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A method of two-step laser etching for bulk micromachining of 4H–SiC membranes through a femtosecond (fs) laser with a wavelength of 532 nm, a pulse width of 290 fs and a repetition rate of 100 kHz is present in this paper. Using a control variable method, the first step of fs-laser etching for rapid material removal and the second step of fs-laser etching mainly for improving surface morphology are studied by changing the laser fluence, scanning spacing, number of scans and scanning speed. The average surface roughness of the membrane bottom after the first step of laser etching is 691 nm, which is reduced to 237 nm after the second step. Compared with one-step laser etching, two-step laser etching obtains a better surface morphology, and it only takes 38% of the processing time of one-step laser etching. The finite element analysis shows that the sensitivity of the SiC pressure sensor drops with the decrease of the membrane roughness. The sensor sensitivity of the membrane fabricated by two-step laser etching is only 3.0% lower than that of the ideal smooth model. Furthermore, a 4H–SiC laser-prepared membrane with a diameter of 1.2 mm and a thickness of 75 μm applied in pressure sensor is tested, showing good linearity and repeatability at a load of up to 10 MPa. [ABSTRACT FROM AUTHOR]

4H–SiC is one of the most promising materials for pressure sensing in harsh environments. A Yb:KGW femtosecond laser was employed to fabricate 4H–SiC sensor membranes with size of Φ1200 × 80 μm. The optimal parameter combination under 15 μJ single pulse energy was obtained with the laps of 16, the scanning speed of 130 mm/s, the scanning line interval of 2 μm and the repetition rate of 100 kHz. High size accuracy (±1%) and steep sidewall (87.4°) were achieved. Wet cleaning and inductively coupled plasma (ICP) etching can obviously improve the membrane bottom surface morphology. The surface roughness Ra in X direction was reduced from 0.82 μm to 0.15 μm, and that in Y direction was reduced from 1.32 μm to 0.16 μm. Pinhole defect was related to the nonuniform distribution of laser fluence. This defect can be avoided by reducing the laser spot overlap ratio. Energy-Dispersive X-ray Spectroscopy (EDS) and Raman spectrum were adopted to analyse the changes of material properties after laser processing. The analysis indicated that the crystal properties of the membrane bottom and the thin epitaxial layers on the front side of membrane are not damaged by the integrating micromachining. The results indicate the potential of utilizing the femtosecond laser combined with ICP etching to fabricate 4H–SiC sensor membranes. [ABSTRACT FROM AUTHOR]

In order to mitigate carbon emissions and address environmental concerns, an increasing number of industries have started investing in green technologies to produce environmentally friendly products. This research develops a game theoretical model to examine the phenomenon of manufacturer encroachment in the context of carbon emission reduction and asymmetric information. Our analysis reveals that when the manufacturer does not encroach, a reduction in carbon emissions benefits all members of the supply chain. However, under encroachment, only the manufacturer stands to benefit from the reduction in carbon emissions. Moreover, with a low direct selling cost, we recommend that the manufacturer should aim to achieve a lower level of carbon emissions under encroachment compared to non-encroachment scenarios. Another key finding is that the benefits of encroachment for the manufacturer depend on the relative costs of direct selling and carbon emission reduction. Encroachment is advantageous to the manufacturer when either the direct selling cost or the carbon emission reduction cost is low. On the other hand, encroachment benefits the retailer only when both the direct selling cost and the carbon emission reduction cost are high. Furthermore, we demonstrate that it is in the retailer's best interest to voluntarily share demand information with the manufacturer, particularly when the direct selling cost is either low or high. By sharing demand information, the retailer can enhance the overall performance of the supply chain. Overall, this study provides valuable insights for managers regarding encroachment and carbon emission decisions in the context of low carbon manufacturing, carbon cap-and-trade policies, and asymmetric information. These findings can guide decision-making processes and help optimize the performance of supply chains in environmentally conscious settings. [ABSTRACT FROM AUTHOR]

Abstract Channels packed with disordered particles are of great importantance for enhancing heat transfer. This paper builds the convective heat transfer experiment platform and studies the heat transfer coefficient in a channel packed with disordered cement particles experimentally. Under the given heat sources, cooling the channel with air at steady state obtains the data, which calculates the convective heat transfer coefficient. Then fitting the Nusselt and Reynolds numbers offers the experimental correlation. Error analysis and comparison with the existing correlations validate the fitted correlation. Discussion on the Nusselt number and wall temperature shows that the Nusselt number in the packed channel is approximately eight times than that in the smooth channel, which provides an effective method for intensifying the effect of channel wall cooling. Moreover, the inner wall temperature of channel with smaller particles is lower, which means the heat transfer enhancement performs better. [ABSTRACT FROM AUTHOR]

Background & Aims: There is controversy regarding the term biliary intraductal papillary neoplasms (IPN-B) and their pathology, which frequently are confused with hepatic mucinous cystic neoplasms (MCN). We aimed to summarize the clinicopathologic features of IPN-B and differentiate them from MCN. Methods: From January 1998 to December 2007, there were 19 patients with intrahepatic IPN-B and 13 patients with MCN who underwent surgical treatment at Zhongshan Hospital. Multiple demographic and clinicopathologic parameters were reviewed retrospectively and compared between the groups. Results: The mean ages of patients with IPN-B and MCN were 59.5 ± 11.1 and 44.4 ± 9.7 years, respectively (P = .0004); the male:female ratios also differed (11:8 vs 2:11; P = .028). Tumors were significantly smaller (6.0 vs 11.2 cm; P = .006) in patients with IPN-B than in those with MCN. More patients with IPN-B also had hepatolithiasis (47.4% vs 0%, P = .004); cholangiectasis and communication between the cyst and main bile duct were more frequent in patients with IPN-B than in those with MCN (P < .001). The IPN-B consisted of 4 subtypes—the gastric subtype was the least invasive. Malignant lesions were more common in patients with IPN-B than in those with MCN (78.9% vs 38.5%; P = .03). The overall 5-year survival rates of patients with IPN-B and MCN were 82% and 100%, respectively. Conclusions: Intrahepatic IPN-B represents a distinct clinicopathologic entity that differs clinically, histologically, and radiologically from MCN. Curative resection has a favorable prognosis for patients with IPN-B, but further studies of its subtype are required. [Copyright &y& Elsevier]

Background & Aims: Cancer progression/metastases and embryonic development share many properties including cellular plasticity, dynamic cell motility, and integral interaction with the microenvironment. We hypothesized that the heterogeneous nature of hepatocellular carcinoma (HCC), in part, may be owing to the presence of hepatic cancer cells with stem/progenitor features. Methods: Gene expression profiling and immunohistochemistry analyses were used to analyze 235 tumor specimens derived from 2 recently identified HCC subtypes (EpCAM+ α-fetoprotein [AFP+] HCC and EpCAM− AFP− HCC). These subtypes differed in their expression of AFP, a molecule produced in the developing embryo, and EpCAM, a cell surface hepatic stem cell marker. Fluorescence-activated cell sorting was used to isolate EpCAM+ HCC cells, which were tested for hepatic stem/progenitor cell properties. Results: Gene expression and pathway analyses revealed that the EpCAM+ AFP+ HCC subtype had features of hepatic stem/progenitor cells. Indeed, the fluorescence-activated cell sorting–isolated EpCAM+ HCC cells displayed hepatic cancer stem cell–like traits including the abilities to self-renew and differentiate. Moreover, these cells were capable of initiating highly invasive HCC in nonobese diabetic, severe combined immunodeficient mice. Activation of Wnt/β-catenin signaling enriched the EpCAM+ cell population, whereas RNA interference-based blockage of EpCAM, a Wnt/β-catenin signaling target, attenuated the activities of these cells. Conclusions: Taken together, our results suggest that HCC growth and invasiveness is dictated by a subset of EpCAM + cells, opening a new avenue for HCC cancer cell eradication by targeting Wnt/β-catenin signaling components such as EpCAM. [Copyright &y& Elsevier]

The prevalence of kidney stones continues to increase worldwide, however, there are still short of effective drugs against urinary stones. In our study, we developed and utilized porous Se@SiO 2 nanospheres as the novel antioxidant agent to detect its potential effects on crystallization inhibition. Porous Se@SiO 2 nanospheres enable to deliver Se sustainably with lower cytotoxicity and preferred biocompatibility. In vivo, we found that porous Se@SiO 2 nanospheres markedly decreased CaOX crystal deposition in renal parenchyma and alleviated kidney oxidative damage. In vitro, we found that the antioxidant effects of porous Se@SiO 2 nanospheres were mediated by upregulation of HO-1 and activation of Keap1/Nrf2 pathway. These results suggests that porous Se@SiO 2 nanospheres may be a new promising therapeutic option for stone formers. [ABSTRACT FROM AUTHOR]

Background & Aims: We combined gene expression and metabolic profiling analyses to identify factors associated with outcomes of patients with hepatocellular carcinoma (HCC). Methods: We compared metabolic and gene expression patterns between paired tumor and nontumor tissues from 30 patients with HCC, and validated the results using samples from 356 patients with HCC. A total of 469 metabolites were measured using liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry. Metabolic and genomic data were integrated, and Kaplan–Meier and Cox proportional hazards analyses were used to associate specific patterns with patient outcomes. Associated factors were evaluated for their effects on cancer cells in vitro and tumor formation in nude mice. Results: We identified 28 metabolites and 169 genes associated with aggressive HCC. Lipid metabolites of stearoyl-CoA-desaturase (SCD) activity were associated with aberrant palmitate signaling in aggressive HCC samples. Expression of gene products associated with these metabolites, including SCD, were associated independently with survival times and tumor recurrence in the test and validation sets. Combined expression of SCD and α-fetoprotein were associated with outcomes of patients with early-stage HCC. Levels of monounsaturated palmitic acid, the product of SCD activity, were increased in aggressive HCCs; monounsaturated palmitic acid increased migration and invasion of cultured HCC cells and colony formation by HCC cells. HCC cells that expressed small interfering RNA against SCD had decreased cell migration and colony formation in culture and reduced tumorigenicity in mice. Conclusions: By using a combination of gene expression and metabolic profile analysis, we identified a lipogenic network that involves SCD and palmitate signaling and was associated with HCC progression and patient outcomes. The microarray platform and data have been submitted to the Gene Expression Omnibus public database at NCBI following MIAME guidelines. Accession numbers: GPL4700 (platform), and GSE6857 (samples). [Copyright &y& Elsevier]

Background & Aims: Antiangiogenic agents can sometimes promote tumor invasiveness and metastasis, but little is known about the effects of the antiangiogenic drug sorafenib on progression of hepatocellular carcinoma (HCC). Methods: Sorafenib was administered orally (30 mg · kg−1 · day−1) to mice with orthotopic tumors grown from HCC-LM3, SMMC7721, or HepG2 cells. We analyzed survival times of mice, along with tumor growth, metastasis within liver and to lung, and induction of the epithelial-mesenchymal transition. Polymerase chain reaction arrays were used to determine the effects of sorafenib on gene expression patterns in HCC cells. We analyzed regulation of HIV-1 Tat interactive protein 2 (HTATIP2) by sorafenib and compared levels of this protein in tumor samples from 75 patients with HCC (21 who received sorafenib after resection and 54 who did not). Results: Sorafenib promoted invasiveness and the metastatic potential of orthotopic tumors grown from SMMC7721 and HCC-LM3 cells but not from HepG2 cells. In gene expression analysis, HTATIP2 was down-regulated by sorafenib. HCC-LM3 cells that expressed small hairpin RNAs against HTATIP2 (knockdown) formed less invasive tumors in mice following administration of sorafenib than HCC-LM3 without HTATIP2 knockdown. Alternatively, HepG2 cells that expressed transgenic HTATIP2 formed more invasive tumors in mice following administration of sorafenib. Sorafenib induced the epithelial-mesenchymal transition in HCC cell lines, which was associated with expression of HTATIP2. Sorafenib regulated expression of HTATIP2 via Jun-activated kinase (JAK) and signal transducer and activator of transcription (STAT)3 signaling. Sorafenib therapy prolonged recurrence-free survival in patients who expressed lower levels of HTATIP2 compared with higher levels. Conclusions: Sorafenib promotes invasiveness and the metastatic potential of orthotopic tumors from HCC cells in mice, down-regulating expression of HTATIP2 via JAK-STAT3 signaling. [Copyright &y& Elsevier]

Background & Aims: Hepatocellular carcinoma (HCC) is an aggressive malignancy; its mechanisms of development and progression are poorly understood. We used an integrative approach to identify HCC driver genes, defined as genes whose copy numbers associate with gene expression and cancer progression. Methods: We combined data from high-resolution, array-based comparative genomic hybridization and transcriptome analysis of HCC samples from 76 patients with hepatitis B virus infection with data on patient survival times. Candidate genes were functionally validated using in vitro and in vivo models. Results: Unsupervised analyses of array comparative genomic hybridization data associated loss of chromosome 8p with poor outcome (reduced survival time); somatic copy number alterations correlated with expression of 27.3% of genes analyzed. We associated expression levels of 10 of these genes with patient survival times in 2 independent cohorts (comprising 319 cases of HCC with mixed etiology) and 3 breast cancer cohorts (637 cases). Among the 10-gene signature, a cluster of 6 genes on 8p, (DLC1, CCDC25, ELP3, PROSC, SH2D4A, and SORBS3) were deleted in HCCs from patients with poor outcomes. In vitro and in vivo analyses indicated that the products of PROSC, SH2D4A, and SORBS3 have tumor-suppressive activities, along with the known tumor suppressor gene DLC1. Conclusions: We used an unbiased approach to identify 10 genes associated with HCC progression. These might be used in assisting diagnosis and to stage tumors based on gene expression patterns. [ABSTRACT FROM AUTHOR]

Background & Aims: Mutations in TP53, a tumor suppressor gene, are associated with prognosis of many cancers. However, the prognostic values of TP53 mutation sites are not known for patients with hepatocellular carcinoma (HCC) because of heterogeneity in their geographic and etiologic backgrounds. Methods: TP53 mutations were investigated in a total of 409 HCC patients, including Chinese (n = 336) and white (n = 73) patients, using the direct sequencing method. Results: A total of 125 TP53 mutations were found in Chinese patients with HCC (37.2%). HCC patients with TP53 mutations had a shorter overall survival time compared with patients with wild-type TP53 (hazard ratio [HR], 1.86; 95% confidence interval [CI]: 1.37–2.52; P < .001). The hot spot mutations R249S and V157F were significantly associated with worse prognosis in univariate (HR, 2.11; 95% CI: 1.51–2.94; P < .001) and multivariate analyses (HR, 1.79; 95% CI: 1.29–2.51; P < .001). Gene expression analysis revealed the existence of stem cell-like traits in tumors with TP53 mutations. These findings were validated in breast and lung tumor samples with TP53 mutations. Conclusions: TP53 mutations, particularly the hot spot mutations R249S and V157F, are associated with poor prognosis for patients with HCC. The acquisition of stem cell-like gene expression traits might contribute to the aggressive behavior of tumors with TP53 mutation. [ABSTRACT FROM AUTHOR]

• Constructing an experimental platform of a packed channel with disordered cement granules. • Fitting the data of Nusselt and Reynolds numbers provides an experimental correlation. • A mathematical model of the channel packed with granules is proposed. • Using the inverse problem method determines the average local velocity of cooling air. The channels packed with disordered granules are common in industry, which permits an improved performance of the facility as well as the energy efficiency. This paper describes the construction of an experimental platform of a packed channel with disordered cement granules. Using the method of dimensionless number correlation, fitting the data of Nusselt and Reynolds numbers provides an experimental correlation. Analysis shows that the Nusselt number in a packed channel is approximately eight times that in a smooth channel. The inner-wall temperature of a channel with smaller granules is lower, implying the heat transfer is stronger. The inverse problem method is adopted to measure the local average velocity and obtain the temperature distribution, permitting then a determination of the Reynold number based on the local average velocity in the channel combined with the fitted experimental correlation and a mathematical model of the experimental section. Comparisons with the Reynold number obtained from the superficial flow velocity shows that the Reynold number obtained from the average local velocity is much smaller and in particular, for the same mass flow rates, the latter Reynold number of the channel packed with smaller granules is larger than that packed with larger granules. It provides useful tools to analysis the local heat transfer performance to improve the energy efficiency in actual applications. [ABSTRACT FROM AUTHOR]

Asia-Pacific ground-based Optical Space object Observation System (APOSOS) is an international cooperation project, which is initiated and supported by Asia-Pacific Space Cooperation Organization (APSCO). Currently, APOSOS consists of three Observation Nodes in Pakistan, Peru and Iran, and a Data and Operation Management Center in National Astronomical Observatories, Chinese Academy of Sciences. Each Observation Node is equipped with a dedicated 15 cm aperture refracting telescope, which is capable of real-time astrometric data reduction. APOSOS aims to develop a tracking network of space object to acquire accurate astrometric measurements of space objects owned by APSCO member states. In this paper, we present an overview of APOSOS's design and development. The APOSOS's detecting capability of tracking a space object is darker than 12 m in LEO or 16 m in GEO, the size of which is equivalent to a diameter of 10-cm class in LEO or meter class in GEO respectively. A parametric estimation model is setup to profile APOSOS's capability in different tracking missions, which is verified by experimental observations. Preliminary results of tracking observations of SLR satellites showed that RMS of APOSOS astrometric measurements in RA/DEC is better than 5 ″ . [ABSTRACT FROM AUTHOR]

The bistatic radar system has been one of the effective methods to detect the space debris in low earth orbit (LEO). Tianlai radio array with cylindrical-parabolic antennas is designed for dark energy detection, which has large field of view and high sensitivity, offering a fan-beam during the observation. We propose a bistatic radar system, which consists of Tianlai radio array and an incoherent scattering radar (ISR) assumed as a transmitter in the Qujing city of China, to detect space debris. In this paper, we calculate and analyze the detection capabilities of this system. The results show the bistatic radar system has the potential to detect small space debris of less than 10 cm in LEO. We provide a space debris detection method to obtain the position of the cross-beam satisfying the observation requirement with the TLE data of the space debris. The method can solve the problem of space synchronization between the radio array and ISR. We used the long-short baseline method of the radio array to locate the space target. The relationship among positioning error, the azimuth and the elevation angle are also discussed. [ABSTRACT FROM AUTHOR]

Abstract The presence of operational satellites or small-body space debris is a challenge for autonomous ground-based space object observation. Although most space objects exceeding 10 cm in diameter have been cataloged, the position of each space object (based on six orbital parameters) remains important and should be updated periodically, as the Earth's orbital perturbations cause disturbances. Modern ground-based passive optical telescopes equipped with complementary metal-oxide semiconductors have become widely used in astrometry engineering, being combined with image processing techniques for target signal enhancement. However, the detection and tracking performance of this equipment when employed with image processing techniques primarily depends on the size and brightness of the space target, which appears on the monitor screen under variable background interference conditions. A small and dim target has a highly sensitive tracking error compared to a bright target. Moreover, most image processing techniques for target signal enhancement require large computational power and memory; therefore, automatic tracking of a space target is difficult. The present work investigates autonomous space target detection and tracking to achieve high-sensitivity detection and improved tracking ability for non-Gaussian and dynamic backgrounds with a simple system mechanism and computational efficiency. We develop an improved particle filter (PF) using the ensemble Kalman filter (KF) for track-before-detect (TBD) frameworks, by modifying and optimizing the computational formula for our non-linear measurement function. We call this extended version the "ensemble Kalman PF-TBD (EnKPF-TBD)." Three sequential astronomical image datasets taken by the Asia-Pacific Ground-Based Optical Space Objects Observation System (APOSOS) telescope under different conditions are used to evaluate three proposed TBD baseline frameworks. Given an optimal random sample size, the EnKPF-TBD exhibits superior performance to PF-TBD and threshold-based unscented KF with two-dimensional peak search (2dPS). The EnKPF-TBD scheme achieves satisfactory performance for all variable background interference conditions, especially for a small and dim space target, in terms of tracking accuracy and computational efficiency. [ABSTRACT FROM AUTHOR]

The signal-to-noise ratio (SNR) of debris laser ranging (DLR) data is extremely low, and the valid returns in the DLR range residuals are distributed on a curve in a long observation time. Therefore, it is hard to extract the signals from noise in the Observed-minus-Calculated (O-C) residuals with low SNR. In order to autonomously extract the valid returns, we propose a new algorithm based on randomized Hough transform (RHT). We firstly pre-process the data using histogram method to find the zonal area that contains all the possible signals to reduce large amount of noise. Then the data is processed with RHT algorithm to find the curve that the signal points are distributed on. A new parameter update strategy is introduced in the RHT to get the best parameters. We also analyze the values of the parameters in the algorithm. We test our algorithm on the 10 Hz repetition rate DLR data from Yunnan Observatory and 100 Hz repetition rate DLR data from Graz SLR station. For 10 Hz DLR data with relative larger and similar range gate, we can process it in real time and extract all the signals autonomously with a few false readings. For 100 Hz DLR data with longer observation time, we autonomously post-process DLR data of 0.9%, 2.7%, 8% and 33% return rate with high reliability. The extracted points contain almost all signals and a low percentage of noise. Additional noise is added to 10 Hz DLR data to get lower return rate data. The valid returns can also be well extracted for DLR data with 0.18% and 0.1% return rate. [ABSTRACT FROM AUTHOR]

Summary The mechanism of cancer metastasis remains poorly understood. Using gene profiling of hepatocellular carcinoma (HCC) tissues, we have identified GOLM1 as a leading gene relating to HCC metastasis. GOLM1 expression is correlated with early recurrence, metastasis, and poor survival of HCC patients. Both gain- and loss-of-function studies determine that GOLM1 acts as a key oncogene by promoting HCC growth and metastasis. It selectively interacts with epidermal growth factor receptor (EGFR) and serves as a specific cargo adaptor to assist EGFR/RTK anchoring on the trans -Golgi network (TGN) and recycling back to the plasma membrane, leading to prolonged activation of the downstream kinases. These findings reveal the functional role of GOLM1, a Golgi-related protein, in EGFR/RTK recycling and metastatic progression of HCC. [ABSTRACT FROM AUTHOR]

Summary Blood neutrophils perform an essential host-defense function by directly migrating to bacterial invasion sites to kill bacteria. The mechanisms mediating the transition from the migratory to bactericidal phenotype remain elusive. Here, we demonstrate that TRPM2, a trp superfamily member, senses neutrophil-generated reactive oxygen species and restrains neutrophil migration. The inhibitory function of oxidant sensing by TRPM2 requires the oxidation of Cys549, which then induces TRMP2 binding to formyl peptide receptor 1 (FPR1) and subsequent FPR1 internalization and signaling inhibition. The oxidant sensing-induced termination of neutrophil migration at the site of infection permits a smooth transition to the subsequent microbial killing phase. [ABSTRACT FROM AUTHOR]

Abstract: Semiconductor quantum dots (QDs) have several photo-physical advantages over organic dyes making them good markers in biomedical application. We used CdSe/ZnS QDs with maximum emission wavelength of 590nm (QD590) linked to alpha-fetoprotein (AFP) monoclonal antibody (Ab) to detect AFP in cytoplasm of human hepatocellular carcinoma (HCC) cell line HCCLM6. For the in vivo studies, we used QD–AFP–Ab probes for targeted imaging of human HCC xenograft growing in nude mice by injecting them into the tail vein. In addition, the cytotoxicity in vitro, the acute toxicity in vivo, the hemodynamics and tissue distribution of these probes were also investigated. The results in vitro and in vivo indicate that our QD-based probes have good stability, specificity and biocompatibility for ultrasensitive fluorescence imaging of molecular targets in our liver cancer model system. [Copyright &y& Elsevier]

Summary: Hepatocellular carcinoma (HCC) is an aggressive malignancy mainly due to metastases or postsurgical recurrence. We postulate that metastases are influenced by the liver microenvironment. Here, we show that a unique inflammation/immune response-related signature is associated with noncancerous hepatic tissues from metastatic HCC patients. This signature is principally different from that of the tumor. A global Th1/Th2-like cytokine shift in the venous metastasis-associated liver microenvironment coincides with elevated expression of macrophage colony-stimulating factor (CSF1). Moreover, a refined 17 gene signature was validated as a superior predictor of HCC venous metastases in an independent cohort, when compared to other clinical prognostic parameters. We suggest that a predominant humoral cytokine profile occurs in the metastatic liver milieu and that a shift toward anti-inflammatory/immune-suppressive responses may promote HCC metastases. [Copyright &y& Elsevier]