Global teacher shortage is a serious concern with grave implications for the future of education. This calls for novel ways of addressing teacher roles. The economic benefits of tireless labour inspires the need for teachers who are unlimited by natural human demands, highlighting consideration for the affordances of robotics and Artificial Intelligence in Education (AIED) as currently obtainable in other areas of human life. This however demands designing robotic personalities that can take on independent teacher roles despite strong opinions that robots will not be able to fully replace humans in the classroom of the future. In this paper, we argue for a future classroom with independent robot teachers, highlighting the minimum capabilities required of such personalities in terms of personality, instructional delivery, social interaction and affect. We describe our project on the design of a robot teacher based on these. Possible directions for future system development and studies are highlighted.

Chronic hemodialysis (HD) patients have very high cardiovascular risk. Acute vascular changes during dialysis mediated by factors of the endothelium may have a crucial role in this. Aim: To study acute vascular changes during HD. In 29 consecutive chronic HD patients (age: 65.6±10.4 years) pre-, mid-, and post-HD plasma syndecan-1 (SDC-1) and endothelin-1 (ET-1) levels were measured. Applanation tonometry was performed before HD. SDC-1 levels increased during HD (p=0.004). Males had higher ET-1 levels. Patients were divided into 2 groups based on pulse wave velocity (PWV): PWV≥12 m/s and PWV<12 m/s. Pre-HD and mid-HD SDC-1 levels were higher in the group with PWV≥12 m/s (10.174±2.568 vs. 7.928±1.794 ng/ml, p=0.013, and 10.319±3.482 vs. 8.248±1.793 ng/ml, p=0.044, respectively). Post-HD ET-1 levels were higher in the patient group having PWV≥12 m/s (10.88±3.00 vs. 8.05±3.48 pg/l, p=0.027). Patients having PWV≥12 m/s had higher pre-HD peripheral and aortic systolic blood pressure (p<0.05). Total cholesterol correlated with the SDC-1 decrease during HD (r=0.539; p=0.008). Pre-, mid-, and post-HD SDC-1 correlated with the ultrafiltration (r=0.432, p=0.019; r=0.377, p=0.044; and r=0.401, p=0.012, respectively). SDC-1 and ET-1 contribute to vascular changes observed during HD, and they have correlations with some cardiovascular risk factors.

A Global Historical Megatsunami Catalog (GHMCat) is presented, including all the events documented to date. The oldest event is from 1674 the Santorini event, ~3600 BP, is considered a particular case, and the most recent is from 2020. Although there is no formal definition of the term megatsunami, it is usually associated to the maximum height or runup reached by the waves when hitting the coast. Here we adopt this criterion and define a megatsunami when the wave reaches a height of 40 m or more. The catalog is initially based on tsunamis that meet this condition from the two existing Global Historical Tsunami Databases (GHTDs). Then, each of the events have been researched for its available references including earliest in order to verify the data, mainly on the maximum height of the waves and their causes. After a comprehensive review of published or on-line literature on historical tsunamis, including regional and local catalogs, papers, books, studies, reports and other available references, some of the oldest events have been ruled out. On the other hand, the literature review has also led to include in the catalog some new megatsunamis not included in the GHTDs. The global catalog contains 37 events from 1674 to 2023, 11 of which are either not included in the GHTDs or included with (erroneous) wave heights &lt;40 m. All of them are described and characterized as far as can be gathered within the limitations of the scope of a global catalog and the available information on each historical case. The analysis of recorded historical megatsunamis shows that virtually all have been originated by large landslides, most of them subaerial landslides, with an unusual frequency of events in certain glaciated areas of Alaska and Norway, mainly in the first decades of the 20th century. In contrast, it is worth noting the small number of megatsunamis caused by submarine landslides or associated with volcanic explosions.

There is little understanding of patients' experiences and perceptions with satisfaction by health professionals such as medical and dental clinicians. Furthermore, patient satisfaction is not well understood. The objective of this article is to better understand patients' satisfaction with their medical and dental care. The methods of the current article are based on a narrative review of the literature strategy. Patient satisfaction's multidimensional nature has been established since the perceived reasons for satisfaction varied widely among patients. Many aspects of the treatment influence participant satisfaction at different stages of the intervention's process. An improved understanding of the basis for managing patients' expectations with information reiteratively and efficiently may ultimately reduce patients' potential for negative feelings toward the medical and dental treatment experience. The consumerist method may misrepresent the concept of satisfaction in health service.

Why is it that in the neighborhood of a calm ordinary star (the Sun) located at the quiet periphery of its galaxy (the Milky Way), non-native heavy elements are abundant in such concentrated form? Where did these elements really come from? Where did Earth's gold come from? Our analysis of the known data offers a fact-reconciling hypothesis: What if, in the early solar system, an explosive collision occurred -- of a traveling from afar giant-nuclear-drop-like object with a local massive dense object (perhaps a then-existent companion of the Sun) -- and the debris, through the multitude of reaction channels and nuclei transformations, was then responsible for (1) the enrichment of the solar system with the cocktail of all detected exogenous chemical elements, and (2) the eventual formation of the terrestrial planets that pre-collision did not exist, thus offering a possible explanation for their inner position and compositional differences within the predominantly hydrogen-helium rest of the solar system.

Redox balance is increasingly identified as a major player in cellular signaling. A fundamentally simple reaction of oxidation and reduction of cysteine residues in cellular proteins is the central concept in this complex mode of protein function regulation. Oxidation of key cysteine residues occurs at the physiological levels of reactive oxygen species (ROS) but are reduced by a supply of thiol antioxidant molecules including glutathione, glutaredoxin and thioredoxin. While these molecules show complex compensatory roles in experimental conditions, transgenic animal models provide a comprehensive picture to pinpoint the role of each antioxidant. In this review we have specifically focused on the available literature on Thioredoxin-1 system transgenic models that includes Thioredoxin and Thioredoxin reductase proteins. As identification of Thioredoxin protein targets is technically challenging the true contribution of this system in maintaining cellular balance remains unidentified, including the role of this system in the brain.

Emerging applications of optical technologies are driving the development of miniaturised light sources, which in turn require the fabrication of matching micro-optical elements with sub-1 mm cross sections and high optical quality. This is particularly challenging for spatially-constrained biomedical applications where reduced dimensionality is required, such as endoscopy, optogenetics, or optical implants. Planarisation of a lens by the Fresnel lens approach was adapted for a conical lens (axicon) and was made by direct femtosecond 780 nm/100 fs laser writing in SZ2080™polymer with photo-initiator. Optical characterisation of the positive and negative fraxicons is presented. Numerical modeling of fraxicon optical performance under illumination by incoherent and spatially extended light sources is compared with the ideal case of plane wave illumination. Considering the potential for rapid replication in soft polymers and resists, this approach holds great promise for the most demanding technological applications.

The paper discusses the classification of fuzzy metrics based on their continuity conditions, dividing them into Erceg, Deng, Yang-Shi, and Chen metrics. It explores the relationships between these types of fuzzy metrics, concluding that a Deng metric in [0,1]-topology must also be Erceg, Chen, and Yang-Shi metrics. The paper also proves that the product of countably many Deng pseudo-metric spaces remains a Deng pseudo-metric space, and demonstrates some σ-locally finite properties of Deng metric space. Additionally, the paper constructs two interrelated mappings based on normal space and concludes that if a [0,1]-topological space is T1 and regular, and its topology has a σ-locally finite base, then it is Deng metrizable, and thus Erceg, Yang-Shi, and Chen metrizable as well.

Melanocortins play crucial roles in regulating the stress response, inflammation, and skin pigmentation. In this review, we focus on the melanocortin 1 receptor (MC1R), a G protein-coupled receptor primarily known for regulating skin pigmentation and exhibiting anti-inflammatory effects. First, we provide an overview of the structure, signaling pathways, and related diseases of MC1R. Next, we discuss the potential therapeutic use of synthetic peptides and small molecule modulators of MC1R, highlighting the development of various drugs that enhance stability through amino acid sequence modifications and small molecule drugs to overcome limitations associated with peptide characteristics. Notably, MC1R-targeted drugs have applications beyond skin pigmentation-related diseases, which predominantly affect MC1R in melanocytes. These drugs can also be useful in treating inflammatory diseases with MC1R expression present in various cells. Our review underscores the potential of MC1R-targeted drugs to treat a wide range of diseases and encourages further research in this area.

The RV144 trial represents the only vaccine trial to demonstrate any protective effect against HIV-1 infection. While the reason(s) for this protection are still being evaluated, it serves as justification for widespread efforts aimed at developing new, more effective HIV-1 vaccines. Advances in our knowledge of HIV-1 immunogens and host antibody responses to these immunogens are crucial to informing vaccine design. While the envelope (Env) protein is the only viral protein present on the surface of virions, it exists in a complex trimeric conformation and is decorated with an array of variable N-linked glycans, making it an important but difficult target for vaccine design. Thus far, efforts to elicit a protective humoral immune response using structural mimics of native Env trimers have been unsuccessful. Notably, the aforementioned N-linked glycans serve as a component of many of the epitopes crucial for the induction of potentially protective broadly neutralizing antibodies (bnAbs). Thus, a greater understanding of Env structural determinants, most critically Env glycosylation, will no doubt be of importance in generating effective immunogens. Recent studies have identified the HIV-1 Env signal peptide (SP) as an important contributor to Env glycosylation. Further investigation into the mechanisms by which the SP directs glycosylation will be important, both in the context of understanding HIV-1 biology and in order to inform HIV-1 vaccine design.

In recent decades, a number of high-profile cases involving fraud as research misconduct have been in the media and resulted in severe consequences for those convicted. According to the increased cases of allegations and coverage in the media, this reflects a heightened awareness that fraudulent actions exist. Nonetheless, the Office of Research Integrity data suggests that despite the growth in the number of the cases of allegation there has not been a commensurate increase in findings of misconduct. The purpose of this paper is to explore misconduct to better understand what it entails. An analysis of misconduct from the perspective of the definitions of allegations and fraud of is conducted and potential frameworks for understanding both are considered. The paper considers serial-positioning effects of primacy and recency on allegation phenomena, as well as supervenience theory and contextualism as a lens for understanding fraud. Discussion of the relational semantics of the core aspects of fraud and de facto grouping of forms of misconduct. It is concluded that the interrogative pronouns of “what” and “when” could be used to categorize forms of misconduct laying the foundation for the next paper that deconstructs the definition of falsification according to the Public Health Service.

Introduction: Mucopolysaccharidosis type I (MPSI) is an autosomal recessive lysosomal storage disorder characterized by deficient or absent α-L-iduronidase (IDUA) enzyme activity due to pathogenic variants in IDUA gene. Early treatment with hematopoietic stem cell transplantation and/or enzyme replacement therapy is associated with improved outcomes in this progressive multisystem disease. The diagnosis is usually delayed due to late presentation and nonspecific symptoms resulting in high morbidity and mortality. The incidence of MPSI in US is estimated to be 0.26:100,000, however, it is unknown in Kuwait. This pilot study was undertaken to screen MPSI in all Kuwaiti neonates born at Farwaniya Hospital over a period of 12-months. This study examined the incidence of MPSI in a major center in Kuwait for inclusion in the national newborn screening program to enable its early detection and adequate treatment. Methods: All Kuwaiti neonates born at Farwaniya Hospital, Kuwait from December 2021 to December 2022, were screened for MPSI. The screening consisted of determining IDUA enzyme activity in dried blood spots (DBS)-derived samples by Tandem Mass Spectrometry. A follow-up genetic analysis of IDUA gene is planned to screen the cases with diminished IDUA enzyme activity as second-tier testing. Results: A total of 618 newborns, including 331 (54%) males and 287 (46%) females, were screened. Twenty of them had deficient IDUA enzyme activity but showed negative genetic testing for IDUA. However, we have diagnosed one additional female baby with MPSI, who belonged to Farwaniya Hospital, but the parents chose to deliver in a private hospital. She presented at age three months with recurrent upper airway infections, snoring and extensive Mongolian spots. The molecular study revealed previously reported pathogenic nonsense variant in IDUA c.1882C>T; p.(Arg628Ter), associated with severe phenotype. That being included, MPSI is estimated to be about 0.3% among tested females and 0.2% of all screened cases in Kuwait. Conclusion: Our study is the first to evaluate the incidence of MPSI in Kuwait. Given the single center, small number of screened babies and the short study duration thus far, it is premature to calculate the incidence of MPSI. It is anticipated that as the study continues and more infants are examined, we would be able to estimate the incidence of this disease in our population correctly. Further studies including screening newborns in all maternity hospitals in Kuwait are needed to calculate the actual incidence of MPSI. Our data supports including MPSI in national newborn screening program to allow early initiation of treatment and thus improve disease outcome.

The level of technological development of any civilization can be gaged in large part by the amount of energy they produce for their use, but also encompasses that civilization’s stewardship of their home world. Following the Kardashev definition, a Type I civilization is able to store and use all the energy available on its planet. In this study, we develop a model based on Carl Sagan’s K formula and use this model to analyze the consumption and energy supply of the three most important energy sources: fossil fuels (e.g., coal, oil, natural gas, crude, NGL and feedstocks), nuclear energy and renewable energy. We also consider environmental limitations suggested by United Nations Framework Convention on Climate Change, the International Energy Agency, and those specific to our calculations to predict when humanity will reach the level of a Kardashev scale Type I civilization.

Progression of oral squamous cell carcinoma (OSCC) has been associated with an escape of tumor cells from the host immune surveillance due to an increased knowledge of its underlying molecular mechanisms and its modulation by the tumor microenvironment and immune cell repertoire. In this study the expression of HLA class I (HLA-I) antigens and of components of the antigen processing machinery (APM) was analyzed in 160 pathologically classified human papilloma virus (HPV)-negative OSCC lesions and correlated to the intra-tumoral immune cell response, IFN- signaling and to the patients outcome. A heterogeneous, but predominantly lower constitutive protein expression of HLA-I APM components was found in OSCC sections when compared to non-neoplastic cells. Tumoral HLA-I APM component expression was further categorized into the three major phenotypes HLA-Ihigh/APMhigh, HLA-Ilow/APMlow and HLA-Idiscordant high/low/APMhigh. In the HLA-Ihigh/APMhigh group, the highest frequency of intra-tumoral CD8+ T cells and lowest number of CD8+ T cells close to FoxP3+ cells was found. Patients within this group presented the most unfavorable survival, which was significantly evident in stage T2 tumors. Despite a correlation with the number of intra-tumoral CD8+ T cells, tumoral JAK1 expression as a surrogate marker for IFN- signaling was not associated with HLA-I/APM expression. Thus, the presented findings strongly indicate the presence of additional factors involved in the immunomodulatory process of HPV-negative OSCC with a possible tumor-burden-dependent complex network of immune escape mechanisms beyond HLA-I/APM components and T cell infiltration in this tumor entity.

Looking at different operating climatic conditions, the electrical behavior predicting photovoltaic modules gets very important. For the estimation of output power from photovoltaic (PV) plants this is a very essential and basic aspect. In this paper, the relationship between the I-V curve and the irradiation spectrum is discussed by combining the single diode model. An explicit elementary analytical model with two defined shape parameters is discussed and improved with three approximations and second order Taylor expansion. Then, the explicit elementary analytical model is investigated under varying conditions leveraging the four parameters I_ph, I₀, R_s and R_sh from the single diode model. The relationship between the physical parameters and the condition parameters are discussed and applied to extract the shape parameters at different scenarios. Considering the aging effect, the process of calculation to predict the I-V curve under different splitting spectra is simplified as follow: (1) two shape parameters are gotten from the I-V data at measurement reference conditions (MRC); (2) the short circuit current, open circuit voltage and shape parameters under any splitting spectrum can be calculated based on the relationship provided in article; (3) the performance of PV panel can be predicted with parameters. The validation of this model was experimentally proven leveraging monocrystalline silicon photovoltaic module with different splitting films. Results showed that the model accurately predicts the I-V characteristics for the examined PV modules at different irradiance spectra and cell temperatures. Moreover, the presented model performs superior compared to other investigated models when looking at accuracy and simplicity.

Radio loud active galactic nuclei are composed of different spatial features, each one characterized by different spectral properties in the radio band. Among them, blazars are the most common class of sources detected at gamma-rays by \fermi, and their radio emission is dominated by the flat spectrum compact core. In this contribution, we explore the connection between emission at high energy revealed by \fermi\ and at radio frequency. Taking as a reference the strong and very highly significant correlation found between gamma rays and cm-$\lambda$ radio emission, we explore different behaviours found as we change the energy range in gamma rays and in radio, therefore changing the physical parameters of the zones involved in the radiation emission. We find that the correlation weakens when we consider (1) gamma rays of energy above 10 GeV (except for high synchrotron peaked blazars) or (2) low frequency radio data taken by the Murchison Widefield Array; on the other hand, the correlation strengthens when we consider mm-$\lambda$ data taken by ALMA.

In green chemistry, filamentous fungi are regarded as a kind of robust microorganism for the biotransformation of natural products. Nonetheless, the screening of microorganisms is crucial for the effective biotransformation of natural products such as phenazine compounds. The precursor metabolite of most phenazine derivatives in Pseudomonas spp. is phenazine-1-carboxylic acid (PCA), the key constituent of shenqinmycin, widely used to control rice sheath blight in southern China. In this study, a new fungus strain Aspergillus sclerotiorum was isolated, which can efficiently convert PCA into 3-hydroxy-phenazine 1-carboxylic acid (3-OH-PCA). Moreover, an effective whole cells biotransformation system was constructed by screening optimal reaction conditions and carbon sources. Hence, Aspergillus sclerotiorum exhibited desirable adaptation by consumption of different carbon sources and maximum whole cell biomass (10.6 g/L DCW) was obtained as a biocatalyst from glucose. Optimal conditions for whole-cell biocatalysis of PCA were evaluated, including PCA concentration of 1120 mg/L, pH 7.0, temperature of 25°C, rotation rate 200 rpm and dry cell weight 15 g/L for 60 h, thus 1060 mg/L of 3-OH-PCA was obtained and the conversion efficiency of PCA was 94%. Hence, the results of repeated batch mood revealed that the biotransformation efficiency of fungus pellets reduced with each subsequent cycle but remained stable in all five cycles with the provision of glucose supplement. These findings open the prospective of using filamentous fungi for the whole cell biocatalysis of phenazine in enormous amount and efficient production of 3-OH-PCA. Moreover, these results laid the foundation for further research to disclose the genetic based mechanism of the strain responsible for PCA biotransformation.

Chronic kidney disease (CKD) affects approximately 12% of the global population posing a significant health threat. Inflammation plays a crucial role in the uremic phenotype of CKD contributing to elevated cardiovascular and overall mortality in affected individuals. This study aimed to explore novel metabolic pathways in non-dialysis dependent stage 5 CKD patients using semitargeted metabolomics. In a prospective observational design involving 50 patients, blood samples collected before the initial hemodialysis session underwent liquid chromatography and high resolution mass spectrometer analysis. Univariate (Mann-Whitney test) and multivariate (logistic regression with LASSO regularization) methods identified metabolomic variables associated with inflammation. Notably, adenosine-5’-phosphosulfate (APS), dimethylglycine, pyruvate, lactate, and 2-ketobutyric acid exhibited significant differences in the presence of inflammation. Cholic acid, homogentisic acid, and 2-phenylpropionic acid displayed opposing patterns. Multivariate analysis indicated increased inflammation risk with certain metabolites (N-Butyrylglycine, dimethylglycine, 2-Oxoisopentanoic acid, and pyruvate), while others (homogentisic acid, 2-Phenylpropionic acid, and 2-Methylglutaric acid) suggested decreased probability. These findings unveil potential inflammation-associated biomarkers related to defective mitochondrial fatty acid beta oxidation and branched-chain amino acid breakdown in CKD, shedding light on cellular energy production and offering insights for further clinical validation.

Five new cembrane-type diterpenes, lobocalines A–E (1–5), and four new steroids, lobocalines F–I (9–12), along with six known related compounds (6–8 and 13–15) were isolated from the Yalong Bay soft coral Lobophytum catalai. The structures of the new compounds were elucidated by extensive spectroscopic analysis, NMR calculation with DP4+ analysis, time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations, X-ray diffraction analyses, and the comparison with the reported spectroscopic data of known compounds. Further, with the aid of X-ray diffraction analysis, the structure of lobocrasol B (15) was firmly revised as 15a. In in vitro bioassays, compound 2 showed moderate antibacterial activities against fish pathogenic bacteria Streptococcus parauberis KSP28 and Phoyobacterium damselae FP2244 with minimum inhibitory concentration (MIC) values of 8.7 and 17.3 µg/mL, respectively. All the steroids exhibited antibacterial activities against the S. parauberis KSP28 with MIC values ranging from 12.3 to 53.6 µg/mL. Compounds 2, 7 and 14 have remarkable inhibitory effects on the hemolysin production of Staphylococcus aureus, while compounds 8–12 have medium inhibitory effects on the pyocyanin production in Pseudomonas aeruginosa.

Personal Information Management Systems (PIMS) are acquiring a prominent role in the data economy by promoting services that help individuals to have more control over the processing of their personal data, in line with the European data protection law. One of the highlighted solutions in this area is Solid, a new protocol that is decentralizing the storage of data, through the usage of interoperable Web standards and semantic vocabularies, to empower its users to have more control over the processing of data by agents and applications. However, to fulfill this vision and gather widespread adoption, Solid needs to be aligned with the law governing the processing of personal data in Europe, the main piece of legislation being the General Data Protection Regulation (GDPR). To assist with this process, we analyze the current efforts to introduce a policy layer in the Solid ecosystem, in particular, related to the challenge of obtaining consent for processing personal data, focusing on the GDPR. Furthermore, we investigate if, in the context of using personal data for biomedical research, consent can be expressed in advance, discuss the conditions for valid consent and how it can be obtained in this decentralized setting, namely through the matching of privacy preferences, set by the user, with requests for data and whether this can signify informed consent. Finally, we discuss the technical challenges of an implementation that caters to the previously-identified legal requirements.

Metal complexes feature a wide range of available geometries, diversified lability, controllable hydrolytic stability, and easily available rich redox activity. These characteristics combined with the specific properties of the coordinated organic molecules result in many different mechanisms of biological action, making each of the myriads of the classes of metal coordination compounds unique. This focused review presents combined and systematized results of the studies of a group of copper(I) (pseudo)halide complexes with aromatic diimines and tris(aminomethyl)phosphines of a general formula [CuX(NN)PR₃], where X = I^- or NCS^-, NN = 2,2’-bipyridyl, 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline or 2,2’-biquinoline, and PR₃ = Air-stable tris(aminomethyl)phosphines. The structural and electronic properties of the phosphine ligands and luminescent complexes are discussed. The complexes with 2,9-dimethyl-1,10-phenanthroline, apart from being air- and water-stable, exhibit a very high in vitro antimicriobial activity against the Staphylococcus aureus and Candida albicans. Moreover, some of the complexes also show a strong in vitro antitumor activity against human ovarian carcinoma cell lines: MDAH 2774 and SCOV 3, CT26 (mouse colon carcinoma), and A549 (human lung adenocarcinoma) cell lines. The tested complexes are moderately able to induce DNA lesions through free radical processes, however the trends do not reflect observed differences in biological activity.

The SARS–CoV-2 infection has caused both acute and chronic COVID–19 disease during the recent pandemic with emerging more transmissible SARS–CoV–2 Omicron variants (BQ1 and XBB1) that have increased demands for more effective immunogens and therapeutic approaches to protect the lives of numerous SARS–CoV-2 affected individuals and reduce overall disease burden that could be affected by concurrent other pathogens causing diseases. Following a worldwide campaign of mass vaccination, there is still a significant demand to quell the harmful effects of novel SARS–CoV–2 infections due to higher mutation rates within specific areas of the SARS–CoV-2 domain, leading to enhanced viral entry, especially within individuals with one or more significant comorbidities, and there is still a dilemma of how prevention of future pandemics will occur as within host animal mutations and cross species transfer naturally occurs. Concerns intersect at a specific point; a gained evolutionary ability of several viruses over the previous centuries to remain undetected during the first stages of infection by means of capping the 5' end of their DNA and RNA genes respectively. This may occur by reducing the rate of host Type I and Type III Interferons (IFN) cellular synthesis, that would usually occur and affect both apoptotic pathways, that facilitate viral replication and clearance, as well as immune cells, that process and present pathogenic antigen epitopes. Furthermore, although methods of vaccination exist, other methods in clinical development remain that could evoke an immune response in different cellular, serum or mucosal compartments being cellular, serum and mucosal that evoke differential antibody responses. Antibodies are classed as natural and adaptive. Natural antibodies are further classed into neutralizing and non-neutralizing, whilst adaptive antibodies are also further classed into monoclonal and polyclonal. As a result of single cell study transcriptome research, viruses do utilize an array of protein receptors for receptor-mediated cellular entry. This, therefore suggests that potential differential production of antibody immunoglobulins (Ig) within serum and mucosal areas remains affected by cytokines, adhesion molecules and chemokines that can be upregulated or downregulated upon host viral infection. Serum plasma antibodies can be multimeric that may not efficiently cross the nasal epithelium cell layer, therefore offering less protection against mucosal inflammation due to mucin proteins. On the other hand, antibodies produced by mucosal plasma cells at epithelial surfaces are known to provide effective immune responses in some viral infections. The existence of developments that stimulate mucosal immune responses has so far only been seen with influenza nasal immunogens. Nevertheless, scientists developed ways of immunization and early treatment worldwide that generally showed good success rates and fewer risks of adverse events, and the still early present stages of COVID-19 research should also be taken into consideration. For example, the administration of human interferons I and III into the nasal mucosa cellular layer, as key mediators of anti–viral activity, can stimulate cellular activity to train the innate and adaptive immune system cells to develop and appropriately stimulate an adequate immune response through B and T cells. Recently, it was discovered that specific plants secrete proteins that also stimulate the production of Type I Interferons. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. Naturally-selected polymorphic viruses through genetic recombination pose challenges to traditional concepts of cellular and molecular immune system neutralization of these viruses during the first stages of cellular infection. It is until the scientific community realizes this potentially crucial aspect that we will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades, evidenced with dengue fever and more recently monkeypox. Type I IFNs tend to be produced faster than Type III IFNs, and the first induce slightly more abundant pro-inflammatory signals than the latter, meaning that type III IFNs, if produced early, may further decrease the extent of excessive proinflammatory signals. Hence, we believe that nasal sprays containing a low dosage of Type I and Type III IFNs not only represent a relevant COVID-19 therapeutic, but also a potential unknown modulatory therapy of the future. Of note, it has been indicated that IFN I and / or III display significant early therapeutic effects for other viral evoked diseases like Influenza (A)H1N1 (Influenza), Rabies lyssavirus (rabies), measles virus (measles), Rubivirus rubellae (rubella), Hepatitis B, HIV-induced AIDS, as well as bacterial diseases, such as lower respiratory tract infectious disease induced by Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus, and a number of oncological diseases, like hepatic melanoma.

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the association between ACE I/D polymorphism and cardiovascular mortality risk among non-hemodialyzed chronic kidney disease patients. This cross-sectional study examined 70 patients of Javanese ethnic origin with stable CKD who did not receive hemodialysis. ACE I/D polymorphisms, plasma ACE levels, atherosclerotic cardiovascular disease (ASCVD) risk, and cardiovascular mortality risk were investigated. As per our findings, the I allele was found to be more frequent (78.6) than the D allele (21.4), and the DD genotype was less frequent than the II genotype (4.3 vs. 61.4). The ACE I/D polymorphism had a significant direct positive effect on plasma ACE levels (path coefficient = 0.302, p = 0.021). Similarly, plasma ACE levels had a direct and significant positive effect on the risk of atherosclerotic cardiovascular disease (path coefficient = 0.410, p = 0.000). Moreover, atherosclerotic cardiovascular disease risk had a significant positive effect on cardiovascular mortality risk (path coefficient = 0.918, p = 0.000). The ACE I/D polymorphism had no direct effect on ASCVD and cardiovascular mortality risk. However, our findings show that the indirect effects of high plasma ACE levels may be a factor in the increased risk of ASCVD and cardiovascular mortality in Javanese CKD patients.

A novel low-power MOS-only voltage reference is presented. The Enz-Krummenacher-Vittoz (EKV) model is adopted to provide a new perspective on the operating principle. The normalized charge density, introduced as a new variable, serves as an indicator when trimming the output temperature coefficient. The proposed voltage reference consists of a specific current generator and a 5-bit trimmable load. Thanks to the well-match between the current source stage and the output stage, the non-linear temperature dependence of carrier mobility is automatically canceled out. The circuit is designed in 55 nm COMS technology. The operating temperature ranges from -40 ∘C to 120 ∘C. The average temperature coefficient of the output voltage can be reduced to 21.7 ppm/∘C by trimming. The power consumption is only 23.2 nW with a supply voltage of 0.8 V. The line sensitivity and the power supply rejection ratio at 100 Hz are 0.011 %/V and -89 dB respectively.

Here we draw insights from the latest serendipitous findings made on the opposing roles of a validated drug-target protein Keap1. We weigh up how natural reactive electrophiles and electrophilic small-molecule drugs in clinical use directly impinge on seemingly conflicting, yet both Keap1-electrophile-modification-dependent, cell-survival- vs. cell-death-promoting behaviors. In the process, we convey how understanding reactive chemical-signal regulation at a single-protein-specific level is an enabling necessity in deconstructing otherwise intricate reactive-small-molecule-responsive cellular pathways. We hope this opinion piece further spurs the broader interests of basic and pharmaceutical research communities toward better understanding of molecular mechanisms underpinning reactive small-molecule-regulated signaling subsystems.

HIV-1 Tat protein interacts with TAR RNA and recruits CDK9/cyclin T1 and other host factors to induce HIV-1 transcription. Thus Tat-TAR RNA interaction, which is unique for HIV-1, represents an attractive target for anti-HIV-1 therapeutics. To target Tat-TAR RNA interaction, we used a crystal structure of TAR RNA with acetylpromazine bound to the bulge of TAR RNA, to dock compounds from Enamine database containing 1.6 million individual compounds. Docking identified 173 compounds that were analyzed for the inhibition of HIV-1 infection. Top ten inhibitory compounds with IC50 ≤ 6 µM were selected and the three least toxic compounds, T6780107 (IC50=2.97 μM), T0516-4834 (IC50=0.2 μM) and T5628834 (IC50=3.46 μM), were further tested for HIV-1 transcription inhibition. Only T0516-4834 compound showed selective inhibition of Tat-induced HIV-1 transcription, whereas T6780107 compound inhibited equally basal and Tat-induced transcription and T5628834 compound only inhibited basal HIV-1 transcription. The T0516-4834 compound also showed strongest inhibition of HIV-1 gag RNA expression and p24 production in CEM T cells infected with HIV-1 IIIB. Of the three compounds, only the T0516-4834 compound disrupted Tat-TAR RNA interaction indicating that it might target TAR RNA. Also, of the three tested compounds, T5628834 but not T6780107 or T0516-4834 disrupted Tat-CDK9/cyclin T1 interaction. Taken together, our study identified novel compound T0516-4834 that disrupted Tat-TAR RNA interaction and inhibited Tat-induced transcription and HIV-1 infection suggesting that this compound might serve as a new lead for anti-HIV-1 therapeutics.

The quantitative and qualitative assessment of gold grains from samples of glacial till is a well-established method for exploring gold deposits hidden under glaciated cover. This method, widely used by the industry and which produced numerous successes in locating gold deposits in glaciated terrain, is still based on artisanal gravity separation techniques and visual identification. However, being artisanal, it is limited by inconsistent recoveries and the difficulty to visually identify the predominantly occurring small gold grains. These limitations hinder its capability to deceipher subtle or complex signal. To improve detection limits through recovery of small gold grains, a new approach has recently been introduced in the industry (commercially referred as “ARTGold” procedure) using an optimized miniature sluice box coupled with an automated scanning electron microscopy routine. The capabilities of this improved method are highlighted by comparing till surveys conducted around the Borden gold deposit (Ontario, Canada) using the conventional and improved methods at both local and regional scales. Relative to the conventional approach, the improved method recovered almost one order of magnitude more gold grains from samples (regional and down-ice mineralization), dominantly in small size fractions. Increasing the counts in low-abundance regional samples enables better discrimination between background signals and significant dispersions. The method offers an alternative to improve characterization of gold dispersal in glaciated terrain and the related gold deposit footprints.

Skin involvement is an overlooked aspect in the management of paediatric patients with type 1 diabetes. A comprehensive search of published literature using the PubMed database was carried out using the following key terms: “children”, “pediatric/paediatric patients”, “skin”, “skin disorders”, “type 1 diabetes”. Dermatological side effects are frequently observed among diabetic children and adolescents. Insulin-induced lipodystrophies and allergic contact dermatitis caused by insulin pumps or glycaemic sensors are the most common skin reactions in these patients. Furthermore, several diabetes-associated skin diseases such as necrobiosis lipoidica, granuloma annulare, vitiligo, and bullosis diabeticorum may already be present in paediatric age. Paediatric diabetes specialists should pay attention to their patients’ skin so as to recognize these disorders, identify the potential causes, and choose the most suitable treatment. Finally, the evaluation of skin concentrations of advanced glycation end-products using non-invasive diagnostic techniques may be used to assess the risk of chronic complications of diabetes as early as adolescence.

Astronauts at are risk of losing 1.0 – 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs designed to preserve the musculoskeletal system. This article reviews the basics of bone formation and resorption and details how exposure to microgravity or simulated microgravity affects the structure and function of osteoblasts, osteocytes, osteoclasts, and their mesenchymal and hematologic stem cell precursors. It details the critical roles that insulin-like growth facor-1 and its receptor IGFR1 play in maintaining bone homeostasis and how exposure of bone cells to microgravity affects the function of these growth factors. Lastly, it discusses the potential of tumor necrosis factor-related apoptosis-inducing ligand, syncytin-A, and sclerostin inhibitors and recombinant IGF-1 as a bone-saving treatment for astronauts in space and during their colonization of the Moon.

For any odd positive integer $x$, define $(x_n)_{n\geqslant 0} $ and $(a_n )_{n\geqslant 1} $ by setting $x_{0}=x, \,\, x_n =\cfrac{3x_{n-1} +1}{2^{a_n }}$ such that all $x_n $ are odd. The 3x+1 problem asserts that there is an $x_n =1$ for all $x$. Usually, $(x_n )_{n\geqslant 0} $ is called the trajectory of $x$. In this paper, we concentrate on $(a_n )_{n\geqslant 1} $ and call it the E-sequence of $x$. The idea is that, we consider any infinite sequence $(a_n )_{n\geqslant 1} $ of positive integers and call it an E-sequence. We then define $(a_n )_{n\geqslant 1} $ to be $\Omega-$convergent to $x$ if it is the E-sequence of $x$ and to be $\Omega-$divergent if it is not the E-sequence of any odd positive integer. We prove a remarkable fact that the $\Omega-$divergence of all non-periodic E-sequences implies the periodicity of $(x_n )_{n\geqslant 0} $ for all $x_0$. The principal results of this paper are to prove the $\Omega-$divergence of several classes of non-periodic E-sequences. Especially, we prove that all non-periodic E-sequences $(a_n )_{n\geqslant 1} $ with $\mathop {\overline {\lim } }\limits_{n\to \infty } \cfrac{b_n }{n}>\log _23$ are $\Omega-$divergent by using the Wendel's inequality and the Matthews and Watts's formula $x_n =\cfrac{3^n x_0 }{2^{b_n }}\prod\limits_{k=0}^{n-1} {(1+\cfrac{1}{3x_k })} $, where $b_n =\sum\limits_{k=1}^n {a_k } $. These results present a possible way to prove the periodicity of trajectories of all positive integers in the 3x + 1 problem and we call it the E-sequence approach.

The author had previously set out devices to communicate over space-like intervals, with a full proof for the 2‑photon device and only a partial proof for the 1-photon device. The 2-photon device exploits entangled pairs; the 1-photon device utilises path-entanglement. The 1-photon device is fully analysed, then similarities (and differences) are drawn to the 2-photon device to show the holes in the No-communications Theorem: the creation operators representing the sum of paths through the device can be mapped outside the device and quantum state reduction/measurement is a space-like operation. A common misconception on faux rank-3 systems made from rank-2 components is elucidated, avoiding the criticism and null result obtained by naively taking the partial trace.

1-[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]methanamine compound has been successfully synthesized by reacting p-Toluic hydrazide and glycine via polyphosphoric acid condensation route. The course of the reaction was found to be high yielding and the title compound was spectroscopically characterized by FT-IR, DSC, 13C/1H-NMR and Mass spectrometric techniques.

Vilsmeier–Haack reaction of (E)-1-(1-(3,5-difluorophenyl)ethylidene)-2-phenylhydrazine (1) using dimethyl formamide in excess of phosphorous oxychloride by conventional method, resulted in the synthesis of title compound 3-(3,5-difluorophenyl)-1-phenyl-1H-pyrazole-4- carbaldehyde (2) in good yield and high purity. Structure characterization of the novel title compound was done by IR, ¹H NMR, ¹³C NMR and mass spectral analysis.

Acid proteins capable of nucleating Ca2+ and displaying aggregation capacity play key roles in the formation of calcium carbonate biominerals. EF-hands are among the largest Ca2+-binding motif in proteins. Gad m 1, an Atlantic cod β-parvalbumin isoform, is a monomeric EF-hand protein that acts as a Ca2+ buffer in fish muscle and is able to form amyloids under acidic conditions. Since nucleating Ca2+ protein have a propensity to form extended β-strand structures, we wondered whether amyloid assemblies of a protein containing refolded EF-hand motifs were able to influence the in vitro calcium carbonate crystallization. Here we have used the Gad m 1 chain as model to generate monomeric and amyloid assemblies and analyze their effect on in vitro calcite formation. We found that only amyloid assemblies alter calcite morphology.

Ethylene is an essential plant hormone critical in various physiological processes. These processes include seed germination, leaf senescence, fruit ripening, and the plant's response to environmental stressors. Ethylene biosynthesis is tightly regulated by two key enzymes, namely 1-aminocyclopropane-1-carboxylate synthase (ACS) and 1-aminocyclopropane-1-carboxylate oxidase (ACO). Initially, the prevailing hypothesis suggested that ACS is the limiting factor in the ethylene biosynthesis pathway. Nevertheless, accumulating evidence from various studies has demonstrated that ACO, under specific circumstances, acts as the rate-limiting enzyme in ethylene production. Under normal developmental processes, ACS and ACO collaborate to maintain balanced ethylene production, ensuring proper plant growth and physiology. However, under abiotic stress conditions, such as drought, salinity, extreme temperatures, or pathogen attack, the regulation of ethylene biosynthesis becomes critical for plants’ survival. This review highlights the structural characteristics, examines the transcriptional, post-transcriptional, and post-translational regulation of ACS and ACO, and their role under abiotic stress conditions. Reviews on the role of ethylene signaling in abiotic stress adaptation are available. However, a review that delineates the role of ACS and ACO in abiotic stress acclimation is not available.

(3+1)D quantum mechanics is a four-dimensional quantum formalism, which is developed neither in a Minkowski spacetime, nor in a purely Hilbert space and not its metric is Lorentzian. This quantum mechanics also yields the quantum Einstein field equation in (3+1)D quantum spacetime. Every observable (3+1)D quantum spacetime can be found to contain internally hidden opposite spin quantum state, that results Supersymmetry. Closed continuous mappings of this hidden quantum state immediately yield more extra hidden dimensions including string. This string is found to be fundamentally eleven-dimensional (rather than lower dimensional) by nature within this quantum spacetime, which is necessarily a natural phenomenon of (3+1)D Quantum Mechanics.

Sentinel-1 SAR data preprocessing is essential for several earth observation applications, including land cover classification, change detection, vegetation monitoring, urban growth, natural hazards, etc. The information can be extracted from the 2x2 covariance matrix [C2] of Sentinel-1 dual-pol (VV-VH) acquisitions. To generate the covariance matrix from Sentinel-1 single look complex (SLC) data, several preprocessing steps are required. The ESA SNAP S-1 toolbox can be used to preprocess the data to generate a [C2] matrix. The polarimetric analysis in respective application fields often starts with the covariance matrix. However, due to limited availability of Sentinel-1 SLC data preprocessing workflow standards for polarimetric applications in contemporary research methods, downstream applications unable to comply with these workflows directly. In this paper, we propose a couple of generic practices to preprocess Sentinel-1 SLC data in SNAP S-1 toolbox, which would be beneficial for the radar remote sensing user community.

Shot peening has become a well-established technique for the introduction of beneficial compressive Residual Stresses (RS) into the near-surface layers of metallic materials for the purpose of preventing or suppressing fatigue crack nucleation and growth. Ti-alloys are widely used to fabricate compressor blades of aeroengines. Titanium blades that may be susceptible to different modes of damage under cyclic loading (high cycle fatigue, fretting fatigue) are often subjected to shot peening to extend their safe operating time. The control and monitoring of residual stresses in titanium blades is of great importance to assure the safety of aeroengines. The techniques for residual stress evaluation include mechanical methods (material removal) as well as physical methods such as X-ray diffraction. Perhaps the most common and practically accessible form of the latter is the method. Conventional laboratory X-ray diffractometers typically probe samples to the depths up to ~20 µm that correspond to 1x...5x the average grain size for typical metals and alloys. The limitations of the method have been identified and reviewed in the literature, motivating the use of other semi-destructive approaches to evaluate the residual stresses in deeper layers and at more sharply defined locations. In the present report we present a case study of the comparison between non-destructive and semi-destructive evaluation techniques, namely the X-ray diffraction method against the mechanical and FIB-DIC ring-core drilling applied to the samples of VT6 (Russian designation of Ti-6Al-4V) titanium alloy after shot peening with 1 mm steel balls. Mechanical drilling of circular holes of ~2 mm diameter with laser speckle interferometry monitoring of strains gives a rough spatial resolution of a few millimeters, while the Korsunsky FIB-DIC method of Ga-ion beam micro-ring core milling within FIB-SEM with Digital Image Correlation (DIC) deformation analysis delivers spatial resolution down to a few micrometers. Good agreement has been found between the X-ray and FIB-DIC estimates of RS variation profiles as a function of depth in shot peened titanium alloy samples. Some advances in the FIB-DIC method are presented and discussed in terms of the acceleration of data acquisition and interpretation.

Lung cancer is a common malignant tumor of the lung and the leading cause of cancer mortality worldwide. Non-small-cell lung cancer (NSCLC) accounts for 80%–85% of lung cancer, 40% of NSCLCs will have spread beyond the lungs by the time it is diagnosed. Long non-coding RNA (LncRNA) prostate androgen-regulated transcript 1 (PART-1) was reported that promote the development of several cancers. In the current study, we conducted experiments to investigate the role of PART-1 in the proliferation, invasion, and migration of NSCLC. The expression level of the PART-1 gene increased significantly in the NSCLC cell lines, including A549, H1229, H1650, H1975, and PC9. Knocking down of PART-1 inhibited the proliferation, invasion, and migration of A549 cells, moreover, decreased the tumor proliferation in nude mice. We confirmed that PART-1 targeted miR-204-3p directly, and miR-204-3p targeted the insulin-like growth factor binding protein 2 (IGFBP-2) directly. Furthermore, we discovered that PART-1 involved the NSCLC progression by regulating the miR-204-3p-targeted IGFBP-2 pathway. LncRNA PART-1 might be a target for treating NSCLC, and a warning sign of diagnosis of early lung cancer.

The provenance of the aminoacyl-tRNA synthetases (aaRS) poses challenging questions because of their role in the emergence and evolution of genetic coding. We investigate evidence about their ancestry from curated structure-based multiple sequence alignments of a structurally invariant “scaffold” shared by all 10 canonical Class I aaRS. Three uncorrelated phylogenetic metrics—residue-by-residue conservation, its variance, and row-by-row cladistic congruence—imply that the Class I scaffold is a mosaic assembled from distinct, successive genetic sources. These data are especially significant in light of: (i) experimental fragmentations of the Class I scaffold into three partitions that retain catalytic activities in proportion to their length; and (ii) evidence that two of these partitions arose from an ancestral Class I aaRS gene encoding a Class II ancestor in frame on the opposite strand. Phylogenetic metrics of different modules vary in accordance with their presumed functionality. A 46-residue Class I “protozyme” roots the Class I molecular tree prior to the adaptive radiation of the Rossmann dinucleotide binding fold that refined substrate discrimination. Such rooting is consistent with near simultaneous emergence of genetic coding and the origin of the proteome, resolving a conundrum posed by previous inferences that Class I aaRS evolved long after the genetic code had been implemented in an RNA world. Further, pinpointing discontinuous enhancements of aaRS fidelity establishes a timeline for the growth of coding from a binary amino acid alphabet.

Introduction: In general, everyone believes that the smallest preterm infants should achieve normal intrauterine growth rates, but many thinks that this is not possible with current nutrition guidelines. There is resistance to giving enough nutrition for fear of "toxicity". The difference in weight Z-score between birth and a corrected gestational age (CGA) at discharge is assess in postnatal growth in our unit. Material and methods: An observational study was done between January 2018 and December 2020 where all cases that had ≤ 29 weeks of GA at birth and survived to 36 weeks corrected GA or that were discharged home. An aggressive nutrition protocol including parenteral as well as enteral nutrition was followed. Patients and their weight trajectory was plotted on the Fenton 2013 growth curve. The patients who had had a smaller WZP difference were also plotted. Results: A total of 32 cases were found. The median change in Z-score between birth and discharge of the whole group was -0.52 (IQR 0.53). Six of 32 (19%) had a more than one WZP, all of whom had severe pathologies. The median decline in Z score for this group with poor growth was 1.24 (IQR 0.22). There were 26 cases with a < 1 WZP (81%) and a median Z score fall of 0.39 (IQR 0.55). No important complications secondary to the ingested volumes or parenteral nutrition were reported. Conclusion: The group of cases with a > 1 WZP drop had severe pathologies. All the other cases had adequate growth parallel to normal weight growth charts and a few cases had some catch-up growth. The study showed that it is possible for many preterm infants to achieve normal intrauterine growth rates if they are given enough nutrition, but bigger multicenter studies are needed to confirm these findings.

Analyzing big data poses a great challenge for numerous researchers to explore the data structure. Dimension reduction methods can be used to reduce data dimensionality, taking it from occupying a high-dimensional space to existing in a lower-dimensional space while retaining as much information as possible. Principal Component Analysis is one of the most popular used to reduce the dimensional space. The bootstrap sample is obtained by randomly sampling n times with replacement from the original sample, the method provides easy tool to understand the interactive component and develop the process. There are not enough researches discussed the stability of PCA method using bootstrap method. In this paper, the bootstrap method is used to analyze the stability of PCA results and to estimate the number of PCA in efficient way. The method is used to estimate the number of PCA that needed to classify the data set, and the effectiveness of the discussed techniques is demonstrated through real data sets.

Wireless Sensor Networks (WSNs) continue to provide essential services for various applications such as surveillance, data gathering, and data transmission from the hazardous environments to safer destinations. This has been enhanced by the energy-efficient routing protocols that are mostly designed for such purposes. Gateway-based Energy-Aware Multi-hop Routing protocol (MGEAR) is one of the homogenous routing schemes that was recently designed to more efficiently reduce the energy consumption of distant nodes. However, it has been found that the protocol has a high energy consumption rate, lower stability period, less data transmission to the Base station (BS). In this paper, an enhanced Heterogeneous Gateway-based Energy-Aware multi-hop routing protocol ( HMGEAR) is proposed. The proposed routing scheme is based on the introduction of heterogeneous nodes in the existing scheme, selection of the head based on the residual energy, introduction of multi-hop communication strategy in all the regions of the network, and implementation of energy hole elimination technique. Results show that the proposed routing scheme outperforms two existing ones.

P53 is known as the most critical tumor suppressor and is often referred to as the guardian of our genome. More than 40 years after its discovery, we are still struggling to understand all molecular details on how this transcription factor prevents oncogenesis or how to leverage current knowledge about its function to improve cancer treatment. Multiple cues, including DNA-damage or mitotic errors, can lead to the stabilization and nuclear translocation of p53, initiating the expression of multiple target genes. These transcriptional programs may well be cell type and stimulus-specific, as is their outcome that ultimately imposes a barrier to cellular transformation. Cell cycle arrest and cell death are two well-studied consequences of p53 activation, but, while being considered as critical, they do not fully explain the consequences of p53 loss-of-function phenotypes in cancer. Here, we discuss how mitotic errors alert the p53 network and give an overview on multiple ways how p53 can trigger cell death. We argue that a comparative analysis of different types of p53 responses, elicited by different triggers in a time-resolved manner in well-defined model systems is critical to understand cell type specific cell fate induced by p53 upon its activation, in order to resolve the remaining mystery of its tumor suppressive function.

Origin, mechanics and properties of the Solar System are analysed in the framework of the Complete Relativity theory (by the same author). According to Complete Relativity, everything is relative. Any apparent absolutism (notably invariance to scale of dimensional constants, absolute elementariness, invariance to time) is an illusion stemming from limits imposed by [or on] polarized observers that will inevitably lead to misinterpretation of phenomena (another illusion) occurring on non-directly observable scales or even on observable but distant scales in space or time. If everything is relative, reference frames will exist where particles are planets and where planets are living beings. Earth is, therefore, analysed here in more detail, both as a particle and, as a living evolving being (of, hypothesized, extremely introverted intelligence). The analysis confirms the postulates and hypotheses of the theory (ie. existence of discrete vertical energy levels) with a significant degree of confidence. During the analysis, some new hypotheses have emerged. These are discussed and confirmed with various degrees of confidence. To increase confidence or refute some hypotheses, experimental verification is necessary. Main conclusions that stem from my research and are further confirmed in this paper are: universes are, indeed, completely relative; Solar System is a scaled (inflated, in some interpretations) Carbon isotope with a nucleus in a condensed (bosonic) state and components in various vertically excited states; life is common everywhere, albeit extroverted complex forms are present on planetary surfaces only during planetary neurogenesis; anthropogenic climate change is only a part (trigger from one perspective) of bigger global changes; major extinction events on a surface of a planet are relative extinctions, a regular part of transformation and transfer of life in the process of planetary neurogenesis.

The following series of Articles about a contextual system-theory, with focus on biological systems, shall give a guideline of how to explore complex systems. It is written not only for scientists, and therefore I will try to describe part of the way of understanding as an intuitive approach. This approach will also help scientists to get a deeper understanding of complexity. Some definitions and rules may seem at first simple and obvious. If practiced in a multidimensional complex system, one will see the difficulties. Even without mathematization or computer modeling the multidimensional sub space, which we try to describe phenomenologically for approaching the understanding of this Subsystem, will need a lot of training. Easily we get lost in the multidimensional world. Some of the chapters here and in the following publications of this series are written for specialists, but it will always come back to the essence of a phenomenological description. Concepts like Symbolic programming, Object oriented modeling, simulation and optimizing as well as experimental and mathematical approaches are the described tools to unpuzzle a complex scenario.

Myocardial fibrosis is a pivotal pathophysiological step of various cardiovascular diseases, which eventually leads to heart failure and death. Cardiac fibroblasts activation and subsequently differentiate into myofibroblasts are pivotal pathophysiological step in myocardial fibrosis. Phosphoglycerate mutase 1 (PGAM1) directly interacts with α-smooth muscle actin (ACTA2) and participate in fibrosis regulation. Allosteric inhibitor of PGAM1 could attenuates fibrosis through break the interaction of PGAM1 and ACTA2. In this study, we aimed to screen and identify novel ligand of PGAM1 in natural product library. Firstly, various natural products were screened via DARTS assay and Carthamus tinctorius L. was identified as a target pool for molecular docking. Then, in silico screening assay identified baicalein as a novel ligand. In addition, baicalein could directly bind to the PGAM1 protein with a KD value of 34.6 μM. Molecular dynamics simulation revealed that baicalin and PGAM1 interactions were stable. These findings indicate that PGAM1 is a direct pharmacological target of baicalein. Immunoblot analysis further demonstrated that baicalin inhibits the activation of fibroblasts in vitro. Finally, the anti-myocardial fibrosis effect of baicalein was verified in vivo. Taken together, our findings suggest that baicalein is a novel PGAM1 templates for developing new therapeutics against myocardial fibrosis.

B-1 cells, a subtype of B lymphocytes, are found in lymphoid tissues and peritoneal and pleural cavities. They play diverse roles, releasing cytokines, generating antibodies, regulating the immune response, engaging in phagocytosis, and moving to inflammatory sites. However, their physiology remains partially understood, especially in stressful conditions like sleep restriction. This study aimed to investigate murine B-1 cell activation and differentiation under sleep restriction. Male C57BL/6J mice underwent an 18-hour sleep restriction for 21 days, followed by Candida albicans or Paracoccidioides brasiliensis infection. Purified peritoneal B-1 cells were evaluated for activation markers, microbicidal molecules, cytokine gene expression, Toll-like receptors, and commitment factors. Results showed that sleep restriction minimally influenced activation marker expression in B-1 cells across infection models. However, under sleep restriction, microbicidal molecule production increased in P. brasiliensis (NO) and C. albicans (ROS) infections. Gene expression revealed elevated TLR-2 and cytokines (IL-12, IL-6, TNF-α) in sleep-restricted animals. Lineage commitment analysis indicated myeloid polarization in sleep-restricted B-1 cells for all infection models. These findings underscore the impact of sleep restriction on B-1 cell activation and differentiation, with outcomes varying based on infection type. This study highlights the importance of investigating immunological changes resulting from sleep restriction.

Herpesvirus is a prevalent pathogen that primarily infects human epithelial cells and has the ability to reside in neurons. In the field of otolaryngology, herpesvirus infection primarily leads to hearing loss and vestibular neuritis, and is considered the primary hypothesis regarding the pathogenesis of vestibular neuritis. In this review, we provide a summary of the effects of herpes virus on cellular processes in both host cells and immune cells, with a focus on HSV-1 as illus-trative examples.

In May 2022, WHO reported an outbreak of Mpox in several European countries which were previously Mpox free. Mpox (formerly known as monkeypox) is a zoonotic viral disease endemic in Central and West Africa. The sudden emergence of Mpox outside Africa and its subsequent rapid spread lead the WHO to declare the outbreak as Public Health Emergency of International Concern. As of May 15, 2023, a total of 87,704 confirmed cases and 140 deaths had been reported from 111 countries and territories worldwide. Looking back on this outbreak one year later, several important questions have arisen. Here, we address these questions using the classic five Ws: What, When, Where, Who and Why? We discuss these questions and outline what needs to be done to prevent, or at least minimize, outbreaks from emerging and re-emerging viral infection.

In recent years, with the popularity of smart mobile devices, the interaction between devices and users, especially in the form of voice interaction, has become increasingly important. If smart devices can understand more users' emotional states through voice data, more customized services can be provided for users. This paper proposes a novel machine learning model for speech emotion recognition, which combines convolutional neural networks (CNN), long short-term memory neural networks (LSTM), and deep neural networks (DNN), called CLDNN. To make the designed system can recognize the audio signal closer to the human auditory system does, this article uses the Mel frequency cepstral coefficients (MFCCs) of audio data as the input of the machine learning model. First, the MFCCs of the voice signal is extracted as the input of the model, and the feature values of the data are calculated using several local feature learning blocks (LFLB) composed of one-dimensional CNN. Because the audio signals are time-series data, the feature values obtained from LFLBs then input into LSTM layer to enhance the learning on time-series level. Finally, fully connected layers are used for classification and prediction. Three databases RAVDESS, EMO-DB and IEMOCAP are used for the experiments in this paper. The experimental results show that the proposed method can improve the accuracy compared to other related researches in speech emotion recognition.

Abstract Chaga´s disease caused by Trypanosoma cruzi infections is included in the group of neglected diseases, and efforts to develop new therapeutic or immunoprevention approaches have not been successful. After the publication of the T. cruzi genome, the number of molecular and biochemical studies on this parasite have increased considerably, many of which are focused on families of variant-surface-proteins, especially the trans-sialidases, mucins and mucin-associated proteins. The disperse gene protein 1 family (DGF-1) is one of the most abundant families in the T. cruzi genome, however, the large gene size, high copy numbers, and low antibody titers detected in infected humans make it an unattractive study target. Here, we argue that the DGF-1 gene family although not being the most obvious participant of the host-parasite immunological gamble, where T. cruzi appears to have the upper hand, it may play an important role in more basic host-parasite interactions that deserve further examination.

In this research, new setting is introduced for new SuperHyperNotions, namely, an 1-failed SuperHyperForcing and Neutrosophic 1-failed SuperHyperForcing. Assume a SuperHyperGraph. Then an ``1-failed SuperHyperForcing'' $\mathcal{Z}(NSHG)$ for a neutrosophic SuperHyperGraph $NSHG:(V,E)$ is the maximum cardinality of a SuperHyperSet $S$ of black SuperHyperVertices (whereas SuperHyperVertices in $V(G) \setminus S$ are colored white) such that $V(G)$ isn't turned black after finitely many applications of ``the color-change rule'': a white SuperHyperVertex is converted to a black SuperHyperVertex if it is the only white SuperHyperNeighbor of a black SuperHyperVertex. The additional condition is referred by ``1-'' about the usage of any black SuperHyperVertex only once to act on white SuperHyperVertex to be black SuperHyperVertex; a ``neutrosophic 1-failed SuperHyperForcing'' $\mathcal{Z}_n(NSHG)$ for a neutrosophic SuperHyperGraph $NSHG:(V,E)$ is the maximum neutrosophic cardinality of a SuperHyperSet $S$ of black SuperHyperVertices (whereas SuperHyperVertices in $V(G) \setminus S$ are colored white) such that $V(G)$ isn't turned black after finitely many applications of ``the color-change rule'': a white SuperHyperVertex is converted to a black SuperHyperVertex if it is the only white SuperHyperNeighbor of a black SuperHyperVertex. The additional condition is referred by ``1-'' about the usage of any black SuperHyperVertex only once to act on white SuperHyperVertex to be black SuperHyperVertex. Assume a SuperHyperGraph. Then an ``$\delta-$1-failed SuperHyperForcing'' is a \underline{maximal} 1-failed SuperHyperForcing of SuperHyperVertices with \underline{maximum} cardinality such that either of the following expressions hold for the (neutrosophic) cardinalities of SuperHyperNeighbors of $s\in S:$ $~|S\cap N(s)| > |S\cap (V\setminus N(s))|+\delta,~|S\cap N(s)| < |S\cap (V\setminus N(s))|+\delta.$ The first Expression, holds if $S$ is an ``$\delta-$SuperHyperOffensive''. And the second Expression, holds if $S$ is an ``$\delta-$SuperHyperDefensive''; a``neutrosophic $\delta-$1-failed SuperHyperForcing'' is a \underline{maximal} neutrosophic 1-failed SuperHyperForcing of SuperHyperVertices with \underline{maximum} neutrosophic cardinality such that either of the following expressions hold for the neutrosophic cardinalities of SuperHyperNeighbors of $s\in S:$ $~|S\cap N(s)|_{neutrosophic} > |S\cap (V\setminus N(s))|_{neutrosophic}+\delta,~ |S\cap N(s)|_{neutrosophic} < |S\cap (V\setminus N(s))|_{neutrosophic}+\delta.$ The first Expression, holds if $S$ is a ``neutrosophic $\delta-$SuperHyperOffensive''. And the second Expression, holds if $S$ is a ``neutrosophic $\delta-$SuperHyperDefensive''. A basic familiarity with SuperHyperGraph theory and neutrosophic SuperHyperGraph theory are proposed.

For over a century, viruses have left a long trail of evidence implicating them as frequent suspects in the development of type 1 diabetes. Through vigorous interrogation of viral infections in individuals with islet autoimmunity and type 1 diabetes using serological and molecular virus detection methods, and mechanistic studies of virus infected human pancreatic β-cells, the prime suspects have been narrowed down to predominantly human enteroviruses. Here we provide a comprehensive overview of evidence supporting the hypothesised role of enteroviruses in the development of islet autoimmunity and type 1 diabetes. We also discuss concerns over the historical focus and investigation bias toward enteroviruses, and summarise current unbiased efforts aimed at characterising the complete population of viruses (the “virome”) contributing early in life to the development of islet autoimmunity and type 1 diabetes. Finally, we review the range of vaccine and antiviral drug candidates currently being evaluated in clinical trials for the prevention and potential treatment of type 1 diabetes.

Myocardial infarction (MI) remains the leading cause of death in the western world. Although medical advancements have been made in interventional revascularization technologies, a large percentage of patients are not candidates for them due to co-morbidities or lack of local resources. Thus, there remains a need for the development of novel non-invasive strategies to treat MI. Approaches to accelerate revascularization within ischemic tissues through angiogenesis by providing Vascular Endothelial Growth Factor (VEGF) in protein or gene form has been shown to be effective in animal models but not in humans likely due to its short half-life and systemic toxicity. We previously showed that a small peptide (PR1P) we developed stabilizes VEGF in its active dimer state, increases VEGF binding to its receptors and potentiates VEGF activity. Here we show that systemic PR1P treatment targeted, stabilized and upregulated endogenous VEGF within ischemic myocardium following left coronary artery surgery in mice and rats. Targeted VEGF upregulation led to augmentation of heart function at two weeks following surgery. We conclude that PR1P is a potential candidate therapeutic for MI.

Traditional applications of Interferometric Synthetic Aperture Radar (InSAR) data involved inverting an interferogram stack to determine the average displacement velocity. While this approach has useful applications in continuously deforming regions, much information is lost by simply fitting a line through the time series. Thanks to regular acquisitions across most of the the world by the ESA Sentinel-1 satellite constellation, we are now in a position to explore opportunities for near-real time deformation monitoring. In this paper we present a simple statistical approach for detecting offsets and gradient changes in InSAR time series. Our key assumption is that 5 years of Sentinel-1 data is sufficient to calculate the population standard deviation of the detection variables. Our offset detector identifies statistically significant peaks in the first, second and third difference series. The gradient change detector identifies statistically significant movements in the second derivative series. We exploit the high spatial resolution of Sentinel-1 data and the spatial continuity of geophysical deformation signals to filter out false positive detections that arise due to signal noise. When combined with near-real time processing of InSAR data these detectors, particularly the gradient change, could be used to detect incipient ground deformation associated with geophysical phenomena, for example from landslides or volcanic eruptions.

Cardiovascular Diseases (CVDs) are still menacing and killing adults worldwide, notwithstanding the tremendous effort, to decrease their related mortality and morbidity. Lately, a growing body of evidences indicated that inflammation plays a pivotal role in the pathogenesis and complications of CVDs. A receptor of the immunoglobulin superfamily, triggering receptor expressed on myeloid cells -1 (TREM-1) was shown to induce and to amplify the inflammation in both acute and chronic diseases pathogenesis and progression and hence it is one of the important factors that complicates CVDs. Thus, studies endeavored to investigate the role played by TREM-1 in CVDs with respect to their etiologies, complications and possible therapeutics. We examined here, for the first time, the most relevant studies regarding TREM-1 involvement in CVDs. We summarized the finding after critically analyzing them and made some suggestions for furtherance of the investigations with the aim to utilize TREM-1 and its pathways for diagnostic, management and prognosis of CVDs. Overall, TREM-1 was found to be involved in the pathogenesis of acute and chronic cardiovascular conditions like Acute myocardial infraction (AMI) and atherosclerosis as well. Although most therapeutic approaches are yet to be elucidated, present research outcome displays a promising future to utilize TREM-1 pathway as potential target to understand and manage CVDs.

The first part of the paper was aimed at analyzing the given nonlinear problem by different methods of computation of the Lyapunov exponents (Wolf method [1], Rosenstein method [2], Kantz method [3], method based on the modification of a neural network [4, 5], and the synchronization method [6, 7]) for the classical problems governed by difference and differential equations (Hénon map [8], hyper-chaotic Hénon map [9], logistic map [10], Rössler attractor [11], Lorenz attractor [12]) and with the use of both Fourier spectra and Gauss wavelets [13]. It was shown that a modification of the neural network method [4, 5] makes it possible to compute a spectrum of Lyapunov exponents, and then to detect a transition of the system regular dynamics into chaos, hyper-chaos, hyper hyper-chaos and deep chaos [14-16]. Different algorithms for computation of Lyapunov exponents were validated by comparison with the known dynamical systems spectra of the Lyapunov exponents. The carried out analysis helps comparatively estimate the employed methods in order to choose the most suitable/optimal one to study different kinds of dynamical systems and different classes of problems in both this and the next paper parts.

Background: Schizophrenia and treatment-resistant schizophrenia (TRS) are associated with aberrations in immune-inflammatory pathways. Increased High Mobility Group Protein 1 (HMGB1), an inflammatory mediator, and Dickkopf-Related Protein (DKK1), a Wnt/β-catenin signaling antagonist, affect the blood-brain-barrier and induce neurotoxic effects and neurocognitive deficits.Aim of the study: The present study aims to examine HMGB1 and DDK1 in non-responders to treatments with antipsychotics (NRTT, n=60), partial RTT (PRTT, n=55) and healthy controls (n=43) in relation to established markers of schizophrenia including IL-6, IL-10 and CLL11 (eotaxin); and to delineate whether these proteins are associated with the schizophrenia symptom subdomains and neurocognitive impairments.Results: HMGB1, DKK1, IL-6 and CCL11 were significantly higher in schizophrenia patients than in controls. DKK1 and IL-6 were significantly higher in NRTT than in PRTT and controls while IL-10 was higher in NRTT than in controls. Binary logistic regression analysis showed that schizophrenia was best predicted by increased DDK1 and HMGB1 while NRTT (versus PRTT) was best predicted by increased IL-6 and CCL11 levels. A large part of the variance in psychosis, hostility, excitation, mannerism and negative (PHEMN) symptoms, and formal thought disorders was explained by HMGB1, IL-6, and CCL11 while most neurocognitive functions were predicted by HMGB1, DDK1 and CCL11. Conclusion: The neurotoxic effects of HMGB1, DKK1, IL-6 and CCL11 including effects on the blood-brain-barrier and the Wnt/β-catenin signaling pathway may cause impairments in executive functions, and working, episodic and semantic memory and explain, in part, PHEMN symptoms and a non-response to treatment with antipsychotic drugs.

There is a growing interest in glial cells in the central nervous system due to their important role in maintaining brain homeostasis both under physiological conditions and after injury. A significant amount of evidence has been accumulated regarding their capacity to exert either pro-inflammatory or anti-inflammatory effects under different pathological conditions. In combination with their known proliferative potential, they contribute not only to the limitation of brain damage and tissue remodeling but also to neuronal repair and synaptic recovery. Moreover, reactive glial cells can modulate the processes of neurogenesis, proliferation, and migration of neurons in the existing neural circuits in the adult brain. By discovering precise signals within specific niches, the regulation of sequential processes in adult neurogenesis holds the potential to unlock strategies that can stimulate the generation of functional neurons, whether in response to injury or as a means of addressing degenerative neurological conditions. Cerebral ischemic stroke, a condition falling within the realm of acute vascular disorders affecting the circulation of the brain, stands as a prominent global cause of disability and mortality. Extensive investigations into glial plasticity and their intricate interactions with other cells in the central nervous system have predominantly relied on studies conducted on experimental animals, including rodents and primates. However, valuable insights have also been gleaned from in vivo studies involving post-stroke patients, utilizing highly specialized imaging techniques. Following the attempts to map brain cells, the role of various transcription factors in modulating gene expression in response to cerebral ischemia is gaining increasing popularity. Although the results obtained thus far remain incomplete and occasionally ambiguous, they serve as a solid foundation for the development of strategies aimed at influencing the recovery process after ischemic brain injury.

Floating Offshore Wind Turbine (FOWT) is an innovative technology with little industry guidance for its hull design. Various FOWT floaters with different hull shapes claim to support the same turbines. Structural integrity and material expense analyses of different pontoon shapes were conducted, and it was found that some configurations, such as those with every two columns connected by both pontoon and bracing, have advantages over others. However, it is important to note that the choice of pontoon shape should be based on the wave loading conditions the floater will be exposed to. While a T-shaped pontoon provides a cost-effective solution under certain wave loading scenarios, it may not be the best option for all conditions. Specifically, ring pontoon designs with full bracing were found to be necessary for withstanding certain wave loads. Therefore, it is important to consider different Dominant Load Parameters (DLP) and ensure that a FOWT floater can withstand all applicable DLPs. An uneven hexahedral column shape, which combines the best attributes of square and round shapes, is proposed as a better alternative to cylindrical columns. It offers ease of manufacture and reasonably low drag. Bracing is found to be necessary for withstanding the wind turbine’s incurred moment and forces. The conclusion is that platform design should prioritize manufacturing costs and strength over maximizing hydrodynamic performance.

With climate change projected to increase the frequency and severity of episodic insect outbreak events, assessing potential consequences for soil microbial communities and nutrient dynamics is of importance for understanding forest resilience. The forest tent caterpillar (Malacosoma disstria) is an important defoliator of deciduous tree species in temperate and mixed forests of eastern North America with an invasion cycle every 10-12 years and outbreak events that can last 3-6 years. Following a defoliation episode on trembling aspen (Populus tremuloides) from 2015 to 2017 in Abitibi-Témiscamingue, QC, Canada, we sought to test if defoliation resulted in changes to soil bacterial and fungal communities. We hypothesized an increase in soil microbial biomass due to increased caterpillar frass inputs and potential changes in community structure following the event. Soils were sampled in July 2018, May 2019 and July 2019 from sites that had been subject to defoliation during the outbreak and from sites where no defoliation had been recorded. We assessed soil microbial biomass and fungal to total microbial activity ratio on all sampling dates, and Community Level Physiological Profiles (CLPPs) for 2018 only using a substrate induced respiration method. Contrary to our hypothesis, we observed a significant 50% decrease in microbial biomass (g biomass-C g-1 soil hour-1) in defoliated stands suggesting tree carbon normally allocated towards root exudates was reallocated towards foliage regeneration. We noted a differentiated carbon-based substrate usage following defoliation, but no change in the fungal to total microbial activity ratio. The observed changes in the two years following the defoliation event suggest that defoliation episodes aboveground could trigger changes in soil chemistry belowground with effects on soil microbial communities that may, in turn, feedback to influence forest plant dynamics.

Work reviews the new isolated isolated cembranoid diterpene derivatives from species belonging to the family Alcyoniidae, which comprises the genera Sarcophyton, Sinularia, and Lobophytum as well as their biological properties, during 2016–2017. The compilation permitted to conclude that much more new cembranoid diterpenes were found in the soft corals of the genus Sarcophyton sp. (33 new compounds) than in those belonging to the genera Lobophytum (17) or Sinularia (8). Several methods have been used for identifying these new compounds, after extraction with organic solvents and fractionation. The fractions obtained, in some cases, were followed by TLC, and again subjected to chromatographic procedures, including semi-preparative HPLC. Beyond the chemical composition, the biological properties were also evaluated, namely anti-microbial against several Gram-positive and Gram-negative bacteria and fungi, anti-inflammatory and anti-tumoral against several types of cancer cells. Although the biological activities detected in almost all samples, they were not outstanding ones.

Developing particles of different anisotropic shapes are the hot topic since decades as they guarantee some special features of properties not possible through other means. Again, controlling atoms to develop certain size and shape particle is a quite challenging job. In this study, gold particles of different shapes are developed via pulse-based electronphoton-solution interface process. Gold atoms of certain transition state develop monolayer assembly at solution surface around the light glow (known in argon plasma) being generated at bottom of copper capillary (known in cathode). The rate of uplifting gold atoms to solution surface is being controlled by forcing energy (travelling photons) pursuing electrons and high energy photons (in high density) entering to solution. Gold atoms dissociated from the precursor under dissipating heat energy into the solution supplied under propagating photons characteristic current through immersed graphite rod (known in anode). Placing packets of nano shape energy of tuned pulse protocol over compact monolayer assembly comprising transition state atoms develop tiny-sized particles of formed shape. On separation of joint tiny particles into two equilateral triangular-shaped tiny particles, exerting forces of surface format elongate atoms of one-dimensional arrays converting them into structures of smooth elements. Due to immersing level of force, such tiny-shaped particles pack from different zones at centre of light glow where they assembled structures of smooth elements for developing mono-layers of different shapes of particles. Developing one-dimensional particles deal assembling of structures of smooth elements of packing tiny-shaped particles from nearly rearward zones of reflection of north-south poles, whereas, developing multi-dimensional particles deal assembling of structures of smooth elements of packing tiny-shaped particles from the east-west poles and near regions. Depending on the number of assembled structures of smooth elements at point of nucleation, packing of tiny-shaped particles from different zones develop different shapes of the anisotropic particles. At fixed precursor concentration, increasing the process time results into develop particles of low aspect ratio. Under tuned parameters, developing mechanisms of particles exhibiting unprecedented features are discussed.

Inhalational anesthetics was previously reported to suppress glioma cell malignancy, but underlying mechanisms remain unclear. The present study aims to investigate the effects of sevoflurane and desflurane on glioma cell malignancy changes via microRNA (miRNA) modulation. The cultured H4 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 hrs. The miR-138, -210 and -335 expression were determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and cell count kit 8 (CCK8) assay with/without miR-138/-210/-335 inhibitor transfections. The miRNA downstream proteins, hypoxia inducible factor-1α (HIF-1α) and matrix metalloproteinase 9 (MMP9), were also determined with immunofluorescent staining. Sevoflurane and desflurane exposure to glioma cells inhibited their proliferation and migration. Sevoflurane exposure increased miR-210 expression whereas desflurane exposure upregulated both miR-138 and miR-335 expressions. The administration of inhibitor of miR-138, -210 or -335 inhibited the suppressing effects of sevoflurane or desflurane on cell proliferation and migration, in line with the HIF-1α and MMP9 expression changes. These data indicated that inhalational anesthetics, sevoflurane and desflurane, inhibited glioma cell malignancy via miRNA upregulation and their downstream effectors, HIF-1α and MMP9, downregulation. The implication of the current study warrants further study.

There are two major proposed forms of dark energy: the cosmological constant and the quintessence scalar field. However, the former has the cosmological constant problem and the latter does not have observational evidence to support the theory. In this paper, we propose a dark energy paradigm to solve the cosmological constant problem and to predict lepton masses as evidence. The dark energy paradigm is a unified dark sector that is based on Planck's dimensional analysis, Lambda CDM, energy conservation, and force equilibrium. We find that dark energy can vary from the cosmological constant to the Planck scale. We find that the predicted values of lepton masses based on the dark energy paradigm agree with the observed values to 1% (or within error ranges).

Background: Increase of collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. We hypothesized that COL I/COL III ratio is increased in the brain arteriovenous malformations (bAVMs), which is associated with bAVM hemorrhage. Method: Surgically resected human bAVM samples and mouse bAVMs induced in three transgenic mouse lines with activin receptor-like kinase 1 or endoglin deletion in the endothelial cells or in the brain focally. Colony-stimulating factor receptor inhibitor was used to transiently deplete microglia. COL I and COL III levels, hemorrhage, and gene expression in bAVMs were analyzed. Results: The COL I and COL III levels and the COL I/COL III ratio were higher on human and mouse bAVMs than controls, which was associated with bAVM hemorrhage. Col I and Col III mRNAs were also increased in mouse bAVMs. The degree of microhemorrhage in mouse bAVMs was positively correlated with Col I/Col III ratios. Transient depletion of microglia reduced Col I/Col III ratio and microhemorrhage in mouse bAVMs. Conclusion: COL I/COL III ratio are increased in bAVM vessels, which is associated with bAVM hemorrhage. Depletion of microglia reduces Col I/Col III ratio and hemorrhage in mice bAVMs.

Numerous studies were published suggesting that troponin level is related to adverse outcomes in chronic cardiac and non-cardiac conditions. Our study investigated whether troponin levels gathered from an unselected blood sample taken during outpatient care are associated with adverse outcomes in a population with stable coronary artery disease. In a cohort of 949 patients with stable coronary artery disease, average age of 67.5 ± 9.5 years, 69.5% male, 52.1% diabetics, 51.6% with previous myocardial infarction, 57.9% with triple-vessel disease, 21.7% of patients encountered new events during an average period of monitoring of 2.07 ± 0.81 years. Troponin I/99th percentile categorized into tertiles emerged as an independent predictor of death and combined events risk (hazard ratio: 2.02 (1.13-3.60), p=0.017; 2.30 (1.37-3.88, p=0.002, respectively). A troponin ratio > 0.24 was able to identify 53.3% of patients at risk of death and heart failure hospitalization. In patients with stable coronary artery disease and adherent to treatment, troponin level is independently associated with death and heart failure hospitalization in a medium-term follow up.

Inflammation is natural protective response of the body tissue caused by various stimuli. Macrophages start and control the inflammatory response. Microalgae have high value of ingredients including carotenoids which are well known for anti-inflammatory properties and used for various products in functional food industries. A green microalgal, Tetraselmis species contains a various type of carotenoids such as lutein, violaxanthin, astaxanthin, fucoxanthin, α-carotene and β-carotene. Therefore, we studied whether carotenoids isolated from Tetraselmis sp. with different culture conditions in Raw 264.7 cells and zebrafish (Danio rerio) have an anti -inflammatory effect. Carotenoid extracts of natural seawater (NS) and magma seawater (MS) showed inhibitory activity of nitric oxide (NO) overproduction without toxicity. In addition, carotenoid extracts of NS and MS inhibited pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)- 1β and IL-6. Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, which are inflammatory mediators also decreased by pretreatment of NS and MS. Carotenoid extracts of NS and MS pretreatment also reduced phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kB (NF-kB). In conclusion, the carotenoid extract of Tetraselmis sp. has an anti -inflammatory effect and can be potential industrial ingredient.

Stable half-sandwich iron(II) dihalido complexes of the type [Fe(5-Cp’)X2] are extremely scarce, being limited to congeners containing the bulky C5H2-1,2,4-tBu3 ligand. We have extended this to homologues [Fe(5-Cp*)X2] (X = Cl – I) containing the particularly popular C5Me5 (Cp*) ligand. Corresponding ionic compounds ER4[Fe(5-Cp*)X2] are easily accessible from FeX2, MCp* (M = Li, K) and a suitable halide source R4EX (E = N, P) in THF. The new compounds NnPr4[Fe(5-Cp*)X2] (X = Cl, Br), NnPr4[Fe(5-Cp*)BrCl] and PPh4[Fe(5-Cp*)X2] (X = Cl, Br, I) have been structurally characterised by single-crystal X-ray diffraction. NnPr4[Fe(5-Cp*)Cl2] reacts readily with CO to afford [Fe(5-Cp*)Cl(CO)2], indicating the synthetic potential of ER4[Fe(5-Cp*)X2] in FeCp* half-sandwich chemistry.

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.

Choroid plexus insufficiency or glymphatic stasis are often classified as prequels to harmful accretion of toxic proteins in neurodegenerative disease. Cognitive decline and memory loss subsequently become cardinal features of Alzheimer’s disease (AD), typically progressing with amyloid-ß and tau protein accumulation. For Parkinson’s disease (PD), α-synuclein deposits and dopamine depletion are linked to impaired movement, resting tremor, and rigidity. Importantly, both diagnoses are accompanied by hyperinflammation and intrathecal cytokine changes. Thus far, numerous clinical trials for investigational drugs have produced nothing effective for AD or PD, yet the anti-inflammatory and regenerative potential of platelet-rich plasma (PRP) remains largely unexamined in this context. This report explores a proposed Phase I study on intrathecal condensed plasma growth factors processed from autologous thrombin-activated PRP as monotherapy for AD or PD. The concept gains support from related work where cytokines of platelet origin successfully lowered inflammation, corrected background fibrosis, deactivated abnormal cells, and recovered local tissue function—all desirable outcomes in AD and PD. PRP-mediated effects on membrane potentials, electrolyte balance, and water clearance are less well characterized, but experimental evidence suggests these pathways could likewise influence glymphatic drainage to ameliorate proteinopathies. As a well-tolerated ‘orthobiologic’ with no hypersensitivity risk, intrathecal PRP and its derivatives bring advantages distinct from synthetic pharmaceuticals. If age-associated neuroinflammation in AD and PD is an upstream event contributing to neural disruption, then dampening local oxidative stress by a patient’s own platelet cytokines (as already proven in other tissues) could offer therapeutic relevance to these neurodegenerative conditions as well.

Abstract: Oxidative metabolism is crucial for leukemic stem cell (LSC) function and drug resistance in acute myeloid leukemia (AML). Mitochondrial metabolism also affects the immune system and therefore the antitumor response. Modulation of oxidative phosphorylation (OxPHOS) has emerged as a promising approach to improve therapy outcome for AML patients. However, the effect of mitochondrial inhibitors on the immune compartment in the context of AML is yet to be explored. Immune checkpoints such as the ecto-nucleotidase CD39 and programmed dead ligand 1 (PD-L1) have been reported to be expressed in AML and linked to chemoresistance and poor prognosis. In the present study, we first demonstrated that a novel selective electron transfer chain complex (ETC) I inhibitor, EVT-701, decreased OxPHOS metabolism of murine and human cytarabine (AraC)-resistant leukemic cell lines. Furthermore, we showed that, while AraC induced immune response regulation by increasing CD39 expression and by reinforcing interferon-γ/PD-L1 axis, EVT-701 reduced CD39 and PD-L1 expression in vitro in a panel of both murine and human AML cell lines, especially upon AraC treatment. Altogether, this work uncovers a non-canonical function of ETCI in controlling CD39 and PD-L1 immune checkpoints, thereby improving the anti-tumor response in AML.

Growing body of evidence endorse the hypothesis of a protective role played by the in-utero environment on a suitable fetal programming, mainly sustained by fitting maternal diet. Our purpose was to assess the linkage between maternal food intake and poor obstetric results, with a special focus on typical Italian food. A cross sectional study including delivering women was designed. A self-reported questionnaire about socio-demographic data, obstetric history, and food frequency intake during pregnancy was administrated. A composite of adverse perinatal outcomes (APO) was constructed. Statistically significant differences were found between APO and control group in smoking habit (9.7 vs. 3.2%, p=0.045) and BMI at delivery (27.9±4.9 vs. 26.9±3.9, p=0.003). Women complicated by any or more APOs reported increased rates of pasta (5.3± 3.6 vs.4.4±1.9 times per week, p<0.001) and pizza (1.9±3.4 vs. 1.1±0.6, p<0.001) intake, with lower consumption of vegetables (5.4±3.9 vs. 7.1±2.9, p<0.001). By logistic regression analysis and after adjustments for maternal age, ethnicity, SES, maternal BMI at delivery, excessive ingestion of pizza (aOR 1.676, 95%CI 1.199-2.343, p=0.033), but not pasta (aOR 1.077, 95%CI 0.950-1.211, p=0.244), was found associated with APO. Vegetable consumption showed a protective role in reducing APOs (aOR 0.897, 95%CI 0.818-0.985, p=0.022). Nutrition in pregnancy should minimalize pizza intakes.

We have presented a controllable and human-readable polynomial neural network (CR-PNN) that is the first human-readable neural network. One can imagine its influence on system identification. Subsequently, we developed a relation spectrum in a medical application, which is likely to stand alongside the Fourier spectrum. However, the system analysis methodology is incomplete in contrast to signal processing methodology. Here, we presented the system filters for the first time. In this paper, we used the simulation system to verify the availability of the system analysis methodology. The system analysis methodology showed great properties in system identification and filter. The contribution of this paper is the system analysis methodology: transform method (CR-PNN), relation spectrum, and system filter design.

Every land plant exists in close relationship with microbial communities of several niches: rhizosphere, endosphere, phyllosphere, etc. The growth and yield of potato – a critical food crop worldwide – highly depend on the diversity and structure of bacterial and fungal communities with which the potato plant coexists. The potato plant has a specific part – tubers, and the soil near the tubers as sub-compartment is usually called “geocaulosphere”, which is associated with storage process and tare soil microbiome. Specific microbes can help the plant to adapt to particular environment conditions and resist to pathogens. There is a number of approaches to modulate the microbiome that provides organisms with desired traits during inoculation. The mechanisms of plant–bacterial communication remain understudied, and for the further engineering of microbiomes with particular features the knowledge on potato microbiome should be summarized. The most recent approaches to microbiome engineering include construction of a synthetic microbial community or management of plant microbiome using genome engineering. In this review, the various factors that form the microbiome of potato and the role of these factors in overcoming the negative impact of drought and pathogens are surveyed.

The review concerns the chemical structures of all the triterpene glycosides from the most valuable commercially harvesting North Atlantic sea cucumber Cucumaria frondosa and their biological activities. The isolation and structural elucidation of 17 specific triterpene glycosides are described along with isolation and identification of two known glycosides. Antitumor, immunomodulatory, antithrombotic and anti-Alzheimer disease activities are also described. Frondoside A, the major component of the glycosidic fraction seems to be very perspective leader-compound for creation of useful medicinal preparations.

The rising importance of Big Data in modern information analysis is supported by vast quantities of user data, but it is only possible to collect sufficient data for all tasks within certain data-gathering contexts. There are many cases where a domain is too novel, too niche, or too sparsely collected to adequately support Big Data tasks. To remedy this, we have created ADG Engine that allows for the generation of additional data that follows the trends and patterns of the data that’s already been collected. Using a database structure that tracks users across different activity types, ADG Engine can use all available information to maximize the authenticity of the generated data. Our efforts are particularly geared towards data analytics by identifying abnormalities in the data and allowing the user to generate normal and abnormal data at custom ratios. In situations where it would be impractical or impossible to expand the available dataset by collecting more data, it can still be possible to move forward with algorithmically expanded data datasets.

Biocidal compositions based on interpolyelectrolyte complexes and a low molecular weight antibiotic can become a promising material for creating biocidal coatings, as they combine wash-off resistance and dual biocidal action due to the biocide and the polycation. Molecular mass characteristics of polymers play essential role in physics and mechanical properties of the coatings. In this work, the properties of polydiallyldimethylammonium chloride (PDADMAC) coatings of various molecular weights are investigated and assumptions are made about the optimal molecular weight needed to create antibacterial compositions. To study the resistance to washing off and moisture saturation of the coatings, the gravimetric method was used, the adhesive properties of the coatings were studied by dynamometry. It has been established that an increase in molecular weight affects the wash-off resistance of coatings, but does not affect moisture absorption and adhesion mechanics of coatings. All samples of PDADMAC were demonstrated to exhibit the same antibacterial activity. Thus, when developing systems for creating antibacterial coatings, it must be taken into account that in order to create stable coatings. The requirement to use PDADMAC with a high degree of polymerization is necessary for control the desorption of coating during wash off-but not mandatory for the control of mechanical and antibacterial properties of the coating.

Luminophores featuring thermally activated delayed fluorescence (TADF luminophores) are the workhorse of the third- and fourth-generation OLEDs. While these compounds had usually been used as dopants embedded in the host, non-doped TADF OLEDs have recently shown significant progress as well reaching the performance comparable to the host-dopant ones. For efficient operation of the non-doped OLEDs, charge transport in neat films and single crystals of TADF luminophores is important; however, this issue was nearly unexplored theoretically. In the current study, we calculated charge mobilities in four TADF single crystals, which have different molecular packing motifs. Specifically, in one of them both donor and acceptor moieties form uniform π-stacks, while in the others donors (acceptors) show alternating lateral shifts along the stacks; the difference in molecular packing results in the difference of transfer integral between the molecules. Reorganization energies differ as well up to four times for the studied crystals. As a result, charge mobilities vary from 0.001 to ~0.3 cm2/(V∙s), the largest being predicted for the crystal of the luminophore consisting of rigid donor and acceptor. We anticipate that the results obtained can be useful for the design of TADF luminophores for non-doped OLEDs, OLETs and other organic light-emitting devices.

Abundant animal manure in livestock areas has the potential to be used as organic fertilizer which can restore soil fertility by turning it into compost and biochar. The goal of this study was to as-sess how well soil fertility and red chili yield might be increased by using biochar and poschar made from various animal wastes. In this investigation, a factorial pattern and randomized block design were used. The first factor was the biochar treatment type, which included no biochar, biochar made from cow manure, biochar made from goat manure, and biochar made from chicken manure. The second factor was the type of poschar, which included no poschar, poschar made from cow manure, poschar made from goat manure, and poschar made from chicken manure. The findings of this study suggest that using biochar in conjunction with poschar can significantly improve soil parameters such as soil water content, pH, EC, humic acid, fulvic acid, C, N, P, K, and CEC. Red chilies grow and yield more per hectare when different types of biochar and poschar are used. The use of biochar from cow manure together with poschar from chicken manure shows the best agronomic effectiveness.

The methods for constructing solutions to integro-differential equations of the Volterra type are considered. The equations are related to fractional conformable derivatives. Explicit solutions of homogeneous and inhomogeneous equations are constructed and a Cauchy-type problem is studied. It should be noted that the considered method is based on the construction of normalized systems of functions with respect to a differential operator of fractional order.

Adult T-cell leukemia (ATL) is an aggressive hematologic disease caused by human T-cell leukemia virus type 1 (HTLV-1) infection. Various animal models of HTLV-1 infection/ATL have been established to elucidate the pathogenesis of ATL and develop appropriate treatments. For analyses employing murine models, transgenic and immunodeficient mice are used because of the low infectivity of HTLV-1 in mice. HTLV-1 Tax and HBZ transgenic mice spontaneously develop tumors, and roles for both Tax and HBZ in cell transformation and tumor growth have been established. Severely immunodeficient mice were able to engraft ATL cell lines and have been used in preclinical studies of candidate molecules for the treatment of ATL. HTLV-1-infected humanized mice with an established human immune system are a suitable model to characterize cells in the early stages of HTLV-1 infection. This review outlines the characteristics of mouse models of HTLV-1 infection/ATL and describes progress made in elucidating the pathogenesis of ATL and developing related therapies using these mice.

Diabetes may cause an increase blood levels of cytokines inducing a rising of C reactive protein (PCR) and fibrinogen stimulating a subclinical inflammation which lead to adhesive molecules expression and to endothelial disfunction. A comprehensive panel of type 1 diabetes mellitus (T1DM) interleukins polymorphisms is not provided yet. As chronic periodontitis (CP) is considered the sixth complication of DM, a clarification is needed about the inflammatory role managed by single nucleotides polymorphisms (SNPs). The goal of this review is to focus on the significant diversity of SNPs in T1DM patients with and without CP. After a digital search on PubMed and Scopus with reference to the last 5 years, 21 items were enrolled. Several ILs were analyzed. T1DM still needs to be thoroughly explored regarding the ILs polymorphisms panel, however the last 5 years have led to the increased independence of this condition, causing autonomous inflammatory effects which requires further investigations. CP and T1DM association in children and adolescents represents a severe gap in literature that should be filled, the scarce presence of studies also about adults serves as a motivation for ulterior clinical researches

Soil moisture maps are essential for hydrological, agricultural and risk assessment applications. To best meet these requirements, it is essential to develop soil moisture products at high spatial resolution which is now made possible using the free Sentinel-1 (S1) SAR (Synthetic Aperture Radar) data. Some soil moisture retrieval techniques using S1 data relied on the use of a priori weather information in order to increase the precision of soil moisture estimates, which required access to a weather forecasting framework. This paper presents an improved and fully automated solution for high-resolution soil moisture mapping in bare agricultural areas. The proposed solution derives a priori weather information directly from the original Sentinel images, thus bypassing the need for a weather forecasting framework. For soil moisture estimation, the neural network technique was implemented to ensure the optimum integration of radar information. The neural networks were trained using synthetic data generated by the modified Integral Equation Model (IEM) model and validated on real data from two study sites in France and Tunisia. Main findings showed that the use of radar signal averaged over grids of a few km2 in addition to radar signal at plot scale instead of a priori weather information, provides good soil moisture estimations. The accuracy is even slightly better comparatively to the accuracy obtained using a priori weather information.

Currently SARS-CoV-2 is spreading around the world as an Omicron strain. Recently, the Omicron variants (BQ.1 and BQ.1.1) were identified as novel Variants of Concern. UpToDate, there is little information about the Omicron Variants BQ.1 and BQ.1.1. The widely altered Omicron variants are spread globally, providing a high risk of infection surges with devastating consequences in some areas. The Omicron type of SARS-CoV-2 has a harm risk of reinfection, according to early reported findings. COVID-19 Variants particularly, BQ.1 and BQ.1.1 have gained global attention and caused a worldwide sensation since their discovery. Therefore, this communication discusses the present status of COVID-19 Variants BQ.1 and BQ.1.1, and their consequences.

Abstract The expression patterns of microRNAs (small non-coding RNAs) are altered in many biological processes such as myogenesis. In this study, we aimed to investigate the impact of predicted miR-202, its target genes Akt2 and Rock-1 as a potential regulator of myoblast in the myocyte differentiation process using the C2C12 cell line. After confirmation of the differentiation process induced by 3% horse serum, the expression level of miRNA and its targets were evaluated. In the following, a luciferase assay was conducted to approve the effect of miRNA on its target. Our results indicated that miR-202 and Akt2 were significantly up-regulated during differentiation, while Rock-1 was downregulated. Co-transfection of miRNA with psiCHECK2-Rock-1 significantly presented that Rock-1 was directly targeted by miR-202. On the contrary, miR-202 has failed to enforce its inhibitory effect on Akt2 expression. In particular, miR-202 seems to be a regulator of muscle differentiation pathway thought targeting Rock-1.

Many years and $$$ spent for research did not yet produced a universally effective gene therapy of prostate cancer (PCa). Our studies indicated that not only each human, but even each cancer nodule in the same tumor has unique and dynamic gene expression profile, control and coordination. The tumor heterogeneity of the transcriptome topology is a strong argument in favor of personalized gene therapies, tailored on patients’ primary tumor unique characteristics. Here, we propose a bioinformatics procedure by which to identify the Gene Master Regulators (GMR) of cancer cells from transcriptomic data and predict consequences of their experimental manipulation. The procedure, based on our Genomic Fabric Paradigm (GFP), can determine the most important gene in each cancer nodule whose controlled alteration would selectively kill the cancer cells. In this report, the method is applied to our microarray data on two men PCs (each with three distinct cancer nodules) and two standard human PCa cell lines (DU145 and LNCaP). We expect the industry to produce ready-to-use CRISPR constructs for all genes allowing the clinical oncologist to prescribe the adequate personalized CRISPR cocktail for his/her patient. Thus, the GMR approach may provide the most effective, yet affordable solution in fighting cancer.

Neurokinin-1 receptor (NK-1R) antagonists exert an antitumor action, are safe and do not cause serious side-effects. These antagonists (via the NK-1R) exerted multiple actions against cancer: antiproliferative and anti-Warburg effects, apoptosis, anti-angiogenic and antimetastatic. These multiple effects have been shown in a broad-spectrum of cancers. The drug aprepitant (an NK-1R antagonist) is currently used in clinical practice as antiemetic. In in vivo and in vitro studies, aprepitant also showed the aforementioned multiple antitumor actions against many types of cancer. A successful combination therapy (aprepitant and radiotherapy) has recently been reported in a patient suffering from lung carcinoma: the tumor mass disappeared and side-effects were not observed. Aprepitant could be considered as an intelligent bullet against cancer. The administration of aprepitant in cancer patients to prevent recurrence and metastasis after surgical procedures, thrombosis and thromboembolism is discussed as well as the possible link, through the SP/NK-1R system, between cancer and depression. Our main aim is to review the multiple antitumor actions exerted by aprepitant and the use of this drug is suggested in cancer patients. Altogether, the data support the reprofiling of aprepitant for a new therapeutic use as an antitumor agent.

Soil moisture (SM) plays an essential role in environmental studies related to wetlands, an ecosystem sensitive to climate change. Hence, there is the need for its constant monitoring. SAR (Synthetic Aperture Radar) satellite imagery is the only mean to fulfill this objective regardless of the weather. The objective of the study was to develop the methodology for SM retrieval under wetland vegetation using Sentinel-1 (S-1) satellite data. The study was carried out during the years 2015–2017 in the Biebrza Wetlands, situated in northeastern Poland. At the Biebrza Wetlands, two Sentinel-1 validation sites were established, covering grassland and marshland biomes, where a network of 18 stations for soil moisture measurement was deployed. The sites were funded by the European Space Agency (ESA), and the collected measurements are available through the International Soil Moisture Network (ISMN). The NDVI (Normalized Difference Vegetation Index) was derived from the optical imagery of a MODIS (Moderate Resolution Imaging Spectroradiometer) sensor onboard the Terra satellite. The SAR data of the Sentinel-1 satellite with VH (vertical transmit and horizontal receive) and VV (vertical transmit and vertical receive) polarization were applied to soil moisture retrieval for a broad range of NDVI values and soil moisture conditions. The new methodology is based on research into the effect of vegetation on backscatter () changes under different soil moisture and vegetation (NDVI) conditions. It was found that the state of the vegetation may be described by the difference between  VH and  VV, or the ratio of  VV/VH, as calculated from the Sentinel-1 images. The most significant correlation coefficient for soil moisture was found for data that was acquired from the ascending tracks of the Sentinel-1 satellite, characterized by the lowest incidence angle, and SM at a depth of 5 cm. The study demonstrated that the use of the inversion approach, which was applied to the new developed models and includes the derived indices based on S-1, allowed the estimation of SM for peatlands with reasonable accuracy (RMSE ~ 10 vol. %). Due to the temporal frequency of the two S-1 satellites’ (S-1A and S-1B) acquisitions, it is possible to monitor SM changes every six days. The conclusion drawn from the study emphasizes a demand for the derivation of specific soil moisture retrieval algorithms that are suited for wetland ecosystems, where soil moisture is several times higher than in agricultural areas.

1) This study describes the good evolution of a 6-year-old girl genetically diagnosed with Rett syndrome (RTT), after having been treated with IGF-1, MT (MT), blackcurrant extracts (BC), and rehabilitation during 6 months. 2) The patient stopped her normal development from the first year of age. The patient showed low weight and height and met the main criteria for typical RTT. Curiously, there was pubic hair (Tanner II), very high plasma testosterone, despite low gonadotropins. No adrenal enzymatic deficits existed, and ultrasound abdominal studies were normal. Treatment consisted in IGF-1 (0.04 mg/kg/day, 5/week, sc) during 3-months and then 15-days resting, MT (50 mg/day, orally, uninterruptedly) and neurorehabilitation. The new blood tests were absolutely normal and the pubic hair disappeared. Then, a new treatment with IGF-1, MT, and BC started for another 3 months. After it, pubic Tanner stage increased to III, without a known cause. 3) The treatment followed led to clear improvements in most of the initial impairments, perhaps because of the effect of IGF-I, the antioxidant effects of MT and BC, and the increase in cyclic-glycine-proline (cGP) after BC administration. 4) A continuous treatment with IGF-1, MT and BC may recover most of the neurologic disabilities that occur in RTT.

Radar altimetry provides valuable measurements to characterize the state and the evolution of the Antartica and Greenland ice sheet cover. Global Navigation Satellite System Reflectometry (GNSS-R) has the potential capacity of complementing the dedicated radar altimeters incrementing the temporal and spatial resolution of the surface height measurements. In this work we perform an study of the Greenland ice sheet using data obtained by the GNSS-R instrument aboard the British TechDemoSat-1 (TDS-1) satellite mission, designed primarily to provide sea state information, like sea surface roughness or wind, but not altimetric products. The data has been analyzed with altimetric methodologies, already proved in aircraft based experiments, to extract signal delay observables to be used to infer the topography of the Greenland cover. The penetration depth of the GNSS signals into ice has also considered. The topographic signal obtained is consistent with those obtained with other passive or active microwave sensors. The main conclusion derived from this work is that GNSS-R also provides valuable measurements of the ice sheet cover and, as taken at a variety of geometries and at least two frequency bands, they prospect different depths into the ice. They have thus potential to complement our understanding of the ice firn and its evolution.

The mitochondrial network (MN) is a dynamic structure undergoing constant remodeling in the cell. It is assumed that the violation of MN may be associated with various pathologies, including Parkinson’s disease (PD). Using automatic image analysis and super-resolution microscopy, we have assessed the MN parameters in fibroblasts from patients with established hereditary PD mutations (associated with PINK1, LLRK2, α-synuclein, PINK1 and Parkin simultaneously proteins) under normal conditions and after hydrogen peroxide-induced stress. Fibroblasts with Pink1/Parkin mutation are the most different in morphology from fibroblasts obtained from conditionally healthy donors: MN is larger, contains longer mitochondria and accumulated individual mitochondria. In addition to MN, we evaluated other cellular parameters, such as: cytosolic and mitochondrial ROS production and mitochondrial membrane potential. It has been shown that mitochondria of fibroblasts with mutations in genes encoding PINK1, α-synuclein and Pink/Parkin tends to hyperpolarization and cytosolic ROS overproduction, while mitochondrial ROS production was higher only in fibroblasts with PINK1 and α-synuclein mutation.

Interpolyelectrolyte complexes Eudragit® EPO/L100 received in different pH were characterized by different degree of swelling in mimicking fasted stomach medium (0.1 M HCl) and saved their shape during 6 hours of the experiment. The microenvironmental changes in IPECs structure during swelling testing were inves-tigated using FT-IR spectroscopy, thermal and elemental analysis. Both samples of IPECs during swelling were transformed to a similar structure with approximately the same composition. IPEC samples showed bioadhesive properties that was not significantly different from the positive control (Carbopol) in the test with the mucin compacts. The release rate of metronidazole (class I BCS) from IPEC matrices increased with the increasing degree of swelling. IPEC 1 provided 49.62 ± 6.20% and IPEC 2 – 87.69 ± 5.15 % of metronidazole release after 6 hours in mimicking fasted stomach medium (0.1 M HCl). Total amount of released acyclovir (class III BCS) from IPEC 1 was 25.76 ± 5.67 % and from IPEC 2 was 21.48 ± 5.00 %. Release of both drugs was controlled by relaxation of polymeric chains in matrices according to the Peppas-Sahlin model. According to the received results, investigated interpolymer complexes are perspective for further evalua-tion as carriers for gastroretentive bioadhesive systems.

Capsaicin, a lipophilic, volatile compound, is responsible for the pungent properties of chili peppers. In recent years, a significant increase in investigations into its properties has allowed the production of new formulations and the development of tools with biotechnological, diagnostic, and potential therapeutic applications. In this way, the possible clinical application of such compound is expanding every year. This opinion article aims to provide a synthesis of recent findings regarding the mechanisms by which capsaicin participates in the control of non-communicable diseases such as obesity, diabetes, and dyslipidemia. This opinion review also discusses the recent findings and clinical studies of the use of capsaicin in body weight control.

This report is on online banking and information systems in online banking. It throws some light on the introduction and historical background of online banking. Next, in this term report online banking information is explained in detailed. We collected a few articles, related to internet banking, on which other researchers have worked. Then further we have brief them into a table where we have mentioned their problems and limitations. Next, we discussed them in detail, giving an overview of each article. Lastly, recommendations for the online banking sectors are also mentioned.

Security in the Internet of Things (IoT) is a critical concern due to the growing number of connected devices and the limited resources to implement robust security mechanisms in most of them. Adopting standard assessment frameworks, such as CVSS (Common Vulnerability Score System), allows for systematic vulnerability assessment. At the same time, CVE (Common Vulnerabilities and Exposures) records provide unique identifiers for known security issues, making it easier to share information. However, comparing security solutions is still challenging due to the diverse nature of IoT devices and the ever-evolving threat landscape, requiring continual innovation and collaboration between stakeholders. Furthermore, there still needs to be a simple way to compare technologies and solutions, taking into account the security provided by them. In this sense, in this article, we propose a tool for calculating a security score based on the CVSS index of each existing vulnerability in a given technology. We explain how the tool performs the calculation, discuss some challenges, and propose improvements for future work.

In this paper, the technical aspects of a multi-lidar instrument, the long-range WindScanner system, will be presented accompanied by an overview of the results from several field campaigns. The long-range WindScanner system consists of three spatially separated coherent Doppler scanning lidars and a remote master computer that coordinates them. The lidars were carefully engineered to perform arbitrary and time controlled scanning trajectories. Their wireless coordination via the master computer allows achieving and maintaining lidars’ synchronization within ten milliseconds. As a whole, the long-range WindScanner system can measure an entire wind field by emitting and directing three laser beams to intersect, and then by moving the beam intersection over the points of interest. The long-range WindScanner system was developed to tackle the need for high-quality observations of wind fields from scales of modern wind turbine and wind farms. It has been in operation since 2013.

Emotion plays a powerful role in humans’ interaction with robots. In order to express more human-friendly emotions, robots need the capability of contextual appraisal that expresses the emotional relevance of various targets in the spatiotemporal situation. In this paper, an emotional appraisal methodology is proposed in this study to cope with such contexts. Specifically, the Ortony, Clore, and Collins model is abstracted and simplified to approximate an emotional appraisal model in the form of a sentence-based cognitive system. The contextual emotion appraisal is modeled by formulating the emotional relationships among multiple targets and the emotional transition with events and time passing. To verify the proposed robotic system’s feasibility, simulations were conducted for scenarios where it emotional interacts with humans manipulating liked or disliked objects on a table. This experiment demonstrated that the robot's emotion can variously change over time like human by using a proposed formula for emotional valence, which is moderated by emotion appraisal of occurring events.

In this study, the decision-making process management of forest tending in the forestry business is decentralized, and forest tending decision-making activities at different points in time are integrated by decision makers at different geographical locations. The decision-making process was analyzed and optimized from a system perspective. Based on the optimized decision-making process, a forest tending business group decision support system (FTGDSS) was established. We first reviewed and discussed the characteristics and development of the forest tending business and forestry decision support system. Business Process Modeling Notation was used to draw a current state flow chart of the forest tending business, to identify and discover important decision points in the process of tending decision-making. We also analyzed the content and attributes of each decision point, and described the system structure, functional framework, knowledge base structure, and reasoning algorithm of FTGDSS in detail. Finally, FTGDSS was evaluated from the two dimensions of the technology adoption model. FTGDSS integrates different levels of time-space decision-making activities, historical tending data, business plans, decision-makers' management tendencies into the decision-making process and automatically extracts decision-making data from the forest business process management enterprise resource planning system (Smartforest) that improves the ease of use of the decision support system (DSS). It also improves the quality of forest tending decisions, and enables the DSS to better support multi-target management strategies.