Background: Dendrobium officinale is not only an ornamental plant, but also a valuable medicinal herb that is both effective and widely used in traditional Chinese medicine. However, distinguishing D. officinale from other Dendrobium species is usually a difficult task that need much time and complex technologies due to their very similar external morphologies. The aim of this study is to develop a fast, even on-spot approach to identify D. officinale. Methods: We used DNA barcode-based loop-mediated isothermal amplification (LAMP) method with species-specific LAMP primers targeting the internal transcribed spacer (ITS) region of the rDNA of D. officinale. LAMP reaction time and temperature were optimized and the specificity and sensitivity of LAMP species-specific primers were assessed. Results: This technique showed a high specificity and sensitivity to amplify the genomic DNA of D. officinale and allowed for rapid amplification (within 40 min) of the ITS region under a constant and mild temperature range of 65 °C without using thermocyclers. Besides, by using SYBR® Green I dye as the color developing agent, the color change was easily observed with naked eye. Reaction mixture containing DNA of D. officinale changed from orange to green, while the other Dendrobium species and the negative control retained original orange color. The specificity of this LAMP-based method was confirmed by testing 17 samples of D. officinale and 32 adulterant samples from other Dendrobium species. Conclusions: This LAMP-based rapid identification method does not require expensive equipment or specialized techniques and can be used in field surveys for accurate and fast on site identification.

Equines play an important role throughout the world, whether for work, culture, or leisure, providing an ever-growing significant contribution on the economy. The increase in importation and movement of horses, both nationally and internationally, has inevitably allowed for the global equine industry to grow. Subsequently however, the potential for transmission of fatal equine bacterial diseases has also escalated, and devasting outbreaks continue to occur. To prevent such events, disease surveillance and diagnosis must be heightened throughout the industry. Current common, or "gold-standard" techniques, have shown to be inadequate at times, thus requiring newer technology to impede outbreaks. Loop-mediated isothermal amplification (LAMP) has proven to be a reliable, rapid, and accessible tool in both diagnostics and surveillance. This review will discuss equine bacterial diseases of biosecurity relevance and their current diagnostic approaches, as well as their respective LAMP assay developments. Additionally, we will provide insight regarding newer technology and advancements associated with this technique, and their potential use for the outlined diseases.

The upregulated expression of thyrosine kinase AXL has been reported in several hematologic and solid human tumors including gastric, breast, colorectal, prostate, and ovarian cancers. Thus, AXL can potentially serve as a diagnostic and prognostic biomarker for various cancers. This paper reports the first-ever use of loop-mediated isothermal amplification (LAMP) of the AXL gene as a diagnostic method for ovarian cancer. We demonstrated simple instrumentation toward a point-of-care device to perform LAMP. This paper also reports the first-ever use of core-shell beads as a microreactor to perform LAMP as an attempt to promote environmentally friendly laboratory practices.

Rice false smut caused by Ustilaginoidea virens is one of the most devastating diseases on rice worldwide, which results in serious reduction of rice quality and yield. As an airborne fungal disease, early diagnosis of rice false smut, monitoring the epidemics and distribution of its pathogens, is particularly important to management the infection. In this study, a quantitative loop-mediated isothermal amplification (q-LAMP) method for the U. virens detection and quantifying was developed. This method has higher sensitivity and efficiency compared to quantitative real-time PCR (q-PCR) method. The species-specific primer sets UV-2 used was design based on the unique sequence of U. virens ustiloxins biosynthetic gene (NCBI accession number: BR001221.1). The q-LAMP assay was able to detect a concentration of 6.4 spores/mL at an optimal reaction temperature of 63.4℃ within 60 min. Moreover, the q-LAMP assay can even achieve accurate quantitative detection when there were only 9 spores on the tape. A linearized equation for the standard curve, y =-0.2866x + 13.829 (x is the amplification time, the spore number = 100.65y), was established for detection and quantifying of U. virens. In field detection applications, this q-LAMP method is more accurate and faster than traditional observation method. Collectively, this study has established a powerful and simple monitoring tool for U. virens, which provide valuable technical supports for forecast and management of rice false smut, and theoretical basis for precise fungicide application.

The availability of simple SARS-CoV-2 detection methods is crucial to contain the COVID-19 pandemic. This study examined whether a commercial LAMP assay can reliably detect SARS-CoV-2 genomes directly in respiratory samples without having to extract nucleic acids (NA) beforehand. Nasopharyngeal swabs (NPS, n = 220) were tested by real-time reverse transcription (RT)-PCR and with the LAMP assay. For RT-PCR, NA were investigated. For LAMP, NA from 26 NPS in viral transport medium (VTM) were tested. The other 194 NPS were analyzed directly without prior NA extraction [140 samples in VTM; 54 dry swab samples stirred in phosphate buffered saline]. Ten NPS were tested directly by LAMP using a sous-vide cooking unit. The isothermal assay demonstrated excellent specificity (100%) but moderate sensitivity (68.8%), with a positive predictive value of 1 and a negative predictive value of 0.65 for direct testing of NPS in VTM. The use of dry swabs, even without NA extraction, improved the analytical sensitivity; up to 6% of samples showed signs of inhibition. The LAMP could be performed successfully with a sous-vide cooking unit. This technique is very fast, requires little laboratory resources and can replace rapid antigen tests or verify reactive rapid tests on site.

Schistosoma infection in snails can be monitored by microscopy or indirectly by sentinel mice. As both these approaches sometimes miss infections, more sensitive tests are needed, particularly in low-level transmission settings. In this study, the loop-mediated isothermal amplification (LAMP) technique, designed to detect a specific 28S ribosomal S. japonicum gene with high sensitivity, was compared to microscopy using snail samples from 51 areas endemic for schistosomiasis in five Chinese provinces. The results were compared with those by polymerase chain reaction (PCR) adding DNA sequencing as a reference when needed. The testing of pooled snail samples showed that a dilution factor of 1/50, i.e., one infected snail plus 49 non-infected ones, would still result in a positive reaction after the recommended number of amplification cycles. Testing a total of 232 pooled samples, emanating from 4,006 snail specimens, with the LAMP assay showed a 6.5% rate of infection, while traditional microscopy found only 0.04% positive samples in the same materials. Parallel PCR analysis confirmed the diagnostic accuracy of the LAMP assay, with DNA sequencing even giving LAMP a slight lead. Microscopy and the LAMP test were carried out at local schistosomiasis-control stations demonstrating that the potential of the latter assay to serve as a point-of-care (POC) test with results available within 60–90 minutes, while the more complicated PCR test had to be carried out at the National Institute of Parasitic Diseases (NIPD) in Shanghai, China. In conclusion, LAMP was found to be clearly superior to microscopy and as good as, or better, than PCR. Application of LAMP testing would be useful for surveillance and risk prediction as it requires less time than other techniques and can be used under field conditions, which improves and accelerates schistosomiasis control.

We report a small footprint cost-effective isothermal rapid DNA amplification system, with integrated microfluidics for automated sample analysis and detection of SARS-CoV-2 in human and environmental samples. Our system measures low-level fluorescent signal in real-time during amplification, while maintaining the desired assay temperature, on a low power, portable system footprint. A unique soft microfluidic chip design was implemented to mitigate thermocapillary effects and facilitate optical alignment for automated image capture and signal analysis. The system-on-board prototype coupled with the LAMP primers designed by BioCoS, is sensitive enough to detect viral loads of SARS-CoV-2 in a broad concentration range corresponding to a threshold cycle range of 16 to 39. Clinical specimens were tested at Kingston Health Sciences using a clinically validated PCR assay and variants were determined using whole genome sequencing.

This paper reports the design, development, and testing of a novel, yet simple and low-cost portable device for the rapid detection of SARS-CoV-2. The device performs loop mediated isothermal amplification (LAMP) and provides visually distinguishable images of the fluorescence emitted from the samples. The device utilises an aluminium block embedded with a cartridge heater for isothermal heating of the sample and a single-board computer and camera for fluorescence detection. The device demonstrates promising results within 20 minutes using clinically relevant starting concentrations of the synthetic template. Time-to-signal data for this device are considerably lower compared to standard qPCR machine (~10-20 minutes vs >38 minutes) for 1×105 starting template copy number. The device in its fully optimized and characterized state can potentially be used as simple to operate, rapid, sensitive, and inexpensive platform for population screening as well as point-of-need SARS-CoV-2 detection and patient management.

Abstract Successful treatment against infectious agents depends on rapid and accurate detection of the causative organisms. Misdiagnosis can hamper such success while leading to improper advising of antibiotics. In Bangladesh, the majority of the diagnostic centers detect and identify pathogens through culture and biochemical test-based methods and suggest antibiotics based solely on the results of disk-diffusion methods. This pilot study tried to validate the identity of the isolates characterized by diagnostic facilities near Dhaka. One hundred and twenty pre-characterized clinical isolates were analyzed biochemically and genotypically. Random Amplification of Polymorphic DNA-PCR, rcsA, and phoA genes-based PCR, and Loop-Mediated Isothermal Amplification (LAMP)-based identification of Klebsiella pneumoniae and Escherichia coli, respectively, followed by 16S rRNA sequencing confirmed misidentification of some clinical pathogens of other genera as Klebsiella spp. and E. coli. According to the antibiotic susceptibility testing guidelines, antibiotic choice, sensitivity pattern, and breakpoint measurement are different for each group of organisms. The lack of adherence to proper standards results in misdiagnosis and may facilitate the development of antibiotic resistance. The pilot study observers misidentification of clinical pathogens identified by the diagnostic centers. Well-characterized rapid molecular techniques like LAMP are suggested in clinical diagnosis to avoid misdiagnosis and subsequently circumvent antibiotic resistance development.

This hypothesis demonstrates that the efficiency of Loop-Mediated Isothermal Amplification (LAMP) for nucleic acid detection can be positively influenced by preconcentration of microbial cells onto hydrophobic paper surfaces. The mechanism of this model is based on the high attraction of microbes towards hydrophobic surfaces. Extensive studies have demonstrated that hydrophobic surfaces exhibit enhanced bacterial and fungal adhesion. The preconcentration approach by exploiting this inherent affinity of hydrophobic paper substrates enables the adherence of a greater number of target cells, resulting in a higher concentration of target templates for amplification directly from urine samples. In contrast to conventional methods, which often involve complex procedures, this approach offers a simpler, cost-effective, and user-friendly alternative. Moreover, the integration of cell adhesion, LAMP amplification, and signal readout within paper origami-based devices can provide a portable, robust, and highly efficient platform for rapid nucleic acid detection. This innovative hypothesis holds significant potential for point-of-care (POC) diagnostics and field surveillance applications. Further research and development in this field will advance the implementation of this technology, contributing to improved healthcare systems and public health outcomes.

A supply chain management (SCM) system is a strategic cooperative that organically integrates all supply chains to improve the performance of a company. The greatest critical success factor of SCM is partnership. Without cooperation between companies, SCM performance is limited. Does this imply, therefore, that companies within the supply chain can achieve mutual transactions equally? If the power between companies is unequal, how does this affect their partnership? The focus of this study is to assess whether power types enhance SCM performance through partnerships. We categorize power types as mediated and non-mediated. Mediated power is categorized based on coercion, reward, and legitimate, while non-mediated power is categorized based on information, expert, and reference. Therefore, this study examines how power types form a causal partnership relationship within the supply chain, and performs an empirical investigation on how the partnerships influence SCM performance.

Recent advancements in experimental and computational methods for RNA secondary structure detection have revealed the crucial role of RNA structural elements in diverse molecular processes within living cells. It has been demonstrated that the secondary structure of the entire viral genome is often responsible for performing crucial functions in the viral life cycle and also influences virus evolution. To investigate the role of viral RNA secondary structure, alongside experimental techniques, the use of bioinformatics tools is important for analyzing various secondary structure patterns, including hairpin loops, internal loops, multifurcations, external loops, bulges, stems, and pseudoknots. Here, we have introduced a Python package for analyzing RNA secondary structure elements in viral genomes, which includes the recognition of common secondary structure patterns, the generation of descriptive statistics for these structural elements, and the provision of their basic properties. We applied the developed package to analyze the secondary structures of complete viral genomes collected from the literature, aiming to gain insights into viral function and evolution. Both the package and the collection of secondary structures of viral genomes are available at http://github.com/KazanovLab/RNAsselem.

Evidence supports an association between low magnesium (Mg) intake and coronary heart disease and between Mg intake and endothelial function. The aim of this study was to assess the effect of one week of Mg supplementation on endothelial function, assessed by flow mediated dilatation (FMD). Nineteen healthy men and women completed this cross-over pilot study in which participants were randomised to take an over-the-counter magnesium supplement for one week or to follow their usual diet. Weight, FMD and blood pressure (BP) were taken on completion of each intervention and 24hour urine collections and blood samples were taken to assess compliance. Baseline serum Mg was within normal range for all participants. Urinary Mg and urinary magnesium-creatinine ratio (Mg/Cr) significantly increased between interventions, (p = 0.03, p = 0.005 respectively). No significant differences in FMD or BP were found between the interventions. A significant negative correlation was seen between age and FMD (r = -0.496, p = 0.031). When adjusted for age, saturated fat was negatively associated with FMD (p = 0.045). One week of Mg supplementation did not improve FMD in a healthy population.

Evidence supports an association between low magnesium (Mg) intake and coronary heart disease and between Mg intake and endothelial function. The aim of this study was to assess the effect of one week of Mg supplementation on endothelial function, assessed by flow mediated dilatation (FMD). Nineteen healthy men and women completed this cross-over pilot study in which participants were randomised to take an over-the-counter magnesium supplement for one week or to follow their usual diet. Weight, FMD and blood pressure (BP) were taken on completion of each intervention and 24hour urine collections and blood samples were taken to assess compliance. Baseline serum Mg was within normal range for all participants. Urinary Mg and urinary magnesium-creatinine ratio (Mg/Cr) significantly increased between interventions, (p = 0.03, p = 0.005 respectively). No significant differences in FMD or BP were found between the interventions. A significant negative correlation was seen between age and FMD (r = -0.496, p = 0.031). When adjusted for age, saturated fat was negatively associated with FMD (p = 0.045). One week of Mg supplementation did not improve FMD in a healthy population.

Magnesium (Mg) deficiency may be a catalyst in the process of endothelial dysfunction, an early event in the pathogenesis of atherosclerosis. The aim was to determine the acute effect of an oral Mg supplement compared to control on endothelieal function assessed by flow-mediated-dilatation (FMD). Nineteen participants (39 years, body mass index (BMI) 22.9kg/m2) completed this randomised cross-over study. Blood pressure (BP) and FMD were measured and blood samples taken before participants drank 200ml water with or without an over the counter Mg supplement (450mg and 300mg for men and women). Measurements were repeated at 60 and 120 minutes. There was a statistically significant two-way interaction between treatment and time on serum Mg (p = .037). A difference of -0.085mm in FMD was observed 60 minutes post drink in the control group compared to baseline FMD, and no difference was observed in the supplement group compared to baseline. Despite the non-significant interaction between treatment and time on FMD, the difference seen in the control group and the lack of change in the supplement group at 60 minutes post-drink suggests that Mg may attenuate the reduction in FMD post-prandially.

The understanding of black holes in loop quantum gravity is becoming increasingly accurate. This review focuses on the possible experimental or observational consequences of the underlying spinfoam structure of space-time. It adresses both the aspects associated with the Hawking evaporation and the ones due to the possible existence of a bounce. Finally, consequences for dark matter and gravitational waves are considered.

The successful vaccination implies the induction of effective specific immune responses. We intend to find biomarkers among various immune cell subpopulations, cytokines and antibodies which could be used to predict the levels of specific antibody- and cell-mediated responses after measles-mumps-rubella vaccination. We measured 59 baseline immune status parameters (frequencies of 42 immune cell subsets, levels of 13 cytokines, immunoglobulins) before vaccination and 13 response variables (specific IgA and IgG, antigen-induced IFN-γ production, CD107a expression on CD8+ T lymphocytes, and cellular proliferation levels by CFSE dilution) 6 weeks after vaccination for 19 individuals. Statistically significant Spearman correlations between some baseline parameters and response variables were found for each response variable (p<0.05). Due to the low number of observations relative to the number of baseline parameters and missing data for some observations, we utilized three feature selection strategies to select potential predictors of the post-vaccination responses among baseline variables: (a) screening of the variables based on the correlation analysis, (b) supervised screening based on the information of changes of baseline variables at day 7, (c) implicit feature selection is performed using regularization-based sparse regression. We identified optimal multivariate liner regression models for predicting the effectiveness of vaccination against measles-mumps-rubella using the baseline immune status parameters. It turned out that the sufficient number of predictor variables ranges from one to five depending on the response variable of interest.

The interaction between nanoparticles and cells has been studied extensively, but most research has focused on the effect of various nanoparticle characteristics, such as size, morphology, and surface charge, on the cellular uptake of nanoparticles. In contrast, there have been very few studies to assess the influence of cellular factors, such as growth factor responses, on the cellular uptake efficiency of nanoparticles. The aim of this study was to clarify the effects of epidermal growth factor (EGF) on the uptake efficiency of polystyrene nanoparticles (PS NPs) by A431 cells, a human carcinoma epithelial cell line. The results showed that EGF enhanced the uptake efficiency of A431 cells for PS NPs. In addition, inhibition and localization studies of PS NPs and EGF receptors (EGFRs) indicated that cellular uptake of PS NPs is related to the binding of EGF-EGFR complex and PS NPs. Different pathways are used to enter the cells depending on the presence or absence of EGF. In the presence of EGF, cellular uptake of PS NPs is via clathrin-mediated endocytosis, whereas in the absence of EGF, uptake of PS NPs does not involve clathrin-mediated endocytosis. Our findings indicate that EGF enhances cellular uptake of PS NPs by clathrin-mediated endocytosis. This result could be important for developing safe nanoparticles and their safe use in medical applications.

Improvement of agronomic traits in crops through gene editing (GE) relies on efficient trans-formation protocols for delivering the CRISPR/Cas9-coded transgenes. Recently, a few embryo-genesis-related genes have been described, the co-delivery of which significantly increases the transformation efficiency with reduced genotype dependency. Here we characterized the trans-genic and GE events in wheat (cv. Fielder) when transformed with the GROWTH-REGULATING FACTOR 4 (GRF4) and its cofactor GRF-INTERACTING FACTOR 1 (GIF1) chimeric gene. Trans-formation efficiency in our experiments ranged from 22% to 68%, and the editing events were faithfully propagated into the following generation. Both low and high copy number integration events were recovered in the T0 population with the various level of integrity of the left and right T-DNA borders. We also generated a population of wheat plants with ten different gRNAs targeting 30 loci in the genome. Comparison of the epigenetic profiles at the target sites and editing efficiency revealed a significant positive correlation between chromatin accessibility and muta-genesis rate. Overall, preliminary screening of the transgene quality and GE events in the T0 population of plants regenerated through the co-delivery of GRF-GIF can allow for the propagation of the best candidates for further phenotypic analysis.

Solids in the interstellar medium consist of an intimate mixture of silicate and carbonaceous grains. Because 99% of silicates in meteorites were reprocessed at high temperatures in the inner regions of the Solar Nebula, we propose that similar levels of heating of carbonaceous materials in the oxygen-rich Solar Nebula would have converted nearly all carbon in dust and grain coatings to CO. We discuss catalytic experiments on a variety of grain surfaces that not only produce gas-phase species such as CH4, C2H6, C6H6, C6H5OH or CH3CN, but also produce carbonaceous solids and fibers that would be much more readily incorporated into growing planetesimals. CO and other more volatile products of these surface mediated reactions were likely transported outwards along with chondrule fragments and small Calcium Aluminum Inclusions (CAIs) to enhance the organic content in the outer regions of the nebula where comets formed. Carbonaceous fibers formed on the surfaces of refractory oxides may have significantly improved the aggregation efficiency of chondrules and CAIs. Carbonaceous fibers incorporated into chondritic parent bodies might have served as the carbon source for the generation of more complex organic species during thermal or hydrous metamorphic processes on the evolving asteroid.

Selenium is a trace metal essential to human health, and its deficiency has been related to, for instance, cardiovascular and myodegenerative diseases, infertility and osteochondropathy Kashin-Beck disease. It is incorporated as selenocysteine to selenoproteins, which protect against reactive oxygen and nitrogen species. They also participate in the activation of thyroid hormone, and play a role in immune system functioning. The synthesis and incorporation of selenocysteine occurs via a special mechanism, which differs from the one used for standard amino acids. The codon for selenocysteine is the regular in-frame stop codon, which can be passed by specific complex machinery participating in translation elongation and termination. This includes the presence of selenocysteine insertion sequence (SECIS) in the 3’-untranslated part of the selenoprotein mRNAs. Selenium deficiency is known to control both selenoprotein and non-selenoprotein transcriptomes. Nonsense-mediated decay is involved in the regulation of selenoprotein mRNA levels, both other mechanisms are also possible.

Estimates of dog population sizes are a prerequisite for delivering effective canine rabies control. However, dog population sizes are generally unknown in most rabies-endemic areas. Several approaches have been used to estimate dog populations but without rigorous evaluation. We compare post-vaccination transects, household surveys and school-based surveys to determine which most precisely estimates dog population sizes. These methods were implemented across 28 districts in southeast Tanzania, in conjunction with mass dog vaccinations, covering a range of settings, livelihoods and religious backgrounds. Transects were the most precise method, revealing highly variable patterns of dog ownership, with human: dog ratios ranging from 12.4:1 to 181.3:1 across districts. Both household and school-based surveys generated imprecise and sometimes inaccurate estimates, possible due to low sample size. Transect data were subsequently used to develop a predictive model for estimating dog populations in districts lacking transect data. We predicted a dog population of 2,316,000 (95% CI 1,573,000-3,122,000) in Tanzania and an average human: dog ratio of 20.7:1. Our modelling approach has the potential be applied to predicting dog population size in other districts where mass dog vaccination is carried out, given census and livelihood data. We recommend transects as a rapid and effective method to refine dog population estimates across large geographic areas and guide dog vaccination programs.

This study investigates the magnetization of Cobalt (Co) nanoparticles with two different crystal structures: a centered cubic (fcc) and an hexagonal close packed (hcp), under the magnetic field of the Earth. For that reason, the hysteresis loops of the two material samples are exported and compared with the corresponding value by experimental procedure in the laboratory under the Earth’s magnetization. For both samples, the nanoparticle number variation and the nearest neighbor distance effect, in the Co hysteresis loop are investigated, structural information that is useful for the sample preparation. For the simulations the Finite Element Method (FEM) was used, while experiments are conducted using a measurement set-up based on fluxgate magnetometers. From the simulation, it is proven that, for both samples, the nanoparticle number effect does not change the hysteresis loop. In contrast, when the distance between the nanoparticles increases, the magnetization obtains smaller value. This study aims to build a novel, simple and economical measurement arrangement enabling in situ magnetic measurements for ferromagnetic nano-material characterization. As the need for continuous knowledge of the condition and the phase of ferromagnetic nanoparticles that is crucial in many applications, like catalytic processes, this work aims to introduce an alternative approach that will add another dimension to conventional chemical reaction engineering this of the magnetic state of the material resolved in time and space and to contribute in the field of the monitoring and the early fault diagnosis of nanoparticle materials.

In coastal areas around the world, seagrass meadows play a crucial ecological and economic role. A large amount of seagrass beds dominates primary production and contributes to the high secondary productivity of this ecosystem. The microbial loop (consuming bacterial biomass by grazers and using seagrass-derived detritus by bacteria) may be an important mechanism for transferring seagrass-derived organic matter to the aquatic food chain. This study aims to improve our understanding of how bacterial growth and mortality (grazing and viral lysis rates) differ in seagrass and adjacent unvegetated meadow habitats. We found that viral lysis and grazing caused similar mortality rates of bacteria in a seagrass environment during the summer. It has been found, however, that bacterial production is controlled by the availability of resources (bottom-up control) and is cycled within the bacteria-virus-DOC loop in adjacent unvegetated waters. Our study region may be affected by this shift in organic matter fate and cycling.

In this paper, a horizontally moving suspended mass pendulum base is designed and controlled using robust control theory. H infinity optimal loop shaping with first and second order desired loop shaping function controllers are used to improve the performance of the system using Matlab/Simulink Toolbox. Comparison of the H infinity optimal loop shaping with first and second order desired loop shaping function controllers for the proposed system have been done to track the desired angular position of the pendulum using step and sine wave input signals and a promising result has been obtained succesfully.

Vehicle windshield wiper system increases the driving safety by contributing a clear shot viewing to the driver. In this paper, modelling, designing and simulation of a vehicle windshield wiper system with robust control theory is done successfully. H∞ loop shaping and robust pole placement controllers are used to improve the wiping speed by tracking a reference speed signals. The reference speed signals used in this paper are step and sine wave signals. Comparison of the H∞ loop shaping and robust pole placement controllers based on the two reference signals is done and convincing results have been obtained. Finally the comparative results prove the effectiveness of the proposed H∞ Loop Shaping controller to improve the wiping mechanism for the given two reference signals.

Phialemonium inflatum is a useful fungus known for its ability to mineralise lignin during primary metabolism and decompose polycyclic aromatic hydrocarbons (PAHs). However, no functional genetic analysis techniques have been developed yet for this fungus, specifically in terms of transformation. In this study, we applied an Agrobacterium tumefaciens-mediated transformation (ATMT) system to P. inflatum for functional gene analysis. We generated 3,689 transformants using the binary vector pSK1044, which carried either the hygromycin B phosphotransferase (hph) gene or the enhanced green fluorescent protein (eGFP) gene to label the transformants. Southern blot analysis showed that the probability of a single copy of T-DNA insertion was approximately 50% when the co-cultivation time of fungal spores and Agrobacterium tumefaciens cells was performed at 24–36 h, whereas at 48 h, it was approximately 35.5%. Therefore, when performing gene knockout using ATMT, co-cultivation was reduced to ≤ 36 h. The resulting transformants were mitotically stable, and PCR analysis confirmed gene integration into the transformant genome. Additionally, hph and eGFP gene expressions were confirmed by PCR amplification and fluorescence microscopy. This optimised transformation system will enable functional gene analysis to study genes of interest in P. inflatum.

Non-alcoholic fatty liver disease (NAFLD) is defined as the accumulation of lipids in the form of lipid droplets in more than 5% of hepatocytes. It is regarded as a range of diverse pathologies, including simple steatosis and steatohepatitis. The structural characteristics of lipid droplets have been implicated in the etiology of the disease, along with their protein composition, mainly perilipins. These proteins have garnered increasing attention as a pivotal regulator, since their levels and distinct expression appear to be associated with the progression from simple steatosis to steatohepatitis. Perilipins are target proteins of chaperone-mediated autophagy, and their degradation is a prerequisite for lipolysis and lipophagy to access the lipid core. Both lipophagy and chaperone-mediated autophagy have significant implications in the development of the disease, as evidenced by their upregulation during the initial phases of simple steatosis, and their subsequent downregulation once steatosis is established. On the contrary, during steatohepatitis, the process of chaperone-mediated autophagy is enhanced, although lipophagy remains suppressed. Evidently, the reduced levels of autophagic pathways observed in simple steatosis serve as a defensive mechanism against lipotoxicity. Conversely, in steatohepatitis chaperone mediated autophagy fails to compensate for the continuous generation of small lipid droplets and thus cannot protect hepatocytes from lipotoxicity.

The concept of targeted drug delivery can be described in terms of the drug’s ability to mimic the other biological objects’ property to localize to target cells or tissues. For example, drug delivery systems based on red blood cells or mimicking some of their useful features, such as long circulation in stealth mode, have been known for decades. On the contrary, therapeutic strategies based on macrophages have gained very limited attention until recently. Here we review two biomimetic strategies associated with macrophages, that can be used to develop new therapeutic modalities: First, the mimicry of certain types of macrophages (i.e., the use of macrophages, including tumor-associated, or macrophage-like particles as a carrier for targeted delivery of therapeutic agents); and Second, the mimicry of ligands, naturally absorbed by macrophages (i.e., the use of therapeutic agents specifically targeted at macrophages). We discuss potential applications of biomimetic systems involving macrophages for the new advancements in treatment of infections, inflammatory diseases, and cancer.

The aim of this article is to analyze the evidence against the effectiveness of intervention programs based on the participation of parents of children with autism. To obtain the data, a systematic search was carried out in four databases (ProQuest-PsychArticles, ProQuest-ERIC, ProQuest-PubMed, and Scopus). These documents were refined under the inclusion/exclusion criteria and a total of 51 empirical studies were selected. They were classified, first, according to the function of the intervention objective and, later, by the methodology applied (19 studies based on comprehensive interventions, 11 focused on the nuclear symptoms of ASD, 12 focused on the promotion of positive parenting and 9 interactions focused on children play). Once all the documents have been analyzed, the evidence indicates scientific efficacy in most studies, mainly in those based on child development and the application of behavioral analysis principles. Also, the positive influence of parent participation in such programs was demonstrated.

This article theoretically derives the magnetic field and vector potential produced by a steady current I flowing in an arbitrary plane loop at an arbitrary point r. Numerical examples are presented to demonstrate the behavior of the magnetic field produced by loops of various shapes such as polygons, circles, ellipses, and p-norm balls. Taking the limit as the loop shrinks to a point and the current I grows to infinity so that the magnetic dipole moment m of the loop (defined as the current I times the vector area of the loop) is kept constant, the magnetic field and vector potential are theoretically shown to converge to those of an ideal point magnetic dipole m.

The human ABCG2 multidrug transporter plays a crucial role in the absorption and excretion of xeno- and endobiotics, contributes to cancer drug resistance and the development of gout. In this work we have analyzed the effects of selected variants, residing in a structurally unresolved cytoplasmic region (a.a. 354-367) of ABCG2, on the function and trafficking of this protein. A cluster of four lysines (K357-360) and the phosphorylation of a threonine (T362) residue in this region have been previously suggested to significantly affect the cellular fate of ABCG2. Here we report that the naturally occurring K360del variant in human cells increased ABCG2 plasma membrane expression and accelerated cellular trafficking. The variable alanine replacements of the neighboring lysines had no significant effect on transport function, and the apical localization of ABCG2 in polarized cells has not been altered by any of these mutations. Moreover, in contrast to previous reports, we found that the phosphorylation incompetent T362A, or the phosphorylation mimicking T362E variants in this loop, had no measurable effects on the function or expression of ABCG2. Molecular dynamics simulations indicated an increased mobility of the mutant variants with no major effects on the core structure of the protein. These results may help to decipher the potential role of this unstructured region within this transporter.

Loop detectors are probably the widest-used technology for traffic state estimation. Previous research has shown that loop detector positions within the link significantly affect the estimation of the macroscopic fundamental diagram (MFD) of a given network. This paper examines the biases produced by the positioning of loop detectors on the MFD, using both analytical and simulation methods, as well as empirical data from UTD-19. We confirm earlier results that a uniform distribution of loop detector positions reduces the bias. For non-uniform distribution, we found that: (i) the subsets of the MFD by the loop detector position help estimate whether the loop detector MFD will have a bias; (ii) if the detectors in the network are positioned more downstream with a larger variation, the loop detector MFD is more likely to have a discrepancy in position subsets of the MFD; (iii) a lower ratio of link length to green signal time elevates the MFD bias as well. This research opens the possibility for the bias of MFD induced by the loop detector data to be corrected by only using itself.

ASEAN SME has a role as the regional socioeconomic stabilizer. This particular role is inseparable from endogenous multi-sector collaboration. Although, Indonesian SMEs were struggled in adopting Industry 4.0 correspond to digital infrastructure and digital literacy problems. This study evaluates Indonesian SME collaboration dynamics with government and technology startup (TS). The integration of agent-based model and causal loop simulation were employed to assess the TS collaboration impact on SME Industry 4.0 adoption and SME competition with larger competitors. The simulation results imply the SME collaboration with TS can lead to early adoption of Industry 4.0 which balances the business competition environment. The model also shows rising the government aid exponentially can help the SME to late adoption of Industry 4.0 which unable to sustain the SME in business competition. Thus, the developed integrative simulation model is a state-action planning model with each state result bounded to the previous state result that determined by initial input parameters. Conclusively, the model can be used as a resiliency planner for SME Industry 4.0 adoption.

We continue our recent endeavor in which a time-dependent black hole solution of a one-loop quantum-corrected Einstein-scalar system was obtained and its near-horizon behavior was analyzed. The energy analysis led to a trans-Planckian scaling behavior near the event horizon. In the present work the analysis is extended to a rotating black hole solution of an Einstein-Maxwell-scalar system with a Higgs potential. Although the analysis becomes much more complex compared to that of the previous, we observe the same basic features, including the quantum-gravitational trans-Planckian energy near the horizon.

Existing methods for detecting magnetic leakage signals from damaged wire ropes require axial saturation magnetisation, and the accuracy of the detection equipment depends on the saturation degree of magnetisation. Moreover, the expected magnetisation effect is usually difficult to achieve owing to the special characteristics of the rope structure, diameter, and operating environment of the wire rope. Consequently, in addition to other issues, the detection accuracy and versatility of the equipment are low. In this study, a method based on spatial multidimensional orthogonal array loop magnetisation for detecting mine wire rope defects is proposed. Firstly, a new sensor excitation structure model is developed. Then a method of radiant magnetic flux of permanent magnet array is analysed, and the influence law of the number of permanent radiant magnetic blocks on the magnetisation effect is studied. In addition, a method of wire rope detection based on the principle of clustering is investigated, according to which the influence law of the shape, structure, and size of the polyurethane device on the effect of magnetisation is discussed. Finally, through laboratory experiments, the test model and proposed method are verified. The results show that the magnetisation effect is better and more cost-effective when the number of permanent magnet radiation magnetic block is n=8, and the proposed detection method can effectively distinguish damaged wire rope joints. Furthermore, the proposed equipment achieved signal-to-noise ratio of the signals, improving the reliability of damage detection.

The new class of mRNA vaccines is studied extensively, leading to many novel prospects based on the pivotal success of vaccines against the SARS-Cov-2 virus. Many novel mechanisms of immune response discovered have led to the possibility of mutation-resistant vaccines by combining multiple conserved epitopes as antigens to manipulate the T-cell and B-cell responses; these antigens can also come from different organisms, providing protection against numerous diseases and of most tremendous significance is the utility of mRNA vaccines in preventing and treating more than 100 autoimmune disorders. This is a significant humanitarian breakthrough given the ease and faster and low cost of mRNA vaccines, being a chemical entity. This paper provides a prospective analysis of mRNA vaccines with much broader applications than anticipated when these vaccines entered treating SARS-Cov-2 infections.

Immune-mediated bowel diseases (IMBD), including Ulcerative colitis and Crohn's disease, represent a significant global health burden with their complex etiology and increasing prevalence. The connection between intestinal parasites and the gut microbiome in immune-mediated bowel disease is a complex and evolving field of research. Several studies have demonstrated that intestinal parasites can modulate the composition and function of the gut microbiome. Parasitic infections can result in alterations in the gut microbial community, including changes in microbial diversity, abundance, and metabolic activity. These changes can influence the immune response and contribute to the development of IMBDs. In contrast, the gut microbiome serves a pivotal function in maintaining intestinal homeostasis and immune regulation. Dysbiosis, characterized by changes in the gut microbial composition, has been associated with the pathogenesis of IMBDs. Imbalances in the gut microbiota can result in increased gut permeability, chronic inflammation, and aberrant immune responses, all of which are hallmarks of IMBDs. The bidirectional interaction between intestinal parasites and the gut microbiome further complicates the understanding of immune-mediated bowel diseases. Certain parasites, such as hookworms and Necator americanus, have been found to downregulate immune responses and may have therapeutic potential in treating celiac disease. On the other hand, infections with parasites like Strongyloides stercoralis and Blastocystis have been shown to mimic the symptoms of IBD, highlighting the intricate relationship between parasites and the pathogenesis of these diseases. Additional investigation is required to comprehensively elucidate the mechanisms that underlie the association between intestinal parasites and the gut microbiome in immune-mediated bowel disease. This knowledge could potentially lead to the development of targeted therapeutic strategies that aim to restore gut microbiota homeostasis and alleviate the symptoms of these debilitating conditions. By understanding and harnessing the complex interplay between parasites, the gut microbiome, and the host immune system, researchers may uncover novel approaches for the management and treatment of immune-mediated bowel diseases.

This qualitative inquiry explores how, during the early stage of the COVID-19 pandemic in Lithuania (European Union), the stakeholders in education system – university teachers, general education teachers, students and children’s parents – coped with the encountered challenge and what was important to them under changed conditions. This paper uses a communication management objective to describe how participants in the education system respond to the emerging distance learning situation and its challenges.The phenomenographic research approach was chosen to carry out the qualitative study. The 37 interviews from higher education teachers, university students, school teachers and parents of minor school-aged children were conducted during the early stage of COVID-19 quarantine. The research allows concluding that after a successful transition to distance learning the dimensions of communion and supportive collaboration acquired importance among stakeholders in education. Starting new activities, a need for communion and mobilization for joint activities under the crisis situation emerged. The research showed that the adaptation period was necessary at the beginning of the new activity. Competent leadership was expected from the teacher also advance preparation of all the actors in education process was needed. The data do offer a window into the dynamics of online teaching in crisis situation and experiences in new activity that are key to success.

The study of hydrothermal travertines contributes to the understanding of the interaction between physico-chemical processes and the role played by microbial mats and biofilms in influencing carbonate precipitation. Three active travertine sites were investigated in Central Italy to identify the types of carbonate precipitates and the associated microbial mats at varying physico-chemical parameters. Carbonate precipitated fabrics at the decimetre- to millimetre-scale and microbial mats vary with decreasing water temperature: a) at high temperature (55-44°C) calcite or aragonite crystals precipitate on microbial mats of sulphide oxidizing, sulphate reducing and anoxygenic phototrophic bacteria forming filamentous streamer fabrics, b) at intermediate temperature (44-40°C), rafts, coated gas bubbles and dendrites are associated with Spirulina cyanobacteria and other filamentous and rod-shaped cyanobacteria, c) low temperature (34-33°C) laminated crusts and oncoids in a terraced slope system are associated with diverse Oscillatoriales and Nostocales filamentous cyanobacteria, sparse Spirulina and diatoms. At the microscale, carbonate precipitates are similar in the three sites consisting of prismatic calcite (40-100 µm long, 20-40 µm wide) or acicular aragonite crystals organized in radial spherulites, overlying or embedded within biofilm EPS (Extracellular Polymeric Substances). Microsparite and sparite crystal size decreases with decreasing temperature and clotted peloidal micrite dominates at temperatures < 40°C, also encrusting filamentous microbes. Carbonates are associated with gypsum and Ca-phosphate crystals; EPS elemental composition is enriched in Si, Al, Mg, Ca, P, S and authigenic aluminium-silicates form aggregates on EPS. This study confirms that microbial communities in hydrothermal travertine settings vary as a function of temperature. Carbonate precipitate types at the microscale do not vary considerably, despite different microbial communities suggesting that travertine precipitation, driven by CO2 degassing, is influenced by biofilm EPS acting as template for crystal nucleation (EPS-mediated mineralization) and affecting the fabric types, independently from specific microbial metabolism.

Ranging from traditional food packaging, clothing, and furniture to the current small and large electronic devices and automobiles, plastics serve to fulfill diverse demands in our daily lives. However, the global plastic waste generation is dramatically escalating, currently standing at approximately 150 million metric tonnes annually. While some of regenerated plastics recycled by mechanical methods can be used as their parent plastics, cost and energy savings are limited by multiple preliminary processes such as plastic sorting, shredding, washing, and drying. Moreover, the continuous mechanical recycling process degrades the physical properties of the materials. In this context, chemical recycling is emerging as a promising alternative method due to its high efficiency, simple preliminary steps, reducing reliance on fossil resources, and conversion of plastic waste into value-added chemicals. This review provides a state-of-the-art overview of contemporary chemical recycling of polymeric materials via i) depolymerization: “polymers to small valuable molecules” and ii) closed-loop cycles: “polymers to monomers, and/or to polymers”, by encompassing both traditional/advanced depolymerization chemistries and the remaining challenges. These recycling approaches are contextualized within the present industrial technologies, key design principles, and specific recycling case studies related to distinct polymeric materials.

Diabetes mellitus leads to cardiovascular complications including impaired cardiac β-adrenoceptor (β-AR) function. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, such as empagliflozin (EMPA) improve outcomes in heart failure patients and animal models thereof. Therefore, we have investigated the effects of EMPA on in vivo cardiac function (pressure-volume loop analysis) and β-AR-mediated contractile responses (papillary strips) in streptozotocin (STZ; 40 mg/kg, i.p.)-induced diabes in male Sprague Dawley rats (control, EMPA-treated control, diabetic, EMPA-treated diabetic) in a design reflecting late-onset treatment. 13-16 weeks after STZ injection treatment with a low dose of EMPA (10 mg/kg/day, daily oral gavage) or vehicle was administered for another 8 weeks. EMPA did not change cardiac function in control rats. Diabetic rats had a reduced heart rate, cardiac output, stroke work, rate of contration and rate of relaxation and increased isovolumic relaxation, whereas in vitro responses were not markedly attenuated. Treatment with EMPA showed a trend for improvement of some but not all parameters. Our results indicate that low dose EMPA treatment had limited effects on cardiac impairment despite reducing blood glucose when initiated after diabetes is manifest. Future studies with a higher dose and greater sample sizes could help to clarify the possible benefits of EMPA on the diabetic heart.

The PI3K/mTOR signalling pathway plays a central role in the governing of cell growth, survival and metabolism. As such, it must integrate and decode information from both external and internal sources to guide efficient decision-making by the cell. To facilitate this, the pathway have evolved an intricate web of complex regulatory mechanisms and elaborate crosstalk with neighbouring signalling pathways, making it a highly non-linear system. Here, we describe the mechanistic biological details that underpin these regulatory mechanisms, covering a multitude of negative and positive feedback loops, feed-forward loops, competing protein interactions, and crosstalk with major signalling pathways. Further, we highlight the non-linear and dynamic network behaviours that arise from these regulations, uncovered through both computational and experimental studies. Given the pivotal role of the PI3K/mTOR network in cellular homeostasis and its frequent dysregulation in pathologies including cancer and diabetes, a coherent and systems-level understanding of the complex regulation and consequential dynamic signalling behaviours within this network is imperative for advancing biology and development of new therapeutic approaches.

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.

Sensor fusion technology is one of extensive used methods in the field of robot, aerospace and target tracking control. In this paper, the generalized sensor fusion framework, named the closed-loop fusion (CLF) is analyzed and the optimal design principle of filter is proposed in detail. Fusion error optimization problem, which is the core issue of fusion design, is also solved better through the feedback compensation law of CLF framework. Differently from conventional methods, the fusion filter of CLF can be optimally designed and the determination of superposition of fusion information is avoided. To show the validity, simulation and experimental results are to be submitted.

Previous studies generally reckon that the full converter-base wind power generation (FCWG) is a ’decoupled’ power source from the grid, which hardly participates in electromechanical oscillations. However, it is found recently that strong interaction could be induced which might incur severe resonance incidents in electromechanical dynamic timescale. In this paper, the participation of FCWG in electromechanical dynamics is extensively investigated, and particularly, an unusual transition of electromechanical oscillation mode (EOM) is uncovered for the first time. The detailed mathematical models of open-loop and closed-loop power systems are firstly established, and modal analysis is employed to quantify the FCWG participation in electromechanical dynamics, with two new mode identification criteria, i.e., FCWG dynamics correlation ratio (FDCR) and quasi-electromechanical loop correlation ratio (QELCR). On this basis, the impact of different wind penetration levels and controller parameter settings on the participation of FCWG is investigated. It is revealed that if an FOM has a similar oscillation frequency to the system EOMs, there is a high possibility to induce strong interactions between FCWG dynamics and system electromechanical dynamics of the external power systems. In this circumstance, an interesting phenomenon may occur that an EOM may be dominated by FCWG dynamics, and hence is transformed into a quasi-EOM, which actively involves the participation of FCWG quasi-electromechanical state variables.

As urban populations and transport demand expand, Pakistani metropolitan centers face traffic congestion and environmental challenges. This research aims to assess carpooling (CP) to alleviate traffic congestion, fuel demand, and pollution. This study was conducted in Islamabad, a fast-growing city with a high percentage of personal cars in Pakistan, to assess the travelers’ perceptions, and public acceptance of CP and determine the effects on traffic congestion, fuel consumption, and CO2 emissions. The investigation of travelers' perceptions towards CP was conducted through a stated preference questionnaire survey. A total of 700 responses from one million population of Islamabad were collected as per Sloven's Formula. SPSS and Smart PLS software were used for data analysis. Various factors influencing peoples’ travel perceptions, mode choice, and tendency to carpool, were categorized to evaluate the relationship between travelers’ perception and the tendency to carpool in the presence of mode choice as a mediating variable. Confirmatory factor analysis was conducted in SMART PLS to refine the number of scale items for each variable. One-way ANOVA, step-wise and mediated multiple regression analysis was conducted in SPSS to check the direct and mediating relationship between different variables. Moreover, the probability of reducing traffic congestion and assessing fuel reduction resulting from CP was also analyzed. The findings imply that travelers’ mode choice acts as a mediator between the relationship between travelers’ perception and tendency to carpool. Furthermore, results predicted that CP might reduce 0.25 million cars on the road, about 33.6% of the total private vehicles. Thereby, saving up to 546,810 barrels per year, about 3.42% of Pakistan's total petrol consumption. The findings of this study could be helpful for transport planners, environmentalists, and policymakers to implement carpool systems. Thus, reducing traffic congestion and harmful CO2 emissions and maintaining a sustainable environment.

The main aim of this study was to determine the prevalence of plasmid-mediated colistin resistance mcr-1 to mcr-5 genes among colistin and multi-drug resistant Enterobacterales, Pseudomonas aeruginosa and Acinetobacter sp strains isolated from patients in a tertiary hospital in the city of Toluca, Mexico. 241 strains were included in the study. The presence of mcr genes among these strains was assessed by PCR and sequencing. In the case of mcr-carrying E. coli, further PCR tests were performed to determine the presence of blaCTX-M and whether the strains belonged to the O25b-ST131 clone. Conjugation experiments were carried to assess plasmid-mediated colistin resistance horizontal transmission. 12 strains (5.0%), of which four were E. coli; four, P. aeruginosa; three, K. pneumoniae and one, E. cloacae, were found to be resistant to colistin. Of these strains, two E. coli isolates were found to carry mcr-1. Both mcr-1-carrying E. coli strains were found to co-express blaCTX-M, belong to the O25b-ST131 clone and horizontally transmit their colistin resistance. The results of this study confirm the presence of plasmid-mediated colistin resistance in hospitalized patients in Mexico and demonstrated that the multidrug-resistant O25b-ST131 E. coli clone can acquire mcr genes and transmit such resistance trait to other bacteria.

In this work, a high throughput nanozymatic method was developed for green nanozyme-mediated biodegradation of organic dyes in real water media. The nanozymes were synthesized and characterized for their size and morphology by TEM and DLS analysis. The nanozymatic properties of the as-prepared nanomaterials were evaluated by standard enzyme activity assay, revealing high peroxidase-like performances for the as-prepared nanozymes. Therefore, for exploring more precise, the kinetics behavior of the as-prepared nanozymes was evaluated by the standard Lineweaver-Burk method, revealing a V_max as high as 0.263 µM sec^-1 and a K_m as low as 0.03 mM, revealing high catalytic efficiency and affinity of the as-prepared nanozymes. Hence, the as-prepared nanozymes were utilized for organic dye degradation in real water media using methylene blue as a model organic dye. The effective factors on the dye degradation including pH, ionic strength, degradation time, nanozyme amount, etc. were optimized by the one-factor-at-a-time optimization method. At optimal experimental conditions, the as-prepared nanozymes can degrade about 99.0% of the organic dye within a degradation time as low as 7 min. The developed method was finally employed for the nanozyme-mediated degradation of methylene blue from real water media such as pool, mineral, river, and tap water samples. The results of this study revealed an excellent biodegradation yield of over 94.3%-99.0% for the different real samples, proving the suitability of the developed method for dye degradation in real water media.

Therapeutic antibodies targeting immune checkpoints have shown limited efficacy in clinical trials in glioblastoma (GBM) patients. Ultrasound-mediated blood-brain barrier opening (UMBO) using low-intensity pulsed ultrasound improved drug delivery to the brain. We explored the safety and the efficacy of UMBO plus immune checkpoint inhibitors in preclinical models of GBM. A Blood-brain barrier (BBB) opening was performed using a 1 MHz preclinical ultrasound system in combination with 10µl/g microbubbles. Brain penetration of immune checkpoint inhibitors was determined, and immune cell populations were evaluated using flow cytometry. The impact of repeated treatments on survival was determined. In syngeneic GL261-bearing immunocompetent mice, we showed that UMBO safely and repeatedly open the BBB. BBB opening was confirmed visually and microscopically using Evans’s blue dye and magnetic resonance imaging. UMBO plus anti-PDL-1 was associated with a significant improvement of the overall survival compared to anti-PD-L1 alone. Using mass spectroscopy, we showed that the penetration of therapeutic antibodies can be increased when delivered intravenously compared to non-sonicated brains. Furthermore, we observed an enhancement of activated microglia percentage when combined with anti-PD-L1. Here, we report that the combination of UMBO and anti-PD-L1 dramatically increases GL261-bearing mice's survival compared to their counterparts treated with anti-PD-L1 alone. Our study highlights the BBB as a limitation to overcome to increase the efficacy of anti-PD-L1 in GBM and supports clinical trials combining UMBO and in GBM patients.

The transition from a dormant to a germinating seed represents a crucial developmental switch in the life cycle of a plant. Subsequent transition from a germinating seed to an autotrophic organism also requires a robust and multi-layered control. Seed germination and seedling growth are multistep processes, involving both internal and external signals, which lead to a fine-tuning control network.

Coccidioidomycosis (Valley Fever) is a disease caused by inhalation of Coccidioides spp. This neglected tropical disease of the Americas has substantial public health impact despite its geographic restriction to desert areas of the southwestern U.S., Mexico, Central and South America. The incidence of this infection in California and Arizona has been increasing over the past fifteen years. The burden of disease in outside the U.S. remains poorly understood. Several large cities are within the endemic region in the U.S. Coccidioidomycosis accounts for 25,000 hospital admissions per year in California. While most cases of coccidioidomycosis resolve spontaneously, up to 40% are severe enough to require anti-fungal treatment, and a significant number disseminate beyond the lungs. Disseminated infection, especially involving the meninges, is fatal without appropriate treatment. Infection with Coccidioides spp. is protective against a second infection, so vaccination seems biologically plausible. This review of efforts to develop a vaccine against coccidioidomycosis focuses on vaccine approaches and the difficulties in identifying protein antigen/adjuvant combinations that protect in experimental mouse models. Although the quest for a vaccine has not yet resulted in a clinically useful product, scientific efforts of vaccine development pave the way for future success.

Software-In-The-Loop (SITL) simulation tools have been extensively used in development of safety-critical software. Utilizing these tools substantially accelerates software development eliminating potential risks and resource costs of physical experiments. This paper investigates the effects of model specific parameters on the development and testing of custom module in PX4 SITL environment. Models of a fixed-wing unmanned aerial vehicle with vertical takeoff and landing capabilities and steerable sensor platform/gimbal are used as case study for this investigation. The effects of parameters of these aerial vehicle and sensor platform models are taken into consideration in the development of custom module that controls the dynamics of steerable sensor platform mounted on the vehicle model. The work also presents steps necessary to customize PX4 SITL and Gazebo simulation environment to incorporate parameters of the vehicle and sensor platform models in the development and testing process of custom module. Based on these instances, simulation results are obtained and discussed. The results show that reliability of PX4 SITL simulation framework is justified by proper customization and integration of PX4 SITL and Gazebo simulator.

We develop a quantitative microscopic theory of decaying Turbulence by studying the dimensional reduction of the Navier-Stokes loop equation for the velocity circulation. We have found an infinite dimensional manifold of solutions of the Navier-Stokes loop equation\cite{M93, M23PR} for the Wilson loop in decaying Turbulence in arbitrary dimension $d >2$. This family of solutions corresponds to a fractal curve in complex space $\mathbb C^d$, described by an algebraic equation between consecutive positions plus a nonlinear periodicity condition. We derive the constrained SDE for the evolution of the fractal curve at a fixed moment of physical time as a function of an auxiliary stochastic time. We expect this stochastic process to cover our fixed manifold of the solutions of the decaying Turbulence. The energy density of the fluid decays as $\mathcal E_0/t$, where $\mathcal E_0$ is an initial dissipation rate. Presumably, we have found a new phase of extreme Turbulence yet to be observed in real or numerical experiments.

A novel scheme that can simultaneously measure the Doppler frequency shift (DFS) and angle of arrival (AOA) of microwave signals is proposed. At the signal receiving unit (SRU), two echo signals and the reference signal are modulated by a Sagnac loop structure and sent to the central station (CS) for processing. At the CS, two low-frequency electrical signals are generated after polarization control and photoelectric conversion. The DFS without direction ambiguity and wide AOA measurement can be real-time acquired by monitoring the frequency and power of the two low-frequency electrical signals. In the simulation, an unambiguous DFS measurement with errors of ±3×10-3 Hz and a -90° to 90° AOA measurement range with errors of less than ±0.5° are realized. The safety and robustness of the system to environmental disturbance are improved, and it is more suitable for the modern electronic warfare system.

To overcome the two-phase flow instability of traditional boiling heat dissipation technologies, a porous wick was used for liquid-vapor isolation, thus realizing efficient and stable boiling heat dissipation. A pump-assisted capillary phase-change loop with methanol as working medium was established to study the effect of liquid-vapor pressure difference and heating power on its start-up and steady-state characteristics. The results indicated that the evaporator undergoes four heat transfer modes including flooded, partial flooded, thin film evaporation and overheating. The thin film evaporation mode was the most efficient one with the shortest start-up period. Besides, the heat transfer modes were determined by liquid-vapor pressure difference and power. The heat transfer coefficient could be significantly improved and the thermal resistance could be reduced by increasing liquid-vapor pressure difference as long as it did not exceed 8 kPa. However, when the liquid-vapor pressure difference exceeded 8kPa, its influence on the heat transfer coefficient weakened. In addition, a two-dimensional heat transfer mode distribution diagram considering both liquid-vapor pressure difference and power was drawn through a great number of experiments. During engineering application, the liquid-vapor pressure difference can be controlled to maintain efficient thin film evaporation in order to achieve the optimum heat dissipation effect.

Quorum sensing (QS) describes a process by which bacteria can sense the local cell density of their own species, thus enabling them to coordinate gene expression and physiological processes on a community-wide scale. Small molecules called autoinducers or QS signals, which act as intraspecies signals, mediate quorum sensing. As our knowledge of QS has progressed, so too has our understanding of the structural diversity of QS signals, along with the diversity of bacteria conducting QS and the range of ecosystems in which QS takes place. It is now also clear that QS signals are more than just intraspecies signals. QS signals mediate interactions between species of prokaryotes, and between prokaryotes and eukaryotes. In recent years, our understanding of QS signals as mediators of algae–bacteria interactions has advanced such that we are beginning to develop a mechanistic understanding of their effects. This review will summarize the recent efforts to understand how different classes of QS signals contribute to the interactions between planktonic microalgae and bacteria in our oceans, primarily N-acyl-homoserine lactones, their degradation products tetramic acids, and 2-alkyl-4-quinolones. In particular, this review will discuss the ways in which QS signals alter microalgae growth and metabolism, namely as direct effectors of photosynthesis, regulators of the cell cycle, and as modulators of other algicidal mechanisms. Furthermore, the contribution of QS signals to nutrient acquisition is discussed, and finally how microalgae can modulate these small molecules to dampen their effects.

Noise reduction is the major issue in the loudspeaker for the application of the musical instruments and related areas. In this paper, a noise disturbance control of a loudspeaker with optimal and robust controllers has been done successfully. The noise of the loudspeaker has been analyzed by simply track a reference cone displacement with the actual cone displacement. Static output feedback and H infinity optimal loop shaping controllers have been used to compare the actual and reference cone displacements by using a sine wave and random cone displacement signals and a promising results have been analyzed.

This paper presents a 612–1152 MHz Injection Locked Frequency Multiplier (ILFM). The proposed ILFM is only used for sending an input signal to the receiver in the I/Q mismatch calibration mode. Using the Phase-Locked Loop (PLL) to calibrate the receiver places a burden on this system due to the extra area required and power consumption. Instead of the PLL, to satisfy high frequency, low jitter, and low area, a Ring Oscillator is proposed. The free-running frequency of the ILFM is automatically digitally calibrated to reflect the frequency of the injected signal from the harmonics of the reference clock. To control the frequency of the ILFM, the load current is digitally tuned with 6-bit digital control signal. The proposed ILFM locks to the target frequency using a digitally controlled Frequency Locked Loop (FLL). This chip is fabricated using 1-poly 6-metal 0.18 µm CMOS and achieve the wide tuning range of 612–1152 MHz. The power consumption is 0.95 mW from a supply voltage of 1.8 V. The measured phase noise of the ILFM is −108 dBc/Hz at a 1 MHz offset.

In this work, we present some results related with the issue of the Loop Quantum Black Holes (LQBH) thermodynamics by the use of the tunneling radiation formalism. The information loss paradox is also discussed in this context, where we have considered the influence of back reaction effects.

Drug resistance in tumor cells is a significant roadblock in the clinical management of advanced or recurrent diseases in endometrial cancers. As a part of the tumor-stromal ecosystem, tumor cells are ecologically connected to the cancer-associated fibroblasts (CAFs), which form contributory elements of the tumor microenvironment (TME). We recently reported a novel model of patient-derived CAF-based 2-cell Hybrid Co-Culture (HyCC) to evaluate CAFs' role in developing drug resistance and understanding personalized tumor cell-CAF dialogue. Using our 2-cell HyCC model of patient-derived endometrial CAFs, we present data to demonstrate the direct counter-inhibitory effect of CAFs to combinations of cytotoxic and targeted drugs in developing drug resistance. CAFs derived from resected endometrial tumor samples were first passage-wise characterized before and after freeze-thaw for their positive and negative CAF markers expression pattern. Paclitaxel and its combination with copanlisib, TAK228, lenvatinib, and trametinib were used to test the 3D clonogenic growth of endometrial AN3CA cells on endometrial CAFs. We demonstrate that CAF-mediated resistance to antitumor drugs occurs via direct and indirect contact with CAFs in HyCC. Our data established the strength of the 2-cell HyCC model of patient-derived CAFs in solid tumors and provided a model of resistance to antitumor drugs tailored on a patient-to-patient basis.

Antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) lymphocytes eliminates cells infected with viruses. Antiviral ADCC requires three components: 1) antibody; 2) effector lymphocytes with the Fc-IgG receptor CD16A; and 3) viral proteins in infected cell membranes. Fc-afucosylated antibodies bind with greater affinity to CD16A than fucosylated antibodies; individuals’ variation in afucosylation contributes to differences in ADCC. Current assays for afucosylated antibodies involve expensive methods. We report an improved bioassay for antibodies that support ADCC which encompasses afucosylation. This assay utilizes externalization of CD107a by NK-92-CD16A cells after antibody recognition. We used anti-CD20 monoclonal antibodies, GA101 WT or glycoengineered (GE), 10% or ~50% afucosylated, and CD20-positive Raji target cells. CD107a increased detection 7-fold compared to flow cytometry to detect Raji-bound antibodies. WT and GE antibody effective concentrations (EC50s) for CD107a externalization differed by 20-fold, with afucosylated GA101-GE more detectable. The EC50s for CD107a-externalization vs. 51Cr cell death were similar for NK-92 CD16A and blood NK cells. Notably, the %CD107a-positive cells negatively correlated with dead Raji cells and was nearly undetectable at high NK:Raji ratios required for cytotoxicity. This bioassay is very sensitive and adaptable to assess anti-viral antibodies but unsuitable as a surrogate assay to monitor cell death after ADCC.

UPF3B is a constituent of the classical nonsense-mediated mRNA decay (NMD) pathway that degrades both the aberrant transcripts and a set of physiological transcripts. In higher eukaryotes, UPF3B have significant biochemical functions in diverse cellular processes including NMD and translation. UPF3B plays a crucial role in neuronal development and differentiation. Next-generation sequencing technologies identified several loss-of-function mutations in the UPF3B gene that results in neuro-developmental disorders in humans. To uncover the mechanistic role of UPF3B in neuronal functions, we have generated the UPF3B-knockout mammalian cell line model system using CRISPR-Cas9 gene editing method. RNA-Sequencing Analysis of cellular transcriptome from UPF3B-KO cells identified specific genes involved in cell growth and neuronal functions. Altered expression of genes related to the axon guidance pathway delineated the UPF3B function to regulate the neuron-specific genes. Functional enrichment analysis identified the genes involved in the disorders related to mental health and intellectual disability. Our study has the potential to identify the direct players of intellectual disability and will have broader implications.

(1) Background: Presentation of the method of increasing the competitiveness of the mining industry through the demonstration of the possibility and potential in closing the loop of supply chains through waste management; (2) Methods: The source literature analysis and an arithmetic analysis of the data of statistical materials and data obtained from business in static and dynamic perspectives; (3) Results: According to the latest data available, in Poland, mining wastes account for over a half of industrial wastes, while the annual growth of mining wastes is on the level of 4%. The recorded recovery of mining wastes is on the level of ca. 19%. The exemplary company that deals with the recovery of carbon wastes recovers ca. 80% of material, which is handed over for utilization (4) Conclusions: It has been found that the structure of the level of mining wastes and the level of their recovery rates demonstrate a large potential of closing the loop of chains in this industry and, at the same time, a potential to extend the chains through directing the material from recovery to various sectors. This constitutes an example of the direction of activities that are in line with the EU strategies for the economies of other states which possess this type wastes.

The feed-forward loop (FFL) is an important and basic network motif to understand specific biological functions. Cyclic-AMP (cAMP) receptor protein (CRP), a transcription factor (TF), mediates catabolite repression and regulates more than 400 genes in response to changes in intracellular concentrations of cAMP in Escherichia coli. CRP participates in some FFLs like araBAD and araFGH operons and adapt to fluctuating environmental nutrients thus enhancing the survivability of E. coli. Although computational simulations have been used to explore the potential functionality of FFLs, a comprehensive study of the functions of all structural types based on in vivo data is lacking. Also, the regulatory role of CRP-mediated feed-forward loops (CRP-FFLs) remain unclear to date. Using EcoCyc and RegulonDB, we identified 393 CRP-FFLs in the E. coli. Dose-response genomic microarray of E. coli revealed dynamic gene expression of each target gene of CRP-FFLs in response to a range of cAMP dosages. All eight types of FFLs were present in CRP regulon with various expression patterns of each CRP-FFL, that were further divided into five functional groups. Microarray and reported regulatory relationships identified 202 CRP-FFLs which were directly regulated by CRP in these eight types of FFLs. Interestingly, 30% (147/482) of genes were directly regulated by CRP and CRP-regulated TFs, indicating that these CRP-regulated genes were also regulated by other CRP-regulated TFs responding to environmental signals through CRP-FFLs. Furthermore, we applied gene ontology annotation to reveal the biological functions of CRP-FFLs.

Age-related diseases (ARDs) are the leading cause of death worldwide, and contribute to 90% of mortality in developed countries. Interestingly, the mortality rates of individual ARDs increase exponentially with age. Processes described by the exponential growth function typically involve a branching chain reaction or, more generally, a positive feedback loop. Here I propose that each ARD is mediated by one or several positive feedback loops (vicious cycles). I then identify critical vicious cycles in five major ARDs: atherosclerosis, hypertension, diabetes, Alzheimer’s and Parkinson’s. I also propose that the progression of ARDs can be halted by selectively interrupting the vicious cycles and suggest the most promising targets. An evolutionary perspective is also offered.

This paper proposes an innovative mechatronic piezo-actuated module to control vibrations in modern machine tools. Vibrations represent one of the main issues that compromise seriously the quality of the workpiece. The active vibration control (AVC) device is composed by a host part integrated with sensors and actuators synchronized by a regulator, able to make a self-assessment and adjust to the environmental alteration. This study presents the mechatronic model based on the kinematic and dynamic analysis of the AVC device. To ensure a real time performance, a H2-LQG controller has been developed and validated by simulations involving machine tool, PZT actuator and controller models. The Hardware-in-the-loop (HIL) architecture is adopted to control and attenuate the vibrations. A set of experimental tests has been performed to validate the AVC module on a commercial machine tool. The feasibility of the real time vibration damping is demonstrated and the simulation accuracy is evaluated.

Initial attempts to develop monoclonal antibodies as therapeutics to resolve influenza infections focused mainly on searching for antibodies with the potential to neutralise the virus in vitro with classical haemagglutination inhibition and micro-neutralisation assays. This led to the identification of many antibodies that bind to the head domain of haemagglutinin (HA) which generally have potent neutralisation capabilities that block viral entry or viral membrane fusion. However, this class of antibodies has a narrow breadth of protection in that they are usually strain specific. This led to the emphasis on stalk targeting antibodies which are able to bind a broad range of viral targets that span across different influenza subtypes. Recently, a third class of antibodies targeting the vestigial esterase (VE) domain have been characterised. In this review, we describe the key features of neutralising VE targeting antibodies and compare them with head and stalk class antibodies.

The rapid advancement of technology has led to increased electronic consumption and a corresponding rise in e-waste generation. To address this issue, this study develops a low-carbon e-commerce closed-loop supply chain (LCE-CLSC) system with remanufacturer, platform, and the government as key stakeholders. An evolutionary game approach is employed to investigate the system's dynamics, analyzing the impact of stakeholder strategies on system equilibrium. Numerical simulations reveal important findings: Firstly, government initiatives promoting recycling, carbon taxes on traditional products, can incentivize remanufacturers to produce low-carbon items and encourage platform investment in recycling services. Secondly, higher sales revenues motivate remanufacturers to produce low-carbon products. Thirdly, consumer sensitivity to recycling services strengthens waste recovery when platforms increase investments in these services, leading to remanufacturers choosing low-carbon production. Lastly, government subsidies may become ineffective if the cost of remanufacturers' carbon reduction and platforms' recycling services exceeds their affordability. These findings offer insights for the sustainable development of obsolete electronic product recycling systems.

Leasing and recycling are important issues to achieve low-carbon sustainable development of construction machinery industry, however there are some dilemmas bothering which is caused by excessive restriction of product service life. Focusing on the problem of pricing and coordination, a two-stage model of leasing closed-loop supply chain based on the Industrial Internet platform practical application was proposed. Under the centralized and decentralized decision-making scenarios, the price of leasing and selling, maintenance effort and recovery rate are calculated respectively. By using the Shapley value method to optimize the selling price, and the two-part pricing contract to calculate the compensation fee, the global profit is reasonably distributed, while the supply chain achieving Pareto optimality. The performance of different contracts on the improvement of supply chain profit was investigated. And the correlation among parameters was also explored through sensitivity analysis and numerical simulation. The findings showed that maintenance and recycling of construction machinery can be improved with the advantage of the Industrial Internet platform, while achieving the supply chain coordination by contracts. The enhancement of maintenance effort can decrease the remanufacturing cost which is positively correlated to the selling price and leasing price of product, furthermore promoting the recovery rate of used products. In the future, reasonable control of platform cost can help improve the recycling of construction machinery.

Loop quantum gravity (LQG) quantizes gravity through the quantization of the space-time. It begins with general relativity (GR) and brings some concepts from quantum field theory to quantize the space-time. The conceptual background of GR is necessary to comprehend the LQG framework. Therefore, in this paper, prerequisite concepts such as special relativity, general relativity, covariant electromagnetism, tensor analysis, Lagrangian formulation, Hamiltonian formulation and basics of quantum mechanics are briefly introduced; that, are needed to study loop quantum gravity(LQG).

G-quadruplexes are noncanonical nucleic acid structures formed from stacked guanine tetrads. They are frequently used as building blocks and functional elements in fields such as synthetic biology and also thought to play widespread biological roles. G-quadruplexes are often studied as monomers but can also form a variety of higher-order structures. This increases the structural and functional diversity of G-quadruplexes, and recent evidence suggests that it could also be biologically important. In this review we describe the types of multimeric topologies adopted by G-quadruplexes and highlight what is known about their sequence requirements. We also summarize the limited information available about potential biological roles of multimeric G-quadruplexes and suggest new approaches that could facilitate future studies of these structures.

A programmable DC power supply with Real-time Digital Simulator (RTDS)-based photovoltaic (PV) Power Hardware-In-the-Loop (PHIL) simulators have been used to improve the control algorithm and reliability of PV Inverter. This paper proposes a supervisory control algorithm for PV PHIL simulator with non-RTDS device that is an alternative solution of high cost PHIL simulator. However, when such a simulator with conventional algorithm which is used in RTDS is connected to a PV inverter, the output is in the transient state and it makes it impossible to evaluate the performance of the PV Inverter. Therefore proposed algorithm controls the voltage and current target values according to the constant voltage (CV) and constant current (CC) modes to overcome the limitation of the Computing Unit, DC power supply and also uses a multi-rate system to account for the characteristics of each component of simulator. A mathematical models of a PV system, programmable DC power supply, isolated DC measurement device and Computing Unit are integrated to form a real-time processing simulator. Performance tests using a PV PHIL simulator which is applied proposed algorithm connected a PV inverter are carried out and proved superiority and utility of this method against conventional methods.

This paper introduces a sliding mode control (SMC) based equivalent control method to a novel high output gain Cuk converter. An additional inductor and capacitor improves the efficiency and output gain of the classical Cuk converter. Classical PI controllers are widely used in DC-DC converters. However, it is a very challenging task to design a single PI controller operating in different load and disturbances. SMC based equivalent control method which achieves a robust operation in a wide operation range is also proposed. Switching frequency is kept constant in appropriate interval in different loading and disturbance conditions by implementing a dynamic hysteresis control method. Numerical simulations conducted on Matlab/Simulink confirm the accuracy of analytical analysis of high output gain modified Cuk converter. In addition, proposed equivalent control method is validated in different perturbations to demonstrate the robust operation in wide operation range.

With the development of higher voltage power grid, the high and low voltage parallel loops are emerging, which lead to energy losses, even threaten the security and stability of power system. The multi-infeed HVDC configurations widely appearing in AC/DC interconnected power system make this situation even worse. Aimed at energy saving and system security, a decision optimization method for power grid operating condition with high and low voltage parallel loops is proposed in this paper. Firstly, considering hub substation distribution and power grid structure, parallel loop opening schemes are generated with GN algorithm. Then, candidate opening schemes are preliminarily selected from all these generated schemes based on a filtering index. Finally, with the influence on power system security, stability and operation economy in consideration, an evaluation model for candidate opening schemes is founded based on analytic hierarchy process (AHP). And a fuzzy evaluation algorithm is used to find the optimal scheme. Simulation results of New England 39-bus system and an actual power system validate the effectiveness and superiority of this proposed method.

Steroid-responsive meningitis-arteritis (SRMA) is a predominantly Th-2 immune-mediated dis-ease, but exact pathomechanism remains still unclear. Interleukin-31 (IL-31) is predominantly produced by T cells with a Th-2 phenotype during proinflammatory conditions. We hypothesize, IL-31 might be involved in the pathogenesis of SRMA. IL-31 was measured in archived samples (49 serum and 52 CSF samples) of dogs with SRMA, Meningoencephalitis of unknown origin (MUO), infectious meningoencephalitis, atopic dermatitis and of healthy control dogs using a competitive canine IL-31 ELISA. Mean serum IL-31 level in dogs with SRMA (n=18) was mildly higher compared to dogs with atopic dermatitis (n=3) and MUO (n=15) and markedly higher than in healthy controls (n=10) and dogs with infectious meningoencephalitis (n=3). Dogs with SRMA in the acute stage of the disease and without any pre-treatment had the highest IL-31 levels. The mean CSF IL-31 value of dogs with SRMA (n=23) was quite similar to healthy controls (n=8) and did not differ significantly from dogs with MUO (n=19) and infectious meningoencephalitis (n=2). Based on this study, an involvement of IL-31 in the pathogenesis of the systemic Th-2 im-mune-mediated immune response in SRMA can be assumed as a further component leading to an aberrant immune reaction.

We report the first case of Daratumumab interference of allogeneic crossmatch tests repeatedly causing aberrant false-positive results, which inadvertently delayed transplant for a waitlisted renal patient with multiple myeloma. Daratumumab is an IgG1κ human monoclonal antibody commonly used to treat multiple myeloma, characterized by cancerous plasma cells and often leads to renal failure requiring kidney transplant, by depleting CD38-expressing plasma cells. In this case study, the patient had end-stage renal disease secondary to multiple myeloma and was continuously receiving Daratumumab infusions. The patient did not have any detectable antibodies to human leukocyte antigens but repeatedly had unexpected positive crossmatch by the flow cytometry-based method with 26 of the 27 potential deceased organ donors, implying donor-recipient immunological incompatibility. However, further review and analysis suggested that the positive crossmatches were likely false-positive as a result of interference from Daratumumab binding to donor cell surface CD38 as opposed to the presence of donor-specific antibodies. The observed intensity of the false-positive crossmatches was also highly variable, potentially due to donor- and/or cell-dependent expression of CD38. The variability of CD38 expression was, therefore, for the first time, characterized on the T and B cells isolated from various tissues and peripheral blood of 78 individuals. Overall, T cells were found to have a lower CD38 expression profile than the B cells, and no significant difference was observed between deceased and living individuals. Finally, we show that a simple cell treatment by dithiothreitol can effectively mitigate Daratumumab interference thus preserving the utility of pre-transplant crossmatch in multiple myeloma patients awaiting kidney transplant.

We investigate a single-particle density of states in the three-dimensional system described by effective two-band Hamiltonian which describes a ground state in two distant electronic phases: the semimetalic nodal-loop phase and the insulating gapped phase. Analysis of valence bands and Fermi surfaces in both phases indicates that the density of states crucially depends on the parameter in the Hamiltonian of the system that controls a topological alternation of the Fermi surface. The signature of that alternation is expected to play an important role in all quantities closely related to the density of electronic states, such as charge transport and optical conductivity of the system for example.

The entropy and charge distributions have been calculated for a simple model of polyelectrolytes attached to the surface of DNA using a field-theoretic method that includes fluctuations to the lowest one-loop order beyond mean-field theory. Experiments have revealed correlation-driven behavior of DNA in charged solutions, including charge inversion and condensation. In our model, the condensed polyelectrolytes are taken to be doubly charged dimers of length comparable to the distance between sites along the phosphate chains. Within this lattice-gas model, each adsorption site is assumed to have either a vacancy or a positively-charged dimer attached with the dimer oriented either parallel or perpendicular to the double helix DNA chain. We find that the inclusion of the fluctuation terms decreases the entropy by ∼50% in the weak binding regime. There, the bound dimer concentration is low because the dimers are repelled from the DNA molecule, which competes with the chemical potential driving them from the solution to the DNA surface. Surprisingly, this decrease in entropy due to correlations is so significant that it overcompensates for the entropy increase at the mean field level, so that the total entropy is even lower than in the absence of interactions between lattice sites. As a bonus, we present a transparent exposition of the methods used that could be useful to students and others wishing to use this formulation to extend this calculation to more realistic models.

The three-dimensional structure of Gulf of Mexico’s warm-core rings, detaching from the Loop Current, is investigated using satellite altimetry and a large set of ARGO float profiles. Reconstruction of the Loop Current rings (LCRs) vertical structure from sea surface height observations is made possible by the use of the gravest empirical modes method (GEM). The GEMs are transfer functions that associate a value of temperature and salinity for each variable pair {dynamic height;pressure}, and are computed by estimating an empirical relationship between dynamic height and the vertical thermohaline structure of the ocean. Between 1993 and 2021, 40 LCRs were detected in the altimetry and their three-dimensional thermohaline structure was reconstructed, as well as a number of dynamically relevant variables (geostrophic and cyclogeostrophic velocity, relative vorticity, potential vorticity, available potential energy and kinetic energy density etc.). The structure of a typical LCR was computed by fitting an analytical stream function to the LCRs dynamic height signature and reconstructing its vertical structure with the GEM. The total heat and salt contents and energy of each LCR were computed and their cumulative effect on the Gulf of Mexico’s heat, salt and energy balance is discussed. We show that LCRs have a dramatic impact on these balances and estimate that residual surface heat fluxes of -13 Wm−2 are necessary to compensate their heat input, while the fresh water outflow of the Mississippi river approximately compensates for their salt excess input. An average energy dissipation of O[10−10−10−9] Wkg−1 would be necessary to balance their energy input.

Nutrient regulation in aquaponic environments has been the topic of research for many years. Most have focused on appropriate control of nutrients in an aquaponic set-up, but very little research has been done on commercial scale applications. In our model, the input data was sourced on a weekly basis from three commercial aquaponic farms in South-East Texas over the course of a year. Due to limited number of data points, dimensionality reduction techniques like pair-wise correlation matrix was used to remove the highly correlated predictors. Feature selection techniques like the XGBoost classifier and Recursive Feature Elimination with ExtraTreesClassifier were used to rank the features in order of their relative importance. Ammonium and calcium were found to be the top two nutrient predictors and based on the months in which lettuce was cultivated, the median of these nutrient values from the historical dataset served as the optimal concentrations to be maintained in the aquaponic solution. To accomplish this, Vernier sensors were used to measure the nutrient values and actuator systems were built to dispense the appropriate nutrient into the ecosystem via a closed loop.

Influence of Joule heating on magnetic properties, giant magnetoimpedance (GMI) effect and domain wall (DW) dynamics of Fe75B9Si12C4 glass-coated microwires was studied. A remarkable increase in GMI ratio is observed in Joule heated samples. The hysteresis loops of Joule heated samples maintain a rectangular shape, while a slight decrease in coercivity after Joule heating is observed. On the other hand, a modification of MOKE hysteresis loops is observed upon Joule heating. Additionally, DW dynamics improvement after Joule heating is observed. The observed GMI ratio improvement along with the change in MOKE loops and DW dynamics improvement has been discussed considering magnetic anisotropy induced by Oersted magnetic field in the surface layer during Joule heating and the internal stress relaxation. A remarkable GMI ratio im-provement observed in Fe-rich Joule-heated microwires with a rectangular hysteresis loop and fast DW propagation, together with the fact that Fe is a more common and less expensive metal than Co, makes them suitable for use in magnetic sensors.

Null-flux Electro-dynamic suspension (EDS) system promises to be one of the feasible high-speed maglev systems above 600 km/h. On account of its greater current-carrying capacity, superconducting magnet can provide super-magnetomotive force that is required for null-flux EDS system and cannot be provided by electromagnets and permanent magnets. There is already a relatively mature high-speed maglev technology with low temperature superconducting (LTS) magnets as the core, which works in the liquid helium temperature region (T≤4.2 K). 2-Generation high temperature superconducting (HTS) magnet winded by REBa2Cu3O7−δ (REBCO, RE=rare earth) tapes works above 20 K region and do not need to count on liquid helium which is rare on earth. This paper designed HTS no-insulation closed-loop coils applied for EDS system and energized with persistent current switch. The coils can work at persistent current model and has premier thermal quench self-protection. Besides, a full size double-pancake module was designed and manufactured in this paper, and it was tested in liquid nitrogen. The double-pancake module’s critical current is about 54 A and it is capable of working at persistent current model, whose average decay rate measured in 12 hours is 0.58%/day.

This document focuses attention on the fundamental solution of an autonomous linear retarded functional differential equation (RFDE) along with its supporting cast of actors: kernel matrix, characteristic matrix, resolvent matrix, and the Laplace transform. The fundamental solution is presented in a form of the convolutional powers of the kernel matrix in the manner of a convolutional exponential matrix function. The fundamental solution combined with a solution representation gives an exact expression in explicit form for the solution of a RFDE. Algebraic graph theory is applied to the RFDE in the form of a weighted loop-digraph to illuminate the system structure and system dynamics and to identify the strong and weak components. Examples are provided in the document to elucidate the behavior of the fundamental solution. The paper introduces fundamental solutions of other functional differential equations.

Multiferroics, showing both ferroelectric and magnetic order, are promising candidates for future electronic devices. Especially, the fundamental understanding of ferroelectric switching is of key relevance for further improvements, which however is rarely reported in literature. On a prime example for a spin-driven multiferroic, LiCuVO₄, we present an extensive study of the ferroelectric order and the switching behavior as function of external electric and magnetic fields. From frequency-dependent polarization switching and using the Ishibashi-Orihara theory, we deduce the existence of ferroelectric domains and domain-walls. These have to be related to counterclockwise and clockwise spin-spirals leading to the formation of multiferroic domains. A novel measurement – multiferroic hysteresis loop – is established to analyze the electrical polarization simultaneously as a function of electrical and magnetic fields. This technique allows characterizing the complex coupling between ferroelectric and magnetic order in multiferroic LiCuVO₄.

Recycling waste products is an environmental-friendly activity that can bring benefits to accompany, saving manufacturing costs and improving economic efficiency. For the beer industry, recycling bottles can reduce manufacturing costs and reduce the industry's carbon footprint. This paper presents a model for a multi-objective collection-distribution center location and allocation problem in a closed loop supply chain for the beer industry, in which the objective is to minimize total costs and transportation pollution. Uncertainties in the form of randomness and fuzziness are jointly handled in this paper to ensure a more practical problem solution, for which returned bottle sand unusable bottles are considered fuzzy random variables. A heuristic algorithm based on priority-based global-local-neighbor particle swarm optimization (pb-glnPSO) is applied to ensure reliable solutions for this NP-hard problem. A case study on a beer operation company is conducted to illustrate the application of the proposed model and demonstrate the priority-based global-local-neighbor particle swarm optimization.

The presence of premature termination codons (PTCs) in transcripts is dangerous for the cell as they encode potentially deleterious truncated proteins that can act with dominant-negative or gain-of-function effects. To avoid synthesis of these shortened polypeptides, several RNA surveillance systems can be activated to decrease the level of PTC-containing mRNAs. Nonsense-mediated mRNA decay (NMD) ensures an accelerated degradation of mRNAs harboring PTCs by using several key NMD factors such as up-frameshift (UPF) proteins. Another pathway called nonsense-associated altered splicing (NAS) upregulates transcripts that have skipped disturbing PTCs by alternative splicing. Therefore, these RNA quality control processes eliminate abnormal PTC-containing mRNAs from the cells by using positive and negative responses. In this review, we will describe the general mechanisms of NMD and NAS and their respective involvement in the decay of aberrant immunoglobulin and TCR transcripts in lymphoid cells.

The turnover of the RNA molecules is determined by the rates of transcription and RNA degradation. Several methods have been developed to study mRNA turnover since the beginnings of molecular biology. Here we summarize the main methods to measure RNA half-life: transcription inhibition, gene control and metabolic labelling. These methods were used to detect the cellular activity of the mRNAs degradation machinery, including the exo-ribonuclease Xrn1 and the exosome. Less progress has been made in the study of the differential stability of mature RNAs because the different methods have often yielded inconsistent results so that an mRNA considered to be stable can be classified as unstable by another method. Recent advances in the systematic comparison of different method variants in yeast have permitted the identification of the least invasive methodologies that reflect half-lives the most faithfully, which is expected to open the way for a consistent quantitative analysis of the determinants of mRNA stability.

The port environments have some structures that still need regular control. However, the nature of these environments presents a number of challenges in determining an accurate vehicle position and consequently performing successful image similarity detection. These scenarios, however, can have poor visibility conditions and are highly dynamic, making place recognition difficult because the appearance of a place can change over time. Under these operational conditions, imaging sonars are a promising solution. There are some factors that affect the quality of the captured images, but the fact that they do not suffer from haze is a plus. Therefore, in this paper, a purely acoustic similarity detection method based on forward-looking sonar (FLS) data is proposed to overcome the inherent perceptual problems in a port scenario. Considering the lack of available data in this context and to facilitate the variation of environmental parameters and sensor configurations, a port scenario was simulated using the Stonefish simulator. Experiments were conducted on predefined trajectories near structures. The place recognition approach performs better compared to the results obtained with optical imagery. In general, it provides a good compromise in terms of distinctiveness and achieves a performance of 87.5% when appropriate constraints and assumptions are made.

We have found an infinite dimensional manifold of exact solutions of the Navier-Stokes loop equation for the Wilson loop in decaying Turbulence in arbitrary dimension $d >2$. This solution family is equivalent to a fractal curve in complex space $\mathbb C^d$ with random steps parametrized by $N$ Ising variables $\sigma_i=\pm 1$, in addition to a rational number $\frac{p}{q}$ and an integer winding number $r$, related by $\sum \sigma_i = q r$. This equivalence provides a \textbf{dual} theory describing a strong turbulent phase of the Navier-Stokes flow in $\mathbb R_d$ space as a random geometry in a different space, like ADS/CFT correspondence in gauge theory. From a mathematical point of view, this theory implements a stochastic solution of the unforced Navier-Stokes equations. For a theoretical physicist, this is a \textbf{quantum} statistical system with integer-valued parameters, satisfying some number theory constraints. Its long-range interaction leads to critical phenomena when its size $N \rightarrow \infty$ or its chemical potential $\mu \rightarrow 0$. The system with fixed $N$ has different asymptotics at odd and even $N\rightarrow \infty$, but the limit $\mu \rightarrow 0$ is well defined. The energy dissipation rate is analytically calculated as a function of $\mu$ using methods of number theory. It grows as $\nu/\mu^2$ in the continuum limit $\mu \rightarrow 0$, leading to anomalous dissipation at $\mu \propto \sqrt{\nu} \to 0$. The same method is used to compute all the local vorticity distribution, which has no continuum limit but is renormalizable in the sense that infinities can be absorbed into the redefinition of the parameters. The small perturbation of the fixed manifold satisfies the linear equation we solved in a general form. This perturbation decays as $t^{-\lambda}$, where the anomalous dimensions $\lambda$ satisfy the spectral equation \eqref{spectralEq}. The spectrum becomes a continuum in the statistical limit $N \to \infty$, presumably leading to multifractal phenomena.

Hand, foot and mouth disease (HFMD) is a childhood disease caused by enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16). We hypothesize that capsid loops are important epitopes for EV-A71 and CV-A16. Seven chimeric EV-A71 (ChiE71) involving VP1 BC, DE, EF, GH and HI loops, VP2 EF loop, and VP3 GH loop were substituted with corresponding CV-A16 loops. VP3 GH loop is the most conserved (91.3%) while VP1 BC loop has only 45.5% similarity. Only ChiE71-1-BC, ChiE71-1-EF, ChiE71-1-GH and ChiE71-3-GH were viable. EV-A71 and CV-A16 antiserum neutralized ChiE71-1-BC and ChiE71-1-EF. Mice immunized with inactivated ChiE71 elicited high IgG, IFN-γ, IL-2, IL-4 and IL-10. Neonatal mice receiving passive transfer of WT EV-A71, ChiE71-1-EF and ChiE71-1-BC immune sera had 100%, 80.0% and no survival, respectively, against lethal challenges with EV-A71, suggesting that the substituted CV-A16 loops disrupted EV-A71 immunogenicity. Passive transfer of CV-A16, ChiE71-1-EF and ChiE71-1-BC immune sera provided 40.0%, 20.0% and 42.9% survival, respectively, against CV-A16. One-day-old neonatal mice actively immunized with WT EV-A71, ChiE71-1-BC, ChiE71-1-EF and CV-A16 achieved 62.5%, 60.0%, 57.1% and no survival respectively, after the EV-A71 challenge. Active immunization using CV-A16 provided full protection while WT EV-A71, ChiE71-1-BC, ChiE71-1-EF immunization showed partial cross-protection in CV-A16 lethal challenge with survival rates of 50.0%, 20.0%, and 40%, respectively. Taken together, the EV-A71 VP1 BC loop is essential in immunogenicity of EV-A71 and substitution with CV-A16 VP1 BC loop was insufficient to confer protection against CV-A16. The EF loop maintains the cross-protective immune responses. Disruption of a capsid loop could affect virus immunogenicity, and future vaccine design should include conservation of the enterovirus capsid loops.

Deep-Brain Stimulation (DBS) is a a highly effective and safe medical treatment that improves the lives of patients with a wide range of neurological and psychiatric deceases, and has been consolidated as a first-line tool in the treatment of these conditionsin the last two decades. Closed Loop Deep-Brain Stimulation (CLDBS) pushes this tool further by automatically adjusting the stimulation parameters to the brain response in real time. In this context, this paper presents a Low-Noise Amplifier (LNA) and a Neurostimulator circuits fabricated in the low-power/low-voltage 65 nm CMOS process from the TSMC, which were designed targeting implantable applications. To achieve the best trade-off between input-referred noise and power consuption, metaheuristic algorithms were employed to determine and optimizes the dimentions of the LNA devices during the design phase. The measurement results showed that the LNA had a gain of 40.6 dB, a 3 dB bandwidth spanning over three decades from 10 Hz to 8.6 kHz, and a power consumption of 6.19 uW. Simulations results indicated an input-referred noise of 4.86 uVrms for the LNA. The circuit of the Neurostimulator is a programmable Howland Current-Pump, whose measurements showed its ability to generate currents with arbitrary shapes ranging from between 325 uA to +318 uA. The simulations showed a quiescent power consumption of 0.13 W with a zero neurostimulation current. The LNA and the Neurostimulator circuits are supplied with 1.2 V voltage and occupy a microdevice area of 145 um x 311 um and 88 um x 89 um, respectively, making them suitable for implantation in applications involving Closed Loop Deep-Brain Stimulation.

Physics and neuroscience share overlapping objectives, the major of which is probably the attempt to reduce the observed universe to a set of rules. The approaches are complementary, attempting to find a reduced description of the universe or of the observer, respectively. We propose here that combining the two approaches within an observer-inclusive physical scheme, bears significant advantages. In such a scheme, the same set of rules applies to the universe and its observers, and the two descriptions are entangled. We show here that analyzing special relativity in an observer-inclusive framework can resolve its contradiction with the observed non-locality of physical interactions. The contradiction is resolved by reducing the universe (including the observer) to a dynamic distribution of closed strings (“ceons”) whose vibration waves travel at c. This ceons model is consistent with general relativity, non-locality, the holographic principle and loop quantum gravity; it also eliminates Zeno’s motion paradoxes. Yet, the model entails several new empirical predictions. Finally, the ceons model suggests a fundamental physical implementation of active biological perception. Paraphrasing Torricelli, this paper suggests that we live submerged in a c of light.

This paper presents a study on the influence of the frequency variation of a nonlinear1 control allocation technique execution, developed by the author [1], named by Fast Control2 Allocation (FCA) for the Quadrotor Tilt-Rotor (QTR) aircraft. Then, through Software In The3 Loop (SITL) simulation, the proposed work considers the use of Gazebo, QGroundControl, and4 Matlab applications, where different frequencies of the FCA can be implemented separated in5 Matlab, always analyzing the QTR stability conditions from the virtual environment performed in6 Gazebo. TheresultsshowedthattheFCAneedsatleast200HzoffrequencyfortheQTRsafeflight7 conditions, i. e., 2 times smaller than the main control loop frequency, 400 Hz. Lower frequencies8 than this one would case instability or crashes during the QTR Operation.

The work is devoted to the study of a MEMS resonator dynamics under the action of phase-locked and automatic gain control loops. Particular attention is directed to the study of the nonlinearity factor of the resonator elastic restoring force. It was found that the determination of control system parameters based on the stability analysis of the operating resonant mode, in the general case, does not provide the required phase adjustment and stabilization of the oscillation amplitude. Stable multifrequency modes of oscillations are found, an analytical study of the mechanisms of their appearance and evolution is carried out under variation of the key parameters of the system. The real regions of the control system stable operation are determined (which do not coincide, as was found, with the regions of stability of the operating resonant mode, due to the presence of hidden attractors in the phase space of the system). A methodology has been developed for identifying such areas of stable operation. A significant complication of the structure of possible motions in the system with an increase in the Q-factor of the resonator is revealed.

Grid energy storage system for PV Applications is connected with three different power sources i.e. PV Array, Battery and the Grid. It is advisable to have Isolation between these three different sources to provide safety for the equipment. The configuration proposed in this paper provides the complete isolation between the three sources. A Power Balancing Control (PBC) for this configuration is proposed to operate the system in three different modes of operation. Control of a dual active bridge (DAB) based battery charger which provides a galvanic isolation between batteries and other sources is explained briefly. Various modes of operation of a Grid energy storage system are also presented in this paper. Hardware-In-Loop (HIL) Simulation is carried out to check the performance of the system and the PBC algorithm. Power circuit (comprises of inverter, dual active bridge based battery charger, grid, PV cell, batteries, contactors and switches) is simulated and the controller hardware and user interface panel are connected as HIL with the simulated power circuit through Real Time Digital Simulator (RTDS). HIL simulation results are presented to explain the control operation, steady state performance in different modes of operation and the dynamic response of the system.

This research integrates systemic and participatory techniques to model the Russian Federation construction innovation system. Understanding this complex construction innovation system, and determining the best levers for enhancing it, requires the dynamic modelling of a number of factors such as flows of resources and activities, policies, uncertainty and time. To build the foundations for such a dynamic model, the employed study method utilised an integrated stakeholder-based participatory approach coupled with structural analysis (MICMAC - Matrice d'Impacts Croisés Multiplication Appliquée à un Classement Cross-Impact Matrix). This method identified the key factors of the Russian Federation construction innovation system, their causal relationship (i.e. influence/dependence map) and ultimately a causal loop diagram. The generated model reveals pathways to improving construction innovation in the Russian Federation, and underpins the future development of an operationalised systems dynamic model.

Hippocampal neuronal activity generates dendritic and somatic Ca2+ signals, which depending on stimulus intensity, rapidly propagate to the nucleus and induce the expression of transcription factors and genes with crucial roles in cognitive functions. Soluble Amyloid-beta Oligomers (AβOs), the main synaptotoxins engaged in the pathogenesis of Alzheimer's disease, generate aberrant Ca2+ signals in primary hippocampal neurons, increase their oxidative tone and disrupt structural plasticity. Here, we explored the effects of sub-lethal AβOs concentrations on activity-generated nuclear Ca2+ signals and on the Ca2+-dependent expression of neuroprotective genes. To induce neuronal activity, neuron-enriched primary hippocampal cultures were treated with the GABAA receptor blocker gabazine (GBZ), and nuclear Ca2+ signals were measured in AβOs-treated or control neurons transfected with a genetically encoded nuclear Ca2+ sensor. Incubation (6 h) with AβOs significantly reduced the nuclear Ca2+ signals and the enhanced phosphorylation of cyclic AMP response element binding protein (CREB) induced by GBZ. Likewise, incubation (6 h) with AβOs significantly reduced the GBZ-induced increases in the mRNA levels of Neuronal Per Arnt Sim domain protein 4 (Npas4), Brain-derived Neurotrophic Factor (Bdnf), Ryanodine Receptor type-2 (RyR2), and the antioxidant enzyme NADPH-Quinone-Oxidoreductase (Nqo1). Based on these findings we propose that AβOs, by inhibiting the generation of activity induced nuclear Ca2+ signals, disrupt key neuroprotective gene expression pathways required for hippocampal-dependent learning and memory processes.

The α(1,2)fucosyltransferase (Se enzyme) encoded by FUT2 is involved in the secretor status of ABH(O) blood group antigens. The sedel2 allele is one of the non-functional FUT2 (se) alleles in which 9.3 kb containing the entire coding region of FUT2 is deleted by Alu-mediated nonhomologous recombination. In addition to this allele, three SNPs of FUT2, c.375A>G, c.385A>T, and c.571C>T, appear to be prevalent in certain Oceanian populations such as Polynesians. Recently, we developed an endpoint genotyping assay to determine the sedel2 zygosity, using a FAM-labeled probe for detection of the sedel2 allele and a VIC-labeled probe for detection of FUT2. In this study, instead of the VIC probe, a HEX-labeled probe covering both c.375A>G and c.385A>T and a Cy5-labeled probe covering c.571C>T were added to the sedel2 allele assay mixture to allow simultaneous detection of these four variations by endpoint genotyping for the sedel2 zygosity and fluorescence melting curve analysis for c.375A>G, c.385A>T, and c.571C>T genotyping. The results obtained from 24 Samoan subjects with this method were identical to those obtained with previous methods. Therefore, it appears that present method can accurately determine these four variations simultaneously.

Nitric oxide (NO) is a key molecule in cardiovascular homeostasis and its abnormal delivery is highly associated with the occurrence and development of cardiovascular disease (CVD). The assessment and manipulation of NO delivery is crucial to the diagnosis and therapy of CVD, such as endothelial dysfunction, atherosclerotic progression, pulmonary hypertension, and cardiovascular manifestations of Coronavirus (COVID-19). However, due to the low concentration and fast reaction characteristics of NO in cardiovascular system, the clinical applications centered on the NO delivery are challenging. In this tutorial review, we first summarized the methods to estimate the in vivo NO delivery process based on the clinical images and mathematical modeling to assess the endothelial function and vulnerability of atherosclerotic plaque. Then, the emerging bioimaging technologies that have the potential to directly measure the arterial NO concentration were discussed, including the Raman spectroscopy and electrochemical sensor. Aside from the diagnostic methods, therapies aimed at controlling NO delivery to regulate CVD were reviewed, including the inhaled NO therapy to treat the pulmonary hypertension and COVID-19, stem cell therapy and NO-releasing platform to treat endothelial dysfunction and atherosclerosis.