Mycobacterium tuberculosis pantothenate kinase: possible changes in location of ligands during enzyme action

The crystal structures of complexes of Mycobacterium tuberculosis pantothenate kinase with the following ligands have been determined: (i) citrate; (ii) the nonhydrolysable ATP analogue AMPPCP and pantothenate (the initiation complex); (iii) ADP and phosphopantothenate resulting from phosphorylation of pantothenate by ATP in the crystal (the end complex); (iv) ATP and ADP, each with half occupancy, resulting from a quick soak of crystals in ATP (the intermediate complex); (v) CoA; (vi) ADP prepared by soaking and cocrystallization, which turned out to have identical structures, and (vii) ADP and pantothenate. Solution studies on CoA binding and catalytic activity have also been carried out. Unlike in the case of the homologous Escherichia coli enzyme, AMPPCP and ADP occupy different, though overlapping, locations in the respective complexes; the same is true of pantothenate in the initiation complex and phosphopantothenate in the end complex. The binding site of MtPanK is substantially preformed, while that of EcPanK exhibits considerabl plasticity. The difference in the behaviour of the E. coli and M. tuberculosis enzymes could be explained in terms of changes in local structure resulting from substitutions. It is unusual for two homologous enzymes to exhibit such striking differences in action. Therefore, the results have to be treated with caution. However, the changes in the locations of ligands exhibited by M. tuberculosis pantothenate kinase are remarkable and novel.

An on-line algorithm for the location of cross point faults in programmable logic arrays

An on-line algorithm is developed for the location of single cross point faults in a PLA (FPLA). The main feature of the algorithm is the determination of a fault set corresponding to the response obtained for a failed test. For the apparently small number of faults in this set, all other tests are generated and a fault table is formed. Subsequently, an adaptive procedure is used to diagnose the fault. Functional equivalence test is carried out to determine the actual fault class if the adaptive testing results in a set of faults with identical tests. The large amount of computation time and storage required in the determination, a priori, of all the fault equivalence classes or in the construction of a fault dictionary are not needed here. A brief study of functional equivalence among the cross point faults is also made.

Transmission loss analysis of rectangular expansion chamber with arbitrary location of inlet/outlet by means of Green's functions

Transmission loss of a rectangular expansion chamber, the inlet and outlet of which are situated at arbitrary locations of the chamber, i.e., the side wall or the face of the chamber, are analyzed here based on the Green's function of a rectangular cavity with homogeneous boundary conditions. The rectangular chamber Green's function is expressed in terms of a finite number of rigid rectangular cavity mode shapes. The inlet and outlet ports are modeled as uniform velocity pistons. If the size of the piston is small compared to wavelength, then the plane wave excitation is a valid assumption. The velocity potential inside the chamber is expressed by superimposing the velocity potentials of two different configurations. The first configuration is a piston source at the inlet port and a rigid termination at the outlet, and the second one is a piston at the outlet with a rigid termination at the inlet. Pressure inside the chamber is derived from velocity potentials using linear momentum equation. The average pressure acting on the pistons at the inlet and outlet locations is estimated by integrating the acoustic pressure over the piston area in the two constituent configurations. The transfer matrix is derived from the average pressure values and thence the transmission loss is calculated. The results are verified against those in the literature where use has been made of modal expansions and also numerical models (FEM fluid). The transfer matrix formulation for yielding wall rectangular chambers has been derived incorporating the structural–acoustic coupling. Parametric studies are conducted for different inlet and outlet configurations, and the various phenomena occurring in the TL curves that cannot be explained by the classical plane wave theory, are discussed.

An On-Line Algorithm for the Location of Cross Point Faults in Programmable Logic Arrays

An on-line algorithm is developed for the location of single cross point faults in a PLA (FPLA). The main feature of the valgorithm is the determination of a fault set corresponding to the response obtained for a failed test. For the apparently small number of faults in this set, all other tests are generated and a fault table is formed. Subsequently, an adaptive procedure is used to diagnose the fault. Functional equivalence test is carried out to determine the actual fault class if the adaptive testing results in a set of faults with identical tests. The large amount of computation time and storage required in the determination, a priori, of all the fault equivalence classes or in the construction of a fault dictionary are not needed here. A brief study of functional equivalence among the cross point faults is also made.

Location of concentrators in a computer communication network: a stochastic automation search method

The following problem is considered. Given the locations of the Central Processing Unit (ar;the terminals which have to communicate with it, to determine the number and locations of the concentrators and to assign the terminals to the concentrators in such a way that the total cost is minimized. There is alao a fixed cost associated with each concentrator. There is ail upper limit to the number of terminals which can be connected to a concentrator. The terminals can be connected directly to the CPU also In this paper it is assumed that the concentrators can bo located anywhere in the area A containing the CPU and the terminals. Then this becomes a multimodal optimization problem. In the proposed algorithm a stochastic automaton is used as a search device to locate the minimum of the multimodal cost function . The proposed algorithm involves the following. The area A containing the CPU and the terminals is divided into an arbitrary number of regions (say K). An approximate value for the number of concentrators is assumed (say m). The optimum number is determined by iteration later The m concentrators can be assigned to the K regions in (mk) ways (m > K) or (km) ways (K>m).(All possible assignments are feasible, i.e. a region can contain 0,1,…, to concentrators). Each possible assignment is assumed to represent a state of the stochastic variable structure automaton. To start with, all the states are assigned equal probabilities. At each stage of the search the automaton visits a state according to the current probability distribution. At each visit the automaton selects a 'point' inside that state with uniform probability. The cost associated with that point is calculated and the average cost of that state is updated. Then the probabilities of all the states are updated. The probabilities are taken to bo inversely proportional to the average cost of the states After a certain number of searches the search probabilities become stationary and the automaton visits a particular state again and again. Then the automaton is said to have converged to that state Then by conducting a local gradient search within that state the exact locations of the concentrators are determined This algorithm was applied to a set of test problems and the results were compared with those given by Cooper's (1964, 1967) EAC algorithm and on the average it was found that the proposed algorithm performs better.

Location of Pathogenic Bacteria during Persistent Infections: Insights from an Analysis Using Game Theory

Bacterial persistent infections are responsible for a significant amount of the human morbidity and mortality. Unlike acute bacterial infections, it is very difficult to treat persistent bacterial infections (e.g. tuberculosis). Knowledge about the location of pathogenic bacteria during persistent infection will help to treat such conditions by designing novel drugs which can reach such locations. In this study, events of bacterial persistent infections were analyzed using game theory. A game was defined where the pathogen and the host are the two players with a conflict of interest. Criteria for the establishment of Nash equilibrium were calculated for this game. This theoretical model, which is very simple and heuristic, predicts that during persistent infections pathogenic bacteria stay in both intracellular and extracellular compartments of the host. The result of this study implies that a bacterium should be able to survive in both intracellular and extracellular compartments of the host in order to cause persistent infections. This explains why persistent infections are more often caused by intracellular pathogens like Mycobacterium and Salmonella. Moreover, this prediction is in consistence with the results of previous experimental studies.

Role of free valences and spin densities on the migrating atom in location of saddle points in radical-exchange reactions

The principle of the conservation of bond orders during radical-exchange reactions is examined using Mayer's definition of bond orders. This simple intuitive approximation is not valid in a quantitative sense. Ab initio results reveal that free valences (or spin densities) develop on the migrating atom during reactions. For several examples of hydrogen-transfer reactions, the sum of the reaction coordinate bond orders in the transition state was found to be 0.92 +/- 0.04 instead of the theoretical 1.00 because free valences (or spin densities) develop on the migrating atom during reactions. It is shown that free valence is almost equal to the square of the spin density on the migrating hydrogen atom and the maxima in the free valence (or spin density) profiles coincide (or nearly coincide) with the saddle points in the corresponding energy profiles.

Optimal location of centre of gravity for swashplateless helicopter UAV and MAV

To investigate the use of centre of gravity location on reducing cyclic pitch control for helicopter UAV's (unmanned air vehicles) and MAV's (micro air vehicles). Low cyclic pitch is a necessity to implement the swashplateless rotor concept using trailing edge flaps or active twist using current generation low authority piezoceramic actuators. Design/methodology/approach – An aeroelastic analysis of the helicopter rotor with elastic blades is used to perform parametric and sensitivity studies of the effects of longitudinal and lateral center of gravity (cg) movements on the main rotor cyclic pitch. An optimization approach is then used to find cg locations which reduce the cyclic pitch at a given forward speed. Findings – It is found that the longitudinal cyclic pitch and lateral cyclic pitch can be driven to zero at a given forward speed by shifting the cg forward and to the port side, respectively. There also exist pairs of numbers for the longitudinal and lateral cg locations which drive both the cyclic pitch components to zero at a given forward speed. Based on these results, a compromise optimal cg location is obtained such that the cyclic pitch is bounded within ±5° for a BO105 helicopter rotor. Originality/value – The reduction in the cyclic pitch due to helicopter cg location is found to significantly reduce the maximum magnitudes of the control angles in flight, facilitating the swashplateless rotor concept. In addition, the existence of cg locations which drive the cyclic pitches to zero allows for the use of active cg movement as a way to replace the cyclic pitch control for helicopter MAV's.

Ranking of Prospective New Generation Location for a Power Network in a Deregulated System

In developing countries high rate of growth in demand of electric energy is felt, and so the addition of new generating units becomes necessary. In deregulated power systems private generating stations are encouraged to add new generations. Finding the appropriate location of new generator to be installed can be obtained by running repeated power flows, carrying system studies like analyzing the voltage profile, voltage stability, loss analysis etc. In this paper a new methodology is proposed which will mainly consider the existing network topology into account. A concept of T-index is introduced in this paper, which considers the electrical distances between generator and load nodes.This index is used for ranking significant new generation expansion locations and also indicates the amount of permissible generations that can be installed at these new locations. This concept facilitates for the medium and long term planning of power generation expansions within the available transmission corridors. Studies carried out on a sample 7-bus system, EHV equivalent 24-bus system and IEEE 39 bus system are presented for illustration purpose.

Experimental investigation of cowl shape and location on inlet characteristics at hypersonic Mach number

An experimental study is presented to show the effect of the cowl location and shape on the shock interaction phenomena in the inlet region for a 2D, planar scramjet inlet model. Investigations include schlieren visualization around the cowl region and heat transfer rate measurement inside the inlet chamber.Both regular and Mach reflections are observed when the forebody ramp shock reflects from the cowl plate. Mach stem heights of 3.3 mm and 4.1 mm are measured in 18.5 mm and 22.7 mm high inlet chambers respecively. Increased heat transfer rate is measured at the same location of chamber for cowls of longer lenghs is indicating additional mass flow recovery by the inlet.

Phenyl-Ring-Bearing Cationic Surfactants: Effect of Ring Location on the Micellar Structure

A series of isomeric cationic surfactants (S1-S5) bearing a long alkyl chain that carries a 1,4-phenylene unit and a trimethyl ammonium headgroup was synthesized; the location of the phenyl ring within the alkyl tail was varied in an effort to understand its influence on the amphiphilic properties of the surfactants. The cmc's of the surfactants were estimated using ionic conductivity measurements and isothermal calorimetric titrations (ITC); the values obtained by the two methods were found to be in excellent agreement. The ITC measurements provided additional insight into the various thermodynamic parameters associated with the micellization process. Although all five surfactants have exactly the same molecular formula, their micellar properties were seen to vary dramatically depending on the location of the phenyl ring; the cmc was seen to decrease by almost an order of magnitude when the phenyl ring was moved from the tail end (cmc of S1 is 23 mM) to the headgroup region (cmc of S5 is 3 mM). In all cases, the enthalpy of micellization was negative but the entropy of micellization was positive, suggesting that in all of these systems the formation of micelles is both enthalpically and entropically favored. As expected, the decrease in cmc values upon moving the phenyl ring from the tail end to he headgroup region is accompanied by an increase in the thermodynamic driving force (Delta G) for micellization. To understand further the differences in the micellar structure of these surfactants, small-angle neutron scattering (SANS) measurements were carried out; these measurements reveal that the aggregation number of the micelles increases as the cmc decreases. This increase in the aggregation number is also accompanied by an increase in the asphericity of the micellar aggregate and a decrease in the fractional charge. Geometric packing arguments are presented to account for these changes in aggregation behavior as a function of phenyl ring location.

Location and conformation of pantothenate and its derivatives in Mycobacterium tuberculosis pantothenate kinase: insights into enzyme action

Previous studies of complexes of Mycobacterium tuberculosis PanK (MtPanK) with nucleotide diphosphates and non-hydrolysable analogues of nucleoside triphosphates in the presence or the absence of pantothenate established that the enzyme has dual specificity for ATP and GTP, revealed the unusual movement of ligands during enzyme action and provided information on the effect of pantothenate on the location and conformation of the nucleotides at the beginning and the end of enzyme action. The X-ray analyses of the binary complexes of MtPanK with pantothenate, pantothenol and N-nonylpantothenamide reported here demonstrate that in the absence of nucleotide these ligands occupy, with a somewhat open conformation, a location similar to that occupied by phosphopantothenate in the `end' complexes, which differs distinctly from the location of pantothenate in the closed conformation in the ternary `initiation' complexes. The conformation and the location of the nucleotide were also different in the initiation and end complexes. An invariant arginine appears to play a critical role in the movement of ligands that takes place during enzyme action. The work presented here completes the description of the locations and conformations of nucleoside diphosphates and triphosphates and pantothenate in different binary and ternary complexes, and suggests a structural rationale for the movement of ligands during enzyme action. The present investigation also suggests that N-alkylpantothenamides could be phosphorylated by the enzyme in the same manner as pantothenate.

Selection of Static VAR Compensator Location and Size for System Voltage Stability Improvement

This paper presents a methodology for selection of static VAR compensator location based on static voltage stability analysis of power systems. The analysis presented here uses the L-index of load buses, which includes voltage stability information of a normal load flow and is in the range of 0 (no load of system) to 1 (voltage collapse). An approach has been presented to select a suitable size and location of static VAR compensator in an EHV network for system voltage stability improvement. The proposed approach has been tested under simulated conditions on a few power systems and the results for a sample radial network and a 24-node equivalent EHV power network of a practical system are presented for illustration purposes. © 2000 Published by Elsevier Science S.A. All rights reserved.