Miracle-dz/UniFAR-FTUs huggingface dataset:
Arrhythmogenic cardiomyopathy: pathology, genetics, and concepts in pathogenesis

Arrhythmogenic cardiomyopathy (ACM) is a rare, heritable heart disease characterized by fibro-fatty replacement of the myocardium and a high degree of electric instability. It was first thought to be a congenital disorder, but is now regarded as a dystrophic heart muscle disease that develops over time. There is no curative treatment and current treatment strategies focus on attenuating the symptoms, slowing disease progression, and preventing life-threatening arrhythmias and sudden cardiac death. Identification of mutations in genes encoding desmosomal proteins and in other genes has led to insights into the disease pathogenesis and greatly facilitated identification of family members at risk. The disease phenotype is, however, highly variable and characterized by incomplete penetrance. Although the reasons are still poorly understood, sex, endurance exercise and a gene-dosage effect seem to play a role in these phenomena. The discovery of the genes and mutations implicated in ACM has allowed animal and cellular models to be generated, enabling researchers to start unravelling it's underlying molecular mechanisms. Observations in humans and in animal models suggest that reduced cell-cell adhesion affects gap junction and ion channel remodelling at the intercalated disc, and along with impaired desmosomal function, these can lead to perturbations in signalling cascades like the Wnt/β-catenin and Hippo/YAP pathways. Perturbations of these pathways are also thought to lead to fibro-fatty replacement. A better understanding of the molecular processes may lead to new therapies that target specific pathways involved in ACM.
The Complex Reality of Convergence and Diversification in European Industrial Relations Systems: A Review of the 1996 IREC Conference

The central theme for discussion at the IREC (Industrial Relations in the European Community network) Conference held in Copenhagen in September 1996 was `Industrial Relations in Europe: Convergence or Diversification? '. This article - by three of the organizers - presents a comparative assessment of three of the sub-themes treated at the conference, weighing their significance in relation to the overall pattern of convergence and divergence in European industrial relations.
Italian industrial districts as cognitive systems: Are they still reproducible?

Adopting a knowledge-based perspective, this study develops a framework of how Italian industrial districts (IDs) operate and evolve as cognitive systems. First, we analyse the mechanisms that facilitate knowledge diffusion across firms within IDs, the enabler of cross-firm knowledge transfer (absorptive capacity) and the process of producing new knowledge by combination. Within this analysis, we consider the formation of new firms resulting from the break-away of human resources from existing district firms (spin-offs) as a particular form of knowledge transfer and production within districts. Knowledge production by combination may take place not only within boundaries of IDs, but also involve external sources. We suggest that innovations made by combining internal and external knowledge have played an important role in shaping the evolutionary trajectories of IDs. Finally, again from the cognitive perspective, we address the issue of how globalization impacts on district systems, concentrating on the positive role that two different types of local actors play in their reproduction and evolution: the global–local firms and institutions providing knowledge-intensive business services.
An Allelic Series Uncovers Novel Roles of the BRCT Domain-Containing Protein PTIP in Mouse Embryonic Vascular Development

ABSTRACT Pax transactivation domain-interacting protein (PTIP, or PAXIP1) is required for mouse development and has been implicated in DNA damage responses and histone modification. However, the physiological roles of PTIP during embryogenesis remain unclear due to early embryonic lethality of null mutants. We describe two N-ethyl N-nitrosourea-induced hypomorphic missense alleles of Ptip, each of which alters one of the six encoded BRCT domains. Phenotypic characterization of these mutants revealed important functions of PTIP in vasculogenesis and chorioplacental development that appear unrelated to activities in DNA repair or global histone modification. The results of gene expression profiling and in vitro angiogenesis assays indicated that PTIP modulates a transcriptional program, centered around Vegfa, that drives the migration of endothelial cells to properly form the embryonic vasculature. These and other data suggest that PTIP has multiple functions, one of which is to promote the formation of transcriptional complexes that provide specificity of developmental gene expression.
How the curse of intractability can be cognitive science's blessing

Intractability has been a thorny issue in cognitive science. Informally, intractability refers to the problem that computations that work for small toy domains cannot scale to domains of real-world complexity due to prohibitive resource consumption. It is not uncommon for cognitive scientists to try to discredit theories in competing frameworks by pointing out that those frameworks run into intractability issues. For instance, both connectionists and Bayesians have argued against symbolic and logic approaches, respectively, because the latter two would yield intractable theories of cognition (Haselager, 1997; Oaksford & Chater, 1998). Yet, it is now well known that also connectionist and Bayesian theories can be intractable (Frank, Haselager, & van Rooij, 2009; Kwisthout, Wareham, & van Rooij, 2011). Moreover, even heuristic and dynamical systems theories, both often lauded for being tractable, seem unable to live up to that image when forced to scale beyond toy domains (van Rooij, Wright, & Wareham, 2012; van Rooij, 2012). Evidently, intractability is not a problem for specific theories, or even for specific theoretical frameworks. Instead, it seems a ubiquitous feature of theoretical frameworks with high degrees of generality. In this talk, I put forth the argument that cognitive science may have been too quick in seeing intractability as “just bad news” and that the field has been losing out on the opportunity to turn what seems to be a curse into a blessing. The upshot of my argument will be that the ubiquity of intractability can better be seen as a useful theoretical guide to the boundaries of cognition’s domain-generality. Using formal notions from computational complexity theory, I will explain how intractability helps demarcate those boundaries.
The Degree of Decoupling of Area Payments for Arable Crops in the European Union

In 1992, the Common Agricultural Policy (CAP) of the European Union (EU) significantly changed direction in the arable crop sector, with the so-called MacSharry reform. This reform, which reduced cereal intervention prices, eliminated output payments for oilseeds, and introduced per hectare compensatory payments and a compulsory set-aside requirement attached to these payments, implied a significant change in the policy incentives to produce. In 1999, intervention prices were cut further, bringing them closer to world market levels as well as aligning payments of cereals and oilseeds. The most recent reform in
Automating the process of critical appraisal and assessing the strength of evidence with information extraction technology.

BACKGROUND Critical appraisal, one of the most crucial steps in the practice of evidence-based medicine, is expertise-dependent and time-consuming. The objective of this study was to develop and evaluate an automated text-mining system that could determine the evidence level provided by a medical article. METHODS A text processor was designed and built to interpret the abstracts of medical literature. The system extracted information about: (1) the impact factor of the journal; (2) study design; (3) human subject involvement; (4) number of subjects; (5) P-value; and (6) confidence intervals. We used a classification tree algorithm (C4.5) to create a decision tree using supervised classification. Each article was categorized into evidence level A, B or C, and the output was compared to that determined by domain experts (the reference standard). RESULTS We used a corpus of 3180 cardiovascular disease original research articles, of which 1108 were previously assigned evidence level A, 1705 level B and 367 level C by domain experts. The abstracts were analysed by our automated system and an evidence level was assigned. The algorithm accurately classified 85% of the articles. The agreement between computer and domain experts was substantial (κ-value: 0.78). Cross-validation showed consistent results across repeated tests. CONCLUSION The automated engine accurately classified the evidence level. Misclassification might have resulted from incomplete information retrieval and inaccurate data extraction. Further efforts will focus on assessing relevance and using additional study design features to refine evidence level classification.
Trends in Rankings of Economics Departments in the U.S.: An Update

Economics departments in the United States are ranked based on the number of pages published in thirty-six economics journals, publications in five of the top journals, output per faculty member, and an index of the concentration of research in a department. Evidence shows that the top twenty departments have generally retained their positions since the 1970s but rather large changes have occurred in departments ranked from 240 to 100. An 'Economists Hall of Fame' is developed listing the top fifty individual producers of research in the thirty-six journal set and the top five journals. Copyright 1996 by Oxford University Press.
Human resource management in transitional economies: the case of Poland and the Czech Republic

This is an exploratory study to examine human resource management (HRM) policies and practices in Poland and the Czech Republic in their transition to free market economies. A questionnaire survey was administered to 120 Czech and forty-three Polish firms. This was supplemented by in-depth interviews with ten Czech and nine Polish companies. It was found that macro-environmental variables had a major impact on the development of HRM policies and practices in both countries. HR/personnel departments in Czech state-owned firms were less likely to be involved in training and development activities under the present system because of their former association with the ‘secret police’under the communist system. Because of the Czech Republic’s historically closer linkage with Austria and Germany and its higher level of industrialization, many aspects of its HRM policies and practices tend to resemble those of the industrialized West. The egalitarian tradition in Poland continues to be reflected in a more equitab.
Do We Have a New E-Conomy?

Used properly, the term 'new e-conomy' is warranted. Since 1995, there has been a wave of innovation associated with both the production and use of information technology that has been translated into improved US economic performance. In particular, there has been a substantial acceleration in trend total factor productivity growth. Most of this acceleration actually took place outside of the computer sector. Almost none of the acceleration was cyclical. There is now clear supportive evidence of an acceleration of productivity in service industries that are major purchasers of information technology such as finance and wholesale and retail trade. These gains reflect not only increased investment in information technology but also complementary innovations in business organization and policy. To be sure, as evidenced by recent financial market volatility, there have been speculative excesses, but these should not obscure the fundamental gains that have been made.
The Increasing Use of Non-Executive Directors: Its Impact on UK Board Structure and Governance Arrangements

The last decade has seen a sharp increase in the number of non-executive directors (NEDs) on the boards of UK listed firms. Using a sample period spanning the publication of the Cadbury Report (1992), this paper evaluates the implications of this increase. The main findings can be summarised as follows. First, the increased demand for NEDs has been more pronounced for firms classified as having proportionately too many executive board members in the pre-Cadbury period. Secondly, the probability of compliance with the Cadbury Report's proposal for a minimum of three NEDs is positively related to the magnitude of the expected net benefits of adding further non-executives to the board. Finally, there is little evidence that the increased use of NEDs caused firms to make costly adjustments to other elements of their control systems in an attempt to re-equilibrate their governance portfolios. These findings are consistent with claims that the recent trend towards greater NED representation on UK boards may have helped to raise general governance standards. Copyright Blackwell Publishers Ltd 2000.
Economic Restructuring, Unemployment, and Growth in a Transition Economy

This paper develops a model of the process of reallocation of labor from the state sector to the private sector. When growth is exogenously determined, we show that in the initial stages of transition unemployment will rise. After a critical stage in the transition process, restructuring is accompanied by a decline in unemployment. When growth is endogenously determined, and human capital is acquired by learning-by-doing, we show that whether or not restructuring eventually occurs is determined by the level of human capital in the private sector and the rate of unemployment. The effects of various shocks and government policies on the costs, speed, and eventual outcome of restructuring are analyzed.
Synergies of syntheses : a comparison of systematic review and scientific realist evaluation methods for crime prevention

This thesis makes two significant contributions to the advancement of knowledge within crime prevention. The first of these is to evaluate the success of repeat victimisation prevention interventions. Interventions across four crime types are assessed herein, and the context-mechanisms-outcome configurations examined. The second contribution of this thesis is to assess two techniques of meta-evaluation: systematic reviews and realist syntheses. Each of these techniques is used in turn to assess the repeat victimisation prevention interventions. The contribution of each technique to the knowledge pool is then discussed, and the question of whether they are complementary or contradictory approaches answered. The thesis is framed in the context of evolutionary epistemology, which is the philosophy underpinning both approaches to meta-evaluation addressed herein. The thesis starts, with an examination of: firstly, how the evaluation methods in question have evolved, and the background to their scientific worth; and secondly, how situational crime prevention measures have evolved over time. The thesis then examines the two competing approaches for their contribution to the evaluation ecosystem by using both to assess repeat victimisation prevention interventions. Finally, the last section poses the question of whether it is survival of the fittest, or whether co-existence or adaptation could be the key to survival for these two meta-evaluative methodologies. Repeat victimisation prevention is revealed as an effective way of reducing crime, with a need for further research to apply the principle across further crime types. A requirement is identified for a greater breadth and depth of information to be included in future crime prevention evaluations. The systematic review is shown to be a useful way of assessing the overall effectiveness of the interventions, whilst the realist synthesis fills in the detail of why some interventions work and others fail. It is concluded that both approaches to meta-evaluation have useful contributions to make, and that a third way incorporating the best elements from each method should be developed.
Developing intrabodies for the therapeutic suppression of neurodegenerative pathology

Many neurodegenerative diseases have misfolded proteins as a primary occurrence in pathogenesis. A combination of antibody and genetic engineering has emerged as a powerful tool for developing reagents that specifically target the misfolding process itself, and/or abnormal interactions of the misfolded protein species. This review focuses on the selection and testing of intracellular antibody fragments (intrabodies), with a particular focus on Huntington's disease (HD) and Parkinson's disease (PD), both of which show prominent intracellular protein aggregates in affected neurons. The most dramatic advances are in HD, where in vivo efficacy of intrabodies has been demonstrated. Targets in other neurodegenerative disorders, including Alzheimer's disease and prion diseases, are noted more briefly, with an emphasis on the potential for intracellular manipulations. Given the specificity and versatility of antibody-based reagents, the wide range of options for conformational and post-translationally-modified targets, and the recent improvement in gene delivery, this should be a fertile field for 21st century pharmacology.
Institutions, incentives, and behavior: essays in public economics and mechanism design

The economic outcomes realized by a society are a function of the institutions put in place, the incentives they create, and the behavior of agents in the face of those incentives. Selecting the appropriate institutions for a given economy is particularly important in the domain of public economics, where individual incentives are often inconsistent with efficiency. Three major concerns in institutional design are addressed. First, do agents select the equilibrium strategies at which efficient allocations obtain? Second, does the repeated game nature of a long-lived institution impact behavior? Third, what degree of coercion is necessary for a planner to guarantee that the allocation selected by a mechanism can be enforced? Answering these questions helps to understand which institutions are most appropriate in various environments. In Chapter 2, five public goods mechanisms are experimentally tested in a repeated game environment. Behavior is well approximated by a model in which agents best respond to an avrage of recently observed data. This model provides various sufficient conditions a mechanism must satisfy for play to converge to an efficient equilibrium. In Chapter 3, it is assumed that the designer of a one-shot mechanism must allow agents a 'no trade' option in which they are free to contribute nothing but enjoy the public good produced by others' contributions. It is shown that a large set of economies exist in which there is some agent at every allocation who prefers this option. Even in economies where this is not true, it becomes true as the economy is replicated, making it impossible to implement any allocation except the endowment in large economies. In the final chapter, a model of group reputations is developed to explain why moral hazard problems are significant in some laboratory experiments and less significant in others. If firms believe that either all workers are selfish or all workers are reciprocal, then selfish workers may have an incentive to develop a 'group reputation' of being reciprocal for a fixed number of periods in order to extract higher wages. As predicted, only in those experiments in which this incentive is sufficiently large is the moral hazard problem mitigated.
An oligogalacturonide‐derived molecular probe demonstrates the dynamics of calcium‐mediated pectin complexation in cell walls of tip‐growing structures

Pectic homogalacturonan (HG) is one of the main constituents of plant cell walls. When processed to low degrees of esterification, HG can form complexes with divalent calcium ions. These macromolecular structures (also called egg boxes) play an important role in determining the biomechanics of cell walls and in mediating cell-to-cell adhesion. Current immunological methods enable only steady-state detection of egg box formation in situ. Here we present a tool for efficient real-time visualisation of available sites for HG crosslinking within cell wall microdomains. Our approach is based on calcium-mediated binding of fluorescently tagged long oligogalacturonides (OGs) with endogenous de-esterified HG. We established that more than seven galacturonic acid residues in the HG chain are required to form a stable complex with endogenous HG through calcium complexation in situ, confirming a recently suggested thermodynamic model. Using defined carbohydrate microarrays, we show that the long OG probe binds exclusively to HG that has a very low degree of esterification and in the presence of divalent ions. We used this probe to study real-time dynamics of HG during elongation of Arabidopsis pollen tubes and root hairs. Our results suggest a different spatial organisation of incorporation and processing of HG in the cell walls of these two tip-growing structures.
Price and Volatility Spillovers in the Case of Stock Markets Located in Different Time Zones

This paper investigates the interdependence of price volatility across the U.S. stock market and two emerging markets: Poland and Hungary. Using daily data for countries located in different time zones, we point out the problems caused by the presence of nonsynchronous trading effects. To address this problem we use open-to-close logarithmic returns of major stock market indexes. The asymmetric impact of good and bad news is described by a multivariate exponential general autoregressive conditional heteroskedastic model. We investigate the sample from May 2004 to December 2011. The evidence is that the U.S. prices spill over to other markets. Our results show no pronounced volatility spillovers among the three examined markets. Moreover, we observe the presence of negative asymmetry in the case of all markets.
The Macroeconomy and the Yield Curve: A Nonstructural Analysis

We estimate a model with latent factors that summarize the yield curve (namely, level, slope, and curvature) as well as observable macroeconomic variables (real activity, inflation, and the stance of monetary policy). Our goal is to provide a characterization of the dynamic interactions between the macroeconomy and the yield curve. We find strong evidence of the effects of macro variables on future movements in the yield curve and much weaker evidence for a reverse influence. We also relate our results to a traditional macroeconomic approach based on the expectations hypothesis.