical modeling and field measurements indicate that the compressive stresses in the sill mat induced by rock wall closure due to a stope excavation beneath the sill mat can be significant.It is thus highly necessary to investigate the required strength of the sill mat by considering rock wall closure.In this study,the crushing failure of sill mat due to rock wall closure generated by underground excavation and a new failure mode called"crushing and caving”is revealed by numerical modeling.An analytical solution corresponding to each failure mode is then developed to estimate the minimum required cohesion(cmin)of the sill mat.A criterion is also proposed to determine if the sill mat fails by crushing or crushing-and-caving failure.The proposed analytical solution does not involve any correction coefficients.The validity of the proposed analytical solution is demonstrated by numerical modeling.The proposed analytical solution can thus be employed to predict the cmin of sill mat subjected to wall closure generated by underlying stope excavation.
文摘Through the Economic-Value-Added(EVA)valuation model,the expected market value of equity can be determined by adding the book value of equity with the present value of expected EVAs under the assumption of constant required return and constant return on equity.The equation of EVA valuation model has taken its shape under the assumption of constant required return and constant return on equity.However,a large body of empirical evidence indicates that required rate of return never remain constant.The EVA-valuation model formulated under constant required return cannot be implemented under the scenario of changing required return.In this study,we explored whether the EVA valuation model could be implemented under changing required return by making any changes in the model and found that it could be implemented under the scenario of changing required return by replacing the book value of the equity of the existing model with the present value of required earnings or normal market earnings.We further examined whether the explanatory ability of the EVA valuation model under the assumption of changing required return is better than that of the valuation model under the assumption of constant required return.Relative information content analyses were conducted by considering sample of the intrinsic value of equities determined by valuation models and the market value of equities of 69 large-cap,88 mid-cap,and 79 small-cap companies.The results showed that the EVA-based valuation model with changing normal market return outperformed the EVA-based valuation model with constant required return.
文摘To evaluate the differences in outcomes of treatment with denosumab alone or denosumab combined with vitamin D and calcium supplementation in patients with primary osteoporosis. Patients were split into a denosumab monotherapy group （18 cases） or a denosumab plus vitamin D supplementation group （combination group; 23 cases）. We measured serum bone alkaline phosphatase （BAP）, tartrate-resistant acid phosphatase （TRACP）-5b and urinary N-terminal telopeptide of type-I collagen （NTX） at baseline, 1 week, as well as at I month and 2, 4, 8 and 12 months. We also measured bone mineral density （BMD） of L1-4 lumbar vertebrae （L）-BMD and bilateral hips （H）-BMD at baseline and at 4, 8 and 12 months. There was no significant difference in patient background. TRACP-5b and urinary NTX were significantly suppressed in both groups from I week to 12 months （except at 12 months for NTX）. In the combination group, TRACP-5b was significantly decreased compared with the denosumab monotherapy group at 2 and 4 months （P 〈 0.05）. BAP was significantly suppressed in both groups at 2-12 months. L-BMD significantly increased at 8 and 12 months （8.9%） in the combination group and at 4, 8 and 12 months （6.0%） in the denosumab monotherapy group, compared with those before treatment. H-BMD was significantly increased in the combination group （3.6%） compared with the denosumab group （1.2%） at 12 months （P 〈 0.05）. Compared with denosumab monotherapy, combination therapy of denosumab with vitamin D and calcium stopped the decrease in calcium caused by denosumab, inhibited bone metabolism to a greater extent, and increased BMD （especially at the hips）.
基金supported by the National Natural Science Foundation of China [81601809]the Natural Science Foundation of Jiangsu Province [BK20160505]
文摘Vibrio parahaemolyticus, the leading cause of seafood-borne gastroenteritis, has the ability to form biofilms on biotic and abiotic surfaces. Biofilm formation is a complicated process involving many specific structures and regulatory processes. The most significant of the structures and processes include polar and lateral flagella, mannose-sensitive hemagglutinin typeⅣpili, chitin-regulated pili,capsular polysaccharide (CPS), exopolysaccharide
文摘Mesenchymal stem cell （MSC）-based treatments have shown promise for improving tendon healing and repair. MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical stimuli, including into tenocytes. Cell elongation and cytoskeletal tension have been shown to be instrumental to the process of MSC differentiation. Previous studies have shown that inhibition of stress fiber formation leads MSCs to default toward an adipogenic lineage, which suggests that stress fibers are required for MSCs to sense the environmental factors that can induce differentiation into tenocytes. As the Rho/ROCK signal transduction pathway plays a critical role in both stress fiber formation and in cell sensation, we examined whether the activation of this pathway was required when inducing MSC tendon differentiation using rope-like silk scaffolds. To accomplish this, we employed a loss-of-function approach by knocking out ROCK, actin and myosin （two other components of the pathway） using the specific inhibitors Y-27632, Latrunculin A and blebbistatin, respectively. We demonstrated that independently disrupting the cytoskeleton and the Rho/ ROCK pathway abolished the expression of tendon differentiation markers and led to a loss of spindle morphology. Together, these studies suggest that the tension that is generated by MSC elongation is essential for MSC teno-differentiation and that the Rho/ROCK pathway is a critical mediator of tendon differentiation on rope-like silk scaffolds.
基金supported by National Institutes of Health Grant DK083350 to M. W
文摘Lipoprotein receptor-related protein 6 （LRP6） plays a critical role in skeletal development and homeostasis in adults. However, the role of LRP6 in mesenchymal stem cells （MSCs）, skeletal stem cells that give rise to osteoblastic lineage, is unknown. In this study, we generated mice lacking LRP6 expression specifically in nestin＋ MSCs by crossing nestin-Cre mice with LRP6 flox mice and investigated the functional changes of bone marrow MSCs and skeletal alterations. Mice with LRP6 deletion in nestin＋ cells demonstrated reductions in body weight and body length at I and 3 months of age. Bone architecture measured by microCT （uCT） showed a significant reduction in bone mass in both trabecular and cortical bone of homozygous and heterozygous LRP6 mutant mice. A dramatic reduction in the numbers of osteoblasts but much less significant reduction in the numbers of osteoclasts was observed in the mutant mice. Osterix＋ osteoprogenitors and osteocalcin＋ osteoblasts significantly reduced at the secondary spongiosa area, but only moderately decreased at the primary spongiosa area in mutant mice. Bone marrow MSCs from the mutant mice showed decreased colony forming, cell viability and cell proliferation. Thus, LRP6 in bone marrow MSCs is essential for their survival and proliferation, and therefore, is a key positive regulator for bone formation during skeletal growth and remodeling.
基金financial support of the Natural Sciences and Engineering Research Council (NSERC) of Canada and the partners of Research Institute on Mines and the Environment (RIME UQAT-Polytechnique http://rime-irme.ca)
文摘Backfill is increasingly used in underground mines to reduce the surface impact from the wastes produced by the mining operations. But the main objectives of backfilling are to improve ground stability and reduce ore dilution. To this end, the backfill in a stope must possess a minimum strength to remain self-standing during mining of an adjacent stope. This required strength is often estimated using a solution proposed by Mitchell and co-workers, which was based on a limit equilibrium analysis of a wedge exposed by the open face. In this paper, three dimensional numerical simulations have been performed to assess the behavior of the wedge model. A new limit equilibrium solution is proposed, based on the backfill displacements obtained from the simulations. Comparisons are made between the proposed solution and experimental and numerical modeling results. Compared with the previous solution, a better agreement is obtained between the new solution and experimental results for the required cohesion and factor of safety. For large scale(field) conditions, the results also show that the required strength obtained from the proposed solution corresponds quite well to the simulated backfill response.
基金Project supported by the National Natural Science Foundation of China(Grant No.12064034)the Leading Talents Project of Science and Technology Innovation in Ningxia Hui Autonomous Region,China(Grant No.2020GKLRLX08)+1 种基金the Natural Science Foundation of Ningxia Hui Autonomous Region,China(Grant Nos.2022AAC03643 and2022AAC03117)the Major Science and Technology Project of Ningxia Hui Autonomous Region,China(Grant No.2022BDE03006)。
文摘Methods to remove dust deposits by high-speed airflow have significant potential applications,with optimal design of flow velocity being the core technology.In this paper,we discuss the wind speed required for particle removal from photovoltaic(PV)panels by compressed air by analyzing the force exerted on the dust deposited on inclined photovoltaic panels,which also included different electrification mechanisms of dust while it is in contact with the PV panel.The results show that the effect of the particle charging mechanism in the electric field generated by the PV panel is greatly smaller than the effect of the Van der Waals force and gravity,but the effect of the particle charged by the contact electrification mechanism in the electrostatic field is very pronounced.The wind speed required for dust removal from the PV panel increases linearly with the PV panel electric field,so we suggest that the nighttime,when the PV electric field is relatively small,would be more appropriate time for dust removal.The above results are of great scientific importance for accurately grasping the dust distribution law and for achieving scientific removal of dust on PV panels.
基金supported by a Johns Hopkins Musculoskeletal Research Pilot and Feasibility Grant (RKT) and NIH R01 AR062074 (DJD)
文摘A large body of literature suggests that bone metabolism is susceptible to the ill effects of reactive species that accumulate in the body and cause cellular dysfunction. One of the body＇s front lines in defense against such damage is the transcription factor, Nrf2. This transcription factor regulates a plethora of antioxidant and cellular defense pathways to protect cells from such damage. Despite the breadth of knowledge of both the function of Nrf2 and the effects of reactive species in bone metabolism, the direct role of Nrf2 in skeletal biology has yet to be thoroughly examined. Thus, in the current study, we have examined the role of Nrf2 in postnatal bone metabolism in mice. Mice lacking Nrf2 （Nrf2-/-） exhibited a marked deficit in postnatal bone acquisition, which was most severe at 3 weeks of age when osteoblast numbers were 12-fold less than observed in control animals. While primary osteoblasts from Nrf2-/- mice functioned normally in vitro, the colony forming capacity of bone marrow stromal cells （BMSCs） from these mice was significantly reduced compared to controls. This defect could be rescued through treatment with the radical scavenger N-acetyl cysteine （NAC）, suggesting that increased reactive species stress might impair early osteoblastogenesis in BMSCs and lead to the failure of bone acquisition observed in Nrf2-/- animals. Taken together, these studies suggest Nrf2 represents a key pathway in regulating bone metabolism, which may provide future therapeutic targets to treat osteoporosis.
基金supported by the grants from the National Natural Science Foundation of China(Nos.31271582 and 31471384)Temasek Life Sciences Laboratory and Singapore Millennium FoundationBeijing Municipal Commission of Education (No.010135336400)
文摘Precise regulation of stem cell self-renewal versus differentiation is important for the maintenance of tissue ho- meostasis. Early loss of stem cell activity results in premature ageing, while excess stem cell activity leads to over- proliferation and cancer initiation （Fuchs et al., 2004; Scadden, 2006; Jones and Wagers, 2008; Morrison and Spradling, 2008）. Thus, understanding the mechanism con- trolling stem cell self-renewal and differentiation is critical for development of potential clinic therapy in the future.
基金We greatly appreciate Prof.Charles Wood(University of Nebraska,Lincoln,USA)for the gift of the infectious molecular clones(pNL4.3,pNL4.3ΔEnvEGFP,and pVSV-G).the National Natural Science Foundation of China(81571987)Natural Science Foundation of Tianjin Municipal Science and Technology Commission(20JCQNJC01750,21JCQNJC01600).
文摘Human immunodeficiency virus-1(HIV-1)encodes simply 15 proteins and thus depends on multiple host cellular factors for virus reproduction.Spastin,a microtubule severing protein,is an identified HIV-1 dependency factor,but the mechanism regulating HIV-1 is unclear.Here,the study showed that knockdown of spastin inhibited the production of the intracellular HIV-1 Gag protein and new virions through enhancing Gag lysosomal degradation.Further investigation showed that increased sodium tolerance 1(IST1),the subunit of endosomal sorting complex required for transport(ESCRT),could interact with the MIT domain of spastin to regulate the intracellular Gag production.In summary,spastin is required for HIV-1 replication,while spastin-IST1 interaction facilitates virus production by regulating HIV-1 Gag intracellular trafficking and degradation.Spastin may serve as new target for HIV-1 prophylactic and therapy.
基金supported by Grants-in-Aid from the Japanese MEXT and MHLWsupported by the Innovative Areas’ Scientific Research(Glial Assembly)the Takeda Science Foundation
文摘Myelin plays important roles in vertebrates,ensuring the rapid propagation of action potentials and the long-term integrity of axons,but the molecular mechanisms of myelin formation remain poorly understood.Recent studies have demonstrated that myelination is regulated by the TYRO3,AXL（also known as UFO）and MERTK.
基金supported by the National Basic Research Program of China (No. 2010CB731805)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (No. 60921001)the Special Fund for Basic Research on Scientific Instruments of China (No. 2011YQ04008301)
文摘In required navigation performance（RNP）, total system error（TSE） is estimated to provide a timely warning in the presence of an excessive error. In this paper, by analyzing the underlying formation mechanism, the TSE estimation is modeled as the estimation fusion of a fixed bias and a Gaussian random variable. To address the challenge of high computational load induced by the accurate numerical method, two efficient methods are proposed for real-time application, which are called the circle tangent ellipse method（CTEM） and the line tangent ellipse method（LTEM）,respectively. Compared with the accurate numerical method and the traditional scalar quantity summation method（SQSM）, the computational load and accuracy of these four methods are extensively analyzed. The theoretical and experimental results both show that the computing time of the LTEM is approximately equal to that of the SQSM, while it is only about 1/30 and 1/6 of that of the numerical method and the CTEM. Moreover, the estimation result of the LTEM is parallel with that of the numerical method, but is more accurate than those of the SQSM and the CTEM. It is illustrated that the LTEM is quite appropriate for real-time TSE estimation in RNP application.
基金supported by the grants from the National Basic Research Program of China (973 Program)(No.2013CB945602)the National Natural Science Foundation of China(No.31270825 and 31171043)
文摘Animal behaviors and higher-order functions rely on complex neural circuits built by synaptic connections （synapses） to deliver messages among different brain cells. As the major mediator in the nervous system, neurons communicate via synapses, which undergo constant structural remodeling with strict regulation.
文摘Selenocysteine, a selenium-containing analog of cysteine, is found in the prokaryotic and eukaryotic kingdoms in active sites of enzymes involved in oxidation-reduction reactions. This aminoacid is cotranslationally incorporated at UGA codons which usually act as translation stop codons. In eukaryotes, decoding of selenocysteine necessitates the participation of the selenocysteine insertion sequence (SECIS), an element lying in the 3' -untranslated region of selenoprotein mRNAs. A detailed experimental study of the secondary structures of the SECIS elements of rat and human type 1 iodothyronine deiodinases and rat glutathione peroxidase was performed. Enzymatic and chemical structure probing led us to propose a secondary structure model, supported by sequence comparison of 23 SECIS mRNAs. The secondary structure model revealed the existence of a novel type of RNA motif composed of four consecutive non-Watson-Crick base-pairs. Using gel shift experiments, we identified in several mammalian cell type extracts the protein SBP,for SECIS-binding protein, that specifically recognizes the iodothyronine deiodinases and glutathione peroxidase SECIS elements. The structural model that we derived for the SECIS RNAs discloses RNA features possibly implicated in the binding of SBP and/or SECIS function
文摘Nedd1 (neural precursor cell expressed, developmentally down-regulated gene 1) is an evolutionarily conserved protein that has previously been characterized as a new member
文摘It is well known that there is abundant water resources in basin of the Yangtze River, the first largest river in China, which is mainly located in Southern China. However, water resources is very scarce in the basin of the Yellow River, which is mainly located in Northern China. So the western route project of south-north water transfer scheme （WRP-SNWTS） aims to transfer water from the Yangtze River to the Yellow River. The area of WRP-SNWT, located in the upper reaches of the Yangtze River and the main areas of Sichuan and the marginal areas of the Qinghai-Tibet Plateau, has sufficient water resources but fragile ecology and environment. Therefore, it is necessary for WRP-SNWT to analyze the ecology water required. Based on the planning principles of from low elevation to high elevation, from small to large, from short to long and from easy to difficulty, the WRP-SNWT will be constructed through three stage projects. The western route first stage project of the south-north water transfer scheme （WRFST-SNWTS） is planned to transfer 4×10^9m^3/a from six tributaries of the Yalong river and from Dadu river to Jiaqu of Yellow River.. Daqu river and Niqu river are the branches of Xianshui river. Sequ river, Duke river, Make river and Ake river are the branches of Dadu river, which account for 65-70% of the total river run-off. It need more research and the rest run-off can satisfy channel ecology water required. According to analysis ecological water required which mainly satisfy for aquicolous biology in water-exporting region, such as low air temperature. Fish and aquicolous biology main living from May to August, and rivers are iced up from December to March of next year, ecology water required mainly for fish and aquicolous biology. The flow criterion of Tennant method is modified. The ecology water required of WRFSP-SNWTS is estimated by the flow data of Zhuwo gauging station, Zhuba gauging station, Chuosijia gauging station and Zumuzu gauging station. The result show that the ecology water required calculated by modified Tennant less 1 l percent than that of Tennant. This estimating result can supply more water resources for transferring to Yellow River. Meanwhile, this can supply gist for research transferring water of WRFSP-SNWTS.
文摘In order to build a high-quality team of teachers in vocational higher education institutions, and investigate the current situation of teachers of common required courses in vocational higher education institutions of Hainan Province, an empirical research is conducted. A questionnaire survey was carried out in aspects of satisfaction of teaching and scientific research, professional quality, work saturation and teacher’s job satisfaction. The research results shows that the professional quality of teachers of common required courses cannot significantly influence the satisfaction of teaching and scientific research;Job saturation can positively influence teaching and research satisfaction;teaching and research satisfaction can positively influence teachers’ job satisfaction.
文摘We apply the method of guidance by a required velocity for solving the optimal control problem over spacecraft’s reorientation from known initial attitude into a required final attitude.We suppose that attitude control is carried out by impulse jet engines.For optimization of fuel consumption,the controlling moments are calculated and formed according to the method of free trajectories together with principle of iterative control using the quaternions for generating commands to actuators.Optimal solution corresponds to the principle“acceleration-free rotation-separate corrections-free rotation-braking”.Rotation along a hitting trajectory is supported by insignificant correction of the uncontrolled motion at discrete instants between segments of acceleration and braking.Various strategies of forming the correction impulses during stage of free motion are suggested.Improving accuracy of achievement of spacecraft's final position is reached by terminal control using information about current attitude and angular velocity measurements for determining an instant of beginning of braking(condition for start of braking based on actual motion parameters is formulated in analytical form).The described method is universal and invariant relative to moments of inertia.Developed laws of attitude control concern the algorithms with prognostic model,the synthesized control modes are invariant with respect to both external perturbations and parametric errors.Results of mathematical modeling are presented that demonstrate practical feasibility and high efficiency of designed algorithms.
文摘Chinese enterprises in Africa need to understand local conditions to succed LIKe all local officials in Africa, Veueza Kasiringua from Namibia hopes she can provide momentum for local economic development and the improvement of people＇s livelihood during her tenure. ＂China has more than 30 years＇ experience in this regard that could be shared with Africa,＂ Veueza Kasiringua, Chairperson of the Management Committee of Tsumeb Municipality in Namib-
