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The paper studies the existence of the technology diffusion in M&A with the model of SFA, and the influence of target companies’ technical efficiencies on acquisition premium. The results are as follows: There exists technology diffusion in M&A. High technology gap and industry relevance between acquirers and targets could make the technology diffusion more possible, and then increase M&A premium. It shows that the technical efficiency of the target should serve as a reference for pricing decision of related M&A.

Background Testicular germ cell tumor (TGCT) is the most common malignancy among young men. We conduct this study in order to further understand the genetic determinants of TGCT. Methods Eighteen TGCTs and matched normal controls were obtained from individuals newly diagnosed with TGCT in the hospital. Genomic DNAs were extracted from these samples and whole-exome sequencing was conducted by Hiseq 2000 platform. Copy number variations were called by exomeCNV based on the BWA alignments. Potential somatic substitutions and preliminary list of somatic indels were detected by the analyzed from our data. And these detected mutations were validated by Sanger sequencing. Results We identified a total of 77 nonsynonymous mutations with a uniformly low mutation rate of 0.14 mutations/Mb per tumor, on average. Notably, no somatic SNV was identified in 16.7% (3/18) of the tumors. Nevertheless, CTNNB1 and FZD10 were previously reported related to TGCT, potentially involved in the Wnt signaling pathway, contributing to the reprogram process during human embryonal carcinoma differentiation. Besides, KIAA1486 was the only recurrent gene identified in two tumors samples. With genetic evidence from United Kingdom, our study confirmed that gain of 12p (40/60; 66.7%) is the most frequent chromosomal aberration. Conclusions Our study uncovered a uniformly low mutation rate of these tumors, consistent with previous studies, supporting the embryonical origins of TGCT. Besides, the chromosomal aberrations were invariable presence, and no somatic SNV was identified in 16.7% (3/18) of the tumors, suggesting that chromosomal aberrations held a more critical role in the tumorigenesis of TGCT.

Significance The mammalian circadian clock is controlled by a transcription-translation feedback loop consisting of transcriptional activators circadian locomotor output cycles kaput (CLOCK)–brain and muscle Arnt-like protein-1 (BMAL1), which function as a complex at E/E'-box elements, and repressors Cryptochrome 1 (CRY1)/CRY2 and PER1/PER2. CRYs repress upon binding as CRY–CLOCK–BMAL1–E-box complexes. Period proteins (PERs) repress by removing the heterotrimeric complexes from the E-box. We report here that in the Cry1 promoter, the CRY1–CLOCK–BMAL1–E-box complex represses a transcriptional activator acting in cis, and removal of the heterotrimeric complex by PER2 de-represses the transcriptional activator. ChIP-seq and RNA-seq experiments identified other genes also de-repressed by PER2. These data clarify the role of PER2 and reveal the level of complexity in regulation of Cry1 and other circadian-controlled genes.

Mechanical stimuli play important roles in regulating chondrogenic differentiation, but seldom studies have focused on when and how mechanical stimuli should be initiated. We have previously shown that Col2α1 mRNA was increased by delayed dynamic compressive stress initiated at the 8th day of chondrogenic culture. The current work is to further study the possibility of using delayed mechanical stress to relay chondrogenesis initiated by exogenous TGF-β1. Mechanical stimulation was delivered from day 8 to day 14 of chondrogenic culture. It showed that delayed compressive stress not only stimulated gene expression and protein synthesis of chondrocyte-specific markers, but also stimulated the endogenous TGF-β1 gene transcription, protein expression and the subsequent activation even when exogenous TGF-β1 was discontinued. Furthermore, mechanical stress also promoted protein phosphorylation and nuclear translocation of Smad2/3, the TGF-β1 downstream effectors. Inhibition TGF-β with SB431542 significantly affected the stress-induced chondrogenic gene expression. In addition, phosphorylated-p38 and RhoB were upregulated by delayed loading in a TGF-β-related manner. Phosphorylated-ERK1/2 and Wnt7a were also increased, but in a TGF-β-independent way. It indicates that delayed compressive stress can be used as an effective substitute for TGF-β1 supplement in inducing chondrogenic differentiation.

Suspended matter is an important indicator of water quality in freshwater systems. The flood-induced turbidity current plays a dominant role in the seasonal dynamic of suspended matter in the Liuxihe Reservoir (23°45′50″N; 113°46′52″E), a large, stratified reservoir at the Tropic of Cancer in southern China. Field measurements show that loading and distribution of suspended matter in the reservoir differ in typical wet, dry and medium years, as a result of different discharge volumes and water level variation patterns. Using historical data and the practical demand for water supply and flood control, we generalized two feasible reservoir operational modes: flood impounding mode (drawing down the reservoir to a low level before flood events to impound inflow during the flooding season) and moderate level change mode (drawing down the reservoir to a moderate level before flood events, then keeping the level within the flood control level during runoff events). To examine the effects of different operational modes and outlet depths on the reservoir's flood-induced turbidity current, a numerical simulation model was applied in three types of hydrological conditions. The results show that the mode with moderate drawdown and recharge processes can decrease loading of suspended matter in spring and promote turbidity current release during flood events, and upper withdrawal can improve the effects of turbid water release. We suggest that more attention should be focused on water quality management in the reservoir operation stage, severe artificial water level fluctuation being avoided and selective withdrawal becoming an optional management measure. Copyright © 2012 John Wiley & Sons, Ltd.

The self-assembled organocatalyst of cinchona alkaloid derivatives and amino acids has been applied to a direct asymmetric vinylogous Michael addition of α,α-dicyanoolefins to nitroolefins; the corresponding products could be obtained in moderate to good yields and enantioselectivities.

To solve the cooling problem in modern electronic device, a kind of heat pipe radiator was designed and manufactured in this paper. The heat transfer performance of heat pipe radiator and its relationship with air velocity were investigated by experimental method. The experimental results show that the heat pipe radiator can meet the temperature requirement of electronic device with the power range from 40W to 160W. To keep the operational temperature of electronic device with power of 160W under 75°C，the air velocity should be keep at 1.7m/s. The heat dissipation performance of heat pipe radiator was enhanced with the air velocity increased from 0.2m/s to 1.7m/s.for the electronic equipment with power of 160W.

In recent years, water quality degradation associated with rapid socio-economic development in the Taihu Lake Basin, China, has attracted increasing attention from both the public and the Chinese government. The primary sources of pollution in Taihu Lake are its inflow rivers and their tributaries. Effective water quality improvement programs need to be implemented in these rivers to improve the water quality of Taihu Lake, and to ensure sustainable development in the region. To ensure effectiveness and efficiency, it is important that the optimal water quality improvement program for a specific situation be selected. The aim of this study was to facilitate the selection of this optimal program. The QUAL2K model for river and stream water quality was used to simulate the effects of a range of water quality improvement scenarios in the Hongqi River, which is a polluted tributary in the Taihu Lake Basin. These scenarios consisted of a series of three water treatment technologies in different configurations, from upstream to downstream. The results showed that the optimal scenario comprised a bio-contact oxidation system upstream, followed by an ecological floating bed, and a vertical moveable eco-bed downstream. The reduction rates achieved by this scenario for biochemical oxygen demand (BOD), ammonia nitrogen (NH 3 –N), total nitrogen (TN), and total phosphorus (TP) were 49.50%, 32.81%, 35.94%, and 45.27%, respectively. The QUAL2K model proved to be an effective tool in the comparative evaluation of potential water quality improvement programs. The method applied in this study can prevent the implementation of water quality improvement programs that would not achieve the desired goals.

The innate immune system of fish is the primary defense against acute diseases. The marine medaka Oryzias melastigma has been shown to be a potential marine fish model for ecotoxicology, but little is known about the innate immune system of this small fish. In this study, suppression subtractive hybridization (SSH) was used to identify differentially expressed immune genes in the liver of O. melastigma infected with Vibrio parahaemolyticus. Among the 396 genes identified, based on NCBI BLAST search of the 1279 sequenced clones in the SSH libraries, 38 (9.6%) were involved in the immune process. Besides, genes involved in biological regulations (5.6%); cellular metabolism (24.7%); general response to stimuli (4.8%); cellular component organization (2.3%); signal transduction (2.5%) and transport process (2.8%) were also obtained. Ten complement component genes involved in four activation pathways were quantified (using q-PCR) and exhibited different patterns of transcription between the control and challenged individuals. The results reported upon here support the feasibility of developing O. melastigma as a marine model fish to understand the basic biological processes related to immune function and for immunotoxicological research. Findings of this study established a genetic platform for studying immune function using O. melastigma.

Treated effluent from wastewater treatment plants has become an important source of excess nutrients causing eutrophication in water. In this study, an ecological purification method was used to further treat eutrophic water. A three-season ecological purification scheme which comprised an emergent plant (Eme.), a submerged plant (Sub.) and a novel biological rope (Bio.), was designed for the treated effluent canal of a wastewater treatment plant. The removal parameters determined from the experiment were input into a QUAL2K model to simulate downstream water quality of the treated effluent canal. Respective removal rates of total nitrogen and total phosphorus of the Eme., Sub. and Bio. were 32.48–37.33% and 31.63–39.86% in summer, 14.12–33.61% and 17.74–23.80% in autumn, and 14.13–18.03% and 10.05–12.75% in winter, with 1-day reaction time. Optimal combinations for summer, autumn/spring, and winter are Eme. + Bio., Eme. + Bio. + Sub., and Sub. + Bio., respectively. Simulated load reduction rates of total nitrogen and total phosphorus for the treated effluent canal were 42.64–78.40% and 30.98–78.29%, respectively, year round with 2.5-day reaction time. This study provides an efficient evaluation and design method for ecological purification engineering.

The spontaneous emission (SE) of Er3+ embedded in a double slot dielectric structure was studied by a quantum-electrodynamical formalism. The study shows that the slot width and the position of Er3+ in slot structure have a significant effect on the SE. The double slot waveguides were fabricated by embedding two low-index Er/Yb silicate material layers into high-index silicon. The radiative efficiency of Er3+ in the double slot waveguides is found to be higher than that of the single slot waveguide, which is consistent with the theory simulation. The 0.67 dB signal enhancement at 1.53 µm in a 4.6-mm-long slot waveguide was observed pumped by 1476 nm laser. These results show the relevance of our model to study the SE processes in multilayer structures and are important for future realization of silicon-compatible active optical devices.

In this paper, the heat transfer characters of heat pipe radiator for cooling electronic device with high heat flux were investigated by visualization method. The surface temperature of heat pipe radiator was measured at different heat flux and constant fan speed of 0.7m/s, and the results show that the surface temperature of electronic apparatus is below 75°C for the heat flux 8W/cm2 at constant fan speed of 0.7m/s; The error in measured value using thermocouple and technique of infrared thermography was analyzed based on the principles of temperature measurement of infrared thermal imager.

The current consensus model for the circadian clock in mammals is based on a transcription-translation feedback loop. In this model, CRY and PER proteins repress their own transcription by suppressing the transactivator function of the CLOCK:BMAL1 heterodimer directly (physical model) and by facilitating post-translational modifications (chemical model). Most of the data for this model come from genetic and cell biological experiments. Here, we have purified all of the core clock proteins and performed in vitro and in vivo biochemical experiments to test the physical model. We find that CLOCK:BMAL1 binds to an E-box sequence in DNA and that CRY binds stably to the CLOCK:BMAL1:E-box ternary complex independently of PER. Both CRY and PER bind to CLOCK and BMAL1 off DNA but, in contrast to CRY, PER does not bind to the CLOCK:BMAL1:E-box complex. Unexpectedly, PER actually interferes with the binding of CRY to the CLOCK:BMAL1:E-box ternary complex. CRY likely destabilizes the CLOCK:BMAL1 heterodimer on DNA by a post-translational mechanism after binding to the complex. These findings support some aspects of the canonical model, but also suggest that some key features of the model need to be revised.

Cryptochromes (CRYs) are blue-light photoreceptors with known or presumed functions in light-dependent and light-independent gene regulation in plants and animals. Although the photochemistry of plant CRYs has been studied in some detail, the photochemical behavior of animal cryptochromes remains poorly defined in part because it has been difficult to purify animal CRYs with their flavin cofactors. Here we describe the purification of type 4 CRYs of zebrafish and chicken as recombinant proteins with full flavin complement and compare the spectroscopic properties of type 4 and type 1 CRYs. In addition, we analyzed photoinduced proteolytic degradation of both types of CRYs in vivo in heterologous systems. We find that even though both types of CRYs contain stoichiometric flavin, type 1 CRY is proteolytically degraded by a light-initiated reaction in Drosophila S2, zebrafish Z3, and human HEK293T cell lines, but zebrafish CRY4 (type 4) is not. In vivo degradation of type 1 CRYs does not require continuous illumination, and a single light flash of 1 ms duration leads to degradation of about 80% of Drosophila CRY in 60 min. Finally, we demonstrate that in contrast to animal type 2 CRYs and Arabidopsis CRY1 neither insect type 1 nor type 4 CRYs have autokinase activities.

A rice (Oryza sativa) T-DNA insertion population, which included more than 63 000 independent transgenic lines and 8 840 identified flanking sequence tags (FSTs) that were mapped onto the rice genome, was developed to systemically study the rice seed quality control. Genome-wide analysis of the FST distribution showed that T-DNA insertions were positively correlated with expressed genes, but negatively with transposable elements and small RNAs. In addition, the recovered T-DNAs were preferentially located at the untranslated region of the expressed genes. More than 11 000 putative homozygous lines were obtained through multi-generations of planting and resistance screening, and measurement of seed quality of around half of them, including the contents of starch, amylose, protein and fat, with a nondestructive near-infrared spectroscopy method, identified 551 mutants with unique or multiple altered parameters of seed quality. Analysis of the corresponding FSTs showed that genes participating in diverse functions, including metabolic processes and transcriptional regulation, were involved, indicating that seed quality is regulated by a complex network.

To investigate the regulatory effect of miR-29b on gastric cells' resistance to cisplatin.The expression of miR-29b in gastric cancer cell line treated with cisplatin concentration gradient was detected using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. CCK8 was used to measure the cell viability after cisplatin treatment in condition of miR-29b knock-down and overexpression.The expression of miR-29b was significantly upregualted by cisplatin treatment,while its target gene AKT2 was downregulated. The up-regulation of miR-29b enhanced the sensitivity of gastric cancer cells to cisplatin,while the knock-down of miR-29b enhanced the cisplatin resistance. Rescue experiments demonstrated that the miR-29b might regulate cisplatin resistance of gastric cancer cell by targeting PI3K/Akt pathway. The expressions of the other two members of miR-29 family, miR-29a/c, were promoted by cisplatin treatment,but they had no significant effect on gastric cancer cell's resistance to cisplatin.miR-29b can enhance the sensitivity of S gastric cancer cell by directly targeting PI3K/Akt pathway.

Traditional trust evaluation models in wireless sensor networks separate detection and evaluation from data aggregation. Data accuracy is ignored in these models. Algorithms like WTE alleviate some of the problem, but not all. For example, it cannot resist attacks from nodes with a good reputation. Another ignored problem is the false detection caused by occasional abnormal behavior, hash environment and model flaw. To solve the problems mentioned above, this paper proposes a multidimensional trust evaluation model based on redemption and data aggregation. One malicious node can launch various attacks. Bad data attack is one of them. When data are aggregated, Spatial and temporal correlation are taken into consideration. Nodes recognized to transmit bad data are refused to join the data aggregation. Isolated nodes are given a chance to return to networks if certain conditions are satisfied. But the network has less tolerance to them. The simulation prevents that the model has high detection rate and more accurate data.

// Yongqiang Wang 1, 2, * , Yuan Yu 3, * , Rui Ye 3, * , Duo Zhang 3, * , Qiaoling Li 3 , Dan An 3 , Lu Fang 4 , Youcheng Lin 5 , Yong Hou 3 , Abai Xu 5 , Yu Fu 6 , Wei Lu 4 , Xin Chen 1 , Mingwei Chen 4 , Meng Zhang 4 , Huiling Jiang 7 , Chuanxia Zhang 8 , Pei Dong 1 , Chong Li 9 , Jun Chen 10 , Guosheng Yang 6 , Chunxiao Liu 5 , Zhiming Cai 11 , Fangjian Zhou 1 , Song Wu 2, 11 1 Department of Urology, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangzhou, 510060, China 2 The Affiliated Luohu Hospital of Shenzhen University, Shenzhen Luohu Hospital Group, Shenzhen 518000, China 3 BGI-Shenzhen, Shenzhen 518083, China 4 Anhui Medical University, Hefei 230032, China 5 Department of Urology, Zhujiang Hospital of Southern Medical University, Guangzhou 510280, China 6 The Second People’s Hospital of Guangdong Province, Guangzhou 510310, China 7 The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China 8 Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China 9 CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China 10 The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China 11 Department of Urological Surgery, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, China * These authors contributed equally to this work Correspondence to: Song Wu, e-mail: doctor_wusong@126.com Fangjian Zhou, e-mail: zhoufj@sysucc.org.cn Keywords: bladder cancer, epigenetics, methylation, biomarkers, qMSP Received: May 07, 2015 Accepted: November 20, 2015 Published: December 19, 2015 ABSTRACT To develop a routine and effectual procedure of detecting bladder cancer (BlCa), an optimized combination of epigenetic biomarkers that work synergistically with high sensitivity and specificity is necessary. In this study, methylation levels of seven biomarkers ( EOMES , GDF15 , NID2 , PCDH17 , POU4F2 , TCF21 , and ZNF154 ) in 148 individuals—which including 58 urothelial cell carcinoma (UCC) patients, 20 infected urinary calculi (IUC) patients, 20 kidney cancer (KC) patients,20 prostate cancer (PC) patients, and 30 healthy volunteers (HV)—were quantified by qMSP using the urine sediment DNA. Receiver operating characteristic (ROC) curves were generated for each biomarker. The combining predictors of possible combinations were calculated through logistic regression model. Subsequently, ROC curves of the three best performing combinations were constructed. Then, we validated the three best performing combinations and POU4F2 in another 72 UCC, 21 IUC, 26 KC and 22 PC, and 23 HV urine samples. The combination of POU4F2/PCDH17 has yielded the highest sensitivity and specificity of 90.00% and 93.96% in all the 312 individuals, showing the capability of detecting BlCa effectively among pathologically varied sample groups.

Lake Taihu has undergone severe eutrophication in the past three decades, and harmful cyanobacteria blooms occur nearly every year in Meiliang Bay at the north end of the lake. To elucidate the potential relationship between seasonal nutrient limitation and phytoplankton proliferation, a 20-year (1991-2012) time series of nutrient limitation in Meiliang Bay was analyzed for deviations between trophic state index (TSI) parameters. Results showed that patterns of nutrient limitation in Meiliang Bay were distinctly seasonal, where phytoplankton growth was generally phosphorus (P)-limited in winter and spring, but nitrogen (N)-limited mainly occurred in summer and fall. This general pattern, however, shifted into N limitation across the four seasons during the mid-1990s because a rapid increase in industrialization led to a significant rise in the input of N and P from inflowing tributaries. The initial patterns were restored by environmental regulation in the end of 1990s, including the Zero Actions plan. Using routine monitoring data, a generalised additive model (GAM) with time and deviations between trophic state indexes for nitrogen and phosphorus (TSIN-TSIP) as explanatory variables was used to explore which nutrient was responsible for limitation of phytoplankton chlorophyll-a (Chl-a) in different seasons. Surprisingly, the model revealed a weak N limitation (TSIN-TSIP = -10) corresponded to peak values of Chl-a in summer-autumn season, which is probably because the phytoplankton community is co-limited by N & P during the period. The shift of nutrition limitation during winter-spring would partially explain high values of Chl-a throughout 1996. This study suggests that seasonal patterns of nutrient limitation must be considered to develop effective management measures to control cyanobacterial blooms.

Industrialization and urbanization have caused water pollution and ecosystem degradation, especially in urban canals and rivers in China, accordingly, effective water quality improvement programs are needed. In this study, the Tianlai River in Jiangsu, China was taken as a research site, and a combination of ecological purification technologies consisting of biological rope, phytoremediation, and activated carbon were applied in a laboratory-scale study to examine degradation coefficients under dynamic water conditions. Coefficients were then input into the QUAL2K model to simulate various hypothetical scenarios and determine the minimum density of ecological purification combination and hydraulic retention time (HRT) to meet Grade V or IV of the China standard for surface water. The minimum densities for Grade V and IV were 1.6 times and 2 times the experimental density, while the minimum HRTs for Grade V and IV were 2.4 day and 3 day. The results of this study should provide a practical and efficient design method for ecological purification programs.

The isothermal curing of polymethacrylimide (PMI) is studied through the use of dynamic mechanical analysis (DMA). Based on the growth rate of measured dynamic mechanical property, the relative conversion is defined to investigate the evolution of storage modulusE′at different curing temperatures. Hsich’s nonequilibrium thermodynamic fluctuation theory, Avrami equation, and isoconversional methods are used to analyze isothermal cure kinetics of PMI. The results show that there are different increase modes ofE′at low temperature range and high temperature range, respectively. In low temperature range, the relative conversion curves include a transitional stage which is found to be strongly frequency-dependent, but this stage is not observed in the relative conversion curve in high temperature range. During the isothermal curing process, the relative evolution ofE′can be described by Hsich’s nonequilibrium thermodynamic fluctuation theory and Avrami equation. Moreover, the values and evolutions of activation energy are different in two temperature ranges, which suggest that the curing mechanism probably has changed.

The deterioration of water quality in Taihu Lake, China, has caused widespread concern in recent years. The primary pollution sources of Taihu Lake are its inflow rivers. Effective environmental water management strategies need to be implemented in these rivers to improve the water quality of Taihu Lake and to promote sustainable development in the region. In this study, the QUAL2K model is used in conjunction with the trial and error approach to assess permissible load capacities for the Wujin River (a major tributary of Taihu Lake) in terms of COD, NH3-N, TN, and TP. Results show that permissible annual loads for these pollutants are 5216.31, 491.71, 948.53, and 104.38 t, respectively. This suggests that COD, NH3-N, TN, and TP loads in the Wujin River catchment need to be reduced by 13.35, 27.26, 47.75, and 37.08 %, respectively, to satisfy national water quality objectives. Total amount control measures are proposed to control and reduce pollution loads of the Wujin River catchment. The method applied in this study should provide a sound basis for water environmental management decision-making.

Inositol polyphosphates, such as inositol trisphosphate, are pivotal intracellular signaling molecules in eukaryotic cells. In higher plants the mechanism for the regulation of the type and the level of these signaling molecules is poorly understood. In this study we investigate the physiological function of an Arabidopsis (Arabidopsis thaliana) gene encoding inositol polyphosphate kinase (AtIPK2α), which phosphorylates inositol 1,4,5-trisphosphate successively at the D-6 and D-3 positions, and inositol 1,3,4,5-tetrakisphosphate at D-6, resulting in the generation of inositol 1,3,4,5,6-pentakisphosphate. Semiquantitative reverse transcription-PCR and promoter-β-glucuronidase reporter gene analyses showed that AtIPK2α is expressed in various tissues, including roots and root hairs, stem, leaf, pollen grains, pollen tubes, the flower stigma, and siliques. Transgenic Arabidopsis plants expressing the AtIPK2α antisense gene under its own promoter were generated. Analysis of several independent transformants exhibiting strong reduction in AtIPK2α transcript levels showed that both pollen germination and pollen tube growth were enhanced in the antisense lines compared to wild-type plants, especially in the presence of nonoptimal low Ca2+ concentrations in the culture medium. Furthermore, root growth and root hair development were also stimulated in the antisense lines, in the presence of elevated external Ca2+ concentration or upon the addition of EGTA. In addition, seed germination and early seedling growth was stimulated in the antisense lines. These observations suggest a general and important role of AtIPK2α, and hence inositol polyphosphate metabolism, in the regulation of plant growth most likely through the regulation of calcium signaling, consistent with the well-known function of inositol trisphosphate in the mobilization of intracellular calcium stores.

We conducted an open-label single-arm phase II study by combining irinotecan (FOLFIRI) and bevacizumab (BV) plus erlotinib (ER) in 2nd-line chemotherapy for patients with metastatic colorectal cancer (mCRC). Eligible mCRC patients received 1st-line standard chemotherapy but still had progressive disease. They were given FOLFIRI plus BV at 2.5 mg/kg on day 1 per 2-week cycle, and daily 150 mg ER. The primary endpoint is progression-free survival (PFS). A total of 122 patients enrolled in the study. Among them, 55.7% were male patients and median age was 58.4 years (29–72 years). Median PFS was 7.1 months (95% CI 4.3–10.2). Median overall survival (OS) was 13.5 months (95% CI 9.7–16.4). No patients had complete responses, 24 patients had partial response (19.6%) and 59 had stable disease (48.4%). The most frequent adverse event (AE) was rash, with 66 patients (54.1%) had grade 3/4 rash. Other frequent grade 3/4 AEs were fatigue (n = 36, 29.5%), bleeding (n = 31, 25.4%), neutropenia (n = 23, 18.9%), and platelets (n = 14, 11.5%). Combining FOLFIRI and BV plus ER in 2nd-line chemotherapy is efficient to treat mCRC patients with acceptable safety.

We sequenced whole exomes of ten clear cell renal cell carcinomas (ccRCCs) and performed a screen of ∼1,100 genes in 88 additional ccRCCs, from which we discovered 12 previously unidentified genes mutated at elevated frequencies in ccRCC. Notably, we detected frequent mutations in the ubiquitin-mediated proteolysis pathway (UMPP), and alterations in the UMPP were significantly associated with overexpression of HIF1α and HIF2α in the tumors (P = 0.01 and 0.04, respectively). Our findings highlight the potential contribution of UMPP to ccRCC tumorigenesis through the activation of the hypoxia regulatory network.

After discovery of extraordinary transmission (EOT) subwavelength hole arrays structures patterned on a metal film have generated wide interest as they offer high optical transmission and strong localized electric near-field intensities. However, the large ohmic losses exhibited by SPs in the optical regime represent a fundamental limitation that reduces drastically the practical applicability of EOT properties. Furthermore, not compatible with silicon platform make it difficult for application purposes. As a possible solution to this fundamental problem, gain medium have been introduced to compensate the loss created by metallic film. But the most important yet challenging requirements for gain material are to be silicon compatible and working at telecommunication regime. The aim of this paper is to theoretically study optical amplification of EOT properties in periodic hole arrays incorporating optically pumped gain media. The gain media was selected Erbium/Ytterbium(Er/Yb) silicate that is silicon compatible with photoluminescence peak at telecommunication regime. Use of Er 3+ ions has the advantages of proven, stable, and low-noise operation at the technologically important 1.54 m region. To excite the active material a laser with a maximum power of 372 mW at the wavelength of 1480 nm is applied. Geometrical parameters was obtained by solving the surface plasmon dispersion relation on periodic hole arrays. The condition for lossless propagation was obtained analytically. Simulation results shows that for lossless propagation we will need higher gain value. By considering higher gain values the absorption was approached to zero 30% transmission enhancements was observed at telecommunication wavelength.

The circadian clock is a global regulatory system that interfaces with most other regulatory systems and pathways in mammalian organisms. Investigations of the circadian clock–DNA damage response connections have revealed that nucleotide excision repair, DNA damage checkpoints, and apoptosis are appreciably influenced by the clock. Although several epidemiological studies in humans and a limited number of genetic studies in mouse model systems have indicated that clock disruption may predispose mammals to cancer, well-controlled genetic studies in mice have not supported the commonly held view that circadian clock disruption is a cancer risk factor. In fact, in the appropriate genetic background, clock disruption may instead aid in cancer regression by promoting intrinsic and extrinsic apoptosis. Finally, the clock may affect the efficacy of cancer treatment (chronochemotherapy) by modulating the pharmacokinetics and pharmacodynamics of chemotherapeutic drugs as well as the activity of the DNA repair enzymes that repair the DNA damage caused by anticancer drugs.

The mammalian circadian clock is based on a transcription–translation feedback loop (TTFL) in which CLOCK and BMAL1 proteins act as transcriptional activators of Cryptochrome and Period genes, which encode proteins that repress CLOCK–BMAL1 with a periodicity of ∼24 h. In this model, the mechanistic roles of CRY and PER are unclear. Here, we used a controlled targeting system to introduce CRY1 or PER2 into the nuclei of mouse cells with defined circadian genotypes to characterize the functions of CRY and PER. Our data show that CRY is the primary repressor in the TTFL: It binds to CLOCK–BMAL1 at the promoter and inhibits CLOCK–BMAL1-dependent transcription without dissociating the complex (“blocking”-type repression). PER alone has no effect on CLOCK–BMAL1-activated transcription. However, in the presence of CRY, nuclear entry of PER inhibits transcription by displacing CLOCK–BMAL1 from the promoter (“displacement”-type repression). In light of these findings, we propose a new model for the mammalian circadian clock in which the negative arm of the TTFL proceeds by two different mechanisms during the circadian cycle.

OBJECTIVE: To evaluate the function of Piezo1, an evolutionarily conserved mechanically activated channel, in periodontal ligament (PDL) tissue homeostasis under compressive loading. MATERIALS AND METHODS: Primary human PDL cells (hPDLCs) were isolated, cultured, and then subjected to 2.0 g/cm(2) static compressive loading for 0.5, 3, 6, and 12 hours, respectively. The expressions of Piezo1 and osteoclastogenesis marker gene were assessed by semiquantitative reverse transcription–polymerase chain reaction. In addition, Piezo1 inhibitor, GsMTx4, was used to block the function of Piezo1, and tumor necrosis factor–α was also used as a positive control. After 12 hours of compressive loading the PDLCs were co-cultured with murine monocytic cell line RAW264.7. Immunofluorescence, western blot, enzyme-linked immunosorbent assay, and tartrate-resistant acid phosphatase staining were also used to test the potency of PDLCs to induce osteoclastogenesis and the activation of nuclear factor (NF)-κB. RESULTS: Piezo1, cyclooxygenase-2, receptor activator of NF-κB ligand, and prostaglandin E2 were significantly upregulated under static compressive stimuli. GsMTx4 repressed osteoclastogenesis in the mechanical stress–pretreated PDLCs-RAW264.7 co-culture system. Furthermore, NF-κB signaling pathway was involved in the mechanical stress–induced osteoclastogenesis. CONCLUSIONS: Piezo1 exerts a transduction role in mechanical stress–induced osteoclastogenesis in hPDLCs.

To create the fingerprint library of Yunnan Yersinia pestis by pulse field gel electrophoresis(PFGE)with Fse I enzyme digestion method and to study its epidemiological significance.We used rare cutting restriction enzyme Fse? to digest Yunnan Yersinia pestis strains that were isolated from foci including Rattus flavipectus Plague Focus,Apodemus chevrieri-Eothenomys miletus Plague Focus and Yulong Plague Focus. Fingerprints to Bionumerics software were used for cluster analysis.30 tested strains were divided into 16 genotypes with the similarity value as 79.8%-100.0% . 16 genotypes wee formed into 4 clusters, with one consisted of only EV76 while the other three belonged to Rattus flavipectus,Apodemus chevrieri- Eothenomys miletus and Yulong clusters, respectively.PFGE genotypes of Yunnan Yersinia pestis accorded with its ecotypes and biovars, with clustered regional features. The strains isolated from Yulong showed an unique PFGE type, indicating a new clone group was identified.

A chiral nickel complexes-catalyzed enantioselective Michael addition of 1,3-dicarbonyl compounds to 3-nitro-2H-chromenes has been developed; the products could be obtained in high yields and good enantioselectivities.

Chondrocytes integrate numerous microenvironmental cues to mount physiologically relevant differentiation responses, and the regulation of mechanical signaling in chondrogenic differentiation is now coming into intensive focus. To facilitate tissue-engineered chondrogenesis by mechanical strategy, a thorough understanding about the interactional roles of chemical factors under mechanical stimuli in regulating chondrogenesis is in great need. Therefore, this study attempts to investigate the interaction of rat MSCs with their microenvironment by imposing dynamic and static hydrostatic pressure through modulating gaseous tension above the culture medium. Under dynamic pressure, chemical parameters (pH, pO2, and pCO2) were kept in homeostasis. In contrast, pH was remarkably reduced due to increased pCO2 under static pressure. MSCs under the dynamically pressured microenvironment exhibited a strong accumulation of GAG within and outside the alginate beads, while cells under the statically pressured environment lost newly synthesized GAG into the medium with a speed higher than its production. In addition, the synergic influence on expression of chondrogenic genes was more persistent under dynamic pressure than that under static pressure. This temporal contrast was similar to that of activation of endogenous TGF-β1. Taken altogether, it indicates that a loading strategy which can keep a homeostatic chemical microenvironment is preferred, since it might sustain the stimulatory effects of mechanical stimuli on chondrogenesis via activation of endogenous TGF-β1.

Objective: To investigate the relationship between primary dysmenorrhea (PD) and orthodontic pain in female patients, and to test the hypothesis that the intensity and duration of orthodontic pain could be roughly predicted by severity of PD. Materials and Methods: One hundred twenty college females were enrolled and put into one of three groups—mild (Mi), moderate (Mo), or severe (S)—according to level of menstrual pain. Intensity of the orthodontic pain was measured by visual analog scale (VAS) on days 1, 2, 4, 7, 14, and 28 after archwire placement. Results: As the intensity of orthodontic pain declined with time, the three groups demonstrated different changes during the initial week. Mi had the lowest VAS scores, whereas S possessed the highest scores. In contrast, Mo stayed in between. Significantly positive correlations were found between the severity of PD and the intensity of orthodontic pain at each time point within the first 2 weeks. In addition, though the majority of subjects reported disappearance of pain by the end of the second week in both Mi and Mo, a large proportion of females still perceived pain in S. Conclusion: Females with higher levels of menstrual pain tended to perceive orthodontic pain with higher intensity and more prolonged duration. Thus, PD could potentially serve as a reference to predict orthodontic pain in clinical settings.

Cancer stem cells (CSCs), or cancer cells with stem cell properties, represent a small fraction of tumor bulk and are thought to be responsible for tumor formation and metastasis. However, the mechanisms of how CSCs are generated and regulated at the molecular level are poorly understood. Recent progress has highlighted the significance of microRNAs (miRNAs) in cancer progression and CSC function. The function and dysfunction of miRNAs in the development of cancer and CSCs have become a burgeoning area of intense research. A new finding has elucidated a mechanism of antagonistic miRNA crosstalk whereby one miRNA can inhibit another miRNA in regulating CSCs. Herein we make this short review to summarize the current understanding of the regulatory mechanisms of miRNAs in cancer and CSCs and discuss the implications of targeting CSCs for cancer therapeutics.

Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide and has no effective treatment, yet the molecular basis of hepatocarcinogenesis remains largely unknown. Here we report findings from a whole-genome sequencing (WGS) study of 88 matched HCC tumor/normal pairs, 81 of which are Hepatitis B virus (HBV) positive, seeking to identify genetically altered genes and pathways implicated in HBV-associated HCC. We find beta-catenin to be the most frequently mutated oncogene (15.9%) and TP53 the most frequently mutated tumor suppressor (35.2%). The Wnt/beta-catenin and JAK/STAT pathways, altered in 62.5% and 45.5% of cases, respectively, are likely to act as two major oncogenic drivers in HCC. This study also identifies several prevalent and potentially actionable mutations, including activating mutations of Janus kinase 1 (JAK1), in 9.1% of patients and provides a path toward therapeutic intervention of the disease.

Cancer stem cells (CSCs) represent a small subset of cancer cell populations that possess characteristics associated with normal stem cells. They have the ability to self-renew, and are able to generate diverse tumor cells and account for metastases. Therefore, CSCs are widely accepted as potential mediators of therapeutic resistance and novel targets for anti-cancer treatments. Recent progress has highlighted the significance of epithelial-mesenchymal transition (EMT) process in CSC formation, as well as the crucial role of microRNAs in controlling EMT and cancer metastasis. MicroRNAs are also reported to take part in the control of CSC functions and the regulation of cancer progression by affecting EMT process. Thus, it is highly crucial to develop deeper understanding of the mechanisms that how microRNAs control EMT processes and regulate CSC functions for better therapeutics of cancer disease. Herein we make this review to summarize the current understanding of the regulatory mechanisms of EMT in CSC initiation, with a special focus on the role of microRNAs in EMT control, and discuss the implications of targeting CSCs for cancer therapeutics.

Summary Objectives To describe the clinical characteristics of septic pulmonary embolism in adults in order to improve its diagnosis and treatment. Methods Specific search terms were used for retrieval from commonly used Chinese and English databases and the articles were selected in accordance with the inclusion and exclusion criteria. Cases from the included articles were pooled; then the following parameters were analyzed: major risk factors, clinical manifestations, imaging findings, characteristics of pathogenic microorganisms, complications and other clinical characteristics. Results After strictly selected by the inclusion and exclusion criteria , 76 articles were selected (2 Chinese articles and 74 English articles) that described 168 cases. The major risk factors for SPE were intravenous drug use ( n = 44), intravascular indwelling catheter ( n = 21) and skin or soft tissue purulent infection ( n = 10). The most frequent clinical manifestations were fever ( n = 144), dyspnea ( n = 81), chest pain ( n = 82) and cough ( n = 69). Chest CT showed multiple peripheral nodules in both lungs ( n = 89), cavitation ( n = 75), focal or wedge-shaped infiltrates ( n = 48) and pleural effusion ( n = 40). Echocardiography often revealed vegetations ( n = 52). Blood cultures grew methicillin-resistant Staphylococcus aureus (MRSA) ( n = 27), methicillin-sensitive Staphylococcus aureus (MSSA) ( n = 48) and Candida ( n = 6). Seventeen cases died and 101 cases were cured. Conclusions SPE is a rare disease without specific clinical manifestations. For high-risk groups, such as intravenous drug users or patients with intravascular indwelling catheters, fever and imaging findings of multiple nodules or local infiltrates, with or without cavitation, are highly suggestive of SPE. Early diagnosis and prompt antimicrobial therapy or surgical intervention can lead to a successful treatment outcome.

In an effort to decrease the aggregation of tetracalcium phosphate (TTCP, Ca4(PO4)2O) in composites and develop better bone substitute materials, a series of poly(l-lactic acid) (PLLA)-grafted TTCP (g-TTCP) particles were prepared by a ring-opening polymerization with l-lactide (the monomer for synthesizing PLLA) in the presence of catalyst stannous octoate [Sn(Oct)2]. The g-TTCP/poly(1,4-butylene succinate) (PBS) composites with the different g-TTCP contents were prepared via melting processing. The bonding between the PLLA and the TTCP particles was analyzed by FTIR, TG, (1)H NMR and XPS. The results confirmed that the PLLA was grafted on the surface of the TTCP particles. Time-dependent phase monitoring indicated that the g-TTCP had enhanced dispersion in the PBS solution. Water contact angle measurement and cell culture were also used to investigate the properties of the g-TTCP/PBS composites. The g-TTCP in composites provided more favorable environments for rat osteoblast to attach and grow on the surface of the g-TTCP/PBS composites. Cell proliferated well in the extracted solution of the g-TTCP/PBS composites with different g-TTCP content, and there was no necrotic or suspended cells appeared.

Carbon nanotubes (CNT) are allotropes of carbon with a cylindrical nanostructure. They have recently aroused great interests as drug carriers, but their pharmacokinetic profiles which determine their potentials in clinical application are yet to be fully understood. Therefore, this overview attempts to outline the processes of absorption, distribution, metabolism and excretion (ADME) that govern the pharmacokinetics of CNT. In addition, the molecular mechanisms of intracellular internalization and drug release are also discussed.

The cancer stem cell (CSC) concept, which arose about a decade ago, proposes that tumor growth is sustained by a subpopulation of highly malignant cells. These cells, termed CSCs, are capable of extensive self-renewal that contributes to metastasis and treatment resistance. Therefore, therapeutic strategies that target CSCs should be developed for improving outcomes of cancer patients. Recent progress has highlighted the importance of physical properties of the extracellular matrix and mechanotransduction pathway in cancer cells during cancer development. On the other hand, the significance of CXCR1, an upstream signal of FAK/PI3K/Akt has been revealed in CSCs. FAK/PI3K/Akt is a key signal mediator in mechanotransduction pathway. Therefore, mechanotransduction could be a new target for CSCs, and would be an innovative way to treat cancer by inhibiting FAK/PI3K/Akt.

To investigate the relationship between occlusal plane and sagittal position of the mandible by examining dental and skeletal morphologies of average angle patients for better understanding of etiologies and definitive clinical guidelines of mandibular malpositions.The lateral cephalograms of 114 female average angle patients with neutral maxillary positions were selected and divided into three groups according to sagittal mandibular positions (ANB angle). Twenty-five skeletal and dental measurements were compared. The correlations between skeletal and dental measurements were analyzed by rectilinear correlation.Cant of posterior occlusal plane (OP-P) and height of the upper second molar were significantly related to sagittal position of the mandible (P0.05). Height of the upper second molar was relatively inadequate and OP-P was sloped when the mandible was positioned posteriorly; conversely, height of the upper second molar was excessive and OP-P tended to be flat when the mandible was positioned anteriorly. Tooth axial inclinations were affected by sagittal position of the mandible. Maxillary teeth proclined distally and mandibular ones mesially for patients with retrognathia. On the other hand, maxillary teeth proclined mesially while mandibular ones distally for patients with prognathia.There was a definite relationship between cant of posterior occlusal plane and sagittal position of the mandible in average angle patients, consistent with the dental morphologies of different skeletal configurations. In treating malocclusions of sagittal discrepancy of mandible, the height of posterior teeth and cant of OP-P might be a primary concern.

Salinity is among the environmental factors that affect plant growth and development and constrain agricultural productivity. Salinity stress triggers increases in cytosolic free Ca(2+) concentration ([Ca(2+)]i) via Ca(2+) influx across the plasma membrane. Salinity stress, as well as other stresses, induces the production of reactive oxygen species (ROS). It is well established that ROS also triggers increases in [Ca(2+)]i. However, the relationship and interaction between salinity stress-induced [Ca(2+)]i increases and ROS-induced [Ca(2+)]i increases remain poorly understood. Using an aequorin-based Ca(2+) imaging assay we have analyzed [Ca(2+)]i changes in response to NaCl and H2O2 treatments in Arabidopsis thaliana. We found that NaCl and H2O2 together induced larger increases in [Ca(2+)]i in Arabidopsis seedlings than either NaCl or H2O2 alone, suggesting an additive effect on [Ca(2+)]i increases. Following a pre-treatment with either NaCl or H2O2, the subsequent elevation of [Ca(2+)]i in response to a second treatment with either NaCl or H2O2 was significantly reduced. Furthermore, the NaCl pre-treatment suppressed the elevation of [Ca(2+)]i seen with a second NaCl treatment more than that seen with a second treatment of H2O2. A similar response was seen when the initial treatment was with H2O2; subsequent addition of H2O2 led to less of an increase in [Ca(2+)]i than did addition of NaCl. These results imply that NaCl-gated Ca(2+) channels and H2O2-gated Ca(2+) channels may differ, and also suggest that NaCl- and H2O2-evoked [Ca(2+)]i may reduce the potency of both NaCl and H2O2 in triggering [Ca(2+)]i increases, highlighting a feedback mechanism. Alternatively, NaCl and H2O2 may activate the same Ca(2+) permeable channel, which is expressed in different types of cells and/or activated via different signaling pathways.