Induced neural stem cells regulate microglial activation through Akt-mediated upregulation of CXCR4 and Crry in a mouse model of closed head injury

Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological recovery.However,the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear.In this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 expression.However,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial activation.In agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury mice.Notably,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head injury.In conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neural stem cells on microglial activation via upregulation of CXCR4 and Crry,thereby promoting induced neural stem cell–mediated improvement of neuronal injury,cerebral edema,and neurological disorders following closed head injury.

Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury

Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.

On Fuzzy Regularly Closed Filters in Michálek Fuzzy Topological Space

C.L. Chang’s introduction of fuzzy topology in 1981 opened up new avenues for parallel theories in topology. However, Chang’s work appears to focus more on the topology of fuzzy sets rather than fuzzy topology itself. In 1975, Michálek presented a functional definition of ordinary topology and later developed fuzzy topology as a distinct extension of this idea, setting it apart from Chang’s approach. While there has been significant research on Chang’s fuzzy topology, Michálek’s version has not received as much attention. This paper introduces the concept of fuzzy regularly closed filters, or FRCM filters, within Michálek’s fuzzy topological space and explores some properties of FRCM ultrafilters.

Sensing-Communication-Computing-Control Closed Loop for NOMA-UAV Systems

In the areas without terrestrial communication infrastructures,unmanned aerial vehicles(UAVs)can be utilized to serve field robots for mission-critical tasks.For this purpose,UAVs can be equipped with sensing,communication,and computing modules to support various requirements of robots.In the task process,different modules assist the robots to perform tasks in a closed-loop way,which is referred to as a sensing-communication-computing-control(SC3)loop.In this work,we investigate a UAV-aided system containing multiple SC^(3)loops,which leverages non-orthogonal multiple access(NOMA)for efficient resource sharing.We describe and compare three different modelling levels for the SC^(3)loop.Based on the entropy SC^(3)loop model,a sum linear quadratic regulator(LQR)control cost minimization problem is formulated by optimizing the communication power.Further for the assure-to-be-stable case,we show that the original problem can be approximated by a modified user fairness problem,and accordingly gain more insights into the optimal solutions.Simulation results demonstrate the performance gain of using NOMA in such task-oriented systems,as well as the superiority of our proposed closed-loop-oriented design.

Design and Test of Closed Hydraulic Transmission System of 4WD High-clearance Wheeled Sprayer

In conjunction with the working characteristics of the high-clearance wheeled sprayer and the benefits of the closed hydraulic system,a series of reasonable working parameters should be established,and a hydraulic system that fulfills the requisite specifications should be designed.The AMESim software model is employed to construct a closed hydraulic transmission system,and the simulation analysis is then performed according to the data of hydraulic components.According to analysis results,the prototype can be optimized and upgraded,and a verification test is further carried out.The test results demonstrate that the designed closed hydraulic transmission system meets the actual working requirements of the high-clearance wheeled sprayer and provides a stable experimental platform for intelligent control of agricultural machinery.

Simulation Modelling and Techno-Economics of Supercritical Carbon Dioxide Recompression Closed Brayton Cycle

In recent years, there has been global interest in meeting targets relating to energy affordability and security while taking into account greenhouse gas emissions. This has heightened major interest in potential investigations into the use of supercritical carbon dioxide (sCO2) power cycles. Climate change mitigation is the ultimate driver for this increased interest;other relevant issues include the potential for high cycle efficiency and a circular economy. In this study, a 25 MWe recompression closed Brayton cycle (RCBC) has been assessed, and sCO2 has been proposed as the working fluid for the power plant. The methodology used in this research work comprises thermodynamic and techno-economic analysis for the prospective commercialization of this sCO2 power cycle. An evaluated estimation of capital expenditure, operational expenditure, and cost of electricity has been considered in this study. The ASPEN Plus simulation results have been compared with theoretical and mathematical calculations to assess the performance of the compressors, turbine, and heat exchangers. The results thus reveal that the cycle efficiency for this prospective sCO2 recompression closed Brayton cycle increases (39% - 53.6%) as the temperature progressively increases from 550˚C to 900˚C. Data from the Aspen simulation model was used to aid the cost function calculations to estimate the total capital investment cost of the plant. Also, the techno-economic results have shown less cost for purchasing equipment due to fewer components being required for the cycle configuration as compared to the conventional steam power plant.

OPEN表和CLOSED表的合一

在人工智能传统的搜索方法中,一直是将OPEN表和CLOSED表分开的。这不仅增加了搜索算法的复杂性,久而久之,也许禁锢了人们的思想。文章试图改变这种状况,提出了一种与众不同的新思路,巧妙地将OPEN表和CLOSED表合二为一,减少了一些工作量,在一定程度上降低了算法的复杂性。

Singular Points, Closed Orbits, Stable Manifolds and Unstable Manifolds of Second Order Autonomous Birkhoff Systems

Aim To study singular points, closed orbits, stable manifolds and unstable manifolds of a second order autonomous Birkhoff system. Methods Qualitative methods of ordinary differential equation were used. Results and Conclusion The criteria for singular points, closed orbits and hyperbolic equilibrium points of a second order autonomous Birkhoff system are given. Moreover the stability of equilibria, stable manifolds and unstable manifolds are obtained.

New algorithm of mining frequent closed itemsets

A new algorithm based on an FC-tree （frequent closed pattern tree） and a max-FCIA （maximal frequent closed itemsets algorithm） is presented, which is used to mine the frequent closed itemsets for solving memory and time consuming problems. This algorithm maps the transaction database by using a Hash table,gets the support of all frequent itemsets through operating the Hash table and forms a lexicographic subset tree including the frequent itemsets.Efficient pruning methods are used to get the FC-tree including all the minimum frequent closed itemsets through processing the lexicographic subset tree.Finally,frequent closed itemsets are generated from minimum frequent closed itemsets.The experimental results show that the mapping transaction database is introduced in the algorithm to reduce time consumption and to improve the efficiency of the program.Furthermore,the effective pruning strategy restrains the number of candidates,which saves space.The results show that the algorithm is effective.

Evaluation of Two Cooling Methods for Closed Greenhouses

Special cooling methods are needed for normal growth of crops in closed greenhouses which permit no ventilation, especially during warm seasons. Experi- ments were designed to evaluate two cooling methods （Watergy chimney method and pool method） in a closed greenhouse in Beijing during warm seasons. Prelimi- nary results showed that average temperature at daytime （from 8：00 to 18：00） at 100 cm above ground surface in the closed greenhouse could be reduced by 8 with the Watergy chimney method. Average relative humidity fluctuated between 45% and 75% during daytime at 100 cm above ground surface within the closed greenhouse. With the pool method, average temperature was about 10 ℃ lower than that of the control greenhouse without pool at 50 cm above the ground surface. The peak temperature at 50 cm height was about 32℃ between 11：30 and 15：00 and, close to outside temperature. Temperature in this system satisfied normal growth of most crops, but relative humidity at 50 cm height were above 90% at daytime.

The Predetermined Failure of Murphy＇s Quest for Freedom in Closed Systems--Narritivity Temporality in Murphy

This essay aims at an analysis of Murphy's failure of his quest for freedom from the aspect of narrative temporality whichwill focus on order, duration and frequency. From the perspective of temporal order, the essay will endeavor to probe into the pro-lepsis in the novel to analyse predetermined narrative and its function. Considering with temporal duration, this essay will penetratethe deceleration of narrative—scene and pause in Murphy to explore its thematic meaning. To investigate the temporal frequency,iterative narrative within text will be exemplified to discuss closed systems in the novel. Based on the analysis of the narrativity tem-porality in Murphy, the essay will focuses on that how its narrative strategy well embodies its theme—the predetermined failure ofMurphy's quest for freedom in closed systems.

Novel therapeutic approaches for hepatitis B virus covalently closed circular DNA

Hepatitis B virus(HBV) infection is a major global health problem. Although current therapies, such as the use of nucleos(t)ide analogs, inhibit HBV replication efficiently, they do not eliminate covalently closed circular DNA(ccc DNA), which persists in hepatocyte nuclei. As HBV ccc DNA is a viral transcription template, novel therapeutic approaches to directly target HBV ccc DNA are necessary to completely eradicate persistent HBV infections. HBV ccc DNA levels in HBV-infected human liver cells are extremely low; thus, more reliable and simple measurement methods are needed to correctly monitor their levels during therapeutic treatment. Although reverse transcription-polymerase chain reaction or Southern blot procedures are currently used in research studies, these methods are not completely reliable and are also time-consuming and labor-intensive. Genome editing technologies, such as zinc finger nucleases, transcription activator-like effector nucleases, and the clustered regularly interspaced short palindromic repeats/Cas9(CRISPR/Cas9) system, which are designed to target specific DNA sequences, represent highly promising potential therapeutic tools. In particular, the CRISPR/Cas9 system is an easily customizable sequencespecific nuclease with high flexibility and may be the most feasible approach to target HBV ccc DNA. Further research to develop easier, safer, and more effective protocols should be pursued.

Closed form solutions for free vibrations of rectangular Mindlin plates

A new two-eigenfunctions theory, using the amplitude deflection and the generalized curvature as two fundamental eigenfunctions, is proposed for the free vibration solutions of a rectangular Mindlin plate. The three classical eigenvalue differential equations of a Mindlin plate are reformulated to arrive at two new eigenvalue differential equations for the proposed theory. The closed form eigensolutions, which are solved from the two differential equations by means of the method of separation of variables are identical with those via Kirchhoff plate theory for thin plate, and can be employed to predict frequencies for any combinations of simply supported and clamped edge conditions. The free edges can also be dealt with if the other pair of opposite edges are simply supported. Some of the solutions were not available before. The frequency parameters agree closely with the available ones through pb-2 Rayleigh-Ritz method for different aspect ratios and relative thickness of plate.

SUMMARY OF STUDIES ON CLOSED-POLYCULTURE OF PENAEID SHRIMP WITH FISHES AND MOLUSCANS

Closed polyculture of Chinese penaeid shrimp,Taiwan red tilapia ,and molluscans(constricted tagelus and bay scallop) was studied from 1995 to 1997 with the enclosure experiment method, on a shrimp farm in Haiyang County,Shandong Province. Four structure optimized closed polyculture systems, i.e., the “shrimp tagelus" system, the “shrimp scallop" system,the “shrimp tilapia" system and the “shrimp tilapia tagelus" system,were worked out. All these polyculture systems were superior to shrimp monoculture system in economic and ecological efficiencies. The order of these polyculture systems in efficiencies was “shrimp tilapia tagelus">“shrimp tagelus">“shrimp tilapia">“shrimp scallop". The “shrimp tilapia tagelus" system raised the production by 28% and the utilization efficiency of input nitrogen by 85%.These closed polyculture systems reduced the nitrogen discharge ratio to 6%-8%, instead of 40%-90% in the usual open culture systems. The ecological features of the systems were also investigated and many meaningful results have been obtained. The mechanism enhancing the efficiencies of these systems, the ways to enhance the efficiencies further and those to reuse the sedimented materials are disscussed.

SPALLATION ANALYSIS WITH A CLOSED TRANS-SCALE FORMULATION OF DAMAGE EVOLUTION

A closed,trans-scale formulation of damage evolution based on the statistical mi- crodamage mechanics is summarized in this paper.The dynamic function of damage bridges the mesoscopic and macroscopic evolution of damage.The spallation in an aluminium plate is studied with this formulation.It is found that the damage evolution is governed by several dimensionless parameters, i.e.,imposed Deborah numbers De~* and De,Mach number M and damage number S.In particular, the most critical mode of the macroscopic damage evolution,i.e.,the damage localization,is deter- mined by Deborah number De~*.Deborah number De~* reflects the coupling and competition between the macroscopic loading and the microdamage growth.Therefore,our results reveal the multi-scale nature of spallation.In fact,the damage localization results from the nonlinearity of the microdamage growth.In addition,the dependence of the damage rate on imposed Deborah numbers De~* and De, Mach number M and damage number S is discussed.

Closed-form solutions for free vibration of rectangular FGM thin plates resting on elastic foundation

This article presents closed-form solutions for the frequency analysis of rectangular functionally graded material (FGM) thin plates subjected to initially in-plane loads and with an elastic foundation. Based on classical thin plate theory, the governing differential equations are derived using Hamilton's principle. A neutral surface is used to eliminate stretching-bending coupling in FGM plates on the basis of the assumption of constant Poisson's ratio. The resulting governing equation of FGM thin plates has the same form as homogeneous thin plates. The separation-of-variables method is adopted to obtain solutions for the free vibration problems of rectangular FGM thin plates with separable boundary conditions, including, for example, clamped plates. The obtained normal modes and frequencies are in elegant closed forms, and present formulations and solutions are validated by comparing present results with those in the literature and finite element method results obtained by the authors. A parameter study reveals the effects of the power law index n and aspect ratio a/b on frequencies.

Distinct proteins in cortex of rats with closed traumatic brain injury detected by a WCX-2 protein chip

BACKGROUND： Mechanical injury can cause the changes of polygene expression spectrum in rat cerebral cortical nerve cells, and then result in the changes of intracellular protein expression. At present, dielectrophoresis is combined with mass spectrum technique to detect the expression of different proteins in rat cortex after brain injury, but the protein chip technique requires further investigation. OBJECTIVE： To analyze the differences of protein expression spectrum in rat cerebral cortex before and after closed traumatic brain injury using WCX-2 protein chip technique. DESIGN： A randomized controlled animal experiment. SETTING： Training Division of the Medical College of Chinese People＇s Armed Police Force. MATERIALS： Seventy-two male SD rats of clean degree, 350 - 450 g, were provided by the Experimental Animal Center, Academy of Military Medical Sciences of Chinese PLA. Urea, trifluoroacetic acid, CHAPS and Tris （Sigma, USA）; WCX-2 （Ciphergen, USA）. Ultra-high speed hypothermia centrifuger （Bechman, USA）; Rotary tissue microtome （Keuca, Germany）; Biochip processor and PBS II-C protein chip reader （Ciphergen, USA）. METHODS： The experiments were carried out in the Institute of Molecular Pathology, Central Laboratory, and Department of Pathology, Medical College of Chinese People＇s Armed Police Force from June 2005 to March 2006. ① Grouping and treatment： The experiments were completed in molecular pathological institute, central laboratory and pathological department. ② The rats were randomly divided into control group （n =12） and brain injury group （n =60）. Marmarou＇s weight-dropping models were duplicated at different time points in the brain injury group. In the control group, the rats were only treated by incising the skin of head top, without fixing the stainless steel hitting backup plate at the vault of skull, and obtain brain cortex for pathological and protein chip research, and they were killed after 24 hours. The rats in the brain injury group were killed at 4, 8, 12, 24 and 48 hours after model establishment. ③ Pathological observation： Longitudinal section was made on cerebral cortex, and sections of 5 μm were prepared, then stained with hematoxylin and eosin （HE）. ④Protein chip analysis： 100 mg cerebral cortex was collected from each rat, and the protein content in sample was detected with Bradford method, meanwhile, WCX-2 protein chip was used to analyze the protein spectrum. The data were automatically collected with Ciphergen proteinchip 3.0 software, and the results were analyzed using Biomarker Wizard software to compare the differences of protein spectrum in rat cortex between the groups. MAIN OUTCOME MEASURES： Results of the pathological observation of cerebral cortex and the protein spectrum analysis. RESULTS：①Pathological changes of cerebral cortex： In the control group, no necrosis and edema was observed. In the brain injury group, injures of different severity occurred at different time points; After 4 hours, focal or scattered red nerve cells could be observed, the size of some cells was increased, cytoplasm was lightly stained, and only nuclear fragments were seen; After 8 hours, the necrotic nerve cells were increased, and the number of nerve cells was reduced, astrocytes （neuronophagia） could be seen in partial cytoplasm; there was small vascular dilatation, and endothelial cell proliferation; interstitial edema, regional rarefaction lightly stained. After 12- 48 hours, the necrotic nerve cells were reduced, and astrocytes proliferated. ② Results of protein spectrum analysis： The WCX-2 experiment found that the expressions of 5 639, 3 212 and 7 536 u proteins in cerebral cortex changed after injury in the brain injury group. The peak intensity of 5 639 u protein in the brain injury group at 8 hours after injury was higher than that in the control group （P 〈 0.05）; The peak intensity of 3 212 u protein in the brain injury group at 48 hours after injury was higher than that in the control group （P 〈 0.05）; The peak intensity of 7 536 u protein at 24 hours after injury was higher than that in the control group （P 〈 0.05）. CONCLUSION： Brain injury can cause the changes of protein expression spectrum in cerebral cortex, it is suggested that brain injury can induce the expression of protein.

GENERALIZATIONS AND CARTESIAN CLOSED SUBCATEGORIES OF SEMICONTINUOUS LATTICES

In this article, the authors mainly study how to obtain new semicontinuous lattices from the given semicontinuous lattices and discuss the conditions under which the image of a semicontinuous projection operator is also semicontinuous. Moreover, the authors investigate the relation between semicontinuous lattices and completely distributive lattices. Finally, it is proved that the strongly semicontinuous lattice category is a Cartesian closed category.

Finite-time stability with respect to a closed invariant set for a class of discontinuous systems

This paper discusses the problem of finite-time stability with respect to a closed, but not necessarily compact, invariant set for a class of nonlinear systems with discontinuous right-hand sides in the sense of the Filippov solutions. When the Lyapunov function is Lipschitz continuous and regular, the Lyapunov theorem on finite-time stability with respect to a closed invariant set is presented.

The remote sensing composite information of Nansha reef's closed atoll and the model of its spatial structure evolution——Ⅰ

Based on the feature of the growth and the local limitation of the Nansha reef's closed atoll, also the related remote sensing information of it, the composite analysis is made. The closed atoll conception remote sensing system is constructed through the formation mechanism, development law and the space-time distribution of the closed atoll. Solution of the equation consisting of information function value and isostatic value of closed atoll and half-closed atoll using this system, and topologic analysis on the two kinds of atoll's morphologic growth are the basic foundation for the research of their evolutionary comparative model.