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Background and AimsHistone deacetylase inhibitors [HDACi] exert potent anti-inflammatory effects. Because of the ubiquitous expression of HDACs, clinical utility of HDACi is limited by off-target effects. Esterase-sensitive motif [ESM] technology aims to deliver ESM-conjugated compounds to human mononuclear myeloid cells, based on their expression of carboxylesterase 1 [CES1]. This study aims to investigate utility of an ESM-tagged HDACi in inflammatory bowel disease [IBD].MethodsCES1 expression was assessed in human blood, in vitro differentiated macrophage and dendritic cells, and Crohn’s disease [CD] colon mucosa, by mass cytometry, quantitative polymerase chain reaction [PCR], and immunofluorescence staining, respectively. ESM-HDAC528 intracellular retention was evaluated by mass spectrometry. Clinical efficacy of ESM-HDAC528 was tested in dextran sulphate sodium [DSS]-induced colitis and T cell transfer colitis models using transgenic mice expressing human CES1 under the CD68 promoter.ResultsCES1 mRNA was highly expressed in human blood CD14+ monocytes, in vitro differentiated and lipopolysaccharide [LPS]-stimulated macrophages, and dendritic cells. Specific hydrolysis and intracellular retention of ESM-HDAC528 in CES1+ cells was demonstrated. ESM-HDAC528 inhibited LPS-stimulated IL-6 and TNF-α production 1000 times more potently than its control, HDAC800, in CES1high monocytes. In healthy donor peripheral blood, CES1 expression was significantly higher in CD14++CD16- monocytes compared with CD14+CD16++ monocytes. In CD-inflamed colon, a higher number of mucosal CD68+ macrophages expressed CES1 compared with non-inflamed mucosa. In vivo, ESM-HDAC528 reduced monocyte differentiation in the colon and significantly improved colitis in a T cell transfer model, while having limited potential in ameliorating DSS-induced colitis.ConclusionsWe demonstrate that monocytes and inflammatory macrophages specifically express CES1, and can be preferentially targeted by ESM-HDAC528 to achieve therapeutic benefit in IBD.

SummaryAnastomotic leakage (AL) is a frequent and potentially life-threatening postoperative complication in patients undergoing colorectal surgery with a multifactorial yet unknown pathophysiology. In the present study, we aimed to unravel AL etiology and intestinal anastomotic healing (AH) physiology focusing on both host epithelial and gut microbial components. We make use of patients-related samples and two high throughput next generation sequencing analysis approaches, including anastomotic tissue-associated bulk RNA sequencing and preoperative fecal 16S rRNA gene sequencing. We find that in the absence of host epithelial gene expression differences, the preoperative fecal microbiota of patients who undergo colorectal resection with successful AH differs in the group of patients who develop AL in the abundance of Prevotella and suggests a potential beneficial role of Prevotella that may prove useful as predictive biomarker for AH.

In this study, we sought to characterize synovial tissue obtained from individuals with arthralgia and disease-specific auto-antibodies, and patients with established rheumatoid arthritis (RA) by applying an integrative multi-omics approach where we investigated changes at the level of DNA methylation and gene expression and its relation to disease pathogenesis. We performed genome-wide DNA methylation and gene expression profiling of synovial tissue obtained from the knee and ankle from 4 auto-antibody positive arthralgia patients and thirteen RA patients. Through multi-omics factor analysis we observed that the latent factor explaining the variance in gene expression and DNA methylation was associated with Swollen Joint Count 66 (SJC66) where patients with SJC66 of 9 or more displayed reasonable separation from the rest. Specifically, combined DNA methylation and gene expression patterns of patients with SJC66 ≥ 9 displayed activation of the immune response as well as dysregulation of cell adhesion pathways. Through an integrative analysis framework, we reveal differences in both methylation and expression at 59 genes associated with the difference between SJC66 ≥ 9 and 0 < SJC66 ≤ 8, for which we identify specific transcripts correlated with differential methylation. Our results highlight the utility of genome-wide multi-omics profiling of synovial samples for improved understanding of the changes associated with an increasing number of swollen joints in RA patients, and point to novel candidate targets for the treatment of the disease. Funding Statement: AYFLY was funded by the European Union’s Horizon 2020 research and innovation program under Grant Agreement No. ITN-2014-EID-641665. Declaration of Interests: AYFLY, KM, GR, EC, HDL, DFT, CL, DG, and RB are employees of GSK. EF and PPT are employees of Novartis and Kintai Therapeutics, respectively. WJJ is financially supported by GSK and Mead Johnson. All declarations are correct for the time of writing and/or conducting this study. Ethics Approval Statement: All subjects provided written informed consent and the collection and use of the samples received Institutional Review Board review and approval. Characteristics of patients included in this study are listed in Table S1.

Crohn’s disease (CD) is a multifactorial incurable chronic disorder. Current medical treatment seeks to induce and maintain a state of remission. During episodes of inflammation, monocytes infiltrate inflamed mucosa whereupon they differentiate into macrophages with a pro-inflammatory phenotype. Here, we sought to characterize the circulating monocytes by profiling their DNA methylome and relate it to the level of CD activity. We gathered an all-female age-matched cohort of 16 CD patients and 7 non-CD volunteers. CD patients were further subdivided into 8 CD patients with active disease (CD-active) and 8 CD patients in remission (CD-remissive) as determined by physician global assessment. We identified 15 and 12 differentially methylated genes (DMGs) when comparing CD with non-CD and CD-active with CD-remissive, respectively. Differential methylation was predominantly found in the promoter regions of inflammatory genes. Comparing our observations with gene expression data on classical (CD14++CD16-), non-classical (CD14+CD16++) and intermediate (CD14++CD16+) monocytes indicated that while 7 DMGs were differentially expressed across the 3 subsets, the remaining DMGs could not immediately be associated with differences in known populations. We conclude that CD activity is associated with differences in DNA methylation at the promoter region of inflammation-associated genes.

Betatron radiation based on laser-plasma accelerator has properties of collimated, ultrafast, small sources size, high brightness, and broad energy spectrum. These features make it suitable for many applications, such as phase-contrast imaging or X-ray absorption spectroscopy. In this paper, we present two methods to improve the photon energy and photon number of betatron radiation. As a result, high-brightness photon sources with high yield, adjustable photon energy range from hard X-ray to gamma ray and polarization were generated. The main reason for the enhancement is due to the accelerated electrons efficiently wiggling in a laser field.

For an aerostatic circular thrust bearing with a single pocketed orifice-type restrictor, the flow field in the bearing clearance is analyzed numerically, and the formation mechanism of the bearing micro-vibration is investigated. Through flow field analysis, the flow structures in the bearing clearance are discussed and classified. The formed vortex flow in flow field is analyzed, and the influence of the vortex flow on bearing dynamic stability related to micro-vibration is discussed. For each flow structure, the vortex flow always exists and induces the bearing micro-vibration. The Reynolds number is used to represent the degree of bearing micro-vibration and the rationality is verified. Based on the flow analysis results, the maximum Reynolds number in the bearing clearance flow field is taken as the optimization objective to reduce the micro-vibration amplitude, the approximate model for design optimization is established by using the radial basis functions method and the optimization methodology is illustrated. Several cases of optimization are carried out with different given bearing loads. Through optimization, the maximum Reynolds number is reduced greatly, which means the enhancement of the bearing dynamic stability. The optimization results show that in order to suppress the micro-vibration, the air supply pressure should be kept as small as possible, the small air pocket diameter and orifice diameter are also needed.

In the last decade, energy consumption has significantly risen within the manufacturing industry. This issue has not only considerably increased energy costs but has also posed an environmental concern among society. Consequently, many researchers have designed and developed methods so as to reduce energy consumption. From this vantage point, the aim of this research is to design a fuzzy controller to turn-off the machine when it tends to be idle for energy saving purposes. A one buffer one machine manufacturing system with random part arrival is considered in this paper. The decision of the controller is based on the real-time status of the machine, the upstream buffer level and the required production rate. The controller was tested through simulation experiments and it was observed that large amount of energy can be saved without affecting the throughput significantly. The warm-up energy which results from turning off and on machine is also considered.

BackgroundThe chronic remitting and relapsing intestinal inflammation characteristic of Crohn's disease frequently leads to fibrosis and subsequent stenosis of the inflamed region. Approximately a third of all Crohn's disease patients require resection at some stage in their disease course. As the pathogenesis of Crohn's disease associated fibrosis is largely unknown, a strong necessity exists to better understand the pathophysiology thereof.MethodsIn this study, we investigated changes of the DNA methylome and transcriptome of ileum-derived fibroblasts associated to the occurrence of Crohn's disease associated fibrosis. Eighteen samples were included in a DNA methylation array and twenty-one samples were used for RNA sequencing.ResultsMost differentially methylated regions and differentially expressed genes were observed when comparing stenotic with non-inflamed samples. By contrast, few differences were observed when comparing Crohn's disease with non-Crohn's disease, or inflamed with non-inflamed tissue. Integrative methylation and gene expression analyses revealed dysregulation of genes associated to the PRKACA and E2F1 network, which is involved in cell cycle progression, angiogenesis, epithelial to mesenchymal transition, and bile metabolism.ConclusionOur research provides evidence that the methylome and the transcriptome are systematically dysregulated in stenosis-associated fibroblasts.

This paper reports a pattern transfer technique based on an anodic oxidation reaction (AOR) using two kinds of flexible conductive molds (FCMs). This technique enables fine pattern transfer on an uneven surface with 1.8-µm-deep recesses and also improves the transfer uniformity on a flat surface. Both FCMs consist of a base, a flexible insulating pattern on the top of the base and a nanometric thick metal film deposited on the top of the base and the insulating pattern as a conductive layer. Oxide patterns corresponding to the conductive pattern are transferred on the surface of the target material via an AOR between the FCM and the target. The flexibility of the base and the insulating pattern not only enables the FCM to come close enough to the recess of the target material with an uneven surface to generate oxide patterns but also enables a uniform electrical contact between the FCM and the target material with a flat surface to improve transfer uniformity. The conductive pattern on the FCM makes it possible to generate oxide patterns on the surface of the target material in a resistless process via the AOR. A microelectromechanical system technique is used to fabricate the proposed FCMs, and two kinds of FCMs are developed: A film-type FCM with a conductive pattern whose line width is from 5 to 20 µm and a resin-type FCM with a 200-nm half-pitch conductive pattern. Oxide patterns with a line width and a half pitch corresponding to the conductive patterns of the two developed FCMs were collectively transferred on an uneven surface with 1.8-µm-deep recesses and a flat surface of silicon substrate in a millimeter-scale area.

SummaryBackground Development of drug therapies and other techniques for wound care have resulted in significant improvement of the cure rate and shortening of the healing time for wounds. A modified technique of regulated oxygen-enriched negative pressure-assisted wound therapy (RO-NPT) has been reported. Aim To evaluate the efficacy and impact of RO-NPT on wound recovery and inflammation. Methods Infected wounds were established on 40 adult female white rabbits, which were then randomized to one of four groups: O2 group, regulated negative pressure-assisted wound therapy (RNPT) group, regulated oxygen-enriched negative pressure-assisted wound therapy (RO-NPT) group and healthy control (HC) group. Each day, the O2 group was treated with a constant oxygen supply (1 L/min) to the wound, while the RNPT group was treated with continuous regulated negative pressure (70 ± 5 mmHg) and the RNPT + O2 group was treated with both. The HC group was treated with gauze dressing alone, which was changed every day. Leucocyte count, colony count and wound-healing rate were calculated. Levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-8 were evaluated by ELISA. Results RO-RNPT significantly decreased bacterial count and TNF-α level, and increased the wound-healing rate. IL-1β, IL-8 and leucocyte count had a tendency to increase in the early phase of inflammation and a tendency to decrease in the later phase of inflammation in the RO-RNPT group. Conclusions RO-NPT therapy assisted wound recovery and inflammation control compared with the RNPT and oxygen-enriched therapies. RO-NPT therapy also increased levels of IL-1β and IL-8 and attenuated expression of TNF-α in the early phase of inflammation.

To create image objects for subsequent classification in object-based image analysis, an optimal segmentation threshold (OST) is a pre-requisite for image segmentation. However, an OST is practically acquired by assessing and ranking an exhaustive segment data stack constructed after foregoing image segmentation. In this paper, we propose an iterative exploration method via recognition of the Euclidean distance 2 (ED2)–scale parameter (SP) pattern with the least five tiles of segment data stack in each cycle among the Potential Segmentation Error (PSE)–Number-of-Segments Ratio (NSR)–ED2 patterns along with SP. We conducted two experiments. In the first experiment, we validated the general italic U-shaped ED2–SP pattern by constructing exhaustive segment data stacks and corresponding segment data stacks. In the second experiment, we adopted the proposed iterative exploration method for OST selection based on the ED2–SP pattern with respect to five equal-spacing SPs in each cycle. The bottom of the pattern was persistently approached by constructing updated segment data stacks and corresponding segment data stacks with five dynamically adjusted tiles. Our results showed that the PSE–NSR–ED2 discrepancy measure system is advantageous to OST selection

The characterization of multilayer graphene surface impedance at W-band frequency is addressed for the basic application at W-band. On the Cu foil substrate, small area and continuous graphene films are prepared by chemical vapor deposition method using methane as the catalyst. We have got the once and twice transferred samples, corresponding to 6, 12 layers and they are successfully transferred to the polycarbonate substrates. Based on the reflection coefficient and transmission line model, the surface impedance of the graphene at W-band is extracted. The results show that, the approach has been successfully applied to characterize graphene samples at W-band. The extracted surface impedances provide a wideband frequency independent resistance less than 0.5 KΩ level and a weak capacitive behavior which fit with the Drude conductivity model. The approach is successfully applied to characterize multilayer graphene surface impedance. The resistance decreases and the conductivity increased with the more layers graphene.

Due to the requirement of stringent rules for ultra-low sulfur content of diesel fuels, it is necessary to develop alternative methods for desulfurization of fossil fuel derived oil. The desulfurization of aromatic sulfur containing compounds in catalytic cracking diesel oil was carried out using hydrogen peroxide/tri-fluoroacetic acid oxidation system, at the same time, adding power ultrasound to oxidative process, and later the oxidized organic sulfur compounds (sulfones) were extracted by suitable polar solvent. At first, we drew a conclusion of the optimal operating conditions in the laboratory, which is the quantity of the oxidation reagents (oxidant/oil volume ratio) is 1:10; the oxidation temperature is 70°C; reaction time is 60 min; extraction solvent is DMF; S/O is 1:1. In these optimal operating conditions, the power ultrasound can not only make reaction time short, but also increase sulfur removal rate at more than 10%.

SUMMARYIn the near future, the inactivated enterovirus 71 (EV71) vaccine is expected to become available on the market in China. Since EV71 is a major cause of hand, foot and mouth disease (HFMD), the vaccine is expected to significantly reduce the number of cases, as well as the detrimental economic effect of the disease. However, for a national vaccination strategy to be developed, policy-makers need more information on the socioeconomic burden of EV71 HFMD infection. Based on the 2011 population data, we estimated the clinical and economic effect of EV71 HFMD infection in children aged 0–9 years in Shanghai, China. The annual cost related to HFMD is >US$7.66 million for a population of 1·42 million children aged 0–9 years with an average cost of US$208.2/case. The extrapolated cost for EV71 HFMD infection was US$3.53 million, comprising 46·1% of the overall cost associated with HFMD. Around 97% of all of the HFMD-related expenses were paid for by the families creating a considerable economic burden. Our findings could provide the necessary recommendations on the most effective national EV71 vaccine implementation, as well as a baseline data for assessing the cost-effectiveness of the vaccine in China.

RuPeng15 Powder (RPP15) is a herbal multicompound remedy that originates from traditional Tibetan medicine and possesses antigout, anti-inflammatory, and antihyperuricemic properties based on the traditional conceptions. The present study was undertaken to evaluate the therapeutic effect of PRP15 in rat gouty arthritis induced by monosodium urate (MSU) crystals. In the present study, we found that treatment with RPP15 (0.4, 0.8, and 1.2 g/kg) in rats with gouty arthritis induced by MSU crystals significantly attenuated the knee swelling. Histomorphometric and immunohistochemistry analyses revealed that MSU-induced inflammatory cell infiltration and the elevated expressions of nuclear transcription factor-κB p65 (NF-κB p65) in synovial tissues were significantly inhibited, and enzyme-linked immunosorbent assay (ELISA) result showed that MSU-induced high levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-8 (IL-8) in synovial fluid were reduced by treatment with RPP15 (0.4, 0.8, and 1.2 g/kg). We conclude that RPP15 may be a promising candidate for the development of a new treatment for gout and its activity of antigout may be partially related to inhibiting TNF-α, IL-1β, IL-8, and NF-κB p65 expression in the synovial tissues.

As a new clean energy source, the demands for and use of hydrogen fuel are rapidly increasing. Therefore, biohydrogen production technology is being developed to reduce operation costs in many countries. Improvement of biohydrogen production capacity and cost reduction are key factors to bring about industrial implementation. One of the most effective production methods is microbiological: the use of bacteria with high hydrogen-production capacity and performance. The anaerobic process of biohydrogen production was developed in the 1990s. The isolation and identification of highly efficient biohydrogen producing anaerobic bacteria is an important foundation for the fermentative production of hydrogen by anaerobic digestion of organic wastewater.

In this paper, analytical and experimental studies on the shear-failure and confinement of circular section RC bridge columns retrofitted by carbon fiber reinforced plastic (CFRP) jacketing were performed. An effective confined concrete constitutive model named Modified L-L Model proposed by Li et al. (Li, Y.-F., Lin, C.-T. and Sung, Y.-Y. (2003). A Constitutive Model for Concrete Confined with Carbon Fiber Reinforced Plastics, Mechanics of Materials, 35:603–619.) is introduced and used to determine the thickness of CFRP for retrofitting bridge columns, and to analyze the lateral force–displacement relationship of circular sectioned bridge columns. In the Modified L-L Model, the lateral confinement of the concrete comes from both steel reinforcement and CFRP composite material. Three 40%-scale bridge columns with shear-failure mode were tested under cyclic loading at the National Center for Research on Earthquake Engineering (NCREE). The analytical lateral force–lateral displacement relationship of bridge columns using the Modified L-L Model can predict the lateral force–lateral displacement relationship of experimental result very well, and the prediction shows that the Modified L-L Model can be used in seismic retrofit analysis. In the meantime, the performance of retrofitted bridge columns can be greatly improved by using CFRP composite material.

As the utmost downstream dam in the main stream of Xijiang River, Changzhou Hydro-Junction has changed the original hydrological characteristics and ecological environment of Xijiang River. In order to grasp the fish distribution and standing crops after reservoir impoundment, a split beam echo-sounder EY60 (120 kHz) was used in the river channel from Guiping to Wuzhou in April 2014, 2015, and 2016. The average fish density in the survey area was 0.1215±0.4198 ind.m-3 in 2014, 0.0190±0.1232 ind.m-3 in 2015 and 0.0107±0.0186 ind.m-3 in 2016. According to the horizontal distribution data, fish density showed significant difference in different area and the density in the upper area was significantly higher than that in other areas. Moreover, fish density was negatively correlation with water depth. As a whole, the Target Strength (TS) decreased in the past three year, TS was significantly different among the three areas and showed a decreasing tendency from the dam area to the upper area. Fish resources decreased gradually, as indicated by the decreased fish density and miniaturized fish sizes in the past three years.

The temperature dependence of field emission characteristics from ZnO nanotrees is studied. An evident thermo-enhanced field emission effect is found in field emission from ZnO nanotrees. The turn-on field decreases obviously from 15.3 MV/m to 11.9 MV/m when the temperature increases from 293 to 773K. A defect-assisted emission model is used to explain the results.

In order to evaluate the performance of ZnO nanowire field emission display under different temperature, the temperature dependence of field emission current of a fully-sealed diode-structured field emission device using ZnO nanowire cold cathode was studied when the temperature changed from -60°C to 80°C. The pressure inside the device was also measured. It is found that the emission current decreases with increasing temperature, which is attributed to the increasing pressure. The findings are crucial to optimize the manufacture process of the FED using ZnO nanowire cold cathode.

Conventionally, thermal management of LEDs lighting is achieved by natural convection with different types of heat sink. However, as high-power LEDs lighting developing, passive cooling system can't afford sufficient cooling ability for LEDs lighting. Previous study developed a novel piezoelectric (PZT) fan with multiple magnetic fans cooling system which only used one piezoelectric actuator to provide more air flow. In this study, micro multiple piezoelectric-magnetic fans (called “m-MPMF”) is developed to provide an innovative cooling solution on thermal management of LEDs lighting. Moreover, efficiency of MPMF system in this study is defined as the improvement of thermal resistance compared with natural convection. The results show the carbon fiber sheet of magnetic fan can perform better cooling ability than PVC fan because of higher Young's modulus. Efficiency of MPMF system showed 74% improvement by using carbon fiber sheet, in contrary, only 64% improvement of PVC fan. The m-MPMF system is also developed for small scale LEDs lighting cooling. The result showed m-MPMF system can keep temperature of 9W LEDs lighting substrate below 55°C and T-shape design of m-MPMF can further reduce temperature to 45.2°C with only 0.13W power consumption.

This paper presents the velocity and temperature measurements of a heated jet issuing from a square nozzle into stagnant ambient air. Measurements were accomplished by means of hot-wire and cold-wire anemometers. Experimental results showed that the jet initial boundary layer was laminar. Based on the local maximum velocity and half-width, the interaction region was determined from 5De to 8De. It is found that the temperature has higher spreading rate and root mean square values than those of the velocity. It is thus suggested that the heated jet could enhance the mixing better.

Spatial deformation is an important tool in both computer animation and shape design. In this paper, we present a new three-dimensional deformation method using directional polar coordinates. The user specifies a source control object and a destination control object, which act as embedding spaces. The source and the destination control objects determine a three-dimensional volume morphing which maps the space enclosed in the source control object to that of the destination control object. By embedding the object to be deformed into the source control object, the three-dimensional volume morphing determines the deformed object automatically without the cumbersome moving of control points. Experiments show that this deformation model is efficient and intuitive, and it can achieve some deformation effects which are difficult with traditional methods.

A systematic flow is described for characterizing, modeling, and simulating single event transient-induced soft errors in cell-based designs. Pulse broadening effects are quantified for a 65 nm CMOS process.

There are many constraints in a semiconductor wafer fabrication facility (fab), especially time-constraints on processes. This paper gives a dispatching rule considering time-constraints (DRTC) that makes use of such information as due date of a job, workload of a machine, occupation time of a job on a machine, and time constraint of a process. The relative importance of each category is determined by weighting parameters, which are set by learning simulation samples with a backward propagation neural network (BPNN). A real fab simulation model is used to demonstrate the proposed method. The simulation results indicate that DRTC is superior to common rules (such as FIFO, EDD, CR and SRPT ) and the existing dispatching rule used in the fab (called as PRIOR) with more movements of WIP and higher time-constraints satisfaction proportion.

In the previous chapter, the DLP projector is used as a virtual camera and the structured light system is treated as a stereoscopic vision system. In this chapter, we take the projector as a collection of light planes and study the possible algorithms for 3D Euclidean reconstruction with such a system. The plane-based formulation is explored to take advantage of the light planes in the pattern projection. The computational complexity of the algorithm is also analyzed and compared with the traditional triangulation method. The image-to-world transformation is employed for the 3D Euclidean reconstruction considering two different cases, i.e. two-known-plane case and one-known-plane case. Finally, some examples and experimental results are presented using the suggested system.

Wide field of view of a vision system is desirable in many applications. The Catadioptric vision system, which combines reflective mirror and refractive lens, is an effective way to enlarge its viewing angle compared with the traditional system. In this chapter, we will present some recent development in the related research field. We firstly introduce the backgrounds of the Catadioptric vision system. Then three different systems are elaborated and they are: (1) panoramic stereoscopic system which cooperates a fisheye lens camera and a convex reflective mirror; (2) parabolic camera system which consists of a paraboloid-shaped mirror and a CCD camera with orthographic projection; and (3) hyperbolic camera system which combines a hyperboloid-shaped mirror and a CCD camera. All of these systems have two important characteristics: one is a single effective viewpoint and the other is wide field of view. The mathematical models of the imaging process are investigated and the calibration algorithms with different tools are explored.

The integrated knowledge in the application of mechanical engineering, microprocessor and electronic sensor technologies is becoming the basic skill of a modern engineer in machinery based processes. To meet this objective, we have developed a cross-disciplinary industrial training to teach essential hard technical and soft project skills to the mechanical engineering students in mid-curriculum. Ten groups of students were selected to participate in a 150 hour program. The students were required to design and build a robot with ability to follow tracks and pick/place target blocks in specific locations. The students were trained to integrate the knowledge of computer aid design, electronics, sensor theories and motor technology to fabricate a workable robot as a major outcome of this course. On completion of the project, students competed for top robot honors by demonstrating their robots' movements and performance in pick/place to a panel of judges.

SUMMARYWe retrospectively analysed the epidemiological data of all hand, foot, and mouth disease (HFMD) cases from the largest paediatric infectious diseases centre in Shanghai between 2007 and 2010. A total of 28 058 outpatients were diagnosed with HFMD, of which 3948 (14·07%) were hospitalized, 730 (2·60%) had complications with neurological disorders and pulmonary oedema/haemorrhage, and 11 (0·04%) died. The peak season was the summer months. Boys were more affected than girls. Since 2008, the major population group affected has shifted from native Shanghainese children attending preschool to migrant children and younger children cared for at home. Children aged 1–4 years constituted 82·27% of cases. EV-A71 was tested in clinical samples taken from severe cases in 2009 and 2010, and from most inpatients in 2010. EV-A71 was positive in 99·17% and 86·31% of severe cases, respectively in 2009 and 2010. All 12 cases with pulmonary oedema or haemorrhage were infected with EV-A71. Ten (90·90%) of 11 fatal cases were attributable to EV-A71 infection. In 2010, EV-A71-positive cases accounted for 54·12% of inpatients. The dominant circulation of EV-A71 led to the outbreak of HFMD and occurrence of severe and fatal cases.

Analyze the drawbacks of common real-value negative selection algorithm applied on fault diagnosis, and the modified real-value negative selection algorithm is presented based on the corresponding innovations. Firstly, the fault detector set is partitioned into remember-detector set covering known-fault space and random-detector set covering unknown-fault space. Secondly, taking all known states including normal state as self set in training period, get the random-detector set through negative selection and distribution optimization. Lastly, in order to avoid ‘Fail to Alarm’ event caused by the Hole, the two-time-matching method is presented in detecting period which takes the normal state as self set. A resistance circuit fault diagnosis experiment shows that compared with the common real-value negative selection algorithm, the modified real-value negative algorithm can effectively avoid ‘Fail to Alarm’ event, and has higher diagnostic accuracy.

Background In this study, we assessed the prognostic value of the lymph node ratio (LNR), established a hypothetical tumor–ratio–metastasis (TRM) staging system and compared it with the 7th edition International Union Against Cancer pathological N (pN) and tumor–node–metastasis (TNM) system. Patients and methods A total of 1343 gastric cancer patients undergoing D2 resection were staged using the TRM staging system and the 7th edition TNM system. Optimal cut points of LNR were calculated using X-tile software and validated by bootstrapping. Homogeneity, discriminatory ability, and monotonicity of gradients of the TRM and TNM systems were compared using linear trend χ2, likelihood ratio χ2 statistics, and Akaike information criterion (AIC) calculations. Results Optimal cut points classified patients into LNR0 (0%), LNR1 (1%–30%), LNR2 (31%–60%), and LNR3 (61%–100%) groups. In univariate, multivariate and stratified analyses, the LNR staging showed superiority to the 7th edition pN staging. The TRM staging system had higher linear trend and likelihood ratio χ2 scores and smaller AIC values compared with those for the TNM system, which represented the optimum prognostic stratification. Conclusions The novel TRM staging system predicts survival of gastric cancer more accurately than the 7th edition TNM system. It may be considered as an alternative to TNM system.

To estimate the biological doses for two severely exposed subjects (A and B) in a radiation accident in Shandong Jining, China in 2004.Conventional chromosome aberration analysis and cytokinesis-block micronuclei (CBMN) assay were performed in peripheral blood and bone marrow samples on two subjects after the accident. A new dose-effect curve and the nuclear division index (NDI) obtained from in vitro irradiation experiments using high dose of (60)Co gamma-rays were used to estimate the exposed doses.No metaphases or binucleated cells were observed in the peripheral blood cultures from either of the subjects. However, metaphases and binucleated cells were obtained from both subjects after bone marrow cultures. Both dicentric/ring and micronuclei yields were very high. The dose estimated for A and B were 20.0 Gy and 8.8 Gy, respectively, by dicentric/ring scoring, similar to the data by combination of the CBMN and NDI (CBMN + NDI) assay. The estimated doses by the two methods were in accordance with the clinical symptoms.The new curve, together with the CBMN + NDI assay, are reliable for estimating higher doses of irradiation. In future radiation accidents, the accuracy and significance of these methods can be further tested.

Lignans are widely distributed in nature. The earliest recorded medicinal use of lignans dated back to over 1000 years ago. Lignan-rich plant products were also active ingredients in Chinese and Japanese folk medicines for the treatment of various diseases. The dried root and stem of this plant are listed in the Chinese pharmacopoeia for the treatment of rheumatoid arthritis, gastric, duodenal ulcers and many other diseases. This review highlights synthetic strategies for the Wuweizisu C analogs and the important pharmacological activities as well as therapeutic findings related to the treatment of HBV and other diseases. Notably a significant and ongoing project on Wuweizisu C and its analogs has led to the discovery and development of two potent derivatives alpha-DDB and BICYCLOL which are currently in clinical trials against HBV, especially in lowering elevated SGPT levels. Further design, synthesis, and evaluation of Wuweizisu C analogs are discussed.

The unified wave approach is used to compute both the like- and the cross-polarized scattering cross sections for composite rough surfaces characterized by a family of gamma functions of order K ranging from K=1 to K=25. This family of joint height probability density functions properly decorrelates to the product of the marginals as the surface height autocorrelation function vanishes. These results are compared with the like and cross-polarized cross sections for the surface with Gaussian characteristics (K to infinity ). It is shown how radar could be used most effectively to remotely sense the rough surface statistics of non-Gaussian rough surfaces. >

Fire-induced air flow in a large span building by computational fluid dynamics (CFD) will be discussed in this paper. The CFD model is based on Reynolds Averaging Navier-Stokes (RANS) equations with k-e based turbulence model for predicting velocity, pressure and temperature distribution. This technique is commonly used in practical design for smoke management system. The fire is taken as a volumetric heat source and buoyancy effects are included in equations for the vertical momentum and turbulent parameters. Several key points to note in the simulation will be discussed. These are: • Relaxation factor and convergence criteria. • False diffusion. • Sudden changes in flow parameters across the heat source. A large terminal hall with 1 MW fire is taken as an example to discuss the above points. The fire scenarios in a region of interest will be assessed by CFD.Copyright © 2004 by ASME

5582 Purpose: To evaluate the clinical activity of oral Letrozole in patients with recurrent and advanced low malignant potential or low grade serous ovarian tumors and to determine the impact of steroid receptor expression on this observed activity. Methods: In a phase II design, we recruited patients with confirmed recurrent advanced stage low malignant potential tumors and recurrent low-grade serous carcinomas. Measurable disease was required. Steroid hormone expression (ER and PR), EGFR, and Her2/neu expression were determined on available pathological material by IHC from the initial surgery or at documentation of recurrent disease and blood was obtained before enrollment and every other month while on therapy. Letrozole was administered orally at a dose of 2.5 mg once a day. The endpoints were objective response rate assessed by Response Evaluation Criteria in Solid Tumor. Adverse events were graded using the National Cancer Institute Common Toxicity Criteria. Results: Thirteen patients meeting eligibility have been enrolled are evaluable for response and toxicity. From objective clinical parameters (RECIST) no patients had a CR or PR; five patients (38%) had disease stabilizations, eight patients had progressive disease. However, using criteria for CA 125 response, we obtained a complete serologic response in 2 of 13 patients (15%), and a partial serologic response in 2 additional patients (15%); marker stabilization was seen in 5 other patients (38%). CA125 increased in four patients (31%). We also detected the presence of ER, PR, EGFR, Her-2/Neu by IHC, and estradiol in the plasma by ELISA. No significant correlation was observed between tumor marker response and ER expression alone. However, when we evaluated the co-expression of ER/PR we found 3 of 5 (60%) patients had a serologic response compared to just 1 of 8 patients with ER+/PR- tumors (P=0.07). We observed no severe adverse events. Conclusion: Our preliminary data suggests that oral Letrozole has some antitumor activity in recurrent advanced low grade or borderline ovarian tumors and is well tolerated. The analysis of correlation between objective response and combined prediction markers including phosphorylated ER, PR, AKT, and IGFR is ongoing (Supported by CTRF). No significant financial relationships to disclose.

A radial basis-function network (RBFN) is proposed for the intelligent control of a wind-turbine emulator and an induction-generator (IG) system with an AC/DC power converter. First, the indirect field-oriented mechanism is designed for the control of the IG system. Since the IG system is a nonlinear and time-varying dynamic system, an on-line trained RBFN is developed for the tracking controller of DC-link power to improve the control performance. The rotor speed of the IG, the DC-link voltage and current of the power converter are detected simultaneously to yield maximum power output of the converter through DC-link power control. Then, a closed-loop wind-turbine emulator, also using the RBFN, is designed to produce the maximum power for the IG system at various wind speeds to confront the parameter dependency of the wind-turbine emulator. Further, some experimental results are provided to show the effectiveness of the proposed wind-turbine emulator and IG system using the RBFN controller. Finally, the control performance of the DC-link voltage control using the RBFN is also discussed.

Myoelectric recordings of the opossum gastrointestinal tract were performed during continuous infusion of 16,16-dimethyl prostaglandin E2 at 0.1, 1, 2 and 5 micrograms/kg X h. Continuous administration of prostaglandin caused a dose-dependent reduction of the duration of the migrating myoelectric complex cycle and an increase in the velocity of phase III migration from the duodenum to the terminal ileum. The reduction of the migrating myoelectric complex cycle was due to a shortening of the duration of both phase I and II. Bolus administration of 16,16-dimethyl prostaglandin E2 caused intense spike activity for 2-4 min in all recording sites simultaneously. Administration of indomethacin did not change the myoelectric activity of the gastrointestinal tract. Infusion of prostaglandin E2 caused diarrhoea in eight of forty experiments. These changes in gastrointestinal motility may be important contributory factors in the pathogenesis of prostaglandin-induced diarrhoea.