气象观测场在汽车试验场中的应用研究

汽车试验场作为汽车开展道路测试的重要场所,用于验证汽车产品的品质以及可靠性。除了场地道路外,气象条件作为汽车道路测试的重要一环,在《GB/T12534-1990汽车道路试验方法通则》中也有明确要求,如:试验时应是无雨无雾天气,相对湿度小于95%,气温0-40℃,风速不大于3m/s。同时气象条件也作为试验场道路管控的重要依据,实时风速、雨量、能见度等信息为场地管理者发布限速、限行、封场等通知提供必要参考依据,直接影响道路测试安全管控的及时性。因此,文章从气象观测场的建设、气象服务、异常天气道路管控等方面开展气象观测场在汽车试验场中的应用研究。

Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR

Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.

Fast and Accurate Identification of <i>M. tuberculosis</i>Complex Using an Immunochromatographic MPT64 Antigen Detection Test

Background: A new rapid Immunochromatographic test (ICT) kit (MPT64 TB Ag Kit) for detection of MPT64 Antigen in M. tuberculosis (MTB) isolates used for rapid identification of MTB isolates developed by SD (Standard Diagnostics) Bio line, South Korea was evaluated. The ICT is a rapid, reliable and cheaper method that can be used instead of conventional biochemical tests for confirming MTB in culture isolates in resource limited laboratories. The study also evaluated the ability of ICT to detect MPT64-Antigen before the micro MGIT could signal positive. Material/Methods: A total of 450 sputum samples of individual patients were used for the study. 152 isolates of Mycobacteria were recovered from solid and liquid media. These strains were tested for the detection of MPT64-antigen. H37Rv strain was served as the positive reference control and also used for early detection of Antigen experiment. Findings: The development of bands on both test and sample region when H37Rv strain was tested were seen (MPT64 antigen positive). When 138 MTB isolates were tested, it showed a similar banding pattern indicating 100% sensitivity. MPT64 band formation was not detected in any of the 14 isolates indicating 100% specificity. Both PPV & NPV were 100%. All the isolates negative for MPT64 Ag were confirmed as MOTT by conventional bio-chemical PNBA. The H37Rv strain showed a faint band from the 2nd day onwards from inoculation till 3rd day in the earlier Antigen detection experiment. Conclusion: Rapid identification of MTB culture isolate is a pressing need for diagnosis and proceeding to perform drug susceptibility testing. MPT64 TB Ag detection ICT kit is a rapid, reliable method, good substitute for molecular identification methods, and conventional biochemical test which is time-consuming and technically demanding. The early detection of Antigen can be used as an effective tool in diagnosis.

Mechanisms mediating cholinergic antral circular smooth muscle contraction in rats

AIM:To investigate the pathway(s)mediating rat antral circular smooth muscle contractile responses to the cholinomimetic agent,bethanechol and the subtypes of muscarinic receptors mediating the cholinergic contraction. METHODS:Circular smooth muscle strips from the antrum of Sprague-Dawley rats were mounted in muscle baths in Krebs buffer.Isometric tension was recorded.Cumulative concentration-response curves were obtained for(+)-cis- dioxolane(cD),a nonspecific muscarinic agonist,at 10^(-8)- 10^(-4)mol/L,in the presence of tetrodotoxin(TTX,10^(-7)mol/L). Results were normalized to cross sectional area.A repeat concentration-response curve was obtained after incubation of the muscle for 90 min with antagonists for M1(pirenzepine), M2(methoctramine)and M3(darifenadn)muscarinic receptor subtypes.The sensitivity to PTX was tested by the ip injection of 100 mg/kg of PTX 5 d before the experiment.The antral circular smooth muscles were removed from PTX-treated and non-treated rats as strips and dispersed smooth muscle cells to identify whether PTX-linked pathway mediated the contractility to bethanechol. RESULTS:A dose-dependent contractile response observed with bethanechol,was not affected by TTx.The pretreatment of rats with pertussis toxin decreased the contraction induced by bethanechol.Lack of calcium as well as the presence of the L-type calcium channel blocker,nifedipine,also inhibited the cholinergic contraction,with a reduction in response from 2.5±0.4 g/mm^2 to 1.2±0.4 g/mm^2(P<0.05).The dose- response curves were shifted to the right by muscarinic antagonists in the following order of affinity:darifenacin (M_3)>methocramine(M_2)>pirenzepine(M_1). CONCLUSION:The muscarinic receptors-dependent contraction of rat antral circular smooth muscles was linked to the signal transduction pathway(s)involving pertussis-toxin sensitive GTP-binding proteins and to extracellular calcium via L-type voltage gated calcium channels.The presence of the residual contractile response after the treatment with nifedipine,suggests that an additional pathway could mediate the cholinergic contraction.The involvement of more than one muscarinic receptor(functionally predominant type 3 over type 2)also suggests more than one pathway mediating the cholinergic contraction in rat antrum.

Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future

Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored functionality.Conversely,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various technologies.Advancements in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in mice.Nevertheless,there remain issues that hinder improving reprogramming efficiency and maturity.Thus,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming strategies.This review describes recent progress in relatively successful Müller glia reprogramming strategies.It also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.

人脑初级体感皮质M_(20)反应的性别差异-脑磁图研究

目的:应用脑磁图(MEG)研究健康受试者初级体感皮质反应M20的潜伏期、波幅及位置的性别差异。方法:对40例受试者给予双侧腕部正中神经电刺激,固定电流脉冲0.3ms,刺激间期0.5s,诱发初级体感皮质兴奋。脑磁图检查后进行MR扫描,层厚1.5mm。大脑初级体感皮质反应由等电流偶极(ECD)评价。将脑磁图所获得的M20反应叠加到MRI上,形成磁源性影像(MSI)。结果:依照给予电刺激后反应潜伏期不同分别称为M20、M35及M60,因M35及M60易受刺激间期(ISI)的影响,只对M20的潜伏期、波幅及反应位置的性别差异进行分析。结果为(1)M20左、右半球潜伏期男性20.6±1.0ms和20.7±1.2ms,女性20.1±0.9ms和20.2±0.9ms,男女性同侧半球潜伏期无显著性差异(P>0.05);(2)M20左、右半球波幅男性23.6±11.2nAm和25.4±11.2nAm,女性25.8±10.5nAm和27.6±7.8nAm,男女性同侧半球波幅无显著性差异(P>0.05);(3)左半球男女性M20偶极位置在X轴位存在显著性差异(P<0.05),显示男性X轴上与女性相比稍偏外侧,右半球男女性M20偶极位置在X轴位无显著性差异(P>0.05),Y,Z轴无显著性差异(P>0.05);(4)磁源性影像显示所有受试者M20反应峰值均位于中央后回。结论:脑磁图可明确不同性别的大脑初级体感皮质反应M20潜伏期、波幅及位置。磁源性影像显示M20峰值位于?

Microglia:a promising therapeutic target in spinal cord injury

Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal regeneration.In this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor cells.Despite a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive research.This review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.

On a Grouping Method for Constructing Mixed Orthogonal Arrays

Mixed orthogonal arrays of strength two and size smn are constructed by grouping points in the finite projective geometry PG(mn-1, s). PG(mn-1, s) can be partitioned into [(smn-1)/(sn-1)](n-1)-flats such that each (n-1)-flat is associated with a point in PG(m-1, sn). An orthogonal array Lsmn((sn)(smn-)(sn-1) can be constructed by using (smn-1)/( sn-1) points in PG(m-1, sn). A set of (st-1)/(s-1) points in PG(m-1, sn) is called a (t-1)-flat over GF(s) if it is isomorphic to PG(t-1, s). If there exists a (t-1)-flat over GF(s) in PG(m-1, sn), then we can replace the corresponding [(st-1)/(s-1)] sn-level columns in Lsmn((sn)(smn-)(sn-1) by (smn-1)/( sn-1) st -level columns and obtain a mixed orthogonal array. Many new mixed orthogonal arrays can be obtained by this procedure. In this paper, we study methods for finding disjoint (t-1)-flats over GF(s) in PG(m-1, sn) in order to construct more mixed orthogonal arrays of strength two. In particular, if m and n are relatively prime then we can construct an Lsmn((sm)smn-1/sm-1-i(sn-1)/ (s-1)( sn) i(sm-1)/ s-1) for any 0i(smn-1)(s-1)/( sm-1)( sn-1) New orthogonal arrays of sizes 256, 512, and 1024 are obtained by using PG(7,2), PG(8,2), and PG(9,2) respectively.

半边旗提取物5F对人高转移卵巢癌细胞HO-8910PMETS-1mRNA和VEGF蛋白表达的影响

目的:研究半边旗提取物5F(以下简称5F)对HO-8910PM细胞内VEGF蛋白及ETS-1mRNA表达的影响,探讨其抗肿瘤侵袭转移的作用机制.方法:RT-PCR分析ETS-1mRNA的表达;Western blot分析VEGF蛋白的表达.结果:25～100 μmol/L 5F作用HO-8910PM细胞24 h后,明显下调ETS-1mRNA的表达;5F明显下调VEGF蛋白表达水平.结论:5F抗肿瘤侵袭转移能力与ETS-1mRNA和VEGF蛋白的表达有关.

Einstein’s General Relativity and Pure Gravity in a Cosserat and De Sitter-Witten Spacetime Setting as the Explanation of Dark Energy and Cosmic Accelerated Expansion

Ordinary energy and dark energy density are determined using a Cosserat-Cartan and killing-Yano reinterpretation of Einstein’s special and general relativity. Thus starting from a maximally symmetric space with 528 killing vector fields corresponding to Witten’s five Branes model in eleven dimensional M-theory we reason that 504 of the 528 are essentially the components of the relevant killing-Yano tensor. In turn this tensor is related to hidden symmetries and torsional coupled stresses of the Cosserat micro-polar space as well as the Einstein-Cartan connection. Proceeding in this way the dark energy density is found to be that of Einstein’s maximal energy mc2 where m is the mass and c is the speed of light multiplied with a Lorentz factor equal to the ratio of the 504 killing-Yano tensor and the 528 states maximally symmetric space. Thus we have E (dark) = mc2 (504/528) = mc2 (21/22) which is about 95.5% of the total maximal energy density in astounding agreement with COBE, WMAP and Planck cosmological measurements as well as the type 1a supernova analysis. Finally theory and results are validated via a related theory based on the degrees of freedom of pure gravity, the theory of nonlocal elasticity as well as ‘t Hooft-Veltman renormalization method.

Quantum Coherent Entangled Hydrogen Atom Non-Locality

The discovery of a data based informational wave pattern infuses coherent entanglement into the system. This discovery of how to add coherent entanglement into the model provides the missing key, that has opened the door to understanding the universe. It is found that the inclusion of coherence and entanglement at the start of the system is extremely simple and in fact it is so simple that it has simply been overlooked. Entanglement and coherence are the most fundamental aspects of our universe. It is demonstrated that the basic model of the hydrogen atom is made from the CMB. If we add entanglement into this basic model of the hydrogen atom a math system called Wave Pattern Entangled Math is unveiled. This system of wave interference mathematics creates a data system in which entanglement and coherence can easily be understood. The final outcome is an unbreakable pattern of information, including entangled energy, entropy, spin, universal expansion, compression, velocity of light, C2, and Quantum Coherence.

Risk of connective—tissue disease in men with testicular or penile prostheses：a preliminary study

AIM: To help clarifying the possibility of connective-tissue diseases in men with penile or testicular prostheses. METHODS: Eight patients underwent inflatable penile prostheses and 15, testicular prostheses consented to the study. Their medical records were reviewed and a follow-up interview and physical and serological examinations were performed. RESULTS: In patients with penile prostheses, there was no abnormal antinuclear antibody (ANA) or IgM elevation. The serum levels of the rheumatoid factor (RF), C4, IgA and IgG were abnormal in one patient, and the levels of erythrocyte sedimentation rate (ESR) and C3, abnormal in two. Four had elevated IgE. In patients with testicular prostheses, there was no abnormal RF, ANA or IgM. The serum levels of ESR and IgA were abnormal in two, and three had abnormal C4, ten abnormal C3, and eleven decreased IgG. All had increased IgE. Men with penile prostheses had higher serum levels of IgG and IgM than those with testicular prostheses (P=0.001, P=0.016, respectively). The rates of abnormal values of IgE and IgG were higher in men with testicular prostheses than in men with penile prostheses (P=0.008, P=0.009, respectively). Physical examination was normal in all patients and nobody had documented symptoms pertinent to connective-tissue diseases. CONCLUSION: Our findings suggest that the risk of connective-tissue diseases is not higher in patients wearing prostheses as the ANA is negative and there is no apparent manifestation suggestive of connective-tissue diseases.

ErbB-3结合蛋白—ebp1对ACC-M细胞生长的影响

目的:探讨ErbB- 3结合蛋白—ebp1 对腺样囊性癌ACC M细胞生长增殖作用的影响。方法:通过免疫组化筛选到erbB 2/erbB -3双阳性的ACC M细胞系;转染pcDNA3.1 -ebp1 质粒至ACC M细胞,G418 筛选被转染的阳性细胞;RT- PCR检测转染后细胞中ebp1的转录水平;细胞生长曲线及3H- TdR摄入法观察转染前后细胞生长增殖能力的改变。结果:ACC- M细胞同时表达erbB 2/erbB 3;RT -PCR显示转染后细胞中ebp1转录水平明显升高;ACC- M- ebp1 细胞生长曲线平缓,生长减慢,3H- TdR摄入量明显减少,细胞增殖能力减弱。结论:ebp1在体外能显著抑制ACC- M肿瘤细胞增殖。

Dark Energy Explained via the Hawking-Hartle Quantum Wave and the Topology of Cosmic Crystallography

The aim of the present paper is to explain and accurately calculate the missing dark energy density of the cosmos by scaling the Planck scale and using the methodology of the relatively novel discipline of cosmic crystallography and Hawking-Hartle quantum wave solution of Wheeler-DeWitt equation. Following this road we arrive at a modified version of Einstein’s energy mass relation E = mc2 which predicts a cosmological energy density in astonishing accord with the WMAP and supernova measurements and analysis. We develop non-constructively what may be termed super symmetric Penrose fractal tiling and find that the isomorphic length of this tiling is equal to the self affinity radius of a universe which resembles an 11 dimensional Hilbert cube or a fractal M-theory with a Hausdorff dimension where. It then turns out that the correct maximal quantum relativity energy-mass equation for intergalactic scales is a simple relativistic scaling, in the sense of Weyl-Nottale, of Einstein’s classical equation, namely EQR = (1/2)(1/) moc2 = 0.0450849 mc2 and that this energy is the ordinary measurable energy density of the quantum particle. This means that almost 95.5% of the energy of the cosmos is dark energy which by quantum particle-wave duality is the absolute value of the energy of the quantum wave and is proportional to the square of the curvature of the curled dimension of spacetime namely where and is Hardy’s probability of quantum entanglement. Because of the quantum wave collapse on measurement this energy cannot be measured using our current technologies. The same result is obtained by involving all the 17 Stein spaces corresponding to 17 types of the wallpaper groups as well as the 230-11=219 three dimensional crystallographic group which gives the number of the first level of massless particle-like states in Heterotic string theory. All these diverse subjects find here a unified view point leading to the same result regarding the missing dark energy of the universe, which turned out to by synonymous with the absolute value of the energy of the Hawking-Hartle quantum wave solution of Wheeler-DeWitt equation while ordinary energy is the energy of the quantum particle into which the Hawking-Hartle wave collapse at cosmic energy measurement. In other words it is in the very act of measurement which causes our inability to measure the “Dark energy of the quantum wave” in any direct way. The only hope if any to detect dark energy and utilize it in nuclear reactors is future development of sophisticated quantum wave non-demolition measurement instruments.

Müller cells are activated in response to retinal outer nuclear layer degeneration in rats subjected to simulated weightlessness conditions

A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.

The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease

Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

酚糖酯-免疫球蛋白M和鼻分泌物中麻风菌PCR检测在麻风流行病学中的应用

目的通过对流行乡村(同烘和南丘)麻风病患者、家内接触者及普通人群麻风菌感染的检测,评估实验流行病学对预测麻风病传播的意义。方法采用酚糖酯-酶联免疫吸附试验(PGL-ELISA)和检测鼻携带麻风菌的PCR方法,开展流行病学调查。结果(1)麻风病家内接触者的酚糖酯-免疫球蛋白M(PGL-IgM)阳性率和PCR检测的麻风菌鼻携带率分别为30.4%和23.1%;但PGL抗体阳性率在家内接触者和普通村民之间却无显著性差异。(2)两村普通村民的PGL-IgM阳性率,在统计学上无显著差异。然而,在<20岁的年龄组中,同烘村的PGL-IgM阳性率却显著高于南丘村。无论同烘或南丘村,PGL-IgM阳性率高峰均在<20岁的年龄组。随年龄的增加,阳性率逐渐下降。此外,女性的PGL-IgM阳性率高于男性。结论两村的新发现病人主要为年轻人,这与两村PGL-IgM阳性高峰位于<20岁年龄组相关。在<20岁的年龄组中,同烘村的PGL-IgM阳性率显著高于南丘村,除与同烘村患病率和发现率均高于南丘村相关,也与消除麻风病运动(LEC)后,同烘村仍有新病人出现有关。这一现象似乎支持麻风患病率与PGL-IgM阳性率相关。为评价麻风病的传播是否得到控制,以PGL的血清学仍是一种有用的方法。

对二羟基硼酰苯丙氨酸的^(99)Tcm标记及其生物分布

对 二羟基硼酰苯丙氨酸(BPA)由于具有在肿瘤处富集的性质而用于硼中子俘获治疗(BNCT)。按文献方法合成了BPA,并用99Tcm 对其标记,生成一种新的锝包合型螯合物BATO(Boronic acid adducts of techne tium dioxime)配合物,并进行了99Tcm DMG BPA配合物在小鼠体内的生物分布研究。实验结果表明,99Tcm DMG BPA可以选择性富集在肿瘤处,并且清除较慢,在肿瘤中的放射性活度明显高于肌肉和心、肺、血液等组织。随着时间的延长,肿瘤/正常组织的摄入比在不断增加。最大值出现在摄入后 4 h,这时的 R(肿瘤/肌肉)为6 0,R(肿瘤/血液)为4 5,R(肿瘤/心)为 6 0,R(肿瘤/肺)为 3 0,R(肿瘤/肝)为 0 41,R(肿瘤/肾)为0 134。通过分子轨道理论计算推测了99Tcm DMG BPA配合物可能的结构。

Likelihood and Quadratic Distance Methods for the Generalized Asymmetric Laplace Distribution for Financial Data

Maximum likelihood (ML) estimation for the generalized asymmetric Laplace (GAL) distribution also known as Variance gamma using simplex direct search algorithms is investigated. In this paper, we use numerical direct search techniques for maximizing the log-likelihood to obtain ML estimators instead of using the traditional EM algorithm. The density function of the GAL is only continuous but not differentiable with respect to the parameters and the appearance of the Bessel function in the density make it difficult to obtain the asymptotic covariance matrix for the entire GAL family. Using M-estimation theory, the properties of the ML estimators are investigated in this paper. The ML estimators are shown to be consistent for the GAL family and their asymptotic normality can only be guaranteed for the asymmetric Laplace (AL) family. The asymptotic covariance matrix is obtained for the AL family and it completes the results obtained previously in the literature. For the general GAL model, alternative methods of inferences based on quadratic distances (QD) are proposed. The QD methods appear to be overall more efficient than likelihood methods infinite samples using sample sizes n ≤5000 and the range of parameters often encountered for financial data. The proposed methods only require that the moment generating function of the parametric model exists and has a closed form expression and can be used for other models.

Modified constraint-induced movement therapy alters synaptic plasticity of rat contralateral hippocampus following middle cerebral artery occlusion

Modified constraint-induced movement therapy is an effective treatment for neurological and motor impairments in patients with stroke by increasing the use of their affected limb and limiting the contralateral limb.However,the molecular mechanism underlying its efficacy remains unclear.In this study,a middle cerebral artery occlusion(MCAO)rat model was produced by the suture method.Rats received modified constraint-induced movement therapy 1 hour a day for 14 consecutive days,starting from the 7^th day after middle cerebral artery occlusion.Day 1 of treatment lasted for 10 minutes at 2r/min,day 2 for 20 minutes at 2 r/min,and from day 3 onward for 20 minutes at 4 r/min.CatWalk gait analysis,adhesive removal test,and Y-maze test were used to investigate motor function,sensory function as well as cognitive function in rodent animals from the 1st day before MCAO to the 21^st day after MCAO.On the 21^st day after MCAO,the neurotransmitter receptor-related genes from both contralateral and ipsilateral hippocampi were tested by micro-array and then verified by western blot assay.The glutamate related receptor was shown by transmission electron microscopy and the glutamate content was determined by high-performance liquid chromatography.The results of behavior tests showed that modified constraint-induced movement therapy promoted motor and sensory functional recovery in the middle cerebral artery-occluded rats,but had no effect on cognitive function.The modified constraint-induced movement therapy upregulated the expression of glutamate ionotropic receptor AMPA type subunit 3(Gria3)in the hippocampus and downregulated the expression of the beta3-adrenergic receptor gene Adrb3 and arginine vasopressin receptor 1 A,Avprla in the middle cerebral artery-occluded rats.In the ipsilateral hippocampus,only Adra2 a was downregulated,and there was no significant change in Gria3.Transmission electron microscopy revealed a denser distribution the more distribution of postsynaptic glutamate receptor 2/3,which is an a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor,within 240 nm of the postsynaptic density in the contralateral cornu ammonis 3 region.The size and distribution of the synaptic vesicles within 100 nm of the presynaptic active zone were unchanged.Western blot analysis showed that modified constraint-induced movement therapy also increased the expression of glutamate receptor 2/3 and brain-derived neurotrophic factor in the hippocampus of rats with middle cerebral artery occlusion,but had no effect on Synapsin I levels.Besides,we also found modified constraint-induced movement therapy effectively reduced glutamate content in the contralateral hippocampus.This study demonstrated that modified constraint-induced movement therapy is an effective rehabilitation therapy in middle cerebral artery-occluded rats,and suggests that these positive effects occur via the upregulation of the postsynaptic membrane a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor expression.This study was approved by the Institutional Animal Care and Use Committee of Fudan University,China(approval No.201802173 S)on March 3,2018.