The direction aftereffect is driven by adaptation of local motion detectors

The processing of motion information by the visual system can be decomposed into two general stages; point-by-point local motion extraction, followed by global motion extraction through the pooling of the local motion signals. The direction aftereVect (DAE) is a well known phenomenon in which prior adaptation to a unidirectional moving pattern results in an exaggerated perceived direction diVerence between the adapted direction and a subsequently viewed stimulus moving in a diVerent direction. The experiments in this paper sought to identify where the adaptation underlying the DAE occurs within the motion processing hierarchy. We found that the DAE exhibits interocular transfer, thus demonstrating that the underlying adapted neural mechanisms are binocularly driven and must, therefore, reside in the visual cortex. The remaining experiments measured the speed tuning of the DAE, and used the derived function to test a number of local and global models of the phenomenon. Our data provide compelling evidence that the DAE is driven by the adaptation of motion-sensitive neurons at the local-processing stage of motion encoding. This is in contrast to earlier research showing that direction repulsion, which can be viewed as a simultaneous presentation counterpart to the DAE, is a global motion process. This leads us to conclude that the DAE and direction repulsion reflect interactions between motion-sensitive neural mechanisms at different levels of the motion-processing hierarchy.

Enhanced cAMP generation and insulin-releasing potency of two novel Tyr(1)-modified enzyme-resistant forms of glucose-dependent insulinotropic polypeptide is associated with significant antihyperglycaemic activity in spontaneous obesity-diabetes

Glucose-dependent insulinotropic polypeptide (GIP) is an important incretin hormone, which potentiates glucose-induced insulin secretion. Antihyperglycaemic actions of GIP provide significant potential in Type 11 diabetes therapy. However, inactivation of GIP by the enzyme dipeptidyl peptidase IV (DPP IV) and its consequent short circulating half-life limit its therapeutic use. Therefore two novel Tyr(1)-Modified analogues of GIP, N-Fmoc-GIP (where Fmoc is 9-fluorenylmethoxycarbonyl) and N-palmitate-GIP, were synthesized and tested for metabolic stability and biological activity. Both GIP analogues were resistant to degradation by DPP IV and human plasma. In Chinese hamster lung (CHL) cells expressing the cloned human GIP receptor, both analogues exhibited a 2-fold increase in cAMP-generating potency compared with native GIP (EC50 values of 9.4, 10.0 and 18.2 nM respectively). Using clonal BRIN-BD11 cells, both analogues demonstrated strong insulinotropic activity compared with native GIP (P <0.01 to P <0.001). In obese diabetic (ob/ob) mice, administration of N-Fmoc-GIP or N-palmitate-GIP (25 nmol/kg) together with glucose (18 mmol/kg) significantly reduced the peak 15 min glucose excursion (1.4- and 1.5-fold respectively; P <0.05 to P <0.01) compared with glucose alone. The area under the curve (AUC) for glucose was significantly lower after administration of either analogue compared with glucose administered alone or in combination with native GIP (1.5-fold; P <0.05). This was associated with a significantly greater AUC for insulin (2.1-fold; P <0.001) for both analogues compared with native GIP. A similar pattern of in vivo responsiveness was evident in lean control mice. These data indicate that novel N-terminal Tyr(1) modification of GIP with an Fmoc or palmitate group confers resistance to degradation by DPP IV in plasma, which is reflected by increased in vitro potency and greater insulinotropic and antihyperglycaemic activities in an animal model of Type 11 diabetes mellitus.

Mechanisms and chemistry of dye adsorption on manganese oxides-modified diatomite

The investigations into structural changes which occur during adsorbent modification and the adsorption mechanisms are essential for an effective design of adsorption systems. Manganese oxides were impregnated onto diatomite to form the type known as delta-birnessite. Initial investigations established the effectiveness of manganese oxides-modified diatomite (MOMD) to remove basic and reactive dyes from aqueous solution. The adsorption capacity of MOMD for methylene blue (MB), hydrolysed reactive black (RB) and hydrolysed reactive yellow (RY) was 320, 419, and 204 mg/g, respectively. Various analytical techniques were used to characterise the structure and the mechanisms of the dye adsorption process onto MOMD such as Fourier transform infrared (FTIR), X-ray diffraction (XRD) and atomic absorption spectrometry (A.A.). A small shift to higher values of the cl-spacing of dye/MOMD was observed indicating that a small amount of the dye molecules were intercalated in the MOMD structure and other molecules were adsorbed on the external surface of MOMD. Two mechanisms of dye adsorption onto MOMD were proposed; intercalation of the dye in the octahedral layers and adsorption of the dye on the MOMD external surface. Moreover, the results demonstrated that the MOMD structure was changed upon insertion of MB and RY with an obvious decrease in the intensity of the second main peak of the MOMD X-ray pattern. (C) 2009 Elsevier Ltd. All rights reserved.

Shell Model Study of Local and Global Energy Barriers in KDP

We perform a study of the energetics of KH2PO4 (KDP) by using a shell model (SM) which was constructed by adjusting the interaction parameters to ab initio calculations, and was fitted to reproduce phonons, polarization-inversion energies and structural properties. We calculate the energy profiles by performing global displacements and local distortions following the ferroelectric (FE) mode pattern in clusters of different sizes embedded in a paraelectric (PE) phase matrix. These properties are expected to be relevant to the PE-FE phase transition. The obtained SM results are compared to corresponding ab initio (AI) data. The global instabilities are found in good agreement for both KDP and DKDP. We also find qualitative good agreement in the KDP structure and even quantitative agreement in the expanded DKDP structure for the local distortions. The SM results reproduce well different trends like increasing instabilities as the cluster sizes grows, as the heavier atoms are included, and as the volume is increased, in accordance with the corresponding data from AI calculations.

A modified Tat peptide for selective intracellular delivery of macromolecules

Objectives The Tat peptide has been widely used for the intracellular delivery of macromolecules. The aim of this study was to modify the peptide to enable regulation of cellular uptake through a dependency on activation by proteases present in the local environment.

Methods The native Tat peptide sequence was altered to inhibit the initial interaction of the peptide with the cell membrane through the addition of the consensus sequence for urokinase plasminogen activator (uPA). uPA expression was characterised and semi-quantitatively rated in three cell lines (U251mg, MDA-MB-231 and HeLa). The modified peptide was incubated with both recombinant enzyme and with cells varying in uPA activity. Cellular uptake of the modified Tat peptide line was compared with that of the native peptide and rated according to uPA activity measured in each cell line.

Key findings uPA activity was observed to be high in U251mg and MDA-MB-231 and low in HeLa. In MDA-MB-231 and HeLa, uptake of the modified peptide correlated with the level of uPA expression detected (93 and 52%, respectively). In U251mg, however, the uptake of the modified peptide was much less (19% observed reduction) than the native peptide despite a high level of uPA activity detected.

Conclusions Proteolytic activation represents an interesting strategy for the targeted delivery of macromolecules using peptide-based carriers and holds significant potential for further exploitation.

The effect of construction pattern and unit interlock on the structural behaviour of block pavements

The maintenance or even replacement of cracked pavements requires considerable financial resources and puts a large burden on the budgets of local councils. In addition to these costs, local councils also face liability claims arising from uneven or cracked pedestrian pavements. These currently cost the Manchester City Council and Preston City Council around £6 million a year each. Design procedures are empirical. A better understanding of the interaction between paving blocks, bedding sand and subbase was necessary in order to determine the mode of failure of pavements under load. Increasing applied stress was found to mobilise ‘‘rotational interlock’’, providing increased pavement stiffness and thus increased load dissipation resulting in lower transmitted stress on the subgrade. The indications from the literature
review were that pavements are designed to fail by excessive deformation and that paving blocks remained uncracked at failure. This was confirmed with experimental data which was obtained from tests on segments of pavements that were laid/constructed in a purpose built test frame in the laboratory.

Local-field and excitonic effects in the optical response of alpha-alumina

This paper introduces key ingredients of the dielectric response of a-alumina that go beyond an independent-particle (IP) treatment of the valence-electron excitations. The optical-response functions were calculated from first-principles both at the Bethe-Salpeter and the random-phase approximation (RPA) levels. Excitonic effects obtained within the Bethe-Salpeter framework were found essential for reproducing the low-energy part of the experimental spectra (below 15 eV) and the bound exciton in particular. For higher energies, local-field effects introduced through the RPA modified considerably the IP results and provided a satisfactory account of the reflectivity spectra and of the position and shape of the dominant bulk plasmon resonance in the electron energy-loss spectra.

Deciphering the Acylation Pattern of Yersinia enterocolitica Lipid A

Pathogenic bacteria may modify their surface to evade the host innate immune response. Yersinia enterocolitica modulates its lipopolysaccharide (LPS) lipid A structure, and the key regulatory signal is temperature. At 21°C, lipid A is hexa-acylated and may be modified with aminoarabinose or palmitate. At 37°C, Y. enterocolitica expresses a tetra-acylated lipid A consistent with the 3'-O-deacylation of the molecule. In this work, by combining genetic and mass spectrometric analysis, we establish that Y. enterocolitica encodes a lipid A deacylase, LpxR, responsible for the lipid A structure observed at 37°C. Western blot analyses indicate that LpxR exhibits latency at 21°C, deacylation of lipid A is not observed despite the expression of LpxR in the membrane. Aminoarabinose-modified lipid A is involved in the latency. 3-D modelling, docking and site-directed mutagenesis experiments showed that LpxR D31 reduces the active site cavity volume so that aminoarabinose containing Kdo(2)-lipid A cannot be accommodated and, therefore, not deacylated. Our data revealed that the expression of lpxR is negatively controlled by RovA and PhoPQ which are necessary for the lipid A modification with aminoarabinose. Next, we investigated the role of lipid A structural plasticity conferred by LpxR on the expression/function of Y. enterocolitica virulence factors. We present evidence that motility and invasion of eukaryotic cells were reduced in the lpxR mutant grown at 21°C. Mechanistically, our data revealed that the expressions of flhDC and rovA, regulators controlling the flagellar regulon and invasin respectively, were down-regulated in the mutant. In contrast, the levels of the virulence plasmid (pYV)-encoded virulence factors Yops and YadA were not affected in the lpxR mutant. Finally, we establish that the low inflammatory response associated to Y. enterocolitica infections is the sum of the anti-inflammatory action exerted by pYV-encoded YopP and the reduced activation of the LPS receptor by a LpxR-dependent deacylated LPS.

Compositional Divergence and Convergence in Local Communities and Spatially Structured Landscapes

Community structure depends on both deterministic and stochastic processes. However, patterns of community dissimilarity (e.g. difference in species composition) are difficult to interpret in terms of the relative roles of these processes. Local communities can be more dissimilar (divergence) than, less dissimilar (convergence) than, or as dissimilar as a hypothetical control based on either null or neutral models. However, several mechanisms may result in the same pattern, or act concurrently to generate a pattern, and much research has recently been focusing on unravelling these mechanisms and their relative contributions. Using a simulation approach, we addressed the effect of a complex but realistic spatial structure in the distribution of the niche axis and we analysed patterns of species co-occurrence and beta diversity as measured by dissimilarity indices (e.g. Jaccard index) using either expectations under a null model or neutral dynamics (i.e., based on switching off the niche effect). The strength of niche processes, dispersal, and environmental noise strongly interacted so that niche-driven dynamics may result in local communities that either diverge or converge depending on the combination of these factors. Thus, a fundamental result is that, in real systems, interacting processes of community assembly can be disentangled only by measuring traits such as niche breadth and dispersal. The ability to detect the signal of the niche was also dependent on the spatial resolution of the sampling strategy, which must account for the multiple scale spatial patterns in the niche axis. Notably, some of the patterns we observed correspond to patterns of community dissimilarities previously observed in the field and suggest mechanistic explanations for them or the data required to solve them. Our framework offers a synthesis of the patterns of community dissimilarity produced by the interaction of deterministic and stochastic determinants of community assembly in a spatially explicit and complex context.

An intelligent configuration-sampling based local motion planner for robotic manipulators

Manipulator motion planning is a task which relies heavily on the construction of a configuration space prior to path planning. However when fast real-time motion is needed, the full construction of the manipulator's high-dimensional configu-ration space can be too slow and expensive. Alternative planning methods, which avoid this full construction of the manipulator's configuration space are needed to solve this problem. Here, one such existing local planning method for manipulators based on configuration-sampling and subgoal-selection has been extended. Using a modified Artificial Potential Fields (APF) function, goal-configuration sampling and a novel subgoal selection method, it provides faster, more optimal paths than the previously proposed work. Simulation results show a decrease in both runtime and path lengths, along with a decrease in unexpected local minimum and crashing issues.

Modified crack closure integral technique for extraction of SIFs in meshfee methods

A new approach for extracting stress intensity factors (SIFs) by the element-free Galerkin (EFG) class of methods through a modified crack closure integral (MCCI) scheme is proposed. Its primary feature is that it allows accurate calculation of mode I and mode II SIFs with a relatively simple and straightforward analysis even when a coarser nodal density is employed. The details of the adoption of the MCCI technique in the EFG method are described. Its performance is demonstrated through a number of case studies including mixed-mode and thermal problems in linear elastic fracture mechanics (LEFM). The results are compared with published theoretical solutions and those based on the displacement method, stress method, crack closure integral in conjunction with local smoothing (CCI–LS) technique, as well as the M-integral method. Its advantages are discussed.

Improved APF strategies for dual-arm local motion planning

Manipulator motion planning is a classic problem in robotics, with a number of complete solutions available for their motion in controlled (industrial) environments. Owing to recent technological advances in the field of robotics, there has been a significant development of more complex robots with high-fidelity sensors and more computational power. One such example has been a rise in the production of humanoid robots equipped with dual-arm manipulators which require complex motion planning algorithms. Also, the technological advances have resulted in a shift from using manipulators in strictly controlled environments, to investigating the deployment of manipulators in dynamic or unknown environments. As a result, a greater emphasis has been put on the development of local motion planners, which can provide real-time solutions to these problems. Artificial Potential Fields (APFs) is one such popular local motion planning technique, which can be applied to manipulator motion planning, however, the basic algorithm is severely prone to local minima problems. Here, two modified APF-based strategies for solving the dual-arm motion planning task in unknown environments are proposed. Both techniques make use of configuration sampling and subgoal selection to assist the APFs in avoiding these local minima scenarios. Extensive simulation results are presented to validate the efficacy of the proposed methodology.

Ecological dynamics of extinct species in empty habitat networks. 1. The role of habitat pattern and quantity, stochasticity and dispersal

We examined a remnant host plant (Primula veris L.) habitat network that was last inhabited by the rare butterfly Hamearis lucina L. in north Wales in 1943, to assess the relative contribution of several spatial parameters to its regional extinction. We first examined relationships between P. veris characteristics and H. lucina eggs in surviving H. lucina populations, and used these to predict the suitability and potential carrying capacity of the habitat network in north Wales. This resulted in an estimate of roughly 4500 eggs (ca 227 adults). We developed a discrete space, discrete time metapopulation model to evaluate the relative contribution of dispersal distance, habitat and environmental stochasticity as possible causes of extinction. We simulated the potential persistence of the butterfly in the current network as well as in three artificial (historical and present) habitat networks that differed in the quantity (current and X3) and fragmentation of the habitat (current and aggregated). We identified that reduced habitat quantity and increased isolation would have increased the probability of regional extinction, in conjunction with environmental stochasticity and H. lucina's dispersal distance. This general trend did not change in a qualitative manner when we modified the ability of dispersing females to stay in, and find suitable habitats (by changing the size of the grid cells used in the model). Contrary to most metapopulation model predictions, system persistence declined with increasing migration rate, suggesting that the mortality of migrating individuals in fragmented landscapes may pose significant risks to system-wide persistence. Based on model predictions for the present landscape we argue that a major programme of habitat restoration would be required for a re-established metapopulation to persist for > 100 years.

Local Conventions in Game Play in an Evolving Dual Social Network Framework

People usually perform economic interactions within the social setting of a small group, while they obtain relevant information from a broader source. We capture this feature with a dynamic interaction model based on two separate social networks. Individuals play a coordination game in an interaction network, while updating their strategies using information from a separate influence network through which information is disseminated. In each time period, the interaction and influence networks co-evolve, and the individuals’ strategies are updated through a modified naive learning process. We show that both network structures and players’ strategies always reach a steady state, in which players form fully connected groups and converge to local conventions. We also analyze the influence exerted by a minority group of strongly opinionated players on these outcomes.