DOSE-RESPONSE OF CHRONIC ULTRAVIOLET EXPOSURE ON EPIDERMAL FORWARD SCATTERING-ABSORPTION IN SK-1 HAIRLESS MOUSE SKIN

This work provides a dose-response model of UV-induced epidermal-stratum corneum thickening induced by irradiation at wavelength lambda. This model assumes that photobiochemical reaction(s) can give rise to hyperplasia in a manner which is predictable from a simple photochemical kinetic scheme. In this work, we derive an equation which predicts an approximately linear relationship between the logarithm of the increase in optical skin thickening measured at 320 nm (delta OD320) and total cumulative dose (DT) seen by the target cells in or near the basal layer. For each excitation wavelength lambda, the slope R(lambda) of the log delta OD320 vs DT plot is proportional to epsilon(lambda) phi rx, where epsilon(lambda) is the extinction coefficient for the target chromophore at excitation wavelength, and phi rx is the quantum yield for the photochemical reaction(s) leading to hyperplasia. Our data previously obtained from irradiation of SK-1 hairless mice with "monochromatic" UV wavebands at 280, 290, 300, 307 and 313 nm (Menter et al., 1988, Photochem. Photobiol. 47, 225-260.) and data from Sterenborg and van der Leun at 254 and 313 nm (1988, Photodermatology 5, 71-82) are in good agreement with this model, except for 254 and 280 nm excitation, which are greatly attenuated by epidermis-stratum corneum. For excitation at the latter wavelengths, "dark" regressive processes successfully compete with the "light" reaction(s) which lead to (pre)cancerous lesion. This difficulty notwithstanding, the "intrinsic" action spectrum for hyperplasia derived from these measurements indicates that the target chromophore preferentially absorbs in the UV-C region.(ABSTRACT TRUNCATED AT 250 WORDS)     

Co-monotone allocations,Bickel-Lehmann dispersion and the Arrow-Pratt measure of risk aversion

For every integrable allocation (X ₁,X ₂, ...,X _n ) of a random endowmentY= _i ^=1/n X _i amongn agents, there is another allocation (X ₁*,X ₂*, ...,X _n *) such that for every 1in,X _i * is a nondecreasing function ofY (or, (X ₁*,X ₂*, ...,X _n *) areco-monotone) andX _i * dominatesX _i by Second Degree Dominance.If (X ₁*,X ₂*, ...,X _n *) is a co-monotone allocation ofY= _i ^=1/n X _i *, then for every 1in, Y is more dispersed thanX _i * in the sense of the Bickel and Lehmann stochastic order.To illustrate the potential use of this concept in economics, consider insurance markets. It follows that unless the uninsured position is Bickel and Lehmann more dispersed than the insured position, the existing contract can be improved so as to raise the expected utility of both parties, regardless of their (concave) utility functions.     

Study of the chromonic liquid-crystalline phases of bis-(N,N-diethylaminoethyl)perylene-3,4,9,10-tetracarboxylic diimide dihydrochloride by polarized optical microscopy and 2H NMR spectroscopy

The chromonic liquid-crystalline properties of bis-(N,N-diethylaminoethyl)perylene-3,4,9,10-tetracarboxylic diimide dihydrochloride in an aqueous solution were investigated by polarized light microscopy and 2H NMR spectroscopy. Both techniques indicate a narrow I + N biphasic region and a broad N phase region at concentrations ranging from approximately 6.9 to approximately 30 wt % at room temperature. Optical microscopy indicates that a hexagonal M phase exists at higher concentrations. The variation of the I --> N + I and N + I --> N transition temperatures with concentration was studied by 2H NMR spectroscopy. Finally, the effects of temperature and concentration on the order parameter of the N phase were investigated by 2H NMR using a tetra-deuterated derivative. A value of 0.97 was obtained for the N phase at its upper concentration limit.     

Adsorption kinetics and electrode processes

Prof. H. A. Laitinen (Urbana):We have used double layer capacity measurements to measure adsorption as a function of time during the life of slowly forming mercury drops. For many substances that are not extremely surface active, so that the solution concentration is 1 to 10 mM, the double layer capacity per unit area is essentially constant during the time interval of 5 to 15 sec of drop life. It appears, therefore, that adsorption equilibrium has essentially been attained during the later portions of drop life.Prof. P. Delahay:We have also used a similar method of following the differential capacity during drop life. I would agree that one can achieve conditions for which adsorption equilibrium with respect to bulk concentration is practically reached (high enough concentration and long drop time). But this is quite often not the case (drop time of 3–4 sec in polarography).Mr. G.C. Whitnack (China Lake, U.S.A.);In determination of nitrate esters in presence of phthalate esters we have observed considerable dropping of current height of nitrate ester wave before start of phthalate ester wave. Is this due to an adsorption process occurring at the DME?Prof. P. Delahay:It might well be, but I would hesitate to comment any further on this point because more information would be required. You probably have quite a complicated situation. Perhaps we can discuss the matter later?Prof. Dr. H. Fischer (Ettingen):Ich möchte hinzufügen, class es Fälle geben kann, in denen mcht allem der Blockierungseffekt don Grenzstrom verringert, sondern eine Veränderung des Diffusionsfilmes durch Sekundärreaktion des Inhibitors. Dies ist z.B. bei der Abscheidung von Wasserstoff an einer festen Elektrode (Fe) der Fall, wenn der Inhibitor sich spaltet in eine schwerlösliche Verbindung und ein Proton (RNH⁺ → [RN] + H⁺). Dies beobachtet man z.B, bei den Kationen von heterozyklischen Aminen (Acridin). Offentlich bildet sich eine diffusionshindernde Barriere aus.Prof. P. Delahay:The case of the hydrogen electrode is complicated, and I shall attempt to answer your question only in the case of an ideally smooth electrode. Then, diffusion toward the electrode (partially covered with an adsorbed substance) is little affected by adsorption because the size of “the holes” in the film is very small in comparison with the diffusion layer thickness. Of course, there is no diffusion where there is complete blocking.Prof. B. Breyer (Sydney):The importance of the chemical nature of the film adsorbed at the interface, which has been mentioned by Prof. delahay, seems to me to play a major part in the type of processes discussed. Thus it must be kept in mind that complex formation between the diachargeable ion and the adsorbed film might occur (cf. e.g. heyrovsky? and matyas, 1941). The fact that T1+ ion is little influenced by the presence of an adsorbed film at the electrode solution interface could then be partly explained by the notoriously low co-ordination tendency of that ion.Prof. P. Delahay:The difficulty involved in the “blocking” of the limiting current for thallium is due, I think, to the small size of this ion (large diffusion coefficient of Tl+ in comparison with other ions). Of course, complex ions can be relatively very bulky and this enhances “blocking”.Prof. E. Lange (Erlangen):I agree with prof. delahay that it is very important to investigate the connections between the adsorption and electrode reaction.This is easy for a steady state, e.g., each heterogeneous reaction between two phases that is accompanied by a transfer of ions or electrons, i.e. of electrical charges, from one phase to the other. In such a case, the Galvani tension does not change and the transfer between the two phases must be compensated by a corresponding transfer of charges within the phases.But in the non-steady state, also, an adsorption process may behave as an “electrode reaction” for instance, even an adsorption of a dipole molecule may cause a “transfer of charge” accompanied by a corresponding change of the Galvani tension. In this manner, it seems to me that for the non-steady state it is necessary to define precisely what one means by “electrode reaction”.Prof. P. Delahay:I entirely agree with Prof. i.ange about the necessity of clear definitions. I think that the fact that a steady state with respect to diffusion of the reductible or oxidizable substance has not been reached is not too serious because this scarcely affects the Galvani potential (large excess of supporting electrolyte).Variations in the amount of adsorbed organic substances indeed affect the Galvani potential (dipole orientation), but this effect is included in the dependence of the rate constant ks (at the standard potential) on the electrode coverage.Prof. N. Tanaka (Sendai, Japan).I am very grateful to Prof. delahay for his beautiful work on adsorption kinetics. I should like to make one comment in connection with the rotated dropping mercury electrode. The relation between log i and log t on the current — time curve was found to be 0.5 only in the absence of the surface-active substance. In the presence of surface-active substance, the slope of log i vs. log t changed at a certain point of the current — time curve. This can be explained when the slow adsorption of the surface-active substance on the surface of the electrode is taken into consideration.Prof. P. Delahay:Even for stirred solutions, adsorption equilibrium is not reached very rapidly. A simple calculation based on a model of the Nernst diffusion layer shows that perhaps 1–5 sec are required. Your conclusion is, therefore, quite correct.Prof. W. Kemula (Warsaw):We have recently published that, in several cases, the addition of extremely small concentrations of organic surface-active substances provokes at first a rise of the diffusion current, this current then being suppressed by additional quantities of the substance.     

On the origin of dynamic instability of molecular systems

The vibronic origin of dynamic instability of molecular systems considered earlier, is here given a more complete and rigorous treatment. It is shown that the nonvibronic contribution to the curvature of the adiabatic potential arising due to nuclear displacements under fixed electronic density distribution, is always positive, and hence the only reason for dynamic instability is the pseudo Jahn-Teller effect. For some examples of special interest (planar equilateral NH₃, planar square CH₄ and linear H ₃ ⁺ ) the molecular excited states, responsible for the instability of the ground state, are revealed by means of ab initio calculations.     

PHOTOCHEMISTRY OF TYPE I ACID-SOLUBLE CALF SKIN COLLAGEN: DEPENDENCE ON EXCITATION WAVELENGTH

Although previous studies have demonstrated that the predominant photochemistry of type I collagen under 254 nm irradiation may be attributed either to direct absorption by tyrosine/phenylalanine or to peptide bonds, direct collagen photochemistry via solar UV wavelengths is much more likely to involve several age- and tissue-related photolabile collagen fluorophores that absorb in the latter region. In this study, we compare and contrast results obtained from irradiation of a commercial preparation of acid-soluble calf skin type I collagen in solution with UVC (primarily 254 nm), UVA (335–400nm) and broad-band solar-simulating radiation (SSR; 290^1–00nm). Excitation spectroscopy and analysis of photochemically induced disappearance of fluorescence (fluorescence fading) indicates that this preparation has at least four photolabile fluorescent chromophores. In addition to tyrosine and L-3,4-dihydroxyphenylalanine, our sample contains two other fluorophores. Chromophore I, with emission maximum at 360 nm, appears to be derived from interacting aromatic moieties in close mutual proximity. Chromophore II, with broad emission at430–435 nm, may be composed of one or more age-related molecules. Collagen fluorescence fading kinetics are sensitive to excitation wavelength and to conformation. Under UVC, chromophore I fluorescence disappears with second-order kinetics, indicating a reaction between two proximal like molecules. Adherence to second-order kinetics is abrogated by prior denaturation of the collagen sample. A new broad, weak fluorescence band at400–420 nm, attributable to dityrosine, forms under UVC, but not under solar radiation. This band is photolabile to UVA and UVB wavelengths. Amino acid analysis indicates significant destruction of aromatic amino acids under UVC, but not under UVA or SSR. When properly understood, collagen fluorescence fading phenomena may act as a sensitive molecular probe of structure, conformation and reactivity.     

Unprecedented eta(1)-P(basal) coordination of P(4)X(3) molecules (X = S, Se). An experimental and theoretical study of the apical vs basal complexation dichotomy

Reaction of [(triphos)Re(CO)(2)(OTf)] (1) [triphos = MeC(CH(2)PPh(2))(3); OTf = OSO(2)CF(3)] with P(4)S(3) and P(4)Se(3) yields pairs of coordination isomers, namely, [(triphos)Re(CO)(2)[eta(1)-P(apical)-P(4)X(3)]](+) (X = S, 2; Se, 5) and [(triphos)Re(CO)(2)[eta(1)-P(basal)-P(4)X(3)]](+) (X = S, 3; Se, 6). The latter represent the first examples of the eta(1)-P(basal) coordination achieved by the P(4)X(3) molecular cage. Further reaction of 2/3 and 5/6 mixtures with 1 affords the dinuclear species [[(triphos)Re(CO)(2)](2)[mu,eta(1:1)-P(apical,)P(basal)-P(4)X(3)]](2+) (X = S, 4; Se, 7) in which the unprecedented M-eta(1)-P(basal)/eta(1)-P(apical)-M' bridging coordination of the P(4)X(3) molecule is accomplished. A theoretical analysis of the bonding properties of the two coordination isomers is also presented. The directionality of apical vs basal phosphorus lone pairs is also discussed in terms of MO arguments.     

Synthesis, binding affinity, and relaxivity of target-specific MRI contrast agents

Although magnetic resonance imaging (MRI) is one of the most important imaging modalities of the central nervous system (CNS), one of the main drawbacks of MRI is its limited specificity. This can potentially be partially alleviated by target-specific contrast agents. In the present paper we describe a simple high yield synthesis of two such gadolinium-based spiperone targeted MRI contrast agents, 1a and 1b. The R₁ relaxivities of 1a and 1b were evaluated and found to be 5.94 and 8.31 mM⁻¹ s⁻¹, respectively at 9.4T, while their R₂ relaxivities at the same magnetic field were found to be 18.05 and 22.60 mM⁻¹ s⁻¹, respectively. In addition and very importantly compound 1a, which is a gadolinium-based, spiperone-targeted MRI contrast agent, was found to preserve some of the spiperone affinity toward the dopamine D2 receptor. Compounds 1a and 1b thus represent potential agents for in vitro dopamine receptor imaging using MRI in experimental models. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

The synthesis of 6,6′-cyclo-6′-deoxyhexofuranosyluracils via a diazomethane-promoted ring-enlargement reaction

The protected 5′-oxo-6,5′-cyclouridine 13 reacts with diazomethane to afford mostly the spiro-epoxide 18 (79%), but it also undergoes ring-expansion to give the corresponding 5′-oxo-6,6′-cyclonucleoside 16. Under the conditions of the reaction, ketone 16 reacts further with diazomethane to give the enol ether 20 (12% overall), the isomeric 4-methoxy nucleoside 15 (2%), and the spiro-epoxide 19 (4.4%). Acid hydrolysis of the enol ether 20 , followed by reduction of the resulting ketone with sodium borohydride, affords a separable mixture of the 5′S (L-talo) and 5′R (D-allo) methylene-bridged cyclonucleosides 7 and 8 , respectively. From proton nmr measurements, it appears that the 6′-methylene groups of these cyclonucleosides project towards the 2′,3′-edge of the furanose ring.