A Dynamic Binding Strategy for Multiple Inheritance and Asynchronously Communicating Objects

Background: The ability of Pseudouridimycin (PUM) to occupy the nucleotide addition site of bacterial RNA Polymerase (RNAP) underlies its inhibitory potency as previously reported. PUM has gained high research interest as a broad-spectrum nucleoside analog that has demonstrated exciting potentials in treating drug-resistant bacterial infections. Objective: Herein, we identified, for the first time, a novel complementary mechanism by which PUM elicits its inhibitory effects on bacterial RNAP. Methods: The dynamic binding behavior of PUM to bacterial RNAP was studied using various dynamic analyses approaches. Results and Discussion: Findings revealed that in addition to occupying the nucleotide addition site, PUM also interrupts the unimpeded entry and exit of DNA by reducing the mechanistic extension of the RNAP cleft and perturbing the primary conformations of the switch regions. Moreover, PUM binding reduced the distances between key residues in the β and β’ subunits that extend to accommodate the DNA. Conclusion: This study’s findings present structural insights that would contribute to the structure-based design of potent and selective PUM inhibitors.

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A practical example of multiple inheritance in C++

ACM SIGPLAN Notices ◽

10.1145/68127.68134 ◽

1989 ◽

Vol 24 (9) ◽

pp. 112-115 ◽

Cited By ~ 1

Author(s):

R. S. Wiener ◽

L. J. Pinson

Keyword(s):

Multiple Inheritance

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Efficient handling of multiple inheritance hierarchies

Proceedings of the eighth annual conference on Object-oriented programming systems, languages, and applications - OOPSLA '93 ◽

10.1145/165854.165905 ◽

1993 ◽

Cited By ~ 29

Author(s):

Yves Caseau

Keyword(s):

Multiple Inheritance

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Phosphorylation and an ATP-dependent process increase the dynamic exchange of H1 in chromatin

The Journal of Cell Biology ◽

10.1083/jcb.200202131 ◽

2002 ◽

Vol 158 (7) ◽

pp. 1161-1170 ◽

Cited By ~ 65

Author(s):

Yali Dou ◽

Josephine Bowen ◽

Yifan Liu ◽

Martin A. Gorovsky

Keyword(s):

Negative Charge ◽

Histone H1 ◽

Linker Histone ◽

Global Effect ◽

Dynamic Binding ◽

Linker Histone H1 ◽

Dependent Process ◽

Dynamic Exchange

In Tetrahymena cells, phosphorylation of linker histone H1 regulates transcription of specific genes. Phosphorylation acts by creating a localized negative charge patch and phenocopies the loss of H1 from chromatin, suggesting that it affects transcription by regulating the dissociation of H1 from chromatin. To test this hypothesis, we used FRAP of GFP-tagged H1 to analyze the effects of mutations that either eliminate or mimic phosphorylation on the binding of H1 to chromatin both in vivo and in vitro. We demonstrate that phosphorylation can increase the rate of dissociation of H1 from chromatin, providing a mechanism by which it can affect H1 function in vivo. We also demonstrate a previously undescribed ATP-dependent process that has a global effect on the dynamic binding of linker histone to chromatin.

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On Object-Oriented Databases, Materialized Views, and Concurrent Engineering

ASME 1991 5th Annual Database Symposium: Engineering Databases — An Enterprise Resource ◽

10.1115/edm1991-0187 ◽

1991 ◽

Author(s):

Martin Hardwick ◽

Blair R. Downie

Keyword(s):

Concurrent Engineering ◽

Object Oriented ◽

Materialized Views ◽

Design Tools ◽

Design Data ◽

Multiple Inheritance ◽

File Formats ◽

Definition Of ◽

Application Specific ◽

Object Oriented Database

Abstract Concurrent engineering seeks to reduce the length of the design life cycle by allowing multiple engineers to work on a design concurrently using their different design tools. A major stumbling block in achieving this goal is that most design tools use different file formats. Emerging standards such as STEP/PDES/EXPRESS reduce this barrier, but conformance to standards is not enough. One reason design tools have different file formats is because each tool requires a different perspective or view of the design. Engineering databases must provide designers with the ability to define application specific views of design data, and the ability to propagate changes among those related views. In this paper, we examine how an object-oriented database system can support the definition of application views using a class hierarchy and multiple inheritance.

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