Enhancing the acoustical quality in learning environments is mandatory, especially for Hearing Aids (HAs) users. When in-field evaluations cannot be performed, Virtual Reality (VR) can be adopted for the acoustical quality assessment of existing and new buildings, contributing to the acquisition of subjective impressions in lab settings. To ensure an accurate spatial reproduction of the sound field in VR also for HAs users, multispeaker-based systems can be employed to auralize a given environment. However, most systems are effortful due to costs, size and construction. This work deals with the validation of a VR-system based on a 16-speaker-array synced with a VR-headset, arranged to be easily replicated in small non-anechoic spaces and suitable for HAs users. Both objective and subjective validations are performed against a real university lecture room of 800 m3 and with 2.3 s of Reverberation Time at mid-frequencies. Comparisons of binaural and monoaural room acoustic parameters are performed between measurements in the real lecture room and its lab reproduction. To validate the AudioVisual experience, 32 normal-hearing subjects were administered the Igroup Presence Questionnaire (IPQ) on the overall sense of perceived presence. The outcomes confirm that the system is a promising and feasible tool to predict the perceived room acoustical quality.

Copper (Cu) is a critical element for cancer cell proliferation and considerably accumulates in the nucleus. 64Cu2+ is an anticancer radiopharmaceuticals targeting the copper requirement of cancer cells. However, intravenously injected 64Cu2+ ions primarily accumulate in the liver. Ligand complexation of 64Cu2+ would be a promising method for increasing tumor delivery by reducing liver uptake. Herein, we used three tripodal amine ligands [tris(2-aminoethyl)amine (Tren), diethylenetriamine (Dien), and tris(2-pyridylmethyl)amine (TPMA)] to enclose 64Cu2+ ions and compared their in vivo tumor and liver uptake using a tumor-bearing xenograft mouse model of the extrahepatic bile duct carcinoma cell line TFK-1. We examined intracellular Cu distribution using microparticle-induced X-ray emission (micro-PIXE) analysis for these compounds. 64Cu2+-Tren and 64Cu2+-Dien showed higher tumor uptake than 64Cu2+-TPMA and 64Cu2+ ions in TFK-1 tumors. Among the three 64Cu2+ complexes and 64Cu2+ ions, liver uptake was inversely correlated with tumor uptake. Micro-PIXE analysis showed that in vitro cellular uptake was similar to in vivo tumor uptake and nuclear delivery was the highest for 64Cu2+-Tren. Conclusively, an inverse correlation between tumor and liver uptake was observed using three 64Cu2+ complexes of tripodal amine ligands and 64Cu2+ ions. These results provide useful information for the future development of anticancer 64Cu radiopharmaceuticals.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (>12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

Reducing fertilizer-N rate, applying nitrification inhibitor (NI), and incorporating straw are widely recommended to improve N use efficiency of crops and decrease N losses. However, how these practices affect crop N uptake by regulating the fertilizer-N fate during the growing season is not well understood. We conducted a field 15N tracer study to explore the effectiveness of reduced N application, NI, and straw incorporation on fertilizer-N fates for maize cultivation in Northeast China. The following six treatments were used: 1) no N fertilization (control); 2) 200 kg urea-N ha−1 (100%N); 3) 200 kg urea-N ha−1 and 2400 kg dry-straw ha−1 (100%N+S); 4) 160 kg urea-N ha−1 (80%N, i.e., 20% reduction of N fertilization); 5) 160 kg urea-N ha−1 and nitrification inhibitor (Nitrapyrin) (80%N+NI); 6) 160 kg urea-N ha−1, nitrification inhibitor and 2400 kg dry-straw ha−1 (80%N+NI+S). Our results showed that the five N fertilization treatments yielded 16%–25% more grain and 39%–60% more crop N uptake than the control receiving no N fertilizer, but the differences among the five treatments were not statistically significant. In contrast to plant growth, changes in fertilizer-N fates in soil and plant pools were more pronounced. Compared with the 100%N treatment, 20% fertilizer-N reduction (80%N) decreased 15N concentration in topsoil and plant pools but increased the proportion of plant 15N recovery at harvesting (N use efficiency, NUE15N, 60% vs. 50%) (P < 0.05). Nitrapyrin co-application (80%N+NI) delayed soil nitrification and increased soil 15N retention at harvesting (52% vs. 36%), thereby decreasing NUE15N significantly (P < 0.05). Straw incorporation (100%N+S) decreased fertilizer-N retention compared with NI co-application because it promoted NUE15N significantly (P < 0.05). The combined application of NI and straw (80%N+NI+S) was more conducive to fertilizer-N retention in soil. Our findings demonstrate that NI and straw additions are efficient strategies for stabilizing fertilizer-N in soils and potentially minimizing N loss; however, their effects on NUE15N vary and the related mechanism must be further clarified in long-term trials.

In recent years, 360o videos have gained the attention of researchers investigating their educational potential. Given the ongoing debate about their impact on learning, particularly with young students where existing research is minimal, a comprehensive study was conducted to evaluate their effectiveness relative to other media forms. The study involved 44 kindergarten students learning about wild animals over nine sessions. The 360o videos were compared to printed materials and conventional videos to measure knowledge acquisition, motivation, enjoyment/positive feelings, immersion, and ease of use. The findings suggest that, compared to printed materials, 360o videos enhance knowledge acquisition. However, this advantage does not extend to comparisons with conventional videos. Similarly, while enjoyment and motivation were higher for 360o videos compared to printed materials, they did not surpass those associated with conventional videos. Despite their potential, 360o videos were deemed the least easy to use, likely due to the employment of low-cost HMDs. Immersion emerged as the only factor where 360o videos excelled, demonstrating a notable influence on learning outcomes. The implications of the study are also discussed.

The electronic nose (e-nose) is an innovative device that mimics the human olfactory system, allowing for the detection and identification of numerous scents. This abstract gives an in-depth examination of the current status of electronic nose technologies, with an emphasis on sensing mechanisms, applications, and recent breakthroughs. The research delves into the many uses of e-nose, such as food quality control, environmental monitoring, medical diagnostics, and industrial operations. It also covers the problems and potential future applications of electronic nose technology. The literature review highlights the importance of this technology in improving our capacity to evaluate complex scents in several domains.

The present work offers a contemporary synthesis of the application of the Oxford Nanopore^® MinION^™ within the context of cultural heritage biodeterioration investigations, while also providing a comprehensive discussion of possible future perspectives for their utilization in this research field. Owing to the distinctive characteristics of this device, the past few years have witnessed the consistent increase on the application of this system in a variety of cultural heritage materials. In fact, the technique has been useful to understand microbial biodeteriogens diversity and some of their metabolic and biodeteriogenic features. Considering the immense potential for application of this system, this manuscript explores and discusses further possibilities of the technique, focusing on helping understand critical questions on the cultural heritage biodeterioration area. Its application in various differential contexts, has opened doors for prospective applications on other interesting sub-areas of research meriting future investigations, including: biodeteriogens genome and transcriptome analysis, metatranscriptomics, biodeteriorative metabolism studies, inter and intra kingdom interactions analysis, resistome profiling, object history and context studies, in situ applications, bioprospecting and biotechnology.

Edible oils have commercial and nutritional value due to the presence of essential fatty acids. They can be consumed fresh in the form of capsules known as nutraceuticals. The quality of such products is of interest to the consumer. In this context, this study describes a method based on high resolution nuclear magnetic resonance (NMR) and Fourier transform mid-infrared spectroscopic analysis (FTIR), combined with statistical analyzes to differentiate different edible oils used as nutraceuticals in Brazil by fatty acid content. Through the analysis of 1H NMR spectra, the levels of saturated and unsaturated fatty acids in edible oils were characterized and quantified. Statistical analysis of the data confirmed the real distinction between nutraceutical raw materials, with emphasis on ω-9, ω-6 and ω-3 fatty acids. The analytical approach presented also demonstrated potential to identify the origin (animal or vegetable) of edible oils used as nutraceuticals.

Alignment of picornavirus proteinase/polymerase sequences reveals this family evolved into five ‘supergroups’. Interestingly, the nature of the 2A region of the picornavirus polyprotein is highly correlated with this phylogeny. Viruses within supergroup 4, the Paavivirinae, have complex 2A regions with many viruses encoding multiple 2A^NPGP sequences. In vitro transcription/translation analyses of a synthetic polyprotein comprising green fluorescent protein (GFP) linked to b-glucuronidase (GUS) via individual 2A^NPGPs showed two main phenotypes: highly active 2A^NPGP sequences - similar to Foot-and-Mouth Disease Virus 2A^NPGP and, surprisingly, a novel phenotype of some 2A^NPGP sequences which apparently terminate translation at the C-terminus of 2A^NPGP - without detectable re-initiation of downstream sequences (GUS). Probing databases with the short sequences between 2A^NPGPs did not reveal any potential ‘accessory’ functions. The novel, highly active, 2A-like sequences we identified substantially expands the toolbox for biomedical / biotechnological co-expression applications.

This study aimed to explore the genetic information about the yield traits in perennial Chinese rice "Shendao3^#" and provide a series of theoretical bases for the innovative utilization of perennial Chinese rice germplasm. The F₂ population derived from the cross between perennial Chinese rice "Shendao3^#" and one annual rice "XiqingzaoB" was developed to identify QTLs’ underlying yield-related traits. Fifteen yield traits including plant height, panicle plant^-1, and thousand-grain weight were measured for the QTL mapping. The software packages Excel 2010, GraphpadPrism 5.0, and QTLIciMapping 4.10 were used to perform the phenotypic data analysis, construction of molecular map, and QTL mapping, respectively. Results indicated 15 yield-related traits displaying normal distribution and belonging to quantitative trait inheritance. A total of 25 QTLs associated with the yield-related traits and 26 epistatic QTLs were detected on the whole genome except for the 6th and 12th chromosomes. This finding explained phenotypic variance with ranging from 4.21% to 27.30% and 1.15% to 19.30%, respectively. Six pleiotropic QTL (chromosomal regions) underlying two or more yield-related traits were detected on the 1st , 4th, 7th, 8th, and 11th chromosomes, respectively. Among 25 QTLs underlying a single yield-related trait, 11 were primarily identified in the perennial Chinese rice "Shendao3^#". All QTLs underlying 15 yield-related traits followed the genetic model of additive, dominant, and digenic epistatic of additive by additive, additive by dominant, dominant by additive, and dominant by dominant. This work can serve as a good foundation for yield-related gene mining and its utilization in breeding the perennial Chinese rice "Shendao3^#".

Dietary intake of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA) exerts antiarrhythmic effects, although the mechanisms are poorly understood. Here we investigated the possible beneficial actions of EPA on saturated fatty acid-induced changes of the L-type Ca2+ channel in cardiomyocytes. Cardiomyocytes were cultured with oleic acid/palmitic acid mixture (OAPA) in the presence or absence of EPA. Beating rate reduction of cardiomyocytes caused by OAPA were reversed by EPA. EPA also retrieved a reduction of Cav1.2-L-type Ca2+ current, mRNA and protein caused by OAPA. Immunocytochemical analysis revealed a distinct downregulation of the Cav1.2 channel caused by OAPA with a concomitant decrease in the phosphorylated component of a transcription factor adenosine-3’, 5’-cyclic monophosphate (cAMP) response element binding protein (CREB) in the nucleus, which were rescued by EPA. A free fatty acid receptor 4 (FFAR4) agonist TUG-891 reversed expression of Cav1.2- and CREB-mRNA caused by OAPA, whereas an FFAR4 antagonist AH-7614 abolished the effects of EPA. Excessive reactive oxygen species (ROS) accumulation caused by OAPA decreased Cav1.2- and CREB-mRNA expressions, which were reversed by an ROS scavenger. Our data suggest that EPA rescues cellular remodeling caused by OAPA lipotoxicity and oxidative stresses via both free fatty acid receptor 4-dependent and -independent pathways.

A novel Gram-stain-negative, facultatively anaerobic and mixotrophic bacterium, designated as strain LZ166T, was isolated from the bathyplagic seawater in the western Pacific Ocean. Cells were short rod-shaped, oxidase- and catalase- positive, and motile by means of lateral flagella. Growth of strain LZ166T was observed at 10-45 ℃ (optimum, 34-37 ℃), at pH 5-10 (optimum, 6-8) and in the presence of 0-5% NaCl (optimum, 1-3%). Phylogenetic analysis based on the 16S rRNA gene showed that strain LZ166T shared the highest similarity (98.58%) with Aquibium oceanicum B7T, and formed a distinct branch within the Aquibium genus. Genomic characterization, including average nucleotide identity (ANI, 90.73-76.79%), average amino identity (AAI, 88.50-79.03%) and digital DNA-DNA hybridization (dDDH, 36.1-22.2%) values between LZ166T and other species within the Aquibium genus, further substantiated its novelty. The genome of strain LZ166T was 6,119,659 bp in size with a 64.7 mol% DNA G+C content. The predominant fatty acid was summed feature 8 (C18:1ω7c and/or C18:1ω6c). The major polar lipids identified were Diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), glycolipid (GL) and phosphatidylglycerol (PG), with ubiquinone-10 (Q-10) as the predominant respiratory quinone. Genomic annotation indicated the presence of genes for a diverse metabolic profile, including pathways for carbon fixation via the Calvin–Benson–Bassham cycle and inorganic sulfur oxidation. Based on polyphasic taxonomic results, strain LZ166T represented a novel species of the genus Aquibium, for which the name Aquibium pacificus sp. nov., is proposed, with the type strain LZ166T (= MCCC M28807T = KACC 23148T = KCTC 82889T).

There has been an increased focus on new technologies to monitor habitat use and behaviour of cattle, to develop a more sustainable livestock grazing system, without compromising animal welfare. The currently most used method for monitoring cattle behaviour is tri-axial accelerometer data from systems such as virtual fencing technology or bespoke monitoring technology. This method requires high frequency data, and as such, quickly drains contemporary systems of power making it unsuitable for long-term monitoring. In this paper, we explore the possibility of determining habitat preference and habitat utilisation patterns in cattle, using low frequency activity and location data. We do this by (1) calculating habitat selection ratios, (2) determining daily activity patterns and based on those, (3) inferring grazing and resting sites in a group of cattle wearing virtual fencing collars in a coastal setting with grey, wooded and decalcified dunes, humid dune slacks and salt meadows. We found that GPS data, and a measure of activity, combined with accurate mapping of habitats can be an effective tool in assessing habitat preference. The animals preferred salt meadows over the other habitats, with wooded dunes and humid dune slacks being the least preferred. We were able to identify daily patterns in activity. By comparing general trends in activity levels to existing literature, it was possible to somewhat infer resting and grazing behaviour in the different habitats. According to our inference of behaviour the herd predominantly used the salt meadows for resting and ruminating. The approach used in this study allowed us to use GPS location data for measuring the activity and combine it with accurate habitat mapping in a cheap and effective way, which can be an important tool for guiding management decisions.

In this work, a ZIF-67/MWCNTs/Nafion sensor platform was constructed based on the good adsorption capacity of ZIF-67, the electrical conductivity of multiwalled carbon nanotubes (MWCNTs) and the excellent chemical stability of Nafion for the detection of Cu2+ in water. Meanwhile, the modified materials were characterized by scanning electron microscopy (SEM), Transmission electron microscopy (TEM), BET specific surface area test, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and Fourier transform infrared spectrometry (FT-IR). Cyclic voltammetry (CV), electrochemical impedance (EIS), and square wave solvation voltammetry (SWSV) electrochemical methods were used to perform applied test studies on ZIF-67/MWCNTs/Nafion/GCE. The results show that ZIF-67/MWCNTs/Nafion/GCE has high sensitivity (57.5 μA/μM) and a low limit of detection (15.0 nM) for the electrochemical detection of Cu2+ ions in an electrochemical sensing system. It has high adsorption selectivity for Cu2+, and the recovery of Cu2+ in real water reached 98.6%-103%. The modified electrode has good repeatability, reproducibility, anti-interference, and stability, which makes this sensing platform can be practically applied to the detection of domestic water.

When it is in the template RNA, the naturally occurring m¹A epitranscriptomic RNA modification was recently reported to be able to stop the RNA polymerization reaction catalyzed by the RNA dependent RNA polymerase (RdRp) of SARS-CoV-2. In this report, we report that m¹A via its triphosphate form (m¹ATP) can be incorporated into RNA by the same RdRp. These two findings point a new direction for antiviral drug development based on m¹A for combatting COVID-19. More broadly, it is possible that the large pool of epigenetic RNA as well as DNA modifications could serve as a treasury for drug discovery aimed at combating various infectious and other diseases.

Exploring therapeutic options is crucial in the ongoing COVID-19 pandemic caused by SARS-CoV-2. Nirmatrelvir, a potent inhibitor targeting the SARS-CoV-2 Mpro, shows promise as an antiviral treatment. Additionally, Ivermectin, a broad-spectrum antiparasitic drug, has demonstrated effectiveness against the virus in laboratory settings. However, its clinical implications are still debated. Using computational methods such as molecular docking and 100 ns molecular dynamics simulations, we investigated how Nirmatrelvir and Ivermectin interact with SARS-CoV-2 Mpro(A). Calculations using density functional theory have been instrumental in elucidating the behavior of isolated molecules, primarily by analyzing the frontier molecular orbitals. Our analysis revealed distinct binding patterns: Nirmatrelvir formed strong interactions with amino acids like MET49, MET165, HIS41, HIS163, HIS164, PHE140, CYS145, GLU166, and ASN142, showing stable binding with a root mean square deviation (RMSD) of around 2.0 Å. On the other hand, Ivermectin interacted with THR237, THR239, LEU271, LEU272, and LEU287, displaying an RMSD of 1.87 Å, indicating enduring interactions. Both ligands stabilized Mpro(A), with Ivermectin showing stability and persistent interactions despite forming fewer hydrogen bonds. These findings offer detailed insights into how Nirmatrelvir and Ivermectin bind to the SARS-CoV-2 main protease, providing valuable information for potential therapeutic strategies against COVID-19.

PET imaging with [¹⁸F]F-DOPA has demonstrated high potential for the evaluation and management of pediatric brain gliomas. Manual extraction of PET parameters is time-consuming, lacks reproducibility, and varies with operator experience. In this study, we tested whether a semi-automated image processing framework could overcome these limitations. Pediatric patients with available static and/or dynamic [¹⁸F]F-DOPA PET studies were evaluated retrospectively. We developed a Python software to automate clinical index calculations, including preprocessing to delineate tumor volumes from structural MRI, accounting for lesions with low [¹⁸F]F-DOPA uptake. 73 subjects with treatment-naïve low and high-grade gliomas, who underwent brain MRI within two weeks of [¹⁸vF]F-DOPA PET, were included and analyzed. Static analysis was conducted on all subjects, while dynamic analysis was performed on 32 patients. For 68 subjects, the Intraclass Correlation Coefficient for T/S between manual and ground truth segmentation was 0.91. Using our tool, ICC improved to 0.94. Our method demonstrated good reproducibility in extracting static tumor-to-striatum ratio (p = 0.357), though significant differences were observed in tumor slope (p < 0.05). No significant differences were found in time-to-peak (p = 0.167) and striatum slope (p = 0.36). Our framework aids in analyzing [¹⁸F]F-DOPA PET images of pediatric brain tumors by automating clinical score extraction, simplifying segmentation and Time Activity Curve extraction, reducing user variability, and enhancing reproducibility.

Palmitoylethanolamide (PEA) has been prescribed for neuropathic pain for several years. This study is mainly addressed to summarize what has been published on the topic in the last decades, and how appropriate the numerous prescriptions are. Among others, it examines the innovative EquiPEA^® patent, which aims to address obstacles encountered with conventional PEA formulations. EquiPEA^® seems to partially ameliorate the bioavailability and the targeted distribution. It seems to introduce novel advancements that have the potential to enhance the therapeutic effectiveness of PEA in terms of its anti-inflammatory, antioxidant, and analgesic properties. The deep literature analysis aims to examine the potential advantages of this innovative formulation, in the context of several pathological conditions that may benefit from this molecule. In particular, it investigates the potential enhanced bioavailability and targeted delivery system of EquiPEA^®. Also, it tries to understand if it can modernize the field of therapy based on PEA, thus offering a better treatment option for individuals with long-term inflammation, oxidative stress, and neuropathic or mixed pain with a neuropathic component. The study examines the possible impact of EquiPEA^® on personalized medicine strategies and its potential for translation into clinical practice. It analyses the possibilities that EquiPEA^® has in enhancing patient outcomes in a range of central nervous system and inflammatory conditions. This narrative review makes a valuable contribution to the ongoing comprehension of PEA therapy. It establishes a foundation for further exploration in research and potential uses in clinical settings.

Piezoelectric c-axis oriented zinc oxide (ZnO) thin films, from 1.8 up to 6.6 µm thick, have been grown by radio frequency magnetron sputtering technique onto fused silica substrates. A delay line consisting in two interdigital transducers (IDTs) with wavelength λ = 80 µm was photolith-ographically implemented onto the surface of the ZnO layers. Due to the IDTs split finger con-figuration and metallization ratio (0.5), the propagation of both the fundamental, third and nineth harmonic Rayleigh waves is excited; also, three leaky surface acoustic waves (SAWs) were detected travelling at velocity close to that of the longitudinal bulk wave in SiO2. The acoustic waves propagation in ZnO/fused silica was simulated by using 2D finite-element method (FEM) tech-nique to identify the nature of the experimentally detected waves. It turned out that, in addition to the fundamental and harmonic Rayleigh waves, also high-frequency leaky surface waves are ex-cited by the harmonic wavelengths; such modes are identified as leaky-Sezawa (LS) waves under cut-off. The velocity of all the modes was found in good agreement with the theoretically calcu-lated values. The existence of a low-loss region for the Sezawa wave below the cut off was theo-retically predicted and experimentally assessed.

The regulation of intracellular pH in yeast (Saccharomyces cerevisiae) cells is critical for cell function and viability. In yeast, protons (H+) can be excreted from cell by the plasma membrane ATPase Pma1 and pumped into vacuoles by the vacuolar H+-ATPase. Because Pma1 is critical to the survival of yeast cells, it is unknown whether other compensatory components are involved in the pH homeostasis in the absence of Pma1. To elucidate how intracellular pH is regulated independently of Pma1, we employed a screening approach by exposing the yeast haploid deletion mutant library (ver 4.0) to the selective plant plasma membrane H+-ATPase inhibitor PS-1, which we previously reported. After repeated screenings and verification, we identified two proteins, ALY1 and ALY2, that play a role in the regulation of intracellular pH when Pma1 is deficient. Our research uncovers a new perspective on the regulation of intracellular pH related to Pma1 and also preliminarily reveals a role for ALY1 and ALY2 in the regulation of intracellular pH.

The construction of tunnels excavated by the conventional method in densely populated urban environments requires an adequate characterization of the loads acting on the primary lining during the excavation process to ensure that the ground is deformed and stresses around the tunnel are relieved, simultaneously complying with the failure and serviceability limits of international standards while minimizing damage to nearby structures. In this paper, common lining design criteria are revisited, through the numerical simulation of an instrumented tunnel section which is part of a 4.5 km long metro line currently under construction in Mexico City. Key needs for improvement in current design approaches are identified. The tunnel was instrumented with load cells, extensometers, and topographical references for convergences and divergences. A three-dimensional finite difference model of the instrumented section was developed, and the load transfer mechanisms between the excavated soil and the primary lining was analyzed. Then, the numerical simulation of the contribution of the secondary lining in the overall stability for sustained load was established, along with the expected ground settlements, which can significantly affect nearby structures. Results gathered from this research are key for updating lining design criteria for urban tunnels built in stiff brittle soils.

The effect of sonication on the molecular characteristics of poliacrylic acid (Carbopol® Ultrez 10) and its rheological behavior in aqueous dispersions and microgels containing 0.25 wt. % of the polymer was analyzed in this work by rheometry, weight-average molecular weight (Mw) measurements via static light scattering (SLS), Fourier transform infrared (FTIR) spectroscopy and confocal microscopy. For this, the precursor dispersion and the microgels were sonicated in a commercial ultrasound bath at constant power and different times. We observed a softening of the microgel microstructure consisting of a systematic decrease in its shear modulus, yield stress and viscosity with increasing sonication time, while their overall Herschel-Bulkley (H-B) behavior was preserved. SLS measurements evidenced a reduction of Mw of polyacrylic acid with sonication time. Separately, FTIR measurements indicate that sonication produces scission in the C-C links of the Carbopol® backbone, which results in chains with the same chemistry but lower molecular weight. Finally, confocal microscopy measurements revealed a concomitant diminution of the size of the microsponge domains with sonication time, which is reflected in a softer microstructure resulting from reduction of the molecular weight of polyacrylic acid. The present results indicate that both the microstructure and the rheological behavior of Carbopol® microgels, in particular, and complex fluids in general, may be manipulated or tailored by high-power ultrasonication.

Background: Existing human cell immortalization methods made the cells obtain oncogenesis phenotype and/or caused the cells gain and/or lose chromosomes. Immortalized normal human T cells lines provide critical in vitro models for basic research and therapeutic products development.Methods: We utilized a CRISPR/Cas9 system to replace a single copy of the exon 2 of the cell cycle inhibitor gene CDKN2A (encoding p16 and p14 proteins) with a single copy of human telomerase reverse transcriptase (hTERT) to immortalize human primary CD8⁺ T cells (hCD8⁺T-TERT). By using Cas9 protein and low donor DNA copies/cell, we successfully immortalized hCD8⁺T cells with a single copy of hTERT transgene, which also avoided uncontrolled insertion of Cas9 gene and guide RNA vector.Results: Human primary CD8+ cells were immortalized and expanded more than 2.6 × 10⁷ times. Characterization of the cells revealed that the immortalized CD8⁺ T-TERT cells retained most of the cell surface markers and normal karyotype. The CD8⁺ T-TERT cells also retained the dependence of IL-2 and CD3/CD28 activator for survival and expansion.Conclusion: we established a stable immortalized CD8⁺ T cell line that had a phenotype consistent with T cells and will be a useful research model.

Manganese porphyrins reportedly exhibit synergic effects when combined with irradiation. However, an in-depth understanding of intratumoral heterogeneity and immune pathways, as affected by Mn porphyrins, remains limited. Here, we explored the mechanisms underlying immunomodulation of a clinical candidate, MnTnBuOE-2-PyP5+ (BMX-001, MnBuOE), using single-cell analysis in murine carcinoma model. Mice bearing 4T1 tumors were divided into 4 groups: control, MnBuOE, radiotherapy (RT), combined MnBuOE and radiotherapy (MnBuOE/RT). In epithelial cells, epithelial-mesenchymal transition, TNF-α signaling via NF-кB, angiogenesis, and hypoxia-related genes were significantly downregulated in the MnBuOE/RT compared to the RT. All subtypes of cancer-associated fibroblasts (CAFs) were clearly reduced in MnBuOE and MnBuOE/RT. Inhibitory receptor-ligand interactions, in which epithelial cells and CAFs interacted with CD8+ T cells, were significantly lower in the MnBuOE/RT than in the RT. Trajectory analysis showed that DC maturation-associated markers were increased in MnBuOE/RT. M1 macrophages were significantly increased in the MnBuOE/RT compared to the RT, whereas myeloid-derived suppressor cells were decreased. CellChat analysis showed that the number of cell-cell communications was the lowest in the MnBuOE/RT. Our study is the first to provide evidence for the combined radiotherapy with a novel Mn porphyrin clinical candidate, BMX-001 from the perspective of each cell-type within the tumor microenvironment.

Lenalidomide-based regimens are effective treatment options for patients with relapsed/refractory multiple myeloma (RRMM). However, they are associated with an increased risk of infectious complications. This study examines the clinical factors influencing the occurrence of infection in MM patients treated with lenalidomide and dexamethasone (Rd). A retrospective analysis of all patients who received the Rd regimen between 2017-2021 at our institution was performed. The study group consisted of 174 patients and the median age was 65 years. Most patients (n=110, 63.2%) received the Rd treatment in second-line treatment. The majority of patients (64.3%) received bortezomib-based regimens in the first line of treatment. The median progression-free survival was 12.6 (95% CI: 9.5 – 16.2) months, and the median overall survival was 22.3 (95% CI: 15.9 – 28.6) months. The overall response rate was 64.1%, 12.7% of patients achieved complete response and 20.4% had a very good partial response. In multivariate logistic regression analysis, hypoalbuminemia (OR 4.2, 95%CI:1.6-11.2, p= 0.0039), autologous hematopoietic stem cell transplantation (AHSCT) before Rd (OR 2.6, 95% CI:1.0- 6.7, p= 0.048) and anemia grade ≥3 (OR 5.0, 95%CI: 1.8-14.0, p= 0.002) were independent factors related to the occurrence of infections. In conclusion, in this large cohort of RRMM patients, AHSCT before Rd regimen therapy, hypoalbuminemia and anemia during treatment were identified as three independent factors influencing the frequency of infections during Rd therapy. Patients with established risk factors may benefit from optimal supportive therapy.

The consumption of insects in the Democratic Republic of Congo is an ancient practice. The taxonomic identification and characterization of “entomophagy” seem urgent in Kinshasa following the related anthropogenic pressures (demographic pressure, uncontrolled urbanization) leading to a food crisis. This study aims to assess the diversity of edible insects and their consumption by the population of Kinshasa. A total of 360 people were surveyed to identify the insect species consumed in Kinshasa, the ecosystems that provide them, and the preference for species in relation to ethnolinguistic groups, churches (faith) and household size. Three species of insects most consumed in Kinshasa are: Gonimbrasia jamesonii, Cirina forda and Brachytrupes membranaceus. 41.9% of these insects are consumed by the Kongo ethno-linguistic group, 23.6% by the Luba, 20.6% by the Ngala and 13.9% by the Swahili. Inhabitants of the communes of Kassa Vubu (57%), Maluku (54%), Masina (54%) and Mont-Ngafula (39%) mainly consume C. forda and G. jamesonii. Luba and Kongo ethnolinguistic groups mainly consume C. forda while the Swahili and Ngala consume G. jamesonii. Catholic, Revivalist Church, Kimbagu, Islam, Protestant and Johovah's Witness believers mainly consume C. forda and G. jamesonii. This study made it possible to understand the socio-cultural influence on the degradation (pressure) of biodiversity and; contributes to SDGs 2 and 12 by 2023..

The aim of the paper is to provide an overview of the monastic houses operated on the northernmost periphery of Roman Catholic Europe during the Middle Ages. The intention is to debunk the long-held theory of Iceland and Norse Greenland’s supposed isolation from the rest of the world, as it is clear that medieval monasticism reached both of these societies, just as it reached their counterparts elsewhere in the North Atlantic. During the Middle Ages, fourteen monastic houses were opened in Iceland and two in Norse Greenland, all following the Benedictine or Augustinian Order.

This paper presents a numerical algorithm for solving high-order BVPs. We introduce the construction method of multiscale orthonormal basis in W^m[0; 1] by multiscale orthonormal basis in W¹[0; 1]. We define approximate solution, and obtain the approximate solution of high-order BVPs by using the approximate theory. Moreover, the convergence and stability of the algorithm are improved. At last, several numerical experiments show the feasibility of the proposed method.

This paper presents the preservation property of the average intensity order and the preservation property of the monotonic average intensity classes under distorted distributions. Several sufficient conditions are given to get the preservation properties. It is shown that the imposed conditions are achievable as we examine in some examples. The preservation of the average intensity order and the preservation of the decreasing average intensity class under the structure of a parallel system with independent and identically distributed components' lifetime are made. A lower bound for the average intensity function of a random lifetime with an increasing failure rate in average distribution is derived. The results are applied to some semiparametric models as a particular standard family of distorted distribution.

This paper discusses the concept of fractional derivative with complex order from the application point of view. It is shown that a fractional derivative is hermitian, if and only if the order is real. The hermitian part of complex order derivatives behave like allpass filters with almost logarithmic phase.

In this paper we consider a failed cold standby systems and obtain some stochastic bounds on the idle time of such systems. It is assumed that, at a time t the failure of a cold standby system is observed, but the actual time of the failure is a time before t. The idle time of the inactive cold standby system is measured as the time between the exact time of failure, which is a random variable, and time t. We use the idle times of the components of the system to obtain lower and upper bounds on the lifetime of the standby system to which they are assembled. We bring some examples to show that the results and the conditions imposed to get them are achievable.

Background: Most sepsis patients died during their first episode and the long-term survival post discharge was low. Major adverse cardiovascular events and repeated infections were regarded as the major causes in such conditions. No definite medications were proven to effectively improve the long-term outcome. We aimed to examine the benefit of statins on the long-term outcome of survived sepsis patients. Methods: Between 1999 and 2013, a total of 220,082 patients with the first episode of sepsis hospitalization were included and 134,448 ones (61.09%) survived to discharge. The survived patients who subsequently had statins use of >30 cumulative defined daily doses (cDDDs) post discharge were defined as the statin users. After propensity score matching of 1:5, a total of 7,356 and 36,780 survived patients were retrieved as the study (statin-users) and comparison cohort (non-statin users), respectively. The main outcome was the long term survival post discharge. HR with 95% CI was calculated using the Cox regression model to evaluate the effectiveness of statins with further stratification analyses according to cDDDs. Results: The study cohort, that is, the statin users had an adjusted HR of 0.29 (95% CI, 0.27-0.31) in long term mortality rate compared with the comparison cohort. For statin users with the cDDDs of 30–180, 180–365, and >365, the adjusted HRs were 0.32, 0.22, and 0.16, respectively, (95% CI, 0.30-0.34, 0.19-0.26, and 0.12-0.23, respectively) compared with the non-statin users (defined as statins use <30 cDDDs post discharge), and the P for trend <.0001. In the sensitivity analysis, after excluding the survived patients who died within three and six months post discharge, the adjusted HR of statins use remained significant (0.35, 95% CI 0.32-0.37 and 0.42, 95% CI 0.39-0.45, respectively). Conclusions: Statins decreased the long-term mortality post sepsis. Further randomized control trial deserved to be conducted to confirm this observation.

This paper presents the analysis of four error models that can appear in the field of adaptive systems, where adaptive laws for parameter estimation are represented as fractional order differential equations whose order can switch between an order within the range (0,1) and 1. These switched adaptive laws have been proposed in the past few years to improve the balance between control energy and system performance, which is often a challenge when using traditional integer-order or fractional-order adaptive laws in adaptive identification and control. Boundedness of the solutions is proved for all cases, together with the convergence to zero of the estimation/tracking error. Additionally, sufficient conditions for parameter convergence are presented, showing that the excitation condition required for parameter convergence in the vector case is also sufficient for parameter estimation in the matrix case.

The theory of fractional calculus extends the order of classical integer calculus from integer to non-integer. As a new engineering application tool, it has made many important research achievements in many fields, including image processing. This paper mainly studies the application of fractional calculus theory in image enhancement and denoising, including the basic theory of fractional calculus and its amplitude frequency characteristics, the application of fractional differential operator in image enhancement, and the application of fractional integral operator in image denoising. The experimental results show that the fractional calculus theory has more special advantages in image enhancement and denoising. Compared with the existing integer order image enhancement operators, the fractional differential operator can more effectively enhance the "weak edge" and "strong texture" details of the image. The fractional order integral image denoising operator can not only improve the signal-to-noise ratio of the image compared to traditional denoising methods, but also better preserve detailed information such as edges and textures of the image.

W. L. Edge proved that the internal points of a conic in PG(2,5), together with the collinear triples on the non-secant lines, form the Desargues configuration. M. Saniga showed an intimate connection between Desargues configurations and the generalized quadrangles of order two, GQ(2,2), whose representation has been dubbed “the doily” by Stan Payne in 1973. In this paper we prove that the external points of a conic in PG(2,5), together with the collinear and non-collinear triples on the non-tangent lines, form the generalized quadrangle of order two.

In this paper, inspired by recent articles of G. Anatriello and G. Vincenzi (see \cite{Ana}), and G. Cerda-Morales (see \cite{Cer1,Cer2}), we will introduce the third-order $\overline{h}$-Jacobsthal and third-order $\overline{h}$-Jacobsthal--Lucas sequences and their associated quaternions. The new results that we have obtained extend most of those obtained in \cite{Cer2}.

In this paper, we identify several relative ordering properties of the modified proportional hazard rate and modified proportional reversed hazard rate models. For this purpose, we use two well-known relative orderings, namely the relative hazard rate ordering and the relative reversed hazard rate ordering. The investigation is to see how a relative ordering between two possible base distributions for the response distributions in these models is preserved when the parameters of the underlying models are changed. We will give some examples to illustrate the results and the conditions under which they are obtained.

The enhancement of Fusarium head blight (FHB) resistance is one of the best options to reduce mycotoxin contamination in wheat. This study has aimed to verify that the genotypes with high tolerance to deoxynivalenol could guarantee an overall minimization of the sanitary risk, by evaluating the contamination of regulated, modified and emerging mycotoxins on durum wheat cvs with different degrees of FHB susceptibility, grown under different meteorological condi-tions, in 8 growing seasons in North-West Italy. The years which were characterized by frequent and heavy rainfall in spring, were also those with the highest contamination of deoxynivalenol, zearalenone, moniliformin and enniatins. The most FHB resistant genotypes resulted in the lowest contamination of all the mycotoxins but showed the highest deoxyniva-lenol-3-glucoside/deoxynivalenol ratio and moniliformin/deoxynivalenol ratio. An inverse re-lationship between the amount of deoxynivalenol and the deoxyniva-lenol-3-glucoside/deoxynivalenol ratio was recorded for all the cvs and all the years. Converse-ly, the enniatins/deoxynivalenol ratio had a less intense relationship with cv tolerance to FHB. In conclusion, even though the more tolerant cvs, showed higher relative relationships between modified/emerging mycotoxins and native/target mycotoxins than the susceptible ones, they showed lower absolute levels of contamination of both emerging and modified mycotoxins.

In this paper, we first establish upper stochastic bounds on the lifetime of a used cold standby system with arbitrary age, using the likelihood ratio order and the usual stochastic order. Then, stochastic comparisons are made between the lifetime of a used cold standby system with age t and the lifetime of a cold standby system consisting of used components with age t using the likelihood ratio order and the usual stochastic order. We use illustrative examples to explore the results presented.

In this work, we demonstrate that cutting diamond crystals with a laser (532 nm wavelength, 0.5 mJ energy, 200 ns pulse duration at 15 kHz) produces a ≲20nm thick surface layer with magnetic order at room temperature. We have measured the magnetic moment with a SQUID magnetometer of six natural and six CVD diamond crystals of different size, nitrogen content and surface orientations. A robust ferromagnetic response at 300 K is observed only for crystals that were cut with the laser along the (100) surface orientation. The magnetic signals are much weaker for the (110) and negligible for the (111) orientations. We attribute the magnetic order to the disordered graphite layer produced by the laser at the diamond surface. The ferromagnetic signal vanished after chemical etching or after moderate temperature annealing. The obtained results indicate that laser treatment of diamond may pave the way to create ferromagnetic spots at its surface.

I deal with perception and action (e.g. movements) using results from Synergetics, a comprehensive mathematical theory of the selforganized formation ("emergence“) of spatial, temporal, or functional structures in complex systems. I illustrate basic concepts such as order parameters (ops), enslavement, complexity reduction, circular causality first by examples of well known collective, spontaneous modes of human behavior such as rhythmic clapping of hands etc., and then by face recognition. The role played by ops depends on context. In the case of face (or pattern) recognition an op represents the concept of an individual face (action of mind) and it enslaves the action (firing rates) of neurons (body). This insight allows me to interpret syndroms as order parameters playing their mind/body double role. I present criteria for the identification of ops and discuss their general properties including error correction and "remedy“ of deficiencies. Contact is made with a recent paper by Sabine Koch on embodied aesthetics. My approach includes the saturation of attention at various time scales (ambiguous figures/fashion). Adopting a psychological perspective, I discuss some ingredients of beauty such as proportionality and symmetry, but also the importance of irregularities.

In this work, we explore Conjecture 1 proposed in the newly released pioneering paper “Volatility transformers: an optimal transport-inspired approach to arbitrage-free shaping of implied volatility surfaces” by Zetocha Valer, which posits that the “One-X” property is both a necessary and sufficient condition for convex order between non-negative continuous strictly increasing distributions with the same mean. We provide a counterexample demonstrating that the conjecture, as originally stated, does not hold. By examining stochastic orders, particularly the increasing convex order, and the “One-X” property, we propose an enhanced version of the conjecture which is shown to be valid. Furthermore, we discuss the implications of these findings in the context of equity implied volatility fitting and the construction of implied volatility surfaces, highlighting the challenges posed by real-market conditions. In the end, we propose several applications in implied volatility surface construction or simulation.

Due to the nonlinear stiffness and fractional-order damping characteristics of some real suspension systems, coupled with the presence of viscoelastic materials, fractional-order nonlinear suspension system modeling has become a focus of research in recent years. In this study, an electric oil and gas actuator based on fractional-order PID position feedback control is proposed, through which the damping coefficient of the suspension system is adjusted to realize the active control of the suspension. A fractional order PID algorithm is used to control the motor's rotational angle to realize the damping adjustment of the suspension system. In this process, the road roughness is collected by the sensors as the criterion of damping adjustment, and the particle swarm algorithm is utilized to find the optimal objective function under different road surface slopes, to obtain the optimal cornering value. According to the mathematical and physical model of the suspension system, the simulation model and the corresponding test platform of this type of suspension system are built. The simulation and experimental results show that the simulation results of the fractional-order nonlinear suspension model are closer to the actual experimental values than those of the traditional linear suspension model, and the accuracy of each performance index is improved by more than 18.5%. The designed active suspension system optimizes the body acceleration, suspension dynamic deflection, and tire dynamic load to 89.8%, 56.7%, and 73.4% of the passive suspension, respectively. Notably, the designed fractional order PID control circuit for the motor shows better control results compared to the conventional PID control circuit. This study provides an effective theoretical and empirical basis for the control and optimization of fractional-order nonlinear suspension systems.

We investigated the dynamics of a simple master equation describing the evolution of a probability distribution between two states, \( p_1 \) and \( p_2 \) (with \( p_1 + p_2 = 1 \)). Our focus is on the behavior of the entropy \( S \), the distance \( D \) from the uniform distribution (\( p_1 = p_2 = 1/2 \)), and the free energy \( F \). We define two ratios, \( \eta_S = \frac{dS/dt}{dF/dt} \) and \( \eta_D = \frac{dD/dt}{dF/dt} \), and find that both diverge to plus-minus infinity as the system evolves towards the uniform distribution. This divergence marks a critical transition point where the master equation temporarily loses physical meaning. However, after this divergence, the system settles into a new, well-behaved regime where the solutions stabilize at finite values, representing a new equilibrium or steady state. This two-regime behavior underscores the intricate dynamics of simple probabilistic systems as they approach and surpass equilibrium, providing insights into the complex interplay of entropy, distance, and free energy in statistical mechanics.

The manufacturing geometrical variability in axial compressors is a stochastic source of uncertainty, implying that the real geometry differs from the nominal design. This causes the real geometry to lose the ideal axial symmetry. Considering the aerofoils of a stator vane, the geometrical variability affects the flow traversing it. This impacts the downstream rotor, especially when considering the aeroelastic excitation forces. Optical surface scans coupled with a parametrization method allow for acquiring the information relative to the real aerofoils geometries. The measured data are included in a multi-passage and multi-stage CFD setup to represent the mistuned flow. In particular, low excitation harmonics on the rotor vane are introduced due to the geometrical deviations of the upstream stator. The introduced low engine orders as well as their amplitude depend on the stator geometries and their order. A method is proposed to represent the phenomena in a reduced CFD domain, limiting the size and number of solutions required to probabilistically describe the rotor excitation forces. The resulting rotor excitation forces are reconstructed as a superposition of disturbances due to individual stator aerofoils geometries. This indicates that the problem is linear in in the combination of disturbances from single passages.

This work is intended to lead a study of necessary and sufficient optimality conditions for scalar optimization problems on Hadamard manifolds. In the context of this geometry, we obtain and present new function types characterized by the property of having all their second-order stationary points to be global minimums. In order to do so, we extend the concept convexity in Euclidean space to a more general notion of invexity on Hadamard manifolds. This is done employing notions of second-order directional derivative, second-order pseudoinvexity functions and the second-order Karush-Kuhn-Tucker-pseudoinvexity problem. Thus, we prove that every second-order stationary point is a global minimum if and only if the problem is either second-order pseudoinvex or second-order KKT-pseudoinvex depending on whether the problem regards unconstrained or constrained scalar optimization respectively. This result has not been presented in the literature before. Finally, examples of these new characterizations are provided in the context of \textit{"Higgs Boson like"} potentials among others.

In the present study, nonlinear vibration of a nanobeam resting on fractional order viscoelastic Winkler-Pasternak foundaion is studied using nonlocal elasticity theory. D'Alembert principle is used to derive the governing equation and the associated boundary conditions. The approximate analytical solution is obtained by applying the multiple scales method. Detailled parametric study is conducted, the effects of variation in different parameters belonging to the application problems on the system are calculated numerically and depicted. We remark that the order and the coefficient of the fractional derivative have significant effect on the natural frequency and the amplitude of vibrations

Background: Amyloid beta peptides (Aβ) have been identified as the main pathogenic agents in Alzheimer’s disease (AD). Soluble Aβ oligomers, rather than monomer or insoluble amyloid fibrils, show membrane-binding capacity to red blood cells (RBCs) and trigger several morphological and functional alterations in RBCs that can result in impaired oxygen transport and delivery. Since bioactive lipids have been recently proposed as potent protective agents against Aβ toxicity, we investigated the role of sphingosine-1-phosphate (S1P) in signaling pathways involved in the mechanism underlying ATP release in Aβ-treated RBCs. Methods: In RBCs following different treatments, ATP, 2,3 DPG, cAMP levels, and caspase 3 activity were determined by spectrophotometric and immunoassay. Results: S1P rescued the inhibition of ATP release from RBCs triggered by Aβ through a mechanism involving caspase-3 and restoring 2,3 DPG and cAMP levels within the cell. Conclusions: These findings reveal the molecular basis of S1P protection against Aβ in RBCs and suggest new therapeutic avenues in AD.

This work addresses the problem of automatic head pose estimation and its application in 3D gaze estimation using low quality RGB--D sensors without any subject cooperation or manual intervention. The previous works on 3D head pose estimation using RGB--D sensors require either an offline step for supervised learning or 3D head model construction which may require manual intervention or subject cooperation for complete head model reconstruction. In this paper, we propose a 3D pose estimator based on low quality depth data, which is not limited by any of the aforementioned steps. Instead, the proposed technique relies on modeling the subject's face in 3--D rather than the complete head, which in turn, relaxes all of the constraints with the previous works. The proposed method is robust, highly accurate and fully automatic. Moreover, it does not need any offline step. Unlike some of the previous works, the method only uses depth data for pose estimation. The experimental results on the Biwi head pose database confirm the efficiency of our algorithm in handling large pose variations and partial occlusion. We also evaluate the performance of our algorithm on IDIAP database for 3D head pose and eye gaze estimation.

Build a special identical equation, use its calculation characters to prove and search for solution of any odd converging to 1 equation through (*3+1)/2^k operation, change the operation to (*3+2^m-1)/2^k, and get a solution for this equation, give a specific example to verify. Thus prove the Collatz Conjecture is true. Furthermore, analysis the sequences produced by iteration calculation during the procedure of searching for solution, build a weight function model, prove it decrease progressively to 0, build a complement weight function model, prove it increase to its convergence state. Build a (*3+2^m-1)/2^k odd tree, prove if odd in (*3+2^m-1)/2^k long huge odd sequence can not converge, the sequence must outstep the boundary of the tree after infinite steps of (*3+2^m-1)/2^k operation.

Despite the technological advancements of 3-D city models, the 3-D shape abstraction methods for urban vegetation are recent and still limited to support spatial analysis of individual or groups of trees and forest patches. In this paper, a scheme for individual urban tree abstraction, which retains the semantic complexity of the object, is proposed. Our contribution is three-fold. First, an initial tree structure based on a new 3-D aggregation operator is proposed. Second, we developed Gestalt rules for 3-D urban vegetation mapping. Third, current state-of-the-art deep learning is adapted for the abstraction of individual urban trees. Quantitative and qualitative results show the effectiveness of our proposed approach in accurately reducing the spatial density of trees and the degree of fragmentation of the total green area, which can access information about the location, size, and spatial distribution of mapped urban trees.

In this research article we solve the problem of synchronization and anti-synchronization of chaotic systems described by discrete and time-delayed variable fractional order differential equations. To guarantee the synchronization and anti-synchronization of these systems, we use the well-known PID control theory and the Lyapunov-Krasovskii stability theory for discrete systems of variable fractional order.We illustrate the results obtained through simulation with examples, in which it can be seen that our results are satisfactory, thus achieving synchronization and anti-synchronization of chaotic systems of variable fractional order with discrete time delay.

Ageing is associated with a decline in both Nrf2 activity and DNA repair efficiency, leading to the accumulation of DNA damage and an increased risk of cancer. Understanding the mechanisms behind the increased level of damaged DNA during ageing is crucial for developing interventions to mitigate age-related cancer risk and improve overall health in older individuals. (Poly)phenols are plant-derived bioactive compounds that undergo metabolism into simpler phenolic catabolites following ingestion. While these compounds have been associated with various health benefits, further analysis of their bioavailable catabolites is necessary. To this end, four phenolic catabolites derived from colonic microbiota were investigated for their ability to reduce DNA damage in response to oxidative challenge and modulate the Nrf2-Antixoidant Response Element pathway. Normal and adenocarcinoma colonocyte cell lines (CCD 841 CoN, & HT29 respectively) were exposed to sub cytotoxic concentrations (>10 µM,) of hydroxylated (4-hydroxybenzoic acid, 3-(3’-hydroxyphenyl) propionic acid) and non-hydroxylated (benzoic acid or 3-phenylpropionic acid) phenolic acids. Using the COMET assay, each catabolite demonstrated significant (p<0.001) geno-protective activity, albeit with varying potency. They also significantly modulated expression of key genes in the Nrf2-ARE pathway, including Nrf2, Heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1). Hydroxylation of the phenolic acids appeared to have a limited effect with respect to bioactivity. Overall, the colon derived phenolic metabolites, when assessed at physiologically relevant concentrations, reduced DNA damage in both normal and adenocarcinoma colonic cells in response to oxidative challenge, mediated – at least in part via upregulation of the Nrf2-ARE pathway.

This article introduces a novel two-step fifth-order Jacobian-free iterative method aimed at efficiently solving systems of nonlinear equations. The method leverages the benefits of Jacobian-free approaches, utilizing divided differences to circumvent the computationally intensive calculation of Jacobian matrices. This adaptation significantly reduces computational overhead and simplifies the implementation process while maintaining high convergence rates. We demonstrate that this method achieves fifth-order convergence under specific parameter settings, with a broad applicability across various types of nonlinear systems. The effectiveness of the proposed method is validated through a series of numerical experiments which confirm its superior performance in terms of accuracy and computational efficiency compared to existing methods.

The experimental realization of twisted bilayer graphene strongly pushed the inspection of bilayer systems. In this context, it was recently shown that a two layer Haldane model with a thirty degree rotation angle between the layers represents a higher order topological insulator, with zero-dimensional states isolated in energy and localized at the physical vertices of the nanostructure. We show, within a numerical tight binding approach, that the energy of the zero dimensional states strongly depends on the geometrical structure of the vertices. In the most extreme cases, once a specific band gap is considered, these bound states can even disappear just by changing the vertex structure.

The beautiful structures of single and multi-domain proteins are clearly ordered in some fashion but cannot be readily classified using group theory methods that are successfully used to describe periodic crystals. For this reason, protein structures are considered to be aperiodic, and may have evolved this way for functional purposes, especially in instances that require a combination of softness and rigidity within the same molecule. By analyzing the solved protein structures, we show that orientational symmetry is broken in the aperiodic arrangement of the secondary structural elements (SSEs), which we deduce by calculating the nematic order parameter, $P_2$. We find that the folded structures are nematic droplets with a broad distribution of $P_2$. We argue that non-zero values of $P_2$, leads to an arrangement of the SSEs that can resist mechanical forces, which is a requirement for allosteric proteins. Such proteins, which resist mechanical forces in some regions while being flexible in others, transmit signals from one region of the protein to another (action at a distance) in response to binding of ligands (oxygen, ATP or other small molecules).

The Aβ cascade and alternations of biomarkers in neuro-inflammation, synaptic dysfunction and neuronal injury followed by Aβ have progressed. But the question is how to use the biomarkers. Here, we examine the evidence and pathogenic implications of protein interactions and the time order of alternation. After the deposition of Aβ, the change of tau, NfL and NG is the main alternation and connection to others. The neuro-inflammation, synaptic dysfunction and neuronal injury function is exhibited prior the structural and metabolic changes in the brain following Aβ deposition. The time order of such biomarkers compared to the tau protein is not clear. Despite the close relationship between biomarkers and plaque Aβ deposition, several factors favor one or the other. There is an interaction between the proteins that CSF SNAP-25, VILIP-1 and YKL-40 can predict the brain amyloid burden. The Aβ cascade hypothesis could be the pathway, but not all subjects are converted to AD, even with very high elevated Aβ. The interaction of biomarkers and the time order of change require further research to identify the right subjects and right molecular target for precision medicine therapies.

The study of order patterns of three equally spaced values $x_t,x_{t+d},x_{t+2d}$ in a time series is a powerful tool. The lag $d$ is changed in a wide range so that differences of frequencies of order patterns become autocorrelation functions. Similar to a spectrogram in speech analysis, four ordinal autocorrelation functions are used to visualize big data series, as for instance heart and brain activity over many hours. The method applies to real data without preprocessing, outliers and missing data do not matter. On the theoretical side, we study properties of order correlation functions and show that the four autocorrelation functions are orthogonal in a certain sense. An analysis of variance of a modified permutation entropy can be performed with four variance components associated with the functions.

The commonly quoted bistable Higgs potential is not a proper description of the Higgs field because, among other technical reasons, one of its stable states acquires a negative expectation value in vacuum. We rely on formal catastrophe theory to derive the form of the Higgs potential that admits only one positive mean value in vacuum. No symmetry is broken during the ensuing phase transition that assigns mass to the Higgs field; only gauge redundancy is “broken” by the appearance of phase in the massive state, but this redundancy is not a true symmetry of the massless field. Furthermore, a secondary, certainly amusing conclusion is that, in its high-energy state, the field oscillates about its potential minimum between positive and negative masses; but it is doubtful that such evanescent states can survive below the critical temperature of 159.5 GeV, where the known particles were actually created.

IntroductionGlycogen synthase kinase 3 (GSK-3) has been associated with a lot of diseases, such as Alzheimer’s Disease and diabetes. Its role in depression is connected to stress and neuroinflammation. Lithium is an essential inhibitor of GSK-3. Some studies have suggested that the use of this psychiatric medication may lower suicide rates. Here, we outline the current understanding and discoveries regarding the link between GSK-3 and suicide. MethodWe used the PRISMA statement and defined the PECOS strategy, such as Population (P) = individuals; exposure (E) = GSK-3 alteration function; comparison (C) = without GSK-3 alteration function; outcome (O) = suicide; and study design(S) = all kinds of studies with an association between GSK-3 and suicide.ResultsTwelve studies were included in this review. GSK-3 appears to be related to suicidal behavior by activating inflammatory pathways, activating genes, altering neurotransmission, and increasing impulsivity. Clinical studies do not present robust results that allow defining an epidemiological profile of greater risk for suicidal behavior in association with changes in the functioning of GSK-3.ConclusionThe interference of GSK-3 functioning in suicidal behavior seems inevitable, with solid evidence from laboratory animal studies. However, there is a need for further clinical studies on this crucial topic to answer better some questions about the association between GSK-3 and suicide.

Spinocerebellar ataxia type 3 is a neurodegenerative disease caused by an abnormal expansion of CAG repeats in the disease gene ATXN3, leading to prolonged polyglutamine (polyQ) tracts in the respective protein ataxin-3. The polyQ-expanded protein forms polyQ-containing aggregates in several brain regions which leads to neuronal cell loss. Autophagy is thought to play a significant role in clearing these polyQ-containing protein aggregates. Therefore, the autophagy mechanism was investigated in SCA3 with focus on the autophagic protein p62/sequestosome-1. Human and mouse RNA sequencing data were analyzed to determine RNA expression level of autophagic genes. Additionally, autophagy was studied in the SCA3 304Q knock-in mouse model and through several cell culture experiments using HEK-293T cells transfected with ATXN3 of differ-ent polyQ lengths. For cell culture experiments, autophagy was induced with rapamycin treat-ment, proteasomal degradation was blocked with MG132 and degradation of autophagic pro-teins was investigated using cycloheximide treatment. Here, we report an increased autophagy impairment with SCA3 disease progression seen in HEK-293T cells transfected with ATXN3 plasmid with expanded polyQ tracts, higher aged 304Q-knock-in mice, or human post-mortem brain material. Furthermore, co-localized aggregation of the autophagic protein p62 and the dis-ease protein ATXN3 was observed in the course of SCA3 disease. Therefore, we suggest a signifi-cant role for p62 in aggregate formation seen in the neurodegenerative disease SCA3.

To understand the biological relevance and mode of action of artificial protein ligands, crystal structures with their protein targets are essential. Here, we describe and investigate all known crystal structures that contain a so-called “molecular tweezer” or one of its derivatives with an attached natural ligand on the respective target protein. The aromatic ring system of these compounds is able to include lysine and arginine side chains, supported by one or two phosphate groups that are attached to the half-moon shaped molecule. We analyse the corresponding crystal structures with 14-3-3 proteins in complex with mono- and diphosphate tweezers. Furthermore, we solved crystal structures of two different tweezer variants in complex with the enzyme 1-Pyrroline-5-carboxyl-dehydrogenase (P5CDH), and found that the tweezers are bound to a lysine and methionine side chain, respectively. The different binding modes and their implications for affinity and specificity are discussed, as well as the general problems in crystallizing protein complexes with artificial ligands.

For Interferometry Synthetic Aperture Radar (InSAR), the normal baseline is one of the main factors that affect the accuracy of the ground elevation. For Gaofen-3 (GF-3) InSAR processing, the poor accuracy of the real-time orbit determination resulting in a large baseline error, leads to the modulation error in azimuth and the slope error in range for timely Digital Elevation Model (DEM) generation. In order to address this problem, a baseline estimation method based on external DEM is proposed in this paper. Firstly, according to the characteristic of the real-time orbit of GF-3 images, orbit fitting is executed to remove the non-linear error factor. Secondly, the height errors are obtained in slant-range plane between Shuttle Radar Topography Mission (SRTM) DEM and the GF-3 generated DEM after orbit fitting. At the same time, the height errors are used to estimate the baseline error which has a linear variation. In this way, the orbit error can be calibrated by the estimated baseline error. Finally, DEM generation is performed by using the modified baseline and orbit. This procedure is implemented iteratively to achieve a higher accuracy DEM. Based on the results of GF-3 interferometric SAR data for Hebei, the effectiveness of the proposed algorithm is verified and the accuracy of GF-3 real-time DEM products can be improved extensively.

This paperfocusesontheoscillatorypropertiesofthesemi-canonicalnonlineardelaydifferential equation ofthird-order (δ2(t)(δ1(t)ζ′(t))′)′ + η(t)ζα(τ(t))= 0, t ≥ t0, under theconditions ∞t01δ2(t)dt = ∞ andZ ∞t01δ1(t)dt < ∞. Using the new canonical transform method, we transformed the studied equation into a canonical type equation and then we find the conditions for the oscillation of the studied equation from the canonical equations. The obtained results are new and complement to the existing results mentioned in the literature. Examples are provided to illustrate the importance and novelty of the main results.

Understanding the contribution of protected areas to pollinating insect conservation is crucial, especially in Haiti because of intense deforestation and environmental degradation. We compared pollinating insect assemblage composition and abundance in two protected areas: the suburban Wynne Farm Ecological Reserve (WFER) and the Urban National Park of Martissant (UNPM). Both sites encompass forest patches, agroforestry, and agricultural crops. Using colored pan-traps, we collected 3722 insects from six Orders, with 68.2% identified to family level due to taxonomic limitations. WFER exhibited significantly higher insect abundance than UNPM, though habitat differences varied between sites. Site, habitat, and their interaction significantly influenced insect composition. Among 118 identified families, only 30.51% were shared between sites. Our data suggest combined protection offers broader and more even insect diversity. We discovered patrimonial lepidopteran and hymenopteran species previously unrecorded in Haiti, emphasizing the importance of protected areas and the need for enhanced entomological expertise.

This paper presents an observer-based dynamic output feedback controller design procedure using Linear Matrix Inequality (LMI) optimization for second-order systems with uncertainty and persistent perturbation in the states. Using linear-quadratic criteria, cost functions are minimized in a two-stage procedure to compute optimal state feedback gains, and observer gains are coupled into a dynamic output feedback optimal controller. The LMI set used in the two stages is matrix inversion-free, a key issue for polytope formulation when uncertainty is present. The approach is tested in a mobile inverted pendulum robotic platform, and the effectiveness is verified in this underactuated and undesensed case.

The photodegradation of azithromycin present was carried out in water using H2O2 under UV irradiation. The reaction variables considered in this study were the amount of H2O2 solution and the initial concentration of azithromycin to evaluate the performance of the photodegradation process. The azithromycin degradation was not observed in the dark during stirring for 20 minutes. The study showed efficient photodegradation of azithromycin using H2O2 as an oxidant in the presence of UV irradiation. The azithromycin degradation was affected significantly by the pH of the irradiated solution. The degradation was low at an acidic pH and showed an increasing trend as the pH changed to basic. The azithromycin degradation was increased with a higher amount (higher concentration) of H2O2. The degradation of azithromycin decreased with a higher concentration of azithromycin in the reacting solution. The highest degradation of AZT was achieved in 1 hour using a 1.0 ppm AZT solution containing 3 ml of H2O2. The experimental data obtained was well-fitted to zero-order reaction kinetics. The results of this study were found to be superior when compared with those reported in the literature, with photocatalysis using nanomaterials and photolysis using irradiation and H2O2. The UV/H2O2 system was found to be quite efficient for the photodegradation of azithromycin, and this system can be applied to degrade other organic pollutants present in industrial wastewater. To this point, such a study has not been reported specifically for AZT photodegradation.

On-chip integration of two-dimensional (2D) materials with unique structures and distinctive properties endow integrated devices with new functionalities and improved performance. With a high flexibility in modifying its properties and a strong compatibility with various integrated platforms, graphene oxide (GO) becomes an attractive 2D material for implementing functional hybrid integrated devices. Here, we demonstrate novel functionalities that go beyond the capabilities of conventional photonic integrated circuits, by harnessing the photo-thermal effects in 2D GO films integrated onto them. These include all-optical control and switching, optical power limiting, and non-reciprocal light transmission. The 2D layered GO films are on-chip integrated with precise control of their thicknesses and sizes. Benefitting from the broadband response of 2D GO films, all the three functionalities feature a very wide operational bandwidth. By fitting the experimental results with theory, we also extract the changes in material properties induced by the photo-thermal effects, which reveal interesting insights about 2D GO films. These results highlight the versatility of 2D GO films in implementing functional integrated photonic devices for a range of applications.

In this article, an iterative method of two step is proposed for finding all roots simultaneously of polynomial equations. The order of convergence of the proposed algorithm is 2m, by using any iterative scheme of order m. Numerical tests are performed to confirm the theoretical results and to compare the proposed scheme with existing methods for finding all roots simultaneously.

This article introduces a new fractional approach to the concept of information dimension of complex networks, based on a (q,q′)-entropy proposed in the literature. The q parameter measures how far is the number of subsystems (for a given size ε) from the mean number of overall sizes. The q′ (interaction index) measures when the interactions between subsystems are greater (q′&gt;1), lesser (q′&lt;1) or equal to the interactions into these subsystems. The computations of the proposed information dimension are carried out on several real-world and synthetic complex networks. The results from the proposed information dimension are compared with those from the information dimension based on the Shannon entropy.

Reading is a complex cognitive task involving processes from different systems. The present work aims to identify some points of divergence reported in the reading literature and discuss them in a new experimental paradigm framework. Inspired by the paradigms of perceptual identification and rapid parallel presentation (RPVP), we emphasize that the originality of our experimental paradigm lies in the recruitment of multi-stable Arabic percepts within the region where low-level processing occurs (i.e., the visual span area). With good flexibility, the current paradigm has reached higher-order processing levels. In agreement with previous works highlighting the parafoveal-on-foveal effect, results suggest parallel word processing. Furthermore, they suggest a rapid extraction of syntactic and semantic information from words in sentences while attributing an advantage to semantic processing in the emergence of the sentence superiority effect.

As various services have been generating large scale graphs to represent multiple relationships between objects, studies have been conducted to obtain subgraphs with particular patterns. In this paper, we propose a distributed query processing method to efficiently search a subgraph for a large graph on Spark. To reduce unnecessary processing costs, the search order is determined by filtering scores using the probability distribution. The partitioned queries are searched in parallel in the distributed graph of each slave node according to the search order, and the local search results obtained from each slave node are combined and returned. The query is partitioned in triplets based on the determined search order. The performance of the proposed method is compared with the performance of existing methods to demonstrate its superiority.

All-optical signal processing based on nonlinear optical devices is promising for ultrafast information processing in optical communication systems. Recent advances in two-dimensional (2D) layered materials with unique structures and distinctive properties have opened up new avenues for nonlinear optics and the fabrication of related devices with high performance. This paper reviews the recent advances in research on third-order optical nonlinearities of 2D materials, focusing on all-optical processing applications in the optical telecommunications band near 1550 nm. First, we provide an overview of the material properties of different 2D materials. Next, we review different methods for characterizing the third-order optical nonlinearities of 2D materials, including the Z-scan technique, third-harmonic generation (THG) measurement, and hybrid device characterization, together with a summary of the measured n₂ values in the telecommunications band. Finally, the current challenges and future perspectives are discussed.

We make use of generalized iterations of the Sacks forcing to define cardinal-preserving generic extensions of the constructible universe L in which the axioms of ZF hold and in addition either 1) the parameter-free countable axiom of choice AC* fails, or 2) AC* holds but the full countable axiom of choice AC fails in the domain of reals. In another generic extension of L, we define a set X⊆P(ω), which is a model of the parameter-free part PA2* of the 2nd order Peano arithmetic PA2, in which CA(Σ21) (Comprehension for Σ21 formulas with parameters) holds, yet an instance of Comprehension CA for a more complex formula fails. Treating the iterated Sacks forcing as a class forcing over $L_{\omega_1}$, we infer the following consistency results as corollaries. If the 2nd order Peano arithmetic PA2 is formally consistent then so are the theories: 1) PA2 + negation of AC*, 2) PA2 + AC* + negation of AC, 3) PA2* + CA(Σ21) + negation of CA.

A novel phase-field method based numerical approach to modeling the compaction process of sedi- ments is presented. Water-logged rock or soil sediments are deposited on the water basins over time and the increasing volume of the sediment compacts under its own weight and external pressure. Coupled evolution of mass conservation, Darcy flow, and the viscoelastic constitutive response, in conjunction with the evolution of porosity and permeability, make this problem highly non-linear and involve moving boundaries. We adopt a phase-field approach to represent the moving sediment interface, and the underlying multiphasic model permits for studying compaction in dynamically evolving sediments. This approach does not necessitate a change of domain sizes as is the case of existing traditional models of sedimentation but rather treats sedimentation growth as a problem of interface motion. We first model a classical compaction problem in 1D to compare with existing results in the literature, and then extend the framework to 2D to model the compaction process taking place under the influence of gravity. The model is then extensively applied to understand the effect of the sediment initial state and the sediment material properties on the compaction process and its spatiotemporal evolution. Lastly, a strong validation of our phase-field treatment results against predictions from traditional methods of solving open boundary sediment compaction problems, and a good agreement between the conventional understanding and the numerical predictions of porosity dependence on the fluid pore pressure for various cases of geological interest, are used to demonstrate the applicability and scalability of this novel numerical framework to model more advanced sediment compaction problems and geometries.

COVID-19 outbreak started in the Chinese city of Wuhan and spread around the globe in months due to its high contagious level. Hence, this disease posed a great challenge to researchers and mathematicians. Numerous mathematical models have been suggested to visualize the spreading speed and trends of this pandemic. In this paper, a comparison of a widely established and accepted method, the Susceptible-Exposed-Infected-Quarantined-Recovered-Death-Insusceptible (SEIQRDP) model with a newly-proposed fractional-order SEIQRDP is studied. Densely populated Countries of Asia (Pakistan, India, and Bangladesh) have been chosen as data sets and both algorithms have been applied to their data. The same comparison technique has also been used on the data of two polar countries, New Zealand and Russia, that validated our findings. Error comparison of both algorithms has been recorded in a tabulated form which shows multi-fold erroneous trends over WHO data of selected countries.

This paper proposes a forecast-centric adaptive learning model that engages with the past studies on the order book and high-frequency data, with applications to hypothesis testing. In line with the past literature, we produce brackets of summaries of statistics from the high-frequency bid and ask data in the CSI 300 Index Futures market and aim to forecast the one-step-ahead prices. Traditional time series issues, e.g. ARIMA order selection, stationarity, together with potential financial applications are covered in the exploratory data analysis, which pave paths to the adaptive learning model. By designing and running the learning model, we found it to perform well compared to the top fixed models, and some could improve the forecasting accuracy by being more stable and resilient to non-stationarity. Applications to hypothesis testing are shown with a rolling window, and further potential applications to finance and statistics are outlined.

We discuss the role of the opposing principles of order and disorder in physical and biological systems in determining stability, growth and evolution and bring forth the potential role of a cosmic ordering agency. We analyze its role in decreasing entropy by coarse-graining and hence in determining the initial low entropy state of the big bang universe. Since all physical and biological systems have either cycles of order and disorder alternating, or may have chaotic evolution with non-linear laws, the same is expected of the dynamics of the whole universe as well. The entropy of the initial state of the universe could be low because of the reduction of degrees of freedom (DoF) as one moves from physical encoding to neural encoding and then on to psychic encoding of information in a nested manner by coarse-graining. It is by such encoding that this cosmic agency enables the universe to pass through the big crunch phase and then rolls it out as the big bang universe from the initial state of low entropy.

A classical origin for the Bohmian quantum potential, as that potential term arises in the quantum mechanical treatment of black holes and Einstein-Rosen (ER) bridges, can be based on 4th-order extensions of Einstein's equations. In Bohm's ontological interpretation, black hole radiation, and the analogous tunneling process of quantum transmission through an ER bridge, are classically allowed if the dynamics are modified to include such a quantum potential. The 4th-order extension of general relativity required to generate the quantum potential is given by adding quadratic curvature terms with coefficients that maintain a fixed ratio, as their magnitudes approach zero. Quantum transmission through the classically non-traversable bridge is replaced by classical transmission through a traversable wormhole. If entangled particles are connected by a Planck-width ER bridge, as conjectured by Maldacena and Susskind, then the classical wormhole transmission effect gives the ontological nonlocal connection between the particles posited in Bohm's interpretation of their entanglement. It is hypothesized that higher-derivative extensions of classical gravity can account for the nonlocal part of the quantum potential generally.

A probabilistic description is essential for understanding the dynamics of stochastic systems far from equilibrium, given uncertainty inherent in the systems. To compare different Probability Density Functions (PDFs), it is extremely useful to quantify the difference among different PDFs by assigning an appropriate metric to probability such that the distance increases with the difference between the two PDFs. This metric structure then provides a key link between stochastic systems and information geometry. For a non-equilibrium process, we define an infinitesimal distance at any time by comparing two PDFs at times infinitesimally apart and sum these distances in time. The total distance along the trajectory of the system quantifies the total number of different states that the system undergoes in time, and is called the information length. By using this concept, we investigate the information geometry of non-equilibrium processes involved in disorder-order transitions between the critical and subcritical states in a bistable system. Specifically, we compute time-dependent PDFs, information length, the rate of change in information length, entropy change and Fisher information in disorder-to-order and order-to-disorder transitions, and discuss similarities and disparities between the two transitions. In particular, we show that the total information length in order-to-disorder transition is much larger than that in disorder-to-order transition, and elucidate the link to the drastically different evolution of entropy in both transitions. We also provide the comparison of the results with those in the case of the transition between the subcritical and supercritical states and discuss implications for fitness.

Breast cancer develops upon sequential acquisition of driver mutations in mammary epithelial cells; however how these mutations collaborate to transform normal cells remains unclear in most cases. We aimed to reconstitute this process in a particular case. To this end, we combined the activated form of the PI 3-kinase harboring the H1047R mutation with the inactivation of the histone lysine methyl-transferase KMT2D in the non-tumorigenic human mammary epithelial cell line MCF10A. We found that PI 3-kinase activation promoted cell cycle progression, especially when growth signals were limiting, as well as cell migration, both in a collective monolayer and as single cells. Furthermore, we showed that KMT2D inactivation had relatively little influence on these processes, except for single cell migration that KMT2D inactivation promoted in synergy with PI 3-kinase activation. Combination of these two genetic alterations induced expression of the ARPC5L gene that encodes a subunit of the Arp2/3 complex. ARPC5L depletion fully abolished the enhanced migration persistence exhibited by double-mutant cells. Our reconstitution approach in MCF10A has thus revealed both the cell function, single cell migration, and the underlying Arp2/3-dependent mechanism, which are synergistically regulated when KMT2D inactivation is combined with the activation of the PI 3-kinase.

Among cross-sectional imaging modalities, computed tomography (CT) is more available and faster; however, magnetic resonance (MR) performs better in terms of sensitivity and specificity, due to its higher contrast resolution. The appearance of peritoneal deposits on CT and MR depends mainly on the primary tumour histology: in case of unknown primary tumour (3-5% of cases), their behaviour at imaging may provide insights on the tumour origin. The time-point of tumour evolution, previous or ongoing treatments and the peritoneal spaces where they occur, also play an important role in determining the appearance of peritoneal deposits. Thus, knowledge of peritoneal anatomy and fluid circulation is mandatory in detection and characterization of peritoneal deposits. Several benign and malignant conditions may show similar imaging features that overlap those of PC, making the differential diagnosis challenging. Clinical history, laboratory findings and previous imaging examinations must be considered to achieve the correct diagnosis.

Cellulose nanocrystals (CNCs) are a kind of nano-inclusions that have experienced tremendous expansion in the material industry due to their outstanding mechanical qualities, sizable surface area, and capacity for functional tuning. Due to their vast potential, however, present practises fall short of fully using them. For example, employing CNCs in various matrices with various surface chemistries can be challenging; this problem tends to get worse if the focus is furthered on bio-based applications. This paper reviews the use of CNCs as fillers in natural and man-made polymers; we have explored in depth the production, characterisation, and of CNCs from various sources and their inclusion into various matrices. Surface alterations and the introduction of CNCs in biodegradable polymer can have a significant impact on several industrial behemoths such as tissue engineering and biomedical applications; therefore, pursue of current manuscript is extremely warranted. Throughout the manuscript various assembly techniques that involves alteration and adjustment of polymer network in building up a hydrogel with higher fracture energy and mechanical properties are also included. From rheological perspective the hydrogel processing is also discussed with some models routinely used in the literature to describe these hydrogels. Finally, bio-based hydrogels mechanically reinforced with CNCs such as Xanthan Gum, Alginate, protein, and polysaccharides were discussed.

Background: Monoclonal antibodies against PD-1 or PD-L1 are established in clinical practice for the treatment of both early and advanced/metastatic triple-negative breast cancer. Beyond the established immune checkpoints (ICPs) (PD-1 and CTLA-4) additional ICPs such as lymphocyte activation gene-3 (LAG-3) are subject of current research. In the present retrospective gene ex-pression analysis, we evaluated the prognostic significance of LAG-3 in 461 patients with early breast cancer. In addition, we examined whether there was a correlation between the different ICPs and CD8 expression. Methods: Using microarray-based gene expression analysis, we examined the prognostic signif-icance for metastasis-free survival (MFS) of LAG-3 mRNA expression in the whole cohort of 461 breast cancer patients and among different molecular subtypes. Correlations were analyzed us-ing Spearman-Rho correlation coefficient. Results: In the whole cohort, LAG-3 expression had no significant impact on MFS (p = 0.712, Log Rank). In the subgroup analyses, there was a trend, that higher LAG-3 expression was associated with favorable outcome in the luminal B (p = 0.217), basal-like (p = 0.370) and HER2 (p = 0.089) subtypes, although significance was not reached. In contrast, in multivariate Cox regression analysis adjusted for age, tumor size, axillary nodal status, histological grade of differentiation and the proliferation marker Ki-67, LAG-3 showed a significant influence on MFS (HR 0.574; 95% CI 0.369–0.894; p = 0.014). High LAG-3 significantly correlated with CD8 ( = 0.571; p < 0.001). Conclusion: LAG-3 expression had an independent impact on MFS. In addition to PD-1 and PD-L1, further immune checkpoints such as LAG-3 could serve as therapeutic targets in breast cancer.

Salivarian trypanosomes are extracellular parasites causing anthroponotic and zoonotic infections. Anti-parasite vaccination in considered the only sustainable method for global trypanosomosis control. Unfortunately, not a single field applicable vaccine solution has been successful so far. Active destruction of the host’s adaptive immune system by trypanosomes is believed to contribute to this problem. Here we show Trypanosome brucei brucei infection results in the lasting obliteration of immunological memory, including vaccine-induced memory against non-related pathogens. Using the well-established DTPa vaccine model in combination with a T. b. brucei infection and diminazene diaceturate anti-parasite treatment scheme, our result demonstrate that while the latter ensured the full recovery from the T. b. brucei infection, it failed to restore an efficacious anti-pertussis vaccine recall response. DTPa vaccine failure coincided with a shift in the IgG1/IgG2a anti-pertussis antibody ratio in favor of the latter, and a striking impact on all spleen immune cell populations. Interestingly, an increased plasma IFNy level in DTPa vaccinated trypanosome infected mice did result in a temporary antibody-independent improvement of early-stage trypanosomosis control. In conclusion, our results are the first to show that trypanosome inflicted immune damage is permanent, and is not restored by successful anti-parasite treatment.

NS-3 is one of the most used Network Simulators because it includes different modules, applications and protocols to simulate a wide range of network. Since new proposals usually involve a large number of simulations, a procedure to automatize the simulation process and extract statistics is very useful. "Statistical Framework" (SF) is an important module of NS-3 because it fulfills this need. SF allows us to collect simulation data and obtain statistical reports for NS-3. In this report, we present a detailed description of statistical framework module and two useful examples of its configuration.

Network Simulators is typically used to study services and applications in complex scenarios due to the infeasibility of deploying real testbeds. Many problems can be solved by using network simulators such as NS-3. With this in mind, the aim of this article is to introduce new NS-3 users through detailed information. It is sometimes difficult to handle by new users the traditional manuals developed by NS-3 project official website. In this article, NS-3 for communication network and Eclipse Integrated Development Environment (IDE) for powerful programming language are integrated step-by-step, explaining the main features of these open source software packages and concluding with an example simulation. Our effort is to make it easy for a beginner to be part of the NS-3 research community and to maintain an open environment of knowledge.

The co-occurrence of depression and obesity has become a significant public health concern worldwide. Recent studies have shown that metabolic dysfunction, which is commonly observed in obese individuals and characterized by inflammation, insulin resistance, leptin resistance, and hypertension, is a critical risk factor for depression. This dysfunction may induce structural and functional changes in the brain, ultimately contributing to depression's development. Given that obesity and depression mutually increase each other's risk of development by 50-60%, there is a need for effective interventions that address both conditions. The comorbidity of depression with obesity and metabolic dysregulation is thought to be related to chronic low-grade inflammation, characterized by increased circulating levels of pro-inflammatory cytokines, and C-reactive protein (CRP). As pharmacotherapy fails in at least 30-40% of cases to adequately treat major depressive disorder, a nutritional approach is emerging as a promising alternative. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are a promising dietary intervention that can reduce inflammatory biomarkers, particularly in patients with high levels of inflammation, including pregnant women with gestational diabetes, patients with type 2 diabetes mellitus, and overweight individuals with major depressive disorder. Further effort directed to implement these strategies in clinical practice could contribute to improved outcomes in patients with depression and comorbid obesity and/or metabolic dysregulation.

Rationale: The 14-3-3 protein family is known to interact with many proteins in non-cardiac cell types to regulate multiple signaling pathways, particularly those relating to energy and protein homeostasis; and the 14-3-3 network is a therapeutic target of critical metabolic and proteostatic signaling in cancer and neurological diseases. Although the heart is critically sensitive to nutrient and energy alterations, and multiple signaling pathways coordinate to maintain the cardiac cell homeostasis, neither the structure of cardiac 14-3-3 protein interactome, nor potential functional roles of 14-3-3 protein-protein interactions (PPIs) in heart has been explored. Objective: To establish the comprehensive landscape and characterize the functional role of cardiac 14-3-3 PPIs. Methods and Results: We evaluated both RNA expression and protein abundance of 14-3-3 isoforms in mouse heart, followed by co-immunoprecipitation of 14-3-3 proteins and mass spectrometry in left ventricle. We identified 52 proteins comprising the cardiac 14-3-3 interactome. Multiple bioinformatic analyses indicated that more than half of the proteins bound to 14-3-3 are related to mitochondria; and the deduced functions of the mitochondrial 14-3-3 network are to regulate cardiac ATP production via interactions with mitochondrial inner membrane proteins, especially those in mitochondrial complex I. Binding to ribosomal proteins, 14-3-3 proteins likely coordinate protein synthesis and protein quality control. Localizations of 14-3-3 proteins to mitochondria and ribosome were validated via immunofluorescence assays. The deduced function of cardiac 14-3-3 PPIs is to regulate cardiac metabolic homeostasis and proteostasis. Conclusions: Thus, the cardiac 14-3-3 interactome may be a potential therapeutic target in cardiovascular metabolic and proteostatic disease states, as it already is in cancer therapy.

In the paper the new, fractional order, state space model of a heat transfer in a one- 1 dimensional metallic rod is addressed. The fractional orders of derivative along space and time 2 are not exactly known and they are described by intervals. The proposed model is the interval 3 expanding of the state space fractional model of the one dimensional heat transfer. It is expected to 4 better describe the reality because interval order of each real process is hard to estimate. Elementary 5 properties of the proposed model are analysed. Theoretical results are experimentally validated using 6 data from real experimental laboratory system.

Uncertain fractional differential equation (UFDE) is an excellent tool for describing complicated dynamic systems. This paper analyzes the valuation problems of currency option based on UFDE under optimistic value criterion. Firstly, an uncertain fractional currency model is formulated to describe the dynamics of foreign exchange rate. Then, the pricing formulae of European, American and Asian currency option are obtained under optimistic value criterion, respectively. Finally, numerical simulations are provided to illustrate the validity of our theoretical results.

For many engineering applications it is sufficient to use the concept of simple materials. However, higher gradients of the kinematic variables are taken into account to model materials with internal length scales as well as to describe localization effects using gradient theories in finite plasticity or fluid mechanics. In many approaches length scale parameter have been introduced that are related to a specific micro structure. An alternative approach is possible, if a thermodynamically consistent framework is used for material modelling as shown in the present contribution. However, even if sophisticated and thermodynamically consistent material models can be established there are still not yet standard experiments to determine higher order material constants. In order to contribute to this ongoing discussion system identification based on the method of self-adaptive filtering is proposed in this paper. To evaluate the effectiveness of this approach it has been applied to second-order gradient materials considering longitudinal vibrations. Based on thermodynamically consistent models that have been solved numerically it has been possible to prove that system identification based on self-adaptive filtering can be used effectively for both narrow-band and broadband signals in the field of second-order gradient materials. It has also been found that the differences identified for simple materials and gradient materials allow for condition monitoring and detection of gradient effects in the material behavior.

Endoscopic medical images can suffer from uneven illumination, low contrast, and lack of texture information due to the use of point directional light sources and the presence of narrow tissue structures, posing diagnostic difficulties for physicians. In this paper, a deep learning-based su-pervised illumination enhancement network is designed for low-light endoscopic images, aiming to improve both global illumination and local details. Initially, a global illumination enhancement module is formulated utilizing a higher-order curve function to improve global illumination. Sec-ondly, a local feature extraction module incorporating dual attention is designed to capture local detailed features. Considering the significance of color fidelity in biomedical scenarios, the designed loss function prioritizes introducing color loss to alleviate image color distortion. Compared with seven state-of-the-art enhancement algorithms on Endo4IE endoscopic datasets, experimental re-sults show that the proposed method can better enhance low-light endoscopic images and avoid image color distortion. It provides an efficient method to enhance images captured by endoscopes which can effectively assist clinical diagnosis and treatment.

In this paper, we give the Galois adjunction form of the regular relation, and by using residuated mapping, we find the connection between it and order-generating set. Furthermore, we obtain the equivalent conclusion of "regular". In addition, by using the specialization order of topological space and the lower approximate operator in the rough set, we find a continuous homeomorphic mapping from a regular space to a Alexandrov topological space

Aiming to reveal the kinetic characteristics of ceramic ball grinding of fine magnetite comprehensively, two types of ceramic balls ground with the same filling rate and total weight as steel balls were researched. The results show that the breakage rate of ceramic ball grinding is only half of that of steel ball grinding with the same media filling rate. With the same total media weight and the feed size less than 0.212 mm, the breakage rate of the ceramic ball grinding approaches the steel ball grinding and is 21.43% higher than that of the steel ball grinding. The main crushing form of magnetite changed from impact to abrasion in ceramic ball grinding compared with steel ball grinding, which significantly affected the value of the zero-order output constant a. Consequently, there is a noticeable difference in the variation of the parameter β related to the fines generation rate of the ceramic ball grinding compared with the steel ball grinding.

Resonant light scattering by mesoscale dielectric spheres has received enormous attention and found many interesting applications. The recently emerged field of Mesotronics provides novel opportunities for wavelength-scaled optics and new fundamental aspects are still being uncovered. It has recently been demonstrated that high-order Mie resonances can be excited in homogeneous low-dissipation mesoscale dielectric spheres, leading to the generation of intense magnetic fields. This Letter describes a simple and effective way to drastically enhance the superresonance effect. Proof-of-principle results for the first time show that yet one more novel phenomenon of increasing the intensity of the magnetic field without changing the resonant Mie size parameter of the sphere by introducing an air cavity. In such a dielectric cenosphere (from two Greek words “kenos” - hollow and “sphaira” - sphere), by correct choosing of the air cavity size, it is possible to increase the intensity of the electromagnetic fields at the poles of the sphere by an order of magnitude due to increasing of amplitude of resonant partial wave coefficient.

Data-Flow and Higher-Order Mutation are white-box testing techniques. To our knowledge, no work has been proposed to compare data flow and higher-order mutation. This paper compares all def-uses data-flow and second-order mutation criteria. This compassion investigates the subsumption relation between these two criteria and evaluates the effectiveness of test data developed for each. To compare the two criteria, a set of test data satisfying each criterion is generated, which is used to explore whether one criterion subsumes the other criterion and assess the effectiveness of the test set that was developed for one methodology in terms of the other. The results showed that the mean mutation coverage ratio of the all du-pairs adequate test cover is 80.9%, and the mean data flow coverage ratio of the 2nd-order mutant adequate test cover is 98.7%. Consequently, 2nd-order mutation “ProbSubsumes” the all du-pairs data flow. The failure detection efficiency of the mutation (98%) is significantly better than the failure detection efficiency of data flow (86%). Consequently, 2nd-order mutation testing is “ProbBetter” than all du-pairs data flow testing. In contrast, the size of the test suite of 2nd-order mutation is more significant than the size of the test suite of all du-pairs.

The efficiency of a new composite material of the layered double hydroxide (LDH) of ZnMgAl and rice husk biochar (RHB) for the removal of Cu(II) and Pb(II) ions from synthetic wastewater was investigated in this study. The images of scanning electron microscope showed extremely fine crystalline LDH particles decorated on the rough surface of the RHB while the succesful formation of the composite adsorbent (LDH/RHB) was confirmed by the corresponding energy dispersive X-ray and the Fourier-transform infrared spectroscopy. An equilibrium contact time of 30 and 15 min for Cu2+ and Pb2+, respectively, was proposed for the optimum performance of the batch adsorption process. The dose of the LDH/RHB adsorbent was optimized at 0.4 g yielding maximum adsorption capacities of 117 and 124 mg g-1 for Cu2+ and Pb2+, respectively, with corresponding maximum removal efficiencies of nearly 94% and 99%. The initial meta concentrations was optimized at 50 or 60 mg L-1 corresponding to maximum removal efficiencies or adsorption capacities. For the changing initial metal’s concentration, the removal efficiencies remained unchanged for up to 50 mg L-1 and decreased by about 50% by increasing the initial concentrations from 50 to 100 mg L-1. The adsorption capacities observed a linear increasing trend by increasing the initial concentrations from 5 to 60 mg L-1 and remained unchanged afterward up to 100 mg L-1. A solution pH of 6.0 yielded optimum results with an increasing trend in adsorption capacities and percentage removal by changing the solution pH from 2.0 to 7.0. Based on the best-fit of the pseudo second-order kinetic model to the experimental data, the chemisorption was suggested to be the controlling mechanism of adsorption. The fitting of the Langmuir model suggested a monolayer sorption of Cu2+ and Pb2+ in addition to a heterogeneous adsorption as supported by the fitting of the Temkin isotherm. The application of the Dubinin–Radushkevich isotherm proposed a physical adsorption (mean free energy of adsorption less than 8 kJ mol−1) of both heavy metal ions on the surface of the LDH/RHB adsorbent.

The operation status of manufacturing equipment is directly related to the reliability of the operation of manufacturing equipment and the continuity of operation of the production system. Based on the analysis of the operation status of manufacturing equipment and its characteristics, it is proposed that the concept of assessing the operation status of manufacturing equipment can be realized by applying real-time acquisition of accurate inspection data of important parts of weak motion units and comparing them with their motion status evaluation criteria. Through the study of the application characteristics of fractional-order calculus theory, a differential data fusion model based on the fractional-order differential operator is established. The advantages of Internet of Things (IoT）technology and fractional order differential fusion algorithm are integrated to obtain real-time high-precision data of the operating parameters of manufacturing equipment, and the research objective of operating condition assessment of manufacturing equipment is realized. The feasibility and effectiveness of the method are verified by the application of the method in machining center operation status assessment.

Aim: To investigate the application of anterior and posterior corneal higher order aberrations (HOAs) in detecting keratoconus (KC) and suspect keratoconus (SKC). Method: This is a retrospective, case-control study which evaluated non-ectatic (normal) eyes, SKC eyes, and KC eyes. The Sirius Scheimpfug (CSO, Italy) analyzer was used to measure HOAs of the anterior and posterior corneal surfaces. Sensitivity, specificity and area under receiver operating characteristic curve (AUC) were calculated. Results: Two-hundred and twenty eyes were included in the analysis (normal n = 108, SKC n= 42, KC n= 70). Receiver operating characteristic (ROC) curve analysis revealed a high predictive ability for anterior corneal HOAs parameters: Root mean square (RMS) total corneal HOAs, RMS trefoil and RMS coma to detect keratoconus (AUC > 0.9 for all). RMS Coma (3, ±1) derived from the anterior corneal surface was the parameter with the highest ability to discriminate between suspect keratoconus and normal eyes (AUC = 0.922; cutoff > 0.2). All posterior corneal HOAs parameters were insufficient in discriminating between SKC and normal eyes (AUC < 0.8 for all). In contrast, their ability to detect KC was excellent with AUC of > 0.9 for all except RMS spherical aberrations (AUC = 0.846). Conclusion: Anterior and posterior corneal higher order aberrations can differentiate between keratoconus and normal eyes, with a high level of certainty. In suspect keratoconus disease however, only anterior corneal HOAs, and in particular coma-like aberrations, are of value. Corneal aberrometry may be of value in screening for keratoconus in populations with a high prevalence of the disease.