Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamics of a predator-prey model with non-monotonic response function

A five-parameter family of planar vector fields, which models the dynamics of certain populations of predators and their prey, is discussed. The family is a variation of the classical Volterra-Lotka system by taking into account group defense strategy, competition between prey and competition between predators. Also we initiate computer-assisted research on time-periodic perturbations, which model seasonal dependence. We are interested in persistent features. For the planar autonomous model this amounts to structurally stable phase portraits. We focus on the attractors, where it turns out that multi-stability occurs. Further, the bifurcations between the various domains of structural stability are investigated. It is possible to fix the values of two of the parameters and study the bifurcations in terms of the remaining three. Here we find several codimension 3 bifurcations that form organizing centres for the global bifurcation set. Studying the time-periodic system, our main interest is the chaotic dynamics. We plot several numerical examples of strange attractors.
Seismic Fragility Analysis of Structural Systems

A method is presented for the evaluation of the seismic fragility function of realistic structural systems. The method is based on a preliminary, limited, simulation involving nonlinear dynamic analyses performed to establish the probabilistic characterization of the demands on the structure, followed by the solution of a general system reliability problem with correlated demands and capacities. The results compare favorably with the fragility obtained by plain Monte Carlo simulation, while the associated computational effort is orders of magnitude lower. The method is demonstrated with two applications, a steel-concrete box girder viaduct with RC piers subjected to both uniform and nonuniform excitations, and a three-dimensional RC building structure subjected to bidirectional excitation.
Kinematics of 13 Brightest Cluster Galaxies

Velocity dispersion profiles and rotation curves have been determined for a sample of 13 brightest duster galaxies (BCGs) in order to study their internal stellar kinematics and investigate their relationship to ellipticals. We find that BCGs generally display velocity dispersion profiles with gradients similar to those found in normal bright ellipticals. A rising velocity dispersion profile is found for the BCG IC 1101, the dominant member of Abell 2029, confirming Dressier's (1979) result. No other rising velocity dispersion profiles are found in our sample suggesting that they are not a feature common to brightest duster galaxies. Significant rotation is found in only two of the galaxies, a result in agreement with previous studies showing the declining importance of rotation with increasing luminosity for elliptical galaxies. Our data suggest that environment plays a role in the kinematic characteristics of BCGs. We find a correlation between the rotation of BCGs and the velocity dispersion of their parent clusters in the sense that very slowly rotating galaxies (V-m/(sigma))(not asymptotic to) 650 km s(-1)) clusters. This relation between the internal stellar kinematics of BCGs and the cluster velocity dispersion is in the sense expected if ellipticals formed by merging. Brightest duster galaxy mass-to-light ratios derived from photometric and kinematic modeling are found to be similar to normal elliptical M/L values. For the galaxy NGC 4073, the dominant galaxy in the poor cluster MKW 4, we find that it contains a counterrotating stellar core suggestive of the occurrence of an accretion event(s).
NANOPARTICULATE SYSTEMS FOR NUCLEIC ACID DELIVERY

Development of carrier systems with controllable physicochemical and delivery properties has opened up the possibility of nanomedicines containing nucleic acids. In the last decades, much effort has been dedicated to two exciting approaches in biomedicine, namely gene and RNA interference (RNAi)-based therapeutics. These two approaches have faced many hurdles as far as delivery issues are concerned, as an efficient cytosolic delivery of siRNA and nuclear delivery of plasmid DNA is necessary for RNAi and gene therapy, respectively. In this PhD project, several biodegradable and non-biodegradable polymeric delivery systems such as TMC, TMC-SH, pHPMA-MPPM, QNPHOS, pDMAEMA, PEI and also carbon nanotubes (CNTs) were studied for nucleic acid delivery in vitro and in vivo. All these carrier systems were able to form nanoparticles with siRNA. However, based on characteristics of the carrier systems such as their chemical structure and cationic charges, the size, zeta potential and colloidal stability of the particles were different. It was shown those polymers with two cationic groups per monomer unit and the polymers which formed disulfide bonds (due to presence of thiol groups in the structure) were able to form stronger complexes with nucleic acid. However, based on the data presented in this thesis, it was concluded that formation of strong siRNA complexes is indeed advantageous, since it enhances the stability of the polyplexes in biological fluids, contributing to an improved siRNA delivery resulting in a high gene silencing activity. On the other hand, formation of too stable polyplexes with DNA with a limited release, resulted in lack of gene expression. The results of this PhD project show high gene silencing activity of thiolated TMC (TMC-SH) (up to 70%), with a low cytotoxicity (less than 20%). Formation of disulfide bonds in the polyplexes based on this polymer, improved the colloidal stability of the particles. Also, pHPMA-MPPM and non thiolated TMC showed high gene silencing activity (up to 70%) after application of endosomal escape methods such as photochemical internalization (PCI). Functionalized CNTs showed a low silencing activity (up to 20%) and a high cytotoxicity (more than 50%). The biodegradable polymers studied in this thesis showed a much lower cytotoxicity than non-biodegradable carrier systems.
Influence of air gaps in stacked transformer cores consisting of several packages

The influence of air gap length g on core loss P and excitation S was investigated in model cores including linearized overlap regions. Special emphasis was put on the interaction of core packages with shifted air gap regions. There, normal flux components /spl Phi//sub Z/ arise into neighbouring, gapless package regions. The resulting planar eddy current losses proved to be proportional to the square of /spl Phi//sub Z/. A correlation was established between local distributions of g, /spl Phi//sub Z/, P and S. >
Effects of a Novel Infant Formula on the Fecal Microbiota in the First Six Months of Life: The INNOVA 2020 Study

Exclusive breastfeeding is highly recommended for infants for at least the first six months of life. However, for some mothers, it may be difficult or even impossible to do so. This can lead to disturbances in the gut microbiota, which in turn may be related to a higher incidence of acute infectious diseases. Here, we aimed to evaluate whether a novel starting formula versus a standard formula provides a gut microbiota composition more similar to that of breastfed infants in the first 6 months of life. Two hundred and ten infants (70/group) were enrolled in the study and completed the intervention until 12 months of age. For the intervention period, infants were divided into three groups: Group 1 received formula 1 (INN) with a lower amount of protein, a proportion of casein to whey protein ratio of about 70/30 by increasing the content of α-lactalbumin, and with double the amount of docosahexaenoic acid/arachidonic acid than the standard formula; INN also contained a thermally inactivated postbiotic (Bifidobacterium animalis subsp. lactis). Group 2 received the standard formula (STD) and the third group was exclusively breastfed (BF) for exploratory analysis. During the study, visits were made at 21 days, 2, 4, and 6 months of age, with ±3 days for the visit at 21 days of age, ±1 week for the visit at 2 months, and ±2 weeks for the others. Here, we reveal how consuming the INN formula promotes a similar gut microbiota composition to those infants that were breastfed in terms of richness and diversity, genera, such as Bacteroides, Bifidobacterium, Clostridium, and Lactobacillus, and calprotectin and short-chain fatty acid levels at 21 days, 2 and 6 months. Furthermore, we observed that the major bacteria metabolic pathways were more alike between the INN formula and BF groups compared to the STD formula group. Therefore, we assume that consumption of the novel INN formula might improve gut microbiota composition, promoting a healthier intestinal microbiota more similar to that of an infant who receives exclusively human milk.
Suppression of Macrophage Activation by Sodium Danshensu via HIF-1α/STAT3/NLRP3 Pathway Ameliorated Collagen-Induced Arthritis in Mice

It is still a clinical challenge to sustain the remission of rheumatoid arthritis (RA); thus, identifying more effective and safer agents for RA treatment remains an urgent demand. We investigated the anti-arthritic activity and potential mechanism of action of sodium Danshensu (SDSS), a structurally representative water-soluble derivative of Danshen, on collagen-induced arthritis (CIA) mice. Our results showed that paw edema, synovium hyperplasia, bone destruction, and the serum levels of both IL-1β and IL-6 were ameliorated by SDSS (40 mg/kg·d) in CIA mice. In addition, there was no difference between SDSS and methotrexate (MTX, 2 mg/kg·3d) treatment in the above indicators. Further mechanism studies illustrated that SDSS inhibited IL-1β secretion by downregulating the HIF-1α/STAT3/NLRP3 pathway in macrophages. On the other hand, HIF-1α accumulation and HIF-1α/STAT3/NLRP3 pathway activation by IOX4 stimulation reduced the therapeutic effect of SDSS. These findings demonstrate that SDSS displays anti-arthritic activity in CIA mice and prevents proinflammatory cytokines secretion in macrophages by suppressing the HIF-1α/STAT3/NLRP3 pathway.
Gastric Emptying of New-World Milk Containing A1 and A2 Β-Casein Is More Rapid as Compared to Milk Containing Only A2 Β-Casein in Lactose Maldigesters: A Randomized, Cross-Over Trial Using Magnetic Resonance Imaging

Lactose maldigesters report an increase in abdominal pain due to the consumption of milk containing a mixture of A1 and A2 β-casein as compared to milk containing only A2 β-casein. Gastric transit affects gastrointestinal symptoms and rapid transit has been associated with an increase in abdominal pain. We conducted a double-blinded, randomized, crossover trial in 10 lactose maldigesters. Subjects consumed each of the two types of milk: conventional milk containing 75% A1 β-casein and 25% A2 β-casein and A2 milk containing 100% A2 β-casein. Magnetic resonance images were acquired, and abdominal pain was rated and recorded at 0, 10, 30, 60 and 120 min after milk consumption. The volume of milk in the stomach was calculated using FSL software. The volume of milk in the stomach after consuming milk with 75% A1 β-casein and 25% A2 β-casein was significantly lower at 30 (p = 0.01), 60 (p = 0.002) and 120 (p < 0.001) minutes as compared to milk with 100% A2 β-casein in the 10 lactose maldigesters. The transit of New-World milk containing A1 and A2 β-casein was more rapid as compared to Old-World milk containing only A2 β-casein. This difference in transit may mediate symptoms of lactose intolerance.
Tumor-suppressive disruption of cancer subtype-associated super enhancer circuits by small molecule treatment

Abstract Transcriptional cancer subtypes which correlate with traits such as tumor growth, drug sensitivity or the chances of relapse and metastasis, have been described for several malignancies. The core regulatory circuits (CRCs) defining these subtypes are established by chromatin super enhancers (SEs) driving key transcription factors (TFs) specific for the particular cell state. In neuroblastoma (NB), one of the most frequent solid pediatric cancer entities, two major SE-directed molecular subtypes have been described: A more lineage-committed adrenergic (ADRN) and a mesenchymal (MES) subtype. Here, we found that a small isoxazole molecule (ISX), a frequently used pro-neural drug, reprogrammed SE activity and switched NB cells from an ADRN subtype towards a growth-retarded MES-like state. The MES-like state shared strong transcriptional overlap with ganglioneuroma (GN), a benign and highly differentiated tumor of the neural crest. Mechanistically, ISX suppressed chromatin binding of N-MYC, a CRC-amplifying transcription factor, resulting in loss of key ADRN subtype-enriched components such as N-MYC itself, PHOX2B and ALK, while concomitently, MES subtype markers were induced. Globally, ISX treatment installed a chromatin accessibility landscape typically associated with low risk NB. In summary, we provide evidence that CRCs and cancer subtype reprogramming might be amenable to future therapeutic targeting.
Ubiquitylation of BBSome is required for ciliary assembly and signaling

Bardet‐Biedl syndrome (BBS) is a ciliopathy characterized by retinal degeneration, obesity, renal abnormalities, postaxial polydactyly, and developmental defects. Genes mutated in BBS encode for components and regulators of the BBSome, an octameric complex that controls the trafficking of cargos and receptors within the primary cilium. Although both structure and function of the BBSome have been extensively studied, the impact of ubiquitin signaling on BBSome is largely unknown. We identify the E3 ubiquitin ligase PJA2 as a novel resident of the ciliary compartment and regulator of the BBSome. Upon GPCR‐cAMP stimulation, PJA2 ubiquitylates BBSome subunits. We demonstrate that ubiquitylation of BBS1 at lysine 143 increases the stability of the BBSome and promotes its binding to BBS3, an Arf‐like GTPase protein controlling the targeting of the BBSome to the ciliary membrane. Downregulation of PJA2 or expression of a ubiquitylation‐defective BBS1 mutant (BBS1K143R) affects the trafficking of G‐protein‐coupled receptors (GPCRs) and Shh‐dependent gene transcription. Expression of BBS1K143R in vivo impairs cilium formation, embryonic development, and photoreceptors' morphogenesis, thus recapitulating the BBS phenotype in the medaka fish model.
The evaluation map and EHP sequences

Let L(ΣB, X) be the space of maps from ΣB (the reduced suspension of B) to X with the compact-open topology, let S\ ΣB-> X and L(ΣB, X; /) the path component of L(ΣB, X) containing /. For nice spaces the evaluation map ω: L(ΣB, X,s)->X defined by ω(f) = /(*) is a fibration and gives rise to a long exact sequence in homotopy. The purpose of this paper is to show that the boundary map in that long exact sequence can be given by a generalized Whitehead product and that the sequence generalizes the EHP sequence of G. W. Whitehead.
I329L: A Dual Action Viral Antagonist of TLR Activation Encoded by the African Swine Fever Virus (ASFV)

The African Swine Fever Virus (ASFV) is an economically important, large DNA virus which causes a highly contagious and frequently fatal disease in domestic pigs. Due to the acute nature of the infection and the complexity of the protective porcine anti-ASFV response, there is no accepted vaccine in use. As resistance to ASFV is known to correlate with a robust IFN response, the virus is predicted to have evolved strategies to inhibit innate immunity by modulating the IFN response. The deletion of virus host evasion gene(s) inhibiting IFN is a logical solution to develop an attenuated virus vaccine. One such candidate, the ASFV ORF I329L gene, is highly conserved in pathogenic and non-pathogenic virus isolates and in this study we confirm and extend the conclusion that it has evolved for the inhibition of innate immunity initiated through Toll-like receptors (TLRs). Specifically, the ASFV I329L extracellular (ECD) and intracellular (ICD) domains inhibit TLR signalling by two entirely different mechanisms. Bioinformatics modelling suggests that the ECD inhibits several TLR signalling pathways through a short sequence homologous to the conserved TLR dimerization domain, here termed the putative dimerization domain (PDD). Remarkably, both full length and PDD constructs of I329L were demonstrated to inhibit activation, not only of TLR3, but also TLR4, TLR5, TLR8 and TLR9. Additionally, the demonstration of a weak association of I329L with TLR3 is consistent with the formation of a non-signalling I329L-TLR3 heterodimer, perhaps mediated through the PDD of I329L. Finally, the ICD associates with TRIF, thereby impacting on both TLR3 and TLR4 signalling. Thus, I329L offers potential as a general inhibitor of TLR responses and is a rational candidate for construction and testing of an I329L deletion mutant vaccine.
Safety and Efficacy of Outpatient Treatments for COVID-19: Real-Life Data from a Regionwide Cohort of High-Risk Patients in Tuscany, Italy (the FEDERATE Cohort)

Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.
Detecting Individual Differences in Change: Methods and Comparisons

This study examined and compared various statistical methods for detecting individual differences in change. Considering 3 issues including test forms (specific vs. generalized), estimation procedures (constrained vs. unconstrained), and nonnormality, we evaluated 4 variance tests including the specific Wald variance test, the generalized Wald variance test, the specific likelihood ratio (LR) variance test, and the generalized LR variance test under both constrained and unconstrained estimation for both normal and nonnormal data. For the constrained estimation procedure, both the mixture distribution approach and the alpha correction approach were evaluated for their performance in dealing with the boundary problem. To deal with the nonnormality issue, we used the sandwich standard error (SE) estimator for the Wald tests and the Satorra–Bentler scaling correction for the LR tests. Simulation results revealed that testing a variance parameter and the associated covariances (generalized) had higher power than testing the variance solely (specific), unless the true covariances were zero. In addition, the variance tests under constrained estimation outperformed those under unconstrained estimation in terms of higher empirical power and better control of Type I error rates. Among all the studied tests, for both normal and nonnormal data, the robust generalized LR and Wald variance tests with the constrained estimation procedure were generally more powerful and had better Type I error rates for testing variance components than the other tests. Results from the comparisons between specific and generalized variance tests and between constrained and unconstrained estimation were discussed.
The Effect of Combining Millet and Corn Straw as Source Forage for Beef Cattle Diets on Ruminal Degradability and Fungal Community

Simple Summary Millet straw and corn straw as roughages for the ruminant diet have broad application prospects. A variety of roughage combinations affect the ruminal degradability and rumen fungal community. The effects of roughage mixture on the rumen of beef cattle are little understood. This research focuses on the impact of straw on beef cattle feed nutrition, as well as different ratios of millet straw and corn straw diets on ruminal degradability and rumen fungal community. The results proved the feeding effect of different proportions of millet straw and corn straw combinations in beef cattle. Abstract Three ruminal cannulated Simmental crossbreed bulls (approximately 3 years of age and with 380 ± 20 kg live weight at initiation of the experiment) were used in a 3 × 3 Latin square experiment in order to determine the effects of the treatments on ruminal pH and degradability of nutrients, as well as the rumen fungal community. The experimental periods were 21 d, with 18 d of adjustment to the respective dietary treatments and 3 d of sample collection. Treatments consisted of a basal diet containing a 47.11% composition of two sources of forage as follows: (1) 100% millet straw (MILLSTR), (2) 50:50 millet straw and corn straw (COMB), and (3) 100% corn straw (CORNSTR). Dry matter (DM), crude protein (CP), neutral detergent fiber (NDF), and acid detergent fiber (ADF) were tested for ruminal degradability using the nylon bag method, which was incubated for 6, 12, 24, 36, 48, and 72 h, and rumen fungal community in rumen fluid was determined by high-throughput gene sequencing technology. Ruminal pH was not affected by treatments. At 72 h, compared to MILLSTR, DM degradability of CORNSTR was 4.8% greater (p < 0.05), but when corn was combined with millet straw, the difference in DM degradability was 9.4%. During the first 24 h, degradability of CP was lower for CORNSTR, intermediate for MILLSTR, and higher for COMB. However, at 72 h, MILLSTR and COMB had a similar CP degradability value, staying greater than the CP degradability value of the CORNSTR treatment. Compared to MILLSTR, the rumen degradability of NDF was greater for CORNSTR and intermediate for the COMB. There was a greater degradability for ADF in CORNSTR, intermediate for COMB, and lower for MILLSTR. In all treatments, Ascomycota and Basidiomycota were dominant flora. Abundance of Basidiomycota in the group COMB was higher (p < 0.05) than that in the group CORNSTR at 12 h. Relative to the fungal genus level, the Thelebolus, Cladosporium, and Meyerozyma were the dominant fungus, and the abundance of Meyerozyma in COMB and CORNSTR were greater (p < 0.05) than MILLSTR at 12, 24, and 36 h of incubation. In conclusion, it is suggested to feed beef cattle with different proportions of millet straw and corn straw combinations.