Proton stopping powers: Binary encounter calculations based on accurate speed distributions for target electrons

Atomic and molecular electronic stopping powers for medium energy protons (≈ 10 keV-10 MeV) have been calculated using the binary-encounter approximation in conjunction with (1) either an energy or maximum impact parameter cut-off based on minimum excitation energies; and (2) ab initio electronic speed distributions. The maximum impact parameter approach yields good agreement with experiment for inert gases and closed-shell polyatomic molecules comprised of first-row atoms.     

An improved synthesis of 2-oxa-7-azaspiro[3,5]nonane and analogs as novel reagents in medicinal chemistry

A detailed synthesis of novel spirocyclic oxetane analogs is described for the first time.     

F-to-HF reactions. IX. Nonthermal complications for the CH4/C3F6/C2F6 moderated nuclear recoil system

Results are reported from moderated nuclear recoil ¹⁸F experiments with the CH₄/C₃F₆/C₂F₆ mixture system. At a 99.5% confidence level measurement precision of ±3.4%, non-thermal F-to-HF reactions are phenomenologically suppressed at C₂F₆ moderator concentrations in the range of 95.0–99.95 mol-%. Effectively equilibrium reaction conditions can be established in well-designed experiments of this type.     

Ultrafast changes of molecular crystal structure induced by dipole solvation

Femtosecond photoexcitation of organic chromophores in a molecular crystal induces strong changes of the electronic dipole moment via intramolecular charge transfer as is evident from transient vibrational spectra. The structural response of the crystal to the dipole change is mapped directly for the first time by ultrafast x-ray diffraction or diffuse scattering. Changes of diffracted and transmitted x-ray intensity demonstrate an angular rearrangement of molecules around excited dipoles following the 10 ps kinetics of charge transfer and leaving lattice plane spacings unchanged. Transient x-ray scattering is governed by solvation, masking changes of the chromophore molecular structure.     

Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism

Most patients with the pediatric neurodegenerative disease spinal muscular atrophy have a homozygous deletion of the survival motor neuron 1 (SMN1) gene, but retain one or more copies of the closely related SMN2 gene. The SMN2 gene encodes the same protein (SMN) but produces it at a low efficiency compared with the SMN1 gene. We performed a high-throughput screen of approximately 47,000 compounds to identify those that increase production of an SMN2-luciferase reporter protein, but not an SMN1-luciferase reporter protein. Indoprofen, a nonsteroidal anti-inflammatory drug (NSAID) and cyclooxygenase (COX) inhibitor, selectively increased SMN2-luciferase reporter protein and endogenous SMN protein and caused a 5-fold increase in the number of nuclear gems in fibroblasts from SMA patients. No other NSAIDs or COX inhibitors tested exhibited this activity.     

Shorter response times and improved selectivity for potentiometric electrodes

The response times of potentiometric electrodes of the coated-wire variety are shortened by the addition of non-selective charge carriers to the ion-selective membrane. As a charge carrier, ferrocene was effective in decreasing the response time by a factor of 2–3, e.g. from 19 to 6 s. The optimum amount of ferrocene in the polymer film was 1.5% (w/w). As an unexpected benefit, the selectivity of the electrodes containing ferrocene improved by up to two orders of magnitude.     

Biological mechanism profiling using an annotated compound library

We present a method for testing many biological mechanisms in cellular assays using an annotated library of 2036 small organic molecules. This annotated compound library represents a large-scale collection of compounds with diverse, experimentally confirmed biological mechanisms and effects. We found that this chemical library is (1) more structurally diverse than conventional, commercially available libraries, (2) enriched in active compounds in a tumor cell viability assay, and (3) capable of generating hypotheses regarding biological mechanisms underlying cellular processes. We elucidated biological mechanisms relevant to the antiproliferative activity of 85 compounds from this library that were selected using a high-throughput cell viability screen. We developed a novel automated scoring system for identifying statistically enriched mechanisms among such a subset of compounds. This scoring system can identify both previously known and potentially novel antiproliferative mechanisms.