The specificity of the N-terminal SH2 domain of SHP-2 is modified by a single point mutation

SH2 domains are small protein domains of approximately 100 amino acids that bind to phosphotyrosine (pY) in the context of a specific sequence surrounding the target pY. In general, the residues C-terminal to the pY of the binding target are considered most important for defining the binding specificity, and in particular the pY + 1 and pY + 3 residues (i.e., the first and third amino acids C-terminal to the pY). However, our previous studies with the SH2 domains of the protein tyrosine phosphatase SHP-2 [Huyer, G., Li, Z. M., Adam, M., Huckle, W. R., and Ramachandran, C. (1995) Biochemistry 34, 1040-1049] indicated important interactions with the pY - 2 residue as well. In the SH2 domains of SHP-2, the highly conserved alphaA2 Arg is replaced by Gly. A comparison of the published crystal structures of the Src SH2 domain and the N-terminal SH2 domain of SHP-2 complexed with high-affinity peptides suggested that the alphaA2 Gly of SHP-2 creates a gap which is filled by the side chain of the pY - 2 residue of the bound peptide. It was predicted that replacing this Gly with Arg would alter or eliminate the involvement of the pY - 2 residue in binding. The alphaA2 Gly --> Arg mutant was constructed, and indeed, this mutant no longer required residues N-terminal to the target pY for high-affinity binding, making its specificity more like that of other SH2 domains. The alphaA2 Gly is clearly involved in directing the unusual requirement for the pY - 2 residue in the binding sequence of this SH2 domain, which has important implications for its in vivo targeting and specificity.     

Experiences with network-based user agents for mobile applications

Wireless networks are characterized by simple end devices and limited bandwidth. One solution to address these and other limitations of the wireless mobile environment that has been widely pursued is the placement of proxies, or agents, inside the network to assist with application processing that would normally take place on end devices. These agents can additionally manipulate data to reduce bandwidth requirements and assist in providing services. The design and implementation of a user agent is heavily impacted by the application it supports. In this paper we present our experiences with user agents in two different types of applications: telephony-based Personal Communication Services (PCS) and two-way messaging. To provide low latency service, the PCS user agents are mobile so that they may be kept close to their end devices. The design of the PCS agents limits migration overhead to the transfer of approximately 100 bytes of information in about 150 milliseconds. To provide advanced messaging services, the messaging user agent supports flexible messages while limiting air interface bandwidth usage. The messaging agents reduce uplink bandwidth usage by approximately 35% when applied to a cellular PCS system, and reduce message payloads by 97%. This revised version was published online in June 2006 with corrections to the Cover Date.     

Optimal Equalization of Discrete Signals Passed Through a Random Channel

The problem of equalizing a discrete signal that has been transmitted through a channel selected at random from an ensemble of channels is considered. Using mean-square error as the performance index, the minimum number of adjustable parameters required to achieve a given level of performance is sought. For certain special cases, it is shown that, using nonrecursive sampled data filters, the optimum tap weights are given by the eigenvectors of the matrix formed from the covariances of the channel's impulse response. A numerical algorithm is developed to find the optimum equalizer structure for a wide class of channels with the restriction that the number of channels in the given ensemble is finite. Results worked out for several examples show that the optimum equalizer structure requires significantly fewer adjustable parameters than the standard transversal equalizer in order to obtain the same level of performance.     

Laminar film boiling on a porous vertical wall with uniform suction velocity

Laminar free convection film boiling on a porous vertical wall with uniform suction or blowing is analysed using boundary layer theory. The solutions are obtained assuming suction or blowing to be a disturbance superposed on the isothermal, impermeable wall case. Using a parameter involving the suction or blowing velocity, universal functions are derived for various values of Prandtl Number and c_p(T_w — T_sat)/h_fgPr. These universal functions can be used to estimate the heat transfer rate in the presence of suction or blowing. As expected, suction increases the heat transfer rate while blowing decreases the heat-transfer. Even small velocities of suction or blowing could significantly affect the heat transfer. It is also found that the effects of suction or blowing are more pronounced at lower wall superheats.     

Significance of low water—solid ratio and temperature on the physico-mechanical characteristics of hydrates of tricalcium aluminate

Hydration characteristics are reported of tricalcium aluminate studied at 20 and 80 °C using water-solid ratios of 0.2 and 1.0. Hydration products were subjected to differential thermal analysis, thermogravimetric analysis, scanning electron microscopy, length change, porosity and pore size distribution, and micro-hardness measurements. Hydration proceeds faster at 80 °C than at 20 °C and the cubic C₃AH₆ phase is detected in the first few seconds. At 20 °C hydration occurs with the initial formation of the hexagonal phases and expansion is continuous. At higher temperatures and a water-solid ratio of 0.2, after an initial small expansion, the dimensional change is low. The product at 80 °C develops more than fourfold the hardness value developed at 20 °C. After 2 days of hydration, porosity, per cent C₃AH₆ and microhardness are 15.2%, 83% and 38.9 kg/mm²; corresponding values for the product obtained at 20 °C are 21.5%, 75% and 9.1 kg/mm². Microstructural examination of the material formed at 80 °C indicates a closely welded and continuous network of the cubic phase. These results reveal that at a low water-solid ratio and higher temperatures the formation of the cubic phase from C₃A results in an enhancement of strength.     

Synthesis of transfer functions by nonsymmetrical lattice networks using lossy coils

A method for realising a v.t.f.by a nonsymmetrical lattice in which all coils can be made lossy is given.     

Influence of crack closure on the stress intensity factor for plates subjected to bending—A 3-D finite element analysis

Plates with central through cracks subjected to bending is analysed taking into account the closure of the crack faces on the compression side. A three-dimensional finite element method employing three-dimensional degenerate solid element is used for the analysis. The crack faces have been modelled such that they come in contact over an area on the compression side and interfere with each other. The influence of the crack closure on the variation of the stress intensity factor across the plate thickness is obtained for finite and infinite plate geometries.     

Large amplitude vibrations of circular plates with mixed boundary conditions

In this paper, a method of analysing large amplitude vibrations of circular plates with mixed boundary conditions is explained and is illustrated with an example where part of the boundary is clamped and the remaining simply-supported     

A high-performance computing method for data allocation in distributed database systems

Enhancing the performance of the DDBs (Distributed Database system) can be done by speeding up the computation of the data allocation, leading to higher speed allocation decisions and resulting in smaller data redundancy and shorter processing time. This paper deals with an integrated method for grouping the distributed sites into clusters and customizing the database fragments allocation to the clusters and their sites. We design a high speed clustering and allocating method to determine which fragments would be allocated to which cluster and site so as to maintain data availability and a constant systemic reliability, and evaluate the performance achieved by this method and demonstrate its efficiency by means of tabular and graphical representation. We tested our method over different network sites and found it reduces the data transferred between the sites during the execution time, minimizes the communication cost needed for processing applications, and handles the database queries and meets their future needs.