Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation thérapeutique du phénotype du macrophage dans la polyarthrite rhumatoïde

La polyarthrite rhumatoide (PR) est le rhumatisme inflammatoire chronique le plus frequent. Cette maladie est caracterisee par une auto-immunite et une synovite hypertrophique, responsables d'une destruction des articulations peripheriques. Les macrophages contribuent aux phenomenes inflammatoires de la PR. Ces cellules peuvent presenter differents etats d'activation ou " polarisation ", reversibles, dependant de leur environnement, notamment cytokinique. Les biotherapies (bDMARDs) ont represente une avancee majeure dans la prise en charge des manifestations inflammatoires des formes severes de PR. Toutefois, peu d'etudes ont evalue si ce benefice etait lie a une action specifique sur le macrophage. L'objectif de ce travail de transversal etait : (i) d'evaluer in vitro l'effet des principales biotherapies de la PR (anti-TNF : etanercept, adalimumab, certolizumab ; anti-IL- 6R : tocilizumab ; CTLA4-Ig : abatacept) sur la differenciation et l'activation de macrophages derives de monocytes issus de patients atteints de PR et de sujets sains, (ii) d'identifier des marqueurs de polarisation du macrophage, correles a l'activite de la maladie (DAS28). Parmi les bDMARDs evalues, seuls les anti-TNF ont montre une action sur la polarisation des macrophages. En contexte de differenciation avec M-CSF, les bDMARDs anti-TNF ont induit un biais vers une polarisation non inflammatoire dite alternative. En contexte d'activation inflammatoire, les bDMARDs anti-TNF ont induit une preservation selective des marqueurs de polarisation lies a l'IL-10 (CD16, CD163, MerTK) et une inhibition des marqueurs inflammatoires (CD40, CD80). Nous avons montre que ce changement phenotypique s'accompagnait : (i) d'un changement fonctionnel concordant avec une polarisation induite par l'IL-10, (ii) d'une inhibition de la production des cytokines de l'inflammation (TNF, IL-6, IL-12), (iii) et d'une majoration de la phagocytose. Nous avons montre que ce mecanisme etait du a une production precoce d'IL-10 et dependant de STAT3. De plus, nous avons pu montrer que le certolizumab, un anti-TNF, induisait une reponse anti-inflammatoire, impliquant le facteur de transcription NRF2 (nuclear factor erythroid-2-related factor 2), un regulateur central dans la reponse au stress oxydatif. Enfin, nous avons observe que l'expression de CD16, a la surface des macrophages non actives, etait correlee negativement a l'activite de la PR. Ces travaux concourent a montrer l'interet du ciblage du macrophage dans la PR et nous ont d'identifier de potentielles cibles theranostiques dans le traitement de la PR par anti-TNF.
Dysosma versipellis Extract Inhibits Esophageal Cancer Progression through the Wnt Signaling Pathway

Objective In this study, we aim to investigate the effect of Dysosma versipellis extract on biological behavior of esophageal cancer cells and its underlying mechanisms. Methods A total of 30 BALB/C nude mice (class SPF) were equally and randomly divided into the control group, model group, and Dysosma versipellis group. CP-C cell of esophageal cancer was subcutaneously injected into the model group as well as the Dysosma versipellis group, and the same amount of normal saline into the control group, in order to compare the tumorigenesis of nude mice of three groups. Wnt, β-catenin, and p-GSK3β/GSK3β expression in tumor tissues was detected using Western blot. CP-C cells in logarithmic growth were selected and divided into 4 groups, including the control group, podophyllotoxin group, Wnt activator group, and combined group (mixture of podophyllotoxin and Wnt activator). The cell viability, apoptosis, and invasion ability, Wnt, β-catenin, and p-GSK3β/GSK3β expression level of CP-C cells in each group were detected via MTT assay, flow cytometry, transwell, and Western blot, respectively. Results The tumorigenesis rates of the control group, model group, and Dysosma versipellis group were 0%, 90% (1 tumor-free mouse), and 80% (2 tumor-free mice), respectively. The tumor mass in the Dysosma versipellis group was significant less than that in the model group. Based on the results of Western blot, Wnt, ß-catenin, and p-GSK3β/GSK3β expression of the Dysosma versipellis group was lower than that of the control group. The in vitro viability test indicated that there was a significant difference in cell viability exhibited among four groups. Cell viability level in the 3 groups, including the combined group, blank group, and Wnt activator group, was higher than the podophyllotoxin group at each time point. In vitro apoptosis assay revealed that significant differences in cell apoptosis exhibited among four groups. Cell apoptosis rate was higher in the podophyllotoxin group compared to the remaining three groups. The Wnt activator group showed the lowest cell apoptosis rate. The in vitro invasion assay demonstrated that numbers of transmembrane cell in the 3 groups, involving the combined group, blank group, and Wnt activator group, showed a higher level than the podophyllotoxin group. The results of Western blot manifested that the podophyllotoxin group showed lower level of Wnt, ß-catenin, and p-GSK3β/GSK3β expression compared to the other 3 groups. Conclusion Podophyllotoxin in Dysosma versipellis has an excellent antiesophageal cancer effect and is able to inhibit cell viability as well as invasion ability and promote apoptosis of esophageal cancer cells by inhibiting the Wnt signaling pathway, which could be potentially used in future clinical treatment of esophageal cancer.
N- and P- type Doping in Al-rich AlGaN and AlN

Attaining a high conductivity in both p-type and n-type Al-rich AlGaN epitaxial films is necessary for highly efficient deep-UV emitters. While reliable n-type conductivity has been demonstrated in AlxGa1-xN up to x < 0.8, achieving a reasonable p-type conductivity is a challenge even in Ga-rich AlGaN films. As one increases the x in AlxGa1-xN, several point defects and charge compensators appear in the epitaxial film. This report reviews recent observations on doping, conductivity, point defect control of Al-rich AlGaN films. Discussions on activation energy, state-of-the-art epitaxial material quality, contact formation and surface treatments are also presented.
Dietary Options in Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is the disease condition in which our gastrointestinal (GI) tract is affected and cause abdominal pain and discomfort that is associated with change in the stools form and frequency. In this condition one may suffer from diarrhea, constipation or both at the same time. This disorder is very common now days because of unhealthy eating habits mostly in females. Many factors are responsible for IBS like food, environment, genetic and psychological factors. IBS can be overcomed by improving our eating habits and lifestyle and also by following different diets like FODMAP and GLUTEN FREE diet. Probiotics and herbs are also very beneficial in curing IBS.
Identification of Key Amino Acid Residues Determining Product Specificity of 2,3-Oxidosqualene Cyclase in Siraitia grosvenorii

Sterols and triterpenes are structurally diverse bioactive molecules generated through cyclization of linear 2,3-oxidosqualene. Based on carbocationic intermediates generated during the initial substrate preorganization step, oxidosqualene cyclases (OSCs) are roughly segregated into a dammarenyl cation group that predominantly catalyzes triterpenoid precursor products and a protosteryl cation group which mostly generates sterol precursor products. The mechanism of conversion between two scaffolds is not well understood. Previously, we have characterized a promiscuous OSC from Siraitia grosvenorii (SgCS) that synthesizes a novel cucurbitane-type triterpene cucurbitadienol as its main product. By integration of homology modeling, molecular docking and site-directed mutagenesis, we discover that five key amino acid residues (Asp486, Cys487, Cys565, Tyr535, and His260) may be responsible for interconversions between chair–boat–chair and chair–chair–chair conformations. The discovery of euphol, dihydrolanosterol, dihydroxyeuphol and tirucallenol unlocks a new path to triterpene diversity in nature. Our findings also reveal mechanistic insights into the cyclization of oxidosqualene into cucurbitane-type and lanostane-type skeletons, and provide a new strategy to identify key residues determining OSC specificity.
Interaction of CuO nanoparticles with plant cells: internalization, oxidative stress, electron transport chain disruption, and toxicogenomic responses

This study investigated the toxicity of CuO nanoparticles (NPs) to Nicotiana tabacum L. cv. Bright Yellow-2 (BY-2) cells. CuO NPs with concentrations higher than 2 mg L−1 began to exhibit significant inhibition of the growth of plant cells, and the 24 h median effective concentration was calculated to be 12 mg L−1. CuO NPs (12 mg L−1) showed much higher toxicity than the released Cu2+ (0.8 mg L−1) and bulk particles (BPs, 12 mg L−1) during all the exposure times (0–24 h). CuO NPs were internalized by plant cells through endocytosis, and then located in the cytoplasm, mitochondria and vacuoles. Under CuO NP exposure, the generation of total reactive oxygen species increased by 38.3% and 40.9% compared with CuO BPs and Cu2+ treatments, respectively. The main radical species were identified as H2O2 and OH˙. CuO NPs significantly reduced the activities of complexes I and III on the mitochondrial electron transport chain, blocked the electron transfer from NADH to ubiquinone, and from ubisemiquinone to ubiquinol, induced oxidative stress, and finally led to membrane damage as indicated by an increase in the contents of malondialdehyde and lactate dehydrogenase. Global gene expression analysis from RNA-sequencing showed that CuO NPs (12 mg L−1) significantly induced the expression of 2692 differentially expressed genes (P-value 2) including 1132 up-regulated and 1560 down-regulated genes in BY-2 cells. The differentially expressed genes related to oxidative stress and mitochondria were identified according to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. This work provides insights into the molecular mechanism of nanotoxicity toward plants.
Short-Term Effects of the Repeated Exposure to Trip-like Perturbations on Inter-Segment Coordination during Walking: An UCM Analysis

The minimum toe clearance (MTC) results from the coordination of all bilateral lower limb body segments, i.e., a redundant kinematic chain. We tested the hypothesis that repeated exposure to trip-like perturbations induces a more effective covariation of limb segments during steady walking, in accordance with the uncontrolled manifold (UCM) theory, to minimize the MTC across strides. Twelve healthy young adults (mean age 26.2 ± 3.3 years) were enrolled. The experimental protocol consisted of three identical trials, each involving three phases carried outin succession: steady walking (baseline), managing trip-like perturbations, and steady walking (post-perturbation). Lower limb kinematics collected during both steady walking phases wereanalyzed in the framework of the UCM theory to test the hypothesis that the reduced MTC variability following the perturbation can occur, in conjunction with more effective organization of the redundant lower limb segments. Results revealed that, after the perturbation, the synergy underlying lower limb coordination becomes stronger. Accordingly, the short-term effects of the repeated exposure to perturbations modify the organization of the redundant lower limb-related movements. In addition, results confirm that the UCM theory is a promising tool for exploring the effectiveness of interventions aimed at purposely modifying motor behaviors.
Alternatives for Chemical and Biochemical Lignin Valorization: Hot Topics from a Bibliometric Analysis of the Research Published During the 2000–2016 Period

A complete bibliometric analysis of the Scopus database was performed to identify the research trends related to lignin valorization from 2000 to 2016. The results from this analysis revealed an exponentially increasing number of publications and a high relevance of interdisciplinary collaboration. The simultaneous valorization of the three main components of lignocellulosic biomass (cellulose, hemicellulose, and lignin) has been revealed as a key aspect and optimal pretreatment is required for the subsequent lignin valorization. Research covers the determination of the lignin structure, isolation, and characterization; depolymerization by thermal and thermochemical methods; chemical, biochemical and biological conversion of depolymerized lignin; and lignin applications. Most methods for lignin depolymerization are focused on the selective cleavage of the β-O-4 linkage. Although many depolymerization methods have been developed, depolymerization with sodium hydroxide is the dominant process at industrial scale. Oxidative conversion of lignin is the most used method for the chemical lignin upgrading. Lignin uses can be classified according to its structure into lignin-derived aromatic compounds, lignin-derived carbon materials and lignin-derived polymeric materials. There are many advances in all approaches, but lignin-derived polymeric materials appear as a promising option.
A CONCEPTUAL MODEL OF ICE SHELF SEDIMENTATION

Modern glacimarine sedimentation can be thought of as a thermal spectrum characterized by two thermal end members: a cold ice (polar) end member typical of higher-latitude margins like Antarctica and Eastern Greenland, and a warm ice (temperate) end member representative of the more mild SE Alaskan and Patagonian systems. Areas with intermediate thermal regimes composed of different ratios of both warm and cold ice (polythermal) like Svalbard fall somewhere in the middle between these two end members. As one gets progressively colder along this spectrum, less meltwater is present in the system as increasingly less ice is below the pressure melting point. The strength of the ice also increases, eventually allowing the formation of a stable floating terminus under certain conditions, called an ice shelf.
Fabrication of advanced nanofiltration membranes with nanostrand hybrid morphology mediated by ultrafast Noria–polyethyleneimine codeposition

Polyphenol chemistry-based surface modification has received extensive attention in membrane science for its simplicity and low-cost. However, the limited molecular structures combined with the generally time-consuming process have largely restricted their further applications. Herein, we report an ultrafast and universal surface modification strategy based on the co-deposition of a macrocycle polyphenol molecule, Noria, and polyethyleneimine (PEI), for which only several seconds are required to obtain a uniform coating. Moreover, nanofiltration membranes were fabricated by traditional interfacial polymerization (IP) using the Noria–PEI co-deposited coating as the interlayer. Interestingly, the host–guest heterogeneous interaction between anchored Noria on the support surface and amine monomers in the aqueous phase could significantly alter the IP process and contribute to a unique nanostrand-hybrid morphology for piperazine and trimesoyl chloride-based membranes. Consequently, such novel morphology-based nanofiltration membranes exhibited a high permeance of up to 28 L m−2 h−1 bar−1 while still maintaining comparable divalent salt (Na2SO4, MgSO4, MgCl2 and CaCl2) rejections of above 96.0%, which are among the best performances for nanofiltration membranes. In addition to membrane science, this ultrafast surface modification strategy could arouse intense interest in host–guest chemistry at interfaces for fabricating multifunctional materials.
Can machine learning augment clinician adjudication of events in cardiovascular trials? A case study of major adverse cardiovascular events (MACE) across CVRM trials

Accurate identification of clinical outcome events is critical to obtaining reliable results in cardiovascular outcomes trials (CVOTs). Current processes for event adjudication are expensive and hampered by delays. As part of a larger project to more reliably identify outcomes, we evaluated the use of machine learning to automate event adjudication using data from the SOCRATES trial (NCT01994720), a large randomized trial comparing ticagrelor and aspirin in reducing risk of major cardiovascular events after acute ischemic stroke or transient ischemic attack (TIA). We studied whether machine learning algorithms could replicate the outcome of the expert adjudication process for clinical events of ischemic stroke and TIA. Could classification models be trained on historical CVOT data and demonstrate performance comparable to human adjudicators? Using data from the SOCRATES trial, multiple machine learning algorithms were tested using grid search and cross validation. Models tested included Support Vector Machines, Random Forest and XGBoost. Performance was assessed on a validation subset of the adjudication data not used for training or testing in model development. Metrics used to evaluate model performance were Receiver Operating Characteristic (ROC), Matthews Correlation Coefficient, Precision and Recall. The contribution of features, attributes of data used by the algorithm as it is trained to classify an event, that contributed to a classification were examined using both Mutual Information and Recursive Feature Elimination. Classification models were trained on historical CVOT data using adjudicator consensus decision as the ground truth. Best performance was observed on models trained to classify ischemic stroke (ROC 0.95) and TIA (ROC 0.97). Top ranked features that contributed to classification of Ischemic Stroke or TIA corresponded to site investigator decision or variables used to define the event in the trial charter, such as duration of symptoms. Model performance was comparable across the different machine learning algorithms tested with XGBoost demonstrating the best ROC on the validation set for correctly classifying both stroke and TIA. Our results indicate that machine learning may augment or even replace clinician adjudication in clinical trials, with potential to gain efficiencies, speed up clinical development, and retain reliability. Our current models demonstrate good performance at binary classification of ischemic stroke and TIA within a single CVOT with high consistency and accuracy between automated and clinician adjudication. Further work will focus on harmonizing features between multiple historical clinical trials and training models to classify several different endpoint events across trials. Our aim is to utilize these clinical trial datasets to optimize the delivery of CVOTs in further cardiovascular drug development. Type of funding sources: Private company. Main funding source(s): AstraZenca Plc
A computationally efficient engineering aerodynamic model for non-planar wind turbine rotors

Abstract. In the present work, a computationally efficient engineering model for the aerodynamic load calculation of non-planar wind turbine rotors is proposed. The method is based on the vortex cylinder model, and can be used in two ways: either as a correction to the currently widely used blade element momentum (BEM) method, or used as the main model, replacing the BEM method in the engineering modelling complex. The proposed method needs the same order of computational effort as the ordinary BEM method, which makes it ideal for time-domain aero-servo-elastic simulations. The results from the proposed method are compared with results from two higher-fidelity aerodynamic models: a lifting-line method and a Navier-Stokes solver. For planar rotors, the aerodynamic loads are identical to the current BEM model when the drag force is excluded during the calculation of the induced velocities. For non-planar rotors, the influence of the blade out-of-plane shape, measured by the difference of the load between the non-planar rotor and the planar rotor, is in very good agreement with higher-fidelity models. Meanwhile, the existing BEM methods, even with a correction of radial induction included, show relatively large deviations from the higher-fidelity method results.
Assessment of variability in proximate/anti-nutritive composition of cocoyam within Nigeria and Uganda

The availability of cheaper food energy sources which compares favourably with other high priced cereals is of importance and should be encouraged. This study investigated the proximate/anti-nutritive contents of cocoyam collected from Southern Nigeria and Eastern Uganda to investigate if agronomic or climatic factors play a role in its composition. The proximate/mineral composition of cormels (crude protein:0.35 – 6.9%; carbohydrates: 60.01 – 83.66%; Fe: 3.65 - 16.80 mg/100g, Zn: 1.39 – 2.45 mg/100g) show that cocoyam can conveniently replace yams and potatoes in diets due to its similar carbohydrate contents though lower in crude fibre content (0.99 – 2.80%). Cocoyam samples contained high anti-nutrients (Cyanides 0.94 – 2.16 %; Oxalates 8.45 – 181.4 mg/Kg) which may limit its utilization. An analysis of variance indicate cocoyam differ significantly (p<0.05) in proximate/anti-nutritive contents across the two locations with a higher content of crude fibre, crude protein and carbohydrates observed in samples collected in southern Nigeria.
The removal of arsenic during drinking water treatment by sorption and coagulation processes

One of the most wide-spread problems with current drinking water resources is the natural presence of arsenic in groundwaters. The toxicity of arsenic in humans can be expressed in a variety of ways, with chronic exposure being linked to increased likelihoods of cardiovascular disease, respiratory illness, skin lesions, and cancers of the skin, liver, kidney, lung and bladder. The inorganic arsenic species are generally more toxic than the organic ones. The extremely negative impact of chronic arsenic exposure on human health led the World Health Organisation to recommend a maximum allowable concentration of 10 μg As/l for drinking water, which was adopted into EU and Serbian law. In many cases, groundwaters used as drinking water resources which are naturally contaminated with arsenic also contain significant amounts of NOM, which may also pose its own health risks or interfere with arsenic removal processes. In order to identify, develop, optimise and implement new drinking water treatment technologies capable of efficiently removing As and NOM from waters, it is therefore necessary to investigate how As and NOM interact in source waters and during their removal. The aim of this dissertation is to investigate effective, affordable and sustainable arsenic removal technologies and to investigate the interactions between arsenic and natural organic matter in raw groundwaters, as well as during the treatments. This was achieved through development and investigation of new adsorbents based on iron oxides for the removal of arsenic from drinking water, and investigation into how certain competitive ions affect their behaviour. Furthermore, the removal of arsenic by a variety of coagulation and combined oxidation/coagulation processes was investigated, in order to identify and optimise the most critical process parameters. Finally, Design of Experiments and Response Surface Methodology (RSM) was utilized to develop mathematical models describing the interactions between arsenic and natural organic matter during the process of iron chloride coagulation, to facilitate the optimisation of coagulation processes for waters with different amounts of these contaminants. These investigations will contribute a