865 resultados para Susskind, Leonard: The Cosmic Landscape: string theory and the illusion of intelligent design


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ABSTRACTParliaments and audit agencies have critical and complementary roles in the oversight of the budget and the enforcement of government accountability. Yet, the nexus between parliaments and audit agencies is one of the weakest links in the accountability chain, generating an accountability gap in the budget process. This articles analyses the interactions between parliaments and audit agencies in the oversight of government finances during the latter stages of the budget process. Using proxies to evaluate the quality of those linkages, such as the follow-up to audit findings and the discharge of government, it shows important dysfunctions in the interactions between parliaments and audit agencies due to a combination of technical capacity constraints and political economy disincentives. It suggests that the effective functioning of the system of checks and balances in public budgeting critically hinges on the agility of the linkages between accountability institutions. As such, the failure of budget accountability is due to systemic dysfunctions in the systems of accountability, rather than the failure of an individual accountability institution acting in isolation. In addition, the effectiveness of the horizontal accountability architecture depends on the political economy incentives shaping the budget process, which are generated by the interactions between the choice of institutional design and budget rules, with the degree of political competition and electoral rules.

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Depicted by pen and camera.

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El concepto de organización saludable cada vez toma más fuerza en el ámbito empresarial y académico, a razón de su enfoque integral y al impacto generado en distintos grupos de interés. Debido a su reciente consolidación como concepto, existe un limitado cuerpo de investigación en torno al tema. Para contribuir a la generación de conocimiento en este sentido, se desarrolló un estudio exploratorio el cual tenía como objetivo identificar la relación existente entre la implementación de prácticas saludables en las organizaciones y los valores culturales. En el estudio participaron 66 sujetos a quienes se les administró un cuestionario compuesto por nueve variables, cinco provenientes del modelo de Hofstede (1980) y cuatro más que evaluaban la implementación de prácticas organizacionales saludables. Los resultados obtenidos muestran que los valores culturales predicen la implementación de prácticas saludables.

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Pressing global environmental problems highlight the need to develop tools to measure progress towards "sustainability." However, some argue that any such attempt inevitably reflects the views of those creating such tools and only produce highly contested notions of "reality." To explore this tension, we critically assesses the Environmental Sustainability Index (ESI), a well-publicized product of the World Economic Forum that is designed to measure 'sustainability' by ranking nations on league tables based on extensive databases of environmental indicators. By recreating this index, and then using statistical tools (principal components analysis) to test relations between various components of the index, we challenge ways in which countries are ranked in the ESI. Based on this analysis, we suggest (1) that the approach taken to aggregate, interpret and present the ESI creates a misleading impression that Western countries are more sustainable than the developing world; (2) that unaccounted methodological biases allowed the authors of the ESI to over-generalize the relative 'sustainability' of different countries; and, (3) that this has resulted in simplistic conclusions on the relation between economic growth and environmental sustainability. This criticism should not be interpreted as a call for the abandonment of efforts to create standardized comparable data. Instead, this paper proposes that indicator selection and data collection should draw on a range of voices, including local stakeholders as well as international experts. We also propose that aggregating data into final league ranking tables is too prone to error and creates the illusion of absolute and categorical interpretations. (c) 2004 Elsevier Ltd. All rights reserved.

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The urban heat island (UHI) is a well-known effect of urbanisation and is particularly important in world megacities. Overheating in such cities is expected to be exacerbated in the future as a result of further urban growth and climate change. Demonstrating and quantifying the impact of individual design interventions on the UHI is currently difficult using available software tools. The tools developed in the LUCID (‘The Development of a Local Urban Climate Model and its Application to the Intelligent Design of Cities’) research project will enable the related impacts to be better understood, quantified and addressed. This article summarises the relevant literature and reports on the ongoing work of the project.

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In the UK, architectural design is regulated through a system of design control for the public interest, which aims to secure and promote ‘quality’ in the built environment. Design control is primarily implemented by locally employed planning professionals with political oversight, and independent design review panels, staffed predominantly by design professionals. Design control has a lengthy and complex history, with the concept ofdesignoffering a range of challenges for a regulatory system of governance. A simultaneously creative and emotive discipline, architectural design is a difficult issue to regulate objectively or consistently, often leading to policy that is regarded highly discretionary and flexible. This makes regulatory outcomes difficult to predict, as approaches undertaken by the ‘agents of control’ can vary according to the individual. The role of the design controller is therefore central, tasked with the responsibility of interpreting design policy and guidance, appraising design quality and passing professional judgment. However, little is really known about what influences the way design controllers approach their task, providing a ‘veil’ over design control, shrouding the basis of their decisions. This research engaged directly with the attitudes and perceptions of design controllers in the UK, lifting this ‘veil’. Using in-depth interviews and Q-Methodology, the thesis explores this hidden element of control, revealing a number of key differences in how controllers approach and implement policy and guidance, conceptualise design quality, and rationalise their evaluations and judgments. The research develops a conceptual framework for agency in design control – this consists of six variables (Regulation; Discretion; Skills; Design Quality; Aesthetics; and Evaluation) and it is suggested that this could act as a ‘heuristic’ instrument for UK controllers, prompting more reflexivity in relation to evaluating their own position, approaches, and attitudes, leading to better practice and increased transparency of control decisions.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Objective: This in situ blind crossover study investigated the effect of calcium (Ca) rinse prior to the use fluoride (F) dentifrice on remineralisation of artificially demineralised enamel and on the composition of biofilm. Design: During four phases of 14 days, 10 volunteers wore appliances containing two artificially demineralised bovine enamel blocks. Three times a day, they rinsed with 10 mL, of Ca (150 mM) or placebo rinse (1 min). A slurry (1:3, w/v) of F (1030 ppm) or placebo dentifrice was dripped onto the blocks. During I min, the volunteers brushed their teeth with the respective dentifrice. The appliance was replaced into the mouth and the volunteers rinsed with water. The biofilm formed on the blocks was analysed for F and Ca. Enamel alterations were evaluated by the percentage of surface microhardness change (%SMHC), cross-sectional microhardness (% mineral volume) and alkali-soluble F analysis. Data were analysed by ANOVA (p < 0.05). Results: the use of the Ca pre-rinse before the F dentifrice produced a six- and four-fold increase in biofilm F and Ca concentrations, respectively. For enamel, the remineralisation was significantly improved by the Ca pre-rinse when compared to the other treatments. There was a significantly higher concentration of alkali-soluble F in enamel when the F dentifrice was used, but the Ca pre-rinse did not have any significant additive effect. Conclusions: According to our protocol, the Ca pre-rinse significantly increased biofilm F concentration and, regardless the use of F dentifrice, significantly enhanced the remineralisation of artificially demineralised enamel. (c) 2007 Elsevier Ltd. All rights reserved.

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Aim. The aim of this study was to evaluate the internal reliability and validity of the BrazilianPortuguese version of Duke Anticoagulation Satisfaction Scale (DASS) among cardiovascular patients. Background. Oral anticoagulation is widely used to prevent and treat thromboembolic events in several conditions, especially in cardiovascular diseases; however, this therapy can induce dissatisfaction and reduce the quality of life. Design. Methodological and cross-sectional research design. Methods. The cultural adaptation of the DASS included the translation and back-translation, discussions with healthcare professionals and patients to ensure conceptual equivalence, semantic evaluation and instrument pretest. The BrazilianPortuguese version of the DASS was tested among subjects followed in a university hospital anticoagulation outpatient clinic. The psychometric properties were assessed by construct validity (convergent, known groups and dimensionality) and internal consistency/reliability (Cronbachs alpha). Results. A total of 180 subjects under oral anticoagulation formed the baseline validation population. DASS total score and SF-36 domain correlations were moderate for General health (r = -0.47, p < 0.01), Vitality (r = -0.44, p < 0.01) and Mental health (r = -0.42, p < 0.01) (convergent). Age and length on oral anticoagulation therapy (in years) were weakly correlated with total DASS score and most of the subscales, except Limitation (r = -0.375, p < 0.01) (Known groups). The Cronbachs alpha coefficient was 0.79 for the total scale, and it ranged from 0.76 (hassles and burdens)0.46 (psychological impact) among the domains, confirming the internal consistency reliability. Conclusions. The BrazilianPortuguese version of the DASS has shown levels of reliability and validity comparable with the original English version. Relevance to clinical practice. Healthcare practitioners and researchers need internationally validated measurement tools to compare outcomes of interventions in clinical management and research tools in oral anticoagulation therapy.

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The aspartic protease BACE1 (β-amyloid precursor protein cleaving enzyme, β-secretase) is recognized as one of the most promising targets in the treatment of Alzheimer's disease (AD). The accumulation of β-amyloid peptide (Aβ) in the brain is a major factor in the pathogenesis of AD. Aβ is formed by initial cleavage of β-amyloid precursor protein (APP) by β-secretase, therefore BACE1 inhibition represents one of the therapeutic approaches to control progression of AD, by preventing the abnormal generation of Aβ. For this reason, in the last decade, many research efforts have focused at the identification of new BACE1 inhibitors as drug candidates. Generally, BACE1 inhibitors are grouped into two families: substrate-based inhibitors, designed as peptidomimetic inhibitors, and non-peptidomimetic ones. The research on non-peptidomimetic small molecules BACE1 inhibitors remains the most interesting approach, since these compounds hold an improved bioavailability after systemic administration, due to a good blood-brain barrier permeability in comparison to peptidomimetic inhibitors. Very recently, our research group discovered a new promising lead compound for the treatment of AD, named lipocrine, a hybrid derivative between lipoic acid and the AChE inhibitor (AChEI) tacrine, characterized by a tetrahydroacridinic moiety. Lipocrine is one of the first compounds able to inhibit the catalytic activity of AChE and AChE-induced amyloid-β aggregation and to protect against reactive oxygen species. Due to this interesting profile, lipocrine was also evaluated for BACE1 inhibitory activity, resulting in a potent lead compound for BACE1 inhibition. Starting from this interesting profile, a series of tetrahydroacridine analogues were synthesised varying the chain length between the two fragments. Moreover, following the approach of combining in a single molecule two different pharmacophores, we designed and synthesised different compounds bearing the moieties of known AChEIs (rivastigmine and caproctamine) coupled with lipoic acid, since it was shown that dithiolane group is an important structural feature of lipocrine for the optimal inhibition of BACE1. All the tetrahydroacridines, rivastigmine and caproctamine-based compounds, were evaluated for BACE1 inhibitory activity in a FRET (fluorescence resonance energy transfer) enzymatic assay (test A). With the aim to enhancing the biological activity of the lead compound, we applied the molecular simplification approach to design and synthesize novel heterocyclic compounds related to lipocrine, in which the tetrahydroacridine moiety was replaced by 4-amino-quinoline or 4-amino-quinazoline rings. All the synthesized compounds were also evaluated in a modified FRET enzymatic assay (test B), changing the fluorescent substrate for enzymatic BACE1 cleavage. This test method guided deep structure-activity relationships for BACE1 inhibition on the most promising quinazoline-based derivatives. By varying the substituent on the 2-position of the quinazoline ring and by replacing the lipoic acid residue in lateral chain with different moieties (i.e. trans-ferulic acid, a known antioxidant molecule), a series of quinazoline derivatives were obtained. In order to confirm inhibitory activity of the most active compounds, they were evaluated with a third FRET assay (test C) which, surprisingly, did not confirm the previous good activity profiles. An evaluation study of kinetic parameters of the three assays revealed that method C is endowed with the best specificity and enzymatic efficiency. Biological evaluation of the modified 2,4-diamino-quinazoline derivatives measured through the method C, allow to obtain a new lead compound bearing the trans-ferulic acid residue coupled to 2,4-diamino-quinazoline core endowed with a good BACE1 inhibitory activity (IC50 = 0.8 mM). We reported on the variability of the results in the three different FRET assays that are known to have some disadvantages in term of interference rates that are strongly dependent on compound properties. The observed results variability could be also ascribed to different enzyme origin, varied substrate and different fluorescent groups. The inhibitors should be tested on a parallel screening in order to have a more reliable data prior to be tested into cellular assay. With this aim, preliminary cellular BACE1 inhibition assay carried out on lipocrine confirmed a good cellular activity profile (EC50 = 3.7 mM) strengthening the idea to find a small molecule non-peptidomimetic compound as BACE1 inhibitor. In conclusion, the present study allowed to identify a new lead compound endowed with BACE1 inhibitory activity in submicromolar range. Further lead optimization to the obtained derivative is needed in order to obtain a more potent and a selective BACE1 inhibitor based on 2,4-diamino-quinazoline scaffold. A side project related to the synthesis of novel enzymatic inhibitors of BACE1 in order to explore the pseudopeptidic transition-state isosteres chemistry was carried out during research stage at Università de Montrèal (Canada) in Hanessian's group. The aim of this work has been the synthesis of the δ-aminocyclohexane carboxylic acid motif with stereochemically defined substitution to incorporating such a constrained core in potential BACE1 inhibitors. This fragment, endowed with reduced peptidic character, is not known in the context of peptidomimetic design. In particular, we envisioned an alternative route based on an organocatalytic asymmetric conjugate addition of nitroalkanes to cyclohexenone in presence of D-proline and trans-2,5-dimethylpiperazine. The enantioenriched obtained 3-(α-nitroalkyl)-cyclohexanones were further functionalized to give the corresponding δ-nitroalkyl cyclohexane carboxylic acids. These intermediates were elaborated to the target structures 3-(α-aminoalkyl)-1-cyclohexane carboxylic acids in a new readily accessible way.

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How can we explain the decline in support for the European Union (EU) and the idea of European integration after the onset of the great recession in the fall of 2007? Did the economic crisis and the austerity policies that the EU imposed—in tandem with the IMF—on several member countries help cause this drop? While there is some evidence for this direct effect of EU policies, we find that the most significant determinant of trust and support for the EU remains the level of trust in national governments. Based on cue theory and using concepts of diffuse and specific support, we find that support for the EU is derived from evaluations of national politics and policy, which Europeans know far better than the remote political system of the EU. This effect, however, is somewhat muted for those sophisticated Europeans that are more knowledgeable about the EU and are able to form opinions about it independently of the national contexts in which they live. We also find that the recent economic crisis has led to a discernible increase in the number of those who are disillusioned with politics both at the national and the supranational level. We analyze 133 national surveys from 27 EU countries by estimating a series of cross-classified multilevel logistic regression models.

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The article investigates the intriguing interplay of digital comics and live-action elements in a detailed performance analysis of TeZukA (2011) by choreographer Sidi Larbi Cherkaoui. This dance theatre production enacts the life story of Osamu Tezuka and some of his famous manga characters, interweaving performers and musicians with large-scale projections of the mangaka’s digitised comics. During the show, the dancers perform different ‘readings’ of the projected manga imagery: e.g. they swipe panels as if using portable touchscreen displays, move synchronously to animated speed lines, and create the illusion of being drawn into the stories depicted on the screen. The main argument is that TeZukA makes visible, demonstrates and reflects upon different ways of delivering, reading and interacting with digital comics. In order to verify this argument, the paper uses ideas developed in comics and theatre studies to draw more specifically on the use of digital comics in this particular performance.

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The challenges of research ethics and methodologies have been reflected on extensively, but – aside from the context of feminist methodologies – less so in relation to research on particular migration sites such as in transit, detention centres, at the borders or within migration administration. First attempts in this direction have been made (Düvell et al. 2010, Fresia et al. 2005, Riedner 2014, van Liempt/Bilger2009), however, more reflection and theorization is needed, considering the contested nature of these temporal and volatile sites. In this workshop, we thus aim at examining methodological as well as ethical questions that arise during field work: We attempt to reflect the power relations involved in the research process, the ethics of research design, the dissemination of research results, the question of gaining access to and – whenever necessary – staying in contact with our research subjects. How can we negotiate informed consent with subjects whose life is currently marked by transit and insecurity concerning their own future, and who are in an uncertain situation in which substantial information (legal, social, cultural etc.) is likely to be missing? How do we deal with the dilemma of possibly contributing to knowledge production that might facilitate removals and deportations in the future, considering that the reception of the results is not in the hands of the researchers? How do we deal with the anticipated as well as unexpected impacts of our research on social and political practice? Regarding fieldwork in state institutions, how do we negotiate the multiple loyalties we often find ourselves faced with as social researchers, both with the excluded migrants and with the authorities implementing the exclusions – two groupings considered to be opposite to each other (Lavanchy 2013)? Which different roles do researchers need to take on? The aim of our workshop is first and foremost to exchange experiences on fieldwork with others doing qualitative research on related topics and to consider its possible implications – including affective dimensions – for all participants involved in the research process: the migrants, the security staff of detention centres, its social workers, border police and bureaucrats and, last but not least, the researchers themselves. Furthermore, we generally wish to reflect upon the question of how best to conduct research in this contested field, applying an interdisciplinary perspective.

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This paper presents some brief considerations on the role of Computational Logic in the construction of Artificial Intelligence systems and in programming in general. It does not address how the many problems in AI can be solved but, rather more modestly, tries to point out some advantages of Computational Logic as a tool for the AI scientist in his quest. It addresses the interaction between declarative and procedural views of programs (deduction and action), the impact of the intrinsic limitations of logic, the relationship with other apparently competing computational paradigms, and finally discusses implementation-related issues, such as the efficiency of current implementations and their capability for efficiently exploiting existing and future sequential and parallel hardware. The purpose of the discussion is in no way to present Computational Logic as the unique overall vehicle for the development of intelligent systems (in the firm belief that such a panacea is yet to be found) but rather to stress its strengths in providing reasonable solutions to several aspects of the task.

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Transport is responsible for 41% of CO2 emissions in Spain, and around 65% of that figure is due to road traffic. Tolled motorways are currently managed according to economic criteria: minimizing operational costs and maximizing revenues from tolls. Within this framework, this paper develops a new methodology for managing motorways based on a target of maximum energy efficiency. It includes technological and demand-driven policies, which are applied to two case studies. Various conclusions emerge from this study. One is, that the use of intelligent payment systems is recommended; and another, is that the most sustainable policy would involve defining the most efficient strategy for each motorway section, including the maximum use of its capacity, the toll level which attracts the most vehicles, and the optimum speed limit for each type of vehicle.