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Studies investigating the association between cytochrome glutathione S-transferase P1 (GSTP1) Ala114Val polymorphism and colorectal cancer (CRC) risk report conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine databases. Summary odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for GSTP1 polymorphism and CRC were calculated in a fixed effects model (the Mantel–Haenszel method) and a random effects model (the DerSimonian and Laird method) when appropriate. The pooled ORs were performed for co-dominant model (ValVal vs. AlaAla, AlaVal vs. AlaAla), dominant model (ValVal + AlaVal vs. AlaAla), and recessive model (ValVal vs. AlaVal + AlaAla). This meta-analysis included seven case–control studies, which included 3,173 CRC cases and 3,323 controls. Overall, the variant genotypes (ValVal and AlaVal) of the Ala114Val were not associated with CRC risk when compared with the wild-type AlaAla homozygote. Similarly, no associations were found in the dominant and recessive models. When stratifying for ethnicity, Hardy–Weinberg equilibrium in controls, study sample size, and source of controls, a significantly increased risk was observed among Asians (AlaVal vs. AlaAla, OR = 1.67, 95 % CI = 1.08–2.59; dominant model, OR = 1.74, 95 % CI = 1.14–2.67). No heterogeneity or publication bias was found in the present study. This meta-analysis suggests that the GSTP1 Ala114Val polymorphism may not be associated with CRC risk, while the observed increase in risk of CRC may be due to small-study bias.

Identifying target genetic mutations in hepatocellular carcinoma (HCC) for therapy is made challenging by intratumoral heterogeneity. Circulating cell-free DNAs (cfDNA) may contain a more complete mutational spectrum compared to a single tumor sample. This study aimed to identify the most efficient strategy to identify all the mutations within heterogeneous HCCs.Whole exome sequencing (WES) and targeted deep sequencing (TDS) were carried out in 32 multi-regional tumor samples from five patients. Matched preoperative cfDNAs were sequenced accordingly. Intratumoral heterogeneity was measured using the average percentage of non-ubiquitous mutations (present in parts of tumor regions). Profiling efficiencies of single tumor specimen and cfDNA were compared. The strategy with the highest performance was used to screen for actionable mutations.Variable levels of heterogeneity with branched and parallel evolution patterns were observed. The heterogeneity decreased at higher sequencing depth of TDS compared to measurements by WES (28.1% vs. 34.9%, p0.01) but remained unchanged when additional samples were analyzed. TDS of single tumor specimen identified an average of 70% of the total mutations from multi-regional tissues. Although genome profiling efficiency of cfDNA increased with sequencing depth, an average of 47.2% total mutations were identified using TDS, suggesting that tissue samples outperformed it. TDS of single tumor specimen in 66 patients and cfDNAs in four unresectable HCCs showed that 38.6% (26/66 and 1/4) of patients carried mutations that were potential therapeutic targets.TDS of single tumor specimen could identify actionable mutations targets for therapy in HCC. cfDNA may serve as secondary alternative in profiling HCC genome.Targeted deep sequencing of single tumor specimen is a more efficient method to identify mutations in hepatocellular carcinoma made from mixed subtypes compared to circulating cell-free DNA in blood. cfDNA may serve as secondary alternative in profiling HCC genome. Identifying mutations may help clinicians choose targeted therapy for better individual treatments.

The resolution and observing width of optical remote sensing camera can be enhanced by increasing the detector length of focal plane. Optical butting is used to increase the imaging length owing to its simple structure, low cost and the simultaneously-imaging detectors. But butting process is influenced by many factors, which result in imaging gaps, so overlapping pixels between adjacent detectors is the key. In this paper, the factors causing imaging gap are analyzed, and calculation of overlapping pixel number is given out based on the analysis. Firstly an optical-butting focal plane system is built on optical imaging principles. Then the factors causing imaging gap are listed and analyzed, under the consideration of telecentric and non-telecentric optical system. Based on the imaging gap analysis, a formula for overlapping pixel number calculation is obtained, with the MTF assurance in vignetting districts resulted from optical butting. Finally a calculation example of a camera is given.

Klebsiella pneumoniae is one of the most significant nosocomial pathogens in healthcare settings. Over the last decade, K. pneumoniae producing extended-spectrum β-lactamases (ESBLs) have been prevalent worldwide. ESBL-producing isolates are considered resistant to all penicillins, cephalosporins and aztreonam, and carbapenems are the only β-lactams that still remain consistently active.1 But owing to the overuse of carbapenems, resistant strains have become endemic in many countries as well. In addition, most carbapenem-resistant K. pneumoniae (CR-KP) are resistant to other antimicrobial classes, referred to as multidrug-resistant (MDR) and extensively drug-resistant strains.2 The lack of active antimicrobials against CR-KP continues to threaten public health.

The advance of single cell sequencing advocates a new era to delineate intratumor heterogeneity and traces the evolution of single cells at molecular level. However, current single cell technology is hindered by an indispensable step of genome amplification to accumulate enough samples to reach the sequencing requirement. Multiple Displacement Amplification (MDA) method is the major technology adopted for genome amplification. But it suffers from a major drawback of large amplification bias, resulting in time and label consuming. To fulfill this gap, we have presented a simulation software for the MDA process in this paper. The proposed simulator was based on an original hypothesis for catering to empirical MDA process. It was implemented to achieve high efficiency with affordable computational cost, thus allowing for an individual MDA experiment to be simulated quickly. Surprising nice experiments demonstrated the simulator is promising in providing guidance and cross-validation for experimental MDA.

In this paper, we decompose the electricity consumption changes of the whole indus- tries of Shandong province in 2006 -2012 into activity effect, structure effect and intensity effect, using LMDI method. The results show that the expansion of economic volume mainly attributes the electricity consumption growth in this period, while industry structure adjustment and power effi- ciency improvement slow down the increase of electricity consumption, promoting the reduction of electricity consumption. Compared with other industries, industrial economic growth is the main driving force of electricity consumption growth, but industrial structure adjustment and efficien- cy enhancement are the dominant factors to reduce the electricity consumption.

In its upper-middle reaches the Yellow River has high sand contents after traversing through large areas of desert and the China Loess Plateau. Understanding riverbed sediment composition in the channel is critical for the interpretation of the potential provenance, aeolian sand transport and the linkage between the Loess Plateau and the Yellow River. To address these issues, we collected 52 samples from the modern riverbed, proximal deserts, and major tributaries and used analyses of grain size, grain morphology, and heavy-mineral compositions, to establish the spatial distribution and characteristics of source regions and riverbed sediments. The heavy-mineral assemblages demonstrate significant variations for the different sections of the Yellow River. The riverbed samples from the upper reach are dominated by opaque minerals (limonite and magnetite), amphibole and epidote, with minor zircon, tourmaline and rutile. Riverbed sediments from the middle reach are garnet-rich, reflecting the widespread distribution of Mesozoic sandstones. This variability closely reflects the source regions. Our data show that seasonal tributaries (the “Ten Great Gullies”) carrying detritus from the Ordos Plateau may account for the localized high garnet concentrations in the Inner Mongolia section of the upper reach. Scanning electron microscope (SEM) imaging of quartz grains show that the river sediments are characterized by composite microtextures acquired in both fluvial and eolian environments of the Hedong, Ulan Buh and Kubuq Deserts. The mineralogical composition in the upper reach (Lanzhou–Yinchuan) is similar to that of sediments in the Loess Plateau and Northeast Tibet Plateau (Western Lanzhou). However, the composition differs markedly from that in the Inner Mongolia section of the upper and middle reaches. This variation indicates that in the upper reach the Northeast Tibet Plateau contributes significant volumes of sediment to the Yellow River and Loess Plateau, but compositions change across the Inner Mongolia section of the upper and middle reaches owing to local sediment supply from arid desert areas and seasonal tributaries.

SummaryClear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and has very few mutations that are shared between different patients. To better understand the intratumoral genetics underlying mutations of ccRCC, we carried out single-cell exome sequencing on a ccRCC tumor and its adjacent kidney tissue. Our data indicate that this tumor was unlikely to have resulted from mutations in VHL and PBRM1. Quantitative population genetic analysis indicates that the tumor did not contain any significant clonal subpopulations and also showed that mutations that had different allele frequencies within the population also had different mutation spectrums. Analyses of these data allowed us to delineate a detailed intratumoral genetic landscape at a single-cell level. Our pilot study demonstrates that ccRCC may be more genetically complex than previously thought and provides information that can lead to new ways to investigate individual tumors, with the aim of developing more effective cellular targeted therapies.

SummaryTumor heterogeneity presents a challenge for inferring clonal evolution and driver gene identification. Here, we describe a method for analyzing the cancer genome at a single-cell nucleotide level. To perform our analyses, we first devised and validated a high-throughput whole-genome single-cell sequencing method using two lymphoblastoid cell line single cells. We then carried out whole-exome single-cell sequencing of 90 cells from a JAK2-negative myeloproliferative neoplasm patient. The sequencing data from 58 cells passed our quality control criteria, and these data indicated that this neoplasm represented a monoclonal evolution. We further identified essential thrombocythemia (ET)-related candidate mutations such as SESN2 and NTRK1, which may be involved in neoplasm progression. This pilot study allowed the initial characterization of the disease-related genetic architecture at the single-cell nucleotide level. Further, we established a single-cell sequencing method that opens the way for detailed analyses of a variety of tumor types, including those with high genetic complex between patients.

Hypereutectic Al–Si alloy-based composite pistons reinforced with SiC particles locally at the head were fabricated by centrifugal casting. The effects of various technique parameters, i.e., the slurry temperature of the alloy, the mold temperature and the rotation speed of the mold, on the particle segregation were investigated, and the macromorphologies and microstructures of pistons were observed. The mechanical properties, such as hardness and wear resistance along the axis of the piston and the thermal expansion coefficient at the piston head, were measured. The results showed that, (1) centrifugal casting can be used as a new and effective method in manufacturing pistons, and reasonable parameters were 850 °C, 600 °C and 800 rpm for the slurry temperature of the alloy, the mold temperature and the rotation speed of the mold, respectively; (2) the hardness values of pistons fabricated by centrifugal casting gradually increased from the piston skirt to the piston head, and the average hardness value in piston heads was improved by 23.7HRB over that of pistons fabricated by gravity permanent mold casting; (3) the piston heads showed excellent wear resistance, and the wear rate of piston heads decreased by 70.3% over that of the piston fabricated by gravity permanent mold casting; and (4) the average linear expansion coefficient of the piston head was 15.3 × 10−6 K−1 and decreased by 23.1% over that of pistons fabricated by gravity permanent mold casting.

ZnO and ZnS composited tri-crystal nanoribbons were fabricated by one-step thermal evaporation of ZnS and CuO powders. The tri-crystal nanoribbons have typical length of about 10 μm and width of 100–300 nm. The tri-crystal nanoribbon was composed of three intersected nanoribbons by 120°, which had a thickness of 50 nm with a growth direction along [10–10]. The rough nanoribbon contained several grains and the averaged elemental enrichment of Zn:O:S was 1:0.72:0.28. The tri-crystal nanoribbons exhibited three emission peaks at room temperature, which are associated to band gap and defect emissions of ZnO and ZnS. This 3D composited nanocrystal has potential applications in optoelectronics and energy-harvesting devices.

Neovascularization is critical to destabilization of atheroma. We previously reported that the angiogenic growth factor pleiotrophin (PTN) coaxes monocytes to assume the phenotype of functional endothelial cells in vitro and in vivo. In this study we show that PTN expression is colocalized with capillaries of human atherosclerotic plaques. Among the various reagents that are critical to the pathogenesis of atherosclerosis, interferon (IFN)-gamma was found to markedly induce PTN mRNA expression in a dose-dependent manner in macrophages. Mechanistic studies revealed that the Janus kinase inhibitors, WHI-P154 and ATA, efficiently blocked STAT1 phosphorylation in a concentration- and time-dependent manner. Notably, the level of phosphorylated STAT1 was found to correlate directly with the PTN mRNA levels. In addition, STAT1/STAT3/p44/42 signaling molecules were found to be phosphorylated by IFN-gamma in macrophages, and they were translocated into the nucleus. Further, PTN promoter analysis showed that a gamma-activated sequence (GAS) located at -2086 to -2078 bp is essential for IFN-gamma-regulated promoter activity. Moreover, electrophoretic mobility shift, supershift, and chromatin immunoprecipitation analyses revealed that both STAT1 and STAT3 bind to the GAS at the chromatin level in the IFN-gamma stimulated cells. Finally, to test whether the combined effect of STAT1/STAT3/p44/42 signaling is required for the expression of PTN in macrophages, gene knockdowns of these transcription factors were performed using siRNA. Cells lacking STAT1, but not STAT3 or p42, have markedly reduced PTN mRNA levels. These data suggest that PTN expression in the human plaques may be in part regulated by IFN-gamma and that PTN is involved in the adaptive immunity.-Li, F., Tian, F., Wang, L., Williamson, I. K., Sharifi, B. G., Shah, P. K. Pleiotrophin (PTN) is expressed in vascularized human atherosclerotic plaques: IFN-gamma/JAK/STAT1 signaling is critical for the expression of PTN in macrophages.

// Dakai Xiao 1, 2, 3, * , Hui Pan 1, 2, * , Fuqiang Li 4 , Kui Wu 4 , Xin Zhang 1, 3 , Jianxing He 1, 3 1 Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China 2 Research Center for Translational Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China 3 Guangzhou Institute of Respiratory Disease and State Key Laboratory of Respiratory Disease, Guangzhou, China 4 BGI-Shenzhen, Shenzhen, China * These authors contributed equally to this work Correspondence to: Jianxing He, e-mail: Drjianxing.he@gmail.com Keywords: lung adenocarcinoma, targeted NGS sequencing, mutation burden Received: December 21, 2015 Accepted: February 23, 2016 Published: March 19, 2016 ABSTRACT Gender-associated difference in incidence and clinical outcomes of lung cancer have been established, but the biological mechanisms underlying these gender-associated differences are less studied. Recently we have characterized the genomic landscape of lung adenocarcinoma derived from Chinese population (Reference [ 1 ]). In this study we evaluated the clinical significance of mutation burden in lung adenocarcinoma and found that the male tumors harbored statistically greater burden of genetic alterations than female counterparts (Male median 3 (range 0–34) vs female median = 2 (0–24), male to female ratio = 1.636, 95% CI = 1.343–1.992) after adjustment of age at surgery, stage, smoking status. Kaplan-Meier survival analysis revealed that greater burden of genetic alterations was associated with worse overall survival. Moreover, multivariable analysis demonstrated mutation burden was an independent prognostic factor for the patients. Taken together, our analysis demonstrated gender disparity of mutation burden and their prognostic value in lung adenocarcinoma. This gender difference in mutation burden might provide an explanation for the distinct difference in the clinical outcomes between sexes in lung adenocarcinoma.

Single cell sequencing provides revolutionary insight into genomic heterogeneity at the molecular level. A key procedure for successful sequencing is whole genome amplification (WGA) that permits the genomic DNA of a single cell to be amplified by several orders of magnitude. A very recently reported WGA method, Multiple Annealing and Loop-Based Amplification Cycles (MALBAC), distinguished itself by providing uniformity of amplification across the genome with low amplification bias. However, MALBAC still has limitations. For example, the polymerase enzyme is prone to introduce errors and a large proportion of single-nucleotide variations are lost. The complex biological reactions involved in MALBAC are largely unaddressed and no systematic analysis for it has been reported. To reduce both the labor and costs involved in MALBAC, we have developed a computer simulation for MALBAC. By capturing several key variables, MALBAC was formulated by a mathematical model and simulated. We compared the simulated data with empirical sequencing data of Escherichia coli genomes. The experimental results demonstrated that the coverage distribution matches very well. We believe that the proposed simulator can provide both theoretical guidance and experimental cross-validation for MALBAC, thus aiding improvement of its performance.

To explore the clinical efficacy of acupoint catgut embedding therapy on chronic pelvic cavity pain syndrome differentiated as kidney deficiency and stagnation of damp heat, and explore the impacts on plasma P substance (SP), plasma beta-endorphin (β-EP).One hundred and eighty cases were randomly divided into a catgut embedding group (90 cases) and a western medication group (90 cases). In the western medication group, tamsulosin capsules 0. 2 mg were prescribed for oral administration, once a day; indometacin sustained release tablets, 25 mg, three times a day. Totally, the oral administration for 8 weeks was required. In the catgut embedding group, the acupoint catgut embedding therapy was applied to Qugu (CV 2), Shenshu (BL 23), Zhibian (BL 54), Huiyin (CV 1) and Sanyinjiao (SP 6), once every two weeks; the treatment of 4 weeks made one session, and two sessions were required. Before and after treatment, TCM symptom score, NIH-CPSI (the National Institute of Health Chronic Prostatitis Symptom Index) score, lecithin body numbers in prostatic fluid, score in SAS (self-rating anxiety scale), score in SDS (self-rating depression scale), the levels of SP and β-EP, etc. were observed in the two groups, and the clinical efficacy was assessed in the two groups.(1) Ten cases were dropped in either group. The total effective rate was 91. 25% (73/80) in the catgut embedding group, higher than 78. 75% (63/80) in the western medication group (P0. 05). (2) After treatment, TCM symptom score, total score in NIH-CPSI, pain score and the scores in SAS and SDS were all reduced as compared with those before treatment in the two groups (all P0. 05). After treatment, TCM symptom score, total score and pain score in NIH-CPSI, and the scores in SAS and SDS in the catgut embedding group were both lower than those in the western medication group (all P0. 05). (3) After treatment, the lecithin body numbers were both increased as compared with those before treatment in the two groups (both P0. 05), and the result in the catgut embedding group was higher than that in the western medication group (P0. 05). (4)After treatment, the SP level was lower than that before treatment in the two groups (both P0. 05); the level of p-EP was increased as compared with that before treatment (both P0. 05). The SP level in the catgut embedding group was lower than that in the western medication group (P0. 05); the level of β-EP was higher than that in the western medication group (P0. 05).The acupoint catgut embedding therapy apparently relieves the clinical symptoms of chronic pelvic cavity pain syndrome differentiated as kidney deficiency and stagnation of damp heat as well as the condition of anxiety and depression, increases lecithin body numbers in prostatic fluid and β-EP level and reduces SP level.

Pumps and valves are primary power and control devices in water supply piping systems. A collaborative operational scheme is very important for a series pump–valve system to decrease the transient pressure during the startup process. In order to analyze the influence of the operational time differences between the pump and the valve on the transient process, a complicated pump system was numerically simulated using the method of characteristics (MOC). The boundary conditions of the pump and the valve were separately established by equating an auxiliary element in the discrete mesh. The transient pressure, pump speed, and flow were studied for various time differences and the valve opening process for the series pump–valve startup process. Furthermore, an optimal collaborative scheme was presented to prevent inverse rotation and overpressure during the startup process. The results show that a reasonable time-lapse and fast opening can prevent the backward flow and reverse rotation, as well as control the transient maximal pressure during the system startup process.

Summary With deep development, Bohai oilfield has increased exploration and development strength in complex fault block reservoir. Restricted by the geological conditions and seismic data acquisition or processing method, the seismic data qualities of some oilfield are not fine enough to recognize part of the small faults. In order to overcome the above difficulties, this paper presents the three-step fracture system identification technology. The first step is to utilize the spectrum equalization method, which is based on wavelet transform, to increase the frequency of seismic data. This method can effectively increase the seismic frequency and improve fault identification capability of seismic data. The second step is to use anisotropic diffusion filtering method based on the control operator to filter out noise, and further increase the fault features identification ability of seismic data. The third step is to apply the discrete frequency angle coherent method to carry out fine multi-scale fracture system identification.

Previous studies have demonstrated focal but limited molecular similarities between circulating tumor cells (CTCs) and biopsies using isolated genetic assays. We hypothesized that molecular similarity between CTCs and tissue exists at the single cell level when characterized by whole genome sequencing (WGS). By combining the NanoVelcro CTC Chip with laser capture microdissection (LCM), we developed a platform for single-CTC WGS. We performed this procedure on CTCs and tissue samples from a patient with advanced prostate cancer who had serial biopsies over the course of his clinical history. We achieved 30X depth and ≥ 95% coverage. Twenty-nine percent of the somatic single nucleotide variations (SSNVs) identified were founder mutations that were also identified in CTCs. In addition, 86% of the clonal mutations identified in CTCs could be traced back to either the primary or metastatic tumors. In this patient, we identified structural variations (SVs) including an intrachromosomal rearrangement in chr3 and an interchromosomal rearrangement between chr13 and chr15. These rearrangements were shared between tumor tissues and CTCs. At the same time, highly heterogeneous short structural variants were discovered in PTEN, RB1, and BRCA2 in all tumor and CTC samples. Using high-quality WGS on single-CTCs, we identified the shared genomic alterations between CTCs and tumor tissues. This approach yielded insight into the heterogeneity of the mutational landscape of SSNVs and SVs. It may be possible to use this approach to study heterogeneity and characterize the biological evolution of a cancer during the course of its natural history.

Dextran-coated superparamagnetic iron oxide nanoparticles (DSPIONs) have gained considerable interest, because of their biocompatibility and biosafety in clinics. Doxorubicin (Dox), a widely used chemotherapeutic drug, always has limited applications in clinical therapy due to its serious side effects of dose-limiting irreversible cardiotoxicity and myelo suppression. Herein, DSPIONs were synthesized and developed as magnetic carriers for doxorubicin. The Dox-DSPION conjugates were evaluated in the in vitro test of Dox release, which showed pH-dependence with the highest release percentage of 50.3% at pH 5.0 and the lowest release percentage of 11.8% in a physiological environment. The cytotoxicity of DSPIONs and Dox-DSPIONs evaluated by the MTT assay indicated that DSPIONs had no cytotoxicity and the conjugates had significantly reduced the toxicity (IC50 = 1.36 μg mL(-1)) compared to free Dox (IC50 = 0.533 μg mL(-1)). Furthermore, confocal microscopic data of cell uptake suggest that less cytotoxicity of Dox-DSPIONs may be attributed to the cellular internalization of the conjugates and sustainable release of Dox from the formulation in the cytoplasm. More importantly, the results from the rabbit VX2 liver tumor model test under an external magnetic field showed that the conjugates had approximately twice the anti-tumor activity and two and a half times the animal survival rate, respectively, compared to free Dox. Collectively, our data have demonstrated that Dox-DSPIONs have less toxicity with better antitumor effectiveness in in vitro and in vivo applications, suggesting that the conjugates have potential to be developed into chemo-therapeutic formulations.

A simple, specific, and sensitive liquid chromatography-mass spectrometry (LC-MS) method for determination of cyasterone in rat plasma was developed in our laboratory. Cucurbitacin B was used as an internal standard (IS). After protein precipitation with twofold volume of acetonitrile, the analyte and IS were separated on a Luna C18 column (100 × 4.6 mm, i.d., 3.0 µm; Phenomenex) by isocratic elution with acetonitrile-water (80:20, v/v) as the mobile phase at a flow rate of 0.4 mL/min. An electrospray ionization source was applied and operated in the positive ion mode; selected ion monitoring scan mode was used for quantification, and the target ions m/z 543.3 for cyasterone and m/z 581.3 for IS were chosen. Good linearity was observed in the concentration range of 0.40-400 ng/mL for cyasterone in rat plasma. Intra-day and inter-day precision were both7.4%. This method was proved to be suitable for pharmacokinetic studies after oral (5.0 mg/kg) or intravenous (0.5 mg/kg) administration of cyasterone in rats. Copyright © 2015 John WileySons, Ltd.

To investigate the effects and mechanisms of the inflammatory reaction related to nonalcoholic steatohepatitis (NASH) and induced by activation of the cholinergic anti-inflammatory pathway.A mouse model of NASH was established by feeding a high-fat and high-sugar diet.Activation of the cholinergic anti-inflammatory pathway was achieved by nicotine administration to the NASH modeled mice and normal controls. Liver biopsies were taken and the concentrations of cytokines were measured. Isolated liver primary Kupffer cells and RAw264.7 cells were cultured, pre-treated or not with lipopolysaccharide (LPS) and exposed to nicotine, after which the supernatant concentrations of IL-6 and TNFa were determined by ELISA. The protein expression levels of phosphorylated (p)-NF-kB and I k B were detected in primary cultured Kupffer cells by western blotting.The mouse model of NASH was successfully established, as evidenced by findings from liver biopsy and serum liver function tests. The degree of liver inflammation in the NASH mice decreased after nicotine administration, and the level of serum TNFa also significantly decreased. The levels of serum TNFa were 21.95+/-0.8 pg/mL in nicotine-treated mice and 38.07+/-1.7 pg/mL in the non-nicotine-treated NASH mice (P less than 0.05). The nicotine treatment also significantly reduced the concentration of TNFa in the culture supernatants of Kupffer cells after LPS stimulation; moreover, the supernatant level of TNFa decreased significantly after the nicotine treatment (Pless than 0.05). LPS stimulation of the RAw264.7 cells led to an increased level ofp-NF-kB and a reduced level ofI-kB, suggesting that the NF-kB pathway had been activated; different doses of nicotine pre-treatment led to down-regulation of the p-NF-kB level and up-regulation of the I-kB level, both in dose-dependent manners.Activating the cholinergic anti-inflammatory pathway inhibits the NASH-related inflammatory reaction, and the mechanism for this inhibition involves the NF-kB signaling pathway.

Purpose To describe the clinical finding of subretinal fluid (SRF) in the posterior pole by spectral domain optical coherence tomography (SD-OCT) in eyes with active ocular toxoplasmosis (OT). Design Retrospective case series. Participants Thirty-eight eyes from 39 patients with active OT. Methods Eyes with active OT which underwent SD-OCT were reviewed. SRFs in the posterior pole were further analyzed. Main Outcome Measures Presence of SRF; its accompanying features, e.g. retinal necrosis, cystoid macular edema (CME), choroidal neovascularization (CNV); and longitudinal changes of SRF, including maximum height and total volume before and after treatment. Results SRF presented in 45.5% (or 15/33) of eyes with typical active OT and in 51.3% (or 20/39) of eyes with active OT. The mean maximum height and total volume of SRF were 161.0 (range: 23–478) µm and 0.47 (range: 0.005–4.12) mm3, respectively. For 12 eyes with SRF related to active retinal necrosis, SRF was observed with complete absorption after conventional anti-toxoplasmosis treatment. The mean duration for observation of SRF clearance was 33.8 (range: 7–84) days. The mean rate of SRF clearance was 0.0128 (range: 0.0002–0.0665) mm3/day. Conclusions SRF (i.e., serous retinal detachment) is a common feature in patients with active OT when SD-OCT is performed. The majority of SRF was associated with retinal necrosis and reacted well to conventional therapy, regardless of total fluid volume. However, SRF accompanying with CME or CNV responded less favorably or remained refractory to conventional or combined intravitreal treatment, even when the SRF was small in size.

Extramedullary hematopoiesis has been shown to contribute to the pathogenesis of a variety of diseases including cardiovascular diseases. In this process, the spleen is seeded with mobilized bone marrow cells that augment its hematopoietic ability. It is unclear whether these immigrant cells that are produced/reprogrammed in spleen are similar or different from those found in the bone marrow. To begin to understand this, we investigated the relative potency of adult splenocytes per se to repopulate bone marrow of lethally-irradiated mice and its functional consequences in atherosclerosis. The splenocytes were harvested from GFP donor mice and transplanted into myeloablated wild type recipient mice without the inclusion of any bone marrow helper cells. We found that adult splenocytes repopulated bone marrow of myeloablated mice and the transplanted cells differentiated into a full repertoire of myeloid cell lineages. The level of monocytes/macrophages in the bone marrow of recipient mice was dependent on the cell origin, i.e., the donor splenocytes gave rise to significantly more monocytes/macrophages than the donor bone marrow cells. This occurred despite a significantly lower number of hematopoietic stem cells being present in the donor splenocytes when compared with donor bone marrow cells. Atherosclerosis studies revealed that donor splenocytes displayed a similar level of atherogenic and atheroprotective activities to those of donor bone marrow cells. Cell culture studies showed that the phenotype of macrophages derived from spleen is different from those of bone marrow. Together, these results demonstrate that splenocytes can seed bone marrow of myeloablated mice and modulate atherosclerosis. In addition, our study shows the potential of splenocytes for therapeutic interventions in inflammatory disease.

Background Single-cell resequencing (SCRS) provides many biomedical advances in variations detection at the single-cell level, but it currently relies on whole genome amplification (WGA). Three methods are commonly used for WGA: multiple displacement amplification (MDA), degenerate-oligonucleotide-primed PCR (DOP-PCR) and multiple annealing and looping-based amplification cycles (MALBAC). However, a comprehensive comparison of variations detection performance between these WGA methods has not yet been performed. Results We systematically compared the advantages and disadvantages of different WGA methods, focusing particularly on variations detection. Low-coverage whole-genome sequencing revealed that DOP-PCR had the highest duplication ratio, but an even read distribution and the best reproducibility and accuracy for detection of copy-number variations (CNVs). However, MDA had significantly higher genome recovery sensitivity (~84 %) than DOP-PCR (~6 %) and MALBAC (~52 %) at high sequencing depth. MALBAC and MDA had comparable single-nucleotide variations detection efficiency, false-positive ratio, and allele drop-out ratio. We further demonstrated that SCRS data amplified by either MDA or MALBAC from a gastric cancer cell line could accurately detect gastric cancer CNVs with comparable sensitivity and specificity, including amplifications of 12p11.22 (KRAS) and 9p24.1 (JAK2, CD274, and PDCD1LG2). Conclusions Our findings provide a comprehensive comparison of variations detection performance using SCRS amplified by different WGA methods. It will guide researchers to determine which WGA method is best suited to individual experimental needs at single-cell level. Electronic supplementary material The online version of this article (doi:10.1186/s13742-015-0068-3) contains supplementary material, which is available to authorized users.

dissipation energy, steady point identification Abstract.Low frequency oscillation has been a serious threat to security and stability of power grid, and how to locate the disturbance source accurately is an important issue to suppress low frequency oscillation. The existing location method has poor adaptability to oscillation with time-varying steady points because of the limitations in the derivation of location criterion. This paper presents a disturbance source location method of low frequency oscillation with a better versatility. Firstly, the mechanism and response characteristics of oscillation with time-varying steady points is analyzed, then the energy function of a specific construction form is decomposed into state energy, reciprocation energy and dissipation energy by mathematical derivation. The flow of dissipation energy shows the origin and destination of disturbance energy, so it can be used to identify the specific location of disturbance source. A recognition method for electrical quantities' steady points is also proposed based on cubic spline interpolation in order to meet the needs of energy calculation. The calculation results of examples show that the derivation and analysis of energy structure in this paper is correct, and it is able to locate the disturbance source accurately according to the dissipation energy.

The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scale sequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma., Despite lung adenocarcinoma having a high global mortality, the genetic mutations present in Asian patients are uncharacterized. Here the authors use genomic and transcriptomic analysis to identify thirteen significantly affected genes, including RHPN2, GLI3, MRC2, TP53 and IQGAP3.

electrical distance Abstract. It may lead to low frequency oscillation in interconnected power grid if part of the lines of power transmission section are disconnected. Reducing the output of generators in sending end urgently is an effective measurement to restrain oscillation, and different control strategy may lead to different effect. The damping of generators' control system and its electrical distance to the receiving end are the two important factors which impact the effect of generators tripping. The factors above are quantified respectively by damping contribution and voltage phase angle difference of nodes in this paper, and they are weighted to order according to priority of generators tripping. The damping contribution accumulates the effect of damping torque segmentally by decoupling the electromagnetic torque to synchronous torque and damping torque. The actual power grid system of North China is used to verify the correctness of the method. By comparing the existing security control strategy with the result of the proposed method, it shows that the method in this paper can optimize control performance and reduce control cost. Therefore, this method has some practical value.

Small-for-size syndrome (SFSS) is a serious complication after living donor liver transplantation (LDLT) that can disrupt liver regeneration and result in hepatic dysfunction. Until now, the treatment options for SFSS after LDLT have been very limited. Here we describe a patient with SFSS after LDLT who was successfully treated with a transjugular intrahepatic portosystemic shunt (TIPS). A 56-year-old man who had undergone adult-to-adult LDLT because of decompensated liver cirrhosis started displaying signs of acute jaundice and ascites within 72 hours of the operation. The patient was diagnosed with SFSS, and because he had already undergone splenectomy before the transplant, partial splenic embolization was not feasible. Consequently, the TIPS procedure was chosen in an attempt to reduce portal hyperperfusion. After the procedure, the patient's symptoms were gradually ameliorated and were eventually resolved. In conclusion, when partial splenic embolization is not feasible, TIPS placement may be a feasible option for the treatment of SFSS after LDLT. Liver Transpl, 2012. © 2012 AASLD.

Mouse model induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) is generally accepted as an ideal object to study on the carcinogenesis mechanisms of human colorectal cancer (CRC). The genomic responses to the AOM/DSS treatment in mouse that possibly lead to elucidation of CRC pathological mechanism are still poorly understood. For the first time, we investigated the cancer genome landscape of AOM/DSS mouse model by exome sequencing, to testify its molecular faithfulness to human CRC. Of 14 neoplastic samples, 7575 somatic variants were identified, which resulted in 2507 mutant genes and exhibited a large diversity in both colorectal aberrant crypt foci (ACF) and tumors even those tissues that were gained from the similar morphology or same treatment period. Cross-species comparison of the somatic variants demonstrated the totally different patterns of variable sites, mutant genes and perturbed pathways between mouse and human CRC. We therefore come to a conclusion that the tumorigenesis at genomic level in AOM/DSS model may not be properly comparable with that in human CRC, and the molecular mechanism elicited from this animal model should be carefully evaluated.

Formvar films were treated with different doses of silver ions implantation. The implanted silver ions were found to form silver quantum dots (AgQDs) uniformly distributed in the formvar films. While density of the AgQDs increases as the implantation dose increases, their sizes are not sensitive to the dose. It was found that the formvar films implanted with AgQDs have excellent bacteria killing capability. The same implantation approach can also be extended for application in other matrices. As an example, ZnS nanoribbon was implanted with the same approach to obtain uniformly distributed AgQDs with monodispersed size.

We propose a statistical algorithm MethylPurify that uses regions with bisulfite reads showing discordant methylation levels to infer tumor purity from tumor samples alone. MethylPurify can identify differentially methylated regions (DMRs) from individual tumor methylome samples, without genomic variation information or prior knowledge from other datasets. In simulations with mixed bisulfite reads from cancer and normal cell lines, MethylPurify correctly inferred tumor purity and identified over 96% of the DMRs. From patient data, MethylPurify gave satisfactory DMR calls from tumor methylome samples alone, and revealed potential missed DMRs by tumor to normal comparison due to tumor heterogeneity. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0419-x) contains supplementary material, which is available to authorized users.

In large scale wireless sensor and actuator network (WSAN), unreliable wireless and multihop communications make challenges in designing centralized control due to severe packet dropout and latency. To this end, distributed collaborative control (DCC) scheme based on adaptive chaos mutation particle swarm optimization (ACMPSO) is proposed. In this scheme, control task is carried out collaboratively based on hierarchical clustering using only local information. Moreover, DCC is formulated as an optimization problem, and chaos mutation is introduced to improve the optimal performance of PSO. Simulation shows that the improved PSO has better convergence property, and the proposed scheme works well to obtain control objective.

In large scale wireless sensor and actuator network (WSAN), severe packet dropout and latency make challenges in designing centralized control scheme. Moreover, if system runs stably with little fluctuation of states, period sampling always leads to waste of energy and communication resources. To this end, adaptive distributed event-triggered collaborative control scheme is proposed. In this scheme, distributed event-triggered (DET) mechanism is replaced by adaptive DET mechanism with variable triggering threshold in order to reduce updates of controller law further. Based on local information, distributed collaborative control (DCC) is carried out and formulated as optimization problem. And an improved particle swarm optimization (PSO) with linearly decreasing inertia weight is used to make a good tradeoff between global and local search ability. Simulation shows that, comparing with DET scheme, while guaranteeing required closed-loop performance, ADET scheme needs fewer executions of control task.

A growth of SnO 2 –ZnS heterostructure was realized by a rational two-step thermal evaporation method. Starting with Sn powder, the SnO 2 bicrystalline nanoribbons were grown on the silicon wafers. The secondary growth of ZnS on the former SnO 2 nanostructures correspondingly resulted in the SnO 2 –ZnS nanocomb structures. We investigated the morphology, detailed structure by X-ray diffraction (XRD), scanning electron microscopy (SEM) and high resolution transmission electron microscopy (HRTEM). It revealed that the ZnS nanobranches with [001] growth direction are epitaxial grown from the (− 101) crystal plane of the SnO 2 trunks with a good lattice match. The nanocomb exhibited an effective photocatalytic activity.

The damage and collapse accidents of wind turbines during violent typhoons and rainstorms have increased in recent years. To determine the dynamic response characteristics of high-power wind turbines under extreme conditions, wind load and rain load are simulated. The typhoon average wind velocity and fluctuating wind velocity are simulated by the unstable wind profile and harmony superposition method. The raindrop size distribution is simulated by the M-P spectrum, and the rain load is calculated according to the momentum theorem. A finite element model is established to study the aerodynamic responses of a wind turbine under random typhoon load and typhoon-rain loads. The maximum displacements and accelerations at the tower top and the maximum von Mises stresses at the tower bottom are calculated and compared after considering various combinations of wind direction deflections and rainfall intensities. The results indicate that instantaneous wind direction deflection has a substantial impact on the dynamic responses of wind turbines, and after introducing the effect of rain, the dynamic responses increase up to 13.7% with increasing rainfall intensities. This study has significant implications for analysing collapse accidents of wind turbines and for optimising the design of wind turbines under extreme typhoon conditions.

11580Background: Glioblastoma (GBM) is a common intracranial tumor and the most malignant form of brain cancer in adults and results in a high global mortality. GBM displays mutational complexity b...

The electricity consumption and economic growth are highly correlated. The financial crisis in 2008 brought a negative effect on China’s economic growth, which also influenced the electricity consumption. The electricity demand of North China region was also greatly influenced by this financial crisis, the whole social electricity consumption growth rate of which decreased by 14.31% in 2008 compared to that in 2007. In order to analyze the random impulse effect of the financial crisis on the demand of electricity in North China, the monthly data is decomposed into deterministic trend, stochastic impact effect, and periodic trend using the Beveridge-Nelson decomposition method. After comparatively analyzing the impulse effect of the financial crisis on electricity consumption of six provinces in North China, we can draw the conclusions: (1) the electricity consumption of the whole society and the secondary industry are under larger negative impacts, and the random impulse effect of the secondary industry is more intense; and (2) the impact of the financial crisis on the tertiary industry, which is mainly influenced by seasonal changes, is smaller. Finally, some policy implications are proposed.