The presence of mutated genes strongly correlates with the incidence of cancer. Decades of research, however, has not yielded any specific causative gene or set of genes for the vast majority of cancers. The Cancer Genome Atlas program was supposed to provide clarity but it only gave much more data without any accompanying insight into how the disease begins and progresses. It may be time to notice that epidemiological studies consistently show that the environment, not genes, has the principal role in causing cancer. Since carcinogenic chemicals in our food, drink, air and water are the primary culprits, we need to look at the biochemistry of cancer, with a focus on enzymes which invariably facilitate transformations in a cell. In particular, attention should be paid to the rate-limiting enzyme in DNA synthesis, ribonucleotide reductase (RnR) whose activity is tightly linked to tumor growth. Besides circumstantial evidence that cancer is induced at this enzyme’s vulnerable free-radical-containing active-site by various carcinogens, its role in initiating retinoblastoma and HPV-related cervical cancers is well documented. Blocking the activity of malignant RnR is a certain way to arrest cancer.

Following the development of tyrosine kinase inhibitors (TKI), the survival of patients with chronic myeloid leukaemia (CML) drastically improved. With the introduction of these agents, CML is now considered a chronic disease, for some patients. Taking into consideration the side effects, toxicity, and high cost, discontinuing TKIs became a goal for patients with chronic phase CML. Patients who achieved deep molecular response (DMR) and discontinued TKI, remained in treatment-free remission (TFR). Currently, the data from the published literature demonstrate that 40-60% of patients achieve TFR, with relapses occurring within the first six months. In addition, almost all patients who relapsed regained a molecular response upon re-treatment, indicating TKI discontinuation is safe. However, there is still a gap in the understanding the mechanisms behind TFR, and whether there are prognostic factors that can predict the best candidates who qualify for TKI discontinuation with a view to keeping them in TFR. Furthermore, the information about a second TFR attempt and the role of gradual de-escalation of TKI before complete cessation is limited. This review highlights the factors predicting success or failure of TFR. In addition, it ex-amines the feasibility of a second TFR attempt after the failure of the first one, and the current guidelines concerning TFR in clinical practice.

This article presents, for the first time, the kinetics and the general conversion features of a 3-component system, BT(BC)/iodonium/Amine, based on proposed mechanism of Liu et al, for both free radical polymerization (FRP) of acrylates and the free radical promoted cationic polymerization (CP) of epoxides using the new multi-functional initiator of benzophenone–triphenylamine (BT). The additives, iodonium and EDB, have the dual function of (i) regeneration BT and (ii) produce of extra radicals for improved FRP and CP. Analytic formulas are developed to explore the new features including: (i) the conversion efficacy (CE) of FRP is an increasing function of the light intensity, the effective absorption coefficient, and the concentration sum of each of the components, BT, Iod, amine, for transient state. However, CE at steady-state is independent to the light intensity; (ii) the trifunctional hybrid structures of BT3 leads to larger light absorption than other types of BT; it also provides more active sites for the H-abstraction in the presence of EDB, leading to high CE; (iii) the efficacy of FRP is an increasing function of the amine (EDB) concentration, in contrast to that of CP having an opposite dependence; (iv) the consumption rate of BT3 in the BT3/ Iod/EDB system is slower than that of the BT3/Iod system due to photoredox catalytic cycle, and the larger initiator regeneration (RGE)
in the three-component system. A comprehensive model is also proposed that the CE (for both FRP and CP) is governed by (N_jK_jbI), whereas more complex formulas are developed; where Kj is an effective rate constant proportional to the electron transfer quantum yield, and the combined effects of other coupling rate constants; b is an effective absorption coefficient given by the light absorption and excited state quantum yield.

This review covers some of the central relationships between artificial intelligence, psychology, and economics through the lens of information theory, specifically focusing on formal models of decision-theory. In doing so we look at a particular approach that each field has adopted and how information theory has informed the development of the ideas of each field. A key theme is expected utility theory, its connection to information theory, and the Bayesian approach to decision-making and forms of (bounded) rationality. What emerges from this review is a broadly unified formal perspective derived from three very different starting points that reflect the unique principles of each field. Each of the three approaches reviewed can, in principle at least, be implemented in a computational model in such a way that, with sufficient computational power, they could be compared with human abilities in complex tasks. However, a central critique that can be applied to all three approaches was first put forward by Savage in {\it The Foundations of Statistics} and recently brought to the fore by the economist Binmore: Bayesian approaches to decision-making work in what Savage called `small worlds' but cannot work in `large worlds'. This point, in various different guises, is central to some of the current debates about the power of artificial intelligence and its relationship to human-like learning and decision-making. Recent work on artificial intelligence has gone some way to bridging this gap but significant questions still need to be answered in all three fields in order to make progress on these problems.

Objectives: There are limited data regarding the efficacy of methylprednisolone in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation. We aimed to determine whether methylprednisolone increases the number of ventilator-free days (VFDs) among these patients. Design: Retrospective single-center study Setting: Intensive care unit Patients: All patients with ARDS due to confirmed SARS-CoV-2 infection and requiring invasive mechanical ventilation between 1 March and 29 May 2020 were included Interventions: None Measurements and Main Results: The primary outcome was ventilator-free days (VFDs) during the first 28 days, defined as being alive and free from mechanical ventilation. The primary outcome was analyzed with competing-risks regression based on Fine and Gray’s proportional subhazards model. Death before day 28 was considered to be the competing event. A total of 77 patients met the inclusion criteria. Thirty-two patients (41.6%) received methylprednisolone. The median dose was 1 mg.kg-1 (IQR: 1-1.3 mg.kg-1) and median duration of 5 days (IQR:5-7 days). Patients who received methylprednisolone had a mean 18.8 VFDs (95% CI, 16.6-20.9) during the first 28 days vs. 14.2 VFDs (95% CI, 12.6-16.7) in patients who did not receive methylprednisolone (difference, 4.61; 95% CI, 1.10-8.12; P = 0.001). In the multivariable competing-risks regression analysis and after adjusting for potential confounders (ventilator settings, prone position, organ failure support, severity of the disease, tocilizumab, and inflammatory markers), methylprednisolone was independently associated with a higher number of VFDs (subhazards ratio: 0.10, 95%CI: 0.02-0.45; p=0.003). Hospital mortality did not differ between the two groups (31.2% vs. 28.9%, p=0.82). Hospital length of stay was significantly shorter in the methylprednisolone group (24 days [IQR:15-41 days] vs. 37 days [IQR:23-52 days], p=0.046). The incidence of positive blood cultures was higher in patients who received methylprednisolone (37.5% vs. 17.8%, p=0.052). However, 91% of patients who received methylprednisolone also received tocilizumab. The number of days with hyperglycemia was similar in the two groups. Conclusions: Methylprednisolone was independently associated with increased VFDs and shortened hospital length of stay. The combination of methylprednisolone and tocilizumab was associated with a higher rate of positive blood cultures. Further trials are needed to evaluate the benefits and safety of methylprednisolone in moderate or severe COVID-19 ARDS.

It is of merit to study the appropriate amount of fiber to add to free-range chickens feed to improve the microbial diversity and gut health in times of plant fiber deprivation. OptiCell is a useful source of fiber as a type of eubiotic lignocellulose, and its positive effects on the growth performance and laying performance of chickens has already been proven. However, few researchers have researched the effects of adding OptiCell on the gut microbiota of chickens. In this research we added three different levels of OptiCell (0%, 2% and 4%) to the feed of caged and free-range Bian chickens from September to November, aiming to observe the effects of adding OptiCell and different feeding modes on the gut microbial diversity and gut health of chickens, and aiming to determine an appropriate amount of OptiCell. The results showed that adding OptiCell could increase the thickness of the cecum mucus layer and the abundance of Akkermansia and Faecalibacterium in caged chickens, and 4% OptiCell was optimum. In addition, adding OptiCell increased the microbial diversity and the abundance of the butyrate-producing bacteria Faecalibacterium and Roseburia of fee-range chickens. The α-diversity and the length of the small intestine with 2% OptiCell in free-range chickens were better than with 2% OptiCell in caged chickens. In addition, compared with caged chickens, the free-range chickens had longer small intestine and lower GLP-1. Taken together, an appropriate amount of OptiCell benefitted the microbial diversity and health of chickens; it was necessary to add dietary fiber to the feed of free-range chickens when plant fibers was lacking, and 2% OptiCell was found to be optimum.

The current study aims to study the optimal fermentation conditions for producing microbial bioactive compounds. The microwave parameters consist on 2450 MHz, and 500-watt for 20, 30, and 40 seconds. The solubility of solvents was tested for the extraction of antioxidant compounds from fermented rice (Koji) by A. flavus, Ethyl acetate was the best solvent used for extraction purposes. Antioxidant properties were differentiated by blocking the oxidation of the linoleic acid with an inhibition rate of 73.13% at a concentration of 200 mg/mL, in addition to increasing its effectiveness for free radical extraction and reduction strength by increasing concentrations gradually. The bond ability to irons was lower compared to the EDTA-2Na, in addition to the obtained total content corresponding to phenolic compounds in the ethyl acetate extract of fermented rice (Koji) by A. flavus was 232.11 mg, on the basis of galic acid/mg. The stability of the antioxidant compounds of the ethyl acetate extract of fermented rice (Koji) by A. flavus was also studied; showing stability under neutral conditions, as well as at high temperatures (185 °C during two hours). However, no stability was obtained under acidic and alkaline conditions.

The simplistic morphological characteristics of the Carica papaya, papaya or ‘pawpaw’ should not be the cause for underestimating its potential as a nutraceutical. The market for papaya has been expanding at a staggering rate, partly due to its applicability as a biofortified product, but mostly for its phytochemical properties and traditional health benefits. Recent characterization studies have showed that the entirety of papaya or using a formulation of fermented papaya promotion (FPP) displays effective free radical scavenging abilities, thought to be influenced by its phenolic, carotenoids, flavonoid or amino acid profile. Aiming at reducing the impact of free radical-induced oxidative damage in the human system, the antioxidant properties of FPP have been found to potently target a broad spectrum of diseases ranging from neurological impairments such as senile dementia to systemic diseases, to its interference at the cellular level and support of normal biological ageing processes. FPP has thus been extensively investigated for its ability to exert cellular protective effects and reduce oxidative stress via mitigation of genetic damage, lipid peroxidation and enzymatic inactivation in diseases. Oxidative stress reduction strategies using FPP and its holistic approach in disease prevention and management, with a focus on diabetes, cancer and cognitive health, contributes unequivocally to wellness in an aging population.

The processing of cloud free geo-referenced imagery is one of the preliminary processing step of any land application. This letter describe the methodology developed to obtain a seamless cloud free composite of Africa for 2016 using Sentinel-2A data at 10 meters resolution freely available from the European Space Agency. The method is based on an hybrid method resulting from the merging of the two most robust time series methods namely the "darkest pixel" and the "maximum NDVI" previously developed with AVHRR time series.

Rapidly digestible starch can be obtained by gelatinization (cooking), cooking extrusion, use of small granule starch, breaking down starch granules, or by hydrolysis to maltodextrins. Resistant starch includes five groups: the first group is physically encapsulated starch within a food/polymer matrix, the second one is some native starch, the third one is recrystallized starch, the fourth one is chemically modified starch, and the fifth one is starch-lipid complexes. Starch digestion in the human body is also influenced by the degree of chewing, activity of α-amylase in the intestine, and transit time through the stomach and small intestine. Resistant starch or dietary fiber (DF) enriches specific bacterial groups located in the large intes-tine. They produce short chain fatty acids (SCFAs) and gases, causes the lowering of the pH, and inhibits pathogens. SCFAs are considered endogenous signaling molecules, acting through their free fatty-acid receptors 2 and 3 which can trigger the secretion of glucagon-like peptide-1 and peptide PYY, being released together following a meal to mediate postprandial satiety. A sufficient intake of DF reduces the risk of cardiovascular disease, coronary heart disease, stroke, hyperten-sion, colorectal cancer, and type 2 diabetes. Gluten matrix or phenolic compounds can lead to a low digestion rate of starch.

To date, various chimeric lysins have been developed as efficacious antibiotics against multidrug-resistant bacteria, but direct comparisons of their antibacterial activities have been difficult due to the preparation of multiple recombinant chimeric lysins. Previously, we reported an E. coli cell-free expression method to screen better chimeric lysins against Staphylococcus aureus, but we still needed to increase the amounts of expressed proteins enough to be able to detect them non-isotopically for quantity comparisons. In this study, we improved the previous cell-free expression system by adding a previously reported artificial T7 terminator and reversing the different nucleotides between the T7 promoter and start codon to those of the T7 phage. The new method increased the expressed amount of chimeric lysins enough for us to detect them using Western blotting. Therefore, the qualitative comparison of activity between different chimeric lysins has become possible via the adjustment of the amount variables between samples without protein purification. We applied it to select more active chimeric lysins derived from our previously reported chimeric lysin (ALS2). Finally, we compared the antibacterial activities of our selected chimeric lysins with reported chimeric lysins (ClyC and ClyO) and lysostaphin, and determined the rank orders of antibacterial activities on different S. aureus strains in our experimental conditions.

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders globally, and leads to an excessive loss of dopaminergic neurons in the substantia nigra of the brain. Circulating cell-free DNA (ccf-DNA) are double-stranded DNA fragments of different sizes and origins that are released into the serum and cerebrospinal fluid (CSF) due to cell death (i.e., necrosis and apoptosis) or are actively released by viable cells via exocytosis and NETosis. Methods: Using droplet digital polymerase chain reaction (ddPCR) we comprehensively analyzed and distinguished ccfDNA and ccf mtDNA in the serum and CSF of PD and control patients. Results: The quantitative analysis of serum ccf-DNA in PD patients demonstrated significant increase of ccf mtDNA and ccfDNA compared to healthy control patients and significantly higher copy of ccf mtDNA when compared to ccfDNA. Next, the serum ccf mtDNA levels significantly increased in male PD patients compared to healthy male controls. Furthermore, CSF ccf mtDNA in PD patients increased significantly compared to ccfDNA, and ccf mtDNA decreased in PD patients compared to healthy controls. These decreases were not statistically significant, but were in agreement with previous data. In-terestingly, ccf mtDNA increased in healthy control patients in both serum and CSF as compared to ccfDNA. Limitations: the small sample size of serum and CSF were the main limitations of this study. Conclusion: To the best of our knowledge, this is the first comprehensive study on serum and CSF of PD patients using ddPCR and indicating the distribution of the copy number of ccf mtDNA, as well as ccfDNA. If validated, we suggest that ccf mtDNA has greater than ccfDNA potential to lead the development of novel treatments for PD patients.

Space–air–ground integrated network (SAGIN) is considered as an enabler for the sixth-generation (6G) networks. By integrating terrestrial and non-terrestrial (satellite, aerial) networks, SAGIN seem to be a quite promising solution to provide reliable connectivity everywhere and all the time. Their availability can be further enhanced if hybrid free space optical (FSO)/radio frequency (RF) links are adopted. In this paper, the performance of a hybrid FSO/RF communication system operating in SAGIN has been analytically evaluated. In the considered system, a high altitude platform station (HAPS) is used to forward the satellite signal to the ground station. Moreover, the FSO channel model assumed takes into account the turbulence, pointing errors and path losses, while for the RF links, a relatively new composite fading model has been considered. In this context, a new link selection scheme has been proposed that is designed to reduced the signaling overhead required for the switching operations between the RF and FSO links. The analytical framework that has been developed is based on the Markov chain theory. Capitalizing on this framework, the performance of the system has been investigated using the criteria of outage probability and the average number of link estimations. The numerical results presented reveal that the new selection scheme offers a good compromise between performance and complexity.

Resveratrol is currently considered an option for chemoprevention and treatment of oral cancer, but the instability and unfavorable pharmacokinetics hinder its use in clinical practice. The present study deals with the preparation of resveratrol liposomes by a method that preserves stability and provides payload high enough for chemoprevention and/or treatment of oral cancer. Different temperatures, RSV concentrations and molar fractions, as well as the presence or absence of vitamin C in the hydration media were assayed. Liposome hydrodynamic diameter, polydispersity and zeta potential were evaluated by dynamic light scattering. In vitro biocompatibility, antioxidant activity and permeability were evaluated using TR146 cells and PermeaPad® membranes. Liposomes were included in hydrogels and films, and their suitability for buccal application was evaluated. According to the results, a temperature of 37ºC was optima to efficiently produce the resveratrol liposomes. Vitamin C was found to influence the liposome size, while resveratrol concentration significantly influenced the entrapment efficiency. High cell biocompatibility and potent intracellular antioxidant activity were observed and the inclusion of vitamin C reinforced the antioxidant effects. High permeation across PermeaPad® membranes and efficient uptake by TR146 cells was proved for resveratrol loaded liposomes. Liposomal hydrogels and films appropriated for buccal application were obtained and the payload of the formulations was high enough to produce mucosa concentrations above resveratrol IC50 values reported for cancer cells.

(1) Background: Most patients with mycosis fungoides (MF), a form of cutaneous T-cell lym-phoma (CTCL), develop relapsed/refractory (R/R) disease following front-line systemic therapy. This report describes treatment patterns and outcomes from the subpopulation with R/R MF. (2) Methods: This observational, retrospective, cohort study analysed patient records (1984–2016) from 27 clinical sites in Eurpe. Outcomes included treatments received, response to first-, second- and third-line treatment, overall survival (OS), and progression-free survival (PFS). (3) Results: Of 104 patients with MF, 100 received second-line and 61 received third-line therapy. Median (range) times from start of first-line therapy to first R/R MF and from first to second R/R MF were 11.2 (0.3–166.5) and 13.5 (0.0–174.6) months, respectively. Second-and third-line treatment options varied and comprised systemic therapies (85% and 79% of patients, respectively), radio-therapy (32% and 34%, respectively) and topical therapies (48% and 36%, respectively). Median (95% confidence interval [CI]) OS from the diagnosis of first R/R MF was 11.5 (6.5–not reached [NR]) years and was higher with non-chemotherapy (NR) versus chemotherapy (6.5 years); es-timated median PFS (95% CI) from the time of first R/R MF was 1.3 (1.0–2.1) years. (4) Conclu-sion: High rates of R/R disease were observed after second- and third-line treatments in this re-al-world cohort, with longer median OS in patients receiving non-chemotherapy versus chemo-therapy. Following the standard management of MF and using recently approved targeted therapies can help improve patient outcomes in advanced-stage MF.

In the framework of mean field approximation, we consider a spin system consisting of two interacting sub-ensembles: spins interactions with in each sub-ensemble are ferromagnetic, while the inter-ensemble interactions are antiferromagnetic. We define the effective number of the nearest neighbors, and show that if the two sub-ensembles have the same effective number of the nearest neighbors, the classical form of critical exponents (, , , ) gives way to the non-classical form (, , , ), and the scaling function changes simultaneously. We demonstrate that this system allows for two second-order phase transitions and two first-order phase transitions. We observe that an external magnetic field does not destroy the phase transitions, but only shifts their critical points, allowing for control of the system’s parameters. We discuss the regime when the magnetization as a function of the magnetic field develops a low-magnetization plateau, and show that the height of this plateau abruptly rises to the value of one when the magnetic field reaches a critical value. Our analytical results are supported by a Monte Carlo simulation of a three-dimensional layered model.

A topical challenge for algorithms in general and for automatic image categorization and generation in particular is presented with the aim of highlighting strengths and deficiencies of current Artificial Intelligence approaches while sketching a way forward. A general lack of encompassing symbol-embedding and (not only) -grounding in some bodily basis is made responsible for current deficiencies. A concomitant dearth of hierarchical organization of concepts follows suite. As a remedy for these shortcomings, it is proposed to take a wide step back and to newly incorporate aspects of cybernetics and analog control processes. It is claimed that a promising overarching perspective is provided by the Ouroboros Model with a valid and versatile algorithmic backbone for general cognition at all accessible levels of abstraction and capabilities.

Keywords: head-and-neck cancer; chemoradiation; cisplatin; carboplatin; loco-regional control; metastases-free survival; overall survival; toxicity.

Variable Angle Tow (VAT) laminates offer a promising alternative to classical straight fiber composites in terms of design and performance. However, analyzing these structures can be more complex due to the introduction of new design variables. Carrera's Unified Formulation (CUF) has been successful in previous works for buckling, vibrational, and stress analysis of VAT plates. Typically, one-dimensional (1D) and two-dimensional (2D) CUF models are used, with a linear law describing the fiber orientation variation in the main plane of the structure. The objective of this article is to expand the CUF 2D plate finite elements family to perform free vibration analysis of composite laminated plate structures with curvilinear fibers. The primary contribution is the application of Reissner's Mixed Variational Theorem (RMVT) to a CUF finite element model. The Principle of Virtual Displacements (PVD) and RMVT are both used as variational statements for the study of monolayer and multilayer VAT plates dynamic behavior. The proposed approach is compared to Abaqus three-dimensional (3D) reference solutions, classical theories and literature results to investigate the effectiveness of the developed models. Results demonstrate that mixed theories provide the best approximation of the reference solution in all cases.

The objective of parsing is to transform a natural language sentence it in to a standard order. and in a same way a sentence is tokenized with an appropriate format. There are certain English grammar evaluation rules and the parsing approach which is to be followed for the proper formation of a particular sentence syntactically and semantically using the parsing approach. A sentence in English language is the main element in the semantic parser, which creates a parse tree with the help of applying semantic dating technique to a number of phrases. A parser divides a token into smaller components by applying sets of guidelines that characterize and a series of the tokens to determine its structure of the language, which specified by grammar. The illustration provides easy records on grammatical connections, which can simply know and put into practice with those who have no prior knowledge of the language, such as those who need to obtain textual family members. The semantic family members represent the relationships of a number of the words in the sentence. We advocate utilizing our parser to acquire the tagged sets as well as a context-free layout grammatical representation for the source form. All pronouns, adverbs, singular, plural, nouns, verbs, people, adjectives, tenses and other words are kept in a database.

Apple replant disease is a severe problem in orchards and tree nurseries. Evidence for the involvement of a nematode-microbe disease complex was reported. To search for this complex, plots with a history of apple replanting, and control plots cultivated for the first time with apple were sampled in two fields in two years. Shoot weight drastically decreased with each replanting. Nematodes were extracted from soil samples by floatation-centrifugation, washed on a 20 µm-sieve, and used for DNA extraction. Nematode communities and co-extracted fungi and bacteria were analyzed by high-throughput sequencing of amplified ribosomal fragments. The nematode community and co-extracted fungal and bacterial communities significantly differed between replanted and control plots. Free-living nematodes of the genera Aphelenchus, Cephalenchus, and an unidentified Dorylaimida were associated with replanted plots, as indicated by linear discriminant analysis effect size. Among the co-extracted fungi and bacteria, Mortierella was most indicative of replanting. Some genera, mostly Rhabditis, indicated healthy control plots. Isolating and investigating the putative disease complexes will help to understand and alleviate stress-induced root damage of apple in replanted soil.

The synergic features and enhancing strategies for various photopolymerization systems are reviewed by kinetic schemes and the associated measurements. The important topics include: (i) photo crosslinking of corneas for the treatmnet of corneal deseases using UVA-light (365 nm) light and riboflavin as the photosensitizer; (ii) synergic effects by a dual-function enhancer in a 3-initiator system; (iii) synergic effects by a 3-initiator C/B/A system, having an electron-transfer and oxygen-mediated energy-transfer pathways; (iv) copper-complex (G1) photoredox catalyst in G1/Iod/NVK systems for free radiical (FRP) and cationic photopolymeriation (CP); (v) radical-mediated thiol-ene (TE) photopolymerizations; (vi) superbase photogenerator based-catalyzed thiol−acrylate Michael (TM) addition reaction; and the combined system of TE and TM usinghual wavelength; (vii) dual-wavelength (UV and blue) controlled photopolymerization confinement (PC); (viii) dual-wavelength (UV and red) selectively controlled 3D printing; and (ix) 3-wavelength selectively controlled in 3D printing and additive manufacturing (AM). With minimum mathematics, we present ( for the first time), the synergic features and enhancing strategies for various systems of multi-commponents, initiators, monomers, and under one- two- and there-wavelength light. Therefore, this Review provides not only the bridging between modeling and measurements, but also guidances for further experimantal stuides and new applications in 3D printings and additive manufacturing (AM), based on the innovative concepts (kinetics/schemes).

The development of platinum group metal-free (PGM-free) electrocatalysts derived from cheap and environmentally friendly biomasses for oxygen reduction reaction (ORR) is a topic of relevant interest, particularly from the point of view of sustainability. Fe-nitrogen-doped carbon materials (Fe-N-C) have attracted particular interest as alternative to Pt-based materials, due to the high activity and selectivity of Fe-Nx active sites, the high availability and good tolerance to poisoning. Recently, many studies focused on developing synthetic strategies, which could transform N-containing biomasses into N-doped carbons. In this paper chitosan was employed as a suitable N-containing biomass for preparing Fe-N-C catalyst in virtue of its high N content (7.1%) and unique chemical structure. Moreover, the major application of chitosan is based on its ability to strongly coordinate metal ions, a precondition for the formation of Fe-Nx active sites. The synthesis of Fe-N-C consists in a double step thermochemical conversion of a dried chitosan hydrogel. In acidic aqueous solution, the preparation of physical cross-linked hydrogel allows to obtain sophisticated organization, which assure an optimal mesoporosity before and after the pyrolysis. After the second thermal treatment at 900 °C, a highly graphitized material was obtained, which has been fully characterized in term of textural, morphological and chemical properties. RRDE technique was used for understanding the activity and the selectivity of the material versus the ORR in 0.5 M H2SO4 electrolyte. Special attention was put in the determination of the active site density according to nitrite electrochemical reduction measurements. It was clearly established that the catalytic activity expressed as half wave potential linearly scales with the number of Fe-Nx sites. It was also established that the addition of the iron precursor after the first pyrolysis step leads to an increased activity because of both an increased number of active sites and of a hierarchical structure, which improves the access to active sites. At the same time, the increased graphitization degree, and a reduced density of pyrrolic nitrogen groups are helpful to increase the selectivity toward the 4e- ORR pathway.

As reported by us and others previously (1, 2), the D614G mutation appeared in the spike glycoprotein (SPG) of the SARS-CoV-2 (the pathogen behind COVID-19) at the early stages of the pandemic and then G614 containing variant of SARS-CoV-2 became the predominant strain in most human populations across the world. However, one of the most recent reports from India (3) stated the incidence of G614 to be only 26% in the Indian population. This report is contradictory to the information available through the GenBank (4) SARS-CoV-2 sequence deposits made by various laboratories from India. The above stated report currently circulating in the Indian media is likely to create a public perception that the Indian strain is less contagious and such a notion could be harmful to people’s welfare. In view of this concern we have re-evaluated, updated and recalculated the incidence of the G614 variant in the Indian population by analyzing 395 Indian SARS-CoV-2 genomic sequences available in the GenBank as of June 26, 2020. In our analysis we have categorized the samples by the month in which the samples were collected. We have used an alignment-free software tool named Compare (5, 6), and the Basic Local Alignment Search Tool (BLAST) (7) in the present analysis. We finally inspected each of the 395 sequences physically for the presence of aspartic acid (D) or glycine (G) at the 614^th position of the spike glycoprotein. We analyzed an Australian cohort in parallel for comparison. We have found that the prevalence of G614 variant in the Indian samples for the month of June 2020 is 90.6%. The trends are similar with the Australian samples.

Reduced nutrient mineralization rates under minimum tillage are usually compensated by mineral fertilizer application. These cannot be applied in organic farming systems, however. We hypothesized that organic minimum tillage based on frequent cover cropping and application of dead mulch will improve soil fertility and can compensate for the potential negative effects of minimum tillage. Two long-term field experiments were set up in 2010 and 2011 comparing plough versus minimum tillage including application of transferred mulch. As second factor, the application of compost versus mineral potassium and phosphorus was compared. In 2019, soils were analyzed for soil pH, organic carbon, macro-, micronutrients, microbial biomass, microbial activity and total nematode abundance. In addition, performance of pea in the same soils was determined under greenhouse conditions. Across both experiments, macronutrients (+52%), micronutrients (+11%), microbial biomass (+51%), microbial activity (+86%), and bacterivorous nematodes (+112%) increased in minimum tillage compared with the plough-based system. In the greenhouse, pea biomass was 45% higher in the soil that had been subjected to minimum tillage compared to the plough. In conclusion, soil fertility can be improved in organic minimum tillage systems by intensive cover cropping and application of dead mulch to levels higher than in a plough-based system.

In this paper, we study a generalised CIR process with externally-exciting and self-exciting jumps, and focus on the distributional properties and applications of this process and its aggregated process. The first and second moments of this jump-diffusion process are used to calculate the insurance premium based on mean-variance principle. The Laplace transform of the aggregated process is derived, and this leads to an application for pricing default-free bonds which could capture the impacts of both exogenous and endogenous shocks. Illustrative numerical examples and comparisons with other models are also provided.

Background: Video assisted thoracoscopic surgery (VATS) has become the recommended approach for treatment of resectable lung cancer. However, no large randomized clinical trial has been conducted formally comparing surgical resections completed by VATS to those done by open thoracotomy (OT) in low volume centers. The current study sought to assess differences in recurrence-free survival (RFS), overall survival (OS), positive margins and postoperative length of stay (LOS) between VATS and OT lobectomies in our center. Method: A single institution retrospective chart review from May 2005 through May 2015 was conducted. All patients diagnosed with stage I through III lung cancer who underwent surgical resection were selected. Patient and tumor characteristics recorded included age at diagnosis, sex, tobacco use, tumor location (side and lobe), stage, size and receipt of chemotherapy or radiotherapy. Chis-square and Wilcoxon-Mann-Whitney tests were used to compare demographics, tumor characteristics and LOS. Multiple logistic and Cox regression analyses were used to compute relative risk (RR) for positive margins and mortality hazard ratios along with 95 percent confidence intervals (95%CI), respectively. Results: Of the 235 patients, 101 subjects had VATS while OT was performed in 134 patients. Age at diagnosis, sex, tobacco use, tumor location, and size were comparable for VATS and OT. No significant difference was observed in the relative risk of positive margins for VATS versus OT, RR = 0.56 (95%CI = 0.26, 1.05). However, VATS had shorter median LOS compared to OT (4 vs. 6 days, respectively), p = 0.002. A comparison of VATS versus OT showed no significant difference in the risk of recurrence, HR = 1.21 (95%CI = 0.74, 2.00), or death, HR = 1.34 (95%CI = 0.88, 2.06), in the intent-to-treat population. Similarly, no significant differences in recurrence or mortality risk were observed between VATS versus OT for analyses conducted separately for each cancer stage group or those limited to patients with negative margins. Conclusion: Our study indicates that compared to OT, VATS leads to shorter LOS while achieving comparable margins status, recurrence-free and overall survival regardless of tumor stage at diagnosis.

Bodybuilders utilize peaking strategies in a bid to fine-tune their aesthetics for competition day. The most prevalent peaking strategies utilized by natural bodybuilders are unreported in the current literature. Eighty-one (M - 59, F - 22) natural bodybuilders were recruited from competitions during the 2016 and 2017 British Natural Bodybuilder Federation seasons. Competitors completed a 34-item questionnaire designed to investigate peaking and contest day strategies. The questionnaire listed commonly utilized peaking strategies and provided additional space for qualitative information. Analysis of the data indicated that carbohydrate (CHO), water and sodium manipulation were the most commonly utilized peak week strategies. The consumption of high glycemic index CHO was the most common competition day strategy. Only 6.2 % of competitors reported following their regular diet the week prior to competition. The CHO manipulation strategies were similar to classical CHO loading, whereby bodybuilders attempt to maximize muscle glycogen concentrations. Furthermore, bodybuilders attempted to remove superfluous water by exploiting the diuretic/polyuria effect associated with water loading/restriction. The potentially deleterious effects of peaking on bodybuilders' health is considered and the efficacy of these strategies to enhance appearance is discussed. The findings of the present investigation are likely to be of interest to bodybuilders and their coaches.

A new optical steganography scheme is proposed that transmits a stealth optical code-division multiple-access (OCDMA) signal through a public binary phase-shift keying (BPSK) channel. Polarization beam splitters and arrayed waveguide gratings are used to implement a spectral-polarization coding (SPC) system with an incoherent optical source. We employ a Walsh–Hadamard code as the signature code of the user who wants to transmit stealth information using the system. A free space optical link applied to this system maintains the polarization states of light during propagation. The secret data is extracted using correlation detection and balanced subtraction in the OCDMA decoder of the intended receiver, and the other signal from the public channel is reduced by the OCDMA decoder. At the demodulator of the public channel, BPSK demodulation eliminates the stealth signal so that the public channel is not affected by the stealth signal. The two signals cannot interfere with each other. The results of this study show that our proposed optical steganography system is highly secure. The stealth signal can be favorably hidden in the public channel when the average source power of the stealth signal, public noise, and public signal are −5, −3, and 0 dBm, respectively.

The activity and cyclability of Cu-MOF-74 as catalyst was studied for the ligand-free C-O cross-coupling reaction of 4-nitrobenzaldehyde (NB) with phenol (Ph) to form 4-formyldiphenyl ether (FDE). Cu-MOF-74 is characterized by unsaturated copper sites in a highly porous metal-organic framework. The influence of solvent, reaction temperature, NB/Ph ratio, catalyst concentration and basic agent (type and concentration) were evaluated. High conversions were achieved at 120°C, 5 mol% of catalyst, NB/Ph ratio of 1:2, DMF as solvent and 1 equivalent of K2CO3 base. The activity of Cu-MOF-74 material was higher than other ligand-free copper catalytic systems tested in this study. This catalyst was easily separated and reused in five successive runs, achieving a remarkable performance without significant porous framework degradation. The leaching of copper species in the reaction medium was negligible. The O-arylation between NB and Ph took place only in the presence of Cu-MOF-74 material, being negligible without the solid catalyst.

Sepsis is a life-threatening syndrome triggered by infection and accompanied by high mortality, with antimicrobial resistances (AMRs) further escalating clinical challenges. Rapid and reliable detection of causative pathogens and AMRs are key factors for fast and appropriate treatment, in order to improve outcome in septic patients. However, current sepsis diagnostics based on blood culture is limited by low sensitivity and specificity while current molecular approaches fail to enter clinical routine. Therefore, we developed a Suppression PCR-based selective enrichment sequencing approach (SUPSETS), providing a molecular method combining multiplex suppression PCR with Nanopore sequencing to identify most common sepsis-causative pathogens and AMRs using plasma cell-free DNA. Applying only 1 mL of plasma, we target eight pathogens across three kingdoms and ten AMRs in a proof-of-concept study. SUPSETS was successfully tested on first ten clinical samples and revealed comparable results to clinical metagenomics while clearly outperforming blood culture. Several clinically relevant AMRs could be detected additionally. Furthermore, SUPSETS provided first pathogen and AMR-specific sequencing reads within minutes of starting sequencing, thereby potentially decreasing time to results to 11 - 13 hours and suggesting diagnostic potential in sepsis.

Fast Field-Cycling (FFC) Nuclear Magnetic Resonance (NMR) relaxometry is a powerful non-destructive magnetic resonance technique that enables, among other things, the investigation of slow molecular dynamics at low magnetic field intensities. FFC-NMR relaxometry measurements provide insight into molecular motion across various timescales within a single experiment. This study focuses on a \textit{model-free} approach, representing the NMRD profile $R_1$ as a linear combination of Lorentzian functions, thereby addressing the challenges of fitting data within an ill-conditioned linear least-squares framework. Tackling this problem, we present a comprehensive review and experimental validation of three regularization approaches to implement the model-free approach to analysing NMRD profiles. These include: (1) \nameUpe, utilizing locally adapted $L_2$ regularization; (2) \nameL, based on $L_1$ penalties; and (3) a hybrid approach combining locally adapted $L_2$ and global $L_1$ penalties. Each method's regularization parameters are determined automatically, according to the Balancing and Uniform Penalty principles. % Our contributions include the implementation and experimental validation of the \nameUpe{} and \nameUp{} algorithms, and the development of a "dispersion analysis" technique to assess the existence range of the estimated parameters. The objective of this work is to delineate the variance in fit quality and correlation time distribution yielded by each algorithm, thus broadening the set of software tools for the analysis of sample structures in FFC-NMR studies. The findings underline the efficacy and applicability of these algorithms in the analysis of NMRD profiles from samples representing different potential scenarios. 1

This study evaluates audiogenic epilepsy in Krushinsky-Molodkina rats using a wireless EEG system to overcome the limitations of traditional methods that restrict animal movement. Nine male KM rats, prone to audiogenic seizures, were implanted with electrodes in areas critical for seizure activity (inferior colliculus, ventrolateral periaqueductal gray, dorsal area of the secondary auditory cortex, and motor cortex). This setup allowed for the observation of seizures without movement restriction. Results showed that targeted neural intervention via electrode implantation reduced the intensity of convulsive seizures in half of the subjects, suggesting a potential therapeutic approach. The severity of seizures was influenced by the pre-phonostimulation EEG background activity in specific brain regions, identifying them as key in the genesis and generalization of seizures. Observations of dual generalized seizure waves and induced hyperkinesis challenge conventional epilepsy models and suggest new directions for research and therapy development.

Abstract: The ever-increasing use of motor vehicles causes a number of traffic safety and community issues, which are particularly severe in cities, accompanied with scarcity of parking spaces and challenges encountered in the road layout alteration projects. The commonly applied solutions include designation of through streets and implementation of on-street parking on residential streets and retrofitted traffic calming measures (TCMs). This article presents the results of the study conducted on a two-way street where Metered Parking System MPS was implemented together with diagonal and parallel parking spaces, refuge islands, horizontal deflection and lane narrowing by a single-sided chicane. The aim of this study was to identify those TCMs that effectively helped to reduce the island approach speed. Heuristic method was applied to assess the effect of the respective TCMs on reducing the island approach speed and the key speed reduction determinants were defined using cause and effect diagram and Pareto chart. Comparative analyses were carried out to rate the respective TCMs as effective, moderately effective or ineffective. Section 1 of this article presents the output of the literature review on urban parking analyses and TCM efficacy. Section 2 presents the study site and the applied heuristic method. The study results are presented in Section 3. Section 3 defines the determinants on the cause and effect diagram and analyses the determinants using the Pareto chart. The final conclusions and comments are given in Section 5. Although the study was limited to a single street in Poland, the findings may hold true in other countries where similar TCMs are used.

Background and Objectives: C-arm free MIS techniques can offer significantly reduced rates of postoperative complications such as blood loss and hospitalization time. Another advantageous long-term aspect is the notably diminished exposure to radiation which is known to cause ma-lignant changes. This study emphasizes that, in some cases of spinal conditions which require a procedural intervention, C-arm free MIS techniques hold stronger indications than open surgeries guided by image intensifier. Materials and Methods: In this research, a retrospective analysis and review of various cervical and thoracic spinal procedures, performed in our hospital, by applying C-arm free techniques. The course of the study explains the basic steps of the procedures and demonstrating postoperative or intra-operative results. For anterior cervical surgery, we performed OPLL resection, while for posterior cervical surgery, we performed posterior fossa decompression for Chiari malformation, minimally invasive cervi-cal pedicle screw fixation (MICEPS) and modified Goel technique with C1 lateral mass screw for atlantoaxial subluxation. Re-garding the thoracic spine, we performed anterior correction for Lenke type 5 scoliosis, and transdiscal screw fixation for DISH fractures. Results: C-arm free techniques are safe procedures that offer precise and high-quality postoperative results by offering sufficient spine alignment and adequate decompression depending on the case. Blood loss, postoperative pain and wound infection are other important aspects of spine surgery that must be always taken into consideration. Conclusions: Navigated C-arm free techniques are safe and precise procedures implemented in the treatment of surgically demanding conditions. They can significantly increase accuracy while decreasing the operative time. They represent the advancement in the field spine surgery and are hailed as the future of the same

Continual learning (CL), a.k.a lifelong learning, is an emerging research topic that has been attracting increasing interest in the field of machine learning. With human activity recognition (HAR) playing a key role in enabling numerous real-world applications, an essential step towards the long-term deployment of such systems is to extend the activity model to dynamically adapt to changes in people’s everyday behavior. Current research in CL applied to HAR domain is still under-explored with researchers exploring existing methods developed for computer vision in HAR. Moreover, analysis has so far focused on task-incremental or class-incremental learning paradigms where task boundaries are known. This impedes the applicability of such methods for real-world systems. To push this field forward, we build on recent advances in the area of continual learning and design a lifelong adaptive learning framework using Prototypical Networks, LAPNet-HAR, that processes sensor-based data streams in a task-free data-incremental fashion and mitigates catastrophic forgetting using experience replay and continual prototype adaptation. Online learning is further facilitated using contrastive loss to enforce inter-class separation. LAPNet-HAR is evaluated on 5 publicly available activity datasets in terms of its ability to acquire new information while preserving previous knowledge. Our extensive empirical results demonstrate the effectiveness of LAPNet-HAR in task-free CL and uncover useful insights for future challenges.

Under the oxidative stress condition, the small RNA (sRNA) Oxys that acts as essential post-transcriptional regulators of gene expression is produced and plays a regulatory function with the assistance of the RNA chaperone Hfq protein. Interestingly, experimental studies found that the N48A mutation of Hfq protein could enhance the binding affinity with OxyS while resulting in defection of gene regulation. But, how the Hfq protein interacts with sRNA Oxys and the origin of the stronger affinity of N48A mutation are both unclear. In this paper, molecular dynamics (MD) simulations were performed on the complex structure of Hfq and OxyS to explore their binding mechanism. The molecular mechanics generalized Born surface area (MM/GBSA) and interaction entropy (IE) method were combined to calculate the binding free energy between Hfq and OxyS sRNA, and the computational result is in excellent correlation with the experimental result. Per-residue decomposition of the binding free energy revealed that the enhanced binding ability of the N48A mutation mainly comes from the increased van der Waals interactions (vdW). This research explores the binding mechanism between Oxys and chaperone protein Hfq, and revealed the origin of the strong binding affinity of N48A mutation. The results provided important insights on the mechanism of gene expression regulation affected by protein mutations.

Bioenergetics, genetic coding, and catalysis are all difficult to imagine emerging without pre-existing historical context. That context is often posed as a “Chicken and Egg” problem; its resolution is concisely described by de Grasse Tyson: “the egg was laid by a bird that was not a chicken”. The concision and generality of that answer furnish no details—only an appropriate framework from which to examine detailed paradigms that might illuminate paradoxes underlying these three life-defining biomolecular processes. We examine experimental aspects here of five examples that all conform to the same paradigm. The paradox in each example is resolved by coupling if, and only if, conditions for two related transitions between levels. One drives, and each restricts fluxes through, or “gates” the other. That reciprocally-coupled gating, in which two gated processes constrain one another, maps onto the formal structure of “strange loops”. That mapping may help unite the axiomatic foundations of genetics, bioenergetics, and catalysis. As a physical analog for Gödel’s logic, biomolecular strange-loops provide a natural metaphor around which to organize these data, linking biology to the physics of information, free energy, and the second law of thermodynamics.

Gut microbiota and its metabolites like short chain fatty acids (SCFAs) are linked with pathology of Alzheimer’s disease (AD)- a debilitating public health problem in older adults. However, strategies to beneficially modulate gut microbiota and its sensing signaling pathways remain largely unknown. Here, we screened, validated and established the agonists of free fatty acid receptor 2 (FFAR2) signaling, which senses beneficial signals from SCFAs produced by microbiota in the gut. We demonstrated that inhibition of FFAR2 signaling increases amyloid-beta (Aβ) stimulated neuronal toxicity. Thus, we screened FFAR2 agonists, using in-silico library of more than 144,000 natural compounds, and 15 compounds were selected based on binding with FFAR2 agonist sites. Further, cell culture toxicity and FFAR2 stimulatory experiments demonstrated that Fenchol (a natural compound commonly present in basil) was potent FFAR2 agonist in neuronal cells. Interestingly, we also demonstrated that Fenchol protects Aβ-stimulated neurodegeneration in FFAR2 dependent manner. In addition, Fenchol reduced AD like phenotypes such as Aβ-accumulation and, learning and memory behaviors in Caenorhabditis (C.) elegans. Fenchol increased Aβ-clearance by increasing proteasome/lysosome activity and reduced senescence in neuronal cells. These results demonstrated that the inhibition of FFAR2 signaling promotes Aβ-induced neurodegeneration, while activating it by Fenchol as a natural agonist reverse it by promoting Aβ-clearance and reducing cellular senescence; thus stimulation of FFAR2 signaling can be a therapeutic approach to prevent/ treat AD.

The Thermodynamic Formalism provides a rigorous mathematical framework to study quantitative and qualitative aspects of dynamical systems. At its core there is a variational principle and corresponding, in its simplest form, to the Maximum Entropy principle, used as a statistical inference procedure to represent, by specific probability measures (Gibbs measures), the collective behaviour of complex systems. This framework has found applications in different domains of scienThe Thermodynamic Formalism provides a rigorous mathematical framework to study quantitative and qualitative aspects of dynamical systems. At its core there is a variational principle and corresponding, in its simplest form, to the Maximum Entropy principle, used as a statistical inference procedure to represent, by specific probability measures (Gibbs measures), the collective behaviour of complex systems. This framework has found applications in different domains of science, in particular, has been fruitful and influential in neurosciences. In this article, we review how the Thermodynamic Formalism can be exploited in the field of theoretical neuroscience, as a conceptual and operational tool, to link the dynamics of interacting neurons and the statistics of action potentials from either experimental data or mathematical models. We comment on perspectives and open problems in theoretical neuroscience that could be addressed within this formalism.ce, in particular, has been fruitful and influential in neurosciences. In this article, we review how the Thermodynamic Formalism can be exploited in the field of theoretical neuroscience, as a conceptual and operational tool, to link the dynamics of interacting neurons and the statistics of action potentials from either experimental data or mathematical models. We comment on perspectives and open problems in theoretical neuroscience that could be addressed within this formalism.

Starting from December 2019, coronavirus disease 2019 (COVID-19) has emerged as a once-in-a-century pandemic with deadly consequences, which urgently calls for new treatments, cures and supporting apparatuses. Remdesivir was reported by World Health Organization (WHO) as the most promising drug currently available for the treatment of COVID-19. Here, we use molecular dynamics simulations and free energy perturbation methods to study the inhibition mechanism of remdesivir to its target SARS-CoV-2 virus RNA-dependent RNA polymerase (RdRp). In the absence of a crystal structure of the SARS-CoV-2 RdRp, we first construct the homology model of this polymerase based on a previously available structure of SARS-CoV NSP12 RdRp (with a sequence identify of 95.8%). We then build the putative binding mode by aligning the remdesivir + RdRp complex to the ATP bound poliovirus RdRp. The putative binding structure is further optimized with molecular dynamics simulations and demonstrated to be stable, indicating a reasonable binding mode for remdesivir. The relative binding free energy of remdesivir is calculated to be -8.28 ± 0.65 kcal/mol, much stronger than the natural substrate ATP (-4.14 ± 0.89 kcal/mol) which is needed for the polymerization. The ~800-fold improvement in the K_d from remdesivir over ATP indicates an effective replacement of APT in blocking of the RdRp binding pocket. Key residues D618, S549 and R555 are found to be the contributors to the binding affinity of remdesivir. These findings demonstrate that remdesivir can potentially act as a SARS-CoV-2 RNA-chain terminator, effectively stopping its RNA reproduction, with key residues also identified for future lead optimization and/or drug resistance studies.

Cellular agriculture is defined as the production of agricultural products from cell cultures rather than from whole plants or animals. With growing interest in cellular agriculture as a means to address the public health, environmental, and animal welfare challenges of animal agriculture, the concept of producing seafood from fish cell- and tissue-cultures is emerging as a means to address similar challenges with industrial aquaculture systems and marine capture. Cell-based seafood - as opposed to animal-based seafood - can combine developments in biomedical engineering with modern aquaculture techniques. Biomedical engineering developments such as closed-system bioreactor production of land animal cells create a basis for large scale production of marine animal cells. Aquaculture techniques such as genetic modification and closed system aquaculture have achieved marked gains in production that can pave the way for innovations in cell-based seafood production. Here, we present the current state of innovation relevant to the development of cell-based seafood across multiple species as well as specific opportunities and challenges that exist for advancing this science. The authors find that the physiological properties of fish cell- and tissue- culture may be uniquely suited to cultivation in vitro. These physiological properties, including hypoxia tolerance, high buffering capacity, and low-temperature growth conditions, make marine cell culture an attractive opportunity for scale production of cell-based seafood; perhaps even more so than mammalian and avian cell cultures for cell-based meats. This, coupled with the unique capabilities of crustacean tissue-friendly scaffolding such as chitosan, a common seafood waste product and mushroom derivative, presents great promise for cell-based seafood production via bioreactor cultivation. To become fully realized, cell-based seafood research will require more understanding of fish muscle culture and cultivation; more investigation into serum-free media formulations optimized for fish cell culture; and bioreactor designs tuned to the needs of fish cells for large scale production.

Modern organic synthesis is majorly focused on developing environmentally benign synthetic protocols by employing green chemistry principles. Accordingly, in our recent research work, we herein report the use of modified supramolecular host cyclodextrin as an effective solid based green catalyst for accessing structurally diverse and medicinally relevant pyrimidone architectures. The catalyst and the synthesized compounds 4 (a-r) were characterized using FT-IR, NMR and GC-Mass spectroscopy. Major highlights of the reported work include: atom economical process, extremely milder reaction conditions, operational simplicity, high isolated yields, and excellent catalyst turnover number. The molecular docking studies suggest that the compound 4n has the hydrogen bonding, hydrophobic and π-pair interactions with the active site of active sites of CXT M 15 receptor.

This study comprehensively evaluates the DNA/RNA Defend Pro (DRDP) sample collection buffer designed to inactivate and stabilize patient samples. The primary objectives encompassed assessing DRDP's efficacy in ensuring sample stability, facilitating extraction-free polymerase chain reaction (PCR), and ensuring compatibility with rapid antigen testing.Ninety-five diagnostic nasopharyngeal swab samples tested for influenza A/B, RSV A/B, and/or SARS-CoV-2 were diluted 1/10 with DRDP and anonymized. Stability testing involved incubating 31 positive samples at 4 °C, 20 °C, and 37 °C for 7 days, with regular extraction-free nucleic acid amplification testing (NAAT).Results demonstrated that DRDP guaranteed viral RNA stability at all temperatures for influenza, SARS-CoV-2 and RSV showing stability up to 7 days at 4 °C. DRDP-diluted samples exhibited robust compatibility with direct PCR, as 72 out of 88 samples positive for cobas Liat also tested positive for direct PCR. Non-concordant results could be explained by the 200-fold lower input in the extraction-free NAAT.Compared to NAAT, rapid antigen testing demonstrated lower sensitivity, as expected, while maintaining perfect specificity. Clear cutoffs between positive and negative rapid antigen testing results were observed in both cobas Liat and direct PCR analyses, validating DRDP's compatibility with these techniques. In conclusion, DRDP is an effective stabilizing medium compatible with direct PCR and rapid antigen testing and shows great potential for optimizing diagnostic processes, particularly in resource-limited or time-sensitive scenarios.

Biochar (BC) is a carbonaceous material obtained by pyrolysis at 200−1000 °C in the limited presence of O2 of different vegetable and animal biomass feedstocks. BC has demonstrated great potential, mainly in environmental applications, due to its high sorption ability and persistent free radicals (PFRs) content. These characteristics enable BCs to carry out the direct and PFRs-mediated removal/degradation of environmental organic and inorganic contaminants. The types of PFRs possibly present in BC depend mainly on the pyrolysis temperature and the kind of pristine biomass. Since they also can cause ecological and human damage, a systematic evaluation of the environmental behavior, risks, or management techniques of BC-derived PFRs is urgent. PFRs generally could consist of a mixture of carbon- and oxygen-centered radicals, and of oxygenated carbon-centered radicals, depending on the pyrolytic conditions. Here, to promote a more productive and beneficial use of BC and related PFRs and stimulate further studies to make them environmentally safer and less hazardous to humans, we have first reviewed the most common methods used to produce BC, its main environmental applications, the primary mechanisms by which BC remove xenobiotics, as well as the reported mechanisms for PFRs formation in BCs. Secondly, we have discussed the PFRs environmental migration and transformation; we have reported the main PFRs-mediated applications of BCs to degrade inorganic and organic pollutants, the correlated environmental potential risks, and the possible strategies to limit them.

The theories of Evolution and Big Bang have brought a major impact upon the scientific and societal perception upon the origins, abilities and roles of mankind on Earth. It is conclusively evident that Mother Nature and the physical realm is autonomous and all phenomena in the world occur without an imposition against the “free will” of such events and patterns. Nevertheless, this extent of freedom does not imply that life on Earth represents an accident and has no purpose. By careful analysis of ancient religious texts, it can be suggested even otherwise, that it is especially free will that is offered as a gift from outside of the physical dimensions of existence, with the purpose of a continuous edification and improvement of the overall life conditions and of the human perception. It may be that the multi-generational focus on improvement and progress have been misattributed as a long-term evolution of species, that humans came from animal ancestors and that there is a blurred line associating humans with animals. Furthermore, it may be that scientists based their suggestions that no outside Creator would have brought the Earth into existence on physical perspectives, when the extra-dimensional process of Creation implies that all elements of the physical existence undergo a process of Creation from the outside, where time, space and physical matter do not exist, in spite of such elements possibly reflecting unseen elements of the meta-physical world. Finally, there is the following example that deserves attention within the scientific community; just because all living cells - human, animal and plant - contain DNA chromosomes, ribosomes, mitochondria and a plasma membrane, it does not indicate that humans are animals, just as this does not indicate that plants are animals. In Science, there is a golden statement, that correlation does not imply causation. This example is in complete agreement with the verses of the Book of Genesis in the Holy Scriptures regarding the origins of life; namely, that animals could have been created by an Author of all life on Earth so that man would experience companionship. An improved scientific perception of the timeline of life on Earth may be reached via an approach that combines molecular biology with quantum physics, given that the three layers of Science - Biology, Chemistry and Physics - together with their foundational layer of Mathematics, are in fact situated in a relationship of complete harmony.

In thermodynamic theory, free energy (i.e., available energy) is the concept facilitating the combined applications of the theory’s two fundamental laws, the first and the second laws of thermodynamics. The critical step was taken by Kelvin, then by Helmholtz and Gibbs— that in natural processes, free energy dissipates spontaneously. With the formulation of the second law of entropy growth, this may be referred to as the dissymmetry proposition manifested in the spontaneous increase of system/environment-entropy towards equilibrium. Because of Kelvin’s pre-entropy-law formulation of free energy, our concept of free energy is still defined, energy-centrally, as body’s internal energy or enthalpy, subtracted by energy that is not available within a framework on the premise of primacy of energy, in which free energy dissipates spontaneously and universally. This primacy of energy is called into question because the driving force to cause a system’s change is the purview of the second law. This paper makes a case for an engineering thermodynamics framework, instead, to be based on the premise of the primacy of dissymmetry over free energy. With Gibbsian thermodynamics undergirded with dissymmetry proposition and engineering thermodynamics with the dissymmetry premise, the two branches of thermodynamics are unified to become classical thermodynamics.

Usually, the vector control of the induction machine (IM) is done by using cascade control structures with conventional linear PI controllers, the inner loop being designed for current control, and the outer loop for rotor flux and speed control. In this paper, starting from the dq model of the IM with the rotor magnetic flux space vector aligned along the d axis, advanced control algorithms are proposed for the two control loops of the cascade structure. For the current inner loop, after the decoupling control of the two dq currents, predictive algorithms with constraints are used to control and limit the currents. Since the outer loop has a nonlinear affine multivariable plant model, a homotopy-based variant of feedback linearization is used to obtain a non-singular decoupling matrix of the feedback transformation even when the rotor flux is zero at the start-up of the motor. During the continuous variation of the homotopy parameter, the model of the plant is variable, in which case the model free algorithms are properly used to control the flux and speed of the IM. The comparative analysis obtained for the cascade structure with conventional PI controllers and advanced algorithms, respectively, shows that the last lead to improve the dynamical performance of the IM.

Celiac disease is an autoimmune disease triggered by oral ingestion of gluten, with certain gluten residues resistant to digestive tract enzymes. Within the duodenum, the remaining peptides incite immunogenic responses, including the generation of autoantibodies and inflammation, leading to irreversible damage. Our previous exploration unveiled a glutenase called Bga1903 derived from the Gram-negative bacterium Burkholderia gladioli. The cleavage pattern of Bga1903 indicated its moderate ability to mitigate the toxicity of pro-immunogenic peptides. The crystal structure of Bga1903, along with the identification of subsites within its active site, was determined. To improve its substrate specificity toward prevalent motifs like QPQ within gluten peptides, the active site of Bga1903 underwent site-directed mutagenesis according to structural insights and enzymatic kinetics. Among the double-site mutants, E380Q/S387L exhibits an approximately 38-fold increase in its specificity constant toward the QPQ sequence, favoring glutamines at the P1 and P3 positions compared to the wild type. Not only does the heightened specificity of E380Q/S387L improve the hydrolytic activity against pro-immunogenic peptides, but also holds this version of the enzyme as a promising candidate as an oral therapy enzyme for celiac disease.

Background: Glioblastoma is the most common primary brain neoplasm in adults, with still a poor prognosis despite a constant effort to improve patients’ survival. Some neuroradiological volumetric parameters seem to play a predictive role on Overall Survival (OS) and Progression Free Survival (PFS). The aim of this study is to analyze the impact that the volumetric areas of contrast-enhancing tumor and perineoplastic edema have on survival of patients treated for glioblastoma; Methods: A series of 87 patients who underwent surgery was retrospectively analyzed; OS and PFS were considered as the end points of the study. For each patient a multidisciplinary revision was conducted in collaboration with the Neuroradiology and Neuro-Oncology board. A manual and semi-automatic measurement were adopted to perform the radiological evaluation: contrast Enhancement Preoperative (CE-PTV) and Postoperative Tumor Volume (CE-RTV), Edema/Infiltration Preoperative (T2/FLAIR-PV) and Postoperative Volume (T2/FLAIR-RV); necrosis volume inside the tumor (NV); total tumor volume, including necrosis (TV); Results: The median OS value was 9 months and the median PFS value was 4 m; the mean values were respectively 12,3 m and 6,9 m. Multivariate analysis showed that the OS related factors were: adjuvant chemo-radiotherapy (p < 0,0001), CE-PTV < 15 cm³ (p=0,03), surgical resection > 95% (p=0,004) and the presence of a “pseudo-capsulated” radiological morphology (p=0,04); Conclusions: maximal safe resection is one of the most relevant predictive factors for patients’ survival. The semi-automatic pre-operative MRI evaluation could play a key role in prognostically categorizing these tumors.

Caries are lesions caused by acidic compounds derived from the metabolism of bacteria such as streptococci. It is not merely the presence of acidogenic bacteria that causes caries but an imbalance in the oral biofilm microhabitat and its behavior. One factor underlying biofilm formation is quorum sensing (QS), that in gram-positives relies on peptidic molecules, whereas in gram-negatives is driven by small diffusible signals. Strategies based on QS inhibition have been proposed as alter-natives to antimicrobial therapies. Here, we investigate the antibiofilm potential of the lactonase enzyme Aii20J, previously reported as effective against biofilms of periodontal disease origin. We generated in vitro polymicrobial biofilms dominated by gram-positive taxa using supragingival samples from caries-free and caries-active children. The effect of Aii20J on the biofilms was evalu-ated regarding its biomass-reducing ability, as assessed with crystal violet assay, and its effects on the bacterial composition of the polymicrobial biofilms, as assessed by 16S community profiling. We describe significant biomass reductions upon Aii20J exposure without significant changes in bac-terial composition at the genus level. Our results support the use of Aii20J to prevent oral biofilm formation while highlighting the influence of the polymicrobial environment on bacterial commu-nities and their response to antibiofilm treatments.

The enteric nervous system is affected by inflammatory bowel diseases (IBD). Gut microbiota ferment dietary fibers and produce short-chain fatty acids, such as Butyrate, which bind to G protein-coupled receptors, such as GPR41, and contribute to maintaining intestinal health. This work aimed to study the GPR41 in myenteric neurons and analyze the effect of Butyrate in mice submitted to experimental ulcerative colitis. The 2, 4, 6 trinitrobenzene sulfonic acid (TNBS) was injected intrarectally in C57BL/6 mice (Colitis). Sham group received ethanol (vehicle). One group was treated with 100mg/kg of Sodium Butyrate (Butyrate), and the other groups received saline. Animals were euthanized 7 days after colitis induction. Analyzes demonstrated colocalization of GPR41 with neurons immunoreactive (-ir) to nNOS and ChAT-ir, and absence of colocalization of the GPR41 with GFAP-ir glia. Quantitative results demonstrated losses of nNOS-ir, ChAT-ir, and GPR41-ir neurons in Colitis group, and Butyrate treatment attenuated neuronal loss. The number of GFAP-ir glia increased in Colitis group, whereas Butyrate reduced the number of these cells. In addition, morphological alterations observed in Colitis group were attenuated in Butyrate group. The presence of GPR41 in myenteric neurons was identified and the treatment with Butyrate attenuated the damage caused by experimental ulcerative colitis.

A consistent factor in the epidemic of chronic disease is a pro-inflammatory metabolic state. The ability of clinicians to use nutrients to balance inflammation by supporting oxidant homeostasis rests on the quality of research within the field of antioxidants. Understanding the intersection of two prominent theories regarding the role of antioxidants in quelling inflammation, nutritional hormesis and oxidant scavenging, will enable the therapeutic use of antioxidants in clinical practice. This review investigates the less well-established theory, nutritional hormesis, which has not been comprehensively reviewed recently to our knowledge. To understand the state of research on the hormetic response, we conducted a comprehensive literature review describing the relationship between dietary antioxidants, hormesis, and chronic disease. We used an adaptive search strategy in PubMed and Scopus, retrieving a total of 343 articles, of which 218 were unique. Title and abstract screenings were conducted by two reviewers independently with a third as a tiebreaker, resulting in 152 articles included in this review. Most studies reviewed the hormetic response in plant and cell models (73.6%) while only 2.2% were conducted in humans. Limitations exist in translating plant/cell/animal models into the complexities of human biochemistry and physiology that warrant consideration before extrapolating such results into clinical practice. A critical hurdle in our literature review process is the lack of standardized nomenclature describing the hormetic effect in the research community that challenges the ability to comprehensively review the subject matter. Further, aA knowledge gap exists between the cell culture and animal model research that shows a biphasic, hormetic quality to the role of antioxidants and the observational human studies, which have yet to corroborate these findings. Therefore, we cannot accurately translate this research into clinical care at this time.

A method is proposed for describing the dynamics of systems of interacting particles in terms of an auxiliary field, which in the static mode is equivalent to given interatomic potentials, and in the dynamic mode is a classical relativistic composite field. It is established that for interatomic potentials, the Fourier transform of which is a rational algebraic function of the wave vector, the auxiliary field is a composition of elementary fields that satisfy the Klein-Gordon equation with complex masses. The interaction between particles carried by the auxiliary field is nonlocal both in space variables and in time. The temporal non-locality is due to the dynamic nature of the auxiliary field and can be described in terms of functional-differential equations of retarded type. Due to the finiteness mass of the auxiliary field, the delay in interactions between particles can be arbitrarily large. A qualitative analysis of the dynamics of few-body and many-body systems with retarded interactions has been carried out, and a non-statistical mechanisms for both the thermodynamic behavior of systems and synergistic effects has been established.

Free-living amoebae (FLA) are protozoa widely distributed in the environment, found in a great diversity of terrestrial biomes. However, few genera of FLA are linked to human infections. Within these genera, Acanthamoeba spp., classified by genotypes (T1-T23), being T1, T2, T4, T5, T10, T12, and T18 as capable of causing granulomatous amoebic encephalitis (GAE) in immunocompromised patients mostly and Acanthamoeba keratitis related to genotypes T2, T3, T4, T5, T6, T10, T11, T12 and T15 in apparently healthy patients. Meanwhile, Naegleria fowleri is the causative agent of an acute infection called primary amoebic meningoencephalitis (PAM), while Balamuthia mandrillaris, like some Acanthamoeba genotypes, causes GAE, differing from the latter in the description of numerous cases in patients immunocompetent. Finally, other FLA related to the pathologies mentioned above have been reported; Sappinia pedata is responsible for one case of amoebic encephalitis; Vermamoeba vermiformis has been found in cases of ocular damage, and its extraordinary capacity as endo-cytobiont for microorganisms of public health importance such as Legionella pneumophila, Bacillus anthracis, Pseudomonas aeruginosa, among others. In this review, issues related to the epidemiology of each one are addressed, updating their geographic distribution and cases reported in recent years for pathogenic FLA.

Tobacco Free Nicotine (TFN) Electronic Nicotine Delivery Systems (ENDS) are yet to be classified as tobacco products; consequently, there is ambiguity over whether Food and Drug Administration (FDA) regulatory authority can be extended to include TFN e-cigarettes. In recent years, a more significant number of e-cigarette companies have been manufacturing TFN-containing e-cigarettes and e-liquids to circumvent FDA regulations. While studies have shown that aerosols generated from tobacco-derived nicotine-containing e-cigarettes contain significant Reactive Oxygen Species (ROS) levels, no comparison studies have been conducted using TFN e-cigarettes. This study uses a single puff aerosol generator to aerosolize TFN and tobacco-derived nicotine-containing vape-products and subsequently involves semi-quantifying ROS generated by these vape products in H2O2 equivalents. We found that the differences between ROS levels generated from TFN and tobacco-derived nicotine-containing vape products vary by flavor. TFN tobacco flavors and fruit flavors are more toxic in terms of ROS generation than menthol/ice and drink/beverage flavored products using TFN. The type of salt nicotine used in vape products, TFN or tobacco-derived nicotine, impacts the level of ROS generated from flavored vape products. Thus, a better understanding of the type of salt nicotine used in e-cigarettes (tobacco-derived or synthetic), has modulating effect on lung oxidative stress.

The mechanisms of natural oscillations and resonance are described, considering the peculiarities of the transformation of elastic and kinetic energy in the implementation of the law of conservation of energy in local and integral volumes of the body, using the concept of mechanics based on the concepts of space, time and energy. When describing the motion in the Lagrange form, the elastic deformation energy of the particles is determined by the quadratic invariant of the tensor, whose components are the partial derivatives of Euler variables with respect to Lagrange variables. The increment of the invariant due to elastic deformation is represented as the sum of two scalars, one of which depends on the average value of the relative lengths of the edges of the particles in the form of an infinitesimal parallelepiped, the second is equal to the standard deviation of these lengths from the average value. It is shown that each of the scalars can be represented in the form of two dimensionless kinematic parameters of elastic energy, which participate in different ways in the implementation of the law of conservation of energy. One part of the elastic energy passes into kinetic energy and participates in the implementation of the law of conservation of energy for the body as a whole, considering external forces. The second part is not converted into kinetic energy but changes the deformed state of the particles in accordance with the equations of motion while maintaining the same level of the part of the elastic energy of the particles used for this. The kinematic parameters differ from the volume density of the corresponding types of energy by a factor equal to the elastic modulus, which is directly proportional to the density and heat capacity of the material and inversely proportional to the volume compression coefficient. Transverse, torsional, and longitudinal vibrations are considered free and under resonance conditions. The mechanisms of transformation of forced vibrations into their own after the termination of external influences and resonance at the superposition of free and forced vibrations with the same or similar frequency are considered. The formation of a new free wave at each cycle with an increase in the amplitude, which occurs mainly due to internal energy sources, and not external forces, is justified.

Manipulating autophagy is a promising strategy for treating cancer as several autophagy inhibitors shown to induce autophagic cell death. One of these, autophagonizer (APZ), induces apoptosis-independent cell death by binding an unknown target via an unknown mechanism. To identify APZ targets we used a label-free drug affinity responsive target stability (DARTS) approach with a liquid chromatography/tandem mass spectrometry (LC-MS/MS) readout. Of 35 protein interactors, we identified Hsp70 as a key target protein of unmodified APZ in autophagy. Either APZ treatment or Hsp70 inhibition attenuates integrity of lysosomes, which leads to autophagic cell death exhibiting an excellent synergism with a clinical drug, temozolomide, in vitro, in vivo, and orthotropic glioma xenograft model. These findings demonstrate the potential of APZ to induce autophagic cell death and its development to combinational chemotherapeutic agent for glioma treatment. Collectively, our study demonstrated that APZ, a new autophagy inhibitor, can be used as a potent antitumor drug candidate to get over unassailable glioma and revealed a novel function of Hsp70 in lysosomal integrity regulation of autophagy.

Paenibacillus sp. tmac-D7 was isolated from coastline growing Trifolium macraei (double-head clover) root nodules from Bodega Bay, California. The draft genome is 5,567,337 bp with a G+C% of 52.4%, an N50 of 114,261 bp, and 5,282 predicted protein-coding genes. Paenibacillus, while found in many other environments, is frequently isolated from root nodules, with many acting as plant pathogen antagonists. Paenibacillus sp. tmac-D7 is the first genome of a non-rhizobial endophyte isolate from wild Trifolium macraei (double-head clover).

In this paper, we look at how Artificial Swarm Intelligence can evolve using evolutionary algorithms that try to minimize the sensory surprise of the system. We will show how to apply the free-energy principle, borrowed from statistical physics, to quantitatively describe the optimization method (sensory surprise minimization), which can be used to support lifelong learning. We provide our ideas about how to combine this optimization method with evolutionary algorithms in order to boost the development of specialized Artificial Neural Networks, which define the proprioceptive configuration of particular robotic units that are part of a swarm. We consider how optimization of the free-energy can promote the homeostasis of the swarm system, i.e. ensures that the system remains within its sensory boundaries throughout its active lifetime. We will show how complex distributed cognitive systems can be build in the form of hierarchical modular system, which consists of specialized micro-intelligent agents connected through information channels. We will also consider the co-evolution of various robotic swarm units, which can result in development of proprioception and a comprehensive awareness of the properties of the environment. And finally, we will give a brief outline of how this system can be implemented in practice and of our progress in this area.

The mutual information between the state of a neural network and the state of the external world represents the amount of information stored in the neural network that is associated with the external world. In contrast, the surprise of the sensory input indicates the unpredictability of the current input. In other words, this is a measure of inference ability, and an upper bound of the surprise is known as the variational free energy. According to the free-energy principle (FEP), a neural network continuously minimizes the free energy to perceive the external world. For the survival of animals, inference ability is considered to be more important than simply memorized information. In this study, the free energy is shown to represent the gap between the amount of information stored in the neural network and that available for inference. This concept involves both the FEP and the infomax principle, and will be a useful measure for quantifying the amount of information available for inference.

Surface initiated atom transfer radical polymerization (SI-ATRP) is one of the most versatile technique to modify the surface properties of material. Recent developed metal free SI-ATRP makes such technique more widely applicable. Herein photo-induced metal-free SI-ATRP of methacrylates, such as methyl methacrylate, N-isopropanyl acrylamide, and N,N- dimethylaminoethyl methacrylate, on the surface of SBA-15 was reported to fabricate organic-inorganic hybrid materials. SBA-15 based polymeric composite with adjustable graft ratio was obtained. The structure evolution during the SI-ATRP modification of SBA-15 was monitored and verified by FT-IR, XPS, TGA, BET, and TEM. The obtained polymeric composite showed enhanced adsorption ability for the model compound toluene in aqueous. This procedure provides a low cost, ready availability, and facile modification way to synthesize the polymeric composites without the contamination of metal.

Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 x 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 x 2.633 Gy (41.6 Gy10) or 18 x 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score adjusted Cox regression) to a historical control group (N=266) receiving 10 x 3.0 Gy (32.5 Gy10). In the phase 2-cohort, 50 (of 62 planned) patients were evaluable for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 x 2.633 Gy or 18 x 2.333 Gy was well tolerated and appeared superior to 10 x 3.0 Gy.

Reactive oxygen species (ROS) play a pivotal role in cellular function, and their overproduction contributes to oxidative stress, fatigue, aging, and diseases. To counteract these effects, incorpo-rating antioxidant-rich nutrients is recommended. Functional waters, including electrolyzed hydrogen water (EHW), are gaining attention for potential antioxidant effects through daily in-take. This study employs aquaphotomics and near-infrared spectroscopy (NIRS) to elucidate the molecular mechanisms behind the antioxidant activity of EHW. Previous investigation reported a 100% loss in antioxidant functionality through autoclaving, and a 40% decrease with hydrogen gas removal, prompting the current investigation into the mechanisms of antioxidant effects and especially the role of water molecular structure in it. Aquaphotomics analysis of near infrared (NIR) spectral data revealed that the primary characteristic of EHW associated with anti-radical function is presence of water solvation shells. Autoclaving and degassing led to loss of these water molecular species and a significant increase in free water molecules. The study suggests that water shells (solvation shells) in EHW play a crucial role in neutralizing ROS, although the specific ions or nanoparticles responsible for creating these shells remain unidentified. This concept aligns well with existing proposals of the crucial role of water solvation shells in ROS neutralization.

This manuscript employs a surface stress-driven nonlocal model to explore the combined effects of long-range interaction and surface energy on higher vibration modes of functionally graded nanobeams. The nanobeam theory, based on Bernoulli-Euler kinematics, incorporates surface effects such as surface elasticity, surface residual stresses, surface density, and rotary inertia. Hamilton's principle is applied to derive the governing equation with size-dependent considerations. The main outcomes of a parametric investigation, considering four different kinematic boundary conditions (Cantilever, Simply-Supported, Clamped-Pinned, and Doubly-Clamped) while varying the nonlocal parameter and material gradient index, are presented and discussed. Additionally, the normalized natural frequencies for the second, third, fourth and fifth modes of vibrations are provided and analyzed for each case under study. The results underscore the model's effectiveness in capturing surface energy effects on the overall dynamic behavior of functionally graded Bernoulli-Euler nanobeams, offering a cost-effective approach for designing and optimizing nano-scaled structures.

The strength of laser joined metal and plastic hybrids is based purely on adhesion. Unpolar plastics like polypropylene depend solely on the mechanical adhesion while polar plastics like polyamide 6.6 develop covalent bonds with the metal. In this research the influence of different surface metallizations on the lap shear strength of laser joined hybrids was investigated. Sandblasted AISI 304 was used as base metal and reference. Aluminum and titanium coatings were deposited by the means of Arc-PVD. Polypropylene and polyamide 6.6 were utilized as polar und unpolar plastics. The lap shear strength of all hybrids with polyamide 6.6 was higher than the polypropylene samples. For all investigated variations of the laser power, scanning speed and the cohesive and adhesive failure modes, the samples joined with the sandblasted AISI 304 showed the highest lap shear strength. The reduction in lap shear strength for the coated samples was due to the increased difference in thermal conductivity between the plastics and the coating materials. This lead to increased warping and residual stresses. It can be concluded that the thermal properties of the metallization in laser joined metal and plastic hybrids has a high impact on the lap shear strength.

G-protein-coupled receptors (GPCRs) are ubiquitous sensors and regulators of cellular functions. Each GPCR exists in complex aggregates with multiple resting and active conformations. Designed to detect weak stimuli, GPCRs can also activate spontaneously, resulting in basal ligand-free signaling. Agonists trigger a cascade of events leading to an activate agonist-receptor-G protein complex with high agonist affinity. However, the ensuing signaling process can further remodel the receptor complex to reduce agonist affinity, causing rapid ligand dissociation. The acutely activated ligand-free receptor can continue signaling, as proposed for rhodopsin and  opioid receptors, resulting in robust receptor activation at low agonist occupancy with enhanced agonist potency. Continued receptor stimulation can further modify the receptor complex, regulating sustained ligand-free signaling - proposed to play a role in opioid dependence. Basal, acutely agonist-triggered, and sustained elevated ligand-free signaling could each have distinct functions, reflecting multi-state conformations of GPCRs. This review addresses basal and stimulus-activated ligand-free signaling, its regulation, genetic factors, and pharmacological implications, focusing on opioid and serotonin receptors, and the growth hormone secretagogue receptor (GHSR). Ligand-free signaling of intracellular 5-HT2A receptors could mediate therapeutic effects of psychedelic drugs. Research avenues are suggested to close gaps in our knowledge of ligand-free GPCR signaling.

With the intensive development of data transmitting and processing devices of the terahertz (THz) frequency range, an important part of which are integrated plasmonic components and communication lines, it becomes necessary to measure correctly the optical constants of their conductive surfaces. In the paper we describe a reliable method for determining the effective permittivity εm of a metal surface from the measured characteristics (refractive and absorption indices) of THz surface plasmon polaritons (SPPs). The novelty of the method is the conduction of measurements on a metal surface with a dielectric layer of subwavelength thickness, suppressing the radiative losses of SPPs, which are not taken into account by the SPP dispersion equation. The method was tested on a number of flat "gold sputtering - zinc sulfide layer - air" structures with the use of the THz radiation (λ0 = 141 μm) of the Novosibirsk free electron laser (NovoFEL). The SPP characteristics were determined from interferograms measured with a plasmon Michelson interferometer. It was found that the method allowed a significant increase in the accuracy of εm in comparison with measurements on the same metal surface without a dielectric layer.

Biosensors detect specific bio-analytes by generating a measurable signal from the interaction between the sensing element and the target molecule. Surface acoustic wave (SAW) biosensors offer unique advantages due to their high sensitivity, real-time response capability, and label-free detection. The typical SAW modes are the Rayleigh mode and the shear-horizontal mode. Both present pros and cons for biosensing applications and generally need different substrates and device geometries to be efficiently generated. This study investigates and characterizes ultra-high-frequency (UHF-) SAW resonator biosensors. It reveals the simultaneous presence of the two typical SAW modes, clearly separated in frequency, called slow and fast. The two modes are studied by numerical simulations and biosensing experiments with the glial-fibrillary-acidic-protein (GFAP) biomarker. The slow mode is generally more sensitive to changes in surface properties, such as temperature and mass changes, by a factor of about 1.4 with respect to the fast mode.

Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this work, we combined atomistic simulations and conformational dynamics analysis with the ensemble-based mutational profiling of binding interactions for a diverse panel of SARS-CoV-2 spike complexes with nanobodies. Using this computational toolkit, we identified dynamic signatures and binding affinity fingerprints for the SARS-CoV-2 spike protein complexes with nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E+U, a biparatopic nanobody VHH VE, and a combination of CC12.3 antibody and VHH V/W nanobodies. Through ensemble-based deep mutational profiling of stability and binding affinities, we identify critical hotspots and characterize molecular mechanisms of SARS-CoV-2 spike protein binding with single ultra-potent nanobodies, nanobody cocktails and biparatopic nanobodies. By quantifying dynamic and energetic determinants of the SARS-CoV-2 S binding with nanobodies, we also examine the effects of circulating variants and escaping mutations. We found that mutational escape mechanisms may be controlled through structurally and energetically adaptable binding hotspots located in the host receptor-accessible binding epitope that are dynamically coupled to the stability centers in the distant epitope targeted by VHH U/V/W nanobodies. The results of this study suggested a mechanism in which through cooperative dynamic changes, nanobody combinations and biparatopic nanobody can modulate the global protein response and induce the increased resilience to common escape mutants.

Clausius’ virial theorem set a basis for relating kinetic energy in a body of independent material particles to its potential energy, pointing to their complementary role with respect to the second law of maximum entropy. In action mechanics, expressing the entropy of ideal gases as a capacity factor for sensible heat or enthalpy plus the configurational work to sustain the relative translational, rotational and vibrational action yields algorithms for estimating chemical reaction rates and positions of equilibrium. All properties of state including entropy, work potential as Helmholtz and Gibbs energies and activated transition state reaction rates can be estimated, using easily accessible molecular properties, such as atomic weights, bond lengths, moments of inertia and vibrational frequencies. Understanding how Clausius’ virial theorem balances the internal kinetic energy with field potential energy justifies partitioning between thermal and statistical properties of entropy, yielding a more complete view of the evolutionary nature of the second law of thermodynamics. The ease of performing these operations is illustrated by three important chemical gas phase reactions, the reversible dissociation of the hydrogen molecules, lysis of water to hydrogen and oxygen and the reversible formation of ammonia from nitrogen and hydrogen. Employing the ergal also introduced by Clausius to define the reversible internal work to overcome molecular interactions plus the configurational internal work of negative Gibbs energy as a function of volume or pressure may provide a practical guide for managing risk in industrial processes and climate change at the global scale.

In 2004, first absolute gravity (AG) measurements were performed on the mountain tops of Mt. Zugspitze (2 sites) and Mt. Wank (1 site), and at the Wank foot (1 site). Wank (summit height 1780 m) and Zugspitze (2960 m) are about 20 km apart from each other and belong geologically to different parts of the Northern Limestone Alps. Bridging a time span of 15 years, the deduced gravity variations for Zugspitze are in the order of 0.30 μm/s² with a standard uncertainty of 0.04 μm/s². The Wank stations (foot and top) show no significant gravity variation. The vertical stability of Wank summit is also confirmed by results of continuous GNSS recordings. Because an Alpine mountain uplift of 1 or 2 mm/yr cannot explain the obtained gravity decline at Zugspitze, the dominating geophysical contributions are assumed to be due to the diminishing glaciers in the vicinity. The modelled gravity trend caused by glacier retreat between epochs 1999 and 2018 amounts to -0.012 μm/s²/yr at both Zugspitze AG sites. This explains more than half of the observed gravity decrease. Long-term variations on inter-annual and climate-relevant decadal scale will be investigated in the future using as a supplement superconducting gravimetry (installed in 2019) and GNSS equipment (since 2018).

Glutathione peroxidases (GPxs) form a broad family of antioxidant proteins essential for maintaining redox homeostasis in eukaryotic cells. In this study, we used an integrative approach that combines bioinformatics, molecular biology, and biochemistry to investigate the role of GPxs in reactive oxygen species detoxification in the unicellular eukaryotic model organism Tetrahymena thermophila. Both phylogenetic and mechanistic empirical model analyses provided indications about the evolutionary relationships among the GPXs of Tetrahymena and the orthologous enzymes of phylogenetically related species. In-silico gene characterization and text mining were used to predict the functional relationships between GPxs and other physiologically-relevant processes. The GPx genes contain conserved transcriptional regulatory elements in the promoter region, which suggest that transcription is under tight control of specialized signaling pathways. The bioinformatic findings were next experimentally validated by studying the time course of copper (Cu)-dependent regulation of gene transcription and enzymatic activity. Results emphasize the role of GPxs in the detoxification pathways that, by complex regulation of Cu-dependent GPx gene expression, enables Tetrahymena to survive in high Cu concentrations and the associated redox environment.

There has been a growing interest in incorporating psychological and neuroscientific knowledge about the development of cognitive functions in educational policies and academic practices. In this paper, we argue that the current knowledge about the interactions between these functions and their neurodevelopmental characteristics should also be considered in order to develop practices that could be better suited to pupils depending on their age. To facilitate this, we review current neuroscientific knowledge on the competitive interactions between two neural circuitry underlying distinct learning functions, their developmental trajectories and how they are linked to other functions such as cognitive control. The incorporation of this knowledge in education could help improve academic outcomes.

We put forward a co-axial pump(optical)-probe(X-rays) experimental concept and show performance of the optical component. A Bessel beam generator with a central 100 micrometers-diameter hole (on the optical axis) was fabricated using femtosecond (fs) laser structuring inside a silica plate. This flat-axicon optical element produces a needle-like axial intensity distribution which can be used for the optical pump pulse. The fs-X-ray free electron laser (X-FEL) beam of sub-1 micrometer diameter can be introduced through the central hole along the optical axis onto a target as a probe. Different realisations of optical pump are discussed. Such optical elements facilitate alignment of ultra-short fs-pulses in space and time and can be used in light-matter interaction experiments at extreme energy densities on the surface and in the volume of targets. Full advantage of ultra-short 10 fs X-FEL probe pulses with fs-pump(optical) opens an unexplored temporal dimension of phase transitions and the fastest laser-induced rates of material heating and quenching. A wider field of applications of fs-laser-enabled structuring of materials and design of specific optical elements for astrophotonics is presented.

In this paper, spatial pulse position modulation (SPPM) is used as a case study to investigate the performance of the optical spatial modulation (SM) technique in outdoor atmospheric turbulence (AT). A closed-form expression for the upper bound on the asymptotic symbol error rate (SER) of SPPM in AT is derived and validated by closely-matching simulation results. The error performance is evaluated in weak to strong AT conditions. As the AT strength increases from the weak to strong, the channel fading coefficients become more dispersed and differentiable. Thus, a better error performance is observed under moderate-to-strong AT compared to weak AT. The performance in weak AT can be improved by applying unequal power allocation to make FSO links more distinguishable at the receiver. Receive diversity is considered to mitigate irradiance fluctuation and improve the robustness of the system to turbulence-induced channel fading. The diversity order is computed as half of the number of detectors. Performance comparisons, in terms of energy and spectral efficiencies, are drawn between the SPPM scheme and conventional MIMO schemes such as repetition coding and spatial multiplexing.

Barriers to inventing electronic devices involve challenges of iterating electronic designs due to long lead times for professional circuit board milling or high-costs of commercial milling machines. To overcome these barriers this study provides open source (OS) designs for a low-cost circuit milling machine. First, design modifications for mechanical and electrical sub-systems of the OS D3D Robotics prototyping system are provided. Next, Copper Carve, an OS custom graphical user interface, is developed to enable circuit board milling by implementing backlash and substrate distortion compensation. The performance of the OS D3D circuit mill is then quantified and validated for: positional accuracy, cut quality, feature accuracy and distortion compensation. Finally, the return on investment is calculated for inventors using it. The results show by properly compensating for motion inaccuracies with Copper Carve, the machine achieves a motion resolution of 10 microns, which is more than adequate for most circuit designs. The mill is at least five times less expensive than all commercial alternatives and the material costs of the D3D mill are repaid from fabricating 20-43 boards. The results show that the OS circuit mill is of high-enough quality to enable rapid invention and distributed manufacturing of complex products containing custom electronics.

Abstract: High step-up voltage gain nonisolated DC-DC converter have attracted much attention in photovoltaic, fuel cells and other renewable energy system applications. In this paper, by combining input current ripple-free boost cell with coupled-inductor voltage-doubler cell, an input current ripple-free high voltage gain nonisolated converter is proposed. In addition, passive lossless clamp circuit is adopted to recycle the leakage inductor energy and to reduce the voltage spike across the power switch. By utilizing voltage-doubler cell consisting of diode and capacitor, the voltage stress of switch is further reduced and the resonance between the leakage inductor and the stray capacitor of the output diode is eliminated. A low switch-on-resistance low-voltage-rated MOSFET can therefore be employed to reduce the conduction loss and cost. The reverse recovery loss of output diode is reduced, and the efficiency of converter can be improved. Furthermore, the proposed converter can achieve nearly zero input current-ripple and make the design of electromagnetic interference (EMI) filter easy. Steady state analysis and operation mode of the converter is performed. Finally, experimental results are presented to verify the analysis results of the proposed converter.

We conducted a comparative study on the development of two synthetic methods. The solvent-free synthesis is a green chemistry method developed in a bid to ameliorate environmental adverse effects of the conventional solvent-based synthesis. The synthesis of novel dichloro and polymethoxy p-nitrophenylhydrazones through solvent free technique gave moderate to high yields which were however lower than those of the solvent-based method. The established solvent-free approach has several benefits, including universality and simplicity of the approach, catalyst-free conditions, non-use of an organic solvent, quick reaction time, fast and efficient workup, and un-solvated pure products in moderate to high yields.

Background: Metastatic oral squamous cell carcinoma (OSCC) is associated with poor patient prognosis. Metastasis is a complex process involving various proteins, tumor cell alterations including changes caused by the epithelial-to-mesenchymal transition (EMT) process, and interactions with the tumor microenvironment (TME). In this study, we investigate a combined protein marker system consisting of connexin 43 (Cx43), EMMPRIN (CD147), E-cadherin and vimentin during the invasive metastatic process of OSCC and the possibility of using this system for prognosis prediction. Methods: The protein expression profiles of Cx43, EMMPRIN, E-cadherin and vimentin were investigated by immunohistochemistry in tissue samples from 24 OSCC patients. The metastatic process was mapped through different regions of interest (ROI) of adjacent healthy oral mucosa (OM), center of primary OSCC, invasive front (IF), and local cervical lymph node metastases (LNM). Disease-free survival (DFS) and overall survival (OS) were the primary clinical endpoints. Results: Significant changes in the expression profiles of the different marker proteins were detected between the different ROIs (all p values < 0.05). Multivariable Cox regression analysis revealed a significant effect of increased EMMPRIN expression towards IF on DFS (p = 0.019) and OS (p = 0.023). The combined predictive analysis showed a significant predictive value of the marker system for DFS (p = 0.0017) and OS (p = 0.00044). Conclusions: The combined marker system was able to significantly predict patient prognosis. An increase in EMMPRIN expression towards IF showed the strongest effect and could be an interesting new antimetastatic therapy approach.

Functional gastrointestinal disorders (FGIDs) are common in children and adolescents. In recent years, interest in the role of diet in the treatment of FGIDs has increased. Currently, interest focus-es on the low-FODMAP diet (LFD), the fructose- or lactose-restricted diet (FRD or LRD), the glu-ten-free diet (GFD), and the Mediterranean diet (MD). In this review, we focus on the role of these dietary patterns in the FGIDs most commonly diagnosed in clinical practice, namely irritable bowel syndrome (IBS), functional abdominal pain (FAP), functional dyspepsia (FD), and func-tional constipation (FC). Fifteen clinical trials were systematically reviewed (both RCTs and sin-gle arm clinical trials). We demonstrated the lack of high-quality intervention trials. Based on current evidence, low-FODMAP diet, LRD, FRD, or GFD have no place in daily practice for the management of children and adolescents with FGIDs. Nevertheless, some patients with IBS or RAP may have some benefit from the use of a low-FODMAP diet or FRD/LRD. Limited data sug-gest that MD may be promising in the management of FGIDs, especially in IBS patients, but more data are required to investigate the mechanisms of its protective effects.

An attempt is made to model the atomic nucleus as a combination of bound and free or unbound nucleons. Due to strong interaction, bound nucleons help in increasing nuclear binding energy and due to electroweak interaction, free or unbound nucleons help in decreasing nuclear binding energy. In this context, with reference to proposed 4G model of final unification and strong interaction, recently we have developed a unified nuclear binding energy scheme with four simple terms, one energy coefficient of 10.1 MeV and two small numbers 0.0016 and 0.0019. In this paper, by eliminating the number 0.0019, we try to fine tune the estimation procedure of number of free or unbound nucleons pertaining to the second term with an energy coefficient of 11.9 MeV. It seems that, some kind of electroweak interaction is playing a strange role in maintaining free or unbound nucleons within the nucleus. It is possible to say that, strong interaction plays a vital role in increasing nuclear binding energy and electroweak interaction plays a vital role in reducing nuclear binding energy. Interesting observation is that, Z can be considered as a characteristic representation of range of number of bound isotopes of Z. For medium, heavy and super heavy atoms, beginning and ending mass numbers pertaining to bound states can be understood with 2Z+0.004Z^2 and 3Z+0.004Z^2 respectively. With further study, neutron drip lines can be understood. Based on this kind of data fitting procedure and by considering the mass ratio of pions and electroweak bosons, existence of our 4G model of electroweak fermion of rest energy 584.725 GeV can be confirmed confidently.

The objective of this study was to develop an ultrasonic-assisted procedure for the extraction of total phenolics from Citrus aurantium L. blossoms (CAB) and evaluate the free radical scavenging activity, anti-HMG-CoA reductase activity of total phenolics. In this work, a Box-Behnken design based on the single-factor experiments was used to explore the optimum extraction process. Under the optimum conditions (extraction solvent 70.31% ethanol, extraction temperature 61.94 °C, extraction time 51.73 min and liquid-to-solid ratio 35.63 mL/g), the extraction yield of total phenolics was 95.84 mg gallic acid equivalents (GAE)/g dry matter (DM), which was highly consistent with the theoretical value (96.12 mg GAE/g DM). The total phenolic extract showed excellent free radical scavenging properties against DPPH·, ABTS+·, ·OH and ·O2-, with the IC50 values of 197.007, 83.878, 218.643 and 158.885 μg/mL, respectively, and the extracts also showed good inhibition of HMG-CoA reductase activity, with the IC50 value of 117.165 μg/mL. Total phenolics from CAB could be a potential source of natural free radical scavenger and HMG-CoA reductase inhibitor.

Celiac disease (CD) is an immune-mediated gluten-induced enteropathy that affects predisposed individuals of all ages. Many patients with CD do not report gastrointestinal symptoms making it difficult to reach an early diagnosis. On the other hand, CD is related to a wide spectrum of extra-intestinal manifestations, being dermatitis herpetiformis (DH) the best characterized. These associated conditions may be the clue for reaching the diagnosis of CD. Over the last years, there have been multiple reports of the association between CD and several cutaneous manifestations that may improve with a gluten-free diet (GFD). The presence of some of these skin diseases, even in absence of gastrointestinal symptoms, should give rise to an appropriate screening for CD. The aim of this paper is to describe the different cutaneous manifestations that have been associated to CD and the possible mechanisms involved.

This paper investigates if the polar groups induced by a plasma treatment can increase the lap shear strength of laser joined metal and plastic hybrids. Optimal laser joining parameters for cold-rolled AISI304 – Polyamide 6.6 and sandblasted AISI304 - Polypropylene hybrids are developed. The OWRK-method was utilized to identify the change in surface free energy of a low-pressure plasma treatment. Plasma treated samples were joined and tested. The fractured surfaces were investigated via light microscopy and SEM. The arithmetic means of the plasma treated hybrids lap shear strength with polyamide 6.6 varied slightly but all measured values were within the range of the untreated samples. The lap shear strengths of the polypropylene hybrids were significantly reduced. This was attributed to an overaging and the development of low molecular weight oxidized materials which lead to a weak boundary layer. No correlation between surface free energy and the lap shear strength could be found.

The work carried out first-principles calculations within the framework of density functional theory to study the structural stability of the CsSnI₃ compound and the influence of phase transitions on their electronic and optical properties. Using the GGA and SCAN functionals, the relaxed structures of the CsSnI₃ phases were obtained and their geometric characteristics were assessed. Using the Phonopy code based on VASP, calculations of phonon and thermodynamic properties were performed, and the temperatures of phase transitions of CsSnI₃ were determined. The temperature dependences of the thermodynamic parameters α-, β-, γ- and δ-phases of CsSnI₃ were analyzed. The trends in free energy, entropy, enthalpy, heat of formation energy and heat capacity were justified in terms of the pattern of changes in the total energy of the four phases of CsSnI₃ from VASP calculations. It is shown that at 0 K the non-perovskite structure of the CsSnI₃ compound (δ-CsSnI₃) is the most stable (followed by γ-CsSnI₃), and the tetragonal phase (β) is quite unstable, having the highest energy among the perovskite phases. It was revealed that at temperatures above 450 K the tetragonal phase becomes stable, and when the temperature drops, it transforms into the cubic phase (α-CsSnI₃). The phase transition between the β and γ phase of perovskite occurs in the range of 300-320 K, and at 320 K a black-yellow transformation of CsSnI₃ occurs in which the cubic phase (black perovskite) undergoes a phase transition to a non-perovskite conformation (yellow phase). The presence of temperature phase transitions between two orthorhombic phases of CsSnI₃ at 360 K was discovered, although direct transitions of the α⟷γ and γ⟷δ types have not yet been reported in any experiment, except for γ→δ transitions under the influence of moisture. Based on well-relaxed structures (from the SCAN calculations), the band gap widths for four CsSnI₃ phases were calculated and compared with experimental measurements. Electronic properties and Fermi level shifts as a result of phase transformations of CsSnI₃ were assessed using the HSE06 functional and machine learning prediction. The values of the complex dielectric constant and the refractive index of all phases of the CsSnI₃ were determined.

In the seasonally frozen regions, during the grouting of prestressed bridge ducts in low-temperature environments, incompletely cured grout materials undergo volumetric changes due to the freeze-thaw cycling, resulting in structural cracks along the prestressing ducts of the bridge, thereby diminishing the bridge's operational lifespan. To investigate the frost heaving characteristics of grout materials under freeze-thaw cycles and propose potential enhancements, this study was devised to conduct frost heaving stress tests on grout materials. Through this research, we gained insights into how various additives affect the frost heaving stress characteristics of grout materials under freeze-thaw cycles. Incorporating analyses of free water content, setting time, compressive strength, as well as macroscopic examinations such as XRD and SEM, this study delves into the mechanisms for enhancing frost heaving characteristics of grout materials. Furthermore, it proposes a research approach that utilizes multiple admixtures to improve the frost heaving properties of grout materials. Through frost heaving stress tests and other macroscopic experiments, the study investigates the influence of these combined admixtures on frost heaving stress in grout materials and elucidates the underlying improvement mechanisms. The results indicate that reducing the water-cement ratio, incorporating calcium formate, sulfoaluminate cement, air-entraining agents, and carbamide all have a positive impact on mitigating frost heaving stress in grout materials. However, the improvement mechanisms differ, and employing a single measure alone is insufficient to effectively reduce frost heaving stress while meeting performance criteria such as compressive strength, setting time, and flowability. Free water content emerges as a crucial indicator determining the magnitude of frost heaving stress in grout materials, with 11.5% of free water content representing the critical threshold for frost heaving in grout materials. Utilizing composite admixtures can simultaneously decrease free water content, lower the freezing point of free water, and alleviate frost heaving deformation, resulting in more efficient reduction of frost heaving stress. When the admixture content reaches 9.9%, frost heaving stress is eliminated, and the comprehensive performance parameters including compressive strength, setting time, and flowability meet the specified requirements.

The study of the surface thermodynamic properties of solid materials is primordial for the determination of the dispersive surface energy, polar enthalpy of adsorption and Lewis’s acid base properties of solid particles. Inverse gas chromatography technique (IGC) at infinite dilution is the best surface technique for the determination of the surface physicochemical properties of materials. (1) Background: This paper was devoted to study the surface properties of solid materials such as alumina particles by using IGC technique. (2) Methods: Different methods and molecular models such as spherical, cylindrical, van der Waals, Redlich-Kwong, Kiselev and geometric models, were used to determine the London dispersive surface energy of solid surfaces. Hamieh model was also used and highlighted the thermal effect on the surface area of solvents. (3) Results: The variations of the dispersive surface energy and the free energy of adsorption were determined for alumina particles as a function of the temperature as well as their Lewis’s acid base constants. Alumina surfaces were proved to exhibit a strong Lewis amphoteric character three time more basic than acidic (4) Conclusions: The new methodology based on Hamieh model gave the more accurate results of the physicochemical properties of the particle surfaces.

Identifying or authenticating a computer user are necessary steps to keep systems secure on the network and to prevent fraudulent users from accessing accounts. Keystroke dynamics authentication can be used as an additional authentication method. Keystroke dynamics involves in-depth analysis of how you type on the keyboard, analysis of how long a key is pressed or the time between two consecutive keys. This field has seen a continuous growth in scientific research. In the last five years alone, about 10,000 scientific researches in this field have been published. One of the main problems facing researchers is the small number of public data sets that include how users type on the keyboard. This paper aims to provide researchers with a data set that includes how to type free text on the keyboard by 80 users. The data were collected in a single session via a web platform. The dataset contains 410,633 key-events collected in a total time interval of almost 24 hours. In similar research, most datasets are with texts written by users in English. The language in which the users wrote for this research is Romanian. This paper also provides an extensive analysis of the data set collected and presents relevant information for the analysis of the data set in future research.

Humanity faces serious social and environmental problems, including climate change and biodiversity loss. Risks are increasing and conditions deteriorating. Increasingly, scientists, global policy experts, and the general public conclude that incremental approaches are insufficient and transformative change is needed across all sectors of society. However, the meaning of transformation is still unsettled in the literature, as is the proper role of science in fostering it. This paper is the first in a three-part series that adds to the discussion by proposing a novel science-driven research-and-development program aimed at societal transformation. More than a proposal, it offers a perspective and conceptual framework from which societal transformation might be approached and understood. While acknowledging the necessity of reform to existing societal systems (e.g., governance, economic, and financial systems), the focus of the series is on transformation understood as systems change or systems migration—the de novo development of and migration to new societal systems. The series provides definitions, aims, reasoning, worldview, and a theory of change, and discusses fitness metrics and design principles for new systems. This first paper proposes a worldview built using ideas from evolutionary biology, complex systems science, cognitive sciences, and information theory that is intended to serve as the foundation for the R&D program.

Celiac disease (CD) is a genetically conditioned autoimmune process that appears in susceptible people. It can affect people of any age, and slightly predominates in females. It has a fairly homogenous global distribution, with an average prevalence of 1-2%, the frequency having increased in recent decades. The only effective treatment is a strict and permanent gluten-free diet (GFD), although the level of compliance with it is poor, at about 50% of cases. To monitor the effectiveness of the GFD, several procedures involving various approaches are employed: a) periodic interviews by nutritionists; b) clinical follow-up; c) serological controls of specific antibodies; d) endoscopies with collection of duodenal biopsies; e) structured questionnaires; f) determination of gluten peptides derived from gluten in feces and/or urine. All of these procedures are useful when applied, alone or in combination, depending on the cases. Some patients will only need to consult to their doctors, while others will require a multidisciplinary approach to assess their compliance with the GFD. In children, normalization of duodenal mucosa was achieved in 95% of cases within 2 years, while it is more delayed in adults, whose mucosa take longer to heal completely.

Meixner's historical remark in 1969 "... it can be shown that the concept of entropy in the absence of equilibrium is in fact not only questionable but that it cannot even be defined...." is investigated from today's insight. Several statements --such as the three laws of phenomenological thermodynamics, the embedding theorem and the adiabatical uniqueness-- are used to get rid of non-equilibrium entropy as a primitive concept. In this framework, Clausius inequality of open systems can be derived by use of the defining inequalities which establish the non-equilibrium quantities contact temperature and non-equilibrium molar entropy which allow to describe the interaction between the Schottky system and its controlling equilibrium environment.

Despite huge effort has been devoted to the design of the initiators and reaction conditions, it remains challenging to synthesize high molecular weight polypeptides with conventional solution phase synthesis. In this work, surface-initiated vapor deposition polymerization (SI-VDP) was utilized to graft synthetic polypeptides poly (γ-benzyl L-glutamate) (PBLG) from polystyrene (PS) resin beads by ring-opening polymerization of N-carboxyanhydrides (NCAs). It was demonstrated for the first time that high molecular weight bulk PBLG (> 500,000) could be readily obtained within one hour via solvent-free synthetic method which paves the way for the synthesis of copolypeptides with high molecular weight.

The present study aims to develop an efficient numerical method for computing the diffraction and radiation of water waves with horizontal long cylindrical structures, such as floating breakwaters. A higher-order scheme is used to discretize geometry of the structure as well as the relevant physical quantities. As the kernel of this method, Wehausen’s free-surface Green function is calculated by a newly-developed Gauss-Kronrod adaptive quadrature algorithm after elimination of its Cauchy-type singularities. To improve computational efficiency, a Chebyshev approximation approach is applied to a fast calculation of the Green function that needs evaluation thousands of times. In addition, OpenMP parallel technique is used to the formation of influence coefficient matrix, which significantly reduces CPU time. Finally, computations are performed on wave exciting forces and hydrodynamic coefficients for the long cylindrical structures, either floating or submerged. Comparison with other numerical and analytical methods demonstrates good performance of the present method.

Background: This study retrospective evaluates patients with stage IV melanoma treated with Nivolumab and Ipilimumab combination therapy from two regional oncology centers from Romania between the years of 2019 up to the end of 2022. Methods: The data were analyzed in SAS for Windows, V9.4. The survival curves were estimated using the Kaplan-Meier method, and survival distributions were compared with log-rank test. The effects of the main clinical and pathological variables on OS and PFS were investigated with Cox regression. Results: Kaplan-Meier curve of OS in all evaluable patients enrolled in the study resulted in a median OS of 346 days (95% CI: 150-NA) and a median PFS of 211 days (95% CI: 113-430). 45.3% of the patients experienced adverse events during the Nivolumab + Ipilimumab treatment with some of them having multiple organ systems involved. Discussion: The OS values were lower than that reported in approval clinical trials, but the results show a marked improvement when comparing to results obtained by chemotherapy regimens previously used in these scenarios. Conclusion: This study provides real-world insights into the survival data and safety profiles of combination therapy with anti-PD-1 antibodies and anti-CTLA-4 antibodies.

We have considered a SEIR-SEI Vector-host mathematical model which captures malaria transmission dynamics, described and built on 7-dimensional nonlinear ordinary differential equations. We compute the basic reproduction number of the model; examine the positivity and boundedness of the model compartments in a region using well established methods viz: Cauchy’s differential theorem, Birkhoff & Rota’s theorem which verifies and reveals the well-posedness, and carrying capacity of the model respectively, the existence of the Disease-Free (DFE) and Endemic (EDE) equilibrium points were determined and examined. Using the Gaussian elimination method and the Routh-hurwitz criterion, we convey stability analyses at DFE and EDE points which indicates that the DFE (malaria-free) and the EDE (epidemic outbreak) point occurs when the basic reproduction number is less than unity (one) and greater than unity (one) respectively. We obtain a solution to the model using the Variational iteration method (VIM) (an unprecedented method) to each population compartments and verify the efficacy, reliability and validity of the proposed method by comparing the respective solutions via tables and combined plots with the computer in-built Runge-kutta-Felhberg of fourth-fifths order (RKF-45). We illustrate the combined plot profiles of each compartment in the model, showing the dynamic behavior of these compartments; then we speculate that VIM is efficient and capable to conduct analysis on Malaria models and other epidemiological models.

Pteridine reductase 1 is a trypanosomatid multifunctional enzyme that provides a mechanism for escape of Dihydrofolate reductase (DHFR) inhibition. This is because PTR1 can reduce pterins and folates. Trypanosomes require folates and pterins for survival and are unable to synthesize them de novo. Currently there are no anti-folate based Human African Trypanosomiasis (HAT) chemotherapeutics in use. Thus, successful dual inhibition of TbDHFR and TbPTR1 has implications in the exploitation of anti-folates. We carried out molecular docking of a ligand library of 5742 compounds against TbPTR1 and identified 18 compounds showing promising binding modes. The protein-ligand complexes were subjected to Molecular dynamics to characterize their molecular interactions and energetics followed by in vitro testing. In this study, we identified five potential TbPTR1 inhibitors that showed low micromolar Trypanosome growth inhibition in in vitro experiments with no significant human cell cytotoxicity. Compounds RUBi004, RUBi007, RUBi014, and RUBi018 displayed moderate to strong antagonism when used in combination with the known TbDHFR inhibitor, WR99210. This gave an indication that the compounds might inhibit both TbPTR1 and TbDHFR. RUBi016 showed an additive effect in the isobologram assay. Our results provide a basis for scaffold optimization for further studies in the development of HAT antifolates.

Free volume is an extremely important intrinsic defect in polymers. Structurally, the free volume is the randomly distributed holes in the polymer molecular chain segments. From the perspective of molecular movement, it is also the space needed for the movement of molecular segments. In proton exchange membrane fuel cells, the free volume is also the space needed for the directional conduction of protons. Irradiation grafting sulfonated polyvinylidene fluoride (PVDF) is one of the methods to produce proton exchange membrane with good proton channel rate. Using the LYS-1 program, based on the linear absorption coefficient and backscatter coefficient models, the percentage of annihilated positrons in PVDF in the two-layer model and the three-layer model was studied, and comparing the two fitting results it is determined that the model closest to the positron annihilation percentage required by the PALS experiment is the two-layer model, which allows the percentage of positrons that are annihilated in PVDF films with a thickness of 100 μm to reach 46% using the high energy positron source ⁴⁴Ti without using the positron moderator. Using positron annihilation lifetime spectrum (PALS) analysis methods, based on Eldrup's classical model of free volume, the influence of absorbed doses of α particles on the free volume and crystallinity of PVDF was investigated, respectively. Based on the two test results the model of cross-linking and degradation of polyvinylidene fluoride irradiated by α particles was determined. Afterwards, X-ray diffraction (XRD) methods was used to study the change of PVDF crystal area before and after irradiation. The XRD results are consistent with the results measured by PALS.

This paper is devoted to an accurate determination of the London dispersive and polar free energy of adsorption, the two Lewis acid γs+ and base γs- components of polar surface energy γsAB of 2D single-crystalline and polycrystalline covalent organic frameworks such as TAPPy-TPA-COFs. Inverse gas chromatography (IGC) at infinite dilution was used to quantify the different surface parameters of the different materials. From IGC measurements, one determined the net retention time of the adsorption of n-alkanes and several polar solvents on single-crystalline and polycrystalline covalent organic frameworks. The free surface Gibbs energy of adsorption was obtained for the various organic molecules at different temperatures from their net retention volume values. The separation between the London dispersive energy and the polar energy of adsorbed molecules was carried out by using a new thermodynamic parameter PSX chosen as new indicator variable and taken into account the deformation polarizability and the harmonic mean of the ionization energies of solvents and solid materials, derived from London dispersion equation. The obtained results are very promising for the accurate determination of the surface thermodynamic parameters of adsorption of organic solvents on solid surfaces.

Trans-arterial radioembolization (TARE) is a form of radiation therapy performed for hepatocellular carcinoma (HCC) via selective intra-arterial injection of Yttrium-90 loaded microspheres. This was a multicenter retrospective study of consecutive patients with HCC who underwent TARE between July 2009 and May 2019. Using pre-treatment computed tomography imaging, the total cross-sectional area (cm2) of the abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI) was calculated by normalizing the muscle area to patient height. In total, 347 patients (median age, 65 years; 284 male) were included in the study. A total of 108 (31.1%) patients had portal vein tumor thrombus (PVTT) and 126 (36.3%) were classified as sarcopenic. The median overall survival (OS) was 28.1 months (95% CI, 24.8-35.7) and median progression-free survival was 8.0 months (95% CI, 6.4-9.4). Multivariate Cox regression analysis revealed that sarcopenia (hazard ratio [HR], 1.36; 95% CI, 1.00-1.85, p = 0.05), PVTT (HR, 1.82; 95% CI, 1.33-2.49, p < 0.01), alpha-fetoprotein (AFP) (≥200 ng/mL) (HR 1.41; 95% CI, 1.04-1.92, p = 0.03), and albumin-bilirubin grade (2-3) (HR 1.74; 95% CI, 1.24-2.43, p < 0.01) were independently associated with poor OS. TARE provided favorable long-term outcomes for patients with advanced HCC. Pre-treatment sarcopenia independently associated with survival, suggesting its utility as a surrogate biomarker for identifying TARE candidates.