Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Mechanical Strain Characterization of Ventilated ex vivo Porcine and Murine Lung using Digital Image Correlation

Respiratory illnesses, such as bronchitis, emphysema, asthma, and COVID-19, substantially remodel lung tissue, deteriorate function, and culminate in a compromised breathing ability. Yet, the structural mechanics of the lung is significantly understudied. Classical pressure-volume air or saline inflation studies of the lung have attempted to characterize the organ’s elasticity and compliance, measuring deviatory responses in diseased states; however, these investigations are exclusively limited to the bulk composite or global response of the entire lung and disregard local expansion and stretch phenomena within the lung lobes, overlooking potentially valuable physiological insights, as particularly related to mechanical ventilation. Here, we present a method to collect the first non-contact, full-field deformation measures of ex vivo porcine and murine lungs and interface with a pressure-volume ventilation system to investigate lung behavior in real time. We share preliminary observations of heterogeneous and anisotropic strain distributions of the parenchymal surface, associative pressure-volume-strain loading dependencies during continuous loading, and consider the influence of inflation rate and maximum volume. This study serves as a crucial basis for future works to comprehensively characterize the regional response of the lung across various species, link local strains to global lung mechanics, examine the effect of breathing frequencies and volumes, investigate deformation gradients and evolutionary behaviors during breathing, and contrast healthy and pathological states. Measurements collected in this framework ultimately aim to inform predictive computational models and enable the effective development of ventilators and early diagnostic strategies.
Recent Progress in the Drug Development Targeting SARS-CoV-2 Main Protease as Treatment for COVID-19

The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) rapidly turned into an unprecedented pandemic of coronavirus disease 2019 (COVID-19). This global healthcare emergency marked the third occurrence of a deadly coronavirus (CoV) into the human society after entering the new millennium, which overwhelmed the worldwide healthcare system and affected the global economy. However, therapeutic options for COVID-19 are still very limited. Developing drugs targeting vital proteins in viral life cycle is a feasible approach to overcome this dilemma. Main protease (Mpro) plays a dominant role in processing CoV-encoded polyproteins which mediate the assembly of replication-transcription machinery and is thus recognized as an ideal antiviral target. Here we summarize the recent progress in the discovery of anti-SARS-CoV-2 agents against Mpro. Combining structural study, virtual screen, and experimental screen, numerous therapeutic candidates including repurposed drugs and ab initio designed compounds have been proposed. Such collaborative effort from the scientific community would accelerate the pace of developing efficacious treatment for COVID-19.
Cathepsins in Bacteria-Macrophage Interaction: Defenders or Victims of Circumstance?

Macrophages are the first encounters of invading bacteria and are responsible for engulfing and digesting pathogens through phagocytosis leading to initiation of the innate inflammatory response. Intracellular digestion occurs through a close relationship between phagocytic/endocytic and lysosomal pathways, in which proteolytic enzymes, such as cathepsins, are involved. The presence of cathepsins in the endo-lysosomal compartment permits direct interaction with and killing of bacteria, and may contribute to processing of bacterial antigens for presentation, an event necessary for the induction of antibacterial adaptive immune response. Therefore, it is not surprising that bacteria can control the expression and proteolytic activity of cathepsins, including their inhibitors – cystatins, to favor their own intracellular survival in macrophages. In this review, we summarize recent developments in defining the role of cathepsins in bacteria-macrophage interaction and describe important strategies engaged by bacteria to manipulate cathepsin expression and activity in macrophages. Particularly, we focus on specific bacterial species due to their clinical relevance to humans and animal health, i.e., Mycobacterium, Mycoplasma, Staphylococcus, Streptococcus, Salmonella, Shigella, Francisella, Chlamydia, Listeria, Brucella, Helicobacter, Neisseria, and other genera.
Simulation of Human-Operator Behavior in Solving Intellectual Problems during Control of Technological Processes in Stresses

The mathematical model of the human-operator of technological process from the point of view of the mathematical systems theory is developed. The apparatus of set theory was used for modeling. The model takes into account the influence of the human factor on the quality of process control. The concept of stress-resistance of the human operator is considered. The stress resistance index is introduced and the geometric interpretation is given. The model of exit of the person-operator from a stressful condition which considers its individuality is resulted.
Méthodes de représentation de la langue pour l’analyse syntaxique multilingue (Language representation methods for multilingual syntactic parsing )

L’existence de modèles universels pour décrire la syntaxe des langues a longtemps été débattue. L’apparition de ressources comme le World Atlas of Language Structures et les corpus des Universal Dependencies rend possible l’étude d’une grammaire universelle pour l’analyse syntaxique en dépendances. Notre travail se concentre sur l’étude de différentes représentations des langues dans des systèmes multilingues appris sur des corpus arborés de 37 langues. Nos tests d’analyse syntaxique montrent que représenter la langue dont est issu chaque mot permet d’obtenir de meilleurs résultats qu’en cas d’un apprentissage sur une simple concaténation des langues. En revanche, l’utilisation d’un vecteur pour représenter la langue ne permet pas une amélioration évidente des résultats dans le cas d’une langue n’ayant pas du tout de données d’apprentissage.
Argumentation and Logic Programming for Explainable and Ethical AI

In this paper we sketch a vision of explainability of intelligent systems as a logic approach suitable to be injected into and exploited by the system actors once integrated with sub-symbolic techniques. In particular, we show how argumentation could be combined with different extensions of logic programming – namely, abduction, inductive logic programming, and probabilistic logic programming – to address the issues of explainable AI as well as some ethical concerns about AI.
Approaching Explainable Recommendations for Personalized Social Learning: the Current Stage in the Educational Platform "WhoTeach"

Learning and training processes are starting to be aﬀected by the diﬀusion of Artiﬁcial Intelligence (AI) techniques and methods. AI can be variously exploited for supporting education, though especially deep learning (DL) models are normally suﬀering from some degree of opacity and lack of interpretability. Explainable AI (XAI) is aimed at creating a set of new AI techniques able to improve their output or decisions with more transparency and interpretability. Deep attentional mechanisms proved to be particularly eﬀective for identifying relevant communities and relationships in any given input network that can be exploited with the aim of improving useful information to interpret the suggested decision process. In this paper we provide the ﬁrst stages of our ongoing research project, aimed at signiﬁcantly empowering the recommender system of the educational platform ”WhoTeach” by means of explainability, to help teachers or experts to create and manage high-quality courses for personalized learning. The presented model is actually our ﬁrst tentative to start to include ex-plainability in the system. As shown, the model has strong potentialities to provide relevant recommendations. Moreover, it allows the possibility to implement eﬀective techniques to completely reach explainability 3 .
Transforming from paramagnetism to room temperature ferromagnetism in CuO by ball milling

In this work, we experimentally demonstrate that it is possible to induce ferromagnetism in CuO by ball milling without any ferromagnetic dopant. The magnetic measurements indicate that paramagnetic CuO is driven to the ferromagnetic state at room temperature by ball milling gradually. The saturation magnetization of the milled powders is found to increase with expanding the milling time and then decrease by annealing under atmosphere. The fitted X-ray photoelectron spectroscopy results indicate that the observed induction and weaken of the ferromagnetism shows close relationship with the valence charged oxygen vacancies (Cu1+-VO) in CuO.
Otimização dos tempos de mistura e decantação no processo de coagulação/floculação da água bruta por meio da Moringa oleifera Lam - DOI: 10.4025/actascitechnol.v30i2.5493

Several natural coagulants/flocculants are being studied to remove color and turbidity from raw water; however, natural coagulants have demonstrated advantages over chemical ones. Moringa oleifera Lam is a natural polymer that has become an important alternative in water treatment, acting as a clarifying agent due to the presence of a cationic protein that destabilizes the particles contained in water in liquid form. This work proposes the optimization of the coagulation, flocculation and decantation times, using different concentrations of the solution extracted from the pulp of Moringa oleifera Lam seeds as coagulant, in order to verify its efficiency in removing color and turbidity from water. Jar tests were carried out, using different mixture and decantation times, with varying concentrations of the biopolymer. It was verified that the time required to achieve a fast and slow mixture, as well as the concentration of the coagulant, influenced the removal of parameters during the process of coagulation/flocculation/sedimentation.
Post-exertion oxygen saturation as a prognostic factor for adverse outcome in patients attending the emergency department with suspected COVID-19: a substudy of the PRIEST observational cohort study

Background Measurement of post-exertion oxygen saturation has been proposed to assess illness severity in suspected COVID-19 infection. We aimed to determine the accuracy of post-exertional oxygen saturation for predicting adverse outcome in suspected COVID-19. Methods We undertook a substudy of an observational cohort study across 70 emergency departments during the first wave of the COVID-19 pandemic in the UK. We collected data prospectively, using a standardised assessment form, and retrospectively, using hospital records, from patients with suspected COVID-19, and reviewed hospital records at 30 days for adverse outcome (death or receiving organ support). Patients with post-exertion oxygen saturation recorded were selected for this analysis. We constructed receiver-operating characteristic curves, calculated diagnostic parameters, and developed a multivariable model for predicting adverse outcome. Results We analysed data from 817 patients with post-exertion oxygen saturation recorded after excluding 54 in whom measurement appeared unfeasible. The c-statistic for post-exertion change in oxygen saturation was 0.589 (95% CI 0.465 to 0.713), and the positive and negative likelihood ratios of a 3% or more desaturation were, respectively, 1.78 (1.25 to 2.53) and 0.67 (0.46 to 0.98). Multivariable analysis showed that post-exertion oxygen saturation was not a significant predictor of adverse outcome when baseline clinical assessment was taken into account (p=0.368). Secondary analysis excluding patients in whom post-exertion measurement appeared inappropriate resulted in a c-statistic of 0.699 (0.581 to 0.817), likelihood ratios of 1.98 (1.26 to 3.10) and 0.61 (0.35 to 1.07), and some evidence of additional prognostic value on multivariable analysis (p=0.019). Conclusions Post-exertion oxygen saturation provides modest prognostic information in the assessment of selected patients attending the emergency department with suspected COVID-19. Trial registration number ISRCTN Registry (ISRCTN56149622) http://www.isrctn. com/ISRCTN28342533.
Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2

Background Upadacitinib is a Janus kinase inhibitor under evaluation for the treatment of psoriatic arthritis (PsA). We evaluated upadacitinib in patients with PsA and prior inadequate response or intolerance to at least one biologic disease-modifying antirheumatic drug (DMARD). Methods In this 24-week randomised, placebo-controlled, double-blind, phase 3 trial, 642 patients were randomised (2:2:1:1) to once per day upadacitinib 15 mg or 30 mg, placebo followed by upadacitinib 15 mg or placebo followed by upadacitinib 30 mg at week 24. The primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 12. Achievement of minimal disease activity (MDA) was assessed at week 24. Treatment-emergent adverse events are reported for all patients who received at least one dose of trial drug. Results At week 12, significantly more patients receiving upadacitinib 15 mg and 30 mg versus placebo achieved ACR20 (56.9% and 63.8% vs 24.1%; p<0.001 for both comparisons). At week 24, MDA was achieved by more upadacitinib 15 mg-treated (25.1%) and 30 mg-treated patients (28.9%) versus placebo (2.8%; p<0.001 for both comparisons). Generally, the rates of treatment-emergent adverse events were similar with placebo and upadacitinib 15 mg and higher with upadacitinib 30 mg at week 24. Rates of serious infections were 0.5%, 0.5% and 2.8% with placebo, upadacitinib 15 mg and upadacitinib 30 mg, respectively. Conclusion In this trial of patients with active PsA who had inadequate response or intolerance to at least one biologic DMARD, upadacitinib 15 mg and 30 mg was more effective than placebo over 24 weeks in improving signs and symptoms of PsA. Clinical trial registration number NCT03104374
Adjustment of the PIF7‐HFR1 transcriptional module activity controls plant shade adaptation

Shade caused by the proximity of neighboring vegetation triggers a set of acclimation responses to either avoid or tolerate shade. Comparative analyses between the shade‐avoider Arabidopsis thaliana and the shade‐tolerant Cardamine hirsuta revealed a role for the atypical basic‐helix‐loop‐helix LONG HYPOCOTYL IN FR 1 (HFR1) in maintaining the shade tolerance in C. hirsuta, inhibiting hypocotyl elongation in shade and constraining expression profile of shade‐induced genes. We showed that C. hirsuta HFR1 protein is more stable than its A. thaliana counterpart, likely due to its lower binding affinity to CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), contributing to enhance its biological activity. The enhanced HFR1 total activity is accompanied by an attenuated PHYTOCHROME INTERACTING FACTOR (PIF) activity in C. hirsuta. As a result, the PIF‐HFR1 module is differently balanced, causing a reduced PIF activity and attenuating other PIF‐mediated responses such as warm temperature‐induced hypocotyl elongation (thermomorphogenesis) and dark‐induced senescence. By this mechanism and that of the already‐known of phytochrome A photoreceptor, plants might ensure to properly adapt and thrive in habitats with disparate light amounts.
Comprehensive insight into the molecular interaction of an anticancer drug-ifosfamide with human alpha-2-macroglobulin: biophysical and in silico studies

Abstract Ifosfamide is an active alkylating chemotherapeutic drug chemically related to nitrogen mustard. The pharmacokinetics of drugs is affected upon binding with protein, making the studies on drug-protein interaction promising. The present study investigates the interaction between ifosfamide and human antiproteinase-alpha-2-macroglobulin (α2M) by using multi-spectroscopic and in silico techniques. The UV-visible absorption, intrinsic fluorescence and circular dichroism (CD) spectroscopic methods were employed to unveil the mode and mechanism of ifosfamide–α2M interaction. Fluorescence quenching studies performed at three different temperatures indicated that ifosfamide–α2M complex formation involves static quenching. Far UV-CD spectra revealed a minor alteration in the secondary structure of α2M instigated by ifosfamide. The thermodynamic parameters determined by fluorescence quenching experiment and isothermal titration calorimetry (ITC) suggested that the complex between ifosfamide and α2M involves hydrogen bonding and hydrophobic interactions. Molecular docking illustrates that ifosfamide binds with moderate affinity to Lys1240, Asn173, Ser957, Leu955, Asp953, Lys1216 and Thr1236 residues during the interaction. Molecular dynamic (MD) simulation suggested that the ifosfamide forms a stable complex with α2M. Communicated by Ramaswamy H. Sarma
Regulation of VP30-Dependent Transcription by RNA Sequence and Structure in the Genomic Ebola Virus Promoter

A detailed understanding of how the Ebola virus (EBOV) protein VP30 regulates activity of the viral polymerase complex is lacking. Here, we studied how RNA sequence, length, and structure at the transcription start site (TSS) in the 3′-leader promoter influence the impact of VP30 on viral polymerase activity. ABSTRACT Viral transcription and replication of Ebola virus (EBOV) are balanced by transcription factor VP30, an RNA-binding protein. An RNA hairpin at the transcription start site (TSS) of the first gene (NP hairpin) in the 3′-leader promoter is thought to mediate the VP30 dependency of transcription. Here, we investigated the constraints of VP30 dependency using a series of monocistronic minigenomes with sequence, structure, and length deviations from the native NP hairpin. Hairpin stabilizations decreased while destabilizations increased transcription in the absence of VP30, but in all cases, transcription activity was higher in the presence than the absence of VP30. This also pertains to a mutant that is unable to form any RNA secondary structure at the TSS, demonstrating that the activity of VP30 is not determined simply by the capacity to form a hairpin structure at the TSS. Introduction of continuous 3′-UN5 hexamer phasing between promoter elements PE1 and PE2 by a single point mutation in the NP hairpin boosted VP30-independent transcription. Moreover, this point mutation, but also hairpin stabilizations, impaired the relative increase of replication in the absence of VP30. Our results suggest that the native NP hairpin is optimized for tight regulation by VP30 while avoiding an extent of hairpin stability that impairs viral transcription, as well as for enabling the switch from transcription to replication when VP30 is not part of the polymerase complex. IMPORTANCE A detailed understanding of how the Ebola virus (EBOV) protein VP30 regulates activity of the viral polymerase complex is lacking. Here, we studied how RNA sequence, length, and structure at the transcription start site (TSS) in the 3′-leader promoter influence the impact of VP30 on viral polymerase activity. We found that hairpin stabilizations tighten the VP30 dependency of transcription but reduce transcription efficiency and attenuate the switch to replication in the absence of VP30. Upon hairpin destabilization, VP30-independent transcription—already weakly detectable at the native promoter—increases but never reaches the same extent as in the presence of VP30. We conclude that the native hairpin structure involving the TSS (i) establishes an optimal balance between efficient transcription and tight regulation by VP30, (ii) is linked to hexamer phasing in the promoter, and (iii) favors the switch to replication when VP30 is absent.
In Situ HREM Irradiation Study of an Intrinsic Point Defects Clustering in FZ-Si

Various extended defects produced by in situ electron irradiation in a high resolution electron microscope (JEOL 4000EX ) at room temperature on {113} and {111} habit planes are reviewed on the base of the results recently obtained. It was observed that both interstitials and vacancies tend to aggregate in the shape of -oriented chain-like defects on {113}, in addition to well-known rod-like defect of interstitial type. These defects are characterized by a different magnitude and opposite type of lattice relaxation introduced in surrounding. -oriented interstitial chains are also formed by agglomeration of interstitials to the core of vacancy or interstitial Frank partial dislocations to provide a relaxation of the strongly deformed crystal areas.
Drainage basins serve as multiple glacial refugia for alpine habitats in the Sierra Nevada Mountains, California

The evolutionary histories of alpine species are often directly associated with responses to glaciation. Deep divergence among populations and complex patterns of genetic variation have been inferred as consequences of persistence within glacier boundaries (i.e., on nunataks), while shallow divergence and limited genetic variation are assumed to result from expansion from large refugia at the edge of ice shields (i.e., massifs de refuge). However, for some species, dependence on specific microhabitats could profoundly influence their spatial and demographic response to glaciation, and such a simple dichotomy may obscure the localization of actual refugia. In this study, we use the Nebria ingens complex (Coleoptera: Carabidae), a water‐affiliated ground beetle lineage, to test how drainage basins are linked to their observed population structure. By analysing mitochondrial COI gene sequences and genome‐wide single nucleotide polymorphisms, we find that the major drainage systems of the Sierra Nevada Mountains in California best explain the population structure of the N. ingens complex. In addition, we find that an intermediate morphotype within the N. ingens complex is the product of historical hybridization of N. riversi and N. ingens in the San Joaquin basin during glaciation. This study highlights the importance of considering ecological preferences in how species respond to climate fluctuations and provides an explanation for discordances that are often observed in comparative phylogeographical studies.
Metabolite Characterization and Correlations with Antioxidant and Wound Healing Properties of Oil Palm (Elaeis guineensis Jacq.) Leaflets via 1H-NMR-Based Metabolomics Approach

Oil palm (Elaeis guineensis Jacq.) leaflets (OPLs) are one of the major agricultural by-products generated from the massive cultivation of Malaysian palm oil. This biomass is also reported to be of potential value based on its health-improving effects. By employing proton nuclear magnetic resonance (1H-NMR) spectroscopy combined with multivariate data analysis (MVDA), the metabolite profile of OPLs was characterized and correlated with their antioxidant and wound healing properties. Principal component analysis (PCA) classified four varieties of extracts, prepared using solvents ranging from polar to medium polarity, into three distinct clusters. Cumulatively, six flavonoids, eight organic acids, four carbohydrates, and an amine were identified from the solvent extracts. The more polar extracts, such as, the ethyl acetate-methanol, absolute methanol, and methanol-water, were richer in phytochemicals. Based on partial least square (PLS) analysis, the constituents in these extracts, such as (+)-catechin, (−)-epicatechin, orientin, isoorientin, vitexin, and isovitexin, were strongly correlated with the measured antioxidant activities, comprising ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and nitric oxide (NO) free radical scavenging activities, as well as with cell proliferation and migration activities. This study has provided crucial evidence on the importance of these natural antioxidant compounds on the wound healing properties of OPL.