Miracle-dz/UniFAR-FTUs huggingface dataset:
1‐[2‐(4‐Benzyloxyphenoxy)Ethyl]Imidazole inhibits monoamine oxidase B and protects against neuronal loss and behavioral impairment in rodent models of Parkinson's disease

Monoamine oxidase B (MAO‐B) is well known as a therapeutic target for Parkinson's disease (PD). MAO‐B inhibitors retain antiparkinsonism abilities to improve motor function and prevent neuronal loss by decreasing dopamine metabolism and oxidative stress in the brain. From the study to find novel antiparkinsonism drugs that can inhibit MAO‐B activity, neuronal loss, and behavioral deficits in the mouse model of PD, we identified that 1‐[2‐(4‐benzyloxyphenoxy)ethyl]imidazole (BPEI) or safinamide strongly and selectively inhibited MAO‐B activities in a dose‐dependent manner (IC50 of BPEI and safinamide for MAO‐B were 0.016 and 0.0021 µM and for MAO‐A were 70.0 and 370 µM, respectively). In ex vivo studies after an administration (30 mg/kg, i.p.) of BPEI or safinamide to normal mice, the MAO‐B activity in the brain was reduced by up to 90.6% or 82.4% at 1.0 hr. BPEI (20 mg/kg, i.p.) or safinamide (20 mg/kg, i.p.) significantly reversed the behavioral impairments, dopamine levels in the striatum, and neuronal loss in the substantia nigra of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated mice compared with the MPTP‐alone‐treated group. In the 6‐hydroxydopamine‐induced PD rat model, behavioral improvement by levodopa sparing activity was observed in the BPEI‐ or safinamide‐treated (20 mg/kg, i.p.) rats. Moreover, BPEI revealed additional curative activities for nonmotor symptoms of PD such as pain, anxiety, epilepsy, and depression in rodent disease models. Therefore, BPEI has broad therapeutic potential for treating motor symptoms via strong and selective inhibitory effects on MAO‐B, with additional benefits for comorbid symptoms in PD. © 2015 Wiley Periodicals, Inc.
Characterization of Arachidonic Acid Metabolism by Rat Cytochrome P450 Enzymes: The Involvement of CYP1As

Cytochrome P450 (P450) enzymes mediate arachidonic acid (AA) oxidation to several biologically active metabolites. Our aims in this study were to characterize AA metabolism by different recombinant rat P450 enzymes and to identify new targets for modulating P450-AA metabolism in vivo. A liquid chromatography-mass spectrometry method was developed and validated for the simultaneous measurements of AA and 15 of its P450 metabolites. CYP1A1, CYP1A2, CYP2B1, CYP2C6, and CYP2C11 were found to metabolize AA with high catalytic activity, and CYP2A1, CYP2C13, CYP2D1, CYP2E1, and CYP3A1 had lower activity. CYP1A1 and CYP1A2 produced ω-1→4 hydroxyeicosatetraenoic acids (HETEs) as 88.7 and 62.7%, respectively, of the total metabolites formed. CYP2C11 produced epoxyeicosatrienoic acids (EETs) as 61.3%, and CYP2C6 produced midchain HETEs and EETs as 48.3 and 29.4%, respectively, of the total metabolites formed. The formation of CYP1A1, CYP1A2, CYP2C6, and CYP2C11 major metabolites followed an atypical kinetic profile of substrate inhibition. CYP1As inhibition by α-naphthoflavone or anti-CYP1As antibodies significantly reduced ω-1→4 HETE formation in the lungs and liver, whereas CYP1As induction by 3-methylcholanthrene resulted in a significant increase in ω-1→4 HETEs formation in the heart, lungs, kidney, and livers by 370, 646, 532, and 848%, respectively. In conclusion, our results suggest that CYP1As and CYP2Cs are major players in the metabolism of AA. The significant contribution of CYP1As to AA metabolism and their strong inducibility suggest their possible use as targets for the prevention and treatment of several diseases.
Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent

Female 129:Stat1-null mice (129S6/SvEvTac-Stat1tm1Rds homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment.
Intelligent Robust Tracking Control for a Class of Uncertain Strict-Feedback Nonlinear Systems

This paper addresses the problem of designing robust tracking controls for a large class of strict-feedback nonlinear systems involving plant uncertainties and external disturbances. The input and virtual input weighting matrices are perturbed by bounded time-varying uncertainties. An adaptive fuzzy-based (or neural-network-based) dynamic feedback tracking controller will be developed such that all the states and signals of the closed-loop system are bounded and the trajectory tracking error should be as small as possible. First, the adaptive approximators with linearly parameterized models are designed, and a partitioned procedure with respect to the developed adaptive approximators is proposed such that the implementation of the fuzzy (or neural network) basis functions depends only on the state variables but does not depend on the tuning approximation parameters. Furthermore, we extend to design the nonlinearly parameterized adaptive approximators. Consequently, the intelligent robust tracking control schemes developed in this paper possess the properties of computational simplicity and easy implementation. Finally, simulation examples are presented to demonstrate the effectiveness of the proposed control algorithms.
Spiritual Experience and Psychopathology

A recent study of the relationship between spiritual experience and psychopathology (reported in detail elsewhere) suggested that psychotic phenomena could occur in the context of spiritual experiences rather than mental illness. In the present paper, this finding is illustrated with three detailed case histories. Its implications are then explored for psychopathology, for psychiatric classification, and for our understanding of the concept of mental illness. It is argued that pathological and spiritual psychotic phenomena cannot be distinguished by 1) form and content alone (as in traditional psychopathology), 2) by their relationship either with other symptoms or with pathological causes (as in psychiatric classification), or 3) by reference to the descriptive criteria of mental illness implied by the "medical" model. The distinction is shown to depend, rather, on the way in which psychotic phenomena themselves are embedded in the values and beliefs of the person concerned. This in turn is shown to have implications for diagnosis (it shows the need for clinicians to attend to the values and beliefs of individual patients), for treatment (it points to a cognitive problem-solving model), and for research in psychopathology (especially as related to the emerging sciences of dynamic brain imaging and cognitive neuroscience).
Ecological niche modeling of coastal dune plants and future potential distribution in response to climate change and sea level rise

Climate change (CC) and sea level rise (SLR) are phenomena that could have severe impacts on the distribution of coastal dune vegetation. To explore this we modeled the climatic niches of six coastal dunes plant species that grow along the shoreline of the Gulf of Mexico and the Yucatan Peninsula, and projected climatic niches to future potential distributions based on two CC scenarios and SLR projections. Our analyses suggest that distribution of coastal plants will be severely limited, and more so in the case of local endemics (Chamaecrista chamaecristoides, Palafoxia lindenii, Cakile edentula). The possibilities of inland migration to the potential ‘new shoreline’ will be limited by human infrastructure and ecosystem alteration that will lead to a ‘coastal squeeze’ of the coastal habitats. Finally, we identified areas as future potential refuges for the six species in central Gulf of Mexico, and northern Yucatán Peninsula especially under CC and SLR scenarios.
Development and psychometric validation of the Menstrual Health Instrument (MHI) for adolescents in Korea

ABSTRACT The aims of the researchers were to develop and test initial psychometric properties of the Menstrual Health Instrument, a measure of menstrual health in adolescents that comprehensively evaluates menstrual health. Data were collected with a convenience sample of 230 Korean adolescent girls. As a result of exploratory factor analysis with the 29-item instrument, five factors were extracted: affective symptoms, somatic symptoms and school life, daily habits for menstrual health, menstrual cycle characteristics, and attitudes and perceptions on menstruation. The reliability and validity estimates indicate the Menstrual Health Instrument could be used for screening in school or community settings.
Regional right ventricular deformation in patients with open and closed atrial septal defect.

AIMS This study aimed at (i) evaluating regional right ventricular (RV) deformation in patients with an atrial septal defect (ASD)-type secundum using strain and strain rate imaging and (ii) investigating the relation of regional deformation with functional capacity using cardiopulmonary exercise testing (CPET) in order to identify subclinical changes in RV function. METHODS AND RESULTS Forty-five patients with ASD-type secundum (18 open, 27 closed) and 20 age-matched controls were included. All underwent standard echocardiography and colour-Doppler myocardial velocity imaging. Longitudinal deformation was measured in the RV free wall divided in two segments. ASD patients underwent symptom-limited CPET. When compared with controls, apical strain was higher (-38.2 ± 9.9 vs. -29.9 ± 6.6%; P= 0.004) and lower (-25.2 ± 6.1 vs. -29.9 ± 6.6%; P= 0.006) in patients with an open and a closed ASD, respectively. Apical strain was higher (-38.2 ± 9.9 vs. -27.9 ± 6.6%; P= 0.001) and lower (-25.2 ± 6.1 vs. -28.7 ± 7.4%; P= 0.022) than basal strain in patients with an open and a closed ASD, respectively. In patients with an open ASD, apical strain correlated with shunt-ratio (R = -0.78; P< 0.0001), RV end-diastolic area (R = -0.68; P= 0.002), and RV stroke volume (R = -0.67; P= 0.002). Peak oxygen consumption (peak vO₂) was below average in patients with an open (79 ± 19% predicted; P< 0.0001) and a closed ASD (89 ± 18% predicted; P= 0.002). After ASD repair, apical strain correlated with peak vO₂ (R = -0.49; P= 0.01) and with ventilatory efficiency (R = 0.62; P= 0.001). CONCLUSION Volume overload of the right ventricle in patients with ASD-type secundum causes a regional deformation pattern with higher apical strain, related to parameters of volume load severity. After ASD repair, lower apical strain values correlated with functional capacity. Measurement of apical strain seems sensitive for detecting mild RV dysfunction.
Epidemiological Screening for Hepatitis E Virus in Bile Specimens from Livestock in Northwest China

Hepatitis E has been hypothesized as a zoonosis. However, there is no definite conclusion about which animal species contribute to hepatitis E virus (HEV) infection in humans. In this study, HEV RNA was detected only in swine bile specimens and not in bile specimens collected from cattle, goats, or dogs. We postulate that swine are the main animal reservoir for HEV.
The Diffusion of Innovations in Social Networks ∗

This paper determines how different network structures influence the diffusion of innovations. We develop a model of diffusion where: 1. an individual’s decision to adopt a new technology is influenced by his contacts; and 2. contacts can discuss, coordinate, and make adoption decisions together. A measure of connectedness, ‘cohesion’, determines diffusion. A cohesive community is defined as a group in which all members have a high proportion of their contacts within the group. We show a key trade-off: on one hand, a cohesive community can hinder diffusion by blocking the spread of a technology into the group; on the other hand, cohesive communities can be particularly effective at acting collectively to adopt an innovation. We find that for technologies with low externalities (that require few people to adopt before others are willing to adopt), social structures with loose ties, where people are not part of cohesive groups, enable greater diffusion. However, as externalities increase (technologies require more people to adopt before others are willing to adopt), social structures with increasingly cohesive groups enable greater diffusion. Given that societal structure is known to differ systematically along this dimension, our findings point to specialization in technological progress exhibiting these patterns. ∗Bryony Reich, Faculty of Economics, University College London. Email: b.reich@ucl.ac. uk. I would like to thank Alberto Alesina, Antonio Cabrales, Sanjeev Goyal, and Jorgen Weibull for their invaluable guidance and support. I benefited greatly from conversations with and comments of Marco Bassetto, Lars Nesheim and Imran Rasul. I am grateful to Jonathan Newton for numerous interactions at all stages of this project. For helpful comments I would also like to thank Lucie Gadenne, Terri Kneeland, and Sueyhun Kwon, as well as seminar participants at Alicante, Cambridge, INET Contagion Conference, Oxford, PET Luxembourg, and UCL. I gratefully acknowledge financial support from the UK Economic and Social Research Council (grant number ES/K001396/1).
The Surprising Breadth of Harbingers of Failure

Previous research has shown that there exist “harbinger customers” who systematically purchase new products that fail (and are discontinued by retailers). This article extends this result in two ways. First, the findings document the existence of “harbinger zip codes. ” If households in these zip codes adopt a new product, this is a signal that the new product will fail. Second, a series of comparisons reveal that households in harbinger zip codes make other decisions that differ from other households. The first comparison identifies harbinger zip codes using purchases from one retailer and then evaluates purchases at a different retailer. Households in harbinger zip codes purchase products from the second retailer that other households are less likely to purchase. The analysis next compares donations to congressional election candidates; households in harbinger zip codes donate to different candidates than households in neighboring zip codes, and they donate to candidates who are less likely to win. House prices in harbinger zip codes also increase at slower rates than in neighboring zip codes. Investigation of households that change zip codes indicates that the harbinger zip code effect is more due to where customers choose to live, rather than households influencing their neighbors’ tendencies.
Edge Separators of Planar and Outerplanar Graphs with Applications

Abstract We consider the problem of finding a small set of edges (an edge separator) whose removal divides a given graph into roughly equal parts. We show that every planar graph with n vertices and a maximum degree k has an O ([formula])-edge separator, which bound is asymptotically optimal. This improves the previously best known upper bound of O ( k [formula]). We prove that the bisection width of the class of planar graphs and trees of n vertices and maximum degree k is O ([formula] and O ( k log n /log k ), respectively, both optimal within a constant factor. All proofs are constructive and yield optimal O ( n ) algorithms. The separator theorems are applied to embed efficiently planar and outerplanar graphs into binary trees, hypercubes, butterfly graphs, CCC graphs, shuffle-exchange graphs, de Brujn graphs, and d -dimensional meshes. The embeddings are shown to be optimal or almost optimal with respect to the average dilation and the expansion of the embedding.
Acute Coronary Syndrome: The Risk to Young Women

Background Although acute coronary syndrome (ACS) mainly occurs in patients >50 years, younger patients can be affected as well. We used an age cutoff of 45 years to investigate clinical characteristics and outcomes of “young” patients with ACS. Methods and Results Between October 2010 and April 2016, 14 931 patients with ACS were enrolled in the ISACS‐TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry. Of these patients, 1182 (8%) were aged ≤45 years (mean age, 40.3 years; 15.8% were women). The primary end point was 30‐day all‐cause mortality. Percentage diameter stenosis of ≤50% was defined as insignificant coronary disease. ST‐segment–elevation myocardial infarction was the most common clinical manifestation of ACS in the young cases (68% versus 59.6%). Young patients had a higher incidence of insignificant coronary artery disease (11.4% versus 10.1%) and lesser extent of significant disease (single vessel, 62.7% versus 46.6%). The incidence of 30‐day death was 1.3% versus 6.9% for the young and older patients, respectively. After correction for baseline and clinical differences, age ≤45 years was a predictor of survival in men (odds ratio, 0.24; 95% confidence interval, 0.10–0.58), but not in women (odds ratio, 1.35; 95% confidence interval, 0.50–3.62). This pattern of reversed risk among sexes held true after multivariable correction for in‐hospital medications and reperfusion therapy. Moreover, younger women had worse outcomes than men of a similar age (odds ratio, 6.03; 95% confidence interval, 2.07–17.53). Conclusion ACS at a young age is characterized by less severe coronary disease and high prevalence of ST‐segment–elevation myocardial infarction. Women have higher mortality than men. Young age is an independent predictor of lower 30‐day mortality in men, but not in women. Clinical Trial Registration URL: http://clinicaltrials.gov/. Unique identifier: NCT01218776.
Automated Detection of Reflection Hyperbolas in Complex GPR Images With No A Priori Knowledge on the Medium

In this paper, we propose an automated detection algorithm for well- and ill-shaped ground-penetrating radar reflection hyperbolas for complex media, calibrated with human recognition principles. The algorithm detects the apex of the hyperbolas by fitting an analytical function of a hyperbola to the profile edge dots detected with a Canny filter. The existence of a hyperbola is determined using a set of carefully chosen criteria calibrated in order to fit the ambiguity zone for the human brain. The inherent misshapedness of field hyperbolas is further considered by defining a buffer zone around the theoretical hyperbola. First, the method was tested in the laboratory over tree roots and PVC pipes and on field images over tree root systems. Both time- and frequency-domain radars were used on-ground. After around 1-3 min of computation time for 10 000 edge dots in a MATLAB environment (single 1.96-GHz processor), the results showed rates of false alarm and nondetection of maximum 20% and 28%, respectively. In comparison with the semiautomated hyperbola detection provided by a commercial software, these rates were lower. Second, we conducted a sensitivity analysis to estimate the validity of the fitting of a hyperbola equation neglecting the object radius. The fitting was close, but the derivation of the relative permittivity from the analytical equation neglecting the radius led to high errors. In conclusion, owing to the low computational time and its good performances, the proposed algorithm is suitable for complex environments.
Muscle cytoskeletal disruption occurs within the first 15 min of cyclic eccentric contraction.

The time course of loss of the 55,000-Da intermediate filament protein desmin was measured in rabbit muscles subjected to cyclic eccentric contraction. Rabbit extensor digitorum longus (EDL) and tibialis anterior (TA) muscles were examined 5 or 15 min after eccentric exercise and 1 h or 1 day after 30 min of an eccentric exercise protocol (n = 16 rabbits). The earliest change noted was a significant loss of desmin labeling in 2.5 +/- 0.63% of the rabbit EDL muscle fibers (P < 0.005) 5 min after initiation of eccentric exercise. Some loss of TA fiber desmin was also apparent at this time period (0.24 +/- 0.19%), but the magnitude was not significantly different from zero (P > 0.2). Fifteen minutes after initiation of exercise, desmin loss was more pronounced, increasing to 7.4 +/- 1.4 and 4.6 +/- 1.0% in the EDL and TA, respectively (P < 0.005). Finally, 1 day after 30 min of eccentric exercise, the percentage of fibers without desmin staining rose to 23.4 +/- 3.7 and 7.7 +/- 2.4% in the EDL and TA, respectively (P < 0.001). Loss of desmin staining occurred in the absence of contractile or metabolic protein disruption. Increased staining intensity of the intrasarcomeric cytoskeletal protein titin and an inability to exclude plasma fibronectin were also observed in most but not all fibers that had lost desmin staining. Desmin disruption thus represents a very early structural manifestation of muscle injury during eccentric contraction. Cytoskeletal disruption may predispose the contractile apparatus to previously reported structural damage.
The Natural History of Portal Hypertensive Gastropathy in Patients with Liver Cirrhosis and Mild Portal Hypertension

BACKGROUND:Portal hypertensive gastropathy is a potential cause of bleeding in patients with liver cirrhosis. Studies on its natural history have often included patients submitted to endoscopic or pharmacological treatment for portal hypertension.PATIENTS AND METHODS:A total of 222 cirrhotic patients with mild degree of portal hypertension (i.e., with no or small varices at entry, without previous gastrointestinal bleeding and medical, endoscopic, or angiographic treatment) were followed up with upper endoscopy every 12 months for 47 ± 28 months.RESULTS:Upon enrollment 48 patients presented portal hypertensive gastropathy (43 mild and 5 severe) and the presence of esophageal varices was the only independent predictor of the presence of this gastric lesion at multivariate analysis. The incidence of portal hypertensive gastropathy was 3.0% (1.1–4.9%) at 1 yr and 24% (18.1–29.9%) at 3 yr, while the progression was 3% (1–6.9%) at 1 yr and 14% (4.2–23.8%) at 3 yr. The presence of esophageal varices and the Child-Pugh class B or C at enrollment were predictive of the incidence of portal hypertensive gastropathy, while only Child-Pugh class B or C was correlated with the progression from mild to severe, at multivariate analysis. During follow-up 16 patients bled from portal hypertensive gastropathy (9 acutely and 7 chronically) and one patient died of exsanguination from this lesion.CONCLUSIONS:The natural history of portal hypertensive gastropathy is significantly influenced by the severity of liver disease and severity of portal hypertension. Acute bleeding from portal hypertensive gastropathy is infrequent but may be severe.