scholarly journals Safe Dynamic Binding in the Join Calculus

Author(s):  
Alan Schmitt
Keyword(s):  
Author(s):  
Ali H. Rabbad ◽  
Fisayo A. Olotu ◽  
Mahmoud E. Soliman

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.


2002 ◽  
Vol 158 (7) ◽  
pp. 1161-1170 ◽  
Author(s):  
Yali Dou ◽  
Josephine Bowen ◽  
Yifan Liu ◽  
Martin A. Gorovsky

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.


Nature ◽  
2012 ◽  
Vol 488 (7410) ◽  
pp. 165-166 ◽  
Author(s):  
Andrew J. Baldwin ◽  
Lewis E. Kay
Keyword(s):  

2011 ◽  
Vol 1218 (49) ◽  
pp. 8925-8936 ◽  
Author(s):  
Stefan Hofer ◽  
Alexander Ronacher ◽  
Jeannie Horak ◽  
Heiner Graalfs ◽  
Wolfgang Lindner

2018 ◽  
Vol 44 (3-4) ◽  
pp. 123-208 ◽  
Author(s):  
Philippe Schlenker

AbstractWhile it is now accepted that sign languages should inform and constrain theories of ‘Universal Grammar’, their role in ‘Universal Semantics’ has been under-studied. We argue that they have a crucial role to play in the foundations of semantics, for two reasons. First, in some casessign languages provide overt evidence on crucial aspects of the Logical Form of sentences, ones that are only inferred indirectly in spoken language. For instance, sign language ‘loci’ are positions in signing space that can arguably realize logical variables, and the fact that they are overt makes it possible to revisit foundational debates about the syntactic reality of variables, about mechanisms of temporal and modal anaphora, and about the existence of dynamic binding. Another example pertains to mechanisms of ‘context shift’, which were postulated on the basis of indirect evidence in spoken language, but which are arguably overt in sign language. Second, along one dimensionsign languages are strictly more expressive than spoken languagesbecause iconic phenomena can be found at their logical core. This applies to loci themselves, which maysimultaneouslyfunction as logical variables and as schematic pictures of what they denote (context shift comes with some iconic requirements as well). As a result, the semantic system of spoken languages can in some respects be seen as a simplified version of the richer semantics found in sign languages. Two conclusions could be drawn from this observation. One is that the full extent of Universal Semantics can only be studied in sign languages. An alternative possibility is that spoken languages have comparable expressive mechanisms, but only when co-speech gestures are taken into account (as recently argued by Goldin-Meadow and Brentari). Either way, sign languages have a crucial role to play in investigations of the foundations of semantics.


Author(s):  
W. Du ◽  
H. Fan ◽  
J. Li ◽  
H. Wang

A lot of work has been done on the geospatial service composition to support advanced processing, spatial calculation, and invoking of heterogeneous data. However, the quality of service chain is rarely considered and the process model cannot be reused. A modeldriven way of geospatial web service composition is proposed in this work, the service composition is treated as an optimization problem by <i>GwcsFlow</i> model and dynamic binding mechanism. The case of facility location analysis is provided to demonstrate the improvements in geospatial service composition through optimization algorithms.


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