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Aegilops species represent the most important gene pool for breeding bread wheat (Triticum aestivum). Thus, understanding the genome evolution, including chromosomal structural rearrangements and syntenic relationships among Aegilops species or between Aegilops and wheat, is important for both basic genome research and practical breeding applications. In the present study, we attempted to develop subgenome D-specific fluorescence in situ hybridization (FISH) probes by selecting D-specific oligonucleotides based on the reference genome of Chinese Spring. The oligo-based chromosome painting probes consisted of approximately 26 000 oligos per chromosome and their specificity was confirmed in both diploid and polyploid species containing the D subgenome. Two previously reported translocations involving two D chromosomes have been confirmed in wheat varieties and their derived lines. We demonstrate that the oligo painting probes can be used not only to identify the translocations involving D subgenome chromosomes, but also to determine the precise positions of chromosomal breakpoints. Chromosome painting of 56 accessions of Ae. tauschii from different origins led us to identify two novel translocations: a reciprocal 3D-7D translocation in two accessions and a complex 4D-5D-7D translocation in one accession. Painting probes were also used to analyze chromosomes from more diverse Aegilops species. These probes produced FISH signals in four different genomes. Chromosome rearrangements were identified in Aegilops umbellulata, Aegilops markgrafii, and Aegilops uniaristata, thus providing syntenic information that will be valuable for the application of these wild species in wheat breeding.

Simple encapsulation of 3 nm gold nanoparticles in ordered mesoporous carbon with large pores of 17 nm and thick pore walls of 16 nm was achieved by a metal-ligand coordination assisted-self-assembly approach. Polystyrene-block-polyethylene-oxide (PS-b-PEO) diblock copolymer with a large molecular weight of the PS chain and mercaptopropyltrimethoxysilane were used as the template and the metal ligand, respectively. Small-angle X-ray scattering, X-ray diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy showed that monodispersed aggregation-free gold nanoparticles approximately 3 nm in size were partially embedded in the large open pore structure of the ordered mesoporous carbon. The strong coordination between the gold species and the mercapto groups and the thick porous walls increased the dispersion of the gold nanoparticles and essentially inhibited particle aggregation at 600 °C. The gold nanoparticles in the ordered mesoporous carbon are active and stable in the reduction of nitroarenes involving bulky molecules using sodium borohydride as a reducing agent under ambient conditions (30 °C) in water. The large interconnected pore structure facilitates the mass transfer of bulky molecules.

Fusarium head blight (FHB), caused by Fusarium graminearum, is a devastating disease in wheat (Triticum aestivum) that results in substantial yield losses and mycotoxin contamination. Reliable genetic resources for FHB resistance in wheat are lacking. In this study, we characterized glycoside hydrolase 12 (GH12) family proteins secreted by F. graminearum. We established that two GH12 proteins, Fg05851 and Fg11037, have functionally redundant roles in F. graminearum colonization of wheat. Furthermore, we determined that the GH12 proteins Fg05851 and Fg11037 are recognized by the leucine-rich-repeat receptor-like protein RXEG1 in the dicot Nicotiana benthamiana. Heterologous expression of RXEG1 conferred wheat responsiveness to Fg05851 and Fg11037, enhanced wheat resistance to F. graminearum and reduced levels of the mycotoxin deoxynivalenol in wheat grains in a Fg05851/Fg11037-dependent manner. In the RXEG1 transgenic lines, genes related to pattern-triggered plant immunity, the salicylic acid, jasmonic acid, and anti-oxidative homeostasis signaling pathways were upregulated during F. graminearum infection. However, expression of these genes was not significantly changed during infection by the deletion mutant ΔFg05851/Fg11037, suggesting that the recognition of Fg05851/Fg11037 by RXEG1 triggered plant resistance against FHB. Moreover, introducing RXEG1 into three other different wheat cultivars via crossing also conferred resistance to F. graminearum. Expression of RXEG1 did not have obvious deleterious effects on plant growth and development in wheat. Our study reveals that N. benthamiana RXEG1 remains effective when transferred into wheat, a monocot, which in turn suggests that engineering wheat with interfamily plant immune receptor transgenes is a viable strategy for increasing resistance to FHB.

Basing on the unique advantages of uniform and rapid volumetric heating of microwave irradiation, microwave hydrothermal method has been used to fabricate Br/Bi2WO6 for streamlining the preparation procedure and enhancing the photocatalytic activity. The results indicated that Br was successfully introduced into the lattice of Bi2WO6, which improved the absorption ability of visible light. Moreover, Br/Bi2WO6 exhibited smaller size and the enhanced separation efficiency of photogenerated carriers as compared with Bi2WO6. Br/Bi2WO6 exhibited superior reusability and photocatalytic activity of Rhodamine B (RhB) and tetracycline (TC). Furthermore, the enhanced photocatalytic activity of Br/Bi2WO6 was mainly ascribed to the increased specific surface area, wide UV-vis light absorption range, and high separation efficiency of photogenerated charge carriers originating from Br doping and microwave heating.

Fructose 1,6-bisphosphatase (FBPase) has attracted substantial interest as a target associated with cancer and type 2 diabetes. Herein, we found that disulfiram and its derivatives can potently inhibit FBPase by covalently binding to a new C128 allosteric site distinct from the original C128 site in APO FBPase. Further identification of the allosteric inhibition mechanism reveals that the covalent binding of a fragment of 214 will result in the movement of C128 and the dissociation of helix H4 (123-128), which in turn allows S123 to more easily form new hydrogen bonds with K71 and D74 in helix H3 (69-72), thereby inhibiting FBPase activity. Notably, both disulfiram and 212 might moderately reduce blood glucose output in vivo. Therefore, our current findings not only identify a new covalent allosteric site of FBPase but also establish a structural foundation and provide a promising way for the design of covalent allosteric drugs for glucose reduction.

For the accuracy requirements of commodity image detection and classification, the FPN network is improved by DPFM ablation and RFM, so as to improve the detection accuracy of commodities by the network. At the same time, in view of the narrowing of channels in the application of traditional MWI-DenseNet network, a new GTNet network is proposed to improve the classification accuracy of commodities.The results show that at different levels of evaluation indexes, the dpFPN-Netv2 algorithm improved by DPFM + RFM fusion has higher target detection accuracy than RetinaNet-50 algorithm and other algorithms. And the detection time is 52 ms, which is significantly lower than 90 ms required for RetinaNet-50 detection. In terms of target recognition, compared with the traditional MWI-DenseNet neural network, the computation amount of the improved MWI DenseNet neural network is significantly reduced under different shunt ratios, and the recognition accuracy is significantly improved. The innovation of this study lies in improving the algorithm from the perspective of target detection and recognition, so as to change the previous improvement that only can be made in a single way.

In this paper we are concerned with the plane wave method for the discretization of time-harmonic Maxwell’s equations in three dimensions. As pointed out in Hiptmair et al. (Math. Comput. 82 (2013) 247–268), it is difficult to derive a satisfactory L2 error estimate of the standard plane wave approximation of the time-harmonic Maxwell’s equations. We propose a variant of the plane wave least squares (PWLS) method and show that the new plane wave approximations yield the desired L2 error estimate. Moreover, the numerical results indicate that the new approximations have sightly smaller L2 errors than the standard plane wave approximations. More importantly, the results are derived for more general models in inhomogeneous media.

The author briefly describes the business philosophy and recycling project of Guangzhou medicine, points out the current opportunities and Breakthrough Strategies, studies them, obtains the corresponding methods and results through data analysis, sorts out the problems we need to improve, gives some suggestions and programs, and formulates a series of marketing programs to realize one by one.

Basing on the unique advantages of uniform and rapid volumetric heating of microwave irradiation, microwave hydrothermal method has been used to fabricate Br/Bi

De novo drug design actively seeks to use sets of chemical rules for the fast and efficient identification of structurally new chemotypes with the desired set of biological properties. Fragment-based de novo design tools have been successfully applied in the discovery of noncovalent inhibitors. Nevertheless, these tools are rarely applied in the field of covalent inhibitor design. Herein, we present a new protocol, called Cov_FB3D, which involves the in silico assembly of potential novel covalent inhibitors by identifying the active fragments in the covalently binding site of the target protein. In this protocol, we propose a BA-SAMP strategy, which combines the noncovalent moiety score with the X-Score as the molecular mechanism (MM) level, and the covalent candidate score with the PM7 as the QM level. The synthetic accessibility of each suggested compound could be further evaluated with machine-learning-based synthetic complexity evaluation (SCScore). An in-depth test of this protocol against the crystal structures of 15 covalent complexes consisting of BTK inhibitors, KRAS inhibitors, EGFR inhibitors, EphB1 inhibitors, MAGL inhibitors, and MAPK inhibitors revealed that most of these inhibitors could be de novo reproduced from the fragments by Cov_FB3D. The binding modes of most generated reference poses could accurately reproduce the known binding mode of most of the reference covalent adduct in the binding site (RMSD ≤ 2 A). In particular, most of these inhibitors were ranked in the top 2%, using the BA-SAMP strategy. Notably, the novel human ALDOA inhibitor (T1) with potent inhibitory activity (0.34 ± 0.03 μM) and greater synthetic accessibility was successfully de novo designed by this protocol. The positive results confirm the abilities of Cov_FB3D protocol.

Fructose-1,6-bisphosphatase (FBPase), as a key rate-limiting enzyme in the gluconeogenesis (GNG) pathway, represents a practical therapeutic strategy for type 2 diabetes (T2D). Our previous work first identified cysteine residue 128 (C128) was an important allosteric site in the structure of FBPase, while pharmacologically targeting C128 attenuated the catalytic ability of FBPase. Herein, ten approved cysteine covalent drugs were selected for exploring FBPase inhibitory activities, and the alcohol deterrent disulfiram displayed superior inhibitory efficacy among those drugs. Based on the structure of lead compound disulfiram, 58 disulfide-derived compounds were designed and synthesized for investigating FBPase inhibitory activities. Optimal compound 3a exhibited significant FBPase inhibition and glucose-lowering efficacy in vitro and in vivo. Furthermore, 3a covalently modified the C128 site, and then regulated the N125-S124-S123 allosteric pathway of FBPase in mechanism. In summary, 3a has the potential to be a novel FBPase inhibitor for T2D therapy.

Chromosome painting is a useful technique for distinguishing specific chromosomes (fragments), elucidating the genetic relationships of different genomes or chromosomes, and identifying chromosomal rearrangements. The development of chromosome- or genome-specific probes is fundamental for chromosome painting. The possibility for developing such probes specifically painting homoeologous chromosomes in allopolyploid species has been questioned since that chromosomes belonging to the same homoeologous group share highly conserved sequences. In the present study, we attempted to construct a wheat chromosome 4D-specific oligo probe library by selecting 4D-specific sequences in reference genome of common wheat cv. Chinese Spring (CS, 2n = 6x = 42, AABBDD). The synthesized library contains 27,392 oligos. Oligo painting using the probe library confirmed its specificity, shown by that only chromosome 4D could be painted in three wheat genotypes and CS nulli-tetrasomic line N4AT4D. Oligo painting was successfully used to define the 4D breakpoints in CS deletion lines involving 4D and two wheat-Haynaldia villosa 4D–4V translocation lines. Thirteen wheat relatives and a Triticum durum-H. villosa amphiploid were used for oligo painting. Except the 4D in two Aegilops tauschii accessions, the 4M in Ae. comosa and 4U in Ae. umbellulata could be painted. In tetraploid Ae. ventricosa, both 4D and 4M could be painted; however, the signal intensity of 4M was less compared with 4D. No painted chromosome was observed for the other alien species. This indicated that the relationship among D/M/U was closer than that among D/A/B as well as D with genomes H/R/Ss/Sc/Y/P/N/J. Our successful development of 4D-specific oligo probe library may serve as a model for developing oligo probes specific for other homoeologous chromosomes.

Tetracycline (TC) and ciprofloxacin (CIP) cause serious environmental and health issues upon their uncontrolled release to the aquatic system and hence their control required serious attention. In this study, adsorption and desorption performances of TC and CIP by sodium carboxymethylcellulose (CMC) and polyethyleneimine (PEI) modified magnetic bentonite (MBCP) were explored. It was found that active functional groups such as –COOH, –OH and –NH2 loaded on the surface of MBCP increased the selective adsorption performance of MBCP for TC and CIP. Meanwhile, MBCP had superior adsorption performance in a wide pH range, magnetic separation capability and good regeneration. Based on the adsorption kinetics, isotherm, pHPZC, FE–SEM, TEM, FT–IR, XRD, BET, XPS and VSM results, the mechanisms of MBCP adsorption and desorption were investigated which mainly involved electrostatic interaction, pores deposition, complexation and ions exchange phenomena. MBCP was realized higher adsorption capacity for TC (476 mg/g), and CIP (457 mg/g) than MB (300 and 270 mg/g, respectively). This study provides important reference information for the fabrication of MBCP as a novel and promising adsorbent for the remediation of antibiotics from wastewater on the industrial level.

Background The present study was intended to investigate the protective effect of estradiol against Parkinson’s disease through the use of rotenone-induced neurotoxicity model. Methods To define the effect on the behavioral function, Tail suspension test, morris water maize test and cylinder tests were performed. Several biochemical and histological markers related to Parkinson’s disease was determined in animal and cell culture models. To evaluate the effect of estradiol on the cellular architecture in rotenone-induced brain tissue, the histopathological examination was carried out by using Haemotoxylin and Eosin staining. Moreover, estradiol effect was also been investigated for its protective effect against Parkinson’s disease using cell culture model with use of brain endothelial cells. The flowcytometric analysis was carried out to measure apoptosis in cell culture model. Results The abnormal level of antioxidant enzymes and lipid peroxidation were regulated toward the normal intensity under the influence of estradiol. Furthermore, intracellular ROS level and apoptosis were found to be reduced following estradiol treatment. During the 6-OHDA induced PD, the level of antioxidant marker such as GSH, ROS and TRAP, found to be significantly modulated by the estradiol. Conclusion In view of the above results, it may be suggested that the estradiol may be as a useful therapeutic agent against rotenone-induced neurotoxicity such as Parkinson’s disease.

MicroRNAs (miRNAs/miRs) are a class of conserved non-coding endogenous small regulatory RNAs that regulate target gene expression by binding to the 3′-untranslated region of target mRNAs in a base-pairing manner, resulting in repression of transcription or degradation of target mRNAs. It has been demonstrated previously that the abnormal expression of miRNAs is involved in the carcinogenesis and progression of cervical cancer. The aim of the present study was to investigate the expression, biological functions and underlying molecular mechanisms of miR-195 in cervical cancer. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of miR-195 in cervical cancer tissues and cell lines. Following transfection, an MTT assay, cell migration and invasion assays, western blot analysis and a dual-luciferase reporter assay were performed in human cervical cancer cells. In the present study, it was identified that miR-195 was downregulated in cervical cancer tissues and cell lines. Additionally, upregulation of miR-195 and knockdown of hepatoma-derived growth factor (HDGF) inhibited proliferation, migration and invasion of cervical cancer cells. Furthermore, a dual-luciferase reporter assay identified that HDGF was a direct target gene of miR-195. RT-qPCR and western blot analysis demonstrated that miR-195 mimic inhibited HDGF expression at the mRNA and protein levels, whereas miR-195 inhibitor enhanced HDGF expression at the mRNA and protein levels. These results indicated that miR-195 targeted HDGF to inhibit the behavior of tumors in cervical cancer. These results also suggested that miR-195 was a potential therapeutic biomarker of cervical cancer.

Fructose-1,6-bisphosphatase (FBPase) is an essential enzyme of GNG pathway. Significant advances demonstrate the FBPase plays a critical role in treatment of diabetes. Numerous FBPase inhibitors were developed by targeting AMP site, nevertheless, none of these inhibitors has exhibited suitable potency and druggability. Herein, a new allosteric site (C128) on FBPase was discovered, and several nitrostyrene compounds exhibiting potent FBPase inhibitions were found covalently bind to C128 site on FBPase. Mutagenesis suggest that C128 is the only cysteine that can influence FBPase inhibition, the N125-S124-S123 pathway was most likely involved in allosteric signaling transmission between C128 and active site. However, these nitrostyrenes may bind with multiple cysteine besides C128 in FBPase. To improve pocket selectivity, a series of novel compounds (14a-14n) were re-designed rationally by integrating fragment-based covalent virtual screening and machine-learning-based synthetic complexity evaluation. As expected, the mass spectrometry validated that the proportion of title compounds binding to the C128 in FBPase was significantly higher than that of nitrostyrenes. Notably, under physiological and pathological conditions, the treatment of compounds 14b, 14c, 14i or 14n led to potent inhibition of glucose production, as well as decreased triglyceride and total cholesterol levels in mouse primary hepatocytes. We highlight a novel paradigm that molecular targeting C128 site on FBPase can have potent hypoglycemic effect.

In this paper we are concerned with numerical methods for nonhomogeneous Helmholtz equations in inhomogeneous media. We design a least squares method for discretization of the considered Helmholtz equations. In this method, an auxiliary unknown is introduced on the common interface of any two neighboring elements and a quadratic subject functional is defined by the jumps of the traces of the solutions of local Helmholtz equations across all the common interfaces, where the local Helmholtz equations are defined on elements and are imposed Robin-type boundary conditions given by the auxiliary unknowns. A minimization problem with the subject functional is proposed to determine the auxiliary unknowns. The resulting discrete system of the auxiliary unknowns is Hermitian positive definite and so it can be solved by the PCG method. Under some assumptions we show that the generated approximate solutions possess almost the optimal error estimates with little "wave number pollution". Moreover, we construct a substructuring preconditioner for the discrete system of the auxiliary unknowns. Numerical experiments show that the proposed methods are very effective for the tested Helmholtz equations with large wave numbers., 34 pages

Objectives: This study was intended to investigate whether treatment with resveratrol and melatonin alone or in combination can exert neurorestorative effects in a rat model of vascular dementia. Methods: Briefly, male Wistar rats were subjected to permanent bilateral common carotid artery occlusion (BCCAO) by surgery. After 4 weeks, the cognitive deficits were assessed using the Morris water maze and novel object recognition tests. The biochemical parameters of oxidative stress and inflammation were also assessed. Results: Rats in the BCCAO group showed cognitive deficits, accompanied by oxidonitrosative stress, neuroinflammation, and a reduction in brain-derived neurotrophic factor (BDNF) in the hippocampus region. Moreover, the acetylcholinesterase activity in the hippocampus was found to be increased in the BCCAO group compared to the sham group. The 4-week treatment with melatonin (10 mg/kg) and resveratrol (20 mg/kg) alone and in combination (melatonin 5 mg/kg and reseveratrol 10 mg/kg) caused a significant improvement in the cognitive deficits induced by BCCAO, accompanied by a reversal of oxidonitrosative stress, neuroinflammation, and BDNF depletion in the hippocampus region. Additionally, the treatment with melatonin and resveratrol significantly decreased acetylcholinesterase activity compared to in the BCCAO group. Melatonin and resveratrol ameliorated the BDNF expression of hippocampal protein. Conclusion: These results emphasize that coadministration of melatonin and resveratrol can be beneficial in BCCAO-induced vascular dementia through changes in BDNF expressions.

Fructose-1, 6-bisphosphatase (FBPase) has been regarded as an attractive drug target to control blood glucose against Type 2 diabetes (T2D). In this study, by using the strategy of pharmacophore-based virtual screening, a novel scaffold inhibitor targeted the AMP allosteric site of human liver FBPase were screened, their inhibitory activities were further tested. The experimental results showed that compound H27 exhibited high inhibitory activities with the IC50 value of 5.3 μM. Therefore, compound H27 was chosen as the probe molecule, it's possible binding conformation targeted into FBPase was identified by using DOX2.0 strategy. The importance of key residues (T27, T31, K112 and R140) in allosteric site of FBPase for the binding inhibitors were validated by mutation experiments. The agreement between theory and experiment suggest that the interactional information of FBPase and inhibitors (H27) were reliable. On basis of these rational interactional information, the compound H29 was further designed to exhibit more potential FBPase inhibition (IC50 = 2.5 μM).

This paper addresses the problem of asymmetric flange wear of a particular type of 3-axle (2C 0 -type) locomotive that runs on the Chinese railway system. In particular, the influence on wheelset asymmetric wear of errors in the longitudinal location of the journal box is examined. Based on a 2C 0 -type locomotive dynamics model, the influence of the journal positioning deviation at each wheelset on wheelset lateral displacement and wheelset deflection direction within the same bogie have been researched. Simulation results indicate that a positioning deviation at the first wheelset has a great effect on the lateral displacement of the first wheelset, whereas deviations at the middle and the third wheelset have a great influence on the lateral displacement of the middle wheelset and less influence on other wheelsets. When a positioning deviation exists in two wheelsets at the same time, an anti-phase deviation will have a greater influence and more easily produce asymmetric flange wear than a same-phase positioning deviation. This study suggests that asymmetric flange wear can be minimised by eliminating or decreasing positioning deviations of wheelset journal boxes.

This paper discusses the mechanism responsible for the formation of polygon-shaped wheels; the aim is to solve the problem of their occurrence on subway vehicles. This phenomenon occurs mainly as a result of wheel/rail vertical forces created by the vibration of the wheelset over several complete revolutions of the wheel. In addition, a relationship linking the phase angle between two adjacent vertices, the main vibration frequency and running speed of the polygonal wheel is derived. Then, considering a subway vehicle that is powered by a linear induction motor and applying the multi-body system dynamics model, the main frequency of the wheel/rail vertical force under various running speeds is investigated. Analysis of the speed and main frequency value of a subway vehicle covered in this study revealed that a polygonal wheel with nine vertices can be generated in the speed range 72 to 80 km/h.

The influence of the wheel axle bending stiffness to the wheel/rail contact dynamic force and wheelset vertical vibration of the linear metro vehicle on a straight track was investigated. Based on a vehicle dynamic model and two kinds of elastic wheelset models, a comparison was carried out between the wheelset vertical vibration and the wheel/rail vertical force. Simulation results showed that the wheelset vibration and the wheel/rail vertical force of the elastic wheelset model were different with that of the rigid wheelset model; this was due to the BM3000 type wheelset not having high enough bending stiffness. In contrast, the result of the elastic wheelset model of the wheelset of the Beijing metro railway vehicle was quite similar to the results of the rigid model since a larger bending stiffness was used. Consequently, the wheelset vibration and wheel/rail vertical force can be decreased by increasing the wheel axle bending stiffness which will improve wheel/rail dynamic contact conditions. First published online:16 Oct 2013

In this paper, a train dynamic model was developed to study the dynamic performance of heavy haul locomotives, taking into account the use of different coupler and buffer systems under conditions of severe longitudinal coupler compressive forces. The model consists of four locomotives each having 38 independent degrees of freedom and one dummy freight vehicle connected to each other by couplers and buffers. Simulation results showed that the longitudinal coupler compressive forces withstood by large rotation angle couplers with coupler shoulders were larger than those withstood by small rotation angle couplers. The results obtained for the large rotation angle coupler model showed that it had higher safety curve negotiation speeds. Due to the smaller static impedance, it was found that large capacity elastic clay (or cement) buffers cannot satisfy the requirement of heavy haul locomotives during cycle braking in long heavy downgraded tracks; the use of friction clay buffers can solve this problem.

We recently found that TMPRSS2:ERG fusion genes and PTEN loss, which are common in Western prostate cancers are infrequent in Chinese cases. As previous studies indicated a higher frequency of RAS and BRAF mutation rates in Eastern Asian than in Western prostate cancers and fusion genes involving the RAF family genes BRAF and RAF1 were recently identified in prostate cancer in the American population, we investigated BRAF and RAF1 alterations in Chinese prostate cancer. Using fluorescence in situ hybridization, we found that BRAF was truncated in five of 200 informative Chinese cases (2.5%) and that RAF1 was truncated in three of 204 informative cases (1.5%) and genomic rearrangements of these genes were significantly correlated with high Gleason scores (>7; P < 0.01) and have a trend to appear in high clinical stage disease. A high frequency of BRAF and RAF1 copy number gain was found (29 and 15%, respectively). BRAF copy number gain in Chinese cancers was significantly higher than in UK cases (9.2%)(P < 0.001) and correlated with a number of clinical parameters. High-level expression of BRAF was found by immunohistochemistry in Chinese cancer samples compared with adjacent nonmalignant epithelial cells, which was correlated with high BRAF copy number. We also identified KRAS codon 12 mutations in three of 96 Chinese cases, no BRAF V600E mutations were observed. Our finding suggests that the activation of the RAS/RAF/MEK/ERK pathway may be frequent in Chinese prostate cancer, with RAF gene copy number gain potentially being the main contributor. (c) 2012 Wiley Periodicals, Inc.

To investigate ALK genomic rearrangements and expression in prostate cancer, and their clinical implications.Two hundred and eighty-one cases of prostate cancer were included. ALK gene rearrangements were assessed by FISH in all cases, and ALK protein expression was assessed by immunohistochemistry in 191 cases.The ALK gene was truncated (mostly 5' deletion) in 18 of 281 (6.4%) cases. EML4-ALK fusion gene was not detected. Genomic rearrangement of ALK gene was not statistically associated with Gleason score, age, TNM or baseline PSA level (P0.05). In all 18 cases, there were nuclear expression of ALK protein; in 12 cases, the expression was seen in 5%-30% of the tumor cells, and in the remaining 6 cases, the expression was seen in5% of the tumor cells.ALK gene rearrangements occurred in 6.4%, of prostate cancer, and these may not be associated with disease progressions. The ALK protein expresses in the nucleus. The EML4-ALK fusion gene was not found in prostate cancer.

As the existing of the wheel/rail wear and abrade, wheel/rail contact state will have a deviation with the symmetrical state. The wheel/rail unsymmetrical problem caused by the change of wheel/rail geometric contact parameters was analyzed. The classification of typical wheel/rail unsymmetrical contact has been done according to the wheel/rail unsymmetrical form reason. Wheel tread wear, crack, spalling, etc. wheel tread shape change and rail corrugation and side grinding, rail surface shelling and spalling, and asymmetry and geometrical irregularity about right and left rails all can lead to the happening of unsymmetrical contact, and the wheel diameter difference is also an important reason. The influence of wheel/rail unsymmetrical contact was studied. By choosing reasonable wheel/rail profile, rail grinding, vehicle parameter optimization and timely detection, strong wheel/rail unsymmetrical contact can be avoided.

Acidosis and alkalosis, associated with metabolic disorders, lead to the pathological changes of cognition and behaviors in clinical practices of neurology and psychology. Cellular mechanisms for these functional disorders in the central nervous system remain unclear. We have investigated the influences of acidosis and alkalosis on the functions of cortical GABAergic neurons. Both acidosis and alkalosis impair the ability of encoding sequential spikes at these GABAergic neurons. The impairments of their spiking are associated with the increases of refractory periods, threshold potential and afterhyperpolarization. Our studies reveal that acidosis and alkalosis impair cortical GABAergic neurons and in turn deteriorate brain functions, in which their final targets may be voltage-gated channels of sodium and potassium.

Germany high-speed track irregularity was commonly used during the railway vehicle dynamic simulation for the less of the uniform standard of track irregularity spectrum in China. It was failed for it not response the real condition of China track; it also has a speed limit, maybe not suitable for the 250 km/h and above high-speed dynamic simulation. The component of track irregularity was analysis to acquire the reasonable high-speed track irregularity spectrum. The synthesis principle of the track irregularity spectrum was derived, and given the transfer method from the frequency domain PSD to the time domain PSD. The approximate track irregularity spectrum of civil better track and worse track was put forward based on the Germany high-speed track irregularity spectrum and combined the experience of civil railway vehicle dynamic simulation. By the way, the approximate track irregularity spectrum of the determined track can be acquired through the back-stepping method according to the exact dynamic simulation results and the shortly real measured ride index data. This can be used as the simulation input of the high-speed train. Point out that under the condition of without the real measured track irregularity, Germany low disturb track irregularity can used in the 250 km/h railway vehicle dynamic simulation.

The anti-overturning ability of the coupler has become more and more important with the increase of the length of the heavy haul train, especially when the dynamic brake mode was adopted by the train on the curved track. Aimed to the derailment problem during dynamic braking, take the HX(subscriptD)2 locomotive for example to research the running safety of the heavy haul locomotive with the function of the longitudinal press force on coupler. The coupler anti-overturning mechanism of the LAF coupler and No. 13 coupler were compared. The coupler dynamic model in which coupler buffer character, coupler shoulder/position stop character were considered in detail was setup, and let it into the 10000t train model with the 4 HX(subscriptD)2 locomotives in series to traction. The locomotive dynamic performances of the HX(subscriptD)2 locomotive under the longitudinal press force on coupler with the two different coupler models were researched. There is a rigidly impact between the coupler and the coupler yoke of No. 13 coupler with the longitudinal press force as it hasn't the coupler shoulder settings. The coupler overturning was caused by the existing of the longitudinal press force on coupler; this leads the wheel/rail lateral force increased to balance the lateral force. Locomotive derailment will occur when the wheel/rail lateral force were exceed the limit value of criterion.

Wheel set longitudinal vibration was a normal phenomenon in railway vehicle dynamic analysis. The coupling of the two wheels in the same wheel set by the axle rigidly or elastic was the precondition of the existing of wheel set longitudinal vibration resonance. The wheel set longitudinal vibration model which has 7 degree of freedom and in which the axle torsion vibration was considered has set up to research the wheel set longitudinal vibration resonance mechanism. The wheel/rail normal contact was simulated by the one sided spring damper force element, and the wheel set longitudinal vibration resonance mechanism was researched by the combine of theory analysis and numerical simulation methods. Put forward the happening mechanism of the wheel set longitudinal vibration has something related with running speed and given a simple forecast formula of wheel set longitudinal vibration resonance speed.

Wheel surface damage can divided into three types: wheel tread spalling, out-of-round of wheel and wheel flange wear. Not only the ride index and comfort can be influenced by the wheel tread damage, but also the lateral stability can be affected by wheel tread damage. The railway vehicle derailment maybe happen when the wheel surface damage serious enough. The unsymmetrical wheel/rail contact was an important reason which can leads to the wheel surface damage problem. The unsymmetrical wheel/rail contact was consisted of symmetrical wheel tread combined with the unsymmetrical rail, unsymmetrical wheel tread combined with the symmetrical rail and unsymmetrical wheel tread combined with the unsymmetrical rail. The unsymmetrical wheel/rail contact can be formed when the wheel surface damage or the rail head damage. The forming of the unsymmetrical wheel/rail contact can exacerbate the damage of wheel surface. To improve the dynamic performance and the stability of the vehicle, the strong wheel/rail unsymmetrical contact must be avoided.

Spalling like scales of fish will emerge on the connection area between wheel tread and flange of one metro vehicle after it running a period of time on the track. The method of polish the track has not solved the phenomena yet. When wheel is out-of-round, the vertical vibration of the car-body is very big, and the tread must be cut to eliminate the phenomena of vertical vibration big of the car-body, but this method could not solve the problem indeed. These phenomena show that the secondary suspension of the vehicles has not damp function. Both the results of linear frequency analyses and the nonlinear analyses show that the too big stiffness of the traction bar which connected the car-body and the bogie in longitudinal direction has big relation with the vertical dynamic performance of the metro vehicle. From the point of view of the wheel-set longitudinal vibration find that the wheel-set resonance speed is in the usually running speed scope of the metro vehicle and this may be the reason of wheel tread easy splling and out-of-round. The stiffness of the traction bar was depressed by change the two ends to big rubber joints, so the longitudinal force affected by the traction bar is depressed notability, and the vertical dynamic performance of the metro vehicles is then be improved.

BACKGROUND: Chlorpromazine (CPZ), a commonly used antipsychotic drug, was found to play a neuroprotective role in various models of toxicity. However, whether CPZ has the potential to affect brain apoptosis in vivo is still unknown. The purpose of this study was to investigate the potential effect of CPZ on the apoptosis induced by exogenous stimuli. METHODOLOGY: The ethanol treated infant rat was utilized as a valid apoptotic model, which is commonly used and could trigger robust apoptosis in brain tissue. Prior to the induction of apoptosis by subcutaneous injection of ethanol, 7-day-old rats were treated with CPZ at several doses (5 mg/kg, 10 mg/kg and 20 mg/kg) by intraperitoneal injection. Apoptotic cells in the brain were measured using TUNEL analysis, and the levels of cleaved caspase-3, cytochrome c, the pro-apoptotic factor Bax and the anti-apoptotic factor Bcl-2 were assessed by immunostaining or western blot. FINDINGS: Compared to the group injected with ethanol only, the brains of the CPZ-pretreated rats had fewer apoptotic cells, lower expression of cleaved caspase-3, cytochrome c and Bax, and higher expression of Bcl-2. These results demonstrate that CPZ could prevent apoptosis in the brain by regulating the mitochondrial pathway. CONCLUSIONS: CPZ exerts an inhibitory effect on apoptosis induced by ethanol in the rat brain, intimating that it may offer a means of protecting nerve cells from apoptosis induced by exogenous stimuli.