Alternative Architectures for Distributed Cooperative Problem-Solving in the National Airspace System

The air traffic management system in the United States is an example of a distributed problem solving system. It has elements of both cooperative and competitive problem-solving. This system includes complex organizations such as Airline Operations Centers (AOCs), the FAA Air Traffic Control Systems Command Center (ATCSCC), and traffic management units (TMUs) at enroute centers and TRACONs, all of which have a major focus on strategic decision-making. It also includes individuals concerned more with tactical decisions (such as air traffic controllers and pilots). The architecture for this system has evolved over time to rely heavily on the distribution of tasks and control authority in order to keep cognitive complexity manageable for any one individual operator, and to provide redundancy (both human and technological) to serve as a safety net to catch the slips or mistakes that any one person or entity might make. Currently, major changes are being considered for this architecture, especially with respect to the locus of control, in an effort to improve efficiency and safety. This paper uses a series of case studies to help evaluate some of these changes from the perspective of system complexity, and to point out possible alternative approaches that might be taken to improve system performance. The paper illustrates the need to maintain a clear understanding of what is required to assure a high level of performance when alternative system architectures and decompositions are developed

The biological and structural characterization of Mycobacterium tuberculosis UvrA provides novel insights into its mechanism of action

Mycobacterium tuberculosis is an extremely well adapted intracellular human pathogen that is exposed to multiple DNA damaging chemical assaults originating from the host defence mechanisms. As a consequence, this bacterium is thought to possess highly efficient DNA repair machineries, the nucleotide excision repair (NER) system amongst these. Although NER is of central importance to DNA repair in M. tuberculosis, our understanding of the processes in this species is limited. The conserved UvrABC endonuclease represents the multi-enzymatic core in bacterial NER, where the UvrA ATPase provides the DNA lesion-sensing function. The herein reported genetic analysis demonstrates that M. tuberculosis UvrA is important for the repair of nitrosative and oxidative DNA damage. Moreover, our biochemical and structural characterization of recombinant M. tuberculosis UvrA contributes new insights into its mechanism of action. In particular, the structural investigation reveals an unprecedented conformation of the UvrB-binding domain that we propose to be of functional relevance. Taken together, our data suggest UvrA as a potential target for the development of novel anti-tubercular agents and provide a biochemical framework for the identification of small-molecule inhibitors interfering with the NER activity in M. tuberculosis