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Designing a high-fidelity cutting device is one of the difficulties in hydrate samples pressure-holding transfer. Due to the limitations of the existing mechanical system, there is much damage to the cut surface of hydrate samples, with many chips produced, which seriously affects the quality of samples. In this paper, a new cutting device utilizes two servo motors to achieve a high degree of automation. Using the Archimedes spiral, it achieves low disturbance of the cut surface and provides accurate control of the process. In addition, due to the operation of the sample long-stroke push unit, cutting hydrate samples of any length with almost no chips within a short cutting time can be achieved. Laboratory and sea tests have achieved all design requirements of the equipment and strongly demonstrate its benefit and stability. It is concluded that this new high-fidelity cutting technology is practically efficient. The physical state of the hydrate can be maintained to the greatest extent, and thus the new equipment provides significant support for the exploration and development of hydrate resources.

Information storage and corresponding encryption/decryption are highly important owing to the prevalence of counterfeit activities and information leakage in the current age. Herein, we propose a novel method to store information viacontrollable ionoprinting onto fluorescent hydrogel for hierarchical and multi-dimensional decryption. Through incorporating pyrene moieties and carboxylic groups into polymeric hydrogel network, fluorescence changing and controllable shape deformation behaviors could be achieved and integrated by ionoprinting of Fe3+ions. The diffusion of Fe3+ions into fluorescent hydrogel can quench the fluorescence of pyrene moieties, and chelate with carboxylic groups to generate anisotropic structures for shape deformation simultaneously. Thus, fluorescence quenching-based 2D information and actuation-based 3D information could be hierarchically decrypted when exposed to UV light and being put into water, respectively. Importantly, the stored information could be erased by replacing Fe3+with H+, which allows the fluorescent hydrogel as a recyclable information storage material. This work may provide new insights in designing and fabricating novel soft devices for hierarchical and multidimensional information encryption, against the rising problems of counterfeiting and confidential information disclosure. 本文通过离子印染的方式, 赋予荧光水凝胶信息, 并将其用于逐级、多维度信息存储. 通过铁离子的引入, 荧光水凝胶中的芘基团会发生荧光淬灭, 在紫外灯下可用于二维平面的信息存储; 同时, 铁离子的扩散会赋予水凝胶各向异性的结构, 使得其在水中驱动得到三维的信息. 并且, 储存的二维、三维信息可以通过氢离子取代铁离子进行擦除, 这使得材料具有很好的可重复利用性. 总之, 本文为新型柔性信息存储装置的设计和制备提供了新的思路.

A method for analyzing the dynamic energy spectrum of intense pulsed ion beam (IPIB) was proposed. Its influence on beam energy deposition in metal target was studied with IPIB produced by two types of magnetically insulated diodes (MID). The emission of IPIB was described with space charge limitation model, and the dynamic energy spectrum was further analyzed with time-of-flight method. IPIBs generated by pulsed accelerators of BIPPAB-450 (active MID) and TEMP-4M (passive MID) were studied. The dynamic energy spectrum was used to deduce the power density distribution of IPIB in the target with Monte Carlo simulation and infrared imaging diagnostics. The effect on the distribution and evolution of thermal field induced by the characteristics of IPIB dynamic energy spectrum was discussed.

By observing rock thin sections, starting from the analysis on rock samples, mercury injection curves, casting thin sections and scanning electron microscopy, a detailed study of under Jurassic Badaowan Formation of the North Lake Oilfield heterogeneity in terms of content is done for the prediction and evaluation of favorable reservoir.

Hot compression deformation test were conducted on 20CrMo alloy steel on a Gleeble-1500D thermal simulator when the deformation amount was 30%, temperature ranged from 1273 to 1373K and strain rate from 0.0015 to 0.015s-1. Flow stress curves were obtained under different deformation conditions; DRX activation energy was calculated using mathematical method. The starting time of DRX was analyzed and the kinetic equation of DRX was established. This model fits well with test data and can meet the requirement of engineering calculation.

Accurately predicting the subgrade deep horizontal displacement is important to subgrade stability. The study on subgrade deep horizontal displacement is not sufficient. It studies several displacement prediction methods,and builds matching prediction models to predict horizontal displacement. Referring to the posteriori error ratio and small error probability, we get the following results. GM(1,1) model is suitable for predicting the subgrade horizontal displacement,and the trend of GM(1,1) model is consistent with actual values. Its accuracy is higher than the logarithmic curve fitting.What more, the stability is better than the exponential smoothing model.

Src-family Kinases (SFKs) participate in the regulation of proliferation, differentiation, apoptosis, autophagy, adhesion, migration, invasion and angiogenesis in normal and cancer cells. Abnormal expression of SFKs has been documented in cancers that arise in breast, colon, ovary, melanocyte, gastric mucosa, head and neck, pancreas, lung, and brain. Targeting SFKs in cancer cells has been shown to be a promising therapeutic strategy in solid tumors, particularly in ovarian, colon and breast cancers. Paclitaxel is one of most widely used chemotherapeutic agents for the management of ovarian, breast, lung and head/neck cancers. As a microtubule-stabilizing agent, paclitaxel possesses both mitosis-dependent and mitosis-independent activities against cancer cells. A variety of mechanisms such as deregulation of P-glycoprotein, alteration of tubulin isotypes, alteration of microtubule-regulatory proteins, deregulation of apoptotic signaling pathways, mutation of tubulins and overexpression of copper transporters have been implicated in the development of primary or secondary resistance to paclitaxel. By affecting cancer cell survival, proliferation, autophagy, microtubule stability, motility, and/or angiogenesis, SFKs interact with mechanisms that regulate paclitaxel sensitivity. Inhibition of SFKs can potentiate the anti-tumor activity of paclitaxel by enhancing apoptosis, autophagy and microtubule stability. Based on pre-clinical observations, administration of SFK inhibitors in combination with paclitaxel could improve treatment for ovarian, breast, lung and head/neck cancers. Identification and validation of predictive biomarkers could also permit personalization of the therapy.

We have previously reported that breast cancer cells which overexpress HER2 produce higher levels of VEGF than cells with low levels of HER2. This study tested the hypothesis that dual targeting of the VEGF (with VEGF-Trap) and HER2 (with trastuzumab) pathways would result in greater growth inhibition of HER2-overexpressing breast cancer xenografts than either agent alone. In this study we found that human and murine endothelial cells expressed high levels of VEGF receptors (VEGFR1, VEGFR2, & VEGFR3). VEGF-Trap decreased levels of secreted VEGF derived from both human and murine cells and effectively blocked VEGF-induced tyrosine phosphorylation of VEGFR2. VEGF-Trap as a single treatment inhibited tumor microvessel density (MVD), tumor vasculature, cell proliferation, and tumor growth of BT474 xenografts in a dose-dependent manner from 2.5 mg/kg to 25 mg/kg. VEGF-Trap decreased levels of both human VEGF and PlGF protein in vivo. Trastuzumab as a single agent effectively inhibited BT474 tumor growth in a dose-dependent manner, associated with a decrease in human VEGF, tumor MVD and tumor cell proliferation. Treatment with a combination of VEGF-Trap (2.5-10 mg/kg) and trastuzumab (1 mg/kg) produced significantly greater inhibition of BT474tumor growth than either individual agent, associated with greater inhibition of tumor MVD and tumor cell proliferation. Thus, VEGF-Trap in combination with trastuzumab produces superior growth inhibition of tumor xenografts which overexpress HER2, which may result from inhibition of both tumor angiogenesis and proliferation. Similar mechanisms may contribute to the clinical anti-tumor activity of trastuzumab in combination with inhibitors of VEGF signaling pathway in women with breast cancers which overexpress HER2.

Anti-HER2 antibody trastuzumab (Herceptin®) has been used effectively to treat patients with breast cancer that overexpresses HER2. We have demonstrated that p27Kip1 upregulation is one of the key events that cause G1 arrest upon trastuzumab treatment. Here, we have examined the effect of trastuzumab on CDK2, Rb, E2F1, NPAT, histone H4, and their associated signaling pathway. Results showed that trastuzumab was able to dramatically inhibit the kinase activity and expression of CDK2, whereas the kinase activity and expression of CDK4 were not affected by trastuzumab treatment. Unlike the p27Kip1 upregulation that occurs primarily through post-translational mechanisms, CDK2 was mainly downregulated at a transcriptional level as shown by Northern blotting and real-time RT-PCR analyses. Trastuzumab decreased the kinase activity of cyclin E (because of CDK2 inhibition) although it had little effect on cyclin E protein level. Overexpression of wild-type cyclin E or its lower molecular weight forms did not influence the response to trastuzumab. Levels and activities of CDK6, cyclin A, and cyclin D1 were all suppressed by trastuzumab. As a result, Rb phosphorylations that associates with CDK2, cyclin E, CDK6, cyclin A, or cyclin D1 were substantially inhibited by trastuzumab. Trastuzumab decreased the DNA-binding activity of E2F1. Trastuzumab decreased the level of NPAT protein. Trastuzumab decreased the level of histone H4 mRNA. Blockade of PI3K pathway with LY294002 produced similar effects to trastuzumab treatment. Taken together, these results demonstrated that anti-HER2antibody trastuzumab inhibits CDK2, Rb phosphorylation, E2F1 activity, NPAT, and histone H4 via PI3K signaling pathway, which are essential to both DNA and histone synthesis during the progression of G1 phase to S phase of the cell cycle.

Anti-HER2 antibody trastuzumab is emerging as a frontline therapy for patientswith metastatic breast cancers that overexpress HER2. Understanding the molecularmechanisms by which the antibody inhibits tumor growth should permit the design ofeven more effective trastuzumab-based protocols. Several groups including our own havedemonstrated that induction of cyclin-dependent kinase (CDK) inhibitor p27Kip1 protein isone of the key mechanisms of action of HER2-targeting antibodies. In this review, wediscuss currently available data regarding the multiple signaling targets and pathways bywhich HER2-targeting antibodies upregulate p27Kip1 protein in breast cancer cells thatoverexpress HER2. Anti-HER2 antibodies inhibits HER2-mediated signaling in cancercells, ultimately upregulating the levels and activity of p27Kip1 protein. At least sixsignaling targets and pathways are modulated by trastuzumab. By inhibiting CDK2 anddecreasing Thr187 phosphorylation of p27Kip1, trastuzumab abrogates targeting of SCFubiquitinE3 ligase and minimizes proteasome degradation of p27Kip1. By inhibiting AKTand human kinase interacting stathmin (hKIS), trastuzumab blocks Thr157-, Thr198-, andSer10-induced p27Kip1 translocation from the nucleus to the cytosol, which increases theinhibitory effect of p27Kip1. By inhibiting Jun activation domain-binding protein 1 (Jab1)trastuzumab increases nuclear retention of p27Kip1. By inhibiting cyclin D and c-Myc,trastuzumab releases the sequestrated p27Kip1 protein from cyclin D-CDK4/6 complexesand increase the effect of p27Kip1 on CDK2-cyclin E complexes. By stimulating minibrainrelated kinase (MIRK), trastuzumab stabilizes p27Kip1 in the nucleus, which increasesinhibitory action of p27Kip1 on CDK2. The targets and pathways affected by trastuzumab work in concert to maximize the expression and inhibitory effect of p27Kip1, which leadsto cell cycle G1 arrest and growth inhibition.

AML2 is a member of the acute myelogenous leukemia, AML family of transcription factors. The biologic functions of AML1 and AML3 have been well characterized; however, the functional role of AML2 remains unknown. In this study, we found that AML2 protein expressed predominantly in cells of hematopoietic origin is a nuclear serine phosphoprotein associated with the nuclear matrix, and its expression is not cell cycle-related. In HL-60 cells AML2 expression can be induced by all three natural retinoids, all-trans-retinoic acid (RA), 13-cis-RA, and 9-cis-RA in a dose-dependent manner. A synthetic retinoic acid derivative, 4HPR, which neither activates RA receptor (RAR) α nor retinoic X receptor α was unable to induce the expression of AML2. A RAR-selective activator, TTNPB, induced AML2 expression similar to RA. Our study further showed that AGN193109, a potent RARα antagonist, suppressed AML2 expression induced by RA and that a retinoic X receptor pan agonist AGN194204 had no effect on its expression. Taken together, these studies conclusively demonstrated that the expression of AML2 in HL-60 cells is regulated through the RARα-specific signaling pathway. Our study further showed that after all-trans-retinoic acid priming, AML2 expression could be augmented by vitamin D3. Based on these studies we hypothesize that AML2 expression is normally regulated by retinoid/vitamin D nuclear receptors mainly through the RARα-dependent signaling pathway and that it may play a role in hematopoietic cell differentiation.

The promyelocytic leukemia gene (PML) involved in the t(15;17) (q22;q12) translocation in acute promyelocytic leukemia is a growth suppressor. To elucidate the functional domains of PML, several mutants lacking the nuclear localization signal (PMLnls-), the dimerization domain (PMLdim-), the proline-rich domain at the N-terminal (PMLpro-), the proline-rich RING finger motif (PMLpr-), the proline-rich RING finger B-box-1 (PMLprb-), the serine-proline-rich domain at the C-terminal (PMLsp-), and the double mutant (PMLprb-nls-) have been constructed. Immunofluorescence staining of transiently transfected NIH3T3 cells demonstrated that the RING finger motif, dimerization domain, and nuclear localization signal are all required for the formation of PML oncogenic domains (PODs). Immunofluorescence staining of transiently transfected GM637D human fibroblasts indicated that expression of PMLprb-, PMLnls-, and PMLprb-nls- led to a significant reduction or, in some cases, complete elimination of PODs. PMLdim-, PMLnls-, PMLpr-, PMLprb-, and PMLprb-nls- mutants were found to lose their ability to suppress transformation of NIH3T3 cells by activated neu, while PMLpro- and PMLsp- mutants did not. These results suggest that the ability of PML to form a POD is essential for suppression of growth and transformation. Furthermore, since PMLprb-, PMLnls-, and PMLprb-nls- mutants could block the suppression effect of wild-type PML on transformation of NIH3T3 cells by the neuoncogene, these PML mutants are potential dominant negative inhibitors of PML. Our study also suggests that the RING finger motif may interact with other nuclear proteins.

A continuously operating monitoring method for total mercury at sub-ng/ml level in environmental and biological samples by cold vapour atomic-absorption spectrometry with NaBH4 as a reductant was developed. The mercury vapour generator and absorption cell closed-end by quartz were used in this study. The detection limit (S/N = 3) and relative standard deviation of 12 determinations of 10 ng/ml Hg(II) were 0.11 ng/ml and 1.1%, respectively. The range of standard calibration curve was 0–50 ng/ml Hg, The proposed method was successfully applied to the completely continuous monitoring of total mercury in waste water, sediments and pork liver.

Patients with acute promyelocytic leukemia (APL) are characterized by the presence of a t(15;17) chromosomal translocation. The fusion protein PML-RARa encoded from the breakpoint can form a heterodimer and acts as a dominant negative inhibitor against the normal function of PML. Recently we demonstrated that PML is a growth suppressor and transcription suppressor expressed in all cell lines tested. We also found that PML suppresses the clonogenicity and tumorigenicity of APL-derived NB4 cells, as well as the transformation of rat embryo fibroblasts by cooperative oncogenes and NIH/3T3 by neu. Overexpression of PML in human tumor cell lines induces a remarkable reduction in growth rate in vitro and in vivo. More recently, we have shown that PML is a phospho-protein associated with the nuclear matrix and that its expression is cell cycle related. PML expression is altered during human oncogenesis, implying that PML may be an anti-oncogene involved not only in APL but also in other oncogenic events. Mutation analysis of the functional domains of PML demonstrated that its ability to form PML nuclear bodies or PODs (PML oncogenic domains) is essential for suppressing growth and transformation. In light of the above studies it appears that disruption of the normal function of PML plays a critical role in the pathogenesis of APL.

A heat-stable microparticle platform improves oral micronutrient delivery.