Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Caffeine Metabolism by Apiaceous and Rutaceae Families of Plant Products in Humans: In Vivo and In Vitro Studies

Daily consumption of caffeinated beverages is considered safe but serious health consequences do happen in some individuals. The Apiaceous and Rutaceae families of plant (ARFP) products are popular foods and medicines in the world. We previously reported significant amounts of furanocoumarin bioactive such as 8-methoxypsoralen, 5-methoxypsoralen, and isopimpinellin in ARFP products. As both caffeine and furanocoumarin bioactive are metabolized by the same hepatic CYP1A1/2 isozyme in humans, caffeine/ARFP product interactions may occur after co-administration. The objectives of the present study were to study in vivo loss of caffeine metabolizing activity by comparing the pharmacokinetics of caffeine in volunteers before and after pre-treatment with an ARFP extract, study the correlation between the decrease in hepatic CYP1A2 activity and the content of furanocoumarin bioactive in ARFP extracts, characterize CYP1A2 inactivation using in vitro incubations containing 14C-caffeine, a furanocoumarin bioactive, and human liver microsomes (HLMs), and provide a mechanistic explanation for both in vivo and in vitro data using the irreversible inhibition mechanism. The study results showed pre-treatment of volunteers with four ARFP extracts increased the area-under-the-concentration-time-curve (AUC0-inf) ratio of caffeine in the plasma ranging from 1.3 to 4.3-fold compared to the untreated volunteers indicating significant caffeine metabolism inhibition. The increases in AUC0-inf ratio also were linearly related to the effect-based doses of the furanocoumarins in the ARFP extracts, a finding which indicated caffeine metabolism inhibition was related to the content of furanocoumarin bioactive in an ARFP product. In vitro incubation studies also showed individual furanocoumarin bioactive were potent inhibitors of caffeine-N-demethylation; the IC50 for 8-methoxypsoralen 5-methoxypsoralen, and isopimpinellin were 0.09, 0.13, and 0.29 µM, respectively. In addition, CYP1A2 inactivation by individual furanocoumarin bioactive was concentration- and time-dependent involving the irreversible inhibition mechanism. The proposed irreversible inhibition mechanism was investigated further using 14C-labeled 8-methoxypsoralen and HLMs. The formation of 14C-adducts due to 14C-8-MOP-derived radioactivity bound to HLMs confirmed the irreversible inhibition of CYP1A2 activity. Thus, furanocoumarin bioactive metabolism in humans would result in reactive metabolite(s) formation inactivating CYP1A2 isozyme and inhibiting caffeine metabolism. Once the CYP1A2 isozyme was deactivated, the enzymic activity could only be regained by isozyme re-synthesis which took a long time. As a result, a single oral dose of ARFP extract administered to the human volunteers 3.0 h before still was able to inhibit caffeine metabolism.
Capturing Behavior in Small Doses: A Review of Comparative Research in Evaluating Thin Slices for Behavioral Measurement

Thin slices are used across a wide array of research domains to observe, measure, and predict human behavior. This article reviews the thin-slice method as a measurement technique and summarizes current comparative thin-slice research regarding the reliability and validity of thin slices to represent behavior or social constructs. We outline decision factors in using thin-slice behavioral coding and detail three avenues of thin-slice comparative research: (1) assessing whether thin slices can adequately approximate the total of the recorded behavior or be interchangeable with each other (representativeness); (2) assessing how well thin slices can predict variables that are different from the behavior measured in the slice (predictive validity), and (3) assessing how interpersonal judgment accuracy can depend on the length of the slice (accuracy-length validity). The aim of the review is to provide information researchers may use when designing and evaluating thin-slice behavioral measurement.
Nitric Oxide Alleviated High Salt–Induced Cardiomyocyte Apoptosis and Autophagy Independent of Blood Pressure in Rats

The present study aimed to explore whether high-salt diet (HSD) could cause cardiac damage independent of blood pressure, and whether nitric oxide (NO) could alleviate high-salt–induced cardiomyocyte apoptosis and autophagy in rats. The rats received 8% HSD in vivo. H9C2 cells or primary neonatal rat cardiomyocytes (NRCM) were treated with sodium chloride (NaCl) in vitro. The levels of cleaved-caspase 3/caspase 3, cleaved-caspase 8/caspase 8, Bax/Bcl2, LC3 II/LC3 I, Beclin-1 and autophagy related 7 (ATG7) were increased in the heart of HSD rats with hypertension (HTN), and in hypertension-prone (HP) and hypertension-resistant (HR) rats. Middle and high doses (50 and 100 mM) of NaCl increased the level of cleaved-caspase 3/caspase 3, cleaved-caspase 8/caspase 8, Bax/Bcl2, LC3 II/LC3 I, Beclin-1, and ATG7 in H9C2 cells and NRCM. The endothelial NO synthase (eNOS) level was increased, but p-eNOS level was reduced in the heart of HSD rats and H9C2 cells treated with 100 mM NaCl. The level of NO was reduced in the serum and heart of HSD rats. NO donor sodium nitroprusside (SNP) reversed the increases of cleaved-caspase 3/caspase 3, cleaved-caspase 8/caspase 8, Bax/Bcl2 induced by NaCl (100 mM) in H9C2 cells and NRCM. SNP treatment attenuated the increases of cleaved-caspase 3/caspase 3, Bax/Bcl2, LC3 II/LC3 I, Beclin-1, and ATG7 in the heart, but had no effect on the blood pressure of HSD rats with HR. These results demonstrated that HSD enhanced cardiac damage independently of blood pressure. Exogenous NO supplementarity could alleviate the high salt–induced apoptosis and autophagy in cardiomyocytes.
Mitogen-Activated Protein Kinase CaDIMK1 Functions as a Positive Regulator of Drought Stress Response and Abscisic Acid Signaling in Capsicum annuum

Protein phosphorylation by kinase is an important mechanism for adapting to drought stress conditions. Here, we isolated the CaDIMK1 (Capsicum annuum drought-induced MAP kinase 1) from dehydrated pepper leaf tissue and functionally characterized it. Subcellular localization analysis revealed that the CaDIMK1 protein was localized in the cytoplasm and nucleus. CaDIMK1-silenced pepper plants exhibited drought-susceptible phenotypes that were characterized by increased transpiration rates, low leaf temperatures, and decreased stomatal closure. In contrast, CaDIMK1-overexpressing (OX) transgenic Arabidopsis plants were hypersensitive to abscisic acid (ABA) from germination to adult growth stages. Furthermore, the CaDIMK1-OX plants were tolerant to drought stress. The transcript levels of several stress-related genes were high in CaDIMK1-OX plants than in wild-type plants. Taken together, our data demonstrate that CaDIMK1 acts as a positive modulator of drought tolerance and ABA signal transduction in pepper plants.
Quercetin Ameliorates Gut Microbiota Dysbiosis That Drives Hypothalamic Damage and Hepatic Lipogenesis in Monosodium Glutamate-Induced Abdominal Obesity

Monosodium glutamate (MSG)-induced abdominal obesity, conventionally caused by hypothalamic damage, is a critical risk factor for health problem. Microbiota-gut-brain axis plays important roles in a variety of metabolic diseases. However, whether gut microbiota is involved in the pathogenesis for MSG-induced abdominal obesity and the effect of quercetin on it remains unclear. Herein, we find that MSG-induced gut microbiota dysbiosis contributes to neuronal damage in the hypothalamus, as indicated by antibiotics-induced microbiota depletion and co-house treatment. Inspired by this finding, we investigate the mechanism in-depth for MSG-induced abdominal obesity. Liver transcriptome profiling shows retinol metabolism disorder in MSG-induced abdominal obese mice. In which, retinol saturase (RetSat) in the liver is notably up-regulated, and the downstream lipogenesis is correspondingly elevated. Importantly, microbiota depletion or co-house treatment eliminates the difference of RetSat expression in the liver, indicating gut microbiota changes are responsible for liver retinol metabolism disorder. Moreover, this study finds dietary quercetin could modulate MSG-induced gut microbiota dysbiosis, alleviate hypothalamic damage and down-regulate liver RetSat expression, thus ameliorating abdominal obesity. Our study enriches the pathogenesis of MSG-induced abdominal obesity and provides a prebiotic agent to ameliorate abdominal obesity.
Allele Sorting as a Novel Approach to Resolving the Origin of Allotetraploids Using Hyb-Seq Data: A Case Study of the Balkan Mountain Endemic Cardamine barbaraeoides

Mountains of the Balkan Peninsula are significant biodiversity hotspots with great species richness and a large proportion of narrow endemics. Processes that have driven the evolution of the rich Balkan mountain flora, however, are still insufficiently explored and understood. Here we focus on a group of Cardamine (Brassicaceae) perennials growing in wet, mainly mountainous habitats. It comprises several Mediterranean endemics, including those restricted to the Balkan Peninsula. We used target enrichment with genome skimming (Hyb-Seq) to infer their phylogenetic relationships, and, along with genomic in situ hybridization (GISH), to resolve the origin of tetraploid Cardamine barbaraeoides endemic to the Southern Pindos Mts. (Greece). We also explored the challenges of phylogenomic analyses of polyploid species and developed a new approach of allele sorting into homeologs that allows identifying subgenomes inherited from different progenitors. We obtained a robust phylogenetic reconstruction for diploids based on 1,168 low-copy nuclear genes, which suggested both allopatric and ecological speciation events. In addition, cases of plastid–nuclear discordance, in agreement with divergent nuclear ribosomal DNA (nrDNA) copy variants in some species, indicated traces of interspecific gene flow. Our results also support biogeographic links between the Balkan and Anatolian–Caucasus regions and illustrate the contribution of the latter region to high Balkan biodiversity. An allopolyploid origin was inferred for C. barbaraeoides, which highlights the role of mountains in the Balkan Peninsula both as refugia and melting pots favoring species contacts and polyploid evolution in response to Pleistocene climate-induced range dynamics. Overall, our study demonstrates the importance of a thorough phylogenomic approach when studying the evolution of recently diverged species complexes affected by reticulation events at both diploid and polyploid levels. We emphasize the significance of retrieving allelic and homeologous variation from nuclear genes, as well as multiple nrDNA copy variants from genome skim data.
The Challenges of Designing and Implementing Clinical Trials With Broccoli Sprouts… and Turning Evidence Into Public Health Action

Broccoli sprouts are a convenient and rich source of the glucosinolate glucoraphanin, which can generate the chemopreventive agent sulforaphane through the catalytic actions of plant myrosinase or β-thioglucosidases in the gut microflora. Sulforaphane, in turn, is an inducer of cytoprotective enzymes through activation of Nrf2 signaling, and a potent inhibitor of carcinogenesis in multiple murine models. Sulforaphane is also protective in models of diabetes, neurodegenerative disease, and other inflammatory processes, likely reflecting additional actions of Nrf2 and interactions with other signaling pathways. Translating this efficacy into the design and implementation of clinical chemoprevention trials, especially food-based trials, faces numerous challenges including the selection of the source, placebo, and dose as well as standardization of the formulation of the intervention material. Unlike in animals, purified sulforaphane has had very limited use in clinical studies. We have conducted a series of clinical studies and randomized clinical trials to evaluate the effects of composition (glucoraphanin-rich [± myrosinase] vs. sulforaphane-rich or mixture beverages), formulation (beverage vs. tablet) and dose, on the efficacy of these broccoli sprout-based preparations to evaluate safety, pharmacokinetics, pharmacodynamic action, and clinical benefit. While the challenges for the evaluation of broccoli sprouts in clinical trials are themselves formidable, further hurdles must be overcome to bring this science to public health action.
Early Emergence of Adaptive Mechanisms Sustaining Ig Production: Application to Antibody Therapy

Antibody therapy, where artificially-produced immunoglobulins (Ig) are used to treat pathological conditions such as auto-immune diseases and cancers, is a very innovative and competitive field. Although substantial efforts have been made in recent years to obtain specific and efficient antibodies, there is still room for improvement especially when considering a precise tissular targeting or increasing antigen affinity. A better understanding of the cellular and molecular steps of terminal B cell differentiation, in which an antigen-activated B cell becomes an antibody secreting cell, may improve antibody therapy. In this review, we use our recently published data about human B cell differentiation, to show that the mechanisms necessary to adapt a metamorphosing B cell to its new secretory function appear quite early in the differentiation process i.e., at the pre-plasmablast stage. After characterizing the molecular pathways appearing at this stage, we will focus on recent findings about two main processes involved in antibody production: unfolded protein response (UPR) and endoplasmic reticulum (ER) stress. We’ll show that many genes coding for factors involved in UPR and ER stress are induced at the pre-plasmablast stage, sustaining our hypothesis. Finally, we propose to use this recently acquired knowledge to improve productivity of industrialized therapeutic antibodies.
Transcranial Alternating Current Stimulation (tACS) Does Not Affect Sports People’s Explosive Power: A Pilot Study

Purpose: This study is aimed to preliminary investigate whether transcranial alternating current stimulation (tACS) could affect explosive power considering genetic background in sport subjects. Methods: Seventeen healthy sports volunteers with at least 3 years of sports activities participated in the experiment. After 2 weeks of familiarization performed without any stimulation, each participant received either 50 Hz-tACS or sham-tACS. Before and after stimulation, subjects performed the following tests: (1) the squat jump with the hands on the hips (SJ); (2) countermovement jump with the hands on the hips (CMJ); (3) countermovement jump with arm swing (CMJ-AS); (4) 15-s Bosco’s test; (5) seated backward overhead medicine ball throw (SBOMBT); (6) seated chest pass throw (SCPT) with a 3-kg rubber medicine ball; and (7) hand-grip test. Additionally, saliva samples were collected from each participant. Genotyping analysis was carried out by polymerase chain reaction (PCR). Results: No significant differences were found in sport performance of subjects after 50 Hz-tACS. Additionally, we did not find any influence of genetic background on tACS-related effect on physical performance. These results suggest that tACS at gamma frequency is not able to induce an after-effect modulating sport performance. Further investigations with larger sample size are needed in order to understand the potential role of non-invasive brain stimulation techniques (NIBS) in motor performances. Conclusions: Gamma-tACS applied before the physical performance fails to improve explosive power in sport subjects.
Software Requirements Elicitation Techniques Selection Method for the Project Scope Management

Project Scope Management is one of the ten knowledge areas described in PMBOK. It refers to the set of processes that ensures a project’s scope is accurately defined and mapped. Elicitation is a critical part of the “Collect Requirements” process of the Scope Management that helps to derive and extract information from stakeholders or other sources. The results of elicitation are used as inputs for requirement analysis and management activities. Multiple elicitation techniques may be applied alternatively or in conjunction with other techniques to accomplish the elicitation. Business analysts can modify existing techniques or create new ones to adjust the project context. The selection of the best-suited techniques inﬂuences the business analysis approach, which is an important part of the scope management plan. This paper is intended to analyze the current practice of elicitation techniques application in the software development projects, define factors influencing technique selection based on the two-classification Machine Learning model, and predict the usage of a particular elicitation technique depending on the project attributes and business analyst background. We conducted a survey study involving 328 specialists from Ukrainian IT companies. Gathered data was used to build and evaluate the prediction models.
Robust design of a robot gripper mechanism using new hybrid grasshopper optimization algorithm

Structural design and optimization are important topics for the control and design of industrial robots. The motivation behind this research is to design a robot gripper mechanism. To explore robust design of the robot gripper mechanism, a new optimization approach based on a grasshopper optimization algorithm and Nelder–Mead algorithm is developed for requiring a fast and accurate solution. Additionally, a vehicle side crash design problem, a multi‐clutch disc problem, and a manufacturing optimization problem are solved with the developed method to show the advantages of the new technique (HGOANM). Both engineering comparisons and production problem results in which HGOANM is applied are compared with the latest optimization techniques in the literature. The results of the problems resolved in this article reveal that the developed HGOANM is an essential optimization approach by solving real‐world engineering problems quickly and accurately.
An examination of the inter-dependence of heat exchange pathways and morphology in humans

ii MANUSCRIPTS PUBLISHED DURING DOCTORAL STUDIES . v ACKNOWLEDGEMENTS . vi TABLE OF CONTENTS . vii LIST OF FIGURES . xv LIST OF TABLES . xx CHAPTER 1: INTRODUCTION . 1 1.1 CONCEPTUAL INTRODUCTION . 1 1.1.1 Biophysics of heat transfer . 1 1.1.1.1 Metabolic heat production . 3 1.1.1.2 Dry, evaporative and respiratory heat exchange . 4 1.1.2 Body temperature regulation: a control systems approach . 6 1.1.2.1 The passive sub-system . 8 1.1.2.2 The active sub-system . 12 1.1. 3 Thermoeffector function during exercise in the heat . 13 1.1. 3.1 Cutaneous vasodilatation . 13 1.1. 3.2 Eccrine sweating . 14 1.1. 3.3 Inter-individual variations in vasomotor and sudomotor function . 15 1.2 AIMS AND HYPOTHESES . 15 1.2.1 The morphological dependency of vasomotor and sudomotor function . 16 1.2.2 The interrelation between morphology and gender on vasomotor
A Survey on Applications of Deep Learning in Cloud Radio Access Network

The necessity for high-speed and low-latency connectivity of the vast number of mobile users is rising with the immense usage of mobile applications. A cloud radio access network (C-RAN) is a promising framework for next-generation cellular communication, which can satisfy the requirements of significantly increasing data traffic and user demands. In C-RAN, the data processing unit can be centralized and virtualized in data centers and can be shared among distributed base stations. Deep learning (DL) appears to be a feasible approach for facilitating the data processing capability, resource management in the cloud, and predicting dynamic traffic in cellular communication. The convergence of C-RAN and DL is expected to bring new prospects to both interdisciplinary research and industrial applications. In this regard, different approaches have been proposed for DL-based C-RAN in the literature. This article provides a comprehensive survey of the state-of-the-art DL techniques applied in C-RAN. A brief introduction of the C-RAN architecture and DL techniques is given to provide insights into these two emerging technologies. Existing surveys are also discussed to highlight the research gap. The reviewed works are categorized into power consumption optimization, network performance maximization, and QoS maximization based on their optimization objectives. The key ideas of DL applied in the reviewed schemes are also mentioned, and the performance evaluation techniques used in the research are discussed and compared. Lastly, research challenges and open research issues are highlighted to provide future research directions.
Characterization of Android Memory References and Implication to Hybrid Memory Management

In this article, we analyze Android applications’ memory reference behaviors, and observe that smartphone memory accesses are different from traditional computer systems with respect to the following five aspects: 1) A limited number of hot pages account for a majority of memory writes, and these hot pages have similar logical addresses regardless of application types; 2) The identities of these hot pages are shared library, linker, and stack regions; 3) The memory access behaviors of hot pages do not change significantly as time progresses even after applications finish their launching; 4) The skewness of memory write accesses in Android is extremely stronger than that of desktop systems; 5) In predicting re-reference likelihood of hot pages, temporal locality is better than reference frequency. Based on these observations, we present a new smartphone memory management scheme for DRAM-NVM hybrid memory. Adopting NVM is effective in power-saving of smartphones, but NVM has weaknesses in write operations. Thus, we aim to identify write-intensive pages and place them on DRAM. Unlike previous studies, we prevent migration of pages between DRAM and NVM, which eliminates unnecessary NVM write traffic that accounts for 32-42% of total write traffic. By judiciously managing the admission of hot pages in DRAM, our scheme reduces the write traffic to NVM by 42% on average without performance degradations.
Comparison of Diffuse Roughness Scattering from Material Reflections at 500-750 GHz

In this paper, an ultra-wideband Terahertz (THz) channel measurement campaign in the 500-750 GHz frequency band is presented. Power levels received from signal transmission by reflections off 14 different materials were measured in an indoor environment at Non-Line-of-Sight (NLoS) between the Transmitter (Tx) and Receiver (Rx), and compared to power levels received at Line-of-Sight (LoS) transmission. Frequency up-converters were used to transmit the signal using 26 dBi horn antennas at the Tx and Rx side and the signal was measured using a Vector Network Analyzer (VNA). From the data collected, the signal losses due to absorption and diffuse scattering from the rough surface of each Material Under Test (MUT) are calculated. The power delay profile (PDP) is presented, where multipath clustering due to diffuse scattering is observed for materials which have a high frequency selectivity, while less scattering and mostly specular reflection is shown for materials with low frequency selectivity.
Developments in the Analysis of Large Antenna Arrays with Disjoint Elements

Efficient electromagnetic analysis of very large antenna arrays is important for various applications, including e.g., radio astronomy. The method of moments (MoM) is generally the most suitable computational electromagnetics method to deal with such open-region problems. However, its computational cost grows rapidly with problem size. This paper presents a brief overview of past work as well as the latest developments by the authors, on devising fast MoM-based methods for arrays with identical disjoint elements and arbitrary layouts. Two different lines of development are reported on, namely methods aimed at efficiently solving the full MoM system through the use of macro basis functions and adaptive cross approximation (ACA) acceleration, and a fast-converging iterative method involving localised solutions.