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Robust, reliable quantification of large sample cohorts is often essential for meaningful clinical or pharmaceutical proteomics investigations, but it is technically challenging. When analyzing very large numbers of samples, isotope labeling approaches may suffer from substantial batch effects, and even with label-free methods, it becomes evident that low-abundance proteins are not reliably measured owing to unsufficient reproducibility for quantification. The MS1-based quantitative proteomics pipeline IonStar was designed to address these challenges. IonStar is a label-free approach that takes advantage of the high sensitivity/selectivity attainable by ultrahigh-resolution (UHR)-MS1 acquisition (e.g., 120-240k full width at half maximum at m/z = 200) which is now widely available on ultrahigh-field Orbitrap instruments. By selectively and accurately procuring quantitative features of peptides within precisely defined, very narrow m/z windows corresponding to the UHR-MS1 resolution, the method minimizes co-eluted interferences and substantially enhances signal-to-noise ratio of low-abundance species by decreasing noise level. This feature results in high sensitivity, selectivity, accuracy and precision for quantification of low-abundance proteins, as well as fewer missing data and fewer false positives. This protocol also emphasizes the importance of well-controlled, robust experimental procedures to achieve high-quality quantification across a large cohort. It includes a surfactant cocktail-aided sample preparation procedure that achieves high/reproducible protein/peptide recoveries among many samples, and a trapping nano-liquid chromatography-mass spectrometry strategy for sensitive and reproducible acquisition of UHR-MS1 peptide signal robustly across a large cohort. Data processing and quality evaluation are illustrated using an example dataset ( http://proteomecentral.proteomexchange.org ), and example results from pharmaceutical project and one clinical project (patients with acute respiratory distress syndrome) are shown. The complete IonStar pipeline takes ~1-2 weeks for a sample cohort containing ~50-100 samples.

Atypical chemokine receptor 3 (ACKR3) has emerged as a key player in various biological processes. Its atypical "intercepting receptor" properties have established ACKR3 as the major regulator in the pathophysiological processes in many diseases. In this study, we investigated the role of ACKR3 activation in promoting colorectal tumorigenesis. We showed that ACKR3 expression levels were significantly increased in human colon cancer tissues, and high levels of ACKR3 predicted the increased severity of cancer. In Villin-ACKR3 transgenic mice with a high expression level of CKR3 in their intestinal epithelial cells, administration of AOM/DSS induced more severe colorectal tumorigenesis than their WT littermates. Cancer cells of Villin-ACKR3 transgenic mice were characterised by the nuclear β-arrestin-1 (β-arr1)-activated perturbation of rRNA biogenesis. In HCT116 cells, cotreatment with CXCL12 and AMD3100 selectively activated ACKR3 and induced nuclear translocation of β-arr1, leading to an interaction of β-arr1 with nucleolar and coiled-body phosphoprotein 1 (NOLC1). NOLC1, as the phosphorylated protein, further interacted with fibrillarin, a conserved nucleolar methyltransferase responsible for ribosomal RNA methylation in the nucleolus, thereby increasing the methylation in histone H2A and promoting rRNA transcription in ribosome biogenesis. In conclusion, ACKR3 promotes colorectal tumorigenesis through the perturbation of rRNA biogenesis by the β-arr1-induced interaction of NOLC1 with fibrillarin.

Accurate, in-depth mapping of proteins on whole-tissue levels provides comprehensive insights into the spatially-organized regulatory processes/networks in tissues, but is challenging. Here we describe a micro-scaffold assisted spatial proteomics (MASP) strategy, based on spatially-resolved micro-compartmentalization of tissue using a 3D-printed micro-scaffold, capable of mapping thousands of proteins across a whole-tissue slice with excellent quantitative accuracy/precision. The pipeline includes robust tissue micro-compartmentalization with precisely-preserved spatial information, reproducible procurement and preparation of the micro-specimens, followed by sensitive LC-MS analysis and map generation by a MAsP app. The mapping accuracy was validated by comparing the MASP-generated maps of spiked-in peptides and brain-region-specific markers with known patterns, and by correlating the maps of the two protein components of the same heterodimer. The MASP was applied in mapping >5000 cerebral proteins in the mouse brain, encompassing numerous important brain markers, regulators, and transporters, where many of these proteins had not previously been mapped on the whole-tissue level.

Megalin and cubilin, endocytic proteins present in the proximal tubule of the kidney, are responsible for reabsorbing filtered proteins from urine. Our hypothesis was that potential substrates of megalin/cubilin could be identified by examining urinary protein differences between control (WT) mice and kidney-specific megalin knockdown (KD) mice. Using the IonStar proteomics approach, 877 potential megalin/cubilin substrates were discovered, with 23 of these compounds representing known megalin/cubilin substrates. Some of the proteins with the largest fold changes in the urine between KD and WT included the known megalin substrates retinol-binding protein and vitamin D-binding protein. Of the total proteins identified as novel substrates, about three-quarters of compounds had molecular weights (MWs) below 69 kDa, the MW of albumin, and the remaining had higher MWs, with about 5% of the proteins having MWs greater than 150 kDa. Sex differences in the number of identified substrates occurred, but this may be due to differences in kidney megalin expression between both male and female megalin KD and WT animals, with the ratio of megalin between WT and KD being 2.76 and 2.14 for female and male mice, respectively. The top three ingenuity canonical pathways based on the urinary proteins in both female and male KD mice were acute phase response signaling, liver X receptor/retinoid X receptor activation, and intrinsic prothrombin activation pathways. In conclusion, analysis of urine samples from kidney-specific megalin KD and WT mice was found to be useful for the identification of potential endogenous substrates for megalin and cubilin.

Objective To estimate the effect of catheter ablation combined with left appendage occlusion in the treatment of non-valvular atrial fibrillation (NVAF) by a method of meta-analysis. Methods Pubmed, Embase, and Cochrane Library were searched for the studies about catheter ablation combined with left appendage occlusion in treating NVAF. The data analysis was performed using R 4.0.5 software. The retrieval time was from inception to May 12, 2021. Results A total of 18 published studies were identified in the meta-analysis, including 1385 participants. During the perioperative period of catheter ablation combined with left appendage occlusion in treating NVAF, the pooled incidences of pericardial effusion, major or minor bleeding events, and residual flow documented were 0.5%(95%CI 0.0002–0.0099), 1.42%(95% CI 0.00–0.04), 7.24%(95% CI 0.0447–0.0975), respectively. During the follow-up, the incidences of all-cause mortality, embolism events, and bleeding events were 0.32%(95%CI 0.0000–0.0071), 1.29%(95%CI 0.0037–0.0222), 2.07%(95% CI 0.0075–0.0339), respectively. In the follow-up period of the transesophageal echocardiography, the most complication was residual flow event with an incident rate of 10.80%(95% CI 0.054–0.1620). The maximum occurrence probability of residual flow events was 17.92% (95% CI 0.1133–0.2452). Moreover, the incident rate of NVAF recurrence was 29.23% (95% CI 0.2222–0.3623). Conclusion The meta-analysis suggests that the “one-stop” procedure is effective for those patients undergoing NVAF. However, Patients with more residual blood flow have a higher incidence of bleeding complications. More studies are warranted to verify the safety and efficacy of catheter ablation combined with left appendage occlusion in terms of the “one-stop” procedure.

Aberrant sphingolipid metabolism has been implicated in chemoresistance, but the underlying mechanisms are still poorly understood. Herein we revealed a previously unrecognized mechanism of 5-fluorouracil (5-FU) resistance contributed by high SphK2-upregulated dihydropyrimidine dehydrogenase (DPD) in colorectal cancer (CRC), which is evidenced from human CRC specimens, animal models, and cancer cell lines. TMA samples from randomly selected 60 CRC specimens firstly identified the clinical correlation between high SphK2 and increased DPD (p

BackgroundData are lacking about the extent of drug-related problems in hospitalized patients with COPD in China.ObjectiveIdentify types and causes of drug-related problems and assess interventions performed by pharmacists.SettingStudy was conducted in an academic teaching hospital in Shanghai, China.MethodBetween June 2017 and July 2018, 393 patients admitted to hospital for acute exacerbation of COPD hospitalized were enrolled. Patient demographics and clinical characteristics were collected. The drug-related problems and interventions were recorded and analyzed based on the Pharmaceutical Care Network Europe (PCNE)-DRP V 8.02 classification.Main outcome measuresThe number, types, causes, interventions, and outcomes of the problems were analyzed.ResultsA total of 640 DRPs, with 763 corresponding causes, were identified for 393 patients. “Treatment safety P2” was the most common type of problem (54.2%; 347/640), and the most common causes were “drug selection C1” (24.2%; 185/763), “dose selection C3” (21.5%; 164/763) and “treatment duration C4” (17.7%; 135/763). Antibiotics, corticosteroids, and proton pump inhibitors were the three primary medication classes associated with DRPs. Patients, hospitalized for more than eight days, taking ten or more drugs or having renal dysfunctions were more likely to have drug-related problems. Pharmacists totally proposed 1557 interventions to address the problems. Most interventions (91.0%; 1418/1557) were accepted, and 91.6% of the problems were solved.ConclusionThe prevalence of drug-related problems among the studied COPD patients was high. Pharmacists can have an important role in addressing the problems and optimizing the safety and effectiveness of therapies for hospitalized COPD patients.

As alternative lubricant anti-wear additives are sought to reduce friction and improve overall fuel economy, it is important that these additives are also compatible with current emissions control catalysts. In the present work, a second-generation oil-miscible phosphorous-containing ionic liquid (IL), is evaluated for its impact on Pd-based three-way catalyst (TWC) reactivity and benchmarked against the industry standard zinc dialkyl-dithio-phosphate (ZDDP). The TWCs are exposed to the lubricant additives in an engine bench under four different scenarios: base case with no additive (NA), ZDDP-only, IL-only, and IL + ZDDP. The engine-aged TWC samples, along with the as-received TWC, are characterized through various analytical techniques including catalyst reactivity evaluation in a bench-flow reactor. The temperature of 50% conversion (T50) for the ZDDP-aged TWC increases by 11, 21, and 36 °C for CO, C3H6, and C3H8, respectively, as compared with the no-additive case. Similarly, the T50 for IL-only and IL + ZDDP-aged TWCs also increase as compared with the no-additive case. Even though the water-gas-shift (WGS) reactivity is similar for all engine-aged samples, the IL-aged TWC had higher oxygen storage capacity than the ZDDP-aged TWC. EPMA analysis reveals penetration of phosphorus deep into the washcoat for all engine-aged TWCs. Results from XRD indicate the presence of CePO4 and AlPO4 on the washcoat of IL, ZDDP, and IL + ZDDP-aged TWC samples but not on the fresh and NA TWC samples. Additionally, ICP-OES results show a large amount of phosphorus in the washcoat of IL, ZDDP and IL + ZDDP-aged TWC samples and a lesser amount in NA TWC samples.

The leaching processes and mechanisms of weathered crust elution-deposited rare earth (RE) ores with ammonium sulfate were investigated for their high efficiency and low consumption exploitation. The leaching process is a typical reversible heterogeneous ion exchange reaction in liquid–solid systems. The raw ore and leached tailings were analyzed by SEM and FTIR. Results indicated that no dissolution or structural changes of the ores occurred during the leaching process. The migrations of RE3+, Al3+, and $$ {\mathrm{NH}}_4^{+} $$ in the leaching process were studied under various liquid–solid ratios. With increasing liquid–solid ratio, the content of $$ {\mathrm{NH}}_4^{+} $$ adsorbed on clay mineral by physical effect decreased, $$ {\mathrm{NH}}_4^{+} $$ adsorbed by ion-exchange increased, and the content of exchanged RE and Al increased until reaching equilibrium. The adsorption capacity of the RE ores for $$ {\mathrm{NH}}_4^{+} $$ remained about 0.61–0.63 mg/g. It was difficult to desorb $$ {\mathrm{NH}}_4^{+} $$ from RE ores with washing water alone. The leaching mechanism of Al was the same as RE, but the leaching of Al slightly lagged behind RE. At the optimal liquid–solid ratio of 0.4:1, the leaching efficiencies of RE and Al were 95.51% and 90.99%, respectively, and 56.65% of $$ {\mathrm{NH}}_4^{+} $$ remained in the leachate. After impurity removal and RE precipitation, the leachate can be reused by replenishing fresh leaching agent. The aim of this study is to enhance the leaching process of RE, restrain the leaching of impurities, and decrease the consumption of leaching agents.

Phlogopite was activated by ball milling at a mild milling speed of 300 rpm to be directly used as heavy metal ions (Cu2+, Zn2+, Cd2+, and Ni2+) adsorbent. Without the need of final breakdown of its crystal structure, which is usually observed at intensive milling over 600 rpm, phase transformation of trigonal phlogopite into monoclinic by milling at 300 rpm occurred, accompanied with enhanced dissolutions of K+, Mg2+, and OH−, allowing easy removal of Cu2+, Zn2+, and Ni2+ ions (initial 100 ppm) by 2 g/L dosage of the activated phlogopite. Higher dosage up to 5 g/L was needed for nearly complete removals Cd2+ ion (initial 100 ppm). Several analytical methods such as XRD, laser particle size analyzer, and SEM were used to characterize the activated sample and to understand the reason for the easier absorption of metal ions. The adsorption data confirmed that the heavy metal ions were adsorbed with surface precipitation and cation exchange as the main pathways. The proposed craft to produce heavy metal ions adsorbent with outstanding heavy metal ions removal efficiency may have a great potentiality for practical application.

Both chemokine receptors (CXCRs) 7 and 4 can facilitate immune cell migration and mediate a vast array of physiological and pathological events. Herein we report, in both human and animal studies, that these two CXCRs can form heterodimers in vivo and promote colorectal tumorigenesis through histone demethylation. Compared with adjacent non-neoplastic tissue, human colorectal cancer (CRC) tissue showed a significant higher expression of CXCR4 and CXCR7, which was colocalized in the cancer cell epithelium. The CXCR/CXCR4 heterodimerization was associated with increased histone demethylase JMJD2A. Villin-CXCR7-CXCR4 transgenic mice demonstrated a greater degree of exacerbated colitis and tumorigenesis than villin-CXCR7 and villin-CXCR4 mice. The CXCR7/CXCR4 heterodimerization also promoted APC mutation-driven colorectal tumorigenesis in APCMin/+/villin-CXCR7-CXCR4 mice. Further analysis showed that the CXCR7/CXCR4 heterodimer induced nuclear βarr1 recruitment and histone demethylase JMJD2A, leading to histone demethylation and resulting in transcription of inflammatory factors and oncogenes. This study uncovered a novel mechanism of colorectal tumorigenesis through the CXCR7/CXCR4 heterodimer-induced histone demethylation. Inhibition of CXCR7/CXCR4 heterodimer-induced histone demethylation could be an effective strategy for the prevention and treatment of colorectal cancer.

A multiscale pharmacodynamic model was developed to characterize the receptor-mediated, transcriptomic, and proteomic determinants of corticosteroid (CS) effects on clinically relevant hepatic processes following a single dose of methylprednisolone (MPL) given to adrenalectomized (ADX) rats. The enhancement of tyrosine aminotransferase (TAT) mRNA, protein, and enzyme activity were simultaneously described. Mechanisms related to the effects of MPL on glucose homeostasis, including the regulation of CCAAT-enhancer binding protein-beta (C/EBPβ) and phosphoenolpyruvate carboxykinase (PEPCK) as well as insulin dynamics were evaluated. The MPL-induced suppression of circulating lymphocytes was modeled by coupling its effect on cell trafficking with pharmacogenomic effects on cell apoptosis via the hepatic (STAT3-regulated) acute phase response. Transcriptomic and proteomic time-course profiles measured in steroid-treated rat liver were utilized to model the dynamics of mechanistically relevant gene products, which were linked to associated systemic end-points. While time-courses of TAT mRNA, protein, and activity were well described by transcription-mediated changes, additional post-transcriptional processes were included to explain the lack of correlation between PEPCK mRNA and protein. The immune response model quantitatively discerned the relative roles of cell trafficking versus gene-mediated lymphocyte apoptosis by MPL. This systems pharmacodynamic model provides insights into the contributions of selected molecular events occurring in liver and explores mechanistic hypotheses for the multi-factorial control of clinically relevant pharmacodynamic outcomes.

Aims. To identify the range of emotional labour employed by healthcare professionals in a healthcare setting and implications of this for staff and organisations. Background. In a healthcare setting, emotional labour is the act or skill involved in the caring role, in recognizing the emotions of others and in managing our own. Design. A thematic synthesis of qualitative studies which included emotion work theory in their design, employed qualitative methods and were situated in a healthcare setting. The reporting of the review was informed by the ENTREQ framework. Data sources. 6 databases were searched between 1979–2014. Review methods. Studies were included if they were qualitative, employed emotion work theory and were written in English. Papers were appraised and themes identified. Thirteen papers were included. Results. The reviewed studies identified four key themes: (1) The professionalization of emotion and gendered aspects of emotional labour; (2) Intrapersonal aspects of emotional labour – how healthcare workers manage their own emotions in the workplace; (3) Collegial and organisational sources of emotional labour; (4) Support and training needs of professionals Conclusion. This review identified gendered, personal, organisational, collegial and socio-cultural sources of and barriers to emotional labour in healthcare settings. The review highlights the importance of ensuring emotional labour is recognized and valued, ensuring support and supervision is in place to enable staff to cope with the varied emotional demands of their work.

This study was designed to investigate the risk of local anesthetic toxicity and efficacy of simultaneous bilateral axillary brachial plexus block performed under the guidance of ultrasound or a neurostimulator. One hundred and twenty patients who were anesthetized with bilateral axillary plexus block simultaneously between February 2012 and March 2014 were enrolled in the study. The patients were anesthetized under the guidance of a neurostimulator (group N, n = 60) or ultrasound (group U, n = 60). The block performance time, procedure-related pain, adverse events, total and free plasma concentrations of ropivacaine, and other data were recorded. The comparison was analyzed statistically. The block performance time, and onset of the sensory and motor block, of group N was longer than that of group U (p

The mitochondria-associated ER membrane (MAM) plays a critical role in cellular energetics and calcium homeostasis; however, how MAM is affected under diabetic condition remains elusive. This study presented a comprehensive proteome profiling of isolated brain MAM from long-term type 2 diabetic mice vs. non-diabetic controls. MAM protein was extracted efficiently by a surfactant-aided precipitation/on-pellet digestion (SOD) method, and MAM proteome was quantified by an ion-current-based MS1 method combined with nanoLC-MS/MS. A total of 1,313 non-redundant proteins of MAM were identified, among which 144 proteins were found significantly altered by diabetes. In-depth IPA analysis identified multiple disease-relevant signaling pathways associated with the MAM proteome changes in diabetes, most significantly the unfolded protein response (UPR), p53, hypoxia-related transcription factors, and methyl CpG binding protein 2. Using immunofluorescence labeling we confirmed the activation of three UPR branches and increased ERp29 and calreticulin in diabetic retinas. Moreover, we found GRP75, a key MAM tethering protein, was drastically reduced by long-term diabetes. In vitro, acute high glucose treatment reduces ER-mitochondrial contact in retinal endothelial cells. This study provides first insight into the significant alterations in MAM proteome associated with activation of the UPR in diabetes, which may serve as novel benchmarks for the future studies of diabetic complications.

JWA (Arl6ip5), a homologous gene of glutamate-transporter-associated protein 3-18 (GTRAP3-18) and addicsin, is highly expressed in hippocampus. We generated systemic and neuronal JWA knockout (JWA-KO and JWA-nKO) mice to investigate the influence of JWA deficiency on spatial cognitive performance, process of neurogenesis, and induction of long-term potentiation (LTP) in hippocampal dentate gyrus (DG). In comparison with wild-type (WT) mice and JWA (loxP/loxP) (control of JWA-nKO) mice, 8-week-old JWA-KO mice and JWA-nKO mice showed spatial cognitive potentiation as assessed by Morris water maze test. In hippocampal DG of JWA-nKO mice, either survival and migration or neurite growth of newborn neurons were significantly enhanced without the changes in proliferation and differentiation of stem cells. In addition, the increase of LTP amplitude and the decline of LTP threshold were observed in DG, but not in CA1 region, of JWA-nKO mice compared to control mice. The levels of hippocampal FAK, Akt, and mTOR phosphorylation in JWA-nKO mice were higher than those in control mice. The PI3K or FAK inhibitor could abolish the enhanced neurogenesis and LTP induction in JWA-nKO mice, which was accompanied by disappearance of the spatial cognitive potentiation. The treatment of JWA-nKO mice with 3'-azido-3'-deoxythymidine (AZT), a telomerase inhibitor, suppressed not only the enhanced neurogenesis but also the enhanced LTP induction in DG, but it did not affect the LTP induction in CA1 region. The results suggest that the JWA deficiency through cascading FAK-PI3K-Akt-mTOR pathway increases the newborn neurons and enhances the LTP induction in hippocampal DG, which leads to the spatial cognitive potentiation.

Xihu desert wetland is an important and unusual environment in China or even in the world. However, until now, little research has been focused on the microclimate and CO2 flux characteristics in this area. This paper reports the characteristics of daily variations of microclimate and CO2 flux in the Dunhuang Xihu desert wetland, based on data observed in the desert wetland during a period of continuous fine weather in summer 2012. Results indicate that the characteristics of the micrometeorology were significantly affected by the land–lake breeze during the study period, and updrafts were prevalent in this region. The friction wind speed and the vertical velocity were much greater than those in the Maqu grasslands. The energy budget was strongly imbalanced: the latent heat flux was significantly higher than the sensible flux. The daily mean values of total solar radiation and net radiation were larger than those in Maqu grasslands and Jinta oasis. There was a temperature inversion and inverse humidity gradient in the atmospheric surface layer at night. The desert wetland ecosystem was a carbon sink during the whole of the observation period, and the maximum rate of carbon absorption usually occurred at about 11:00 hr each day in this region.

By taking the machine stiffness into the classic Hertzian solution rather than assuming a constant machine stiffness, we developed an approach to simultaneously derive the spherical indenter tip radius and machine stiffness in arbitrary ranges of loads and indenter radii. In contrast, the direct Hertzian fitting method tends to underestimate the radius, especially for larger indenter tips. The success is based on indention tests on two materials with known material stiffness, and the displacement difference under the same load is not affected by the machine stiffness. A total of eight spherical indenter tips with the radii ranging from a few microns to hundreds of microns have been indented on fused silica and single crystal sapphire. Our method gives correct indenter radii for all indenters. The machine stiffness is found to indeed vary with the indentation load and indenter radius. This method has many potential applications in the area of nano-indentation with spherical indenters, such as indentation size effect, modulus and hardness measurement, and micropillar testing.

SL-01, dodecyl-3-((1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl) carbamoyl) pyrazine-2-carboxylate, is a prodrug of gemcitabine. Our previous reports suggested that SL-01 possesses superior bioavailability and anticancer activity to gemcitabine in mice. In this study, its pharmacokinetics and metabolisms were investigated in rats.The pharmacokinetics of SL-01 was studied following intravenous or oral administration of SL-01 to Sprague-Dawley rats. The metabolites profile of SL-01 was further determined in rats receiving intravenous administration of SL-01. Blood samples were analyzed by using LC-MS or LC-MS/MS assay.Following administration with SL-01 intravenously or orally, SL-01, plasma gemcitabine released from SL-01 as well as the sum of gemcitabine (gemcitabine converted from SL-01 and plasma gemcitabine) exhibited higher values of V z /F and CL z /F, and longer MRT and t 1/2 than those of gemcitabine administered intravenously. The C max of gemcitabine produced by intravenous SL-01 was higher than that of gemcitabine dosed intravenously. The absolute bioavailability for the sum of gemcitabine was 32.2 % for intravenous and 22.2 % for oral administration with SL-01, respectively. After a single intravenous administration, a total of 5 components (M1, M2, M3, M4, and M5) were detected and identified as the metabolites of SL-01 in the plasma of rats. M1 and M2 were formed from the methylation and reduction of SL-01, respectively. Hydrolysis of the amide bond of SL-01 gave M3 and M4. M5 was produced from further dealkylation of M3.SL-01 displayed improved absorption, good distribution, high clearance, long mean residence time, and moderate bioavailability after administered intravenously or orally to rats. The major metabolic pathways of SL-01 involved methylation, reduction, hydrolysis, and dealkylation. These results suggested that SL-01 acts as a prodrug of gemcitabine in rats.

Previous studies have shown that androgen receptor (AR) is involved in the progression of prostate cancer (CaP) by several mechanisms. However, how AR is regulated has not been fully understood. In this study, miR-185 was found to be down-regulated in clinical CaP samples. Targets prediction revealed that AR had putative complementary sequences to miR-185, which was confirmed by the following dual luciferase reporter assay. Overexpression of miR-185 could reduce the expression of AR protein but not mRNA in LNCaP cells. The proliferation of LNCaP cells was inhibited by overexpression of miR-185. Cell cycle analysis revealed cell cycle arrest at G0/G1 phase. The invasive and migration abilities of cells could also be suppressed by miR-185. Furthermore, miR-185 inhibited tumorigenicity in a CaP xenografts model. CDC6, one target of AR and an important regulatory molecule for cell cycle, was found to be down-regulated by overexpression of miR-185. Our findings suggest that miR-185 could function as a tumor-suppressor gene in CaP by directly targeting AR, and act as a potential therapeutic target for CaP.

In this work, we investigated the feasibility of five quaternary (aprotic) and four tertiary (protic) ammonium ionic liquids (ILs) with an identical organophosphate anion as lubricant anti-wear additives. Viscosity, oil solubility, thermal stability and corrosivity of the candidate ILs were characterized and correlated to the molecular structure. The protic group exhibits higher oil solubility than the aprotic group, and longer alkyl chains seem to provide better oil solubility and higher thermal stability. Selected ILs were applied as oil additives in steel–cast iron tribological tests and demonstrated promising anti-scuffing and anti-wear functionality. The thickness, nanostructure, and composition of the tribofilm formed by the best performing IL were revealed by surface characterization for mechanistic understanding of the tribochemical interactions between the IL and metal surface. Results provide fundamental insights of the correlations among the molecular structure, physiochemical properties and lubricating performance for ammonium-phosphate ILs.

Tribological behavior of alumina-particle-reinforced aluminum composites made by powder metallurgy process has been investigated. The nanocomposite containing 15 vol% of Al2O3 nanoparticles exhibits excellent wear resistance by showing significantly low wear rate and abrasive wear mode. The wear rate of the nanocomposite is even lower than stainless steel. We have also demonstrated that such excellent wear resistance only occurred in the composite reinforced with the high volume fraction of nanosized reinforcing particles. The results were discussed in terms of the microstructure of the nanocomposite.

Epidemiological studies found inconsistent results on the association of two variants on TGFBR1 (TGFBR1*6A and Int7G24A) with colorectal cancer (CRC) risk. The present study was aimed to evaluate the association of these two variants with CRC susceptibility via the meta-analysis methods. For variant TGFBR1*6A, nine reports including 6,765 CRC patients and 8,496 unrelated controls were identified. The heterozygotes *6A/*9A showed a significant increased risk of CRC with the pooled OR was 1.12 (95% CI = 1.02-1.23), and the pooled OR for the homozygotes *6A/*6A was 1.13 (95% CI = 0.80-1.58) compared to the homozygotes *9A/*9A. However, under the dominant effect model, the TGFBR1*6A carriers showed a significantly increased CRC risk (pooled OR = 1.12, 95% CI = 1.03-1.23, *6A/*6A and *6A/*9A vs. *9A/*9A). For variant Int7G24A, three case-control studies with 1,074 cases and 1,945 controls were found. Although no significant association was found for heterozygosity Int7G24A carriers with CRC risk (pooled OR = 0.97, 95% CI = 0.67-1.42), the homozygosity A/A carriers showed a significant elevated risk of CRC (pooled OR = 1.68, 95% CI = 1.14-2.47) compared to G/G homozygotes. Under the recessive effect model, homozygotes A/A showed a 71% increase of CRC risk compared to the A/G and G/G genotype carriers (pooled OR = 1.71, 95% CI = 1.17-2.51). These data strongly suggested that the two polymorphisms of TGFBR1 may confer low-penetrance susceptibility of CRC risk.

Since the idea of using ionic liquids (ILs) as lubricants was raised in 2001, many studies have been conducted in this area and results have demonstrated superior lubricating performance for a variety of ILs. It is widely believed that a protective tribo-boundary film is formed on the contact area by tribochemical reactions between the metal surface and the IL during the wear process and, as a result, reduces friction and wear. However, the study of this critical boundary film in the literature has been limited to two-dimensional topography examination and chemical analysis from the top surface. This study demonstrates a multi-technique three-dimensional approach to characterize the boundary films on IL-lubricated metallic surfaces. The complementary characterizations at the top surface, cross-section, and different layers of the boundary film provide direct measurement of the film thickness, visualization of the nanostructure, and analysis of the composition change. The boundary films observed on different alloys are substantially distinct from both physical and chemical perspectives. The measured mean film thicknesses for cast iron, steel, and aluminum worn surfaces are 300, 60, and 200 nm, respectively. The boundary films on ferrous alloys are dominated by amorphous phase mixing with well-dispersed very fine (a few nm) nanocrystals, while the film on aluminum contains many larger size (tens of nm) metallic particles in a less organized manner.

Haishengsu (HSS) is a seashell protein extracted from Tegillarca L. granosa, a type of Malaysian shellfish. Previous in vitro studies showed that HSS might possess biological anticancer activity. In this combined in vitro and in vivo study, we investigated the inhibitory effects of HSS on tumor growth, invasion, and metastasis using human lung carcinoma cell lines A549 and NCI-H292, both intensely positive for matrix metalloproteinases-2 (MMP-2) and MMP-9. HSS significantly inhibited the proliferation of A549 and NCI-H292 as estimated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The transwell chamber assay showed that HSS effectively blocked the invasion and migration of the carcinoma cells through the reconstituted extracellular matrix (Matrigel). Gelatin zymography analysis revealed that the secretion and activity of MMP-2 and MMP-9 in the supernatants of the cultured cells A549 and NCI-H292 were decreased after treatment with HSS. The levels of MMP-2 and MMP-9 in these cancer cells were further examined by Western blot assay in which a significant decrease of MMP-2 and MMP-9 was observed in A549 and NCI-H292 cells after 24 h of exposure to HSS. The anticancer activity of HSS was verified in a mouse model in which HSS delayed the growth of A549 xenografts after 3 weeks of oral administration. Inhibition of MMP-2 and MMP-9 expression was also demonstrated in the A549 xenografts as determined by Western blot analysis. These results suggest that HSS is a novel seashell protein that cannot only inhibit tumor growth but also prevent tumor invasion and metastasis through suppressing the activity of MMP-2 and MMP-9.

Based on the extended Huygens–Fresnel Principle and the unified theory of coherence and polarization, the analytical formulas for the polarization degree and spectral coherence degree of partially coherent electromagnetic elegant Laguerre–Gaussian (PCEELG) beams through turbulent atmosphere are obtained theoretically in detail. It is found that the polarization degree of PCEELG beams tends to the value of its source plane after a sufficiently long propagation distance in turbulent atmosphere. Furthermore, this value is independent of the beam orders, the correlation length in the source plane and the structure constant of the turbulent atmosphere ( $C_{n}^{2}$ ). The polarization degree of PCEELG beams also acquires a particular value at a certain distance in free space, which is different from the value in the source plane. The spectral coherence degree of PCEELG beams has an oscillatory behavior for different propagation distance, beam orders and $C_{n}^{2}$ .

We studied the effect of riccardin D, a macrocyclic bisbibenzyl, which was isolated from the Chinese liverwort plant, on human leukemia cells and the underlying molecular mechanism. Riccardin D had a significant antiproliferative effect on human leukemia cell lines HL-60, K562 and its multidrug resistant (MDR) counterpart K562/A02 cells, but showed no effect on the topoisomerase-II-deficient HL-60/MX2 cells, as measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The pBR322 DNA relaxation assay revealed that riccardin D selectively inhibited the activity of topoisomerase II (topo II). The suppression of topo II activity by riccardin D was stronger than that of etoposide, a known topo II inhibitor. After treatment with riccardin D, nuclear extracts of leukemia K562 and K562/A02 cells left the majority of pBR322 DNA in a supercoiled form. Further examination showed that riccardin D effectively induced HL-60, K562 and K562/A02 apoptosis as evidenced by externalization of phosphatidylserine and formation of DNA ladder fragments. The activation of cytochrome c, caspase-9, caspase-3 and cleaved poly ADP-ribose polymerase (PARP) was also enhanced, as estimated by Western blot analysis. By contrast, riccardin D was unable to induce apoptosis in the topoisomerase-II-deficient HL-60/MX2 cells, indicating that the induction of apoptosis by riccardin D was due to the inhibition of topo II activity. In addition, riccardin D was able to significantly decrease P-glycoprotein (P-gp) expression in K562/A02 cells. Taken together, our data demonstrate that riccardin D is a novel DNA topo II inhibitor which can induce apoptosis of human leukemia cells and that it has therapeutic potential for both regular and MDR strains of leukemia cells.

Synergistic effects of layered double hydroxide (LDH) with intumescent flame retardanct (IFR) of phosphorus-nitrogen (NP) compound in the polypropylene/ethylene-propylene-diene/IFR/LDH (PP/EPDM/IFR/LDH) nanocomposites and related properties were studied by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), limiting oxygen index (LOI), UL-94 test, cone calorimeter test (CCT) and thermo-gravimetric analysis (TGA). The XRD and TEM results show that the intercalated and/or exfoliated nanocomposites can be obtained by direct melt-intercalation of PP/EPDM into modified LDH and that LDH can promote the IFR additive NP to disperse more homogeneously in the polymer matrix. The SEM results provide positive evidence that more compact charred layers can be obtained from the PP/EPDM/NP/LDH sample than those from the PP/EPDM/LDH and PP/EPDM/NP samples during burning. The LOI and UL-94 rating tests show that the synergetic effects of LDH with NP can effectively increase the flame retardant properties of the PP/EPDM/NP/LDH samples. The data from the CCT and TGA tests indicate that the PP/EPDM/NP/LDH samples apparently decrease the HRR and MLR values and thus enhance the flame retardant properties and have better thermal stability than the PP/EPDM/LDH and PP/EPDM/NP samples.

To reduce data variance caused by individual differences of different samples, a new experimental method is proposed by loading and unloading the axial forces with different frequencies and different waves of a certain load amplitude to the same rock sample without damaging it. Lag time segments are defined and fractionized into segments I and II. Criterions for segmentation, definitions of relevant parameters and empirical analysis are also offered afterwards. In the course of sinusoidal loading, the serious peak value dislocation of the displacement variation rate and the loading rate is defined as peak dislocation. Meanwhile, the definition of the apparent tangent modulus is put forward and the linear relation between it and the vertical force in the frequency of 0.1, 0.2, 0.5 Hz sinusoidal loading segment is confirmed to be ever-present on the basis of the test data. Then the calculating formula of the deformation rate in non-lag time is deduced. It is thus suggested that the deformation rate should be codetermined by the loading rate df/dt and instant load f(t), which well explains the peak dislocation of the time-variable curve peak value of dl/dt and deformation rate of df/dt. Finally the lag time derivation model is established and by comparing the calculated values with the measured ones, it is demonstrated that the above formula offers a better simulation of the sandstone deformation rate in the sinusoidal loading segment, with the load amplitude being 96 kN and the frequency ranging from 0.1 Hz to 0.5 Hz.

QA3 is a derivative of the substituted 1,3-dimethyl-1H-quinoxalin-2-ones, which are compounds that may selectively antagonize P-glycoprotein (P-gp) in multidrug resistance (MDR) cancer cells. Our previous work identified QA3 as a candidate compound for reversing MDR in cancer cells. In the present study, we found that QA3 significantly decreases the intracellular level of ATP, stimulates ATPase activity in membrane microsomes and decreases protein kinase C (PKC) activity. These results indicated that QA3 inhibits P-gp activity by blocking ATP hydrolysis and ATP regeneration. Furthermore, QA3 triggered and increased adriamycin-induced K562/A02 cell apoptosis as evidenced by Annexin V-FITC plus PI staining. Western blot analysis showed that the levels of cleaved caspase-9 and cleaved caspase-3 proteins increased, and similarly, the levels of procaspase-9 and procaspase-3 decreased after QA3 treatment. Consequently, poly ADP-ribose polymerase (PARP) activity increased as evidenced by the presence of the PARP cleavage product in K562/A02 cells. QA3 also enhanced the potency of adriamycin against K562/A02 cells as demonstrated by increased apoptosis and activation of caspase-9,-3 and PARP. These data support the observation that P-gp activity is inhibited after QA3 treatment. Moreover, these results indicate that QA3 is a novel MDR reversal agent with potent inhibitory action against P-gp MDR cancer cells.

LYP is a bestatin dimethylaminoethyl ester which inhibits aminopeptidase N (APN/CD13). Our goal in this study was to evaluate LYP as a candidate compound for cancer treatment, beginning by studying its inhibitory effects on tumors and then comparing it to bestatin. Experiments were performed on human ovarian carcinoma (OVCA) ES-2 and SKOV-3 cell lines, which have high and low levels of APN/CD13 respectively. LYP effectively inhibited ES-2 cell growth as estimated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and the trypan blue dye-exclusion test. LYP significantly suppressed APN/CD13 activity on the surface of ES-2 cells as measured by quantifying the enzymatic cleavage of the substrate L-leucine-p-nitroanilide. The inhibitory effects of LYP were greater than those of bestatin at the same concentrations. In contrast, LYP was a weak inhibitor of SKOV-3 cell growth, suggesting that LYP may inhibit ES-2 cell growth via suppression of APN/CD13. Inhibition of APN/CD13 expression was also demonstrated with immunofluorescent flow cytometry and Western blot analysis. Inhibitory effects of LYP were confirmed by using a mouse model in which LYP delayed the growth of ES-2 xenografts in mice after 2 weeks of LYP injections. Inhibition of APN/CD13 expression was demonstrated in the ES-2 xenografts using Western blot analysis. The inhibitory effects of LYP on the ES-2 xenografts were stronger than those of bestatin. These results suggest that LYP has a powerful inhibitory effect on the growth of OVCA cells and that the mechanism may be via a decrease in the expression of APN/CD13.

Firm joins were obtained between Ti(C,N)-based cermet and steel with Ag-Cu-Zn-Ni filler metal by vacuum brazing. The effects of technological parameters such as brazing temperature, holding time, and filler thickness on the shear strength of the joints were investigated. The microstructure of welded area and the reaction products of the filler metal were examined by scanning electron microscopy (SEM), metallographic microscope (OM), energy-dispersive X-ray analysis (EDS), and X-ray diffraction (XRD). The brazing temperature of 870°C, holding time of 15 min, and filler thickness of 0.4 mm are a set of optimum technological parameters, under which the maximum shear strength of the joints, 176.5 MPa, is achieved. The results of microstructure show that the wettability of the filler metal on Ti(C,N)-based cermet and steel is well. A mutual solution layer and a diffusion layer exist between the welding base materials and the filler metal.

Photoinitiated crosslinking of ethylene-propylene-diene terpolymer (EPDM) blends filled with calcium carbonate, talc and calcined kaolin (CK) in the presence of benzil dimethyl ketal as photoinitiator and trimethylolpropane triacrylate as crosslinker and their related properties have been studied by different analytical methods. The results from gel content and heat extension determination show that the efficiency of photocrosslinking of EPDM increases with increasing the content of diene and its molecular weight. The EPDM blends with 100 phr different inorganic fillers can be photocrosslinked to gel content of above 60% by 5 s UV-irradiation under optimum conditions. Under the same conditions of irradiation, the orders of photocrosslinking rate and final gel content are EPDM/CaCO3 > EPDM/talc > EPDM/CK. The data from thermogravimetric analysis, dynamic mechanical thermal analysis, electrical properties, mechanical tests and scanning electron microscopy show that UV irradiation crosslinking apparently enhances the thermal stability, mechanical properties and electrical properties of the photocrosslinked EPDM/inorganic filler samples. Although the attenuated total-reflection FTIR data show that inorganic fillers can promote the surface photo-oxidation of EPDM/inorganic filler samples with increasing the irradiation time, the above related properties of the photocrosslinked EPDM blends irradiated within 5 s are enough to satisfy many applications in the cable industry.

Purpose N3-o-toluyl-fluorouracil (TFU), the prodrug of 5-fluorouracil (5-FU), is the metabolite of N1-acetyl-N3-o-toluyl-fluorouracil (atofluding). In the present study, we aimed to evaluate the efficacy of TFU on the inhibition of human hepatocellular carcinoma cells via sustained release of 5-FU. The metabolism of TFU underlying the inhibitory effect was also analyzed. Methods In vitro assays, inhibition of cell growth by TFU was evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide method. The levels of TFU and 5-FU in the cell culture supernatant fluid were measured by high-performance liquid chromatography (HPLC). In vivo assays, the efficacy of TFU was evaluated in a human hepatocellular carcinoma xenograft mice model after 3 weeks of oral administration. The distributions of TFU and 5-FU in plasma and homogenate tissues including liver, lung and tumor were determined by HPLC. Results N3-o-toluyl-fluorouracil weakly inhibited the proliferation of SMMC-7721 and PLC/PRF/5 cells in the absence of liver microsomal enzymes. In contrast, the inhibition rates were significantly increased in the presence of these enzymes. HPLC results revealed that TFU was metabolized slowly by liver microsomal enzymes and therefore the concentration of 5-FU was gradually increased with a longer retention time in cell culture supernatant fluid. The efficacy of TFU was confirmed in SMMC-7721 xenografts in Balb/c athymic (nu+/nu+) mice model. TFU treatment induced inhibition of SMMC-7721 growth with few side effects. HPLC results showed that high levels of TFU were still in liver 48 h after the end of oral administration, implying that TFU preferentially accumulated in liver with slow conversion to 5-FU by enzymes. This led to a long-lasting concentration of 5-FU in plasma. Further, a high level of 5-FU was found in tumors with a relatively low level in lungs. These results suggest that the metabolite of TFU was preferentially converted or taken up by tumor cells. The distributions of 5-FU may contribute to its high anti-tumor activity and low adverse reactions in vivo. Conclusion These results demonstrate that TFU is a promising prodrug of 5-FU for cancer treatment via sustained release of 5-FU in liver.

The lubricating properties of two ionic liquids (ILs) with the same anion but different cations, one ammonium IL [C8H17]3NH.Tf2N and one imidazolium IL C10mim.Tf2N, were evaluated both in neat form and as oil additives. Experiments were conducted using a standardized reciprocating sliding test with a segment of a Cr-plated diesel engine piston ring against a gray cast iron flat specimen. The cast iron surface was prepared with simulated honing marks as on a typical internal combustion engine cylinder liner. The selected ILs were benchmarked against conventional hydrocarbon oils. Substantial friction and wear reductions, up to 55% and 34%, respectively, were achieved for the neat ILs compared to a fully formulated 15W40 engine oil. Adding 5 vol% ILs into mineral oil has demonstrated significant improvement in the lubricity. One blend even outperformed the 15W40 engine oil with 9% lower friction and 34% less wear. Lubrication regime modeling, worn surface morphology examination, and surface chemical analysis were conducted to help understand the lubricating mechanisms for ILs. Results suggest great potential for using ionic liquids as base lubricants or lubricant additives for diesel engine applications.

Seismic ground motions of two neighboring mountains and the free surface between them are calculated under the SV seismic waves with three different incident angles. The results are then taken as the inputs of multi-point seismic excitations for the foundation of a long-span bridge built over the valley in the analysis considering the integrated influence of traveling wave and topography. On the basis of a dynamic analytical method, a finite element model is created for the seismic responses of a four-span rigid-frame bridge of 440 m. The pier-top displacement and the pier-bottom internal force of the bridge are calculated. Then the results are compared with those considering traveling-wave effect only. The conclusions can serve as a seismic design reference for the structures located on the complex mountain topography.

Based on data of earthquake sequences with M S≥5.0 in Chinese mainland from 1970 to 2004, for different sequence types and different rupture modes of the main shock, the relationship between aftershock distribution size R and the magnitude of the main shock M 0 has been studied statistically. Considering the rupture mode of the main shock, we give the quantitative statistical relationships between R and M 0 under 95% confidence level for different sequence types. Qualitatively, lgR, the logarithm of the aftershock distribution size, is positively correlative to the M 0, but the data distribution is dispersed. Viewing from different sequence types, the correlation between R and M 0 is very weak for isolated earthquake type (IET) sequence, R distributes in the range from 5 to 60 km; For mainshock-aftershock type (MAT), lgR is positively correlative to M 0; For multiple main shock type (MMT), the correlation between lgR and M 0 is not very obvious when M 0≤6.2 and R distributes in the range from 5 to 70 km, while it shows a linear correlation when M 0≥6.3. The statistical results also show that the occupational ratios of different sequence types for strike-slip and oblique slip are almost the same. But for dip-slip (mostly are thrust mechanisms), the ratio of MAT is higher than that of IET and MMT. Comparing with previous results, it indicates that, when M 0 is large enough, R is mainly determined by M 0 and there is almost no relationship with the rupture mode of the main shock.

A new class of more effective lubricants could lead to huge energy savings. Limited recent literature has suggested potential for using room-temperature ionic liquids as lubricants, however, only a few out of millions (or more) of species possible have been evaluated. In this study, a series of new protic alkylammonium ionic liquids were synthesized by neutralization and metathesis reactions, and have demonstrated promising lubricating properties as neat lubricants or lubricant additives, particularly for use with difficult-to-lubricate metals like aluminum. More than a 30% friction reduction was observed with ammonium-based ionic liquids compared to conventional hydrocarbon oils in reciprocating sliding tests of 52100 bearing steel on aluminum alloy 6061-T6511. The inherent polarity of ionic liquids is believed to provide strong adsorption to contact surfaces and can form a boundary lubricating film leading to friction and wear reductions. Other advantages of ionic liquids include (1) negligible volatility, (2) high thermal stability, (3) non-flammability, and (4) better intrinsic properties that may eliminate the need for more complex and expensive additive packages. With very flexible molecular structures, this new class of lubricants, particularly ammonium-based ionic liquids, can be tailored to fit a variety of applications.

Based on 294 earthquake sequences with magnitude greater than or equal to 5.0 occurred in Chinese mainland since 1970, the spatial distribution features of sequence types have been studied. In southwestern China, it takes mainshock-aftershock sequence type (MAT) as the major in Chuan-Dian rhombic block and concerned Xianshuihe-Anninghe-Xiaojiang seismic belt, as well as in Jinshajiang-Honghe seismic belt. Multiple mainshock type (MMT) mainly distributes in western Yunnan, and Longlin and Lancang areas in Tengchong-Baoshan block in west of Nujiang-Lancangjiang fault zone. A few isolated earthquake type (IET) mainly occurred in northwestern Sichuan and there is no IET occurred in Yunnan region. In northwestern China, it takes mainshock-aftershock sequence type (MAT) as the major in west segment of South Tianshan in Xinjiang region. Some MMT also occurred in this area in the intersection of Kalpin block and the Puchang fault zone. It takes IET as the major in middle Tianshan in Xinjiang. Along the Qilianshan seismic belt, most of sequences are MAT. In Qinghai region, it takes MAT as the major, but the regional feature of the spatial distribution of sequence types is not very clear. In North China, it takes MAT as the major in Yinshan-Yanshan-Bohai seismic belt, north edge of North China, and in Hebei plain seismic belt, as well as in sub-plate of lower river area of Yangtze River. In intersection of north segment of Shanxi seismic belt and the NW-trending Yinshan-Yanshan-Bohai seismic belt, there are several moderate or strong MMT with magnitude from 5.0 to 6.0 occurred. In south of North China around the latitude line of 35°N, it takes IET as the major. The spatial distribution of sequence types is relevant to the patterns of tectonic movements. MAT is mostly produced by the ruptures of locked units or asperities or the neonatal separating segments inside the fault zones. MMT is generally relevant to the conjugate structures or intersection of many tectonic settings. Further extension of simple fault often produces IET. Spatial distribution of sequence types is also correlative to the regional and deep environment of crustal medium to some extent. MAT mainly distributes in high velocity area in upper crust or in the transition zone between high velocity area and low velocity area, MMT mostly occurred in the low velocity area in upper crust.

While the use of ORNL developed high-thermal-conductivity graphitic foam materials has been focused on thermal management applications, recent experiments have revealed their potential as bearing surfaces as well. The three primary tribological advantages are: (1) they can efficiently remove frictional heat, (2) their natural porosity can trap wear debris, and (3) their porosity can serve as a lubricant reservoir for the contact surface. A series of pin-on-disk experiments were conducted at both room temperature and 400 °C to compare the sliding friction and wear characteristics of the densified graphitic foam (mated against M-50 tool steel or against alumina) to those of conventional bearing materials like graphite, bearing bronze, poly- tetrafluoroethylene, bearing steel, and a Co-based superalloy. At room temperature and under low contact pressure, the tribological behavior of the densified graphitic foam material was comparable to that of graphite and better than that of other bearing materials. At 400 °C, traditional graphite exhibited a “dusting” wear regime accompanied by a high friction coefficient. In contrast, the graphitic foam demonstrated an ability to maintain low friction and wear at that temperature.

This paper outlines an algorithm for the continuous non-linear approximation of procedurally defined curves. Unlike conventional approximation methods using the discrete L_2 form metric with sampling points, this algorithm uses the continuous L_2 form metric based on minimizing the integral of the least square error metric between the original and approximate curves. Expressions for the optimality criteria are derived based on exact B-spline integration. Although numerical integration may be necessary for some complicated curves, the use of numerical integration is minimized by a priori explicit evaluations. Plane or space curves with high curvatures and/or discontinuities can also be handled by means of an adaptive knot placement strategy. It has been found that the proposed scheme is more efficient and accurate compared to currently existing interpolation and approximation methods.

A new cytotoxic indole-3-ethenamide (1) and two known compounds, 7-(3-methylbut-2-enyl)-1H-indole-3-carbaldehyde (2) and emodin (3) were isolated and identified from the ethyl acetate extract of Aspergillus sclerotiorum PT06-1 in a hypersaline nutrient-rich medium. On the basis of spectroscopic analysis and amino-acid analysis, the new structure of 1 was determined to be (S,E)-3-methyl-2-(N- methylacetamido)-N-(2-(7-(3-methylbut-2-enyl)-1H-indol-3-yl)vinyl)butanamide within 3:1 ratio of rotamers along the acetamido single bond in DMSO-d6 at room temperature. Compound 1 showed moderate cytotoxicity against A-549 cells and weak cytotoxicity against HL-60 cells with the IC50 values of 3.0 and 27mM, respectively. Compound 2 has been separated as natural product for the first time, and its NMR data were also reported for the first time in this study. The Journal of Antibiotics advance online publication, 27 July 2011; doi:10.1038/ja.2011.63

This paper puts forward a model for the power spectrum of spatially variant ground motion. As compared with the other existing models, this model has two features: (1) It is the average result of multiple models and multiple earthquakes rather than the model proposed on the basis of the record of an earthquake given by a certain station array. (2) It has taken into account the variation of self-power spectral parameters from point to point.

To study the micro-meteorological effects of different underlying surfaces of structures to protect the Mogao Grottoes, we analyzed basic meteorological measurements collected at weather stations located in front of the grottoes, on top of the grottoes and in the artificial Gobi. The results show that the shelterbelts in front of the grottoes have a heat-retaining effect. The profile of average daily solar radiation in front of the grottoes forms a sharp peak and the profile in the Gobi forms a parabola, but these patterns vary in different seasons. The artificial Gobi was more susceptible to extremes in temperature and had a faster response and wider response range to ground temperature. The average monthly air temperature, average monthly relative humidity, and the average wind speed in the artificial Gobi tend to first decrease and then increase with measurement height.

The effects of three organic colorants on photo-initiated crosslinking and photo-oxidation degradation of polyethylene (PE) samples irradiated by microwave excited (MWE) UV lamp in the melt and the related mechanism have been studied by gel content and thermal extension rate determinations, X-ray photoelectron spectroscopy (XPS), mechanical property tests, UV spectroscopy, and light microscope. The data from the gel content and thermal extension rate determinations of photo-crosslinked polyethylene (XLPE) samples show that the three colorants can decrease the efficiency of photo-initiated crosslinking of polyethylene to some different degree, in which the effect of red colorant is the largest among the three colorants. The colorized samples of 1 mm thickness are easily to be crosslinked to a satisfactory gel content of about 70% by the MWE lamp and optimized reaction conditions, such as the concentration of colorant, irradiation time, and so on. The XPS results give the evidence that the colorants can accelerate the surface photo-oxidation during the photo-crosslinking of polyethylene. The photo-oxidation products such as -CH2-O- and -C(C=O)- groups on the surface of XLPE samples with the colorants apparently increase with increasing the irradiation time. The data from the mechanical tests show that the colorants reduce the tensile strength and improve the elongation at break of XLPE samples. All the above results show that the effects of the three colorants on photo-initiated crosslinking and photo-oxidative degradation decrease with the order of red > blue > green colorants. The light microscope photos show that the colorant can disperse well in PE resin. The mechanism of the colorant effects can be elucidated by comparison of the UV absorption spectra of photo-initiator and colorants. This is because the colorants absorb the same UV wavelength regions as photo-initiator, and thus decrease the photo-crosslinking efficiency of photo-initiator and accelerate the surface photo-oxidation of XLPE materials.