Healthiness from Duality

Healthiness is a good old question in program logics that dates back to Dijkstra. It asks for an intrinsic characterization of those predicate transformers which arise as the (backward) interpretation of a certain class of programs. There are several results known for healthiness conditions: for deterministic programs, nondeterministic ones, probabilistic ones, etc. Building upon our previous works on so-called state-and-effect triangles, we contribute a unified categorical framework for investigating healthiness conditions. We find the framework to be centered around a dual adjunction induced by a dualizing object, together with our notion of relative Eilenberg-Moore algebra playing fundamental roles too. The latter notion seems interesting in its own right in the context of monads, Lawvere theories and enriched categories.Comment: 13 pages, Extended version with appendices of a paper accepted to LICS 201

Purification, crystallization and preliminary X-ray crystallographic analysis of 3-ketosteroid Delta(1) -dehydrogenase from Rhodococcus erythropolis SQ1

3-Ketosteroid Delta(1)-dehydrogenase plays a crucial role in the early steps of steroid degradation by introducing a double bond between the C1 and C2 atoms of the A-ring of its 3-ketosteroid substrates. The 3-ketosteroid Delta(1)-dehydrogenase from Rhodococcus erythropolis SQ1, a 56 kDa flavoprotein, was crystallized using the sitting-drop vapour-diffusion method at room temperature. The crystals grew in various buffers over a wide pH range (from pH 5.5 to 10.5), but the best crystallization condition consisted of 2%(nu/nu) PEG 400, 0.1 M HEPES pH 7.5, 2.0 M ammonium sulfate. A native crystal diffracted X-rays to 2.0 angstrom resolution. It belonged to the primitive orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 107.4, b = 131.6, c = 363.2 angstrom, and contained eight molecules in the asymmetric unit. The initial structure of the enzyme was solved using multi-wavelength anomalous dispersion (MAD) data collected from a Pt-derivatized crystal

Detection of walking periods and number of steps in older adults and patients with Parkinson's disease: accuracy of a pedometer and an accelerometry-based method

The aim of this study was to examine if walking periods and number of steps can accurately be detected by a single small body-fixed device in older adults and patients with Parkinsons disease (PD). Results of an accelerometry-based method (DynaPort MicroMod) and a pedometer (Yamax Digi-Walker SW-200) worn on each hip were evaluated against video observation. Twenty older adults and 32 PD patients walked straight-line trajectories at different speeds, of different lengths and while doing secondary tasks in an indoor hallway. Accuracy of the instruments was expressed as absolute percentage error (older adults versus PD patients). Based on the video observation, a total of 236.8 min of gait duration and 24,713 steps were assessed. The DynaPort method predominantly overestimated gait duration (10.7 versus 11.1%) and underestimated the number of steps (7.4 versus 6.9%). Accuracy decreased significantly as walking distance decreased. Number of steps were also mainly underestimated by the pedometers, the left Yamax (6.8 versus 11.1%) being more accurate than the right Yamax (11.1 versus 16.3%). Step counting of both pedometers was significantly less accurate for short trajectories (3 or 5 m) and as walking pace decreased. It is concluded that the Yamax pedometer can be reliably used for this study population when walking at sufficiently high gait speeds (> 1.0 m/s). The accelerometry-based method is less speed-dependent and proved to be more appropriate in the PD patients for walking trajectories of 5 m or more

Phase behaviour of charged colloidal sphere dispersions with added polymer chains

We study the stability of mixtures of highly screened repulsive charged spheres and non-adsorbing ideal polymer chains in a common solvent using free volume theory. The effective interaction between charged colloids in an aqueous salt solution is described by a screened-Coulomb pair potential, which supplements the pure hard-sphere interaction. The ideal polymer chains are treated as spheres that are excluded from the colloids by a hard-core interaction, whereas the interaction between two ideal chains is set to zero. In addition, we investigate the phase behaviour of charged colloid-polymer mixtures in computer simulations, using the two-body (Asakura-Oosawa pair potential) approximation to the effective one-component Hamiltonian of the charged colloids. Both our results obtained from simulations and from free volume theory show similar trends. We find that the screened-Coulomb repulsion counteracts the effect of the effective polymer-mediated attraction. For mixtures of small polymers and relatively large charged colloidal spheres, the fluid-crystal transition shifts to significantly larger polymer concentrations with increasing range of the screened-Coulomb repulsion. For relatively large polymers, the effect of the screened-Coulomb repulsion is weaker. The resulting fluid-fluid binodal is only slightly shifted towards larger polymer concentrations upon increasing the range of the screened-Coulomb repulsion. In conclusion, our results show that the miscibility of dispersions containing charged colloids and neutral non-adsorbing polymers increases, upon increasing the range of the screened-Coulomb repulsion, or upon lowering the salt concentration, especially when the polymers are small compared to the colloids.Comment: 25 pages,13 figures, accepted for publication on J.Phys.:Condens. Matte

Kinetic Characterization and X-ray Structure of a Mutant of Haloalkane Dehalogenase with Higher Catalytic Activity and Modified Substrate Range

Conversion of halogenated aliphatics by haloalkane dehalogenase proceeds via the formation of a covalent alkyl-enzyme intermediate which is subsequently hydrolyzed by water. In the wild type enzyme, the slowest step for both 1,2-dichloroethane and 1,2-dibromoethane conversion is a unimolecular enzyme isomerization preceding rapid halide dissociation. Phenylalanine 172 is located in a helix-loop-helix structure that covers the active site cavity of the enzyme, interacts with the Clβ of 1,2-dichloroethane during catalysis, and could be involved in stabilization of this helix-loop-helix region of the cap domain of the enzyme. To obtain more information about the role of this residue in dehalogenase function, we performed a mutational analysis of position 172 and studied the kinetics and X-ray structure of the Phe172Trp enzyme. The Phe172Trp mutant had a 10-fold higher kcat/Km for 1-chlorohexane and a 2-fold higher kcat for 1,2-dibromoethane than the wild-type enzyme. The X-ray structure of the Phe172Trp enzyme showed a local conformational change in the helix-loop-helix region that covers the active site. This could explain the elevated activity for 1-chlorohexane of the Phe172Trp enzyme, since it allows this large substrate to bind more easily in the active site cavity. Pre-steady-state kinetic analysis showed that the increase in kcat found for 1,2-dibromoethane conversion could be attributed to an increase in the rate of an enzyme isomerization step that preceeds halide release. The observed conformational difference between the helix-loop-helix structures of the wild-type enzyme and the faster mutant suggests that the isomerization required for halide release could be a conformational change that takes place in this region of the cap domain of the dehalogenase. It is proposed that Phe172 is involved in stabilization of the helix-loop-helix structure that covers the active site of the enzyme and creates a rigid hydrophobic cavity for small apolar halogenated alkanes.

The role of arginine 47 in the cyclization and coupling reactions of cyclodextrin glycosyltransferase from Bacillus circulans strain 251 - Implications for product inhibition and product specificity

Cyclodextrin glycosyltransferase (CGTase) (EC 2.4.1.19) is used for the industrial production of cyclodextrins. Its application, however, is hampered by the limited cyclodextrin product specificity and the strong inhibitory effect of cyclodextrins on CGTase activity. Recent structural studies have identified Arg47 in the Bacillus circulans strain 251 CGTase as an active-site residue interacting with cyclodextrins, but not with linear oligosaccharides. Arg47 thus may specifically affect CGTase reactions with cyclic substrates or products. Here we show that mutations in Arg47 (to Leu or Gln) indeed have a negative effect on the cyclization and coupling activities; Arg47 specifically stabilizes the oligosaccharide chain in the transition state for these reactions. As a result, the mutant proteins display a shift in product specificity towards formation of larger cyclodextrins. As expected, both mutants also showed lower affinities for cyclodextrins in the coupling reaction, and a reduced competitive (product) inhibition of the disproportionation reaction by cyclodextrins. Both mutants also provide valuable information about the processes taking place during cyclodextrin production assays. Mutant Arg47-->Leu displayed an increased hydrolyzing activity, causing accumulation of increasing amounts of short oligosaccharides in the reaction mixture, which resulted in lower final amounts of cyclodextrins produced from starch. Interestingly, mutant Arg47-->Gln displayed an increased ratio of cyclization/coupling and a decreased hydrolyzing activity. Due to the decreased coupling activity, which especially affects the production of larger cyclodextrins, this CGTase variant produced the various cyclodextrins in a stable ratio in time. This feature is very promising for the industrial application of CGTase enzymes with improved product specificity

Older adults can improve compensatory stepping with repeated postural perturbations

The ability to respond quickly and accurately to an external perturbation with a stepping response is critical to avoid falls and this ability is impaired in older, compared to young adults. However, little is known about whether young and older adults improve compensatory stepping responses similarly with practice. This study compares the extent to which young and older adults can improve, retain, and generalize postural compensatory steps in response to external perturbations. Centre of mass displacement, step characteristics and lower leg muscle activation latencies were measured during one training session of compensatory stepping in response to large surface translations in 13 young and 12 older adults. Retention was tested 24 h later. Older adults decreased their center of mass displacements over repeated exposure to large surface translations in both the anterior and posterior directions and retained these improvements. In contrast, young adults only showed adaptation and retention of forward stepping responses. Neither group was able to generalize improvements in stepping responses across directions. These results suggest step training may be beneficial for older adults, however additional, multidirectional training may be necessary to facilitate generalization of postural stepping responses for any direction of a slip or trip

Sedimentation of binary mixtures of like- and oppositely charged colloids: the primitive model or effective pair potentials?

We study sedimentation equilibrium of low-salt suspensions of binary mixtures of charged colloids, both by Monte Carlo simulations of an effective colloids-only system and by Poisson-Boltzmann theory of a colloid-ion mixture. We show that the theoretically predicted lifting and layering effect, which involves the entropy of the screening ions and a spontaneous macroscopic electric field [J. Zwanikken and R. van Roij, Europhys. Lett. {\bf 71}, 480 (2005)], can also be understood on the basis of an effective colloid-only system with pairwise screened-Coulomb interactions. We consider, by theory and by simulation, both repelling like-charged colloids and attracting oppositely charged colloids, and we find a re-entrant lifting and layering phenomenon when the charge ratio of the colloids varies from large positive through zero to large negative values

Effects of polymer polydispersity on the phase behaviour of colloid-polymer mixtures

We study the equilibrium behaviour of a mixture of monodisperse hard sphere colloids and polydisperse non-adsorbing polymers at their $\theta$-point, using the Asakura-Oosawa model treated within the free-volume approximation. Our focus is the experimentally relevant scenario where the distribution of polymer chain lengths across the system is fixed. Phase diagrams are calculated using the moment free energy method, and we show that the mean polymer size $\xi_{\rm c}$ at which gas-liquid phase separation first occurs decreases with increasing polymer polydispersity $\delta$. Correspondingly, at fixed mean polymer size, polydispersity favours gas-liquid coexistence but delays the onset of fluid-solid separation. On the other hand, we find that systems with different $\delta$ but the same {\em mass-averaged} polymer chain length have nearly polydispersity-independent phase diagrams. We conclude with a comparison to previous calculations for a semi-grandcanonical scenario, where the polymer chemical potentials are imposed, which predicted that fluid-solid coexistence was over gas-liquid in some areas of the phase diagram. Our results show that this somewhat counter-intuitive result arose because the actual polymer size distribution in the system is shifted to smaller sizes relative to the polymer reservoir distribution.Comment: Changes in v2: sketch in Figure 1 corrected, other figures improved; added references to experimental work and discussion of mapping from polymer chain length to effective radiu