New designed DNA light switch Ruthenium complexes as DNA photocleavers and Topoisomerase I inhibitors

Two ruthenium complexes containing a new ligand phipz (phipz = 2‐(1,10‐phenanthroline)‐1H‐imidazo[4,5‐b]phenazine) were designed and synthesized. These complexes were found to inhibit the DNA supercoiled relaxation mediated by topoisomerase I (topo I), cleave DNA under irradiation and bind to calf thymus DNA through intercalative mode. Furthermore, complex 2 shows higher photocleavage activity, topo I inhibition activity and DNA affinity than complex 1 . Additionally, introduction of phenazine unit may be the reason that two complexes exhibit DNA ‘light switch’ behavior. The present work shows that two complexes might be potential as new DNA ‘light switches’, DNA photocleavers and topo I inhibitors.     

衰减振荡电流下火花电阻的光谱诊断

气体开关是脉冲功率系统的关键部件,开关的火花通道阻抗直接影响负载电压的陡度及其能量传输效率。提出一种光谱学诊断方法,通过对火花通道成像光谱的时空分辨测量,获得通道半径及电导率,从而计算时变的火花电阻。光谱测量结果表明,氮气间隙火花放电通道电子温度为2~3eV,通道电导率先增大后减小,最大值约16 000S,随着放电发展,火花通道电阻从绝缘状态快速跌落并趋于稳定值,时变趋势与电学计算结果基本吻合。3~100kPa范围内,随着气压增大,放电通道半径减小,火花通道电阻增大。     

Competitive hydrogen bonding of cyclopropenium ions: Implications of an anion switch

This work demonstrates how modulating hydrogen bonding between intermolecular, bifurcated, and intramolecular interactions can be used to tune the structural, electronic, and photophysical properties of cyclopropenium ions and their respective fluorophores. The basis of this switchability was examined using X-ray diffraction analysis, ¹H NMR spectroscopy, DFT calculations, and fluorescence spectroscopy.     

Regularized inversion of the Laplace transform for series of experiments

Not only in low-field nuclear magnetic resonance, Laplace inversion is a relevant and challenging topic. Considerable conceptual and technical progress has been made, especially for the inversion of data encoding two decay dimensions. Distortion of spectra by overfitting of even moderate noise is counteracted requiring a priori smooth spectra. In this contribution, we treat the case of simple and fast one-dimensional decay experiments that are repeated many times in a series in order to study the evolution of a sample or process. Incorporating the a priori knowledge that also in the series dimension evolution should be smooth, peak position can be stabilized and resolution improved in the decay dimension. It is explained how the standard one-dimensional regularized Laplace inversion can be extended quite simply in order to include regularization in the series dimension. Obvious improvements compared with series of one-dimensional inversions are presented for simulated as well as experimental data. For the latter, comparison with multiexponential fitting is performed.     

Switching the Switch: Ligand Induced Disulfide Formation in HDAC8

Human histone deacetylase 8 is a well-recognized target for T-cell lymphoma and particularly childhood neuroblastoma. PD-404,182 was shown to be a selective covalent inhibitor of HDAC8 that forms mixed disulfides with several cysteine residues and is also able to transform thiol groups to thiocyanates. Moreover, HDAC8 was shown to be regulated by a redox switch based on the reversible formation of a disulfide bond between cysteines Cys₁₀₂ and Cys₁₅₃. This study on the distinct effects of PD-404,182 on HDAC8 reveals that this compound induces the dose-dependent formation of intramolecular disulfide bridges. Therefore, the inhibition mechanism of HDAC8 by PD-404,182 involves both, covalent modification of thiols as well as ligand mediated disulfide formation. Moreover, this study provides a deep molecular insight into the regulation mechanism of HDAC8 involving several cysteines with graduated capability to form reversible disulfide bridges.     

FHIT-Substrate Complexes: a New Paradigm in Reversible Protein Phosphorylation

Fhit is a tumor suppressor protein encoded at the most fragile site in the human genome that is inactivated by genetic deletions early in the development of many cancers. A member of the Histidine Triad (HIT) superfamily of nucleotide-binding proteins, Fhit binds diadenosine triphosphate (ApppA) and cleaves it to produce AMP + ADP. The His96Asn mutation of Fhit, which reduces k_cat by more than a million-fold, does not reduce tumor suppressor activity in a nude mouse assay. Thus, genetic and biochemical evidence suggest that ApppA binding but not cleavage is required for tumor suppression. Crystal structures of Fhit bound to a nonhydrolyzable ApppA analog revealed that Fhit binds two substrates per dimer, presenting all of the phosphates and two of the adenosines on the surface of the protein in place of a deep, positively charged groove in the empty Fhit protein dimer. It is proposed that signaling by Fhit is mediated by presentation of nucleotide substrates to cytosolic effectors.     

Delayed stability switches in singularly perturbed predator–prey models

In this paper we provide an elementary proof of the existence of canard solutions for a class of singularly perturbed planar systems in which there occurs a transcritical bifurcation of the quasi steady states. The proof uses the one-dimensional result proved by V.F. Butuzov, N.N. Nefedov and K.R. Schneider, and an appropriate monotonicity assumption on the vector field. The result is applied to identify all possible predator–prey models with quadratic vector fields allowing for the existence of canard solutions.     

Real‐Time Measurement of the Size Distribution of Diesel Exhaust Particles using a Portable 4‐stage Electrical Low Pressure Impactor

For this study, a 4 stage electrical low pressure impactor was designed to measure the real‐time size distribution of diesel particulate matter (DPM). For the performance evaluation, sodium chloride (NaCl) particles and dioctyl sebacate (DOS) particles were used. After evaluating the collection efficiency of each stage of the impactor, the size distributions of test particles were estimated using electrical current data and their inversion algorithm, and this was found to agree with the results obtained by a scanning mobility particle sizer (SMPS). For measurement of DPM, a common‐rail direct injection (CRDI) diesel engine, for engine speeds of 1,200 rpm and 1,500 rpm at 2.7 kgf·m, was used. Therefore, it was found that the size distribution of the DPM could be easily obtained, with the currents measured by the impactor and the data inversion algorithm, in less than 5 seconds. Furthermore, the effective density of the DPM could be obtained using the calculated results and the SMPS data.