Understanding cell migration is a key step to unravel many physiological phenomena and predict several pathologies, like cancer metastasis. In particular, mechanical confinement has been proved to be a key factor in the cellular migration strategy choice. As our insight in the field improves, new tools are needed in order to empower biologists’ analysis capabilities. In this framework, microfluidic devices have been used to engineer the mechanical stimuli and to investigate cellular migration response in a more controlled way. In this work, we will review the existing technologies employed in the realization of microfluidic cellular migration assays, namely soft lithography of PDMS and hydrogels and femtosecond laser micromachining. We will give an overview of the state of the art of these devices, focusing on the different geometrical configurations that have been exploited to study specific aspects of cellular migration. Our scope is to highlight the advantages and possibilities given by each approach and to envisage the future developments in in-vitro migration studies under mechanical confinement in microfluidic devices.

Enhancing the degree of functional multiplexing while assuring operational reliability and manufacturability at competitive costs are crucial ingredients for enabling comprehensive sample-to-answer automation, e.g., for use in common, decentralized “Point-of-Care” or “Point-of-Use” scenarios. This paper demonstrates a model-based ‘digital twin’ approach which efficiently supports the algorithmic design optimization of exemplary centrifugo-pneumatic (CP) dissolvable-film (DF) siphon valves towards larger-scale integration (LSI) of well-established “Lab-on-a-Disc” (LoaD) systems. Obviously, the spatial footprint of the valves and their upstream laboratory unit operations (LUOs) have to fit, at a given radial position prescribed by its occurrence in the assay protocol, into the locally accessible disc space. At the same time, the retention rate of a rotationally actuated CP-DF siphon valve and, most challenging, its band width related to unavoidable tolerances of experimental input parameters, need to slot into a defined interval of the practically allowed frequency envelope. To accomplish particular design goals, a set of parametrized metrics is defined, which are to be met within their practical boundaries while (numerically) minimizing the band width in the frequency domain. While each LSI scenario needs to be addressed individually on the basis of the digital twin, a suite of qualitative design rules and instructive showcases structures are presented.

Eastern boundary upwelling systems feature strong zonal gradients of physical and biological ocean properties between cool, productive coastal oceans and warm, oligotrophic subtropical gyres. Zonal currents and jets (striations) are therefore likely to contribute to the transport of water properties between coastal and open oceanic regions. Multi-sensor satellite data are used to characterize the signatures of striations in sea surface temperature (SST), salinity (SSS), and chlorophyll-a (Chl-a) in subtropical eastern North/South Pacific (ENP/ESP) upwelling systems. In the ENP, tracers exhibit striated patterns extending up to ~2500 km offshore. Striations in SST and SSS are highly correlated with quasi-zonal jets, suggesting that these jets contribute to SST/SSS mesoscale patterns via zonal advection. Chl-a striations are collocated with sea surface height (SSH) bands, a possible result of mesoscale eddy trains trapping nutrients and forming striated signals. In the ESP, striations are only found in SST and coincide with SSH bands, consistently with quasi-zonal jets located outside major zonal tracer gradients. An interplay between large-scale SST/SSS advection by the quasi-zonal jets, mesoscale SST/SSS advection by the large-scale meridional flow and eddy advection may explain the persistent ENP hydrographic striations. These results underline the importance of quasi-zonal jets for surface tracer structuring at the mesoscale.

Cutaneous wound healing is a complex multi-stage process involving direct and indirect cell communication events with the aim of efficiently restoring the barrier function of the skin. One key aspect in cutaneous wound healing is associated with cell movement and migration into the physically, chemically and biologically injured area resulting in wound closure. Understanding the conditions under which cell migration is impaired and elucidating the cellular and molecular mechanisms that improve healing dynamics is therefore crucial in devising novel therapeutic strategies to elevate patient suffering, reduce scaring and eliminate chronic wounds. Following the global trend towards automation, miniaturization and integration of cell-based assays into microphysiological systems, conventional wound healing assays such as the scratch assay or cell exclusion assay have recently been translated and improved using microfluidics and lab-on-a-chip technologies. These miniaturized cell analysis systems allow precise spatial and temporal control over a range of dynamic microenvironmental factors including shear stress, biochemical and oxygen gradients to create more reliable in vitro models that resemble the in vivo microenvironment of a wound more closely on a molecular, cellular, and tissue level. The current review provides (a) an overview on the main molecular and cellular processes that take place during wound healing, (b) a brief introduction into conventional in vitro wound healing assays, and (c) a perspective on future cutaneous and vascular wound healing research using microfluidic technology.

Wearable technology will become available and allow prolonged electroencephalography (EEG) monitoring in the home environment of patients with epilepsy. Neurologists analyse the EEG visually and annotate all seizures, which patients often under report. Visual analysis of a 24 hour EEG recording typically takes one to two hours. Reliable automated seizure detection algorithms will be crucial to reduce this analysis. We study a dataset of behind-the-ear EEG measurements. Our first aim was to develop a methodology to reduce the EEG dataset by classifying part of the data automatically, while retaining 100% detection sensitivity (DS). Prediction confidences are determined by temperature scaling of the classification model outputs and trust scores. A DS of approximately 90% (99%) can be achieved when automatically classifying around 90% (60%) of the data. Perfect DS can be achieved when automatically classifying 50% of the data. Our second contribution demonstrates that a common modelling strategy, where predictions from several short EEG segments are used to obtain a final prediction, can be improved by filtering out untrustworthy segments with low trust scores. The false detection rate shows a relative decrease between 21% and 43%, and the DS shows a small increase or decrease.

In this paper we analyze and propose new method and algorithm of selecting the optimal labor time as a function of skills following our main references Mirrlees (1971), Saez (2001) and Stancheva (2014). The optimal labor time is a situation when the utility function of individual reaches a maximum. One of the main differences with Saez (2001) is our algorithm for creation the skill distribution

An attractive option for realizing applications in radiation environments is to employ All-Programmable System-on-Chips (APSoCs) thanks to their high-performance computing and power efficiency merits. Despite APSoC's advantages, like any other electronic device, they are prone to radiation effects. Processors found in APSoCs must, therefore, be adequately hardened against ionizing-radiation to become a viable alternative for harsh environments. This paper proposes a novel triple-core lockstep (TCLS) approach to secure the Xilinx Zynq-7000 APSoC dual-core ARM Cortex-A9 processor against radiation-induced soft errors by coupling it with a MicroBlaze TMR subsystem in Zynq's programmable logic (PL) layer. The proposed strategy uses software-level checkpointing principles along with roll-back and roll-forward mechanisms (i.e. software redundancy), and hardware-level processor replication as well as checker circuits (i.e. hardware redundancy). Results of fault injection experiments show that the proposed solution achieved high soft error security by mitigating about 99% of bit-flips injected into both ARM cores' register data.

It has been widely described that chronic intake of fructose causes metabolic alterations which can be associated with brain function impairment. In this study, we evaluated the effects of fructose intake on the sleep-wake cycle, locomotion and neurochemical parameters in Wistar rats. The experimental group was fed with 10% fructose in drinking water for five weeks. After treatment, metabolic indicators were quantified in blood. Electroencephalographic recordings were used to evaluate the sleep architecture and the spectral power of frequency bands. Likewise, the locomotor activity and the concentrations of orexin A and monoamines were estimated. Our results show that fructose diet significantly increased the blood levels of glucose, cholesterol, and triglycerides. Fructose modified the sleep-wake cycle of rats increasing the waking duration and conversely decreasing the non-rapid eye movement sleep. Furthermore, these effects were accompanied by increases of the spectral power at different frequency bands. Chronic consumption of fructose caused a slight increase in the locomotor activity as well as an increase of orexin-A and dopamine levels in the hypothalamus and brainstem. Specifically, immunoreactivity for orexin-A was increased in the ventral tegmental area after the intake of fructose. Our study suggests that fructose induces metabolic changes and stimulates the activity of orexinergic and dopaminergic neurons which may be responsible for alterations of the sleep-wake cycle.

Low-frequency electron paramagnetic resonance (EPR) is used to extract the EPR parameter A-mid and support the approximate X-band value of g-mid for Ba(Co_yZn_1/3-yTa_2/3)O₃. Although cobalt hyperfine structure for the [+/−1/2> state is often unresolved at X-band or S-band, it is resolved in measurements on this compound. This allows for detailed analysis of the molecular orbital for the [+/−1/2> state, which is often the ground state. Moreover, this work shows that the EPR parameters for Co substituted into Zn compounds gives important insight into the properties of zinc binding sites.

1) Landsat operational land imager (OLI) data and consequent laboratory measurements were used to predict Chlorophyll-a (Chl-a) concentration and the trophic states for an inland lake within the East Kolkata Wetland, India; 2) The most suitable band ratio was identified by performing Pearson correlation analysis between Chl-a concentrations and possible OLI band and band ratios from the study points; 3) The results showed highest correlation coefficient from the band ratio OLI5/OLI4 with an R value of 0.85. The prediction model was then developed by applying regression analysis between the band ratio OLI5/OLI4 and Chl-a concentration of the study points. The reflectance ratios of the validation points were given as input on the prediction model and the model output was considered as predicted Chl-a values of the validation points to check the efficiency of the prediction model. The regression model between laboratory-derived Chl-a value and model-fitted Chl-a value of the validation points revealed a high correlation with an R² value of 0.78. Trophic State Index (TSI) of the lake was also calculated from laboratory-derived Chl-a value and model-fitted Chl-a value of the validation points. The study presented a high correlation of TSI determined from predicted data with TSI from laboratory reference data (R = 0.88). The TSI values of the lake ranged from 65 to 75 which indicate that the lake is appeared to be eutrophic to hypereutrophic conditions. 4) This empirical study showed that Landsat 8 OLI imagery can be effectively applied to estimate Chl-a levels and trophic states for inland lakes.

Food-borne transmission is a recognized route for many viruses associated with gastrointestinal, hepatic or neurological diseases. Therefore, it is essential to identify new bioactive compounds with broad-spectrum antiviral activity is needed to exploit innovative solutions against these hazards. Lately, antimicrobial peptides (AMPs) have been recognized as promising antiviral agents. Indeed, while the antibacterial and antifungal effects of these molecules have been widely reported, their use as potential antiviral agents has not yet been fully investigated. Herein, the antiviral activity of previously identified or newly designed AMPs, was evaluated against the non-enveloped RNA viruses, Hepatitis A virus (HAV), and Murine Norovirus (MNV), a surrogate for human Norovirus. Moreover, specific assays were performed to recognize at which stage of the viral infection cycle the peptides could function. Results showed that almost all peptides displayed virucidal effects with about 90% of infectivity reduction on HAV or MNV. However, the decapeptide RiLK1 demonstrated, together with its antibacterial and antifungal properties, a notable reduction in viral infection for both HAV and MNV, possibly through direct interaction with viral particles or inhibition of the viral bonding to the cell receptors. Hence, RiLK1 could represent a versatile ‘antimicrobial agent effective against various foodborne pathogens including viruses, bacteria, and fungi.

Matrices and their inverses allow accurate calculations to be produced quickly and compactly and can be used to control any process represented by a system of equations. Singular matrices require extensive workarounds (costing time and money) to solve these systems of equations because they have no inverse. Finding their inverse involves division by zero. Nevertheless, recently a new number set called semi-structured complex numbers was developed to enable division by zero in algebraic equations. The aim of this research was to demonstrate that the inverse of a singular matrix can be found using semi-structured complex numbers. This research reveals (1) Singular matrices and their inverses can be used to find a unique solution to a pair of simultaneous equations that appear to have infinitely many solutions or appear to have no solution; (2) Singular matrices map coordinates in projective space to coordinates in Euclidean space and their inverse maps coordinates in Euclidean space to coordinates in projective space; (3) the inverse of a singular matrix proves that parallel lines in Euclidean space do not intersect but in projective space intersect at a “point at infinity” and (4) collinear lines that intersect at infinitely many points in Euclidean space only intersect at one point in projective space.

In recent years, online review system attracts attention to assess seller-customer relations in the world of e-commerce. To address the quality concern of online review, especially incentivized ones, this study evaluates credibility and consistency based on reviews’ volume, length, and content to distinguish the impact of incentives on customer review behavior, improving review quality, and purchase decision-making. Software product reviews collected from software review websites, including Capterra, Software Advice, and GetApp undergo Exploratory Data Analysis (EDA) to reveal critical features such as cost, support, usability, and product features. The indirect impact of companies’ size, direct impact of users’ experience, and different impacts of changing situations during years on the incentive reviews’ volume are major findings of sentiment analysis. A/B testing results show a minimal to no impact of such reviews on purchasing decisions, highlighting discrepancies in credibility and consistency in volume, length, and content. Employing advanced techniques like Sentence-BERT (SBERT) and TF-IDF, the study explores semantic differences in reviews to improve recommendation systems for a more customized shopping experience. This approach seeks to establish a framework that discerns between review types and their effect on customer behavior. The findings contribute to developing more sophisticated and consistent e-commerce solutions, emphasizing the importance of authentic and reliable online reviews in influencing consumer choices.

This contribution deals with the assessment of air pollution caused by atmospheric aerosol particulate matter fraction PM10 and benzo[a]pyrene (BaP) in the urban agglomeration of Ostrava, located in the Czech Republic in Central Europe. The motivation for this research was the need to identify the sources of air pollution in the area, particularly in locations where the contribution of different sources to concentrations of pollutants of concern has not been elucidated yet. In this study, source apportionment in the vicinity of the industrial hot-spot was performed by statistically evaluating measured pollutant concentrations as a function of meteorological variables and using the Positive Matrix Factorization (PMF) receptor model. A significant methodological innovation and improvement over previous assessments was the higher monitoring resolution of benzo[a]pyrene, with samples collected at three-hour intervals instead of the standard 24-hour collection period. The key findings indicate that in the cold part of the year, secondary particles - specifically sulphates and ammonium nitrates - were responsible for the most significant portion of PM10 air pollution throughout the area of interest. The contribution of these particles ranged from one third to two fifths of the total concentration, except at the industrial site of Ostrava-Radvanice (TORE), where they accounted for approximately one fifth of the measured pollution concentration level. Emissions from individual household heating were identified as the main source of this type of pollution. With regards to benzo[a]pyrene air pollution, the study found that in the whole area of interest, except for the Ostrava-Radvanice site, it mainly originated from individual heating with coal (90%). In contrast, at the Ostrava-Radvanice site, two-thirds of the benzo[a]pyrene pollution came from the premises of Liberty Ostrava a.s., primarily from coke production, and less than one-third from local domestic heating. This study also determined the spatial extent of the occurrence of extremely high benzo[a]pyrene concentrations (above 5 ng/m3), which are estimated to affect nearly 10,000 inhabitants. The results confirm that the data from the TORE station are only representative of its immediate surroundings and are not applicable to the assessment of air quality and causes of air pollution in the whole city of Ostrava or the urban area of Ostrava-Radvanice as a whole. After years of research, these findings provide the Ministry of the Environment of the Czech Republic and the government with an accurate basis for implementing measures to address the identified pollution sources in the area of interest. The success of this study was made possible by the adoption of a more detailed sampling approach, which involved a resolution of 3 hours instead of 24 hours. This methodological improvement is a significant finding and will be useful for future source apportionment studies.

Replication protein A (RPA) is a heterotrimeric protein complex and the main single-stranded DNA (ssDNA) binding protein in eukaryotes. RPA has key functions in most of the DNA-associated metabolic pathways and DNA damage signalling. Its high affinity for ssDNA helps to stabilise ssDNA structures and prevents the DNA sequence from nuclease attacks. RPA consists of multiple DNA-binding domains which are oligonucleotide/oligosaccharide-binding (OB)-folds, responsible for DNA binding, and interactions with proteins. These RPA-ssDNA and RPA-protein interactions are crucial for DNA replication, DNA repair, DNA damage signalling, and the conversation of the genetic information of cells. Proteins such as ATR use RPA to locate to regions of DNA damage for DNA damage signalling. Recruitment of nucleases and DNA exchange factors to sites of double strand breaks are also an important RPA function to ensure effective DNA recombination to correct these DNA lesions. Due to its high affinity to ssDNA, RPA’s removal from ssDNA is of central importance to allow these metabolic pathway to proceed and processes to exchange RPA against downstream factors are established in all eukaryotes. These facetted and multi-layered functions of RPA will be discussed in detail in the review. RPA is also a major player in a variety of human diseases, which will be discussed.

Ewing sarcoma (EWS) is an aggressive pediatric malignancy of the bone and soft tissues in need of novel therapeutic options. To identify potential therapeutic targets, we focused on essential biological pathways that are upregulated by EWS-FLI1, the primary oncogenic driver of EWS, including mitotic proteins such as Aurora Kinase A (AURKA), Kinesin Family Member 15 (KIF15) and its binding partner, targeting protein for Xklp2 (TPX2). KIF15/TPX2 cooperates with KIF11, a key mitotic kinesin essential for mitotic spindle orientation. Given the lack of clinical grade KIF15/TPX2 inhibitors, we chose to target KIF11 (using SB-743921) in combination with AURKA (using VIC-1911), given phosphorylation of KIF15S1169 by Aurora A is required for its targeting to the spindle. In vitro, the drug combination demonstrated strong synergy (Bliss score ≥10) at nanomolar doses. Colony formation assay revealed significant reduction in plating efficiency (1-3%) and increased percent accumulation of cells in G2/M phase with the combination treatment (45-52%) upon cell-cycle analysis indicating mitotic arrest. In vivo studies in EWS xenograft mouse models showed significant tumor reduction and overall effectiveness: drug combination vs vehicle control (p≤0.01), SB-743921 (p≤0.01) and VIC-1911 (p≤0.05). Kaplan-Meier curves demonstrated superior overall survival with the combination compared to vehicle or monotherapy arms (p≤0.0001).

The rationalization and modeling of an electric discharge in a fluid require the knowledge of electron swarm parameters. In this work, transport coefficients of alcohols, including methanol, ethanol, propanol, and butanol are reported. The electron energy distribution function, mean energy, reduced mobility, and diffusion coefficient, are calculated using the two-term expansion of the electron Boltzmann equation in the frame of BOLSIG+ and the Monte Carlo collision code METHES. For such, experimental and theoretical values of the electron-alcohol collision cross-section, covering a range of electron impact energy from 1 eV to 1000 eV, are employed. A temperature of 300K, reduced fields E/N between $1-10^4$ Td (1Td = $10^{-21}~\rm Vm^2$), and Plasma density of $10^{19}~\rm m^{-3}$ were used in simulations. The calculated coefficients are compared with data available from previous studies.

A time interval only description necessarily needs its own independent definitions, without one moment time coordinates to it. In this paper derived are time interval only set properties, including commutation relations, addition, multiplication and derivatives. Time interval only set commutation relations, consistent with one moment time set properties, are introduced by defining correspondence relations for these sets. Time development and equilibrium within the time interval description depend on the well-known ‘mean velocity theorem’ and the time interval version of the Legendre transform. In contrast, usually applied is only the traditional vector and one moment time coordinate kinematic approach from Newton’s laws. The main results of this paper are correspondences and time interval only set commutation relations. All other properties are derived from these results, while for the time interval only set, different from the one moment time set the canonical property is not valid. The time interval only description can be applied assuming spherical symmetric star-source radiation propagation, with finite time intervals for realistic measurement events. From time development with (a-)symmetry of time intervals, and from Curie’s principle, change can be described with a set theoretic approach. Time interval only set properties include the time interval only version of Noether charges and structure constants. A time interval only description for wave propagation, including group-velocity, for zero and non-zero mass wave particles, relates to the properties of the time interval only set. A second result in terms of the time interval only description is propagation wave energy equivalence with gravitation energy, derived from time interval only set commutation relations. A time interval approach, however including one moment time description dependence, was introduced in earlier publications of this author. In part 1 investigated are the time interval only set and its properties, a forthcoming part 2 to application of the time interval only description to specific groups of stars as emission sources.

In recent, Chae found that, at weak gravitational acceleration g_N≲10⁻⁹ms⁻², the observed orbit of the wide binary stars is not accordant with current theory of binary star. Here, we present, this finding should be an observational evidence for that Newtonian theory of orbit perturbation is still valid in galactic scale.

: Ovarian cancer has a dismal prognosis. Standard treatment following surgery relies on platinum-based chemotherapy. However, sizeable percentages of patients are unresponsive. Identification of markers predicting response to chemotherapy might help select eligible patients while sparing unresponsive ones treatment-associated toxicity. Cancer/testis antigens (CTA) are expressed by healthy germ cells and malignant cells of diverse histological origin. This expression profile identifies them as attractive targets of cancer immunotherapies. We analyzed correlations between expression of MAGE-A10 and New York esophageal-1 cancer (NY-ESO-1) CTAs at protein level and effectiveness of platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). MAGE-A10 and NY-ESO-1 protein expression was analyzed by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded samples from 93 patients with advanced-stage HGSOC treated at our institutions between January 1996 and December 2013. Correlation between expression of these markers and response to platinum-based chemotherapy, evaluated according to RECIST 1.1 criteria, platinum sensitivity, measured as platinum free interval (PFI), progression free (PFS) and overall survival (OS) was explored. MAGE-A10 protein expression predicts unresponsiveness to platinum-based chemotherapy (p=0.005), poor platinum sensitivity (p<0.001), and poor PFS (p<0.001) and OS (p<0.001). Multiva-riate analysis identifies MAGE-A10 protein expression as independent predictor of poor platinum sensitivity (p=0.005) and shorter OS (p<0.001). Instead, no correlation was observed between NY-ESO-1 protein expression and response to platinum-based chemotherapy (p=0.832), platinum sensitivity (p= 0.168), PFS (p=0.126) and OS (p=0.335). MAGE-A10 protein expression reliably identifies advanced-stage HGSOC unresponsive to platinum-based chemotherapy. Targeted im-munotherapy could represent an important alternative therapeutic option in these cancers.

Polycyclic aromatic hydrocarbons (PAHs) have been reported to cause oxidative stress in metabolic processes. This study aimed to evaluate the relationship between exposure to PAHs, including benzo[a]pyrene (BaP) and 1-nitropyrene (1-NP), in the atmosphere and oxidative stress levels in the human body. This study included 44 Korean adults who lived in Cheongju, South Korea. Atmospheric BaP and 1-NP concentrations and urinary 6-hydroxy-1-nitropyrene (6-OHNP), N-acetyl-1-aminopyrene (1-NAAP), and 1-hydroxypyrene (1-OHP) concentrations were measured. The oxidative stress level was assessed by measuring urinary thiobarbituric acid reactive substances (TBARS) and 8-hydroxydeoxyguanosine (8-OHdG) concentrations. Urinary TBARS and 6-OHNP concentrations significantly differed between winter and summer. BaP exposure was significantly associated with urinary 8-OHdG concentrations in summer. However, atmospheric 1-NP did not show a significant correlation with oxidative stress marker concentrations. Urinary 1-NAAP concentration was a significant determinant for urinary 8-OHdG concentration in summer. Oxidative stress in the body increases in proportion to inhalation exposure to BaP, and more 8-OHdG is produced in the body as the amount of 1-NP, which is metabolized to 1-AP or 1-NAAP, increases.

Conducted within the scope of geochemical exploration in Eastern Thailand, this study aims to detect geochemical anomalies and potential mineral deposits. The objective was to interpret intricate spatial dispersion patterns and concentration levels of deposit pathfinder elements, specifically arsenic (As), copper (Cu), and zinc (Zn), using a comprehensive array of stream sediment geochemistry data. Methodologies involved integrating multifractal properties and traditional statistics, facilitated by the GeoDAS and ArcGIS platforms as instrumental analytical tools. In total, 5,376 stream sediment samples were collected and evaluated, leading to the development of an in-depth geochemical map. The results indicated distinct geological units marked by substantially elevated average values of the aforementioned elements. Identification of geochemical anomalies was achieved through the spatial distribution method and the subsequent application of the Spectrum-Area (S-A) multifractal model. An intriguing link was found between high As concentrations and gold deposits in the area, suggesting As as a viable pathfinder element for gold mineralization. The anomaly maps, generated from the stream sediment data, spotlighted potential zones of interest, offering valuable guidance for future mineral exploration and geological inquiries. Nonetheless, it is vital to recognize that the increased values noted in these maps may be influenced by regional geological factors, emphasizing the necessity for a diverse set of analytical methods for accurate interpretation. The study's significance lies in its pioneering use of the S-A multifractal model in geochemical data analysis. This innovative approach has deepened our comprehension of geochemical dispersion patterns and improved the precision of mineral exploration.

The visual appearance of humans derives significantly from our skin and hair color. While melanin from epidermal melanocytes protects our skin from the damaging effects of ultraviolet radiation, the biological value of pigmentation in the hair follicle, particularly in the scalp, is less clear. In this study, we explore the heterogeneity of pigment cells in the human scalp anagen hair follicle bulb, a site conventionally viewed to be focused solely on pigment production for transfer to the hair shaft. Using c-KIT/CD117 microbeads, we isolated bulbar c-KIT-positive and c-KIT-negative melanocytes. While both subpopulations expressed MITF, only the c-KIT-positive fraction expressed SOX10. We further localized bulbar melanocyte subpopulations (expressing c-KIT, SOX10, MITF, and DCT) that exhibited distinct/variable expression of downstream differentiation-associated melanosome markers (e.g., gp100 and Melan-A). Localization of a second ‘immature’ SOX10 negative melanocyte population, which was c-KIT/MITF double positive, was identified outside of the melanogenic zone in the most peripheral/proximal matrix. These studies describe an approach to purifying human scalp anagen hair bulb melanocytes, allowing us to identify unexpected levels of melanocyte heterogeneity. The function of the more immature melanocytes in this part of the hair follicle remains to be elucidated. Could they be in-transit migratory cells destined to synthesize mela-nin ultimately or could they contribute to the hair follicle in non-melanogenic ways.

This paper proposes an AI-based approach to overcome the limitations of the SHM system in measuring global stress with limited sensors. Feature elements are selected based on correlation analysis among finite elements and used as stress-measured points. An ANN is used to establish the solution relationship between the feature and correlation elements. The proposed method is applied to the connector structure of an offshore platform, and an optimal ANN is established to optimize accuracy by considering factors like the number of sensors, neural network framework, and convergence criteria. The accuracy of the ANN is verified through a real-scale model test, demonstrating 93.6% accuracy. This technology represents a significant advancement, enhancing the practicality of the structural health monitoring (SHM) system from “point monitoring" to “field monitoring".

Metachromatic leukodystrophy (MLD) is a hereditary neurodegenerative disease characterized by demye-lination and motor and cognitive impairment due to the deficiency of the lysosomal enzyme arylsulfatase A (ARSA) or the saposin B activator protein (SapB). Current treatments are limited; however, gene therapy using adeno-associated virus (AAV) vectors for ARSA delivery has shown promising results. The main challenges for MLD gene therapy include optimizing AAV dosage, selecting the most effective serotype, and determining the best route of administration for ARSA delivery into the central nervous system. This study aims to evaluate the safety and efficacy of AAV serotype 9 encoding ARSA (AAV9-ARSA) gene therapy when administered intrave-nously or intrathecally in minipigs, a large animal model with anatomical and physiological similarities to humans. By comparing these two administration methods, this study contributes to the understanding of how to improve the effectiveness of MLD gene therapy and offers valuable insights for future clinical applications.

This study explores the implications of merging two fundamentally different types of banks: Islamic and conventional banks. The research aims to provide insight into such a merger's unique opportunities and challenges and offer strategic guidance for future mergers. A balanced scorecard-based strategic analysis using Quantum Spherical Fuzzy Decision-Making Approach was used to develop the merged bank's short- and long-term strategic plans. The balanced scorecard included 12 key performance indicators (KPIs) in 4 groups, and the methodology also incorporated several questions to guide the analysis. The study results offer valuable insights into the potential opportunities and challenges of merging these two types of banks and strategic recommendations for stakeholders at all levels. The study is a valuable guideline for future mergers between similar or different types of banks. Overall, the findings suggest that a well-planned merger strategy is essential for avoiding challenges and maximizing the benefits of merging Islamic and conventional banks. By integrating the strengths of both types of banks, a merged entity could create a competitive advantage and potentially improve financial performance. However, this requires careful consideration of cultural differences, regulatory challenges, and other factors that could impact the merger's success.

In the presence of absorbing aerosol in the atmosphere a number of systematic errors of standard Ocean Color algorithms were noted, for example, negative values of remote sensing reflectance in the short-wavelength region at 412 nm and 443 nm. The main goal of this work is to develop an algorithm for additional correction of remote sensing reflectance level 2 satellite data, taking into account the presence of absorbing aerosol over the Black Sea, where a large number of dust transfers from the Sahara are observed annually. To implement the algorithm, an analytical and experimental evaluation of the interpolation function is carried out, taking into account the optical effects caused by the stratification of the absorbing aerosol. This algorithm is based on the constancy of the color index value, characteristic of the selected region. For the Black Sea the average value of CI(412/443) = 0.80±0.08, a small standard deviation indicates that the sample is slightly variable. Therefore, CI(412/443) = 0.80 will be further considered as the reference value of the color index for calculating new restored Rrs(λ).

Cancer stem cells remain a challenge to isolate and characterize because of their plastic phenotype. Using a microfluidic lab-on-a-chip based on ultra-high frequency dielectophoresis, we measured the electromagnetic signature of colorectal cancer cells and demonstrated that cancer stem cells show a distinct and lower electromagnetic signature than differentiated cells. The release of extracellular vesicles from tumor cells can drive tumor progression and metastasis development. As extracellular vesicles from cancer stem cells carry more aggressive content, we treated colorectal cancer cells with these vesicles to test whether the lab-on-a-chip can detect a change in phenotype. The electromagnetic signature of treated cells is modified in comparison to untreated cells and sometimes even when no biological change is observed. The lab-on-a-chip provides rapid and relevant result without prior labeling compared to conventional biological approaches. It could be useful in the clinic for early detection of cancer stem cells in the tumor mass and for monitoring the aggressive potential of extracellular vesicles in the bloodstream in order to adapt therapeutic management and prevent relapse.

Songorine (SON) is a diterpenoid alkaloid from Aconitum plants. Preparations of Aconitum roots have been employed in traditional oriental herbal medicine, however, their mechanisms of action are still unclear. Since GABA-receptors are possible brain targets of SON, we investigated which subtypes of GABA-receptors contribute to the effects of SON, and how SON affects anxiety-like trait behavior and psychomotor cognitive performance of rats. First, we investigated the effects of microiontophoretically applied SON alone and combined with GABA-receptor agents picrotoxin and saclofen on neuronal firing activity in various brain areas. Next, putative anxiolytic effects of SON (1.0-3.0 mg/kg) were tested against the GABA-receptor positive allosteric modulator refer-ence compound diazepam (1.0-5.0 mg/kg) in the elevated zero maze (EOM). Furthermore, basic cognitive effects were assessed in a rodent version of the psychomotor vigilance task (PVT). Local application of SON predominantly inhibited the firing activity of neurons. This inhibitory effect of SON was successfully blocked by GABA(A)-receptor antagonist picrotoxin but not by GABA(B)-receptor antagonist saclofen. Similar to GABA(A)-receptor positive allosteric modulator diazepam, SON increased the time spent by animals in the open quadrants of the EOM without any signs of adverse psychomotor and cognitive effects observed in the PVT. We showed that, under in vivo conditions SON acts as a potent GABA(A)-receptor agonist and effectively decreases anxiety without observable side effects. The present findings facilitate the deeper understanding of the mechanism of action and the widespread pharmacological use of diterpene alkaloids in various CNS indications.

In the present study, we studied the effect of apolipoprotein A-1 (APOA1) on the spatial and molecular characteristics of bone marrow adipocytes, using well-characterized ApoA1 knockout mice. APOA1 is a central regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, and thus HDL; our recent work showed that deficiency of APOA1 increases bone marrow adiposity in mice. We found that ApoA1 deficient mice have greatly elevated adipocytes within their bone marrow compared to wild type counterparts. Morphologically, the increased adipocytes were similar to white adipocytes, and displayed proximal tibial-end localization. Marrow adipocytes from wild type mice were significantly fewer and did not display bone-end distribution pattern. The mRNA levels of the brown/beige adipocyte-specific markers Ucp1, Dio2, Pat2, Pgc1a, and the expression of leptin were greatly reduced in the ApoA1 knock-out in comparison to the wild-type mice. In the knock-out mice adiponectin was remarkably elevated. In keeping with the close ties of hematopoietic stem cells and marrow adipocytes, we found that the elevated adiposity in the ApoA1 knock out mice is associated with a significant reduction of the hematopoietic stem cells and common myeloid, but not common lymphoid, progenitors. Moreover, the “beiging”-related marker osteopontin and the angiogenic factor VEGF were also reduced in the ApoA1 knock-out mice, further supporting the notion that APOA1, and most probably HDL-C, regulate bone marrow microenvironment, favouring beige/brown adipocyte characteristics.

Organ-on-a-Chip (OoC) systems bring together cell biology, engineering, and material science for creating systems that recapitulate the in vivo microenvironment of tissues and organs. The versatility of OoC systems enables in vitro models for studying physiological processes, drug development, and testing in both academia and industry. This paper evaluates current platforms from the end-user perspective, elaborating on usability, complexity, and robustness. We surveyed 165 peers in over 30 countries and grouped the responses according to preliminary knowledge and the source of the OoC systems that are used. The survey clearly shows that current commercial OoC platforms provide a substantial level of robustness and usability - which is also indicated by an increasing adaptation of the pharmaceutical industry but a lack of complexity can challenge their use as a predictive platform. Self-made systems on the other hand are less robust and standardized but provide the opportunity to develop customized and more complex models which are often needed for human disease modeling. This review serves as a guide for researchers in the OoC field and encourages the development of next-generation OoCs.

Alzheimer’s and Parkinson's diseases (AD and PD) are amongst top of the prevalent neurodegenerative disease. One-third of PD patients are diagnosed with dementia, a pre-symptom of AD, but the underlying mechanism is elusive. Amyloid beta (Aβ) and α-synuclein are two of the most investigated proteins, whose pathological aggregation and spreading are crucial to the pathogenesis of AD and PD, respectively. Transcriptomic studies of the mammalian central nervous system shed light on gene expression profiles at molecular levels, regarding the complexity of neuronal morphologies and electrophysiological inputs/outputs. In the last decade, the booming of the single-cell RNA sequencing technique helped to understand gene expression patterns, alternative splicing, novel transcripts, and signal pathways in the nervous system at single-cell levels, providing insight for molecular taxonomy and mechanistic targets of the degenerative nervous system. Here, we re-visited the cell-cell transmission mechanisms of Aβ and α-synuclein in medi-ating disease propagation, and summarized recent single-cell transcriptome sequencing from different perspectives and discussed its understanding of neurodegenerative diseases.

The Betz limit sets a theoretical upper limit for the power production by turbines expressed as a maximum power coefficient of 16/27. Betz’s theory is accurate and it is based on the calculation of kinetic energy.

Pandemics caused by viruses have threatened lives of thousands of people. Viral infection is a complex and diverse process, and substantial studies have been complemented in understanding the biochemical and molecular interactions between viruses and hosts. However, the physical microenvironment where infections implement is often less carefully considered, and the role of mechanobiology in viral infection remains elusive. Mechanobiology focuses on sensation, transduction and response to intracellular and extracellular physical factors by tissues, cells and extracellular matrix. The intracellular cytoskeleton and mechanosensors have been proved to be extensively involved in virus life cycle. Furthermore, innovative methods in vivo and in vitro are being utilized to elucidate how extracellular factors including stiffness, forces and topography in regulating viral infection. Our current review covers how physical factors from different sources coordinate virus infection. We further discuss how this knowledge can be harnessed in future research on cross-fields of mechanobiology and virology.

The scale and accessibility of passive global surveillance have rapidly increased over time. This provides an opportunity to calibrate the performance of models, algorithms, and reflectance ratios between remote sensing devices. Here we test the sensitivity and specificity of Eucalypt chlorophyll-a reflectance ratio (ECARR) and Eucalypt chlorophyll-b reflectance ratio (ECBRR) to remotely identify eucalypt vegetation in Queensland, Australia. We compare reflectance ratio values from Sentinel-2 and Planet imagery across four sites of known vegetation composition. All imagery was transformed to reflectance values and Planet imagery was additionally scaled to harmonize across Planet Scenes. ECARR can identify eucalypt vegetation remotely with high sensitivity, but shows low specificity and is impacted by the density of the vegetation. ECBRR reflectance ratios show similar sensitivity and specificity when identifying eucalypt vegetation but with values an order of magnitude smaller than ECARR. We find that ECARR was better at identifying eucalypt vegetation in the Sentinel-2 imagery than Planet imagery. ECARR can serve as a general chlorophyll indicator but is not a specific index to identify Eucalyptus vegetation with certainty.

Cloud robotics is becoming an alternative to support advanced services of robots with low computing power as network technology advances. Recently, fog robotics has gained attention since the approach has merit relieving latency and security issues over the conventional cloud robotics. In this paper, a Function-as-a-Service based Fog Robotic (FaaS-FR) for cognitive robots is proposed. The model distributes the cognitive functions according to the computational power, latency and security with a public robot cloud and fog robot server. During the experiment with a Raspberry Pi as an edge, the proposed FaaS-FR model shows efficient and practical performance in the proper distribution of the computational work of the cognitive system.

Influenza virus imprinting is now understood to significantly the influence immune responses and clinical outcome of influenza virus infections that occur later in life. Due to the yearly cycling of influenza viruses, humans are imprinted with the circulating virus of their birth year to subsequently build a complex influenza virus immune history but very little is known about how the imprinting strain influences vaccine responses. To investigate the imprinted host immune responses to split-virion vaccination, we imprinted ferrets with a sublethal dose of the historical seasonal H1N1 strain A/USSR/90/1977. After a +60 day recovery period was given to build immune memory, ferrets were immunized and the challenge at Day 123. Samples were collected throughout the time course and immunological assays were performed to investigate recall mechanisms. The preimmune-vaccinated ferrets did not experience significant disease during challenge while naïve-vaccinated ferrets had severe disease. Hemagglutination inhibition assays showed preimmune ferrets had a more robust antibody response post vaccination, increased virus neutralization activity. Virus specific immunoglobulins were of predominantly the IgG isotype suggesting B cell maturity and plasticity at vaccination. These results are important and should be considered for vaccine design.

In this study, we actually want to explore the time-fractional Phi-four equation via two methods, the exp _a function method and the hyperbolic function method. We transform a fractional order dierential equation into an ordinary differential equation using a wave transformation and the fractional derivative in conformable form. Then, the resulting equation has successfully been explored for new explicit exact solutions. The procured solutions are simply showed the effectiveness and plainness of the projected methods.

Phylostratigraphic analysis is a way to look anew on phylogenetic data in the evolutionary aspect. It allows counting the evolutionary age based on the analysis of genes, their orthologs and finding the last common ancestor. We performed phylostratigraphic analysis of Arabidopsis thaliana genes associated with several types of abiotic stresses (heat, cold, water-related, light, osmotic, salt, and oxidative) determined by the Gene Ontology annotation. Comparison of the distributions of ages of genes associated with stresses of different type has shown the heat stress to involve older genes while the light stress – younger genes. At the same time, all types of stress are characterized by a significantly higher proportion of old genes (common to all eukaryotes) compared to the whole set of A.thaliana genes. This can be explained by the involvement of basic molecular processes in plant cells into the stress response. Reconstruction and graphical analysis of the gene network of the heat stress educed several clusters associated with different response functions. Some of these clusters contain only ancient genes. The results obtained show that the phylostratigraphic analysis reveals the fundamental features of the organization of gene networks and their evolution.

The purpose of this study was to evaluate the bioactivity and cell response of a well-characterized Nurse´s A-phase (7CaO•P2O5•2SiO2) ceramic and his effect compared to a control (tissue culture polystyrene-TCPS) on the adhesion, viability, proliferation and osteogenic differentiation of ahMSCs in vitro. Cell proliferation (Alamar Blue Assay), Alizarin Red-S (AR-s) staining, alkaline phosphatase (ALP) activity, osteocalcin (OCN) and collagen I (Col I) were evaluated. Also, field emission scanning electron microscopy (FESEM) images were acquired in order to visualise the cells and the topography of the material. The proliferation of cells growing in a direct contact with the material was slower at early stages of the study because of the new environmental conditions. However, the entire surface was colonized after 28 days of culture in growth medium (GM). Osteoblastic differentiation markers were significantly enhanced in cells growing on Nurse´s A phase ceramic and cultured with osteogenic medium (OM), probably due to the role of silica to stimulate the differentiation of ahMSCs. Moreover, calcium nodules were formed under the influence of ceramic material. Therefore, it is predicted that Nurse´s A-phase ceramic would present high biocompatibility and osteoinductive properties being a good candidate to be used as a biomaterial for bone tissue engineering.

The separation of sister chromatids during anaphase is the culmination of mitosis and one of the most strikingly beautiful examples of cellular movement. It consists of two distinct processes: Anaphase A, the movement of chromosomes toward spindle poles via shortening of the connecting fibers, and anaphase B, separation of the two poles from one another via spindle elongation. I focus here on anaphase A chromosome-to-pole movement. The chapter begins by summarizing classical observations of chromosome movements, which support the current understanding of anaphase mechanisms. Live cell fluorescence microscopy studies showed that poleward chromosome movement is associated with disassembly, or ‘melting’ of the kinetochore-attached microtubule fibers that link chromosomes to poles. Microtubule-marking techniques established that kinetochore-fiber disassembly often occurs through a ‘pac-man’ mechanism, where tubulin subunits are lost from kinetochore-attached plus ends and the kinetochore appears to consume its microtubule track as it moves poleward. In addition, kinetochore-fiber disassembly in many cells occurs partly through ‘flux’, where the microtubules flow continuously toward the poles and tubulin subunits are lost from minus ends. Molecular mechanistic models for how load-bearing attachments are maintained to disassembling microtubule ends, and how the forces are generated to drive pac-man and flux-based movements, are discussed.

The article presents the results of cyanide leaching of gold-containing concentrate using the trichlorocyanuric acid (TCCA) oxidizer. Gold-containing concentrate obtained from a gold tailings sample from a gold recovery factory (GRF) in one of the deposits of Kazakhstan that was not previously studied for concentrability. According to X-ray phase analysis and energy dispersive spectrometry (DSM) data, the main compounds in the tailings sample under study are: pyrite FeS2, quartz SiO2, calcite CaCO3, albite NaAlSi3O8, muscovite KAl2Si3AlO10(OH)8, dolomite CaMg(CO3)2, and oxidized iron compounds. Microscopic studies have established the presence of gold grains in free form, ranging in size from 0.9-10.2 mkm Au-ultrafine and fine gold. Obtaining a gold-containg concentrate with a gold content of 15.95 g / t is possible according to the enrichment scheme, which includes centrifugal separation, classification according to the fineness class -0.05 mm, additional grinding of hydrocyclone sands to a fineness of 90.0-95.0% of the class finer than 0.050 mm, and control centrifugal separation. Since pyrite in technogenic raw materials is the main gold-containing mineral, this paper presents studies on the oxidizability of pyrite with the TCCA oxidizer. The results of studies on the oxidation of pyrite using the TCCA oxidizer show that the products of its hydrolysis oxidize pyrite with the formation of various iron compounds on its surface. Pretreatment of gold-containing concentrate with oxidizer TCCA for 3 hours before the cyanidation process (20 hours) allows to increase the recovery of gold in the solution by 5.8 %.

Information geometry (IG) is a fascinating combination of differential geometry and statistics where a Riemannian manifold's structure is applied to a statistical model. It may find numerous fascinating uses in the domains of theoretical neurology, machine learning, complexity, and (quantum) information theory, among others. (IG) aims to provide a differential-geometric perspective on statistical geodesic models' structure. In this case, IG, KD, and J-divergence (JD) are used to define the manifold of the Generalised Brownian Motion (GBM). Consequently, the geodesic equations (GEs) are devised, and GB information matrix exponential (IME) is presented. Moreover, for first time ever, the necessary and sufficient mathematical requirement that characterizes the developability of Generalized Brownian Motion(GBM) manifold is devised. Also, a novel sufficient and necessary conditions which characterizes the regions where the surface describing GBM is minimal is determined. Also, it is shown that GBM has a non-zero 0-Gaussian and Ricci curvatures. Consequently, this advances the establishment of a unified GBM- Relativistic Info-Geometric based analysis.

This comprehensive review is devoted to an under-exploited family of phenolic compounds, the coumarins, and the most relevant strands in which they are involved in some spirit beverages – wine spirit, brandy, whiskey, sugar cane spirits (rum and cachaça) and grape marc spirit – with great importance worldwide in terms of production, trade and consumption. It gathers the key discoveries on the topic considering the production process of each spirit beverage, the related sources of coumarins (different kinds of wood used in the ageing stage) along with the factors that govern them and can influence the sensory properties of the aged beverages. An overview of the analytical methods available for their identification/quantification is also included, as well as the corresponding trends for the advancement of knowledge in this field. Moreover, the remarkable role of coumarins as nutraceuticals, their importance as chemical markers for authenticity purposes, and their relationship with food safety of these spirit beverages are also addressed, highlighting the current gaps and issues, and providing clues for future research.

One of the most widely available and extensively produced varieties of industrial hemp, which generates a substantial amount of consumer-increasing waste in the form of hemp cellulose. In this study, recycling with a compressed and high-speed method that combines crushing and alkali treatment effectively converts leftover hemp fiber into ultrafine powder. SEM (Scanning Electron Microscopy), AFM (Atomic Force Microscope), FTIR (Fourier-transform Infrared Spectroscopy), and XRD (X-ray Diffraction) examined the original morphology of hemp fiber treated with alkali, fiber heated to 200 ℃, and crushed powder. Particle size, crystallinity, fiber surface, and strength increased and decreased. It became apparent that fiber strength decreased and fiber roughness significantly increased after alkali treatment. Fiber increased significantly, and crystallinity decreased after crushing. It was simple and effective for converting the leftover hemp fiber into micron-sized powder. In about 3 to 5 minutes, approximately 1 kg of dry ultrafine powder with a particle size of 10.44 μm was produced. This production method will significantly enhance future industrial applications of waste hemp fiber.

Intestinal mucositis (IM) is a common adverse effect of chemotherapy, limiting its clinical application. Edible Chinese medicine, specifically Codonopsis pilosula-derived CP-A, with anti-inflammatory and gastrointestinal protective effects. The present work was to investigate CP-A's role in ameliorating IM and its mechanism using in vitro and rat models. Western blot, immunohistochemical (IHC) and real-time PCR (RT-PCR) analyses were used to assess protein expression related to the extracellular-regulated protein kinases (ERK)/myosin light chain kinase (MLCK)/myosin light chain 2 (MLC2) signaling pathway and tight junction proteins. Enzyme-linked immunosorbent assay (ELISA) was conducted to measure inflammatory factors, and 16S rRNA Amplicon Sequencing was employed for cecum content analysis. The results indicated that CP-A could restore body weight, food intake and histopathological changes in IM rats. Besides, abnormal MLCK activation induced by 5-fluorouracil (5-FU) was attenuated by CP-A via the ERK/MLCK/MLC2 pathway. CP-A treatment improved tight junction protein levels and reduced inflammatory factor expression. On the other hand, intestinal flora experiment demonstrated that CP-A intervention could increase the abundance of lactobacillus. In conclusion, CP-A mitigates 5-FU-induced IM by inhibiting the ERK/MLCK/MLC2 pathway, reducing the expression of inflammatory factors, improving the intestinal mucosal barrier and regulating intestinal flora. This study sheds light on CP-A's therapeutic potential in IM treatment, providing insights for future research.

We report on the occurrence of natural Magnesium Alumina Silicate Hydrate (M-(A)-S-H) cement at Feragen and Leka in eastern and western Trøndelag Norway, respectively. Both occurrences are located in the sub-arctic climate zone and form in glacial till and moraine material deposited on ultramafic rock during the Weichselian glaciation. Weathering of serpentinized peridotite dissolve brucite and result in a relative high pH alkaline fluid that subsequently reacts with the felsic minerals of the till (quartz, plagioclase, K-feldspar) to form a cement consisting of an amorphous material or a mixture of nanocrystalline Mg-rich phyllosilicates, including illite. The presence of plagioclase in the till results in the enrichment of alumina in the cement, i.e., forms M-A-S-H instead of the M-S-H cement. Dissolution of quartz results in numerous etch-pits and negative quartz crystals filled with M-A-S-H cement. Where the quartz dissolution is faster that the cement precipitation, a honeycomb-like texture is formed. Compositionally the cemented till (tillite) contains more MgO and has a higher loss of ignition than the till, suggesting that the cement is formed by a MgO fluid that previously reacted with the peridotite. The M-(A)-S-H cemented till represent a new type of duricrust, coined magsilcrete. The study of natural Mg-cement provides information on peridotites as a Mg-source for Mg-cement and as a feedstock for CO2 sequestration.

Vascular endothelial growth factors (VEGFs) are regarded as the key vasculogenic mediators in the human body, of which VEGF-A is considered as one of the important types. It is the major growth factor possessing increasing vascular permeability as well as angiogenesis properties. This article provides intuition into the different effects of VEGF-A on vessels in ovarian hyper stimulation syndrome (OHSS) which is defined as a complication of in-vitro fertilization for infertility treatment, and obesity, a universally health problem. These are two dissimilar pathways outcomes for VEGF-A effects, thereby This article reviews updated information about the mentioned disorders and reveals that how this kind of growth factor yields different results on vasculature by activating distinct intracellular signaling in endothelial cells.

We assume that the current mathematical knowledge K is a finite set of statements from both formal and constructive mathematics, which is time-dependent and publicly available. Any theorem of any mathematician from past or present belongs to K. The set K exists only theoretically. Ignoring K and its subsets, sets exist formally in ZFC theory although their properties can be time-dependent (when they depend on K) or informal. In every branch of mathematics, the set of all knowable truths is the set of all theorems. This set exists independently of K. Algorithms always terminate. We explain the distinction between algorithms whose existence is provable in ZFC and constructively defined algorithms which are currently known. By using this distinction, we obtain non-trivial statements on decidable sets X⊆N that belong to constructive and informal mathematics and refer to the current mathematical knowledge on X. This and the next sentence justify the article title. For any empirical science, we can identify the current knowledge with that science because truths from the empirical sciences are not necessary truths but working models of truth about particular real phenomena.

Hund's rule of maximum multiplicity is a powerful empirical tool for determining the electron population of electronic shells. It was recently discovered that it is also the rule of minimum Shannon entropy. This study extends these findings to the Aufbau rule and discusses them from the perspective of emergent dimensionality, providing a monotonically increasing entropy function. We observed that some elements that violate the Aufbau rule have the same entropies in the actual and Aufbau electron configurations. On the other hand, lower entropies of all actual elements' configurations are associated with higher or equal numbers of unpaired electrons in these configurations compared to the Aufbau configurations. The only exception to this rule is palladium.

In this study, we report the first outbreak of highly pathogenic avian influenza (HPAI) A H5N8, clade 2.3.4.4b in Kosovo on May 19, 2021. The outbreak consisted of three temporal phases: May–June 2021, September–November 2021, and January–May 2022. In total, 32 backyard and 10 commercial holdings tested positive for the virus, affecting 179,198 poultry. Interestingly, the third and last phase of the outbreak coincided with the massive H5N1 clade 2.3.4.4b epidemic in Europe. Phylogenetic analyses of 28 viral strains from Kosovo revealed that they were closely related to the H5N8 clade 2.3.4.4.b viruses that have been circulating in Albania, Bulgaria, Croatia, Hungary, and Russia in early 2021. Whole genome sequencing of the 25 and partial sequencing of 3 H5N8 viruses from Kosovo showed high nucleotide identity, forming a distinctive cluster and suggesting a single introduction. The results of the network analysis were in accordance with the three epidemic waves and suggested that the viral diffusion could have been caused by secondary spreads among farms and/or different introductions of the same virus from wild birds. The persistent circulation of the same virus over a one-year period highlights the potential risk of the virus becoming endemic, especially in settings with non-adequate biosecurity.

Oestrogen receptor expression in breast cancer (BC) cells is a marker of high cellular differentiation and allows the identification of two BC groups (ER-positive and ER-negative) that, although not completely homogeneous, differ in biological characteristics, clinical behaviour and therapeutic options. The study, based on three publicly available EWAS datasets, focuses on the comparison between these two groups of breast cancer using an epimutation score. The score is calculated not only based on the presence of the epimutation but also on the deviation amplitude of the methylation outlier value. For each dataset, we performed a functional analysis based first on the functional gene region of each annotated gene (we aggregated the data per gene region TSS1500, TSS200, first-exon, body-gene identified by the information from the Illumina Data Sheet) and then we performed a pathway enrichment analysis through the REACTOME database based on the genes with the highest epimutation score. Thus, we blended our results and found common pathways for all three data sets. We found that a higher and significant epimutation score due to hypermethylation in ER-positive BC is present in the promoter region of the genes belonging to the SUMOylation pathway, the NOTCH pathway, the IFN-$\gamma$ signalling pathway and the deubiquitination protease pathway; while a higher and significant level of epimutation due to hypomethylation in ER-positive BC is present in the promoter region of the genes belonging to the ESR-mediated pathway. The presence of this state of promoter hypomethylation in the ESR-mediated signalling genes is consistent and coherent with an active signalling pathway mediated by oestrogen function in the group of ER-positive BC. SUMOylation and NOTCH pathways are associated with BC pathogenesis and have been found to play distinct roles in the two BC subgroups. We speculated that the altered methylation profile may play a role in regulating signalling pathways with specific functions in the two subgroups of ER-BC.

Type A acute aortic dissection are associated with significant morbidity and mortality with prompt referral imaging and management to tertiary referral centres needed urgently. Surgery is usually needed emergently but the choice of surgery often varies depending on the patient and presentation. Staff and center expertise also play a major role in determining the surgical strategy employed The aim of this study is to compare early and medium term outcomes of patient across 3 European referral centers. We also identified risk factors for poorer outcomes irrespective of surgical strategy employed. A retrospective study was conducted across 3 sites between January 2008 and December 2021. 601 patients were included within the study of which 30% were female and the median age was 64.4 years. The most common operation was ascending aorta replacement (n= 246, 40.9%). The aortic repair was extended proximally (i.e., root n= 105; 17,5%) and distally (i.e., arch n = 250; 41,6%). A more extensive approach, extending from the root to the arch, was employed in 24 patients (4.0%). Operative mortality occurred in 146 patients (24.3%), and the most common morbidity was stroke (75, 12.6%). An increased length of ICU admission was noted in the extensive surgery group who were younger and more frequently male No significant differences were noted in surgical mortality from patients managed with extensive surgery vs those managed conservatively. However, age, arterial lactate levels, “intubated/sedated” status on arrival, and “emergency or salvage” status at presentation were independent predictors of mortality both within the index hospitalization and also during follow-up. Overall survival was similar between the groups.

In this paper, the authors employ Mountain Pass Lemma, the method of weak solution regularization and Lyapunov function method to derive the unique existence of globally exponential stable positive stationary solution of a single-species model with diffusion and delayed feedback. The obtained stability criterion illuminates that under some suitable conditions, a certain internal competition is conducive to the overall stability of the population, and a certain amount of family planning is conducive to the overall stability of the population. A numerical example and three tables show the effectiveness of the proposed methods.

Epithelial-to-mesenchymal transition (EMT) plays a role in chronic obstructive pulmonary diseases (COPD). Cyclic adenosine monophosphate (cAMP) can inhibit transforming growth factor-β1 (TGF-β1) mediated EMT. Although compartmentalization via A-kinase anchoring proteins (AKAPs) is central to cAMP signaling, functional studies on their therapeutic value in the lung EMT process are lacking. Bronchial epithelial (BEAS-2B, primary HAE cells) were exposed to TGF-β1. Epithelial (E-cadherin, ZO-1) and mesenchymal markers collagen Ӏ (mRNA, protein) were analyzed. St-Ht31 disrupted AKAP-PKA interactions. TGF-β1 release was measured by ELISA. TGF-β1-sensitive AKAPs Ezrin, AKAP95 and Yotiao were silenced using siRNA. Cell migration was analyzed by wound healing assay, xCELLigence, Incucyte. Prior to TGF-β1, dibutyryl-cAMP (dbcAMP), fenoterol, rolipram, cilostamide, forskolin were used to elevate intracellular cAMP. TGF-β1 induced morphological changes, decreased E-cadherin but increased collagen Ӏ and cell migration, a process reversed by PF-670462. TGF-β1 altered (mRNA, protein) expression of Ezrin, AKAP95 and Yotiao. St-Ht31 decreased E-cadherin (mRNA, protein), but counteracted TGF-β1-induced collagen Ӏ upregulation. Cigarette smoke (CS) increased TGF-β1 release, activated TGF signaling, augmented cell migration and reduced E-cadherin expression, a process blocked by TGF-β1 neutralizing antibody. Silencing of Ezrin, AKAP95 and Yotiao diminished TGF-β1-induced collagen Ӏ expression, as well as TGF-β1-induced cell migration. Fenoterol, rolipram, and cilostamide, in AKAP silenced cells pointed to distinct cAMP compartments. We conclude that Ezrin, AKAP95 and Yotiao promote TGF-β1-mediated EMT, linked to a TGF-β1 release by CS. AKAP members define the ability of fenoterol, rolipram and cilostamide to modulate the EMT process, and are potential relevant targets in the treatment of COPD.

More than a decade ago, a new mitochondrial Open Reading Frame (mtORF) was discovered in corals of the family Pocilloporidae, which turn out to be an effective barcode gene for these corals. However, its function remains unknown. Recently, this gene revealed the existence of a hybrid Stylophora lineage (RS_LinA) inhabiting in sympatry along the environmental gradient of the Red Sea (18.5°C to 33.9°C) with its parental species (RS_LinB). Furthermore, in RS_LinB, the mtORF uncovered phylogeographic patterns that were strongly correlated with environmental variations. This was similar to the patterns unraveled by hsp70, suggesting that mtORF too might be involved in thermal adaptation. Here we used computational approaches to characterize the mtORF and to identify its potential role. Results showed that this gene encodes a transmembrane protein (0.97<P< 1.00) involved in transport (0.80<P< 0.87), regulation of metabolic processes (0.70<P<0.85), and likely in the cell-surface receptor signaling pathway (0.56<P<0.80). Predicted protein functions differed among Stylophora lineages and interestingly, in RS_LinB only, the protein was intrinsically disordered and displayed domains involved in cellular complexes and stress response (0.0001< P <0.001). These characteristics, exclusive of an endemic lineage adapted to extreme environmental fluctuations, support a role of the mtORF in stress response, speciation and adaptation.

Recent developments in optical biosensors based on integrated photonic devices are reviewed with a special emphasis on silicon-on-insulator ring resonator. The review is mainly devoted to the following aspects: (1) Principles of sensing mechanism, (2) sensor design, (3) biofunctionalization procedures for specific molecule detection and (4) measurement set-ups and advances in chip-integration. The inherent challenges of implementing photonics-based biosensors to meet specific requirements of applications in medicine, food analysis, and environmental monitoring are discussed.

Control as a Service (CaaS) is an emerging paradigm where low-level control of a device is moved from a local controller to the Cloud, and provided to the device as an on-demand service. Among its many benefits, CaaS gives the device access to advanced control algorithms which may not be executable on a local controller due to computational limitations. As a step toward 3D printer CaaS, this paper demonstrates the control of a 3D printer by streaming low-level stepper motor commands (as opposed to high-level G-codes) directly from the Cloud to the printer. The printer is located at the University of Michigan, Ann Arbor, while its stepper motor commands are calculated using an advanced motion control algorithm running on Google Cloud computers in South Carolina and Australia. The stepper motor commands are sent over the Internet using the user datagram protocol (UDP) and buffered to mitigate transmission delays; checks are included to ensure accuracy and completeness of the transmitted data. All but one part printed using the cloud-based controller in both locations were hitch free (i.e., no pauses due to excessive transmission delays). Moreover, using the cloud-based controller, the parts printed up to 54% faster than using a standard local controller, without loss of accuracy.

There is no formal difference between particles and black holes. This formal similarity lies in the intersection of gravity and quantum theory; quantum gravity. Motivated by this similarity, `wave-black hole duality' is proposed, which requires having a proper energy-momentum tensor of spacetime itself. Such a tensor is then found as a consequence of `principle of minimum gravitational potential'; a principle that corrects the Schwarzschild metric and predicts extra periods in orbits of the planets. In search of the equation that governs changes of observables of spacetime, a novel Hamiltonian dynamics of a Pseudo-Riemannian manifold based on a vector Hamiltonian is adumbrated. The new Hamiltonian dynamics is then seen to be characterized by a new `tensor bracket' which enables one to finally find the analogue of Heisenberg equation for a `tensor observable' of spacetime.

As matrix representations of magic labelings of related hypergraphs, magic squares and their various variants have been applied to many domains. Among various subclasses, trimagic squares have been investigated for over a hundred years. The existence problem for trimagic squares with singly even orders and orders 16n has been solved completely. However, very little is known for the existence of trimagic squares with other even orders except for the only three examples and three families. We construct normal trimagic squares by using product constructions, row-square magic rectangles, and trimagic pairs of orthogonal diagonal Latin squares. We give a new product construction: For positive integers p, q, and r having the same parity other than 1, 2, 3, 6, if normal p × q and r × q row-square magic rectangles exist, then a normal trimagic square with order pqr exists. As its application, we construct normal trimagic squares of orders 8q^3 and 8pqr for all odd integers q not less than 7 and p,r ∈ {7, 11, 13, 17, 19, 23, 29, 31, 37}. Our construction can easily be extended to construct multimagic squares.

Organic light-emitting diodes (OLEDs) have garnered considerable attention in academic and industrial circles due to their potential applications in flat panel displays and solid-state lighting technologies, leveraging the advantages offered by organic electroactive derivatives over their inorganic counterparts. The thin and flexible design of OLEDs enables the development of innovative lighting solutions, facilitating the creation of customizable and contoured lighting panels. Among the diverse electroactive components employed in the molecular design of OLED materials, the benzophenone core has attracted much attention as fragment for synthesis of organic semiconductors. On the other hand, the benzophenone also functions as a classical phosphor with high intersystem crossing efficiency. This characteristic makes it as compelling candidate for effective reverse intersystem crossing, potentially leading to the development of thermally activated delayed fluorescent (TADF) emitters. These emitting materials witnessed a pronounced interest in recent years due to their incorporation in metal-free electroactive frameworks and the capability to convert triplet excitons into emissive singlet excitons through reverse intersystem crossing (RISC), consequently achieving exceptionally high external quantum efficiencies (EQEs). This review article comprehensively overviews the synthetic pathways, thermal characteristics, electrochemical behaviour and photo-physical properties of the derivatives based on benzophenone. Furthermore, we explore their applications in OLED devices, both as host materials and emitters, shedding light on the promising opportunities that benzophenone-based compounds present in advancing OLED technology.

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here we studied the effect of 12 weeks drug medication by daily oral feeding of clozapine and haloperidol on the perirenal fat tissue as part of VAT of male and female Sprague Dawley rats in the context of complex former investigations on brain, liver, and blood. Adipocyte area values were determined as well as triglycerides, non-esterified fatty acids (NEFAs), glucose, glycogen, lactate, malondialdehyde equivalents, ferric iron and protein levels of Perilipin-A, hormone-sensitive-lipase (HSL), hepcidin, glucose transporter-4 (Glut-4) and insulin receptor-ß (IR-ß). We found increased adipocyte mass in males with slightly higher adipocyte area values in both males and females under clozapine medication. Triglycerides, NEFAs, glucose and oxidative stress in the medicated groups were unchanged or slightly decreased. In contrast to controls and haloperidol medicated rats, perirenal adipocyte mass and serum leptin levels were not correlated under clozapine. Protein expressions of perilipin-A, Glut-4 and HSL were decreased under clozapine medication. IR-ß expression changed sex-specifically in the clozapine medicated groups associated with higher hepcidin levels in the perirenal adipose tissue of clozapine-medicated females. Taken together, clozapine and haloperidol have a smaller effect than expected on perirenal adipose tissue. The perirenal adipose tissue shows only weak changes in lipid and glucose metabolism. The main changes can be seen in the proteins examined and probably in their effect on liver metabolism.

The effects of simulated acid rain (SAR) on the photosynthetic performance of subtropical coniferous species have not been thoroughly investigated. In this study, we treated two coniferous species, Pinus massoniana (PM) and Cunninghamia lanceolata (CL), with SAR and then analyzed photosynthetic activities via the simultaneous measurement of prompt fluorescence(PF), delayed fluorescence(DF), and modulated reflection at 820 nm(MR820). Following the low-pH SAR treatment, the I–P phase of the OJIP curves of PM and CL decreased significantly and then the K-band and L-band were detectable. The delayed fluorescence for both PM and CL decreased as the pH of the SAR solution decreased, with a more significant decrease in the I1 peak than in the I2 peak. According to the MR820 curve, the exposure to SAR stress inhibited the rapid decrease and slow increase in the MR820 transients of PM and CL. The gradients of the decreasing and increasing phases were lower for CL than for PM at pH 2.5. In addition, SAR decreased the light energy captured per unit area (ABS/CSm) and the quantum yield of electron transfer per unit area (ETO/CSm), but it increased the accumulation of QA−, thereby decreasing primary photochemical efficiency (TRO/CSm, φPO). These changes in photosystem II (PSII) resulted in a decrease in the maximum quantum yield of PSII (Fv/Fm) and the performance index (PIABS). Moreover, PSII was protected from thylakoid membrane photodamages through the increase in heat dissipation per unit area (DIO/CSm) in response to SAR. The increase in δRO as the pH of the SAR solution decreased was observed for PM, but not for CL. Considered together, the study findings suggest that SAR treatments can decrease chlorophyll contents and damage the OEC in PM and CL, which obstructs the transfer of electrons on the donor and acceptor sides of PSII. However, PM is better able to withstand SAR stress than CL, likely because of the activation of a protective mechanism (reflected by the change in δRO). Therefore, in coniferous forest areas severely affected by acid rain, CL may need to be protected more than PM.

Bisphenol is a chemical substance widely used in plastic products and food containers. In this study, we observed a relationship between DNA methylation and atopic dermatitis (AD) in the peripheral blood mononuclear cells (PBMCs) of pregnant women exposed to bisphenol A (BPA) and its alternatives, bisphenol S (BPS) and bisphenol F (BPF). DNA methylation is an epigenetic mechanism that regulates gene expression, which can be altered by environmental factors, and affects the onset and progression of diseases. We found that genes belonging to the JAK-STAT and PI3K-AKT signaling pathways were hypomethylated in the blood of pregnant women exposed to bisphenols. These genes play important roles in skin barrier function and immune responses, and may influence AD. Therefore, we suggest that not only BPA but also BPS and BPF, which are used as alternatives, can have a negative impact on AD through epigenetic mechanisms.

The pharmacokinetic profile of fat-soluble vitamins A, E, K1, and D3 co-administered with liquid paraffin or water in an experimental rat model was investigated. Animals received a solution of the four vitamins orally through a probe, followed 10 minutes later by the administration of either the liquid paraffin product dissolved in water (Emuliquen Simple®) or water (control). Vitamin formulations were 20, 50, 0.30 and 0.10 mg/kg for vitamins A, E, K1, and D3, respectively. Blood samples were collected before dosing and at 0.17, 1, 2, 4, 8, and 24 hours post-dosing. Vitamin concentrations were quantified by liquid chromatography coupled with mass spectrometry. No relevant differences in the absorption of vitamins in terms of AUC0-last (area under the curve up to the last measurable concentration) or Cmax in the absence or presence of co-administration of the liquid paraffin product were observed. The difference of these parameters between the treatment groups for all vitamins was in the range of bioequivalence (≤ 20%). The liquid paraffin-based laxative product did not interfere with the absorption of vitamins A, E, K1, and D3 that are ingested in the diet, which is clinically relevant due to the high prevalence of functional constipation in children and adults.

The aims of the review were to elucidate the spatial variation in sea ice algae primary production rates and biomasses (Chl a) in the Canadian Arctic – Greenland region, characterized by comparable physical settings. A database was compiled from 30 studies of sea ice algae primary production rates, biomasses (Chl a), snow and ice thicknesses, ice types, nutrient (Si(OH)4, PO4, (NO3+NO2), and (NH4) concentrations in ice and below ice from the region. Production rates were significantly high (463 mg C m-2 d-1) in Resolute Bay and in Northern Baffin Bay (317 mg C m-2 d-1) both in Canadian Arctic, as compared to a rate of 0.2 mg C m-2 d-1 in northeast Greenland. The biomasses reached 340 mg Chl a m-2 in Resolute Bay in comparison to a 0.02 mg Chl a m-2 in southwest Greenland. Primary production at other Canadian and Greenland sites were comparable but sea ice Chl a was higher (15.0 ± 13.4 mg Chl a m-2) at Canadian sites as compared to Greenland (0.8 ± 0.5 mg Chl a m-2). Resolute and Northern Baffin Bays production rates were significantly higher when compared to other Arctic Ocean sites outside the studied region. The review concludes that high production rates and biomasses in Resolute and Northern Baffin Bay’s were related to inflow and mixing of nutrient rich waters of Pacific origin. A conceptual model with drivers and inhibitors of sea ice algae primary production is projected, and the database compiles a dataset of published data for further studies.

Hypercholesterolemia is a major risk for the development of cardiovascular diseases (CVDs), the main cause of mortality worldwide, and it is characterized by high levels of circulating cholesterol. The drugs currently available for hypercholesterolemia control have several side effects, so it is necessary to develop new effective and safer therapies. Seaweeds serve as sources of several bio-active compounds with claimed beneficial effects. Eisenia bicyclis (Aramé) and Porphyra tenera (Nori) are edible seaweeds which were previously recognized as rich in bioactive compounds. In the present study, we aim to evaluate the anti-hypercholesterolemia effect of these two seaweeds ex-tracts and their health potential. Both extracts, but more efficiently Aramé extract demonstrated to have liver 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitory activity and to reduce approximately 30 % cholesterol permeation through human Caco-2 cells simulating the intestinal lining, targets for hypercholesterolemia treatments. An untargeted metabolomic assay on human intestinal Caco-2 and liver Hep-G2 cells lines exposed to Aramé and Nori extracts revealed changes in the cell’s metabolism as indicators of the extract’s health beneficial effects. The metabolic pathways affected by exposure to both extracts were associated to lipid metabolism, such as phospholipids, and fatty acid metabolism, pathways of amino acid, cofactors and vitamins and cellular respiration metabolism. More profound for Aramé treated cells, but also seen for Nori ex-posed cells, the metabolites modifications were associated with the protection against CVDs and other diseases and, to the improvement of cells oxidative stress tolerance. The results obtained for the anti-hypercholesterolemia properties, in addition to the revelation of the positive impact on cells metabolism, are an important contribution for further evaluation of these seaweeds extracts as functional foods or for CVDs prevention.

Considering rotation-induced centrifugal stiffening, spin softening, and Coriolis effects, the three-dimensional finite element model of a rotating blade with a dovetail structure is built through the contact dynamics theory. The fixed-interface component mode synthesis method is then adopted to reduce the model for high computational efficiency and adequate model accuracy. The effects of the number of normal modes on the first-six-order modal characteristics of the model varying with the rotating speed are studied between the reduced and full models. Next, the influence of rotating speed and friction factor on the nonlinear dynamic characteristics of the model under the action of aerodynamic force are elaborately discussed. The results show that: (1) tenon-mortise joint contact-induced nonlinearity under low rotating speeds results in the intermittent interference of contact surfaces and frequency multiplications of aerodynamic excitation frequency in the spectrum cascades, while that under high rotating speeds causes the continuous interface contact and asynchronous excitation at the tenon-mortise joint; (2) the increase of friction factor results in a lower contact pressure distribution and the right shift of the resonance peak (i.e., hard nonlinearity).

A brief overview of the past and present trajectories made by the A(H5N1) avian influenza virus among domestic birds, avian and mammalian wildlife species and humans is presented here, thereby taking into special account the 2.3.4.4b clade of the virus recently emerged in several geographic areas of the globe.

Background: Immunoglobulin A nephropathy (IgAN) is a complex autoimmune disease, and the exact pathogenesis remains to be elucidated. Methods: We conducted summary data-based Mendelian randomization (SMR) analysis and performed functional mapping and annotation using FUMA to explore genetic loci that are po-tentially involved in the pathogenies of IgAN. Both analyses used summarized data of a recent genome-wide association study (GWAS) on IgANs, which included 477,784 Europeans (15,587 cases and 462,197 controls) and 175,359 East Asians (71 cases and 175,288 controls). We performed separate SMR analysis using CAGE and GTEx eQTL data. Results: Using the CAGE eQTL data, our SMR analysis identified 32 probes tagging 25 unique genes that were pleiotropically/potentially causally associated with IgAN, with the top three probes being ILMN_2150787 (tagging HLA-C, PSMR=2.10×10-18), ILMN_1682717 (tagging IER3, PSMR=1.07×10-16) and ILMN_1661439 (tagging FLOT1, PSMR=1.16×10-14). Using GTEx eQTL data, our SMR analysis identified 24 probes tagging 24 unique genes, with the top three probes being ENSG00000271581.1 (tagging XXbac-BPG248L24.12, PSMR=1.44×10-10), ENSG00000186470.9 (tagging BTN3A2, PSMR=2.28×10-10), and ENSG00000224389.4 (tagging C4B, PSMR=1.23×10-9). FUMA analysis identified 3 independent, significant and lead SNPs, 2 genomic risk loci and 39 genes. Conclusion: We identified many genetic variants/loci that are potentially involved in the patho-genesis of IgAN.

This paper reviews the low-resilience problem in many cities, poor designs of cities to cope with disasters, and the need for tolerance of urban constructions. It explores answers concerning the question of how shall we build cities resiliently? The method of this applied research is a multiphase process that considers all physical and socioeconomic elements of a city. It introduces six indicator groups of urban management (M), economy (E), built environments (U), Infrastructures (I), natural environments (N), and health protection (H). The groups include 55 indicators as variables in the mathematical calculations in this paper. This paper builds a mathematical model to maximize the profitability of resilient buildings by optimizing investments in the required projects. The projects will upgrade the firmness and tolerance of cities against nature-based and human-made dangers and risks. There is a linear programming in 55 variables to select optimal solutions from fifty-five factorial alternatives. Then, the programming will develop into non-linear programming. The unique innovation of this paper is its linear programming interpretation by non-linear to give optimal solutions for the problem. Applying the Lagrange function in the Kuhn-Tucker conditions proves the accuracy of the hypothesis that post-COVID urbanization requires maximum resilience. Only in this way, the urban economies will be free of risks. Outcomes in this paper will assist in the pre-planning, design, and building of built environments everywhere resilient and sustainable.

Vitamins are essential compounds obtained through diet that are necessary for normal devel-opment and function in an organism. One of the most important vitamins for human physiology is Vitamin A, a group of retinoid compounds and carotenoids which generally function as a mediator for cell growth, differentiation, immunity, and embryonic development, as well as serving as a key component in the phototransduction cycle in vertebrate retina. For humans, vitamin A is obtained through the diet, where provitamin A carotenoids like β-carotene, or preformed vitamin A such as retinyl esters are absorbed into the body via the small intestine and converted into all-trans retinol within the intestinal enterocytes. Specifically, once absorbed, carotenoids are cleaved by carote-noid cleavage oxygenases (CCOs), such as BCO1, to produce all-trans retinal that subsequently gets converted into all-trans retinol. CRBP2 bound retinol is then converted into retinyl esters (REs) by the enzyme lecithin retinol acyltransferase (LRAT) in the endoplasmic reticulum, which is then packaged into chylomicrons and sent into the bloodstream for storage in hepatic stellate cells in the liver or for functional use in peripheral tissues such as the retina. All-trans retinol also travels through the bloodstream bound to retinol binding protein 4 (RBP4), where it enters cells with the assistance of the transmembrane transporters, stimulated by retinoic acid 6 (STRA6) in peripheral tissues or retinol binding protein receptor 2 (RBPR2) in systemic tissues (e.g. in the retina and the liver respectively). Much is known about the intake, metabolism, storage, and function of vitamin A compounds, especially with regard to its impact on eye development and visual function in the retinoid cycle. However, there is much to learn about the role of vitamin A as a transcription factor in development and cell growth, as well as how peripheral cells signal hepatocytes to secrete all-trans retinol into the blood for peripheral cell use. This article aims to review literature re-garding the major known pathways of vitamin A intake from dietary sources into hepatocytes, vitamin A excretion by hepatocytes, as well as vitamin A usage within the retinoid cycle in the RPE and retina to provide insight on future directions of novel membrane transporters for vitamin A in retinal cell physiology and visual function.

The investigation of the electromagnetic properties of biological particles in microfluidic platforms may enable wireless monitoring and interaction with functional activity of microorganisms. Of high relevance is the membrane potential as it is one of the most important parameters of living cells. In particular, the complex mechanisms of the cell’s membrane potential are comparable to the dynamics of bacteria membranes, providing a simplified platform for advancing the current techniques and knowledge of general bio-particle dynamics. In this work, we provide a theoretical analysis and experimental results on the microwave detection of bacteria on a microfluidic-based framework for sensing the membrane potential of bacteria. The results enable to further advance the state-of-the-art of electromagnetic bacteria sensing and microfluidic control, and their implication for measuring and interacting with the cell and its membrane potentials, which is of great importance for developing new biotechnological engineered systems and solutions.

In this paper a full state feedback control of a double inverted pendulum on a cart (DIPC) are designed and compared. Modeling is based on Euler-Lagrange equations derived by specifying a Lagrangian, difference between kinetic and potential energy of the DIPC system. A full state feedback control with H infinity and H 2 is addressed. Two approaches are tested: open loop impulse response and a double inverted pendulum on a cart with full state feedback H infinity and H 2 controllers. Simulations reveal superior performance of the double inverted pendulum on a cart with full state feedback H infinity controller.

A methodology based on the concepts that arise from Density Functional Theory named Conceptual Density Functional Theory (CDFT) was chosen for the calculation of some global and local reactivity descriptors of the Discodermins A-H family of marine peptides through the consideration of the KID (Koopmans in DFT) technique that was successfully used in previous studies of this kind of molecular systems. The determination of active sites of the studied molecules for different kind of reactivities was achieved by resorting to some CDFT-based descriptors like the Fukui functions as well as the Parr functions derived from Molecular Electron Density Theory (MEDT). A few properties identified with their ability to behave as a drug and the bioactivity of the peptides considered in this examination were acquired by depending on a homology model by studying the correlation with the known bioactivity of related molecules in their interaction with various biological receptors. With the further object of analyzing their bioactivity some parameters of usefulness for future QSAR studies, their predicted biological targets and the the ADME (Absorption, Distribution, Metabolism, and Excretion) parameters related to the Discodermins A-H pharmacokinetics are also reported.

The aim of this study is to evaluate three different strategies to improve classification accuracy in a highly fragmented semiarid area. i) Using different classification algorithms: Maximum Likelihood, Random Forest, Support Vector Machines and Sequential Maximum a Posteriori, with parameter optimisation in the second and third cases; ii) using different feature sets: spectral features, spectral and textural features, and spectral, textural and terrain features; and iii) using different image-sets: winter, spring, summer, autumn, winter+summer, winter+ spring+summer; and a four seasons combination. A 3-way ANOVA is used to discern which of these approaches and their interactions significantly increases accuracy. Tukey-Kramer contrast using a heteroscedasticity-consistent estimation of the kappa covariances matrix was used to check for significant differences in accuracy. The experiment was carried out with Landsat TM, ETM, and OLI images corresponding to the period 2000-2015. A combination of four images was the best way to improve accuracy. Maximum Likelihood, Random Forest and Support Vector Machines do not significantly increase accuracy when textural information is added, but do so when terrain features are taken into account. On the other hand, Sequential Maximum a Posteriori increases accuracy when textural features are used, but reduces accuracy substantially when terrain features are included. Random Forest using the three feature subsets and Sequential Maximum a Posteriori with spectral and textural features had the largest kappa values, around 0.9.

In order to meet the military requirements of the fuze, such as precision strike, efficient mutilates ability and low collateral damages, the microminiaturization is an inevitable trend of secure system. Based on the silicon-based MEMS S&A device designed by our term, the design principles of each module and fabrication process are introduced. The average fracture strength and Young's modulus of the silicon are 726 MPa and 175 GPa from the tensile test, respectively. From Hopkinson impact experiment, we can get the threshold-value judging mechanism being safety under the impact overload of 20526 g, and this value is much more than the standard of the drop overload 12000g; the arming value under the centrifugal overload obtained from theory, simulation and experiment is at the range of 28200 g and 32000 g, it shows that the threshold-value judging mechanism can be arming compared with the value 35951g of design principle. Therefore, the threshold-value judging mechanism can meet the design requirements of overload. Furthermore, the relationship of fracture threshold-values obtained by different theories is found out through parametric design method, as shown in Figure 14, it provides the theory evidence to the follow parametric design.

We present a new interpretation of the Higgs field as a composite particle made up of a positive, with, a negative mass Planck particle. According to the Winterberg hypothesis, space, i.e., the vacuum, consists of both positive and negative physical massive particles, which he called planckions, interacting through strong superfluid forces. In our composite model for the Higgs boson, there is an intrinsic length scale associated with the vacuum, different from the one introduced by Winterberg, where, when the vacuum is in a perfectly balanced state, the number density of positive Planck particles equals the number density of negative Planck particles. Due to the mass compensating effect, the vacuum thus appears massless, charge-less, without pressure, energy density, or entropy. However, a situation can arise where there is an effective mass density imbalance due to the two species of Planck particle not matching in terms of populations, within their respective excited energy states. This does not require the physical addition or removal of either positive or negative Planck particles, within a given region of space, as originally thought. Ordinary matter, dark matter, and dark energy can thus be given a new interpretation as residual vacuum energies within the context of a greater vacuum, where the populations of the positive and negative energy states exactly balance. In the present epoch, it is estimated that the dark energy number density imbalance amounts to, , per cubic meter, when cosmic distance scales in excess of, , are considered. Compared to a strictly balanced vacuum, where we estimate that the positive, and the negative Planck number density, is of the order, particles per cubic meter, the above is a very small perturbation. This slight imbalance, we argue, would dramatically alleviate, if not altogether eliminate, the long standing cosmological constant problem.

The pervasive presence of atmospheric pollution, particularly polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz(a)anthracene, instigates aberrant cellular and tissue conditions, precipitating oxidative damage and inflammatory cascades conducive to the onset of cancer, notably mammary cancer. Given the hepatic metabolism of 7,12-dimethylbenz(a)anthracene, the imperative of employing natural antioxidants becomes apparent. In this study, we delve into the antioxidant and hepato-protective properties of Pistacia lentiscus against 7,12-dimethylbenz(a)anthracene-induced toxicity, alongside exploring its potential anticancer attributes. Our investigations unveil Pistacia lentiscus's anti-proliferative efficacy against human breast cancer cell lines. Notably, 7,12-dimethylbenz(a)anthracene-intoxication escalates body weight, disrupts lipid profiles, and incites serum oxidative damage. Concurrently, hepatic and renal oxidative stress ensue, accompanied by heightened antioxidant enzyme activity in the 7,12-dimethylbenz(a)anthracene-exposed-group compared to controls (p&lt;0.05). Nonetheless, Pistacia lentiscus co-administration rectifies biochemical imbalances, significantly attenuates oxidative stress aberrations, and augments antioxidant enzyme responses (p&lt;0.05). Importantly, histological analysis evinces Pistacia lentiscus's shielding effect against 7,12-dimethylbenz(a)anthracene induced hepatocyte injury and steatosis. Our findings underscore Pistacia lentiscus's robust anti-proliferative, antioxidant, and hepato-protective capacities, mitigating metabolic disturbances, oxidative stress propagation in liver and kidney functions, and potential histological alterations, thereby impeding 7,12-dimethylbenz(a)anthracene-induced mammary cancer initiation. We posit that Pistacia lentiscus may serve as a prophylactic agent against breast cancer instigated by this carcinogen.

Objective To analyze the influence of HIV in penitentiary institutions through an exhaustive lexiconmetric and sentiment analysis of news in the Spanish written press related to HIV and prison. Material an method observational, descriptive, and retrospective design based on news published in Spanish newspapers from 1981 to 2020, linking HIV infection with penitentiary institutions. Natural language processing and lexiconmetry techniques were used, using the Python programming language and ATLAS Ti v.9 software. Result: 318 articles were analyzed, with 10,502 distinct words. The sentiment of news was evaluated in three different periods: the discovery of HIV, and the periods before and after the existence of antiretroviral treatments. N-gram analysis and word cloud creation were carried out for each period. In the initial phase, ignorance predominated, and prominent terms such as "homosexual," "isolate," "test," "trial," or "confirm" were observed. In the period before antiretroviral treatments, news reflected negative feelings and criticism of prison policy, with keywords such as "give birth," "drug," "carrier," or "disease." With the arrival of treatments, news showed an evolution towards a more positive tone, highlighting terms such as "treatment," "release," or "syringes”.Conclusions: The presence of HIV in Spanish prisons has experienced a significant evolution from an alarming situation to an improvement in the care of inmates, driven by institutional adaptation and advances in antiretroviral treatments.

A reduction of melatonin function contributes to the acceleration of Alzheimer's disease (AD), and understanding molecular processes of melatonin-related signaling is critical for intervention of AD progression. Recently, we synthesized and tested a series of melatonin derivates with donepezil fragments in silico and in vitro. In this study, one of the most potent compounds, 3c, was studied in an in vivo rat model of pinealectomy (pin) and subsequent icvAβ1-42 infusion. Melatonin was used as a referent drug. The treatment with melatonin and 3c (10 mg/kg, i.p. for 14 days) exerted a beneficial effect on memory decline and concomitant rise of Aβ1-42 and pTAU in the hippocampus in the pin + icvAβ1-42 rats. Melatonin supplementation facilitated the non-amyloidogenic signaling via a non-receptor (histone deacetylase sirtuin 1, SIRT1) and receptor-related signaling (MT/ERK/CREB). The hybrid 3c derivate up-regulated the MT1A and MT2B receptors, pERK and pCREB. Our findings strongly support the hypothesis that melatonin-related derivates may become a promising drug candidate in AD therapy.

Leishmaniasis remains a significant global health concern, with current treatments relying on outdated drugs associated with high toxicity, lengthy administration, elevated costs, and drug resistance. Consequently, the urgent need for safer and more effective therapeutic options in leishmaniasis treatment persists. Previous research has highlighted selenium compounds as promising candidates for innovative leishmaniasis therapy. In light of this, a library of 10 selenium-containing diverse compounds was designed and evaluated in this study. The compounds were subjected to screening against L. amazonensis promastigotes, and their cytotoxicity was assessed in NIH/3T3 cells. Among the tested compounds, MRK-106 and MRK-108 displayed the highest potency against L. amazonensis promastigotes while demonstrating reduced cytotoxicity. Notably, MRK-106 and MRK-108 exhibited IC50 values of 3.97 µM, 4.23 µM, respectively, and most of the tested compounds showed low cytotoxicity in NIH/3T3 cells (CC50 &gt; 200 µM). Although these results are promising, additional investigations focusing on intracellular amastigotes are required to determine the antileishmanial activity of the compounds. In conclusion, the identified selenium-containing compounds hold considerable potential as antileishmanial drug candidates and warrant further exploration in subsequent studies. These findings represent a significant step towards the development of safer and more effective therapies for leishmaniasis, addressing the pressing need for novel and improved treatments.

Organic light-emitting diodes (OLEDs) have ushered in a technological revolution with their remarkable impact on diverse sectors of our daily lives. These versatile devices known for their outstanding display and lighting capabilities, have become indispensable components in various industries including smartphones, tablets, televisions, and automotive applications. This paper delves into the development of a group of twisted donor-acceptor-donor (D-A-D) derivatives incorporating bicarbazole and benzophenone structures for potential use as blue emitters in OLEDs. The synthesized compounds, namely DB14, DB23 and DB29, were designed with various alkyl side chains to enhance their film forming properties as for blue emitters. Characterization and evaluation of these derivatives included photophysical, electrochemical, thermal, and electroluminescent analysis. Some of the OLED devices incorporating these emitters demonstrated promising performance with maximum current efficiency (CEmax) of 2.6 cd/A and external quantum efficiency (EQEmax) of 5.3%. Notably, the DB23 emitter exhibited the highest EQE among all devices. The study also emphasizes the influence of host-guest energy transfer, optimal doping concentrations, and molecular structures on device performance. This research not only contributes to the understanding of advanced OLED materials but also provides insights into designing efficient blue emitters for future display and lighting applications, thereby advancing the field of organic electronics.

The approach based on molecular modeling was developed to study dNTP derivatives characterized by new polymerase-specific properties. For this purpose, the relative efficiency of PCR amplification with modified dUTPs was studied using Taq, Tth, Pfu, Vent, Deep Vent, Vent (exo-), and Deep Vent (exo-) DNA polymerases. The efficiency of PCR amplification with modified dUTPs was compared with the results of molecular modeling using the known 3D structures of KlenTaq polymerase–DNA–dNTP complexes. The dUTPs were C5-modified with bulky functional groups (the Cy5 dye analogs) or lighter aromatic groups. Comparing the experimental data and the results of molecular modeling revealed the decrease of PCR efficiency in the presence of modified dUTPs with an increase in the number of non-covalent bonds between the substituents and the DNA polymerase (about 15% decrease per one extra non-covalent bond). Generalization of the revealed patterns to all the studied polymerases of the A and B families is discussed herein. The number of non-covalent bonds between the substituents and polymerase amino acid residues is proposed to be a potentially variable parameter for regulating enzyme activity.

Pregnancy associated plasma protein-A (PAPP-A) plays an integral role in breast cancer (BC), especially triple negative breast cancer (TNBC). This subtype accounts for the most aggressive BC, possesses high tumor heterogeneity, is least responsive to standard treatments and has the poorest clinical outcomes. There is a critical need to address the lack of effective targeted therapeutic options available. PAPP-A is a protein that is highly elevated during pregnancy. Frequently, higher PAPP-A expression is detected in tumors than in healthy tissues. The increase in expression coincides with increased rates of aggressive cancers. In BC, PAPP-A has been demonstrated to play a role in tumor initiation, progression, metastasis including epithelial-mesenchymal transition (EMT), as well as acting as a biomarker for predicting patient outcomes. In this review, we present the role of PAPP-A, with specific focus on TNBC. The structure and function of PAPP-A, belonging to the pappalysin subfamily, and its proteolytic activity are assessed. We highlight the link of BC and PAPP-A with respect to the IGFBP/IGF axis, EMT, the window of susceptibility and the impact of pregnancy. Importantly, the relevance of PAPP-A as a TNBC clinical marker is reviewed and its influence on immune-related pathways are explored. The relationship and mechanisms involving PAPP-A reveal the potential for more treatment options that can lead to successful immunotherapeutic targets and the ability to assist with better predicting clinical outcomes in TNBC.

We employ hierarchy of models (HoM) with 2, 3 and 4 parameters to reanalyze the nucleation kinetics in the electrodeposition as quantified by n(t) - “the number of nuclei vs. time” data obtained at different overvoltages from precise experiments on electrodeposition of Hg on two different types of Pt-cathodes by Ivan V. Markov and Evgenia Stoycheva [1]. The obtained two scales, nmax and , are used to rescale the original data mapping it on a master curve in coordinates . Our main result is obtained by studying further the dependence of these two scales on the overvoltage (analogue of supersaturation). Surprisingly, for one of the two cathode types - the “hemispherical single-crystal electrode” (as defined by the authors), there is discontinuity in the “ vs. overvoltage” dependence – an almost horizontal jump from 85 to 86 mV accompanied by a change in the slope of the dependence - it is ~ -1 and ~ -0.5 after. For the other cathode - “plane structureless platinum electrode”,  decreases smoothly. Combined, these two behaviors point at the so called “cusp catastrophe”. We compare our findings with published results on protein nucleation.

This paper presents an innovative testing framework, testFAILS, designed for the rigorous evaluation of AI Linguistic Systems, with a particular emphasis on various iterations of ChatGPT. Leveraging orthogonal array coverage, this framework provides a robust mechanism for assessing AI systems, addressing the critical question, "How should we evaluate AI?" While the Turing test has traditionally been the benchmark for AI evaluation, we argue that current publicly available chatbots, despite their rapid advancements, have yet to meet this standard. However, the pace of progress suggests that achieving Turing test-level performance may be imminent. In the interim, the need for effective AI evaluation and testing methodologies remains paramount. Our research, which is ongoing, has already validated several versions of ChatGPT, and we are currently conducting comprehensive testing on the latest models, including ChatGPT-4, Bard and Bing Bot, and the LLaMA model. The testFAILS framework is designed to be adaptable, ready to evaluate new bot versions as they are released. Additionally, we have tested available chatbot APIs and developed our own application, AIDoctor, utilizing the ChatGPT-4 model and Microsoft Azure AI technologies

Gravity-aided inertial navigation system (GAINS) is an important development in autonomous underwater vehicle (AUV) navigation. An effective path planning algorithm plays an important role in the performance of navigation in long-term underwater missions. By combining the gravity information obtained at each position with the error information from the INS, the posterior Cram\'er-Rao bound (PCRB) of GAINS is derived in this paper. The PCRB is the estimated lower bound of position variance for navigation along the planned trajectory. And the sum of PCRB is used as the minimum cost from the initial state to the current state in the state space, and the position error prediction variance of inertial navigation system (INS) is used as the minimum estimated cost of the path from the current state to the goal state in the A* algorithm. Thus, a path planning method with optimal navigation accuracy is proposed. According to simulation results, traveling along the path planed by the proposed method can rapidly improve the positioning accuracy while consuming just slightly more distance. Even when measuring noise changes, the planned path can still maintain optimal positioning accuracy, and high positioning accuracy is possible for any trajectory located within a certain range of the planned path.

Abstract Eye health is crucial and the onset of diseases can reduce vision and affect the quality of life of patients. The main causes of progressive and irreversible vision loss include various pathologies such as cataracts, ocular atrophy, corneal opacity, age-related macular degeneration, uncorrected refractive error, posterior capsular opacification, uveitis, glaucoma, diabetic retinopathy, retinal detachment, undetermined disease and other disorders involving oxidative stress and inflammation. The eyes are constantly exposed to the external environment and, for this reason, must be protected from damage from the outside. Many drugs, including cortisonics and antinflammatory drugs have widely been used to counteract eye disorders. However, recent advances have been obtained via supplementation of patients with natural antioxidants and nutraceuticals. In particular, evidence has been accumulated that polyphenols (mostly deriving from Citrus Bergamia) represent a reliable source of antioxidants able to counteract oxidative stress accompanying early stages of eye diseases. Luteolin, in particular, has been found to protect foto-receptors thereby improving vision in many disease states. Moreover, a consistent anti-inflammatory response was found to occur when curcumin is used alone or in combination with other nutraceuticals. On the other hand, CoQ10 has been demonstrated to produce consistent effect in reducing ocular pressure thereby leding to protection in patients undergoing glaucoma. Finally, both grape seed extract rich in anthocyanosides and polynsatured fatty acids (PUFAs) seem to contribute in the prevention of retinal disorders. Thus, combination of nutraceuticals and anti-oxidants may represent the right solution for a multiaction activity in eye protection to be associated to current drug therapies, and this will be of potential interest in early stages of eye disorders.

he paper presents an innovative method for tourist route planning inside a destination. The necessity of reorganizing the tourist routes within a destination comes as an immediate response to the Covid-19 crisis. The implementation of the method inside tourist destinations can bring an important advantage in transforming a destination into a safer destination in times of Covid-19 and post-Covid-19. The existing trend of shortening the tourist stay length has been accelerated while the epidemic became a pandemic. Moreover, the wariness for future pandemics has brought into spotlight the issue of overcrowded attractions inside a destination at certain moments. The method presented in this paper proposes a backtracking algorithm, more precisely an adaptation of the travelling salesman problem. The method presented is aimed to facilitate the navigation inside a destination and to revive certain less-visited sightseeing spots inside a destination while facilitating conformation with the social distancing measures imposed for Covid-19 control.

While the angiotensin converting enzyme 2 (ACE2) protein is defined as the primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, the viral serine molecule might be mobilized by the host's transmembrane protease serine subtype 2 (TMPRSS2) enzyme from the viral spike (S) protein and hijack the host’s N-acetyl-D-galactosamine (GalNAc) metabolism. The resulting hybrid, serologically A-like/Tn (T-nouvelle) structure potentially acts as a host–pathogen functional molecular bridge. In humans, this intermediate structure will hypothetically be replaced by ABO(H) blood group-specific, mucin-type structures, in the case of infection hybrid epitopes, implicating the phenotypically glycosidic accommodation of plasma proteins. The virus may, by mimicking the synthetic pathways of the ABO(H) blood groups, bind to the cell surfaces of the blood group O(H) by formation of a hybrid H-type antigen as the potential precursor of hybrid non-O blood groups, which does not affect the highly anti-glycan aggressive anti-A and anti-B isoagglutinin activities, exerted by the germline-encoded nonimmune immunoglobulin M (IgM). In the non-O blood groups, which have developed from the H-type antigen, these IgM activities are downregulated by phenotypic glycosylation, while adaptive immunoglobulins might arise in response to the hybrid A and B blood group structures, bonds between autologous carbohydrates and foreign peptides, suggesting the exertion of autoreactivity. The non-O blood groups thus become a preferred target for the virus, whereas blood group O(H) individuals, lacking the A/B phenotype-determining enzymes and binding the virus alone by hybrid H-type antigen formation, have the least molecular contact with the virus and maintain the critical anti-A and anti-B isoagglutinin activities, exerted by the ancestral IgM, which is considered the humoral spearhead of innate immunity.

Is immediate action at a distance, like gravitational attraction, imaginable using the contrary concept of close up, tactile, events? Tactile events, defined with the term ‘tap-tapping’ as a blind man does, described in a two-way spiritual interaction theory, are implemented in physics to understand gravitation from this respect. The quantum mechanical wave function reduction during measurements receives a new approach. Formulated is a new proof for Einstein’s Equivalence Principle, extending it beyond locality, and a sketch of how tactile interaction could explain dark energy and an accelerated expansion of the universe. Dark energy and dark matter are examples starting from which to discuss properties of matter and space and gravitation as immediate tactile action rather than mediated action such as electromagnetism.

Droplet-based microfluidics has revolutionized numerous fields such as biomedical research, pharmaceuticals, drug discovery, food engineering, flow chemistry, and cosmetics. This paper presents a comprehensive study focusing on the detection and characterization of droplets with volumes in the nanoliter range. Leveraging the precise control of minute liquid volumes, we introduced a novel spectroscopic On-Chip microsensor equipped with integrated microfluidic channels for droplet generation, characterization, and sensing, simultaneously. The microsensor, designed with Interdigitated-Ring-Shaped Electrodes (IRSE) and seamlessly integrated with microfluidic channels, offers enhanced capacitance and impedance signal amplitudes, reproducibility, and reliability in droplet analysis. We were able to make analyses of droplets length in the range 1.0-6.0 mm, velocity 0.66-2.51 mm/s, droplet volume 1.07nL-113.46nL. Experimental results demonstrated that the microsensor's has a great performance in terms of droplet size, velocity, and length, with a significant signal amplitude of capacitance and impedance, and real-time detection capabilities, thereby highlighting its potential for facilitating microcapsule reactions and enabling on-site real-time detection for chemical and biosensor analyses on-chip.

Noninvasive brain stimulation technique can be used for modulation of motor behaviors such as reaction time (RT). The main aim of this study was to investigate whether RT during a sequential visual isometric pinch task (SVIPT) can be affected by anodal transcranial direct current stimulation (a-tDCS) over three different stimulation sites such as dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1) or posterior parietal cortex (PPC). We also aimed to assess if stimulation of these cortical sites affect the transfer of learning during SVIPT. A total of 48 right-handed healthy participants were randomly assigned to one of the four a-tDCS groups: 1) left M1, 2) left DLPFC, 3) left PPC and 4) sham. A-tDCS was applied concurrent with SVIPT in which the participants were precisely controlled their forces to reach seven different target forces from 10 to 40% of maximum voluntary contraction (MVC) presenting on a computer screen with right dominant hand. Four test blocks were randomly performed at baseline and 15 min after the intervention including sequence and random blocks with either hand. Our results showed significant differences between a-tDCS groups on ratio RT in the sequence blocks of both the right trained (P = .041) and left untrained hands (P = .023) for target forces of 15% and 30 % of MVC, respectively. In sequence blocks, M1 showed significant elongation in ratio RT for the target force of 15% and 30 % MVC compared to PPC and Sham groups in the right hand. In sequence blocks with left hand, this negative effect were found between M1-DLPFC and M1-Sham groups. In random blocks, no significant differences were found among four groups at each target forces for the left hand while there were significant differences for 15% (P =. 04) and 40% MVC (P =. 035) in the right hand. Our findings suggest that three different stimulation sites (DLPFC, M1 or PPC) were differentially affected by a single session of a-tDCS at some target forces during SVIPT. The effects of a-tDCS on ratio RT were transferred in the left untrained hand for sequence blocks but not random blocks. Further research is needed to understand fundamental aspects of these main areas of the brain on temporal processing in a precision control task such as SVIPT.

Heterotopic ossification (HO) is most dramatically manifested in the rare and severely debilitating disease, fibrodysplasia ossificans progressiva (FOP), in which heterotopic bone progressively accumulates in skeletal muscles and associated soft tissues. The great majority of FOP cases are caused by a single amino acid substitution in the type 1 bone morphogenetic protein (BMP) receptor ACVR1, a mutation that imparts responsiveness to activin A. Although it is well-established that biological sex is a critical variable in a range of physiological and disease processes, the impact of sex on HO in animal models of FOP has not been explored. We show that female FOP mice exhibit both significantly greater and more variable HO responses after muscle injury. Additionally, the incidence of spontaneous HO was significantly greater in female mice. This sex dimorphism is not dependent on gonadally-derived sex hormones, and reciprocal cell transplantations indicate that apparent differences in osteogenic activity are intrinsic to the sex of the transplanted cells. By circumventing the absolute requirement for activin A using an agonist of mutant ACVR1, we show that the female-specific response to muscle injury or BMP2 implantation is dependent on activin A. These data identify sex as a critical variable in basic and preclinical studies of FOP.

In this work, an evanescent Bragg grating sensor inscribed in a few-mode planar polymer waveguide was integrated in microchannel structures and characterized with various chemical applications. The planar waveguide and the microchannels consisted of epoxide-based polymers. The Bragg grating structure was post-processed using point-by-point direct inscription technology. By monitoring the central wavelength shift of the reflected Bragg signal, the sensor showed a temperature sensitivity of -47.75 pm/K. Moreover, the functionality of the evanescent field-based measurements is demonstrated with two application examples: refractive index sensing of different aqueous solutions and gas-phase hydrogen concentration detection. For the latter application, the sensor was additionally coated with a functional layer based on palladium nanoparticles. During the refractive index sensing measurement, the sensor achieved a sensitivity of 6.5 nm/RIU from air to 99.9% pure isopropyl alcohol. For the gas-phase hydrogen detection, the coated sensor achieved a reproducible concentration detection up to 4 vol% hydrogen. According to the reported experimental results, the integrated Bragg grating-based waveguide sensor demonstrates high potential for applications based on lab-on-a-chip concept.

We propose a phenomenological theory of spin behavior in a magnetic field, which explains from the point of view of classical physics the two-valued result of the Stern-Gerlach experiment. The behavior of the spin and intrinsic magnetic moment of an electron wave of an atom in an external magnetic field is considered. We show that in a weak magnetic field, the intrinsic magnetic moment of an electron wave is always oriented parallel to the magnetic field strength vector, while in a strong magnetic field, depending on the initial orientation of the intrinsic magnetic moment, two orientations are realized: either parallel or antiparallel to the magnetic field strength vector. Within the framework of classical electrodynamics, the calculation of the motion of an atomic beam in an inhomogeneous magnetic field is carried out, which reproduces the results of the Stern-Gerlach experiment.

Bacillus veleznesis RB.EK7 was recently found as a potent rhizobacterial strain for effective management of black pepper root-knot nematodes. This work aimed to produce, purify, and elucidate the chemical structures of antinematode compounds (ANCs). Concerning cost-effectiveness and environmental issues, this study used organic wastes for the bioproduction of ANCs. Among various substrates, shrimp shells powder was the most suitable carbon/nitrogen source to produce ANCs. The fermentation process for enhancement of antinematode activity was investigated. The targeting ANCs were purified from the fermented culture broth, and their structures were elucidated. Two active compounds were thymine (1) and hexahydropyrrolo [1,2-a]pyrazine-1,4-dione (2). Notably, for the first time, these purified compounds showed potential and moderate anti- J2 nematodes and anti-eggs hatching, respectively. The docking study results indicated that the potent antinematode effect of these compounds may be possibly due to the inhibition of the targeting enzyme acetylcholinesterase. The data of this work suggest that organic waste SSP can be potentially reused for the production of thymine and hexahydropyrrolo [1,2-a] pyrazine-1,4-dione with promising use for the management of black pepper nematodes.

Since its inception in the late 2000s, blockchain has emerged as a powerful tool for creating trust without intermediaries to incentivize global communities for working for a common goal, such as the improvement of its very ecosystem, its applications and community adoption. While first blockchains were mainly devised for confirming transactions of their innate cryptocurrencies like Bitcoin, smart-contract blockchains like Ethereum can interface with the real-world through so-called “oracles”, which feed trustful off-chain information. This paper introduces digital twins of physical objects and processes as computational oracles to effectively unleash the tremendous opportunity offered by blockchain to the realm of fundamental science, research and technology development (RTD). The crowdsourcing concept is illustrated with the example of centrifugal flow control in microfluidic “Lab-on-a-Disc” (LoaD) systems.

This theoretical article provides a brief description of the model of living systems' functioning by defining them as resource flows patterns. It reviews the living systems growth limitation between their development cycles by the Fibonacci sequence. Besides, there are presented systems resource base criteria, necessary for accumulating the resources and their investment. The article also considers the conditions for the formation of various systems strategies. Then we reviewed the principles of elemental analysis of information by a person as a living system according to the considered model. The study also shows the possibility of forming priorities in analyzing information for 16 combinations as maximum. At that, it remains crucial to divide a human's information analysis between the two hemispheres of the brain. The described combinations of priorities in a person's information analysis are compared with the existing differential personality models, such as the big five personality traits, the Myers-Briggs type indicator, temperaments model and Honey and Mumford Learning styles.