Expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases in adenocarcinoma cell lines

The levels of mRNA expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases (GalNAc-transferases) were quantified for human adenocarcinoma cell lines from pancreas, colon, stomach, and breast. Two of the GalNAc-transferases, GalNAc-T1 and GalNAc-T2, were expressed constitutively and at low levels in most or all cell lines examined. A third GalNAc-transferase, GalNAc-T3, was differentially expressed. Well-differentiated adenocarcinoma cell lines expressed high levels and moderately differentiated cell lines expressed lower levels of GalNAc-T3. Cell lines classified as poorly differentiated failed to express GalNAc-T3 mRNA at levels that could be detected by Northern blot analysis. Differential expression of the GalNAc-T3 protein was confirmed in these cell lines by Western blotting. We propose that glycosylation in tumor cell lines may be regulated in part by differential expression of GalNAc-transferases, and we suggest that GalNAc-T3 gene expression may be a molecular indicator of differentiated adenocarcinoma.     

THERMODYNAMICS OF ASPHALTENE PRECIPITATION AND DISSOLUTION INVESTIGATION OF TEMPERATURE AND SOLVENT EFFECTS

Petroleum asphaltenes have been precipitated in solvent mixtures of n-heptane and toluene at various temperatures, likewise n-heptane asphaltenes have been dissolved in under similar conditions. This give added evidence to apparent hysteresis phenomenon between the two processes. The Asphaltenes have been characterized showing that although data is scattered convergence to certain structural parameters as incipient flocculation is approached. The asphaltenes are seen to consist of an associating and a non-associating part. The solubility of asphaltenes has been correlated/modelled using the Flory-Huggins equation using two different terms for the Flory parameter. A process for evaluation of best choice of solubility parameter and molar volume for the asphaltenes is proposed. Dissolution processes are seen to be best fitted by the equations. Based on these findings the asphaltenes are proposed to be formed by a colloidal and a true solution part.     

一类专家模型参考自适应控制

本文将专家系统技术和模型参考自适应控制相结合，提出了一种新的基于专家系统模型参考自适应控制，该系统集智能控制思想与专家技术于一身，从而得到很强的控制律，为验证其有效性，以两关节机器人为对象进行仿真，在有负载扰动情况下，该系统能使机器人跟踪上希望轨迹，其系统响应和鲁棒性优于常规的控制算法。     

Effects of citrate on the different phases of calcium oxalate crystallization

Urinary citrate appears to be an important factor in the crystallization process of calcium oxalate and calcium phosphate. The urinary excretion of citrate was found to be significantly lower in patients with calcium oxalate stone disease as compared with normal subjects, and about 30 per cent of the calcium stone formers can be considered as hypocitraturic. The lowest excretion of citrate was recorded in urine collected during the night. Citrate has significant effects on supersaturation with respect to both calcium oxalate and calcium phosphate, it also inhibits the growth of these crystals. In addition, citrate appears to be capable of inhibiting the aggregation of crystals composed of calcium oxalate, brushite, and hydroxyapatite. The heterogenous growth of calcium oxalate on calcium phosphate is also counteracted by citrate. As a consequence of the crucial role of citrate in these processes, stone prevention with alkaline citrate has become an attractive form of treatment in patients with recurrent stone formation. Single evening dose administration of sodium potassium citrate resulted in an of sodium potassium citrate resulted in an increased excretion of citrate, reduced levels of the calcium/citrate ratio as well as supersaturation with respect to calcium oxalate and a decreased rate of stone formation. However, conflicting results of stone preventive treatment with alkaline citrate have been reported by different groups, and long-term follow-up of patients treated in a randomized way is necessary to definitely assess the efficacy of alkaline citrate.     

Microstructure-Property Correlation in AI_4C_3 Dispersion Strengthened Al Composite

The microstructure and tensile properties of Al_4C_3 dispersion strengthened Al composite fabricatedby reaction milling technique were investigated.It is indicated that the rod-like Al_4C_3 dispersoidshaving a diameter of 0.02-0.03 μm and a length of 0.1-0.3μm are formed by reaction of C with Al,and uniformly distributed in the Al matrix.The interface between Al_4C_3 and Al is clean and theinterfacial bonding is good.The matrix consists of the subgrains which have the size of 0.3-0.4μm,and most of the Al_4C_3 dispersoids are distributed on the subgrain boundaries.The 11 vol.-%Al_4C_3/Al composite exhibits an UTS (ultimate tensile strength) of 400 MPa and anelongation-to-failure of 8.0%.     

Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7

Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease.     

Engagement of T cell receptor triggers its recruitment to low-density detergent-insoluble membrane domains

T-cell receptors (TCRs) upon binding to peptide-MHC ligands transduce signals in T lymphocytes. Tyrosine phosphorylations in the cytoplasmic domains of the CD3 (gammadeltaepsilon) and zeta subunits of the TCR complex by Src family kinases initiate the signaling cascades via docking and activation of ZAP-70 kinase and other signaling components. We examined the role of the low-density detergent-insoluble membranes (DIMs) in TCR signaling. Using mouse thymocytes as a model, we characterized the structural organization of DIMs in detail. We then demonstrated that TCR engagement triggered an immediate increase in the amount of TCR/CD3 present in DIMs, which directly involves the engaged receptor complexes. TCR/CD3 recruitment is accompanied by the accumulation of a series of prominent tyrosine-phosphorylated substrates and by an increase of the Lck activity in DIMs. Upon TCR stimulation, the DIM-associated receptor complexes are highly enriched in the hyperphosphorylated p23 zeta chains, contain most of the TCR/CD3-associated, phosphorylation-activated ZAP-70 kinases and seem to integrate into higher order, multiple tyrosine-phosphorylated substrate-containing protein complexes. The TCR/CD3 recruitment was found to depend on the activity of Src family kinases. We thus provide the first demonstration of recuitment of TCR/CD3 to DIMs upon receptor stimulation and propose it as a mechanism whereby TCR engagement is coupled to downstream signaling cascades.     

trans-2-phenylcyclopropylamine is a substrate for and inactivator of horseradish peroxidase

Horseradish peroxidase (HRP) is well known for mediating the electron-transfer oxidation of electron-rich aromatic 'donors' such as phenols and anilines, but has not been described to oxidize aliphatic amines. We here confirm the inability of HRP to oxidize typical aliphatic amines, even those which would exist significantly as free bases at the operative pH. In contrast, trans-2-phenylcyclopropylamine (2-PCPA) is both a substrate (turnover product is cinnamaldehyde) and a time-dependent inactivator of HRP. These activities of 2-PCPA are consistent with either a concerted or rapid sequential one-electron-oxidation/ring-opening to give an intermediate capable of covalent binding to the enzyme. 2-PCPA is the first known example of a simple aliphatic amine which serves as a substrate for HRP under turnover conditions.