41 research outputs found

    GABAergic Gene Expression in Postmortem Hippocampus from Alcoholics and Cocaine Addicts; Corresponding Findings in Alcohol-Naïve P and NP Rats

    Get PDF
    BACKGROUND:By performing identical studies in humans and rats, we attempted to distinguish vulnerability factors for addiction from neurobiological effects of chronic drug exposure. We focused on the GABAergic system within the hippocampus, a brain region that is a constituent of the memory/conditioning neuronal circuitry of addiction that is considered to be important in drug reinforcement behaviors in animals and craving and relapse in humans. METHODOLOGY:Using RNA-Seq we quantified mRNA transcripts in postmortem total hippocampus from alcoholics, cocaine addicts and controls and also from alcohol-naïve, alcohol preferring (P) and non-preferring (NP) rats selectively bred for extremes of alcohol-seeking behavior that also show a general addictive tendency. A pathway-targeted analysis of 25 GABAergic genes encoding proteins implicated in GABA synthesis, metabolism, synaptic transmission and re-uptake was undertaken. PRINCIPAL FINDINGS:Directionally consistent and biologically plausible overlapping and specific changes were detected: 14/25 of the human genes and 12/25 of the rat genes showed nominally significant differences in gene expression (global p values: 9×10⁻¹⁴, 7×10⁻¹¹ respectively). Principal FDR-corrected findings were that GABBR1 was down-regulated in alcoholics, cocaine addicts and P rats with congruent findings in NSF, implicated in GABAB signaling efficacy, potentially resulting in increased synaptic GABA. GABRG2, encoding the gamma2 subunit required for postsynaptic clustering of GABAA receptors together with GPHN, encoding the associated scaffolding protein gephryin, were both down-regulated in alcoholics and cocaine addicts but were both up-regulated in P rats. There were also expression changes specific to cocaine addicts (GAD1, GAD2), alcoholics (GABRA2) and P rats (ABAT, GABRG3). CONCLUSIONS/SIGNIFICANCE:Our study confirms the involvement of the GABAergic system in alcoholism but also reveals a hippocampal GABA input in cocaine addiction. Congruent findings in human addicts and P rats provide clues to predisposing factors for alcohol and drug addiction. Finally, the results of this study have therapeutic implications

    Refinement of Light-Responsive Transcript Lists Using Rice Oligonucleotide Arrays: Evaluation of Gene-Redundancy

    Get PDF
    Studies of gene function are often hampered by gene-redundancy, especially in organisms with large genomes such as rice (Oryza sativa). We present an approach for using transcriptomics data to focus functional studies and address redundancy. To this end, we have constructed and validated an inexpensive and publicly available rice oligonucleotide near-whole genome array, called the rice NSF45K array. We generated expression profiles for light- vs. dark-grown rice leaf tissue and validated the biological significance of the data by analyzing sources of variation and confirming expression trends with reverse transcription polymerase chain reaction. We examined trends in the data by evaluating enrichment of gene ontology terms at multiple false discovery rate thresholds. To compare data generated with the NSF45K array with published results, we developed publicly available, web-based tools (www.ricearray.org). The Oligo and EST Anatomy Viewer enables visualization of EST-based expression profiling data for all genes on the array. The Rice Multi-platform Microarray Search Tool facilitates comparison of gene expression profiles across multiple rice microarray platforms. Finally, we incorporated gene expression and biochemical pathway data to reduce the number of candidate gene products putatively participating in the eight steps of the photorespiration pathway from 52 to 10, based on expression levels of putatively functionally redundant genes. We confirmed the efficacy of this method to cope with redundancy by correctly predicting participation in photorespiration of a gene with five paralogs. Applying these methods will accelerate rice functional genomics

    Predicting Remaining Useful Life of Rolling Bearings Based on Reliable Degradation Indicator and Temporal Convolution Network with the Quantile Regression

    No full text
    High precision and multi information prediction results of bearing remaining useful life (RUL) can effectively describe the uncertainty of bearing health state and operation state. Aiming at the problem of feature efficient extraction and RUL prediction during rolling bearings operation degradation process, through data reduction and key features mining analysis, a new feature vector based on time-frequency domain joint feature is found to describe the bearings degradation process more comprehensively. In order to keep the effective information without increasing the scale of neural network, a joint feature compression calculation method based on redefined degradation indicator (DI) was proposed to determine the input data set. By combining the temporal convolution network with the quantile regression (TCNQR) algorithm, the probability density forecasting at any time is achieved based on kernel density estimation (KDE) for the conditional distribution of predicted values. The experimental results show that the proposed method can obtain the point prediction results with smaller errors. Compared with the existing quantile regression of long short-term memory network(LSTMQR), the proposed method can construct more accurate prediction interval and probability density curve, which can effectively quantify the uncertainty of bearing running state

    Optimization of preventive maintenance schedule of subway train components based on a game model from the perspective of failure risk

    No full text
    With the sustainable development of urban transportation systems, the safety and economy of subway trains have become important criteria. However, in the process of formulating the operation and maintenance strategy of subway trains, there is always a conflict of interest between the operator, who aims to improve the operation reliability, and the maintainer, who aims to reduce the maintenance cost. To resolve this conflict, this paper proposes a preventive maintenance decision-making method for subway train components based on a game model. A failure-rate model based on the memory factor was developed and combined with the dynamic attenuation law of a subway train. The failure risk of subway train components was quantitatively evaluated, and a risk penalty cost model was established. Next, a maintenance cost model based on the maintenance reliability and economy was developed. Then, a non-cooperative dynamic game model with operators and maintainers as players was developed, and the balance was solved using the particle swarm optimization algorithm. Finally, the preventive maintenance of the bogie axle box of a subway train was examined for validation. The validation results indicated that the proposed method can balance the interests of the subway train operation and maintenance departments and improve the operation and maintenance decision-making in the field of sustainable cities

    An Ensemble Learning and RUL Prediction Method Based on Bearings Degradation Indicator Construction

    No full text
    The prediction of the remaining life of a bearing plays a vital role in reducing the accident-related maintenance costs of machinery and in improving the reliability of machinery and equipment. To predict bearing remaining useful life (RUL), the abilities of statistical characteristics to reflect the bearing degradation state differ, and the single prediction model has low generalization ability and a poor prediction effect. An ensemble robust prediction method is proposed here to predict bearing RUL based on the construction of a bearing degradation indicator set: the initial bearing degradation indicator subsets were constructed using the Fast Correlation-Based Filter with Approximate Markov Blankets (FCBF-AMB) and Maximal Information Coefficient (MIC) selection methods. Through the cross-operation of the obtained subsets, we obtained a set of robust degradation indicators. These selected degradation indicators were fed into the long short-term memory (LSTM) neural network prediction model enhanced by the AdaBoost algorithm. We found through calculation that the average prediction accuracy of the proposed method is 91.40%, 92.04%, and 93.25% at 2100, 2250, and 2400 rpm, respectively. Compared with other methods, the proposed method improves the prediction accuracy by 1.8% to 14.87% at most. Therefore, the method proposed in this paper is more accurate than the other methods in terms of RUL prediction

    Molecular characterization and antimicrobial resistance of nine strains of CA-MRSA isolated from clinical inpatients

    No full text
    Objective: To investigate the molecular characterization and antimicrobial resistance of CA-MRSA(community-associated methicillin-resistant Staphylococcus aureus) strains isolated from clinical inpatientsto provide evidence for prevention and treatment of CA-MRSA infections. Methods: Isolates of S. aureus from hospitalized patients were collected within 24 h after admission from April 2014 to Dec. 2015, and mecA gene was detected to distinguish MRSA from MSSA (methicillin-sensitive Staphylococcus aureus). Genotypic CA-MRSA strains carrying SCC mec Ⅳ/Ⅴ were obtainedfor further analysis of molecular epidemiologic characters by spa-typing and MLST(multilocus -sequence typing). Based on the CLSI (Clinical and Laboratory Standards Istitute) guidelines, disk diffusion method was used to test drug susceptibility of CA-MRSA strains. Moreover, the presence of pvl virulence gene was detected by PCR. Results: A total of 147 strains of S. aureus including 58 MRSA strains were collected from hospitalized patients. By SCCmec typing, 9 CA-MRSA strains (SCCmec Ⅳ 3; SCCmec Ⅴ 6) were detected. All CA-MRSA strains developed resistance against different non-β-lactams, among which 8 strains developed drug-resistanceagainst aminoglycosides (mainly kanamycin) and 8 strains developed drug-resistance against erythromycin and clindamycin mediated by erm(B) mainly. Molecular typing revealed that the main CA-MRSA clone was t437-ST59, and other clones were t034-ST804, t127-ST1, t008-ST8 and t437-ST338. In addition, 5 out of 9 CA-MRSA strains were pvl gene positive. Conclusions: More pathogenic CA-MRSA strains are invading healthcare-associated settings and developing more resistance against non-β-lactams, indicating that the CA-MRSA should be closely monitored in hospitals

    The rise of the Himalaya enforced the diversification of SE Asian ferns by altering the monsoon regimes

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>The rise of high mountain chains is widely seen as one of the factors driving rapid diversification of land plants and the formation of biodiversity hotspots. Supporting evidence was reported for the impact of the rapid rise of the Andean mountains but this hypothesis has so far been less explored for the impact of the “roof of the world”. The formation of the Himalaya, and especially the rise of the Qinghai–Tibetan Plateau in the recent 20 million years, altered the monsoon regimes that dominate the current climates of South East Asia. Here, we infer the hypothesis that the rise of Himalaya had a strong impact on the plant diversity in the biodiversity hotspot of the Southwest Chinese Mountains.</p> <p>Results</p> <p>Our analyses of the diversification pattern of the derived fern genus <it>Lepisorus</it> recovered evidence for changes in plant diversity that correlated with the strengthening of South East Asian monsoon. Southwest China or Southwest China and Japan was recovered as the putative area of origin of <it>Lepisorus</it> and enhancing monsoon regime were found to shape the early diversification of the genus as well as subsequent radiations during the late Miocene and Pliocene.</p> <p>Conclusions</p> <p>We report new evidence for a coincidence of plant diversification and changes of the climate caused by the uplift of the Himalaya. These results are discussed in the context of the impact of incomplete taxon sampling, uncertainty of divergence time estimates, and limitations of current methods used to assess diversification rates.</p

    Effects of Rare Earth Ce on the Brazing Performance of High Energy Mechanical Milling Cu-Based Alloy Powder

    No full text
    CuSn and TiH2 powders were milled by high energy mechanical milling to prepare Cu-based alloy powder for brazing diamond, and a small amount of rare earth Ce was added to improve the brazing performance. The effects of Ce on the brazing performance were studied by investigating transverse rupture strength, microstructure of brazing layer, climbing height along the diamond, and wear characteristics of the diamonds. The results indicated that the addition of Ce could effectively improve the transverse rupture strength, the transverse rupture strength reached the maximum value 475 MPa when the Ce content was 0.75 wt %. Rare earth Ce could promote the refinement of Cu6Sn5 and CuTi2 grains in the brazing alloy, which effectively reduced the formation and propagation of cracks. The wettability of the Cu-based alloy was also improved by adding rare earth Ce, and the capillary force pulled the molten alloy up the diamonds and formed a hill-like structure around diamonds. The diamonds brazed with Cu-based alloy containing 0.75 wt % Ce mainly led to integrity, micro-fracture, fracture and rubdown during the grinding process; pull-out of diamonds did not happen easily owing to the presence of strong adhesion between the diamonds and Cu-based alloy

    46, XX disorder of sexual development associated with mixed germ cell tumor of the prostate: a rare case report

    No full text
    Abstract Background Extragonadal germ cell tumors originating from the prostate are exceptionally rare. To the best of our knowledge, there have been no reported cases of mixed germ cell tumors in individuals with 46 XX disorder of sex development. In this study, we conducted a comprehensive analysis using whole genome sequencing to investigate the clinicopathological and molecular genetic characteristics of a submitted case, with the objective of elucidating its underlying pathogenesis. Case presentation A 40-year-old male patient was diagnosed with a combination of 46, XX disorder of sex development and a primary prostate mixed germ cell tumor with yolk sac tumor and teratoma components. Whole-genome sequencing revealed that the tumor cells had a high somatic mutational load. Analysis of genomic structural variations and copy number variants confirmed the patient's karyotype as 46, XX (SRY +). Additionally, the patient exhibited short stature, small bilateral testes, slightly enlarged breasts, elevated serum alpha-fetoprotein concentrations, elevated follicle-stimulating hormone and luteinizing hormone levels, and low testosterone levels. Discussion A case of 46, XX disorder of sex development, along with a primary prostatic mixed germ cell tumor, was diagnosed. This diagnosis has contributed to advancing our understanding of the genetic and phenotypic profile of the disease and may provide some insights for its treatment

    Case Study: Successful Application of a Novel Gas Lift Valve in Low Pressure Wells in Fuling Shale Gas Field

    No full text
    The Fuling shale gas field is facing a rapid gas production decline due to heavy liquid loading issues. Given the condition that most wells are located at remote areas in the mountains, the traditional gas lift methods that require either fixed compressor or skid-mounted gas lift trucks do not seem feasible and occur high operation costs. A new type of gas lift valve that can be opened or closed at a low valve dome pressure indicates the high sensitivity to low production pressure. Thus, the piping line pressure can be utilized to activate the valve due to its new advantages. In addition, the specially designed structure of the gas lift valve can be activated via pressure increases in the tubing to create a channel between the tubing and annulus. The valve that previously functioned as a dummy valve was then switched to a gas lift valve. Field application results show that all wells were successfully restarted by only utilizing the low piping pressure, and loaded liquid was lifted with gas production at an incremental rate that reached up to 27.4 × 10 kscm/d per well. Fewer slickline operations were conducted to replace the dummy valve. The result of the application shows that the new type of gas lift system has a wide range of application prospect for low pressure wells, especially for shale gas wells
    corecore