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To explore the role of beta-catenin in the pathogenesis of mesial temporal lobe epilepsy.Kainic acid-induced rat models of medial temporal lobe epilepsy was established. The expression of beta-catenin in the normal mice and the model mice were detected using Western blot analysis. The expression of beta-catenin at human hippocampus was detected using immunohistochemical analysis and immunofluorescence and compared between patients with non-hippocampal sclerosis temporal lobe epilepsy and those with hippocampal sclerosis epilepsy.The pathologies of model mice were similar with those in mice with hippocampal sclerosis temporal lobe epilepsy, demonstrating that the mice model was successfully established. Western blot analysis showed no significant difference of beta-catenin expression between normal mice and model mice. As shown by immunohistochemical analysis and immunofluorescence, beta-catenin expression in human hippocampus was also not significantly different between patients with temporal lobe epilepsy without hippocampal sclerosis and those with hippocampal sclerosis.Beta-catenin may not be involved in the development of hippocampal sclerosis of mesial temporal lobe epilepsy.

Background Paroxysmal dyskinesias (PDs), a clinically and genetically heterogeneous group of episodic movement disorders, include kinesigenic PD (PKD), exercise-induced PD (PED) and non-kinesigenic PD (PNKD). These disorders are all transmitted as autosomal dominant traits with incomplete penetrance. Several PD-related genetic disorders, including PKD and familial infantile convulsions with paroxysmal choreoathetosis (ICCA), mapped to the same region on chromosome 16. Independent genetic studies have recently revealed that PKD can be caused by loss-of-function mutations in the proline-rich transmembrane protein 2 gene ( PRRT2 ). We tested the hypothesis that other forms of PDs are also due to PRRT2 mutations. Methods/results The whole genomic region of PRRT2 was sequenced in six Han Chinese families and 15 sporadic cases of PD-related phenotypes. The previously reported mutation, c.649dupC (p.R217Pfs*7), was found in two families with PKD, one family with ICCA, one family with PNKD-like phenotype, and two sporadic cases with PED. In an additional ICCA family, a novel frameshift mutation, c.904dupG (p.D302Gfs*38), was identified. A missense mutation, c.913G→A (p.G305R), and a synonymous substitution, c.1011C→T (p.G337G), were also detected in two sporadic PKD cases. Conclusion This study shows that PKD, ICCA and some other PD-related phenotypes are part of the same phenotypic spectrum, caused by mutations in PRRT2 . This underscores the complexity of the phenotypic consequences of PRRT2 mutations.

International audience; In many decision problems, there are two levels of choice: The first one is strategic and the second is tactical. We formalize the difference between both and discuss the relevance of the bandit literature for strate- gic decisions and test the quality of different bandit algorithms in real world examples such as board games and card games. For exploration- exploitation algorithm, we evaluate the Upper Confidence Bounds and Exponential Weights, as well as algorithms designed for simple regret, such as Successive Reject. For the exploitation, we also evaluate Bern- stein Races and Uniform Sampling. As for the recommandation part, we test Empirically Best Arm, Most Played, Lower Confidence Bounds and Empirical Distribution. In the one-player case, we recommend Up- per Confidence Bound as an exploration algorithm (and in particular its variants adaptUCBE for parameter-free simple regret) and Lower Confi- dence Bound or Most Played Arm as recommendation algorithms. In the two-player case, we point out the commodity and efficiency of the EXP3 algorithm, and the very clear improvement provided by the truncation algorithm TEXP3. Incidentally our algorithm won some games against professional players in kill-all Go (to the best of our knowledge, for the first time in computer games).

To study the influence of lipopolysaccharide (LPS) on the permeability of rat brain microvascular endothelial cells (BMECs) and possible molecular mechanism.Monolayers of primary rat BMECs were separated and cultured, and then treated with (LPS group) or without LPS (control group). The barrier integrity was measured by transendothelial electrical resistance (TEER) assay. The degrees of RhoA activation were determined by Pull-down assay. The expression levels of p115RhoGEF, zonula occludens-1 (ZO-1), occludin and claudin-5 proteins were detected by Western blot analysis.The average TEER values of rat BMECs in the LPS group were 108.3±4.2 Ω•cm2 and 85.4±2.5 Ω•cm2 respectively 3 and 12 hrs after LPS treatment, which were significantly lower than that in the control group (159.0±8.6 Ω•cm2). Compared with the control group, the activity of RhoA started to increase 5 minutes after LPS treatment, and the expression of p115RhoGEF protein started to increase 1 hr after LPS treatment and the cellular protein levels of ZO-1, occludin and claudin-5 decreased significantly 3 hrs after LPS treatment in the LPS group (P0.05).LPS may activate the p115RhoGEF/RhoA pathway and decrease protein expression of ZO-1, occludin and claudin-5, resulting in an increased permeability of rat BMECs.

Genetic epilepsy with febrile seizures plus (GEFS+) is a familial autosomal dominant condition characterized by genetic heterogeneity. Five genes for GEFS+ identified in large families account for only a small proportion of families. Mutation in the majority of families with GEFS+ has not identified yet. The aim of our study is to search for the gene responsible for GEFS+ in three Chinese families by linkage analyses and a sequencing approach and to investigate the importance of coding and noncoding regions variations of four known GEFS+ genes (SCN1A, SCN1B, GABRG2 and SCN2A) in Chinese families. Results showed that a 6-cM candidate interval at 5q33-34 with a maximum LOD scores of 2.043 was identified in families B. Sequencing candidate gene GABRG2 and GABRA1 in this region did not identify a causative mutation. Moreover, no mutation was found in coding and noncoding regions of the four genes in three Chinese families. Besides excluding coding regions of four known GEFS+ genes, we also excluded the possibility of a mutation in the promoter, exon-intron boundaries, 5' untranslated regions (5' UTRs), and 3' UTRs of four known GEFS+ genes in three Chinese families. In conclusion, the present study demonstrates the heterogeneity of the etiologies of GEFS+. There are as yet undiscovered mechanisms underlying GEFS+.

This paper presents a developed ontology-based intelligent agent in Monte-Carlo Tree Search (MCTS) for the computer Go application. Unlike previous research, this paper employs features derived from professional Go players’ domain knowledge to transform them into the opening-book sequence and represent them by a computer Go ontology. Afterward, the domain experts validate the built ontology. The developed computer Go ontology has been verified through the invited games for computer Go programs playing against human Go players. The results show that the ontology can work effectively for the intelligent agent and computer Go application.

The purpose of this study was to assess weather the immortalized mouse brain endothelial cell line Bend.3 displays the comparative barrier characteristics as the primary brain microvascular endothelial cells (BEMC).Immortalized mouse brain endothelial cell line, Bend.3 cells were cultured in transwell inserts and their restrictive characteristics were assessed by transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) permeability assays. Western blot and direct fluorescent staining methods were used to detect the tight junction protein expression and F-actin distribution.The TEER in Bend.3 cells increased with the prolonged culture time and increased to 82.3+/-6.0 Omega cm2 10 days after culture, which was significantly higher than that 3 days after culture (37.3+/-3.1 Omega cm2; P0.05). There were significant differences in the permeability rates for HRP 3 and 10 days after culture (4.3+/-0.20)% vs (2.2+/-0.05)% (P0.05). Western blot indicated high level expression of tight junction proteins occludin and ZO-1 in Bend.3 cells 10 days after culture. F-actin was visualized around the cell membrane and presented scrobiculate linear fluorescence 10 days after culture.Bend.3 cells have similar barrier characteristics to BEMC, and their barrier function may reach to the best effect 10 days after culture.

To measure the normal values of a new type of posturography using inclinometer technique.A total of 98 normal persons, including 48 males and 50 females, aged 20 - 59, were measured. The messages of postural average sway angular velocity and the angle of deflection were recorded by an inclined sensor fixed at the waist. Four tests were conducted in opening and closing eyes respectively: standing upright, walking forward, walking forward and backward repeatedly and walking at original site. The subjects were grouped by age and gender. Group A, aged 20-39, had 54 persons. Group B, aged 40-59, had 44 persons. The statistical significance was analyzed by T test.The swaying extent in closing eyes was wider than that in opening eyes. The average sway angular velocities (degree/S, positive value: right and forward, negative value: left and backward) of male patients in the four tests in opening and closing eyes respectively were: 0.99, -0.35, 0.03, 0.02, 1.08, -0.36, 0.10, 0.02. Those of female patients were respectively: 1.04, -0.36, -0.01, 0.01, 1.22, -0.37, 0.04, 0.06. And those of patients in group A and B were respectively: 1.01, 0.41, -0.01, -0.01, 1.10, 0.26, -0.03, 0.03 and 1.02, -0.76, 0.03, 0.04, 1.20, -0.99, 0.17, 0.05. There was no statistical significance grouped by age and gender.The normal reference values are provided here. There is no difference between males and females. It may be applicable in all subjects of 20 - 59 yr. This instrument can quantify the results of walking test so as to evaluate the balance function of vestibo-spinal system more accurately.

To establish the normative data of sinusoidal harmonic acceleration test (SHAT) and evaluate the value of clinical application.One hundred and twenty normal persons, 21 Meniere's disease patients, 2 bilateral vestibular peripheral lesion patients, 15 unilateral vestibular peripheral lesion patients and 10 central lesion patients were tested with SHAT.The calibration time was longer in the older persons. The phase decreased with the frequency, and the gain increased with the frequency, but the reliability of the re-test of the phase was better in the lower frequency. The results of the 7 Meniere's disease patients without symptoms were normal, 14 patients post-attack revealed abnormal, 11 had phase abnormal, 3 had gain decrease, 10 revealed asymmetry and spontaneous nystagmus simultaneously, 8 patients had two parameters abnormal. The unilateral vestibular peripheral lesion patients showed 73% (11/15) phase abnormal, 67% (10/15) gain decrease and 40% (6/15) asymmetry, while 5/6 asymmetry patients had spontaneous nystagmus. The gain of the bilateral vestibular peripheral lesion patients showed severe decrease. The abnormal rate in central lesion patients were 70% (7/10) in phase, 20% (2/10) in gain and 40% (4/10) in asymmetry, but the patients with asymmetry had no spontaneous nystagmus.The normal range of the phase, gain and asymmetry of SHAT is in narrow bandwidth. The phase is the most important abnormal sign.

To study the etiologic genes of generalized epilepsy with febrile seizure plus (GEFS+).Peripheral blood samples were collected from 25 persons of 2 families, including 2 probands. DNA was extracted from the peripheral blood leukocytes using phenol-chloroform method. Ten microsatellite markers spanning the critical regions of SCN1B, SCN1A, SCN2A, and GABRG2 genes were genotyped for linkage analysis by the software LINKAGE v5.1. The two-point linkage relation was determined by LOD score defining the approximate position of etiologic genes of the 2 GEFS+ families. Mutation analysis of the candidate etiologic genes in all members of these 2 families was performed. Results No sharing allele was discovered among the several microsatellite markers flanking SCN1A, SCN2A, and SCN1B genes, and the involvement of these genes in these 2 families could be excluded. In the family named Tian, sharing alleles were discovered among the markers D5S820, D5S422, and D5S1403 flanking GABRG2 gene. The two-point LOD scores at theta = 0 were 0.67, 1.0, and 0.79 for the marker D5S820, D5S422, and D5S1403, thus indicating possible linkage. In the family named Di, sharing allele was discovered only in the marker D5S1403 flanking the GABRG2 gene. Sequence analysis was performed for nine exons of the GABRG2 gene in these 2 families. Three single nucleotide variations were discovered on the exon 5 (c.588 CT), exon 3 (c.604 CT), and noncoding region of the exon 7. No mutation change of the GABRG2 gene was observed in these 2 families.No evidence supports the causal relation between the SCN1B, SCN1A, SCN2A, and GABRG2 mutation and the etiologic genes in the two families with GEFS+. It is still not clear what is the common etiologic genes of GEFS+.

To study the changes of blood-brain barrier-tight junction (BBB-TJ) proteins ZO-1, occludin and actin following hypoxia-ischemia (HI) in order to explore the possible mechanism of permeability increasing of blood-brain barrier (BBB) induced by HI.BBB models were established by co-culture of cell ECV304 and astrocytes (AS) in vitro, then randomly assigned to control and HI groups. Transmission electron microscope was used to observe the changes of BBB-TJ. The distribution of actin was determined by direct-immunofluorescence microscope. Definite permeability of BBB models by 125I-BSA was detected by gamma events-per-unit-time meter. Expression of actin, ZO-1 and occludin was detected by Western blot.After 10-day culture, endothelial cells connected tightly, with plenty of TJ which was smooth, continuous and of high density, in the BBB models. After 5 hrs of HI, the TJ was opened with intercellular gaps formation. The direct immunofluorescence showed that the peripheral filament bands became blurred, the cell-cell junction loosened and fissure appeared in the HI group. The permeability of 125I-BSA in the HI group increased significantly compared with the control group (P0.01). Expression of ZO-1 decreased markedly, while expression of actin and occludin was not different in the HI group compared with the control group.The changes in occludin distribution and decreased expression of ZO-1 lead the reorganization of BBB-actin protein, which may be one of the mechanisms of permeability increasing of BBB following HI.

Bacterial meningitis is a kind of central nervous system infection with a high incidence, disability and fatality in children. Prompt diagnosis and treatment are associated with an improved prognosis. Low positive rate of bacterial cultures of the cerebrospinal fluid (CSF) makes it difficult to make a definite diagnosis. This experiment aimed to investigate a proteome profile of normal CSF of Chinese children by two-dimensional polyacrydamide gel electrophoresis (2-DE), and to sieve the disease-specific proteins of Staphylococcus epidermidis meningitis (SeM) to provide basis for early diagnosis and treatment of SeM.Four mL CSF samples were obtained respectively from SeM and normal children. The separated proteins with immobile pH gradient (IPG) 2-DE technology and protein spots were visualized by Coomassie Brilliant Blue staining. The stained 2-DE gels were scanned on the Imagescanner and pictures were obtained through Labscan software. The images were analyzed with PDQuest software and the differences of protein spots were compared between the SeM and normal children.Mean protein spots of the 2-DE gels were 438 and 425 in the SeM and normal groups respectively. Twenty-five protein spots only occurred in normal CSF and 12 spots only occurred in the SeM group. The expression of 6 protein spots showed up-regulation and that of 19 showed down-regulation in the SeM group compared with that in the normal group.A 2-DE profile of CSF proteome was successfully established in SeM and normal children through proteomic technique. By the differentiated analysis of these CSF 2-DE gels, the differences of CSF proteome profiles were found between SeM and normal children. Future analysis and identification of these spots will contribute to find out the disease specific proteins of SeM and to provide basis for early diagnosis and therapy of this disorder.

This paper investigates the inverse heat transfer problem of laminar forced convection within a circular pipe. The performances of two classical algorithms used in the whole domain function specification method (WDFSM) to obtain simultaneous estimates of the time-varying inlet temperature and outer-wall heat flux are compared. Additionally, this study proposes a modification to the linear assumption employed in the conventional WDFSM to improve its estimation performance. The WDFSM solution procedure is based on future temperature measurements at two different locations within the pipe flow. In the modified algorithm, the variations of the estimations at all time steps for various values of the future-time parameter are investigated, and if large variations in the slope of the function are detected at some time steps, the originally linear assumption for the variation of the unknowns is replaced with the assumption of a constant function at these time steps. Otherwise, the estimates at the other time steps are calculated using the linear assumption. The numerical results confirm that the proposed algorithm yields slightly more accurate estimates of the unknowns than the two classic algorithms.

To explore the effects of the ultrastructural features of sprouted mossy fiber synapses in the mechanism of temporal lobe epilepsy. To explore the correlation between axon guidance molecule-netrin-1 gene expression and mossy fiber synaptic reorganization.Sixty-one SD rats underwent intraperitoneal injection of lithium chloride and pilocarpine to establish models of status epilepticus characterized with temporal lobe epilepsy. Nineteen rats were used as controls. One, 2, and 4 weeks after the injection, a certain numbers of rat were killed with their brains taken out. The sprouted mossy fiber synaptic terminals were labeled by Timm histochemistry and the ultrastructure of new synapses were observed by electron microscopy. By in situ hybridization, the mRNA expression of netrin-1 gene was observed.The sprouted mossy fiber synapses in epileptic rats most commonly formed asymmetric synapses with dendritic spines and occasionally with granule cell somata. Seven days after the injection, up-regulation of netrin-1 mRNA expression was seen in the dentate granule cell layers of hippocampus and continued to 4 weeks after the injection. The time course of the increase of netrin-1 mRNA in the dentate granule cell layers was correlated with the time course of mossy fiber sprouting and synaptic reorganization in hippocampus.The ultrastructural features of sprouted mossy fiber synapses support the viewpoint that the reorganization of synapses prominently involves the formation of recurrent excitatory circuits. The axon guidance molecule- netrin-1 plays an important role in the process of mossy fiber axonal outgrowth and synaptogenesis in the hippocampal dentate gyrus.

To analyze the risk factors for the prognosis of frontal lobe epilepsy in order to predict the refractory frontal lobe epilepsy early, so as to provide theoretic basis for rational therapy early.Forty-seven patients with medically refractory frontal lobe epilepsy and 92 patients with medically controllable epilepsy, totally 139 patients, underwent epidemiological savery, cranial CT or MRI, and video-electroencephalography (VEEG). Single factor analysis and Logistic stepwise regression analysis were done to analyze the relationship between the influential factors and the prognosis of disease.Single factor analysis showed that the factors including earlier onset age, longer duration before taking reasonable medicine, more frequent seizure (1 time/day), asymmetric tonic seizures, seizures with hypermotor automatism, secondary generally tonic-clonic seizures, and a past history of taking medicine, exerted adverse effects on the prognosis of frontal lobe epilepsy (all P0.05). Logistic stepwise regression analysis screened out such factors including duration before taking reasonable medicine (OR = 1.384, 95% CI 1.133 - 1.689) and seizure frequency (OR = 6.512, 95% CI 1.637 - 25.911) as independent predictors for the prognosis of frontal lobe epilepsy.Long duration before taking reasonable medicine and frequent seizure onset are important risk factors for refractory frontal lobe epilepsy. It is possible to improve the prognosis of frontal lobe epilepsy by making a definite diagnosis and beginning rational therapy early.

To study the mutual interaction of vestibular afferent nervous system and vestibular efferent nervous system in vestibular compensation.Build up animal model of vestibular compensation by destroying single side vestibule of wistar rat. In the study the rats were divided into 3 groups: Group A 16 normal rats; Group B 15 rats, after 7 days of left vestibular damage; Group C 7 rats 3 months after left vestibular damage; and Group D 7 rats, after vestibular compensation. Electromyography of the rats was recorded and the expression of calcitonin gene relative peptide (CGRP), choline acetyltransferase (AChT) and Na-K-ATPase were investigated in efferent vestibular nervous system.Electric potential activity of muscles of injury side decreased while that of the opposite side increased. In animals of vestibular compensation electric potential of bilateral musculus longus capitis at quiescent stage recovered symmetrically. CGRP positive cells of efferent vestibular nervous system increased bilaterally, and their activity enhanced, especially obvious at the acute stage. AChT positive cells of injury side of efferent vestibular nervous system decreased, but reaction degree of two sides enhanced. Reaction degree of the opposite side enhanced obviously at the stage of vestibular compensation. Expression of Na-K-ATPase mRNA of the same side was lower, but vestibular signal of the opposite side enhanced, clinically head and neck inclined obliquely by means of medial fasciculus of tractus vestibulospinalis. Months later, vestibular signal of the same side enhanced, and that of the opposite side enhanced also, clinical symptoms improved slightly. At the vestibular compensation stage, expression of Na-K-ATPase mRNA of the same side enhanced, and it was same as that of the opposite side or much higher, clinically it reached vestibular compensation.Comprehensive effect of the above results maybe as follows: Efferent vestibular nervous system inhibited afferent signal of the opposite vestibule, and it modulated excitement of vestibular center of the same side, and it worked in the complicated mechanisms of vestibular compensation. CGRP may have facilitation function to the vestibular afferent signal of injury side. While Ach improved vestibule compensation by means of inhibition of vestibule excitement of the healthy side.

Lennox-Gastaut syndrome (LGS) is one of the most severe and refractory form of childhood epilepsy. The purpose of this study was to investigate the clinical and EEG characteristics of patients with LGS.Sixty-two patients with LGS, including 37 males and 25 females, were followed-up regularly per three months or per six months, therapy was adjusted according to the changes in seizures and EEG, and the clinical data were analyzed in detail.The onset occurred between the age of 8 months and 12 years, with the peak at 1-4 years of age, accounting for 61%; a late onset which occurred after 8 years of age, was unusual. Furthermore, one patient who developed LGS at the age of 13 years and remained to have all the features of seizures and EEG at 35 years of age was identified as adult's LGS. Forty-three patients were classified as symptomatic, perinatal events were the predominant factors in this group. The others were cryptogenic. It was noted that 11 cases had a history of West syndrome. A transformation process from West syndrome to LGS was observed in another 7 cases. Every patient had two or more seizure types during the course of the disease; tonic seizure, atypical absence seizure, head drop or sudden falls were the characteristic types. The degree of mental deficit was variable from slight to profound deterioration, but mental and behavioral disturbances existed in every case as a rule. In all cases electroencephalogram (EEG) background was abnormal and consisted of diffuse slow spike-and-waves (1-1.5CPS), predominant in frontal and temporal regions. Twenty-four cases had the polyspike-wave. Bursts of fast rhythms (10-14CPS) were observed in 29 patients during sleep. The choice of antiepileptic drugs (AEDs) was based on the seizure types; routinely, 2 or more kinds of AEDs were used in combination, the classic drugs, valproate and clonazepam were firstly recommended; the other drugs, such as lamotrigine and topiramate that are used as add-on therapy were further consideration. Although the total effect was not satisfactory, the severity and frequency of seizures in almost all cases had lessened to some extent.LGS shows diverse manifestations; comprehensive diagnosis is crucial, active and efficacious treatment can improve the mental and behavioral development and prognosis as a whole.

To investigate the efficacy of posturography with inclinometer and platform with global bottom to make the subjects contact the ground almost at one point in the evaluation of body balance function.The body balance function of 100 normal persons, 50 males and 50 females, aged 21 approximately 50, and 87 patients with peripheral vertigo due to semicircular canal palsy, aged 20 approximately 60, was measured with a new type of posturograph with inclinometer and platform with global bottom developed by the authors. The subjects with an inclination-sensor being fixed at the waist were asked to adopt four postures during the measurement: standing on the ground with eyes opened (test 1), standing on the ground with the eyes closed (test 2), standing on the platform with the eyes opened (test 3), and standing on the platform with the eyes closed (test 4).The measurement of the normal persons showed the average values of body sway angle velocity were 0.57 +/- 0.24 d/s in test 1, 0.70 +/- 0.18 d/s in test 2, 1.16 +/- 0.32 d/s in test 3, and 2.67 +/- 0.70 d/s in test 4. Sixty-two out of the 87 patients (71.26%) showed abnormality in one or more than one of the 4 tests with a value more than x +/- 2s of the normal value, among them 7 showed abnormal value in test 1, 14 in test 2, 16 in test 16, and 56 in test 4. Two weeks after the onset of vertigo, 55 out of the 87 patients showed abnormal values by this examination.Posturography with inclinometer and platform with global bottom is effective on evaluation of balance function, In particular, the test of standing on the platform with the eyes closed effectively reflects the vestibulospinal reflex.

To explore the management of thoracic spinal trauma (TST) associated with closed thoracoabdominal injuries (CTAI).A retrospective study was made on 259 patients with TST admitted to our department as an emergency treatment from January 1996 to June 2001. We summarized the clinical features of TST associated with CTAI.Among 259 patients with thoracic spinal trauma, 112 were associated with CTAI. Traffic accident was the most common cause. The force causing upper TST was more violent than that causing the lower. Pulmonary complications were the leading cause of death in this group. Surgery could not improve neurological function for completely paraplegic patients.The reason that upper TST has the tendency to be associated with CTAI is its special anatomical feature. Routine ultrasonic examination can avoid misdiagnosis of latent closed abdominal injuries associated with spinal injury. The presence of potential injuries, especially CTAI, should be considered when deciding whether or not to perform surgery early.