Population-modulation study of the filling of mercury ion levels in a He-Hg discharge

The branching ratios for the lines at 615.0 nm and 794.5 nm and the ratios of the partial chargeexchange cross sections are determined through a comparison of the intensities of spectral lines of the mercury ion in a He-Hg discharge with and without emission at the 615.0-nm line (by the population-modulation method). Absolute values are found for the partial cross sections from the calculated contribution of the Hgll levels to the total charge-exchange cross sections. Observations of the shape of the spontaneous afterglow of the lines of the one-electron and Beitler spectra of Hg II and measurements of their intensities show that the charge-exchange cross section is distributed in proportions of approximately 37 between the levels of the one-electron and Beitler spectra of Hg II.Translated from Izvestiya Vysshikh Uchebnykh Zavedenii, Fizika, No. 5, pp. 90–97, May, 1984.     

Systems-based design of bi-ligand inhibitors of oxidoreductases: filling the chemical proteomic toolbox

Genomics-driven growth in the number of enzymes of unknown function has created a need for better strategies to characterize them. Since enzyme inhibitors have traditionally served this purpose, we present here an efficient systems-based inhibitor design strategy, enabled by bioinformatic and NMR structural developments. First, we parse the oxidoreductase gene family into structural subfamilies termed pharmacofamilies, which share pharmacophore features in their cofactor binding sites. Then we identify a ligand for this site and use NMR-based binding site mapping (NMR SOLVE) to determine where to extend a combinatorial library, such that diversity elements are directed into the adjacent substrate site. The cofactor mimic is reused in the library in a manner that parallels the reuse of cofactor domains in the oxidoreductase gene family. A library designed in this manner yielded specific inhibitors for multiple oxidoreductases.     

Serendipitous discovery of light-induced (<Emphasis Type="Italic">In Situ</Emphasis>) formation of an Azo-bridged dimeric sulfonated naphthol as a potent PTP1B inhibitor

Background

Protein tyrosine phosphatases (PTPs) like dual specificity phosphatase 5 (DUSP5) and protein tyrosine phosphatase 1B (PTP1B) are drug targets for diseases that include cancer, diabetes, and vascular disorders such as hemangiomas. The PTPs are also known to be notoriously difficult targets for designing inihibitors that become viable drug leads. Therefore, the pipeline for approved drugs in this class is minimal. Furthermore, drug screening for targets like PTPs often produce false positive and false negative results.

Results

Studies presented herein provide important insights into: (a) how to detect such artifacts, (b) the importance of compound re-synthesis and verification, and (c) how in situ chemical reactivity of compounds, when diagnosed and characterized, can actually lead to serendipitous discovery of valuable new lead molecules. Initial docking of compounds from the National Cancer Institute (NCI), followed by experimental testing in enzyme inhibition assays, identified an inhibitor of DUSP5. Subsequent control experiments revealed that this compound demonstrated time-dependent inhibition, and also a time-dependent change in color of the inhibitor that correlated with potency of inhibition. In addition, the compound activity varied depending on vendor source. We hypothesized, and then confirmed by synthesis of the compound, that the actual inhibitor of DUSP5 was a dimeric form of the original inhibitor compound, formed upon exposure to light and oxygen. This compound has an IC₅₀ of 36 μM for DUSP5, and is a competitive inhibitor. Testing against PTP1B, for selectivity, demonstrated the dimeric compound was actually a more potent inhibitor of PTP1B, with an IC₅₀ of 2.1 μM. The compound, an azo-bridged dimer of sulfonated naphthol rings, resembles previously reported PTP inhibitors, but with 18-fold selectivity for PTP1B versus DUSP5.

Conclusion

We report the identification of a potent PTP1B inhibitor that was initially identified in a screen for DUSP5, implying common mechanism of inhibitory action for these scaffolds.

     

Job assignment in large-scale service systems with affinity relations

We consider load balancing in service systems with affinity relations between jobs and servers. Specifically, an arriving job can be assigned to a fast, primary server from a particular selection associated with this job or to a secondary server to be processed at a slower rate. Such job–server affinity relations can model network topologies based on geographical proximity, or data locality in cloud scenarios. We introduce load balancing schemes that assign jobs to primary servers if available, and otherwise to secondary servers. A novel coupling construction is developed to obtain stability conditions and performance bounds. We also conduct a fluid limit analysis for symmetric model instances, which reveals a delicate interplay between the model parameters and load balancing performance.

     

Lax representations and Bäcklund transformations for one-dimensional nonlinear evolution equations

Translated from Sibirskii Matematicheskii, Vol. 36, No. 1, pp. 164–176, January–February, 1995.     

Affinity liquid chromatography and capillary electrophoresis of seminal plasma proteins

Interactions of boar, bull, and human seminal plasma proteins with heparin and phosphorylcholine were studied by affinity LC using heparin immobilized to a Toyopearl support. A step gradient elution from 0.15 to 1.50 M NaCl was employed to elute the seminal plasma proteins. Relative amounts of the heparin-binding fraction of seminal plasma proteins (H+) in seminal plasma of three species were determined. Further on, the fraction of seminal plasma proteins interacting with phosphorylcholine-binding proteins (P+) was evaluated. P+ proteins were not found in human seminal plasma and their highest amount was present in bull seminal plasma. A CE method was developed for separation of seminal plasma proteins. Various capillaries and separation conditions were tested; the best resolution was obtained in a bare-silica capillary, with a micellar system consisting of a 0.02 M borate buffer and 0.05 M SDS pH 10.0. The optimized conditions were applied to the identification of the components in boar plasma.     

Delay performance in random-access networks

We explore the achievable delay performance in wireless random-access networks. While relatively simple and inherently distributed in nature, suitably designed queue-based random-access schemes provide the striking capability to match the optimal throughput performance of centralized scheduling mechanisms in a wide range of scenarios. The specific type of activation rules for which throughput optimality has been established, may however yield excessive queues and delays. Motivated by that issue, we examine whether the poor delay performance is inherent to the basic operation of these schemes, or caused by the specific kind of activation rules. We derive delay lower bounds for queue-based activation rules, which offer fundamental insight in the cause of the excessive delays. For fixed activation rates, we obtain lower bounds indicating that delays can grow dramatically with the load in certain topologies as well.