Prolongation of allograft survival by administration of mAb specific for the three subunits of IL-2 receptor

Both p15 and p16 are tumor suppressor genes that have 5' CpG islands; aberrant cytosine methylation of these islands has been associated with silencing of their expression. Deoxycytidine kinase (dCK) converts prodrugs to their cytotoxic form, has a 5' CpG island and is a candidate gene for inactivation by hypermethylation. In our study, we used sodium bisulfite sequencing to generate high resolution maps of 5-methylcytosine in the CpG islands associated with p15, p16 and dCK in normal human bone marrow (BM), peripheral blood lymphocytes (PBL) and cytosine arabinoside (ara-C)-resistant acute myeloid leukemia (AML) patients, and established human hematopoietic tumor cell lines. In normal cells the p15, p16 and dCK CpG islands were largely unmethylated. The p16 and dCK CpG islands were also unmethylated in the 8 AML specimens. In contrast, the p15 CpG island was aberrantly methylated in 6 of the 8 AML specimens. Furthermore, bisulfite sequencing revealed that the p15 CpG island is heterogeneously methylated in AML, with large intra-individual and inter-individual variability.     

Inhibition of NO synthesis induces inflammatory changes and monocyte chemoattractant protein-1 expression in rat hearts and vessels

We recently showed that chronic inhibition of NO synthesis by N(omega)-nitro-L-arginine methyl ester (L-NAME) causes coronary vascular remodeling (ie, vascular fibrosis and medial thickening) in rats. To test the hypothesis that the inhibition of NO synthesis induces inflammatory changes in the heart, we characterized the inflammatory lesions that occurred during L-NAME administration and determined whether inflammation involved the induction of monocyte chemoattractant protein-1 (MCP-1) in vivo. During the first week of L-NAME administration to Wistar-Kyoto rats, we observed a marked infiltration of mononuclear leukocytes (ED1-positive macrophages) and fibroblast-like cells (alpha-smooth muscle actin-positive myofibroblasts) into the coronary vessels and myocardial interstitial areas. These inflammatory changes were associated with the expression of proliferating cell nuclear antigen and MCP-1 (both mRNA and protein). The areas affected by inflammatory changes, as well as the expression of MCP-1 mRNA, declined after longer (28 days) treatment with L-NAME and were replaced by vascular and myocardial remodeling. Our results support the hypothesis that the inhibition of NO synthesis induces inflammatory changes in coronary vascular and myocardial tissues and involves MCP-1 expression. Results also suggest that the early stages of inflammatory changes are important in the development of later-stage structural changes observed in rat hearts.     

Mathematical Analysis of the Solidification Behavior of Plain Steel Based on Solute- and Heat-Transfer Equations in the Liquid–Solid Zone

An analytical approximate solution to non-linear solute- and heat-transfer equations in the unsteady-state mushy zone of Fe-C plain steel has been obtained, assuming a linear relationship between the solid fraction and the temperature of the mushy zone. The heat transfer equations for both the solid and liquid zone along with the boundary conditions have been linked with the equations to solve the whole equations. The model predictions (e.g., the solidification constants and the effective partition ratio) agree with the generally accepted values and with a separately performed numerical analysis. The solidus temperature predicted by the model is in the intermediate range of the reported formulas. The model and Neuman’s solution are consistent in the low carbon range. A conventional numerical heat analysis (i.e., an equivalent specific heat method using the solidus temperature predicted by the model) is consistent with the model predictions for Fe-C plain steels. The model presented herein simplifies the computations to solve the solute- and heat-transfer simultaneous equations while searching for a solidus temperature as a part of the solution. Thus, this model can reduce the complexity of analyses considering the heat- and solute-transfer phenomena in the mushy zone.     

Endothelium-dependent relaxation of collateral microvessels after intramuscular gene transfer of vascular endothelial growth factor in a rat model of hindlimb ischemia

BACKGROUND: Recent investigations have demonstrated the ability of vascular endothelial growth factor (VEGF) to augment the development of collateral arteries in vivo. In vitro studies have suggested that the use of VEGF also improves the endothelium-dependent relaxation of collaterals at the microvascular level. The purpose of this study was to determine in vivo the extent to which vasomotor responses of collateral microvessels are altered after VEGF treatment. METHODS AND RESULTS:Ischemia was induced in the hindlimb of 35 rats by excision of the femoral artery. Immediately thereafter, 400 microg of a plasmid encoding VEGF or ss-galactosidase (control) was transfected into limb muscles. Four weeks later, synchrotron radiation microangiography, with a spatial resolution of 30 microm, was performed to document the reactivity of collateral microvessels. Administration of the endothelium-dependent vasodilator acetylcholine failed to induce dilation of collateral microvessels in control animals. By contrast, profound dilation of collaterals was observed after acetylcholine in VEGF-treated animals. This response was evident in vessels with a linear appearance but not in those with an undulating appearance. The resulting blood flow in the ischemic limb after administration of acetylcholine in the control animals was only 64.6+/-17.0% of that of the contralateral normal limb, whereas blood flow was augmented to 106.1+/-8.4% in VEGF-treated animals (P<0.05). CONCLUSIONS: These results demonstrate in vivo that the use of VEGF restores impaired vasomotor responses in some types of collateral microvessels, which may help to provide a basis for understanding the microcirculation after therapeutic angiogenesis with VEGF.     

Visual experience influences 12-month-old infants' perception of goal-directed actions of others.

In the present study, we investigated whether infants' own visual experiences affected their perception of the visual status of others engaging in goal-directed actions. In Experiment 1, infants viewed video clips of successful and failed goal-directed actions performed by a blindfolded adult, with half the infants having previously experienced being blindfolded. The results showed that 12-month-old infants who were previously blindfolded preferred to look longer at the demonstrator's successful actions, whereas no such preference was observed in 8-month-old infants. In Experiment 2, infants watched the same 2 actions when the adult demonstrator was not blindfolded. The responses of 12-month-old infants were the opposite of those observed in Experiment 1: They showed a preference for the failed actions. These findings suggest that previous experience influenced the subsequent perception of others' goal-directed actions in the 12-month-old infants. We favor the interpretation that the preference for the successful actions in the 12-months-old infants provided with blindfolded experience demonstrates the influence of perceptual experience on considering the visual status of others engaging in goal-directed actions. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Effects of thiols on prostaglandin synthesis in bovine bladder epithelium

Immunoaffinity chromatography was shown to be the method achieving the most complete elimination of antigenic admixtures from leukocyte interferon preparations without the loss of the preparation activity. An affinity sorbent has been developed on the basis of covalently linked polyvinyl alcohol (PVA). The immobilization of the antigen-specific rabbit globulin in the preparation of the sorbent is achieved by reaction of protein amino groups with the activated matrix. The proposed sorbent achieved the elimination of the antigenic admixtures from interferon preparations as effectively as those prepared on the basis of sepharose 4B, the productivity of the purification process being at least 5 times higher. The proposed sorbent is stable at the limit values of rH, is not destroyed by detergents, is sterilized in the process of preparation. Owing to the strong linkage of the immobilized immunoglobulin with the PVA-carrier, immunoaffinity chromatography on this sorbent does not involve contamination of the preparations with rabbit globulin allergenic for man. The combination of a large pore structure, wetting ability, stiffness, mechanical and chemical stability allows the proposed sorbent to be recommended for use in modern large-scale biotechnological production.     

Effect of High Magnetic Fields on the Charge–Density–Wave State in NbSe3

We present a systematic study on a large magnetoresistance in NbSe₃ as a function of temperature under various pressures. The large magnetoresistance below T _c2 is observed as long as the T _c2-CDW phase exists. However, when the T _c2-CDW phase is suppressed totally by high pressure and the superconducting phase is induced at the same time, no anomaly, including the large magnetoresistance, is induced by a magnetic field up to 12 T. The origin of the large magnetoresistance is discussed by considering normal carriers on the ungapped Fermi surface created on the CDW transition and comparing this magnetoresistance with the pressure-induced magnetoresistance that is newly observed above T _c2.     

Viewer,converter and preprocessor for smart machining process using an industrial robot

In this paper, viewer and converter softwares are presented for smart machining process using an industrial robot. The viewers for NC, CLS, DXF and STL files illustrate their surface representation with normal direction vectors. For example, the DXF is a data format developed by Autodesk to realize data interoperability among different makers’ CAD systems. The STL means Stereolithography which is a file format proposed by 3D Systems and recently is supported by many design tools and CAD/CAM softwares. In addition, the converters for DXF and STL files generate the corresponding CLS files with normal direction vectors for machining. Further, the proposed preprocessor allows the developed machining robot to work based on information included in STL files. The convenience and user-friendliness of the proposed integrated system are confirmed through experiments of viewing, converting and machining.     

Suppression of the coupled-bunch instability in the SPring-8 storage ring

The bell-shaped single-cell cavities used in the SPring-8 storage ring are devised to suppress the coupled-bunch instabilities arising from the coupling impedances associated with higher-order mode resonances. The inner structures of the cavities are designed to have low longitudinal or transverse shunt impedances of the higher-order modes. The cavities are provided with a systematic modification of inner structures of the cavities and with multiple movable plungers to shift the resonant frequencies of higher-order modes thereby preventing higher-order mode resonances from being excited.     

Local expression of C-type natriuretic peptide markedly suppresses neointimal formation in rat injured arteries through an autocrine/paracrine loop

BACKGROUND: In vivo gene transfer into injured arteries may provide a new means to facilitate molecular understanding of and to treat the intractable fibroproliferative arterial diseases. Selection of an optimal molecule to be transferred will be a key to successful gene therapy in the future. We tested the hypothesis that a secreted multifactorial molecule should act more efficiently through an autocrine/paracrine loop to suppress neointimal formation elicited in injured arteries than a simple growth-inhibiting molecule that might be expressed inside cells. METHODS AND RESULTS: We constructed an adenoviral vector (AdCACNP) expressing C-type natriuretic peptide (CNP), a secreted stimulator of membrane-bound guanyl cyclase. AdCACNP directs cells to secrete large quantities of biologically active CNP. Serum-stimulated DNA synthesis and cell proliferation were only moderately suppressed in arterial smooth muscle cells infected with AdCACNP in vitro. However, when AdCACNP was applied to balloon-injured rat carotid arteries in vivo, neointimal formation was markedly reduced (90% reduction) in an infection-site-specific manner without an increase in plasma CNP level. CONCLUSIONS: Our results showed that CNP, a secreted multifactorial molecule, was indeed effective in suppressing fibroproliferative response in injured arteries and suggest that the potent antiproliferation effect may not be the most critical factor for the effective suppression of neointimal formation. An adenovirus-mediated expression of CNP could be an effective and site-specific form of molecular intervention in proliferative arterial diseases.