Miracle-dz/UniFAR-FTUs huggingface dataset:
THE PATH FROM FUNCTIONAL TO DETAILED DESIGN OF A CONING ROTOR WIND TURBINE CONCEPT

This paper provides a brief overview of functional design theory, which is then used to examine choices in wind turbine design. Definition of function is used to examine fundamental design choices in engineering a machine to capture energy from the wind. Specifically, rationalization is presented for a coning rotor wind turbine concept, potentially able to greatly reduce the cost of wind energy. The work presented here has provided a theoretical basis in design theory to motivate the development of specialized analysis tools and more detailed analysis of the concept.
Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease

Abstract The ability to efficiently adapt metabolism by substrate sensing, trafficking, storage, and utilization, dependent on availability and requirement, is known as metabolic flexibility. In this review, we discuss the breadth and depth of metabolic flexibility and its impact on health and disease. Metabolic flexibility is essential to maintain energy homeostasis in times of either caloric excess or caloric restriction, and in times of either low or high energy demand, such as during exercise. The liver, adipose tissue, and muscle govern systemic metabolic flexibility and manage nutrient sensing, uptake, transport, storage, and expenditure by communication via endocrine cues. At a molecular level, metabolic flexibility relies on the configuration of metabolic pathways, which are regulated by key metabolic enzymes and transcription factors, many of which interact closely with the mitochondria. Disrupted metabolic flexibility, or metabolic inflexibility, however, is associated with many pathological conditions including metabolic syndrome, type 2 diabetes mellitus, and cancer. Multiple factors such as dietary composition and feeding frequency, exercise training, and use of pharmacological compounds, influence metabolic flexibility and will be discussed here. Last, we outline important advances in metabolic flexibility research and discuss medical horizons and translational aspects.
Association of SNPs in the TIMP-2 gene and large artery atherosclerotic stroke in southern Chinese Han population

Tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) regulates the extracellular matrix degradation, which involved in vascular remodeling and dysfunction, destabilization of atherosclerotic plaque and many other pathological processes. The rupture of atherosclerotic plaque is the trigger of Large artery atherosclerotic (LAA) stroke. We speculate that the Single nucleotide polymorphisms (SNPs) in TIMP-2 may have an association with LAA stroke. To prove this hypothesis, we conducted this case-control study. 250 LAA stroke patients and 250 healthy controls were collected for the analysis of TIMP-2 polymorphisms. Among six SNPs, we detected no deviation from Hardy-Weinberg equilibrium in control group. There was a significant difference in rs4789936 T allele frequency between patient and control groups (OR = 0.68, 95% CI = 0.51–0.91, P = 0.009), which means lower risk of LAA stroke. We observed the rs4789936 had a decreased risk of LAA stroke according to the codominant (OR = 0.64, 95% CI = 0.44–0.92, P = 0.026), dominant (OR = 0.62, 95% CI = 0.43-0.88, P = 0.008), overdominant (OR = 0.68, 95% CI = 0.48–0.98, P = 0.039), log-additive (OR = 0.68, 95% CI = 0.51–0.91, P = 0.009) models analyses. However, these findings could only validate under dominant model (OR = 0.65, 95% CI = 0.42–1.00, P = 0.049) after adjustment of gender and age. The results indicate a potential association between TIMP-2 variants and LAA stroke risk in southern Chinese Han population.
Linear-regression convolutional neural network for fully automated coronary lumen segmentation in intravascular optical coherence tomography

Abstract. Intravascular optical coherence tomography (OCT) is an optical imaging modality commonly used in the assessment of coronary artery diseases during percutaneous coronary intervention. Manual segmentation to assess luminal stenosis from OCT pullback scans is challenging and time consuming. We propose a linear-regression convolutional neural network to automatically perform vessel lumen segmentation, parameterized in terms of radial distances from the catheter centroid in polar space. Benchmarked against gold-standard manual segmentation, our proposed algorithm achieves average locational accuracy of the vessel wall of 22 microns, and 0.985 and 0.970 in Dice coefficient and Jaccard similarity index, respectively. The average absolute error of luminal area estimation is 1.38%. The processing rate is 40.6 ms per image, suggesting the potential to be incorporated into a clinical workflow and to provide quantitative assessment of vessel lumen in an intraoperative time frame.
β‐Glucan enhances antitumor immune responses by regulating differentiation and function of monocytic myeloid‐derived suppressor cells

Myeloid‐derived suppressor cells (MDSCs) accumulate in tumor‐bearing hosts and play a major role in tumor‐induced immunosuppression, which hampers effective immuno‐therapeutic approaches. β‐Glucans have been reported to function as potent immuno‐modulators to stimulate innate and adaptive immune responses, which contributes to their antitumor property. Here, we investigated the effect of particulate β‐glucans on MDSCs and found that β‐glucan treatment could promote the differentiation of M‐MDSCs (monocytic MDSCs) into a more mature CD11c+ F4/80+ Ly6Clow population via dectin‐1 pathway in vitro, which is NF‐κB dependent, and the suppressive function of M‐MDSCs was significantly decreased. Treatment of orally administered yeast‐derived particulate β‐glucan drastically downregulated MDSCs but increased the infiltrated DCs and macrophages in tumor‐bearing mice, thus eliciting CTL and Th1 responses, inhibiting the suppressive activity of regulatory T cells, thereby leading to the delayed tumor progression. We show here for the first time that β‐glucans induce the differentiation of MDSCs and inhibit the regulatory function of MDSCs, therefore revealing a novel mechanism for β‐glucans in immunotherapy and suggesting their potential clinical benefit.
Study Design Selection in Early Clinical Anti‐Hyperglycemic Drug Development: A Simulation Study of Glucose Tolerance Tests

In antidiabetic drug development, phase I studies usually involve short‐term glucose provocations. Multiple designs are available for these provocations (e.g., meal tolerance tests (MTTs) and graded glucose infusions (GGIs)). With a highly nonlinear, complex system as the glucose homeostasis, the various provocations will contribute with different information offering a rich choice. Here, we investigate the most appropriate study design in phase I for several hypothetical mechanisms of action of a study drug. Five drug effects in diabetes therapeutic areas were investigated using six study designs. Power to detect drug effect was assessed using the likelihood ratio test, whereas precision and accuracy of the quantification of drug effect was assessed using stochastic simulation and estimations. An overall summary was developed to aid designing the studies of antihyperglycemic drug development using model‐based analysis. This guidance is to be used when the integrated glucose insulin model is used, involving the investigated drug mechanisms of action.
Initiation and propagation of coagulation from tissue factor‐bearing cell monolayers to plasma: initiator cells do not regulate spatial growth rate *

Summary. Exposure of tissue factor (TF)‐bearing cells to blood is the initial event in coagulation and intravascular thrombus formation. However, the mechanisms which determine thrombus growth remain poorly understood. To explore whether the procoagulant activity of vessel wall‐bound cells regulates thrombus expansion, we studied in vitro spatial clot growth initiated by cultured human cells of different types in contact pathway‐inhibited, non‐flowing human plasma. Human aortic endothelial cells, smooth muscle cells, macrophages and lung fibroblasts differed in their ability to support thrombin generation in microplate assay with peaks of generated thrombin of 60 ± 53 nmol L−1, 135 ± 57 nmol L−1, 218 ± 55 nmol L−1 and 407 ± 59 nmol L−1 (mean ± SD), respectively. Real‐time videomicroscopy revealed the initiation and spatial growth phases of clot formation. Different procoagulant activity of cell monolayers was manifested as up to 4‐fold difference in the lag times of clot formation. In contrast, the clot growth rate, which characterized propagation of clotting from the cell surface to plasma, was largely independent of cell type (≤ 30% difference). Experiments with factor VII (FVII)‐, FVIII‐, FX‐ or FXI‐deficient plasmas and annexin V revealed that (i) cell surface‐associated extrinsic Xase was critical for initiation of clotting; (ii) intrinsic Xase regulated only the growth phase; and (iii) the contribution of plasma phospholipid surfaces in the growth phase was predominant. We conclude that the role of TF‐bearing initiator cells is limited to the initial stage of clot formation. The functioning of intrinsic Xase in plasma provides the primary mechanism of sustained and far‐ranging propagation of coagulation leading to the physical expansion of a fibrin clot.
The Effect of External Shocks on Iran’s Oil Economy: A DSGE-BVAR Approach

Given the economy’s high dependence on oil revenues combined with oil influential role in government budget in Iran, we seek to examine the impact of oil revenue shocks on Iran’s economy by means of a DSGE-BVAR model. We are further motivated by the observation that government has been less likely to cut current spending in response to frequent plunges in oil revenues. This, in return, has led to higher macroeconomic instability in times of oil price volatility. We identify technology shocks, oil revenue shocks, foreign exchange rate shocks and money supply shocks as the main sources of business cycle fluctuations. After estimating the model with quarterly data over the period 1990:2-2015:1, the analysis of impulse response functions indicates that production and inflation responses to shocks confirm factual data and the relevant theories. In response to monetary and oil revenue shocks, output rises in the short term; while it falls as result of a surge in the general price level. Foreign exchange rate shock generates a decrease in output but it increases in the long run, due to higher investment. Moreover, positive monetary, foreign exchange rate and oil shocks generate an increase in inflation; while technology shocks induce a decrease in inflation.
Spatial Segregation Measures: A Methodological Review

Quantitative indices of segregation are powerful tools for summarising the spatial relationships between population groups and thereby providing the basis for analysis and public policy intervention. While the broad concept of segregation may be intuitive, measurement is challenging because of the complexity of varied dimensions and spatial arrangements. Many traditional measures can be criticised for over-simplification or over-reduction, not least in their treatment of geographical space. Over the last several decades, however, a series of measures has been developed to explicitly incorporate the spatial arrangement of population groups as well as their interactions. This paper reviews the development of spatial segregation measures, particularly focusing on the mathematical formulation of spatial arrangement/relations. In addition, several related issues are discussed, including representation of spatial interaction, spatial scale and statistical inferences. Also, this paper presents an overview of existing software tools that are readily available for calculating some of the reviewed measures. Finally, discussions on challenges and future research are provided.
A comprehensive analysis of the computed tautomer fractions of the imidazole ring of histidines in Loligo vulgaris

A recently introduced electrostatic-based method to determine the pKa values of ionizable residues and fractions of ionized and tautomeric forms of histidine (His) and acid residues in proteins, at a given fixed pH, is applied here to the analysis of a His-rich protein, namely Loligo vulgaris (pdb id 1E1A), a 314-residue all-β protein. The average tautomeric fractions for the imidazole ring of each of the six histidines in the sequence were computed using an approach that includes, but is not limited to, molecular dynamic simulations coupled with calculations of the ionization states for all 94 ionizable residues of protein 1E1A in water at pH 6.5 and 300 K. The electrostatic-calculated tautomeric fractions of the imidazole ring of His were compared with predictions obtained from an existent NMR-based methodology. Our results indicate that: (i) the averaged electrostatic-based tautomeric predictions for the imidazole ring of all histidines of Loligo vulgaris are dominated by the Nε2-H rather than the Nδ1-H form, although such preferences from the NMR-based methodology are not so well defined; (ii) the computed average absolute difference between the electrostatic- and the NMR-based tautomeric predictions among all six histidines vary among 0% to 17%; (iii) for the His showing the largest fraction of the neutral form (81%), the absolute difference between the NMR- and electrostatic-based computed tautomeric predictions is only 3%; and (iv) the tautomeric predictions for the imidazole ring of His computed with the NMR-based methodology are stable within a certain, well-defined, range of variations of a tautomer-related parameter.
Apoptosis and Autoimmunity Induced by Clodronate in Systemic Lupus Erythematosus Mononuclear Circulating Cells

The aim of this study is to evaluate the effect of clodronate on apoptosis of human systemic lupus erythematosus circulating mononuclear cells and to analyze possible correlations with changes in autoantibody production in vitro. Lympho-monocytes from 20 SLE patients were isolated and incubated with or without addition of 1 μM clodronate for 72 hours. Apoptosis and release of genomic material was assessed by immunofluorescent detection of cleaved caspase-3 and by Cell-Death-Detection ELISAPLUS kit (Roche). Anti-Nucleosome IgG and anti-dsDNA IgM and IgG autoantibody levels were determined in supernatants by commercially available ELISA kits. Clodronate induced apoptosis in monocytes as confirmed by cleaved caspase-3 immunostaining and by quantification of cleaved nucleosome in the supernatants (treated 0.22±0.05 O.D. vs untreated 0.09±0.04 O.D.; P<0.001). This finding was coupled with a significant increasing in supernatants of IgG anti-Nucleosome (treated 6.5±1.1 vs untreated 5.5±0.6 IU/mL; p=0.001) and IgM (treated 3.0±1.3 vs 2.2±0.9 IU/mL; p=0.02) and IgG (treated 4.0±1.8 vs untreated 2.8±1.5 IU/mL; p=0.02) anti-dsDNA autoantibody levels. Our findings stressed the proapoptotic activity of clodronate, as well as its potential autoimmunity induction in SLE mononuclear circulating cells. Clinical studies could clarify the role of bisphosphonates on autoantibody production and worsening of disease activity.
Covalently bound pH-indicator dyes at selected extracellular or cytoplasmic sites in bacteriorhodopsin. 2. Rotational orientation of helices D and E and kinetic correlation between M formation and proton release in bacteriorhodopsin micelles.

The kinetics of the light-induced proton release in bacteriorhodopsin/lipid/detergent micelles was monitored with the optical pH-indicator fluorescein bound covalently to positions 127-134 (helices D and E and the DE loop) on the extracellular side of the protein (the proton release side). Single cysteine residues were introduced in these positions by site-directed mutagenesis, and fluorescein was attached to the sulfhydryl group by reaction with (iodoacetamido)fluorescein. Two characteristic proton release times (approximately 20 and 70 microseconds) were observed. The faster time constant was recorded when fluorescein was attached to positions 127, 130, 131, 132, and 134, while the slower time was observed with the indicator bound to positions 128, 129, and 133. The results are rationalized by assuming specific helical wheel orientations for helics D and E and by making a choice for the residues in the DE loop: (i) The fast time constants occur with fluorescein either attached to residues 130, 131, and 132 that form the DE loop or when pointing toward the interior of the protein with its aqueous proton channel [residues 127 (helix D) and 134 (helix E)]. (ii) The slower time constants are detected with fluorescein exposed to the exterior lipid/detergent phase when bound to residues 128, 129 (both helix D), and 133 (helix E). This interpretation is supported by measurements of the polarity of the label environment which indicate for fluorescein in group i a more hydrophilic environment and for group ii a more hydrophobic environment. The fastest proton release time (10 microseconds) was observed with fluorescein bound to position 127. (ABSTRACT TRUNCATED AT 250 WORDS)
The Demand for Banking and Shadow Banking Services

Abstract We explore the hypothesis that the substitutability/complementarity relationship between banking and shadow banking services is a major factor affecting the transmission mechanism of monetary policy. We take the parametric approach to demand analysis, which allows estimation and testing in a systems-of-equations context, and use the Minflex Laurent flexible functional form for the underlying aggregator function. We relax the homoskedasticity assumption and assume Markov regime switching to relax the assumption of fixed consumer preferences. We generate inference consistent with neoclassical microeconomic theory and provide evidence against simple-sum money supply measures. We also show that the emergence of shadow banking has increased the stability of money demand functions. This means that money supply measures based on a nonlinear aggregator function might be a better measure of the stance of monetary policy than the interest rate.
Robust and accurate localization system for mobile manipulators in cluttered environments

Autonomous robots play a pivotal role in improving productivity and reducing operational costs. They excel at both precision and speed in repetitive jobs and can cooperate with humans in complex tasks within dynamic environments. Self-localization is critical to any robot that must navigate or manipulate the environment. To solve this problem, a modular localization system suitable for mobile manipulators was developed. By using LIDAR data the proposed system is capable of achieving less than a centimeter in translation error and less than a degree in rotation error while requiring only 5 to 25 milliseconds of processing time. The system was tested in two different robot platforms at different velocities and in several cluttered and dynamic environments. It demonstrated high accuracy while performing pose tracking and high reliability when estimating the initial pose using feature matching. No artificial landmarks are required and it is able to adjust its operation rate in order to use very few hardware resources when a mobile robot is not moving.
Isolation, purification and characterization of 5'-phosphodiesterase from Aspergillus fumigatus

5′-Phosphodiesterase (5′-PDE) catalyzes the hydrolysis of ribonucleic acid to obtain a mixture of ribonucleotides, such as 5′-guanosine monophosphate and 5′-adenosine monophosphate. In this study, a 5'-PDE was newly isolated and purified from Aspergillus fumigatus. Following purification, this enzyme exhibited a specific activity of 1036.76 U/mg protein, a molecular weight of 9.5 kDa, and an optimal temperature and pH for enzyme activity of 60°C and 5.0, respectively. However, its activity was partially inhibited by Fe3+, Cu2+, and Zn2+, but slightly improved by the presence of K+ and Na+. Additionally, chemical-modification experiments were also applied to investigate the structural information of 5'-PDE, in which the residues containing carboxyl and imidazole groups were essential for enzyme activity based on their localization in the 5′-PDE active site. Furthermore, purified 5′-PDE could specifically catalyze the synthesis of ribonucleotides with a Vmax 0.71 mmol/mg·min and a KM of 13.60 mg/mL.
What do plasma beta‐endorphin levels reveal about endogenous opioid analgesic function?

Plasma levels of beta‐endorphin (BE), an endogenous opioid analgesic, are often reported as they relate to acute and chronic pain outcomes. However, little is known about what resting plasma BE levels might reveal about functioning of the endogenous opioid antinociceptive system. This study directly examined associations between resting plasma BE and subsequent endogenous opioid analgesic responses to acute pain in 39 healthy controls and 37 individuals with chronic low back pain (LBP). Resting baseline levels of plasma BE were assessed. Next, participants received opioid blockade (8 mg naloxone i.v.) or placebo in a double‐blind, randomized, crossover design. Participants then underwent two acute pain stimuli: finger pressure (FP) pain and ischaemic (ISC) forearm pain. Blockade effects (naloxone minus placebo pain ratings) were derived to index endogenous opioid analgesic function. In placebo condition analyses for both pain stimuli, higher resting BE levels were associated with subsequently greater reported pain intensity (p's < 0.05), with this effect occurring primarily in healthy controls (BE × Participant Type interactions, p's < 0.05). In blockade effect analyses across both pain tasks, higher resting plasma BE predicted less subsequent endogenous opioid analgesia (smaller blockade effects; p's < 0.05). For the ISC task, these links were significantly more prominent in LBP participants (BE × Participant Type Interactions, p's < 0.05). Results suggest that elevated resting plasma BE may be a potential biomarker for reduced endogenous opioid analgesic capacity, particularly among individuals with chronic pain. Potential clinical implications are discussed.
Branding of Nation in an Insurgency Prone Economy: Implications for Entrepreneurship

The wreck on our nation’s image by the incidences of insurgency has caused catastrophic effects and depleted interests in entrepreneurship and investments into the nation’s economy. An insurgency engulfed nation is infested with political disorder, economic disorientation, social vices, infrastructural decay, cultural and value decadence. The primary objective of this study is to explore the relationship between nation branding and entrepreneurial activities, and to determine the relationship between insurgency and entrepreneurial activities. This paper adopted frustration-aggression theory and structural violence theory to explain insurgency. It argues that the nation needs effective marketing and rebranding to orientate the citizenry and international body, to correct the stigma placed by the activities of insurgents. The paper relied on existing literatures, periodicals, and articles to gather information. The study opines that the roles of professional marketing and public relation firms are necessary to shore up the battered images posed by the marauding effects of the insurgencies. The findings revealed numerous lapses on the part of government which precipitate the insurgencies that brought about untold consequences on the nation’s economy. The paper recommends that the nation should adopt a proactive approach in solving the issues by engaging the service of professional marketing and public relation firms while taking lasting corrective measures to stem the tide of insurgency.