Focus on H/D exchange of proteins in solution

Editorial

Focus on H/D exchange of proteins in solution     

Maximum Likelihood Estimates in a M/M/2 Queue with Heterogeneous Servers

Maximum likelihood estimates for the parameters involved in a stationary M/M/2 queueing process with heterogeneous servers are obtained to make inferences about arrival and service rates. The queue is considered to be in a state of equilibrium. One further extension is discussed.     

Mono-coupled periodic systems with a single disorder: Response to convected loadings

This paper presents a general theory of the forced response under convected loading of mono-coupled periodic systems with a single disorder. The general expressions derived have been used to study the response of an infinite periodic beam on simple supports with one of the support spacings different from all the others. Convected harmonic pressure fields and frozen random pressure fields have been considered. Computer studies are presented showing the moment response at supports and the space-time-averaged responses in the disorder and in the nearby periodic beam elements. High response levels can occur due to (i) resonances of the beam length disorder against the stiffness of the attached periodic systems and (ii) hydrodynamic coincidence vibration occurring in the periodic beam. The frequency zones in which these high responses may occur are identified. The high response due to the resonance (ii) is restricted to the vicinity of the disorder, whereas that due to coincidence occurs throughout the system. Computed results show that the highest response levels do not necessarily occur in the beam length disorder, but may occur in one of the nearby periodic beam elements. The dependence of the maximum response levels on the magnitude of the disorder has been investigated. The conditions under which small disorders may be neglected have been pointed out.     

Inventory returns and special sales in a lot-size system with constant rate of deterioration

The problem of returning or of selling the inventory excess to optimal stock level is considered for deteriorating items. Two inventory models, viz. the infinite and the finite horizon models, are developed, in which the deterioration is assumed to be a constant fraction of the on hand inventory. Both the models are developed under the assumptions of instantaneous delivery and no shortages. When there is no deterioration, the developed models are related to the corresponding inventory models for non-deteriorating items. Examples are given to illustrate the derived results.     

Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice

Background  

The pathology of Alzheimer's disease (AD) is comprised of extracellular amyloid plaques, intracellular tau tangles, dystrophic neurites and neurodegeneration. The mechanisms by which these various pathological features arise are under intense investigation. Here, expanding upon pilot gene expression studies, we have further analyzed the relationship between Na+/K+ ATPase and amyloid using APP+PS1 transgenic mice, a model that develops amyloid plaques and memory deficits in the absence of tangle formation and neuronal or synaptic loss.     

Cartan-decomposition subgroups of

For and , we give explicit, practical conditions that determine whether or not a closed, connected subgroup of has the property that there exists a compact subset of with . To do this, we fix a Cartan decomposition of , and then carry out an approximate calculation of for each closed, connected subgroup of .

     

Discovery of aminoglycoside mimetics by NMR-based screening of Escherichia coli A-site RNA

A method is described for the NMR-based screening for the discovery of aminoglycoside mimetics that bind to Escherichia coli A-site RNA. Although aminoglycosides are clinically useful, they exhibit high nephrotoxicity and ototoxicity, and their overuse has led to the development of resistance to important microbial pathogens. To identify a new series of aminoglycoside mimetics that could potentially overcome the problems associated with toxicities and resistance development observed with the aminoglycosides, we have prepared large quantities of E. coli 16 S A-site RNA and conducted an NMR-based screening of our compound library in search for small-molecule RNA binders against this RNA target. From these studies, several classes of compounds were identified as initial hits with binding affinities in the range of 70 microM to 3 mM. Lead optimization through synthetic modifications of these initial hits led to the discovery of several small-molecule aminoglycoside mimetics that are structurally very different from the known aminoglycosides. Structural models of the A-site RNA/ligand complexes were prepared and compared to the three-dimensional structures of the RNA/aminoglycoside complexes.     

Stability of a Pivoting Strategy for Parallel Gaussian Elimination

Gaussian elimination with partial pivoting achieved by adding the pivot row to the kth row at step k, was introduced by Onaga and Takechi in 1986 as means for reducing communications in parallel implementations. In this paper it is shown that the growth factor of this partial pivoting algorithm is bounded above by _n <#60; 3 ^n–1, as compared to 2 ^n–1 for the standard partial pivoting. This bound _n, close to 3 ^n–2, is attainable for class of near-singular matrices. Moreover, for the same matrices the growth factor is small under partial pivoting.This revised version was published online in October 2005 with corrections to the Cover Date.     

Improvement of a low pH antigen-antibody dissociation procedure for ELISA measurement of circulating anti-Aβ antibodies

Background  

Prior work from our group found that acid dissociation (pH 2.5 incubation) of serum from APP transgenic mice vaccinated against Aβ increased the apparent anti-Aβ titers, suggesting antibody masking by antigen in the ELISA assay. Subsequently, we found that pH 2.5 incubation of serum from unvaccinated non-transgenic mice showed antibody binding to Aβ1–42, but no increase when other proteins, including shorter Aβ peptides, coated the ELISA plate. To investigate further the effects of low pH incubation on apparent anti-Aβ1–42 signals, we examined normal sera from nonTg unvaccinated mice, nonTg mice vaccinated with Aβ peptide (to produce authentic anti-Aβ antibodies) or a monoclonal antibody against Aβ (6E10) using competitive-inhibition ELISA and Aβ epitope mapping assays. In addition, we examined use of a less stringent low pH procedure at pH 3.5, to ascertain if it had the same effects as the pH 2.5 procedure.