Rearrangement densification in liquid-phase sintering

Grain rearrangement has a significant role in sintering densification when a liquid phase forms. Although grains may change shape, bringing the grain centers closer to each other and producing overall densification, this contribution is slow and localized to the grain contacts regions. On the other hand, the movement of individual grains through capillary force effects can provide a burst of rapid densification. To describe the spatial grain arrangement quantitatively, a new parameter is proposed, termed the grain-arrangement factor. An increase in the grain-arrangement factor indicates the microstructure is packing to a higher density. Analysis of the relations between this factor and other microstructure parameters provides an indirect method to measure the state of grain arrangement in liquid-phase sintering. Experiments performed on a tungsten heavy alloy show that the grain-arrangement factor mainly depends on the solid volume fraction and the dihedral angle.     

Rearrangement of immunoglobulin genes in chicken B cell development

Immunoglobulin gene rearrangement in the chicken has evolved not to generate antibody diversity per se but to generate an immunoglobulin variable region which can be diversified by subsequent somatic gene conversion events. While the molecular mechanism of V(D)J recombination in chickens cannot be distinguished from that seen in other species, the way in which this recombination is regulated during chicken B lymphocyte development does differ from the more widely known models of gene rearrangement in humans and rodents. In this review we focus on these differences, relating V(D)J recombination to the progression of chicken B cell development in the bursa of Fabricius.     

环己酮肟液相重排工艺危险性分析

国内己内酰胺生产中环己酮肟液相重排反应主要分为溶剂法和非溶剂法.通过时两种工艺装置中的物料和工艺危险性进行分析,表明两种重排反应工艺危险区别主要在于:溶剂法中正己烷溶剂可能导致燃爆危险,非溶剂法中水泄漏将导致失控反应.为己内酰胺的重排装置的安全稳定运行提出建议.     

Rearrangement of the histone H2A C-terminal domain in the nucleosome

Using zero-length covalent protein-DNA crosslinking, we have mapped the histone-DNA contacts in nucleosome core particles from which the C- and N-terminal domains of histone H2A were selectively trimmed by trypsin or clostripain. We found that the flexible trypsin-sensitive C-terminal domain of histone H2A contacts the dyad axis, whereas its globular domain contacts the end of DNA in the nucleosome core particle. The appearance of the histone H2A contact at the dyad axis occurs only in the absence of linker DNA and does not depend on the absence of linker histones. Our results show the ability of the histone H2A C-terminal domain to rearrange. This rearrangement might play a biological role in nucleosome disassembly and reassembly and the retention of the H2A-H2B dimer (or the whole octamer) during the passing of polymerases through the nucleosome.     

Conversion of tyrosine to phenolic derivatives by Taiwan cobra venom

We have examined the ability of Taiwan cobra (Naja naja atra) venom to transform in vitro the amino acid tyrosine to phenolic oxidation products via 4-hydroxyphenylpyruvate. This amino acid can be released from neuropeptide substrates by oligopeptidases present in the venom. Using a variety of analytical techniques to probe a complicated series of reactions, we confirm that the L-amino acid oxidase present in the venom initially releases the keto form of 4-hydroxyphenylpyruvic acid and hydrogen peroxide after reacting with the tyrosine. Thereafter, there is evidence that a tautomerase in the venom promotes a partial conversion of the keto-form 4-hydroxyphenylpyruvic acid into an enol form. The enol is oxidised primarily to 4-hydroxybenzaldehyde and 4-hydroxyphenol (hydroquinone). The keto form is oxidised through to 4-hydroxyphenylacetic acid by the hydrogen peroxide co-released by the L-amino acid oxidase. The venom promotes both these spontaneous oxidation routes and also generates traces of other phenolics, some of which are as yet unidentified. We propose that reactions between the precursors of the major oxidation products may be responsible for generating unusual short-lived phenolics, possibly giving rise to special bioactivities that are relevant to venom action.     

Rearrangement of T-cell receptor delta/gamma genes: application to the study of clonality in childhood B-lineage acute lymphoblastic leukaemia

DNA-based PCR with various sets of primers for T-cell receptor gamma/delta (TCR gamma/delta) chain genes was used to study clonality in childhood B-lineage acute lymphoblastic leukaemia. TCR delta genes rearrangements were the most common and were observed in 77 patients (64.2%). The typical pattern of rearrangements was defined as an incomplete V delta 2 to D delta 3 or to D delta 2 recombination product. Rearrangements of TCR gamma genes were observed in 61 cases (50.8%). Predominantly, TCR gamma genes rearrangements were detected in null-ALL and the early B-ALL (55.2% and 60%, respectively) and were rather rare in other groups. From all eight V segments of V gamma l group rearrangements concerned mostly regions V gamma 2, V gamma 4 and V gamma 7. We have confirmed that TCR gamma and delta genes amplification provides a rapid, sensitive method for assessing clonality in ALL almost in 100%.     

Binding of uracil derivatives to hydrophobic peptides and sodium dodecyl sulfate

The capacities of five hydrophobic peptides to bind 13 alkyl uracil derivatives have been assessed as a first step toward constructing polymeric molecules, related to the nucleic acids, that specifically complement protein molecules. The peptides were Phe-Phe-Phe-Glu-Glu and its structural analogs with leucine, isoleucine, methionine, and valine substituted for phenylalanine. Uracils with the following substituents in position 5' were used: i-propyl, i-butyl, i-pentyl, sec-butyl, n-butyl, phenyl, benzyl, phenylethyl, methylthioethyl, ethylthiomethyl, and ethylthioethyl. 6-Benzyl and 6-i-pentyl uracils were also tested. The variations in base binding patterns are unique for each peptide, and the general effectiveness of the peptides in binding is related to the order in which their hydrophobic amino acid constituents occur in the uracil column of the genetic codon table. Although the method used does not permit precise determination of binding constants, it is apparent that many of them are much lower than 1 mM. 5-Ethylthioethyluracil quite selectively forms a large metastable aggregate with Phe3Glu2. Its close homologues do not. Also, 5-ethylthioethyluracil binds in some measure to Met3Glu2 but not significantly to Ile3Glu2 and Val3Glu2, whereas its homologue, 5-ethylthiomethyluracil, binds better to the latter two than to Met3Glu2. Thus, the two homologues might serve to form hypothetical polymers that discriminatively bind polymers of isoleucine and valine. It is argued that evolution would most reasonably have begun with such crude mechanisms.     

Adjuvant activity of muramyl dipeptide derivatives to enhance immunogenicity of a hantavirus-inactivated vaccine

The adjuvant effect of two lipophilic derivatives of muramyl dipeptide (MDP), B30-MDP and MDP-Lys(L18), on the ability of an inactivated vaccine of B-1 virus (B-1 vaccine) to induce immune response against Hantavirus causing hemorrhagic fever with renal syndrome (HFRS) was examined. When mice were immunized subcutaneously (s.c.) twice at 2-week intervals with B-1 vaccine admixed with or without 100 micrograms mouse-1 of B30-MDP (B-1/B30-MDP) or MDP-Lys(L18) [B-1/MDP-Lys(L18)], mice immunized with B-1/B30-MDP as well as B-1/MDP-Lys(L18) showed significantly higher indirect fluorescent antibody (IFA) titers against HFRS virus than mice immunized with B-1 vaccine alone. Both mice treated with B-1/B30-MDP and B-1/MDP-Lys(L18) also exhibited significantly higher neutralizing antibody titers against HFRS virus than mice immunized with B-1 vaccine alone during 3-9 weeks after the primary immunization. The evaluation of antibody-producing cells by enzyme-linked immunospot (ELISPOT) assay on week 4 revealed that both MDP derivatives enhanced the number of HFRS virus-specific IgG1 and IgM antibody-producing cells. Furthermore, mice treated with B-1/B30-MDP as well as B-1/MDP-Lys(L18) showed a higher level of Th-2 type cytokines, IL-4 and IL-6, in sera than mice treated with B-1 alone. In an in-vitro analysis of T lymphocyte proliferation to baculovirus-expressed recombinant nucleocapsid protein (rNP) of Hantaan 76-118 strain, the splenocytes of mice treated with B-1/B30-MDP and B-1/MDP-Lys(L18) on week 4 showed a significantly higher proliferating activity than those treated with B-1 vaccine alone. In addition, when mice were immunized once with B-1 vaccine admixed with or without B30-MDP and MDP-Lys(L18) and followed by intrafootpad (i.f.) injection of B-1 vaccine on day 7, mice immunized with B-1/B30-MDP and B-1/MDP-Lys(L18) induced a higher delayed-type hypersensitivity (DTH) reaction than mice immunized with B-1 vaccine alone. These results suggest that B30-MDP and MDP-Lys(L18) are useful immunoadjuvants to enhance the ability of inactivated B-1 vaccine to induce a humoral and cellular response to HFRS virus.     

Comparative binding studies of cyclophilins to cyclosporin A and derivatives by fluorescence measurements

The interaction of cyclosporin A and cyclosporin derivatives with cyclophilins A, B, and C has been investigated by means of fluorescence measurement techniques. Since Trp-121 of cyclophilin A is in close contact with bound cyclosporins and changes its fluorescence emission upon binding, direct estimation of Kd values for cyclosporins is straightforward in this case. Cyclophilins B and C, however, display no evident binding-dependent fluorescence changes suitable for the estimation of their binding affinities. This problem can be circumvented by measuring the variations of fluorescence emission intensities of a mixture of cyclophilin A and the fluorescence measurements unsuitable for cyclosporin binder as a function of ligand concentration. Application of a mixed-mode kinetic analysis then allows the calculation of the cyclosporin binding affinity of the second binder in the system. The dissociation constant for cyclosporin A/cyclophilin A was found to be 36.8 nM. Mixed-mode kinetic calculations yielded Kd values of 9.8 and 90.8 nM for cyclophilins B and C, respectively. The analysis was extended to noncyclophilin (weak) cyclosporin binders such as calmodulin and actin, resulting in approximate Kd values of 1.2 and 5.7 microM, respectively. Using the same approach, the Kd values of a series of different cyclosporin derivatives were determined.     

Serotonergic ergoline derivatives

Novel classes of 13- and 14-tertbutyl-ergoline derivatives were prepared, and characterised in vitro for their affinity for adrenergic, dopaminergic and serotonergic binding sites. This study particularly examines the importance of the presence and the position of the tert-butyl group in conferring either significant 5-HT1A or 5-HT2 affinity and selectivity respectively.     

Radioiodinated estrogen derivatives

Monoiodohexestrol exhibits 10 to 15% specific binding to the 8S estrogen receptor while the remainder binds to nonreceptor 4S proteins. Reduction of nonreceptor binding with either thyroxine or 8-anilino-1-naphthalene sulfonic acid was not quantitative. Thus no accurate determination of the concentration of receptor sites in the radioreceptor assay was possible by graphical analysis. Two additional estrogens--17 alpha [125I]iodoethynylestradiol and 17 alpha-[125I]iodoethynyl-11 beta-methoxy estradiol--were synthesized at high specific activity. Although the iodoethynyl derivatives were stable under synthetic conditions, deiodination in the presence of proteins is too fast to allow either in vivo or in vitro use. To make these compounds clinically useful, therefore, chemical modification to reduce nonreceptor binding and the rate of dehalogenation must be undertaken.     

Increased resistance to streptolysin O in mammalian cells treated with oxygenated derivatives of cholesterol

L-cell fibroblast cultures were treated with certain oxygenated derivatives of cholesterol which are known to inhibit cholesterol biosynthesis in mammalian cells. After incubation in the presence of 20-alpha-hydroxycholesterol or 25-hydroxycholesterol for 18 h, the cells became increasingly resistant to streptolysin O. Maximum resistance to toxin was obtained by incubation for 48 h in 0.5 microgram of 20-alpha-hydroxycholesterol or 0.25 microgram of 25-hydroxycholesterol per ml; under these conditions, the cells were 10 to 50 times more resistant than were untreated controls. The ability of the hydroxycholesterol compounds to render the cells resistant was related to the age of the cultures. Maximum protection was found when more sparsely populated cultures were treated with 25-hydroxycholesterol. Older, heavily populated cultures could not be protected even with the high concentrations of 25-hydroxycholesterol. In contrast to control cultures, most of the toxin activity remained in the medium after being incubated with hydroxycholesterol-treated cultures. The results indicate that less toxin binds to the resistant cells and suggest that a reduction in membrane cholesterol content may account for resistance to streptolysin O.     

Photocytotoxicity of water-soluble fullerene derivatives

New water-soluble fullerene carboxylic acids (1 and 2) derived from C60 and C70 fullerenes, respectively, were examined for photocytotoxicity toward Raji cells (B lymphocyte). These compounds did not show any photocytotoxic effect even at 50 microM, while pheophorbide a showed significant photocytotoxicity at 0.5 microM. Therefore, fullerene derivatives derived from C60 and C70 would not be practical agents for photodynamic therapy.     

Pyran derivatives. XX. 2-Aminochromone benzo-fused derivatives with antiproliferative properties

The N-substituted 2-aminochromones 1 and their benzo-fused derivatives 2-4 described herein were mostly prepared by treating the corresponding (methylthio) derivatives 10-13 with an excess of the proper amines. Only the morpholino derivatives 3d and 4c were obtained from the reaction of the ethyl 3-morpholino-3-oxopropanoate/POCl3 reagent with 1-naphthol or 1-methyl-2-naphthol, respectively. The amino derivatives 1-4, as well as their methylthio analogues 10-13, were tested in vitro for their inhibitory activity on the infectivity of T2 bacteriophage, on the macromolecular synthesis in Ehrlich cells and on the clonal growth capacity of HeLa cells. Several of the angular or linear aminonaphthopyranones 2 and 3 or 4, respectively, and the (methylthio) derivatives 10, 11 and 13 induced a significant inhibition of DNA synthesis, but usually a clearly lower inhibition of clonal growth. Only the linear 2-amino-10-methyl-4H-naphtho[2,3-b]pyran-4-ones 4a and 4b significantly inhibited the clonal growth in HeLa cells and T2 bacteriophage infectivity, respectively.