METABOLICALLY CONVERTIBLE LIPOPHILIC DERIVATIVES OF pH-SENSITIVE AMPHIPATHIC PHOTOSENSITIZERS

Abstract We propose the use of acetoxymethyl esters of pH-sensitive amphipathic photosensitizers (PS) for photodynamic therapy (PDT). These compounds may be applicable for PDT involving endocytosis of lipophilic carriers leading to lysosomal uptakc of the esterified PS by target cells. Partial and/or total enzymatic de-esterification may result in the extralysosomal distribution of the photoactive agents, possibly culminating in a multisite photochemical response. We report here the synthesis and properties of chlorin e₆ triacetoxymethyl ester (CAME) and pheophorbide a acetoxymethyl ester (PAME). Chlorin e₆ and pheophorbide a are photocytotoxic chlorins that possess free carboxylate groups and exhibit optimum wavelengths of excitation substantially red shifted relative to hematoporphyrin derivative. Acetoxymethyl esterification of chlorin e₆ and pheophorbide a was accomplished with bromomethyl acetate. High-performance liquid chromatography allowed for the purification of PAME, in 87% purity, and CAME, in 63% yield and 94% purity, as well as the detection of the presumed mono- and diesters of chlorin e₆ as transient intermediates in the synthesis of CAME. The ultraviolet-visible absorption, fluorescence excitation and emission, NMR and mass spectra of the chlorin e₆ tnester are consistent with those expected for CAME. The pH-sensitive amphipathicity of pheophorbide a and chlorin e₆ but not CAME was demonstrated using a water/1-octanol partition assay. The production of pheophorbide a from PAME and the sequential formation of the di- and monoesters and free chlorin e₆ from CAME, by the action of lysosomal esterases obtained from cancer cells, demonstrate the potential of cellular enzymes to convert the lipophilic esters to pH-sensitive amphipathic PS. It is expected that the product of the esterases' action in the acidic lysosome will be hydrophobic and tend to diffuse into the organelle membrane. Contact with the neutral pH of the adjacent cytosol will result in conversion of the PS to a more hydrophilic anionic species, presumably allowing for it lo diffuse into that compartment and partition throughout the lipophilic and aqueous compartments of the cell.     

Influence of the air gap between protective clothing and skin on clothing performance during flash fire exposure

A finite volume model was developed to simulate transient heat transfer in protective clothing during flash fire exposure. The model accounts for the combined conduction-radiation heat transfer in the air gap between the fabric and skin. The variation in the fabric and air gap properties with temperature and the thermochemical reactions in the fabric are also considered. This study investigates the influence of the air gap in protective clothing on the energy transfer through the clothing and hence on its performance. Different parameters that affect the conduction-radiation heat transfer through the air gap such as the air gap absorption coefficient and the air gap width were studied. Finally, the paper demonstrates that an innovative and potentially significant way to improve protective clothing performance is to reduce the emissivity on the backside of the fabric.     

稳态实验考察经模拟道路老化的全配方稀燃Nox捕集催化剂上的Nox还原

Fully formulated lean NOx trap(LNT)catalysts of the type Pt/Rh/BaO/Al2O3 were prepared with and without incorporation of CeO2-ZrO2 in the washcoat,and their NOx reduction behavior was evaluated in steady-state,continuous flow experiments.In the fresh state, the CeO2-ZrO2 addition was found to exert little effect on NOx reduction activity using H2,CO,and NH3 as the reductants.However,after simulated road aging,NOx reduction activity was significantly impaired for the CeO2-ZrO2-free catalyst,whereas the perfo...     

How the Asymmetric Nature of IP Traffic Influences the Cost of the Underlying Optical Layer

In this article the influence of the asymmetric nature of (IP) traffic on the cost of the underlying optical transport network is investigated over a time frame of six years using a realistic traffic forecast for a European fiber-optic network. The currently deployed transport networks contain bidirectional optical line systems and are thus inherently symmetric, although the traffic that has to be conveyed over those networks is asymmetric. This article shows that a cost reduction of up to 38% can be obtained if the bidirectional line systems are replaced by unidirectional ones.     

Orbital contributions to relativistic corrections of the NMR nuclear magnetic shielding tensor originated in scalar field-dependent operators

In this work relativistic corrections to the magnetic shielding constant (σM), which arise from scalar field-dependent operators (both linear and bilinear), are calculated and decomposed into contributions from molecular orbitals (MOs). Numerical results for the magnetic shielding constant of the heavy nucleus X in closed shell atomic ions X^? and HX compounds (X = F, Cl, Br, I) are presented. The relative importance of inner-shell and valence electrons in the definition of each one of these terms is thus assessed and its relation with their sensitivity to changes in a chemical environment is discussed.     

Quantum coherent control of the vibrational dynamics of a polyatomic molecule using adaptive feedback control of a femtosecond laser

We simulate adaptive feedback control to coherently shape a femtosecond infrared laser pulse by means of a 4f-spatial light modulator in order to selectively excite the rovibrational modes of a polyatomic molecule. We preferentially populate an arbitrarily chosen upper rovibrational level by only employing these tailored temporally shaped pulses. A second laser would then allow for mode selective chemistry to interact selectively with the excited population. Alternatively the excited molecules enhanced reactivity could be exploited for selective chemistry.     

S-matrix approach to the equation of state of dilute nuclear matter

Based on the general analysis of the grand canonical partition function in the S-matrix framework, a method is presented to calculate the equation of state of dilute warm nuclear matter. The result is a model-independent virial series for the pressure and density that systematically includes contributions from all the ground and excited states of all the stable nuclear species and their scattering channels. The multiplicity distribution of these species to keep the matter in statistical equilibrium is found out and then the pressure, incompressibility and the symmetry energy of the system are evaluated. The calculated symmetry energy coefficients are found to be in fair agreement with the recent experimental data.     

Probing the density content of the nuclear symmetry energy

The nature of equation of state for the neutron star matter is crucially governed by the density dependence of the nuclear symmetry energy. We attempt to probe the behaviour of the nuclear symmetry energy around the saturation density by exploiting the empirical values for volume and surface symmetry energy coefficients extracted from the precise data on the nuclear masses.