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Evidences suggested that combined blockade of the VEGF and EGFR pathways can improve the treatment efficacy of non-small-cell lung cancer (NSCLC). In our previously clinical practice, we observed that thalidomide, a potent VEGF inhibitor, can significantly decrease the tumor size of one EGFR-TKI resistance patient with lung cancer cachexia. In this pilot study, we tried to assess the efficacy and toxicity of the combination therapy of erlotinib and thalidomide in advanced NSCLC patients with acquired resistance to erlotinib. In all, 52 NSCLC patients with drug resistance to erlotinib were recruited and treated with this combination therapy. After treatment, 4 patients presented with partial remission (PR), 16 with stable disease (SD) and 32 with progressive disease (PD). The objective response rate (ORR) and disease control rate (DCR) was 7.7% and 38.5%, respectively. In this study, we firstly confirmed that thalidomide can reversion of erlotinib-acquired resistance with a 7 weeks median progression-free survival (PFS); besides, this combination therapy shows acceptable drug tolerance; the most common drug related adverse events were astriction, numbness and sleeve-like feeling in the limbs, no thrombosis occurred in any patient. Those evidences indicate that thalidomide may be a useful candidate for reversion of erlotinib-acquired resistance.

Establishing low‐cost, high‐throughput, simple, and accurate single nucleotide polymorphism (SNP) genotyping techniques is beneficial for understanding the intrinsic relationship between individual genetic variations and their biological functions on a genomic scale. Here, a straightforward and reliable single‐molecule approach is demonstrated for precise SNP authentication by directly measuring the fluctuations in electrical signals in an electronic circuit, which is fabricated from a high‐gain field‐effect silicon nanowire decorated with a single hairpin DNA, in the presence of different target DNAs. By simply comparing the proportion difference of a probe‐target duplex structure throughout the process, this study implements allele‐specific and accurate SNP detection. These results are supported by the statistical analyses of different dynamic parameters such as the mean lifetime and the unwinding probability of the duplex conformation. In comparison with conventional polymerase chain reaction and optical methods, this convenient and label‐free method is complementary to existing optical methods and also shows several advantages, such as simple operation and no requirement for fluorescent labeling, thus promising a futuristic route toward the next‐generation genotyping technique.

Soybean saponin (SA) is known as a major anti-nutritional factor that causes metabolic disturbances and growth reduction in fish. However, the mechanisms underlying these effects were far from fully understood. In particular, the influences of SA on nutrient sensing and downstream metabolic pathways remain largely unexplored. Using zebrafish as an animal model, this study was conducted to examine the phenotypic and molecular responses after dietary SA treatment for 2 weeks. SA at both 5 and 10 g/kg diet levels significantly reduced growth performance and feed efficiency, and damaged the morphology of the intestinal mucosa. SA stimulated AMP-activated protein kinase but reduced target of rapamycin (TOR) activities in both feeding trial and cellular studies. Furthermore, SA increased the mRNA expressions of growth axis genes including growth hormone, insulin-like growth factor 1, growth hormone receptor A, and growth hormone receptor B, but decreased insulin-like growth factor-binding protein 2 at both mRNA and protein levels. SA also increased the expressions of key metabolic enzymes involved in glutamine synthetase, glutamate dehydrogenase and lipolysis, hormone-sensitive lipase and lipoprotein lipase. Our results demonstrated that SA modulated nutrient sensing pathways and metabolism, thus provide new aspects on the explanation of the physiological effects of SA.

Hydroxyproline (hyp) is one of the bioactive molecules rich in fishmeal but low in plant protein sources. With increased utilization of plant proteins in aquafeeds, a better understanding is warranted for the necessity of hyp supplementation in high plant protein based diets. In the present study, isonitrogenous and isoenergetic turbot diets were formulated with 40%, 50% and 60% fishmeal substituted by plant proteins, with (or without) addition of 0.6% hyp. After an 8-week feeding trial in juvenile turbot, hyp supplementation significantly improved specific growth rate (SGR) and feed efficiency ratio (FER) in fish fed diets with 50% or higher fishmeal replaced, but not in the group with 40% fishmeal replaced by plant proteins. Hyp levels in plasma and tissues were reduced after plant protein substitutions and replenished by dietary supplementation. Dietary hyp significantly increased muscle hardness, springiness and chewiness of fish ( P

Individual silicon nanowires (SiNWs) doped by in situ dopant incorporation during growth of the SiNWs was investigated. Electrical charge transport measurements were taken before and after removing the material from the boron-doped SiNW surfaces by wet chemical etching. AFM (atomic force microscopy) images showed the radial cross section of the ∼10 nm thick material that was cut off from the SiNW surface. The electrical transport characteristics after each etching cycle revealed the radial core–shell distribution of the activated dopants. The carrier concentration close to the surface of the boron-doped SiNWs was a factor of 6 higher than the value in the core. Using a simple, rapid and reliable technique, the natural distribution of the surface dopants in the SiNWs, which was distinct from many top-down fabricated NWs, explained the enhancement in the charge transport properties of these NWs. This could yield robust properties in ultra-small devices that are often dominated by random dopants fluctuations.

Taurine is essential for development and homeostasis in various fish species. However, very limited information was available on the regulation of taurine biosynthesis in fish. In the present study, the effects of dietary sulfur amino acid supplementation on taurine biosynthesis were examined in juvenile turbot. Fish were fed with a casein-based semi-purified basal diet (CON) and diets supplemented with methionine at 0.5% (MM) and 1.5% (HM), cysteine at 0.3% (MC) and 0.6% (HC), or taurine at 1.5% (MT) and 2.5% (HT) separately, twice per day for 2 weeks. Growth performance, taurine concentration in multiple tissues, hepatic activities of cysteine dioxygenase (CDO) and cysteine sulfinic acid decarboxylase (CSD) were measured. Methionine, cysteine and taurine supplementations promoted growth performance in turbot. Methionine and cysteine supplementations stimulated hepatic CDO but not hepatic CSD activities. Dietary supplementation of methionine, cysteine and taurine increased taurine concentration in the liver. These results suggest the possibility that juvenile turbot has taurine biosynthesis capability, but may not be enough for its endogenous requirement.

A variety of nanomaterial-based biosensors have been developed to sensitively detect biomolecules in vitro, yet limited success has been achieved in real-time sensing in vivo. The application of microneedles (MN) may offer a solution for painless and minimally-invasive transdermal biosensing. However, integration of nanostructural materials on microneedle surface as transdermal electrodes remains challenging in applications. Here, a transdermal H2 O2 electrochemical biosensor based on MNs integrated with nanohybrid consisting of reduced graphene oxide and Pt nanoparticles (Pt/rGO) is developed. The Pt/rGO significantly improves the detection sensitivity of the MN electrode, while the MNs are utilized as a painless transdermal tool to access the in vivo environment. The Pt/rGO nanostructures are protected by a water-soluble polymer layer to avoid mechanical destruction during the MN skin insertion process. The polymer layer can readily be dissolved by the interstitial fluid and exposes the Pt/rGO on MNs for biosensing in vivo. The applications of the Pt/rGO-integrated MNs for in situ and real-time sensing of H2 O2 in vivo are demonstrated both on pigskin and living mice. This work offers a unique real-time transdermal biosensing system, which is a promising tool for sensing in vivo with high sensitivity but in a minimally-invasive manner.

Long chain polyunsaturated fatty acid (LC-PUFA) biosynthesis is limited in many marine species, normally due to lack of Δ5 fatty acyl desaturase (Fad) activity. Among exceptions, abalone possesses considerable LC-PUFA conversion ability from C18 precursors. However, its characterization and relevant enzyme are not well characterized. Here we successfully cloned and characterized two Δ5 Fads in abalone (Haliotis discus hannai Ino). Two Δ5 Fad mRNA transcripts, Hdhfad1 (GQ 470626) and Hdhfad2 (GQ 466197), were found in abalone sharing 96.82% similarity for cDNA sequence and 96.58% similarity for their deduced amino acid sequences. Hdhfad1 cDNA is 1530 bp in length with an opening reading frame (ORF) coding for 438 amino acids. Hdhfad2 cDNA is 1525 bp in length with an ORF encoding for 439 amino acids. Both have characteristic features of front–end desaturase, including three histidine boxes, an N-terminal cytochrome b5 domain with heme-binding motif and transmembrane regions. Both Hdhfad1 and Hdhfad2 were expressed in tissues of abalone, especially in hepatopancreas and intestine. HdhFad1 possessed higher Δ5 desaturase activity but expressed at a lower level than HdhFad2. Both isoforms preferred 20:4n-3 than 20:3n-6 as substrate. These results should provide valuable information on the molecular evolution of Fads and better understanding of LC-PUFA biosynthesis in abalone.

Aberrant regulation of the insulin-like growth factor (IGF)/insulin (IIS)-PI3K-AKT-TOR signaling pathway is linked to major human diseases, and key components of this pathway are targets for therapeutic intervention. Current assays are molecular target- or cell culture-based platforms. Due to the great in vivo complexities inherited in this pathway, there is an unmet need for whole organism based assays. Here we report the development of a zebrafish transgenic line, Tg(igfbp5a:GFP), which faithfully reports the mitotic action of IGF1R-PI3K-Akt-Tor signaling in epithelial cells in real-time. This platform is well suited for high-throughput assays and real-time cell cycle analysis. Using this platform, the dynamics of epithelial cell proliferation in response to low [Ca2+] stress and the distinct roles of Torc1 and Torc2 were elucidated. The availability of Tg(igfbp5a:GFP) line provides a whole organism platform for phenotype-based discovery of novel players and inhibitors in the IIS-PI3K-Akt-Tor signaling pathway.

The formation dynamics of a host-guest complex is successfully investigated in graphene-based single-molecule electronic devices., Single-molecule electronic devices offer unique opportunities to investigate the properties of individual molecules that are not accessible in conventional ensemble experiments. However, these investigations remain challenging because they require (i) highly precise device fabrication to incorporate single molecules and (ii) sufficient time resolution to be able to make fast molecular dynamic measurements. We demonstrate a graphene-molecule single-molecule junction that is capable of probing the thermodynamic and kinetic parameters of a host-guest complex. By covalently integrating a conjugated molecular wire with a pendent crown ether into graphene point contacts, we can transduce the physical [2]pseudorotaxane (de)formation processes between the electron-rich crown ether and a dicationic guest into real-time electrical signals. The conductance of the single-molecule junction reveals two-level fluctuations that are highly dependent on temperature and solvent environments, affording a nondestructive means of quantitatively determining the binding and rate constants, as well as the activation energies, for host-guest complexes. The thermodynamic processes reveal the host-guest binding to be enthalpy-driven and are consistent with conventional 1H nuclear magnetic resonance titration experiments. This electronic device opens up a new route to developing single-molecule dynamics investigations with microsecond resolution for a broad range of chemical and biochemical applications.

Gossypol is known to be a polyphenolic compound toxic to animals. However, its molecular targets are far from fully characterized. To evaluate the physiological and molecular effects of gossypol, we chose turbot ( Scophthalmus maximus L.), a carnivorous fish, as our model species. Juvenile turbots (7.83 ± 0.02 g) were fed diets containing gradient levels of gossypol at 0 (G0), 600 (G1), and 1,200 (G2) mg/kg diets for 11 wk. After the feeding trial, fish growth, body protein, and fat contents were significantly reduced in the G2 group compared with those of the G0 group ( P < 0.05). Gossypol had little impact on digestive enzyme activities and intestine morphology. However, gossypol caused liver fibrosis and stimulated chemokine and proinflammatory cytokine secretions. More importantly, gossypol suppressed target of rapamycin (TOR) signaling and induced endoplasmic reticulum (ER) stress pathway in both the feeding experiment and cell cultures. Our results demonstrated that gossypol inhibited TOR signaling and elevated ER stress pathways both in vivo and in vitro, thus providing new mechanism of action of gossypol in nutritional physiology.

This study was designed to examine the cellular and systemic nutrient sensing mechanisms as well as the intermediary metabolism responses in turbot (Scophthalmus maximus L.) fed with fishmeal diet (FM diet), 45% of FM replaced by meat and bone meal diet (MBM diet) or MBM diet supplemented with essential amino acids to match the amino acid profile of FM diet (MBM+AA diet). During the one month feeding trial, feed intake was not affected by the different diets. However, MBM diet caused significant reduction of specific growth rate and nutrient retentions. Compared with the FM diet, MBM diet down-regulated target of rapamycin (TOR) and insulin-like growth factor (IGFs) signaling pathways, whereas up-regulated the amino acid response (AAR) signaling pathway. Moreover, MBM diet significantly decreased glucose and lipid anabolism, while increased muscle protein degradation and lipid catabolism in liver. MBM+AA diet had no effects on improvement of MBM diet deficiencies. Compared with fasted, re-feeding markedly activated the TOR signaling pathway, IGF signaling pathway and glucose, lipid metabolism, while significantly depressed the protein degradation signaling pathway. These results thus provided a comprehensive display of molecular responses and a better explanation of deficiencies generated after fishmeal replacement by other protein sources.

High dietary protein inclusion is necessary in fish feeds and also represents a major cost in the aquaculture industry, which demands improved dietary conversion into body proteins in fish. In mammals, the target of rapamycin (TOR) is a key nutritionally responsive molecule governing postprandial anabolism. However, its physiological significance in teleosts has not been fully examined. In the present study, we examined the nutritional physiology of turbot after chronic rapamycin inhibition. Our results showed that a 6-week inhibition of TOR using dietary rapamycin inclusion (30 mg/kg diet) reduced growth performance and feed utilization. The rapamycin treatment inhibited TOR signaling and reduced expression of key enzymes in glycolysis, lipogenesis, cholesterol biosynthesis, while increasing the expression of enzymes involved in gluconeogenesis. Furthermore, rapamycin treatment increased intestinal goblet cell number in turbot, while the expressions of Notch and Hes1 were down regulated. It was possible that stimulated goblet cell differentiation by rapamycin was mediated through Notch-Hes1 pathway. Therefore, our results demonstrate the important role of TOR signaling in fish nutritional physiology.

Animals have varied taurine biosynthesis capability, which was determined by activities of key enzymes including cysteine dioxygenase (CDO) and cysteine sulfinate decarboxylase (CSD). However, whether CDO and CSD are differentially regulated across species remains unexplored. In the present study, we examined the regulations of CDO and CSD in rainbow trout and Japanese flounder, the two fish species with high and low taurine biosynthesis ability respectively. Our results showed that the expression of CDO was lower in rainbow trout but more responsive to cysteine stimulation compared to that in Japanese flounder. On the other hand, both the expression and catalytic efficiency (kcat) of CSD were higher in rainbow trout than those of Japanese flounder. A three-residue substrate recognition motif in rainbow trout CSD with sequence of F126/S146/Y148 was identified to be responsible for high kcat, while that with sequence of F88/N108/F110 in Japanese flounder led to low kcat, as suggested by site-directed mutagenesis studies. In summary, our results determined new aspects of taurine biosynthesis regulation across species.

A 70-day feeding trial was conducted to evaluate effects of partial substitution of fish meal (FM) by sunflower meal (SFM) on juvenile turbot (Scophthal musmaximus L.). Five isonitrogenous and isoenergetic diets were formulated with 0%, 15%, 25%, 35%, and 45% replacement of FM protein with protein from SFM. Triplicate groups of juvenile turbot (30 fish per group), were hand-fed twice daily to apparent satiation. Final body weight (FBW), specific growth rate (SGR), and weight gain rate (WGR), were not significantly influenced by type of plant protein at the 15% level (P>0.05), while higher levels showed significant reduction of FBW, SGR, WGR. Feed efficiency ratio (FER) and feed intake (FI) were significantly influenced when FM protein was replaced up to 45% (P0.05). In the SFM diet groups, all superoxide dismutase (SOD) values were significantly higher than the control (P0.05) in microvilli height between diets; parenchyma structure of liver was severely damaged; smaller hepatocyte areas and areas with high levels of hepatocyte vacuolization and disorganization were present. All results indicated that SFM protein can partially replace FM protein in juvenile turbot diets without adverse effects.

Spectrum sensing is the first step of cognitive radio (CR). In this area, previous researches mostly consider distributed local nodes which are under identical channel conditions, hence uniform and fixed detection threshold is set with energy detector. However, the distributions of nodes in real environments are not quite the same. In this paper, the optimal threshold to minimize the total detection error over additive white Gaussion noise (AWGN) channel is derived firstly. Then the dynamic threshold scheme is proposed to reduce the average total detection error. Simulations have shown that, with this scheme, sensing performance is improved.

NiO/Ce0.8Sm0.2O1.9 (NiO/SDC, 65wt.% NiO) composite powders were synthesized by a glycine-nitrate process (GNP) to fabricate Ni/SDC anode-supported solid oxide fuel cell (SOFC). The results show that the composite powders are composed of single cubic phases of NiO and SDC and have a particle size in nanometer range. NiO/SDC ceramics were prepared from the NiO/SDC powders and were converted into Ni/SDC cermets by reduction in H2, which were employed as anode materials for SOFC with SDC electrolyte. It is shown that Ni/SDC cermets from the NiO/SDC composite powders by the GNP have porous and homogeneous microstructures and show good electrical conductivity. A single SOFC based on Ni/SDC anode with about 50µm SDC electrolyte film and about 80µm La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) cathode was constructed. Open circuit voltage (OCV) of the cell is about 0.8V and maximum power density is 361.42 and 394.78 mWcm-2 at 750 and 800°C, respectively.

Overall modes of differential gene expressions were analyzed between human oral/salivary carcinoma cell systems with (MK-1 and ACCM) and without (ZK-1/ZK-2 and ACC2/ACC3) metastatic potential by using micro-array analysis with cancer-associated DNA chips to determine the kinds of genes associated with metastatic behaviors. MK-1 and/or ACCM showed lower levels of gene expression in extracellular matrix-related molecules, such as collagen type IV, laminin, and adhesion molecules such as cadherin 2, but higher levels of genes which control extracellular matrix degradation, such as MMP 9, as well as cell growth and cycle, such as FGF7 and cyclin D1. Among the differentially expressed genes, similar protein expression tendencies for FGF7, laminin, cyclin D1, and collagen type IV were confirmed by immunofluorescence. Metastatic potentials of oral/salivary carcinoma cells seem to have resulted from certain combinations of over-/underexpression of the genes, which were responsible for extracellular matrix metabolism and cell growth in particular.

Using a volume-limited sample of Main Galaxies from the SDSS Data Release 5, we investigate the dependence of galaxy properties on local environment. For each galaxy, the local three-dimensional density is calculated. We find that galaxy morphologies strongly depend on local environment: galaxies in dense environments have predominantly early type morphologies, but other galaxy properties do not present significant dependence on local environment. Clearly, this puts a important constraint on proposed physical mechanisms.

We investigate the Holmberg effect of Luminous Red Galaxy (LRG) pairs of the SDSS Data Release 4 (SDSS4). It is found that the Holmberg effect of LRG pairs has no statistical significance. According to types of the two components in each pair, we divide the isolated LRG pair sample into three subsamples: the early+early subsample, the late+late subsample and the early+late subsample. Further analyses show that all LRG pair subsamples do not exhibit statistically significant Holmberg effect. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Risk Construction project is a process of high risk, and each project has risk which will lead to economical loss, even failure. Thus, the risk management is crucial in project management, and it is integral part of project management. In this paper, AHP model is used to construct risk model to find knowledge relating to risks. A case of Hangqian freeway project is study to show the application the model.

Taurine (2-aminoethane sulfonic acid) plays important roles in multiple physiological processes including osmoregulation, bile salt conjugation and membrane protection. It is known that taurine biosynthesis varies in different fish species. However, its ontogenetic regulation has not been clear. In the present study, we found that the hepatic concentrations of taurine increased marginally with rainbow trout growth. The mRNA expression, protein levels and enzyme activities of key enzymes involved in taurine biosynthesis, cysteine dioxygenase (CDO) and cysteine sulfinate decarboxylase (CSD), were analyzed. Our results showed that the mRNA levels and protein abundances of CSD increased dramatically with the development of rainbow trout stages while the enzyme activities showed a slight improvement. However, the expression and activities of CDO decreased with rainbow trout growth. These results provide valuable information on defining the exact supplementation of taurine in diets for different stages of rainbow trout and give new insights into elucidating the regulation of taurine metabolism in rainbow trout.

In aquaculture, replacing dietary fishmeal with other protein sources is challenging. In order to select substitute sources, it is necessary to determine the apparent digestibility coefficients, many of which have not been well characterized for fish species. We investigated the apparent digestibility of eight protein sources fed to juvenile turbot (Scophthalmus maxima L.). These were Peruvian super red fishmeal (FM), peanut meal (PM), corn gluten meal (CGM), dehulled solvent extracted soybean meal (SBM), wheat gluten (WG), Australian beef meat and bone meal (MBM), spray-dried (pork) hemoglobin meal (SDHM) and American pet-food grade poultry byproduct meal (PBM). The apparent digestibility coefficients of dry matter (DM), crude protein (CP), gross energy (GE), and amino acids were analyzed. Results indicated that turbot utilized high-protein feedstuffs better than high-carbohydrate or high-fiber feedstuffs. This study provides valuable information on ingredient selection and evaluation of feed for turbot.

An artificial immune system was modelled with self/non-self selection to overcome abnormity in a mobile robot demo. The immune modelling includes the innate immune modelling and the adaptive immune modelling. The self/non-self selection includes detection and recognition, and the self/non-self detection is based on the normal model of the demo. After the detection, the non-self recognition is based on learning unknown non-self for the adaptive immunization. The learning was designed on the neural network or on the learning mechanism from examples. The last step is elimination of all the non-self and failover of the demo. The immunization of the mobile robot demo is programmed with Java to test effectiveness of the approach. Some worms infected the mobile robot demo, and caused the abnormity. The results of the immunization simulations show that the immune program can detect 100% worms, recognize all known Worms and most unknown worms, and eliminate the worms. Moreover, the damaged files of the mobile robot demo can all be repaired through the normal model and immunization. Therefore, the immune modelling of the mobile robot demo is effective and programmable in some anti-worms and abnormity detection applications.

Phosphoproteins of the organic matrix of bone and dentin have been implicated as regulators of the nucleation and growth of the inorganic Ca-P crystals of vertebrate bones and teeth. One such protein identified in the dentin matrix is phosphophoryn (PP). It is highly acidic in nature because of a high content of aspartic acid and phosphate groups on serines. The 244-residue carboxyl-terminal domain of rat PP, predominantly containing the aspartic acid-serine repeats, has been cloned, and the corresponding protein has been expressed recombinantly in Escherichia coli. This portion of PP, named DMP2 (dentin matrix protein 2), is not phosphorylated by the bacteria and thus provided a means to study the function of the phosphate groups, the major post-translational modification of native PP. The recombinant DMP2 (rDMP2) possessed much lower calcium binding capacity than native PP. Small angle x-ray scattering experiments demonstrated that PP folds to a compact globular structure upon calcium binding, whereas rDMP2 maintained an unfolded structure. In vitro nucleation experiments showed that PP could nucleate plate-like apatite crystals in pseudophysiological buffer, whereas rDMP2 failed to mediate the transformation of amorphous calcium phosphate to apatite crystals under the same experimental conditions. Collagen binding experiments demonstrated that PP favors the formation of collagen aggregates, whereas in the presence of rDMP2 thin fibrils are formed. Overall these results suggested that the phosphate moieties in phosphophoryn are important for its function as a mediator of dentin biomineralization.

Optical electronic monitoring system is widely used in battlefield assessment, forest fire preventing, road monitoring, etc. This paper proposes an optical electronic monitoring system based on multiple-sensor. Multi-sensors use common optical route in this the system. It means to get the same scene in the same time. In order to extend the transmission distance, reducing the complexity of the wiring, the system design a transform module. Through the transform module, the system transforms CamerLink standard signal to network package and uses network transmission image. (2013) Trans Tech Publications, Switzerland.

Dentin matrix protein 1 (DMP1) is a bone- and teeth-specific protein initially identified from mineralized dentin. Here we report that DMP1 is primarily localized in the nuclear compartment of undifferentiated osteoblasts. In the nucleus, DMP1 acts as a transcriptional component for activation of osteoblast-specific genes like osteocalcin. During the early phase of osteoblast maturation, Ca2+ surges into the nucleus from the cytoplasm, triggering the phosphorylation of DMP1 by a nuclear isoform of casein kinase II. This phosphorylated DMP1 is then exported out into the extracellular matrix, where it regulates nucleation of hydroxyapatite. Thus, DMP1 is a unique molecule that initiates osteoblast differentiation by transcription in the nucleus and orchestrates mineralized matrix formation extracellularly, at later stages of osteoblast maturation. The data presented here represent a paradigm shift in the understanding of DMP1 function. This information is crucial in understanding normal bone formation, remodeling, fracture healing, and skeletal tissue repair.

A study was conducted to investigate the relationship between dietary zinc and shell biomineralization in abalone Haliotis discus hannai Ino. Seven triplicate groups of juvenile abalone (mean weight: 0.74±0.01 g; mean shell length: 16.41±0.04 mm) were fed with one of seven semi-purified diets containing graded levels of dietary zinc (5.6, 10.7, 15.1, 25.2, 34.7, 45.3 and 84.6 mg/kg). To better understand the effects of dietary zinc on the shell deposition, the newly grown shell (NS) was separated from the old shell (OS) after a 16-week rearing period. Mineralogical (aragonite, calcite and dolomite [CaMg(CO 3 ) 2 ]) and chemical (Zn, Fe, Mg, Cu and Sr) compositions in both NS and OS were analyzed. Soluble matrix proteins (SMP) were extracted from both OS and NS, followed by amino acid composition analyses. The results showed that mineralogical and chemical compositions in OS were not significantly influenced by dietary zinc. In NS, however, increasing dietary zinc significantly decreased aragonite content, but significantly increased calcite content. Concentrations of Zn and Fe in NS significantly increased with dietary zinc. Patterns of amino acid compositions in NS significantly changed with dietary zinc levels. The ratio of acidic/basic amino acids positively correlated with the ratio of calcite/aragonite in NS.

The formation of dentin provides one well accepted paradigm for studying mineralized tissue formation. For the assembly of dentin, several cellular signaling pathways cooperate to provide neural crest-derived mesenchymal cells with positional information. Further, "cross-talk" between signaling pathways from the mesenchymal derived odontoblast cells and the epithelially derived ameloblasts during development is responsible for the formation of functional odontoblasts. These intercellular signals are tightly regulated, both temporally and spatially. When isolated from the developing tooth germ, odontoblasts quickly lose their potential to maintain the odontoblast-specific phenotype. Therefore, generation of an odontoblast cell line would be a valuable reproducible tool for studying the modulatory effects involved in odontoblast differentiation as well as the molecular events involved in mineralized dentin formation. In this study an immortalized odontoblast cell line, which has the required biochemical machinery to produce mineralized tissue in vitro, has been generated. These cells were implanted into animal models to determine their in vivo effects on dentin formation. After implantation, we observed a multistep, programmed cascade of gene expression in the exogenous odontoblasts as the dentin formed de novo. Some of the genes expressed include the dentin matrix proteins 1, 2, and 3, which are extracellular matrix molecules responsible for the ultimate formation of mineralized dentin. The biological response was also examined by histology and radiography and confirmed for mineral deposition by von Kossa staining. Thus, a transformed odontoblast cell line was created with high proliferative capacity that might ultimately be used for the regeneration and repair of dentin in vivo.

WC-Co tapes with different Co contents were prepared by rolling the mixtures of WC-Co powders and polymer binders, and layered WC-Co green compacts with discontinuous distribution of Co contents were obtained by laminating the green WC-Co tapes together. After burning off the binders and other organic composition in H2 atmosphere, the green compacts were sintered in vacuum. Microstructure of both the green and the sintered tapes were observed by scanning electron microscope. An electron probe microanalyser was used to measure the linear distribution of Co element in the layered WC-Co cemented carbides. Sintering densification and mechanical property of the multilayered WC-Co alloys were also investigated and compared with those of conventional WC-Co alloys with nominal Co contents of 8% and 12%, respectively. It was shown that by controlling sintering temperature and time, a continuous graded distribution of Co composition can be realized in the laminated WC-Co alloys, with more Co-rich phase in the original high Co content side (12%). Furthermore, the graded WC-Co cemented carbides can realize a combination of high hardness and high strength.

In this paper, a robust model reference adaptive controller based on variable-structure strategy is designed for a class of nonlinear systems with uncertain parameters and bounded external disturbances. Without a priori knowledge of bounded disturbance,both the unknown system parameters and the upper bound of external disturbance are estimated by the design of adaptive law to ensure the accessibility of sliding mode and the global stability of the closed-loop system. Theoretical analysis and simulation results show the robustness and effectiveness of this controller.

Lung metastasis is very common in patients with adenoid cystic carcinoma (ACC). The purpose of the present study is to establish a model for an experimental study of ACC metastatic mechanisms and antimetastatic procedures. After five repeated selections in vivo, combined with an in vitro cloning technique and analysis of platelet aggregation activity, a clone (Acc-M) highly metastatic to the lung was selected from an ACC cell line (Acc-2). The metastatic rate was 96% vs 18% for Acc-M and the Acc-2 cell line. The metastatic rate and the weight of the lung with metastases correlated positively with platelet aggregation activity. The present study might be important for research into mechanisms of ACC metastases.

In this paper, the iterative Retinex algorithm is improved to handle dynamic range compression problems. Based on the analysis of the McCann-Sobel algorithm, the iterative smoothing operation can be interpreted as an asymmetric diffusion. In order to characterized the sharp discontinuities in illumination, an edge-stopping function is introduced into the iterative procedure, which is inspired by anisotropic diffusion. Using the improved illumination estimator, dynamic range of images can be arbitrarily manipulated while suppressing undesirable artifacts. Experiments show that the proposed algorithms outperforms several derivatives for dynamic range compression based on the iterative Retinex.

The spatiotemporal distribution of nano-silver in cut gerbera (Gerbera hybrida cv. Crossfire) flowers were determined by inductively coupled plasma-atomic emission spectrometry technique (ICP-AES). The relative standard deviations of this method were between 0.14% and 2.89%, and the recovery ratio obtained by standard addition method ranged from 93.33% to 106.67%. The method was proved to be simple, rapid, reliable and highly sensitive, which can meet the demands of actual sample analysis. The experimental results also showed that Ag could be found in the basal stem end, upper stem end and petal of the cut gerbera flowers treated in nano-silver solution of 5 mg x L(-1) for 24 h and thereafter placed in distilled water. However, the Ag content in basal stem ends was much higher than those in upper stem ends and petals. The results indicated that nano-silver particles could enter into the flower stems through the cuts of stem ends and then moved to different parts of the cut gerbera flowers, but most of them located in the basal stem ends during the vase period. The fact that Ag was centred in basal stem end implied that the positive preservation effects of nano-silver on cut gerbera flowers is related to its strong and sustainable antiseptic action in the stem ends of cut flowers. The above results provide a reliable method for the determination of nano-silver and theoretical basis for its futher research and application in the preservation of cut flowers.

To study the alteration of thymus matrix lymphocyte generator (TSLP) and change of the Th factor in the course of disease development, and to analyze the curative effect of inhalation of Vitamin A (VA) with corticosteroid for the treatment of asthmatic pneumonia.Asthmatic pneumonia models were prepared by challenging rats with inhalation of ovalbumin for 4 weeks, and rested for 1 week. The treatment with VA and corticosteroid inhalation for 1 week was followed. The rat thymus and lung specimen were examen by histochemical and immunofluorescence staining.After 4 - 5 weeks of stimulation, there were more TSLP-positive cells and alveolar macrophages (AM) found in thymus and lung tissue of asthmatic group, the cell proliferation in spleen and thymus was obvious, and blood Th factors elevated. The inflammation within the lung tissue aggravated gradually. In VA group, the expression of TSLP and Th2 factors were all lowered at the 4th week. The TSLP expression slightly increased at the 5th week, and the cell proliferation within T-cell zone of spleen and thymus was strong at first and weakened later. Alveolar microphages (AM) increased significantly and the inflammation in the lung subsided gradually at the 5th week. In the hormone group, TSLP and Th2 factors expression in both thymus and lung were decreased at the 5th week, while the cell proliferation in thymus and lung was gradually increased. The quantity of AM was decreased, whereas the inflammation of the lung was increased gradually at the 5th week.During asthmatic period elevated TSLP expression was accompanied by Th2 type responses while VA and corticosteroid both suppressed TSLP and Th2 factors expression. VA alone promoted T lymphocyte proliferation as well as the antigen elimination function by AM, after ceasing the usage, the lung inflammation abated gradually. In contrast, after ceasing the use of corticosteroid, inflammation aggravated.

As a benchmark control problem with nonlinearity and instability, the controller design for inverted pendulums becomes more difficult when there are model uncertainties and unknown disturbances in the plant dynamics. In this paper, a kernel-based reinforcement learning controller is developed for inverted pendulums with unknown dynamics and stochastic disturbances. The learning controller makes use of approximate policy iteration with kernel-based least-squares temporal difference learning for policy evaluation. Due to the nonlinear approximation ability of kernel methods, good convergence property and learning efficiency can be realized in the approximate policy iteration process so that the controller performance can be optimized in a few iterations. Simulation results demonstrate that the proposed learning controller for stochastic inverted pendulums can achieve much better performance than previous learning control approaches such as Q-learning with function approximation and least-squares policy iteration (LSPI).

Mechanical mismatch and the lack of interactions between implants and the natural tissue environment are the major drawbacks in bone tissue engineering. Biomaterials mimicking the self-assembly process and the composition of the bone matrix should provide new route for fabricating biomaterials possessing novel osteoconductive and osteoinductive properties for bone repair. In the present study, we employ bio-inspired strategies to design de novo self-assembled chimeric protein hydrogels comprising leucine zipper motifs flanked by dentin matrix protein 1 domain, which was characterized as a mineralization nucleator. Results showed that this chimeric protein could function as a hydroxyapatite nucleator in pseudo-physiological buffer with the formation of highly oriented apatites similar to biogenic bone mineral. It could also function as an inductive substrate for osteoblast adhesion, promote cell surface integrin presentation and clustering, and modulate the formation of focal contacts. Such biomimetic "bottom-up" construction with dual osteoconductive and osteoinductive properties should open new avenues for bone tissue engineering.Mechanical mismatch and the lack of interactions between implants and the natural tissue environment are the major drawbacks in bone tissue engineering. Biomaterials mimicking the self-assembly process and the composition of the bone matrix should provide new route for fabricating biomaterials possessing novel osteoconductive and osteoinductive properties for bone repair. In the present study, we employ bio-inspired strategies to design de novo self-assembled chimeric protein hydrogels comprising leucine zipper motifs flanked by dentin matrix protein 1 domain, which was characterized as a mineralization nucleator. Results showed that this chimeric protein could function as a hydroxyapatite nucleator in pseudo-physiological buffer with the formation of highly oriented apatites similar to biogenic bone mineral. It could also function as an inductive substrate for osteoblast adhesion, promote cell surface integrin presentation and clustering, and modulate the formation of focal contacts. Such biomimetic "bottom-up" construction with dual osteoconductive and osteoinductive properties should open new avenues for bone tissue engineering.

Objective To assess the efficacy and safety of T-614 versus methotrexate (MTX) in patients with active rheumatoid arthritis (RA). Methods In this multicenter, double-blind trial, 489 patients randomly received either T-614 25 mg/day for the first 4 weeks and 50 mg/day for the subsequent 20 weeks (group 1, n = 163), T-614 50 mg/day for 24 weeks (group 2, n = 163), or MTX 10 mg/week for the first 4 weeks and 15 mg/week for the subsequent 20 weeks (n = 163). Clinical and laboratory parameters were analyzed at baseline and at 4, 10, 17, and 24 weeks. Results After 24 weeks of treatment, the American College of Rheumatology 20% improvement criteria response rate for patients in T-614 group 2 (63.8%) was not statistically significantly different from that for patients receiving MTX treatment (62.0%), and was superior to that for patients in T-614 group 1 (50.9%). The result of the noninferiority analysis indicated that the efficacy of T-614 (50 mg/day) was not lower than that of MTX by