Pharmacological distribution diagrams: a tool for de novo drug design

BACKGROUND: There is no empirical data available on attitudes concerning AIDS and habits towards HIV infected patients of physicians in general or private practice. In this study results of a self-evaluation are presented. METHODS: 178 physicians working with out-patients in different medical fields were randomly selected for a cross sectional study and interviewed using a standardised questionnaire. RESULTS: 89% think that they are sufficiently informed about AIDS (in the USA 20%). They regarded the risk of infection to be lower than the Anglo-American physicians. They believed there is a lack of interchange of information between colleagues regarding the degree of infectiousness of referred patients. A third of the physicians fear that other patients will go elsewhere if they find out that their physician is treating AIDS patients. 54% would hold special clinic sessions for HIV-patients outside the normal schedule for practice times. 89% believed that HIV patients were partly to blame for their illness. CONCLUSIONS: Although the physicians recognise the problem of HIV-infection, they partly deny the real necessities and facts. A reason for this could be the emotions underlying the general attitude to everything pertaining to HIV-disease. Attitudes to HIV-disease and the dealing with it in daily practice must be considered on the basis of individual emotional motives.     

Oscillation of the scattering time in a 2D electron system with oval antidots

Electron scattering by a single barrier is predicted to reveal singularities as the magnetic field is changed, because the number of electron collisions with the barrier dramatically increases as chaotic orbits around the barrier are changed into periodic orbits. To test this experimentally we have measured the magnetoresistance of AlGaAs/GaAs heterostructures with a two-dimensional electron gas and a lateral lattice containing a macroscopic number of oval-shaped antidots fabricated using electron lithography. Reproducible fluctuations in the magnetoresistance are observed at low field, which are due to the oscillations of the number of electron collisions with the antidots. The number of collisions N before the electron escapes from the antidot has been calculated as a function of B in an electric field. The position of the maxima in N(B) obtained from calculations and experiment are in reasonable agreement.     

Structural characterization of the cyanelle peptidoglycan of Cyanophora paradoxa by 252Cf plasma desorption mass spectrometry and fast atom bombardment/tandem mass spectrometry

A strategy for the structural characterization of the four major NaBH4-reduced peptidoglycan monomers derived from muramidase-digested peptidoglycan from the cyanelles of the flagellate Cyanophora paradoxa Korschikoff is described. Initial molecular weight determination of these glycopeptides was performed by positive and negative ion plasma desorption mass spectrometry. Due to the presence of two pairs of disaccharide tripeptide and disaccharide tetrapeptide monomers differing in mass by 112 units, respectively, an as yet unknown peptidoglycan modification either at the carbohydrate or at the peptide moiety was assumed. beta-Elimination of the disaccharide unit from the unreduced peptidoglycan monomers yielded the corresponding (modified) N1-lactyltripeptides and -tetrapeptides, respectively. These peptides, N-terminally blocked with lactic acid, unambiguously showed the modification to be located on the peptide moiety. By positive ion fast atom bombardment/hybrid tandem mass spectrometry of the reduced peptidoglycan monomers as well as of the corresponding deglycosylated monomers (= N1-lactylpeptides) the modification was determined to be linked to the glutamic acid moiety. Based on combined data from plasma desorption mass spectrometry, tandem mass spectrometry, accurate mass measurement and amino acid analysis of the acid hydrolysate after derivatization with o-phthaldialdehyde by high-performance liquid chromatography we could establish the structure of the modification as N-acetylputrescine. Finally, the confirmation of the linkage of the glutamic acid to diaminopimelic acid via the gamma-COOH was based on the presence of a-type peptide backbone fragment ions in the positive ion plasma desorption mass spectra of the modified N1-lactylpeptides.     

Positive identification of the specificity of polymerase chain reaction product

A method of positive identification of the specificity of polymerase chain reaction (PCR) product using internal oligonucleotide probe is introduced. The hybridization was done on the agarose gel which was dried after electrophoresis. Detection of the expression of T cell receptor a chain variable (TCR V alpha) genes on mRNA level was used as the experimental model. Twenty nine TCR V alpha gene subfamilies could be distinguished clearly in healthy human peripheral blood lymphocytes by this method. Positive identification of PCR product on dried agarose gel by internal oligonucleotide probe is relatively simple and less time consuming.     

Evidence for a synergistic interaction between isoprenaline and timolol on intraocular pressure in conscious rabbits

1. Interaction between topical isoprenaline and timolol on intraocular pressure was studied in conscious rabbits through changes of the dose-response curves. 2. Both drugs caused a dose-dependent fall of intraocular pressure mainly by reducing the aqueous humour formation. 3. When combined, timolol increased the response to submaximal concentrations of isoprenaline as well as EC50 (from 2.06 x 10(-3) M to 3.63 x 10(-3) M) and slope (from 1.21 to 1.89), but peak response to isoprenaline remained unchanged. 4. Discordance between experimental and theoretical additive curves as well as an interaction index smaller than 1 show that the interaction between both drugs is synergistic.     

Executing algorithms with hypercube topology on torusmulticomputers

Many parallel algorithms use hypercubes as the communication topology among their processes. When such algorithms are executed on hypercube multicomputers the communication cost is kept minimum since processes can be allocated to processors in such a way that only communication between neighbor processors is required. However, the scalability of hypercube multicomputers is constrained by the fact that the interconnection cost-per-node increases with the total number of nodes. From scalability point of view, meshes and toruses are more interesting classes of interconnection topologies. This paper focuses on the execution of algorithms with hypercube communication topology on multicomputers with mesh or torus interconnection topologies. The proposed approach is based on looking at different embeddings of hypercube graphs onto mesh or torus graphs. The paper concentrates on toruses since an already known embedding, which is called standard embedding, is optimal for meshes. In this paper, an embedding of hypercubes onto toruses of any given dimension is proposed. This novel embedding is called xor embedding. The paper presents a set of performance figures for both the standard and the xor embeddings and shows that the latter outperforms the former for any torus. In addition, it is proven that for a one-dimensional torus (a ring) the xor embedding is optimal in the sense that it minimizes the execution time of a class of parallel algorithms with hypercube topology. This class of algorithms is frequently found in real applications, such as FFT and some class of sorting algorithms     

Large-bandwidth frequency conversion in high-NA step index opticalfibers

Using high-NA step index optical fibers, we show, theoretically, that large-bandwidth second-harmonic generation and sum frequency generation can be achieved at conversion frequencies in the visible region of the spectrum