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Repeated cocaine exposure causes compensatory neuroadaptations in neurons in the nucleus accumbens (NAc), a region that mediates reinforcing effects of drugs. Previous studies suggested a role for adenosine monophosphate-activated protein kinase (AMPK), a cellular energy sensor, in modulating neuronal morphology and membrane excitability. However, the potential involvement of AMPK in cocaine addiction is still unclear. The present study employed a cocaine self-administration model in rats to investigate the effect of AMPK and its target cyclic adenosine monophosphate response element binding protein-regulated transcriptional co-activator 1 (CRTC1) on cocaine reinforcement and the motivation for cocaine. We found that intravenous cocaine self-administration significantly decreased AMPK activity in the NAc shell (NAcsh), which persisted for at least 7 days of withdrawal. Cocaine reinforcement, reflected by self-administration behavior, was significantly prevented or enhanced by augmenting or suppressing AMPK activity pharmacologically and genetically, respectively. Cocaine-induced increases in dendritic spine density in the NAcsh were attenuated by AMPK inhibition. No difference in sucrose self-administration behavior was found after the same manipulations. The inhibition of AMPK activity in the NAcsh also increased the motivation for cocaine in progressive-ratio schedules of reinforcement, whereas the activation of AMPK had no effect. The knockdown of CRTC1 in the NAcsh significantly impaired cocaine reinforcement, which was rescued by pharmacologically increasing AMPK activity. Altogether, these results indicate that AMPK is critical for morphological plasticity in the NAcsh and cocaine reinforcement, possibly via the regulation of CRTC1 signaling. These findings may help reveal potential therapeutic targets and have important implications for the treatment of cocaine addiction and relapse.

This paper presents a novel modular differential drive soft robot (MDDSR) and its nonlinear model of crawling locomotion. The MDDSR consists of three differential drive soft modules (DDSMs) in series, and each module constructed by two bending soft actuators in parallel to be equally or differentially driven can achieve inchworm-like crawling movement with capability of straight and steering motion. Through sequential motions of the DDSMs, the MDDSR can perform straight and steering crawling locomotion. A nonlinear state-space kinematic model with the principle of minimum frictional work is built to characterize the MDDSR’s crawling locomotion, which is based on nonlinear bending behavior of the soft actuator and nonlinear crawling motion of the DDSMs. Feasibility of the proposed robot and its model is verified through locomotion experiments.

A micro-grinding approach is proposed to fabricate micro-groove array on tool rake surface. These micro-grooves were used to rapidly dissipate cutting chips and heat from cutting zone for eco-cutting of titanium alloy without any coolant. This tool is called micro-grooved tool. The objective is to replace chemical and high-energy-beam etching approaches because they have not yet been able to control micron-scale groove shape accuracy. In this study, a superhard diamond wheel V-tip was employed to perform a micro-grinding through a traverse grinding. After micro-grinding, these micro-grooves were characterized by the mean depth of 155.1 μm, the mean form error PV of 7.8 μm and the mean tip radius of 45.6 µm. Firstly, traditional plate tool, orthogonal micro-grooved tool and diagonal micro-grooved tool were employed to perform a dry turning of titanium alloy, respectively; then, tool wear, surface roughness, chip topography and shear angle were investigated. It is shown that the sharpened diamond wheel V-tip is valid to grinding micro-groove array on tool rake surface without any burrs. Furthermore, the micro-grooved tools may reduce the cutting sparks, tool wear, 3D chip size and chip saw-tooth size compared to traditional plate tool. The diagonal micro-grooved tool may decrease tool wear by 6.7% and surface roughness by 37.3% and increase shear angle by 24.3% against orthogonal micro-grooved tool, respectively. This is because the diagonal micro-grooving direction is identical to the cutting chip flowing on tool rake surface. It is confirmed that the diagonal micro-grooved tool is applicable to a stable dry cutting of titanium alloy.

To observe the relaxant effect of Aike Mixture (AKM) on isolated bladder and prostatic urethral smooth muscle of rabbits.The isolated bladder and prostatic urethral smooth muscle from male rabbits were placed in a Magnus bath and smooth muscle contraction was measured using a biological signal acquisition and analysis system. The effects of AKM in combination with methoxyamine, carbachol and CaCl2 on the contractile tension of muscle strips were determined by cumulative dosing.AKM dose-dependently reduced contractile tension of bladder trigone smooth muscle (r=0.831, P0.05), reduced contractile wave amplitude (r=0.837, P0.05) and decreased contractile frequency (r=-0.917, P0.01). AKM significantly inhibited the increases in smooth muscle contraction induced by methoxyamine, carbachol and CaCl2.AKM dose-dependently inhibited the contraction of rabbit isolated bladder and prostatic urethral smooth muscle by antagonizing α1-adrenergic receptors and M-cholinergic receptors.

We report a large-scale analysis of the patterns of genome-wide genetic variation in soybeans. We re-sequenced a total of 17 wild and 14 cultivated soybean genomes to an average of approximately ×5 depth and >90% coverage using the Illumina Genome Analyzer II platform. We compared the patterns of genetic variation between wild and cultivated soybeans and identified higher allelic diversity in wild soybeans. We identified a high level of linkage disequilibrium in the soybean genome, suggesting that marker-assisted breeding of soybean will be less challenging than map-based cloning. We report linkage disequilibrium block location and distribution, and we identified a set of 205,614 tag SNPs that may be useful for QTL mapping and association studies. The data here provide a valuable resource for the analysis of wild soybeans and to facilitate future breeding and quantitative trait analysis.

The laparoscopic approach has played a key role in the successful application of the enhanced recovery program (ERP) in perioperative care for postoperative colon surgery patients. Reports of applying ERP in laparoscopic rectal surgery are rare, and the feasibility of doing so has yet to be solidly evaluated. The goal of this study was to evaluate whether it is appropriate to use ERP on patients who undergo rectal surgery via the laparoscopic approach and to further investigate potential factors that may affect the results of this practice modality.Between December 2007 and July 2009, 80 eligible patients (35 women) with a median age of 60 (range, 28-82) years were enrolled. All patients received elective laparoscopic rectal surgery due to malignant or benign rectal lesions. Forty-nine percent of patients received preoperative neoadjuvant chemoradiotherapy (CCRT), because their clinical stage was beyond T3N0 or TanyN(+). The ERP used in this study was modified from a similar protocol used for patients receiving laparoscopic colectomy at the same institution.Sixty-five percent of patients in the study received a sphincter-preserving procedure, whereas 15 other patients underwent abdominoperineal resection (APR). The median operative time was 160 min. The conversion rate of laparoscopic surgery was 7.5%, and the combined intraoperative and postoperative complication rate was 13.8%. Forty-two patients (52.5% of the study pool) received complete postoperative recovery courses as prescribed by ERP.Our preliminary results of applying ERP to patients receiving laparoscopic rectal surgery showed a success rate of 52.5%. The failure of ERP among these patients was related to low rectal lesion locations (below 7 cm AAV) and surgery-related complications. ERP for laparoscopic rectal surgery is feasible but is not advised for all cases requiring laparoscopic rectal surgery.

We have resequenced a group of six elite maize inbred lines, including the parents of the most productive commercial hybrid in China. This effort uncovered more than 1,000,000 SNPs, 30,000 indel polymorphisms and 101 low-sequence-diversity chromosomal intervals in the maize genome. We also identified several hundred complete genes that show presence/absence variation among these resequenced lines. We discuss the potential roles of complementation of presence/absence variations and other deleterious mutations in contributing to heterosis. High-density SNP and indel polymorphism markers reported here are expected to be a valuable resource for future genetic studies and the molecular breeding of this important crop.

Drought stress greatly affects plant growth and crop yield. To understand the transcriptome dynamics during drought stress in maize seedlings, genome-wide gene expression profiling was compared between the drought-tolerant line Han21 and drought-sensitive line Ye478 using Affymetrix Maize Genome Array containing 17,555 probe sets. The results showed that in response to drought, the Han21 line had fewer probe sets with significant expression change than the Ye478 line and both lines had a common set of ~2,600 regulated probe sets under drought stress. The potential components of the abscisic acid signaling pathway were significantly identified from the common probe sets. A total of 827 probe sets with significantly differential expression between the two lines under drought stress were identified. The differential expression levels of cell wall-related and transporter genes may contribute to the different tolerances of the two lines. Additionally, we found that, compared to the sensitive line Ye478, the transcriptional levels of drought-responsive probe sets in the tolerant line Han21 recovered more quickly after re-watering, and more probe sets in the tolerant line Han21 were exclusively up-regulated at the re-watering stage. Our study provides a global gene expression dynamics of two maize inbred lines during drought stress and re-watering and will be valuable for further study of the molecular mechanisms of drought tolerance in maize.

The aim of this study was to evaluate the role of endoplasmic reticulum (ER) stress in diabetic retinopathy (DR) using in vitro and in vivo models. For the in vivo studies, diabetes was induced in rats, and retinal expression of glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), and vascular endothelial growth factor (VEGF) in groups of rats at 1, 3, and 6 months was assessed. For the in vitro studies, human retinal capillary endothelial cells (HRCECs) were cultured in the presence of varying glucose concentrations, and the expression of mRNA and protein for GRP78, ATF4, CHOP, and VEGF was assessed. The chosen glucose concentrations were reflective of those apparent in diabetic patients. Expression of VEGF and CHOP mRNA levels were significantly increased in diabetic rats compared to control rats at 1, 3, and 6 months (P < 0.05). In HRCECs cultured in the presence of high as well as variable glucose concentrations, CHOP expression and apoptosis were significantly increased (P < 0.05). However, GRP78 and ATF4 expression levels were unchanged. Our findings suggest that early progression of DR may be mediated by ER stress, but probably does not involve changes in ATF4 or GRP78.

Neoadjuvant chemoradiation therapy has improved the local control rate and overall survival in locally advanced rectal cancers. The purpose of this retrospective study is to evaluate the correlation between the final pathologic stage and survival in these patients.Patients with biopsy-proven rectal carcinoma, pretreatment staging by magnetic resonance imaging such as T3 or T4 tumors, or node-positive disease were treated with preoperative concomitant 5-fluorouracil-based chemotherapy and radiation, followed by radical surgical resection. Clinical outcome with survival, disease-free survival, recurrence rate, and local recurrence rate were compared with each T and N findings using the American Joint Committee on Cancer Tumor-Node-Metastasis (TNM) staging system.A total of 248 patients were enrolled in this study. Overall survival and disease-free survival at 1, 3, and 5 years were 97.1, 92, and 89.9% and 87.5, 71.1, and 69.5%, respectively. Thirty-six patients (14.5%) had a pathologic complete response after neoadjuvant therapy. The recurrence rate was significantly different between the pathologic complete response group and residual group (5.6 vs 31.1%; P = .002). Five-year disease-free survival was significantly better in the complete response group than the residual tumor group (93 vs 66%; P = .0045). There was no statistical difference in survival or locoregional recurrence rate between these two groups.Posttreatment pathologic TNM stage is correlated to disease-free survival and tumor recurrence rate in locally advanced rectal cancer after preoperative chemoradiation. Also, pathologic complete response to neoadjuvant treatment has its oncologic benefit in both overall recurrence and disease-free survival.

BaFe12O19 powders with nanocrystalline sizes were produced by sol-gel auto-combustion method. The precursors were prepared under the molar ratios of citric acid to the metal nitrate of 0.5, 1.0 and 1.5. Appropriate ethylene diamine (C2H8N2) was added in order to adjust pH of 7. The ions distribution of citric acid at different pH explains the effect of citric acid in the starting solution. The XRD patterns of the as-burnt powders and annealing powders show different phases for different citric acid content. In addition, the lattice constants (a, c) derived from X-ray diffraction pattern were changed from 0.58881 nm to 0.58997 nm and 2.32057 nm to 2.32296 nm respectively. The data from VSM indicated that the powder with high citric acid content took on good magnetic properties. Pure single BaFe12O19 of the specific maximum magnetization M(1 T) ≈ 49.73 Am2/kg, the specific remanent magnetization M r ≈ 30.77 Am2/kg and the coercive force H c ≈ 467 kA/m was produced when the molar ratios of citric acid to the metal nitrate was 1.5.

We recently reported that a conditioned stimulus (CS) memory retrieval-extinction procedure decreases reinstatement of cocaine and heroin seeking in rats and heroin craving in humans. Here we show that non-contingent cocaine or methylphenidate injections (UCS retrieval) 1 h before the extinction sessions decreases cocaine-priming-induced reinstatement, spontaneous recovery, and renewal of cocaine seeking in rats. Unlike the CS-based memory retrieval-extinction procedure, the UCS memory retrieval manipulation decreases renewal and reinstatement of cocaine seeking in the presence of cocaine cues that were not present during extinction training and also decreases cocaine seeking when the procedure commences after 28 days of abstinence. The inhibitory effect of the UCS retrieval manipulation on cocaine-priming-induced reinstatement is mediated by regulation of AMPA-receptor endocytosis in the basolateral amygdala. The UCS memory retrieval-extinction procedure has superior relapse prevention characteristics than the CS memory retrieval-extinction procedure and could be a promising method for decreasing relapse in human addicts., Cue-based therapies for treating drug addiction have proven to be only partially effective. Here the authors demonstrate a new memory retrieval based treatment protocol for drug addiction that results in long-lasting inhibition of drug seeking behavior in rodents.

Supersaturated solid solutions Fe1−x C x (0⩽x⩽0.9) of wide composition range have been prepared by mechanical alloying process. Nanocrystalline phase was formed for 0⩽x⩽0.67 and a large grain phase for 0.75⩽x⩽0.9. The large fraction of graphite volume puts off formation of nanocrystalline phase for high carbon content. In the large grain phase, magnetization follows simple magnetic dilution, and coercivity H c is mainly due to dissolution of carbon at grain boundaries. In the nanocrystalline phase the alloying effect of carbon is revealed by a distinct reduction of average magnetic moment. The increasing lattice constant with increasing carbon content is observed for a;$0.5, suggesting that the high carbon concentration may enhance diffusion of carbon into the Fe lattice. It shows a discontinuity in the H c variation with a grain size D of nanocrystalline phase. For small grain D below the critical value, H c increases with D. For a large grain D, H c decreases with increasing D. The solubility limit of carbon in a-Fe extended by nanocrystalline phase formation is discussed.

Quasi-electrostatic electron and ion-cyclotron instabilities are studied. The result indicates that the higher harmonic ion cyclotron instabilities (ICI) can be excited while the fast ions produced from reconnection are injected into a coronal loop. Part of the energetic ions can be dragged out of the magnetic mirror turning points and a negative plasma potential is generated. The plasma potential may directly accelerate the electrons up to the relativistic velocity within a short time. This acceleration is similar to the processes occurring in the magnetic mirror devices of controlled thermonuclear fusion. The spectrum and flux of accelerated electrons have also been obtained. Some observational results during the solar flare might be explained by this acceleration mechanism.

Nature 463, 311–317 (2010) In this Article, the Latin species name of the giant panda was written incorrectly as Ailuropoda melanoleura. The correct name is Ailuropoda melanoleuca.