Unsteady axisymmetric stagnation flow on a circular cylinder

Unsteady, axisymmetric stagnation flow about a circular cylinderis examined when the far-field flow is a periodic function oftime with a fixed time average and an oscillatory part of prescribedamplitude and frequency. Solutions are computed for arbitraryvalues of the Reynolds number, quantifying the effects of surfacecurvature, and a frequency parameter based on the period ofthe far-field flow. It is found that solutions remain regularand periodic provided that the far-field amplitude lies belowa critical value. Above this value, solutions terminate in afinite-time singularity. The blow-up time is delayed by increasingthe curvature of the surface. These results are corroboratedby asymptotic predictions valid in the limits of small and largeamplitude and frequency. For large Reynolds number, the problemreduces to the two-dimensional stagnation-point flow againsta plane wall studied by previous authors.     

PHOTOBIOLOGICAL ACTIVITY OF 3,4''-DIMETHYL-8-METHOXYPSORALEN, A LINEAR FUROCOUMARIN WITH UNUSUAL DNA-BINDING PROPERTIES

The furocoumarin derivative 3,4'-dimethyl-8-methoxypsoralen (DMe-8-MOP) exhibits remarkable antiproliferative activity, but is devoid of skin phototoxicity. To gain insight into this peculiar behaviour we investigated non-covalent and covalent binding of DMe-8-MOP to calf thymus DNA, along with DNA-synthesis inhibition and mutagenic activity. The non-covalent interaction of DMe-8-MOP with the nucleic acid is quite poor as shown by equilibrium dialysis, spectroscopic, chiroptical and hydrodynamic techniques. However, it exhibits relevant photobinding ability to DNA using both isolated nucleic acid samples and cellular systems. Unlike the large majority of congeners, DMe-8-MOP undergoes predominantly photochemical monoaddition to the double helical polynucleotide. Upon examination of the products obtained by enzymatic hydrolysis of DMe-8-MOP photomodified DNA, the formation of an unusual furan side adduct is proposed, which could account for the peculiar photochemical and photobiological properties of the 3,4'-dimethyl furocoumarin derivative.     

Synthesis of novel 1,4‐dihydropyrido[3′,2′:5,6]thiopyrano[4,3‐c]‐pyrazoles and 5H‐pyrido[3′,2′:5,6]thiopyrano[4,3‐d]pyrimidines as potential antiproliferative agents

The synthesis of new planar derivatives characterized by the presence of a pyridothiopyranopyrazole or pyridothiopyranopyrimidine nucleus, carrying a substituted aryl group, is reported. The novel 1,4‐dihydropyrido[3′,2′:5,6]thiopyrano[4,3‐c]pyrazole derivatives were obtained by condensation of 2,3‐dihydro‐3‐hydroxymethylenethiopyrano[2,3‐b]pyridin‐4(4H)‐ones with appropriate hydrazines. The preparation of 2‐substituted pyrido[3′,2′:5,6]thiopyrano[4,3‐d]pyrimidines was accomplished from the intermediate 2,3‐dihy‐dro‐3‐dimethylaminomethylenethiopyrano[2,3‐b]pyridin‐4(4H)‐ones by reaction with the appropriate binucleophile amidines. The antiproliferative activity of some new products was tested by an in vitro assay on human tumour cell lines (HL‐60 and HeLa), but none of them showed any significant effects in the tests performed. Accordingly, linear flow dichroism measurements indicated their inability to form a molecular complex with DNA.     

KINETIC ANALYSIS OF THE PHOTOREACTION (365 nm) BETWEEN PSORALEN AND DNA

Abstract— Psoralen complexed with DNA under irradiation at 365 nm forms monofunctional and bifunctional adducts with pyrimidine bases of DNA. while the fraction of psoralen which remains free in the aqueous solution forms photodimer and photooxidation products. We havc studied the photoreaction betwecn psoralen and DNA from a kinetic point of view. Only some products of this photoreaction could be measured quantitatively. Thus. in order to present a picture of the overall photoreaction. we have represented this by a mathematical model consisting of a system of seven differential equations. Utilizing all the experimental data that it was possible to obtain. we were able to estimate rate constants for formation of all photoproducts. From the general picture thus obtained. we conclude that monofunctional adducts are formed in a four to one ratio to bifunctional adducts. Among the monofunctional photoproducts. 3,4-cycloadducts occur with a higher yield than 4',5'-cycloadducts. The combined rate constant of formation of photodimer and photooxidation products of psoralen is small. indicating that they are marginal by-products relative to the cycloadducts formed in the photoreactions with DNA.     

PHOTOREACTIONS AT 3655Å BETWEEN PYRIMIDINE BASES AND SKIN-PHOTOSENSITIZING FUROCOUMARINS

Abstract After irradiation at 3655 Å of an aqueous frozen solution containing thymine and psoralen, a new photocompound was isolated by column chromatography. It contains a furocoumarin and a pyrimidine-moiety linked together by the formation of a cyclobutane ring (see formulas II and III). By irradiation at 2537 Å in acetic acid solution, the photocompound breaks up again yielding psoralen and thymine. From an aqueous frozen solution containing cytosine and psoralen irradiated at 3655 Å, an analogous photocompound was obtained, which, however, consists of the addition to psoralen of a uracil molecule, instead of a cytosine one (IV, V). It has been stated that the hydrolytic deamination of the cytosine moiety to the uracil one takes place during the working up of the photocompound in aqueous solution after irradiation. Substances with properties similar to those above were obtained from bergapten (5-methoxy-psoralen) and thymine, from psoralen and thymidine or thymidylic acid, irradiated at 3655 Å.
The new substances may be considered as model compounds in explaining the photoreactions which take place between the skin-photosensitizing furocoumarins and DNA upon irradiation at 3655 Å.     

Polyethylene glycol matrix reduces the rates of photochemical and thermal release of nitric oxide from S-nitroso-N-acetylcysteine

S -nitrosothiols have many biological activities and may act as nitric oxide (NO) carriers and donors, prolonging NO half-life in vivo. In spite of their great potential as therapeutic agents, most S -nitrosothiols are too unstable to isolate. We have shown that the S -nitroso adduct of N -acetylcysteine (SNAC) can be synthesized directly in aqueous and polyethylene glycol (PEG) 400 matrix by using a reactive gaseous (NO/O₂) mixture. Spectral monitoring of the S–N bond cleavage showed that SNAC, synthesized by this method, is relatively stable in nonbuf-fered aqueous solution at 25°C in the dark and that its stability is greatly increased in PEG matrix, resulting in a 28-fold decrease in its initial rate of thermal decomposition. Irradiation with UV light (λ= 333 nm) accelerated the rate of decomposition of SNAC to NO in both matrices, indicating that SNAC may find use for the photogeneration of NO. The quantum yield for SNAC decomposition decreased from 0.65 ± 0.15 in aqueous solution to 0.047 ± 0.005 in PEG 400 matrix. This increased stability in PEG matrix was assigned to a cage effect promoted by the PEG microenvironment that increases the rate of geminated radical pair recombination in the homolytic S–N bond cleavage process. This effect allowed for the storage of SNAC in PEG at −20°C in the dark for more than 10 weeks with negligible decomposition. Such stabilization may represent a viable option for the synthesis, storage and handling of S -nitrosothiol solutions for biomedical applications.     

BENZOFUROCOUMARINS: NEW MONOFUNCTIONAL DNA-PHOTOBINDING AGENTS

Abstract— The tetracyclic furocoumarin 2H-benzofuro[3,2-g]-1-benzo-pyran-2-one and its 4 and/or II methyl analogues have been investigated in their DN A-photobinding properties. Spectrophotometric and radioactivity measurements show that these compounds exhibit prominent ability to bind to the polynucleotide double helix by covalent photoaddition of the furocoumarin 3,4 double bond.
Denaturation-renaturation experiments demonstrate that no cross-link of DNA chains occurs. Benzopsoralens can thus be considered as a new class of monofunctional DNA-photobinding agents.     

An independent component analysis-based approach on ballistocardiogram artifact removing

Interest about simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data acquisition has rapidly increased during the last years because of the possibility that the combined method offers to join temporal and spatial resolution, providing in this way a powerful tool to investigate spontaneous and evoked brain activities. However, several intrinsic features of MRI scanning become sources of artifacts on EEG data. Noise sources of a highly predictable nature such as those related to the pulse MRI sequence and those determined by magnetic gradient switching during scanning do not represent a major problem and can be easily removed. On the contrary, the ballistocardiogram (BCG) artifact, a large signal visible on all EEG traces and related to cardiac activity inside the magnetic field, is determined by sources that are not fully stereotyped and causing important limitations in the use of artifact-removing strategies. Recently, it has been proposed to use independent component analysis (ICA) to remove BCG artifact from EEG signals. ICA is a statistical algorithm that allows blind separation of statistically independent sources when the only available information is represented by their linear combination. An important drawback with most ICA algorithms is that they exhibit a stochastic behavior: each run yields slightly different results such that the reliability of the estimated sources is difficult to assess. In this preliminary report, we present a method based on running the FastICA algorithm many times with slightly different initial conditions. Clustering structure in the signal space of the obtained components provides us with a new way to assess the reliability of the estimated sources.