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Within a tight-binding electron–phonon interaction model modified to include temperature effects, the dynamics of two oppositely charged bipolarons scattering in conjugated polymers are investigated using a nonadiabatic evolution method. In this paper, the temperature effects are introduced by the Langevin equation of motion. In order to further understand the photoelectric conversion mechanism in organic light emitting devices, the yields of the luminescent products are studied. It is found that temperature should promote the formation of luminescent element excitations under relatively weak and strong electric fields. In addition, temperature effects can affect the time of bipolarons recombination. With the increase in temperature, the time of bipolarons recombination increases. The results can provide some research ideas for designing organic light-emitting devices with high electroluminescence efficiency. [ABSTRACT FROM AUTHOR]

A di-nuclear uranyl complex with the formula of [(UO2)2(L)4(H2O)2]⋅4H2O (1) (HL = quinoline-6-carboxylic acid) was synthesized hydrothermally and characterized by elemental analysis, infrared spectroscopy and single-crystal X-ray diffraction. Each U(VI) atom has typical pentagonal bipyramid geometry with two O atoms from uranyl, one O atom from one water molecule, and four O atoms from three L ligands. Complex 1 is linked by versatile hydrogen bonds to generate a 3D supramolecular uranyl organic framework. [ABSTRACT FROM AUTHOR]

Oxidation or decomposition of thermally sprayed coatings during deposition may noticably impair the coating features and characteristics, i.e. the surface integrity of coated components, including coating porosity, phase, microhardness, elastic modulus and toughness, etc., having a profound influence on the final performance of components. Further degradations along with enhanced oxidation of the coatings were observed for an off-angle spraying scheme in industrial practice, where inconsistent results were previously reported for spray angle-dependent degradation of various thermal spray coatings, with the mechanism not being fully understood with the less controlled surface integrity. An improved off-angle HVOF thermal spray has been developed for cemented carbide coatings, using pretreated WC-Ni feedstock powders covered with a nanoscale capsulizing nickel layer. A comprehensive study on the formation of multiple surface integrity parameters and the correlative interactions between them is thus facilitated with controllable surface integrity generation using the capsulized powders. Decarburization is mainly attributed to the exposure of pristine WC grains causing enhanced porosity in inter-splats regions, and then microhardness depends mainly on porosity and partly on phase composition, while the elastic modulus depends on intra-splats cohesion and the indentation fracture toughness on inter-splats cohesion, respectively. Abrasive wear from mild to severe regime transition could be interpreted by the inter-splats and intra-splats cohesion correlation. It has been demonstrated by the improved off-angle thermal spray that a manufacturing process could be designed and optimized on the identified unique correlations between the processes, surface integrity and the final performance. [ABSTRACT FROM AUTHOR]

Chinese giant salamander ( Andrias davidianus) is a rare amphibian species in the world. Microsatellite markers are a promising tool for accurate estimation population structure and genetic diversity. In this paper, we isolated novel microsatellite marker for Chinese giant salamander using fast isolation by AFLP of sequences containing repeats (FIASCO) method. More than 50% sequences in 132 clones had repeat number over ten times with di or trinucleeotide repeat except of (GA). Seventy pairs of primers were designed and eleven polymorphic microsatellite loci were characterized for wild and cultivated Chinese giant salamander populations. The allele number was from 3 to 9 in different loci. Polymorphism information content was from 0.544 to 0.702 in cultivated population. The results implied more alleles and PIC were in the wild population than cultivated population. The observed heterozygosities in two populations were higher than 0.553. The data analysis suggested that the cultivated population has lower genetic diversity than wild population, which it's perhaps owing to inbreeding in artificial breeding. To our knowledge, it's the first time to isolated microsatellite markers for Chinese giant salamander. The result indicated that the markers were suitable for the population genetic analysis of Chinese giant salamander. [ABSTRACT FROM AUTHOR]

The cyclophane ligand, 2,11-dithia[3.3](2,6)pyrazinophane (L), was synthesized by a simpler method and characterized by H NMR, which was used to synthesize coordination complexes by reactions with Cu ( I) and Co ( II) cations. Single-crystal X-ray analysis revealed that the conformation of the ligand L is syn(boat-chair), while in I and II it adopts syn(boat-chair) and syn(chair-chair), respectively. In the former coordination compound, Cu(I) is coordinated with two nitrogen and one sulfur atom of the ligand. In the latter one, Co(II) is coordinated with two nitrogen and two sulfur atoms of the ligand. In complexes I and II, the formation of three-dimensional structure depends on π-π-stacking and hydrogen bonds. [ABSTRACT FROM AUTHOR]

Within an extended Su-Schrieffer-Heeger model including interchain interactions and the extended Hubbard model (EHM), the dynamical relaxation of photoexcitations in the presence of an external electric field is investigated using a nonadiabatic evolution method. Under the action of the interchain interactions both intrachain excitons and interchain excitons are generated after photoexcitation in two coupled polymer chains. Our results show that the field required to dissociate the excitons depends sensitively on the strength of the interchain coupling. As the interchain coupling strength increases, the dissociation field decreases. By analyzing the relation between the yield of intrachain and interchain excitons and the interchain coupling strength, we explain the dependence between the dissociation field and the strength of the interchain interactions. The theoretical results are expected to provide useful predictions concerning which polymers with properly strong interchain interactions are likely to be most suitable for use in organic solar cells. [ABSTRACT FROM AUTHOR]

Under the assumption that µ is a non-doubling measure on ℝ d which only satisfies some growth condition, the authors prove that the maximal multilinear Calderón-Zygmund operator is bounded from $$ L^{p_1 } $$ (µ) × ... × $$ L^{p_m } $$ (µ) into L p(µ) for any p1, ... p m ∈ (1, ∞) and p with 1/ p = 1/ p1 + ... + 1/ p m, and bounded from $$ L^{p_1 } $$ (µ) × ... × $$ L^{p_m } $$ (µ) into weak- L p (µ) if there exists any p i = 1. Furthermore, the authors establish a weighted weak-type estimate for the maximal multilinear Calderón-Zygmund operator. [ABSTRACT FROM AUTHOR]

The LYL1 gene encodes a basic helix–loop–helix transcription factor involved in T-cell acute lymphoblastic leukemia. Using real-time quantitative RT-PCR assay, we found that the expression of LYL1 was at higher levels in the majority cases of acute myeloblastic leukemia (AML) or myelodysplastic syndrome when compared to normal bone marrow. Our study also showed that LYL1 was highly expressed in most AML cell lines and in CD34+ AML cells. To determine whether LYL1 had an affect on the phenotype and behavior of myeloid cells, we introduced full-length LYL1 cDNA into K562 cells using electroporation and U937 cells with retroviral infection. Both of the derivative cell lines with overexpression of LYL1 had an increased growth rate and clonogenecity. Forced expression of LYL1 in K562 cells enhanced spontaneous and hemin-induced erythroid differentiation but blocked spontaneous as well as PMA-induced megakaryocytic differentiation. Overexpression of LYL1 in U937 cells blocked all-trans retinoic acid-induced monocytic differentiation. The LYL1-transfected U937 cells were also more resistant to the cytotoxic drug cytarabine. These results demonstrate that LYL1 may play a role in early hematopoiesis and may be a potential oncogenic factor in AML.Leukemia (2005) 19, 1941–1947. doi:10.1038/sj.leu.2403836; published online 11 August 2005 [ABSTRACT FROM AUTHOR]

Poly(arylene disulfide)s were prepared by thermo-initialized ring-opening polymerization (ROP) of macrocyclic(arylene disulfide) oligomers. These macrocyclic oligomers were synthesized by catalytic oxidation of 4,4'-oxybis(benzenethiol) with oxygen in the presence of a copper-amine catalyst. This is the first work to characterize and investigate the electrical and mechanical properties of the poly(arylene disulfide)s obtained via ring-opening polymerization. The surface resistance and volume resistance of the polyaromatic disulfides cured at 180-220°C were higher than 1014 ohm and 1016 ohm·cm, respectively. The results indicated that the as-made polymers exhibited superior dielectric properties. Both mechanical strength and electrical properties of these polymers varied according to ROP conditions. These properties demonstrated that the macrocyclic(arylene disulfide) oligomers derived from 4,4'-oxybis(benzenethiol) could be used to produce thermally curing insulating material to substitute epoxy resins. [ABSTRACT FROM AUTHOR]

A new Acidithiobacillus sp. strain Acidithiobacillus ferriphilus (A. ferriphilus) SCUT-1 was identified, which belongs to the group IV Fe(II)-oxidizing acidithiobacilli. The genome of A. ferriphilus SCUT-1 was sequenced and assembled, and the genes related to sulfur metabolism were identified. Gene expression profiles of the strain cultured in Fe2+, S0, and FeS2 medium were compared (FeS2/Fe2+, S0/Fe2+, and FeS2/S0) in order to identify the genes involved in RISC (reduced inorganic sulfur compound) and ferrous iron (Fe2+) oxidation in A. ferriphilus SCUT-1, with the method of transcriptome reconstruction based on RNA-Seq and genome-guided transcriptome assembly. The soxY-Z-B genes encoding sulfur oxidation proteins, the soe gene cluster encoding sulfite oxidation complex, the hdr gene cluster involved in encoding HDR complex and sulfur transfer proteins, and the cyoA-B-C-D gene cluster encoding bo3 oxidase were were significantly up-regulated in sulfur-containing media, suggesting their engagement in reduced sulfur oxidation in A. ferriphilus SCUT-1. Based on the differentially expressed genes and the putative genes predicted from the genome sequence, the RISC oxidation model and the genes involved in ferrous iron oxidation in A. ferriphilus SCUT-1 were preliminarily elucidated, which helps to interpret the oxidation mechanism of RISC and Fe2+ in acidithiobacilli. [ABSTRACT FROM AUTHOR]

Summary: Myasthenia gravis (MG) patients had low proximal hip BMD, which could be explained by reduced muscle strength, elevated bone resorption markers, vitamin D deficiency, and increased PTH levels in those with MG compared to controls. Introduction: Muscle strength is closely correlated with bone mineral density (BMD) and vitamin D status. Here, we evaluated muscle strength, BMD, and vitamin D status in a large sample of Chinese patients with MG. Methods: In this cross-sectional survey, 86 patients with MG without glucocorticoid treatment and 86 healthy controls were included. Serum levels of 25-hydroxyvitamin D [25OHD], parathyroid hormone (PTH), bone turnover markers (BTMs), and BMD were measured and compared between the two groups. Grip strength and one-leg standing time (OLST) were also assessed in MG patients. Results: Low grip strength and short OLST were found in 11 (12.8%) and 12 (14.0%) MG patients, respectively. There were 3 (3.5%) MG patients with low bone mass for chronological age. Serum beta C-terminal telopeptide and PTH levels were higher ( p < 0.001 and p = 0.001, respectively), and BMD at the femoral neck and trochanter were lower in MG patients ( p < 0.001 and p < 0.001, respectively) compared to healthy controls. In patients with MG, grip strength was positively correlated with BMD. Serum 25OHD levels were lower in MG patients than in healthy controls (17.36 ± 6.64 vs. 22.11 ± 7.28 ng/ml, p < 0.001). Conclusion: Grip strength was positively correlated with BMD in Chinese patients with MG. MG patients tended to have low proximal hip BMD, which may partially be explained by reduced muscle strength, vitamin D deficiency, increased PTH levels, and elevated bone resorption markers compared to controls. [ABSTRACT FROM AUTHOR]

Wheat-cotton double cropping practices on a large scale in cotton belt of the Yellow River Valley and the Yangtze River Valley in China. Field experiments were conducted to determine the effects of wheat-cotton double cropping on cotton biomass accumulation and yield formation during 2011/12 and 2012/13 growing seasons. Two cotton cultivars, Siza 3 (mid-late maturity) and CCRI 50 (early maturity), were used in three cropping systems including monoculture cotton (MC), wheat/intercropped cotton (W/IC) and wheat/direct-seeded cotton (W/DC). Lint yield in double cropping systems were significantly lower than that in monoculture. Compared with MC for Siza 3, lint yield in W/IC and W/DC were decreased by 10.9 and 41.8%, respectively and 9.9 and 35.9% for CCRI 50, respectively. These reductions were largely ascribed to the fewer cotton bolls per unit area. Growth analysis showed that IC showed a pronounced delay in early development due to the initial shading from wheat on cotton seedlings and owing to delayed sowing, DC was easily affected by lower temperature during flowering and boll formation stage. And that consequently was delaying reproductive development, affecting cotton biomass accumulation and distribution and finally limiting crop productivity. Further, the diminished source capacity coupled with inadequate biomass production was the main determinant factor to limit lint yield in W/IC, while the reduced sink capacity with less partition to reproductive organs was the primary factor limiting lint yield in W/DC. Comparing to mid-late maturity of Siza 3, early maturity cultivar of CCRI 50 had a yield advantage in double cropping sequential system, since its shorter growing period. [ABSTRACT FROM AUTHOR]

The security and stability of accumulation slopes are significant concerns in the field of engineering. In this study, a 3D geological model was established in VISUALBASIC.NET with the use of NURBS surface technology. Rock cores from the virtual drilling and deformation curve of measuring points were comprehensively analyzed to determine the location zone and distribution law of slip faults. 3D cloud maps of monitoring data on clinometer holes were used to identify the deformation and failure mode of the accumulation slope. Analyses show that a significant slip plane exists at a depth of 28.5-29.5 m. The accumulation slope comes from a tractive landslide and is in the stage of creeping deformation. The calculated safety factor indicated that the accumulation slope may be caused by failure as an effect of heavy rains and earthquake, and the early warning research is very important. The data obtained were applied to examine the instability warning indexes, criteria, and thresholds of the accumulation slope. The results achieved dynamic optimization design and information construction based on feedback analysis of various data. These findings can assist in early warnings for disaster management, provide important safeguards to ensure that key support parts are available, and ensure stable engineering operations. The proposed approach can also be used as a valuable reference for other similar projects. [ABSTRACT FROM AUTHOR]

The single layers of TiN, TiAlN and TiN/TiAlN multilayer coatings were deposited on 316L SS bipolar plate by physical vapor deposition technique. The X-ray diffraction studies revealed that the formed coatings exhibited single-phase cubic structure. The low surface roughness and high contact angles of the TiAlN and TiN/TiAlN coatings governed the better water management in the fuel cell. Nyquist and Bode-impedance studies of TiN/TiAlN coating ensured higher electrochemical impedance behavior. The polarization results revealed that the current densities (icorr) of TiN/TiAlN coating were below 1 µA/cm2 in the PEMFC environments, which satisfied the U.S. Department of Energy's 2020 target. The contact resistance of the TiN/TiAlN-coated 316L SS was the lowest and fulfilled the requirements of bipolar plate (≤ 10 mΩ cm2) in PEMFC environment. Surface morphology results revealed that the surface of 316L SS is well protected by multilayer TiN/TiAlN coating. Inductive coupled plasma-optical emission spectroscopy results are in good agreement with electrochemical studies revealing the TiN/TiAlN coating significantly reduced the metal ions dissolution. [ABSTRACT FROM AUTHOR]

Apoptosis-inducing factor (AIF) represents a caspase-independent apoptotic pathway in the cell, and a mitochondrial localization sequence-truncated AIF (AIFΔ1–120) can be relocated from the cytoplasm to the nucleus and exhibit a constitutive proapoptotic activity. Here, we generated a chimeric immuno-AIF protein, which comprised an HER2 antibody, a Pseudomonas exotoxin translocation domain and AIFΔ1–120. Human Jurkat cells transfected with the immuno-AIF gene could express and secrete the chimeric protein, which selectively recognized HER2-overexpressing tumor cells and was endocytosed. Subsequent cleavage of truncated AIF from immuno-AIF and its release from the internalized vesicles resulted in apoptosis of tumor cells. Intramuscular injection of the immuno-AIF gene caused significant suppression of tumors and substantially prolonged mice survival in an HER2-overexpressing xenograft tumor model. Our study demonstrates the feasibility of the immuno-AIF gene as a novel approach to treating cancers that overexpress HER2.Gene Therapy (2006) 13, 313–320. doi:10.1038/sj.gt.3302672; published online 3 November 2005 [ABSTRACT FROM AUTHOR]

Summary: Our network meta-analysis analyzed the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on fracture risk. By combining data from randomized controlled trials, we found that GLP-1 RAs were associated with a decreased bone fracture risk, and exenatide is the best option agent with regard to the risk of fracture. This study is registered with PROSPERO (CRD42018094433).Introduction: Data on the effects of GLP-1 RAs on fracture risk are conflicted. This study aimed to analyze the available evidence on the effects of GLP-1 RAs on fracture risk in type 2 diabetes mellitus patients.Methods: Electronic databases were searched for relevant published articles, and unpublished studies presented at ClinicalTrials.gov were searched for relevant clinical data. All analyses were performed with STATA 12.0 and R software (Version 3.4.4). We estimated the risk ratio (RR) and 95% confidence interval (CI) by combining RRs for fracture effects of included trials.Results: There were 54 eligible random control trials (RCTs) with 49,602 participants, including 28,353 patients treated with GLP-1 RAs. Relative to placebo, exenatide (RR, 0.17; 95% CI 0.03-0.67) was associated with lowest risk of fracture among other GLP-1 RAs. Exenatide had the highest probability to be the safest option with regard to the risk of fracture (0.07 ‰), followed by dulaglutide (1.04%), liraglutide (1.39%), albiglutide (5.61%), lixisenatide (8.07%), and semaglutide (18.72%). A statistically significant inconsistency was observed in some comparisons.Conclusion: The Bayesian network meta-analysis suggests that GLP-1 RAs were associated with a decreased bone fracture risk compared to users of placebo or other anti-hyperglycemic drugs in type 2 diabetes mellitus patients, and exenatide is the best option agent with regard to the risk of fracture. [ABSTRACT FROM AUTHOR]

Previously, we have reported the crystal structures of Fab fragment of Infliximab in complex with TNFα. The structurally identified epitope on TNFα revealed the mechanism of TNFα inhibition by partially overlapping with the TNFα-receptor interface and the possibility to optimize the binding affinity. In this study, we launched a screen of a phage display library to isolate novel anti-TNFα antibodies based on the infliximab epitope. To develop novel anti-TNFα antibodies, structural analysis, the phage display antibody isolation, step by step antibody optimization, CDR residues random mutagenesis, and binding affinity characterization were performed. One of the novel antibodies generated on the backbone of infliximab, Inf3D6, has the superior binding affinity to TNFα, thus, demonstrating the potential for structure guided optimization for improvement of existing antibody-based therapeutics. [ABSTRACT FROM AUTHOR]

Summary: This study aims to detect whether there remains valuable prognostic information in fluctuation of red cell distribution width (RDW) in hip fracture patients. Results show that this readily available parameter may provide a more effective strategy for assessment of mortality risk, therefore providing a reference for clinical planning and decision-making.Introduction: Prognostic values have been found in the fluctuation of some hematologic parameters. The red cell distribution width (RDW) routinely reported with all complete blood cell counts (CBC) has proven to be associated with poor outcomes in various diseases. However, whether the fluctuation in RDW is predictive of long-term mortality in hip fracture patients treated with surgery remains unknown.Methods: One thousand three hundred thirty hip fracture patients who underwent surgery from January 1, 2000 to November 18, 2012 were recruited in this prospective cohort study. Fluctuation in the RDW between admission and discharge was measured, and a Kaplan-Meier (KM) analysis and multivariable Cox regression model were applied to evaluate the relationship between this fluctuation and mortality. Risk factors for a larger fluctuation were detected by using Logistic regression analyses.Results: In addition to the admission RDW, a high RDW level at the time of discharge was also associated with an increased risk of death, while no significant difference was found in the postoperative RDW. Fluctuation in the RDW between admission and discharge was an independent risk predictor for 2-year mortality (HR 1.45 95%CI 1.06-2.00, p = 0.022). Factors affecting the change in the RDW between admission and discharge included both the demographic characteristics of the patients and clinical interventions.Conclusion: Hip fracture patients who experience a greater fluctuation in RDW during the hospital course are at a heightened risk for 2-year all-cause mortality. [ABSTRACT FROM AUTHOR]

Controversy has arisen in regarding the association between serum uric acid (UA) and fracture risk. Therefore, we conducted a systemic review and meta-analysis by pooling estimate of five prospective studies (29,110 participants). Results showed that an increased serum UA level is associated with a lower risk of fracture. Numerous studies have demonstrated that high serum UA is a relevant risk factor for a wide variety of diseases, whereas new understanding in serum uric acid follows recent reports demonstrating a protective role of UA in health status. However, the association between serum UA and fracture remains controversial. Therefore, we conduct a systemic review and meta-analysis to determine whether elevated UA level is a protective factor for fracture among prospective studies. We searched for studies published before May 6, 2016, using PubMed, Embase, and Cochrane databases, without any language restriction. The inclusion criteria were published studies investigating the association between UA and fractures. Two authors independently screened the retrieved articles in accordance to the predefined inclusion criteria. We pooled the study-specific relative risk estimates using a random-effect model for comparison of persons whose UA levels were in the top tertile with those in the bottom tertile. Factors that may predict these associations were evaluated in subgroup analysis and meta-regression. The five included prospective studies included 29,110 participants. In random-effect models that included all five included studies, the summary hazard ratios (HRs) (top vs bottom tertiles) were 079 (95% CI, 0.69 to 0.89), without evidence of heterogeneity ( P for heterogeneity = 0.458; I = 0%). Similar results were shown when pooling estimate of three higher-quality studies (HR 0.80 95% CI, 0.69 to 0.93). The association between UA and fracture remained in sensitivity and subgroup analyses. An increased serum UA level is shown to be associated with a lower risk of fracture, albeit additional large, high-quality prospective studies or a meta-analysis of individual data are still needed to verify the association. [ABSTRACT FROM AUTHOR]

The novel dinuclear complex [Pd(L)(Phen)] (Phen = 1,10-phenanthroline, HL = 2,2'-iminodibenzoic acid) was synthesized and characterized by IR spectra, element analysis, and X-ray single-crystal diffraction (СIF file CCDC no. 1469344). The competitive binding study with ethidium bromide (EtBr) was tested by fluorescence measurement. The result indicated that the complex has an ability to displace the EtBr bound to DNA. Gel electrophoresis assay demonstrated the ability of the complex to cleave the HL-60 DNA. Apoptotic research indicated that [Pd(L)(Phen)] exhibited significant cancer cell inhibitory rate. [ABSTRACT FROM AUTHOR]

Coordination of a pyridine-based bridging ligand, 4-bpmp, with cadmium nitrate afforded an infinite ladder-type complex {[Cd(4-bpmp)(HO)Cl]} ( A) (4-bpmp = 1,4-bis(4-pyridylmethyl)piperazine) containing T-shaped building blocks. IR spectra, elemental analysis, and X-ray single-crystal diffraction were carried out to determine the composition and crystal structure of complex A. Inclined interpenetration of infinite ladders was observed in the solid structure. The combined work demonstrates the ability of bipyridyl coordination polymer leads to a novel metal complex with impressive structural motif. [ABSTRACT FROM AUTHOR]

A novel Mn coordination polymer, {[Mn(L)] · 2HO}, has been synthesized by the reaction of CHMnO · 4HO (manganese acetate) with 3-(2,5-dicarboxyl)-5-carboxylpyridine (L). Elemental analysis, IR spectra, thermal analyses, and X-ray single crystal diffraction (CIF file CCDC no. 1061752) were carried out to determine the composition and crystal structure of the complex. The polymer was characterized by UV spectrum, fluorescence spectrum showing that the complex has the ability of interaction with DNA, Gel electrophoresis assay demonstrated the ability of the complex to cleave the HL-60 DNA (HL-60 DNA, which was extracted by ourselves). Further more, the apoptotic test indicates that the complex has an apoptotic effect on JEKO. [ABSTRACT FROM AUTHOR]

The multi-level evaluation system and rock slope stability were analyzed in this study based on extension and systems engineering theory. An appropriate evaluation index system was selected through hierarchical analysis of geological conditions, excavation and supporting measures, and environmental and monitoring layouts. The comprehensive evaluation system was then divided into three layers: index, description, and target layers. The system can be adopted to conduct a thorough and careful investigation of the research object. The technique matter-element extension transform was employed in the extension model to solve the multi-attribute problem and to prevent incompatibility in rock slope stability evaluation. Qualitative and quantitative grade evaluations were performed by calculating the matter-element dependency degree. The model was then applied to a large-scale rock slope project, and its evaluation criteria for rock slope stability were established. Results were verified through quantitative method of 3D limit equilibrium and qualitative method of 3D nephrogram displacement variation. Results show that extension theory can be utilized to solve problems in rock slope safety. [ABSTRACT FROM AUTHOR]

X-ray microscopy is powerful in that it can probe large volumes of material at high spatial resolution with exquisite chemical, electronic and bond orientation contrast. The development of diffraction-based methods such as ptychography has, in principle, removed the resolution limit imposed by the characteristics of the X-ray optics. Here, using soft X-ray ptychography, we demonstrate the highest-resolution X-ray microscopy ever achieved by imaging 5 nm structures. We quantify the performance of our microscope and apply the method to the study of delithiation in a nanoplate of LiFePO4, a material of broad interest in electrochemical energy storage. We calculate chemical component distributions using the full complex refractive index and demonstrate enhanced contrast, which elucidates a strong correlation between structural defects and chemical phase propagation. The ability to visualize the coupling of the kinetics of a phase transformation with the mechanical consequences is critical to designing materials with ultimate durability. [ABSTRACT FROM AUTHOR]

Although angiogenesis inhibitors have provided substantial clinical benefit as cancer therapeutics, their use is limited by resistance to their therapeutic effects. While ample evidence indicates that such resistance can be influenced by the tumor microenvironment, the underlying mechanisms remain incompletely understood. Here, we have uncovered a paracrine signaling network between the adaptive and innate immune systems that is associated with resistance in multiple tumor models: lymphoma, lung and colon. Tumor-infiltrating T helper type 17 (TH17) cells and interleukin-17 (IL-17) induced the expression of granulocyte colony-stimulating factor (G-CSF) through nuclear factor κB (NF-κB) and extracellular-related kinase (ERK) signaling, leading to immature myeloid-cell mobilization and recruitment into the tumor microenvironment. The occurrence of TH17 cells and Bv8-positive granulocytes was also observed in clinical tumor specimens. Tumors resistant to treatment with antibodies to VEGF were rendered sensitive in IL-17 receptor (IL-17R)-knockout hosts deficient in TH17 effector function. Furthermore, pharmacological blockade of TH17 cell function sensitized resistant tumors to therapy with antibodies to VEGF. These findings indicate that IL-17 promotes tumor resistance to VEGF inhibition, suggesting that immunomodulatory strategies could improve the efficacy of anti-angiogenic therapy. [ABSTRACT FROM AUTHOR]

The development of RNA interference-based cancer gene therapies has been delayed due to the lack of effective tumor-targeting delivery systems. Attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) has a natural tropism for solid tumors. We report here the use of attenuated S. Typhimurium as a vector to deliver shRNA directly into tumor cells. Constitutively activated signal transducer and activator of transcription 3 (Stat3) is a key transcription factor involved in both hepatocellular carcinoma (HCC) growth and metastasis. In this study, attenuated S. Typhimurium was capable of delivering shRNA-expressing vectors to the targeted cancer cells and inducing RNA interference in vivo. More importantly, a single oral dose of attenuated S. Typhimurium carrying shRNA-expressing vectors targeting Stat3 induced remarkably delayed and reduced HCC (in 70% of mice). Cancer in these cured mice did not recur over 2 years following treatment. These data demonstrated that RNA interference combined with Salmonella as a delivery system may offer a novel clinical approach for cancer gene therapy. [ABSTRACT FROM AUTHOR]

In magnetic thin films, a magnetic vortex is a state in which the magnetization vector curls around the centre of a confined structure. In a thin-film disc, vortex states are characterized by the vortex polarity and the winding number. In ferromagnetic (FM) discs, these two parameters have been shown to govern many fundamental properties of the vortex, such as its gyroscopic rotation, polarity reversal, core motion and vortex-pair excitation. In antiferromagnetic (AFM) discs, in contrast, there has been only indirect evidence for a vortex state, obtained through the observation of induced FM-ordered spins in the AFM disc. Here we report the direct observation of an AFM vortex state in the AFM layer of an AFM/FM bilayer system. We have fabricated single-crystalline NiO/Fe/Ag(001) and CoO/Fe/Ag(001) discs, and using X-ray magnetic linear dichroism techniques we observe two types of AFM vortex, one of which has no analogue in FM structures. We also show that a frozen AFM vortex can bias an FM vortex at low temperature. [ABSTRACT FROM AUTHOR]

A natural BH3-mimetic, small-molecule inhibitor of Bcl-2, (−)-gossypol, shows promise in ongoing phase II and III clinical trials for human prostate cancer. In this study we show that (−)-gossypol preferentially induces autophagy in androgen-independent (AI) prostate cancer cells that have high levels of Bcl-2 and are resistant to apoptosis, both in vitro and in vivo, but not in androgen-dependent (AD) cells with low Bcl-2 and sensitive to apoptosis. The Bcl-2 inhibitor induces autophagy through blocking Bcl-2-Beclin1 interaction, together with downregulating Bcl-2, upregulating Beclin1, and activating the autophagic pathway. The (−)-gossypol-induced autophagy is dependent on Beclin1 and Atg5. Our results show for the first time that (−)-gossypol can also interrupt the interactions between Beclin1 and Bcl-2/Bcl-xL at endoplasmic reticulum, thus releasing the BH3-only pro-autophagic protein Beclin1, which in turn triggers the autophagic cascade. Oral administration of (−)-gossypol significantly inhibited the growth of AI prostate cancer xenografts, representing a promising new regimen for the treatment of human hormone-refractory prostate cancer with Bcl-2 overexpression. Our data provide new insights into the mode of cell death induced by Bcl-2 inhibitors, which will facilitate the rational design of clinical trials by selecting patients who are most likely to benefit from the Bcl-2-targeted molecular therapy. [ABSTRACT FROM AUTHOR]

Abnormal high activation of survivin is involved in carcinogenesis of various types of cancer. Survivin has been shown to promote cell proliferation in human hepatocellular carcinoma (HCC). Survivin-targeting approaches have become a promising strategy for treating HCC. Here, we used a reporter system to screen effective survivin siRNA sequences. The effect of vector-based survivin short hairpin RNA (shRNA) on the malignant phenotype of HCC cells in vitro and in vivo was determined, and an adenovirus-mediated shRNA expression vector was developed to decrease survivin expression of the established HCC tumor in nude mice. In vitro study showed that stable survivin knockdown inhibited cancer cell proliferation, enhanced apoptotic susceptibility, arrested cell cycle in the G1 phase and resulted in apparent mitotic catastrophe. Moreover, cells stably expressing survivin shRNA showed decreased tumorigenicity in nude mice. An additional in vivo study showed that intratumoral injection of adenovirus-delivered survivin shRNA suppressed tumor growth by spontaneous apoptosis of cancer cells and significantly prolonged animal survival. In conclusion, we proved the therapeutic potential of survivin shRNA for the treatment of HCC. And our results indicated that adenovirus-delivered shRNA may serve as a novel therapeutic for HCC. [ABSTRACT FROM AUTHOR]

Antibody-drug conjugates enhance the antitumor effects of antibodies and reduce adverse systemic effects of potent cytotoxic drugs. However, conventional drug conjugation strategies yield heterogenous conjugates with relatively narrow therapeutic index (maximum tolerated dose/curative dose). Using leads from our previously described phage display–based method to predict suitable conjugation sites, we engineered cysteine substitutions at positions on light and heavy chains that provide reactive thiol groups and do not perturb immunoglobulin folding and assembly, or alter antigen binding. When conjugated to monomethyl auristatin E, an antibody against the ovarian cancer antigen MUC16 is as efficacious as a conventional conjugate in mouse xenograft models. Moreover, it is tolerated at higher doses in rats and cynomolgus monkeys than the same conjugate prepared by conventional approaches. The favorable in vivo properties of the near-homogenous composition of this conjugate suggest that our strategy offers a general approach to retaining the antitumor efficacy of antibody-drug conjugates, while minimizing their systemic toxicity. [ABSTRACT FROM AUTHOR]

Bone-marrow-derived cells facilitate tumour angiogenesis, but the molecular mechanisms of this facilitation are incompletely understood. We have previously shown that the related EG-VEGF and Bv8 proteins, also known as prokineticin 1 (Prok1) and prokineticin 2 (Prok2), promote both tissue-specific angiogenesis and haematopoietic cell mobilization. Unlike EG-VEGF, Bv8 is expressed in the bone marrow. Here we show that implantation of tumour cells in mice resulted in upregulation of Bv8 in CD11b+Gr1+ myeloid cells. We identified granulocyte colony-stimulating factor as a major positive regulator of Bv8 expression. Anti-Bv8 antibodies reduced CD11b+Gr1+ cell mobilization elicited by granulocyte colony-stimulating factor. Adenoviral delivery of Bv8 into tumours was shown to promote angiogenesis. Anti-Bv8 antibodies inhibited growth of several tumours in mice and suppressed angiogenesis. Anti-Bv8 treatment also reduced CD11b+Gr1+ cells, both in peripheral blood and in tumours. The effects of anti-Bv8 antibodies were additive to those of anti-Vegf antibodies or cytotoxic chemotherapy. Thus, Bv8 modulates mobilization of CD11b+Gr1+ cells from the bone marrow during tumour development and also promotes angiogenesis locally. [ABSTRACT FROM AUTHOR]

A population of 294 recombinant inbred lines (RIL) derived from Yuyu22, an elite maize hybrid extending broadly in China, has been constructed to investigate the genetic basis of grain yield, and associated yield components in maize. The main-effect quantitative trait loci (QTL), digenic epistatic interactions, and their interactions with the environment for grain yield and its three components were identified by using the mixed linear model approach. Thirty-two main-effect QTL and forty-four pairs of digenic epistatic interactions were detected for the four measured traits in four environments. Our results suggest that both additive effects and epistasis (additive × additive) effects are important genetic bases of grain yield and its components in the RIL population. Only 30.4% of main-effect QTL for ear length were involved in epistatic interactions. This implies that many loci in epistatic interactions may not have significant effects for traits alone but may affect trait expression by epistatic interaction with the other loci. [ABSTRACT FROM AUTHOR]

Completely biodegradable foams of poly(propylene carbonate) (PPC) derived from carbon dioxide and propylene oxide were fabricated using N, N′-dinitroso pentamethylene tetramine (DPT) as chemical blowing agent, and urea as the activator to lower the decomposition temperature of DPT. Thermal decomposition behavior and gas evolution behavior of the DPT composite with various urea to DPT ratios were investigated to optimize the composition of the blowing agent. The formulation of blowing agent mixture and foaming condition, the foam morphologies, the molecular weight change, as well as the mechanical properties of produced PPC foams were studied extensively. The experimental results demonstrated that the greatest blowing ratio of 14.8 can be afforded in case 12 phr blowing agent was used at 170 °C for 30 min. Gel permeation chromatography (GPC) and thermal analysis revealed that DPT acted as both chain-extension agent and blowing agent for PPC matrix. The molecular weight of PPC subjected to foaming increased by 76%. The foamed PPC exhibited superior mechanical properties and can be used as packaging material for many practical applications. [ABSTRACT FROM AUTHOR]

Mechanical and thermal properties of poly(arylene disulfide) synthesized by ring-opening reaction of cyclic(aromatic disulfide) oligomer were reported. These oligomers were prepared from 4,4′-oxybis(benzenethiol). Three-point bending tests were performed to measure the flexural properties of the poly(arylene disulfide). DSC and TGA techniques were used to characterize the thermal properties of these polymers. Ring-opening reactions were carried out by hot-press under atmosphere and nitrogen atmosphere, respectively. Oxidation reaction of these polymers was detected from Raman spectra under atmosphere. The glass transition temperature increased but 10% weight loss temperature decreased with increasing ring-opening temperature. The flexural strength decreased with increasing the temperature of ring-opening polymerization under both atmosphere and nitrogen atmosphere. The polydisulfides could be used as high temperature and thermally curing insulating materials to substitute epoxy resins. [ABSTRACT FROM AUTHOR]

Prognosis in patients with myelodysplastic syndromes (MDS) is closely correlated with cytopenia. To date, no factor is available which is able to reliably stimulate megakaryopoiesis in vivo. Recently, the ligand of the mpl receptor was cloned and found to be thrombopoietin (TPO). We measured endogenous TPO serum levels in 69 patients suffering from MDS using an TPO receptor-based ELISA. Twenty-six of the patients suffered from refractory anemia (RA), 12 from RA with excess of blasts (RAEB), 25 from RAEB in transition (RAEBt), and six from chronic myelomonocytic leukemia (CMML). This assay uses a chimeric molecule consisting of the human TPO receptor fused to the Fc portion of human IgG as the capture reagent. Biotinylated antibody to TPO IgG was used for detection and the lower detection limit in serum was found to be 160 pg/ml. Samples obtained from healthy individuals with a normal platelet number were shown to be below detectable levels. In patients with RA, high endogenous serum TPO concentrations correlated with low platelet count and significantly elevated TPO concentrations were only found when megakaryopoiesis was absent or decreased in the bone marrow. This correlation was not detected in RAEB and RAEBt patients and no detectable TPO serum concentrations were found in six CMML patients whether they showed decreased or normal platelet count. Our data show that endogenous TPO production is upregulated by decreased circulating platelet count only in patients with refractory anemia. In the more advanced stages of MDS where the leukemic clone has further progressed, an inadequate TPO response occurs, possibly due to overexpression of the mpl receptor by the malignant clone. [ABSTRACT FROM AUTHOR]