Due to increased energy intensive human activities resulting accelerated demand for electric power coupled with occurrence of natural disasters with increased frequency, intensity, and duration, it becomes essential to explore and advance renewable energy technology for sustainability of the society. Addressing the stated problem and providing a radical solution has been attempted in this study. To harvest the renewable energy, among variety of solar cells reported, a composite a-Si/CZTS photovoltaic devices has not yet been investigated. The calculated parameters for solar cell based on the new array of layers consisting of a-Si/CZTS are reported in this study. The variation of i) solar cell efficiency as a function of CZTS layer thickness, temperature, acceptor, and donor defect concentration; ii) variation of the open circuit current density as a function of temperature, open circuit voltage; iii) variation of open circuit voltage as a function of the thickness of the CZTS layer has been determined. There has been no reported study on a-Si/CZTS configuration-based solar cell, analysis of the parameters, and study to address the challenges imped efficiency of the photovoltaic device and the same has been discussed in this work. The value of the SnO2/a-Si/CZTS solar cells obtained from the simulation is 23.9 %.

Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. The anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents. It seems relevant to develop dual-action drugs with antiviral and anticoagulant properties. At the same time it was shown that azolo[1,5-a]pyrimidines are heterocycles with a broad spectrum of antiviral activity. We have synthesized a new family of azolo[1,5-a]pyrimidines and their condensed polycyclic analogs by cyclocondensation reactions and direct CH-functionalization and studied their anticoagulant properties. Five compounds among 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and 5-alkyl-1,3,4-thiadiazolo[3,2-a]purin-8-ones demonstrated higher anticoagulant activity than the reference drug, dabigatran etexilate. Antithrombin activity of lead compounds was confirmed using lipopolysaccharide (LPS) treated blood to mimic conditions of cytokine release syndrome. The studied compounds affected only the thrombin time value, reliably increasing it 6.5–15.2 times as compared to LPS-treated blood.

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

Fluorescence-linked immunosorbent assay (FLISA) is a commonly used, quantitative technique for detecting biochemical based on antigen–antibody binding reactions using a well-plate platform. With the developments in the manufacturing technology of microfluidic systems, FLISA can be implemented onto microfluidic disk platforms, which allows the detection of trace biochemical with high resolutions. Apart from requiring a lower proportion of reagent (1/10), this method also reduces the time required for the entire process to less than an hour. The incubation process involves antigen–antibody binding reactions as well as the binding of fluorogenic substrates to target proteins. The protocol for FLISA on a microfluidic platform necessitates the appropriate execution of liquid reagent movements during each step in order to ensure sufficient binding reactions. Herein, we propose a novel microfluidic disk comprising a 3D incubation chamber. Vascular endothelial growth factor as concentration with ng mL-1 is detected sequentially using a benchtop process employing this 3D microfluidic disk. The 3D microfluidic disk is implemented without requiring manual intervention or additional procedures for liquid control. During the incubation process, microbead movement is controlled through centrifugal force, generated due to disk rotation, and gravitational force via bead sedimentation on the sloped floor of the chamber.

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.

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.

Proteins having a variety of functions play many essential roles in maintaining various life activities in organisms. Various methods, by which new protein functions can be artificially produced, have progressed rapidly upon development in recombinant DNA technology and effective screening techniques. However, the obtainable scope of the new functions has been restricted in a narrow range, because only functions of presently existing proteins can be used. On the other hand, it has been considered that it would be impossible to create an entirely new protein, which does not show any meaningful homology with any other amino acid sequences of previously existing proteins. The reason is because one amino acid sequence for a protein cannot be selected out from an extraordinary large amino acid sequence diversity as ~10130. As a matter of course, it is impossible to design an amino acid sequence of a protein in advance and a gene encoding the protein cannot be also formed through random process. Nevertheless, extant organisms have generated a variety of entirely new proteins in some way to make full use of them. This means that extant organisms have equipped a mechanism with which entirely new proteins can be produced under the present core life system composed of protein, tRNA (genetic code) and gene. In this article, first I introduce the mechanism, with which entirely new proteins are created in extant organisms, and further propose a novel strategy for application of the mechanism to protein engineering through creation of entirely new proteins, which could contribute to development of various industries.

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.

Along just over a century of research we moved from learning how to cultivate tissues in a dish to grasping the concepts for creating an entire brain in a vat. As we approach the divisive moment in which we can first detect signs of awareness in such artificially developed organoids, we need to lay foundation for what lays ahead. It is crucial that ethical, legal and moral implications of organoid research are clear and that boundaries are set to separate scientific progress from human life preservation. The largest obstacle may be the definition of consciousness itself, which has arguably been historically neglected by philosophy, psychology and neurosciences at large. One reason may be the difficulties posed by the underlying qualities of awareness, such as its subjective and heterogeneous nature. Another reason may lie on the possibly that consciousness is an overarching emergent property of our brain. For the time being, one can see brain organoids as philosophical zombies, physical analogues of the human brain which mimic sentient human reactions but lack experiential properties of sensation (a.k.a. qualia).

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.

In the human organism various carotenoids are present of which, some are retinoid precursors. The bioactive derivatives of these retinoids are the retinoic acids, which can potently activate nuclear hormone receptors like the retinoic acid receptor and the retinoid X receptor. In our study using an HPLC analytical approach we aimed to assess how plasma carotenoid and retinoid concentrations along with the ratio of their isomers are altered in atopic dermatitis (AD) patients (n=20) compared to healthy volunteers (HV, n=20). We found that plasma levels of the carotenoids lutein (HV 198 ± 68 ng/ml, AD 158 ± 57 ng/ml), zeaxanthin (HV 350 ± 142 ng/ml, AD 236 ± 85) as well as the retinoids retinol (HV 216 ± 89 ng/ml, AD 167 ± 76 ng/ml) and all-trans-retinoic acid (HV 1.1 ± 0.6 ng/ml, AD 0.7 ± 0.5 ng/ml) were significantly lower in AD-patients, while lycopene, α-carotene and β-carotene levels were comparable. In addition the ratios of 13-cis vs. all-trans lycopene as well as 13-cis vs. all-trans retinoic acid were increased in the plasma of AD-patients indicating an AD-specific 13C-isomerisation. A positive correlation with SCORRAD was calculated with 13-cis vs. all-trans lycopene ratio, while a negative correlation was observed with zeaxanthin plasma levels. Based on our results we conclude that in the plasma of AD-patients various carotenoids and retinoids are at lower levels, while the ratio of lycopene isomers was also altered. The higher rate of lycopene and retinoic acid isomerisation products might be a consequence of AD or might result in an altered activation of nuclear hormone receptor signaling pathways and thus maybe partly be responsible for the AD-phenotype and additionally may represent a good plasma marker for AD.

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.

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

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.

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.

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

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 consequences of manipulations in structure and amino acid composition of native cyclolinopeptide A (CLA) from linen seeds and its linear precursor on their biological activities and mechanisms of action are reviewed. The modifications included truncation of the peptide chain, replacement of amino acid residues with proteinogenic or non-proteinogenic ones, modifications of peptide bond, and others. The studies revealed changes in the immunosuppressive potency of these analogs investigated in a number of in vitro and in vivo experimental models, predominantly in rodents, as well as differences in their postulated mechanism of action. The modified peptides were compared with cyclosporine A and parent CLA. Some of the synthesized and investigated peptides show potential therapeutic usefulness.

The phenylpropanoid pathway is a major secondary metabolite pathway that helps plants overcome biotic and abiotic stress and produces various by-products that promote human health. Its byproduct, chloroquinic acid (CQA), is a soluble phenolic compound present in many angiosperms. Hy-droxycinnamate-CoA shikimate/quinate transferase(BAHDs superfamily enzyme) is a significant en-zyme that plays a role in accumulating CQA biosynthesis. This study analyzed transcriptome-wide identification of the phenylpropanoid to chloroquinic acid biosynthesis candidate genes in A. spathulifolius flowers and leaves. Transcriptomic analyses of the flowers and leaves showed a differential expression of the PPP and CQA biosynthesis regulated unigenes. An analysis of PPP captive unigenes revealed the following: the major duplication of the key enzyme, PAL, 120 unigenes in leaves and 76 in flowers; the gene encoding C3’H, 169 unigenes in leaves and 140 unigenes in flowers; duplicated unigenes of 4CL, 41 in leaves and 27 in flowers. In addition, C4H unigenes had 12 unigenes in the leaves of A. spathulifolius and four in the flowers. The characterization of the BAHDs superfamily members identified 82 in leaves and 72 in flowers. Among them, phylogenetic analysis showed that five unigenes encoded HQT and three en-coded HCT in A. spathulifolius. The three HQT are common to both leaves and flowers, whereas the two HQT were specialized for leaves. The pattern of HQT synthesis was upregulated in flowers, whereas HCT was expressed strongly in the leaves of A. spathulifolius. Overall, 4CL, C4H, and HQT are expressed strongly in flowers, and caffeic acid and HCT show more expression in leaves. Therefore, CQA biosynthesis occurs in the flowers of A. spathulifolius rather than leaves.

Macro and micronutrients, essential for the maintenance of human metabolism, are daily assimilated through the diet. Wheat and other major cereals are a good source of nutrients, such as carbohydrates and proteins, but cannot supply enough amounts of essential micronutrients which includes provitamin A. As vitamin A deficiency (VAD) lead to several serious diseases spread worldwide, the biofortification of a major staple crop, such as wheat, represents an effective way to preserve human health in developing countries. In the present work, a key enzyme involved in the branch of carotenoids pathway producing β-carotene, lycopene epsilon cyclase, has been targeted by a TILLING approach in a “Block strategy” perspective. The null mutant genotype showed a strong reduction in the expression of lcyE gene and also interesting pleiotropic effects on an enzyme (β-ring hydroxylase) acting downstream in the pathway. Biochemical profiling of carotenoids in the wheat mutant lines showed an increase of roughly 75% in β-carotene in the grains of the complete mutant line vs. the control. In conclusions, here we describe the production and the characterization of a new wheat line biofortified in provitamin A obtained through a non-transgenic approach also shading new light on the molecular mechanism governing carotenoids biosynthesis in durum wheat.

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

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.

Translation is spatiotemporally regulated and ER-associated mRNAs are generally in efficient translation. It is unclear whether the ER-associated mRNAs are deadenylated or degraded on the ER surface in situ or in the cytosol. Here, we showed that ER possessed active deadenylases, particularly the poly(A)-specific ribonuclease (PARN), in common cell lines and mouse tissues. Consistently, purified recombinant PARN exhibited a strong ability to insert into the Langmuir monolayer and liposome. ER-anchored PARN was found to be able to reshape the poly(A) length profile of the ER-associated RNAs by suppressing long poly(A) tails without significantly influencing the cytosolic RNAs. The shortening of long poly(A) tails did not affect global translation efficiency, suggesting that the non-specific action of PARN towards long poly(A) tails was beyond the scope of translation regulation on the ER surface. Transcriptome sequencing analysis indicated that the ER-anchored PARN trigged the degradation of a small subset of ER-enriched transcripts. The ER-anchored PARN modulated the translation of its targets by redistributing ribosomes to heavy polysomes, suggesting that PARN may play a role in dynamic ribosome reallocation. During DNA damage response, MK2 phosphorylated PARN-Ser557 to modulate PARN translocation from the ER to cytosol. By promoting the decay of ER-associated MDM2 transcripts with low ribosome occupancy, the ER-anchored PARN modulated DNA damage response and thereby cell viability. These findings revealed that a highly regulated communication between mRNA degradation rate and translation efficiency is present on the ER surface in situ and that PARN may contribute to this communication by modulating the dynamic ribosome reallocation between transcripts with low and high ribosome occupancies.

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

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.

(1) Background: Deep hypothermic circulatory arrest (DHCA) with selective antegrade cerebral perfusion (ACP) is an established cerebral protection technique for the conduction of complex surgical procedures involving the aortic arch. It is controversial if the duration of DHCA is associated with adverse outcome in patients with acute type A aortic dissection (AAAD). Our goal was to investigate whether DHCA time was associated with surgical outcome in patients undergoing a surgical treatment of AAAD. (2) Methods: 410 Patients were divided into two groups concerning the DHCA time less than 60 minutes and equal or longer than 60 minutes. (3) Results: Patients with longer DHCA time were significantly younger (p=0.001). Intraoperatively, complex procedures with aortic arch surgery were more common in patients with longer DHCA time (p&lt;0.001). Accordingly, cardiopulmonary bypass (p&lt;0.001), cross-clamping (p&lt;0.001) and DHCA times (p&lt;0.001) were significantly longer in this group. Postoperatively, only the duration of mechanical ventilation (p&lt;0.001) and the rate of tracheotomy were significantly higher in these patients. 30-day mortality was satisfactory for both groups (p=0.746). (4) Conclusions: Our results showed that improvements in perioperative management including ACP allow a successful performance of surgical treatment of AAAD under DHCA with duration of even longer than 60 minutes.

Methionine 77 in calmodulin can be stereospecifically oxidized to methionine sulfoxide by mammalian methionine sulfoxide reductase A. Whether this has in vivo significance is unknown. We therefore created a mutant mouse in which wild-type calmodulin-1 was replaced by a calmodulin containing a mimic of methionine sulfoxide at residue 77. Total calmodulin levels were unchanged in the homozygous M77Q mutant, which is viable and fertile. No differences were observed on learning tests, including the Morris water maze and associative learning. Cardiac stress test results were also the same for mutant and wild type mice. .However, young male and female mice were 20% smaller than wild type mice, although food intake was normal for their weight. Young M77Q mice were notably more active and exploratory than wild type mice. This behavior difference was objectively documented on the treadmill and open field tests. The mutant mice ran 20% longer on the treadmill than controls, and in the open field test, the mutant mice explored more than controls and exhibited reduced anxiety These phenotypic differences bore a similarity to those observed in mice lacking calcium/calmodulin kinase Iiα (CaMKIIα). We then showed that M77Q calmodulin was less effective in activating CaMKIIα than wild type calmodulin. Thus, characterization of the phenotype of a mouse expressing a constitutively active mimic of calmodulin led to the identification of the first calmodulin target that can be differentially regulated by the oxidation state of Met77. We conclude that reversible oxidation of methionine 77 in calmodulin by MSRA can regulate cellular function.

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

Under the main features required on portable devices in electrochemical instrumentation is to have a small size, low power consumption, economically affordable, and precision in the measurements. This paper describes the development of a programmable Embedded Potentiostat System (EPS) capable of performing electrochemical sensing over system-on-a-chip platforms. Furthermore, the study explains a circuit design and develops some validation of the entire system. The hardware validation is performed by electrochemical experiments such as Double Step Chronoamperometry (DSC), Linear Sweep Voltammetry (LSV) and Cyclic Voltammetry (CV); moreover, a comparison of the experimental signals between a commercial potentiostat and the EPS was done by analysis of errors on the response signal. Results illustrate that the EPS is capable of handling currents in the range of absolute values of 86.44 to 3000 nA, and having control voltages in the range of ± 2 V. The device can support from 50 to 2000 samples per second. The EPS capabilities were compared with other compact potentiostats. The programmable EPS is an original approach which hugely reduces the hardware complexity and leads the way to create new applications for Point-of-Care or industrial developments with a reusable full electronics module.

We define computable functions $g,h:$ $\mathbb N$ $\setminus \{0\} \to$ $\mathbb N$ $\setminus \{0\}$. For an integer $n \geqslant 3$, let $\Psi_n$ denote the following statement: if a system ${\mathcal S} \subseteq \Bigl\{x_i!=x_k: (i,k \in \{1,\ldots,n\}) \wedge (i \neq k)\Bigr\} \cup \Bigl\{x_i \cdot x_j=x_k: i,j,k \in \{1,\ldots,n\}\Bigr\}$ has only finitely many solutions in positive integers $x_1,\ldots,x_n$, then each such solution $(x_1,\ldots,x_n)$ satisfies $x_1,\ldots,x_n \leqslant g(n)$. For a positive integer $n$, let $\Gamma_n$ denote the following statement: if a system $S \subseteq \Bigl\{x_i \cdot x_j=x_k:~i,j,k \in \{1,\ldots,n\}\Bigr\} \cup \Bigl\{2^{\textstyle 2^{\textstyle x_i}}=x_k:~i,k \in \{1,\ldots,n\}\Bigr\}$ has only finitely many solutions in positive integers $x_1,\ldots,x_n$, then each such solution $(x_1,\ldots,x_n)$ satisfies $x_1,\ldots,x_n \leqslant h(n)$. We prove: (1) if the equation $x!+1=y^2$ has only finitely many solutions in positive integers, then the statement $\Psi_6$ guarantees that each such solution $(x,y)$ belongs to the set $\{(4,5),(5,11),(7,71)\}$, (2) the statement $\Psi_9$ proves the following implication: if there exists a positive integer $x$ such that $x^2+1$ is prime and $x^2+1>g(7)$, then there are infinitely many primes of the form $n^2+1$, (3) the statement $\Psi_9$ proves the following implication: if there exists an integer $x \geqslant g(6)$ such that $x!+1$ is prime, then there are infinitely many primes of the form $n!+1$, (4) the statement $\Psi_{16}$ proves the following implication: if there exists a twin prime greater than $g(14)$, then there are infinitely many twin primes, {\bf (5)}~the statement $\Gamma_{13}$ proves the following implication: if $n \in$ $\mathbb N$ $\setminus \{0\}$ and $2^{\textstyle 2^{\textstyle n}}+1$ is composite and greater than $h(12)$, then $2^{\textstyle 2^{\textstyle n}}+1$ is composite for infinitely many positive integers $n$.

It is discovered that the gravitational field on the surface of a neutron star is with a relativistic mass density of 2.65*10¹⁶~5.87*10¹⁸kgm^-3 which can be larger than the mass density of the neutron star (~10¹⁷kgm^-3). And, the total relativistic mass of the gravitational field of the Sun is ~10⁷ times the mass of the Sun. For different stars, the relativistic mass of the gravitational field is larger as the mass density of the star is larger. In the Milky Way, the total relativistic mass of the gravitational fields is much larger than the total mass of the stars, planets and gas. And, the relativistic mass density of the observed strongest magnetic field is 2.17*10⁸kgm^-3. This discovery should be a new frame to understand the fundamental problem of physics.

Skin ageing is a progressive but modifiable, multi-factorial disorder that involves all skin tissues. Pertaining to its wide range of physiological and psychosocial complications, skin ageing requires rigorous clinical attention. Topical retinoids and per-oral proteoglycans are promising, non-invasive, therapeutic modalities. To overcome the low bioavailability of conventional free retinoids, Nourella® cream with Retilex-A® (Pharma Medico, Aarhus, Denmark) was developed using a proprietary nano-encapsulation technology. The nano-encapsulation is a sophisticated ‘permeation/penetration enhancer’ that optimises topical drug delivery by increasing surface availability and net absorption ratio. Treatment adherence is also improved by minimising skin irritation. Interventional evidence supports the higher efficacy of Retilex-A® in improving skin thickness and elasticity compared with conventional free forms. It is also reported that the rejuvenating efficacy of Retilex-A® and tretinoin are comparable. Another skin anti-ageing approach is proteoglycan replacement therapy (PRT) with Vercilex®. Vercilex® in Nourella® tablet has the potential to ameliorate proteoglycan dysmetabolism in the aged skin by activating skin cells and improving collagen/elastin turnover. Replicated clinical trials evidenced that PRT can significantly enhance the density, elasticity and thickness of both intrinsically aged and photoaged skin. Evidently, Vercilex® and Retilex-A® share a range of bioactivities, which underlies their synergistic activity observed in a clinical trial. Dual therapy with Nourella® tablets and cream produced higher effect sizes on skin characteristics than monotherapy with each of the two treatments. In conclusion, Nourella® cream and tablets are safe and effective treatments for skin ageing; however, combining the two in a ‘dual skin rejuvenation system’ significantly improves treatment outcomes.

Human Parechoviruses, officially known as Parechovirus A (PeV-A), is associated with mild gastrointestinal and respiratory illness in young children, however, they may also give rise to Central Nervous System (CNS) infections and neonatal sepsis. While studies have delved into the detection of PeV-A in different populations, the detection of PeV-A in Hispanic populations in Latin American countries is not well-known. The aim of this study was to determine the presence of PeV-A in respiratory, gastrointestinal, and neurological clinical samples of pediatric patients in Panama. Two hundred samples of pediatric patients with a negative diagnosis for the main respiratory viruses, rotavirus and neurological viruses such as herpesvirus, enterovirus and cytomegalovirus, collected between 2014 and 2015, were analyzed by real-time RT-PCR. Eight positive PeV-A infections were detected, 2 in respiratory samples, 5 in stool samples and one detected in cerebrospinal fluid. This is the fisrt report of PeV-A in Panamá.

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

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.

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

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.

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

The concept of sustainable management in culture has been recognised in global strategic documents on sustainable development for more than a decade. It is also increasingly reflected in the cultural polices of particular states, and – very importantly –cultural managers responsible for shaping the cultural offer in cities are becoming more interested in this concept. Despite the increasing attention being paid to this topic among both practitioners and theoreticians of management, in none of these documents or other works can we find any content directly related to the possibility of applying this concept in a town which, due to political turmoil, has been divided by a national border. Hence, this gap was the direct impulse for taking up research in this field. In the article, by using different notions of the market, our own definition of a cross-border market for cultural services was developed, and the conditions for the functioning of this market were presented based on the example town of Cieszyn (Poland) and Český Těšín (Czech Republic). In the opinion of the authors of the article, the development and functioning of a cross-border market for cultural services is essential for the application of the concept of sustainable management of the cultural offer in a town divided by a border. For the purpose of the article, a survey and individual interviews with experts shaping the cultural offer in Cieszyn and Český Těšín were conducted. The results of the research prove that despite numerous cross-border Czech-Polish projects carried out by cultural institutions, there are still many barriers in the town which make it difficult for the residents to benefit from the cultural offer available on the other side of the border. These barriers limit the full implementation and application of the concept of sustainable management of the cultural offer.

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.

This paper is mainly based on a stricter premise of the twin paradox and the assumption of inertial frame, discusses the properties of time and space under the premise of complete symmetry, and draws an interesting conclusion: the simultaneity of different reference frames is possible realized, and the space is relatively independent. And based on this, the twin paradox, cosmic inflation, ultra-distance action of quantum entanglement, microscopic space motion of particles, measurement problems and other phenomena are tentatively explained from a new angle. This interpretation is exploratory and new. At the same time, the author also proposes an experimental way to test the relative independence of space.At the same time, this paper attempts to strictly prove that Einstein's definition of simultaneity and spatial absoluteness in special relativity may be problematic.

The epigenetic modifications control the pathogenicity of human pathogenic fungi, which have been poorly studied in Mucorales; causative agents of mucormycosis. This order belongs to a group referred to as early-diverging fungi that are characterized by high levels of N6-methyldeoxyadenine (6mA) in their genome with dense 6mA clusters associated with actively expressed genes. AlkB enzymes can act as demethylases of 6mA in DNA, with the most remarkable eukaryotic examples being mammalian ALKBH1 and Caenorhabditis elegans NMAD-1. Mucor lusitanicus (formerly M. circinelloides f. lusitanicus) genome contains one gene, dmt1, and two genes, dmt2 and dmt3, encoding proteins homologs to C. elegans NMAD-1 and ALKBH1, respectively. The function of the three genes was analyzed by the generation of single and double deletion mutants for each gene. Multiple processes were studied in the mutants, but defects were only found in single and double deletion mutants for dmt1. In contrast to the wild-type strain, dmt1 mutants showed an increase of 6mA levels during the dimorphic transition, suggesting that 6mA regulates dimorphism in M. lusitanicus. Furthermore, the spores of dmt1 mutants challenged with macrophages underwent a reduction of polar growth, suggesting that 6mA also has a role during the spore-macrophage interaction that could be important in the infection process.

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

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.

A challenging problem in the aquaculture industry is bacterial disease outbreaks which results in the global reduction of fish supply and foodborne outbreaks. Biofilms in marine pathogens protect against antimicrobial treatment and host immune defence. Zeolites are minerals of volcanic origin made from crystalline aluminosilicates which are useful in agriculture and in environmental management. In this study, silver ion-exchanged zeolite A of four concentrations; 0.25M (AgZ1), 0.50M (AgZ2), 1.00M (AgZ3)and 1.50M (AgZ4) were investigated for biofilm inhibition and antimicrobial properties against two predominant marine pathogens V. campbelli and V. parahemolyticus by employing the Minimum Inhibitory Concentration(MIC), Crystal Violet Biofilm Quantification assays as well as Scanning Electron Microscopy. In the first instance, all zeolite samples AgZ1-AgZ4 showed antimicrobial activity for both pathogens. For V. campbellii AgZ4 exhibited the highest MIC at 125.00 µg/ml while for V. parahaemolyticus the highest MIC was observed for AgZ3 at 62.50 µg/ml. At sublethal concentration, biofilm inhibition of V. campbelli and V. parahemolyticus by AgZ4 were observed at 60.2% and 77.3% inhibition respectively. Scanning electron microscopy exhibited profound structural alteration of the biofilm matrix by AgZ4. This is the first known study that highlights the potential application of ion-exchanged Zeolite A against marine pathogens and their biofilms.

. In this article, a search for a calculation method and an analysis of performance indicators of mutual investment funds is carried out. Many factors can influence the return on investments in portfolio investments, which makes the choice of the fund incredibly difficult. However, in addition to the fact that it is difficult to determine which indicators should be given more attention and which should be omitted, it is not so easy to get these data. Some of them are publicly available on the Internet, while others can only be found in trading systems that are not accessible to people outside of this area. The article proves that a well-trained neural network can easily find existing patterns between risk and expected return on investment. It is a well-trained neural network that provides the ability to use the "what-if" function to justify your choice on real factors, as well as the ability to download available data and calculate the estimated income and its changes. This makes it much easier to choose a Fund, especially for inexperienced investors. The article also presents the results of a study of the dependence of estimated income on correlation, standard deviation, and volatility using a trained neural network. According to the theory, higher values of these three factors correspond to a higher amount of income. The obtained graphs of the calculated income dependence on correlation, standard deviation, and volatility confirmed the correctness of the neural network training and compliance with the relations described in the theory. The paper presents graphs of the dependence of the estimated income on the beta and alpha coefficients. The higher the beta and alpha indicators, the higher the expected return on investment. This corresponds to the dependency accepted in the model. When the values of the beta and alpha coefficients increase, the income also increases, which is completely consistent with the theory.

Influenza is a highly contagious, acute respiratory illness, which represents one of the main health issues worldwide. Even though some antivirals are available, the alarming increase of virus strains resistant to them highlights the need to find new drugs. Previously, Superti et al. have deeper investigated the mechanism of the anti-Influenza virus effect of bovine Lactoferrin (bLf) and the role of its tryptic fragments (the N and C-lobes) in the antiviral activity. Recently, through a truncation library, we identified the tetrapeptides, SKHS (1) and SLDC (2), derived from bLf C-lobe fragment 418-429, which were able to bind hemagglutinin (HA) and inhibit cell infection in a concentration range of femto- to picomolar. Starting from these results, in this work, we initiated a systematic SAR study on the peptides mentioned above, through an Alanine scanning approach. We carried out binding affinity measurements by microscale thermophoresis (MST) and Surface Plasmon Resonance (SPR), and hemagglutination inhibition (HI) and virus neutralization (NT) assays on synthesized peptides. Computational studies were performed to identify possible lig-and-HA interactions. Results obtained led to the identification of an interesting peptide endowed with broad anti-Influenza activity and able to inhibit viral infection to a greater extent of reference peptide.

In plants, water flows are the major driving force behind the growth and play a crucial role in the life cycle. To study hydrodynamics, methods based on tracking small particles inside water flows occupy a special place. Due to these tools, it is possible to get information about the dynamics of the spatial distribution of the fluxes characteristics. In this paper, using contrast-enhanced MRI, we have shown that gadolinium chelate, used as an MRI contrast agent, marks the structural characteristics of xylem bundles of maize stem nodes and internodes. Supplementing MRI data, a high-precision visualization of xylem vessels by laser scanning microscopy was used to reveal structural and dimensional characteristics of the stem vascular system. In addition, we proposed the concept of using the prototype "Y-type xylem vascular bundles" as a model of the elementary connection of vessels within the vascular system. A Reynolds number can match the microchannel model with the real xylem vessels.

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.

In this study, we evaluated the effects of Cyclosporine A (CsA) on Lipopolysaccharide (LPS)-induced cytokine production in the genital tract of female rabbits. Twelve sexually mature and healthy female rabbits were randomly divided into four groups (n = 3 each). The rabbits in the LPS group were given an intrauterine infusion of Escherichia coli LPS (4 mg/kg body weight (BW)). Rabbits in the CsA group were given CsA (20 mg/kg BW). Rabbits in the LPS + CsA group were given LPS (4 mg/kg BW) and CsA (20 mg/kg BW). The control group received only LPS and CsA carrier. The gene expression and protein levels of pro- and anti-inflammatory cytokines were observed using qRT-PCR and immuno-histochemical (IHC) assay, respectively. Our study showed that IL-1β, IL-6, IL-8, TNF-α, IFN-γ, IL-4, IL-10, IL-13, and TGF-β were expressed in female genital organs. The LPS challenge increased the mRNA expression of IL-6 and TNF-α in the uterine body and IL-1β in the uterotubal junction compared to the control group. CsA increased the basal mRNA expression of anti-inflammatory cytokines (i.e., IL-4 in the uterine body, uterotubal junction, and oviductal ampulla; IL-10 in the cervix, oviductal isthmus, and ampulla; and TGF-β in the uterotubal junction and oviductal ampulla) and pro-inflammatory cytokines (i.e., IL-6 and IL-8 in the cervix; IL-1β in the oviductal isthmus; TNF-α in the oviductal ampulla; and IFN-γ in the uterine body compared to the control group). In addition, CsA inhibited the mRNA expression of pro-inflammatory cytokines, such as IL-6 in the uterine body, uterotubal junction, and oviductal isthmus; TNF-α in the uterine body; and IFN-γ in the uterotubal junction and oviductal isthmus induced by the LPS challenge. The IHC assay showed the LPS-induced increase in protein production of IL-6 in the uterine body and oviductal isthmus. CsA increased the protein production of IL-10 in the cervix, uterine body, oviductal ampulla, and isthmus. Moreover, CsA decreased the protein production of IL-6 in the uterine body and oviductal isthmus induced by LPS.

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.

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

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

The conformational state of the activation loop (A-loop) is pivotal for the activation of most protein kinases. Hence, the characterization of the conformational dynamics of the A-loop is important to increase our understanding of the molecular processes related to diseases and to support the discovery of small molecule kinase inhibitors. Here, we carry out a combination of Molecular Dynamics (MD) and Essential Dynamics (ED) analyses to fully map the effects of phosphorylation, ADP, and conformation disrupting (CD) inhibitors (i.e., CD532 and MLN8054) on the dynamics of the A-loop of Aurora-A. MD revealed that the stability of the A-loop in an open conformation is enhanced by single phospho-Thr-288, while paradoxically, the presence of second phosphorylation at Thr-287 decreases such stability and renders the A-loop more fluctuant in time and space. Moreover, we found that such post-translational modification has a significant effect on the direction of A-loop motions. ED analysis suggests that the presence of the phosphate moiety induces the dynamics of Aurora-A to sample two distinct energy minima, instead of a single large minimum, as in unphosphorylated Aurora-A states. This suggests that the conformational distributions of Aurora-A with both single and double phospho-threonine modifications are remarkably different from the unphosphorylated state. In the closed states, binding of CD532 and MLN8054 inhibitors has the effect of increasing the distance of the N- and C-lobes of the kinase domain of Aurora-A, and the angle analysis between those two lobes during MD simulations showed that the N- and C-lobes are kept more open in presence of CD532, compared to MLN8054. As the A-loop is a common feature of Aurora protein kinases, our studies provide a general description of the conformational dynamics of this structure upon phosphorylation and different ligands binding.

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

Schistosomiasis, a crippling ailment that afflicts over 220 million people worldwide. Yet or up till now, there is no vaccine for schistosomiasis, and chemotherapy relies heavily on a single drug, the praziquantel. The present study was undertaken to investigate the therapeutic effect of Monophosphoryl Lipid A (MPLA) as an adjuvant in soluble egg antigen (SEA) vaccinated mice against the deleterious pathological impacts induced in hepatic tissues of mice by Schistosoma mansoni infection. In addition, to study the associated parasitological, immunological and biochemical parameters. Parasitological parameters showed that intraperitoneal injection of MPLA into SEA-vaccinated and S. mansoni-infected mice was effective to a significant degree in reducing the worm and egg burden, granuloma count and diameter as well as the total area of infection in their livers versus SEA-untreated but infected ones. In addition, MPLA showed ameliorative action on the elevated liver oxidative stress marker, including malondialdehyde (MDA) and decrease in the level of the antioxidant enzymes, reduced glutathione (GSH) and catalase (CAT) which may have a role in the liver damage and fibrosis due to S. mansoni infection. In conclusion, treatment with MPLA has multi-functions in attenuating the deleterious impacts of S. mansoni infection in mice livers. Its effects are mediated through a reduction of ova count, worm burden, granuloma diameter and amelioration of antioxidant defense systems, and liver function biomarkers.

Rotaviruses are highly infectious and typically transmitted by fecal-oral route via in the tropics and leading the cause of diarrheal deaths in children of developing countries, besides causing significant economic impacts like neonatal disease agents of domestic animals. This present report aims to present the clinical and diagnostic findings of two confirmed cases of rotavirus (RV) infection in orphaned Leopardus tigrinus (Schreber, 1775) and Leopardus pardalis (Linnaeus, 1758), the first register of the infection by group A rotavirus in these species. Both felids were rescued in the Pará State Amazon Brazil by the IBAMA (the Brazilian Institute of Environment and Renewable Natural Resources), and treated by veterinarians into intensive care ward in a public Environmental Park of Belém city. After the adaptation period to the quarantine, these animals showed non-specific symptoms of acute fulminant gastroenteritis. Rotavirus group A antigen was identified in blood and faecal samples of L. tigrinus analyzed by immunochromatography (ICG) and immunoassay methods (ELISA) at the Virology Laboratory of the Institute Evandro Chagas. The animals died within few days during the clinical exacerbation unresponsive to current treatment, its necropsies and histopathological analysis were performed in the Laboratory of Veterinary Pathology of the Federal Rural University of Amazonia (UFRA). Despite the compatible pathologic findings of rotavirus infection in both animals, the atypical hemorrhagic character was a curious finding, considering the presumed etiology.

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

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

We discuss the influence played by different statistical models in the prediction of porosity and litho-fluid facies from logged and post-stack inverted acoustic impedance (Ip) values. We compare the inversion and classification results obtained under three different a-priori statistical assumptions: an analytical Gaussian distribution, an analytical Gaussian-mixture model and a non-parametric mixture distribution. The first model assumes Gaussian distributed porosity and Ip values, thus neglecting their facies-dependent behaviour caused by different lithologic and saturation conditions. Differently, the other two statistical models relate each component of the mixture to a specific litho-fluid facies, so that the facies-dependency of porosity and Ip values is taken into account. Blind well tests are used to validate the final predictions, whereas the analysis of the maximum-a-posteriori (MAP) solutions, the coverage ratio and the contingency analysis tools are used to quantitatively compare the inversion outcomes. This work points out that the correct choice of the statistical petrophysical model could be crucial in reservoir characterization studies. Indeed, for the investigated zone it turns out that the simple Gaussian model constitutes an oversimplified assumption, while the two mixture models provide more accurate results, although the non-parametric one yields slightly superior predictions with respect to the Gaussian-mixture assumption.

Steels studs are an inevitable part of drywall construction as they are lightweight and offer the required structural stability. However, the studs act as sound bridges between the plasterboards reducing the overall sound insulation of the wall. Overcoming this often calls for wider cavity walls and complex stud decoupling fixtures that increase the installation cost while reducing the floor area. As an alternative approach, this research reveals the potential of perforated studs to improve the acoustic insulation of drywall partitions. The acoustic and structural performance is characterized using a validated finite element model that acted as a prediction tool in reducing the number of physical tests required. The results established that an acoustic numerical model featuring fluid-structure-interaction can predict the weighted sound reduction index of a stud wall assembly at an accuracy of ±1 dB. The model was used to analyze six perforated stud designs and found to outperform the sound insulation of non-perforated drywall partitions by reducing the sound bridging. Overall, the best performing perforated stud design was found to offer improvements in acoustic insulation of up to 4 dB, while being structurally compliant.

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

In this article, a search for a calculation method and an analysis of performance indicators of mutual investment funds is carried out. Many factors can influence the return on investments in portfolio investments, which makes the choice of the fund incredibly difficult. However, in addition to the fact that it is difficult to determine which indicators should be given more attention and which should be omitted, it is not so easy to get these data. Some of them are publicly available on the Internet, while others can only be found in trading systems that are not accessible to people outside of this area. The article proves that a well-trained neural network can easily find existing patterns between risk and expected return on investment. It is a well-trained neural network that provides the ability to use the "what-if" function to justify your choice on real factors, as well as the ability to download available data and calculate the estimated income and its changes. This makes it much easier to choose a Fund, especially for inexperienced investors. The article also presents the results of a study of the dependence of estimated income on correlation, standard deviation, and volatility using a trained neural network. According to the theory, higher values of these three factors correspond to a higher amount of income. The obtained graphs of the calculated income dependence on correlation, standard deviation, and volatility confirmed the correctness of the neural network training and compliance with the relations described in the theory. The paper presents graphs of the dependence of the estimated income on the beta and alpha coefficients. The higher the beta and alpha indicators, the higher the expected return on investment. This corresponds to the dependency accepted in the model. When the values of the beta and alpha coefficients increase, the income also increases, which is completely consistent with the theory.

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

Background: The manifestations, severity, and mortality of COVID-19 are considered to be associated with the changes in various hematological parameters and in immunity. Associations of immunoglobulin G antibodies against severe acute respiratory syndrome-linked coronavirus (IgG-SARS)-positive status with cardiac function and hematological and biochemical parameters in apparently health subjects are poorly understood. Methods: The present cross-sectional study included 307 healthy volunteers (24-69 years of age; 44.8±8.6 years; 80.4% men) and was initiated in 2019 before the COVID-19 pandemic. COVID-19 episodes were confirmed by detection of IgG-SARS against SARS-CoV-2 S1 RBD to reveal 70 IgG-SARS-positive and 237 negative participants. Numerous ultrasound characteristics were assessed by echocardiography, and 15 hematological and biochemical parameters were assayed in the blood. Descriptive and comparative analysis was based on the IgG-SARS status of the participants. Results: The left ventricular mass index, mitral ratio of peak early to late diastolic filling velocity or flow velocity across the mitral valve, and deceleration time of early mitral inflow were decreased (P<0.05) in IgG-SARS-positive participants versus those in IgG-SARS-negative participants according to multivariate logistic regression analysis. Erythrocyte sedimentation rate and platelet count were slightly increased, and blood hemoglobin was decreased in IgG-SARS-positive participants compared with those in IgG-SARS-negative participants. Conclusions: LV filling, inflammation, blood coagulation, and hemoglobin appear to be influenced by COVID-19 infection in healthy participants. These observations contribute to the development of a population recovery strategy after the episodes of COVID-19.

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.

Immobilized metal affinity chromatography (IMAC) is a popular and valuable method for the affinity purification of polyhistidine-tagged recombinant proteins. However, it often shows practical limitations, which might require cumbersome optimizations, additional polishing, and enrichment steps. Here, we present functionalized corundum particles for the efficient, economical, and fast purification of recombinant proteins in a column-free format. The corundum surface is first derivatized with the amino silane APTES, then EDTA dianhydride, and subsequently loaded with nickel ions. The Kaiser test, well-known in solid-phase peptide synthesis, was used to monitor amino silanization and the reaction with EDTA dianhydride. In addition, ICP-MS was performed to quantify the metal-binding capacity. His-tagged protein A/G (PAG), mixed with bovine serum albumin (BSA), was used as a test system. The PAG binding capacity was around 3 mg protein per gram of corundum. Cytoplasm obtained from different E. coli strains was examined as an example of a complex matrix. The imidazole concentration was varied in the loading and washing buffers. As expected, higher imidazole concentrations during loading are usually beneficial when higher purities are desired. Even when higher sample volumes, such as one liter, were used, recombinant protein down to a concentration of 1 µg/mL could be isolated selectively. Comparing the corundum material with standard Ni-NTA agarose beads indicated higher purities of proteins isolated using corundum. His6-MBP-mSA2, a fusion protein consisting of monomeric streptavidin and maltose-binding protein in the cytoplasm of E. coli, was purified successfully. To show that this method is also suitable for mammalian cell culture supernatants, purification of the SARS-CoV-2-S-RBD His8 expressed in human Expi293F cells was performed. The material cost of the nickel-loaded corundum material (without regeneration) is estimated to be less than 30 cents for 1 gram of functionalized support or 10 cents per milligram of isolated protein. Another advantage of the novel system is the corundum particles' extremely high physical and chemical stability. The new material should be applicable in small laboratories and large-scale industrial applications. In summary, we could show that this new material is an efficient, robust, and cost-effective purification platform for the purification of His-tagged proteins, even in challenging, complex matrices and large sample volumes of low product concentration.

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.

Immune surveillance by natural killer (NK) cells and their recruitment to sites of inflammation renders them susceptible to viral infection, potentially modulating their effector function. Here, we analyzed innate RNA receptor signaling in NK cells downstream of direct Influenza A virus (IAV) infection and its impact on NK cell effector function. Infection of NK cells with IAV resulted in the activation of TBK1, NF-κB and subsequent type-I IFN secretion. CRISPR- generated knockouts in primary human NK cells revealed that this effect depended on the antiviral cytosolic RNA receptor RIG-I. Transfection of NK cells with synthetic 3p-dsRNA, a strong RIG-I agonist that mimics viral RNA, resulted in a similar phenotype and rendered NK cells resistant to subsequent IAV infection. Strikingly, both IAV infection and 3p-dsRNA transfection enhanced degranulation and cytokine production by NK cells when exposed to target cells. Thus, RIG-I activation in NK cells both supports their cell intrinsic viral defense and enhances their cytotoxic effector function against target cells.

Nitroxyl radical catalysts oxidize alcohols under an applied electric potential. It is possible to quantify the alcohol concentration from the resulting oxidation current. In this work, we evaluated the catalytic activity of nitroxyl radicals (or their corresponding hydroxylamines), including 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) as representative nitroxyl radicals, acetoamido-TEMPO, which shows higher oxidation potential than TEMPO owing to the acetoamido group, AZADO, Nor-AZADO, and NNO as less-hindered bicyclic nitroxyl radicals, and NHPI as an N,N-diacyl-type hydroxylamine, in acetonitrile solution. TEMPO, AZADO and NNO were also evaluated for their ability to oxidize alcohols in organic solvents, and their reactivity was compared with the electrochemical response. The most active NNO was used for electrochemical detection of cyclosporin A, a drug with a hydroxyl group.

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.

We define degree of dependence of two events A and B in a probability space by using Boltzmann-Shannon entropy function of an appropriate probability distribution produced by these events and depending on one parameter (the probability of intersection of A and B) varying within a closed interval I. The entropy function attains its global maximum when the events A and B are independent. The important particular case of discrete uniform probability space motivates this definition in the following way. The entropy function has a minimum at the left endpoint of I exactly when one of the events and the complement of the other are connected with the relation of inclusion (maximal negative dependence). It has a minimum at the right endpoint of I exactly when one of these events is included in the other (maximal positive dependence). Moreover, the deviation of the entropy from its maximum is equal to average information that carries one of the binary trials defined by A and B with respect to the other. As a consequence, the degree of dependence of A and B can be expressed in terms of information theory and is invariant with respect to the choice of unit of information. Using this formalism, we describe completely the screening tests and their reliability, measure efficacy of a vaccination, the impact of some events from the financial markets to other events, etc. A link is available for downloading an Excel program which calculates the degree of dependence of two events in a sample space with equally likely outcomes.

Patients with lean NAFLD make up an increasing subset of liver diseases. The association between lean NAFLD and feutin-A, which serves as a hepatokine and adipokine, has never been examined. Our study aimed to explore the association of serum fetuin-A among lean and nonlean patients. The study comprised 606 adults from the community, stratified into lean or nonlean (BMI </≥ 24 kg/m2) and NAFLD or non-NAFLD (scoring of ultrasonographic fatty liver indicator, US-FLI ≥ 2/<2). Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD among the tertiles of fetuin-A after adjustment. The least square means were computed by general linear models to estimate marginal means of the serum fetuin-A concentrations in relation to the NAFLD groups. The OR of having NAFLD for the highest versus the lowest tertile of fetuin-A was 2.62 (95% CI: 1.72-3.98; P for trend<0.001). Stratifying by BMI, the OR of having lean NAFLD for the highest versus the lowest tertile of fetuin-A was 2.09 (95% CI: 1.09-3.98; P for trend 0.026), while nonlean NAFLD had no significant association with the fetuin-A gradient after adjustments. Fetuin-A was positively associated with lean NAFLD after adjusting for central obesity and insulin resistance.

In 2018, the author identified a previously unknown/unreported association between dexrazoxane and poly(ADP-ribose) (PAR). Interestingly, PAR is a close structural analogue of the polyadenine nucleotide polymer, polyadenosine monophosphate (poly(A)). In this report, subsequent in silico modelling of the interaction between dexrazoxane and poly(A) reveals some notable differences from the previously reported interaction between dexrazoxane and PAR. Significantly, the supramolecular self-assembly of dexrazoxane and poly(A) is distinguished by vertically-orientated nonelectrostatic forces comparable to the stabilizing interactions between stacked bases within DNA. Notably, the vertical separation of 3.4 Å between each stack is consistent with solvent entropy as a dominant driving force in stabilising the interaction. Additionally, concomitant conformational analysis by the author reveals the existence of low energy planar conformers of dexrazoxane. This analysis enables an explanation for the considerable discrepancies and conflicts that exist within the reported pharmacokinetic data for dexrazoxane. Exploring the significance of the interaction between dexrazoxane and poly(A), the author illustrates that survival, translation and replication of the severe acute respiratory syndrome virus 2 (SARS-CoV-2) is absolutely dependent upon the mature and unhindered poly(A) tail of the SARS-CoV-2 genome. The proposition herein, that dexrazoxane, as a chameleonic agent sequesters the poly(A) tail of the SARS-CoV-2 genome by the catalysis of a supramolecular hybrid assembly establishes SARS-CoV-2 infected cells as deep compartments for the accumulation of dexrazoxane. Taken together, dexrazoxane or its demethylated analogue, represent a novel treatment to kill the SARS-CoV-2 virus by irreversible destabilization of the SARS-CoV-2 poly(A) tail.

Application of chemical pesticides to protect agricultural crops from pests and diseases is discouraged due to their harmful effects on human and environment. Therefore, alternative approaches for crop pro-tection through microbial or microbe originated pesticides have been gaining momentum. Wheat blast is a destructive fungal disease caused by Magnaporthe oryzae Triticum (MoT) pathotype, which poses a seri-ous threat to global food security. Screening of secondary metabolites against MoT revealed that antimy-cin A isolated from a marine Streptomyces sp. had significant inhibitory effect on mycelial growth in vitro. This study aimed to investigate the inhibitory effects of antimycin A on some critical life stages of MoT and evaluate the efficacy of wheat blast disease control by this natural product. Bioassay indicated that antimycin A suppressed mycelial growth, conidiogenesis, germination of conidia and formation of ap-pressoria in germinated conidia of MoT in a dose-dependent manner with minimum inhibitory concen-tration 0.005 μg/disk. If germinated, antimycin A induced abnormal germ tubes (4.8%) and suppressed the formation of appressoria. Interestingly, application of antimycin A significantly suppressed wheat blast disease in both seedling and heading stages of wheat supporting the results from invitro study. This is the first report on inhibition of mycelial growth, conidiogenesis, conidia germination, detrimental morphological alterations in germinated conidia, and suppression of wheat blast disease caused by a Triticum pathotype of M. Oryzae. Further study is required to unravel the precise mode of action of this promising natural compound for considering it as a biopesticide to combat wheat blast.

To demonstrate if botulinum toxin type A (BoNT-A) improves mandibular range of motion and muscle sensibility to palpation in refractory myofascial pain (MFP) patients. METHODS: Eighty consecutive female subjects with refractory MFP, were randomly divided into four equal groups (n=20): BoNT-A low (BoNTA-L/10 U in each temporalis and 30 U in each masseter), BoNT-A medium (BoNTA-M/20 U in each temporalis and 50 U in each masseter), BoNT-A high (BoNTA-H/25 U in each temporalis and 75 U in each masseter) and saline solution 0.9% (SS, placebo control group/0.4 mL in each temporalis and 0.6 mL in each masseter). Clinical measurements of the mandibular movements included: pain-free opening, maximum unassisted and assisted opening, and right and left lateral movements. Palpation tests were performed bilaterally in masseter and temporalis muscle. Results were expressed as median, minimum, maximum, and means ± standard deviation (SD). Chi-Square Test was used to compare differences among groups. A 5% probability level was considered significant in all tests RESULTS: Regardless of dose, all parameters of mandibular range of motion significantly improve after 180 days in BoNT- A groups, when compared to the control group. Pain to palpation on muscles, significantly reduced in all BoNT- A groups regardless of dose, when compared to the control group, after 28 and 180 days of treatment. CONCLUSIONS: Independent of doses, BoNT-A improved mandibular range of motion and muscle sensibility to palpation in refractory MFP patients when compared to SS injections.

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.

It is well known that the photon trajectories follow a curved path in a gravitational field. We explore here the gravitational bending of electric field lines. It seems that the electric field lines of a charge, supported in a gravitational field, follow exactly the trajectories of photons emitted isotropically from a source situated at the charge location. From a detailed examination of the electrostatic field of a charge accelerated uniformly in the instantaneous rest frame, exploiting the strong principle of equivalence, one can determine the bending of the electric field lines of a charge in a gravitational field. The fraction of electric field lines crossing a surface, stationary above or below the charge in the gravitational field, is shown to be exactly similar to the fraction of photon trajectories, emitted from a source placed at the charge location, intersecting that surface. On the other hand, for a freely falling charge in the gravitational field there is no such bending of electric field lines. The field lines continue to extend in radial straight lines from the instantaneous 'present' position of the charge, as do the trajectories of photons streaming away from the instantaneous position of a freely falling source in the gravitational field. The electric field configuration of a freely falling charge in the gravitational field is shown to be exactly the same as that of a charge moving uniformly in an inertial frame with velocity equal to the instantaneous ``present'' velocity of the freely falling charge.

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.

Balínt Syndrome is an acquired disorder manifesting in the inability to recognize several objects at once (simultagnosia), inaccurate visually guided limb movements despite intact motor function (optic ataxia) and the inability to make accurate voluntary saccades to visual targets despite demonstrating unrestricted range of eye movements (ocular motor apraxia). Here we report the first case of a patient presenting with Balínt Syndrome caused by a platelet-derived growth factor receptor A mutation (PDGFRA)-induced Hypereosinophilic Syndrome (HES).

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

Manzamines are complex polycyclic marine-derived β-carboline alkaloids with reported anticancer, immunostimulatory, anti-inflammatory, antibacterial, antiviral, antimalarial, neuritogenic, hyperlipidemia and atherosclerosis suppression bioactivities, putatively associated with inhibition of glycogen synthase kinase-3, cyclin-dependent kinase 5, and vacuolar ATPases. We hypothesized that additional and yet undiscovered molecular targets might be associated with Manzamine A (MZA) reported pharmacological properties. We report herein for the first time to our knowledge that MZA inhibited a 90kDa ribosomal protein kinase S6 (RSK1) when screened against a panel of 30 protein kinases. Furthermore in vitro RSK kinase assays demonstrated a 10-fold selectivity in potency of MZA against RSK1 versus RSK2. MZA’s differential binding and selectivity toward the two isoforms is also supported by computational docking experiments. Specifically, the RSK1-MZA (N- and C-termini) complexes appear to have stronger interactions and preferable energetics contrary to the RSK2-MZA ones. In addition, our computational strategy suggests that MZA binds to the N-terminal kinase domain of RSK1 rather than the C-terminal domain. RSK is a vertebrate family of cytosolic serine-threonine kinases that act downstream of the ras-ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which phosphorylates substrates shown to regulate several cellular processes including growth, survival and proliferation. Consequently, our findings have lead us to hypothesize that MZA and the 80 currently known manzamine-type alkaloids isolated from several sponge genera, may have novel pharmacological properties.

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.

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

Despite a large amount of data on the association of folate metabolism disturbances with different aspects of schizophrenia, the role of the MTHFD1 1958 G>A polymorphism in this disorder is barely studied. The aim of this study was to assess the distribution of alleles and genotypes frequencies of MTHFD1 1958 G>A in patients with schizophrenia and healthy controls and to study the association of allele/genotype carriage of this SNP with biochemical markers of one-carbon metabolism and with the severity of schizophrenia symptoms. Methods: In 57 patients with schizophrenia and 37 healthy volunteers the carriage of alleles/genotypes of the MTHFD1 1958 G>A and biochemical markers of folate metabolism disturbances were evaluated. Clinical symptoms of schizophrenia and the severity of extrapyramidal side effects of therapy were assessed in patients. Results: an association of the wild GG genotype with schizophrenia was shown (GG versus AG / AA: χ2 = 7.31; p = 0.007). The serum folate level in carriers of the wild genotype GG is lower (in all participants p = 0.024, in patients p = 0.10), and the level of cobalamin in this subgroup is higher (in all participants p = 0.047, in patients p = 0.091) than in carriers of other genotypes. Patients carrying the G allele had less severe negative symptoms (p = 0.0041) and extrapyramidal side effects of antipsychotics (p = 0.054), than patients with AA genotype. The age of psychosis manifestation is the later, the more wild alleles G are present in the genotype (p = 0.00195).

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

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

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

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

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

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

Benzo[a]pyrene (B[a]P), is a family member of polycyclic aromatic hydrocarbons and a widespread environmental pollutant and neurotoxicant that contribute to the development of cancer. Microtubules are polymers of tubulin that form part of the cytoskeleton and target for anticancer drugs. Furthermore, NPY significantly increased the percentage of cells in S and G2/M phases. However, little is known about the specific role of NPY in proliferation and the underlying protective mechanism remains unclear. Hence, the aim of this work was to investigate the effect of B[a]P on SH-SY5Y neuroblastoma cells and to explore the potential mechanism for alteration of tubulin-microtubule equilibrium causing mitotic arrest and NPY expression. The present findings showed B[a]P treatment significantly increase number of SH-SY5Y cells in S and G2/M phase as compared to G1 phase and provokes cell cycle arrest that correlated with significant decrease in G0/G1 cells. Immunofluorescence study showed significantly distorted tubulin arrangement from metaphasic plate in formation of bipolar mitotic spindle apparatus. Further, higher doses of B[a]P treatment lead to chromosomal abnormalities accompanied by DNA damage due ROS causing oxidative stress showing significant decrease in tubulin protein around spindle. The results of present study demonstrated that NPY exerts a proliferative and protective effect on B[a]P-induced oxidative stress in a dose-dependent manner in vitro and importantly, these effects may be mediated via mitotic arrest and involved in spindle arrangement during cell division. Our findings addresses a novel pathological outcomes of B[a]P-induced NPY expression by oxidative stress through spindle abnormalities leading to microtubule disruption.

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

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

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

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

Objective: We previously provided evidence to confirm that soluble Fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and their ratio, are useful tools to direct the management of preeclampsia (PE), fetal growth restriction (FGR), and PE+FGR near delivery. In this study we examine the potential additive value of Inhibin-A, a hormone marker of the transforming growth factor family. Methods: We used a cohort of 125 pregnant women enrolled near delivery at clinics of the University Medical Center of Ljubljana, Slovenia. There were 31 cases of PE, 16 of FGR, 42 of PE+FGR, 15 iatrogenic preterm delivery (PTD), and 21 unaffected controls with delivery of a healthy baby at term. Cases delivered before 34 weeks’ gestation included 13 of PE, 12 of FGR, 22 of PE+FGR, and 6 of PTD. We recorded demographic characteristics and medical history and the levels of PlGF, sFlt-1 and Inhibin-A. The predictive accuracy of each biomarker, their ratios, and combinations was estimated from areas under the curve (AUC) of Receiver Operating Characteristics (ROC) curves. We estimated accuracy by the continuous marker model and a cut-off model. Results: Combining Inhibin-A with PlGF or with the sFlt-1 / PlGF ratio showed a 10-20% increase in AUCs and 5-15% increase in the detection rate, at 10% false positive rate, of PE, and a lower, but significant, increase for PE+FGR but not for FGR alone. The use of a cut-off model was adequate, although a bit higher accuracy was obtained from the continuous model. Highest correlation was found for PlGF with all three complications. Conclusion: Inhibin-A improves the accuracy of predicting PE and PE+FGR provided by the angiogenic markers alone, bringing the results to a diagnostic level, thus assisting in directing clinical management. Inhibin-A had no added value for the accuracy of predicting FGR alone.

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.

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