Insights into the structural basis for zinc inhibition of the glycine receptor

Histidines 107 and 109 in the glycine receptor ( GlyR) alpha(1) subunit have previously been identified as determinants of the inhibitory zinc-binding site. Based on modeling of the GlyR alpha(1) subunit extracellular domain by homology to the acetylcholine-binding protein crystal structure, we hypothesized that inhibitory zinc is bound within the vestibule lumen at subunit interfaces, where it is ligated by His(107) from one subunit and His(109) from an adjacent subunit. This was tested by co-expressing alpha(1) subunits containing the H107A mutation with alpha(1) subunits containing the H109A mutation. Although sensitivity to zinc inhibition is markedly reduced when either mutation is individually incorporated into all five subunits, the GlyRs formed by the co-expression of H107A mutant subunits with H109A mutant subunits exhibited an inhibitory zinc sensitivity similar to that of the wild type alpha(1) homomeric GlyR. This constitutes strong evidence that inhibitory zinc is coordinated at the interface between adjacent alpha(1) subunits. No evidence was found for beta subunit involvement in the coordination of inhibitory zinc, indicating that a maximum of two zinc-binding sites per alpha(1)beta receptor is sufficient for maximal zinc inhibition. Our data also show that two zinc-binding sites are sufficient for significant inhibition of alpha(1) homomers. The binding of zinc at the interface between adjacent alpha(1) subunits could restrict intersubunit movements, providing a feasible mechanism for the inhibition of channel activation by zinc.

Mental time travel in animals?

Are humans alone in their ability to reminisce about the past and imagine the future? Recent evidence suggests that food-storing birds (scrub jays) have access to information about what they have stored where and when. This has raised the possibility of mental time travel (MTT) in animals and sparked similar research with other species. Here we caution that such data do not provide convincing evidence for MTT. Examination of characteristics of human MTT (e.g. non-verbal declaration, generativity, developmental prerequisites) points to other avenues as to how a case for animal MTT could be made. In light of the current lack of evidence, however, we maintain that MTT is a uniquely human characteristic.

Evidence and information for health policy: a decade of change

Over the past decade or so, there has been increasing demand for greater clarity about the major causes of disease and injury, how these differentially affect populations, and how they are changing. In part, this demand has been motivated by resource constraints and a realisation that better health is possible with more informed allocation of resources. At the same time, there has been a change in the way population health and its determinants are quantified, with a much closer integration of the quantitative population sciences (such as epidemiology, demography and health economics) to strengthen and broaden the evidence base for healthcare policy.

Molecular dynamics computer simulation of scratch resistance testing of polymers: visualization

Experimental scratch resistance testing provides two numbers: the penetration depth Rp and the healing depth Rh. In molecular dynamics computer simulations, we create a material consisting of N statistical chain segments by polymerization; a reinforcing phase can be included. Then we simulate the movement of an indenter and response of the segments during X time steps. Each segment at each time step has three Cartesian coordinates of position and three of momentum. We describe methods of visualization of results based on a record of 6NX coordinates. We obtain a continuous dependence on time t of positions of each of the segments on the path of the indenter. Scratch resistance at a given location can be connected to spatial structures of individual polymeric chains.

Simulating scratch behavior of polymers with mesoscopic molecular dynamics

Part replacement and repair is needed in structures with moving parts because of scratchability and wear. In spite of some accumulation of experimental evidence, scratch resistance is still not well understood. We have applied molecular dynamics to study scratch resistance of amorphous polymeric materials through computer simulations. As a first approach, a coarse grain model was created for high density polyethylene at the mesoscale. We have also extended the traditional approach and used real units rather than reduced units (to our knowledge, for the first time), which enable an improved quantification of simulation results. The obtained results include analysis of penetration depth, residual depth and recovery percentage related to indenter force and size. Our results show there is a clear effect from these parameters on the tribological properties. We also discuss a "crooked smile" effect on the scratched surface and the reasons for its appearance.

Organizational and accounting change within the context of the environmental agenda: evidence from Portugal

Purpose – The purpose of this paper is to explore the process of organizational change undergone by a large Portuguese business group within the context of the environmental agenda and the role of accounting as a mechanism for change. Design/methodology/approach – The paper reports the results of a case study conducted between 2006 and 2009. Information was obtained from semi-structured interviews and secondary sources. Organizational changes were analyzed using Laughlin’s model in order to identify which category reflected most of the changes introduced to address environmental matters. Findings – This paper offers evidence that change is not a homogeneous phenomenon. Additionally, it confirms previous studies’ findings which found that accounting did not play a significant role in the process of organizational change within the context of the environmental agenda. Originality/value – This paper seeks to complement the research in this area by integrating observations from a case study into an existing model of levels of organizational change according to how a Portuguese business group incorporated environmental issues into its processes, policies and corporate culture.

Factors Influencing the Implementation of the Balanced Scorecard in Portugal: Empirical Evidence From Privately Owned and Publicly Owned Organizations

In this paper we aim to identify and analyze a set of variables that can potentially influence the adoption and knowledge of the Balanced Scorecard (BSC) in Portugal. Hypotheses were tested using data obtained from a questionnaire sent to 591 publicly-owned organizations (local governments, municipal corporations and hospitals) and 549 privately-owned organizations (large companies and small and medium enterprises) in Portugal. The results allow us to conclude that although the majority of respondents claimed to know the BSC, its use in Portugal is still limited and very recent, particularly in the public sector organizations. However, it should be noted that its use has increased in Portugal in recent years. The study also reveals that in spite of the noticeable differences between public and private sector, the BSC is used in the public sector after a few adjustments to the traditional model. Using as theoretical framework the contingency and institutional theories, we found that decentralization, vertical differentiation and the degree of higher education are associated with the implementation of the BSC.

Conditioning information in mutual fund performance evaluation: Portuguese evidence

We estimate and compare the performance of Portuguese-based mutual funds that invest in the domestic market and in the European market using unconditional and conditional models of performance evaluation. Besides applying both partial and full conditional models, we use European information variables, instead of the most common local ones, and consider stochastically detrended conditional variables in order to avoid spurious regressions. The results suggest that mutual fund managers are not able to outperform the market, presenting negative or neutral performance. The incorporation of conditioning information in performance evaluation models is supported by our findings, as it improves the explanatory power of the models and there is evidence of both time-varying betas and alphas related to the public information variables. It is also shown that the number of lags to be used in the stochastic detrending procedure is a critical choice, as it will impact the significance of the conditioning information. In addition, we observe a distance effect, since managers who invest locally seem to outperform those who invest in the European market. However, after controlling for public information, this effect is slightly reduced. Furthermore, the results suggest that survivorship bias has a small impact on performance estimates.

Measuring fund performance using multi-factor models: evidence for the Portuguese market

This paper examines the performance of Portuguese equity funds investing in the domestic and in the European Union market, using several unconditional and conditional multi-factor models. In terms of overall performance, we find that National funds are neutral performers, while European Union funds under-perform the market significantly. These results do not seem to be a consequence of management fees. Overall, our findings are supportive of the robustness of conditional multi-factor models. In fact, Portuguese equity funds seem to be relatively more exposed to smallcaps and more value-oriented. Also, they present strong evidence of time-varying betas and, in the case of the European Union funds, of time-varying alphas too. Finally, in terms of market timing, our tests suggest that mutual fund managers in our sample do not exhibit any market timing abilities. Nevertheless, we find some evidence of timevarying conditional market timing abilities but only at the individual fund level.

Combining Formal Methods and Functional Strategies Regarding the Reverse Engineering of Interactive Applications

Abstract. Graphical user interfaces (GUIs) make software easy to use by providing the user with visual controls. Therefore, correctness of GUI’s code is essential to the correct execution of the overall software. Models can help in the evaluation of interactive applications by allowing designers to concentrate on its more important aspects. This paper describes our approach to reverse engineer an abstract model of a user interface directly from the GUI’s legacy code. We also present results from a case study. These results are encouraging and give evidence that the goal of reverse engineering user interfaces can be met with more work on this technique.

The Knowledge and Use of the Balanced Scorecard in Portugal: Empirical Evidence of the 250 Largest Companies

Balanced Scorecard (BSC) is recognized, both in the academic and business world, as one of the most powerful strategic management accounting tools. Thus, we launched in October 2004 a questionnaire survey applied to the 250 largest Portuguese companies aiming at observing the knowledge, use, and companies’ characteristics which are adopting this management instrument. Despite the majority of the companies inquired recognize BSC more as a strategic management tool than a performance valuation system, the results show that there is still a reduced and recent utilization of BSC in Portugal. Similarly to other countries Portugal is still in the initial state of BSC utilization. Our work has shown that the companies that use more BSC belong mainly to the secondary sector of industry. Nevertheless, unlike other studies, we did not get empirical evidence on the influence of variables such as geographical localization, dimension and internationalization, in the use and knowledge of BSC in Portugal.

Criminal Liability of Organizations, Corporations, Legal Persons, and Similar Entities on Law of Portuguese Cybercrime: A Brief Discussion on the Issue of Crimes of “False Information,” the “Damage on Other Programs or Computer Data,” the “Computer-Software Sabotage,” the “Illegitimate Access,” the “Unlawful Interception,” and “Illegitimate Reproduction of the Protected Program”

Abstract: in Portugal, and in much of the legal systems of Europe, «legal persons» are likely to be criminally responsibilities also for cybercrimes. Like for example the following crimes: «false information»; «damage on other programs or computer data»; «computer-software sabotage»; «illegitimate access»; «unlawful interception» and «illegitimate reproduction of protected program». However, in Portugal, have many exceptions. Exceptions to the «question of criminal liability» of «legal persons». Some «legal persons» can not be blamed for cybercrime. The legislature did not leave! These «legal persons» are v.g. the following («public entities»): legal persons under public law, which include the public business entities; entities utilities, regardless of ownership; or other legal persons exercising public powers. In other words, and again as an example, a Portuguese public university or a private concessionaire of a public service in Portugal, can not commit (in Portugal) any one of cybercrime pointed. Fair? Unfair. All laws should provide that all legal persons can commit cybercrimes. PS: resumo do artigo em inglês.

A Methodology for GUI Layer Redefinition Through Virtualization and Computer Vision

Nowadays despite improvements in usability and intuitiveness users have to adapt to the proposed systems to satisfy their needs. For instance, they must learn how to achieve tasks, how to interact with the system, and fulfill system's specifications. This paper proposes an approach to improve this situation enabling graphical user interface redefinition through virtualization and computer vision with the aim of increasing the system's usability. To achieve this goal the approach is based on enriched task models, virtualization and picture-driven computing.

Determinant factors of the implementation of the balanced scorecard in Portugal: empirical evidence in public and private organizations

In this article we aim to identify and analyze a set of variables that can potentially influence the adoption of the Balanced Scorecard (BSC)in Portugal. Hypotheses were tested using data obtained from a questionnaire sent to 591 publicly-owned organizations (local governments, municipal corporations and hospitals) and 549 privately-owned organizations (large companies and small and medium enterprises) in Portugal, with an overall response rate of 31.3%. The results allow us to conclude that although the majority of respondents claimed to know the BSC, its use in Portugal is still limited and very recent, particularly in the public sector organizations. However, it should be noted that its use has increased in Portugal in recent years. Using as theoretical framework the contingency and institutional theories, we found that decentralization, vertical differentiation and the degree of higher education are associated with the implementation of the BSC.