Effect of Low-Dose Gamma Radiation on HIV Replication in Human Peripheral Blood Mononuclear Cells

Recent studies have demonstrated that UV light and x-irradiation enhance human immunodeficiency virus (HIV) gene expression. There are few published data on related effects of γ-radiation. This may be of clinical relevance, as radiotherapy has been used extensively for the treatment of acquired immunodeficiency syndrome associated conditions. With this in mind, we have studied the effects of γ-radiation on HIV replication in mononuclear cells (MC). These cells were obtained from five seronegative healthy donors, exposed to0–200 cGy γ-radiation, stimulated with phytohemagglutinin-P (PHA-P) for 24 h, infected with a laboratory strain of HIV (HTLV-IIIB, multiplicity of infection = 0.001), then carried in culture for 14 days. Overall, when considering p24 antigen levels on days 7 and 11 in cultures established from cells exposed to 50 cGy, the maximal levels were significantly higher than those measured in the parallel control cultures taken as a whole (P < 0.05), with viral replication enhanced as much as 1000-fold in one case. No significant cytotoxicity was observed following exposure to doses up to 50 cGy. The mechanism of the observed effect remains unknown but may relate to direct gene activation and/or free radical generation, leading to such activation. To date, there is no evidence that viral stimulation occurs following therapeutic radiation in a clinical setting.     

Enantioselective aziridination using copper complexes of biaryl Schiff bases

Racemic 2,2'-diamino-6,6'-dimethylbiphenyl is resolved using simulated moving bed chromatography, and the absolute configuration of the enantiomers is confirmed via the X-ray crystal structure of a derivative. The diamine is condensed with a range of aldehydes to give bidentate aldimine proligands L. Molecular structures of the complexes formed between L and Cu(I) fall into two classes; bimetallic double helices ([Cu(2)L(2)](2+)) and monometallic ([CuL](+)). The latter are strikingly more efficient in the aziridination of alkenes than are the former in terms of rate, turnover, and enantioselection. In particular, the imine ligand formed from the diamine and 2,6-dichlorobenzaldehyde gives, in combination with Cu(I) or Cu(II), up to 99% ee in the aziridination of 6-acyl-2,2-dimethylchromene and 88-98% ee for a range of cinnamate esters. Styrenic and other alkenes are converted with lower selectivities (5-54%). The catalytic system shows a linear response in product ee to catalyst ee, and the product ee does not vary significantly during the reaction. UV spectrophotometric investigations indicate that conversion of Cu(I) to Cu(II) is not essential for catalysis but that Cu(II) is probably also a competent system.     

Irreversibility and polymer adsorption

Physisorption or chemisorption from dilute polymer solutions often entails irreversible polymer-surface bonding. We present a theory of the resultant nonequilibrium layers. While the density profile and loop distribution are the same as for equilibrium layers, the final layer comprises a tightly bound inner part plus an outer part whose chains make only fN surface contacts where N is chain length. The contact fractions f follow a broad distribution, P(f) approximately f(-4/5), in rather close agreement with strong physisorption experiments [H. M. Schneider, Langmuir 12, 994 (1996)]].     

The ultrasensitivity of living polymers

Synthetic and biological living polymers are self-assembling chains whose chain length distributions (CLDs) are dynamic. We show these dynamics are ultrasensitive: Even a small perturbation (e.g., temperature jump) nonlinearly distorts the CLD, eliminating or massively augmenting short chains. The origin is fast relaxation of mass variables (mean chain length, monomer concentration) which perturbs CLD shape variables before these can relax via slow chain growth rate fluctuations. Viscosity relaxation predictions agree with experiments on the best-studied synthetic system, alpha-methylstyrene.     

Experimental evidence for a light and broad scalar resonance in D(+) --> pi(-)pi(+)pi(+) decay

From a sample of 1172 +/- 61 D(+)-->pi(-)pi(+)pi(+) decays, we find gamma(D(+)-->pi(-)pi(+)pi(+))/gamma(D(+)-->K-pi(+)pi(+)) = 0.0311 +/- 0.0018(+0.0016)(-0.0026). Using a coherent amplitude analysis to fit the Dalitz plot of these decays, we find strong evidence that a scalar resonance of mass 478(+24)(-23) +/- 17 MeV/c(2) and width 324(+42)(-40) +/- 21 MeV/c(2) accounts for approximately half of all decays.     

Spin squeezing and quantum correlations

We discuss the notion of spin squeezing considering two mutually exclusive classes of spin-s states, namely, oriented and non-oriented states. Our analysis shows that the oriented states are not squeezed while non-oriented states exhibit squeezing. We also present a new scheme for construction of spin-s states using 2s spinors oriented along different axes. Taking the case of s=1, we show that the ‘non-oriented’ nature and hence squeezing arise from the intrinsic quantum correlations that exist among the spinors in the coupled state.     

Synthesis by radical cyclization and cytotoxicity of highly potent bioreductive alicyclic ring fused [1,2-a]benzimidazolequinones

The key step in the synthesis of new five, six and seven-membered alicyclic ring [1,2-a]-fused bioreductive benzimidazolequinones was radical cyclisation. Six and seven-membered tributyltin hydride-mediated homolytic aromatic substitutions of nucleophilic N-alkyl radicals onto the benzimidazole-2-position occurred in high yields (63-70 %) when quaternising the pyridine-like 3-N of imidazole with camphorsulfonic acid and using large excesses of the azo-initiator, 1,1'-azobis(cyclohexanecarbonitrile), to supplement the non-chain reaction. Elaboration of benzimidazoles to the benzimidazolequinones occurred in excellent yields. The IC50 values for the cytotoxicity of benzimidazolequinones towards the human skin fibroblast cell line GM00637 were in the nanomolar range, as determined by using the MTT assay. The benzimidazolequinones were much more cytotoxic than indolequinone analogues. 1,2,3,4-Tetrahydropyrido[1,2-a]benzimidazole-6,9-dione was the most potent compound prepared being more than 300 times more cytotoxic than the clinically used bioreductive drug, mitomycin C. The latter benzimidazolequinone was more potent under hypoxic conditions (associated with solid tumors), being 4.4 times more cytotoxic than under aerobic conditions, while mitomycin C was 1.8 times more selective towards hypoxia. The cyclopropane fused pyrido[1,2-a]benzimidazolequinone, 1a,2,3,9b-tetrahydro-1H-cyclopropa[3,4]pyrido[1,2-a]benzimidazole-5,8-dione was less cytotoxic and selective than the five-membered ring analogue, 1,1a,8,8a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-a]benzimidazole-3,6-dione. Modifying the structure of the most potent pyrido[1,2-a]benzimidazolequinone by attaching methyl substituents onto the quinone moiety increased reductive potentials and decreased cytotoxicity and selectivity towards hypoxia.     

Interfacial reaction kinetics

We study irreversible A-B reaction kinetics at a fixed interface separating two immiscible bulk phases, A and B. Coupled equations are derived for the hierarchy of many-body correlation functions. Postulating physically motivated bounds, closed equations result without the need for ad hoc decoupling approximations. We consider general dynamical exponent z, where is the rms diffusion distance after time t. At short times the number of reactions per unit area, , is 2nd order in the far-field reactant densities . For spatial dimensions dabove a critical value , simple mean field (MF) kinetics pertain, where Q_b is the local reactivity. For low dimensions , this MF regime is followed by 2nd order diffusion controlled (DC) kinetics, , provided . Logarithmic corrections arise in marginal cases. At long times, a cross-over to 1st order DC kinetics occurs: . A density depletion hole grows on the more dilute A side. In the symmetric case (), when the long time decay of the interfacial reactant density, , is determined by fluctuations in the initial reactant distribution, giving . Correspondingly, A-rich and B-rich regions develop at the interface analogously to the segregation effects established by other authors for the bulk reaction . For fluctuations are unimportant: local mean field theory applies at the interface (joint density distribution approximating the product of A and B densities) and . We apply our results to simple molecules (Fickian diffusion, z=2) and to several models of short-time polymer diffusion (z>2). Received 8 June 1998 and Received in final form 10 September 1999