Artificially designed, chimeric peptide-based recombinant vaccines are novel approaches to combat the phylogenetically diverse Foot and Mouth Disease (FMD) Virus (FMDV) strains. Among seven distinct serotypes, only serotype O and A are dominantly circulating in Bangladesh and neighbouring countries of Asia, where transboundary transmission, recurrent outbreaks and emergence of novel lineages FMDV are highly prevalent. The objective of this study was to develop multi-epitope recombinant peptides, procuring immunogenicity against circulating diverse subtypes of FMDV serotype O and A. Two chimeric peptides, named B1 (41.0 kDa) and B3 (39.3 kDa), have been designed to incorporate potential B-cell and T-cell epitopes selected from multiple FMDV strains, including previously reported and newly emerged sub-lineages. After expression, characterization and immunization of guineapigs with considerable antigen load of B1 and B3 followed by the serological assays revealed the significant protective immunogenicity, developed from the higher (100 µg) doses of both antigens, against most of the currently prevalent serotype O and A strains of FMDV. The efficient expression, antigenic stability, and multivalent immunogenic potency of the chimeric peptides strongly indicate their credibility as novel vaccine candidates for FMDV serotypes O and A circulating in Bangladesh and surrounding territories.

In this paper, impulsive control on a single-species Markovian jumping ecosystem leads to a stability criterion, and the newly-obtained theorems improve the related existing results. Numerical examples illuminate the effectiveness.

Current, application-driven trends towards larger-scale integration (LSI) of microfluidic systems for comprehensive assay automation and multiplexing pose significant technological and economical challenges to developers. By virtue of their intrinsic capability for powerful sample preparation, centrifugal systems have attracted significant interest in academia and business since the early 1990s. This review models common, rotationally controlled valving schemes at the heart of such “Lab-on-a-Disc” (LoaD) platforms to predict critical spin rates and reliability of flow control mainly based on geometries, location and liquid volumes to be processed, and their experimental tolerances. In absence of larger-scale manufacturing facilities during product development, the method presented here facilitates the provision of efficient simulation tools for virtual prototyping and characterization to greatly expedite design optimization according to key performance metrics. This virtual in silico approach thus significantly accelerates, de-risks and lowers costs along the critical advancement from idea, fluidic testing, bioanalytical validation and scale-up to commercial mass manufacture.

Polycyclic aromatic hydrocarbons (PAHs), which consist of low-molecular-weight PAHs (LMW-PAHs) and high-molecular-weight PAHs (HMW-PAHs), form an important class of pollutants. Pyrene and benzo[a]pyrene (BaP) are the main pollutants belonging to HMW-PAHs, and their degradation by microorganisms remains an important strategy for their removal from the environments. Extensive studies have been carried out on the isolation and characterisation of microorganisms that actively degrade LMW-PAHs, and to a certain extent, the HMW-PAH pyrene. However, so far, limited work has been carried out on BaP biodegradation. BaP consists of five fused aromatic rings, which confers this compound a high stability, rendering it less amenable to biodegradation. The current review summarizes the emerging reports on BaP biodegradation. More specifically, work carried out on BaP bacterial degradation and current knowledge gaps that limit our understanding of BaP degradation are highlighted. Moreover, new avenues of research on BaP degradation are proposed, specifically in the context of the development of “omics” approaches

In this paper it is shown that mathematical description of strain, constitutive law and dynamics obtained by direct replacement of integer order derivatives with Caputo or Riemann-Liouville fractional order partial derivatives, having integral representation on finite interval, in case of a guitar string, is nonobjective. The basic idea is that different observers, using this type of descriptions, obtain different results which cannot be reconciled, i.e. transformed into each other using only formulas that link the coordinates of the same point in two fixed orthogonal reference frames and formulas that link the numbers representing the same moment of time in two different choices of the origin of time measuring. This is not an academic curiosity! It is rather a problem: which one of the obtained results is correct?

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.

The article discusses the issue of the sustainable development of the cross-border market for cultural services in a city divided by the state border. The article uses the example of Cieszyn and Český Těšín, a city divided following the decision of the Council of Ambassadors in 1920. The research carried out so far indicates the main constraints in the harmonious functioning of the cross-border market for cultural services in this city, such as: different cultural policies implemented on both sides of the city, language barriers as well as legal and administrative differences. Therefore, the authors undertook research aimed at recognising the role of Euroregional structures in stimulating the sustainable development of this region. On the basis of the analysis of the Cieszyn Silesia Euroregion's documentation and the results of qualitative and quantitative research, the article describes the role of the Euroregion in building a cross-border market for cultural services. Recommendations were also prepared that could constitute the principles of a common cultural policy not only for Cieszyn and Český Těšín, but also for other European cities in the Schengen Area, which, like Cieszyn and Český Těšín, have been divided by a state border.

This study aimed to investigate the healing effect of advanced platelet-rich fibrin (A-PRF) clot membranes in the reduction of palatal wounds resulting from free gingival graft (FGG) harvesting, in the re-epithelization rate and in the pain experience after surgery. Twenty-five patients requiring soft tissue augmentation (gingival recession coverage or keratinized gingiva augmentation) participated in this prospective randomized clinical study. After FGG harvesting, the test group (n=14) received A-PRF clot membranes at the palatal wound and the control group (n=11) a gelatin sponge. Epithelialization rate of the palatal wound, wound healing area, correspondent percentage of reduction and post-surgical pain experience were assessed. The follow-up period was 90 days. There was a significantly higher reduction of the palatal wound area in the A-PRF group vs. the control group, at 7 (p<0.001), 14 (p=0.009) and 30 days (p<0.001) follow-up. The maximum difference between groups was attained at 30 days (91.5% for A-PRF vs. 59.0% for the control group). At 14 days a significant difference in the proportion of patients showing total epithelization was found: 64.3% for A-PRF vs. 9.1% for the control group (p=0.012). At 90 days, both groups showed total recovery. Overall, the control group experienced a higher level of pain and discomfort until the 14th day, being significantly higher on the second day (p=0.013). The results suggest that A-PRF membranes haste the healing process by promoting a greater reduction along the recovery period and an apparent less painful postoperative period.

Within the fields of English for Academic Purposes (EAP) and English for Research Publication Purposes (ERPP), there is an unquestioned orthodoxy that scholars with English as an Additional Language (EAL) are particularly disadvantaged by the pressure to publish in English (though see Kuteeva 2015 and debate between Hyland 2016a, 2016b and Politzer-Ahlesa et al. 2016). In this paper, I challenge this orthodoxy, raising questions about the evidence upon which it is based. Within a framework of ‘verbal hygiene’ (Cameron 1995, 2012), I will argue that the attention accorded to ‘non-nativeness’ may be disproportionate to its significance for publication success. I conclude by proposing some reorientations for researchers and practitioners in the field that centre on broadening the scope to encompass non-linguistic structures of inequity.

The misfolding and aggregation of proteins is the neuropathological hallmark of numerous diseases including Alzheimer’s disease, Parkinson’s disease, and prion diseases. It is believed that misfolded and abnormal -sheets forms of wild-type proteins are the vectors of these diseases by acting as seeds for the aggregation of endogenous proteins. Cellular prion protein (PrPC) is a glycosyl-phosphatidyl-inositol (GPI) anchored glycoprotein which is able to misfold to a pathogenic isoform PrPSc, the causative agent of prion diseases which present as sporadic, dominantly inherited and transmissible infectious disorders. Increasing evidence highlight the importance of prion-like seeding as a mechanism for pathological spread in Alzheimer’s disease and tauophaty, as well as other neurodegenerative disorders. Here, we report the latest findings on the mechanisms controlling protein folding, focusing on the ER quality control of GPI-anchored proteins and describe the “prion-like” properties of amyloid- and tau assemblies. Furthermore, we highlight the importance of pathogenic assemblies interactions with protein and lipid membrane components and their implications in both prion and Alzheimer’s diseases.

Motivated by the theoretical model of health insurance choice with Flexible Spending Accounts (FSAs) presented in Cardon 2012, this study investigates the determinants of optional coverage (SSP) and flexible spending accounts (FSA) enrollment, among the privately insured in post-affordable-care-act (ACA) USA. To this end, we rely on semi-parametric bi-variate probit methods, along with a pooled cross-section of the 2015-2016 National Health Interview Surveys. As predicted by the theoretical model, we find that SSP and FSA are complement health solutions with a positive correlation. Our results emphasize that the most important trigger factors influencing the joint probability of SSP and FSA adoption include not only insurance premium cost, but also age, education, marital status, number of work hours, region of residency, citizenship status, and annual health expenditure level. We find that controlling for these latter factors, health status is not significant especially for FSA adoption. In addition, despite the fact that the relative frequency of individuals with FSA rises with increasing levels of medical expenditure, ACA restrictions on FSA tax exclusion to an annual adjusted maximum of $2600 (in 2017 $s) seems to adversely burden individuals with greater medical expenditure, thereby reducing their likelihood of FSA enrollment in post-ACA USA. Understanding these factors is very crucial to US health care market's stakeholders, including insurance companies, firms looking to design their health insurance offerings, but also policy-makers interested in providing new tailored health solutions for reducing health risks.

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 Total Algae Peak Integration Retrieval TAPIR relates the chlorophyll-a absorption coefficient at 440 nm (a440) to the reflectance peak near 683 nm induced by chlorophyll-a properties. The two-step retrieval provides both the hyperspectral quantification of the phytoplankton fluorescence and scattering and the estimation of a440 from reflectance signals. Integrating the peak, the Total Algae Peak (TAP) accounts for the variance in the peak's magnitude, shape, and central peak wavelength. TAPIR is a solely optical approach estimating a440 and supports the application of retrieval-independent individual regional bio-optical models afterwards to retrieve the chlorophyll-a concentration. Simulations reveal the major sensitivity on the considered model chlorophyll-a absorption spectrum and its single scattering albedo. Additional water and atmosphere constituents have a low impact. An uncertainty assessment reveals uncertainties of less than 30% for TAPIR a440 greater than 0.8 m-1 and less than 38% for lower a440. In optically complex waters, first validation efforts promise the applicability of TAPIR for high chlorophyll-a concentration estimations in the presence of additional water constituents. The technique is generic and considers external conditions (sun zenith angle, number of measurement bands, surface or satellite measurements, and radiometric quantity). TAPIR applies to all kind of waters including optically complex waters, arctic to tropical regions, and inland, coastal, and open ocean waters. Among other hyperspectral satellite sensors, the Environmental Mapping and Analysis Program (EnMAP) provides sufficient sampling bands for the application of TAPIR.

MEMS (Micro-electromechanical Systems) becomes important increasingly due to the smarter and smaller fuze used in OICW (Objective Individual Combat Weapon). MEMS Safety and Arming (S&A) device is employed in different platforms and regions for small caliber projectile. Therefore, it is necessary to make a parametric study of the MEMS S&A device in different apply environments and explore the main sensitive factors of the MEMS S&A device to provide reference for designs. In this paper, based on the MEMS S&A device designed by our term, theory and finite element models are established, and the centrifugal insurance mechanism of the MEMS S&A device is parametric studied under the different speeds, temperature and thickness of the model by nonlinear dynamic method. By comparing the experimental and predicted results, the established FEM model is verified, and the conclusion is that the temperature and the centrifugal force are the main sensitive factors in the centrifugal insurance mechanism. In summary, we can suggest that the application environment, which the MEMS S&A device is suitable for, is the temperature equal to or slightly greater than normal temperature and the rotating speed higher than35000r/min of small caliber projectile.

Using the principle of equivalence, it has recently been shown that the electrostatic field lines of a charge, stationary in the gravitational field, bend exactly like the trajectories of photons emitted isotropically from a source at the charge location and that the fraction of electric flux crossing a surface `below' or `above' the charge is exactly similar to the fraction of photon trajectories intersecting these surfaces, with more flux in the downward direction than upward. As one goes much deeper in the gravitational field, all electric field lines increasingly point in the vertically downward direction as is also the case for a stream of photons. Since photon trajectories as well as electric field lines, at any location in the gravitational field, are affected by the local space-time curvature an inference can be drawn that this parallel between the photon trajectories and the electric field lines is a general result. We could then apply these results in the external gravitational field of a black hole, where the trajectories of photons in the gravitational field are already well-known and the behaviour of electric field lines of a stationary charge could be inferred therefrom. Accordingly, we show that the electric field through an external spherical surface surrounding the black hole steadily reduces as the charge location approaches the event horizon (Schwarzschild radius), and like photons from a source inside the Schwarzschild radius cannot escape outside, the electric field lines of a charge within the black hole too remain trapped inside the event horizon. From this one arrives at a conclusion that, contrary to the conventional wisdom, the electric charge contained inside a static black hole cannot be detected or inferred by an external observer. A black hole, said to have no hair with the only external identifying characteristics being mass, electric charge, and angular momentum, is therefore all the more `hairless', as even its charge cannot be ascertained. The derivation of the Reissner-Nordström metric, supposedly describing the gravitational field of a static charged black hole, presumes an external stress-energy tensor of the electrostatic field, as per Gauss law, even for the charges contained within the black hole. However, the absence of electric flux external to a static charged black hole implies that such a charged black hole is not described correctly by the Reissner-Nordström metric and the consequential peculiarities of the space-time geometry, leading in specific cases to the idea of a naked intrinsic singularity and a need for the ``cosmic censorship'' hypothesis, also do not arise here.

The interaction of matter when separated by a distance is a fundamental question, whether such interactions occur through instantaneous action at a distance or retarded action at a distance (principle of locality)? While the mainstream consensus favors the principle of locality, instantaneous action at a distance offers certain advantages. Previously, instantaneous action at a distance has been viewed as an appearance or representation from specific gauge choices of electromagnetic potentials (retarded). In this paper, we propose a novel approach that combines Weber’s electrodynamics with the concept of vacuum polarization to explore a new possible connection between the two viewpoints: instantaneous action at a distance and the locality principle. This new approach aligns with the observation of locality in signal/energy propagation while retaining the notion of instantaneous action at a distance.

Previous studies showed that some lamellarin-resembling annelated azaheterocyclic carbaldehydes and related imino adducts, sharing the 1-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinoline (1-Ph-DHPIQ) scaffold, are cytotoxic in tumor cells and may reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). Herein, we synthesized and evaluated for their antiproliferative activity in four tumor cell lines (RD, HCT116, HeLa, A549) and ability of inhibiting P-gp-mediated MDR some ten diversely substituted 1-Ph-DHPIQ derivatives bearing at position 2 carboxylate groups (COOH, COOEt), nitriles (CN) and Mannich bases (e.g., morpholinomethyl derivatives). Lipophilicity parametrization and molecular docking calculations improved the understanding of the structure-activity relationships in cytotoxicity and P-gp inhibition of the investigated 1-Ph-DHPIQs, which led us to disclose a novel Mannich base HCl salt (8b’), which proved to be cytotoxic to all the tested tumor cell lines in the low micromolar range (IC50 &lt; 20 M) and to inhibit in-vitro the efflux pumps P-gp and MRP1 responsible for MDR, with IC50s of 0.45 and 12.1 M, respectively.

The present study aims to unravel the mechanisms of salicylic acid and rehydration and the physiological benefits in pepper plants grown under water deficit. 3x4 factorial scheme adopted, with three water regimes (irrigated, dry and rehydration) and four SA concentrations, namely: 0 (control), 0.5, 1 and 1.5 mM. Evaluated leaf moisture percentage, leaf water potential, chlorophylls (a and b), carotenoids, stomatal conductance, chlorophyll a fluorescence and H2O2 concentration at different times throughout the day and water conditions (irrigated, dry and rehydration) and SA applications (without the addition of the regulator (0) and with SA addition at concentrations equal to 0.5, 1 and 1.5 mM). Exogenous SA application favored stomatal conductance responses(gs) and modified fluorescence parameters (Fm, Fo, Fm', Fo', Fv/Fm, qP, ETR and NPQ) of sweet pepper plants subjected to drought followed by rehydration. SA concentration of 0.5 mM allowed a more expressive recovery of gs indices, effective quantum yield of photosystem II, with emphasis on excess energy (E) and maximum quantum yield (FV/FM) over time in plants subjected to drought and rehydration. We discovered that the use of SA, especially in association with rehydration, by modulating the variables gs and chlorophyll a fluorescence, prevents damage to membranes and consequently mitigates water deficit in pepper plants.

This retrospective study aimed to compare risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Baseline data from 30 pre-HD and 85 HD patients were analyzed, in-cluding iPTH, vitamin D, FGF-23, fetuin-A, sclerostin and VC scores (Adragao method). Preva-lence of VC was similar in both groups, but HD patients had more frequent VC scores ≥6. Pre-HD patients were older, with higher prevalence of hypertension and less frequent use of calcium phosphate binders. Both groups showed similar patterns of hyperphosphatemia, low vitamin D, and iPTH. Fetuin-A levels were higher in pre-HD, while FGF-23 was elevated in HD patients. Higher VC risk in pre-HD patients was associated with male gender, older age, lower fetuin-A and higher sclerostin, lower ferritin and no vitamin D treatment, while in HD patients with higher sclerostin, FGF23 and urea, and lower iPTH. Conclusion. Progression of CKD from the pre-HD to the HD stage is accompanied by a decreased effect of the inhibitor and an increase in the promoter VC. However, mineral imbalance, hormonal regulation, treatment options, and patient-specific fac-tors should be considered. Further studies are needed to elucidate the underlying pathways.

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.

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).

Finding the ideal statistical method for grouping phenological data is always an important step for breeders to draw correct conclusions from it possibly. In this paper, K-cluster analysis is presented as a perfect tool for grouping phenological data. The present research was performed based on the phenological data of 61 strawberries (Fragaria × ananassa) cultivars of different geo-graphical origins grown in Estonian conditions. Groups of strawberry cultivars were deter-mined according to flowering and ripening time: early, middle and late, based on the sum of ef-fective temperatures above +5°C. The result of the K-cluster analysis carried out in this way makes it possible to precisely plan the ripening time of berries of different strawberry cultivars. Using such analysis data, it is possible to combine with different early, mid or late strawberry cultivars to extend the picking period. Also, this technique can be used to study the effect of cli-matic changes occurring over the years on the phenology of strawberry cultivars grown in the region.

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.

Based on the elasticity theory, this paper deals with the static analysis of a cracked double beam system in presence of a Winkler medium. The double-beam system is also supposed to be constrained at both ends by elastically flexible springs, with transverse and rotational stiffness. Using a variational formulation, the static governing equations are derived and solved by using analytical and numerical approaches. In the first approach, the closed-form solutions for the displacements functions are obtained based on the Euler-Bernoulli beam theory. In the second approach, the Cell-Discretization Method (CDM) is performed, according to which the two beams are reduced to a set of rigid bars linked together by means of elastic constraints, where the bending stiffness of the bars is concentrated. The resulting stiffness matrix is easily deduced, and the governing equations of the static problem can be immediately solved. A comparative analysis is performed in order to verify the accuracy and validity of the proposed method. This study focuses on the effect of various parameters including the crack depth and position, boundary conditions, elastic medium and slenderness. The validity of the proposed analysis is confirmed by comparing the present results with those obtained from the other approach. In particular, the results obtained by closed-form solution and Cell-discretization method (CDM) are compared by Finite element method (FEM). Accuracy of the results has been evaluated by making comparisons with the results in literature and reported in bibliography. It is demonstrated that the proposed algorithm provides a simple and powerful tool in dealing with the static analysis of a double-beam system. Finally, some concluding remarks are made.

Bisphenol-A (BPA) represents an important co-monomer for obtaining polycarbonate, epoxy resins, flame retardants, in paint, and other chemicals products. Products containing BPA are widely used, and thus, we can find it in the environment: in the air, in the soil, in natural surface water and in sediments, underground water in landfills, and in wastewater. BPA disturbs human and animals’ health. This influences the enzymatic, androgenic, neurological, liver and reproductive systems at different stages of human life: like in fetal stage, children and adults’ stages. Taking these inconveniences into account, it is very important to remove BPA from water. Ultrasonic technology can be considered a verry sustainable and efficient method to remove BPA from water. The advantages of this method is easy to implement on existing water treatment and purification facilities, it does not produce residual compounds that produce sludge, the time required for degradation is of the order of 1-2 hours and the level of degradation is very high. In this work, we presented the studies on the efficiency of ultrasonics under air atmosphere on the degradation of BPA. The influence of the frequency and of some additional compounds such as carbon tetrachloride, FeSO4 7H2O (FS), and ethyl anthraquinone (EAC) was studied. Three different frequencies were used: 1146 KHz, 864 KHz, 580 KHz, at a power of 50 W. It was identified the efficiency of BPA degradation over a period of 60 minutes, with sampling every 15 minutes. Using the LC-MS/MS technique, the degradation compounds were identified that result from the application of ultrasound processes. Pathways of BPA degradation were also proposed.

Bisphenol A (BPA) has been identified as one of endocrine disrupting chemicals (EDCs). Due to its massive production (over 700,000 tons per year) and the extensive use of BPA-based plastics (i.e., polycarbonate and epoxy resin) in Taiwan, it was thus included into a toxic substance by the Ministry of Environment. This work surveyed the updated information about the production of BPA and its environmental distributions in Taiwan over the past decade. Furthermore, the regulatory strategies and countermeasures for managing the environmental risks of BPA by the Taiwan government were summarized to show the cross-ministerial efforts under the relevant acts, including the Toxic and Concerned Chemical Substances Control Act (TCCSCA), the Food Sanitation Management Act (FSMA) and the Commodity Inspection Act (CIA). The findings showed that most of the monitoring data showed far below the acceptable risks. However, the people may pose an adverse threat to the aquatic environment and human health via ecological and food chains. In addition, some countermeasures were further recommended to echo the international actions on environmental endocrine disruptors in recent years.

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.

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.

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.

The natural product Salvinorin A (SalA) was the first nitrogen-lacking agonist discovered for the opioid receptors and exhibits high selectivity for the kappa opioid receptor (KOR) turning SalA into a promising analgesic to overcome the current opioid crisis. Since SalA’s suffers from poor pharmacokinetic properties, particularly the absence of gastrointestinal bioavailability, fast metabolic inactivation and subsequent short duration of action, the rational design of new tailored analogs with improved clinical usability is highly desired. Despite being known for decades, the binding mode of SalA within the KOR remains elusive as several conflicting binding modes of SalA were proposed hindering the rational design of new analgesics. In this study, we rationally determined the binding mode of SalA to the active state KOR by in silico experiments (docking, molecular dynamics simulations, dynophores) in the context of all available mutagenesis studies and structure-activity relationship (SAR) data. To the best of our knowledge this is the first comprehensive evaluation of SalA’s binding mode since the determination of the active state KOR crystal structure. SalA binds above the morphinan binding site with its furan pointing towards the intracellular core while the C2-acetoxy group is oriented towards the extracellular loop 2 (ECL2). SalA is solely stabilized within the binding pocket by hydrogen bonds (C210ECL2, Y3127.35, Y3137.36) and hydrophobic contacts (V1182.63, I1393.33, I2946.55, I3167.39). With the disruption of this interaction pattern or the establishment of additional interactions within the binding site we were able to rationalize the experimental data for selected analogs. We surmise the C2-substituent interactions as important for SalA and its analogs to be experimentally active, albeit moderate frequency within MD simulations of SalA. We further identified the non-conserved residues 2.63, 7.35, and 7.36 responsible for the KOR subtype selectivity of SalA. We are confident that the elucidation of the SalA binding mode will promote the understanding of KOR activation and the facilitate the development of novel analgesics that are urgently needed.

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.

Apis cerana and Apis mellifera, are very important honey species for agriculture in Asian countries. In recent decades, A. cerana populations have sharply declined in all Asian countries as a result of Sacbrood Virus infection and have now recovered to their original size. It can change the genetic structure of local populations of A. cerana. We used the nuclear gene Vitellogenin VG to assess the genetic structure of local populations of A. cerana and the signature of adaptive selection. We performed a population genetic analysis of the honey bees A. cerana from South Korea in comparison with A. cerana samples from Russia, Japan, Nepal, and China. The sequences of the gene VG of a closely related honey bee species, A. mellifera, from India and Poland were used as outgroup samples. A comparative analysis of northern and southern A. cerana populations was performed. The signatures of positive adaptive selection were found in the local population of A. cerana. We performed the Tajima's neutrality D test for A. cerana populations from different local populations based on the gene VG exon sequences. All A. cerana populations showed signs of population size expansion following the possible recent decline in population sizes. The local populations of A. c. koreana were subdivided according to their geographical distribution into southern, northern, and central Korean clusters. The gene VG exon sequences can be used as informative markers for monitoring the changes in genetic structure and adaptation to the environment processes in A. cerana populations.

To both survive and develop continuously, enterprises must overcome many kinds of competition and challenges. Cultivating employees' active and sustainable organizational citizenship behavior is important for enterprises to successfully cope with turbulence and uncertain events during their development. In this study, we investigated the development level of and factors influencing employees' organizational citizenship behavior in current organizations. By using the Belief in a Just World Scale, Organizational Citizenship Behavior Scale, and Interpersonal Intelligence Scale, we investigated 230 employees from 15 different enterprises. The results showed that belief in a just world, interpersonal intelligence, and organizational citizenship behavior were significantly positively correlated. Interpersonal intelligence played a moderating role between belief in a just world and organizational citizenship behavior; the organizational citizenship behavior of individuals with high interpersonal intelligence increased with the strengthening of the belief in a just world, and this increase was larger than that experienced by individuals with low interpersonal intelligence. This meant that under a certain level of belief in a just world, a high level of interpersonal intelligence was more conducive to promoting employees' sustainable organizational citizenship behavior.

This paper provides a methodology for the production of synthetic images for training neural networks to recognise shapes and objects. There are many scenarios in which it is difficult, expensive and even dangerous to produce a set of images that is satisfactory for the training of a neural network. The development of 3D modelling software has nowadays reached such a level of realism and ease of use that it seemed natural to explore this innovative path and to give an answer regarding the reliability of this method that bases the training of the neural network on synthetic images. The results obtained in the two proposed use cases, that of the recognition of a pictorial style and that of the recognition of migrants at sea, leads us to support the validity of the approach, provided that the work is conducted in a very scrupulous and rigorous manner, exploiting the full potential of the modelling software. The code produced, which automatically generates the transformations necessary for the data augmentation of each image, and the generation of random environmental conditions in the case of Blender and Unity3D software, is available under the GPL licence on GitHub. The results obtained lead us to affirm that through the good practices presented in the article, we have defined a simple, reliable, economic and safe method to feed the training phase of a neural network dedicated to the recognition of objects and features, to be applied to various contexts.

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.

In this paper, the stability control of the inverted pendulum on a cart with a disturbance forces has been done using observer based and full state feedback H2 controllers. The Lagrangian equation has been used to model the system equation of motions and linearized the system to the unstable upward position. Comparison of the system stability has been simulated by comparing the proposed controllers using Matlab/Scripts and a promising results has been analyzed successfully.

China is one of the world’s most important countries for waterfowl because of the large amount of potential habitat and its position along major migratory routes. Waterfowl poaching in China is a serious threat, and for over twenty years colleagues and I have tracked waterfowl poaching in China including hunting methods, trade routes and prices involved. According to the latest survey of a NGO, 11.8% of Chinese people have participated in wildlife consumption, and about 32.0% of people have seen wildlife consumption (Not necessarily involved in killing and eating the wildlife). The survey results come from 100 000 internet questionnaires. The current report provides an update focusing on waterfowl poaching in Xinjiang Province of the northwest China, where is highly pathogenic area on the avian influenza, SARS and the Wuhan coronavirus pneumonia (such as COVID-19). The cases in 2011, 2012, and 2014 involved about 1816 to 2760 birds of more than 20 species, with an estimated total of 200 000 wild birds being hunted by a group per year in Xinjiang. Strangely, the poacher was not punished by any law. We know a few waterfowl species are protected as a list of Key Protected Species in China, and hopefully this report will draw attention to the scope of waterfowl poaching in China. China has made great progress with protecting other wildlife, and hopefully more can be done to protect migrating waterfowl.

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.

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.

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.

Purification of biologically-derived therapeutics is a major cost contributor to the production of this rapidly growing class of pharmaceuticals. Monoclonal antibodies comprise a large percentage of these products therefore new antibody purification tools are needed. Small peptides, as opposed to traditional antibody affinity ligands such as Protein A, may have advantages in stability and production costs. Multiple heptapeptides that demonstrate Fc binding behavior that have been identified from a combinatorial peptide library using M13 Phage Display are presented herein. Seven unique peptide sequences of diverse hydrophobicity and charge were identified. All seven peptides showed strong binding to the four major human IgG isotypes, human IgM, as well as binding to canine, rat, and mouse IgG. These seven peptides were also shown to bind human IgG4 from DMEM cell culture media with 5% FCS and 5 g/L ovalbumin present. These peptides may be useful as surface ligands for antibody detection and purification purposes. Molecular docking and classical molecular dynamics (MD) simulations were conducted to elucidate the mechanisms and energetics for the binding of these peptides to the Fc region. The binding site was found to be located between the two glycan chains inside the Fc fragment. Both hydrogen bonding and hydrophobic interactions were found to be crucial for the binding interactions. Excellent agreement for the binding strength was obtained between experimental results and simulations.

The air is not the same as thousands and hundreds of years ago. In the air, suspended particles originate from natural phenomena like dust storms or volcanic activities, as well as anthropogenic pollutants such as fuel engine exhaust and everyday activities at home. The total particles in the air can be classified by sizes, such as PM10, PM2.5 or ultrafine particles. However, there are many other important factors in addition to the particle size, influencing the particle behavior and affecting our health. The surface area, chemical and biological composition, aspect ratio, and the charge are all factors characteristic of particles. OoC microfluidic chips are very useful for the pollutant toxicity measurements on various body tissues. A better understanding of pollutants will help to trace these to the potential sources. The data from the on-the-ground and satellite monitoring can be integrated into models, helping to predict and prevent pollution exposure.

In this work modeling and analysis of an integrated opto-fluidic sensor, with a focus on achievement of single mode optical confinement and continuous flow of micro particles in the microfluidic channel for Lab-on-a Chip (LOC) sensing application is presented. This sensor consists of integrated optical waveguides, microfluidic channel among other integrated optical components. A continuous flow of micro particles in a narrow fluidic channel is achieved by maintaining the two sealed chambers at different temperatures and by maintaining a constant pressure of 1Pa at the centroid of narrow fluidic channel geometry. The analysis of silicon on insulator (SOI) integrated optical waveguide at an infrared wavelength of 1550nm for single mode sensing operation is presented. The optical loss is found to be 0.0005719dB/cm with an effective index of 2.2963. The model presented in this work can be effectively used to detect the nature of micro particles and continuous monitoring of pathological parameters for sensing applications.

Let $f\left(1\right)=1$ , and let $f(n+1)=2^{2^{f\left(n\right)}}$ for every positive integer n. We consider the following hypothesis: if a system S ⊆ {x_i · x_j = x_k : i, j, k ∈ {1, . . . , n}} ∪ {x_i + 1 = x_k : i, k ∈{1, . . . , n}} has only finitely many solutions in non-negative integers x₁, . . . , x_n, then each such solution (x₁, . . . , x_n) satisfies x₁, . . . , x_n ≤ f (2n). We prove: (1) the hypothesisimplies that there exists an algorithm which takes as input a Diophantine equation, returns an integer, and this integer is greater than the heights of integer (non-negative integer, positive integer, rational) solutions, if the solution set is finite; (2) the hypothesis implies that there exists an algorithm for listing the Diophantine equations with infinitely many solutions in non-negative integers; (3) the hypothesis implies that the question whether or not a given Diophantine equation has only finitely many rational solutions is decidable by a single query to an oracle that decides whether or not a given Diophantine equation has a rational solution; (4) the hypothesis implies that the question whether or not a given Diophantine equation has only finitely many integer solutions is decidable by a single query to an oracle that decides whether or not a given Diophantine equation has an integer solution; (5) the hypothesis implies that if a set $\mathfrak{M}$ ⊆ has a finite-fold Diophantine representation, then $\mathfrak{M}$ is computable.

This article lays the foundation for Extended Relativity (ER) – a unified geometric approach to the electromagnetic and gravitational field and relativistic dynamics in them. We explain here the basic tenets of ER, including the influenced spacetime of an object and the Extended Principle of Inertia. These two new ideas enable a unified theory of these fields. We introduce local scaling functions for describing the geometry of a spacetime influenced by a field and construct a simple, universal local scaling function which unifies electromagnetism and gravity. We recover the full electromagnetic theory, including Maxwell’s equations. For gravitation, ER passes all of the tests of General Relativity. Despite the non-linearity of relativistic gravitation, we obtain a method of combining fields from multiple sources. Finally, we identify the differences in the relativistic treatment of the electromagnetic field by Special Relativity and of the gravitational field by General Relativity and indicate how these differences are resolved in ER.

Traditional path planning algorithms have drawbacks in unmanned vehicle path planning, such as low efficiency, unsuitability for dynamic environments, and high computational complexity. To address these issues, this paper proposes a dynamic path planning method for unmanned vehicles that combines the A* algorithm with an improved Dynamic Window Approach (DWA). Firstly, a collision risk function is incorporated into the DWA algorithm to evaluate scores based on the braking distance corresponding to the current vehicle speed and the distance to obstacles, determining whether timely braking or obstacle avoidance is feasible. The earlier the braking or obstacle avoidance, the higher the score, thereby enhancing the evaluation algorithm of the DWA. Secondly, the key points extracted by the A* algorithm are used as temporary target points for the DWA algorithm, reducing the eight search directions to five. Finally, the key points of the A* algorithm’s path are set as the temporary end points for the DWA algorithm, integrating the two algorithms to plan a smoother curved path that can avoid unknown and dynamic obstacles. Simulation data demonstrates that compared to traditional artificial potential field methods, RRT, and Dijkstra’s algorithm, the new fusion algorithm reduces time by 11.71 seconds, a decrease of 6.9%, and shortens path length by 3.093 meters, a reduction of 4.16%, while increasing average linear velocity by 2.9%. The proposed algorithm ensures smoother paths while also making paths more rational and efficient

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.

One of the ways to regulate the sensitivity of human cells to the influenza virus is to knock out genes of the innate immune response. Promising targets for the knockout are genes of the interferon-inducible transmembrane protein (IFITM) family, in particular the IFITM3 gene, whose product limits the entry of a virus into the cell by blocking the fusion of the viral and endosomal membranes. In this study, by means of genome-editing system CRISPR/Cas9, monoclonal cell lines with an IFITM3 knockout were obtained based on WI-38 VA13 cells (human origin). It was found that such cell lines are more sensitive to infection by influenza A viruses of various subtypes. Nonetheless, this feature is not accompanied by an increased titer of newly formed viral particles in a culture medium.

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

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.

Tight junctions (TJ) are cell-cell adhesive structures that define the permeability of barrier-forming epithelia and endothelia. In contrast to this seemingly static function, TJs display a surprisingly high molecular complexity and an unexpected dynamic regulation, which allows the TJs to maintain a barrier in the presence of physiological forces and in response to perturbations. Cell-cell adhesion receptors play key roles during the dynamic regulation of TJs. They connect individual cells within cellular sheets and link sites of cell-cell contacts to the underlying actin cytoskeleton. Recent findings support roles of adhesion receptors in transmitting mechanical forces and promoting phase separation. In this review, we discuss newly discovered functions of cell adhesion receptors localized at the TJs and their role in the regulation of the barrier function.

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.

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.

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.

Prior to clinical trials, preclinical testing of oncology drug candidates is performed by evaluating drug candidates with in vitro and in vivo platforms. For in vivo testing, animal models are used to evaluate the toxicity and efficacy of drug candidates. However, animal models often display poor translational results as many drugs that pass preclinical testing fail when tested in humans, with oncology drugs exhibiting especially poor acceptance rates. The FDA Modernization Act 2.0 promotes alternative preclinical testing techniques, presenting the opportunity to use higher complexity in vitro models as an alternative to in vivo testing, including 3D cell culture models. 3D tissue cultures address many of the shortcomings of 2D cultures by more closely replicating the tumour microenvironment through a combination of realistic drug diffusion, paracrine signaling, cellular phenotype, and vascularization that can better mimic native human tissue. This review will discuss the common forms of 3D cell culture, including cell spheroids, organoids, organs-on-a-chip, and 3D bioprinted tissues. Their advantages and limitations will be presented, aiming to discuss the use of these 3D models to accurately represent human tissue and as an alternative to animal testing. The use of 3D culture platforms for preclinical drug development is expected to accelerate as these platforms continue to improve in complexity, reliability, and translational predictivity.

Mutations in the LMNA gene (encoding lamin A/C proteins) cause several human cardiac diseases, including dilated cardiomyopathies (LMNA-DCM). The main clinical risks in LMNA-DCM patients are sudden cardiac death and progressive left ventricular ejection fraction deterioration, and therefore most human and animal studies have sought to define the mechanisms through which LMNA mutations provoke cardiac alterations, with particular focus on cardiomyocytes. To investigate if LMNA mutations also cause vascular alterations that might contribute to the etiopathogenesis of LMNA-DCM, we generated and characterized Lmnaflox/floxSM22αCre mice, which constitutively lack lamin A/C in vascular smooth muscle cells (VSMCs), cardiac fibroblasts, and cardiomyocytes. Like mice with whole body or cardiomyocyte-specific lamin A/C ablation, Lmnaflox/floxSM22αCre mice recapitulated the main hallmarks of human LMNA-DCM, including ventricular systolic dysfunction, cardiac conduction defects, cardiac fibrosis, and premature death. These alterations were associated with hyperactivation of Smad3 and elevated expression of the proapoptotic protein caspase 3 in the heart. Lmnaflox/floxSM22αCre mice also exhibited perivascular fibrosis in the coronary arteries, and a switch of aortic VSMCs from the ‘contractile’ to the ‘synthetic’ phenotype. Ex vivo wire myography in isolated aortic rings revealed impaired maximum contraction capacity and an altered response to vasoconstrictor and vasodilator agents in Lmnaflox/floxSM22αCre mice. To our knowledge, our results provide the first evidence of phenotypic alterations in VSMCs that might contribute significantly to the pathophysiology of some forms of LMNA-DCM. Future work addressing the mechanisms underlying vascular defects in LMNA-DCM may open new therapeutic avenues for these diseases.

Infectious bursal disease (IBD) is a viral poultry disease known worldwide for impacting the economy and food security. The disease is endemic in Nigeria, with reported outbreaks in vaccinated poultry flocks. To gain insight into the dynamics of infectious bursal disease virus (IBDV) evolution in Nigeria, near-complete genomes of four IBDVs were evaluated. Amino acid sequences in the hypervariable region of the VP2 revealed conserved markers (222A, 242I, 256I, 294I and 299S), associated with very virulent (vv) IBDV, including the serine-rich heptapeptide motif (SWSASGS). Based on the newly proposed classification for segments A and B, the IBDVs clustered in the A3B5 group (where A3 are IBDVs with vvIBDV-like segment A and B5 are from non-vvIBDV-like segment B) forming a monophyletic subcluster. Unique amino acid mutations with yet-to-be-determined biological functions have been observed in both segments. Amino acid sequences of the Nigerian IBDVs showed that they are reassortant viruses. Circulation of reassortant IBDVs may be responsible for the vaccination failures observed in the Nigerian poultry population. Close monitoring of changes in the IBDV genome is recommended to nip deleterious changes in the bud, through the identification and introduction of the most appropriate vaccine candidates and advocacy/extension programs for properly implementing disease control.

Digital microfluidics (DMF) holds great potential for the alleviation of laboratory procedures in assisted reproductive technologies (ARTs). Electrowetting on dielectric (EWOD) provides dynamic culture conditions in vitro that may better mimic the natural embryo microenvironment. Thus far, EWOD microdevices have been proposed for in vitro gamete and embryo handling in mice and for analyzing the human embryo secretome. This article presents the development of the first microfluidic chip utilizing EWOD technology designed for the manipulation of bovine embryos in vitro. The prototype sustains the cell cycles of embryos manipulated individually on the chips during in vitro culture (IVC). Challenges related to the chip fabrication as well as to its application during bovine embryo IVC in accordance with the adapted on-chip protocol are thoroughly discussed, and future directions for DMF in ARTs are indicated.

The lab-on-a-chip concept, enabled by microfluidic technology, promises the integration of multi-ple discrete laboratory techniques into a miniaturised system. Research into microfluidics has generally focused on the development of individual elements of the total system (often with rela-tively limited functionality), without full consideration for integration into a complete fully opti-mised and miniaturised system. Typically, the operation of many of the reported lab-on-a-chip devices is dependent on the support of a laboratory framework. In this paper, a demonstrator platform for routine laboratory analysis is designed and built, which fully integrates a number of technologies into a single device with multiple domains such as fluidics, electronics, pneumatics, hydraulics, and photonics. This facilitates the delivery of breakthroughs in research, by incorpo-rating all physical requirements into a single device. To highlight this proposed approach, this demonstrator microsystem acts as a fully integrated biochemical assay reaction system. The re-sulting design determines enzyme kinetics in an automated process and combines reservoirs, three-dimensional fluidic channels, optical sensing, and electronics in a low-cost, low-power and portable package.

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.

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.

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.

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.

Non-genuine medical products, including diagnostic devices, have become a lucrative business for fraudsters, causing significant damage to revenues and reputation of companies, as well as posing a significant risk to the health of people and societies. Along a “digital twin” representing centrifugal microfluidic flow control on exemplary “Lab-on-a-Disc” (LoaD) systems, a novel, two-pronged strategy to safeguard miniaturized point-of-care devices by means of secret features and manufacturing challenges is outlined; such “hardware encryption” is flexibly programmed for each chip during production, and deciphered from a secure, local or online database at the time of use. This way, unlicensed copying may be efficiently deterred by an unfavourable economy-of-scale, even in absence of legal prosecution.

The aim of the article is to develop geometrized physics of a vacuum on the basis of two basic postulates: 1) the constancy of the speed of light (more precisely, the speed of propagation of electromagnetic waves) in the vacuum; 2) the ‘vacuum balance condition’ associated with the statement that only mutually opposite formations are born from the vacuum, so that, on average, they completely compensate of the manifestations of each other. The Algebra of signatures is proposed as a mathematical basis for geometrized physics of a vacuum.

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.

The current study investigated the use of two-dimensional spatial distribution mapping representing the chlorophyll-a level in a river generated via an unmanned aerial vehicle (UAV) and an unmanned surface vehicle (USV). A domestically developed UAV (Remo-M, Uconsystem Inc., Korea) and a USV developed by our research team were used to collect data from the Nae Seong stream in Korea. An adaptation of the “Data Cleaner” tool was developed and used for USV data processing and analysis. The operation of the autonomous USV was successful. Four previously described indices for quantifying algal blooms in rivers were utilized to create chlorophyll-a images, the normalized difference vegetation index (NDVI), the normalized green red difference index, the green normalized difference vegetation index (GNDVI), and the normalized difference red edge index. The suitability of the linear regression analysis of the correlation between the spectral indices obtained using the UAV and the in situ chlorophyll-a data obtained using the USV was evaluated with the coefficient of determination (R2) at a significance level of p &lt; 0.001. In field application and correlational analysis the NDVI was strongly correlated with chlorophyll-a (R2 = 0.88, p < 0.001), and the GNDVI was moderately correlated with chlorophyll-a (R2 = 0.74, p < 0.001). The map of chlorophyll-a was successfully quantified using the UAV and USV hybrid platforms.

This work presents the results of a computational study of the chemical reactivity and bioactivity properties of the members of the Theopapuamides A-D family of marine peptides by making use of our own proposed methodology named Computational Peptidology (CP) that has been successfully considered in previous studies of this kind of molecular systems. CP allowed for the determination of the global and local descriptors that come from Conceptual Density Functional Theory (CDFT) that can give an idea of the chemical reactivity properties of the marine natural products under study which are already known to be related to their bioactivity. At the same time, the validity of the procedure based on the adoption of the KID (Koopmans in DFT) technique as well as the MN12SX/Def2TZVP/H2O model chemistry has been successfully verified. Together with several Chemoinformatic tools that can be used for the improvement of process of Virtual Screening, some additional properties of these marine peptides were identified related to their ability to behave as useful drugs. With the further object of analyzing their bioactivity some parameters of usefulness for future QSAR studies, their predicted biological targets and the the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) parameters related to the Theopapuamides A-D pharmacokinetics are also reported.

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.

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.

A portable urea sensor for use in the fast flow condition was fabricated using porous polytetrafluoroethylene (PTFE) membranes coated with amine-functionalized parylene, parylene-A, by vapor deposition. To generate a specific electrochemical sensor signal from urea, the urea-hydrolyzing enzyme urease was immobilized on the parylene-A-coated PTFE membranes via chemical crosslinking using glutaraldehyde. The urease-immobilized membranes were assembled in a polydimethylsiloxane (PDMS) fluidic chamber, and a screen-printed carbon three-electrode system was used for electrochemical measurements. The success of urease immobilization was confirmed using fluorescence microscopy, scanning electron microscopy, and Fourier-transform infrared spectroscopy. The optimum concentration of urease for immobilization on the parylene-A-coated PTFE membranes was determined to be 48 mg/mL, and the optimum number of membranes in the PDMS chamber was found to be 8. Using these optimized conditions, we fabricated the urea biosensor and monitored urea samples under various flow rates ranging from 0.5 to 10 mL/min in the flow condition using chronoamperometry. To test the applicability of the sensor for physiological samples, we used it for monitoring urea concentration in the waste peritoneal dialysate of a patient with chronic renal failure, at a flow rate of 0.5 mL/min.

Identifying appropriate animal models is critical in developing translatable in vitro and in vivo systems for therapeutic development and investigating disease pathophysiology. These animal models should have direct biological and translational relevance to the underlying disease they are supposed to mimic. Aging dogs naturally develop a cognitive decline in many aspects including learning and memory, but also exhibit human-like individual variability in the aging process. Neurodegenerative processes that can be observed in both human and canine brains include the progressive accumulation of β-amyloid (Aβ) found as diffuse plaques in the prefrontal cortex, including the gyrus proreus, the hippocampus, and in the cerebral vasculature. A growing body of epidemiological data shows that human patients with neurodegenerative diseases have concurrent intestinal lesions, and histopathological changes in the gastrointestinal (GI) tract occurs decades that evolve before neurodegenerative changes. Gut microbiome alterations also have been observed in many neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases, and inflammatory CNS diseases. Interestingly, only recently has the dog gut microbiome been recognized to more closely resemble in composition and in functional overlap with the human gut microbiome as compared to rodent models. This article aims to review the physiology of the gut-brain axis (GBA), and its involvement with neurodegenerative diseases in dogs and humans. Additionally, we outline the advantages and disadvantages of traditional in vitro and in vivo models and discuss future research directions investigating major human neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases using dogs.

Specific nutrients including n-3 long chain polyunsaturated fatty acids (LCPUFAs), flavonoids, vitamin A, D and E are considered to possess protective properties on human health by impacting on immunological reactions. An ‘inflammation-suppressive’ effect appears to be the common denominator of the beneficial effects of most of these dietary components which may protect against the development of chronic immune disorders such as allergy. However, the majority of these promising data are from preclinical studies such as animal disease models, as the majority of clinical studies only indicate associations. PUFAs, especially n-3 LCPUFAs, have been shown to interact with both the sensitization as well as the effector phase in food allergy. However, it should be noted and realised that PUFAs are highly susceptible to lipid oxidation. Flavonoids and fat-soluble vitamins both contain anti-inflammatory properties and are able to act as anti-oxidants as well. Here, we explore the anti-allergic properties of PUFAs, flavonoids and fat-soluble vitamins in order to create an overview and, more importantly, suggest a strategy to target food allergies using these components and combinations thereof. Dietary n-3 LCPUFAs and the above mentioned micronutrients are promising anti‐allergy agents capable of influencing the allergic immune response through multiple and different biological pathways.

It is known that eumelanin (EM) is photoprotective while pheomelanin (PM) is phototoxic. A recent study using a mouse model demonstrated that PM produces reactive oxygen species (ROS) that cause DNA damage and eventually lead to melanomagenesis. A biochemical study showed that PM possesses a pro-oxidant activity. PM consists of benzothiazine (BT) and benzothiazole (BZ) moieties, the former being transformed to the latter by heat or light. In this study, we compared the effects of ultraviolet A (UVA) irradiation using synthetic PMs with different BT to BZ ratios and using various coat color mouse hairs. We found that UVA irradiation of BZ-PM increased glutathione (GSH) consumption and generated more H₂O₂ than UVA irradiation of BT-PM. Non-irradiated controls did not exhibit strong pro-oxidant activities. Upon UVA irradiation, yellow mouse hairs oxidized GSH and produced H₂O₂ faster than black or albino mouse hairs. Next, to examine the mechanism of the pro-oxidant activity of BT-PM and BZ-PM, we examined the pro-oxidant activities of 7-(2-amino-2-carboxyethyl)-dihydro-1,4-benzothiazine-3-carboxylic acid (DHBTCA) and 6-(2-amino-2-carboxyethyl)-4-hydroxybenzothiazole (BZ-AA) as BT and BZ monomers, respectively. Their pro-oxidant activities were similar, but a large difference was seen in the effects of ROS scavengers, which suggests that the redox reactions may proceed via singlet oxygen in BZ-AA and via superoxide anions in DHBTCA. These results show that UVA enhances the pro-oxidant activity of PM, in particular BZ-PM.

A novel nor-phragmalin-type limonoid, named carapanosin D (1), and two novel mexicanolide-type limonoids, carapanosins E (2) and F (3), were isolated from the seeds oil of Carapa guianensis AUBLET (andiroba), a traditional medicine in Brazil and Latin American countries. Their structures were elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and HRFABMS. Compounds 1—3 were evaluated for their effects on the production of NO in LPS-activated mouse peritoneal macrophages. The NO inhibitory assay suggested that compound 2 may be valuable as potential inhibitors of macrophage activation.

Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics a genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. CS3D competitively inhibits STAT3 binding to target gene promoters, resulting in decreased expression of proteins that promote cellular proliferation and survival. Previous studies have demonstrated antitumor activity of CS3D in preclinical models of solid tumors. However, prior to entering human clinical trials, the efficiency of generating the CS3D molecule and its stability in biological fluids should be determined. CS3D is synthesized as a single-stranded ODN and must have its free ends ligated to generate the final cyclic form. In this study, we report a ligation efficiency of nearly 95 percent. The ligated CS3D demonstrated a half-life of 7.9 hours in human serum, indicating adequate stability for intravenous delivery. These results provide requisite biochemical characterization of CS3D that will inform upcoming clinical trials.

Quantifying the landscape pattern change can effectively demonstrate the ecological progresses and the consequences of urbanization. Based on remotely sensed land cover data in 1994, 2000, 2006 and a gradient analysis with landscape metrics at landscape- and class- level, we attempted to characterize the individual and entire landscape patterns of Shanghai metropolitan during the rapid urbanization. We highlighted that a roadscape transect approach that combined the buffer zone method and the transect-based approach was introduced to describe the urban-rural patterns of agricultural, residential, green, industrial, and public facilities land along the railway route. Our results of landscape metrics showed significant spatiotemporal patterns and gradient variations along the transect. The urban growth pattern in two time spans conform to the hypothesis for diffusion–coalescence processes, implying that the railway is adaptive as a gradient element to analyze the landscape patterns with urbanization. As the natural landscape was replaced by urban landscape gradually, the urban fringe expanded radically. The results also showed that the desakota region expanded its extent widely. Satellite towns witnessed the continual transformation from the predominantly rural landscape to peri-urban landscape. Furthermore, the gap between urban and rural areas remained large especially in public service. More reasonable urban plans and land use policies should push to make more of an effort to transition from the urban-rural separation to coordinated urban-rural development. This study is a meaningful trial in demonstrating a new form of urban–rural transects to study the landscape change of large cities from a strategic viewpoint. By combining gradient analysis with landscape metrics, we addressed the process of urbanization both spatially and temporally, and provided a more quantitative approach to urban studies.

The draconian regulation required by the inherent instability of cognitive phenomena -- gene expression, immune function, cancer suppression, wound healing, animal consciousness, machine intelligence, network stabilization, institutional cognition, and their many and varied composites -- can be viewed through the lens of the asymptotic limit theorems of both information and control theories. Here, we explore the dynamics and sometimes highly punctuated failures of the regulation of cognition under increasing `noise'. The approach parallels, and indeed generalizes, the Data Rate Theorem of control theory, extending the theorem's requirement of a minimum channel capacity necessary for stabilization of an inherently unstable system. Various models are explored across different basic underlying probability distributions characteristic of the system under study, and across different hierarchical scales, finding the addition of adaptive -- learned -- regulation greatly extends the reach of innate -- e.g., AI-driven or otherwise pre-programmed -- regulation. This work points toward the construction of new statistical tools for the analysis of observational and empirical data across a wide spectrum of inherent pathologies and adversarial challenges afflicting a wide variety of cognitive processes.

This study investigates the impact of experienced contact on prejudiced attitudes toward individuals with intellectual disabilities (ID), examining beliefs in a just world (BJW) and social dominance orientation (SDO) as potential serial mediators. Data were collected from 224 university students (M = 23.02, SD = 2.48). Path analysis modeling assessed the structural relationships between the study variables. The findings revealed that experienced contact was negatively and significantly associated with BJW and SDO. Additionally, BJW and SDO fully mediated the relationship between experienced contact and overt prejudice. These findings underscore the influence of individual differences on attitudes toward individuals with ID, establishing a crucial foundation for future research and the development of interventions aimed at reducing prejudice and discrimination.

Salmonella causes various type of disease worldwide with a remarkable pace. Salmonella enteric serotype typhi (S. typhi), a gram-negative bacterium (only cause disease in man) is the mainly causative agent of Typhoid fever. Typhoid fever is most common in poor and unprivileged developing countries of Asia and Africa. One of the major components of virulence factors produced during salmonella infection is Lipid A, which acts as a potent human immuno-modulator bacterial endotoxin. Regulation of Lipid A biosynthetic pathway occurs at second step, catalyzed by LpxC, a Zn2+ dependent metalloamidase. Systematic Screening of a pool of drug datasets like natural products library from Zinc database, Asinex database, Thiophene analogues fruitfully provided us 3 potent lead molecules s1_dl_mseq2, s1_ll_mseq2, and s2_ll_mseq8 which actively binds with LpxC enzyme and could be developed into sound inhibitors of LpxC enzyme after the application of drug development and processing strategies. Wet lab experimentation is required to validate these results for further use.

Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as substitutes for bisphenol A (BPA) in the plastic industry, driven by concerns over the adverse effects of BPA. However, there is a lack of infor-mation on the extent of exposure to these chemicals in children. This study aims to assess the extent of BPA, BPF, and BPS exposure and determine factors that influence such exposure. A group of Thai children (age 6-13 years, n=358) were recruited between October 2019-2020. Two first morning void was collected one week apart. Demographic and exposure-related information was gathered. Urinary concentrations of bisphenols were analyzed by liquid-chromatography and tandem mass spectrometry. Correlation between bisphenol concentrations and various factors was determined using generalized estimating equations with linear model. BPA, BPF, and BPS were detected at 79.6%, 31.0%, and 16.8%, with geometric mean (GM) concentrations of 1.41, 0.013, and 0.014 ng/mL respectively. Younger children aged < 10 years exhibited 1.3-1.6 times higher GM levels of all bisphenols compared to older children. Exposure to food stored in plas-tic containers were associated with higher levels of BPF and BPS. In conclusion, BPA was the most fre-quently detected bisphenol in urine samples from Thai children, followed by BPF and BPS.

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.

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 pathogenesis of porcine circovirus type 2b (PCV2b) and swine influenza A virus (SwIV) during co-infection in swine respiratory cells is poorly understood. To elucidate the impact of PCV2b/SwIV co-infection, newborn porcine tracheal epithelial cells (NPTr) and immortalized porcine alveolar macrophages (iPAM 3D4/21) were co-infected with PCV2b and SwIV (H1N1 or H3N2 genotype). Viral replication, cell viability and cytokine mRNA expression were determined and compared between single-infected and co-infected cells. Finally, 3’mRNA sequencing was performed to identify the modulation of gene expression and cellular pathways in co-infected cells. It was found that PCV2b significantly decreased and improved SwIV replication, in co-infected NPTr and iPAM 3D4/21 cells respectively, compared to single infected cells. Interestingly, PCV2b/SwIV co-infection synergistically up-regulated IFN expression in NPTr cells whereas in iPAM 3D4/21 cells, PCV2b impaired the SwIV IFN induced response, both correlating with SwIV replication modulation. RNA-sequencing analyses revealed that the modulation of gene expression and enriched cellular pathways during PCV2b/SwIV H1N1 co-infection is regulated in a cell type-dependent-manner. This study revealed different outcomes of PCV2b/SwIV co-infection in porcine epithelial cells and macrophages and provides new insights on porcine viral co-infections pathogenesis.

(1) Background: The issue of human adaptation to the Arctic environmental factors is relevant. The adaptation can be assessed through dynamic monitoring of the functional state of a person during his/her stay there. The vitamin D level in blood is one of the markers of the functional reserves of the human body and can contribute to more successful adaptation in the Arctic. (2) Methods: The study involved 38 participants in the scientific and educational expeditionary project "Arctic Floating University-2021". Blood collection for determination of vitamin D content was carried out at the beginning of the expedition. A dynamic study was carried out for 20 days in the morning and in the evening during a marine scientific expedition to the Arctic. The main parameters of the functional state of the participants were assessed using instrumental psychophysiological, projective and questionnaire methods. Statistical methods: Mann-Whitney U-test, correlation analysis using the Spearman coefficient. (3) Results: It was found that at the beginning of the expedition, the functional state of participants with severe vitamin D deficiency is characterized by a shorter average duration of RR intervals and reduced SDNN values, which may indicate a higher level of regulatory mechanisms tension. The pronounced differences in the nature of the dynamic series of objective and projective working capacity parameters were manifested most clearly. According to the subjective questionnaire characteristics of well-being, activity and mood, no significant features of the participants with vitamin D deficiency were revealed. (4) Conclusion: The participants with vitamin D deficiency in blood are characterized by a reduced adaptive capacity during the expedition to the Arctic.

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.

This paper shows that by applying the Nyquist-Shannon sampling theorem, the spatial and temporal resolution of a simulation can be no more than half the resolution of the simulating reality. This has significant implications for not only the values of the observables in the simulation but also its physical laws. This progressive halving of nested simulations coupled with the minimum resolution compatible with the production of a simulation also sets a limit to the nestedness of a lineage of simulations (it is by no means infinite). The limit of nestedness is then used to calculate the probability that we are living in a simulation assuming a single base reality. This will be shown to be significantly lower than popular expectation. A Kardashev-like scale, with three variants, is also developed to gauge the technological advancement of a civilization in relation to the extent to which it can extract information from space and time.

Abstract: The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-45 spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness.

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

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

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

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

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