Miracle-dz/UniFAR-FTUs huggingface dataset:
Kupffer Cell Release of Platelet Activating Factor Drives Dose Limiting Toxicities of Nucleic Acid Nanocarriers

In vivo nanocarrier-associated toxicity is a significant and poorly understood hurdle to clinical translation of siRNA nanomedicines. In this work, we demonstrate that platelet activating factor (PAF), an inflammatory lipid mediator, plays a key role in nanocarrier-associated toxicities, and that prophylactic inhibition of the PAF receptor (PAFR) completely prevents these toxicities. High-dose intravenous injection of siRNA-polymer nano-complexes (si-NPs) elicited acute, shock-like symptoms (vasodilation and vascular leak) in mice and caused a three-fold increase in blood PAF levels. PAFR inhibition completely prevented these toxicities, indicating PAF activity is a primary driver of systemic si-NP toxicity. Pre-treatment with clodronate liposomes fully abrogated si-NP-associated increases in blood PAF and consequent toxicities, suggesting that nanoparticle uptake by Kupffer macrophages is the source of PAF. Assessment of varied si-NP chemistries further confirmed that toxicity level correlated to relative uptake of the carrier by liver Kupffer cells and that this toxicity mechanism is dependent on the endosome disruptive function of the carrier. Finally, the PAF toxicity mechanism was shown to be generalizable to commercial delivery reagent in vivo-jetPEI® and an MC3 lipid nanoparticle formulated to match an FDA-approved siRNA nanomedicine. Greater sensitivity to the PAF mechanism occurs in 4T1 tumor-bearing mice, a mammary tumor model known to exhibit increased circulating leukocytes and potential to respond to inflammatory insult. These results establish Kupffer cell release of PAF as a key mediator of in vivo nucleic acid nanocarrier toxicity and identify PAFR inhibition as an effective prophylactic strategy to increase maximum tolerated dose and reduce nanocarrier-associated adverse events. Significance Non-viral nucleic acid nanocarriers can enable in vivo gene therapy, but their potential interaction with innate immune cells can cause dose-limiting toxicities. Nanoparticle toxicities are currently poorly understood, making it difficult to identify relevant design criteria for maximizing nanoparticle safety. This work connects nanoparticle-associated toxicities to the release of platelet activating factor (PAF) by liver Kupffer cells. Small molecule inhibition of the PAF receptor (PAFR) completely prevents severe adverse events associated with high doses of multiple polymer-based formulations and a lipid nanoparticle matching the composition of the first clinically-approved siRNA nanomedicine. This study identifies PAF as a toxicity biomarker for future nanomedicine discovery programs. Further, PAFR inhibition should be explored as a strategy to expand the therapeutic index of nanomedicines.
Viscosity of K2TiSi4O11 melt at high pressure

The viscosity of alkali titanosilicate melt with a composition of K2TiSi4O11 (KTS4) was measured at pressures up to of 7.41 GPa and temperatures up to of 2133 K. The aim of this study is to determine the effect of pressure on the viscosity change and to estimate the relation between structural change and the viscosity change under high pressures. The viscosity decreased up to 3.30 GPa, whereas it increased from 3.30 to 7.41 GPa. The viscosity change above 3.30 GPa is likely caused by the dominance of six–fold coordinated titanium.
Comprehensive analysis of competing endogenous RNA network in Wilms tumor based on the TARGET database

Background Wilms tumor (WT) was the most common malignant tumor of urinary system in children. With the advances in gene sequencing, research of molecular mechanism of WT tumor was gradually increasing. However, few studies have explored the influence of competing endogenous RNA (ceRNA) in WT. Accordingly, we aimed to explore the mechanisms of ceRNA co-expression network in WT. Methods A total of 6 non-tumor controls and 127 WT patients’ RNA-seq data combined with clinical data was acquired from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Differentially expressed lncRNA, miRNA and mRNA between WT tissues and normal tissues were analyzed using “edgeR” package in R software. Weighted gene co-expression network analysis (WGCNA) was utilized to construct the ceRNA co-expression network while Molecular Complex Detection (MCODE) algorithm was used to extract the pivotal sub-network. Function annotation of mRNA was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Survival analysis was then conducted based on long-rank test and Kaplan-Meier curves using the survival package. Results By applying the “edgeR” package in R, the transcriptome expression data of 127 WT tissues with 6 normal tissues were normalized. Moreover, 146 DElncRNAs, 62 DEmiRNAs, 287 DEmRNAs of them were involved in ceRNA network after applying WGCNA. According to MCODE, we identified that the interactions between LINC002253 (lncRNA) and TRIM71 (mRNA) was mediated by hsa-mir-301a and hsa-mir-301b (miRNA). Furthermore, we detected 13 DElncRNAs which were significantly associated with the progression of WT. Conclusions We used WGCNA method to construct the WT ceRNA network for the first time. TRIM71 was identified to be the most closely related genes involved in hub sub-network by MCDOE, suggesting it might act as a new drug target and prognostic factor based on our comprehensive results.
Numerical simulation of the transition to elastic turbulence in viscoelastic inertialess flows

Le melange de fluides represente un element important du domaine de la dynamique des fluides, ce qui rend la comprehension de ce sujet si significative du point de vue fondamental et applique (p. ex., les processus industriels). Dans les geometries miniaturisees (dans des conditions typiques) le melange est un processus lent, difficile et inefficace. Cela en raison du caractere naturellement laminaire de ces ecoulements, qui oblige l'homogeneisation de differents elements fluides a se produire par diffusion moleculaire au lieu d'un transport advectif, a l'action plus rapide. Cependant, des etudes experimentales recentes sur les ecoulements viscoelastiques a faible nombre de Reynolds ont montre qu'un melange efficace peut etre declenche dans plusieurs configurations geometriques (y compris les dispositifs a l'echelle microscopique), par le phenomene de la turbulence elastique. La premiere partie de cette these est consacree a la comprehension et a l'investigation des defis numeriques presents dans le domaine de la dynamique des fluides non newtonienne, en se concentrant plus particulierement au probleme du haut nombre de Weissenberg. Ce dernier se manifeste par une rupture du schema numerique, lorsque les equations d'evolution d'extra-contraintes polymeriques sont evaluees de facon directe. Ceci pose des limites importantes a la possibilite de simuler avec precision des ecoulements turbulents-elastiques. Nous fournissons des preuves numeriques de l'effet benefique (en termes de gain en stabilite) de la decomposition en racine carree de l'extra-contrainte dans une implementation en volumes finis des equations regissant l'ecoulement dans un canal bidimensionnel. La deuxieme partie de la these traite de l’emergence et de la caracterisation d’instabilites purement elastiques dans des simulations numeriques de fluides Oldroyd-B a nombre de Reynolds zero dans une geometrie du type cross-slot bidimensionnel. Grâce a un travail numerique approfondi, nous presentons une caracterisation detaillee des instabilites purement elastiques. Ces instabilites apparaissant dans le systeme pour de larges plages d'elasticite du fluide et de concentration des polymeres. Pour les solutions concentrees et des nombres de Weissenberg assez grands, nos simulations indiquent l’apparition d’un ecoulement desordonne pointant vers la turbulence elastique. Nous analysons le passage a une dynamique irreguliere et caracterisons les proprietes statistiques de tels ecoulements tres elastiques, en discutant des similitudes et des differences avec les resultats experimentaux de la litterature.
Research on the Influence of Chinese Fiscal Decentralization on Regional Economy Against the Tax Distribution System

Since the reform and opening up, fiscal decentralization reform is an important part of China's economic transformation, and is closely related to marketoriented reform. Under the tax distribution system, the reform and improvement of fiscal decentralization system has great theoretical and practical significance in promoting regional economic growth and studying the impact of Chinese fiscal decentralization on regional economy. In this paper, panel data of 27 provinces are used in the tax classification system and Eviews regression analysis are used to compare the economic growth differences of the four regions in China's fiscal decentralization system, east, central, west and northeast, to analyze the impact of Chinese fiscal decentralization on regional economic growth and draw the following conclusions: Fiscal revenue decentralization can promote the regional economic growth in the eastern region and inhibit that in the central region. Fiscal expenditure decentralization can inhibit the economic growth in the eastern and western regions and promote the economy in the central and northeastern regions. Keywords—tax distribution system; fiscal decentralization system; regression analysis; regional growth disparity
Two-Stage 3D Codebook Design and Fast Beam Search Algorithm for Millimeter-Wave Massive MIMO Systems

For 3D beam access in massive multi-input multi-output (MIMO) systems, this paper proposes a feasible two-stage 3D codebook design and corresponding fast beam training algorithm. The complete codebook consists of a primary codebook and an auxiliary codebook—the primary codebook produces a basic directional beam using a smaller number of phase shifts to maintain lower hardware complexity. The small auxiliary codebook creates finer beams centered on each main beam. In addition, a beam search scheme for two-level codebook design is proposed. The main beam search is performed using a modified binary search algorithm based on the signal-to-noise ratio threshold; with the refined auxiliary codebook, the auxiliary beam search is completed using a basic binary search. The simulation results verify the performance advantages of our proposed codebook in terms of beamforming gain and beam access accuracy in MIMO systems. In addition, the comparison of beam training complexity shows that our specially designed two-stage beam search scheme has significant advantages over other existing solutions.
Explosion impact strength calculation and failure analysis of glass fiber-reinforced composite pipe

Abstract The investigation of failure analysis of the explosion impact strength of glass fiber-reinforced composite tubes was presented in this paper. Scanning electron microscopy was used to perform morphological observation and analysis of the failure cracks of a composite tube under ultra-high-pressure explosion impact. The main failure mode was brittle fiber fracture. Theoretical calculations and numerical simulations were used to analyze the deformation displacement and stress and strain of the composite tube under the impact of ultra-high pressure explosion. The boundary conditions obtained were 49.9 MPa as the minimum failure internal pressure and 0.0782 mm as the radial limit displacement.
Pengaruh Pelatihan Tedi’s Behavior Change Model pada Guru dan Orang Tua terhadap Keterampilan Menggosok Gigi Anak Prasekolah

Dental health problems in Preschool is higher than primary school, it is because children are not capable of independent activity in brushing teeth. Proper behavior change strategies can be done by providing dental health education by parents and teachers using customized learning methods and media development. Model tedi's behavior change is a learning model brushing teeth in efforts to establish the behavior of brushing teeth with a time of 10 days. Purpose of the study: This study aims to produce a model of Tedi's behavior change training towards the formation of the teeth brushing behavior of preschool children. Method: this research uses Research and Development (R&D) and the test model uses quasy experiment pretest and posttest with control group design. The subjects of preschool children were divided into 2 groups: 1. Tedi's behavior change training interventions 2. 21-day brushing model as a control. Independent variables: tedi's behavior change model training and the dependent variable: brushing skills and plaque free scores of preschool children. Data were tested using the intraclass correlation coefficient, repeated measures anova, friedman, t-test and mann whitney. Results: The implementation of the tedi's behavior change model training was equally effective with the 21-day brushing model for increasing the ability to brush teeth (p> 0.304) and equally effective for increasing the plaque-free score (p <0.788) compared to the control group. Conclusion: The application of tedi's behavior change model training to teachers and parents is effective in the teeth brushing skills of preschool children.
SARS-CoV-2 and SARS-CoV Spike-RBD Structure and Receptor Binding Comparison and Potential Implications on Neutralizing Antibody and Vaccine Development

SARS-CoV-2 and SARS-CoV share a common human receptor ACE2. Protein-protein interaction structure modeling indicates that spike-RBD of the two viruses also has similar overall binding conformation and binding free energy to ACE2. In vitro assays using recombinant ACE2 proteins and ACE2 expressing cells confirmed the two coronaviruses’ similar binding affinities to ACE2. The above studies provide experimental supporting evidences and possible explanation for the high transmissibility observed in the SARS-CoV-2 outbreak. Potent ACE2-blocking SARS-CoV neutralizing antibodies showed limited cross-binding and neutralizing activities to SARS-CoV-2. ACE2-non-blocking SARS-CoV RBD antibodies, though with weaker neutralizing activities against SARS-CoV, showed positive cross-neutralizing activities to SARS-CoV-2 with an unknown mechanism. These findings suggest a trade-off between the efficacy and spectrum for therapeutic antibodies to different coronaviruses, and hence highlight the possibilities and challenges in developing broadly protecting antibodies and vaccines against SARS-CoV-2 and its future mutants.
Doctoral Supervisors and PhD Students' Perceptions about the Supervision Process in a Young European University

In the last decade with the Bologna implementation, doctoral supervision gained a new emphasis and emerged as crucial for developing the European research area. Research, on doctoral supervision practices, and the supervisor ideal profile was carried out in a TOP 10 young European university, at Universidade Nova de Lisboa. The results show that meetings (individual or in groups) are the most implemented practice. Usually, students present orally, to a supervisor, the research that they already made regarding the initial work plane. Two supervisors' profiles emerge from the students' voices, the real and the ideal. The ideal supervisor profile that emerges from the questionnaires features supervisors who take students care, give feedback on work on time, and are honest and critical.
Impacts of peristaltic flow of micropolar fluid with nanoparticles through a porous medium under the effects of heat absorption and wall properties: Homotopy perturbation method

In the present examination, we have talked about the impacts of heat absorption, chemical reaction, and wall properties on the peristaltic stream of micropolar nanofluid through a permeable medium. The key conditions of the movement are first regulated and after that streamlined under the suspicions of long wavelength and low Reynolds number. The careful arrangements have been determined for the velocity and the microrotation velocity, while the administering conditions of energy and nanoparticle conditions are solved analytically utilizing the homotopy perturbation technique. At last, graphical outcomes are talked about to represent the impacts of different physical parameters of the issue on these dispersions.
Prognostic Significance of Minimal Residual Disease (MRD) in Childhood B-Precursor ALL and Its Relation to Other Risk Factors. A Children’s Oncology Group (COG) Study.

Early response to therapy, including assessment of MRD is a powerful prognostic factor in childhood ALL. However, there are many other known prognostic factors, and the precise relationship among these and MRD has been incompletely explored. In COG protocol P9900, patients were assigned to one of 3 risk-directed therapies based on NCI risk group, as well as TEL-AML1 translocations (TEL) and simultaneous trisomies of chromosomes 4 and 10 (DT). Infants and Ph+ patients were excluded. Good risk patients (9904) comprised NCI SR patients with either TEL or DT without CNS disease. Poor risk patients (9906) included a subset of NCI HR patients with particularly unfavorable risk factors based largely on age and white count, while 9905 had both NCI SR and HR patients not eligible for 9904 or 9906, including NCI HR patients with TEL or DT. MRD was satisfactorily measured with at least . 01% sensitivity by 4-color flow cytometry in the marrow at end of induction (D29) or in blood at Day 8 (D8). D29 MRD was associated with poor outcome in all studies, and in both HR and SR patients on 9905 as shown: The proportion of D29 MRD positive DT(17.9%) patients was higher than that of TEL patients (9.4%) but MRD was also prognostic when each group was considered separately; similar findings were seen in HR TEL and DT patients. TEL or DT was associated with a significantly better prognosis in both HR and SR patients who were MRD negative, but were not favorable factors in MRD positive patients. D8 blood MRD was also prognostic in all studies, with higher MRD levels generally associated with poorer outcome. Patients who were both D29 and D8 MRD negative had a good outcome overall (93% 4 y EFS); combining all favorable risk factors, including TEL, DT, NCI risk group, D8 and D29 MRD identified a group of patients (about 13% of B-precursor ALL patients) with 98± 1% 4 y EFS. In multivariate analysis, D29 MRD was the most important prognostic factor. NCI Risk group, DT and D8 blood were also significant, but TEL and day 8 morphologic assessment of marrow were not. We conclude that MRD is a major prognostic factor in childhood ALL even accounting for other risk factors. The prognostic significance of TEL and DT depends on MRD status. The combination of good risk clinical and genetic factors, and absence of MRD in both D8 blood and D29 marrow identifies a group of patients with outstanding outcome on limited therapy.
Fractional Order Direct Torque Control of Permanent Magnet Synchronous Machine

Received: 28 June 2019 Accepted: 7 October 2019 This paper designs a fractional order PID direct torque control strategy for permanent magnet synchronous machine (PSMS) based on on fractional calculus. The fractional order controller to control the speed of the machine was synthesized, referring to Bode’s ideal transfer function. In the controller, the fractional order integrator was approximated by Charef’s method. The fractional PID order control was compared with classical PID control, showing that the former has the better accuracy and robustness. Finally, MATLAB/ SIMULINK simulation proved the advantages of our control strategy under oscillating torque load or magnetic field.
Spatial Distribution of Total Factor Productivity (TFP) in the EU Regional Scope

Purpose: The aim of the paper is to analyse the differences in the level of productivity among the EU regions illustrated by the spatial distribution of total factor productivity (TFP). Since the level of productivity has an important geographical component the answer to the question, which regions are characterised with high or low level of productivity is being undoubtedly of high political importance. Design/Methodology/Approach: To calculate TFP defined as the aggregated output-input ratio, we employ the multiplicatively-complete Fare-Primont index. This index satisfies all economically-relevant axioms and tests from index number theory. The research sample consists of 256 European Union (EU) regions at NUTS 2 level. Findings: The results of the study indicate that relatively high TFP values are observed in core Western European regions, while the bottom of the TFP distribution is dominated by regions in Bulgaria, Poland and Romania. This may suggest a polarised specialization of the EU regions and limited interregional diffusion of technological knowledge. Our findings also show a high degree of dispersion in TFP within countries. Practical Implications: Identification of the spatial distribution of Total Factor Productivity (TFP) across European regions has implication for the EU regional and innovation policies. Designing policies basing on smart specialization strategies, which foster linkages to release positive knowledge externalities both within as well as between regions, constitutes the desired strategic development aim to enhance the performance of TFP. In particular, these strategies are crucial for the regions characterized by low TFP levels. Originality/Value: The methodological approach followed in this paper, in contrast to most of the existing studies on productivity differences at the regional level, satisfies all economically-relevant axioms and tests from index number theory.
Monthly and Yearly Variations in Oxygen Radical-scavenging Activity, Ascorbic Acid Content, and Degrees Brix of Komatsuna (Brassica rapa var. perviridis) in the Kanto Region, Japan

It is commonly recognized that vegetables in their best season are delicious and have high nutritional value. We investigated the monthly and yearly variations in radical-scavenging (RS) activity, an indicator of antioxidant activity, ascorbic acid, and degrees Brix of Brassica rapa var. perviridis (komatsuna) cultivated in the Kanto region, Japan. RS activity was significantly higher in December, January, and February than in the other months in all tested years (2010–2015). For two varieties (summer and winter varieties) their RS activity was significantly higher in winter than in summer. The weight proportion of leaf blades and petioles at harvest was similar (leaf blade:petiole = 4:6) both in the summer and winter, indicating that the difference in the RS activity of komatsuna between the two seasons was not due to the weight ratio, but to the increase in the RS activity of leaf blades in the winter. There were no significant differences in the RS activity of komatsuna between summer (30 days) and winter (80 days) cultivation periods, greenhouse and open-field cultivations, and producers. Multiple years of field studies revealed that the antioxidant activity, ascorbic acid content, and degrees Brix of komatsuna in the Kanto region were higher in winter than in other seasons, and suggested that komatsuna with a similar quality level may be produced when grown in regions with similar weather conditions.
Evidence for Late Paleoindian Scavenging of Early Paleoindian Obsidian, Oklahoma Panhandle

ABSTRACT An obsidian channel flake from the Late Paleoindian-aged Bull Creek camp (Oklahoma panhandle), analyzed by energy dispersive x-ray fluorescence, was determined to have been manufactured from obsidian of the Polvadera Peak chemical type in the Jemez Mountain region of north central New Mexico. Although Polvadera Peak is the primary source of the obsidian, the discovery of the channel flake within Late Paleoindian-aged deposits suggests the object was collected from a secondary exposure, in this case a Clovis or Folsom camp of unknown location.