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The microstructure and hardness of rheo-forming AZ91-Y alloy before and after solution treatment (ST) have been investigated by means of optical microscope (OM), scanning electron microscope (SEM) equipped with energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and Vickers. The experimental results showed that the β-Mg17Al12 phase of alloy was nearly dissolved after ST for 5 min. With the increasing of ST duration to 28 h, both the primary and secondarily solidified α-Mg grains faded away. At the same time, the alloy exhibited a much smoother surface due to the diffusion of solute atoms (Al). During ST, the thermal stable phase of Al2Y produced by ultrasonic vibration retained its size and morphology. As the ST duration was increased, the alloy hardness decreased sharply at first, and then gradually reached a minimum level. The alloy's appropriate ST duration at 410 °C was approximately 28 h. [ABSTRACT FROM AUTHOR]

We investigated the role of homeobox B4 (HOXB4) mRNA/protein expression induced by human cytomegalovirus (HCMV) and/or all-trans retinoic acid (ATRA) in proliferation and committed differentiation of human cord blood hematopoietic stem cells (HSCs) into colony-forming-units of T-lymphocyte (CFU-TL) and erythroid (CFU-E) progenitors in vitro. Twelve cord blood samples were collected from the fetal placenta umbilical vein and cultured in vitro. The proliferation and differentiation of cord blood HSCs into CFU-TL and CFU-E were continuously disrupted with HCMV-AD169 and/or 6 × 10 mol/l of ATRA. HOXB4 mRNA/protein expression in CFU-TL and CFU-E was detected in control, ATRA, HCMV and ATRA + HCMV groups on days 3, 7, and 12 of culture by fluorescent qRT-PCR/western blot. We found that HOXB4 mRNA/protein expression was detectable on day 3, increased on day 7 and was highest on day 12. HOXB4 mRNA/protein expression in HCMV group was downregulated compared with control group ( P < 0.05). However, the levels were significantly upregulated in HCMV + ATRA group compared with HCMV group ( P < 0.05). We concluded that the abnormal HOXB4 mRNA/protein expression induced by HCMV could play a role in hematopoietic damage. ATRA, at the concentration used, significantly up-regulated HOXB4 mRNA/protein expression in normal lymphocyte and erythrocyte progenitor cells as well as in HCMV-infected cells. [ABSTRACT FROM AUTHOR]

Soluble guanylate cyclase (sGC), as a nitric oxide (NO) sensor, is a critical heme-containing enzyme in NO-signaling pathway of eukaryotes. Human sGC is a heterodimeric hemoprotein, composed of a α-subunit (690 AA) and a heme-binding β-subunit (619 AA). Upon NO binding, sGC catalyzes the conversion of guanosine 5′-triphosphate (GTP) to 3′,5′-cyclic guanosine monophosphate (cGMP). cGMP is a second messenger and initiates the nitric oxide signaling, triggering vasodilatation, smooth muscle relaxation, platelet aggregation, and neuronal transmission etc. The breakthrough of the bottle neck problem for sGC-mediated NO singling was made in this study. The recombinant human sGC β1 subunit (HsGCβ619) and its truncated N-terminal fragments (HsGCβ195 and HsGCβ384) were efficiently expressed in Escherichia coli and purified successfully in quantities. The three proteins in different forms (ferric, ferrous, NO-bound, CO-bound) were characterized by UV–vis and EPR spectroscopy. The homology structure model of the human sGC heme domain was constructed, and the mechanism for NO binding to sGC was proposed. The EPR spectra showed a characteristic of five-coordinated heme-nitrosyl species with triplet hyperfine splitting of NO. The interaction between NO and sGC was investigated and the schematic mechanism was proposed. This study provides new insights into the structure and NO-binding of human sGC. Furthermore, the efficient expression system of E. coli will be beneficial to the further studies on structure and activation mechanism of human sGC. [ABSTRACT FROM AUTHOR]

Abstract  The biological function and stability of a cytochrome P450 (CYP) mainly depend on the subtle properties of the residues in the active site cavity, which are generally more divergent among proteins than other parts of the protein. As the most unique member of human CYP2C family, CYP2C8 has an isoleucine (Ile) 476 instead of phenylalanine (Phe) in substrate recognizing site 6 (SRS6). However, the role of Ile476 of CYP2C8 is still unknown. Therefore, six site-directed mutants of CYP2C8 were constructed to better define this. By UV–visible and circular dichroism spectroscopy studies, we studied for the first time the structural stability and all-trans-retinoic acid binding capability of the CYP2C8 variants. We found that the ferric CYP2C8 went through three states during thermal unfolding. Combined with substrate binding studies, our data revealed that residue 476 was involved in contact with substrate and was important for maintaining the thermal stability of CYP2C8. [ABSTRACT FROM AUTHOR]

Abstract  In this paper, a memetic algorithm (MA) based on differential evolution (DE), namely MADE, is proposed for the multi-objective no-wait flow-shop scheduling problems (MNFSSPs). Firstly, a largest-order-value rule is presented to convert individuals in DE from real vectors to job permutations so that the DE can be applied for solving flow-shop scheduling problems (FSSPs). Secondly, the DE-based parallel evolution mechanism is applied to perform effective exploration, and several local searchers developed according to the landscape of multi-objective FSSPs are applied to emphasize local exploitation. Thirdly, a speed-up computing method is developed based on the property of the no-wait FSSPs. In addition, the concept of Pareto dominance is used to handle the updating of solutions in sense of multi-objective optimization. Due to the well balance between DE-based global search and problem-dependent local search as well as the utilization of the speed-up evaluation, the MNFSSPs can be solved effectively and efficiently. Simulation results and comparisons demonstrate the effectiveness and efficiency of the proposed MADE. [ABSTRACT FROM AUTHOR]

Abstract  Platinum-based chemotherapy regimens are often recommended for patients with unresectable thymic carcinoma. In more than 60 cases, however, the systemic chemotherapy provides little benefit. In this report, we described a case of advanced KIT- and VEGF-positive thymic carcinoma with liver and lung metastasis. The patient, a 46-year-old man, exhibited a resistance to cisplatin-based chemotherapy, but responded to the treatment with sorafenib, a molecular target-based therapy. After 4 months of sorafenib therapy, his lung and liver metastases as well as the mediastinal tumor shrank dramatically. Moreover, the tumors showed stable disease for at least 9 months. To the best of our knowledge, it is the first report about a response of advanced thymic carcinoma to sorafenib. The preliminary study suggested that molecular target-based therapy could be an alternative treatment to those chemotherapy-refractory patients. [ABSTRACT FROM AUTHOR]

In this paper, a memetic algorithm based on differential evolution (DE), named MODEMA, is proposed for multi-objective job shop scheduling problems (MJSSPs). To balance the exploration and exploitation abilities, both DE-based global search and an adaptive local search are designed and applied simultaneously in the proposed MODEMA. Firstly, a smallest-order-value (SOV) rule is presented to convert the continuous values of individuals (real vectors) in DE to job permutations. Secondly, after the exploration based on DE, several neighborhoods are used in a local search and an adaptive Meta-Lamarckian strategy is employed to dynamically decide which neighborhood should be selected to stress exploitation in each generation. In addition, a solution set is used in MODEMA to hold and update the obtained nondominated solutions. Simulation results and comparisons with Ishibuchi and Murata’s multi-objective genetic local search (IMMOGLS) show the effectiveness and robustness of the proposed MODEMA. [ABSTRACT FROM AUTHOR]

Human metallothionein-3 (hMT3), also named human neuronal growth inhibitory factor (hGIF), is attractive due to its distinct neuronal growth inhibitory activity, which is not shown by other human MT isoforms. It has been reported that the neuronal growth inhibitory activity arises from the N-terminal β-domain rather than its C-terminal α-domain. However, previous bioassay results have shown that the single β-domain is less effective at inhibiting the neuron growth than that in intact hMT3 on a molar basis, which suggests that the α-domain is indispensable to the neuronal growth inhibitory activity of hMT3. In order to confirm this assumption, we constructed two domain-hybrid mutants, the β(MT3)–β(MT3) mutant and the β(MT3)–α(MT1) mutant, and investigated their structural and metal binding properties by UV-vis spectroscopy, CD spectroscopy, pH titration, DTNB reaction, EDTA reaction, etc. The results showed that stability of the Cd3S9 cluster of the β(MT3)–β(MT3) mutant decreased significantly while the Cd3S9 cluster of the β(MT3)–α(MT1) mutant had a similar stability and solvent accessibility to that of hMT3. Interestingly, the bioassay results showed that the neuronal growth inhibitory activity of the β(MT3)–β(MT3) mutant decreased significantly, while the β(MT3)–α(MT1) mutant showed similar inhibitory activity to hMT3. Based on these results, we conclude that the α-domain is indispensable and plays an important role in modulating the stability of the metal cluster in the β-domain by domain–domain interactions, thus influencing the bioactivity of hMT3. [ABSTRACT FROM AUTHOR]

GIF, a member of the metallothionein (MT) family (assigned as MT3), is a neuron growth inhibitory factor that inhibits neuron outgrowth in Alzheimer’s disease. The conserved Thr5 is one of the main differences between GIF and other members in the MT family. However, natural sheep GIF has an unusual Ala5, casting doubt on the role of common Thr5. We constructed a series of human GIF mutants at site 5, and characterized their biochemical properties by UV spectroscopy, circular dichroism spectroscopy, EDTA reaction, 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB) reaction, and pH titration. Their inhibitory activity toward neuron survival and neurite extension was also examined. Interestingly, the T5A mutant exhibited distinct metal thiolate activity in the EDTA and DTNB reactions, and also lost its bioactivity. Meanwhile, the T5S mutant had similar biochemical properties and biological activity as wild-type human GIF, indicating the hydroxyl group on the Thr5 was critical to the bioactivity of human GIF. We suggest the hydroxyl group in human GIF may help stabilize the biologically active conformation. On the other hand, lack of the hydroxyl group in sheep GIF may be partially compensated by its abnormal structure. [ABSTRACT FROM AUTHOR]

Al2O3/25 vol% LaAl11O18 composites were prepared by pressureless sintering at 1550°C with composite powders obtained by copercipiated method using La(NO3) · 6H2O and Al(NO3)3 · 9H2O as starting materials. The enhanced reactive activity of Al2O3 and chemically homogeneous mixing of the constituents made LaAl11O18 phase to be formed at low temperature in composite powders. AlF3 additive was used to reduce the transformation temperature of transition alumina. The LaAl11O18 grains in the composite powder obtained at 1500°C showed rodlike morphology distributed homogeneously in Al2O3 powder. The samples sintered at 1550°C for 4 h with CAS (CaO-Al2O3-SiO2) sintering aid can obtain a high relative density. The effects of the sintering time on the grain growth of Al2O3 and the fracture toughness of the composites were studied and the results showed that LaAl11O18 grains reduced the growth of Al2O3 grains and the rodlike grains increased the fracture toughness. The improvement in fracture toughness of the composites was mainly attributed to the mechanism of crack deflection. [ABSTRACT FROM AUTHOR]