Effect of trace amounts of water on organic solvent transport through gamma-alumina membranes with varying pore sizes

The transport behavior of toluene and n-hexane in gamma-alumina membranes with different pore diameters was studied. It was shown that the permeability of water-lean hexane and toluene is in agreement with Darcy's law down to membrane pore diameters of 3.5 nm. The presence of molar water fractions of 5-8 x 10(-4) in these solvents led to a permeability decrease of the gamma-alumina layer by a factor of 2-4 depending on pore size. In general, a lower permeability was found for hexane than for toluene. Moreover, in the presence of water a minimum applied pressure of 0.5-1.5 bar was required to induce net liquid flow through the membrane. These phenomena were interpreted in terms of capillary condensation of water in membrane pores with a size below a certain critical diameter. This is thought to lead to substantial blocking of these pores for transport, so that the effective tortuosity of the membrane for transport of hydrophobic solvents increases.     

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.     

The multiple roles of computational chemistry in fragment-based drug design

Fragment-based drug discovery (FBDD) represents a change in strategy from the screening of molecules with higher molecular weights and physical properties more akin to fully drug-like compounds, to the screening of smaller, less complex molecules. This is because it has been recognised that fragment hit molecules can be efficiently grown and optimised into leads, particularly after the binding mode to the target protein has been first determined by 3D structural elucidation, e.g. by NMR or X-ray crystallography. Several studies have shown that medicinal chemistry optimisation of an already drug-like hit or lead compound can result in a final compound with too high molecular weight and lipophilicity. The evolution of a lower molecular weight fragment hit therefore represents an attractive alternative approach to optimisation as it allows better control of compound properties. Computational chemistry can play an important role both prior to a fragment screen, in producing a target focussed fragment library, and post-screening in the evolution of a drug-like molecule from a fragment hit, both with and without the available fragment-target co-complex structure. We will review many of the current developments in the area and illustrate with some recent examples from successful FBDD discovery projects that we have conducted.     

Investigation on Impurity Profiling and Degradation Behavior of WCK 771

Chromatographia - WCK 771 is a novel antibacterial drug recently launched in India for the treatment of acute bacterial skin and skin structure infections (ABSSSI). This report describes...     

Synthesis and S-methylation of 2-thioxopyrido[3′,2′:4,5]thieno[3,2-d]-pyrimidin-4(3H)-ones with and without a phase transfer catalyst

A number of 2-thioxopyrido[3′,2′:4,5]thieno[3,2-H]pyrimdin-4(3H-ones (5) have been synthesized by cyclocondensation of 2-carbethoxy-3-amino-4-phenyl-6-substituted-thieno[2,3-b]pyridines (3) with various isothiocyanates. Compounds 5 were S-methylated routinely and the reactions compared under solid-liquid phase transfer conditions to obtain 2-methylthiopyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-^ones (6). The new triheterocyclic pyridothienopyrimidines were prepared with the objective to study their pharmacological properties.     

Immobilization and Characterization of <Emphasis Type="Italic">E. gracilis</Emphasis> Extract with Enriched Laminaribiose Phosphorylase Activity for Bienzymatic Production of Laminaribiose

Immobilization methods and carriers were screened for immobilization of Euglena gracilis extract with laminaribiose phosphorylase activity. The extract was successfully immobilized on three different carriers via covalent linkage. Suitable immobilization carriers were Sepabeads EC-EP/S and ECR 8209M with epoxy groups and ECR 8309M with amino groups as functional units. Immobilization on Sepabeads EC-EP/S resulted in highest retained activity (65%). The immobilizates were characterized for pH, temperature, and buffer molarity preferences. The immobilized enzyme lost 48% of its activity when used seven times. Together with sucrose phosphorylase, laminaribiose phosphorylase was successfully applied for bienzymatic production of laminaribiose from sucrose and glucose with a final laminaribiose concentration of 14.3 ± 2.1 g/L (20% yield).     

The Interplay Between Fairness and Randomness in a Spatial Computer Game

This article describes how children use an expressive microworld to articulate ideas about how to make a game seem fair with the use of randomness. Our aim in this study is to disentangle different flavours of fairness and to find out how children used each flavour to make sense of potentially complex behaviour. In order to achieve this, a spatial computer game was designed to enable children to examine the consequences of their attempts to make the game fair. The study investigates how 23 children, aged between 5.5 and 8 years, engaged in constructing a crucial part of a mechanism for a fair spatial lottery machine (microworld). In particular, the children tried to construct a fair game given a situation in which the key elements happened randomly. The children could select objects, determine their properties, and arrange their spatial layout in the machine. The study is based on task-based interviewing of children who were interacting with the computer game. The study shows that children have various cognitive resources for constructing a random fair environment. The spatial arrangement, the visualisation and the manipulations in the lottery machine allow us gain a view into the children’s thinking of the two central concepts, fairness and randomness. The paper reports on two main strategies by which the children attempted to achieve a balance in the lottery machine. One involves arranging the balls symmetrically and the other randomly. We characterize the nature of the thinking in these two strategies: the first we see as deterministic and the latter as stochastic, exploiting the random collisions of the ball. In this article we trace how the children’s thinking moved between these two perspectives.

A Symbolic Dance: The Interplay Between Movement,Notation, and Mathematics on a Journey Toward Solving Equations

This article analyzes the use of the software Grid Algebra with a mixed ability class of 21 nine-to-ten-year-old students who worked with complex formal notation involving all four arithmetic operations. Unlike many other models to support learning, Grid Algebra has formal notation ever present and allows students to “look through” that notation and interpret it either in terms of physical journeys on a grid or in terms of mathematical operations. A dynamic fluidity was found between the formal notation, imagery of movements on a grid, and the process of mathematical operations. This fluidity is interpreted as a “dance” between these three. The significant way in which this dynamic took place reflects the scaffolding and fading offered by the software, which was crucial to the students’ fluency with formal notation well beyond what has been reported from students of that age.     

The Lie algebra of type G2 is rational over its quotient by the adjoint action

Let G be a split simple group of type $G_2$ over a field k, and let $\mathfrak{g}$ be its Lie algebra. Answering a question of J.-L. Colliot-Thélène, B. Kunyavski?, V.L. Popov, and Z. Reichstein, we show that the function field $k(\mathfrak{g})$ is generated by algebraically independent elements over the field of adjoint invariants $k{(\mathfrak{g})}^G$.