Integration of mass spectrometry into early-phase discovery and development of central nervous system agents.

The early-phase discovery and development of useful central nervous system (CNS) agents present ample opportunities to exploit mass spectrometry and provide detailed compound/mixture characterization, or to make the process faster and/or more economic. Neuropeptide FF antagonists and centrally active thyrotropin-releasing hormone analogues were used as specific examples in this work. We evaluated the characterization of focused libraries of peptide derivatives by electrospray ionization, tandem mass spectrometry and liquid chromatography/tandem mass spectrometry on a quadrupole ion trap and nanoelectrospray on a Fourier transform ion cyclotron resonance mass spectrometer. Immobilized artificial-membrane chromatography was employed as a model to predict/rank new agents against lead compounds for their potential to reach the central nervous system in pharmacologically significant amounts. Measuring brain concentrations in rodents after the intravenous administration of test compounds was used as an in vivo approach, and we took advantage of microdialysis sampling that furnished samples without interfering tissue matrix and afforded the estimation of extracellular concentrations in a localized part of the brain. Overall, making atmospheric-pressure ionization mass spectrometry an integral part of the process has played a major role in increasing throughput, selectivity, specificity and detection sensitivity and thereby providing useful information about the extent or mechanism of transport and metabolic activation/inactivation in early-phase discovery and development of CNS agents.     

The sub-wavelength imaging performance of disordered wire media

An analysis of the sub-wavelength imaging performance of disordered thin wire media is undertaken, in order to understand how its performance may be affected by manufacturing errors. The structure is found to be extremely robust to disorder which keeps the wires parallel. Variation in the orientation of the wires and their longitudinal position causes more significant degradation in the image quality, which is quantified numerically.     

Ueber die Einwirkung einiger Agentien auf in der Natur vorkommende Carbonate

Ohne Zusammenfassung     

A comparative study of modeling and solution approaches for the coordinated lot-size problem with dynamic demand

In the coordinated lot-size problem, a major setup cost is incurred when at least one member of a product family is produced and a minor setup cost for each different item produced. This research consolidates the various modeling and algorithmic approaches reported in the literature for the coordinated replenishment problem with deterministic dynamic demand. For the two most effective approaches, we conducted extensive computational experiments investigating the quality of the lower bound associated with the model’s linear programming relaxation and the computational efficiency of the algorithmic approaches when used to find heuristic and optimal solutions. Our findings indicate the superiority of the plant location type problem formulation over the traditional approach that views the problem as multiple single-item Wagner and Whitin problems that are coupled by major setup costs. Broader implications of the research suggest that other classes of deterministic dynamic demand lot-size problems may also be more effectively modeled and solved by adapting plant location type models and algorithms.     

Solving 0-1 Minimax Problems

It has been shown that it is possible to solve a minimax 0-1 programming problem by transforming the objective function coefficients and solving a minisum problem. This result is very useful for solving a ‘hard’ minimax problem when there exists a ‘relatively easy’ algorithm to solve the minisum problem. We discuss such problems and present a new transformation.     

Novel mixed-valent Co(II)₂Co(III)₄Ln(III)₄ aggregates with ligands derived from tris-(hydroxymethyl)aminomethane (Tris)

Isostructural Co(II)?Co(III)?Ln(III)? (Ln = Y (1), Gd (2) and Dy (3)) coordination clusters formed using the ligand Tris are the first examples of 3d-4f complexes involving this ligand and show weak ferromagnetic coupling between the Co(II) ions and slow relaxation (SMM) behaviour for 3.     

The equivalence of bar recursion and open recursion

Several extensions of Gödel's system T$\mathsf{T}$ with new forms of recursion have been designed for the purpose of giving a computational interpretation to classical analysis. One can organise many of these extensions into two groups: those based on bar recursion, which include Spector's original bar recursion, modified bar recursion and the more recent products of selections functions, or those based on open recursion   which in particular include the symmetric Berardi–Bezem–Coquand (BBC) functional. We relate these two groups by showing that both open recursion and the BBC functional are primitive recursively equivalent to a variant of modified bar recursion. Our results, in combination with existing research, essentially complete the classification up to primitive recursive equivalence of those extensions of system T$\mathsf{T}$ used to give a direct computational interpretation to choice principles.