Miracle-dz/UniFAR-FTUs huggingface dataset:
Multidrug Resistance Protein 2 Genetic Polymorphisms Influence Mycophenolic Acid Exposure in Renal Allograft Recipients

Background. Mycophenolic acid (MPA) is glucuronidated by uridine diphosphate-glucuronosyltransferases (UGTs) to its pharmacologically inactive 7-O-glucuronide metabolite (MPAG). MPAG is excreted into the bile via the multidrug resistance-associated protein 2 (MRP2/ABCC2), which is essential for enterohepatic (re)circulation (EHC) of MPA(G). Methods. The objective of this study was to determine the relationship between single nucleotide polymorphisms (SNPs) in the MRP2 (G-1549A, G-1023A, A-1019G, C-24, G1249A, C3972T and G4544A) and UGT1A9 (C-2152T, T-275AandT98C) genes and MPA pharmacokinetics in 95 renal allograft recipients at days 7, 42, 90, and 360 after transplantation. In addition to mycophenolate mofetil, all patients received tacrolimus and corticosteroids as immunosuppression. Results. At day seven after transplantation, in the absence of the MRP2 C-24T SNP, mild liver dysfunction was associated with significantly lower MPA dose-interval exposure and higher MPA oral clearance, while liver dysfunction did not affect MPA pharmacokinetics in patients with the MRP2 C-24T variant. A similar effect is noted for the C-3972T variant, which is in linkage disequilibrium with C-24T. At later time points after transplantation the MRP2 C-24T SNP was associated with significantly higher dose-corrected MPA trough levels. Patients with the MRP2 C-24T variant had significantly more diarrhea in the first year after transplantation. Conclusions. The MRP2 C-24T and C-3972T polymorphisms protect renal transplant recipients from a decrease in MPA exposure associated with mild liver dysfunction. Furthermore, this study suggests that the C-24T SNP is associated with a lower oral clearance of MPA in steady-state conditions.
Distributed Routing for Wireless Sensor Networks Based on Cluster Maintenance

Saving energy is an important goal in designing of wireless sensor networks, and routing algorithm has an important impact on energy consumption for wireless sensor networks. Therefore, improving the energy efficiency of routing algorithm to reduce energy consumption in the network is very necessary. This paper proposes a new distributed routing algorithm based on cluster maintenance (CMDR-LD). By prolonging the steady-state phase time and retaining the concept of round in routing algorithm, the new algorithm achieves the purpose of saving energy ultimately. Simulation results validate the energy efficiency of that algorithm.
Alpha1-antitrypsin phenotypes and anti-neutrophil cytoplasmic auto-antibodies in inflammatory bowel disease.

OBJECTIVES Alpha1-antitrypsin (alpha1-AT) is encoded by a highly polymorphic gene with over 75 codominantly expressed alleles at the protease inhibitor (Pi) locus classified as normal, deficient, dysfunctional or null. The aim of this study was to determine in patients with inflammatory bowel disease: (i) the prevalence of anti-neutrophil cytoplasmic auto-antibodies (ANCA) and their antigen specificities; (ii) alpha1-AT Pi phenotypes; and (iii) possible associations between ANCA, disease activity and deficient alpha1-AT alleles. DESIGN Study of 95 consecutive patients with ulcerative colitis (UC) and 63 patients with Crohn's disease (CD). METHODS Diagnosis and disease activity were determined by clinical, endoscopic and histological criteria. ANCA by indirect immunofluorescence (IIF) and Pi phenotyping by isoelectric focusing were performed for all patients. Positive IIF sera were tested in antigen-specific enzyme-linked immunosorbent assay: proteinase 3 (PR3), myeloperoxidase (MPO), lactoferrin (LF), lysozyme, human leucocyte elastase (HLE), cathepsin G and bactericidal/permeability increasing protein (BPI). RESULTS Sixty-one patients with UC (64.2%) and only 11 with CD (17.5%) had ANCA (P < 0.001). Antigen specificities were PR3 (7/61), MPO (3/61), LF (6/61), HLE (1/63) and BPI (10/61) in UC, and PR3 (2/11) and BPI (2/11) in CD. Three PiZ alleles were found, matching the prevalence in the normal French control population. No relationship was found between the presence of ANCA, antibody specificity, disease activity and deficient alpha1-AT alleles. CONCLUSION ANCA are more frequent in UC than CD and do not correlate with disease activity. ANCA and protease/antiprotease imbalance do not appear to modulate the clinical course of inflammatory bowel disease.
Evaluation of Semantic Interference Detection in Parallel Changes: an Exploratory Experiment

Parallel developments are becoming increasingly prevalent in the building and evolution of large-scale software systems. Our previous studies of a large industrial project showed that there was a linear correlation between the degree of parallelism and the likelihood of defects in the changes. To further study the relationship between parallel changes and faults, we have designed and implemented an algorithm to detect "direct" semantic interference between parallel changes. To evaluate the analyzer's effectiveness in fault prediction, we designed an experiment in the context of an industrial project. We first mine the change and version management repositories to find sample versions sets of different degrees of parallelism. We investigate the interference between the versions with our analyzer. We then mine the change and version repositories to find out what faults were discovered subsequent to the analyzed interfering versions. We use the match rate between semantic interference and faults to evaluate the effectiveness of the analyzer in predicting faults. Our contributions in this evaluative empirical study are twofold. First, we evaluate the semantic interference analyzer and show that it is effective in predicting faults (based on "direct" semantic interference detection) in changes made within a short time period. Second, the design of our experiment is itself a significant contribution and exemplifies how to mine software repositories rather than use artificial cases for rigorous experimental evaluations.
Generation and Characterization of Indoor Fungal Aerosols for Inhalation Studies

ABSTRACT In the indoor environment, people are exposed to several fungal species. Evident dampness is associated with increased respiratory symptoms. To examine the immune responses associated with fungal exposure, mice are often exposed to a single species grown on an agar medium. The aim of this study was to develop an inhalation exposure system to be able to examine responses in mice exposed to mixed fungal species aerosolized from fungus-infested building materials. Indoor airborne fungi were sampled and cultivated on gypsum boards. Aerosols were characterized and compared with aerosols in homes. Aerosols containing 107 CFU of fungi/m3 air were generated repeatedly from fungus-infested gypsum boards in a mouse exposure chamber. Aerosols contained Aspergillus nidulans, Aspergillus niger, Aspergillus ustus, Aspergillus versicolor, Chaetomium globosum, Cladosporium herbarum, Penicillium brevicompactum, Penicillium camemberti, Penicillium chrysogenum, Penicillium commune, Penicillium glabrum, Penicillium olsonii, Penicillium rugulosum, Stachybotrys chartarum, and Wallemia sebi. They were all among the most abundant airborne species identified in 28 homes. Nine species from gypsum boards and 11 species in the homes are associated with water damage. Most fungi were present as single spores, but chains and clusters of different species and fragments were also present. The variation in exposure level during the 60 min of aerosol generation was similar to the variation measured in homes. Through aerosolization of fungi from the indoor environment, cultured on gypsum boards, it was possible to generate realistic aerosols in terms of species composition, concentration, and particle sizes. The inhalation-exposure system can be used to study responses to indoor fungi associated with water damage and the importance of fungal species composition.
FlexCloud: A Flexible and Extendible Simulator for Performance Evaluation of Virtual Machine Allocation

Cloud Data centers aim to provide reliable, sustainable and scalable services for all kinds of applications. Resource scheduling is one of keys to cloud services. To model and evaluate different scheduling policies and algorithms, we propose FlexCloud, a flexible and scalable simulator that enables users to simulate the process of initializing cloud data centers, allocating virtual machine requests and providing performance evaluation for various scheduling algorithms. FlexCloud can be run on a single computer with JVM to simulate large scale cloud environments with focus on infrastructure as a service, adopts agile design patterns to assure the flexibility and extensibility, models virtual machine migrations which is lack in the existing tools, provides user-friendly interfaces for customized configurations and replaying. Comparing to existing simulators, FlexCloud has combined features for supporting public cloud providers, load-balance and energy-efficiency scheduling. FlexCloud has advantage in computing time and memory consumption to support large-scale simulations. The detailed design of FlexCloud is introduced and performance evaluation is provided.
Geolocalization on the Internet through Constraint Satisfaction

This paper outlines a novel, comprehensive framework for geolocalization, that is, determining the physical location of Internet hosts based on network measurements. The core insight behind this framework is to pose the geolocalization problem formally as one of error-minimizing constraint satisfaction, to create a system of constraints by deriving them aggressively from network measurements, and to solve the system using cheap and accurate geometric methods. The framework is general and accommodates both positive and negative constraints, that is, constraints on where the node can or cannot be, respectively. It can reason in the presence of uncertainty, enabling it to gracefully cope with aggressively derived constraints that may contain errors. Since the solution space is represented geometrically as a region bounded by Bezier curves, the framework yields an accurate set of all points where the target may be located. Preliminary results on PlanetLab show promise; the framework can localize the median node to within 22 miles, a factor of three better than previous approaches, with little error.
Temporal Resolution of Uncertainty and Recursive Models of Ambiguity Aversion

Dynamic models of ambiguity aversion are increasingly popular in applied work. This paper shows that there is a strong interdependence in such models between the ambiguity attitude and the preference for the timing of the resolution of uncertainty, as defined by the classic work of Kreps and Porteus (1978). The modeling choices made in the domain of ambiguity aversion influence the set of modeling choices available in the domain of timing attitudes. The main result is that the only model of ambiguity aversion that exhibits indifference to timing is the maxmin expected utility of Gilboa and Schmeidler (1989). This paper examines the structure of the timing nonindifference implied by the other commonly used models of ambiguity aversion. This paper also characterizes the indifference to long-run risk, a notion introduced by Duffie and Epstein (1992). The interdependence of ambiguity and timing that this paper identifies is of interest both conceptually and practicallyâ€”especially for economists using these models in applications.
Parental Perceptions of Computer-Based Gaming Technology: An Evaluation of Children's Leisure Pursuits in the Computer Age

This study is a quantitative and qualitative analysis of the primary leisure pursuits of children in the computer age. In a society dominated by electronic media, the conceptualisation of ‘leisure’ is rapidly changing and there is a perception that children are increasingly using technology as entertainment. In light of growing concerns that there may be an association between the use of television-based video games such as *Playstation and *Nintendo, and the increasing number of childhood behavioural disorders being diagnosed, these leisure pursuits are worthy of further investigation. The quantitative component of this research is a comparative analysis of leisure activities of six-to-eight-year-old children by gender. The qualitative component draws from parental responses to open-ended questions. The findings confirm the assumption that boys spend substantially more time engaged with interactive technological pursuits than do girls of the same age. However, the findings also suggest there is a growing level of parental anxiety concerning this social phenomenon. The parental concerns expressed in this study justify exploration, especially considering that this data reflects personal and confidential, first-hand observations of the physical and mental health of children.
Resonance in the renal vasculature evoked by activation of the sympathetic nerves

Malpas, Simon C. , Todd A. Hore, Michael Navakatikyan, Elena V. Lukoshkova, Sing Kiong Nguang, and Paul C. Austin. Resonance in the renal vasculature evoked by activation of the sympathetic nerves. Am. J. Physiol. 276 (Regulatory Integrative Comp. Physiol. 45): R1311–R1319, 1999. —We examined the ability of different frequencies in sympathetic nerve activity (SNA) to induce oscillations in renal blood flow (RBF). In anesthetized rabbits the renal nerves were stimulated using modulated sine patterns (base frequency 5 Hz, 5-ms duration pulses) that varied in amplitude between 0 and 10 V at a frequency between 0.04 and 1.0 Hz. The strengths of the induced oscillations in RBF were calculated using spectral analysis. Although faster rhythms in simulated SNA . 0.6 Hz contributed to the level of vascular tone, 95% of the power in the frequency response curve was below this frequency, indicating a low-pass filtering/integrating characteristic of the vasculature. Frequencies ,0.6 Hz were associated with increasing ability to induce oscillations in RBF. The ability of an SNA rhythm at 0.6 Hz to induce a rhythm in RBF was 21 times less than that at 0.25 Hz. At 0.16 Hz there was a distinct peak in the frequency response curve, indicating the vasculature was more sensitive in this frequency band to sympathetic stimulation. Blockade of endogenous nitric oxide by NG-nitro-L-arginine methyl ester (LNAME; 20 mg/kg) did not alter resting RBF levels nor was the low-pass filtering/integrating characteristic of the vasculature to nerve stimulation changed (i.e., the curve was not shifted left or right); however, there was a selective increase in the sensitivity to stimulation at 0.16 Hz, i.e., larger oscillations in RBF were evoked. These results indicate an ability of SNA to induce resonant oscillations in the renal vasculature and that there may be active and passive modulators of these responses. Naturally occurring oscillations in SNA ,0.6 Hz are likely to contribute to the dynamic control of RBF, ensuring it responds rapidly and with high gain to the stimuli of daily life, while filtering out the faster oscillations ensures stable glomerular filtration.
Predicting tourism demand by A.R.I.M.A. models

Abstract The paper provides a short-run estimation of international tourism demand focusing on the case of F.Y. R. Macedonia. For this purpose, the Box–Jenkins methodology is applied and several alternative specifications are tested in the modelling of original time series and international tourist arrivals recorded in the period 1956–2013. Upon the outcomes of standard indicators for accuracy testing, the research identifies the model of A.R. I.M.A.(1,1,1) as most suitable for forecasting. According to the research findings, a 13.9% increase in international tourist arrivals is expected by 2018. The forecasted values of the chosen model can assist in mitigating any potential negative impacts, as well as in the preparation of a tourism development plan for the country.
Parents' confidence in recommended childhood vaccinations: Extending the assessment, expanding the context

ABSTRACT There has been significant and growing interest in vaccine hesitancy and confidence in the United States as well as across the globe. While studies have used confidence measures, few studies have provided in-depth assessments and no studies have assessed parents' confidence in vaccines in relationship to other frequently recommended health-related products for young children. This study used a nationally representative sample of 1000 US parents to identify confidence levels for recommended vaccinations, antibiotics, over-the-counter (OTC) medicines, and vitamins for children. The analyses examined associations between confidence ratings, vaccination behaviors and intentions, and trust in healthcare provider, along with associations between confidence ratings and use of the other health-related products. Parents' confidence in vaccines was relatively high and high relative to antibiotics, OTC medicines and vitamins. For all 4 health-related products examined, past product experience and knowledge of bad or adverse outcomes negatively impacted parents' confidence levels. Confidence levels were associated with both trust in advice from their child's healthcare provider and acceptance of healthcare provider recommendations. Parents in some groups, such as those with lower income and education levels, were more likely to have less confidence not just in vaccines, but also in antibiotics and OTC medicines for children. Overall, the findings extend understanding of vaccine confidence, including by placing it into a broader context.
Diseño de Códigos Correctores de Errores con Algoritmos Genéticos

Resumen— Algunos sistemas de telecomunicaciones no pueden tolerar el coste de la repetición de un mensaje cuando se corrompe por el camino. En su lugar, el mensaje debe ser “corregido” de alguna forma en el destino. En estos casos es adecuado el uso de un código corrector de errores. El problema de encontrar un código corrector de errores de n bits y M palabras que corrija un máximo número de errores dado es NP-Completo. Por esta razón, el problema se ha resuelto en la literatura con técnicas heuŕısticas tales como Recocido Simulado y Algoritmos Genéticos. En este art́ıculo abordamos el problema con algoritmos genéticos en panmixia, estructurados e hibridados con un nuevo algoritmo de búsqueda local hecho a medida para el problema. Los resultados demuestran que las técnicas distribuidas e h́ıbridas obtienen los mejores resultados.
Antifungal susceptibility testing of yeasts: evaluation of technical variables for test automation

The technical parameters for antifungal susceptibility testing with Candida species were reexamined to determine the optimal conditions for testing with semiautomated preparations of broth microdilution cultures, automated spectrophotometric readings of the cultures, and dose-response and endpoint determinations by means of a computer spreadsheet. Tests were based on proposed standard method M27P of the National Committee for Clinical Laboratory Standards for antifungal agents. RPMI 1640 broth with extra glucose to a final concentration of 2% gave higher and more reproducible drug-free control readings without affecting susceptibility endpoint readings. An inoculum of 8 x 10(4) yeasts per ml prepared from a carbon-limiting broth culture without further standardization was found to give optimal control readings after 48 h of incubation at 37 degrees C. For flucytosine, fluconazole, itraconazole, and ketoconazole, endpoints based on 50% growth inhibition (50% inhibitory concentration) gave the minimum variation with inoculum size and the fewest endpoint differences with RPMI 1640 medium obtained from two different suppliers. The 50% inhibitory concentration was also the optimal endpoint for fluconazole and ketoconazole susceptibilities in comparison with broth macrodilution MICs determined by the method of the National Committee for Clinical Laboratory Standards. Intralaboratory reproducibility was determined by retrospective analysis of replicate results for isolates retested at random over a 2-year period. This approach showed less favorable reproducibility than has been reported from purpose-designed, prospective antifungal susceptibility studies, but it may better reflect real-life test reproducibility. Susceptibility data for 616 clinical isolates of yeasts, representing 16 Candida and Saccharomyces spp. , confirmed the tendency of Candida lusitaniae isolates to show relatively low susceptibilities to amphotericin B, the tendency of Candida krusei isolates to show low flucytosine and fluconazole susceptibilities, and the presence of some isolates in the species Candida albicans, Candida glabrata, and Candida tropicalis with low susceptibilities to azole derivative antifungal agents. The study demonstrates the value of automation and standardization in all stages of yeast susceptibility testing, from plate preparation to data analysis.
Isatoribine, an agonist of TLR7, reduces plasma virus concentration in chronic hepatitis C infection

Immune‐based therapy is the mainstay treatment for chronic hepatitis C virus (HCV) infection but causes multiple side effects and achieves durable viral clearance in only approximately 50% of patients. Most new investigational anti‐HCV compounds are direct‐acting antivirals for which durability of response and risk of viral mutations and resistance are not yet known. Therefore, continuing discovery and development of new immune‐based treatments is desirable. Toll‐like receptors (TLRs) are pathogen recognition receptors that initiate the innate immune response. The responsiveness of HCV or other ongoing chronic systemic infections to treatment with a selective TLR agonist has not been reported. Isatoribine is a selective agonist of TLR7. In a proof‐of‐concept study, we found that once‐daily 7‐day treatment with intravenous isatoribine 800 mg caused a significant (P = .001) reduction of plasma HCV RNA (mean, −0.76; range, −2.85 to +0.21 log10 units) in otherwise untreated patients (n = 12) who were chronically infected with HCV. Viral load reduction occurred in patients infected with genotype 1 as well as non‐genotype 1 HCV. The reduction of viral load was correlated with induction of markers of a heightened immune antiviral state, including 2′‐, 5′‐ oligoadenylate synthetase levels in whole blood. This treatment was well tolerated, with a low frequency of mild to moderate adverse events. In conclusion, systemic administration of the selective TLR7 agonist isatoribine resulted in dose‐dependent changes in immunologic biomarkers and a statistically significant antiviral effect with relatively few and mild side effects. (HEPATOLOGY 2005;42:724–731.)
The effects of fat and cholesterol on social behavior in monkeys.

&NA; We report here on the social behavior of 30 adult male cynomolgus monkeys, maintained in social groups of five animals each and assigned for 22 months to one of two dietary conditions: a) “luxury”—relatively high fat, high cholesterol (43% calories from fat, 0.34 mg cholesterol/Calorie of diet); or b) “prudent”—relatively low fat, low cholesterol (30% calories from fat, 0.05 mg cholesterol/Calorie of diet). The dietary manipulation resulted in higher total serum cholesterol (TSC) and lower high density lipoprotein cholesterol (HDLC) concentrations in luxury diet animals than in their prudent diet counterparts (p's less than 0.05). Additionally, we monitored the occurrence of 21 behavioral acts frequently exhibited by this species in captivity. Of these behaviors, only contact aggression differed between dietary conditions (p less than 0.03), with prudent diet monkeys initiating more aggression than luxury diet animals. These results are consistent with studies linking relatively low serum cholesterol concentrations to violent or antisocial behavior in psychiatric and criminal populations and could be relevant to understanding the significant increase in violence‐related mortality observed among people assigned to cholesterol‐lowering treatment in clinical trials.