Total synthesis of deamido bleomycin a(2), the major catabolite of the antitumor agent bleomycin

Metabolic inactivation of the antitumor antibiotic bleomycin is believed to be mediated exclusively via the action of bleomycin hydrolase, a cysteine proteinase that is widely distributed in nature. While the spectrum of antitumor activity exhibited by the bleomycins is believed to reflect the anatomical distribution of bleomycin hydrolase within the host, little has been done to characterize the product of the putative inactivation at a chemical or biochemical level. The present report describes the synthesis of deamidobleomycin demethyl A(2) (3) and deamido bleomycin A(2) (4), as well as the respective aglycones. These compounds were all accessible via the key intermediate N(alpha)-Boc-N(beta)-[1-amino-3(S)-(4-amino-6-carboxy-5-methylpyrimidin-2-yl)propion-3-yl]-(S)-beta-aminoalanine tert-butyl ester (16). Synthetic deamido bleomycin A(2) was shown to be identical to the product formed by treatment of bleomycin A(2) with human bleomycin hydrolase, as judged by reversed-phase HPLC analysis and (1)H NMR spectroscopy. Deamido bleomycin A(2) was found to retain significant DNA cleavage activity in DNA plasmid relaxation assays and had the same sequence selectivity of DNA cleavage as bleomycin A(2). The most significant alteration of function noted in this study was a reduction in the ability of deamido bleomycin A(2) to mediate double-strand DNA cleavage, relative to that produced by BLM A(2).     

Local order around rare earth ions during the devitrification of oxyfluoride glasses

Erbium L(3)-edge extended x-ray absorption fine structure (EXAFS) measurements were performed on rare earth doped fluorosilicate and fluoroborate glasses and glass ceramics. The well known nucleating effects of erbium ions for the crystallization of cubic lead fluoride (based on x-ray diffraction measurements) and the fact that the rare earth ions are present in the crystalline phase (as indicated by Er(3+) emission spectra) seem in contradiction with the present EXAFS analysis, which indicates a lack of medium range structural ordering around the Er(3+) ions and suggests that the lead fluoride crystallization does not occur in the nearest neighbor distance of the rare earth ion. Molecular dynamics simulations of the devitrification process of a lead fluoride glass doped with Er(3+) ions were performed, and results indicate that Er(3+) ions lower the devitrification temperature of PbF(2), in good agreement with the experimental results. The genuine role of Er(3+) ions in the devitrification process of PbF(2) has been investigated. Although Er(3+) ions could indeed act as seeds for crystallization, as experiments suggest, molecular dynamics simulation results corroborate the experimental EXAFS observation that the devitrification does not occur at its nearest neighbor distance.     

Use of cyclic differential scanning calorimetry

Formation of an activated cellulose (Cellulose) species $$CELLULOSE\xrightarrow[{air}]{{heat}}CELLULOSE*$$ is the designated first stage of cellulose degradation in air [1]. Little is known about either the process or the nature of CELLULOSE^*. The transition, designatedT ₂, is observed as an exotherm around 300°C as the sample temperature is raised. No corresponding endotherm is observed on cooling. The process is therefore not reversible but is repeatable as subsequent reheating results in the exotherm being observed again. The exotherm is also found to be oxygen dependant. The effect of all the flame retardant treatments studied was to reduceT ₂ compared to the value for the untreated cotton.     

High pressure experiments on AlxGa1−xAs-GaAs quantum-well heterostructure lasers

Hydrostatic pressure experiments on Al_xGa_1?xAsGaAs quantum-well heterostructure (QWH) laser diodes are described. Data are presented giving ～11.5meV/kbar for the bandgap vs. pressure coefficient at lower pressures, with a change to 8.5–9meV/kbar at higher pressures. We suggest that this behavior is caused by biaxial and shear stresses in the active region induced by doping or composition mismatch relative to the confining layers, or between the n and p confining layers themselves. A model consistent with the experimental data is presented.     

A Preconditioned Conjugate Gradient Approach to Linear Equality Constrained Minimization

We propose a new framework for the application of preconditioned conjugate gradients in the solution of large-scale linear equality constrained minimization problems. This framework allows for the exploitation of structure and sparsity in the context of solving the reduced Newton system (despite the fact that the reduced system may be dense). Numerical experiments performed on a variety of test problems from the Netlib LP collection indicate computational promise.     

Distribution fiber FTTH/FTTC trial results and deployment strategies

This paper details the information SWBT has obtained from our ongoing Fiber-to-the-Home (FTTH) and Fiber-to-the-Curb (FTTC) fiber field trials. The developing architectures, technologies, and Optical Network Unit (ONU) powering strategies are discussed as they impact the development of an SWBT fiber deployment approach for the local loop.     

On RSA moduli with almost half of the bits prescribed

We show that using character sum estimates due to H. Iwaniec leads to an improvement of recent results about the distribution and finding RSA moduli M=pl, where p and l are primes, with prescribed bit patterns. We are now able to specify about n bits instead of about n/2 bits as in the previous work. We also show that the same result of H. Iwaniec can be used to obtain an unconditional version of a combinatorial result of W. de Launey and D. Gordon that was originally derived under the Extended Riemann Hypothesis.