Differential Actions of Ethanol and Trichloroethanol at Sites in the M3 and M4 Domains of the NMDA Receptor GluN2A (NR2A) Subunit

Background and purpose:  Alcohol produces its behavioural effects in part due to inhibition of N-methyl-d-aspartate (NMDA) receptors in the CNS. Previous studies have identified amino acid residues in membrane-associated domains 3 (M3) and 4 (M4) of the NMDA receptor that influence ethanol sensitivity. In addition, in other alcohol-sensitive ion channels, sedative-hypnotic agents have in some cases been shown to act at sites distinct from the sites of ethanol action. In this study, we compared the influence of mutations at these sites on sensitivity to ethanol and trichloroethanol, a sedative-hypnotic agent that is a structural analogue of ethanol. Experimental approach:  We constructed panels of mutants at ethanol-sensitive positions in the GluN2A (NR2A) NMDA receptor subunit and transiently expressed these mutants in human embryonic kidney 293 cells. We used whole-cell patch-clamp recording to assess the actions of ethanol and trichloroethanol in these mutant NMDA receptors. Key results:  Ethanol sensitivity of mutants at GluN2A(Ala825) was not correlated with any physicochemical measures tested. Trichloroethanol sensitivity was altered in two of three ethanol-insensitive mutant GluN2A subunits: GluN2A(Phe637Trp) in M3 and GluN2A(Ala825Trp) in M4, but not GluN2A(Met823Trp). Trichloroethanol sensitivity decreased with increasing molecular volume at Phe637 or increasing hydrophobicity at Ala825 and was correlated with ethanol sensitivity at both sites. Conclusions and implications:  Evidence obtained to date is consistent with a role of GluN2A(Ala825) as a modulatory site for ethanol and trichloroethanol sensitivity, but not as a binding site. Trichloroethanol appears to inhibit the NMDA receptor in a manner similar, but not identical to, that of ethanol

Identities among relations for higher-dimensional rewriting systems

We generalize the notion of identities among relations, well known for presentations of groups, to presentations of n-categories by polygraphs. To each polygraph, we associate a track n-category, generalizing the notion of crossed module for groups, in order to define the natural system of identities among relations. We relate the facts that this natural system is finitely generated and that the polygraph has finite derivation type.Comment: 16 pages, corrected version after review, to appear in S\'eminaires et Congr\`e

Proprioceptive changes impair balance control in individuals with chronic obstructive pulmonary disease

Copyright @ 2013 Janssens et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction: Balance deficits are identified as important risk factors for falling in individuals with chronic obstructive pulmonary disease (COPD). However, the specific use of proprioception, which is of primary importance during balance control, has not been studied in individuals with COPD. The objective was to determine the specific proprioceptive control strategy during postural balance in individuals with COPD and healthy controls, and to assess whether this was related to inspiratory muscle weakness. Methods: Center of pressure displacement was determined in 20 individuals with COPD and 20 age/gender-matched controls during upright stance on an unstable support surface without vision. Ankle and back muscle vibration were applied to evaluate the relative contribution of different proprioceptive signals used in postural control. Results: Individuals with COPD showed an increased anterior-posterior body sway during upright stance (p=0.037). Compared to controls, individuals with COPD showed an increased posterior body sway during ankle muscle vibration (p=0.047), decreased anterior body sway during back muscle vibration (p=0.025), and increased posterior body sway during simultaneous ankle-muscle vibration (p=0.002). Individuals with COPD with the weakest inspiratory muscles showed the greatest reliance on ankle muscle input when compared to the stronger individuals with COPD (p=0.037). Conclusions: Individuals with COPD, especially those with inspiratory muscle weakness, increased their reliance on ankle muscle proprioceptive signals and decreased their reliance on back muscle proprioceptive signals during balance control, resulting in a decreased postural stability compared to healthy controls. These proprioceptive changes may be due to an impaired postural contribution of the inspiratory muscles to trunk stability. Further research is required to determine whether interventions such as proprioceptive training and inspiratory muscle training improve postural balance and reduce the fall risk in individuals with COPD.This work was supported by the Research Foundation – Flanders (FWO) grants 1.5.104.03, G.0674.09, G.0598.09N and G.0871.13N

Aquatic polymers can drive pathogen transmission in coastal ecosystems.

Gelatinous polymers including extracellular polymeric substances (EPSs) are fundamental to biophysical processes in aquatic habitats, including mediating aggregation processes and functioning as the matrix of biofilms. Yet insight into the impact of these sticky molecules on the environmental transmission of pathogens in the ocean is limited. We used the zoonotic parasite Toxoplasma gondii as a model to evaluate polymer-mediated mechanisms that promote transmission of terrestrially derived pathogens to marine fauna and humans. We show that transparent exopolymer particles, a particulate form of EPS, enhance T. gondii association with marine aggregates, material consumed by organisms otherwise unable to access micrometre-sized particles. Adhesion to EPS biofilms on macroalgae also captures T. gondii from the water, enabling uptake of pathogens by invertebrates that feed on kelp surfaces. We demonstrate the acquisition, concentration and retention of T. gondii by kelp-grazing snails, which can transmit T. gondii to threatened California sea otters. Results highlight novel mechanisms whereby aquatic polymers facilitate incorporation of pathogens into food webs via association with particle aggregates and biofilms. Identifying the critical role of invisible polymers in transmission of pathogens in the ocean represents a fundamental advance in understanding and mitigating the health impacts of coastal habitat pollution with contaminated runoff

Impaired Postural Control Reduces Sit-to-Stand-to-Sit Performance in Individuals with Chronic Obstructive Pulmonary Disease

Abstract Background: Functional activities, such as the sit-to-stand-to-sit (STSTS) task, are often impaired in individuals with chronic obstructive pulmonary disease (COPD). The STSTS task places a high demand on the postural control system, which has been shown to be impaired in individuals with COPD. It remains unknown whether postural control deficits contribute to the decreased STSTS performance in individuals with COPD. Methods: Center of pressure displacement was determined in 18 individuals with COPD and 18 age/gender-matched controls during five consecutive STSTS movements with vision occluded. The total duration, as well as the duration of each sit, sit-to-stand, stand and stand-to-sit phase was recorded. Results: Individuals with COPD needed significantly more time to perform five consecutive STSTS movements compared to healthy controls (1966 vs. 1364 seconds, respectively; p = 0.001). The COPD group exhibited a significantly longer stand phase (p = 0.028) and stand-to-sit phase (p = 0.001) compared to the control group. In contrast, the duration of the sit phase (p = 0.766) and sit-to-stand phase (p = 0.999) was not different between groups. Conclusions: Compared to healthy individuals, individuals with COPD needed significantly more time to complete those phases of the STSTS task that require the greatest postural control. These findings support the proposition that suboptimal postural control is an important contributor to the decreased STSTS performance in individuals with COPD

C IV BAL disappearance in a large SDSS QSO sample

Broad absorption lines (BALs) in the spectra of quasi-stellar objects (QSOs) originate from outflowing winds along our line of sight; winds are thought to originate from the inner regions of the QSO accretion disk, close to the central supermassive black hole (SMBH). Winds likely play a role in galaxy evolution and aid the accretion mechanism onto the SMBH. BAL equivalent widths can change on typical timescales from months to years; such variability is generally attributed to changes in the covering factor and/or in the ionization level of the gas. We investigate BAL variability, focusing on BAL disappearance. We analyze multi-epoch spectra of more than 1500 QSOs -the largest sample ever used for such a study- observed by different programs from the Sloan Digital Sky Survey-I/II/III (SDSS), and search for disappearing C IV BALs. The spectra rest-frame time baseline ranges from 0.28 to 4.9 yr; the source redshifts range from 1.68 to 4.27. We detect 73 disappearing BALs in the spectra of 67 sources. This corresponds to 3.9% of disappearing BALs, and 5.1% of our BAL QSOs exhibit at least one disappearing BAL. We estimate the average lifetime of a BAL along our line of sight (~ 80-100 yr), which appears consistent with the accretion disk orbital time at distances where winds are thought to originate. We inspect properties of the disappearing BALs and compare them to the properties of our main sample. We also investigate the existence of a correlation in the variability of multiple troughs in the same spectrum, and find it persistent at large velocity offsets between BAL pairs, suggesting that a mechanism extending on a global scale is necessary to explain the phenomenon. We select a more reliable sample of disappearing BALs following Filiz Ak et al. (2012), where a subset of our sample was analyzed, and compare the findings from the two works, obtaining generally consistent results.Comment: 22 pages, 9 figures. Accepted for publication in A&

Sensory Mechanisms of Perceptual Uniformity

BACKGROUND AND AIMS: Visual experience appears rich in detail despite the poor performance of the vast majority of the visual field, as a result of the integration of coarse peripheral signals with the information of the comparatively tiny fovea. We examined the mechanisms of this integration by employing the uniformity illusion, in which a pattern with different properties in fovea and periphery uniformly takes the appearance of the fovea. We developed an adaptation paradigm to investigate whether the direction of an after-effect in the visual periphery followed the local, physical stimulation or the perception that arose under the Uniformity Illusion. We employed two different perceptual dimensions (orientation and spatial density) to investigate the extent to which the uniformity illusion is associated with changes in sensory encoding. RESULTS AND CONCLUSIONS: Experiments performed on two visual domains indicate that the uniformity illusion is not associated with a change in the sensory encoding on a local basis. Specifically, in our orientation experiments, the (V1-based) tilt after-effect only ever followed the local, physically presented orientation rather than the global orientation perceived under the illusion of uniformity. This was not due to insufficient exposure to the global pattern to produce an after-effect as presentation of physical uniformity for the same durations as participant reports of the illusion did produce an after-effect to the global orientation. Results on spatial-density based experiments showed an intermediate level of adaptation between (physical) low and high density, which could be consistent with an adaptation exerted by the illusory pattern. Thus, we could not rule out that the Uniformity Illusion might directly modify more abstract dimensions (such as numerosity, akin to our formalization of spatial density). However, the time invariance of the effect makes alternative explanations more likely and therefore, suggests that the uniformity illusion arises from high-level perceptual processes

Detecting brute-force attacks on cryptocurrency wallets

Blockchain is a distributed ledger, which is protected against malicious modifications by means of cryptographic tools, e.g. digital signatures and hash functions. One of the most prominent applications of blockchains is cryptocurrencies, such as Bitcoin. In this work, we consider a particular attack on wallets for collecting assets in a cryptocurrency network based on brute-force search attacks. Using Bitcoin as an example, we demonstrate that if the attack is implemented successfully, a legitimate user is able to prove that fact of this attack with a high probability. We also consider two options for modification of existing cryptocurrency protocols for dealing with this type of attacks. First, we discuss a modification that requires introducing changes in the Bitcoin protocol and allows diminishing the motivation to attack wallets. Second, an alternative option is the construction of special smart-contracts, which reward the users for providing evidence of the brute-force attack. The execution of this smart-contract can work as an automatic alarm that the employed cryptographic mechanisms, and (particularly) hash functions, have an evident vulnerability.Comment: 10 pages, 2 figures; published versio

Toward Closing the Loop between Infrastructure Investments and Societal and Economic Impacts

The long-term value proposition of transportation infrastructure investments can be significantly distorted if the short term effects of spatial externalities on land-use patterns, economic expansions, and migration patterns are not properly included in the analysis. Some of these effects occur over a short period of time and soon after the investment materializes, while others take longer and follow more steady patterns. In this paper, we develop a novel dynamical model of a primal society with constructs that are specifically geared toward transportation infrastructure expansions and investments. The model quantifies the impact of these expansions on some key performance indicators and on the overall utility and production capacity of the society. We argue that traditional analytical models that work on the premises of stationary behavior and a static response of society to changes in infrastructure do not correctly capture these effects. The land use patterns and spatial expansion computed from the model are validated against existing theory on land use. Preliminary results on how to use the model for value proposition analysis are also presented using simple case studies.This is the author accepted manuscript. The final version is available from Taylor & Francis via http://dx.doi.org/10.1080/0013791X.2015.106535

Behavioral implications of shortlisting procedures

We consider two-stage “shortlisting procedures” in which the menu of alternatives is first pruned by some process or criterion and then a binary relation is maximized. Given a particular first-stage process, our main result supplies a necessary and sufficient condition for choice data to be consistent with a procedure in the designated class. This result applies to any class of procedures with a certain lattice structure, including the cases of “consideration filters,” “satisficing with salience effects,” and “rational shortlist methods.” The theory avoids background assumptions made for mathematical convenience; in this and other respects following Richter’s classical analysis of preference-maximizing choice in the absence of shortlisting