Research on the reasoning, teaching and learning of probability and uncertainty

In this editorial, we set out the aims in the call to publish papers on informal statistical inference, randomness, modelling and risk. We discuss how the papers published in this issue have responded to those aims. In particular, we note how the nine papers contribute to some of the major debates in mathematics and statistics education, often taking contrasting positions. Such debates range across: (1) whether knowledge is fractured or takes the form of mental models; (2) heuristic or intuitive thinking versus operational thinking as for example in dual process theory; (3) the role of different epistemic resources, such as perceptions, modelling, imagery, in the development of probabilistic reasoning; (4) how design and situation impact upon probabilistic learning.     

Generation of a Recombinant Full-Length Human Antibody Binding to Botulinum Neurotoxin A

In order to develop a recombinant full-length human anti-botulinum neurotoxin A (BoNT/A) antibody, human peripheral blood mononuclear cells (PBMC) were collected from three healthy volunteers and induced for BoNT/A-specific immune response by in vitro immunization. The genes encoding human Fd fragment, consisting of antibody heavy chain variable region and constant region 1 with the genes encoding antibody light chain, were cloned from the immunized PBMC. Afterwards, one combinatory human antigen-binding fragment (Fab) library was constructed using a lambda phage vector system. The size of the constructed library was approximately 10⁵ Escherichia coli transformants. After screening the library by BoNT/A antigen using a plaque lifting with immunostaining approach, 55 clones were identified as positive. The Fab gene of the most reactive clone exhibiting particularly strong BoNT/A binding signal was further subcloned into a full-length human IgG1 antibody gene template in an adenoviral expression vector, in which the heavy and light chains were linked by a foot-and-mouth-disease virus-derived 2A self-cleavage peptide under a single promoter. After the full-length human IgG1 was expressed in mammalian cells and purified with protein L column, sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the heavy and light chains of the antibody were cleaved completely. The affinity expressed as the dissociation constant (K _d) for the recombinant human antibody to bind to BoNT/A was determined by indirect enzyme-linked immunosorbent assay and results confirmed that the recombinant full-length human antibody retained BoNT/A-binding specificity with K _d value of 10⁻⁷ M.     

Ion-trap quantum information processing:experimental status

Atomic ions trapped in ultra-high vacuum form an especially well-understood and useful physical system for quantum information processing. They provide excellent shielding of quantum information from environmental noise, while strong, well-controlled laser interactions readily provide quantum logic gates. A number of basic quantum information protocols have been demonstrated with trapped ions. Much current work aims at the construction of large-scale ion-trap quantum computers using complex microfabricated trap arrays. Several groups are also actively pursuing quantum interfacing of trapped ions with photons.      

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.     

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.