The aditi deductive database system

Deductive databases generalize relational databases by providing support for recursive views and non-atomic data. Aditi is a deductive system based on the client-server model; it is inherently multi-user and capable of exploiting parallelism on shared-memory multiprocessors. The back-end uses relational technology for efficiency in the management of disk-based data and uses optimization algorithms especially developed for the bottom-up evaluation of logical queries involving recursion. The front-end interacts with the user in a logical language that has more expressive power than relational query languages. We present the structure of Aditi, discuss its components in some detail, and present performance figures.     

Cardiovascular effects of conventional sulfonylureas and glimepiride

Sulfonylureas have, in the past, been reported to have adverse cardiovascular effects. Glimepiride is a new sulfonylurea. In spite of stimulating less insulin secretion, it has, depending on the species, equal or higher blood glucose decreasing activity and according to preliminary studies less cardiovascular activity than glibenclamide. Further studies were performed to confirm the lower cardiovascular activity of glimepiride. The IC50 for inhibition of rilmakalim-activated KATP channel currents in isolated ventricular myocytes was 31.6 nM for glimepiride and 6.8 nM for glibenclamide. In endotoxin shock-rats at a dose of 1 x 2 mg/kg i.v., glibenclamide induced a significantly higher blood pressure increase than glimepiride. At two i.v. doses of 20 mg/kg 4 min apart, in normal rats, glibenclamide produced signs of ischemia in the ECG in nearly all animals, glimepiride almost none, in diabetic rats, glibenclamide produced in all animals a lethal cardiogenic shock preceeded by serious ECG changes, glimepiride only in one fifth of the animals. In open-chest dogs, on intracoronary infusion of equieffective blood glucose-lowering doses, glibenclamide, gliclazide and glimepiride all reduced coronary blood flow, increased coronary resistance, depressed the mechanical activity of the heart, enhanced myocardial O2-extraction, reduced the serum potassium level and induced a moderate endocardial ST-segment elevation, but glimepiride to a significantly less extent than glibenclamide and gliclazide. The presented data confirm that glimepiride at equivalent blood glucose decreasing doses has less cardiovascular activity than conventional sulfonylureas.     

Linkages between spouses' psychological distress and marital conflict in the home.

To elucidate the processes that underlie the established association between psychopathology and marital functioning, researchers have given attention to how symptomatic individuals manage their interpersonal contexts, particularly during the handling of disagreements. In the current study, the authors evaluate the role of marital conflict strategies in relation to wives' and husbands' psychological distress levels. A sample of 100 community-based couples completed assessments of psychological distress and diaries describing marital conflict that occurred at home during a 15-day reporting period. Findings from multilevel modeling of dyadic data revealed associations between both spouses' psychological distress and multiple behavioral and emotional conflict expressions in the home. Psychological symptoms uniquely predicted the occurrence of certain conflict expressions, even when accounting for global negative marital sentiments. The findings encourage subsequent consideration of marital conflict expressions and resolution strategies when studying processes involved in the marriage-psychological adjustment link. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

(R,R)-2,2'-[1,2-ethanediylbis[imino(1-methyl-2,1-ethanediyl)]]- bis[5-nitro-1H-benz[de]isoquinoline-1,3-(2H)-dione] dimethanesulfonate (DMP 840), a novel bis-naphthalimide with potent nonselective tumoricidal activity in vitro

(R,R)-2,2'-[1,2-ethanediylbis[imino(1-methyl-2,1-ethanediyl)]]- bis[5-nitro-1H-benz[de]isoquinoline-1,3-(2H)-dione] dimethanesulfonate (DMP 840), is a bis-naphthalimide anticancer tumoricidal agent currently in phase I clinical trials. DMP 840 exhibits curative activity in human tumor xenografts, where it shows selectivity for human solid tumors over murine leukemias. In contrast to the selectivity found for DMP 840 in vivo, DMP 840 exhibits potent antiproliferative activity in vitro against a variety of human and murine leukemia and solid tumor cell lines in culture, with inhibitory doses that reduce the number of treated cells to one half (IC50) values ranging from 2.3 to 53 nM. DMP 840 was growth inhibitory to three doxorubicin-resistant cell lines with IC50 values also in the nanomolar range. Clonogenic survival experiments showed that DMP 840 was equally cytotoxic to both exponentially growing and quiescent human clone A colon carcinoma cells. A 1-h incubation of DMP 840 (1.22-12 microM) caused 5-log cell kill in KB-3-1 human epidermoid carcinoma, clone A human colon carcinoma, and L1210 murine leukemia cell lines. The rapid cell killing by DMP 840 in clonogenic survival experiments and initial mechanism of action studies was consistent with a DNA-interactive mechanism for DMP 840 cytotoxicity. Mechanism of action studies in L1210 leukemia cells demonstrated that DMP 840 inhibited the incorporation of thymidine and uridine into DNA and RNA with IC50 values of 0.55 and 0.08 microM, respectively. DMP 840 produced DNA single-strand breaks in a dose-dependent manner. Double-strand breaks were not observed with DMP 840 treatment, even at higher concentrations of compound. Chinese hamster ovary (CHO) and P388 cells resistant to camptothecin and containing a mutant form of topoisomerase I were also used to evaluate whether DMP 840 was cross-resistant with agents active against topoisomerase I. While the CHOR line was 163-fold resistant to camptothecin, the CHOR line was only 1.7-fold resistant to DMP 840. In summary, DMP 840 is a DNA-interactive agent that demonstrates excellent antiproliferative activity in vitro against cultured tumor cells from both human and murine sources. Its mechanism of tumoricidal activity may be novel.     

Structure-oriented rational design of chymotrypsin inhibitor models

Three peptides modelling a highly potent, 35-residue chymotrypsininhibitor (Schistocerca gregaria chymotrypsin inhibitor) weredesigned and synthesized by convergent peptide synthesis. Foreach model peptide, the inhibitory constant (K_i) on chymotrypsinand the solution structure were determined. In addition, moleculardynamics calculations were performed for all of them. Two modelscontaining approximately half of the parent inhibitor (17 of35 residues) were designed and subsequently found to have nosubstantial inhibitory activity (K_i values in the mM range).The third model composed of 24 amino acid residues proved tobe an effective (K_i 10^–7) inhibitor of bovine chymotrypsin.Both the solution structure properties determined by NMR spectroscopyand the dynamic behaviour of the latter model system are comparableto the native inhibitor. In contrast, the structure and dynamicsof the first two related model peptides show characteristicdifferences. We suggest that the conformation and flexibilityof the modelled protease inhibitor are crucial for its biologicalefficiency. Moreover, the structural and dynamic features ofthe binding loop (28–33) and those of the rest of themolecule appear to be interdependent. Most importantly, thesestructural characteristics can be rationally modified, at leastpartially, by peptide design. Received March 7, 2003; revised August 25, 2003; accepted August 26, 2003.     

Adenosine triphosphate (ATP) and other nucleotides stimulate the hydrolysis of phosphatidylethanolamine in intact fibroblasts

Addition of adenosine triphosphate (ATP) to [¹⁴C]ethanolamine-prelabeled NIH 3T3 fibroblasts resulted in rapid formation of [¹⁴C]ethanolamine from the prelabeled cellular phosphatidylethanolamine (PtdEtn) pool. After 2-min exposure, 10 μM ATP had near maximal effects on PtdEtn hydrolysis. Several other nucleotides, including UTP, ITP, and the stable ATP analog adenosine 5′-O-(3-thiotriphosphate) (ATPγS), also had stimulatory effects on PtdEtn hydrolysis with a potency comparable to that observed with ATP. The same nucleotides which acted on PtdEtn hydrolysis also had similar stimulatory effects on the hydrolysis of phosphatidylcholine (PtdCho) in [¹⁴C]choline-labeled cells. In isolated membranes, Mg²⁺ greatly enhanced the stimulatory effects of ATP and ATPγS, but not of other nucleotides, on the hydrolysis of PtdEtn and PtdCho. Results indicate that in isolated membranes, both ATP and ATPγS stimulate phospholipid hydrolysis by two different mechanisms, but in intact cells only one of these mechanisms appears to be responsive to externally added nucleotides.     

Determination of trace manganese and Ni in neem oil by ETA-AAS with emulsion sample introduction

An emulsion-based method was developed as an alternative for the introduction of oil-based samples into a graphite furnace to produce a more rapid, precise, and accurate method of analysis. The combination of emulsion sampling and electrothermal atomization for atomic absorption spectroscopy was developed and then applied to the determination of Ni and manganese in neem oil from Venezuela. The optimal concentration of neem oil in the emulsion was 30 and 4% for Ni and Mn, respectively, based on the metal concentration of the neem oil. The stability of the emulsion as a function of time was evaluated. The use of aqueous calibration solutions and the accuracy attained using this method make it attractive for the analysis of oil samples. The metal recovery was between 97 and 101%. Based on the emulsion method, the neem oil samples had 1.39 and 0.21 mg of Mn and Ni per kg of oil, respectively. The wet digestion method indicated a Mn and Ni concentration in the neem oil sample of 1.42 and 0.24 mg/kg, respectively.