B7 blockade prevents activation-induced cell death of thymocytes

Although both B7 and its counter-receptor CD28 are expressed in the thymus, the role of B7 in thymic selection is not clear. We investigated the role of B7 in intrathymic deletion of antigen-specific T cells using a TCR transgenic model specific for antigen ovalbumin (OVA) and H-2Ad. Intraperitoneal injection of OVA induced apoptosis of thymocytes and drastic reduction of thymocyte numbers. This was significantly inhibited by co-injection of CTLA-4-Ig which blocks B7 co-stimulation. Deletion of T cells in the thymus following i.p. injection of OVA was associated with T cell pre-activation as demonstrated by T cell proliferation and cytokine production. Injection of CTLA-4-Ig blocked all these activation events and rescued thymocytes from activation-induced cell death. These results demonstrate that B7 is required for the activation-induced cell death of MHC class II-restricted thymocytes in vivo.     

Potency comparison of peptidomimetic inhibitors against HIV-1 and HIV-2 proteinases: design of equipotent lead compounds

The results of investigation of haptoglobin (Hp) types in 596 donor blood samples in some towns of Ukraine (Dnepropetrovsk, Kharkov, Odessa, Kiev, Uzhgorod, Zhitomir) are presented. Three normal Hp types (Hp1-1, Hp2-1 and Hp2-2) have been found. The reliable interpopulation differences in the Hp types frequency were not found. On the whole the Hp types frequency in the type Hp1-1 comprised 12.7%. In the type Hp2-1-48.1% and in the type Hp2-2-36.5%. The frequency of the gene Hp1 is 0.38. The frequency of the Hp types and of the gene Hpl in Ukraine is similar to that in population of Eastern Europe and European Part of Russia.     

The two steps of group II intron self-splicing are mechanistically distinguishable

The two transesterification reactions catalyzed by self-splicing group II introns take place in either two active sites or two conformations of a single active site involving rearrangements of the positions of the reacting groups. We have investigated the effects on the rates of the chemical steps of the two reactions due to sulfur substitution of nonbridging oxygens at both the 5' and 3' splice sites as well as the deoxyribose substitution of the ribose 2' hydroxyl group at the 5' splice site. The data suggest that the two active sites differ in their interactions with several of these groups. Specifically, sulfur substitution of the pro-Sp nonbridging oxygen at the 5' splice site reduces the chemical rate of the step one branching reaction by at least 250-fold, whereas substitution of the pro-Sp oxygen at the 3' splice site has only a 4.5-fold effect on the chemical rate of step two. Previous work demonstrated that the Rp phosphorothioate substitutions at both the 5' and 3' splice sites reduced the rate of both steps of splicing to an undetectable level. These results suggest that either two distinct active sites catalyze the two steps or that more significant alterations must be made in a single bifunctional active site to accommodate the two different reactions.     

On the ontological expressiveness of information systems analysis and design grammars

Abstract. Information systems analysis and design (ISAD) methodologies provide facilities for describing existing or conceived real-world systems. These facilities are ontologically expressive if they are capable of describing all real-world phenomena completely and clearly. In this paper we formally examine the notion of the ontological expressiveness of a grammar and discuss some of its implications for the design and use of ISAD methodologies. We identify some generic ways in which ontological expressiveness may be undermined in a grammar and some potential consequences of these violations. We also examine ontological expressiveness within the context of some other desirable features that might be considered in the design of ISAD methodologies.     

Prognostic significance of cathepsin-D in patients with breast cancer

The expression of the protease cathepsin-D has been evaluated using an immunohistochemical technique with a polyclonal antibody in paraffin-embedded tissue from 359 patients treated between the years 1975-1981 for Stage I and II breast cancer. One hundred and twenty seven patients (35%) have strongly positive, granular staining, 138 (38%) are intermediately stained in the cytoplasm, and in 94 (26%) no staining is observed. There is a strong positive association between expression of cathepsin-D and the presence of tumour in axillary lymph nodes (P < 0.006). Expression of the protease is associated with significantly poorer survival of patients in univariate analysis (P = 0.025); however, this is not independent of other tumour variables.     

Dynamic effects in hot-carrier degradation relevant for CMOS operation

We describe different dynamic degradation effects in n- and p-MOSFETs as they are clearly proven and generally accepted to date. It turns out that they are connected with time constants in the oxide and at the interface and that time constants related to the device operation are too short to be relevant in this context. The effects are detrapping of fixed charges, the slow movement of holes in the oxide, an enhanced-degradation effect caused by alternating voltage conditions, during dynamic stress, and a post-stress interface state formation effect in nitride passivated n-MOSFETs. Furthermore, we discuss the relevance of those effects, under different operation conditions, finding that the fast non-stationary effects are of little significance. Only the “slow” effects, with time constants of seconds and above, play a role in reliability issues of MOSFETs.