Miracle-dz/UniFAR-FTUs huggingface dataset:
Influencing Factors on the Usability of API Classes and Methods

Usability is an important quality attribute for APIs. To create APIs with good usability, appropriate measurement methods are needed. But currently available methods are cost- and time-expensive and the results are not objective and therefore hard to quantify. API design guidelines give a good overview about important usability factors, but lack a scientific basis. When looking at scientific API usability studies, only a very small area of API design has been researched yet. Existing results don't give enough basis for a good API usability measurement method. In this paper we identify influencing usability factors for the two most common concepts of APIs: classes and methods. We therefore conduct a study with 20 programmers and 2 different API variants and evaluate how differences between the APIs influence usability when instantiating classes and calling methods. The results build a basis for API usability measurement methods and should help design more usable APIs.
Model-based analysis of avoidance of ozone stress by stomatal closure in Siebold's beech (Fagus crenata).

BACKGROUND AND AIMS Resistance of plants to ozone stress can be classified as either avoidance or tolerance. Avoidance of ozone stress may be explained by decreased stomatal conductance during ozone exposure because stomata are the principal interface for entry of ozone into plants. In this study, a coupled photosynthesis-stomatal model was modified to test whether the presence of ozone can induce avoidance of ozone stress by stomatal closure. METHODS The response of Siebold's beech (Fagus crenata), a representative deciduous tree species, to ozone was studied in a free-air ozone exposure experiment in Japan. Photosynthesis and stomatal conductance were measured under ambient and elevated ozone. An optimization model of stomata involving water, CO2 and ozone flux was tested using the leaf gas exchange data. KEY RESULTS The data suggest that there are two phases in the avoidance of ozone stress via stomatal closure for Siebold's beech: (1) in early summer ozone influx is efficiently limited by a reduction in stomatal conductance, without any clear effect on photosynthetic capacity; and (2) in late summer and autumn the efficiency of ozone stress avoidance was decreased because the decrease in stomatal conductance was small and accompanied by an ozone-induced decline of photosynthetic capacity. CONCLUSIONS Ozone-induced stomatal closure in Siebold's beech during early summer reduces ozone influx and allows the maximum photosynthetic capacity to be reached, but is not sufficient in older leaves to protect the photosynthetic system.
An alternative model for the transmembrane segments of the yeast H+‐ATPase

An alternative topological model for the yeast plasma membrane H+‐ATPase from K. lactis was deduced by joint prediction, using 11 algorithms for the prediction of transmembrane segments complemented with hydrophobic moment analysis. Similarly to the model currently used in the literature, this alternative model contains 10 transmembrane segments, four in the N‐half and six in the C‐half of the protein. However, the distribution of the membrane‐associated segments on the C‐half of the enzyme differs in both models. Nine of the 10 transmembrane segments are highly hydrophobic with low hydrophobic moments, and are probably involved in structural roles. The fifth transmembrane segment is, on the other hand, less hydrophobic, with the highest hydrophobic moment, suggesting that this segment might have a dynamic role in the coupling of the hydrolysis of ATP with the translocation of protons across the membrane. The alignment of the Ca2+‐ATPase, the Na+/K+‐ATPase and the H+‐ATPase sequences showed that these proteins have the same topology in the N‐half, but important differences were found at the C‐half of the enzymes. In contrast with the mammalian ATPases, the fifth transmembrane segment in the H+‐ATPase appears early in the sequence, giving rise to a shorter cytoplasmic central loop. This alternative model will be useful in the designing of site‐directed mutagenesis experiments and contains information for the fitting of the amino acid sequence into the transmembrane region of the three‐dimensional model of the ATPase. Copyright © 1999 John Wiley & Sons, Ltd.
Gastrointestinal microbiology enters the metagenomics era

Purpose of review Advances in DNA sequence-based technologies now permit genetic analysis of complex microbial populations without the need for prior cultivation. This review summarizes the molecular methods of culture-independent microbiology (‘metagenomics’) and their recent application to studies of the human gastrointestinal tract in both health and disease. Recent findings Culture-independent metagenomic surveys reveal unprecedented microbial biodiversity in the human intestine. Upwards of 40 000 bacterial species are estimated to comprise the collective gastrointestinal microbiome, most of which have not been characterized by culture. Diverse conditions such as antibiotic-associated diarrhea, Crohn's disease, ulcerative colitis, obesity, and pouchitis have been correlated with large-scale imbalances in gastrointestinal microbiota, or ‘dysbiosis’. These findings demonstrate the importance of commensal microorganisms in maintaining gastrointestinal health. Summary Through technological and conceptual innovations in metagenomics, the complex microbial habitat of the human gastrointestinal tract is now amenable to detailed ecological analysis. Large-scale shifts in gut commensal populations, rather than occurrence of particular microorganisms, are associated with several gastroenterological conditions; redress of these imbalances may ameliorate the conditions.
Lysophosphatidic acid receptor 2/3‐mediated IL‐8‐dependent angiogenesis in cervical cancer cells

The expression of lysophosphatidic acid (LPA)‐specific receptors in cervical cancer has not been clearly defined. In this study, we identified LPA1, LPA2 and LPA3 receptors' mRNA in SiHa, HeLa and CaSki cell lines by RT‐PCR. These receptors were not associated with tumor cell proliferation in vitro. We then used a xenograph animal model to evaluate the effects of these receptors on in vivo cervical cancer tumorigenicity. When SiHa cells with different receptor expression patterns were seeded on the backs of SCID mice, the resulting knockout of both LPA2 and LPA3 significantly attenuated tumor growth; this decrease in tumor growth was found to be linked with decreased angiogenesis (microvessel density), suggesting that LPA2 and LPA3 are crucial for in vivo tumor growth through an angiogenic mechanism. We further investigated this mechanism of LPA receptor 2/3‐mediated angiogenic capability by analyzing angiogenic factors in protein lysates from receptor knockout tumors, by detecting interleukin (IL‐8) mRNA expression after treating with siRNA, by evaluating the biological role of LPA‐enhanced IL‐8 via endothelial cell tube formation, monolayer permeability, migration and cell growth assays, and by IL‐8 knockout xenograft mice modeling. We found that the angiogenesis is mediated through IL‐8. Finally, we evaluated the regulation pathways involved in LPA‐induced IL‐8 expression. We found that LPA receptor 2/3‐mediated IL‐8 expression occurs through Gi/PI3K/AKT, Gi/PKC and IκB/NF‐κB signaling. In conclusion, we propose that LPA2 and LPA3 might play an important role in cervical cancer tumor growth through IL‐8‐dependent angiogenesis.
Design of a static full-ring multi-pinhole collimator for brain SPECT

In clinical practice, brain SPECT is mostly performed using a dual-head SPECT scanner with fan-beam or parallel-beam collimators rotating around the patient's head. The resolution of such a system is typically about 6-8 mm, which is rather poor to image the complex structures of the human brain. We developed a non-rotating multi-pinhole collimator for brain SPECT imaging with a resolution of 4 mm. A full-ring geometry allows for complete transaxial sampling. This enables the use of a stationary collimator. The collimator is a tungsten ring with two rows of pinholes. Each pinhole can individually be opened or closed with shutters. A sequence of shutter movements is performed to obtain an acquisition setup that simulates a rotational movement. The collimator is designed for the LaPET system (a PET detector ring made of 24 LaBr3 detectors) and is optimized to maximize the system performance, resulting in a collimator radius of 145 mm and a pinhole diameter of 2 mm. This system has a sensitivity that is 4 times lower than a dual-head system with LEHR parallel-beam collimators. However, the resolution is 2 times better, a trade-off that is supported by Muehllehner [1]. Monte-Carlo simulated projections of a resolution phantom are successfully reconstructed and the resulting image shows that a resolution of 4 mm is indeed achieved.
Gasto público en visitas a servicios sanitarios ocasionados por los hábitos de alimentación de personas mayores

Los habitos de alimentacion en las personas mayores constituyen un factor a tener en cuenta a la hora de analizar la calidad de vida. El objetivo del presente trabajo es valorar los costes sanitarios derivados de las visitas a servicios de salud y hospitalizaciones ocasionados por los habitos de alimentacion de las personas mayores. Para ello se utilizo la Encuesta Europea de Salud en Espana de 2014, y a traves de diferentes modelos se observa la asociacion estadisticamente significativa entre el numero de visitas a urgencias y el incumplimiento de unos criterios minimos de alimentacion saludable. El gasto publico total anual estimado de dichas visitas asciende a 731M€, de los que el 5,6% podria ser debido a una alimentacion no saludable.
COMT Val158Met and 5HTTLPR functional loci interact to predict persistence of anxiety across adolescence: results from the Victorian Adolescent Health Cohort Study

We investigated whether a composite genetic factor, based on the combined actions of catechol‐O‐methyltransferase (COMT) (Val158Met) and serotonin transporter (5HTTLPR) (Long‐Short) functional loci, has a greater capacity to predict persistence of anxiety across adolescence than either locus in isolation. Analyses were performed on DNA collected from 962 young Australians participating in an eight‐wave longitudinal study of mental health and well‐being (Victorian Adolescent Health Cohort Study). When the effects of each locus were examined separately, small dose–response reductions in the odds of reporting persisting generalized (free‐floating) anxiety across adolescence were observed for the COMT Met158 [odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.76–0.95, P = 0.004] and 5HTTLPR Short alleles (OR = 0.88, CI = 0.79–0.99, P = 0.033). There was no evidence for a dose–response interaction effect between loci. However, there was a double‐recessive interaction effect in which the odds of reporting persisting generalized anxiety were more than twofold reduced (OR = 0.45, CI = 0.29–0.70, P < 0.001) among carriers homozygous for both the COMT Met158 and the 5HTTLPR Short alleles (Met158Met + Short‐Short) compared with the remaining cohort. The double‐recessive effect remained after multivariate adjustment for a range of psychosocial predictors of anxiety. Exploratory stratified analyses suggested that genetic protection may be more pronounced under conditions of high stress (insecure attachments and sexual abuse), although strata differences did not reach statistical significance. By describing the interaction between genetic loci, it may be possible to describe composite genetic factors that have a more substantial impact on psychosocial development than individual loci alone, and in doing so, enhance understanding of the contribution of constitutional processes in mental health outcomes.
Refined structure for the complex of 1-deoxynojirimycin with glucoamylase from Aspergillus awamori var. X100 to 2.4-A resolution.

The three-dimensional structure of the complex of 1-deoxynojirimycin with glucoamylase II-(471) from Aspergillus awamori var. X100 has been determined to 2.4-A resolution. The model includes residues corresponding to residues 1-471 of glucoamylase I from Aspergillus niger, two molecules of bound 1-deoxynojirimycin and 605 sites for water molecules. The crystallographic R factor from refinement is 0.119, and the root-mean-squared deviation in bond distances is 0.012 A. The inhibitor complex confirms the location of the active site in the packing void of the alpha/alpha-barrel as proposed by Aleshin et al. [Aleshin, A. , Golubev, A. , Firsov, L. , & Honzatko, R. B. (1992) J. Biol. Chem. 267, 19291-19298]. One inhibitor molecule is associated with strong electron density and represents the principal site of interaction of 1-deoxynojirimycin with the enzyme. The other 1-deoxynojirimycin molecule is associated with weak electron density and therefore, probably represents a binding site of low affinity. Interactions of 1-deoxynojirimycin with the enzyme at its principal site involve Arg 45, Asp 55, Arg 305, and carbonyl 177. In addition, a water molecule (water 500) hydrogen bonds to Glu 400 and the 6-hydroxyl of 1-deoxynojirimycin and is at an approximate distance of 3.3 A from the "anomeric" carbon of the inhibitor. The structural arrangement of functional groups near the inhibitor molecule suggests that Glu 179 is a catalytic acid, Glu 400 a catalytic base, and water 500 the attacking nucleophile in the hydrolysis of maltooligosaccharides. The relevance of the X-ray work to proposed mechanisms of enzymatic hydrolysis of oligosaccharides is discussed.
Influence of the CYP2D6*4 polymorphism on dose, switching and discontinuation of antidepressants.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Most antidepressants are metabolized by CYP2D6. The variant allele CYP2D6*4 is the main polymorphism resulting in reduced enzyme activity in Caucasians. * Reduced enzyme activity potentially leads to increased toxicity of antidepressants, but the relevance of genotyping for clinical practice is unclear. Most clinical studies suffer from small numbers of patients. WHAT THIS STUDY ADDS * This large population-based cohort study in 1198 elderly Dutch patients examines the influence of the CYP2D6*4 polymorphism on intolerability of antidepressants. * The risk of switching to another antidepressant in tricyclic antidepressant users is higher in poor metabolizers (PMs), but not in SSRI users. PMs require a lower maintenance dose of antidepressants compared with extensive metabolizers (EMs). * Antidepressants were initiated in a relatively low dose, with gradual dose increments thereafter, reducing the risk of adverse drug reactions. Therefore, the question remains whether genotyping prior to the start of antidepressant therapy contributes substantially to the optimization of pharmacotherapy. AIMS To study the effect of CYP2D6*4 on antidepressant dose, switching and discontinuation of therapy. METHODS The study consisted of all subjects in the Rotterdam Study, who received a first antidepressant prescription between April 1st 1991 and July 1st 2005 and for whom data on CYP2D6 genotype were available. Binary logistic regression was performed to study the association between CYP2D6*4 and switching to any other antidepressant or discontinuation of therapy within 45 days. The difference in mean antidepressant dose was compared between CYP2D6 genotypes using t-tests and repeated measurements analyses. RESULTS In users of tricyclic antidepressants (TCAs) the risk of switching to another antidepressant was significantly higher in poor metabolizers (PMs:*4/*4) compared with extensive metabolizers (EMs:*1/*1), with an adjusted OR of 5.77 (95% CI 1.59, 21.03; P = 0.01). In SSRI users there was no significant difference (OR 0.91; 95% CI 0.20, 4.15; P = 0.90). Heterozygous patients did not have an increased risk of switching in both TCA and SSRI users. The mean TCA dose was significantly lower in PMs than in EMs at the third and fourth prescription (difference 0.11 DDD, P = 0.03). In SSRI users the difference in mean dose between PMs and EMs was significant at the third prescription (0.17 DDD; P = 0.02). CONCLUSIONS The risk of switching to another antidepressant in TCA users is higher in PMs than in EMs. The maintenance doses of antidepressants were significantly lower in PMs. However, the question whether genotyping prior to the start of antidepressant therapy contributes substantially to the optimization of pharmacotherapy, requires further study.
RGS18 Acts as a Negative Regulator of Osteoclastogenesis by Modulating the Acid‐Sensing OGR1/NFAT Signaling Pathway

We showed that RGS18, a myeloid lineage‐specific RGS protein that is inhibited after activation of the RANK/RANKL system, is a negative regulator of osteoclastogenesis. RGS18 acts through an external acidosis‐sensing osteoclastogenic mechanism through the OGR1/NFAT pathway.
Prenatal exposure to traffic-related air pollution and fetal growth in a cohort of pregnant women

Objectives Scant evidence is available on effects of air pollution on longitudinally measured fetal biometry, and thus it remains unclear as to whether there are critical windows of exposure or specificity of effects. Our objective was to examine the association between exposure to nitrogen dioxide (NO2) during pregnancy and fetal and neonatal anthropometry in a cohort of Spanish women. Methods Temporally adjusted land-use regression was used to estimate exposure to NO2 at home addresses. Biparietal diameter (BPD), abdominal circumference (AC), femur length (FL) and estimated fetal weight (EFW) were evaluated in each trimester by ultrasound. As neonatal outcomes, weight, length and head circumference were analysed. SD scores adjusted by gestational age, mother characteristics and fetus sex were calculated at 12, 20 and 32 weeks of gestation as well as at birth. The association between fetal growth and average exposure to NO2 in the relevant windows was investigated using regression models, adjusted for socio-demographic and lifestyle-related variables. Results Exposure to NO2 was inversely associated with BPD, AC and EFW at week 32 and with growth in these parameters in weeks 20–32. BPD and FL were also affected earlier, at week 20. NO2 levels above the median (38 μg/m3) reduced size at week 32 by around 9% in all parameters except for FL (6%). The critical windows of exposure were in early pregnancy, before 20 weeks. Exposure in this period was also inversely associated with neonatal length and head circumference. Conclusions Maternal exposure to NO2 is associated with impaired fetal growth from mid-gestation onwards.
Influencia de la Innovación Tecnológica en un Proceso de Cambio Organizacional en Empresas Comerciales de la ZMG

Este trabajo estudia el cambio organizacional tomando como perspectiva de analisis la corriente de estudio de la Innovacion Tecnologica. Dado que la Innovacion Tecnologica puede ser un factor que contribuya significativamente para efectuar un proceso de cambio de cultura organizacional. Esta investigacion busca identificar los factores que intervienen en la implantacion de un cambio organizacional en empresas comerciales ubicadas en la Zona Metropolitana de Guadalajara (ZMG).
Assessing the role of social media in tourism recovery in tsunami-hit coastal areas in Tohoku, Japan

Social media have become increasingly popular. However, there has been little investigation on how to effectively mobilize this newly emerging tool to promote tourism in rural areas. The aims of this article are twofold. First, among social media, we explore the role of Twitter for tourism promotion, especially by focusing on the recovery process of tourism in a rural area affected by the huge earthquake and tsunami, Magnitude 9.0, which hit eastern Japan in March 2011. Second, to approach the first purpose, we compare two types of tourism: ordinary tourism and ‘volunteer tourism’. As to the latter, a massive number of volunteers came to these areas to help in the recovery work from the devastation such as removing debris and helping evacuees rehabilitate their lives in Iwate prefecture. We employed a text-mining method to find keywords used in the official Twitter account issued by the Iwate Prefectural government and time-series regression models to identify factors that promote the two types of tourism. Data were collected using official statistics on incoming numbers of ordinary tourists and volunteer tourists. Tweeted information was provided by Iwate Prefecture. The results revealed that, first, tweeted information on cultural and natural heritage had a positive relationship with the number of incoming tourists while information on disaster-related words had negative effects. In contrast, second, tweeted information on tourism resources worked negatively toward the number of volunteer tourists while that on rehabilitation/reconstruction and on volunteers worked positively. Consequently, it is important to design support measures that enable the local tourism sector to attract incoming tourists after a drop-in volunteer tourism as reconstruction of the disaster area progresses. In this context, our results suggest how to effectively utilize Twitter for this purpose.
Preclinical and clinical assessment of the safety and potential efficacy of thalidomide in heart failure.

BACKGROUND Inflammatory mediators, especially tumor necrosis factor (TNF), have been implicated in heart failure (HF). Thalidomide has anti-inflammatory properties and selectively inhibits TNF. Thus far, thalidomide or thalidomide analogues have not been evaluated in patients with heart failure. METHODS Thalidomide was assessed in preclinical and clinical studies. First, isolated cardiac myocytes were pretreated with thalidomide or thalidomide analogues, and TNF production was assessed after lipopolysaccharide (LPS) provocation. Second, to determine the safety and potential efficacy of thalidomide, an open-label dose escalation safety study was conducted in seven patients with advanced heart failure. RESULTS Thalidomide and thalidomide analogues inhibited LPS-induced TNF biosynthesis in cardiac myocytes in a dose-dependent manner. Thalidomide analogues had a greater inhibitory effect on TNF production than did thalidomide. In patients with advanced HF, thalidomide was safe and potentially effective when used at lower doses. However, dose-limiting toxicity was observed in two patients. There was a significant increase in the 6-minute walk distance and a trend toward improvement in left ventricular ejection fraction and quality of life after 12 weeks of maintenance therapy with thalidomide. CONCLUSIONS Taken together these results suggest that thalidomide or its derivatives may be useful in selected patients with HF. This potential needs to be studied in larger clinical trials.