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)     

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.     

Photoprotection of Mammalian Acid-Soluble Collagen by Cuttlefish Sepia Melanin In Vitro

Several important clinical conditions can result in close association between the pigment melanin and dermal collagen. Because melanin and its precursors can be chemically reactive in ground and excited states, it is important to know whether the resulting melanin-collagen interaction results in photoprotection or photoaggression. Acidic and neutral air-saturated collagen suspensions (0.033%) were irradiated with0–2.6 times 104 J/m2 UVC or with0–83 times 104 J/m2 solar-simulating UV radiation (SSR). Photochemical destruction of a photolabile collagen fluorophore (δ_em 360 nm) and collagen chain degradation were monitored as functions of irradiation time in the presence and absence of added (0–100μg) sepia eumelanin. Melanin retarded collagen photodamage but did not qualitatively alter the fluorescence fading kinetics. Both H202 and 02 can be produced by UV irradiation of eumelanin. Added H202 and K02 destroyed collagen fluorescence and caused 50% chain degradation at ca10–20-fold molar excess. Previous studies have demonstrated that eumelanins efficiently scavenge 02 . We demonstrated that eumelanin also efficiently scavenges H202 as evidenced by its ability to (a) compete with scopoletin for peroxide uptake and (b) directly take up H202 through a dialysis bag. The latter observation suggests that peroxide scavenging could occur in vivo by melanin sequestered in melanophages. Thus, neither UV-generated 02 nor H202 are likely to be present in concentrations high enough to cause measurable collagen damage. Absorption and/or scattering of excitation radiation away from the target chromophore appears to be the primary photoprotection mechanism, although scavenging of active 02 intermediates may play an important, if subtle role.     

The Scale-Adaptive Simulation Method for Unsteady Turbulent Flow Predictions. Part 2: Application to Complex Flows

The paper summarises the validation activity performed with the Scale-Adaptive Simulation turbulence model (SAS model) using the two commercial CFD solvers, ANSYS-FLUENT and ANSYS-CFX. Both the KSKL-SAS and the SST-SAS model variants have been tested, although most cases have been computed with the second. The turbulence-resolving capability of the SAS method has been validated with a representative set of test cases, covering both underlying generic flows as well as practical engineering applications. In addition to the purely aerodynamic flows with massive separation and heat transfer they include also such physical phenomena as turbulent combustion and aeroacoustics. The illustrating results show the potentials of the SAS approach for industrial flow simulations. Most of the test case simulations were conducted during the recent EU project “DESider”.     

PHOTOCHEMISTRY OF HEPARIN-ACRIDINE ORANGE COMPLEXES IN SOLUTION: PHOTOCHEMICAL CHANGES OCCURRING IN THE DYE AND POLYMER ON FLUORESCENCE FADING

Abstract— Photolysis of acridine-orange-heparin complexes in N₂- and O₂-saturated solution results in permanent photooxidation of AO with little or no concomitant change in the heparin moiety. The major photoproduct is mono- N -demethylated acridine orange; in O₂-saturated solution an additional minor oxygenated product, most likely the 10-oxide (N-oxide) or the 9-acridanone (acridone) is also formed. The results suggest an intermolecular electron transfer between adjacently adsorbed dye molecules. The heparin moiety plays a significant role in the photochemistry by bringing dye molecules into favorable geometric orientation for biomolecular reaction and by means of specific dye-polymer interactions.     

Transition Modelling for General Purpose CFD Codes

The paper addresses modelling concepts based on the RANS equations for laminar-turbulent transition prediction in general-purpose CFD codes. Available models are reviewed, with emphasis on their compatibility with modern CFD methods. Requirements for engineering transition models suitable for industrial CFD codes are specified. A new concept for transition modeling is introduced. It is based on the combination of experimental correlations with locally formulated transport equations. The concept is termed LCTM – Local Correlation-based Transition Model. An LCTM model, which satisfies most of the specified requirements is described, including results for a variety of different complex applications. An incremental approach was used to validate the model, first on 2D flat plates and airfoils and then on to progressively more complicated test cases such as a three-element flap, a 3D transonic wing and a full helicopter configuration. In all cases good agreement with the available experimental data was observed. The authors believe that the current formulation is a significant step forward in engineering transition modeling, as it allows the combination of transition correlations with general purpose CFD codes. There is a strong potential that the model will allow the 1st order effects of transition to be included in everyday industrial CFD simulations.     

Application of the SAS turbulence model to predict the unsteady flow field behaviour in a forward centrifugal fan

In the current study, the unsteady flow in a centrifugal fan is carried out using Computational Fluid Dynamics calculation based on the Scale Adaptive Simulation (SAS) approach to model the turbulence phenomenon. The SAS concept is based on the introduction of the von Karman length scale into the turbulence scale equation. The information provided by the von Karman length scale allows SAS models to dynamically adjust to resolved structures in an Unsteady Reynolds-Averaged Navier–Stokes (URANS) simulation, which results in a Large Eddy Simulation-like behaviour in unsteady regions of the flow field. At the same time, the model provides standard RANS capabilities in stable flow regions. The introduction of the von Karman length scale is based on the reformulation of Rottas's equation for the integral length scale. To validate the numerical results, the overall performances of the fan and the wall pressure fluctuations computed upon the volute casing surface are compared with the unsteady measured data.     

Real‐Time Interrogation of Aspirin Reactivity,Biochemistry, and Biodistribution by Hyperpolarized Magnetic Resonance Spectroscopy

Hyperpolarized magnetic resonance spectroscopy enables quantitative, non‐radioactive, real‐time measurement of imaging probe biodistribution and metabolism in vivo. Here, we investigate and report on the development and characterization of hyperpolarized acetylsalicylic acid (aspirin) and its use as a nuclear magnetic resonance (NMR) probe. Aspirin derivatives were synthesized with single‐ and double‐¹³C labels and hyperpolarized by dynamic nuclear polarization with 4.7 % and 3 % polarization, respectively. The longitudinal relaxation constants (T₁) for the labeled acetyl and carboxyl carbonyls were approximately 30 seconds, supporting in vivo imaging and spectroscopy applications. In vitro hydrolysis, transacetylation, and albumin binding of hyperpolarized aspirin were readily monitored in real time by ¹³C‐NMR spectroscopy. Hyperpolarized, double‐labeled aspirin was well tolerated in mice and could be observed by both ¹³C‐MR imaging and ¹³C‐NMR spectroscopy in vivo.     

Real‐Time Interrogation of Aspirin Reactivity,Biochemistry, and Biodistribution by Hyperpolarized Magnetic Resonance Spectroscopy

Hyperpolarized magnetic resonance spectroscopy enables quantitative, non‐radioactive, real‐time measurement of imaging probe biodistribution and metabolism in vivo. Here, we investigate and report on the development and characterization of hyperpolarized acetylsalicylic acid (aspirin) and its use as a nuclear magnetic resonance (NMR) probe. Aspirin derivatives were synthesized with single‐ and double‐¹³C labels and hyperpolarized by dynamic nuclear polarization with 4.7 % and 3 % polarization, respectively. The longitudinal relaxation constants (T₁) for the labeled acetyl and carboxyl carbonyls were approximately 30 seconds, supporting in vivo imaging and spectroscopy applications. In vitro hydrolysis, transacetylation, and albumin binding of hyperpolarized aspirin were readily monitored in real time by ¹³C‐NMR spectroscopy. Hyperpolarized, double‐labeled aspirin was well tolerated in mice and could be observed by both ¹³C‐MR imaging and ¹³C‐NMR spectroscopy in vivo.