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Ordinal responses often arise from surveys which require respondents to rate items on a Likert scale. Since most surveys contain more than one question, the data collected are multivariate in nature, and the associations between different survey items are usually of considerable interest. In this paper, we focus on a mixture distribution, called the combination of uniform and binomial (CUB), under which each response is assumed to originate from either the respondent's uncertainty or the actual feeling towards the survey item. We extend the CUB model to the bivariate case for modelling two correlated ordinal data without using copula-based approaches. The proposed model allows the associations between the unobserved uncertainty and feeling components of the variables to be estimated, a distinctive feature compared to previous attempts. This article describes the underlying logic and deals with both theoretical and practical aspects of the proposed model. In particular, we will show that the model is identifiable under a wide range of conditions. Practical inferential aspects such as parameter estimation, standard error calculations and hypothesis tests will be discussed through simulations and a real case study. [ABSTRACT FROM AUTHOR]

A high-intensity compact D–D/D–T neutron generator with a thick adsorption target is designed with an intensity of 1012 n/s. In this work, a radio-frequency (RF) ion source ignited by an internal antenna is designed with magnetic mirror fields in both axial and radial directions, which can facilitate the confinement of high-density plasma and prolong the service life of the ion source. According to the finite element method software COMSOL Multiphysics, a high-current low-energy D+ beam transport line is simulated and designed with the deuterium beam of 200 keV/6 mA. In particular, the adsorption target is fixed at an angle of 45° with respect to the beam direction, which is beneficial to reduce the beam power density of the target. The simulation results show that the maximum temperature of the target surface is 171.0 °C, which would reduce deuterium or tritium release from the adsorption target. According to the Multi-layer computing model, neutron energy spectra, angular distributions and integrated yields of the compact D–D/D–T neutron generator are calculated and evaluated, corresponding to a thick adsorption target at the deuterium beam of 200 keV/6 mA. The compact D–D/D–T neutron generator can produce quasi-mono-energetic neutrons with energy of 2.45 or 14.1 MeV, respectively, corresponding to the neutron yields up to 6.06 × 109 and 1.18 × 1012 n/s. [ABSTRACT FROM AUTHOR]

The pre-neutron-emission mass distribution is a critical physical constant in neutron-induced fission reaction. In this work, the Monte Carlo dropout neural network (MC-Dropout NN) method is applied to evaluate the pre-neutron-emission mass distributions of neutron-induced typical actinides (232Th, 235U, 238U, 237Np, 239Pu) fission. This method can reproduce precise mass distributions and give the uncertainty of predictions. Moreover, based on the MC-dropout NN learning of the existing experimental fission yields, the unknown yields and their uncertainty can be given. Finally, we predict pre-neutron-emission mass distributions of neutron-induced fission of 232Th and 238U at incident neutron energy below 45 MeV and study the influence of pre-fission neutrons on fission yields. Given the good agreements with experimental data, the neural network approach is a very useful tool in the field of nuclear data evaluation. [ABSTRACT FROM AUTHOR]

Based on the Gravel algorithm and the MLEM algorithm, the neutron energy spectrum unfolding algorithms has been developed by using the SY2001 plastic scintillator detector in its entirety to experimentally measure neutron source characterization of the compact D–D neutron generator. In particular, the degree of optimization of the Mean Relative Error (MRE) is proposed as a determinant of the appropriate termination point for iterations to improve the adaptive nature of the algorithm. The developed neutron energy spectrum unfolding algorithms measure the neutron energy spectra and the neutron angular yields of the compact D–D neutron generator, which are compared with Monte Carlo calculated results. Given the good agreement with the existing results, the developed unfolding algorithms can be used to accurately unfolding neutron energy spectrum, especially, for non-pulsed neutron sources. The measured neutron source characterization results show that the compact D–D neutron generator can produce high yields and quasi-mono-energetic neutrons in the range from 2.2 to 2.8 MeV. The D–D neutron angular yields are anisotropic distributions, particularly, which are relatively higher with neutron emission angles ranging from 40 ∘ to 120 ∘ . This work measure the neutron energy spectra and the neutron angular yields of the compact D–D neutron generator in Lanzhou University, which provide detailed neutron source characterization for using it in neutron physics and neutron application technology. [ABSTRACT FROM AUTHOR]

Despite the general consensus that fertilizer is the most important driver of the evolution of soil microbial communities, the specific effects of long-term fertilizer use on microbial communities remain unclear. Here, we collected soil samples from fertilized (NPK) and unfertilized (NF) plots in a subtropical farmland in southwestern China. NPK plots were consistently treated with chemical fertilizer (nitrogen, phosphorous, and potassium) for the 20 years; NF plots were left unfertilized for the same period. To explore the effects of long-term fertilizer use on soil microbial community structure, microbial community composition in the topsoil was assessed using the bacterial 16S rRNA gene and the full-length fungal ITS1 gene. In conjunction, we measured various soil chemical properties. We found that metrics associated with soil fertility (i.e., total nitrogen, total phosphorus, total potassium, available nitrogen, available phosphorus, and available potassium) were significantly greater in the NPK samples as compared to the NF samples, but that soil pH was significantly lower. We also found that long-term fertilizer use reshaped soil microbial community composition but did not alter community α-diversity. Notably, the bacterial phyla Nitrospirae and Planctomycetes and the fungal phylum Ascomycota were closely associated with the NPK plot, influenced by soil organic matter, total nitrogen, available potassium, and available phosphorus, while the bacterial phyla Bacteroidetes and Chloroflexi and the fungal phyla Glomeromycota and Basidiomycota were closely associated with the NF plot, influenced by soil pH. Our results provide long-term data clarifying the microbial regulation mechanisms underlying the response of farmland soil to long-term fertilizer use in subtropical China. [ABSTRACT FROM AUTHOR]

Graphene is known as an atomically thin, transparent, highly electrically and thermally conductive, light-weight, and the strongest 2D material. We investigate disruptive application of graphene as a target of laser-driven ion acceleration. We develop large-area suspended graphene (LSG) and by transferring graphene layer by layer we control the thickness with precision down to a single atomic layer. Direct irradiations of the LSG targets generate MeV protons and carbons from sub-relativistic to relativistic laser intensities from low contrast to high contrast conditions without plasma mirror, evidently showing the durability of graphene. [ABSTRACT FROM AUTHOR]

We elucidate here the significant impact of processing and coiling temperature on microstructure and mechanical properties of Ti-Nb-Mo high-strength ferritic steel through thermodynamic modeling and quantitative analysis of strengthening mechanisms. The study clearly demonstrated that the moderate coiling temperature (570 °C) exhibited superior mechanical properties (yield strength of 773 MPa and elongation of 13%). At this coiling temperature, high percentage (58.64%) of nano-size (4-10 nm) precipitates were obtained with the finest average ferrite grain size of 3.34 ± 0.28 µm. The quantitative analysis of strengthening effects suggested that contributions of precipitation hardening from (Ti, Mo, Nb)C particles and grain refinement were 36.7 and 37.7%, respectively, and were remarkable. A precipitation model was utilized to predict the average size and volume fraction of precipitates and mass fraction of solute elements in the steel matrix. The thermodynamic model predicted precipitate size of 6.81 nm, consistent with the experimentally observed size of 7.01 ± 0.51 nm, when the steel was coiled at 570 °C for 2 h. [ABSTRACT FROM AUTHOR]

Full understanding of the thermomechanical behaviors of materials at high strain rates and high temperatures are of great importance from not only scientific meaning but also practical value in engineering structure design and safety assessment. Great efforts have been made for abilities of operation the split Hopkinson bars, the most popular technique for experimental determination of mechanical behaviors of materials over the strain rates from 102 to 104 s−1 over the past 70 years, at high temperatures since 1960s. A review of experiment work is presented in this paper to give an overview of the development of experimental techniques at high temperatures based on Hopkinson bar systems. The principles of the split Hopkinson bar requires the loading bars avoiding temperature gradient or keeping relatively low temperature when performing high temperature testing. Techniques such as performing temperature gradient corrections, rapid heating or using special designed automatically assembled systems were proposed by researchers to enable the operation of the split Hopkinson bars at temperature as high as possible. Moreover, to the application of high speed photographic technique for capturing the dynamic deformation process of the specimen in high temperature Hopkinson bar testing, some key issues of eliminating the strong thermal radiation induced lights oversaturation and de-blurring of images due to insufficient exposure at high temperature and high strain rate condition, as well as fabrication of high contrast speckle pattern for high temperature digital image correlation measurement were also proposed. The technique can now enable the split Hopkinson bar testing to be performed at high temperature up to 1873 K under the loading conditions of compression or tension with the in situ observation and full field measurement of deformation as well. The paper concludes with summaries of the most important achievements and highlighting of the prospects, trends and remaining challenges for future research. [ABSTRACT FROM AUTHOR]

Introduction: Urothelial carcinoma (UC) is an aggressive malignancy and has a poor prognosis in the metastatic state. Treatment of UC remains a challenge, and as a first-line regimen for advanced UC, standard platinum-based chemotherapy is unfit for many patients due to numerous comorbidities and poor performance status. Recently, five immune checkpoint inhibitors have been approved for the treatment of patients with advanced UC who were ineligible for platinum-based regimens or suffered tumor progression in post-platinum setting. However, not long ago, the U.S. Food and Drug Administration restricted the use of two common immune checkpoint blockades, atezolizumab and pembrolizumab, due to uncertain survival benefit as mono-therapy. In this scenario, we reviewed rapidly surfacing clinical trials to assess the efficacy and safety of immunotherapy targeting the PD-1 pathway for advanced UC. Methods: A comprehensive search was conducted in PubMed, EMBASE and Cochrane Library for all clinical trials where the efficacy and safety were reported. Our primary outcome was efficacy evaluated by objective response rate (ORR), 1-year overall survival (OS) rate and 1-year progression-free survival (PFS) rate, and second outcome was safety assessed by any grade and grade 3–4 treatment-related adverse events (TRAEs). We chose percentages with 95% confidence intervals (CI) as the evaluation indexes and used a random-effects model to account for heterogeneity. Results: We included 14 clinical trials with 2674 total patients in this meta-analysis. After removing unqualified studies on the basis of sensitivity analyses, 13 studies were pooled to evaluate the overall ORR, 8 studies for the 1-year OS rate and 6 studies for the 1-year PFS rate. The pooled data of ORR, 1-year OS rate, and 1-year PFS rate were 0.20 (95% CI 0.18–0.22, I2 = 38.4%, P = 0.078), 0.50 (95% CI 0.46–0.53, I2 = 30.3%, P = 0.186), and 0.17 (95% CI 0.14–0.20, I2 = 0.0%, P = 0.668), respectively. Similarly, 13 trials were utilized to compute the pooled rate of any-grade TRAEs. The pooled estimation of any-grade was 0.65 (95% CI 0.63–0.67, I2 = 1.7%, P = 0.429). The pooled rate of grade 3–4 TRAEs subgroups with Atezolizumab, Pembrolizumab, Durvalumab, Nivolumab and Avelumab were 0.11 (95% CI 0.06–0.15, I2 = 83.5%, P = 0.000), 0.15 (95% CI 0.13–0.18, I2 = 0.0%, P = 0.971), 0.06 (95% CI 0.03–0.09, I2 = 0.0%, P = 0.566), 0.19 (95% CI 0.15–0.23, I2 = 0.0%, P = 0.480) and 0.08 (95% CI 0.05–0.11, I2 = 0.0%, P = 0.702), respectively. Conclusion: This study showed that the immunotherapy targeting the PD-1 pathway had durable efficacy and acceptable safety in patients with advanced UC. The comprehensive role of immune checkpoint inhibitors in comparison to other treatments needs further confirmation basing on RCTs. [ABSTRACT FROM AUTHOR]

A "Quenching and Partitioning" (Q&P)–based heat treatment has been applied to rolled grinding steel (0.75 wt pct C-Mn-Cr) balls of 104-mm diameter to prevent their cracking during heat treatment. The conventional route of ball manufacturing includes rolling, water quenching interrupted when the bulk average temperature is 220 °C to 250 °C, and self-tempering in a large pile. This technology leads to cracking when the balls are made of steel of high hardenability. To overcome this deficiency, the Q&P principle is herein adopted by (a) adjusting the quenching duration to cool the ball center below the martensite start (Ms) temperature and (b) instead of self-tempering applying furnace tempering. The target bulk temperature of the ball that ensures an optimal "martensite/retained austenite" ratio inside the ball at the moment of water quenching interruption is determined as 125 °C to 170 °C. Quenching should be followed by tempering at 200 °C to 250 °C for stress release at the surface and carbon partitioning from martensite to austenite in the core. The resulting microstructure varies from tempered martensite in the "shell" layers to a mixture of martensite-bainite and retained austenite (RA) in the inner zones, where the austenite content is 25 to 30 vol pct. The carbon enrichment in austenite toward the core of the ball leads to balanced stresses and prevention of ball cracking. Q&P-heat-treated balls in an industrial-scale trial attained a uniform hardness of approximately 55 HRC through the cross section and a high fracture resistance under repetitive impacts of 6.8 kJ energy each. [ABSTRACT FROM AUTHOR]

Background: Worsening voice and speech quality was frequently reported in head-and-neck patients after radiotherapy to the neck; omitting the lower neck and sparing the glottic larynx in node-negative nasopharyngeal carcinoma (NPC) patients might be safe and feasible, and improve voice and speech outcomes. Methods: From January 2009 to January 2013, 71 patients were analyzed. All patients received bilateral neck irradiation. Upper group (UG) patients spared the glottic larynx while lower group (LG) patients did not. Voice and speech quality were evaluated at two time-points (T1 and T2) using the Communication Domain of the Head and Neck Quality of Life (HNQOL) instrument and the Speech question of the University of Washington Quality of Life instrument. Results: At a median follow-up time of 32 months (T1),71.6% of patients reported worsened voice and speech quality. UG patients resulted in significant decreases in glottic larynx dose. With a median follow-up time of 71 months (T2), no patients experienced out-of-field nodal recurrence;there was no difference in the 5-year overall survival and nodal recurrence-free survival between two groups (P = 0.235 and 0.750, respectively). At T1, in patients who without concurrent chemotherapy (CCT), UG patients showed significantly better patient-reported voice quality, (P = 0.022). UG patients without CCT also showed higher scores in the HNQOL communication domain and pain domain (P = 0.012 and P = 0.019). Conclusions: For node-negative NPC patients, omitting the lower neck and sparing the glottic larynx was safe and feasible, and better voice outcomes were achieved in patients without CCT. Further prospective longitudinal studies to investigate whether this approach would be beneficial to node-negative patients are warranted. [ABSTRACT FROM AUTHOR]

Coarse-grained, welding heat-affected zone microstructure was simulated in a Nb-bearing microalloyed steel. The granular bainite with a great number of martensite-austenite (M-A) constituents was the predominant phase. Using atom probe tomography (APT), the distributions of niobium at prior austenite grain boundary (PAGB), ferrite/martensite-austenite (M-A) constituent interface (FMAI), and ferrite/ferrite interface (FFI) were investigated. The binding energy of Nb atom and vacancy was predicted to be 0.45 eV, indicating that Nb segregation by welding thermal cycle is probably a result of the nonequilibrium mechanism. The maximum enrichment of Nb was found at FMAI with enrichment factor of 3.50. Intermediate enrichment of Nb was at PAGB with enrichment factor of 3.12. The interfacial excess of Nb solute element ГNb at PAGB determined by APT was 0.27 × 1019 atoms/m2. The segregation energy was calculated to be 22.91 kJ/mol. The minimum enrichment of Nb was at FFI with an enrichment factor of 1.80. [ABSTRACT FROM AUTHOR]

Summary: By integrating the multilevel biological evidence and bioinformatics analyses, the present study represents a systemic endeavor to identify BMD-associated genes and their roles in skeletal metabolism.Introduction: Single-nucleotide polymorphism (SNP)-based genome-wide association studies (GWASs) have already identified about 100 loci associated with bone mineral density (BMD), but these loci only explain a small proportion of heritability to osteoporosis risk. In the present study, we performed a gene-based analysis of the largest GWASs in the bone field to identify additional BMD-associated genes.Methods: BMD-associated genes were identified by combining the summary statistic P values of SNPs across individual genes in the two consecutive meta-analyses of GWASs from the Genetic Factors for Osteoporosis (GEFOS) studies. The potential functionality of these genes to bone was partially assessed by differential gene expression analysis. Additionally, the consistency of the identification of potential bone mineral density (BMD)-associated variants were evaluated by estimating the correlation of the P values of the same single-nucleotide polymorphisms (SNPs)/genes between the two consecutive Genetic Factors for Osteoporosis Studies (GEFOS) with largely overlapping samples.Results: Compared to the SNP-based analysis, the gene-based strategy identified additional BMD-associated genes with genome-wide significance and increased their mutual replication between the two GEFOS datasets. Among these BMD-associated genes, three novel genes (UBTF, AAAS, and C11orf58) were partially validated at the gene expression level. The correlation analysis presented a moderately high between-study consistency of potential BMD-associated variants.Conclusions: Gene-based analysis as a supplementary strategy to SNP-based genome-wide association studies, when applied here, is shown that it helped identify some novel BMD-associated genes. In addition to its empirically increased statistical power, gene-based analysis also provides a higher testing stability for identification of BMD genes. [ABSTRACT FROM AUTHOR]

Four heat treatment schedules were applied to 14.6 wt pct Cr-2.2 wt pct Mn-1 wt pct Ni cast iron to improve its machinability: (a) one-step continuous annealing [holding at 1123 K (950 °C), 2 hours, cooling at 20 to 150 K/h], (b) three-step isothermal annealing [1123 K (950 °C), 2 hours + 923 K (650 °C), 6 hours + 998 K (725 °C), 15 hours], (c) two-step isothermal annealing [923 K (650 °C), 6 hours + 998 K (725 °C), up to 25 hours], (d) quenching [1123 K (950 °C), 2 hours] and tempering [998 K (725 °C), up to 15 hours]. Heat treatments (a) and (b), which include high-temperature holding at 1123 K (950 °C), result in secondary carbide precipitation, and lead to a “martensite/austenite” or “martensite/austenite/pearlite” matrix and a bulk hardness of 56 to 62 HRC with poor machinability. Heat treatments (c) and (d) provide a matrix of “ferrite + granular carbides” with a bulk hardness lower than 40 HRC. Quenching and tempering result in the elimination of retained austenite to 11.6 vol pct. The kinetics of spheroidization and coagulation of eutectoid carbides and carbides as precipitated from martensite are presented and discussed. Drill testing showed that after quenching and tempering, cast iron has a superior machinability compared with other heat treatments. [ABSTRACT FROM AUTHOR]

IFN-γ release assays (IGRAs) based on region of difference 1 (RD1) antigens have improved diagnosis of Mycobacterium tuberculosis ( M. tb) infection. However, IGRAs with these antigens cannot discriminate between active tuberculosis (ATB) and latent tuberculosis infection (LTBI). M. tb heparin-binding-hemagglutinin (HBHA) induces relatively high IFN-γ responses in LTBI individuals and low responses in ATB patients, but purification of the native methylated HBHA from cultures of M. tb for immunological tests is complex and time-consuming. To overcome these cumbersome procedures, we constructed a recombinant Mycobacterium smegmatis strain that over-expressed HBHA under control of a strong furA promoter. The methylated activity of purified protein was verified by hybridization with anti-methylated Lys antibody, and the methylated HBHA (mHBHA) was further evaluated for antigen-specific IFN-γ responses in BCG-vaccinated Chinese population. A total of 138 individuals including 86 active TB (ATB) patients, 15 latent TB infection (LTBI) cases, and 37 healthy controls (HC) were tested by using an IFN-γ enzyme-linked immunospot (ELISPOT) assay. The results showed that T-cell responses against mHBHA were always lower in ATB patients than in LTBI individuals, regardless of the site of infection or the results of bacteriological tests. This allowed for a good discrimination between these two groups of M. tb-infected individuals, even in the BCG-vaccinated and high TB-incidence setting that is China. Additionally, combination of mHBHA and RD1 antigens in an IFN-γ release assay enhanced diagnostic efficacy for active TB cases. Taken together, inclusion of the immune response to mHBHA can discriminate healthy LTBI cases from ATB patients. [ABSTRACT FROM AUTHOR]

Cr - Mn - Mo - Ni pressure vessel steels containing 0.54 and 1.55% Si are studied. Metallographic and fractographic analyses of the steels after tempering at 650 and 700°C are performed. The impact toughness at - 30°C and the hardness of the steels are determined. The mass fraction of the carbide phase in the steels is computed with the help of the J-MatPro 4.0 software. [ABSTRACT FROM AUTHOR]

Summary: Low bone mineral density (BMD) and osteoporosis have become a public health problem. We found that non-Hispanic white, black, and Asian adults with extremely low education and personal income are more likely to have lower BMD. This relationship is gender-specific. These findings are valuable to guide bone health interventions. Introduction: The evidence is limited regarding the relationship between socioeconomic status (SES) and bone mineral density (BMD) for minority populations in the USA, as well as the relationship between SES and BMD for men. This study explored and examined the relationship between SES and BMD by race/ethnicity and gender. Methods: Data ( n = 6568) from the Louisiana Osteoporosis Study (LOS) was examined, including data for non-Hispanic whites ( n = 4153), non-Hispanic blacks ( n = 1907), and non-Hispanic Asians ( n = 508). General linear models were used to estimate the relationship of SES and BMD (total hip and lumbar spine) stratified by race/ethnicity and gender. Adjustments were made for physiological and behavioral factors. Results: After adjusting for covariates, men with education levels below high school graduate experienced relatively low hip BMD than their counterparts with college or graduate education ( p < 0.05). In addition, women reporting a personal annual income under $20,000 had relatively low hip and spine BMD than their counterparts with higher income level(s) ( p < 0.05). Conclusions: Establishing a conclusive positive or negative association between BMD and SES proved to be difficult. However, individuals who are at an extreme SES disadvantage are the most vulnerable to have relatively low BMD in the study population. Efforts to promote bone health may benefit from focusing on men with low education levels and women with low individual income. [ABSTRACT FROM AUTHOR]

Iron powder was coated with phosphate and polysiloxanes for anti-corrosion and insulation. Whether these coating layers sustain the hydraulic pressure of compaction was investigated. Electrochemical measurements were applied on the compacts comprising surface-coated iron powders to understand the performance of the coating layers undergone a series of compaction pressure. As phosphate coating was applied, the corrosion resistance was obviously enhanced; nevertheless, as the compaction pressure exceeded a threshold, the corrosion resistance dropped greatly due to the formation of cracks in the phosphate layer, suggesting the phosphate layer was brittle and could not bear high pressure. As a phosphate layer and a polymeric coating layer of amino polysiloxane were in turn applied, the corrosion resistance of the doubly-coated iron powder in the salt bath declined since the ammonium group absorbed chloride ions and deteriorated the anti-corrosion ability. After salt-fog treatment, the compacts with the grafted silane tended to form the rust layer with akaganeite phase while these without grafted silane did not, attesting that the polysiloxane did attract chloride ions. Interestingly, with the existence of polysiloxane, the cracking of the phosphate layer was effectively avoided. The polysiloxane layer could protect the underneath phosphate layer from cracking. Moreover, with the increase of compaction pressure, the corrosion resistance of the doubly-coated iron powder gradually increased due to the densification of the polysiloxane layer, which consequently hindered the chloride ions from diffusion into the surface of the iron particle. [ABSTRACT FROM AUTHOR]

Summary: In male Caucasians with discordant hip bone mineral density (BMD), we applied the subcellular separation and proteome profiling to investigate the monocytic cytosol. Three BMD-associated proteins (ALDOA, MYH14, and Rap1B) were identified based on multiple omics evidence, and they may influence the pathogenic mechanisms of osteoporosis by regulating the activities of monocytes. Introduction: Osteoporosis is a serious public health problem, leading to significant mortality not only in aging females but also in males. Peripheral blood monocytes (PBMs) play important roles in bone metabolism by acting as precursors of osteoclasts and producing cytokines important for osteoclast development. The first cytosolic sub-proteome profiling analysis was performed in male PBMs to identify differentially expressed proteins (DEPs) that are associated with BMDs and risk of osteoporosis. Methods: Here, we conducted a comparative proteomics analysis in PBMs from Caucasian male subjects with discordant hip BMD (29 low BMD vs. 30 high BMD). To decrease the proteome complexity and expand the coverage range of the cellular proteome, we separated the PBM proteome into several subcellular compartments and focused on the cytosolic fractions, which are involved in a wide range of fundamental biochemical processes. Results: Of the total of 3796 detected cytosolic proteins, we identified 16 significant ( P < 0.05) and an additional 22 suggestive ( P < 0.1) DEPs between samples with low vs. high hip BMDs. Some of the genes for DEPs, including ALDOA, MYH14, and Rap1B, showed an association with BMD in multiple omics studies (proteomic, transcriptomic, and genomic). Further bioinformatics analysis revealed the enrichment of DEPs in functional terms for monocyte proliferation, differentiation, and migration. Conclusions: The combination strategy of subcellular separation and proteome profiling allows an in-depth and refined investigation into the composition and functions of cytosolic proteome, which may shed light on the monocyte-mediated pathogenic mechanisms of osteoporosis. [ABSTRACT FROM AUTHOR]

CoCuCrO ceramics have been synthesized using the sol-gel method. Through annealed at different temperatures, all the samples are pure formation with cubic crystal structure proved by X-ray diffraction. A significant annealing temperature dependence of negative magnetization has been recorded. With increasing annealing temperature, the absolute values of maximum and minimum of the field-cooled magnetization show a monotonous increase. The relative intensity of negative magnetization is enhanced from 750 to 900 °C and then weakened with further increasing the annealing temperature. The relationship between annealing temperature and negative magnetization can be attributed to the particle growth during the annealing process. In addition, magnetic field dependence of magnetization at 10 K is also studied with different annealing temperatures and the crystallographic microstructure has an important effect on the magnetization. Graphical Abstract: Temperature dependence of magnetization in ZFC and FC processes of CoCuCrO ceramics annealed at 750 °C. Inset is the FC inverse susceptibility and the fitting of ferrimagnetic Curie-Weiss law down to nearly T . Experimental result is plotted as circle, and the fitting is presented as the solid line. [ABSTRACT FROM AUTHOR]

The 15 vol.% micron SiC particle (SiCp)-reinforced AZ31B magnesium matrix composite (AZ31B-SiCp) prepared with semisolid stirring-assisted ultrasonic vibration was subjected to a multi-step process. The influence of the multi-step processing route on the microstructure and mechanical properties of the AZ31B-SiCp was investigated. For comparison, the monolithic AZ31B alloy was also processed under the same conditions. The results showed that the grain sizes of the AZ31B alloy and the AZ31B-SiCp were gradually decreased with increasing the processing step. Compared with the AZ31B-SiCp, the grain size of the AZ31B alloy was much larger, and the grain size distribution was inhomogeneous at the same processing condition. The particles of the AZ31B-SiCp were dispersed uniformly through the multi-step processing. Moreover, the tensile properties of the materials were gradually improved with increasing the processing step. In particular, the strength of AZ31B-SiCp and the ductility of AZ31B alloy improved significantly based on the room-temperature tensile test results. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignant tumor of the liver with a poor prognosis. Upregulation of special AT-rich sequence-binding protein 1 (SATB1) promotes tumor progression. However, little is known about the role of SATB1 in ICC tumorigenesis. Methods: We firstly investigated the expression of SATB1 in 88 cases of ICC by immunohistochemistry (IHC), QRT-PCR, and western blot. Meanwhile, we constructed stably knockdown (shRNA) of SATB1 in ICC cell lines to evaluate the effects of SATB1 on the ability of cell proliferation and invasion by MTT and transwell invasion assay. Results: Our result showed that SATB1 was overexpressed in ICC tissues samples. Knockdown of SATB1 could inhibit ICC cell proliferation, and suppress ICC cell invasion of ICC cell lines. In addition, the depletion of SATB1 expression suppressed the MYC levels in vitro. Conclusions: Our results highlight the significance of SATB1 in ICC and suggest that SATB1 could be a promising therapy target and a potential biomarker for prognosis in ICC patients. [ABSTRACT FROM AUTHOR]

A hybrid of micro-lens array and freeform surface produces a novel micro-optic and micro-photovoltaic behaviors, but it is difficult to control both micro-form and macro-form accuracies in micro-machining of brittle photovoltaic glass. Hence, a ductile micro-grinding is proposed to replicate the precision-trued diamond wheel V-tip on macro-freeform glass substrate of solar cell. The objective is to understand the formation mechanism of accurate micro-lens array on freeform glass surface for photovoltaic application. First, the micro-optic properties of freeform micro-lens array were analyzed with regard to micro- and macro-shapes. Second, the precision and mirror micro-grinding along with the form errors of freeform micro-lens array was observed on the base of the transfer from brittle-mode removal to ductile-mode removal. Finally, the photovoltaic properties were experimentally measured. It is shown that the freeform micro-lens array increases luminous flux by 53.8-54.5 % compared with the plane and micro-lens array. The micro-form accuracy and the micro-structure mirror are dominated by micro-meter-scale diamond wheel V-tip with accurate wheel V-tip profile and integrated micro-grains protrusion, respectively. The novel measuring model of freeform micro-lens array may be used to evaluate and control the curved micro-form accuracy. The freeform micro-lens array contributes to the improvement of photovoltaic performance in scattered light illumination. [ABSTRACT FROM AUTHOR]

Advanced technology has been developed for the production of HSLA steel heavy plates over 60 mm thick made from concast slabs. This technology provides steel band feeding to the concaster mould liquid pool by a specially designed device. The developed technology is a convenient tool for optimization of the casting macrostructure. Minimization of the axial segregation and heavy plate Z-direction mechanical property improvement were realized even if the reduction ratio was less than 2-3. The ductility in the Z-direction of heavy plates was increased by 15-20%, and the toughness of heavy plates was increased by 1.5-2.0 times. High level yield (97.5-99.5%) was reached for heavy plates by the implementation of steel band feeding on the basis of ultrasonic tests using European standard SEL 072 class 1-2. Therefore, steel band feeding is an appropriate alternative to soft reduction and electromagnetic stirring technologies for heavy HSLA steel plates. [ABSTRACT FROM AUTHOR]

To detect Salmonella more efficiently and isolate strains more easily, a novel and simple detection method that uses an enrichment assay and two chromogenic reactions on a chromatography membrane was developed. Grade 3 chromatography paper is used as functionalized solid phase support (SPS), which contains specially optimized medium. One reaction for screening is based on the sulfate-reducing capacity of Salmonella. Hydrogen sulfide (HS) generated by Salmonella reacts with ammonium ferric citrate to produce black colored ferrous sulfide. Another reaction is based on Salmonella C8 esterase that is unique for Enterobacteriaceae except Serratia and interacts with 4-methylumbelliferyl caprylate (MUCAP) to produce fluorescent umbelliferone, which is visible under ultraviolet light. A very low detection limit (10 CFU ml) for Salmonella was achieved on the background of 10 CFU ml Escherichia coli. More importantly, testing with more than 1,000 anal samples indicated that our method has a high positive detection rate and is relatively low cost, compared with the traditional culture-based method. It took only 1 day for the preliminary screening and 2 days to efficiently isolate the Salmonella cells, indicating that the new assay is specific, rapid, and simple for Salmonella detection. In contrast to the traditional culture-based method, this method can be easily used to screen and isolate targeted strains with the naked eye. The results of quantitative and comparative experiments showed that the visual detection technique is an efficient alternative method for the screening of Salmonella spp. in many applications of large-sized samples related to public health surveillance. [ABSTRACT FROM AUTHOR]

Background/objectives: Increasing nut consumption has been associated with reduced risk of obesity and type II diabetes, the risk factors for colorectal cancer. However, the association between nut consumption and colorectal cancer risk is unclear. We aimed to examine the association of long-term nut consumption with risk of colorectal cancer.Subjects/methods: We prospectively followed 75,680 women who were free of cancer at baseline in the Nurses' Health Study, and examined the association between nut consumption and colorectal cancer risk. Nut consumption was assessed at baseline and updated every 2-4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models.Results: During 2,103,037 person-years of follow-up, we identified 1503 colorectal cancer cases. After adjustment for other known or suspected risk factors, women who consumed nuts 2 or more times per week (that is, ⩾ 56 g per week) had a 13% lower risk of colorectal cancer compared with those who rarely consumed nuts, but the association was not statistically significant (RR: 0.87; 95% CI: 0.72-1.05; P-trend: 0.06). No association was observed for peanut butter.Conclusions: In this large prospective cohort of women, frequent nut consumption was not significantly associated with colorectal cancer risk after adjusting for other risk factors. [ABSTRACT FROM AUTHOR]

Background: Male pattern baldness is positively associated with androgens as well as insulin-like growth factor 1 (IGF-1) and insulin, all of which are implicated in pathogenesis of colorectal neoplasia.Methods: From 1992 through 2010, we prospectively followed participants in the Health Professionals Follow-Up Study. Hair pattern at age 45 years was assessed at baseline with five image categories (no baldness, frontal-only baldness, frontal-plus-mild-vertex baldness, frontal-plus-moderate-vertex baldness, and frontal-plus-severe-vertex baldness). Cancer analysis included 32 782 men and used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted to men who underwent at least one endoscopy over the study period, adenoma analysis included 29 770 men and used logistic regressions for clustered data to estimate odds ratios (ORs) and 95% CIs.Results: Over the mean follow-up of 15.6 years, 710 cases of colorectal cancer (478 for colon, 152 for rectum, and 80 unknown site) developed. Significantly increased risks associated with frontal-only baldness and frontal-plus-mild-vertex baldness relative to no baldness were observed for colon cancer with respective HR being 1.29 (95% CI, 1.03-1.62) and 1.31 (95% CI, 1.01-1.70). Over the 19-year study period, 3526 cases of colorectal adenoma were detected. Evidence for an increased risk of colorectal adenoma relative to no baldness was significant with frontal-only baldness (OR, 1.16; 95% CI, 1.06-1.26) and borderline insignificant with frontal-plus-severe-vertex baldness (OR, 1.14; 95% CI, 0.98-1.33).Conclusions: Subtypes of male pattern baldness at age 45 years were positively associated with colorectal neoplasia. Future studies are warranted to confirm our results and to determine the predictive value of male pattern baldness to identify those at high risk for colorectal neoplasia. [ABSTRACT FROM AUTHOR]

A novel tundish refining technology has been developed for the production of complex alloying corrosionresistant steel plates made from continuously cast slabs. This technology includes application of filtering elements installed in the tundish buffers to provide a decrease in the nonmetallic inclusion content in the slab body. It also makes use of injection-vertical shrouding of the steel in the area of steel ladle-tundish for the reduction of oxygen and nitrogen content in the steel and for the reduction of aluminum consumption. Argon rinsing of liquid steel in the tundish through ceramic bottom lances with a modern design is proposed for the removal of fi ne inclusions (≤20 μm). There was an overall decrease of the tested steel contamination by 2.0-2.5 times, and the amount of sulfide inclusions decreased, on an average, by 65%, oxide inclusions by 40%, and nitride inclusions by 60%. Hydrogen removal reached up to 0.3-0.8 ppm. Comprehensive metallographic examinations confirmed the efficiency of the novel tundish refining process and the high yield of high-performance rolled plates. [ABSTRACT FROM AUTHOR]

In the present study, magnesium-based composites with three different volume percentages of nano-sized SiC particulates (SiCp) reinforcement were fabricated using a simple and inexpensive technique followed by hot extrusion. Microstructural characterization of the materials revealed uniform distribution of nano-size SiCp and obvious grain refinement. The tensile test result indicates a remarkable improvement on the strength for the as-extruded SiCp/AZ31B nanocomposite, while the elongation to fracture was decreased by comparing with the AZ31B alloy. Although, compared with the as-extruded AZ31B alloy, the ductility of the SiCp-reinforced AZ31B nanocomposite is decreased, but the ductility of the present SiCp-reinforced AZ31B nanocomposite is far higher than that of the conventional micron or submicron SiCp-reinforced magnesium matrix composites. It is concluded that, compared with the larger sized (micron or submicron) particles, the addition of nano SiCp in the AZ31B alloy resulted in the best combination of the strength and ductility. An attempt is made in the present study to correlate the effect of presence of nano-SiCp as reinforcement and its increasing amount with the microstructural and mechanical properties of magnesium. [ABSTRACT FROM AUTHOR]

STIM1 (stromal interaction molecule 1), an endoplasmic reticulum Ca2+ sensor that triggers the store-operated Ca2+ entry activation, has recently been implicated in cancer progression. However, the role of STIM1 in the progression and metastasis of colorectal cancer (CRC) has not been addressed. In this study, we confirmed increased expression of STIM1 in highly invasive CRC cell lines. Enhanced expression of STIM1 promoted CRC cell metastasis in vitro and in vivo, whereas silencing of STIM1 with small interfering RNA resulted in reduced metastasis. Ectopic expression of STIM1 in CRC cells induced epithelial-to-mesenchymal transition (EMT), whereas silencing of STIM1 had the opposite effect. Furthermore, STIM1 expression was markedly higher in CRC tissues than in adjacent noncancerous tissues. STIM1 overexpression correlated with poor differentiation and higher tumor node metastasis stage. CRC patients with positive STIM1 expression had poorer prognoses than those with negative STIM1 expression. Moreover, STIM1 was found to be a direct target of miR-185, a microRNA (miRNA) that has not previously been reported to be involved in EMT, in both CRC tissues and cell lines. Taken together, these findings demonstrate for the first time that STIM1 promotes metastasis and is associated with cancer progression and poor prognosis in patients with CRC. In addition, we show that expression of STIM1 is regulated by a posttranscriptional regulatory mechanism mediated by a new EMT-related miRNA. This novel miR-185-STIM1 axis promotes CRC metastasis and may be a candidate biomarker for prognosis and a target for new therapies. [ABSTRACT FROM AUTHOR]

The median survival time of breast cancer patients with brain metastasis is less than 6 months, and even a small metastatic lesion often causes severe neurological disabilities. Because of the location of metastatic lesions, a surgical approach is limited and most chemotherapeutic drugs are ineffective owing to the blood brain barrier (BBB). Despite this clinical importance, the molecular basis of the brain metastasis is poorly understood. In this study, we have isolated RNA from samples obtained from primary breast tumors and also from brain metastatic lesions followed by microRNA profiling analysis. Our results revealed that the miR-509 is highly expressed in the primary tumors, whereas the expression of this microRNA is significantly decreased in the brain metastatic lesions. MicroRNA target prediction and the analysis of cytokine array for the cells ectopically expressed with miR-509 demonstrated that this microRNA was capable of modulating the two genes essential for brain invasion, RhoC and TNF-α that affect the invasion of cancer cells and permeability of BBB, respectively. Importantly, high levels of TNF-α and RhoC-induced MMP9 were significantly correlated with brain metastasis-free survival of breast cancer patients. Furthermore, the results of our in vivo experiments indicate that miR-509 significantly suppressed the ability of cancer cells to metastasize to the brain. These findings suggest that miR-509 has a critical role in brain metastasis of breast cancer by modulating the RhoC-TNF-α network and that this miR-509 axis may represent a potential therapeutic target or serve as a prognostic tool for brain metastasis. [ABSTRACT FROM AUTHOR]

Advanced fiber placement (AFP) composite manufacturing technology offers a means to tailor composite fibers for complex loading environments and significantly improve the overall structural efficiency. This paper introduces a new method to optimize the continuously varying fiber paths for AFP using a level set method. The paths of the fibers are defined by constant level set function values, describing a series of continuous equally spaced fiber paths. The sensitivity of the structural compliance to a change in level set function definition of the fiber path is derived. The sensitivities are used to optimize the level set defined fiber paths to minimize structural compliance, while maintaining the continuous fiber paths and producing a solution that can be manufactured using AFP. The optimization method is demonstrated in three numerical studies. [ABSTRACT FROM AUTHOR]

Purpose: The commercial humeral implants based on the Western population are currently not entirely compatible with Asian patients, due to differences in bone size, shape and structure. Surgeons may have to compromise or use different implants that are less conforming, which may cause complications of as well as inconvenience to the implant position. The construction of Asian humerus atlases of different clusters has therefore been proposed to eradicate this problem and to facilitate planning minimally invasive surgical procedures [,]. According to the features of the atlases, new implants could be designed specifically for different patients. Furthermore, an automatic implant selection algorithm has been proposed as well in order to reduce the complications caused by implant and bone mismatch. Methods: Prior to the design of the implant, data clustering and extraction of the relevant features were carried out on the datasets of each gender. The fuzzy C-means clustering method is explored in this paper. Besides, two new schemes of implant selection procedures, namely the Procrustes analysis-based scheme and the group average distance-based scheme, were proposed to better search for the matching implants for new coming patients from the database. Both these two algorithms have not been used in this area, while they turn out to have excellent performance in implant selection. Additionally, algorithms to calculate the matching scores between various implants and the patient data are proposed in this paper to assist the implant selection procedure. Results: The results obtained have indicated the feasibility of the proposed development and selection scheme. The 16 sets of male data were divided into two clusters with 8 and 8 subjects, respectively, and the 11 female datasets were also divided into two clusters with 5 and 6 subjects, respectively. Based on the features of each cluster, the implants designed by the proposed algorithm fit very well on their reference humeri and the proposed implant selection procedure allows for a scenario of treating a patient with merely a preoperative anatomical model in order to correctly select the implant that has the best fit. Based on the leave-one-out validation, it can be concluded that both the PA-based method and GAD-based method are able to achieve excellent performance when dealing with the problem of implant selection. The accuracy and average execution time for the PA-based method were 100 % and 0.132 s, respectively, while those of the GAD- based method were 100 % and 0.058 s. Therefore, the GAD-based method outperformed the PA-based method in terms of execution speed. Conclusion: The primary contributions of this paper include the proposal of methods for development of Asian-, gender- and cluster-specific implants based on shape features and selection of the best fit implants for future patients according to their features. To the best of our knowledge, this is the first work that proposes implant design and selection for Asian patients automatically based on features extracted from cluster-specific statistical atlases. [ABSTRACT FROM AUTHOR]

Floating-point (FP) multipliers are the main energy consumers in many FP applications. Recently several FP multipliers with multiple- precision modes have been designed to trade energy consumption with output accuracy of FP multiplication operation (MOP). To effectively apply these multi-mode multipliers to FP applications, this paper presents a fast instruction precision assignment method for reducing energy consumption under accuracy and performance constraints. To easily set and check the accuracy constraint, we first build an affine arithmetic based error model to evaluate the overall output accuracy loss caused by inaccurate FP MOPs. Moreover, a simplified instruction scheduling method is also developed to quickly check the performance constraint. Based on these two check functions and the characteristics of proposed multi-mode multiplier, a fast Tabu search (TS) algorithm is then proposed to assign the precision mode of each FP MOP under the accuracy and performance constraints imposed on the given application. Experimental results show that the proposed fast TS algorithm can find the precision assignment with more energy saving and less searching time when compared to previous methods. [ABSTRACT FROM AUTHOR]

Background:Prolonged TV watching, a major sedentary behaviour, is associated with increased risk of obesity and diabetes and may involve in colorectal carcinogenesis.Methods:We conducted a cross-sectional analysis among 31 065 men with ⩾1 endoscopy in the Health Professionals Follow-up Study (1988-2008) to evaluate sitting while watching TV and its joint influence with leisure-time physical activity on risk of colorectal adenoma. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).Results:Prolonged sitting while watching TV was significantly associated with increased risk of colorectal adenoma (n=4280), and adjusting for physical activity or a potential mediator body mass index did not change the estimates. The ORs (95% CIs) across categories of TV watching (0-6, 7-13, 14-20, and 21+ h per week) were 1.00 (referent), 1.09 (1.01-1.17), 1.16 (1.06-1.27), and 1.10 (0.97-1.25) (OR per 14-h per week increment=1.11; 95% CI: 1.04-1.18; Ptrend=0.001). Compared with the least sedentary (0-6 h per week of TV) and most physically active (highest quintile) men, the most sedentary (14+ h per week) and least active (lowest quintile) men had a significant increased risk of adenoma (OR=1.25; 95% CI: 1.05-1.49), particularly for high-risk adenoma.Conclusions:Prolonged TV viewing is associated with modest increased risk of colorectal adenoma independent of leisure-time physical activity and minimally mediated by obesity. [ABSTRACT FROM AUTHOR]

Purpose: Positioning existing humeral implants into Asian patients poses significant challenges due to the inconsistent statistical shapes between Western population and Asian population. Current humeral orthopedic fixation devices and implants have a generic shape and are not designed for Asian patients who exhibit different sizes and shapes compared to their Western counterparts for which present day designs have been based on. To address this problem, it is necessary to develop Asian-specific implants that accommodate the morphology of Asian humeri. Existing morphological studies of humeri in Asian populations are rare and most previous analyses are either based on the manual measurement of dry bones or the use of dual energy X-ray absorptiometry scans. The purpose of this pilot morphological study is to explore the characteristics of Asian humeri using statistical atlas-based analysis. Methods: Forty-four CT scans of normal upper limbs were obtained from the National University Hospital, Singapore and used to construct statistical humerus atlases. The atlases were subsequently used to study the morphology of the humeri in an Asian population. Humeral shapes of different patient clusters were analyzed based on statistical shape models. Comparison between different clusters was conducted with regard to centerline, length, width and surface curvature. Results: The statistical humerus atlases reflected the mean shape and modes of variation of humeri in an Asian population. Analyses based on these atlases indicated that curvature and shape of the internal humeral canal were similar in males and females while humeral length and width were greater in males. Most importantly, surface curvatures were explicitly different between clusters. Conclusion: Morphologic analysis based on statistical atlases is novel and useful to characterize the Asian humerus. The humerus demonstrates gender-specific morphology. This unique approach provides information that is useful to the clinician and biomedical engineer, not only in the modification of current or design of future humeral implants, but also in the precise dynamic positioning of Asian-specific humeral implants to Asian patients. Our findings support the need for further development of humeral implants, curvilinear robotics, and the questioning of whether gender-specific devices are necessary. [ABSTRACT FROM AUTHOR]

Lowering stacking fault energy (SFE) of face-centered cubic (fcc, e.g., Cu) metals by adding alloying elements (e.g., Al) is an effective way to create nanotwins (NTs). In this work, nanostructured Cu thin films with different Al additions (0, 1, 5, and 10 at.%) were prepared by magnetron sputtering deposition on silicon and polymer substrate, respectively, to investigate the effect of lowering SFE on microstructural features and mechanical properties. The Al addition can effectively reduce the SFE of Cu thin films, which in turn promotes the formation of NTs and facilitate the growth of (111) texture but suppresses (100) texture of Cu-Al thin films. Increasing the Al addition to ~10 %, the crossed NTs network emerges in the nanostructured Cu-Al thin films. The combined effect of texture and NTs on hardness and ductility was demonstrated, and an optimal hardness/ductility (6.2 GPa/6.3 %) combination was achieved in the Cu-5.0 at.% Al film. Our findings provide deep insight into tailoring the mechanical properties of Cu nanostructures by Al alloying. [ABSTRACT FROM AUTHOR]

Background: It could be helpful to ascertain which patients are at risk of poor bowel preparation prior to performing sedated colonoscopy. The aim of the present study was to identify the predictive factors for poor colon preparation prior to colonoscopy. Methods: A prospective study was performed at Kaohsiung Chang Gung Memorial Hospital, Taiwan, from September 2011 to May 2013. Patient characteristics, food consumed within 2 days of colonoscopy, volume of polyethylene glycol (PEG) solution, interval between completing PEG and examination, number of bowel movements, and character of the last stool were evaluated. Results: Seven hundred and three patients were enrolled (mean age 50.3 ± 11.6 years, 43 % female). In univariate analysis, character of the last stool (<0.001), body weight ( p = 0.007), body mass index ( p = 0.047), waist circumference ( p = 0.008), buttock girth ( p = 0.016), meal residue score (<0.001), and interval between end of PEG and colonoscopy ( p = 0.01) were related to inadequate colon preparation. In multivariate analysis, waist circumference ( p < 0.001), meal residue score ( p < 0.001), and characteristics of last stool ( p < 0.001) were variables that predicted poor colon preparation. Conclusions: Patients who have consumed a high residue diet and/or who report that their last stool is semisolid are likely to have poor bowel preparation, and consideration could be given to rescheduling the examination. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in which local versus central bone marrow reticulin grading is being compared under a central pathology review in international trial.

Dysregulation of transcription factors (TFs) is associated with tumor progression, but little is known about TF expression patterns in the context of gastric cancer (GC) metastasis. Using array-based profile analysis, we found that 22 TFs showed differential activities between GC cell lines with low- and high-metastatic potential. Of this group of TFs, serum response factor (SRF) was significantly upregulated in metastatic GC cells. SRF expression was frequently elevated in a panel of metastatic GC cells and tissues, and high-level expression of SRF was significantly associated with a more aggressive phenotype and poor prognosis in patients with GC. In GC cell lines, overexpression of SRF potently promoted cell migration and invasion in vitro as well as the formation of intrahepatic and pulmonary metastases in vivo, whereas loss of SRF inhibited GC cell invasion and metastasis. We also performed a microRNA microarray to screen for transcriptional targets of SRF and found that SRF transactivates miR-199a-5p and miR-199a-3p by directly binding to their promoters. We further determined that overexpression of miR-199a-5p, but not miR-199a-3p, increased GC cell invasion and metastasis. In contrast, inhibition of miR-199a-5p impaired the metastatic potential of GC cells in vitro and in vivo, and E-cadherin was identified as a direct and functional target of miR-199a-5p in GC cells. Specifically, our results showed that SRF promotes GC metastasis and the epithelial to mesenchymal transition (EMT) though miR-199a-5p-mediated downregulation of E-cadherin. The present study thus provides insight into the specific biological behavior of SRF in GC metastasis. As increased activity of the SRF/miR-199a-5p/E-cadherin pathway appears to promote GC cell EMT and metastasis, these regulators may therefore be developed as therapeutic targets or biomarkers for GC progression. [ABSTRACT FROM AUTHOR]

Gastric carcinoma (GC) is an aggressive cancer with a poor prognosis. We previously reported that MGr1-Ag was involved in multidrug resistance and anti-apoptosis in GC. However, the exact function of MGr1-Ag in GC proliferation is not clear. In this study, we found that MGr1-Ag was highly expressed in GC tissues and four GC cell lines compared with nontumor gastric tissues or gastric epithelial mucosa cells. The high expression of MGr1-Ag/37LRP was also consistent with the decreased median survival time of GC patients. We employed lenti-mediated RNA interference technique to knock down MGr1-Ag expression in SGC7901 and MKN45 cells, respectively, and observed its effects on GC cells growth in vitro and in vivo. Further study showed that knockdown of MGr1-Ag could inhibit GC cell proliferation by inhibiting the cell cycle S-phase entry and induced apoptosis. Soft agar colony formation assay indicated that the colony formation ability of SGC7901 and MKN45 cells decreased after lenti-MGr1-Ag small interfering RNA (siRNA) infection. Western blot revealed that cyclin D1 and Bcl-2 expression were downregulated whereas p27 and Bax were upregulated in lenti-MGr-siRNA-infected GC cells. Further study demonstrated that the proliferation effect of MGr1-Ag in GC is dependent on its laminin-binding region. Taken together, these data revealed a novel function of MGr1-Ag that can possibly be used as an independent prognostic factor and a potential therapeutic target for GC. [ABSTRACT FROM AUTHOR]

FOXM1 is implicated in genotoxic drug resistance but its mechanism of action remains elusive. We show here that FOXM1-depletion can sensitize breast cancer cells and mouse embryonic fibroblasts (MEFs) into entering epirubicin-induced senescence, with the loss of long-term cell proliferation ability, the accumulation of γH2AX foci, and the induction of senescence-associated β-galactosidase activity and cell morphology. Conversely, reconstitution of FOXM1 in FOXM1-deficient MEFs alleviates the accumulation of senescence-associated γH2AX foci. We also demonstrate that FOXM1 regulates NBS1 at the transcriptional level through an forkhead response element on its promoter. Like FOXM1, NBS1 is overexpressed in the epirubicin-resistant MCF-7EpiR cells and its expression level is low but inducible by epirubicin in MCF-7 cells. Consistently, overexpression of FOXM1 augmented and FOXM1 depletion reduced NBS1 expression and epirubicin-induced ataxia-telangiectasia mutated (ATM)phosphorylation in breast cancer cells. Together these findings suggest that FOXM1 increases NBS1 expression and ATM phosphorylation, possibly through increasing the levels of the MRN(MRE11/RAD50/NBS1) complex. Consistent with this idea, the loss of P-ATM induction by epirubicin in the NBS1-deficient NBS1-LBI fibroblasts can be rescued by NBS1 reconstitution. Resembling FOXM1, NBS1 depletion also rendered MCF-7 and MCF-7EpiR cells more sensitive to epirubicin-induced cellular senescence. In agreement, the DNA repair-defective and senescence phenotypes in FOXM1-deficent cells can be effectively rescued by overexpression of NBS1. Moreover, overexpression of NBS1 and FOXM1 similarly enhanced and their depletion downregulated homologous recombination (HR) DNA repair activity. Crucially, overexpression of FOXM1 failed to augment HR activity in the background of NBS1 depletion, demonstrating that NBS1 is indispensable for the HR function of FOXM1. The physiological relevance of the regulation of NBS1 expression by FOXM1 is further underscored by the strong and significant correlation between nuclear FOXM1 and total NBS1 expression in breast cancer patient samples, further suggesting that NBS1 as a key FOXM1 target gene involved in DNA damage response, genotoxic drug resistance and DNA damage-induced senescence. [ABSTRACT FROM AUTHOR]

PurposeTo investigate the morphological features of myopic maculopathy with a new and noninvasive retro-mode imaging (RMI) technique using a confocal scanning laser ophthalmoscope.MethodsA total of 42 patients (69 eyes) with myopic maculopathy were included. RMI combined with fundus photography, fundus fluorescein angiography, and optical coherence tomography together were used to observe and evaluate the morphological features of disease.ResultsFour in 4 eyes (100%) with macular retinoschisis were found with a characteristic pattern by RMI (firework pattern centrally with surrounding fingerprint pattern). Twenty-four in 24 eyes (100%) with pigment proliferation were found by RMI as dark plain patches, and 23 in 24 eyes with hemorrhage (95.8%) were found by RMI as gray bump. Atrophy of different degrees (12 in 14 eyes, 85.7%) was found by RMI as an area of pseudo-3D choroidal vessels or a fuzzy shadow but both without a clear boundary. Choroidal neovascularization (12 in 16 eyes, 75%) was identified laboriously by RMI as a vague raised region. Lacquer cracks were difficult to figure out in RMI.ConclusionsRetinoschisis, pigment proliferation, hemorrhage, and atrophy secondary to myopic maculopathy have characteristic morphologic features in RMI; however, choroidal neovascularization and lacquer crack are not easily distinguishable in RMI. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) is usually correlated with the poor prognosis of gastric cancer. In this study, we revealed a total of 11 microRNAs (miRNA) that regulated MDR of gastric cancer via high-throughput functional screening, and miR-508-5p reversed MDR most efficiently among these candidate miRNAs. The overexpression of mlR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1. These findings suggest that a miR-508-5p/ZNRD1/ABCB1 regulatory loop has a critical role in MDR in gastric cancer. In addition, miR-508-5p could be used as a prognostic factor for overall survival in gastric cancer. These data reveal an important role for miR-508-5p in the regulation of MDR in gastric cancer, and suggest the potential application of miR-508-5p in drug resistance prediction and treatment. [ABSTRACT FROM AUTHOR]

The effect of a 12-T high magnetic field on alloy carbide precipitation in an Fe-C-Mo alloy during tempering at an intermediate temperature was investigated. Thin foils and carbon extraction replicas of the treated specimens were examined by transmission electron microscopy (TEM). The results show that the applied high field effectively promoted the precipitation of (Fe,Mo)C alloy carbide. The concentration of Fe atom in FeMoC carbide is increased whereas that of Mo atom decreased when the high magnetic field was applied. However, the high magnetic field almost had no detectable influence on the atom concentration in (Fe,Mo)C and (Fe,Mo)C carbides. First principle calculations have been performed to calculate the magnetic moment per iron atom of the carbides to explore the origin of the effect of the magnetic field. The influence of the high magnetic field on the precipitation behaviors of alloy carbides was closely related to the magnetic moment of (Fe,Mo)C, (Fe,Mo)C, and (Fe,Mo)C. The magnetic field promotes the formation of the carbides with high total magnetic moment. The effect of the high magnetic field on the substitutional solute atom (Fe and Mo) concentration change in the three alloy carbides was attributed to their magnetization differences per Fe atom. [ABSTRACT FROM AUTHOR]

Altered androgen-receptor (AR) expression and/or constitutively active AR are commonly associated with prostate cancer (PCa) progression. Targeting AR remains a focal point for designing new strategy of PCa therapy. Here, we have shown that DAB2IP, a novel tumor suppressor in PCa, can inhibit AR-mediated cell growth and gene activation in PCa cells via distinct mechanisms. DAB2IP inhibits the genomic pathway by preventing AR nuclear translocation or phosphorylation and suppresses the non-genomic pathway via its unique functional domain to inactivate c-Src. Also, DAB2IP is capable of suppressing AR activation in an androgen-independent manner. In addition, DAB2IP can inhibit several AR splice variants showing constitutive activity in PCa cells. In DAB2IP−/− mice, the prostate gland exhibits hyperplastic epithelia, in which AR becomes more active. Consistently, DAB2IP expression inversely correlates with AR activation status particularly in recurrent or metastatic PCa patients. Taken together, DAB2IP is a unique intrinsic AR modulator in normal cells, and likely can be further developed into a therapeutic agent for PCa. [ABSTRACT FROM AUTHOR]

Objective:To perform a quantitative review of the evidence on the diagnostic value of inflammatory markers in maternal serum or umbilical cord blood for the diagnosis of early-onset neonatal sepsis (EONS).Study Design:We searched multiple databases for studies published through March 2013 that evaluated the diagnostic performance of procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6), and leukocyte count (white blood cell, WBC) in either umbilical cord blood or maternal serum for diagnosis of EONS. We summarized test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves and bivariate random effects models.Result:Our search identified 3874 citations, of which 15 studies evaluating 2178 episodes of suspected neonatal infection were included for analysis. IL-6 in cord blood with a pooled-positive likelihood ratio (LR+) of 9.47 (95% confidence interval: 3.86 to 23.3), PCT in cord blood with a LR+ of 5.72 (1.56 to 21.0) and IL-6 in maternal serum with a LR+ of 5.47 (2.10 to 14.2) can be qualified as a valid rule-in test. IL-6 in cord blood with a LR− of 0.10 (0.05 to 0.21) and PCT in cord blood with a LR− of 0.20 (0.12-0.37) can be qualified as a useful rule-out test. Either CRP or WBC was inadequate for diagnosis of EONS.Conclusion:For cord blood sample, IL-6 or PCT can be used as reliable rule-in and rule-out tool. For maternal serum, only IL-6 appeared to be sufficient for rule-in diagnosis. An interventional study may be needed to answer whether the addition of these tests will improve the outcome of patients with EONS. [ABSTRACT FROM AUTHOR]

As a research method, finite element analysis (FEA) with ABAQUS can help researchers to study throughout the whole process of abnormal tire wear. For precise tread wear simulation, this paper introduces a tire finite element model building method. Then, the model is verified by comparing its simulation results with experiment data. Based on the verified model, tire high-speed rolling procedure is presented by combining steady-state transport analysis and dynamic analysis. To predict the wear distribution, micro tread wear calculation method is described. Finally, the wear prediction procedure of tread mesh evolving is introduced and tire polygonal wear pattern is simulated by this procedure. [ABSTRACT FROM AUTHOR]