Intraoperative contrast-enhanced MR-imaging as predictor of tissue damage during cryoablation of porcine liver

This study evaluate intraoperative Magnetic Resonance Imaging (MRI) as predictor of tissue damage following cryoablation of porcine liver with and without concomitant hepatic vascular inflow occlusion.Inflow occlusion was used during freezing in 6 of 12 pigs included. The volumes of the procedural ice-balls were estimated from MR images. Immediately after thawing contrast (MnDPDP) enhanced MRI was performed to estimate the volume of the cryolesion. Four days after ablation MRI was repeated of the in-vivo and the ex-vivo liver. Photography was performed of the sliced liver specimens to estimate the volumes of the lesions. The intraoperative volume of the cryolesion as shown by contrast enhanced MRI corresponded well to the ice-ball volume for lesions made without vascular occlusion (difference 0.3 +/- 0.9 cm(3), p = 0.239). For lesions made during occlusion the volume of the intraoperative cryolesion was larger than the corresponding ice-ball (difference 7.5 +/- 3.3 cm(3), p = 0.003). The volume of the cryolesions as estimated from histopathology four days after freezing and contrast enhanced MRI immediately after freezing corresponded well for lesions made with (difference -2.6 +/- 4.5 cm(3), p = 0.110) and without vascular occlusion (difference -0.5 +/- 2.3 cm(3), p = 0.695).Intraoperative MnDPDP-enhanced MRI of the cryolesion is predictive of the tissue damage induced during cryoablation of porcine liver. The procedural ice-ball is not, if induced during inflow occlusion.     

Single Machine Scheduling of Unit-time Jobs with Controllable Release Dates

The paper presents a bicriterion approach to solve the single-machine scheduling problem in which the job release dates can be compressed while incurring additional costs. The two criteria are the makespan and the compression cost. For the case of equal job processing times, an O(n⁴) algorithm is developed to construct integer Pareto optimal points. We discuss how the algorithm developed can be modified to construct an -approximation of noninteger Pareto optimal points. The complexity status of the problem with total weighted completion time criterion is also established.     

Equitable resolvable coverings

In an earlier article, Willem H. Haemers has determined the minimum number of parallel classes in a resolvable 2‐(qk,k,1) covering for all k ≥ 2 and q = 2 or 3. Here, we complete the case q = 4, by construction of the desired coverings using the method of simulated annealing. Secondly, we look at equitable resolvable 2‐(qk,k,1) coverings. These are resolvable coverings which have the additional property that every pair of points is covered at most twice. We show that these coverings satisfy k < 2q ? , and we give several examples. In one of these examples, k > q. © 2003 Wiley Periodicals, Inc. J Combin Designs 11: 113–123, 2003; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jcd.10024     

Synthesis and structural study of 2′‐ and 2′,6′‐positioned methyl‐ and nitro‐substituted 3‐(arylhydrazono)pentane‐2,4‐diones

A systematic series of ortho‐methyl‐ and nitro‐substituted arylhydrazones 2–6 formed by Japp–Klingemann reaction between pentane‐2,4‐dione and the respective aryldiazonium salts have been synthesized and studied by X‐ray crystal structure analysis, with added quantum chemical calculations. The optimized molecular geometries based on DFT calculations, enabling determination of relevant rotational barriers, and the calculated bond and ring critical points, using the method of ‘atoms in molecules’, were found to correspond with the experimental data, involving specific molecular conformations and hydrogen‐bonded ring structure dependent on the ortho‐substitution, thus making possible reliable structural prediction of this compound class. Copyright © 2007 John Wiley & Sons, Ltd.     

All organic host-guest crystals based on a dumb-bell-shaped conjugated host for light harvesting through resonant energy transfer

Together we glow: Fully organic host-guest crystals with two dyes inserted in their parallel nanochannels display broad emission in the visible range thanks to resonant energy transfer. The conjugated host crystal provides light harvesting in the UV region.     

Metal-directed synthesis and photophysical studies of trinuclear v-shaped and pentanuclear x-shaped ruthenium and osmium metallorods and metallostars based upon 4'-(3,5-dihydroxyphenyl)-2,2':6',2''-terpyridine divergent units

A new series of V-shaped trinuclear metallorods and X-shaped pentanuclear metallostars has been prepared by the reaction of metal complexes bearing pendant phenolic functionalities with complexes containing electrophilic ligands. Specifically, {M(tpy)2} motifs (M=Ru or Os; tpy=2,2':6',2'-terpyridine) bearing one or two pendant 3,5-dihydroxyphenyl substituents at the 4-position of the central ring of the tpy have been reacted with the complexes [Ru(tpy)(Xtpy)]2+ (X=Cl or Br) to form new ether-linked species. The energy transfer from ruthenium to osmium in these complexes has been investigated in detail and the efficiency of transfer shown to be highly temperature dependent; the energy transfer is highly efficient at low temperature, whereas at room temperature nonradiative and nontransfer deactivation of the excited {Ru(tpy)2}* domains is most significant.     

Electrostatic Potential Field and Nucleophilicity of 3, 5, 8, 10-Tetramethyl-aceheptylene

The electrostatic potential (EP.) for aceheptylene (I) is calculated using ab-initio wavefunctions. In addition, the EP. around I is approximated by a monopole expression, using wavefunctions from various semiempirical procedures as a basis. It is found that the previously noted discrepancy between the thoretical prediction of differential nuclophilicity of the individual unsaturated C-atoms in 3,5,8,10-tetramethyl-aceheptylene(II) and the experimental results of protonation is removed, if instead of local atomic charges, the EP. around II, approximated by that of I is considered.     

High Loading Efficiency and Controlled Release of Bioactive Immunotherapeutic Proteins Using Vaterite Nanoparticles

Nanoparticles may limit off-tumor/on-target ubiquitous activation of signaling by protein-based drugs. However, many challenges still exist in the design of a nanoparticle for protein delivery. In this study, conditions to establish vaterite nanoparticles as a pH-sensitive drug delivery system (DDS) for encapsulated protein drugs are comprehensively evaluated. Low coprecipitation pH of vaterite and protein prevents protein denaturation and yields high loading efficiency. Unprotected vaterite recrystallizes in aqueous solutions within 3 h to calcite and releases the loaded protein completely, but surface-modified particles with carboxyl groups containing polymers prove stable for more than 5 months. Notably, modification of vaterite with sulfonated polymers increases the loading of cationic proteins by a multiple. A system is developed for vaterite exposure to (pH) conditions under body-like-flow rates, with the dissolution of vaterite and simultaneous release of active proteins at tumor microenvironmental pH reaching up to 80% and only 20% at physiological pH within 2 h. Importantly, the immunomodulatory protein tumor necrosis factor preserves its native structure and fully retains functional activity in vitro after release from the particles. In conclusion, the studies described here provide a framework for the development of vaterite-based DDS as a carrier for bioactive protein-based therapeutics.     

Ethynyl and Propynylpyrene Inhibitors of Cytochrome P450

Abstract  

The single-crystal X-ray structures and in vivo activities of three aryl acetylenic inhibitors of cytochromes P450 1A1, 1A2, 2A6, and 2B1 have been determined and are reported herein. These are 1-ethynylpyrene, 1-propynylpyrene, and 4-propynylpyrene. To investigate electronic influences on the mechanism of enzyme inhibition, the experimental electron density distribution of 1-ethynylpyrene has been determined using low-temperature X-ray diffraction measurements, and the resulting net atomic charges compared with various theoretical calculations. A total of 82,390 reflections were measured with Mo Kα radiation to a (sinθ/λ)_max = 0.985 Å⁻¹. Averaging symmetry equivalent reflections yielded 8,889 unique reflections. A least squares refinement procedure was used in which multipole parameters were added to describe the distortions of the atomic electron distributions from spherical symmetry. A map of the model electron density distribution of 1-ethynylpyrene was obtained. Net atomic charges calculated from refined monopole population parameters yielded charges that showed that the terminal acetylenic carbon atom (C18) is more negative than the internal carbon (C17). Net atomic charges calculated by ab initio, density functional theory, and semi-empirical methods are consistent with this trend suggesting that the terminal acetylenic carbon atom is more likely to be the site of oxidation. This is consistent with the inhibition mechanism pathway that results in the formation of a reactive ketene intermediate. This is also consistent with assay results that determined that 1-ethynylpyrene acts as a mechanism-based inhibitor of P450s 1A1 and 1A2 and as a reversible inhibitor of P450 2B1. Crystallographic data: 1-ethynylpyrene, C₁₈H₁₀, P2₁/c, a = 14.571(2) Å, b = 3.9094(5) Å, c = 20.242(3) Å, β = 105.042(2)°, V = 1,113.5(2) Å³; 1-propynylpyrene, C₁₉H₁₂, P2₁/n, a = 8.970(2) Å, b = 10.136(1) Å, c = 14.080(3) Å, β = 99.77(2)°, V = 1,261.5(4) Å³; 4-propynylpyrene, C₁₉H₁₂, Pbca, a = 9.904(1) Å, b = 13.174(2) Å, c = 19.401(1) Å, V = 2,531.4(5) Å³.     

Metalated aziridines for cross-coupling with aryl and alkenyl halides via palladium catalysis

The palladium-catalyzed coupling of an aziridinylzinc chloride intermediate with alkenyl and aryl halides has been demonstrated. The method provides products with retention of aziridine stereochemistry. The utility of the coupling procedure is illustrated in the synthesis of structures related to l-furanomycin.