An investigation into the mechanisms of DNA strand breakage by direct ionization of variably hydrated plasmid DNA

The mechanisms by which ionizing radiation directly causes strand breaks in DNA were investigated by comparing the chemical yield of DNA-trapped free radicals to the chemical yield of DNA single strand break (ssb) and double strand break (dsb), as a function of hydration (Gamma). Solid-state films of plasmid pUC18, hydrated to 2.5 < Gamma < 22.5 mol, were X-irradiated at 4 K, warmed to room temperature, and dissolved in water. Free radical yields were determined by EPR at 4 K. With use of the same samples, Gel electrophoresis was used to measure the chemical yield of total strand breaks, which includes prompt plus heat labile ssb; G'total(ssb) decreased from 0.092 +/- 0.016 micromol/J at Gamma= 2.5 to 0.066 +/- 0.008 micromol/J at Gamma= 22.5. Most provocative is that at Gamma= 2.5 the yield of total ssb exceeds the yield of trapped deoxyribose radicals: G'total(ssb) - G'sugar(fr) = 0.06 +/- 0.02 micromol/J. Nearly 2/3 of the strand breaks are derived from precursors other than radicals trapped on the deoxyribose moiety. To account for these nonradical precursors, we hypothesize that strand breaks are produced by two one-electron oxidations at a single deoxyribose residue within an ionization cluster.     

OH-stretch vibrational spectroscopy of hydroxymethyl hydroperoxide

We report measurement and analysis of the photodissociation spectrum of hydroxymethyl hydroperoxide (HOCH(2)OOH) and its partially deuterated analogue, HOCD(2)OOH, in the OH-stretching region. Spectra are obtained by Fourier transform infrared spectroscopy in the 1nu(OH) and 2nu(OH) regions, and by laser induced fluorescence detection of the OH fragment produced from dissociation of HOCH(2)OOH initiated by excitation of the 4nu(OH) and 5nu(OH) overtone regions (action spectroscopy). A one-dimensional local-mode model of each OH chromophore is used with ab initio calculated OH-stretching potential energy and dipole moment curves at the coupled-cluster level of theory. Major features in the observed absorption and photodissociation spectra are explained by our local-mode model. In the 4nu(OH) region, explanation of the photodissocation spectrum requires a nonuniform quantum yield, which is estimated by assuming statistical energy distribution in the excited state. Based on the estimated dissociation threshold, overtone photodissociation is not expected to significantly influence the atmospheric lifetime of hydroxymethyl hydroperoxide.     

The categorified Heisenberg algebra I: A combinatorial representation

We show how Khovanov's categorification of the Heisenberg algebra arises as a linearization of a discrete combinatorial structure in the bicategory of spans of groupoids. We also treat a categorification of $U({\mathrm{sl}}_n)$ in a similar way.     

Methoxyflavone Inhibitors of Cytochrome P450

Abstract  Cytochrome P450 enzymes are a superfamily of enzymes involved in the metabolism of endogenous compounds as well as xenobiotics. Due to the large number of reactions catalyzed by these enzymes and their importance in drug metabolism and carcinogenesis, they have been the focus of many studies over the years. Based on the knowledge that flavones are natural substrates of certain P450 enzymes (such as P450 1A2) involved in carcinogenesis, we have synthesized and studied a number of flavonoids as potential inhibitors of these enzymes. These compounds are structurally very similar to the natural flavone substrates of these enzymes but have methoxy substituents at various positions. Here we are reporting the synthesis, structural analysis, X-ray crystal structures, and preliminary inhibition studies of four methoxyflavones from this series. Crystallographic data: 2′-methoxyflavone, P-1, a = 7.2994(8) ?, b = 8.3322(7) ?, c = 10.8240(10) ?, α = 97.905(8)°, β = 92.779(10)°, γ = 111.105(8)°, V = 604.9(1) ?³; 3′-methoxyflavone, P2₁/n, a = 15.1313(16) ?, b = 3.9699(4) ?, c = 19.9454(16) ?, β = 91.673(8)°, V = 1197.6(2) ?³; 4′-methoxyflavone, P2₁/n, a = 16.451(12) ?, b = 3.881(1) ?, c = 19.529(16) ?, β = 106.65(1)°, V = 1195.1(4) ?³; 3′,4′-dimethoxyflavone, C2/c, a = 30.819(5) ?, b = 4.0857(7) ?, c = 26.100(3) ?, β = 124.21(1)°, V = 2717.6(7) ?³. Index Abstract  Methoxyflavone Inhibitors of Cytochrome P450 Michael McKendall, Tasha Smith, Kien Anh, Jamie Ellis, Terri McGee, Maryam Foroozesh, Naijue Zhu and Cheryl L. Klein Stevens* This paper is a report of the synthesis, structural analysis, X-ray crystal structures, and preliminary inhibition studies of 2′-methoxyflavone, 3′-methoxyflavone, 4′-methoxyflavone, and 3′,4′-dimethoxyflavone.

A General and Air‐tolerant Strategy to Conjugated Polymers within Seconds under Palladium(I) Dimer Catalysis

While current M⁰/M^II based polymerization strategies largely focus on fine‐tuning the catalyst, reagents and conditions for each and every monomer, this report discloses a single method that allows access to a variety of different conjugated polymers within seconds at room temperature. Key to this privileged reactivity is an air‐ and moisture stable dinuclear Pd^I catalyst. The method is operationally simple, robust and tolerant to air.     

A Categorical Framework for the Quantum Harmonic Oscillator

This paper describes how the structure of the state space of the quantum harmonic oscillator can be described by an adjunction of categories, that encodes the raising and lowering operators into a commutative comonoid. The formulation is an entirely general one in which Hilbert spaces play no special role. Generalised coherent states arise through the hom-set isomorphisms defining the adjunction, and we prove that they are eigenstates of the lowering operators. Generalised exponentials also emerge naturally in this setting, and we demonstrate that coherent states are produced by the exponential of a raising morphism acting on the zero-particle state. Finally, we examine all of these constructions in a suitable category of Hilbert spaces, and find that they reproduce the conventional mathematical structures.     

Problem-driven scenario generation: an analytical approach for stochastic programs with tail risk measure

Mathematical Programming - Scenario generation is the construction of a discrete random vector to represent parameters of uncertain values in a stochastic program. Most approaches to scenario...     

Unexpected Hole Doping of Graphene by Osmium Adatoms

The electronic transport of monolayer graphene devices is studied before and after in situ deposition of a sub-monolayer coating of osmium adatoms. Unexpectedly, and unlike all other metallic adatoms studied to date, osmium adatoms shift the charge neutrality point to more positive gate voltages. This indicates that osmium adatoms act as electron acceptors and thus leave the graphene hole-doped. Analysis of transport data suggest that Os adatoms behave as charged impurity scatterers, albeit with a surprisingly low charge-doping efficiency. The charge neutrality point of graphene is found to vary non-monotonically with gate voltage as the sample is warmed to room temperature, suggesting that osmium diffuses on the surface but is not completely removed.     

Glyceride‐Mimetic Prodrugs Incorporating Self‐Immolative Spacers Promote Lymphatic Transport,Avoid First‐Pass Metabolism,and Enhance Oral Bioavailability

First‐pass hepatic metabolism can significantly limit oral drug bioavailability. Drug transport from the intestine through the lymphatic system, rather than the portal vein, circumvents first‐pass metabolism. However, the majority of drugs do not have the requisite physicochemical properties to facilitate lymphatic access. Herein, we describe a prodrug strategy that promotes selective transport through the intestinal lymph vessels and subsequent release of drug in the systemic circulation, thereby enhancing oral bioavailability. Using testosterone (TST) as a model high first‐pass drug, glyceride‐mimetic prodrugs incorporating self‐immolative (SI) spacers, resulted in remarkable increases (up to 90‐fold) in TST plasma exposure when compared to the current commercial product testosterone undecanoate (TU). This approach opens new opportunities for the effective development of drugs where oral delivery is limited by first‐pass metabolism and provides a new avenue to enhance drug targeting to intestinal lymphoid tissue.     

The use of carbon dioxide as the reaction cell gas for the separation of uranium and plutonium in quadrupole inductively coupled plasma mass spectrometry (ICP-MS) for nuclear forensic samples

²²⁶Ra, ²³⁸U, ²³²Th, and ⁴⁰K radionuclides have been determined using gamma-ray spectrometry in soil samples collected from urban areas in the southern governorates of Jordan and showed average concentrations of (39 ± 18), (45 ± 20), (23 ± 13), and (233 ± 128) Bq kg^?1, respectively. The corresponding radio-elemental concentrations in the existing geological features were obtained and examined for the relative depletion/enrichment processes and state of equilibrium in soils. Radium equivalent activity, hazard indices, and annual gonadal dose equivalent do not exceed the permissible limits. Absorbed dose rates in air outdoor and external effective dose showed average values of 44.0 nGy h^?1 and 54.4 μSv y^?1, respectively.