Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure-activity relationship of coumarins in xanthine oxidase inhibition.

Esculetin(4), umbelliferone(7-hydroxycoumarin)(3) and 7-hydroxy-4-methyl coumarin(8) are strong xanthine oxidase inhibitors (IC50 = 20.91, 43.65 and 96.70 microM respectively). Based on this observation, the structure of 7-hydroxy coumarin(3) plays a very important role in xanthine oxidase (XO) inhibition. The 6-hydroxy group present in the molecule of 7-hydroxy coumarin, e.g. esculetin(4) enhanced the activity, whereas substitution by the 6-methoxy group, e.g. scopoletin (5), reduced the inhibitory effect. Furthermore, 6-glycoside group present in the molecule of 7-hydroxy coumarin, e.g. esculin (6,7-dihydroxy coumarin 6-glucoside)(12) strongly decreased the inhibitory effect as well as scoparone(6), the fully methylated derivative of esculetin (4). In contrast to 7-hydroxy coumarin(3), however, 4-hydroxy coumarin(13) showed only a weak effect on XO inhibition. 4-Substituent present in the molecule of 7-hydroxycoumarin also reduced the activity but the degree of reduction depended on the substituents: 7-hydroxy-4-methylcoumarin (8) < 7-hydroxycoumarin-4-acetic acid (7) < 7-hydroxy-4-trifluoromethylcoumarin (9). Their percent inhibition at 100 microM was 62.47, 38.46 and 26.84% respectively. 8-substituent present in the molecule of 7-hydroxy coumarin (3), such as 7,8-dihydroxy-6-methoxycoumarin(10) and fraxin(7-hydroxy-6-methoxycoumarin 8-glucoside)(11) reduced the activity as compared with scopoletin (5). Their percent inhibition at 100 microM was 18.4 and 6.9% respectively, which indicated that the more bulky the 8-substituted in the structure, the weaker the inhibitory activity on XO. 3,4,8-Trimethyl-7-hydroxycoumarin(14) which substitution by the methyl at 3,4 & 8 in the structure of 7-hydroxycoumarin(3) also reduced the activity as compared with 7-hydroxycoumarin(3). It seems that the double bond in the structure of coumarin(1) played an important role in the activity as compared with coumarin(dihydrocoumarin)(2). The apparent inhibition constants(Ki) of esculetin(4), umbelliferone (3) and 7-hydroxy-4-methylcoumarin(8) were 2.056, 21.683 and 4.86 microM respectively and induced competitive, uncompetitive and a mixed type of inhibition of the enzyme with respect to the substrate xanthine.
Forecast Incidence of Dengue Fever Cases in Fiji Utilizing Autoregressive Integrated Moving Average (ARIMA) Model

This paper examined the trend of dengue fever cases obtained from January 1995 to July 2017 from National Notifiable Disease Surveillance System (NNDSS) records, Fiji Ministry of Health and Medical Services. Box-Jenkins technique and model is applied to forecast incidence of dengue cases from August 2017 until December 2018. ARIMA model is proposed to forecast incidence of dengue fever in Fiji through Box-Jenkins approach. The Augmented Dickey Fullers test revealed that the time series data had unit root indicating non-stationary. The Autocorrelation and Partial Auto-correlation plots of the first order difference of the dengue fever data suggested parameters ARIMA(3,0,4) and ARIMA(3,1,4). The model ARIMA(3,0,4) was determined as the best fitted model which made a good forecasting performance in estimating the expected incidence dengue cases with lower Mean Absolute Percentage Error (MAPE) of 1148.319 and lower Bayesian Information Criterion (BIC) of 11.389. Finally, a forecast for dengue cases was obtained indicating the highest number of cases for December 2018 with estimated cases of 265. The ARIMA model method utilized in this paper forecasted the incidence trend of dengue fever cases effectively. Such results would be beneficial to health professionals and policy makers in planning of public health interventions and improvement to such disease epidemics. The efficacy of expected cases of dengue fever accomplish not only in detecting outbreaks, but also in delivering decision makers with a reasonable trend of the variability of future observations encompassing both historical, recent information and for evidence based decision making purposes.
Metabolism and karyotype analysis of oocytes from patients with polycystic ovary syndrome.

BACKGROUND Polycystic ovary syndrome (PCOS) is associated with metabolic disturbances which include impaired insulin signalling and glucose metabolism in ovarian follicles. The oocyte is metabolically dependent upon its follicle environment during development, but it is unclear whether PCOS or polycystic ovarian (PCO) morphology alone affect oocyte metabolism and energy-demanding processes such as meiosis. METHODS Immature human oocytes were donated by PCOS (n = 14), PCO (n = 14) and control (n = 46) patients attending the assisted conception programme at Leeds Teaching Hospitals NHS Trust. Oocytes were cultured individually and carbohydrate metabolism was assessed during overnight in vitro maturation (IVM). Meiotic status was assessed and oocyte intracellular nicotinamide adenine dinucleotide phosphate (NAD(P)H) content and mitochondria activity were measured prior to karyotype analysis by multifluor in situ hybridization. RESULTS Patient aetiology had no significant effect on oocyte maturation potential or incidence of numerical chromosome abnormalities (44%), although PCOS and PCO oocytes were more likely to suffer predivision. Group G chromosomes were most likely to be involved in non-disjunction and predivision. PCOS was associated with increased glucose consumption (2.06 +/- 0.43 and 0.54 +/- 0.12 pmol/h for PCOS and control oocytes, respectively) and increased pyruvate consumption (18.4 +/- 1.2 and 13.9 +/- 0.9 pmol/h for PCOS and control oocytes, respectively) during IVM. Prior prescription of metformin significantly attenuated pyruvate consumption by maturing oocytes (8.5 +/- 1.8 pmol/h) from PCOS patients. Oocytes from PCO patients had intermediate metabolism profiles. Higher pyruvate turnover was associated with abnormal oocyte karyotypes (13.4 +/- 1.9 and 19.9 +/- 2.1 pmol/h for normal versus abnormal oocytes, respectively). Similarly, oocyte NAD(P)H content was 1.35-fold higher in abnormal oocytes. CONCLUSIONS The chromosomal constitution of in vitro matured oocytes from PCOS is similar to that of controls, but aspects of oocyte metabolism are perturbed by PCOS. Elevated pyruvate consumption was associated with abnormal oocyte karyotype.
Joint Service Caching and Task Offloading for Mobile Edge Computing in Dense Networks

Mobile Edge Computing (MEC) pushes computing functionalities away from the centralized cloud to the network edge, thereby meeting the latency requirements of many emerging mobile applications and saving backhaul network bandwidth. Although many existing works have studied computation of-floading policies, service caching is an equally, if not more important, design topic of MEC, yet receives much less attention. Service caching refers to caching application services and their related databases/libraries in the edge server (e.g. MEC-enabled BS), thereby enabling corresponding computation tasks to be executed. Because only a small number of application services can be cached in resource-limited edge server at the same time, which services to cache has to be judiciously decided to maximize the edge computing performance. In this paper, we investigate the extremely compelling but much less studied problem of dynamic service caching in MEC-enabled dense cellular networks. We propose an efficient online algorithm, called OREO, which jointly optimizes dynamic service caching and task offloading to address a number of key challenges in MEC systems, including service heterogeneity, unknown system dynamics, spatial demand coupling and decentralized coordination. Our algorithm is developed based on Lyapunov optimization and Gibbs sampling, works online without requiring future information, and achieves provable close-to-optimal performance. Simulation results show that our algorithm can effectively reduce computation latency for end users while keeping energy consumption low.
Links between profitability, nitrogen surplus, greenhouse gas emissions, and energy intensity on organic and conventional dairy farms

ABSTRACT This study examines the relationships between profitability, nitrogen (N) surplus, greenhouse gas emissions (GHG), and energy intensity and factors influencing these relationships in dairy farming. In-depth data from 10 conventional and 8 organic dairy farms in Western Norway were analyzed. Organic farms had lower N surplus per hectare (local, on-farm) and per unit output (global, cradle-to-farm-gate), and lower estimated GHG emissions and energy intensity per unit output, whereas labor input and farm profits did not differ. Higher profitability tended to be associated with improved performance of the environmental indicators examined. Intensification through increased use of concentrates tended to improve profit and reduce N surplus, GHG emissions, and energy intensity per unit output within each farming system while N surplus per hectare could be negatively affected. To ensure a balanced representation of the environmental consequences of both organic and conventional farming systems, our results give support to extensive examination of both area- and product-based environmental performance indicators.
Identification of Primary Tumors of Brain Metastases by Infrared Spectroscopic Imaging and Linear Discriminant Analysis

This study applies infrared (IR) spectroscopy to distinguish normal brain tissue from brain metastases and to determine the primary tumor of four frequent brain metastases such as lung cancer, colorectal cancer, breast cancer, and renal cell carcinoma. Standard methods sometimes fail to identify the origin of brain metastases. As metastatic cells contain the molecular information of the primary tissue cells and IR spectroscopy probes the molecular fingerprint of cells, IR spectroscopy based methods constitute a new approach to determine the primary tumor of a brain metastasis. IR spectroscopic images were recorded by a FTIR spectrometer equipped with a macro sample chamber and coupled to a focal plane array detector. Unsupervised cluster analysis of IR images revealed variances within each sample and between samples of the same tissue type. Cluster averaged IR spectra of tissue classes with known diagnoses were selected to develop a metric with eight variables. These data trained a supervised classification model based on linear discriminant analysis that was used to identify the origin of 20 cryosections including one brain metastasis with an unknown primary tumor.
Multicenter Evaluation of a Standardized Protocol for Rest and Acetazolamide Cerebral Blood Flow Assessment Using a Quantitative SPECT Reconstruction Program and Split-Dose 123I-Iodoamphetamine

SPECT can provide valuable diagnostic and treatment response information in large-scale multicenter clinical trials. However, SPECT has been limited in providing consistent quantitative functional parametric values across the centers, largely because of a lack of standardized procedures to correct for attenuation and scatter. Recently, a novel software package has been developed to reconstruct quantitative SPECT images and assess cerebral blood flow (CBF) at rest and after acetazolamide challenge from a single SPECT session. This study was aimed at validating this technique at different institutions with a variety of SPECT devices and imaging protocols. Methods: Twelve participating institutions obtained a series of SPECT scans on physical phantoms and clinical patients. The phantom experiments included the assessment of septal penetration for each collimator used and of the accuracy of the reconstructed images. Clinical studies were divided into 3 protocols, including intrainstitutional reproducibility, a comparison with PET, and rest–rest study consistency. The results from 46 successful studies were analyzed. Results: Activity concentration estimation (Bq/mL) in the reconstructed SPECT images of a uniform cylindric phantom showed an interinstitution variation of ±5.1%, with a systematic underestimation of concentration by 12.5%. CBF values were reproducible both at rest and after acetazolamide on the basis of repeated studies in the same patient (mean ± SD difference, −0.4 ± 5.2 mL/min/100 g, n = 44). CBF values were also consistent with those determined using PET (−6.1 ± 5.1 mL/min/100 g, n = 6). Conclusion: This study demonstrates that SPECT can quantitatively provide physiologic functional images of rest and acetazolamide challenge CBF, using a quantitative reconstruction software package.
Oral Sildenafil for Treatment of Severe Pulmonary Hypertension in an Infant

We report the use of oral sildenafil in a 5-month-old preterm infant with severe bronchopulmonary dysplasia and pulmonary arterial hypertension refractory to inhaled nitric oxide treatment, maximal ventilatory support and conventional vasodilator therapy. Sildenafil was prepared as a liquid suspension by the method of trituration and administered via an orogastric tube to the patient. Forty-eight hours after sildenafil treatment, echocardiography revealed that the tricuspid incompetence was substantially diminished and the contractility of both ventricles improved, indicating a marked reduction in pulmonary arterial pressure. Oral sildenafil treatment was continued for 6 months until complete resolution of pulmonary arterial hypertension, and oxygen supplement was weaned off. There was no adverse effect during the treatment period. Oral sildenafil may be useful in reducing pulmonary vascular resistance and can be considered for treatment of severe pulmonary arterial hypertension secondary to bronchopulmonary dysplasia.
An integrated approach to identify normal tissue expression of targets for antibody‐drug conjugates: case study of TENB2

The success of antibody‐drug conjugates (ADCs) depends on the therapeutic window rendered by the differential expression between normal and pathological tissues. The ability to identify and visualize target expression in normal tissues could reveal causes for target‐mediated clearance observed in pharmacokinetic characterization. TENB2 is a prostate cancer target associated with the progression of poorly differentiated and androgen‐independent tumour types, and ADCs specific for TENB2 are candidate therapeutics. The objective of this study was to locate antigen expression of TENB2 in normal tissues, thereby elucidating the underlying causes of target‐mediated clearance.
Presynaptic histamine H1 and H3 receptors modulate sympathetic ganglionic synaptic transmission in the guinea‐pig.

1. To study the effects of histamine on the efficacy of sympathetic ganglionic synaptic transmission, extracellular recordings of the postganglionic compound action potential (CAP) and intracellular recordings of excitatory postsynaptic potentials (EPSPs) elicited by preganglionic electrical stimulation were obtained from isolated guinea‐pig superior cervical ganglia (SCG). 2. In different preparations, superfusion with histamine (0.1‐100 microM) either potentiated or depressed the postganglionic CAP elicited by electrical stimulation of the cervical sympathetic trunk (0.2‐3.0 Hz). The direction of response produced by histamine did not depend on stimulation frequency or histamine concentration; potentiation and depression both showed concentration dependence over the range of histamine concentrations tested. 3. Experiments employing a variety of histamine receptor agonists or antagonists revealed that histamine‐induced potentiation of the postganglionic CAP could be attributed to histamine H1 receptor activation, and depression to H3 receptor activation. 4. Histamine similarly potentiated or depressed the intracellularly recorded EPSP. However, these opposite effects occurred at different synapses. In agreement with the studies on the postganglionic CAP, histamine H1 antagonists prevented histamine‐induced potentiation of the EPSP and H3 receptor antagonists prevented histamine‐induced depression. 5. Direct quantal analyses of histamine‐induced synaptic potentiation and depression were implemented to determine the pre‐ and postsynaptic components of these effects. Quantal size was estimated by measuring the amplitude of spontaneous miniature EPSP amplitudes. Histamine‐induced potentiation and depression of the evoked EPSP were found to be accompanied by increased or decreased quantal content respectively, and unchanged quantal size, providing evidence that presynaptic mechanisms were involved in mediating both effects. 6. Some guinea‐pigs were actively sensitized to ovalbumin. Subsequent exposure of the isolated SCG from these animals to the sensitizing antigen produced changes in the EPSP amplitude that correlated significantly to the response produced by exogenously applied histamine at the same synapse. 7. The correspondence between the effects of specific antigen challenge and exogenous histamine on evoked EPSPs at a synapse provides evidence that endogenous histamine released during an immunological response to antigen challenge can activate histamine H1 and H3 receptors to modulate synaptic efficacy in sympathetic ganglia.
A Regime-Based Effect of Fiscal Policy: Evidence from an Emerging Economy

In recent years, few authors have attempted to address the question of whether the state of the economy influences the impact of fiscal policy on the economy. Key findings have often indicated that expansionary fiscal intervention tends to be more effective when the economy is in a downturn. This favorable impact is more pronounced with an increase in government spending as opposed to a tax reduction. Despite several empirical attempts, the findings on the state-dependent nonlinear relationship of fiscal policy and output growth are often limited to developed economies. Building on the current research trend of using the threshold vector autoregression methodology, this paper bridges this gap and extends the empirical body to estimate the nonlinear relationship for an emerging economy, Tunisia. The paper provides empirical evidence that fiscal policy has a different impact on economic activity depending on the business cycle, the instrument of the fiscal policy used, and the intensity of the shock. The paper argues that in a downturn phase, government spending should be privileged particularly in the short run, with a gradual increase in the tax base to reduce the risk of worsening the budget deficit. Further, the monetary authority should be less inclined to raise its policy rate in the early stage of the recessionary period, as this intervention could have an adverse impact on economic growth. In the expansion phase, a tax cut intervention appears on the contrary to have a stronger positive impact on economic activity, especially in the short run, as the monetary authority is expected to introduce gradual policy hikes more rapidly to control for the inflationary expectations.
The Impact of E-commerce on the Audit Profession in Jordan

This study aims to identify the extent of the impact of E-commerce on audit profession in Jordan. For purpose of this study, researcher selected a random sample consist of (80) auditors licensed practicing auditing in Jordan. Researchers used statistical methods such as frequency distributions and means and test one sample t-test. The study found the need to define the auditors of E-commerce and its institutions and its requirements so that auditors deal with this type of activity efficiently and effectively, and the need for increased training of scientific, practical and technological auditors will positively reflect on the process of checking e-business processes, and the need of specialized courses in the audits E-commerce by the Jordanian Society of Chartered Accountants, as well as the importance of educating auditors by E-commerce dangers and how to deal with during the audit process.
Modeling the expenditure and reconstitution of work capacity above critical power.

PURPOSE The critical power (CP) model includes two constants: the CP and the W' [P = (W' / t) + CP]. The W' is the finite work capacity available above CP. Power output above CP results in depletion of the W' complete depletion of the W' results in exhaustion. Monitoring the W' may be valuable to athletes during training and competition. Our purpose was to develop a function describing the dynamic state of the W' during intermittent exercise. METHODS After determination of V˙O(2max), CP, and W', seven subjects completed four separate exercise tests on a cycle ergometer on different days. Each protocol comprised a set of intervals: 60 s at a severe power output, followed by 30-s recovery at a lower prescribed power output. The intervals were repeated until exhaustion. These data were entered into a continuous equation predicting balance of W' remaining, assuming exponential reconstitution of the W'. The time constant was varied by an iterative process until the remaining modeled W' = 0 at the point of exhaustion. RESULTS The time constants of W' recharge were negatively correlated with the difference between sub-CP recovery power and CP. The relationship was best fit by an exponential (r = 0.77). The model-predicted W' balance correlated with the temporal course of the rise in V˙O(2) (r = 0.82-0.96). The model accurately predicted exhaustion of the W' in a competitive cyclist during a road race. CONCLUSIONS We have developed a function to track the dynamic state of the W' during intermittent exercise. This may have important implications for the planning and real-time monitoring of athletic performance.
The acceptability of self-collected samples for HPV testing vs. the pap test as alternatives in cervical cancer screening.

OBJECTIVE To explore the acceptability of the self-collection of samples for human papillomavirus (HPV) testing in comparison with that of the Pap test. METHODS The study population consisted of 1069 women 20 years and older who were eligible for coverage through the Mexican Institute of Social Security (IMSS). These women were randomly selected among participants in a larger study to evaluate the use of HPV testing as an alternative in cervical cancer screening. All participants provided a self-collected vaginal sample for HPV testing according to explicit instructions and underwent a Pap test. Afterwards, each woman was interviewed about her experience and opinion regarding the two procedures. Acceptability was measured by a calculated score based on discomfort, pain, embarrassment, privacy, perception of personal treatment during the Pap test, and understanding of how to perform the self-sampling method. RESULTS Ninety-three percent of women experienced sufficient privacy with the Pap test, whereas 98% of women reported that privacy with the self-sampling procedure was acceptable. The Pap test consistently provoked more discomfort, pain, and embarrassment than self-sampling. Sixty-eight percent of the women who indicated a test preference chose self-sampling. Preference for this method was positively associated with monthly household income. Women reported a preference for self-sampling because it is more comfortable (71.2%) and causes less embarrassment (55.8%). CONCLUSIONS Self-sampling is more acceptable than the Pap test and could improve coverage rates of early detection programs. The incorporation of self-collected samples to detect HPV could encourage participation in screening programs among those women who reject the Pap test because of the necessary pelvic examination.