Brominated Luciferins Are Versatile Bioluminescent Probes

We report a set of brominated luciferins for bioluminescence imaging. These regioisomeric scaffolds were accessed by using a common synthetic route. All analogues produced light with firefly luciferase, although varying levels of emission were observed. Differences in photon output were analyzed by computation and photophysical measurements. The brightest brominated luciferin was further evaluated in cell and animal models. At low doses, the analogue outperformed the native substrate in cells. The remaining luciferins, although weak emitters with firefly luciferase, were inherently capable of light production and thus potential substrates for orthogonal mutant enzymes.     

Biophysical and Computational Approaches to Study Ternary Complexes: A ‘Cooperative Relationship’ to Rationalize Targeted Protein Degradation

Degraders have illustrated that compound-induced proximity to E3 ubiquitin ligases can prompt the ubiquitination and degradation of disease-relevant proteins. Hence, this pharmacology is becoming a promising alternative and complement to available therapeutic interventions (e. g., inhibitors). Degraders rely on protein binding instead of inhibition and, hence, they hold the promise to broaden the druggable proteome. Biophysical and structural biology approaches have been the cornerstone of understanding and rationalizing degrader-induced ternary complex formation. Computational models have now started to harness the experimental data from these approaches with the aim to identify and rationally help design new degraders. This review outlines the current experimental and computational strategies used to study ternary complex formation and degradation and highlights the importance of effective crosstalk between these approaches in the advancement of the targeted protein degradation (TPD) field. As our understanding of the molecular features that govern drug-induced interactions grows, faster optimizations and superior therapeutic innovations for TPD and other proximity-inducing modalities are sure to follow.     

Effect of current density and sulfuric acid concentration on persulfuric acid generation by boron-doped diamond film anodes

This research investigated the effects of current density and sulfuric acid concentration on the rates of persulfate generation by boron-doped diamond film anodes. Also investigated was the maximum conversion of sulfate to persulfate that could be achieved from electrolysis of sulfuric acid. Experiments were performed in batch systems using a rotating disk electrode (RDE) and a flow-through reactor with parallel plate electrodes. Both the RDE and flow-through experiments showed that there was a linear relationship between persulfate generation rates and current density. Persulfate generation rates became current limited at sulfuric acid concentrations of 2.25 M and above; however, Faradaic efficiencies under current-limited conditions were only ~60 %, and were only weakly dependent on the current density. Persulfate generation rates in the flow-through reactor showed similar dependencies on current density and sulfuric acid concentration as those in the RDE reactor, but were 20–50 % lower. Acid catalyzed and thermal decomposition of persulfate limited the maximum conversion of sulfate to persulfate. A maximum fractional conversion of 78 % was achieved using an initial sulfuric acid concentration of 0.77 M. Surprisingly, this value was independent of the current density over the range of 100–300 mA cm^?2.     

Construction of a Black consciousness measure: Psychotherapeutic implications.

Describes the Developmental Inventory of Black Consciousness (DIB-C). Empirical, theoretical, autobiographical, and biographical studies suggest there are 4 distinct stages of Black consciousness: the preconscious stage, confrontation, internalization, and integration. Items were written for each of these domains and administered to 160 Black male undergraduates. The DIB-C was analyzed by using a sequentially organized psychometric strategy of item discrimination and tests of homogeneity, social desirability, and differential validity. A construct validational study was also performed using the unpublished "Nadanolitization Scale," which measures the degree of internalization by Blacks of stereotypic attitudes held by Whites about Blacks. Results show 65 items remaining for the DIB-C following the sequential analysis. Construct validation showed an inverse linear relationship between the degree of "Nadanolitization" and progressive DIB-C scores. Psychotherapeutic implications are discussed. (12 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

On-shot focal-spot characterization technique using phase retrieval

We present an on-shot focal-spot characterization technique based on a phase-retrieval scheme that retrieves near-field phase from multiplane focal-spot measurements in an experimental target chamber. The technique is easy to implement inside a target chamber and is demonstrated in a multiterawatt laser system. It is also found that phase retrieval can quantitatively detect residual angular dispersion coming from the pulse compressor misalignment.