Dinuclear palladium(II) complexes containing two monofunctional [Pd(en)(pyridine)Cl]+ units bridged by Se or S. Synthesis, characterization, cytotoxicity and kinetic studies of DNA-binding

Two novel dinuclear palladium(II) complexes, ?[Pd(en)Cl]2(bpse)?(NO3)2 (1) and ?[Pd(en)Cl]2 (bpsu)?(NO3)2 (2), (where en is ethylenediamine; bpse is bis(3-methyl-4-pyridyl) selenide; bpsu is bis(3-methyl-4-pyridyl) sulfide) have been synthesized. The complexes have been characterized by elemental analysis, IR, 1H NMR, and 13C NMR. They have been assayed for antitumor activity in vitro against the mice leukemia L1210 and the human coloadenocarcinoma HCT8 cell lines. The results show that compound 1 has a lower I.D.50 value against the two cancer cell lines as compared to compound 2; the compounds also shows a lower I.D.50 value than cisplatin against the HCT8 cell line, but a higher I.D.50 value than cisplatin against the L1210 cell line. Binding studies indicate that compound 1 possibly interacts with DNA by a nonintercalative mode. Kinetics of binding of the two compounds to DNA are firstly studied using ethidium bromide as a fluorescence probe with stopped-flow spectrophotometer under pseudo-first-order condition. The stronger binding of two steps in the process of the compounds interacting with DNA are observed, and the Kobs and Ea of binding of the two steps (where Kobs is the observed pseudo-first-order rate constant, Ea is the observed energy of activation) are obtained.     

Microstructure and mechanical properties of ternary intermetallic compound dispersed P/M Al-Mn-X-Zr (x=Cu,Ni) alloys

Heat-resistant aluminum alloys are generally developed by dispersing stable intermetallic compounds by adding transition metals (TM) whose diffusion coefficient in aluminum alloys is low even at high temperatures. Commonly used intermetallic compounds include Al-TM binary intermetallic compounds, for example, Al₆Fe, Al₃Ti and Al₃Ni. By contrast, multicomponent intermetallic compounds are hardly used. The present study focuses on Al-Mn-Cu and Al-Mn-Ni ternary intermetallic compounds, and by finely dispersing these intermetallic compounds, attempts to develop heat-resistant alloys. Through the atomization method, Al-(4.96–5.96)Mn-(6.82–7.53)Cu-0.4Zr and Al-(5.48–8.76)Mn-(2.23–4.32)Ni-0.4Zr (in mass%) powders were fabricated, and by degassing these powders at 773 K, intermetallic compounds were precipitated. These powders were then solidified into extrudates by hot extrusion at 773 K. The microstructural characterization of powders and exrudates was carried out by XRD analysis, SEM/EDX and TEM. The mechanical properties of extrudates were determined at room temperature, 523 K and 573 K. In Al-Mn-Cu alloys, while a small amount of Al₂Cu was crystallized, precipitated Al₂₀Mn₃Cu₂ intermetallic compounds were mainly dispersed. In Al-Mn-Ni alloys, while a small amount of Al₆Mn intermetallic compounds was precipitated, the precipitated A₆₀Mn₁₁Ni₄ intermetallic compounds were mainly dispersed. Both ternary intermetallic compounds were about 200 nm in size. The compounds were elliptical, and their longitudinal direction was oriented along the extrusion direction. In the Al-Mn-Cu alloys, since the work hardening at room temperature was high, the tensile strength became 569 MPa. At elevated temperatures, since hardly any work hardening was observed, the tensile strength decreased markedly. However, in Al-Mn-Ni alloys, since the work hardening is low even at room temperature, the roomtemperature strength is not high. Thus, the decrease in tensile strength at elevated temperatures is relatively small and a high strength was obtained at 523 K and 573 K: 276 MPa and 207 MPa, respectively.     

Effect of PdO_x structure properties on catalytic performance of Pd/Ce_(0.67)Zr_(0.33)O_2 catalyst for CO,HC and NO_x elimination

Pd/Ce_(0.67)Zr_(0.33)O_2 catalyst was pretreated in different atmosphere respectively, and characterized by CO chemical adsorption, XPS, HR-TEM, H_2-TPR, Raman, OSC and in situ DRIFTS to investigate the effect of the structure properties of PdO_x species on the catalytic performance for CO, HC and NO_x elimination. The results show that Pd/CZ catalyst pretreated in air atmosphere has higher oxidation activity of HC due to having high Pd dispersion and strong interaction between PdO_x and CZ support. Pd/CZ-H catalyst pretreated in reducing atmosphere exhibits better catalytic performance of NO_x elimination because of having relatively big Pd particle size, more Pd species in metallic state and higher concentration of oxygen vacancies. While for the Pd/CZ-RG catalyst pretreated in reactant atmosphere, strong adsorption of HC species on the surface of catalysts would lead to a part of active sites being covered, which inhibits HC and NO conversions.     

The age hardening characteristics of Nb-Base alloys containing carbon and/or silicon as interstitiels: Part II. (Nb-33 At. Pct Hf)

A study was made to investigate the solutioning and aging reactions and their effects on microstructure and microhardness in nine experimental Nb-base alloys involving Nb-33 Hf, Nb-33Hf-C, Nb-33Hf-Si, and Nb-33Hf-C-Si* systems. Alloys were solution treated, quenched, *Alloy compositions are in atomic percent. then aged for 2 h at temperatures ranging from 800 to 1600°C to examine the effect of temperature, and aged at 900 to 1100°C isothermally for times varying from 2 to 20 h. Microstructural changes were determined by optical and electron microscopy, the phases were chemically extracted and identified by X-ray diffraction, and hardness provided the means of evaluating structural effects. The Nb-33Hf-Si and Nb-33Hf-C-Si alloys exhibited age hardening characteristics, which appear to be due to the precipitation of complex monocarbide (Nb, Hf) (C, O, N), while Nb-33Hí-C alloys showed separation of Nb₂C phase from (Nb, Hf) (C, O, N) on aging.     

The age hardening characteristics of Nb-Base alloys containing carbon and/or silicon as interstitiels: Part II. (Nb-33 At. Pct Hf)

Metallurgical and Materials Transactions A - A study was made to investigate the solutioning and aging reactions and their effects on microstructure and microhardness in nine experimental Nb-base...     

DNA strand scission by polycyclic aromatic hydrocarbon o-quinones: role of reactive oxygen species, Cu(II)/Cu(I) redox cycling, and o-semiquinone anion radicals,

In previous studies, benzo[a]pyrene-7,8-dione (BPQ), a polycyclic aromatic hydrocarbon (PAH) o-quinone, was found to be 200-fold more potent as a nuclease than (+/-)-anti-7,8-dihydroxy-9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene, a suspect human carcinogen. The mechanism of strand scission mediated by naphthalene-1,2-dione (NPQ) and BPQ was further characterized using either phiX174 DNA or poly(dG).poly(dC) as the target DNA. Strand scission was extensive, dependent on the concentration of o-quinone (0-10 microM), and required the presence of NADPH (1 mM) and CuCl2 (10 microM). The production of reactive species, i.e., superoxide anion radical, o-semiquinone anion (SQ) radical, hydrogen peroxide (H2O2), hydroxyl radical (OH.), and Cu(I), was measured in the incubation mixtures. The formation of SQ radicals was measured by EPR spectroscopy under anaerobic conditions in the presence of NADPH. A Cu(II)/Cu(I) redox cycle was found to be critical for DNA cleavage. No strand scission occurred in the absence of Cu(II) or when Cu(I) was substituted, yet Cu(I) was required for OH* production. Both DNA strand scisson and OH. formation were decreased to an equal extent, albeit not completely, by the inclusion of OH. scavengers (mannitol, soduim benzoate, and formic acid) or Cu(I) chelators (bathocuproine and neocuproine). In contrast, although the SQ radical signals of NPQ and BPQ were quenched by DNA, no strand scission was observed. When calf thymus DNA was treated with PAH o-quinones, malondialdehyde (MDA) was released by acid hydrolysis. The formation of MDA was inhibited by OH. scavengers suggesting that OH* cleaved the 2'-deoxyribose moiety in the DNA to produce base propenals. These studies indicate that for PAH o-quinones to act as nucleases, NADPH, Cu(II), Cu(I), H2O2, and OH*, were necessary and that the primary species responsible for DNA fragmentation was OH., generated by a Cu(I)-catalyzed Fenton reaction. The genotoxicity of PAH o-quinones may play a role in the carcinogenicity and mutagenicity of the parent hydrocarbons.     

The magic cup: Great apes and domestic dogs (Canis familiaris) individuate objects according to their properties.

Despite current interest in dog (Canis familiaris) cognition, very little is known about how dogs represent objects and how they compare with other species, such as the great apes. Therefore, we investigated how dogs and great apes (chimpanzees [Pan troglodytes], bonobos [Pan paniscus], orangutans [Pongo pygmaeus], gorillas [Gorilla gorilla]) individuate objects in a classical violation of expectation paradigm. We used a container (magic cup) with a double bottom that allowed us to change the type of food that subjects had seen being placed in the container. Using a 2 × 2 design, we varied whether subjects received a generally preferred food and whether the food was substituted (surprise trials) or not (baseline trials). Apes showed increased begging and looking behaviors and dogs showed increased smelling behavior. Both species stayed near the experimenter more frequently in the surprise trials compared with baseline trials. Both species reacted to positive (i.e., good food substituted for bad food) and negative (i.e., bad food substituted for good food) surprises. These results suggest that apes and dogs were able to individuate objects according to their properties or type in comparable ways. In addition, we looked for frustration and elation effects, but subjects' behaviors were not influenced by the food they saw and which they received in previous trials. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Stuttering, language, and cognition: a review and a model of stuttering as suprasegmental sentence plan alignment (SPA)

Extant models of stuttering do not account for the emergence of stuttering at the onset of productive language use; the greater incidence of stuttering during spontaneous speech, on complex sentences, and at sentence-initial positions; the greater incidence of stuttering in bilinguals' 2nd language; the apparent deficiency of stutterers in expressive and receptive language skills; the prevalence of spontaneous recovery from stuttering; and the lack of chronic physiological or articulatory deficits in stuttering children's fluent speech. The author presents a model of stuttering as points of suprasegmental sentence plan alignment (SPA). Such alignment processes occur when, due to on-line sentence production processes, SPAs adopted prior to utterance initiation need to be aligned with revised SPAs. This model parsimoniously accounts for the findings reviewed in the article.     

Calcium induces binding and formation of a spin-coupled dimanganese(II,II) center in the apo-water oxidation complex of photosystem II as precursor to the functional tetra-Mn/Ca cluster

Two new intermediates are described which form in the dark as precursors to the light-induced assembly of the photosynthetic water oxidation complex (WOC) from the inorganic components. Mn2+ binds to the apo-WOC-PSII protein in the absence of calcium at a high-affinity site. By using a hydrophobic chelator to remove Mn2+ and Ca2+ from the WOC and nonspecific Fe3+, a new EPR signal becomes visible upon binding of Mn2+ to this site, characterized by six-line 55Mn hyperfine structure (DeltaHpp = 96 +/- 1 G) and effective g = 8.3. These features indicate a high-spin electronic ground state (S = 5/2) for Mn2+ and a strong ligand field with large anisotropy. This signal is eliminated if excess Ca2+ or Mg2+ is present. A second Mn2+ EPR signal forms in place of this signal upon addition of Ca2+ in the dark. The yield of this Ca-induced Mn signal is optimum at a ratio of 2 Mn/PSII, and saturates with increasing [Ca2+] >/= 8 mM, exhibiting a calcium dissociation constant of KD = 1.4 mM. The EPR signal of the Ca-induced Mn center at 25 K is asymmetric with major g value of approximately 2.04 (DeltaHpp = 380 G) and a shoulder near g approximately 3.1. It also exhibits resolved 55Mn hyperfine splitting with separation DeltaHpp = 42-45 G. These spectral features are diagnostic of a variety of weakly interacting Mn2(II, II) pairs with electronic spins that are magnetic dipolar coupled in the range of intermanganese separations 4.1 +/- 0.4 A, and commonly associated with one or two carboxylate bridges. The calcium requirement for induction of the Mn2(II,II) signal matches the value observed for steady-state O2 evolution (Michaelis constant, KM approximately 1.4 mM), and for light-induced assembly of the WOC by photoactivation. The Ca-induced Mn2(II,II) center is a more efficient electron donor to the photooxidized tyrosine radical, TyrZ+, than is the mononuclear Mn center present in the absence of Ca2+. The Ca-induced Mn2(II,II) signal serves as a precursor for photoactivation of the functional WOC and is abolished by the presence of Mg2+. Formation of the Mn2(II,II) EPR signal by addition of Ca2+ correlates with reduction of flash-induced catalase activity, indicating that calcium modulates the accessibility or reactivity of the Mn2(II,II) core with H2O2. We propose that calcium organizes the binding site for Mn ions in the apo-WOC protein and may even interact directly with the Mn2(II,II) pair via solvent or protein-derived bridging ligands.     

Neoglycoproteins with the synthetic complex biantennary nonasaccharide or its alpha 2,3/alpha 2,6-sialylated derivatives: their preparation, assessment of their ligand properties for purified lectins, for tumor cells in vitro, and in tissue sections, and their biodistribution in tumor-bearing mice

Neoglycoproteins were prepared with chemoenzymatically synthesized complex biantennary N-glycan derivatives the nonreducing ends of which bear typical sequences found in glycoproteins. A chemically obtained biantennary heptasaccharide-azide was reduced and acylated with a 6-aminohexanoyl spacer. Elongation of the deprotected heptasaccharide using glycosyltransferases yielded a biantennary nonasaccharide with terminal galactose residues and two undecasaccharides terminating with alpha 2,6- or alpha 2,3-linked sialic acid. The free amino group of the spacer of these oligosaccharides was converted into an isothiocyanate. Its subsequent coupling to bovine serum albumin gave neoglycoproteins with a yield of 2.4-3.6 glycan chains per carrier molecule. This versatile synthetic pathway allows employment of a wide variety of complex-type glycans, which can be introduced to various test systems in vitro and in vivo to evaluate potential biomedical applications. Solid-phase assays with biotinylated sugar receptors revealed discriminatory binding properties of the three neoglycoproteins, especially for the mistletoe lectin. This direct assay system is preferable to the measurement of inhibitory capacities with respect to model ligands. Ligand type- and cell type-dependent quantitative differences in the binding properties of the probes were detected by FACScan analyses with a panel of tumor cell lines and by monitoring of staining in tissue sections for small cell and non-small-cell lung cancer and mesotheliomas. Biodistribution of iodinated neoglycoproteins in mice gave a prolonged presence of the sialylated probes in serum. Relative to the nonasaccharide, the uptake, especially of the iodinated neoglycoprotein with alpha 2,3-sialylated ligand chains, was clearly elevated in mice for kidneys and Ehrlich tumors. On the basis of the documented feasibility of these applications, it is concluded that the further elaboration of glycan chain variants by the described synthetic approach in combination with the given test panel is warranted to evaluate the potential of complex glycan chain-carrying neoglycoproteins for diagnostic and therapeutic purposes.     

Evaluation of propolis (II): effects of Brazilian and Chinese propolis on histamine release from rat peritoneal mast cells induced by compound 48/80 and concanavalin A

Patients suffering from rheumatoid arthritis (RA) may experience a temporary reduction of disease symptoms during pregnancy. As indicated by the occurrence of RA-disease symptoms during pregnancy, three categories of patients were defined, namely, remission, relapse and unchanged. In all three categories changes in the plasma level and glycosylation of alpha1-acid glycoprotein (AGP) were determined longitudinally in comparison to those occurring in pregnancy of healthy women. In healthy pregnancy, we observed: (i) a peak in the plasma concentration at week 18 and a minimum at week 30; (ii) a continuous increase in the degree of branching of the glycans during the entire pregnancy period, and (iii) a decrease in the degree of alpha3-fucosylation of AGP-glycans with a minimum occurring at week 25. Comparable pregnancy-induced changes in glycosylation were found for two other acute-phase proteins alpha1-protease inhibitor (PI) and alpha1-antichymotrypsin (ACT). Increased oestrogen levels, known to occur during pregnancy, may be one of the factors that induce these changes, because the increased branching and decreased alpha3-fucosylation is in agreement with our earlier findings regarding an involvement of this hormone in the regulation of acute phase protein glycosylation in oestrogen-treated males as well as females. In all three clinical categories in RA, pregnancy also induced a continuous increase in the degree of branching of the glycans of AGP. However, similar changes in concentration and fucosylation were only found during remission of the disease symptoms. In the relapse and unchanged categories in RA, the degree of fucosylation and the plasma concentration of AGP remained constant throughout pregnancy. This indicates a relationship between changes in alpha3-fucosylation of AGP and RA disease activity.