Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of human paraoxonase (PON1) during development.

BACKGROUND Paraoxonase (PON1), a HDL-associated enzyme, protects against toxicity from specific organophosphorus compounds and oxidized lipids. Common polymorphisms in the PON1 gene have been identified and characterized in the coding region, 5' regulatory region and 3' UTR. The Q192R coding region polymorphism determines substrate-dependent differences in catalytic efficiency of hydrolysis. The -108CT polymorphism in the 5' regulatory region has a significant effect on PON1 expression, with the -108C allele expressing on average twice the level of plasma PON1 as the -108T allele. In addition to the effects of regulatory and coding region polymorphisms on PON1 levels and activity, plasma PON1 levels are also developmentally regulated. Since PON1 levels are important in determining resistance to specific organophosphorus compounds, the time course of appearance of PON1 in newborns is of great interest. RESULTS We report here that PON1 levels plateau between 6 to 15 months of age, and that variability in the age at which PON1 levels plateau is quite variable among individuals. In mice and rats, plasma PON1 activity reaches a plateau at 3 weeks of age. In mice that lack endogenous PON1, human transgenes encoding either PON1(Q192) or PON1(R192) under the control of the human PON1 regulatory sequences exhibited a similar time course of expression as that seen in wild-type mice, indicating conservation of the developmental regulatory elements between mouse and human PON1.
Characterization and small-molecule stabilization of the multisite tandem binding between 14-3-3 and the R domain of CFTR

Significance It has been shown that 14-3-3 proteins increase trafficking of cystic fibrosis transmembrane conductance regulator (CFTR) to the plasma membrane by binding to its regulatory (R) domain. This paper contains a detailed characterization of the 14-3-3/CFTR interaction, showing that multiple phosphorylated binding sites in the CFTR R-domain are necessary for significant binding with 14-3-3. We find that one of these binding sites serves as an anchor, while surrounding weaker sites enhance the interaction. Furthermore, we show the druggability of this interaction using natural-product fusicoccin-A, which stabilizes the 14-3-3/CFTR interaction by selectively modifying a weaker binding site. This mechanism of action can serve as a model for the development of new trafficking corrector molecules to treat cystic fibrosis. Cystic fibrosis is a fatal genetic disease, most frequently caused by the retention of the CFTR (cystic fibrosis transmembrane conductance regulator) mutant protein in the endoplasmic reticulum (ER). The binding of the 14-3-3 protein to the CFTR regulatory (R) domain has been found to enhance CFTR trafficking to the plasma membrane. To define the mechanism of action of this protein–protein interaction, we have examined the interaction in vitro. The disordered multiphosphorylated R domain contains nine different 14-3-3 binding motifs. Furthermore, the 14-3-3 protein forms a dimer containing two amphipathic grooves that can potentially bind these phosphorylated motifs. This results in a number of possible binding mechanisms between these two proteins. Using multiple biochemical assays and crystal structures, we show that the interaction between them is governed by two binding sites: The key binding site of CFTR (pS768) occupies one groove of the 14-3-3 dimer, and a weaker, secondary binding site occupies the other binding groove. We show that fusicoccin-A, a natural-product tool compound used in studies of 14-3-3 biology, can stabilize the interaction between 14-3-3 and CFTR by selectively interacting with a secondary binding motif of CFTR (pS753). The stabilization of this interaction stimulates the trafficking of mutant CFTR to the plasma membrane. This definition of the druggability of the 14-3-3–CFTR interface might offer an approach for cystic fibrosis therapeutics.
Digging unintentional displacement for one-handed thumb use on touchscreen-based mobile devices

There is usually an unaware screen distance between initial contact and final lift-off when users tap on touchscreen-based mobile devices with their fingers, which may affect users' target selection accuracy, gesture performance, etc. In this paper, we summarize such case as unintentional displacement and give its models under both static and dynamic scenarios. We then conducted two user studies to understand unintentional displacement for the widely-adopted one-handed thumb use on touchscreen-based mobile devices under both scenarios respectively. Our findings shed light on the following four questions: 1) what are the factors that affect unintentional displacement; 2) what is the distance range of the displacement; 3) how is the distance varying over time; 4) how are the unintentional points distributed around the initial contact point. These results not only explain certain touch inaccuracy, but also provide important reference for optimization and future design of UI components, gestures, input techniques, etc.
Metabolic Syndrome Is Associated With Adherence to an Unhealthy Diet

We read with interest the article by Freire et al. (1), which implicates that total dietary fat might increase the risk for metabolic syndrome. Conversely, they discovered an inverse relationship between linoleic acid intake and the metabolic syndrome. These data add to the mounting evidence describing the association between high dietary fat intake and features of metabolic syndrome either alone or in combination (2,3). We evaluated dietary nutrient intakes and features of metabolic syndrome in a population-based cross-sectional study of 671 subjects (297 …
Influence of Cultural Differences on Multi-National and Multi-Organizational Collaboration in Collaboratories

This study examines the influence of cultural differences on multi-national and multi-organizational scientific collaboration in collaboratories. It is found that the impact of cultural differences interplays with other social and economic factors such as project funding, scientists' own perception of their role within the project, and national policy. Practical implications of the study are also suggested.
Systematic review of the breast cancer screening trials is error-ridden

as the main outcome measure. The advantage of this approach is that the excess mortality estimate is independent of the cause of death determination. Finally, the Nordic Cancer and Cause of Death Registers are constantly monitored and evaluated to maintain its well-known high quality. The authors question the statistical analysis of the overview ignoring that an independent analysis of the first overview by Richard Peto’s group in Oxford arrived at the same result as our analysis (Appendix 3). Autier et al. make an ‘alternative calculation of results of Swedish trials’ using design 3 according to Duffy and Smith in which they showed results in a crude underestimation of the intervention effect, and besides that the assumptions of the number of breast cancers resulting in breast cancer deaths during the first screening round of the control group is based on vague and unfortunately biased assumptions. The authors also assume that there was a difference in the medical management between breast cancer cases diagnosed in the invited and control groups. This statement reveals the authors lack of knowledge about the Swedish healthcare system.
Sequential Coherence in Sentence Pairs Enhances Imagery during Comprehension: An Individual Differences Study

The present study investigates how sequential coherence in sentence pairs (events in sequence vs. unrelated events) affects the perceived ability to form a mental image of the sentences for both auditory and visual presentations. In addition, we investigated how the ease of event imagery affected online comprehension (word reading times) in the case of sequentially coherent and incoherent sentence pairs. Two groups of comprehenders were identified based on their self-reported ability to form vivid mental images of described events. Imageability ratings were higher and faster for pairs of sentences that described events in coherent sequences rather than non-sequential events, especially for high imagers. Furthermore, reading times on individual words suggested different comprehension patterns with respect to sequence coherence for the two groups of imagers, with high imagers activating richer mental images earlier than low imagers. The present results offer a novel link between research on imagery and discourse coherence, with specific contributions to our understanding of comprehension patterns for high and low imagers.
Arthrodesis of the Wrist with Bioabsorbable Fixation in Patients with Rheumatoid Arthritis

Twenty-four wrist arthrodeses were performed on 18 patients with rheumatoid arthritis using a bioabsorbable self-reinforced poly-l-lactide rod as the fixation device. There was one nonunion which required a re-operation and two nonunions which did not need further treatment. The position of the arthrodesis was ulnar deviation and extension in most patients, and there was high patient satisfaction with 21 of the 24 wrists and satisfactory pain relief in 22 of the 24 wrists. This method for fusing the wrist in patients with rheumatoid arthritis appears reliable and simple to perform.
Yield and quality of yellow passion fruits according to organic fertilization and alternative phytosanitary management.

Growing yellow passion fruit is a profitable activity, with a high demand for labor, and it is practiced especially by family-based farmers. However, the production cost is rather high and a significant part of this cost is associated with the expenses related to fertilization and phytosanitary treatments necessary for obtaining satisfactory yields and high commercial quality fruit. Therefore, the objective of this study was to evaluate the effect of using organic compound in fertilization of plants and alternative products in phytosanitary treatments on the yield and quality of fruits. Yellow passion fruits were submitted to three types of fertilization (mineral, organic and organic-mineral) and two types of phytosanitary treatment (‘conventional’ and ‘alternative’). This experiment evaluated fruit yield (kg/plant) and fruit quality by using the following evaluations: seedless pulp yield, soluble solids content (SS), titratable acidity (TA), SS/TA ratio and vitamin C content. The different types of fertilization did not interfere in fruit yield, however, plants under conventional phytosanitary treatment displayed higher yields. The SS content and TA of the fruits were influenced only by fertilization, where plants that received mineral and organic-mineral fertilization produced fruit with higher contents of SS and TA. Pulp yield, SS/TA ratio and vitamin C content were not influenced by any of the evaluated factors. Regarding cultivation of passion fruit, it is possible to substitute some mineral fertilizers for organic fertilizers with no negative effects on the fruit yield or quality. However, the substitution of pesticides for alternative products compromises fruit yield.
Female Veterans of Iraq and Afghanistan seeking care from VA specialized PTSD Programs: comparison with male veterans and female war zone veterans of previous eras.

BACKGROUND Differences in the characteristics and mental health needs of female veterans of the Iraq/Afghanistan war compared with those of veterans of other wars may have useful implications for VA program and treatment planning. METHODS Female veterans reporting service in the Iraq/Afghanistan war were compared with women reporting service in the Persian Gulf and Vietnam wars and to men reporting service in the Iraq/Afghanistan war. Subjects were drawn from VA administrative data on veterans who sought outpatient treatment from specialized posttraumatic stress disorder (PTSD) treatment programs. A series of analyses of covariance (ANCOVA) was used to control for program site and age. RESULTS In general, Iraq/Afghanistan and Persian Gulf women had less severe psychopathology and more social supports than did Vietnam women. In turn, Iraq/Afghanistan women had less severe psychopathology than Persian Gulf women and were exposed to less sexual and noncombat nonsexual trauma than their Persian Gulf counterparts. Notable differences were also found between female and male veterans of the Iraq/Afghanistan war. Women had fewer interpersonal and economic supports, had greater exposure to different types of trauma, and had different levels of diverse types of pathology than their male counterparts. CONCLUSIONS There appear to be sufficient differences within women reporting service in different war eras and between women and men receiving treatment in VA specialized treatment programs for PTSD that consideration should be given to program planning and design efforts that address these differences in every program treating female veterans reporting war zone service.
Secondary Solid Malignancies After High-Grade Glioma Treatment in Pediatric Patients

Due to the poor survival in high-grade glioma (HGG), secondary solid malignancies (SSM) following pediatric HGG are scarce. The authors present the experience from the HIT-HGG database in Germany, Austria, and Switzerland. Five out of 1228 pediatric HGG patients developed a SSM following a latency of 29–122 months from primary HGG diagnosis. In 4 patients, the SSM may be attributed to previous radiotherapy or a tumor predisposition syndrome, reflected by a markedly increased cumulative incidence rate of SSM in patients with tumor predisposition. Survival was devastating, since none of the patients survived beyond 18 months from SSM diagnosis.
Clinical and epidemiological profiles of individuals with drug-resistant tuberculosis

Drug-resistant tuberculosis (TB) is a growing global threat. Approximately 450,000 people developed multidrug-resistant TB worldwide in 2012 and an estimated 170,000 people died from the disease. This paper describes the sociodemographic, clinical-epidemiological and bacteriological aspects of TB and correlates these features with the distribution of anti-TB drug resistance. Mycobacterium tuberculosis (MT) cultures and drug susceptibility testing were performed according to the BACTEC MGIT 960 method. The results demonstrated that MT strains from individuals who received treatment for TB and people who were infected with human immunodeficiency virus were more resistant to TB drugs compared to other individuals (p < 0.05). Approximately half of the individuals received supervised treatment, but most drug-resistant cases were positive for pulmonary TB and exhibited positive acid-fast bacilli smears, which are complicating factors for TB control programs. Primary healthcare is the ideal level for early disease detection, but tertiary healthcare is the most common entry point for patients into the system. These factors require special attention from healthcare managers and professionals to effectively control and monitor the spread of TB drug-resistant cases.
Asian Migration Prospects: 2007-2012

This paper uses a global comparative static general equilibrium (GE) modeling approach to examine the impact of five alternative scenarios aimed at liberalizing migration flows from and within Asia. The first four scenarios consider the impact of liberalizing migration flows into (i) developed Asia; (ii) North America, Europe, and Oceania; (iii) North America, Japan, Europe, and Oceania; and (iv) the Middle East from the less developed economies of Asia. The fifth scenario involves regionally based efforts to improve the working conditions/ legali�ation of migrants among the ASEAN 5 economies. The paper concludes that intra regional policies can offer an important mechanism by which the Asian economies can reap some of the gains from liberali�ing migration; particularly given the reluctance of Europe and the United States to open their borders. Such regionally based policies aimed to offer potential gains in terms of real income and long run economic growth, particularly for those countries in East and Southeast Asia.
Minimizing Glycemic Fluctuations in Patients with Type 2 Diabetes: Approaches and Importance

Abstract Glycemic fluctuations, characterized by short-term oscillations in plasma glucose, are important when managing type 2 diabetes (T2D) and may be considered a target of glucose-lowering therapies. Continuous glucose monitoring (CGM) has been used to evaluate the effects of different treatments on glycemic fluctuations. This review examines approaches to and the importance of minimizing glycemic fluctuations among patients with T2D. Measures of HbA1c, fructosamine, and glycated albumin reflect a long-term average of plasma glucose, and are therefore unable to provide an accurate measure of short-term glycemic oscillations. CGM provides accurate monitoring of real-time glucose fluctuations and has been used to investigate the effects of lifestyle and treatment on daily glycemic control. Dipeptidyl peptidase-4 inhibitors, sodium–glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists have demonstrated significant improvements in measures such as the mean amplitude of glucose excursions and standard deviation of CGM. Case studies of two patients with T2D utilizing CGM are also included in this review, which demonstrated that CGM was a useful tool for diagnosing unrecognized hypoglycemia and hyperglycemia in situations in which it was impractical to check fingerstick concentrations. Altogether, the evidence suggests that glycemic fluctuations are a potential target to consider when managing T2D. CGM allows for the real-time evaluation of glycemic fluctuations and may assist in the development of an individualized treatment plan to adequately control short-term oscillations in blood glucose levels.
Self-presentation and the value of information in Q&A websites

Prior research has shown that social interaction is important for continuation of question-and-answer (Q&A) activity online and that it also leads to monetary rewards. The present research focuses on the link between social interaction and the value of information. Expressions of self-presentation in the interaction between askers and answerers online are studied as antecedents for answer feedback which represents the value of the answer to the asker.This relationship is examined in a Q&A site, specifically, in Google Answers (GA). The results of content analysis performed on sets of questions and answers show that both explicit and implicit social cues are used by the site’s participants; however, only implicit expressions of self-presentation are related to the provision of social and monetary feedback, ratings, and tips. This finding highlights the importance of implicit cues in textual communication and lends support to the notion of social capital where both monetary and social forms of feedback are the result of interaction online.
Free-Form Geometric Modeling by Integrating Parametric and Implicit PDEs

Parametric PDE techniques, which use partial differential equations (PDEs) defined over a 2D or 3D parametric domain to model graphical objects and processes, can unify geometric attributes and functional constraints of the models. PDEs can also model implicit shapes defined by level sets of scalar intensity fields. In this paper, we present an approach that integrates parametric and implicit trivariate PDEs to define geometric solid models containing both geometric information and intensity distribution subject to flexible boundary conditions. The integrated formulation of second-order or fourth-order elliptic PDEs permits designers to manipulate PDE objects of complex geometry and/or arbitrary topology through direct sculpting and free-form modeling. We developed a PDE-based geometric modeling system for shape design and manipulation of PDE objects. The integration of implicit PDEs with parametric geometry offers more general and arbitrary shape blending and free-form modeling for objects with intensity attributes than pure geometric models.
Application of Real-Time PCR for Determination of Antiviral Drug Susceptibility of Herpes Simplex Virus

ABSTRACT A quantitative real-time PCR (TaqMan) assay was developed for determination of antiviral drug susceptibility of herpes simplex virus (HSV). After short-time culture of the virus, the antiviral drug susceptibility of HSV isolates for acyclovir (ACV) was determined by measuring the reduction of the HSV type 1 (HSV-1) DNA levels in culture supernatants using real-time PCR. The 50% inhibitory concentration was reported as the concentration of antiviral drug that reduced the number of HSV-1 DNA copies by 50%. A total of 15 well-characterized ACV-sensitive or -resistant strains and clinical isolates were used for assay evaluation. The new assay with real-time PCR readout permitted rapid (3 days), objective, and reproducible determination of HSV-1 drug susceptibilities with no need for stringent control of initial multiplicity of infection. Furthermore, the real-time PCR assay results showed good correlation (r = 0.86) with those for the plaque reduction assay. In conclusion, the real-time PCR assay described here is a suitable quantitative method for determination of antiviral susceptibility of HSV-1, amenable for use in the routine diagnostic virology laboratory.
Effect of prolyl hydroxylase domain 2 haplodeficiency on liver progenitor cell characteristics in early mouse hepatocarcinogenesis

Activation of the hypoxia-inducible factor (HIF)-pathway in hepatocellular carcinoma (HCC) induces therapy resistant tumours, characterized by increased liver progenitor cell (LPCs) characteristics and poor prognosis. We previously reported corresponding results in mice with HCC in which hypoxia was mimicked by prolyl hydroxylase domain (PHD) inhibition. Here, we aimed at investigating whether induction of LPC characteristics occurs during the onset of hepatocarcinogenesis and if this is associated with activation of Notch signalling. Dietheylnitrosamine (DEN) was used to induce hepatic tumours in PHD2 haplodeficient (PHD2+/-) mice which were euthanized at 5, 10, 15 and 17 weeks following DEN during neoplastic transformation, before tumour formation. Neoplasia and mRNA expression of LPC and Notch markers were evaluated by histology and qPCR on isolated livers. PHD2 haplodeficiency resulted in enhanced expression of HIF target genes after 17 weeks of DEN compared to wild type (WT) littermates but had no effect on the onset of neoplastic transformation. The mRNA expression of Afp and Epcam was increased at all time points following DEN whereas CK19, Prom1 and Notch3 were increased after 17 weeks of DEN, without difference between PHD2+/- and WT mice. MDR1 mRNA expression was increased in all DEN treated mice compared to saline control with increased expression in PHD2+/- compared to WT from 15 weeks. These results indicate that the effects of PHD2 haplodeficiency on the expression of LPC and Notch markers manifest during tumour nodule formation and not early on during neoplastic transformation.