Salt-water up-coning during extraction of fresh water from a tropical island

Rainwater can collect in a lens-shaped region within the rock of a tropical island, and may be separated from the underlying salt water by a sharp interface. This paper presents a nonlinear theory for determining the shape of this interface. The island is assumed to be saturated with rain, and provision is made for the outflow of rain-water through the sides of the island. The effect of a bore well on the shape of the interface is investigated, and the problem is solved using a spectral method. An integral-equation method is also presented for the case when the island has infinite width.     

A novel method for determination of polyester end-groups by NMR spectroscopy

An efficient, convenient and quantitative method for characterising polyester end-groups is described. We have found that trichloroacetyl isocyanate (TAI) reacts rapidly and quantitatively with both carboxyl [C(O)OH] and hydroxyl (OH) chain ends to form derivatives that can be readily determined by ¹H NMR spectroscopy. The TAI capped end-groups give rise to characteristic imidic NH resonances in a normally clear region of the ¹H NMR spectrum [δ∼10-11.5 for C(O)-O-C(O)-NH-C(O)CCl₃ from C(O)OH, δ∼8-9 for O-C(O)-NH-C(O)CCl₃ from OH]. The method has been successfully applied to quantitative determination of the end-groups of a wide variety of oligomeric polyesters. It has also been applied to higher molecular weight polyesters including commercial, bottle grade, poly(ethylene terephthalate) (PET) and PET based copolyesters (e.g. PETG).     

Behavioral model synthesis with Cones

The Cones synthesis system for automatic generation of VLSI implementations is discussed. Named for the cones in sequential logic, Cones takes behavioral models written in C and produces gate-level implementations in technologies such as standard cells and programmable logic arrays or programmable logic devices. The overall design is produced faster, more efficiently, and with fewer errors. Designers are free to concentrate on functions, instead of on the details of the implementation technology     

The additivity of substrate fragments in enzyme-ligand binding

BACKGROUND: Enzymes have evolved to recognise their target substrates with exquisite selectivity and specificity. Whether fragments of the substrate--perhaps never available to the evolving enzyme--are bound in the same manner as the parent substrate addresses the fundamental basis of specificity. An understanding of the relative contributions of individual portions of ligand molecules to the enzyme-binding interaction may offer considerable insight into the principles of substrate recognition. RESULTS: We report 12 crystal structures of Escherichia coli thymidylate synthase in complexes with available fragments of the substrate (dUMP), both with and without the presence of a cofactor analogue. The structures display considerable fidelity of binding mode and interactions. These complexes reveal several interesting features: the cofactor analogue enhances the localisation of substrate and substrate fragments near the reactive thiol; the ribose moiety reduces local disorder through additional specific enzyme-ligand interactions; the pyrimidine has multiple roles, ranging from stereospecificity to mechanistic competence; and the glycosidic linkage has an important role in the formation of a covalent attachment between substrate and enzyme. CONCLUSIONS: The requirements of ligand-protein binding can be understood in terms of the binding of separate fragments of the ligand. Fragments which are subsystems of the natural substrate for the enzyme confer specific contributions to the binding affinity, orientation or electrostatics of the enzymatic mechanism. This ligand-binding analysis provides a complementary method to the more prevalent approaches utilising site-directed mutagenesis. In addition, these observations suggest a modular approach for rational drug design utilising chemical fragments.     

Interactional Order and Constructed Ways of Seeing with Touchless Imaging Systems in Surgery

While surgical practices are increasingly reliant on a range of digital imaging technologies, the ability for clinicians to interact and manipulate these digital representations in the operating theatre using traditional touch based interaction devices is constrained by the need to maintain sterility. To overcome these concerns with sterility, a number of researchers are have been developing ways of enabling interaction in the operating theatre using touchless interaction techniques such as gesture and voice to allow clinicians control of the systems. While there have been important technical strides in the area, there has been little in the way of understanding the use of these touchless systems in practice. With this in mind we present a touchless system developed for use during vascular surgery. We deployed the system in the endovascular suite of a large hospital for use in the context of real procedures. We present findings from a study of the system in use focusing on how, with touchless interaction, the visual resources were embedded and made meaningful in the collaborative practices of surgery. In particular we discuss the importance of direct and dynamic control of the images by the clinicians in the context of talk and in the context of other artefact use as well as the work performed by members of the clinical team to make themselves sensable by the system. We discuss the broader implications of these findings for how we think about the design, evaluation and use of these systems.     

Absolute rate constants for radical-monomer reactions

Summary A method is described for determining the absolute rate constants for the first few propagation steps in radical polymerization. The procedure involves a product analysis of the oligomeric alkoxyamines formed when an initiator is decomposed in monomer containing a very low concentration of a nitroxide radical scavenger. The method is illustrated with analysis of data for methyl acrylate. The rate constants for the first two propagation steps for polymerization of this monomer,k _p(1) andk _p(2), are at least an order of magnitude greater thank _p(average). Values of the absolute rate constants for reactions of phenyl and primary alkyl radicals with methyl acrylate are also estimated.     

Domain flexibility in retroviral proteases: structural implications for drug resistant mutations

Rigid body rotation of five domains and movements within their interfacial joints provide a rational context for understanding why HIV protease mutations that arise in drug resistant strains are often spatially removed from the drug or substrate binding sites. Domain motions associated with substrate binding in the retroviral HIV-1 and SIV proteases are identified and characterized. These motions are in addition to closure of the flaps and result from rotations of approximately 6-7 degrees at primarily hydrophobic interfaces. A crystal structure of unliganded SIV protease (incorporating the point mutation Ser 4 His to stabilize the protease against autolysis) was determined to 2.0 A resolution in a new space group, P3221. The structure is in the most "open" conformation of any retroviral protease so far examined, with six residues of the flaps disordered. Comparison of this and unliganded HIV structures, with their respective liganded structures by difference distance matrixes identifies five domains of the protease dimer that move as rigid bodies against one another: one terminal domain encompassing the N- and C-terminal beta sheet of the dimer, two core domains containing the catalytic aspartic acids, and two flap domains. The two core domains rotate toward each other on substrate binding, reshaping the binding pocket. We therefore show that, for enzymes, mutations at interdomain interfaces that favor the unliganded form of the target active site will increase the off-rate of the inhibitor, allowing the substrate greater access for catalysis. This offers a mechanism of resistance to competitive inhibitors, especially when the forward enzymatic reaction rate exceeds the rate of substrate dissociation.     

Model checking action system refinements

Action systems provide a formal approach to modelling parallel and reactive systems. They have a well established theory of refinement supported by simulation-based proof rules. This paper introduces an automatic approach for verifying action system refinements utilising standard CTL model checking. To do this, we encode each of the simulation conditions as a simulation machine, a Kripke structure on which the proof obligation can be discharged by checking that an associated CTL property holds. This procedure transforms each simulation condition into a model checking problem. Each simulation condition can then be model checked in isolation, or, if desired, together with the other simulation conditions by combining the simulation machines and the CTL properties.