Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment perspectives for the lysosomal storage diseases

Background: The therapy of the lysosomal storage diseases (LSDs) was developed by supplying adequate amounts of the needed enzyme to affected individuals. This approach in Gaucher disease provided a prototype for the basic and clinical sciences, and the economic foundation for other ultra-orphan diseases. Objective: Using the success of enzyme therapy for Gaucher disease, the challenges are highlighted for alternative bioproduction systems, and substrate reduction and molecular chaperone approaches for treatment of Gaucher disease and other ultra-orphan diseases. Methods: Literature review provided insight into the current status of enzyme therapies for LSDs, the proposed mechanisms of alternative approaches to therapy, and the obstacles in a competitive marketplace for treatment of ultra-rare diseases. Results/conclusions: These developments are placed in the contexts of finding rare patients with LSDs, their marked phenotypic spectrum, potential markets, and new orphan drug costs. The confluence of these challenges has led to a competitive environment with the potential for multiple, alternative, expensive treatments for orphan diseases.
Short-term market reaction after extreme price changes of liquid stocks

In our empirical study we examine the dynamics of the price evolution of liquid stocks after experiencing a large intra-day price change, using data from the NYSE and the NASDAQ. We find a significant reversal for both intra-day price decreases and increases. Volatility, volume and, in the case of the NYSE, the bid–ask spread, which increase sharply at the event, stay significantly high days afterwards. The decay of the volatility follows a power law in accordance with the `Omori law'. While on the NYSE the large widening of the bid–ask spread eliminates most of the profits that can be achieved by an outside investor, on the NASDAQ the bid–ask spread stays almost constant, yielding significant short-term profits. The results thus give an insight into the size and speed of the realization of an excess return for providing liquidity in a turbulent market.
An Equilibrium Model of Incentive Contracts in the Presence of Information Manipulation

This paper develops an agency model in which stock-based compensation is a double-edged sword, inducing managers to exert productive effort but also inducing managers to divert valuable firm resources to misrepresent performance. We examine how the potential for manipulation affects the equilibrium level of pay-for-performance sensitivity and derive several new crosssectional implications that are consistent with recent empirical studies. In addition, we analyze the impact of recent regulatory changes contained in the Sarbanes-Oxley Act of 2002 and show that in some cases policies intended to increase firm value by reducing misrepresentation may actually reduce firm value or increase the upward bias in manipulated disclosures.
Homology Modeling of Representative Subfamilies of Arabidopsis Major Intrinsic Proteins. Classification Based on the Aromatic/Arginine Selectivity Filter1[w]

Major intrinsic proteins (MIPs) are a family of membrane channels that facilitate the bidirectional transport of water and small uncharged solutes such as glycerol. The 35 full-length members of the MIP family in Arabidopsis are segregated into four structurally homologous subfamilies: plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs), nodulin 26-like intrinsic membrane proteins (NIPs), and small basic intrinsic proteins (SIPs). Computational methods were used to construct structural models of the putative pore regions of various plant MIPs based on homology modeling with the atomic resolution crystal structures of mammalian aquaporin 1 and the bacterial glycerol permease GlpF. Based on comparisons of the narrow selectivity filter regions (the aromatic/Arg [ar/R] filter), the members of the four phylogenetic subfamilies of Arabidopsis MIPs can be classified into eight groups. PIPs possess a uniform ar/R signature characteristic of high water transport aquaporins, whereas TIPs are highly diverse with three separate conserved ar/R regions. NIPs possess two separate conserved ar/R regions, one that is similar to the archetype, soybean (Glycine max) nodulin 26, and another that is characteristic of Arabidopsis NIP6;1. The SIP subfamily possesses two ar/R subgroups, characteristic of either SIP1 or SIP2. Both SIP ar/R residues are divergent from all other MIPs in plants and other kingdoms. Overall, these findings suggest that higher plant MIPs have a common fold but show distinct differences in proposed pore apertures, potential to form hydrogen bonds with transported molecules, and amphiphilicity that likely results in divergent transport selectivities.
Explanations of a Changing Landscape: A Critical Examination of the British Columbia Bark Beetle Epidemic

This paper focuses on an unprecedented bark beetle epidemic in British Columbia, Canada. The epidemic has killed vast areas of forests, with significant impacts to ecosystems and timber-dependent communities. Explanations of this outbreak continue to overlook or underemphasize important actors and relationships. This paper offers a more detailed explanation of the actors and processes involved in the outbreak and associated responses. Political ecology was applied to guide this analysis, emphasizing both the ecological and social factors involved. Research methods entailed an extensive literature review and over seventy interviews with scientists, policy makers, land managers, and elected officials. Findings illustrate how the outbreak involved many actors, beyond bark beetles and trees, and resulted from complex interactions between ecological and social factors. This study also reveals how actors that prioritized short-term economic gains shaped the conditions that fostered the outbreak and continue to constrain responses. This study illustrates how applications of political ecology that give increased attention to ecology are necessary to fully understand the drivers of environmental change.
Changes in NHS Trust Audit and Non-Audit Fees

We examine how NHS trust audit and non-audit (consultancy) fees changed between 1997 and 2004, providing longitudinal evidence during a period of increased public expenditure and rapid restructuring. We find that audit fees rose dramatically over the period, though non-audit fees fell substantially. NHS trusts pay less to their external auditors than their private sector counterparts, probably in consequence of the trusts being more heavily regulated, with the Audit Commission retaining an influential regulatory role and also being the dominant auditor.
The Pursuit of Elite High Schools and Colleges among Second-Generation Korean Americans

This study examines the educational achievements and attainments of 1.5 and second-generation Korean Americans. Drawing from the 1998 New York and the 2004 IIMMLA surveys as well as forty follow-up in-depth interviews (selected among the 1998 New York survey participants), the study finds that second-generation Korean Americans are attaining high levels of education similar to the educational attainments of their immigrant parents. A high proportion of second-generation Korean Americans also attend elite high schools and colleges, giving the impression of them as model minorities. Closer analysis, however, suggests a more complex dynamic at work, one that involves Korean immigrants’selective educational and occupational background and the particularities of adolescent life. School-related factors, especially teachers’expectations, peers, and degree of socializing, have considerable impact, both positive and negative, on the educational attainments of second-generation Korean Americans.
Field studies into the dynamics of product development tasks

Purpose – This paper aims to describe three exploratory field studies investigating which characteristics add to later time to market and/or low product functionality of newly developed products. The studies are conducted at the level of developments tasks, or work packages. The first and second studies investigate to what extent the unpredictability of the project's outcome is the result of the unpredictability of the completion time of individual work packages, and of the instability of the total network of work packages.Design/methodology/approach – Statistical analysis of the empirical data about the progress of three design projects carried out in the development department of a high‐tech capital equipment manufacturer was used. The third study examines the reasons that members of the product development teams in this firm give for the unpredictability of time and quality of the project's outcome.Findings – The results result indicate the existence of three very different sources of unpredictability:.
SEGGA: a toolset for rapid automated analysis of epithelial cell polarity and dynamics

Epithelial remodeling determines the structure of many organs in the body through changes in cell shape, polarity and behavior and is a major area of study in developmental biology. Accurate and high-throughput methods are necessary to systematically analyze epithelial organization and dynamics at single-cell resolution. We developed SEGGA, an easy-to-use software for automated image segmentation, cell tracking and quantitative analysis of cell shape, polarity and behavior in epithelial tissues. SEGGA is free, open source, and provides a full suite of tools that allow users with no prior computational expertise to independently perform all steps of automated image segmentation, semi-automated user-guided error correction, and data analysis. Here we use SEGGA to analyze changes in cell shape, cell interactions and planar polarity during convergent extension in the Drosophila embryo. These studies demonstrate that planar polarity is rapidly established in a spatiotemporally regulated pattern that is dynamically remodeled in response to changes in cell orientation. These findings reveal an unexpected plasticity that maintains coordinated planar polarity in actively moving populations through the continual realignment of cell polarity with the tissue axes. Highlighted article: SEGGA is an easy to use software that allows for the quantitative analysis of changes in cell shape, movement and polarity at single-cell resolution during epithelial remodeling in various species.
Search for a Third Susceptibility Gene for Maturity-Onset Diabetes of the Young: Studies With Eleven Candidate Genes

Maturity-onset diabetes of the young (MODY) is a model for genetic studies of non-insulin-dependent diabetes mellitus. We have identified 15 MODY families in which diabetes is not the result of mutations in the glucokinase gene. This cohort of families will be useful for identifying other diabetes-susceptibility genes. Nine other candidate genes potentially implicated in insulin secretion or insulin action have been tested for linkage with MODY in these families, including glucokinase regulatory protein, hexokinase II, insulin receptor substrate 1, fatty acid–binding protein 2, glucagon-like peptide-1 receptor, apolipoprotein C-II, glycogen synthase, adenosine deaminase (a marker for the MODY gene on chromosome 20), and phosphoenolpyruvate carboxykinase. None of these loci showed evidence for linkage with MODY, implying that mutations in these genes do not make a major genetic contribution to the development of MODY. In addition to these linkage analyses, one or two affected subjects from each family were screened for the presence of the A to G mutation at nucleotide 3,243 of the mitochondrial tRNALeu(UUR) gene. This mutation was not found in any of these subjects. Finally, we report the localization of the gene encoding the regulatory protein of glucokinase to chromosome 2, band p22.3 and the identification of a restriction fragment length polymorphism at this locus.
MARKET TIMING ABILITY OF POOLED SUPERANNUATION FUNDS JANUARY 1981 TO DECEMBER 1987

: The performance of pooled superannuation funds is analysed within a framework that recognises that risk management or ‘market timing’ is an important aspect of the fund manager's decision-making. Two broad appraoches to the issue of ‘market timing’ are adopted: first, the performance evaluation model developed by Henriksson and Merton [1981] which allows for return differentials to arise from both security selection and market timing; and second, the recursive residuals methodology of Brown, Durbin and Evans [1975] which identifies points in chronological time when the risks of the funds underwent a change. The results indicate that only 5 out of 16 funds had significant shifts in their risk over the period of the study, all of which occurred in late 1986 to early 1987. It follows that the usual Jensen measure of performance is inappropriate for these funds since one component of their performance is due to market timing activities. The return performance of these market timing activities is significantly negative for 15 to 16 funds indicating that their timing ability is perverse. To some extent this is an artifact of the market crash of October 1987 and that all funds had a positive exposure to equities. However, due to their asset allocation policies all funds are assigned significantly positive security selection performance.
Silence, Confessions and Improperly Obtained Evidence

1: Introduction 2: The Principles Behind Exclusion 3: Procedural Issues and Exclusion 4: Confessions - Preliminary Issues 5: Confessions - The Exclusionary Rule 6: Discretionary Exclusion of Confessions and Other Evidence - General Principles 7: Discretionary Exclusion of Confessions and other Evidence - Specific Cases 8: Confessions: Ancillary Issues under the Exclusionary Rule and Discretion 9: Compelled Self-incrimination and Incriminating Silence 10: Vulnerable Suspects 11: The Relevance of the European Convention on Human Rights 12: Alternative Approaches
Breaking stress of neutron star crust

The breaking stress (the maximum of the stress-strain curve) of neutron star crust is important for neutron star physics including pulsar glitches, emission of gravitational waves from static mountains, and flares from star quakes. We perform many molecular dynamic simulations of the breaking stress at different coupling parameters (inverse temperatures) and strain rates. We describe our results with the Zhurkov model of strength. We apply this model to estimate the breaking stress for timescales ~1 s - 1 year, which are most important for applications, but much longer than can be directly simulated. At these timescales the breaking stress depends strongly on the temperature. For coupling parameter <200, matter breaks at very small stress, if it is applied for a few years. This viscoelastic creep can limit the lifetime of mountains on neutron stars. We also suggest an alternative model of timescale-independent breaking stress, which can be used to estimate an upper limit on the breaking stress.
Risk and protective factors associated with health-related quality of life among older gay and bisexual men living with HIV disease.

PURPOSE To identify risk and protective factors associated with mental and physical health-related quality of life, after controlling for key background characteristics, in a population of older gay and bisexual men living with HIV disease. Previous research examining quality of life among persons living with HIV rarely includes older adults. DESIGN AND METHODS Survey responses from 226 gay and bisexual men aged 50 and older, and living with HIV disease, which were part of the Caring and Aging with Pride study, were analyzed using multivariate linear regression models. RESULTS Findings reveal that comorbidity, limitations in activities, and victimization are significant risk factors for decreased physical and mental health-related quality of life. Stigma and HIV progression did not contribute to the overall outcome variables in multivariate models. Social support and self-efficacy serve as protective factors although social support was only significant with mental health-related quality of life. IMPLICATIONS Comorbidity, functional limitations, and lifetime victimization are risks to quality of life among older gay and bisexual men with HIV disease. Self-efficacy and social support represent intrapersonal and interpersonal resources that can be enhanced through interventions to improve health-related quality of life.
On the contingent valuation of mortality risk reduction in developing countries

Using the contingent valuation method in developing countries to value mortality risk reduction is particularly challenging because of the low level education of the respondents. In this article, we investigate whether some brief training regarding probability and risk concepts has any significant effect on the willingness-to-pay (WTP) responses. We elicit individuals’ risk perceptions by providing information on age specific mortality risks and find that people on average overestimate the mortality risk at younger ages and underestimate it at older ages. Our results indicate a significantly higher WTP for the trained sub-sample and WTP is sensitive to the magnitude of risk reduction for both the sub-samples.
Path Following Control of Rhombic Like Vehicles - Performance Assessment with Dynamic Vehicle Model

This paper addresses the path following problem of a wheeled mobile robot with rhombic like kinematics (drivable and steerable wheels both at front and rear) operating in cluttered environments. Four path following controllers are developed to steer the kinematic model of a rhombic like vehicle (RLV) along a desired path: three are based on feedback laws derived at a kinematic level with geometrical inspiration; the fourth is a nonlinear controller built upon a kinematic model of a RLV using Lyapunov functions. All the developed controllers are capable of performing under two situations: when both wheels follow the same path, or when each wheel follows a different path. The dynamic modelling of a RLV is lastly introduced. Simulated results present a comparative performance assessment of the controllers while dealing, or not, with vehicle dynamics. The main conclusions of these controllers are summarized, leading to a possible application in the actual vehicles that will operate in the remote handling missions of the International Thermonuclear Experimental Reactor (ITER).
Using LibQUAL+TM to improve services to libraries: A report on academic libraries of Iran experience

Purpose – This paper aims to urge the new culture of assessment of the quality of library services among Iran academic libraries and to assess the overall services quality of libraries from the users' perspectives based on the LibQUAL model.Design/methodology/approach – In this survey researchers used the LibQUAL model to assess service quality in the central libraries in engineering and technical governmental universities in Tehran city. For gathering data of libraries users, researchers used the LibQUAL questionnaire in a non‐electronic format and translated into Farsi.Findings – It was found that library users were dissatisfied with their library building. But these libraries performed very well in the information control dimension. Furthermore, the examination of users' expectations showed that the proposition “Employees who are consistently courteous” was most important, and “Employees who instill confidence in users” had less importance.Originality/value – Using the LibQUAL Survey has helped the uni.
The impact of stock spams on volatility

This article is dedicated to study the impact of stock spams through the analysis of the variations of volatility. Our sample contains 110 firms quoted on emerging market, namely the penny stock market. The results, based on event study methodology and Generalized Autoregressive Conditional Heteroscedastic (GARCH) modelling, show positive and significant changes in volatility; a widening of the variation (lowest price–highest price) was noticed following the consignment of messages by the spammers. The sending of stock spams affected the behaviour of investors, thus indicating that the spamming activity is a lucrative business.
Chinese Consumers' Demand for Food Safety Attributes: A Push for Government and Industry Regulations

The diet of urban Chinese consumers has changed drastically over the past twenty years, due in part to rising incomes and changing lifestyles. Food consumption has shifted away from grains and toward higher-quality calories from animal proteins and aquaculture products. Dairy demand in urban China has shown remarkable growth in the past decade, driven by mutually reinforcing factors, including rising incomes, government promotion of dairy products, changing urban lifestyles, and the development of more sophisticated marketing channels (Fuller et al. 2006). China’s dairy production has surged from just over 10 million metric tons in 2001 to an expected production level of nearly 48 million metric tons by 2013 (Woolsey, Zhang, and Zhang 2010). Most notable has been the rise in demand for ultra-high temperature (UHT) pasteurized fluid milk among urban consumers in recent years, with a 50% sales increase in 2009 alone (Fuller et al. 2006; Wang, Mao, and Gale 2008; Woolsey, Zhang, and Zhang 2010).
The comparative importance of human resource management practices in the context of business to business (B2B) electronic commerce

Examines the relationship between how people are managed, and the effectiveness of business to business (B2B) e‐commerce implementations. The human resource management practices used to test this relationship are training, employee involvement and participatory culture. A survey instrument was designed for the purpose of testing the research hypotheses based on the themes identified in the review of the literature. This survey was administered within a sample of the membership of EAN Australia. The results indicate that there is a clear link established between effective management of human resources and effective implementation of B2B e‐commerce enabling technologies. In particular, there is evidence to suggest that the development of a participative culture coupled with the involvement of employees, will be more effective than solely investing in training programs. This study has been limited to organizations operating in the Australian fast moving consumer goods sector. The results therefore need to be read in this context, and it would be useful if these hypotheses could be tested in other countries and different industry sectors. The overall impression is that the organizations that will derive the greatest benefit from the use of these technologies will be not only those that invest in training for the use of the technology. More important sources of leverage are likely to derive from involving a broad range of employees directly in implementation, while actively encouraging a culture of participation across the organization. There is a clear link established between effective management of human resources and effective implementation of B2B e‐commerce enabling technologies. In particular, there is evidence to suggest that the development of a participative culture coupled with the involvement of employees, will be more effective than solely investing in training programs.