This study aimed to assess the ecotoxicological effects of the interaction of fullerene (C₆₀) and benzo[a]pyrene (B[a]P) on the marine mussel, Mytilus galloprovincialis. The uptake of nC₆₀, B[a]P and mixtures of nC₆₀ and B[a]P into tissues was confirmed by GC-MS, LC-HRMS and ICP-MS. Biomarkers of DNA damage as well as proteomics analysis were applied to unravel the toxic effect of B[a]P and C₆₀. Antagonistic responses were observed at the genotoxic and proteomic level. Differentially expressed proteins (DEPs) were only identified in the B[a]P single exposure and the B[a]P mixture exposure groups containing 1 mg/L of C₆₀, the majority of which were down-regulated (~52%). No DEPs were identified at any of the concentrations of nC₆₀ (p < 0.05, 1% FDR). Using DEPs identified at a threshold of (p < 0.05; B[a]P and B[a]P mixture with nC₆₀), gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis indicated that these proteins were enriched with a broad spectrum of biological processes and pathways, including those broadly associated with protein processing, cellular processes and environmental information processing. Among those significantly enriched pathways, the ribosome was consistently the top enriched term irrespective of treatment or concentration and plays an important role as the site of biological protein synthesis and translation. Our results demonstrate the complex multi-modal response to environmental stressors in M. galloprovincialis.

Fluidic larger-scale integration (LSI) resides at the heart of comprehensive sample-to-answer automation and parallelization of assay panels for frequent and ubiquitous bioanalytical testing in decentralized the point-of-use / point-of-care settings. This paper develops a novel “digital twin” strategy with an emphasis on rotational, centrifugo-pneumatic flow control. The underlying model systematically connects retention rates of rotationally actuated valves as a key element of LSI to experimental input parameters; for the first time, the concept of band widths in frequency space as the decisive quantity characterizing operationally robustness is introduced, a set of quantitative performance metrics guiding algorithmic optimization of disc layouts is defined, and the engineering principles of advanced, logical flow control and timing are elucidated. Overall, the digital twin enables efficient design for automating multiplexed bioassay protocols on such “Lab-on-a-Disc” (LoaD) systems featuring high packing density, reliability, configurability, modularity and manufacturability to eventually minimize cost, time and risk of development and production.

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.

The concentration of all-trans-retinoic acid, the bioactive derivative of vitamin A, is critically important for the optimal performance of numerous physiological processes. Either too little or too much of retinoic acid in developing or adult tissues is equally harmful. All-trans-retinoic acid is produced by the irreversible oxidation of all-trans-retinaldehyde. Thus, the concentration of retinaldehyde as the immediate precursor of retinoic acid has to be tightly controlled. However, the enzymes that produce all-trans-retinaldehyde for retinoic acid biosynthesis and the mechanisms responsible for the control of retinaldehyde levels have not yet been fully defined. The goal of this review is to summarize the current state of knowledge regarding the identities of physiologically relevant retinol dehydrogenases, their enzymatic properties and tissue distribution, and to discuss potential mechanisms for the regulation of the flux from retinol to retinaldehyde.

This study aimed to investigate the possibility of using one-shot hyperspectral airborne images to recognize crops for an area with many small plots. The results showed that unsupervised clustering methods could classify crops with an accuracy of 80%, which improved to 90% when restricted to only grain crops, using a single airborne hyperspectral recording. However, additional layers such as NDVI, DTM, slope, and aspect did not improve classification accuracy. For comparison, the accuracy of clustering time series Sentinel-2 images with NDVI layers and DTM-derived data yielded an accuracy of: 74% ,Sentinel-2 time series 68% and single one registration before harvest - 39%. The results of the random forest classification were slightly less accurate due to a lack of sufficient reference data. However, it is challenging to verify the reported accuracy of crop recognition in the literature above 90% due to differences in analysis methodologies, reference data selection, pixel/object approaches, metric choice, and calculation formulas used.

A simple line of reasoning, based on the most fundamental concepts of thermodynamics, yields some intriguing results for a better understanding of the processes occurring in the observable Universe. Gravitational mass must be continuously generated within an expanding thermodynamic system for this system to remain closed. The Second Law is a direct consequence of this production of mass. Simple expressions for the entropy and temperature of the Universe were obtained and the results agree well with observable values. Furthermore, it is demonstrated that the conservation laws within the Universe are independent of its energy density. Based on the solution for the quantum state of the Universe, it is conjectured that the Second Law is incomplete and must be complemented to a conservation law, which takes into account the growth of the amount of information within the Universe. Once the Second Law is complemented to a conservation law, the importance of mass generation within the Universe becomes well pronounced – not only gravitational effects play the role of an organising force, but also the amount of mass within the Universe defines both the amount of information within the Universe and the level of the Universe’s complexity.

Bisphenol A diglycidyl ether (BADGE) is widely existed in the inner coating of canned foods. It migrates into food and generate various derivatives in the process of storage, such as Bisphenol A (2, 3-dihydroxypropyl) glycidyl ether (BADGE·H2O), Bisphenol A (3-chloro-2-hydroxypropyl) glycidyl ether (BADGE·HCl) and Bisphenol A (3-chloro-2-hydroxypropyl) (2, 3-dihydroxypropyl) glycidyl ether (BADGE·HCl·H2O), which have negative effects on human health. A gold nanoparticle-based immu-nochromatographic assay for simultaneous detection of BADGE and its derivatives was developed by using a broad-spectrum polyclonal antibody, and the detection can be finished in 15 min. The visuali-zation of results was processed by Adobe Photoshop CC software to achieve quantitative analysis and the detection limit (IC15) is 0.97ng/mL. The recoveries of BADGE and its derivatives at various spiking levels in canned food samples ranged from 79.86% to 93.81%. The detection results of the proposed immu-nochromatographic assay were also validated by HPLC analysis, and got good consistency (R2=0.9580).

Based on the analysis of the spatial distribution of uranium grade in 348 boreholes of a uranium deposit in Xinjiang, the enrichment and spatial variation of uranium ore in two stopes of the deposit are discussed by using multifractal theory. The distribution characteristics of uranium ore of the two stopes are studied by multifractal parameters: the scaling exponent of mass , the scaling exponent of each sub-set and its corresponding fractal dimension , the fractal dimension D0 and information dimension D1. The differences of uranium distribution in two stopes can be well quantified by multifractal spectrum and multifractal parameters( , , ).10m×10m is defined as a fence unit, and the window sizes are respectively set, the singularity exponent of the two stopes are calculated by this element concentration-area(C-A) method. The results show that the multifractal theory and model can organically combine spatial structure information, scale change information and anisotropy information to obtain low-grade and weak mineral resources information, and can effectively distinguish complex and superimposed anomalies. This will provide a basis for local concentration and spatial variation rules of uranium distribution and the design of the parameters of leaching uranium mining well site.

In order to study the petrogenesis and tectonic setting of Permian A-type granites and their relationships with hydrothermal mineralization along the Hegenshan-Heihe suture zone (HHSZ) in northeastern China, we select the newly discovered Hongyan Cu-polymetallic deposit in the northeastern part of the HHSZ that develops three stages of mineralization associated with the Shanshenfu alkali-feldspar granite (SAFG). The zircon U-Pb dating and whole rock geochemistry suggest that the SAFG is a typical A-type granite formed in the Early Permian. The zircon Hf isotopes and trace elements suggest that the SAFG has high Ti-in-zircon temperature (721–990℃), high magmatic oxygen fugacity and largely positive εHf(t) (+6.0 to +9.9). Therefore, we propose that the SAFG was derived from the crustal assimilation and fractional crystallization of the charnockitized juvenile crust. The high oxygen fugacity favors the chalcophile elements (e.g., Cu, Au, Ag) of the source region enriched in the fluid phases after magmatic fractional crystallization, consequently facilitating subsequent hydrothermal mineralization, which is also consistent with the characteristics of ore-forming fluids that changed from the initial high temperature, high salinity, high fO2 and CO2-rich magmatic-hydrothermal fluids of stage I to CO2-poor, dilute, and cooling meteoric fluids of stage III. Combined with regional geological background, the Permian A2-type granites along the HHSZ can be formed in post-collisional slab break-off process. In subsequent exploration for hydrothermal deposits along the HHSZ, the Permian A-type granites with arc-related juvenile crustal source and high fO2 have great potential and need more attention.

Irrigated agriculture determines large blue water withdrawals, and it is considered a key intervention area to reach sustainable development objectives. Precision agriculture technologies have the potential to mitigate water resource depletion that often characterizes conventional agricultural approaches. This study investigates the factors influencing farmers' intentions to adopt variable rate irrigation (VRI) technology. The Technology Acceptance Model 3 (TAM-3) was employed as a theoretical framework to design a survey to identify the factors influencing farmers' decision-making process when adopting VRI. Data were gathered through quantitative face-to-face interviews with a sample of 138 fruit and grapevine producers from the Northeast of Italy (Veneto, Emilia-Romagna, Trentino-Alto Adige, Friuli-Venezia Giulia). Data were analyzed using partial least squares path modelling (PLS-PM). The results highlight that personal attitudes, such as perceived usefulness and subjective norm, positively influence the intention to adopt VRI. Also, the perceived ease of use positively affects intention, but it is moderated by subject experience.

The Influenza A virus (IAV) is a highly infectious virus that poses a significant threat to global public health and food supplies. The current subtype of avian influenza virus (AIV), H5N1, is being closely monitored worldwide due to its unprecedented spread from Europe to North America and now to Central and South America. This review summarizes recent updates on the evolution of the different IAV subtypes in birds and mammals including humans, in Chile. The distribution and spread of AIV H5N1 in Chile indicated a complex interplay between ecological and human factors in that it was negatively correlated with distance to the closest urban center and precipitation and temperature seasonality. It is evident that highly pathogenic avian influenza (HPAI) H5N1 in Chile was introduced from North America via the Atlantic migratory flyways as opposed to local transmission from other countries in South America. The presence of these viruses in Chile underscores the need for increased biosecurity on poultry farms and continuous genomic surveillance approaches to understand and control AIVs in both wild and domestic bird populations in Chile.

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.

Introduction: The objectives of this study were to (1) investigate the association between human blood type and COVID-19 infection in both inpatient and longitudinal populations at our institution in South Florida and (2) identify the association between blood type and severity of COVID-19 infection via presence of cellular biomarkers of severe infection in hospitalized individuals. Methods: This study consists of (1) a single-center retrospective analysis of 669 of 2,741 COVID-19 positive screened patients seen from January 1, 2020 until March 31, 2021 at the University of Miami Emergency Department (ED) who tested positive for COVID-19 infection and had a documented ABO blood type and (2) a longitudinal SARS-CoV-2 immunity study (“CITY”) at the University of Miami Miller School of Medicine consisting of 185 survey participants. COVID-19 outcome rates and 95% confidence intervals were calculated for each ABO blood type and Rh group using Chi-squared tests for categorical and ANOVA for continuous variables in the inpatient cohort and Chi-squared tests for the longitudinal cohort, all executed in R studio. Results: Our inpatient cohort had a mean age of 53.6 (± 17.9) years with 48% males and 52% females. When compared to patients with other blood types, those with O- demonstrated less risk of developing COVID-19 pneumonia (26.7% for O- vs. 69.2% for type A-, 56.5% for A+, 71.4% for AB+, 53.7% for B+, 51.5% for O+, p-value= 0.003 via Chi-squared test) and decreased mortality due to COVID-19 infection (17.0% mortality for O vs. 26.3% for A, 29.2% for B, p-value= 0.012 via Chi-squared test). Blood type O- demonstrated less elevated levels of LDH than did other blood types (p-value= 0.001, ANOVA) and a higher frequency of clinically accepted baseline levels of troponin (0.04 ng/mL) (p-value= 0.026, ANOVA) (Figure 1). Most of the longitudinal cohort was ABO blood grouping type O (47% (87/185)), with 33.5% type A, 14.1% B, and 5.4% AB. Most individuals were Rh positive (85.9%). There was no significant association found between COVID status (infection vs. non-infection) and ABO (Chi-squared test (3, N = 185) = 1.8, p = 0.6) or Rh (Chi-squared test (1, N = 185) = 0.16, p = 0.7) blood typing. Nearly all participants had been vaccinated (95.1% (176/185)), with a majority reporting primary vaccination with Pfizer (57.8% (107/185)), followed by Moderna (33% (61/185)), and Johnson & Johnson (4.3% (8/185)). 8 participants (4.3%) were unvaccinated. Conclusions: In an inpatient setting, blood type O sustained less risk of COVID-19 mortality and O- demonstrated less risk of developing COVID-19 pneumonia. In a longitudinal setting, there was no association found between blood type and COVID-19 severity. As the novelty of COVID-19 infection declines with time, further studies on risk-stratification by blood type are encouraged.

Wireless communications are gaining massive demand for faster video streaming, virtual reality, and 5G-based IoT (Internet of Things) applications. Due to this network congestion increases hastily. The demand for user-specific services, machine learning, forcing the radio access network (RAN) to provide improvement in utilization of spectrum efficiency, minimizing power consumption, and improving data rate. For LTE/LTE-A network specifications provided by third-generation partnership project (3GPP), guarantees to provide qualitative of service (QoS). Release 15/16 utilizes two-dimensional (2D) active antenna array systems (AAS). This kind of AAS provides beam forming in both azimuth and elevation also termed as Full Dimensional MIMO (FD-MIMO). It enhances the radiation pattern of the antenna array element by adjusting the angular power spectra at the base station (BS), it also allows selecting the minimum number of antennas for effective beam forming toward specific user equipment’s (UEs). Spectrum allocation challenge can be dealt with at mm wave band having FR2 (>6GHz) frequency band specified by International Telecommunication Union (ITU-R) in line with IMT-2020 specifications. The spectrum is free at mm Wave for communication of 5G. However, the main challenge is, it faces path loss and atmospheric loss electromagnetic energy absorbed by gases like oxygen. In this work, the 5G new RAN power spectrum and power delay profile at 10GHz carrier frequency with 20MHz to 100MHz channel bandwidth is observed for line of sight (LOS) and non-line of sight (NLOS) communication for guaranteed QoS. To demonstrate the path loss and power delay profile (PDP) in directional and Omni-directional antennas NYUSIM channel simulator is utilized.

The interaction between native and invasive plant species plays a crucial role in understanding invasion mechanisms and developing control strategies. This study investigated the differences in photosynthetic and fluorescence parameters, gene expression profiles, and rhizosphere soil microbial composition between the native species Ficus tikoua Bur. and the invasive species Alternanthera philoxeroides. For the first time, it was demonstrated that that F. tikoua Bur. may enhance photoinhibition ability and the expression of genes involved in carbon metabolism, protein processing in the endoplasmic reticulum, and plant-pathogen interactions to maintain growth. Additionally, it recruits beneficial microbes, e.g. Actinomarina (Bacteria), Nitrosotenuis (Archaea) and Laccaria (fungi), to suppress pathogens, thereby preserving soil DMSP and carbon cycling pathways to resist invasion by A. philoxeroides. These findings provide novel insights into the mechanisms underlying plant invasion and suggest potential strategies for invasive plant management. Further research is needed to investigate this relationship and determine the mechanisms underlying the potential resistance of F. tikoua Bur. to plant invasion.

A simulation test system for the two-dimensional (2D) fuze overload loading process was designed to address the loading issues of recoil overload and centrifugal overload in fuze safety and arming (S&amp;A) devices. By incorporating centrifuge rotation energy storage, impact acceleration simulation, and equivalent centrifugal rotation simulation, a block equipped with a fuze S&amp;A device was accelerated instantly upon being impacted by a centrifuge-driven impact hammer, simulating recoil overload loading. The impact hammer was retracted instantaneously by adopting an electromagnetic brake, which resulted in the centrifugal rotation of the block around its track, to simulate the centrifugal overload loading. The dynamic equations of the simulation test system and the equations of impact hammer motions were established, whereby the rotation speed of the centrifuge and the braking force of the electromagnetic brake were calculated and selected. A dynamic model of the collision between the impact hammer and block was established using ANSYS/LS-DYNA software for simulation analysis. The acceleration curves of the recoil overload and centrifugal overload with variations in the centrifuge speed, cushion material, and buffer thickness were obtained, which verified the feasibility of the proposed loading simulation method. 2D overload loading simulation tests were performed using the developed simulation system, and the acceleration curves of the recoil overload and centrifugal overload were measured. The test results indicated that the proposed system can accomplish 2D overload loading simulations for a recoil overload of several 10000 g and centrifugal overload of several 1000 g.

Artificial membrane systems can serve as models to investigate molecular mechanisms of different cellular processes, including transport, pore formation, and viral fusion. However, the current simulacrums such as SUVs, GUVs, and the supported lipid bilayers suffer from issues, namely high curvature, heterogeneity, and surface artefacts, respectively. Freestanding membranes provide a facile solution to these issues, but current systems developed by various groups use silicon or aluminium oxide wafers for fabrication that involves access to a dedicated nanolithography facility and high cost while conferring poor membrane stability. Here, we report the development, characterization and applications of an easy-to-fabricate suspended lipid bilayer (SULB) membrane platform leveraging commercial track-etched porous filters (PCTE) with defined microwell size. Our SULB system offers a platform to study the lipid composition-dependent structural and functional properties of membranes with exceptional stability in a high throughput fashion. With dye entrapped in PCTE microwells by SULB, we show that sphingomyelin significantly augments the activity of pore-forming toxin, Cytolysin A (ClyA) and the pore formation induces lipid exchange between the bilayer leaflets. Further, we demonstrate high efficiency and rapid kinetics of membrane fusion by dengue virus in our SULB platform. Our suspended bilayer membrane mimetic offers a novel platform to investigate a large class of biomembrane interactions and processes.

Particles in classical physics are distinguishable objects, which can be picked out individually on the basis of their unique physical properties. By contrast, in quantum mechanics the standard view is that particles of the same kind (``identical particles'') are completely indistinguishable from each other. This standard view is problematic: Particle indistinguishability is irreconcilable not only with the very meaning of ``particle'' in ordinary language and in classical physical theory, but also with how this term is used in the practice of present-day physics. Moreover, the indistinguishability doctrine prevents a smooth transition from quantum particles to what we normally understand by ``particles'' in the classical limit of quantum mechanics. Elaborating on earlier work, we here discuss an alternative to the standard view that avoids these and similar problems. As it turns out, this alternative approach connects to recent discussions in quantum information theory concerning the question of when identical particles can be considered to be entangled.

The Physical Random Access Channel (PRACH) plays an important role in LTE and LTE-A systems. It is through the PRACH channel that the user equipment (UE), based on eNodeB's timing estimates, aligns its uplink transmissions to the eNodeB's uplink and gain access to the network. One of the initial operations executed by the PRACH receiver at eNodeB side is the translation of the PRACH signal back to base band, $i.e.$, center the PRACH signal around DC. This operation is a necessary step for preamble detection and can be carried out through a time-domain frequency shift operation. Therefore, in this paper we present the hardware architecture and implementation details of a configurable and optimized FPGA-based time-domain frequency shifter. It is a hardware-efficient and accurate architecture for converting the relevant received PRACH signal into base band before further signal processing. The architecture is manly based on a customized Numerically Controlled Oscillator (NCO), which is used for generating complex exponentials employing only adders, a Look-Up Table (LUT) and plain logic resources. The main advantage of the proposed hardware architecture is that it completely eliminates the need for storing a large number of long complex exponential sequences by employing a single LUT and exploiting quarter wave symmetry of the basis waveform. Our simulation results show that the proposed customized NCO architecture provides high Spurious Free Dynamic Range (SFDR) signals using a minimal amount of FPGA resources. Moreover, the proposed architecture exhibits spur-suppression ranging from 62.13 to 153.58 dB without using Taylor Series correction.

Scrub typhus threatens one billion people in the Asia-Pacific area and cases have emerged outside this region. It is caused by infection with any of the multitude of strains of the bacterium, Orientia tsutsugamushi. A vaccine that affords heterologous protection and a commercially available molecular diagnostic assay are lacking. Herein, we determined that the nucleotide and translated amino acid sequences of outer membrane protein A (OmpA) are highly conserved among 51 O. tsutsugamushi isolates. Molecular modeling revealed the predicted tertiary structure of O. tsutsugamushi OmpA to be very similar to that of the phylogenetically related pathogen, Anaplasma phagocytophilum, including the location of a helix that contains residues functionally essential for A. phagocytophilum infection. PCR primers were developed that amplified ompA DNA from all O. tsutsugamushi strains, but not from negative control bacteria. Using these primers in quantitative real-time PCR enabled sensitive detection and quantitation of O. tsutsugamushi ompA DNA from organs of mice that had been experimentally infected with the Karp or Gilliam strains. The high degree of OmpA conservation among O. tsutsugamushi strains evidences its potential to serve as a molecular diagnostic target and justifies its consideration as a candidate for developing a broadly protective scrub typhus vaccine.

Praeruptorin A(PA), a naturally existing pyranocumarin, is isolated from the dried root of Peucedanum praeruptorum Dunn. So far the anti-cancer effect and molecular mechanism behind Praeruptorin A action in human cervical cancer HeLa cells remain unknown. In the present study, we find that PA reduces cell proliferation and colony formation of human cervical cancer HeLa cells through inducing cell cycle arrest at G0/G1 phase. PA-upregulated p21 and p27 proteins are observed, accompanied with inhibition of cyclin D1 and S-phase kinase-associated protein 2(Skp2) proteins expression. PA could significantly inhibit migration and invasion of human HeLa cells. Meanwhile, PA significantly reduces invasive protein expression of matrix metalloproteinase-2 (MMP-2), and increases protein expression of tissue inhibitor of metalloproteinase-2 (TIMP-2). PA is observed to possess the capacity in suppressing ERK1/2 activation. PD98059 (ERK specific inhibitor) significantly enhances PA-induced downregulation of MMP-2 expression, and upregulation of TIMP-2 expression. Moreover, we found that PA treatment notably inhibits 12-O-tetradecanoylphorbol-13-acetate(TPA)-upregulated ERK1/2 activation, MMP-2 expression, cellular migration and invasion in human HeLa cells. Taken together, these findings are the first to demonstrate the anti-cancer activity of PA, which may act as a promising therapeutic agent for the treatment of human cervical cancer.

Introduction: A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory mediators in epileptogenesis, its association with seizure severity, and its correlation with drug-resistant epilepsy (DRE). Material and Methods: The study analysed articles published in JCR journals from 2019 to 2024, including retrospective, prospective, case-control, or cross-sectional studies. It combined MESH and free terms for "Epileptogenesis" and "Neuroinflammation" and included searches for biomarkers previously reported in narrative reviews. Results: The study analysed 243 articles related to epileptogenesis and neuroinflammation, with 356 from selective searches by biomarker type. After eliminating duplicates, 324 articles were evaluated, with 272 excluded and 52 evaluated by authors. 21 articles were included in the qualitative evaluation, including 18 case-control studies, 2 case series, and 1 prospective study. This systematic review provides acceptable support for five biomarkers: TNF-a and some of its soluble receptors (sTNFr2), HMGB1 and TLR-4, CCL2 and IL-33. Discussions: Certain receptors, cytokines, and chemokines are examples of neuroinflammation-related biomarkers that may be crucial for the early diagnosis of refractory epilepsy or may be connected to the control levels of epileptic patients. Their value will be better defined by future studies.

Recently, there has been increasing attention toward inhaled nanoparticles (NPs) to develop in-halation therapies for diseases associated with the pulmonary system and investigate the toxic ef-fects of hazardous environmental particles on human lung health. Taking advantage of microfluidic technology for cell culture applications, lung-on-a-chip devices with great potential in replicating the lung air-blood barrier (ABB) have opened new research insights in preclinical pathology and therapeutic studies associated with aerosol NPs. Surprisingly, the air interface in such devices, which makes them tremendously unique among the other common liquid-based cellular mi-crosystems and enables exposure of cultivated cells to the drug/toxic aerosols, has been largely disregarded. Accordingly, there exists a significant research gap in the comprehensive under-standing of the NPs’ dynamics in the lung-on-a-chip devices, which is momentous to control the injection of aerosols to the target area and attain a desired physiochemical efficacy. To address this research gap, a numerical parametric study is presented to provide a deep insight into the dynamic behavior of the airborne NPs in a gas-liquid dual-channel lung-on-a-chip device with a porous membrane separating the channels. A finite element multi-physics model is developed to enable a particle tracing investigation simultaneously in both air and medium phases to replicate the in vivo conditions avoiding laborious and costly experimental trials. The results include the impact of fluid flow as well as geometrical properties on the distribution, deposition, and translocation of the NPs with diameters ranging from 10 nm to 900 nm in the lung-on-a-chip. The obtained results strongly suggest the aerosol injection of NPs instead of the aqueous solution for more efficient deposition on the substrate of the air channel and higher translocation to the media channel. The current study proposes to optimize the affecting parameters to control the injection and delivery of aerosol par-ticles into the lung-on-chip device depending on the objectives of biomedical investigations and provides optimized values for some specific cases. Therefore, this study can assist scientists and researchers in complementing their experimental investigation in future preclinical studies on pulmonary pathology associated with inhaled hazardous and toxic environmental particles, as well as therapeutic studies for developing inhalation drug delivery.

Substantial evidence indicates that bisphenol A (BPA), a ubiquitous environmental chemical used in the synthesis of polycarbonate plastics and epoxy resins, can impair brain development. Clinical and epidemiological studies exploring potential connections between BPA and neurodevelopmental disorders in humans have repeatedly identified correlations between early BPA exposure and developmental disorders, like attention deficit/hyperactivity disorder and autism spectrum disorder. Investigations using invertebrate and vertebrate animal models have revealed that developmental exposure to BPA can impair multiple aspects of neuronal development, including neural stem cell proliferation and differentiation, synapse formation, and synaptic plasticity—neuronal phenotypes that are thought to underpin the fundamental changes in behavior associated neurodevelopmental disorders. Consistent with BPA-associated neuronal phenotypes, behavioral analyses of BPA-treated animals have shown significant impacts on behavioral endophenotypes related to neurodevelopmental disorders, including altered locomotor activity, learning and memory deficits, and anxiety-like behavior. To contextualize the correlations between BPA and neurodevelopmental disorders in humans, this review summarizes current literature reporting on the developmental neurotoxicity of BPA in laboratory animals, with an emphasis on neuronal phenotypes, molecular mechanisms, and behavioral outcomes. The collective works described here predominantly support the notion that gestational exposure to BPA should be regarded as a risk factor for neurodevelopmental disorders.

A whole-exome capture and next-generation sequencing applied to an 11 y/o patient with a clinical history of congenital hypotonia, generalized motor and cognitive neurodevelopmental delay, severe cognitive deficit, without any identifiable Syndromic pattern, and to her parents, disclosed a de novo heterozygous pathogenic mutation, c.697_699del p.Phe233del (rs786204835)(ACMG classification PS2, PM1, PM2, PP5), harbored in the PURA gene (MIM*600473) (5q31.3), associated to Autosomal Dominant Mental Retardation 31 (MIM # 616158). We used the significant improvement in the accuracy of protein structure prediction recently implemented in AlphaFold that incorporates novel neural network architectures and training procedures based on the evolutionary, physical, and geometric constraints of protein structures. The wild-type (WT) sequence and the mutated one, missing the Phe233, were reconstructed. The predicted local Distance Difference Test (lDDT) for the PURA WT and the PURA-Phe233del showed that the occurrence of the Phe233del affects between 220-320 amino acids. The distortion in the PURA structural confor-mation in the ~5Å surrounding area after the p.Phe233del produces a conspicuous disruption of the repeat III, where the DNA and RNA helix unwinding capability occurs. PURA Protein-DNA Docking corroborated these results in silico Analysis that showed a loss of the contact of the PURA-Phe233del III repeat domain model with the DNA. Together, i) the energetic and stereochemical, ii) the hydropathic indices and polarity surfaces, and iii) the hybrid Quantum Mechanics-Molecular Mechanics (QM-MM) analyses of the PURA molecular models demarcate at the atomic resolution the specific surrounding region affected by these mutations and paves the way for future cell-based functional analysis. To the best of our knowledge, this is the first report of a de novo mutation underpinning a PURA syndrome in a Latin American patient and highlights the importance of predicting the molecular effects in protein structure using artificial intelligence algorithms and molecular and atomic resolution stereochemical analyses.

Perhaps the greatest challenge in the graft copolymerization of acrylic acid onto starch initiated by Fenton’s is the selectivity of the grafting reaction. Low selectivity means that too much of unwanted homopolymer polyacrylic acid is produced. In this paper, it has been analyzed why with this reaction system, involving a water soluble monomer and indirect initiation, the graft selectivity is such a challenge. Several other grafting reactions, especially with monomers of low water solubility or when direct initiation is applied, show a better grafting performance. A scheme is presented based on reaction engineering principles, that supports an explanation of the observed differences. A more selective activation of starch is a factor, but perhaps even more important is a low monomer to starch ratio at the starting sites of graft reactions. Based on these insights, several methods to improve the graft selectivity are evaluated, with the help of literature data but mostly by experimental explorations in our laboratory. Most promising appears to be a dedicated dosage method, to add monomer in portions over time, tested in a batch reactor with gelatinized cassava starch. This way, both grafting percentage and graft selectivity could be improved. Such could not be realized with the more conventional dosage, which is to add all monomer before the start of the reaction. This can be considered a principal breaktrough. Still, more research and development would be needed to refine the method and to implement the idea also in a continuous reactor at larger scale.

After proving, in a purely categorial way, that the inclusion functor InAlg(Σ) from Alg(Σ), the category of many-sorted Σ-algebras, to PAlg(Σ), the category of many-sorted partial Σ-algebras, has a left adjoint FΣ, the (absolutely) free completion functor, we recall, in connection with the functor FΣ, the generalized recursion theorem of Schmidt, which we will also call the Schmidt construction. Next we define a category Cmpl(Σ), of Σ-completions, and prove that FΣ, labeled with its domain category and the unit of the adjunction of which it is a part, is a weakly initial object in it. Following this we associate to an ordered pair (α,f), where α=(K,γ,α) is a morphism of Σ-completions from F=(C,F,η) to G=(D,G,ρ) and f a homomorphism in D from the partial Σ-algebra A to the partial Σ-algebra B, a homomorphism ΥαG,0(f):Schα(f)B. We then prove that there exists an endofunctor, ΥαG,0, of Mortw(D), the twisted morphism category of D, thus showing the naturalness of the previous construction. Afterwards we prove that, for every Σ-completion G=(D,G,ρ), there exists a functor ΥG from the comma category (Cmpl(Σ)↓G) to End(Mortw(D)), the category of endofunctors of Mortw(D), such that ΥG,0, the object mapping of ΥG, sends a morphism of Σ-completion in Cmpl(Σ) with codomain G, to the endofunctor ΥαG,0.

Public health suffers from noxious gas of beached Sargassum algae. Floating barrages containing them at sea will be useful provided efficiently catch them and resist to hydrodynamic pressure. Nowadays design and installation of algae barrages are empiric. Structural break, anchor and mooring chain drifts can arise. We provide a mechanical model to evaluate stresses and loads on a structure made of nets and moorings. Hydrodynamic uncertainties occur through catches, fouling, and a range of sea currents appearing in lagoons or sheltered bays. We consider a nonlinear finite-element model of elastic membrane in large displacements and small strains. We study some forcings fixed a priori on a standard section of barrage. A section 50 m long, 1 m high, with two net-faces is examined at low and moderate current velocities, 0.05 and 0.35 m.s-1, while assuming specific vertical and horizontal catch pressures. A barrage installed in lagoon at Le François on Martinique Island and being observable by satellite imagery could benefit of the computed net and mooring tensions.

Plant species are precursors of a wide variety of secondary metabolites that, besides having useful activity for themselves, can also be used by humans for their consumption and economic benefit. Pepper (Capsicum annuum L.) fruit is not only a common food and spice source, but it also stands out for containing high amounts of antioxidants (such as vitamins C and A), polyphenols and capsaicinoids. Particular attention has been paid to capsaicin, whose anti-inflammatory, antiproliferative and analgesic activities, have been proven. Due to the potential interest in pepper metabolites for human use, in this project, we carried out an investigation to identify new bioactive compounds of this crop is carried out. To achieve this, we developed a metabolomic approach, using an HPLC (high-performance liquid chromatography) separative technique coupled to metabolite identification by high resolution mass spectrometry (HRMS). After chromatographic analysis and data processing against metabolic databases, 12 differential bioactive compounds were identified in sweet pepper fruits, including quercetin and its derivatives, L-tryptophan, phytosphingosin, FAD, gingerglycolipid A, tetrahydropentoxylin, blumenol C glucoside, colnelenic acid and capsoside A. The abundance of these metabolites varied depending on the ripening stage of the fruits, either immature green or ripe red. We also studied the variation of these 12 metabolites upon treatment with exogenous nitric oxide (NO), a free radical gas involved in a good number of physiological processes in higher plants such as germination, growth, flowering, senescence, and fruit ripening, among others. Overall, it was found that the content of the analysed metabolites was modulated by the ripening stage and by the presence of NO. The metabolic pattern followed by quercetin and its derivatives, as a consequence of the ripening stage and NO treatment, was also corroborated by transcriptomic analysis of genes involved in the synthesis of these compounds. This opens new research windows on the pepper fruit’s bioactive compounds with nutraceutical potentiality, where biotechnological strategies can be applied for optimizing the level of these beneficial compounds.

In December 2019, pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection emerged in Wuhan City, Hubei Province, China. Early in 2020, the World Health Organization (WHO) announced a new name for the 2019-nCoV-caused epidemic disease: coronavirus disease 2019 (COVID-19) and declared COVID-19 to be the sixth international public health emergency. Cellular co-infection is a critical determinant of both viral fitness and infection outcome and plays a crucial role in shaping the host immune response to infections. In this study, sixty-eight public next-generation sequencing libraries from SARS-CoV-2 infected patients were retrieved from the NCBI Sequence Read Archive database using SRA-Toolkit. Using an alignment-free method based on K-mer mapping and extension, SARS-CoV-2 was identified in all except three patients. Influenza A H7N9 (3/68), Human immunodeficiency virus 1 (1/68), rhabdovirus isolate (3/68), Human metapneumovirus (1/68), coronaviruses NL63 (1/68), Parvovirus (1/68), Simian virus 40 (1/68), and hepatitis virus (1/68) genome sequences were detected in SARS-CoV-2 infected patients.

Climate change will pose a challenge for the winemaking sector worldwide, bringing progressively drier and warmer conditions and increasing the frequency and intensity of weather extremes. The short-term adaptation strategy of applying biostimulants through foliar application serves as a crucial measure in mitigating the detrimental effects of environmental stresses on grapevine yield and berry quality. The aim of this study was to evaluate the effect of foliar application of a seaweed based biostimulant (A. nodosum – ANE) and glycine betaine (GB) on berry quality, bioactive compounds, antioxidant activity, and elucidated their action on the secondary metabolism. A trial was installed in a commercial vineyard (cv. ‘Touriga Franca’) in the Cima Corgo (Upper Corgo) sub-region of the Douro Demarcated Region. A total of four foliar sprayings were performed during the growing season: at flowering, pea size, bunch closer, and veraison. There was a positive effect of GB in the berry quality traits. Both ANE and GB increased the synthesis of anthocyanins and other phenolics in berries and influenced the expression of genes related to the synthesis and transport of anthocyanins (CHS, F3H, UFGT, MATE1 and GST). So, they have the potential to act as elicitors of secondary metabolism, leading to improved grape quality, but also sets the foundation for sustainable agricultural practices in the long run.

For order-of-addition experiments, the response is affected by the addition order of the experimental materials. Consequently, the main interest focuses on creating a predictive model and an optimal design for optimizing the response. Van Nostrand (1995) proposed the pairwise-order (PWO) model for detecting PWO effects. Under the PWO model, the full PWO design is optimal under various criteria but is often unaffordable because of the large run size. In this paper, we consider the D-, A- and M.S.-optimal fractional PWO designs. We first present some results on information matrices. Then, a flexible and efficient algorithm is given for generating these optimal PWO designs. Numerical simulation shows that the generated design has an appealing efficiency in comparison with the full PWO design, though with only a small fraction of runs. Several comparisons with existing designs illustrate that the generated designs achieve better efficiencies, and the best PWO designs and some selected 100% efficient PWO designs generated by the new algorithm are reported.

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.

Large values and gradients of stresses and deformations, triggering concentrations of stresses and deformations, arise in the corner areas of a structure. The action of forced deformations, leading to the finite rupture of the contact between the elements of a structure, also triggers the concentration of stresses, while the rupture reaches an irregular point, a line on the area boundary. The theoretical analysis of the stress-strain state (SSS) of areas with angular cutouts in the boundary under the action of discontinuous forced deformations is reduced to the study of singular solutions to the homogeneous problem of the elasticity theory that has power-related features. The calculation of stress concentration coefficients in the domain of a singular solution to the elastic problem makes no sense. It is experimentally proven that the zone, that is close to the vertex of the angular cutout in the area boundary, has substantial deformations, rotations, and it corresponds to rising values of the first and second derivatives of displacements along the radius in cases of sufficiently small radii in the neighbourhood of the irregular point of the boundary. For such areas, it is necessary to consider the plane problem of the elasticity theory, taking into account the geometric nonlinearity under the action of forced deformations. This will allow analyzing the effect of relations between orders of values of deformations, rotations, and forced deformations on the form of the equation of equilibrium. The purpose of this work is to analyze the effect of relations of deformation orders, rotations, forced deformations on the form of the equilibrium equation in the polar coordinate system for a V-shaped area under the action of forced temperature-induced deformations with regard for the geometrical non-linearity and physical linearity.

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.

We work within a Winterberg framework where space, i.e., the vacuum, consists of a two component superfluid/super-solid made up of a vast assembly (sea) of positive and negative mass Planck particles, called planckions. These material particles interact indirectly, and have very strong restoring forces keeping them a finite distance apart from each other within their respective species. Because of their mass compensating effect, the vacuum appears massless, charge-less, without pressure, net energy density or entropy. In addition, we consider two variable models, where, , is Newton’s constant, and, , increases with an increase in cosmological time. We argue that there are at least two competing models for the quantum vacuum within such a framework. The first follows a strict extension of Winterberg’s model. This leads to nonsensible results, if increases, going back in cosmological time, as the length scale inherent in such a model will not scale properly. The second model introduces a different length scale, which does scale properly, but keeps the mass of the Planck particle as, the Planck mass. Moreover we establish a connection between ordinary matter, dark matter, and dark energy, where all three mass densities within the Friedman equation must be interpreted as residual vacuum energies, which only surface, once aggregate matter has formed, at relatively low temperatures. The symmetry of the vacuum will be shown to be broken, because of the different scaling laws, beginning with the formation of elementary particles. Much like waves on an ocean where positive and negative planckion mass densities effectively cancel each other out and form a zero vacuum energy density/ zero vacuum pressure surface, these positive mass densities are very small perturbations (anomalies) about the mean. This greatly alleviates, i.e., minimizes the cosmological constant problem, a long standing problem associated with the vacuum.

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.

As a service business models have been ranked by management consultants the management innovation of 2020, and yet are scarcely theorized. Therein, value stipulations in customer contracts lead to the shift from product to service. However, there is no available research about the nature, formula and decisional process about these value stipulations. The motive for this research is to fill in this gap. The goal is to provide first insight about value stipulations in as a service business models: their formula and decisional methodology. The article is a multiple theory building case study on leading platform as a service providers, which aims to contruct the paradigm of the value decision methodology to invest in this technology by purchasing it from dedicated vendors. The methodology works to identify the management instruments involved in the decisional activities to invest in digital technology, where each management instrument is assumed to match an activity at seller and buyer; the sequence of the activities using the Critical Path Method gives the decisional process. Dependent variables are the elements of the as a service business contracts: the customer offering (product-service solution) and the value created, captured and delivered by the solution. Independent variables are given by empirical data analysis. Findings show a relationship between dependent variable value in the as a service business model contracts and independent variables governance objective, strategy, as a service business model type, activity management techniques (roadmap, program, project, operations, lean start-up), capital allocation techniques (equity, debt, options, venture capital typology). If innovation is exploitative, then the customer offering is known and value is determinable via roadmap – project management techniques (program, project, an operations) and capital allocation techniques for precictable environment, If innovation is radical, then the customer offering is not known and value is a target used to architect the solution via lean start-up innovation techniques funded by venture capital. The contribution is a new theoretical construct and deep insight into the practice of digital transformation considering all inherent issues.

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.

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.

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.

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.

Phosphorus, an essential rare element in aquatic ecosystems, plays a key role in maintaining ecosystem balance. However, an excess of phosphorus will lead to eutrophication and algal pro-liferation. To prevent eutrophication, it is crucial to pretreat and measure the concentration of total phosphorus (TP). Compared with conventional TP pretreatment equipment (autoclave), a lab-on-a-chip detection device fabricated through micro-electromechanical system technology using titania (TiO2) as a photocatalyst is more convenient, efficient, and cost-effective. However, the wide bandgap of TiO2 (3.2 eV) limits the photocatalytic activity. To address this problem, this paper describes the preparation of a TiO2/Au nanocomposite film by electron-beam evaporation and atomic layer deposition, based on the introduction of a gold film and TiO2 on a quartz substrate. The photocatalytic degradation properties of TiO2/Au nanocomposite films with thicknesses of 1, 2, 3, and 4 nm are assessed using rhodamine B as a pollutant. Experimental results demonstrate that the deposition of a gold film with different thicknesses can enhance the photocatalytic degradation efficiency through synergetic reactions in the charge separation process on the surface. The optimal photocatalytic efficiency is achieved when the deposition thickness is 2 nm, and it decreases with further increase in the thickness. When the photocatalytic reaction time is 15 min, the LOC device with a 2-nm-thick gold layer and autoclave exhibit similar TP pretreatment performance. Therefore, the proposed LOC device based on photocatalysis technology can address the limitation of conventional autoclave equipment, such as large volume, long processing time, and high cost, thereby satisfying the growing demand for on-site evaluation.

Heterosis plays a significant role in enhancing variety, boosting yield, and raising economic value, but the molecular mechanism is still unclear. We analyzed the transcriptomes and 3D genomes of hybrid (F1) and its parents (w30 and 082). Analysis of the expression revealed a total of 485 specially expressed genes (SEGs), 173 differentially expressed genes (DEGs) above parental expression level, more actively expressed genes and up-regulated DEGs in F1. Further study revealed that the DEGs detected in F1 and its parents were mainly involved in response to auxin, plant hormone signal transduction, DNA metabolic process, Purine metabolism, starch and sucrose metabolism, which suggested that these biological processes may play a crucial role in the heterosis of B. rapa. The analysis of 3D genome data revealed that hybrid F1 tend to contain more transcriptionally active A compartments after hybridization. Additionally, F1 had a smaller TAD (topologically associated domain) genome length, but the number was the highest, and the expression change of activated TAD was higher than repressed TAD. More specific TAD boundaries were detected between parents and F1. Subsequently, 140 DEGs with genomic structural variants were selected as potential candidate genes. Among them, we found two DEGs with consistent expression changes in A/B compartments and TADs. Our findings suggest that genomic structural variants, such as TADs and A/B compartments, may affect gene expression and contribute to heterosis in B. rapa. This study provides further insight into the molecular mechanism of heterosis in B. rapa.

The acute phase protein Serum Amyloid A (SAA) is synthesised by the liver in response to inflammatory stimuli. Previous studies have revealed that SAA may be a better predictive marker for the course of inflammatory bowel disease (IBD) compared to C-reactive protein (CRP). Hence, this retrospective monocentric study evaluated whether SAA correlates with biomarkers like faecal calprotectin (FC), CRP, the Neutrophil to Lymphocyte ratio (NLR) and clinical disease activity of IBD patients. Serum samples from the IBD outpatient clinic of the University Hospital Heidelberg were analysed for their SAA concentrations if a FC concentration measurement was available from 14 days before or after collection of the serum sample. 306 serum samples from 265 patients (166 with Crohn’s disease, 91 with ulcerative colitis, 8 with IBD unclassified) met the inclusion criteria. There was a significant positive correlation between SAA and FC, CRP, the NLR and the Simple Clinical Colitis Activity Index. The cut-off for SAA serum concentration at 4.55 mg/l achieved a sensitivity of 57.5% and a specificity of 69.7% for the detection of active inflammation in IBD. SAA may be used as an additional biomarker in the disease monitoring strategy of IBD patients, especially in patients with low CRP concentrations.

Audio recording in classrooms is a common practice in educational research, with applications ranging from detecting classroom activities to analysing student behaviour. Previous research has employed neural networks for classroom activity detection and speaker role identification. However, these recordings are often affected by background noise that can hinder further analysis, and the literature has only sought to identify noise with general filters and not specifically designed for classrooms. Although the use of high-end microphones and environmental monitoring can mitigate this problem, these solutions can be costly and potentially disruptive to the natural classroom environment. In this context, we propose the development of a neural network model that can specifically detect and filter out background noise in classroom recordings. This model would allow the use of lower quality recordings without compromising analysis capability, thus facilitating data collection in natural educational environments and reducing the costs associated with high-end recording equipment.

Clarifying the impact mechanism of digital transformation of enterprises on the M&A efficiency of listed companies can provide a factual basis for improving capital market regulatory policies. Taking the mergers and acquisitions of listed companies from 2007 to 2021 as a research sample, the influence mechanism of the digital transformation degree of companies on their M&A efficiency was studied. The research results show that the digital transformation of listed companies will improve their M&A efficiency. Digital transformation will reduce the degree of mispricing of stocks of M&A companies, curb conflicts between managers and agents of M&A companies, and improve their M&A efficiency. Further research finds that the promotion effect of digital transformation on M&A efficiency is more significant in non-state-owned companies, with a higher degree of financing constraint and high analyst attention. In the future, regulatory authorities should actively promote the digital transformation of listed companies, curb mispricing and management agency problems in the capital market with digital governance, and improve the efficiency of mergers and acquisitions in the capital market.

There has been considerable progress in implicit neural representation to upscale an image to any arbitrary resolution. However, existing methods are based on defining a function to predict the RGB value from just four specific loci. Relying on just four loci is insufficient as it leads to losing fine details from the neighboring region(s). We show that by taking into account the semi-local region leads to an improvement in performance. In this paper, we propose applying a new technique called Overlapping Windows on Semi-Local Region (OW-SLR) to an image to obtain any arbitrary resolution by taking the coordinates of the semi-local region around a point in the latent space. This extracted detail is used to predict the RGB value of a point. We illustrate the technique by applying the algorithm to the Optical Coherence Tomography-Angiography (OCT-A) images and show that it can upscale them to random resolution. This technique outperforms the existing state-of-the-art methods when applied to the OCT500 dataset. OW-SLR provides better results for classifying healthy and diseased retinal images such as diabetic retinopathy and normals from the given set of OCT-A images. The project page is available at https://rishavbb.github.io/ow-slr/index.html

Tamanu oil has traditionally been used to treat various skin problems. The oil has wound-healing and skin-regenerating capabilities, and encourages the growth of new skin cells, all of which are helpful for fading scars and hyperpigmentation, as well as promoting an all-around glow. The strong nutty odor and high viscosity are the major disadvantages associated with their application. The aim of this study was to create bigels using tamanu oil for its anti-scarring properties. Bigels were prepared with Tamanu oil ranging from 5 to 20% along with micronized xanthan gum and evaluated for their pH, viscosity, and spreadability. In silico studies were performed to analyze the binding affinity of the protein with the drug, and the anti-scarring activity was established using a full-thickness excision wound model. In silico studies have reported that the components Calanolide A, Inophyllum C, and 4-Norlanosta-17(20),24-diene-11,16-diol-21-oic acid, and 3-oxo-16,21-lactone had docking scores of -9.8, -11.3, and -11.1, respectively with the cytokine TGF- β1 receptor. An acute dermal irritation study in rabbits showed no irritation, erythema, eschar, or edema. In vivo excisional wound healing studies performed on wistar rats and subsequent histopathological studies showed that bigels had better healing properties when compared to the commercial formulation (Murivenna oil). This study substantiates the wound healing and scar reduction potential of Tamanu oil bigels.

Choosing a college major is a crucial issue for twelfth-grade students. Many students feel confused and influenced by their surroundings when making this decision. This can have negative consequences if it does not align with the students interests and talents. This research proposes a web application as a solution, providing introductory information for each major. We employed a design and developement approach to create an application that assists prospective students in identifying majors based on their interests. The primary objective is to alleviate students discomfort during their studies, which often leads to decreased performance. With this application, students can avoid selecting majors solely due to peer pressure or parental coercion.

A pandemic happens when a novel influenza A virus is able to infect and transmit efficiently to a new, distinct host species. Although the exact timing of pandemics is uncertain, it is known that both viral and host factors play a role in their emergence. Species-specific interactions between the virus and the host cell determine the virus tropism. These include binding and entering cells, replicating the viral RNA genome within the host cell nucleus, assembling, maturing, and releasing the virus to neighbouring cells, tissues, or organs before transmitting it between individuals. Influenza has a vast and antigenically varied reservoir. In wild aquatic birds, the infection is typically asymptomatic. Avian influenza virus (AIV) can cross into new species, and occasionally, it can acquire the ability to transmit from human to human. A pandemic might occur if a new influenza virus acquires enough adaptive mutations to maintain transmission between people. This review highlights the key determinants AIV must achieve to initiate a human pandemic and describes how AIV mutates to establish tropism and stable human adaptation. Understanding the tropism of AIV may be crucial in preventing virus transmission in humans and may help design vaccines, antivirals and therapeutic agents against the virus.

Fabry disease is a lysosomal storage disorder caused by the deficiency of the α-galactosidase-A enzyme. Cardiac, renal, and neurological involvement significantly reduces life expectancy. Until a few years ago, treatment options for Fabry disease were limited to enzyme replacement therapy with agalsidase alfa or beta administered by intravenous infusion every 2 weeks. Migalastat (Galafold®) is an oral pharmacological chaperone that increases enzyme activity of “amenable” mutations. The safety and efficacy of migalastat were supported in the phase III FACETS and ATTRACT studies, compared to available enzyme replacement therapies; showing a reduction in left ventricular mass, and stabilization of kidney function and plasma Lyso-Gb3. Similar results were confirmed in subsequent extension publications, both in patients who started migalastat as their first treatment and in patients who were previously on enzyme replacement therapy and switched to migalastat. In this review we describe the safety and efficacy of switching from enzyme replacement therapy to migalastat in patients with Fabry disease and “amenable” mutations, referring to publications available to date.

Neurological / neurovascular disorders constitute the leading cause of disability and second leading cause of deaths in the world. Some of the major neurological / neurovascular disorders or diseases include stroke, Alzheimer’s disease, spinal cord injury, neonatal hypoxic-ischemic encephalopathy, etc. Their pathophysiology is considered as highly complex and has been blamed as the main obstacle in the development of any drugs for these diseases. In this review, we have described the endothelin system, their involvement in neurovascular disorders, importance of endothelin B receptors (ETBRs) as a novel potential drug target, and its agonism by IRL-1620 (INN - sovateltide), which we are developing as a drug candidate for treating the above-mentioned neurological disorders / diseases. We have highlighted the results of our pre-clinical and clinical studies related to these diseases. The phase I, safety and tolerability study of sovateltide has shown it as a highly safe and well tolerable compound at tested dosages, while pre-clinical and clinical phase II studies have demonstrated its efficacy in treating acute ischemic stroke, where it is currently being developed as a “First in Class” drug. Its testing in Alzheimer’s disease (AD), acute spinal cord injury and neonatal hypoxic-ischemic encephalopathy (HIE) is currently being carried out and are at different stages of drug development. Successful completion of these studies will prove the involvement of ETBRs signaling in neurological / neurovascular diseases and help in development of novel neurological drugs in future.

The number of aged individuals is increasing worldwide, rendering essential the comprehension of pathophysiological mechanisms of age-related alterations, that could facilitate the development of interventions contributing to “successful aging” and improvement of quality of life. Cardio-vascular diseases (CVD) include pathologies affecting heart or blood vessels, such as hyperten-sion, peripheral artery disease and coronary heart disease. Indeed, age-associated modifications in body composition, hormonal, nutritional and metabolic factors, as well as a decline in physical activity are all involved in the increased risk of developing atherogenic alterations raising the risk of CVD development. Several factors have been claimed to play a role in the alterations observed in muscle and endothelial cells and leading to increased CVD, such as genetic pattern, smoking, unhealthy lifestyle. Moreover, a difference in the risk of these diseases in women and men has been reported. Interestingly, in the last decades attention has been focused on a potential role of several pollutants which disrupt human health by interfering with hormonal pathways, and more specifically in non-communicable diseases such as obesity, diabetes and CVD. This review will focus on the potential alteration induced by Endocrine Disruptors (Eds) in the attempt to characterize a potential role in the cellular and molecular mechanisms involved in the atheromatic process and CVD progression.

Droplet epitaxy allows the efficient fabrication of a plethora of 3D, III-V-based nanostructures on different crystalline orientations. Quantum dots grown on (311)A-oriented surface are obtained with record surface density, with or without a wetting layer. These are appealing features for quantum-dot lasing, thanks to the large density of quantum emitters and a truly 3D lateral confinement. However, the intimate photophysics of this class of nanostructures has not yet been investigated. Here we address the main optical and electronic properties of s-shell excitons in individual quantum dots grown on (311)A substrates with photoluminescence spectroscopy experiments. We show the presence of neutral exciton and biexciton as well as positive and negative charged excitons. We investigate the origins of spectral broadening, identifying them in spectral diffusion at low temperature and phonon-interaction at higher temperature, the presence of fine interactions between electron and hole spin, and a relevant heavy-hole/light-hole mixing. We interpret the level filling with a simple Poissonian model reproducing the power excitation dependence of the s-shell excitons. These results are relevant for the further improvement of this class of quantum emitters and their exploitation as single photon sources for low density samples as well as for efficient lasers for high density samples.

SARS-CoV2 RNA depended RNA polymerase is an essential enzyme for the survival of the virus in hosts as it helps in the replication of viral RNA. There are no human polymerases that share either sequence or structural homology with viral RNA depended RNA polymerase. These make it a good target for inhibitor discovery, as a specific inhibitor cannot cross-react with the human polymerases. We have used virtual screening, docking, binding energy calculation and simulation to show that valproic acid Co-A, a metabolite from prodrug valproic acid, forms stable interaction with nsP12 of CoV. Our results suggest valproic acid Co-A could be a potential inhibitor of nsP12 of SARS-CoV2.

Microfluidics is facing critical challenges in the quest of miniaturizing, integrating, and automating in vitro diagnostics, including the increasing complexity of assays, the gap between the macroscale world and the microscale devices, and the diverse throughput demands in various clinical settings. Here a “3D extensible” microfluidic design paradigm that consists of a set of basic structures and unit operations was developed for constructing any application-specific assay. Four basic structures- check valve (in), check valve (out), double-check valve (in and out), and on-off valve, were designed to mimic basic acts in biochemical assays. By combining these structures linearly, a series of unit operations can be readily formed. We then proposed a “3D extensible” architecture to fulfill the needs of the function integration, the adaptive “world-to-chip” interface, and the adjustable throughput in the X, Y, and Z directions, respectively. To verify this design paradigm, we developed a fully integrated loop-mediated isothermal amplification microsystem that can directly accept swab samples and detect Chlamydia trachomatis automatically with a sensitivity one order higher than that of the conventional kit. This demonstration validated the feasibility of using this paradigm to develop integrated and automated microsystems in a less risky and more consistent manner.

The aim of this study is to provide a detailed strategy for Safe-by-Design (SbD) 3D printed lab-on-a-chip (LOC) device manufacturing, using Fused Filament Fabrication (FFF) technology. At first, the applicability of FFF in lab-on-a-chip device development is briefly discussed. Subsequently, a methodology to categorize, identify and implement SbD measures for FFF is suggested. Furthermore, the most crucial health risks involved in FFF processes are examined, placing the focus on the examination of ultrafine particle (UFP) and Volatile Organic Compound (VOC) emission hazards. Thus, a SbD scheme for lab-on-a-chip manufacturing is provided, while also taking into account process optimization for obtaining satisfactory printed LOC quality. This work can serve as a guideline for the effective application of FFF technology for lab-on-a-chip manufacturing through the safest applicable way, towards a continuous effort to support sustainable development of lab-on-a-chip devices through cost-effective means.

This research work uses a simplified approach to combine location information from beacons propagation signal interaction with a mobile device with local building information to give real-time location and guidance to a user inside a building. This is an interactive process with visualisation information that can help user’s orientation inside unknown buildings and the data stored from different users can provide useful information about users movements inside a public building. Beacons installed on the building at specific pre-defined position emit signals that give a geographic position with an associated imprecision, related with Bluetooth’s range. This uncertainty is handled by building layout and users’ movement in a developed system that maps users’ position, gives guidance and store user movements. This system is based on an App (Find Me!) for Android OS (Operating System) which captures the Bluetooth Low Energy (BLE) signal coming from the beacon(s) and shows, through a map, the location of the user ‘s smartphone and guide him to the desired destination. Also, the beacons can deliver relevant context information. The application was tested by a panel of new and habitual campus users against traditional wayfinding alternatives yielding navigation times about 30% smaller, respectively.

Wireless sensor networks can provide a cheap and flexible infrastructure to support the measurement of noise pollution. However, the processing of the gathered data is challenging to implement on resource-constrained nodes, because each node has its own limited power supply, low-performance and low-power micro-controller unit and other limited processing resources, as well as limited amount of memory. We propose a sensor node for monitoring of indoor ambient noise. The sensor node is based on a hardware platform with limited computational resources and utilizes a number of simplifications to approximate more complex and costly signal processing stage. Furthermore, to reduce the communication between the sensor node and a sink node, as well as the power consumed by the IEEE 802.15.4 (ZigBee) transceiver, we perform digital A-weighting filtering and non-calibrated calculation of the sound pressure level on the node. According to experimental results, the proposed sound level meter can accurately measure the noise levels of up to 100~dB, with the mean difference of less than 2~dB compared to Class 1 sound level meter. The proposed device can continuously monitor indoor noise for several days. Despite the limitations of the used hardware platform, the presented node is a promising low-cost and low-power solution for indoor ambient noise monitoring.

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.

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.

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.

Stroke causes disability and significantly affects patient quality of life. Post-stroke rehabilitation of upper limb function is crucial, as it affects daily activities and individual autonomy. Traditional rehabilitation methods often require frequent visits to specialized centers, which can be costly and challenging. This study investigated the effectiveness of a home-based self-training device, "Kenko Yusuri," in improving upper limb function in patients with chronic stroke. This multicenter prospective intervention study used a quasi-randomized controlled trial design. Ninety-three outpatients from five hospitals in Japan were enrolled and assigned to either the intervention group who used the "Kenko Yusuri" device or the control group who underwent conventional rehabilitation. All patients received botulinum toxin type A (BoNT-A) injections to treat upper limb spasticity. The primary outcome measure was the Fugl-Meyer Assessment (FMA) of upper-extremity motor function. Secondary outcomes included the modified Ashworth scale (MAS) score, range of motion (ROM), and chronic pain assessments. The intervention group demonstrated significantly greater improvements in FMA total scores than the control group. Patients with moderate paralysis experienced the greatest benefits from the intervention. There were no significant between-group differences in MAS scores or ROM measurements. Pain and wrist ROM showed improvement in the intervention group. Home-based training with a shaking device significantly improved upper limb function in patients with moderate chronic post-stroke paralysis. This approach aligns with the principles of use-dependent plasticity and offers a feasible and cost-effective alternative to traditional rehabilitation methods.

Background: Vascular inflammation plays a crucial role in peripheral arterial disease (PAD), although the role of the mediators involved has not yet been properly defined. The aim of this work is to investigate gene expression and plasma biomarkers in chronic limb-threating ischemia (CLTI). Methods: Using patients from the GHAS trial, both blood and ischemic muscle samples were obtained to analyze plasma markers and mRNA expression, respectively. Statistical analy-sis was performed by using univariate (Spearman, t-Student, X2) and multivariate (multiple lo-gistic regression) tests. Results: 35 patients were available at baseline (29 for mRNA expression). Baseline characteristics (mean): Age:71.4±12.4 (79.4% male); TNF-α:10.7±4.9; hs-CRP:1.6±2.2; Neutrophil-to-lymphocyte ratio (NLR):3.5±2.8. Plasma TNF-α was found elevated (≥8.1) in 68.6% of patients, while high hs-CRP (≥0.5) in 60.5%. Diabetic patients with high level of inflammation showed significantly higher levels of NOX4 expression at baseline (p=0.0346). Plasma TNF-α had a negative correlation with eNOS expression (-0.5, p=0.015) and hs-CRP with VEGF-A (-0.63, p=0.005). The expression of NOX4 was parallel to that of plasma TNF-α (0.305, p=0.037), especial-ly in DM. Cumulative mortality at 12-month was related to NLR ≥3 (p=0.019) and TNF-α ≥8.1 (p=0.048). The best cut-off point for NLR to predict mortality was 3.4. Conclusions: NOX4 and TNF-α are crucial for the development and complications of lower limb ischemia, especially in DM. hs-CRP could have a negative influence on angiogenesis too. NLR and TNF-α represent suita-ble markers of mortality in CLTI. These results are novel because they connect muscle gene expres-sion and plasma information in patients with advanced PAD, deepening the search of new and ac-curate targets for this condition.

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.

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.

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.

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.

We propose a new theory beyond the standard model of elementary-particle physics. Employing the concept of a quantized spacetime, our theory demonstrates that the zero-point energy of the vacuum alone is sufficient to create all the fields, including gravity, the static electromagnetic field, and the weak and strong interactions. No serious undetermined parameters are assumed. Furthermore, the relations between the forces at the quantum-mechanics level is made clear. Using these relations, we quantize Einstein’s gravitational equation and explain the Dark Energy in our universe. Beginning with the zero-point energy of the vacuum, and after quantizing Newtonian gravity, we combine the energies of a static electromagnetic field and gravity in a quantum spacetime. Applying these results to the Einstein gravity equation, we substitute the energy density derived from the zero-point energy in addition to redefining differentials in a quantized spacetime. We thus derive the quantized Einstein gravitational equation without assuming the existence of macroscopic masses. This also explains the existence of the Dark Energy in the universe. For the weak interaction, by considering plane-wave electron and the zero-point energy, we obtain a wavefunction that represents a β collapse. In this process, from a different point of view than Weinberg-Salam theory, we derive the masses of the W and Z bosons and the neutrino, and we calculate the radius of the neutron. For the strong interaction, we previously reported an analytical theory for calculating the mass of a proton by considering a specific linear attractive potential obtained from the zero-point energy, which agrees well with the measurements. In the present study, we calculate the strong interaction between two nucleons, i.e., the mass of the pi-meson. The resulting calculated quantities agree with the measurements, which verifies our proposed theory.

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.

Water quality is the measure of chemical, physical and biological suitability of water in relation to natural effects and intended purpose which may affect human health and aquatic life. Assessment of water quality is very essential for the management of water resources and human health. Traditionally, in-situ measurements have been used to obtain the water quality parameters of the water bodies. However, with the availability of satellite images, researchers have shown that satellite images are a reliable tool that can be used to estimate water quality. Satellite image-derived water quality parameters provide extensive spatial extent and large temporal variations when compared to traditional in situ sample collection and laboratory measurements. The present work estimated several parameters for quality of water in the Kamuzu reservoir of Lilongwe River for the 2013-2020 period using Sentinel-2 and Landsat-8 satellite images. The band ratio algorithms were used to retrieve Chlorophyll a (Chl-a), Turbidity, Total Suspended Matter (TSM), Secchi depth, Coloured Dissolved Organic Matter (CDOM), and Cyanobacteria from the reservoir. Turbidity and TSM were compared with the in-situ data collected over the same period. The comparison indicated R² of 0.9 and 0.69 for TSM and Turbidity respectively from Sentinel-2 images whereas R² of 0.56 and 0.61 was obtained using Landsat 8 images which are quite encouraging. The other set of results included the spatial distribution maps of water quality parameters using Landsat-8 and Sentinel-2 satellite data. It was observed that the spatial distribution of water quality parameters, except for CDOM and Cyanobacteria, showed very good distribution and matches with the theoretical results. However, for CDOM and Cyanobacteria, the distribution was almost similar for the entire study area and the band ratio algorithm may not be able to estimate them quite reasonably. This research reiterates the need for the use of remote sensing in estimating the water quality parameters and may be a substitute to the in-situ data, in terms of spread and frequency, which is very common to most of the water bodies, across the globe.

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.

Migratory and local birds may disperse ticks and their associated pathogens. The aim of this study was to provide information regarding tick infesting birds in Asturias, region that accounts for most of the Lyme disease hospitalizations in Spain. From September 2021 and April 2023 trained and experienced bird- banders collected ticks from birds in six estuary and forest locations. A total of 1,698 birds (52 species, 38 genera and 26 families) were captured. A total 51 ticks (28 larvae, 20 nymphs and 3 females) were collected from 43 birds, belonging to three species: Ixodes ricinus (31), I. frontalis (18) and Haemaphysalis concinna (1). The average prevalence of tick infestation was 2.5% and the average tick burden was 1.2 ticks per host. The bird species Turdus merula, Parus major, Luscinia svecica and Anthus pratensis were among the most infested. Anaplasma phagocytophilum was detected from one Turdus merula. We have not detected B. burgdorferi s.l., Rickettsia spp., Coxiella burnetii or piroplasmids in any of the 51 analyzed ticks. The results of the study suggest low infestation rate in migratory/estuary birds and a higher rate in forest/sedentary ones. Despite this, the detection of pathogens, although with low prevalence, can pose a risk to public health.

In a context of exponential demographic growth, the imbalance between human resources and public health problems is impelling us to envision other solutions to the difficulties faced in the diagnosis, prevention and large-scale management of the most common diseases. Cardiovascular diseases represent the leading cause of morbidity and mortality worldwide. A large-scale screening program would make it possible to promptly identify patients with high cardiovascular risk in order to manage them adequately. Optical coherence tomography-angiography (OCT-A), as a window into the state of the cardiovascular system, is a rapid, reliable, and reproducible imaging examination that enables prompt identification of at-risk patients through the use of automated classification models. One challenge that limits the development of computer-aided diagnostic programs is the small number of open-source OCT-A acquisitions available. To facilitate the development of such models, we have assembled a set of images of the retinal microvascular system from 499 patients. It consists of 814 angiocubes as well as 2005 en face images. Angiocubes were captured with a swept-source OCT-A device of patients with varying overall cardiovascular risk. To the best of our knowledge, our dataset, RASTA, is the only publicly available dataset comprising such a variety of images from healthy and at-risk patients. This dataset will enable the development of generalizable models for screening of cardiovascular diseases from OCT-A retinal images.

Coordination of cellular biological processes is regulated in part via metabolic enzymes acting to match cellular metabolism to current conditions. The acetate activating enzyme, acyl-coenzyme A synthetase short-chain family member 2 (Acss2) has long been considered to have a predominantly lipogenic function. More recent evidence suggests that this enzyme has regulatory functions in addition to its role in providing acetyl-CoA for lipid synthesis. We used Acss2 knockout mice (Acss2-/-) to further investigate the roles this enzyme plays in three physiologically distinct organ systems that make extensive use of lipid synthesis and storage including the liver, brain and adipose tissue. We examined the resulting transcriptomic changes resulting from Acss2 deletion and assessed these changes in relation to fatty acid constitution. We find that loss of Acss2 leads to dysregulation of numerous canonical signaling pathways, upstream transcriptional regulatory molecules, cellular processes, and biological functions, which were distinct in the liver, brain and mesenteric adipose tissues. The detected organ-specific transcriptional regulatory patterns reflect the complementary functional roles of these organ systems within the context of systemic physiology. While alterations in transcriptional states were evident, the loss of Acss2 resulted in few changes in fatty acid constitution in all three organ systems. Overall, we demonstrate Acss2 loss institutes organ-specific transcriptional regulatory patterns reflecting the complementary functional roles of these organ systems. Collectively, these findings provide further confirmation that Acss2 regulates key transcription factors and pathways under well-fed, non-stressed conditions, and acts as a transcriptional regulatory enzyme.

Imidazo[1,2-a]pyridines have been studied regarding drug development. The objective of this work was to evaluate the antileukemic capacity of imidazo[1,2-a]pyridine derivatives by screening its ability as a pro-oxidant. Imidazo[1,2-a]pyridine derivatives were synthesized and oral bioavailability and toxicity were analyzed in silico. Redox screening was performed on human Kasumi, KG-1, K562 and Jurkat leukemia cells. The imidazo[1,2-a]pyridine derivative and the most responsive leukemic cell were selected for cytotoxicity, cell proliferation, cell senescence and oxidative stress assays. The predictive toxicity analysis showed a possible effect on the reproductive system, but without mutagenic, carcinogenic or irritability effects. MRK-107 against K562 cells was the compound that showed the best redox profile. MRK-107 did not induce cell death in K562 and monocyte cells. However, this compound was able to decrease cell proliferation and increase cell senescence after 48 and 72 hours. Furthermore, MRK-107 induced oxidative stress in K562 cells after 72h, increasing lipid peroxidation and decreasing reduced glutathione (GSH) contents. This study demonstrated that MRK-107-induced senescence with the involvement of oxidative stress as a possible mechanism of action, addressing this compound as a potential antitumor drug against chronic myeloid leukemia.

Mycotoxins are deleterious fungal secondary metabolites that contaminate food and feed, thereby creating concerns regarding food safety. Common fungal genera can easily proliferate in Indian tropical and sub-tropical conditions, and scientific attention is warranted to curb its growth. To address this, two nodal governmental agencies, namely the Agricultural and Processed Food Products Export Development Authority (APEDA) and Food Safety and Standards Authority of India (FSSAI), have developed and implemented analytical methods and quality control procedures to monitor mycotoxin levels in a range of food matrices and assess risks to human health over the past two decades. However, comprehensive information on such advancements in mycotoxin testing and issues in implementing these regulations is inadequately covered in recent literature. The aim of this review is thus to uphold a systematic picture of the role played by the FSSAI and APEDA for mycotoxin control at the domestic level and for the promotion of international trade along with certain challenges in dealing with mycotoxin monitoring. Additionally, it unfolds various regulatory concerns regarding mycotoxin mitigation in India. Overall, it provides valuable insights to the Indian farming community, food supply chain stakeholders, and researchers about India’s success story in arresting mycotoxins throughout the food supply chain.

We recently proposed that topological quantum computing might be based on $SL(2,\mathbb{C})$ representations of the fundamental group $\pi_1(S^3\setminus K)$ for the complement of a link $K$ in the $3$-sphere. The restriction to links whose associated $SL(2,\mathbb{C})$ character variety $\mathcal{V}$ contains a Fricke surface $\kappa_d=xyz -x^2-y^2-z^2+d$ is desirable due to the connection of Fricke spaces to elementary topology. Taking $K$ as the Hopf link $L2a1$, one of the three arithmetic two-bridge links [the Whitehead link $5_1^2$, the Berge link $6_2^2$, the double-eight link $6_3^2$] or the link $7_3^2$, the $\mathcal{V}$ for those links contains the reducible component $\kappa_4$, the so-called Cayley cubic. In addition, the $\mathcal{V}$ for the later two links contains the irreducible component $\kappa_3$, or $\kappa_2$, respectively. Taking $\rho$ to be a representation with character $\kappa_d$ ($d<4$), with $|x|,|y|,|z| \le 2$, then $\rho(\pi_1)$ fixes a unique point in the hyperbolic space $\mathcal{H}_3$ and is conjugate to a $SU(2)$ representation (a qubit). Even though details on the physical implementation remain open, more generally, we show that topological quantum computing may be developed from the point of view of three-bridge links, the topology of the $4$-punctured sphere and Painlev\'e VI equation. The $0$-surgery on the $3$ circles of the Borromean rings L6a4 is taken as an example.

BPA is a commonly used compound in many industries and has versatile applications in polycarbonate plastics and epoxy resins production. BPA is classified as endocrine-disrupting chemical which can hamper fetal development during pregnancy and may have long term negative health outcomes in humans. Dietary sources, main route of BPA exposure, can be contaminated by the migration of BPA into food during processing. The global regulatory framework for using this compound in food contact materials is currently not harmonized. This review aims to outline, survey, and critically evaluate BPA contamination in meat products, including level of BPA and/or metabolites present, exposure route, and recent advancements in the analytical procedures of these compounds from meat and meat products. The contribution of meat and meat products to the total dietary exposure of BPA ranges between 10 and 50% depending on the country and exposure scenario considered. From can lining materials of meat products, BPA migrates towards the solid phase resulting higher BPA concentration in solid phase than the liquid phase of the same can. The analytical procedure is comprised of meat sample pre-treatment, followed by cleaning with SPE, and chromatographic analysis. Considering several potential sources of BPA in industrial and home culinary practices, BPA can also accumulate in non-canned or raw meat products. Very few scientific studies have been conducted to identify the amount in raw meat products. Similarly, analysis of metabolites and identification of the origin of BPA contamination in meat products is still a challenge to overcome.

RNA editing involves the insertion, deletion or substitution of single nucleotides within a RNA molecule, without altering the DNA sequence. Adenosine to inosine (A-to-I) editing consists of an RNA modification where single adenosines along the RNA sequence are converted into inosines. Such a biochemical transformation is catalyzed by enzymes belonging to the family of adenosine deaminases acting on RNA (ADARs) and occurs either co- or post-transcriptionally. Initially, the A-to-I RNA editing phenomenon was discovered and studied in messenger RNAs (mRNAs), where it can influence RNA splicing and cause the recoding of codon sequences. The employment of more powerful, high-throughput detection methods has recently revealed that A-to-I editing widely occurs in non-coding RNAs, including microRNAs (miRNAs). MiRNAs are a class of small regulatory non-coding RNAs (ncRNAs) acting as translation inhibitors, known to exert relevant roles in controlling cell cycle, proliferation, and cancer development. Indeed, a growing number of recent researches have evidenced the importance of miRNA editing in cancer biology by exploiting various detection and validation methods. Herein, we briefly overview early and currently available A-to-I miRNA editing detection and validation methods and discuss the significance of A-to-I miRNA editing in human cancer.

Cloud-based CNC is an emerging paradigm of Industry 4.0 where computer numerical control (CNC) functionalities are moved to the cloud and provided to manufacturing machines as a service. Among many benefits, C-CNC allows manufacturing machines to leverage advanced control algorithms running on cloud computers to boost their performance at low cost, without need for major hardware upgrades. However, a fundamental challenge of C-CNC is how to guarantee safety and reliability of machine control given variable Internet quality of service, especially on public Internet networks. We propose a three-tier redundant architecture to address this challenge. We then prototype tier one of the architecture on a 3D printer successfully controlled via C-CNC over public Internet connections, and discuss follow-on research opportunities.

The accurate virus detection, strain discrimination, and source attribution of contaminated food items remains a persistent challenge because of the high mutation rates anticipated to occur in foodborne RNA viruses, such as Hepatitis A virus (HAV). This has led to predictions of the existence of more than one sequence variant between the hosts (inter-host) or within an individual host (intra-host). However, there have been no reports of intra-host variants from an infected single individual, and little is known about the accuracy of the single nucleotide variations (SNVs) calling with various methods. In this study, the presence and identity of viral SNVs, either between HAV clinical specimens or among a series of samples derived from HAV clone1-infected FRhK4 cells, were determined following analyses of nucleotide sequences generated using next-generation sequencing (NGS) and pyrosequencing methods. The results demonstrate the co-existence of inter- and intra-host variants both in the clinical specimens and the cultured samples. The discovery and confirmation of multi-viral RNAs in an infected individual is dependent on the strain discrimination at the SNV level, and critical for successful outbreak traceback and source attribution investigations. The detection of SNVs in a time series of HAV infected FRhK4 cells improved our understanding on the mutation dynamics determined probably by different selective pressures. Additionally, it demonstrated that NGS could potentially provide a valuable investigative approach toward SNV detection and identification for other RNA viruses.

Crosslinking of proteins for their irreversible immobilization on surfaces is a proven and popular method. However, many protocols lead to random orientation and the formation of undefined or even inactive by-products. Most concepts to obtain a more targeted conjugation or immobilization requires the recombinant modification of at least one binding partner, which is often impractical or prohibitively expensive. Here a novel method is presented, which is based on the chemical preactivation of Protein A or G with selected conventional crosslinkers. In a second step, the antibody is added, which is subsequently crosslinked in the Fc part. This leads to an oriented and covalent immobilization of the immunoglobulin with a very high yield. Protocols for Protein A and Protein G with murine and human IgG are presented. This method may be useful for the preparation of columns for affinity chromatography, immunoprecipitation, antibodies conjugated to magnetic particles, permanent and oriented immobilization of antibodies in biosensor systems, microarrays, microtitration plates or any other system, where the loss of antibodies needs to be avoided, and maximum binding capacity is desired. This method is directly applicable even to antibodies in crude cell culture supernatants, raw sera or protein-stabilized antibody preparations without any purification nor enrichment of the IgG. This new method delivered much higher signals as a traditional method and, hence, seems to be preferable in many applications.

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.

The escalation of mining activities in the karst regions of Guizhou Province has heightened the occurrence of water-inrush incidents in deep coal mines. This study focused on water-inrush phenomena within the Xinhua mining area of Jinsha County, Guizhou Province, aiming to investigate the sources of these incidents. The findings indicated that the overlying limestone of the Changxing Formation in the coal seam served as a vulnerable aquifer under certain conditions, leading to water inrushes. The analysis of the spatiotemporal distribution patterns of water-inrush incidents at the working face indicated that previous mining operations damaged the shallow Changxing Formation limestone, resulting in the accumulation of goaf water and the formation of numerous mining-induced fractures. These fractures served as rapid conduits for water inrushes from both atmospheric precipitation and underground sources at the deep working face. The examination of surface water and mine water quality demonstrated that both exhibited similar characteristics, predominantly featuring bicarbonate, sulfate, and sodium compositions. Investigation into the relationship between mine water inflow and atmospheric precipitation established that atmospheric precipitation influenced the mine water supply cycle, with a replenishment period of ~10 months during the operational phase of the Jinyuan Coal Mine and about one month post-closure. The fractures induced by mining activities within the Changxing Formation limestone facilitated water flow, with atmospheric precipitation serving as the primary water source for the mine. This study offered a valuable scientific foundation for addressing water-related damage resulting from atmospheric precipitation in mines susceptible to water inrushes under analogous hydrogeological conditions.

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.

Specific proteolytic cleavages turn on, modify, or turn off the activity of vascular endothelial growth factors (VEGFs). Proteolysis is most prominent among the lymph­angiogenic VEGF-C and VEGF-D, which are synthesized as precursors that need to undergo enzymatic removal of their C- and N-terminal propeptides before they can activate their receptors. The activating cleavage of VEGF-C is mediated by at least five different proteases: plasmin, ADAMTS3, prostate-specific antigen, cathepsin D, and thrombin. All of these proteases except for ADAMTS3 can also activate VEGF-D. Processing by different proteases results in distinct forms of the "mature" growth factors, which differ in affinity and receptor activation potential. The “default” VEGF-C-activating enzyme ADAMTS3 does not activate VEGF-D and therefore, VEGF-C and VEGF-D do function in different contexts. VEGF-C itself is also regulated in different contexts by different proteases. During embryonic development, ADAMTS3 activates VEGF-C. In contrast, thrombin and plasmin likely activate VEGF-C/-D during tissue injury-induced lymphangiogenesis, and PSA and cathepsin D perhaps during tumor-associated pathological lymphangio­genesis. Additionally, cathepsin D from saliva might activate latent VEGF-C/-D upon wound licking, thereby accelerating healing. Similar to tyrosine kinase receptors and VEGFs themselves, these activating proteases could be targeted to modulate angiogenesis and lymphangiogenesis in relevant diseases.

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.

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).

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.

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.

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.

Plant viral nanoparticles (VNPs) are attractive to researchers in nanomedicine due to their safety, easy production, resistance, and straightforward functionalization. In this paper, we developed and successfully purified a VNP derived from turnip mosaic virus (TuMV), a well-known plant pathogen, that exhibits high affinity for immunoglobulins G (IgG) thanks to its functionalization with the Z domain from staphylococcal protein A via gene fusion. We selected cetuximab as a model IgG to prove the versatility of this novel TuMV VNP by developing a fluorescent nanoplatform to mark tumoral cells of the line Cal33, from tongue squamous cell carcinoma. We observed that the fluorescent VNP-cetuximab bound selectively to Cal33 and were internalized by confocal microscopy, revealing the potential of this nanotool in cancer research.

Aim. The analysis of incidence, clinical and morphological manifestations, and the prognosis of IgA nephropathy in the Northeastern Europe (NEE). Materials and methods. We enrolled cases with primary IgA nephropathy (IgAN) from 2005 to 2020 in the single-center retrospective study. Demographic and clinical parameters, histology data, and the treatment were analyzed. The outcomes were the occurrence of complete (PR) or partial remission (CR), renal replacement therapy (RRT), eGFR<15 ml/min/1.73m² and eGFR decrease ≥ 50%. The composite endpoint included all renal outcomes and was used to evaluate the risk of IgAN progression and associated factors. Results. The incidence of IgAN cases was 23.6% of all indication biopsies and 41.2% of primary immune glomerulopathies. At the time of the kidney biopsy, the proteinuria was 2.5 (1.5-5.0) g/24h, eGFR - 69 ± 32 ml/min/1.73 m². Proportions of cases with arterial hypertension and eGFR <60 ml / min / 1.73 m² were 75% and 36%, respectively. The prevalence of histological changes in accordance with the Oxford (MEST-C) classification was M1 - 40.5%, E1 -22.9%, S1-70.2%, T1-22%, T2 - 9%, C1-16.7%, C2 - 4.4%. In the follow-up of 27 (11; 61) months, 6 deaths occured (1.7%). The 10-year cumulative dialysis-free survival was 80% and progression-free survival was 56%. Remissions registered in 50% of cases, being more frequent in patients who received immunosuppression vs renoprotection (60% vs. 40%, p = 0.001). In multivariable Cox regression, the independent factors associated with the increased probability of IgAN progression were male gender, a younger age, higher blood pressure and hematuria, lower eGFR, interstitial fibrosis/ tubular atrophy (≥50%), the presence of peritubular capillaritis and any crescents. Compared to the cohorts of other ethnic or geographical origin, IgAN in the studied cohort were found to have more severe clinical and morphological presentations and faster progression rate. Conclusion. Being the most common glomerulopathy in the NEE population, IgAN has more pronounced clinical and morphological presentations. Considering the distinctive features of the disease, further research is warranted in order to establish approaches for enhancing risk stratification and treatment efficacy.

An ultraviolet (UV) nanosecond pulsed laser with a wavelength of 355 nm was applied to anneal amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistors (TFT) at various laser beam powers ranging from 0 to 280 mW. Laser irradiation was selectively carried out on the a-IGZO channel area using the beam scanning method after the a-IGZO TFT was formed through indium-tin oxide (ITO) electrode patterning and a subsequent lift-off process. After laser annealing, negative shifts in the threshold voltages and enhanced on-currents were observed at laser-beam powers ranging from 54 to 120 mW. No meaningful parameters were investigated for laser beams higher than 200 mW. By extracting the energy band gap and work function of a-IGZO from the transmittance and ultraviolet photoelectron spectroscopy (UPS) results, the ITO electrode/a-IGZO channel energy band structures were established under different laser annealing conditions, and the electron injection mechanism from the ITO to the a-IGZO channel was analyzed and optimized at a laser beam power of 120 mW. The results show that the electrical characteristics of the a-IGZO TFTs can be improved without any heat damage to the substrate because of the selective annealing process.

Weak contact metric structures on a smooth manifold, introduced by V. Rovenski and R. Wolak in 2022, have provided new insight into the theory of classical structures. In this paper, we define new structures of this kind (called weak nearly Sasakian and weak nearly cosymplectic and nearly K\"{a}hlerian structures) and study their geometry. We introduce weak nearly K\"{a}hlerian manifolds (generalizing nearly K\"{a}hlerian manifolds) and characterize weak nearly Sasakian and weak nearly cosymplectic hypersurfaces in such Riemannian manifolds.

In this contribution, we make an attempt to write a theoretical proposal for designing an eco friendly thermal power plant which runs with cold nuclear fusion technology at a temperature of (1500 to 2000) deg.C. In our recently published papers, we have proposed a clear cut mechanism for understanding and implementing cold nuclear fusion technique pertaining to fusion of hydrogen with metals of mass numbers starting from 50. In this context, we would like to stress the point that, fusion of hydrogen under controllable temperature and pressure can be understood as a phenomenon of fusing neutron to the nucleus of the base atom. Part of isotopic nuclear binding energy difference of final and base atomic nuclides can be seen in the form of safe thermal energy of the order of (1 to 3) MeV per atom against 200 MeV released in nuclear fission of one Uranium atom. Due to increased heaviness and weak interaction, sometimes fused neutron splits into proton and electron. Proton seems to be retained by the base atom’s nuclear core and electron seems to join with the electronic orbits of the base atom. In this way, increased mass of base atomic nuclide helps in eco friendly production of thermal energy in large quantity. For this purpose we consider Iron-56 as a fuel. In a simplified view, under strong nuclear attractive forces, Iron-56 absorbs hydrogen atom as a neutron and by emitting 1MeV equivalent thermal energy transforms to Iron-57. Thus, one gram of Iron-56 can generate 1000MJ of heat with 50% efficiency. In a shortcut approach, by bombarding powder and semi-liquid forms of Iron-56 with direct neutrons coming from neutron source, our proposal can be tried, understood and verified experimentally.

In developing countries today, population growth and the penetration of higher standard of living appliances in homes has resulted in a rapidly increasing residential load. In South Africa, the recent rolling blackouts and electricity price increase only highlighted this reality calling for sustainable measures to reduce the overall consumption and peak load. The dawn of the smart grid concept, embedded systems and ICTs have paved the way to novel HEMS design. In this regard, the Internet of Things (IoT), an enabler for smart and efficient energy management systems is seeing increasing attention for optimizing HEMS design and mitigate its deployment cost constraints. In this work, we propose an IoT platform for residential energy management applications focusing on interoperability, low-cost, technology availability and scalability. We focus on the backend complexities of IoT Home Area Networks (HAN) using the OCF IoTivity-Lite middleware. To augment the quality, servicing and reduce cost and complexities, this work leverages open-source Cloud technologies from Back4App as BaaS to provide consumer and Utilities with a data communication platform within an experimental study illustrating time and space agnostic “mind-changing” energy feedback, Demand Response Management (DRM) and appliance operation control via a HEM App via an Android smartphone.