Miracle-dz/UniFAR-FTUs huggingface dataset:
Sequence-dependent denaturation energetics: A major determinant in amyloid disease diversity

Several misfolding diseases commence when a secreted folded protein encounters a partially denaturing microenvironment, enabling its self assembly into amyloid. Although amyloidosis is modulated by numerous environmental and genetic factors, single point mutations within the amyloidogenic protein can dramatically influence disease phenotype. Mutations that destabilize the native state predispose an individual to disease; however, thermodynamic stability alone does not reliably predict disease severity. Here we show that the rate of transthyretin (TTR) tetramer dissociation required for amyloid formation is strongly influenced by mutation (V30M, L55P, T119M, V122I), with rapid rates exacerbating and slow rates reducing amyloidogenicity. Although these rates are difficult to predict a priori, they notably influence disease penetrance and age of onset. L55P TTR exhibits severe pathology because the tetramer both dissociates quickly and is highly destabilized. Even though V30M and L55P TTR are similarly destabilized, the V30M disease phenotype is milder because V30M dissociates more slowly, even slower than wild type (WT). Although WT and V122I TTR have nearly equivalent tetramer stabilities, V122I cardiomyopathy, unlike WT cardiomyopathy, has nearly complete penetrance—presumably because of its 2-fold increase in dissociation rate. We show that the T119M homotetramer exhibits kinetic stabilization and therefore dissociates exceedingly slowly, likely explaining how it functions to protect V30M/T119M compound heterozygotes from disease. An understanding of how mutations influence both the kinetics and thermodynamics of misfolding allows us to rationalize the phenotypic diversity of amyloid diseases, especially when considered in concert with other genetic and environmental data.
An Empirical Study of Customers’ Perceptions of Service Quality and Loyalty with Using Structural Equation Modeling

This paper investigated the relationship between service quality and loyalty between online buyers . electronic service quality is found to be a prime determinant of consumer loyalty which is very important for the growth of any retailer industry. On this study, we have selected four most important dimensions of e-service quality which are: Reliability, Responsiveness, Ease of use, and Security. We adopted a quantitative approach for this study and our survey took place in Isfahan city. After collecting the data we analyzed it with structural equation modeling. We found that all the four dimensions of e-service quality have strong relationship with consumer loyalty which means that they have considerable impact on building and maintaining the loyalty of online banking users. We found out that the users give the highest priority to the organization of website contents and security of transaction.
Microbial Colonization and Competition on the Marine Alga Ulva australis

ABSTRACT Pseudalteromonas tunicata and Roseobacter gallaeciensis are biofilm-forming marine bacteria that are often found in association with the surface of the green alga Ulva australis. They are thought to benefit the plant host by producing inhibitory compounds that are active against common fouling organisms. We investigated factors that influence the ability of P. tunicata and R. gallaeciensis to attach to and colonize the plant surface and also the competitive interactions that occur between these organisms and other isolates from U. australis during biofilm formation on the plant surface. A surprisingly high number of P. tunicata cells, at least 108 cells ml−1, were required for colonization and establishment of a population of cells that persists on axenic surfaces of U. australis. Factors that enhanced colonization of P. tunicata included inoculation in the dark and pregrowth of inocula in medium containing cellobiose as the sole carbon source (cellulose is a major surface polymer of U. australis). It was also found that P. tunicata requires the presence of a mixed microbial community to colonize effectively. In contrast, R. gallaeciensis effectively colonized the plant surface under all conditions tested. Studies of competitive interactions on the plant surface revealed that P. tunicata was numerically dominant compared with all other bacterial isolates tested (except R. gallaeciensis), and this dominance was linked to production of the antibacterial protein AlpP. Generally, P. tunicata was able to coexist with competing strains, and each strain existed as microcolonies in spatially segregated regions of the plant. R. gallaeciensis was numerically dominant compared with all strains tested and was able to invade and disperse preestablished biofilms. This study highlighted the fact that microbial colonization of U. australis surfaces is a dynamic process and demonstrated the differences in colonization strategies exhibited by the epiphytic bacteria P. tunicata and R. gallaeciensis.
Uncovering Waste in U.S. Healthcare

There is widespread agreement that the US healthcare system wastes as much as 5% of GDP, yet little consensus on what care is actually unproductive. This partly arises because of the endogeneity of patient choice of treatment location. This paper uses the effective random assignment of patients to ambulance companies to generate comparisons across similar patients treated at different hospitals. We find that assignment to hospitals whose patients receive large amounts of care over the three months following a health emergency do not have meaningfully better survival outcomes compared to hospitals whose patients receive less. Outcomes are related to different types of treatment intensity, however: patients assigned to hospitals with high levels of inpatient spending are more likely to survive to one year, while those assigned to hospitals with high levels of outpatient spending are less likely to do so. This adverse effect of outpatient spending is predominately driven by spending at skilled nursing facilities (SNF) following hospitalization. These results offer a new type of quality measure for hospitals based on utilization of SNFs. We find that patients quasi-randomized to hospitals with high rates of SNF discharge have poorer outcomes, as well as higher downstream spending once conditioning on initial hospital spending.
Impact of missing data on type 1 error rates in non‐inferiority trials

In this paper, a simulation study is conducted to systematically investigate the impact of different types of missing data on six different statistical analyses: four different likelihood‐based linear mixed effects models and analysis of covariance (ANCOVA) using two different data sets, in non‐inferiority trial settings for the analysis of longitudinal continuous data. ANCOVA is valid when the missing data are completely at random. Likelihood‐based linear mixed effects model approaches are valid when the missing data are at random. Pattern‐mixture model (PMM) was developed to incorporate non‐random missing mechanism. Our simulations suggest that two linear mixed effects models using unstructured covariance matrix for within‐subject correlation with no random effects or first‐order autoregressive covariance matrix for within‐subject correlation with random coefficient effects provide well control of type 1 error (T1E) rate when the missing data are completely at random or at random. ANCOVA using last observation carried forward imputed data set is the worst method in terms of bias and T1E rate. PMM does not show much improvement on controlling T1E rate compared with other linear mixed effects models when the missing data are not at random but is markedly inferior when the missing data are at random. Copyright © 2009 John Wiley & Sons, Ltd.
Altered phosphodiesterase 3-mediated cAMP hydrolysis contributes to a hypermotile phenotype in obese JCR:LA-cp rat aortic vascular smooth muscle cells: implications for diabetes-associated cardiovascular disease.

Cardiovascular diseases represent a significant cause of morbidity and mortality in diabetes. Of the many animal models used in the study of non-insulin-dependent (type 2) diabetes, the JCR:LA-cp rat is unique in that it develops insulin resistance in the presence of obesity and manifests both peripheral and coronary vasculopathies. In this animal model, arterial vascular smooth muscle cells (VSMCs) from homozygous obese (cp/cp) rats, but not from age-matched healthy (+/+ or + /cp, collectively defined +/? ) littermates, display an " activated" phenotype in vitro and in vivo and have an elevated level of cAMP phosphodiesterase (PDE) activity. In this report, we confirm that cp/cp rat aortic VSMCs have an elevated level of PDE3 activity and show that only particulate PDE3 (PDE3B) activity is elevated. In marked contrast to results obtained in + /? VSMCs, simultaneous activation of adenylyl cyclase and inhibition of PDE3 activity in cp/cp VSMCs synergistically increased cAMP. Although PDE3 inhibition did not potentiate the antimigratory effects of forskolin on +/? VSMCs, PDE3 inhibition did markedly potentiate the forskolin-induced inhibition of migration of cp/cp-derived VSMCs. Although PDE3 activity was elevated in cp/cp rat aortic VSMCs, levels of expression of cytosolic PDE3 (PDE3A) and PDE3B in +/? and cp/cp VSMCs, as well as activation of these enzymes following activation of the cAMP-protein kinase A signaling cascade, were not different. Our data are consistent with an increased role for PDE3 in regulating cAMP-dependent signaling in cp/cp VSMCs and identify PDE3 as a cellular activity potentially responsible for the phenotype of cp/cp VSMCs.
Relationship Between Elevated Morning Blood Pressure Surge, Uric Acid, and Cardiovascular Outcomes in Hypertensive Patients

Early morning blood pressure surge (MBPS) is a risk factor for cardiovascular events (CVEs), but the relationship with uric acid is not well understood. The authors aimed to determine the association between MBPS and increased uric acid and the effect of elevated MBPS and uric acid combination on CVEs. A total of 921 patients underwent 24‐hour ambulatory blood pressure monitoring and were followed for a median of 40 months. During this period, 103 (11.2%) CVEs occurred. There was a significant relationship between increasing quartiles of serum uric acid level and increasing values of MBPS (P<.0001). Patients in the highest quartile stratified by elevated MBPS and serum uric acid level had a 3.55 odds of major CVE compared with patients in the lowest quartile. Serum uric acid is associated with MBPS and development of new CVEs.
Brownian Excursions and Parisian Barrier Options

In this paper we study a new kind of option, called hereinafter a Parisian barrier option. This option is the following variant of the so-called barrier option: a down-and-out barrier option becomes worthless as soon as a barrier is reached, whereas a down-and-out Parisian barrier option is lost by the owner if the underlying asset reaches a prespecified level and remains constantly below this level for a time interval longer than a fixed number, called the window. Properties of durations of Brownian excursions play an essential role. We also study another kind of option, called here a cumulative Parisian option, which becomes worthless if the total time spent below a certain level is too long.
Evaluation of the BD Max Cdiff assay for the detection of toxigenic Clostridium difficile in human stool specimens

Summary The Becton Dickinson (BD) PCR-based GeneOhm Cdiff assay has demonstrated a high sensitivity and specificity for detecting Clostridium difficile. Recently, the BD Max platform, using the same principles as BD GeneOhm, has become available in Australia. This study aimed to investigate the sensitivity and specificity of BD Max Cdiff assay for the detection of toxigenic C. difficile in an Australian setting. Between December 2013 and January 2014, 406 stool specimens from 349 patients were analysed with the BD Max Cdiff assay. Direct and enrichment toxigenic culture were performed on bioMérieux ChromID C. difficile agar as a reference method. isolates from specimens with discrepant results were further analysed with an in-house PCR to detect the presence of toxin genes. The overall prevalence of toxigenic C. difficile was 7.2%. Concordance between the BD Max assay and enrichment culture was 98.5%. The sensitivity, specificity, positive predictive value and negative predictive value for the BD Max Cdiff assay were 95.5%, 99.0%, 87.5% and 99.7%, respectively, when compared to direct culture, and 91.7%, 99.0%, 88.0% and 99.4%, respectively, when compared to enrichment culture. The new BD Max Cdiff assay appeared to be an excellent platform for rapid and accurate detection of toxigenic C. difficile.
High-dimensional index structures database support for next decade's applications (tutorial)

During recent years, a variety of new database applications has been developed which substantially differ from conventional database applications. For example, new database applications such as data warehousing produce very large relations which require a multidimensional view on the data, and in areas such as multimedia and CAD a content-based search is essential which is often implemented using some kind of feature vectors. All the new applications have in common that the underlying database system has to support the processing of queries on large amounts of high-dimensional data. Now, we may ask what the difference is between processing lowand high-dimensional data. A result of recent research activities is that basically none of the querying and indexing techniques which provide good results on low-dimensional data also performs sufficiently well on higher-dimensional data. The problem of dealing with high-dimensional spaces has therefore been addressed in a variety of recent database research projects. The goal of the tutorial is to spread the knowledge about high-dimensional spaces and the proposed techniques to a large community of both, researchers and practitioners researchers who are interested in querying and indexing techniques for high-dimensional data, and practitioners who are interested in the state-of-the-art of database support for their applications.
Corporate Social Responsibility, Human Resource Management and Corporate Family Responsibility. When A Company Is “The Best Place to Work”: Elica Group, The Hi-Life Company

Abstract The purpose of the work is to examine the relationship between Corporate Social Responsibility policies, and Human Resource Management, particularly focusing on Corporate Family Responsibility. How do CSR practices impact on employees, their work, and their family life? How effective are these practices and how can they positively impact on the difficult “work-life balance”? With the aim to answer to these questions, the study combines the deductive and inductive approach. After presenting the theoretical framework, the second part of the paper analyzes the case of Elica Group, a large, multinational Italian family company that has been named one of the “best places to work” in the national and European contexts. The points of reflection that emerge from this study are centered on the factors that induce the company to adopt such policies, and the factors that impact their effectiveness. The results reveal that a robust ethical foundation on the parts of the company’s founder and of its management, as well as their commitment to sharing values and objectives with the entire organization, are keys to Elica’s success based on a holistic development (economic, social and environmental development).
Ten years of Solutreans on the ice: a consideration of technological logistics and paleogenetics for assessing the colonization of the Americas

Abstract In 2004, a theory positing that Western Europeans were among the first peoples to colonize North America was published within the pages of World Archaeology. Ten years later this theory continues to provoke academic debate (Balter 2012; Curry 2012; Runnels 2012; Anderson 2013; Bawaya 2013; Morrow 2014) and ignite public imagination (Cook 2012; Vastag 2012; Coghlan 2012) thanks to the publication of Across Atlantic Ice (Stanford and Bradley 2012), the most recent, comprehensive and accessible presentation of what has come to be known as the “Solutrean Hypothesis”. In considering how debates over entry routes into North America can be taken further, we review the technological logistics of a North Atlantic crossing and Amerindian and European genetics, examining the validity of the Solutrean Hypothesis in 2014.
Republished: Use of aspirin as sole oral antiplatelet therapy in acute flow diversion for ruptured dissecting aneurysms

Subarachnoid hemorrhage secondary to rupture of a circumferential dissecting aneurysm continues to be a treatment dilemma. Vessel sacrifice, when possible, continues to be the safest option but in certain cases this is not possible due to lack of collateral supply. In such cases, coil assisted endovascular flow diversion has become a potential option but the requirement for dual antiplatelet therapy in an unsecured intracranial aneurysm continues to raise concern. We present a 48-year-old man with a World Federation of Neurological Surgeons grade 5 subarachnoid hemorrhage, secondary to a ruptured intradural left vertebral artery dissecting aneurysm, who was treated successfully with a pipeline embolization device with Shield technology using aspirin and a single intravenous loading dose of abciximab. To our knowledge, this is the first case of an acute flow diversion performed using only aspirin as the sole oral antiplatelet agent.
Identification and Map-Based Cloning of the Light-Induced Lesion Mimic Mutant 1 (LIL1) Gene in Rice

The hypersensitive response (HR) is a mechanism by which plants prevent the spread of pathogen. Despite extensive study, the molecular mechanisms underlying HR remain poorly understood. Lesion mimic mutants (LMMs), such as LIL1 that was identified in an ethylmethane sulfonate mutagenized population of Indica rice (Oryza sativa L. ssp. Indica) 93-11, can be used to study the HR. Under natural field conditions, the leaves of LIL1 mutant plants exhibited light-induced, small, rust-red lesions that first appeared at the leaf tips and subsequently expanded throughout the entire leaf blade to the leaf sheath. Histochemical staining indicated that LIL1 lesions displayed an abnormal accumulation of reactive oxygen species (ROS) and resulted from programmed cell death (PCD). The LIL1 mutants also displayed increased expression of defense-related genes and enhanced resistance to rice blast fungus (Magnaporthe grisea). Genetic analysis showed that mutation of LIL1 created a semi-dominant allele. Using 1,758 individuals in the F2 population, LIL1 was mapped in a 222.3 kb region on the long arm of chromosome 7. That contains 12 predicted open reading frames (ORFs). Sequence analysis of these 12 candidate genes revealed a G to A base substitution in the fourth exon of LOC_Os07g30510, a putative cysteine-rich receptor-like kinase (CRK), which led to an amino acid change (Val 429 to Ile) in the LIL1 protein. Comparison of the transcript accumulation of the 12 candidate genes between LIL1 and 93-11 revealed that LOC_Os07g30510 was up-regulated significantly in LIL1. Overexpression of the LOC_Os07g30510 gene from LIL1 induced a LIL1-like lesion phenotype in Nipponbare. Thus, LIL1 is a novel LMM in rice that will facilitate the further study of the molecular mechanisms of HR and the rice blast resistance.
The Construct Validity of Subjective Quality of Life for the Severely Mentally Ill

Subjective quality of life is the individual's rating of his or her satisfaction with various domains of everyday living. Given the similarity of this construct with anhedonia due to depression, efforts to establish its construct validity vis-a-vis other psychiatric variables must partial out the influence of depression on subjective quality of life. Forty-nine patients with severe mental illness completed an interview-based measure of quality of life and measures that represent psychiatric symptoms, including depression, social functioning, social support, and intelligence. Findings from a multiple regression analysis suggested that depression, social adjustment, size of the support network, and verbal intelligence are independently associated with quality of life. This suggests that quality of life is not redundant with the anhedonia common to depression. Findings about the multifaceted nature of quality of life have implications for understanding the effects of treatment programs on the construct.
Polymer science applied to petroleum production

Abstract The science of polymers, more specifically, synthesis, characterization, and physicochemical properties in solutions, has wide application in the petroleum industry, which uses polymers as components of fluids or additives to correct problems that affect oil production and/or increase production costs. Polymers are utilized during all phases, from drilling to treatment of oil and water. Research on the synthesis of polymers and their respective characterization aims to develop new molecules, with controlled structures, for various applications, having one or more objectives, namely: (1) to enhance operating efficiency; (2) to reduce costs; and (3) to elucidate mechanisms of action that can help in the development of new technologies. The evaluation of the physicochemical properties of a polymer in solution in many cases permits establishing useful correlations between its properties and performance in a specific application, besides providing insight into the mechanisms inherent in the production system, as is the case of stabilization of asphaltenes. Our research group has applied the knowledge of polymer science to the petroleum industry, focusing on the following functions: viscosification, inhibition of clay swelling, formation of filter cake, drag reduction, divergence, modification of wax crystals, stabilization of asphaltenes, emulsification, demulsification, and cleaning of solids systems contaminated with petroleum, among others.
Chinese parental perceptions of weight and associated health risks of young children

A mixed method was employed to determine how caregivers view preschool children’s body size and associated health risks. A survey of 505 caregivers was nested in 10 in-depth case studies of mothers. Based on the International Obesity Task Force calculation of children’s weight status, the caregivers who had underweight children overestimated their children’s weight status but the caregivers who had overweight/obese children underestimated their children’s weight status. Their estimates were substantially different from those of the caregivers of normal weight children. The mothers’ thoughts revealed the complexity of beliefs and sociocultural experiences about weight preferences and affirmed the quantitative findings.