Optimal solutions for a dock assignment problem with trailer transportation

This paper presents a model for a dock assignment problem, where trailers need to be assigned to gates for a given period of time for loading or unloading activities. The parking lot is used as a buffer zone. Transportation between the parking lot and the gates is performed by additional resources called terminal tractors. The problem is modeled as a three-stage flexible flow shop, where the first and the third stage share the same identical parallel machines and the second stage consists of a different set of identical parallel machines. We examine multiple integer-programming formulations for the parallel-machine model in stage two and for the three-stage flow shop and we provide extensive computational results. Our goal is to explore the limits of the instance sizes that can be solved to guaranteed optimality within acceptable running times using integer programming.     

Synthesis and Resolution of ATPO,a Potent and Selective Ampa Receptor Antagonist

Abstract

The excitatory amino acid (EAA) receptors mediate one of the major signaling systems in the central nervous system, and they are thought to be implicated in some neurodege-nerative disorders, e.g. Alzheimer's disease and stroke. It is of key importance to design selective ligands for every group of EAA receptors. The AMPA receptors are one such group of EAA receptors. (RS)-ATPO is a potent antagonist at the AMPA receptors, but it has hitherto been pharmacologically characterized only as the racemate.[1, 2]     

Metabolic profiling of mouse cerebrospinal fluid by sheathless CE-MS

The need for sensitive analytical technologies applicable to metabolic profiling of volume-restricted biological samples is high. Here, we demonstrate feasibility of capillary electrophoresis (CE) coupled to electrospray ionization mass spectrometry (MS) with sheathless nano-electrospray interface for non-targeted profiling of ionogenic metabolites in body fluids of experimental animals. A representative mixture of the metabolites and body fluids of mice such as cerebrospinal fluid (CSF), urine and plasma were used as examples of low-volume biological samples for method evaluation. An injection volume of only 9?nL resulted in limits of detection between 0.7 and 12?nM for the metabolite mixture. The method allowed the detection of ～350 molecular features in mouse CSF (an injection volume of ca. 45?nL), while ～400 features were observed in mouse plasma and ～3,500 features in mouse urine (an injection volume of ca. 9?nL). The low-volume body fluid samples were analyzed directly after only 1:1 dilution with water, thereby fully retaining sample integrity, which is of crucial importance for non-targeted metabolic profiling. As little is known about the metabolic composition of mouse CSF, we identified a fraction of the molecular features in mouse CSF using accurate mass information, migration times, MS/MS data, and comparison with authentic standards. We conclude that sheathless CE-MS can be used for sensitive metabolic profiling of volume-restricted biological samples.     

Crystal Structure and Quantum Chemical Ab Initio Calculations of Ibotenic Acid,an Excitatory Amino Acid Receptor Agonist

Ibotenic acid, a constituent of Amanita muscaria, is a potent NMDA receptor agonist. The structure of the ibotenic acid zwitterion monohydrate in the crystalline state has been determined by X-ray crystallography. The crystal structure has two ibotenic acid monohydrate formula units in the asymmetric unit and features an extensive hydrogen bond network. The ibotenic acid zwitter-ions in the crystalline state are compared to the in vacuo structure calculated by quantum chemical ab initio calculations at the HF/6-31+G* level and the effects of the hydrogen bond network on the structures in the solid state are discussed. The calculated potential energy curve with respect to side-chain orientation displays a single energy minimum. The conformations corresponding to the solid-state conformations are calculated to be ca. 2 kcal/mol higher in energy than the minimum-energy conformation in vacuo.     

The Crystal Structure of Methyl β-orcinol-carboxylate (= Methyl 2,4-dihydroxy-3,6-dimethylbenzoate)

The mono-arylic compound, methyl β-orcinol-carboxylate ( I ) is one of the principal components of lichens which grow on the oak tree. In the crystal structure of I the molecules are H-bonded to form sheets separated by 3.56 (5) Å. The carbonyl O-atom of the ester group and the ortho-hydroxyl group form a strong intramolecular H-bond. The IR. spectrum of the solid contains two (O--H)-stretching frequencies which, by comparison with the spectra of the 4-methoxy and the 2-methoxy analogues, can be assigned to one intra- and one intermolecular H-bond.     

Issues with the European Pharmacopoeia Quality Control Method for 99mTc-Labelled Macroaggregated Albumin

Technetium-99m macroaggregated albumin ([^99mTc]Tc-MAA) is an injectable radiopharmaceutical used in nuclear medicine for lung perfusion scintigraphy. After changing to a new batch of macroaggregated albumin (MAA), we saw unwanted uptake in the liver and spleen. The batch was therefore tested by both the supplier and us and we found it to comply with the requirements of the European Pharmacopoeia (Ph. Eur.). However, a simple comparison between the problematic batch and a batch supplied by another manufacturer showed that there was a significant difference. The quality testing showed a higher number of small particles in the problem encumbered MAA batch with unwanted in vivo uptake. In this article we present a simple method of testing for particle size of [^99mTc]Tc-MAA, which gives a good indication of how the radioactive drug performs in vivo. We argue that the quality control method described in the Ph. Eur. should be changed. The changes will improve concordance between the laboratory analyzes and what is seen in vivo in human lung perfusion scintigraphy. Furthermore, we hope that the MAA suppliers without delay will replace their release procedure to be in accordance with the method described in this article.     

Chiral Lewis Base-Catalysed Asymmetric Syntheses of Benzo-fused ϵ-Lactones

We herein report a two-step protocol for the asymmetric synthesis of novel chiral benzofused ϵ-lactones starting from O-protected hydroxymethyl-para-quinone methides and activated aryl esters. By using chiral isothiourea Lewis base catalysts a broad variety of differently substituted products could be obtained in yields of around 50 % over both steps with high levels of enantioselectivities, albeit low diastereoselectivities only.