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Background: Bevacizumab (Avastin®) is a monoclonal antibody targeting the vascular endothelial growth factor (VEGF). Used alone or in combination with chemotherapy and/or immunotherapy, Avastin® has shown promising efficacy in many cancers. This study compared the efficacy and safety of TAB008 with Avastin® sourced from the EU (bevacizumab-EU), in patients with non-squamous non-small cell lung cancer (nsNSCLC). Method: In this randomized, double-blind, multicenter, phase III similarity study, treatment naïve for metastatic lung cancer., EGFR wild-type, locally advanced, metastatic, or recurrent non-squamous, non-small cell, lung cancer (nsNSCLC) patients were enrolled and randomized (1:1) into TAB008 or Avastin® groups. Patients received TAB008 or Avastin® 15 mg/kg intravenously plus paclitaxel/carboplatin for 4–6 cycles followed by TAB008 or Avastin® 7.5 mg/kg until disease progression, unacceptable toxicity or death. The primary endpoint compared the objective response rate (ORR) within 6 cycles as read by an independent radiological review committee (IRRC). Secondary endpoints compared disease control rate (DCR) Within 6 cycles, duration of response (DoR), progression-free survival (PFS), a year overall survival rate (OSR), overall survival (OS), safety, immunogenicity, and steady-state pharmacokinetics. Results: A total of 549 nsNSCLC patients were enrolled (277 in TAB008 group and 272 in Avastin® group). In the full analysis set, ORRs were 55.957% for TAB008 and 55.720% for Avastin®, and the ORR ratio was 1 (90% CI 0.89–1.14), well within the predefined equivalence margin of 0.75–1.33. No significant differences were found in DCR within 6 cycles (95.703% vs 95.367%, p = 0.8536), DoR (8.17 vs 7.3 months, p = 0.3526), PFS (9.10 vs. 7.97 months, p = 0.9457), 1 year overall survival rate (66.2% vs 68%, p = 0.6793), or OS (20.4 vs 17.6 months, p = 0.6549). Serious adverse events (SAEs) occurred in 37.55% (104/277) of patients in the TAB008 group and 34.32% (93/271) in the Avastin® group. Anti-drug antibodies were reported in 3 of 277 (1.08%) TAB008 patients, and 5 of 271 (1.85%) Avastin® patients, neutralizing antibody (Nab) was positive in 1 patient on Avastin®, which became negative upon follow-up. The steady-state trough concentrations (Cssmin) were 106.13 μg/mL in TAB008 group and 96.03 μg/mL in Avastin® groups, with the treatment group ratio of LS geometric means fully contained within the bioequivalence limits of 80.00–125.00% (90% CI was 101.74–120.05%). Conclusions: TAB008 is similar to Avastin® in terms of efficacy, safety, and pharmacokinetic parameters, with comparable immunogenicity. Trial registration: ClinicalTrials.gov number; NCT05427305. [ABSTRACT FROM AUTHOR]

Background: Traditional videometric method can not be used in the measurement of large flexible cable-net structure for its large overall size and small partial size. Objective: A videometrics technique was proposed in this work to measure the topography and deformation of a large cable net structure. Methods: Tiny spots with high brightness (and large gray gradient) are used to mark the cable net nodes. By arranging the imaging light path properly, the light spot markers can be enlarged and accurately identified in the captured images. Results: The relationship between the imaging parameters and the gray distribution of the light spot markers were derived and verified. And a topographical measurement experiment of a cable net structure was carried out with the proposed videometrics technique. Conclusions: The topography/deformation of the cable net can be measured with tiny-light spot markers, and the effectiveness and robustness of the technique on topography and deformation measurement of large cable-net structures are demonstrated. [ABSTRACT FROM AUTHOR]

The diffusion couples of Co-Cr-Mo ternary alloys were prepared and annealed at 1473 K for 72 h in order to determine the interdiffusion coefficients by using the electron probe microanalysis combined with Whittle and Green method. The experimental interdiffusion coefficients were critically assessed to the atomic mobilities by means of DICTRA software package. Good agreements were obtained from comprehensive comparison between the model-predicted diffusion properties and the experimental data, meanwhile, considered that the calculated diffusion coefficients were within the acceptable uncertainty of the experimentally measured diffusion coefficients, which verified the reliability of the atomic mobilities. The diffusion phenomena, such as diffusion paths and the concentration-distance profiles in the Co-Cr-Mo ternary system can be reasonably described by the presently obtained atomic mobilities. [ABSTRACT FROM AUTHOR]

Effects of ZnO-BO (ZB) addition on the densification, phase evolution and microwaves dielectric properties of BaSmTiO (BST) ceramics for low-temperature fired applications have been investigated. The sintering temperature of BST ceramics can be effectively lowered to about 1000°C with introduction of ZB. Tungsten bronze like single phase is observed in the BST ceramics with 0.5 and 1.0% ZB. However, SmTiO secondary phase appears when ZB addition reaches 2%, and SmTiO phase gradually increases with the increase ZB addition. Microwave dielectric properties of the present ceramics are strongly dependent on phase constitution and density. Optimal microwave dielectric properties of ε = 63.4, Qf = 2830 GHz, τ =-8.8 ppm/°C is obtained for BST ceramics with 1% ZB addition. [ABSTRACT FROM AUTHOR]

A kind of multiparty quantum secret sharing (MQSS) schemes based on entanglement swapping is analyzed and an effective attack is proposed. Some unauthorized agent groups can recover the secret from the dealer with the help of this special attack. It is shown that entanglement swapping not only makes the MQSS protocols feasible but also brings a fatal drawback to them. Furthermore, a possible improvement on such protocols is proposed, which makes them secure against the proposed attack. [ABSTRACT FROM AUTHOR]

A novel microchannel fabrication technology for quartz using a Q-switched Nd:YAG laser is presented. Complex 3D channel systems inside quartz substrates can be constructed directly using a laser beam by controlled fracturing, and high-quality microchannels can be fabricated by melting quartz using a laser-induced plasma. The behavior of laser-induced plasmas in drilling microchannels is discussed. The diameter of the microchannels can be controlled from 25 to 200 μm. The average roughness of the interior channel wall is less than 0.2 μm. Currently, microchannels longer than 4 mm in fused-quartz cubes can be achieved using laser-induced plasmas. [ABSTRACT FROM AUTHOR]

A symmetry-preserving truncation of the strong-interaction bound-state equations is used to calculate the spectrum of ground-state J = 1 / 2 + , 3 / 2 + (q q ′ q ″) -baryons, where q , q ′ , q ″ ∈ { u , d , s , c , b } , their first positive-parity excitations and parity partners. Using two parameters, a description of the known spectrum of 39 such states is obtained, with a mean-absolute-relative-difference between calculation and experiment of 3.6(2.7)%. From this foundation, the framework is subsequently used to predict the masses of 90 states not yet seen empirically. [ABSTRACT FROM AUTHOR]

Ternary fcc Ni-Mo-Ta diffusion couples annealed at 1473 and 1573 K have been studied by using electron probe microanalysis. Based on the measured concentration-distance profiles and Whittle–Green method, the interdiffusion coefficients were calculated to critically assess the atomic mobilities by means of DICTRA software package. Comprehensive comparisons between calculated and experimental diffusion coefficients show that the atomic mobilities obtained in this work could well reproduce the experimental data. Reasonable agreements between model-predicted diffusion properties and the experimental data indicated that present mobility database can be used to study the diffusion behavior, such as diffusion paths and concentration-distance profiles in the ternary fcc Ni-Mo-Ta alloys. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) from gestational tissues represent promising cell populations with stem cell-like properties for use in regenerative medicine. Previously, we reported that MSCs in the chorionic villi of the human placenta reside in a vascular niche. However, the niche(s) in which MSCs reside in the fetal membranes, another rich source of MSCs, remains to be determined. The cell surface markers STRO-1 and 3G5 were previously employed to identify niches in a variety of tissues and here we use these markers to report the location of the MSC niche in the human decidua parietalis. The cultured decidua parietalis MSCs (DPMSCs) isolated from the choriodecidua component of the fetal membranes possessed stem cell-like properties such as adherence to plastic, colony forming ability, and multipotent differentiation potential. Fluorescence in situ hybridization analysis showed cultured DPMSCs were of maternal origin. Immunocytochemistry demonstrated that cultured DPMSCs stained positively with stem cell surface markers 3G5, CD105, CD106, STRO-1, CD146, CD49a, and α-SMA but were negative for hematopoietic markers (CD117, CD34) and vascular markers (CD34, von Willebrand factor [vWF]). Immunohistochemistry with antibodies to stem cell surface markers and the endothelial markers on term fetal membranes revealed a vascular niche for DPMSCs, which was confirmed by immunofluorescence analysis. Both STRO-1 and vWF fluorescence signals showed substantial overlap, while CD146 and vWF signals showed partial overlap. These observations were consistent with a vascular niche. [ABSTRACT FROM AUTHOR]

Variants within the human UGT1A1 gene are associated with irinotecan induced severely adverse reactions and hyperbilirubinemia. Intra-ethnic differences in the genetic variation and haplotypes of UGT1A1 gene have been analyzed in the present study. Relationship between the concentrations of total serum bilirubin (T-bil) and haplotype structure of UGT1A1 in healthy people were also evaluated. We genotyped five functional polymorphisms including −3279T>G and −3156G>A in the enhancer region, (TA)6>7 in the TATA box, and 211G>A (G71R), 686C>A (P229Q) in the exon1 region of UGT1A1 in three groups of healthy Chinese ethnic populations, consisting of 264 subjects of She origin, 539 of Han origin and 273 of Dong origin. The distribution of −3279T>G, (TA)6>7, 211G>A of UGT1A1 differed greatly as between the three ethnic groups. All of six haplotypes differed considerably between at least two of the three groups, which highlighted the need to analyze clinically irinotecan toxicity relevant SNPs and haplotypes in a variety of different racial groups within the Chinese population. Total bilirubin concentration in homozygous carriers of the −3279G and (TA)7 allele were significantly higher than those in heterozygous carriers or homozygous carriers of wild-type alleles. Carriers of the variant haplotypes (−3279G; −3156A; (TA)7; 211G; 686C) had higher serum T-Bil concentrations compared with the other groups. Our results indicate that heterogeneity among different ethnic populations is possibly the result of microevolution and is relevant to studies into the effect of tailored drug treatment.The Pharmacogenomics Journal (2007) 7, 333–338; doi:10.1038/sj.tpj.6500424; published online 24 October 2006 [ABSTRACT FROM AUTHOR]

Based on the design and preparation of the electrically assisted drawing die, the electric-assisted deep-drawn tests were carried out on high-strength steel plates with different strengths to study the electroplastic effect on high-strength steel drawing. The temperature distribution, macro-morphology, and hardness variation of deep-drawing workpieces undergone different electrical parameters were analyzed. The results showed that the Joule heat generated by the electrically assisted drawing die on the sample was symmetrically distributed along the center of the circular sheet, and the electrical pulse heat effect had little effect on the temperature rise of sheets (same material) with different strength levels. The introduction of pulse current could improve the forming performance of high-strength steel to a certain extent, as well as enhance its deep-drawing deformation ability. The hardness of the work-piece increased after it was deep-drawn. The Joule heat generated by the pulse current did not cause changes in the microstructure of the high-strength steel. The electroplastic effect improved the mechanical properties of the work-piece while increasing the formability of the high-strength steel plates. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury (DILI) is caused by unpredictable adverse drug reaction due mainly to the accumulation of hepatotoxic compounds in the liver resulting in significant damage. Drug-metabolizing enzymes have been prime targets for molecular studies relevant to DILI. The gene UGT1A9 mainly expresses in the liver and has an important role in drug metabolism. The Han Chinese has a very long and complex demographic history, and the population stratification arising from the interplay of different geographic areas may influence the polymorphism pattern. We selected 260 healthy subjects in three different geographic areas (including Xian, Shanghai and Liuzhou) for systemic screening and analysis of single-nucleotide polymorphisms (SNPs) in the promoter region of UGT1A9. Eight SNPs were identified and no regional disparity exists among the three populations. Based on these results, 213 DILI patients from all over the Chinese mainland were further recruited to investigate possible association between UGT1A9 and DILI. We observed statistically significant associations between SNP rs2741045 and DILI at both allele and genotype levels (allele: P=0.032; genotype: P=0.029; after Bonferroni correction). Also, multivariate interaction analysis discovered the interaction between rs2741045 and age associated with DILI significantly. This is the first such screening study to investigate the association between UGT1A9 promoter polymorphisms and DILI in the Chinese population and it could provide the basis for further study of DILI mechanisms. [ABSTRACT FROM AUTHOR]

In this paper, we present a novel design of tri-axis gyroscope which consists of two diagonal-pendulum masses for lateral sensing, coupled with and enclosed in a traditional tuning fork driving frame. The diagonal-pendulums are driven to swing via tilted transforming beams as the driving frame oscillated in plane, and rotate around their torsional beam out-of-plane as orthogonal lateral angular rate applied. The symmetric arrangement of whole structure lowers mechanical complexity and the sensing way of 'one diagonal-pendulum for one lateral axis' eliminates sensing proof mass sharing which can effectively suppress the cross-talk effect. The prototype device has been successfully fabricated by using SOI-based bulk micromachining processes and vacuum packaged by Al-Ge eutectic bonding. The sensitivities for three axes are 4.83, 1.47 and 1.38 mV/(°/s), respectively, with nonlinearity of less 1 % and bandwidth of above 600 Hz. [ABSTRACT FROM AUTHOR]

Emerging chemotherapy drugs and targeted therapies have been widely applied in anticancer treatment and have given oncologists a promising future. Nevertheless, regeneration and recurrence are still huge obstacles on the way to cure cancer. Cancer stem cells (CSCs) are capable of self-renewal, tumor initiation, recurrence, metastasis, therapy resistance, and reside as a subset in many, if not all, cancers. Therefore, therapeutics specifically targeting and killing CSCs are being identified, and may be promising and effective strategies to eliminate cancer. MicroRNAs (miRNAs, miRs), small noncoding RNAs regulating gene expression in a post-transcriptional manner, are dysregulated in most malignancies and are identified as important regulators of CSCs. However, limited knowledge exists for biological and molecular mechanism by which miRNAs regulate CSCs. In this article, we review CSCs, miRNAs and the interactions between miRNA regulation and CSCs, with a specific focus on the molecular mechanisms and clinical applications. This review will help us to know in detail how CSCs are regulated by miRNAs networks and also help to develop more effective and secure miRNA-based clinical therapies. [ABSTRACT FROM AUTHOR]

As a complex mechatronic system, the running stability, safety, and comfort of high-speed train are affected by many design variables. It is of great difficulty to identify a set of effective design parameters to optimize its running performance. The current simulation systems like the SIMPACK can simulate the running dynamics, but cannot be used effectively for optimal design of the train and rail system because there are too many design variables being supposed to be dealt with. Therefore, there is a need to make a software solution from simulation analysis to optimal design so that the computer-aided design (CAD) and engineering (CAE) can be integrated into an integral design process. This paper presents a new method to identify the key design variables against the running performance indicators based on the sensitivity analysis, which in turn bases itself on simulation-oriented surrogate models. In this way, the optimal design of a high-speed train can be successfully conducted because (1) the surrogate model can reduce the simulation time greatly and (2) the design variable space with the key variables will be reduced significantly. The research shows that this method is of practical significance for speeding up the design of high-speed train or similar complex mechatronic systems. [ABSTRACT FROM AUTHOR]

We theoretically demonstrate that an electrically tunable polarizer can be obtained using a periodic array of graphene ribbons supported on a dielectric film on top of a thick piece of metal. The polarizing mechanism originates from anisotropic absorption of the graphene ribbons. The results of fullwave numerical simulations reveal that absorption of 0.0075 for one polarization and 0.9986 for another polarization can be obtained at normal incidence in the THz range. For circular incidence polarization, the corresponding polarizing extinction ratio increases to 65 dB. [ABSTRACT FROM AUTHOR]

In machining process, fixture is used to keep the position and orientation of a workpiece with respect to machine tool frame. However, the workpiece always cannot be at its ideal position because of the setup error and geometric inaccuracy of the locators, clamping force, cutting force, and so on. It is necessary to predict and control the workpiece locating error which will result in machining error of parts. This paper presents a prediction model of a workpiece locating error caused by the setup error and geometric inaccuracy of locaters for the fixtures with one locating surface and two locating pins. Error parameters along 6 degrees of freedom can be calculated by the proposed model and then compensated by either using the 'frame transformation' function of a numerical control (NC) system or modifying NC codes in post-processing. In addition, machining error caused by the workpiece locating error can be predicted based on a multi-body system and homogeneous transfer matrix. This is meaningful to fixture design and machining process planning. Finally, a cutting test has shown that the proposed method is practicable and effective. [ABSTRACT FROM AUTHOR]

An investigation into the high-pressure behavior of ScO was conducted using first-principle calculations based on density functional theory within the generalized gradient approximation. Nine candidate phases were considered and simulated, C-, B-, A-RES, RhO(II), GdS, US, AlEr, corundum and PPv respectively. Our results demonstrate phase transitions of ScO from C- to B-RES phase at 15 GPa, then to GdS phase at 18 GPa. Elastic constants of ScO present softening from about 270 GPa to 337 GPa, associated with a semiconductor-to-metal crossover. The GdS-type ScO is both mechanically and dynamical stable at least up to 302 GPa supported by the mechanically stable criteria and the phonon spectrum. [ABSTRACT FROM AUTHOR]

g nanoparticle embedded silicate glass was prepared by field-assisted diffusion, combined with post-annealing process. Surface plasmon resonance (SPR) bands were observed in the optical absorption measurement. The properties of optical absorption were strongly affected by the process parameters. With increasing electric field intensity and diffusion time, the SPR peak position and the full width at half maximum (FWHM) of the plasmon band were almost invariable. With increasing post-annealing time, the SPR peak was blue-shifted and the FWHM of SPR band decreased. The experimental results could be well simulated using modified Mie scattering theory considering the spill-out effects and the limitation of the mean free path. [ABSTRACT FROM AUTHOR]

Screening of synthetic retinoids for activity against prostate carcinoma cell lines has identified antagonists of retinoic acid receptors (RARs) as potent growth inhibitors (Hammond et al, 2001, Br J Cancer 85, 453-462). Here we report that 5 days of exposure to a high-affinity pan-RAR antagonist (AGN194310) abolished growth of prostate carcinoma cells from 14 out of 14 patients, with half-maximal inhibition between 200 and 800 nM. It had similar effects (at approximately 250 nM) on the prostate carcinoma lines LNCaP, DU-145 and PC-3. AGN194310 inhibited the growth of normal prostate epithelium cells less potently, by 50% at approximately 1 microM. The growth of tumour cells was also inhibited more than that of normal cells when RARbeta together with RARgamma, but not RARalpha alone, were antagonised. Treatment of LNCaP cells with AGN194310 arrested them in G1 of cell cycle within 12 h, with an accompanying rise in the level of p21(waf1). The cells underwent apoptosis within 3 days, as indicated by mitochondrial depolarisation, Annexin V binding and DNA fragmentation. Apoptosis was caspase-independent: caspases were neither cleaved nor activated, and DNA fragmentation was unaffected by the pan-caspase inhibitor Z-VAD-FMK. The ability of AGN 194310 to induce apoptosis of prostate cancer cells and its differential effect on malignant and normal prostate epithelial cells suggests that this compound may be useful in the treatment of prostate cancer. [ABSTRACT FROM AUTHOR]

Presents research findings which show that many systemic memory T cells in blood carry the chemokine receptor CCR4 and therefore respond to its ligands, the chemokines TARC and MDC. How these cells include essentially all skin-homing cells; Details of the research done.

The non-classical correlations presented in quantum random access code experiment are a powerful diagnostic tool for semi-device-independent random number generator protocols. The idea behind it is that if the user observes the optimal non-classical correlations, he has the guarantee that the unknown quantum states and measurements in the devices have carefully calibrated (we say have global reference frame), in a relationship which can bring to random outcomes. This means, for observing the non-classical correlations, the devices must have that calibration in previous. However, that calibration can’t always be guaranteed in reality due to unintentional flaws or failures of the quantum apparatuses, thus the devices do not always occur the wanted non-classical correlations. In this paper, we show there will always have non-classical correlations by the proper operations, when the devices have local reference. The quantity of true randomness in the observed non-classical correlations is then quantified by the violation values of some inequality. Besides we also consider the devices without local reference and show the probability of non-classical correlations occurring in 100 trials. [ABSTRACT FROM AUTHOR]