Our main objective in this work was to examine the possibility of non-intrusive, label-free, detection of whole Zika viruses using terahertz signals with or without a targeting/binding oligonucleotide (aptamers). We report for the first time the use of terahertz electromagnetic waves (0.75 THz – 1.1 THz) to detect Zika viruses. The Zika/aptamer complexes showed a reproducible terahertz reflection coefficient minimum at 1.064 THz while the Zika virus’s reflection minimum was at 1.073 THz. Of different substrates we examined, the polyester petri dish provided a very low loss and excellent terahertz transmission. To increase the interaction between the terahertz signal and the sample we also used polyester microbeads coated with aptamers. We then measured the terahertz reflection from the microbeads as a function of Zika concentration. The resulting terahertz Zika sensor had sensitivity of 63 Hz/Zika and minimum detectable signal of ~ 16x10³ Zika. Other substrates such as Graphene on polyethylene terephthalate (PET), 50 nm-thick gold film on polycarbonate, thin (30 um-thick) glass slide and Teflon were also examined. Graphene substrate enabled direct detection of the Zika without any aptamers.

A new label-free molecular probe for luminescent nucleotide detection in neutral aqueous solution is presented. Phosphate-containing molecules such as nucleotides possess vital role in cell metabolism, energy economy, and signaling. Thus the monitoring of nucleotide concentration and nucleotide related enzymatic reactions is of high importance. Two component lanthanide complex formed from Tb(III) ion carrier and light harvesting antenna, readily distinguishes nucleotides containing different number of phosphates and enable direct detection of enzymatic reactions converting nucleotide triphosphate (NTP) to nucleotide di/monophosphate or the opposite. Developed sensor enables the detection of enzymatic activity with a low nanomolar sensitivity, as highlighted with K-Ras and apyrase enzymes in there hydrolysis assays performed in high throughput screening compatible 384-well plate format.

Food pathogens contaminate food products that allow their growth on the shelf and also under refrigerated conditions. Therefore, it is of utmost importance to lower the limit of detection (LOD) of the method used and to obtain the results within hours to few days. Biosensor methods exploit the available technologies to individuate and provide an approximate quantification of the bacteria present in a sample. The main bottleneck of these methods depend on the aspecific binding to the surfaces and on a change in sensitivity when bacteria are in a complex food matrix in respect to bacteria in a liquid food sample. In this review we introduce Surface Plasmon Resonance (SPR), new advancements in SPR techniques, and Electrochemical Impedance Spectroscopy (EIS), as label-free biosensing technologies for the detection of L. monocytogenes in foods. The application of the two methods has made possible the detection of L. monocytogenes with LOD of 1 log CFU/mL. Further advancement are envisaged through the combination of biosensor methods with immunoseparation of bacteria from larger volumes.

The detection and analysis of small molecules, typically defined as molecules under 1000 Da, is of growing interest ranging from the development of small molecule drugs and inhibitors to the sensing of toxins and biomarkers. However, due to challenges such as their small size and low mass, many biosensing technologies struggle to have the sensitivity and selectivity for the detection of small molecules. Notably, their small size limits the usage of labeled techniques that can change the properties of small molecule analytes. Furthermore, the capability of real-time detection is highly desired for small molecule biosensors’ application in diagnostics or screening. This review highlights recent advances in label-free real-time biosensing technologies utilizing different types of transducers to meet the growing demand for small molecule detection.

Biosensors have shown great potential in realizing rapid, low cost and portable on-site detection for diseases. This work reports the development of a new bioelectronic sensor called AC electrokinetics-based capacitive (ABC) biosensor, for the detection of genomic DNA (gDNA) of methicillin-resistant Staphylococcus aureus (MRSA). The ABC sensor is based on interdigitated microelectrodes biofunctionalized with oligonucleotide probes. It uses a special AC signal for direct capacitive monitoring of topological change on nanostructured sensor surface, which simultaneously induce dieletrophoretic enrichment of target gDNAs. As a result, rapid and specific detection of gDNA/probe hybridization can be realized with high sensitivity. It requires no signal amplification such as labelling, hybridization chain reaction, or nucleic acid sequence-based amplification. This method involves only simple sample preparation. After optimization of nano-structured sensor surface and signal processing, the ABC sensor demonstrated fast turnaround of results (~10 s detection), excellent sensitivity (a detection limit of 4.7 DNA copies /µL MRSA gDNA) and high specificity, suitable for point of care diagnosis. As a bioelectronic sensor, the developed ABC sensors can be easily adapted for detection of other infectious agents.

Label-free confocal photothermal (CPT) microscopy was utilized for the first time to investigate malignancy in mouse skin cells. A laser diode (LD) with 405nm or 488nm was used as a pump and 638nm LD as a probe for the CPT microscope. The Grey Level Cooccurrence Matrix (GLCM) for texture analysis was applied to the CPT images. Nine parameters of GLCM were calculated for the intracellular super-resolved CPT images, and the parameters Entropy and Prominence were found to be most suited among the nine parameters to discriminate between healthy cells and MM cells in case pump wavelength of 488nm is used.

A label-free four-step procedure to identify amino acids (AAs) is described. In Step 1 molecules of AA, a tRNA, the related tRNA synthetase (AARS), and ATP are confined in a cavity to enable charging of tRNA. In Step 2 the tRNA, charged or uncharged, is separated from the other reactants (ATP, AARS, and possibly AMP and free AAs). In Step 3 the separated tRNA is subjected to non-enzymatic deacylation to dissociate the AA if tRNA is charged. In Step 4 the products are transferred to an electrolytic cell with a nanopore, where a current blockade occurs if and only if there is a dissociated AA. If a blockade is observed AA is immediately known, identification is unambiguous because of tRNA superspecificity. The exact blockade size need not be known (for any AA) in Step 4 so there is no need to distinguish among different AAs. This is unlike other nanopore-based methods, which are crucially dependent on precise blockade level measurements. The procedure is done in parallel with N (20 ≤ N ≤ 61) copies of AA, N reservoir-cavities, and N pairs of e-cells each with a different tRNA, related AARS, and ATP. At least one of the tRNAs gets charged. Assuming no charging errors, if N₁ tRNAs get charged in Step 1 and at least one of N₂ (≤ N₁) charged tRNAs is deacylated in Step 3, then with N₁N₂ tRNA molecules entering Step 1 AA can be identified with probability 1.

Food composition data in the EMR countries are often lacking, obsolete or unreliable. The study aims to provide reliable and up-to-date nutrient data of selected food products consumed in Oman in order to evaluate consistency of nutrition labelling and update the current used food composition database. Contents of total fat, fatty acids, carbohydrates, total nitrogen, sugars and sodium were chemically analyzed in 221 foods and beverages purchased in 2022 and label and corresponding laboratory values were compared using the tolerance levels of the European Union. Food items were classified according their nutritional composition, the extent of processing and coded according FoodEx2 system. Results indicate that the nutrient values stated on a label align with the values obtained in the laboratory with the exception of a 6.3% discrepancy in TFAs content, where the reported values are higher than the appropriate reference values. The category with the highest frequency (71.5%) consisted of ultra-processed foods. In terms of inconsistencies in the nutrition claims, 5.1% of food products with claims did not comply with the statement “sugar free” or “low salt”. These findings underscore the significance of vigilant monitoring of nutritional labels as a means to implement measures that promote the well-being of consumers.

Thanks to advanced semiconductor microfabrication technology, chip-scale integration and miniaturization of lab-on-a-chip components, silicon-based optical biosensors have made significant progress for the purpose of point-of-care diagnosis. In this review, we provide an overview of the state-of-the-art in evanescent field biosensing technologies including interferometer, microcavity, photonic crystal, and Bragg grating waveguide-based sensors. Their sensing mechanisms and sensor performances, as well as real biomarkers for label-free detection, are exhibited and compared. We also review the development of chip-level integration for lab-on-a-chip photonic sensing platforms, which consist of the optical sensing device, flow delivery system, optical input and readout equipment. At last, some advanced system-level CMOS-chip packaging examples are presented, indicating the commercialization potential for the low cost, high yield, portable biosensing platform leveraging CMOS processes.

In proteomics, it is essential to quantify proteins in absolute terms if we wish compare results among studies and integrate high-throughput biological data into genome-scale metabolic models. While labeling target peptides with stable isotopes allows protein abundance to be accurately quantified, the utility of this technique is constrained by the low number of quantifiable proteins that it yields. Recently, label-free shotgun proteomics has become the “gold standard” for carrying out global assessments of biological samples containing thousands of proteins. However, this tool must be further improved if we wish to accurately quantify absolute levels of proteins. Here, we used different label-free quantification techniques to estimate absolute protein abundance in the model yeast Saccharomyces cerevisiae. More specifically, we evaluated the performance of seven different quantification methods, based either on spectral counting (SC) or extracted-ion chromatogram (XIC), which were applied to samples from five different proteome backgrounds. We also compared the accuracy and reproducibility of two strategies for transforming relative abundance into absolute abundance: a UPS2-based strategy and the total protein approach (TPA). This study mentions technical challenges related to UPS2 use and proposes ways of addressing them, including utilizing a smaller, more highly optimized amount of UPS2. Overall, three SC-based methods (PAI, SAF, and NSAF) yielded the best results because they struck a good balance between experimental performance and protein quantification.

Biosensors detect specific bio-analytes by generating a measurable signal from the interaction between the sensing element and the target molecule. Surface acoustic wave (SAW) biosensors offer unique advantages due to their high sensitivity, real-time response capability, and label-free detection. The typical SAW modes are the Rayleigh mode and the shear-horizontal mode. Both present pros and cons for biosensing applications and generally need different substrates and device geometries to be efficiently generated. This study investigates and characterizes ultra-high-frequency (UHF-) SAW resonator biosensors. It reveals the simultaneous presence of the two typical SAW modes, clearly separated in frequency, called slow and fast. The two modes are studied by numerical simulations and biosensing experiments with the glial-fibrillary-acidic-protein (GFAP) biomarker. The slow mode is generally more sensitive to changes in surface properties, such as temperature and mass changes, by a factor of about 1.4 with respect to the fast mode.

In this paper, we present and analyze a compact inner-wall grating slot microring resonator (IG-SMRR) with the footprint of less than 13 μm × 13 μm on the SOI platform for label-free sensing, which comprises a slot microring resonator (SMRR) and inner-wall grating (IG). Its detection range is significantly enhanced without the limitation of the free spectral region (FSR) owing to the combination of SMRR and IG. Structural parameters of IG and SMRR are investigated and optimized for favorable transmission properties. The simulation results shows that the IG-SMRR has an ultra-large quasi-FSR of 84.6 nm, and the concentration sensitivities of sodium chloride solutions and D-glucose solutions are up to 960.61 pm/% and 933.06 pm/%, respectively. The investigation on the combination of SMRR and IG is a valuable exploration of label-free sensing application for ultra-large detection range and ultra-high sensitivity in future.

Circulating cell-free DNA (cfDNA) refers to small fragments of DNA molecules released after programmed cell death and necrosis in several body fluids such as blood, saliva, urine, and cerebrospinal fluid. The discovery of cfDNA has revolutionized the field of non-invasive diagnostics in the oncologic field, in prenatal testing, and in organ transplantation. Despite the potential of cfDNA and the solid results published in recent literature, several challenges remain, represented by low abundance, need for highly sensitive assays and analytical issues. In this review, the main technical advances in cfDNA analysis are presented and discussed, with a comprehensive examination of the current available methodologies applied in each field. Considering the potential advantages of cfDNA, this biomarker is increasing its consensus among clinicians, as it consents to monitor patients’ conditions in an easy and non-invasive way, offering a more personalized care. Nevertheless, cfDNA analysis is still considered a research marker to be further validated, and very few centers are implementing its analysis in the real-life assistance. As technical improvements are enhancing the performances of cfDNA analysis, its application will transversally improve patients’ quality of life.

Amid the deepening imbalance in the supply and demand of allogeneic organs, xenotransplanta-tion can be a practical alternative because it makes an unlimited supply of organs possible. How-ever, to perform xenotransplantation on patients, the source animals to be used must be free from infectious agents. This requires breeding of animals using assisted reproductive techniques, such as somatic cell nuclear transfer, embryo transfer, and cesarean-section, without colostrum de-rived in designated pathogen-free (DPF) facilities. Most infectious agents can be removed from animals produced by these methods, but several viruses known to pass through the placenta are not easy to remove, even with these methods. Therefore, in this review, we look at the characteris-tics of several viruses known to cross the placenta and determine how they can be detected. This review is intended to help maintain DPF facilities by preventing animals infected with the virus from entering DPF facilities and to help select pigs suitable for xenotransplantation.

Cancer stem cells play a crucial role in tumor initiation, metastasis and therapy resistance. Cellular heterogeneity and plasticity challenge the isolation of cancer stem cells. The impact of intratumoral cellular heterogeneity in the context of treatment resistance using a label-free approach remains understudied. Here, we use the sedimentation field-flow fractionation technique to separate, without labeling, cell subpopulations of colorectal cancer cell lines and primary cultures according to their biophysical properties. One of the three cell subpopulations sorted by SdFFF exhibits cancer stem cell traits, including high tumorigenicity in vivo, and a higher frequency of tumor-initiating cells compared to the other subpopulations. In vitro two- and three-dimensional chemosensitivity assays emphasize the therapeutic relevance of this cancer stem cell-like subpopulation due to its chemoresistance. Therefore, our findings highlight a label-free cell sorting approach to reveal intratumoral cellular heterogeneity and its implication in therapy resistance. This approach enables the study of the individualized response of each sorted cell subpopulation by breaking down the tumor, thus offering new perspectives for personalized therapy.

Underwater Sensor Networks (UWSNs) can enable a broad range of applications such as resource monitoring, disaster prevention, and navigation-assisted. It is especially relevant for sensor nodes location in UWSNs. Global Positioning System (GPS) is not suitable for using in UWSNs because of the underwater propagation problems. Hence some localization algorithms based on the precise time synchronization between sensor nodes have been proposed which are not feasible for UWSNs. In this paper, we propose a localization algorithm called Two-Phase Time Synchronization-Free Localization Algorithm (TP-TSFLA). TP-TSFLA contains two phases, namely, range-based estimation phase and range-free evaluation phase. In the first phase, we address a time synchronization-free localization scheme base on the Particle Swarm Optimization (PSO) algorithm to decrease the localization error. In the second phase, we propose a Circle-based Range-Free Localization Algorithm (CRFLA) to locate the unlocalized sensor nodes which cannot obtain the location information through the first phase. In the second phase, sensor nodes which are localized in the first phase act as the new anchor nodes to help realize localization. Hence in this algorithm, we use a small number of mobile beacons to help achieve location without any other anchor nodes. Besides, to improve the precision of the range-free method, an extension of CRFLA by designing a coordinate adjustment scheme is updated. The simulation results show that TP-TSFLA can achieve a relative high localization ratio without time synchronization.

Non-alcoholic fatty liver (NAFLD) is a metabolic disorder related with a chronic lipid accumulation within the hepatocytes. This disease is the most common liver disorder worldwide and it is estimated that is present in up to 25% of the world's population. However, the real prevalence of this disease and the associated disorders is unknown mainly because reliable and applicable diagnostic tools are lacking. It is known that the level of albumin, a pleiotropic protein synthetized by hepatocytes, is correlated with the correct function of the liver. The development of a complementary tool that allow the direct, sensitive, and label-free monitoring of albumin secretion in hepatocyte cell culture can provide insight about the mechanism and drugs action in NAFLD. With this aim, we have developed a simple integrated plasmonic biosensor based on gold nanogratings from periodic nanostructures present in commercial Blu-ray optical disc. This sensor allows the direct and label-free monitoring of albumin in a 2D fatty liver disease model under flow conditions using highly specific polyclonal antibody. This technology avoids both the amplification and blocking steps showing a limit of detection within pM range (≈ 0.39 ng/mL). Thanks to this technology, we identified the optimal fetal bovine serum (FBS) concentration to maximize the lipid accumulation within the cells. Moreover, we discovered that at third day from lipids challenge, the hepatocytes increased the amount of albumin secreted. These data demonstrate the ability of hepatocytes to respond to the lipid stimulation releasing more albumin. Further investigation needed to unveil the biological significance of that cell behaviour.

Parkinson’s Disease (PD) is a debilitating neurodegenerative disease, causing loss of motor function, and in some instances, cognitive decline and dementia, in those affected. The quality of life can be improved, and disease progression delayed through early interventions, however, current methods of confirming a PD diagnosis are extremely invasive. This prevents their use as a screening tool for the early onset stages of PD. We propose a surface imprinted polymer (SIP) electroimpedance spectroscopy (EIS) biosensor for detecting α-Synuclein (αSyn) and its aggregates, a biomarker that appears in saliva and blood during the early stages of PD as the blood brain barrier degrades. The surface imprinted polymer stamp is fabricated by low temperature melt stamping polycaprolactone (PCL) on interdigitated EIS electrodes. The result is a low-cost, small footprint biosensor that is highly suitable for non-invasive monitoring of the disease biomarker. The sensors were tested with αSyn dilutions in deionized water, and in constant ionic concentration matrix solutions with decreasing concentrations of αSyn to remove the background effects of concentration. The device response confirmed the specificity of these devices to the target protein of monomeric αSyn. The sensor limit of detection was measured to be 5 pg/L and its linear detection range was 5 pg/L – 5 µg/L. This covers the physiological range of αSyn in saliva and makes this a highly promising method of quantifying αSyn monomers for PD patients in the future. The SIP surface was regenerated, and the sensor reused to demonstrate its capability for repeat sensing as a potential continuous monitoring tool for the disease biomarker.

The unsupervised domain-adaptive vehicle reidentification approach aims to transfer knowledge from a labeled source domain to an unlabeled target domain, however there are knowledge differences between the target domain and the source domain. To reduce domain differences, existing unsupervised domain-adaptive rerecognition methods generally require access to the source domain data to assist in re-training the target domain model. But for security reasons, in many cases, data between different domains cannot communicate. To this end, this paper proposes an unsupervised domain-adaptive vehicle re-identification method based on source-free knowledge transfer. First, by constructing a passive domain knowledge migration module, the target domain is consistent with the source domain model output to train a generator to generate the "source-like samples". Then, it can effectively reduce the model knowledge difference and improve the model generalization performance. According to the experiment and testing of VeRi776 and VehicleID, two mainstream public data sets in this field, the rank-k and mAP indexes obtained are both improved, and are suitable for object re-recognition tasks without source data.

The article reviews the current status of label-free integrated optical sensors focusing on the evolution over the years of their analytical performance. At first a short introduction to the evanescent wave optics is provided followed by detailed description of the main categories of label-free optical sensors including sensors based on surface plasmon resonance (SPR), grating coupler, photonic crystals, ring resonators and interferometric transducers. After a short reference to SPR techniques, including localized SPR, integrated optical sensors i.e., grating-couplers, interferometers, photonic crystals, microring resonators are reviewed. For each type of sensor, the detection principle is first provided followed by description of the different transducer configurations so far developed and their performance as biosensors. Finally, a short discussion about the current limitations and future perspectives of integrated label-free biosensors optical sensors is provided

Transition-metal-free synthesis of 4-pyrones via TfOH-promoted nucleophilic addition/cyclization of diynones and water has been developed. This transformation is simple, atom economical and environmentally benign, providing rapid and efficient access to substituted 4-pyrones.

According to Copenhagen interpretation, a quantum particle can exist in a superposition of all possible states, out of which only one state is observed when it is measured. Interestingly, it has been observed that interaction with the quantum particle during measurement can also affect the outcome of the state. A scheme for interaction free measurement was proposed by Elitzur and Vaidman [Found. Phys. 23, 987 (1993)], where they used Mach Zehnder interferometer to detect whether a bomb is alive or dead. In 25 % of the cases they were able to detect that the bomb is alive without exploding it. Here, we demonstrate the above experiment using quantum computing, which can be realized in a quantum computer designing quantum circuits on it. We explicate all the cases, including whether the bomb is alive or dead by proposing new quantum circuits and executing those in QISKit as provided by IBM Quantum Experience platform and verify the obtained results.

Colorectal cancer is the third most diagnosed cancer in males and in females, representing 8% of estimated new cases and the third cause of cancer-related death in both sexes, accounting for 9% of cancer deaths in men and 8% in women. About 20% of patients diagnosed with CRC present metastatic disease. Although lung metachronous or synchronous metastatic spread without other involved sites has been reported in only a small proportion of patients, considering that this tumor is frequently diagnosed, the clinical approach to CRC pulmonary metastases represents a major issue for thoracic surgeons and CRC oncologists. Among patients diagnosed with pulmonary metastases from CRC, about 9 – 12% are eligible for local treatments with radical intent, including surgical resection, SBRT and ablation therapy. Due to the lack of randomized controlled trials among different local strategies, there is no definitive evidence about the optimal approach, although surgical resection is considered the most effective therapeutic option in this clinical scenario. Oncological achievement of primary radical resection, the biology of primary tumor and metastatic sites, disease free interval and or progression free survival are independent prognostic factors which make it possible to define a cohort of patients which might significantly benefit from pulmonary metastasectomy.

Manipulating autophagy is a promising strategy for treating cancer as several autophagy inhibitors shown to induce autophagic cell death. One of these, autophagonizer (APZ), induces apoptosis-independent cell death by binding an unknown target via an unknown mechanism. To identify APZ targets we used a label-free drug affinity responsive target stability (DARTS) approach with a liquid chromatography/tandem mass spectrometry (LC-MS/MS) readout. Of 35 protein interactors, we identified Hsp70 as a key target protein of unmodified APZ in autophagy. Either APZ treatment or Hsp70 inhibition attenuates integrity of lysosomes, which leads to autophagic cell death exhibiting an excellent synergism with a clinical drug, temozolomide, in vitro, in vivo, and orthotropic glioma xenograft model. These findings demonstrate the potential of APZ to induce autophagic cell death and its development to combinational chemotherapeutic agent for glioma treatment. Collectively, our study demonstrated that APZ, a new autophagy inhibitor, can be used as a potent antitumor drug candidate to get over unassailable glioma and revealed a novel function of Hsp70 in lysosomal integrity regulation of autophagy.

The generation of high-quality wideband frequency sweeps presents a significant challenge, particularly in modern telecommunication, radar, and measurement systems where miniaturization is paramount. While phase-locked loops (PLLs) have become the dominant technique for signal generation, their application in broadband sweeps necessitates fractional-N operation. This, in turn, degrades phase noise and introduces unwanted spurs. This paper proposes a novel approach for broadband signal generation. By cascading two PLLs and utilizing a coaxial resonator, we achieve a high-performance oscillator that operates without the excessive fractional spurs, maintaining their level below -80 dBc across the entire frequency band. The prototype demonstrates non-degraded phase noise performance, reaching -102 dBc/Hz at 100 kHz offset and -121 dBc/Hz at 1 MHz offset for signal at 10 GHz. Despite significant frequency jumps, our design achieves lock times below 41 µs. These results, supported by theoretical analysis, validate the proposed method's effectiveness in generating low-noise broadband frequency sweeps, ideal for local oscillator applications.

The development of plant-based meat analogues has become a significant challenge for the food industry in recent years due to the increasing demand for sustainable and healthier proteins in the context of a global protein transition. Plant-based meat analogues imitate the visual, textural, and chemical properties of traditional meat products and are required to closely resemble meat to appeal to consumers. In addition, consumers demand natural, clean-label, and nutritional and healthy products. To address these challenges, the food industry must develop highly healthy, nutritious, and E-number-free meat analogue products. Understanding the functionality of each ingredient and its role in the food matrix is crucial to being a key player in the innovation of the meat analogues market. This review provides updated information on the primary ingredients utilized for the development of plant-based burger meat alternatives and their functionality. The key components of meat analogue burgers are outlined, including plant proteins, binding agents, fats and oils, flavorings, colorings, preservatives, fortificants, and clean-label considerations.

The mechanistic pathway of TEMPO/I₂-mediated oxidative cyclization of N,N-diaryl amino alcohols 1 is investigated in this study. Based on our direct empirical experiments, three key intermediates (the aminium radical cation 3, the α-aminoalkyl radical 4, and the iminium 5), four kind reactive species (radical TEMPO, cationic TEMPO, TEMPO-I and iodo radical) and three kind pathways (1. SET/PCET mechanism, 2. HAT/1,6-H transfer mechanism, 3. Ionic mechanism) were assumed. Under the assumption, nine free energy diagrams are acquired through DFT calculation. From the comparison of the solution phase free energy, some possibility can be excluded and then the chosen plausible mechanisms are concretized with the more stable intermediate 7.

Oriented object detection is a challenging task in scene text detection and remote sensing image analysis, which has attracted extensive attention in recent years with the development of deep learning. Currently, mainstream oriented object detectors are based on preset anchor boxes. This method increases the computational load of the network and cause a large amount of anchor box redundancy. To solve this problem, we propose anchor-free oriented object detection based on the Gaussian centerness(AOGC), a single-stage anchor-free detection method. Our method uses contextual attention FPN(CAFPN) to obtain the contextual information of the target. Then we design a label assignment method for oriented objects. Finally, we develop a Gaussian kernel-based centerness branch, which can effectively determine the significance of different anchors. AOGC achieves mAP of 74.30% on the DOTA-1.0 datasets and 89.80% on the HRSC2016 datasets, respectively. AOGC exhibits superior performance to other methods in oriented anchor-free object detection methods.

This scoping review investigated how consumers perceive and interpret serving size information on food packages. A search of seven databases (2010 to September 2017) was followed by title and abstract screening, with relevant articles assessed for eligibility in full-text. Fourteen studies met inclusion criteria, with relevant data extracted by one reviewer and checked for consistency by a second reviewer. Five studies reported poor understanding of nutrition facts labelling and portion size, with information to ‘benchmark’ serving size against reported as helpful in two studies. Consumer attitudes towards serving size labelling were measured in six studies and identified that serving size information was interpreted as indicative of nutrient intake regardless of portion size recommendations. Increased labelled serving sizes resulted in increased portion sizes in three studies, with three studies reporting the opposite or neutral effect for discretionary food portion sizes. The influence of labelled serving size on consumer attitudes and consumption is complex and sometimes counterintuitive. As labelled serving size can impact on consumption, any changes may result in unintended public health consequences. The effects of labelled serving size format changes should be tested carefully within experimental and ecological contexts and accompanied by tailored, comprehensive and serving size-specific food literacy initiatives.

Protein import into the endoplasmic reticulum (ER) is the first step in the biogenesis of about 10,000 different soluble and membrane proteins in humans. It involves co- or post-translational targeting of precursor polypeptides to the ER and their subsequent membrane insertion or translocation. So far, three pathways for ER targeting of precursor polypeptides plus four pathways for ER targeting of mRNAs were described. Typically, these pathways deliver their substrates to the Sec61 polypeptide-conducting channel in the ER membrane. Next, the precursor polypeptides are inserted into the ER membrane or translocated into the ER lumen, which may involve auxiliary translocation components, such as the TRAP and Sec62/Sec63 complexes, or auxiliary membrane protein insertases, such as EMC and the TMCO1 complex. Recently, the PEX19/PEX3-dependent pathway, which has a well-known function in targeting and inserting various peroxisomal membrane proteins into pre-existent peroxisomal membranes, was also found to act in targeting and, putatively, inserting monotopic hairpin proteins into the ER. These either remain in the ER as resident ER membrane proteins or are pinched off from the ER as components of new lipid droplets. Therefore, the question arose if this pathway may play a more general role in ER protein targeting, i.e. represents a fourth pathway for ER targeting of precursor polypeptides. Thus, we addressed the client spectrum of the PEX19/PEX3-dependent pathway in both PEX3-depleted HeLa cells and PEX3-deficient Zellweger patient fibroblasts by an established approach, which involves label-free quantitative mass spectrometry of the total proteome of depleted or deficient cells and differential protein abundance analysis. The negatively affected proteins included twelve peroxisomal proteins and two hairpin proteins of the ER, thus confirming two previously identified classes of putative PEX19/PEX3-clients in human cells. Interestingly, fourteen collagen-related proteins with signal peptides or N-terminal transmembrane helices and belonging to the secretory pathway were also negatively affected by PEX3-deficiency, which may suggest compromised collagen biogenesis as a hitherto unknown contributor to organ failures in the respective Zellweger patients.

This article investigates a proposed new mathematical model that considers the infected individuals using various rate coefficients such as transmission, progression, recovery and vaccination. The fact that the dynamic analysis is completely determined by the basic reproduction number is established. More specifically, local and global stabilities of the disease-free equilibrium and the endemic equilibrium are proved under certain parameter conditions when the basic reproduction number is below or above unity. A realistic computer simulation is performed for better understanding of the variations in trends of different compartments after the outbreak of the disease.

This study evaluates audiogenic epilepsy in Krushinsky-Molodkina rats using a wireless EEG system to overcome the limitations of traditional methods that restrict animal movement. Nine male KM rats, prone to audiogenic seizures, were implanted with electrodes in areas critical for seizure activity (inferior colliculus, ventrolateral periaqueductal gray, dorsal area of the secondary auditory cortex, and motor cortex). This setup allowed for the observation of seizures without movement restriction. Results showed that targeted neural intervention via electrode implantation reduced the intensity of convulsive seizures in half of the subjects, suggesting a potential therapeutic approach. The severity of seizures was influenced by the pre-phonostimulation EEG background activity in specific brain regions, identifying them as key in the genesis and generalization of seizures. Observations of dual generalized seizure waves and induced hyperkinesis challenge conventional epilepsy models and suggest new directions for research and therapy development.

In Lagrangian dynamics, the detection of coherent clusters can help understand the organization of transport by identifying regions with coherent trajectory patterns. Many clustering algorithms, however, rely on user-input parameters, requiring a priori knowledge about the flow and making the outcome subjective. Building on the conventional spectral clustering method of Hadjighasem et al (2016), a new parameter-free spectral clustering approach is developed that automatically identifies parameters and does not require any user-input choices. A noise-based metric for quantifying the coherence of the resulting coherent clusters is also introduced. The parameter-free spectral clustering is applied to two benchmark analytical flows, the Bickley Jet and the asymmetric Duffing oscillator, and to a realistic, numerically-generated oceanic coastal flow. In the latter case, the identified model-based clusters are tested using observed trajectories of real drifters. In all examples, our approach succeeded in performing the partition of the domain into coherent clusters with minimal inter-cluster similarity and maximum intra-cluster similarity. For the coastal flow, the resulting coherent clusters are qualitatively similar over the same phase of the tide on different days and even different years, whereas coherent clusters for the opposite tidal phase are qualitatively different.

Over the last several years, large-scale cancer genomics studies involving multi region, multi-sample sequencing indicate that most or at least many cancer patients may have one or more “clonal" mutations in their tumors. Clonal mutations are those that are present in all of a patient’s cancer cells. They can be identified via multiregion, multisample biopsies - or circulating tumor cells/cell-free DNA. Achilles Therapeutics is currently the only company targeting patient-specific, clonal mutations. They have opted to utilize an immunotherapy approach. However, I recently devised another approach for exploiting clonal mutations called “Oncolytic Vector Replication Contingent on Omnipresent Mutation Engagement” (OVERCOME). It is based on the identification of patient-specific, clonal mutations and targeting them using a bioengineered facultative intracellular bacterium. It would be initially non-replicating, but transiently regain the ability to replicate (and also transiently become hyper-virulent) upon mutation detection via molecular switches.

This paper addresses the input coupling problem for the shape memory alloy (SMA) actuated parallel platform with completely unknown nonlinear dynamics. The problem means that in a parallel platform with multiple SMA actuators acting together, the displacement of one of the actuators will simultaneously affect the remaining actuators to change. Due to the coupling problem and nonlinear characteristics of the SMA actuators, it is not easy to control the platform to achieve bi-directional swing with completely unknown nonlinear dynamics. Therefore, a model-free adaptive sliding mode control method is proposed to improve the control accuracy of the complex motion of the platform, avoiding the complex modeling process of the SMA actuated parallel platform. Based on the model-free adaptive control (MFAC) theory, a multiple input and multiple output (MIMO) dynamic linearized mathematical model of the parallel platform is established using the online input and output data of the system. Then, a sliding mode controller is designed based on the dynamic model. A rigorous theoretical analysis proves that the proposed model-free adaptive sliding mode controller is able to stably control the SMA actuated parallel platform, and its tracking error is uniformly ultimately bounded (UUB). Finally, experiments are conducted on the established SMA actuated parallel platform. The results show that the proposed model-free controller is feasible and effective, and can control the system well to achieve the complex motion of bi-directional swing.

Equality and incomparability multi-label ranking have not been introduced to learning before. This paper proposes new native ranker neural network to address the problem of multi-label ranking including incomparable preference orders using a new activation and error functions and new architecture. Preference Neural Network PNN solves the multi-label ranking problem, where labels may have indifference preference orders or subgroups which are equally ranked. PNN is a nondeep, multiple-value neuron, single middle layer and one or more output layers network. PNN uses a novel positive smooth staircase (PSS) or smooth staircase (SS) activation function and represents preference orders and Spearman ranking correlation as objective functions. It is introduced in two types, Type A is traditional NN architecture and Type B uses expanding architecture by introducing new type of hidden neuron has multiple activation function in middle layer and duplicated output layers to reinforce the ranking by increasing the number of weights. PNN accepts single data instance as inputs and output neurons represent the number of labels and output value represents the preference value. PNN is evaluated using a new preference mining data set that contains repeated label values which have not experimented on before. SS and PS speed-up the learning and PNN outperforms five previously proposed methods for strict label ranking in terms of accurate results with high computational efficiency.

We presented unusual case of double left ventricular false aneurysm complicating late presentation AMI successfully treated with the combination of urgent surgical drainage of tamponade, staged PCI of non-culprit lesion, preventive implantation of ICD-DR, guideline directed heart failure medical therapy and delayed but effective reconstructive operation.

Biochar (BC) is a carbonaceous material obtained by pyrolysis at 200−1000 °C in the limited presence of O2 of different vegetable and animal biomass feedstocks. BC has demonstrated great potential, mainly in environmental applications, due to its high sorption ability and persistent free radicals (PFRs) content. These characteristics enable BCs to carry out the direct and PFRs-mediated removal/degradation of environmental organic and inorganic contaminants. The types of PFRs possibly present in BC depend mainly on the pyrolysis temperature and the kind of pristine biomass. Since they also can cause ecological and human damage, a systematic evaluation of the environmental behavior, risks, or management techniques of BC-derived PFRs is urgent. PFRs generally could consist of a mixture of carbon- and oxygen-centered radicals, and of oxygenated carbon-centered radicals, depending on the pyrolytic conditions. Here, to promote a more productive and beneficial use of BC and related PFRs and stimulate further studies to make them environmentally safer and less hazardous to humans, we have first reviewed the most common methods used to produce BC, its main environmental applications, the primary mechanisms by which BC remove xenobiotics, as well as the reported mechanisms for PFRs formation in BCs. Secondly, we have discussed the PFRs environmental migration and transformation; we have reported the main PFRs-mediated applications of BCs to degrade inorganic and organic pollutants, the correlated environmental potential risks, and the possible strategies to limit them.

A theoretical account of development in mesocortical anatomy is derived from the free energy principle, operating in a neural field with both Hebbian and anti-Hebbian neural plasticity. An elementary structural unit is proposed, in which synaptic connections at mesoscale are arranged in paired patterns with mirror symmetry. Exchanges of synaptic flux in each pattern form coupled spatial eigenmodes, and the line of mirror reflection between the paired patterns operates as a Markov blanket, so that prediction errors in exchanges between the pairs are minimized. The theoretical analysis is then compared to the outcomes from a biological model of cortical neurodevelopment, in which neuron precursors are selected by apoptosis for cell body and synaptic connections maximizing synchrony and also minimizing axonal length. It is shown that this model results in patterns of connection with the anticipated mirror symmetries, at micro-, meso- and inter-arial scales, among lateral connections, and in cortical depth, explaining the spatial organization and functional significance of neuron response preferences, and compatible with features of both columnar and noncolumnar cortex. Multi-way interactions of mirrored representations provide a preliminary anatomically realistic model of cortical information processing.

Previous high throughput screening studies indicated trans-eQTLs tend to be tissue specific. In this study, I probed if this feature can be used to identify tissue-specific gene regulatory networks. eQTL data (P<5e-8) for 16,259 genes were identified and their summary association statistics were obtained from the eQTLGene database. Next, eQTLs that display both cis and trans regulatory effects were selected and the association between their corresponding genes were examined using Mendelian randomization. A total of 169 genes that exerted trans-regulatory impacts on 692 genes were identified. 90% of the genes (N=749) aggregated into a gene regulatory network significantly enriched in hemo-immune processes. The robustness of finding was confirmed through simulation. The identified network displayed the scale-free topology. This provided the reason to examine the association of the network’s hub genes with the phenome. The outcome of analyses revealed GSDMB and ORMDL3 impact several disorders of immune origin and ALDH2 overexpression contributes to obesity. This study reports trans-eQTLs can be used to identify tissue-specific gene regulatory networks and describes a workflow to achieve this purpose. The network identified in this study showed scale-free topology indicating the hub genes of a GRN could be targeted to prevent disease outcomes.

Aluminum wire is a common material for wire bonding due to its resistance to oxidation and low price. It does not melt when becoming a free air ball (FAB) during the electronic flame-off (EFO) process with wettability, and is applied by wedge bonding. This study used 20μm Zn-Coated Al-0.5wt.%Si (ZAS) wires to improve the FAB shape after the EFO process, while maintaining stability of the mechanical properties, including the interface bonding strength and hardness. In order to test circuit stability after ball bonding, the current-tensile test was performed. During the experiment, it was found that 80nm ZAS with wire bonding has lower resistance and higher fusing current. For the bias tensile test, the thicker Zn film diffused into the Al-Si matrix easily, after which the strength was reduced. The ball-bond interfaces had no change in their condition before and after the bias. Accordingly, ZAS could be a promising candidate for ball bonding in the future.

Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 x 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 x 2.633 Gy (41.6 Gy10) or 18 x 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score adjusted Cox regression) to a historical control group (N=266) receiving 10 x 3.0 Gy (32.5 Gy10). In the phase 2-cohort, 50 (of 62 planned) patients were evaluable for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 x 2.633 Gy or 18 x 2.333 Gy was well tolerated and appeared superior to 10 x 3.0 Gy.

As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal (n=3) and rectal cancer (n=2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the DIDA-Seq error-correction method, we serially interrogated plasma cell-free DNA at 28-41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted.

Modern organic synthesis is majorly focused on developing environmentally benign synthetic protocols by employing green chemistry principles. Accordingly, in our recent research work, we herein report the use of modified supramolecular host cyclodextrin as an effective solid based green catalyst for accessing structurally diverse and medicinally relevant pyrimidone architectures. The catalyst and the synthesized compounds 4 (a-r) were characterized using FT-IR, NMR and GC-Mass spectroscopy. Major highlights of the reported work include: atom economical process, extremely milder reaction conditions, operational simplicity, high isolated yields, and excellent catalyst turnover number. The molecular docking studies suggest that the compound 4n has the hydrogen bonding, hydrophobic and π-pair interactions with the active site of active sites of CXT M 15 receptor.

Abstract: High step-up voltage gain nonisolated DC-DC converter have attracted much attention in photovoltaic, fuel cells and other renewable energy system applications. In this paper, by combining input current ripple-free boost cell with coupled-inductor voltage-doubler cell, an input current ripple-free high voltage gain nonisolated converter is proposed. In addition, passive lossless clamp circuit is adopted to recycle the leakage inductor energy and to reduce the voltage spike across the power switch. By utilizing voltage-doubler cell consisting of diode and capacitor, the voltage stress of switch is further reduced and the resonance between the leakage inductor and the stray capacitor of the output diode is eliminated. A low switch-on-resistance low-voltage-rated MOSFET can therefore be employed to reduce the conduction loss and cost. The reverse recovery loss of output diode is reduced, and the efficiency of converter can be improved. Furthermore, the proposed converter can achieve nearly zero input current-ripple and make the design of electromagnetic interference (EMI) filter easy. Steady state analysis and operation mode of the converter is performed. Finally, experimental results are presented to verify the analysis results of the proposed converter.

We study Einstein's gravity coupled to nonlinear electrodynamics with two parameters in Anti-de Sitter spacetime. Magnetically charged black holes in an extended phase space is investigated. We obtain the mass and metric functions, their asymptotic and corrections to the Reissner--Nordstr\"{o}m metric function when the cosmological constant vanishes. The first law of black hole thermodynamics in extended phase space is formulated and the magnetic potential and the thermodynamic conjugate to the coupling are obtained. We proved the generalized Smarr relation. The heat capacity and the Gibbs free energy are computed and phase transitions are studied. It was shown that the electric field of charged objects at the origin and electrostatic self-energy are finite within the nonlinear electrodynamics proposed.

Accurate pathogenic detection in wastewater is critical for safeguarding public health and the environment. However, the presence of free nucleic acids in wastewater samples poses significant challenges to molecular detection accuracy. This comprehensive review explores the current status and future potential of pretreatment methods to remove free nucleic acids from wastewater samples. The study contributes a comprehensive analysis of the mechanisms, strengths, and limitations of various pretreatment approaches, including physical, chemical, and enzymatic processes. The effect of various factors on the removal efficiency of these pretreatment methods is also discussed. This review enhances our comprehension of pretreatment techniques and their vital role in achieving precise pathogenic detection in complex wastewater matrices. Furthermore, it outlines future perspectives and developments for improving the speed and effectiveness of pathogenic detection, contributing significantly to disease surveillance, early warning systems, and environmental protection.

Hard tissue apposition along the root canal walls is a slow, normally occurring physiological aging process. In response to tooth wear, local deposition of hard tissue may also occur in the pulp at a slow pace. Sometimes, the rate of hard tissue deposition acceleration may seem to be uncontrolled after dental trauma, autotransplantation, and orthodontic therapy, leading to rapid partial or total obliteration of the root canal space. This situation is called calcific metamorphosis (CM) or pulp canal obliteration (PCO). Although the incidence of pulpal necrosis in these teeth is believed to be infrequent, conventional endodontic therapy in severely calcified canals poses extreme difficulties and a higher risk for procedural accidents. This article aims to review the available approaches for the predictable negotiation of calcified canals and to introduce the buckling resistance activation test (BRAT) technique.

In this paper we investigate some properties of square-free numbers. In particular, we study a function that counts the number of square-free numbers no larger than the given number n. We show that this function has asymptotics consistent with the predictions of the Riemann hypothesis and use this to obtain new and better estimates of the density of square-free numbers. Finally, we present a well-known generalization of the concept of a square-free number to monoids and research on square-free factorizations.

Cell free systems are a widely used research tool in systems and synthetic biology and a promising platform for manufacturing of proteins and chemicals. In the past, cell free biology was primarily used to better understand fundamental biochemical processes. Notably, E. coli cell free extracts were used in the 1960s to decipher the sequencing of the genetic code. Since then, the transcription and translation capabilities of cell free systems have been repeatedly optimized to improve energy efficiency and protein yield. Today, cell free systems, in combination with the rise of synthetic biology, have taken on a new role as a promising technology for just in time manufacturing of therapeutically important biologics and high-value small molecules. They have also been implemented in an industrial scale for the production of antibodies and cytokines. In this review, we discuss the evolution of cell free systems, advancements in cell free protein synthesis, and cell free metabolic engineering, and conclude with discussing the importance and feasibility of mathematical modeling in cell free systems.

As the amount of sensor data made available online increases, it becomes more difficult for users to identify useful datasets. Semantic web technologies improve discovery with meaningful ontologies, but the decision of suitability remains with the users. The GEO label provides a visual summary of the standardised metadata to aid users in this process. This work presents novel rules for deriving the information for the GEO label's multiple facets, such as user feedback or quality information, based on the Semantic Sensor Network Ontology and related ontologies. It enhances an existing implementation of the GEO label API to generate labels for resources of the Semantic Sensor Web. The prototype is deployed to serverless cloud infrastructures. We find that serverless GEO label generation is capable of handling two evaluation scenarios for concurrent users and burst generation. More real-world semantic sensor descriptions and an integration into large scale discovery platforms are needed to develop the presented solutions further.

The present study aims to develop an efficient numerical method for computing the diffraction and radiation of water waves with horizontal long cylindrical structures, such as floating breakwaters. A higher-order scheme is used to discretize geometry of the structure as well as the relevant physical quantities. As the kernel of this method, Wehausen’s free-surface Green function is calculated by a newly-developed Gauss-Kronrod adaptive quadrature algorithm after elimination of its Cauchy-type singularities. To improve computational efficiency, a Chebyshev approximation approach is applied to a fast calculation of the Green function that needs evaluation thousands of times. In addition, OpenMP parallel technique is used to the formation of influence coefficient matrix, which significantly reduces CPU time. Finally, computations are performed on wave exciting forces and hydrodynamic coefficients for the long cylindrical structures, either floating or submerged. Comparison with other numerical and analytical methods demonstrates good performance of the present method.

Surface initiated atom transfer radical polymerization (SI-ATRP) is one of the most versatile technique to modify the surface properties of material. Recent developed metal free SI-ATRP makes such technique more widely applicable. Herein photo-induced metal-free SI-ATRP of methacrylates, such as methyl methacrylate, N-isopropanyl acrylamide, and N,N- dimethylaminoethyl methacrylate, on the surface of SBA-15 was reported to fabricate organic-inorganic hybrid materials. SBA-15 based polymeric composite with adjustable graft ratio was obtained. The structure evolution during the SI-ATRP modification of SBA-15 was monitored and verified by FT-IR, XPS, TGA, BET, and TEM. The obtained polymeric composite showed enhanced adsorption ability for the model compound toluene in aqueous. This procedure provides a low cost, ready availability, and facile modification way to synthesize the polymeric composites without the contamination of metal.

Front-of-pack labelling (FOPL) systems, such as the Nutri-Score, play a crucial role in promoting healthy diets and raising consumer awareness. Our study aimed to gather the opinions of Polish experts on the Nutri-Score and its relation to an ideal information system. We conducted a Poland-wide expert opinion study using a cross-sectional design survey with 75 participants, who had an average of 18±13 years of experience and were mainly employed at medical and agricultural universities. The data were collected with CAWI method. The results showed that the most important features of an FOPL system were clarity, simplicity, consistency with healthy eating recommendations, and the ability to objectively compare products within the same group. While more than half of the respondents believed that the Nutri-Score provides an overall assessment of a product’s nutritional value and facilitates quick purchasing decisions, it falls short in helping consumers compose a balanced diet and cannot be applied to all product groups. The experts also expressed concerns about the system’s ability to account for a product’s degree of processing, full nutritional value and carbon footprint. In conclusion, Poland’s current labelling system needs expansion, but the Nutri-Score requires significant and deep changes and validation against national guidelines and expert expectations before implementation.

Reactive oxygen species (ROS) play a pivotal role in cellular function, and their overproduction contributes to oxidative stress, fatigue, aging, and diseases. To counteract these effects, incorpo-rating antioxidant-rich nutrients is recommended. Functional waters, including electrolyzed hydrogen water (EHW), are gaining attention for potential antioxidant effects through daily in-take. This study employs aquaphotomics and near-infrared spectroscopy (NIRS) to elucidate the molecular mechanisms behind the antioxidant activity of EHW. Previous investigation reported a 100% loss in antioxidant functionality through autoclaving, and a 40% decrease with hydrogen gas removal, prompting the current investigation into the mechanisms of antioxidant effects and especially the role of water molecular structure in it. Aquaphotomics analysis of near infrared (NIR) spectral data revealed that the primary characteristic of EHW associated with anti-radical function is presence of water solvation shells. Autoclaving and degassing led to loss of these water molecular species and a significant increase in free water molecules. The study suggests that water shells (solvation shells) in EHW play a crucial role in neutralizing ROS, although the specific ions or nanoparticles responsible for creating these shells remain unidentified. This concept aligns well with existing proposals of the crucial role of water solvation shells in ROS neutralization.

Raw materials used for producing concrete, such as sand and gravel, are in short supply worldwide. It has been reported that the production of cement, one of the main constituents of concrete, results in the emission of a large amount of CO₂, accounting for 8% of total global CO₂ emissions. In this study, we developed a method to produce a construction material using only sand as the solid raw material. By utilizing a technique to produce organic silicon material from sand, we placed sand, alcohol, and catalyst in a closed vessel and heated it to 240 °C. After 24 h, the sand particles were bonded to each other, and a hardened body was formed. A tradeoff in production conditions, such as temperature, time, and the amount of sand, was confirmed.

This study examines the Willingness-To-Pay (WTP) of consumers and the determinants of eco-labeling for the organic cocoa powder produced in the Dong Nai UNESCO Biosphere Reserve (DNBR), Southern Vietnam. Eco-labels are designed according to Tiers of eco-labeling for biosphere reserves (BR) introduced by UNESCO include BR Destination (Tier 1), BR Quality Label (Tier 2), and Professional Certification Label (Tier 3). Questionnaires are delivered to 203 customers in the DNBR and nearby places, such as Dong Nai and HCMC. This study employs a hybrid approach using descriptive statistics, ANOVA test, and Partial Least Squares Structural Equation Model (PLS-SEM). The results indicate that gender and educational level have a positive effect on consumers' preferences. Customers are willing to pay more for cocoa powder with an eco-label than one with an organic label. Perceived food safety and product knowledge lower customers’ WTP, whereas agricultural environment and pricing concerns increase it. Tier 2 is suggested for labeling cocoa powder in the DNBR. The DNBR Management Board, together with the federal and provincial governments, should all follow a similar certification process. Increased eco-label awareness is crucial for the future of environmentally responsible shopping and responsible business practices.

Development of methods and algorithms to predict the effect of mutations on protein stability, protein-protein, and protein-DNA/RNA binding is necessitated by the needs of protein engineering and for understanding the molecular mechanism of disease-causing variants. The vast majority of the leading methods are either methods with adjustable parameters or machine learning algorithms, both requiring a database of experimentally measured folding and binding free energy changes. These databases are collections of experimental data taken from scientific investigations typically aimed at probing the role of particular residue on the above-mentioned thermodynamics characteristics, i.e., the mutations are not introduced at random and do not necessarily represent mutations originating from single nucleotide variant (SNV). Thus, the reported performance of the leading algorithms assessed on these databases or other limited cases, may not be applicable for predicting the effect of SNVs seen in the human population. Indeed, we demonstrate that the SNVs and non-SNVs are not equally presented in the corresponding databases and the distribution of the free energy changes are not the same. Furthermore, the Pearson correlation coefficients (PCCs) obtained on cases involving SNVs are less impressive than for non-SNVs, indicating that caution should be used in applying them to reveal the effect of human SNVs. All methods are found to underestimate the energy changes by roughly a factor of 2.

Synergy, emerges from synchronized reciprocal positive feedback loops between a network of diverse actors. For this process to proceed, compatible information from different sources synchronically coordinates the actions of the actors resulting in a nonlinear increase in the useful work or potential energy the system can manage. In contrast noise is produced when incompatible information is mixed. This synergy produced from the coordination of different agents achieves non-linear gains in free energy and in information (negentropy) that are greater than the sum of the parts. The final product of new synergies is an increase in individual autonomy of an organism that achieves increased emancipation from the environment with increases in productivity, efficiency, capacity for flexibility, self-regulation and self-control of behavior through a synchronized division of ever more specialized labor. Examples that provide quantitative data for this phenomenon are presented. Results show that increases in free energy density require decreases in entropy density. This is proposed as a law of thermodynamics.

This paper explores the suppression of ideas within academic scholarship by academics, either by self-suppression or because of the efforts of other academics. Legal, moral, and social issues distinguishing freedom of speech, freedom of inquiry, and academic freedom are reviewed. How these freedoms and protections can come into tension is then explored by an analysis of denunciation mobs who exercise their legal free speech rights to call for punishing scholars who express ideas they disapprove of and condemn. When successful, these efforts, which constitute legally protected speech, will suppress certain ideas. Real-world examples over the past five years of academics who have been sanctioned or terminated for scholarship targeted by a denunciation mob are then explored.

The antioxidant activity of molecules constitutes an important factor for the regulation of redox homeostasis and reduction of oxidative stress. Cells affected by oxidative stress can undergo genetic alteration, causing structural changes and promoting the onset of chronic diseases, such as cancer. The in silico study performed here was developed to evaluate the antioxidant potential of two molecules, ZINC08706191 (Z91) and ZINC08992920 (Z20), with recognized epithelial anticancer potential. Molecular docking, chemical-quantum calculations and Pearson's correlation were performed. The Z91 and Z20 molecules showed lower binding free energy (ΔG) values for the receptor-ligand interaction than the reference molecules (caffeine – CAF and ascorbic acid – AA), and better results for values of molecular descriptors correlated with ΔG, resulting in a decrease of ΔG. Strong correlations were observed between ΔG values for the five receptors evaluated and ΔG values of the potential epithelial anticancer activity available in literature. These results attest to the significant antioxidant potential of the Z91 and Z20 molecules and their strong relation with the potential epithelial anticancer activity and may be indicated for further analysis in relation to the control of oxidative stress and epithelial anticancer activity.

This study aimed to investigate the coloring ingredient potential of liver homogenates that form Zn-protoporphyrin (ZnPP), a natural red pigment, after anaerobic incubation. The liver homogenates were used to develop nitrite-free sterile pork liver pâtés. These liver homogenates can be applied in the formulation of pâtés directly or as a centrifuged insoluble fraction that is highly concentrated in ZnPP. Both the whole homogenate and its insoluble fraction were adjusted to pH 7.5 before their use in the formulation of pâtés with and without antioxidant (0.5% ascorbate plus 0.1% tocopherol) addition. Pâtés formulated with the whole homogenate showed color and texture characteristics similar to those of the positive control with nitrite. However, high levels of the insoluble fraction also led to pâtés with improved color characteristics but with a two-fold softened texture. Therefore, the form and amount of ZnPP added played a role in the final appearance of the product. The ZnPP pigment was more stable than heme was in the sterilization treatment, and antioxidant addition proved to be unnecessary. The ZnPP-rich ingredients allowed for the preparation of nitrite-free cooked liver pâtés with a stable red color and could be potentially applied in other uncured cooked meat products.

Like traditional single label learning, multi-label learning is also faced with the problem of dimensional disaster.Feature selection is an effective technique for dimensionality reduction and learning efficiency improvement of high-dimensional data. In this paper, Logistic regression, manifold learning and sparse regularization were combined to construct a joint framework for multi-label feature selection (LMFS). Firstly, the sparsity of the eigenweight matrix is constrained by the $L_{2,1}$-norm. Secondly, the feature manifold and label manifold can constrain the feature weight matrix to make it fit the data information and label information better. An iterative updating algorithm is designed and the convergence of the algorithm is proved.Finally, the LMFS algorithm is compared with DRMFS, SCLS and other algorithms on eight classical multi-label data sets. The experimental results show the effectiveness of LMFS algorithm.

Prostate cancer (PC) is the second most diagnosed cancer among men. It was observed that early diagnosis of disease is highly beneficial for survival of cancer patients. Therefore, extension and increasing quality of life of PC patients can be achieved by broadening the Cancer Screening programs that are aimed at the identification of cancer manifestation in patients at earlier stages before they demonstrate well-understood signs of the disease. Therefore, there is an urgent need in standard, sensitive, robust, and commonly available screening and diagnosis tools for identification of early signs of cancer pathologies. In this respect, “Holy Grail” of cancer researchers and bioengineers for decades have been molecular sensing probes that would allow diagnosis, prognosis, and monitoring of cancer diseases by their interaction with cell-secreted and cellassociated PC biomarkers, e.g. PSA and PSMA correspondinly. At present, most PSA tests are performed at centralized laboratories using high throughput Total PSA immune analyzers which are suitable for dedicated laboratories and are not readily available for the broad health screening. Therefore, the current trend in detection of PC is developments of the portable biosensors for mobile laboratories and individual use. Phage display since its conception by George Smith in 1985 has emerged as a premier tool in molecular biology with widespread applications. This review describes how the paradigm of molecular evolution and phage display revolutionized the methods of early diagnosis and monitoring of PC.

Liquid biopsies are an integral part of the diagnosis of cancer. Here, we have extended previous validation studies of a new targeted NGS panel to include the detection of copy number amplifications (CNAs), fusions, and exon skipping variants. Detection of these gene classes included specimens from clinical and healthy donors and cell lines (fusions: ROS1, EML4-ALK, NTRK1), (exon skipping: MET exon 14), and (CNAs: HER2, CDK6, EGFR, MYC and MET). The limit of detection (LOD) for fusion/skipping was 42 copies (QC threshold = 3 copies) and was verified using 3 additional fusion/skipping variants. LOD for CNAs was 1.40-fold-change (QC threshold = 1.15-fold change) and was verified with 3 additional CNAs. In precision studies, all fusion/skipping variants were detected in all runs and all days of testing (n=18/18; 100%); average CV for repeatability was 20.5% (range 8.7% - 34.8%), and for reproducibility was 20.8% (range 15.7% - 30.5%). For CNAs, 28/29 (96.6%) copy gains were detected. For CNAs, average CV of 1.85% (range 0% to 5.49%) for repeatability and 6.59% (range 1.65% to 9.22%) for reproducibility. The test panel meets the criteria for being highly sensitive and specific and extends its utility for the detection of clinically relevant variants in cancer.

It has been recognized for some time that even for perfect conductors, the interaction Casimir entropy, due to quantum/thermal fluctuations, can be negative. This result was not considered problematic because it was thought that the self-entropies of the bodies would cancel this negative interaction entropy, yielding a total entropy that was positive. In fact, this cancellation seems not to occur. The positive self entropy of a perfectly conducting sphere does indeed just cancel the negative interaction entropy of a system consisting of a perfectly conducting sphere and plate, but a model with weaker coupling in general possesses a regime where negative self-entropy appears. The physical meaning of this surprising result remains obscure. In this paper we re-examine these issues, using improved physical and mathematical techniques, partly based on the Abel-Plana formula, and present numerical results for arbitrary temperatures and couplings, which exhibit the same remarkable features.

In cancer, the lymphatic system is hijacked by tumor cells to escape from primary tumor and to metastasize to the sentinel lymph nodes. Tumor lymphangiogenesis is stimulated by the vascular endothelial growth factors-C (VEGFC) after binding to its receptor VEGFR-3. However, how VEGFC cooperates with other molecules to promote lymphatic neovessels growth is not fully determined. Here, we found that tumor lymphangiogenesis developed in tumoral lesions and in their surrounding adipose tissue (AT). Interestingly, lymphatic vessel density correlated with an increase of circulating free fatty acids (FFA) in the lymph from tumor-bearing mice. We found that adipocyte-released FFA are uploaded by lymphatic endothelial cells (LEC) to stimulate their sprouting. Lipidomic analysis identified the monounsaturated oleic acid (OA) as the major circulating FFA in the lymph in tumoral context. OA transporters FATP-3, -6 and CD36 were only upregulated on LEC in the presence of VEGFC showing a collaborative effect of these molecules. OA released from adipocytes is taken up by LECs to stimulate the fatty acid β-oxidation, leading to increase adipose tissue lymphangiogenesis. Our results provide new insights on the dialogue between tumors and adipocytes via the lymphatic system and identify a key role for adipocyte-derived FFA in the promotion of lymphangiogenesis, revealing novel therapeutic opportunities for inhibitors of lymphangiogenesis in cancer.

Facebook (FB) is the most popular online networking platform. There are several FB pages dedicated to spreading awareness about the Celiac disease (CD). To get the latest information, a huge number of CD patients follow Celiac disease Facebook (CD-FB) pages. Such pages frequently post beneficial information. However, very less is known if they provide appropriate information to CD patients. We conducted this study to know if CD-FB pages spread misleading information to CD patients. CD-FB pages from three celiac-influenced countries were explored using the FB platform and Google search engine. From October 2021 to April 2022, a total of 147 CD-FB, Italy (n=63), the USA (n=46), and India (n=38), were found eligible. Of them, 13% of pages (followers Mean±SD; Italy 2478±2011; USA 12635±12486; India 667±313) shared misleading information, particularly about gluten-free ingredients, and treatment of CD. In total,16% of CD-FB pages discussed alternative treatments option. Surprisingly, 7% of pages (followers Mean±SD; USA 23800±10465; India 628±333) supported alternative treatments for CD. CD-FB pages are useful for disseminating celiac-related information. While most of such pages provide useful information, a few pages sometimes contain misleading information. CD patients must consult their treating unit before following any uncertain information posted on CD-FB pages.

Alzheimer’s disease is the most common neurodegenerative disease and affects persons of all races, ethnic groups, and sexes. The disease is characterized by neuronal loss leading to cognitive decline and memory loss. There is no cure and the effectiveness of existing treatments is limited and depends on the time of diagnosis. The long prodromal period, during which patients’ ability to live a normal life is not affected despite neuronal loss, often leads to a delayed diagnosis because it can be mistaken for normal aging of the brain. In order to make a substantial impact on AD patients, early diagnosis may provide a greater therapeutic window for future therapies to slow AD-associated neurodegeneration. Current gold standards for disease detection include magnetic resonance imaging and positron emission tomography scans, which visualize amyloid β and phosphorylated tau depositions and aggregates. Liquid biopsies, already an active field of research in precision oncology, are hypothesized to provide early disease detection through minimally or non-invasive sample collection techniques. Liquid biopsies in Alzheimer’s disease have been studied in cerebrospinal fluid, blood, ocular, oral, and olfactory fluids. However, most of the focus has been on blood and cerebrospinal fluid due to biomarker specificity and sensitivity attributed to the effects of the blood-brain barrier and inter-laboratory variation during sample collection. Many studies have identified amyloid β and phosphorylated tau levels as putative biomarkers, however, advances in next-generation sequencing-based liquid biopsy methods have led to significant interest in identifying nucleic acids species associated with Alzheimer’s disease from liquid tissues. Differences in cell-free RNAs and DNAs have been described as potential biomarkers for AD and hold the potential to affect disease diagnosis, treatment, and future research avenues.

Wastewater contaminated with antibiotics is a major environmental challenge. We developed here the green synthesis of bio-graphenes by using natural precursors (Xanthan, Chitosan, Boswellia, Tragacanth). The use of these precursors can act as templates to create 3D doped graphene structures with special morphology. Also, this method is a simple method for in-situ synthesis of doped graphenes. The elements present in the natural polymers (N) and other elements in the natural composition (P, S) are easily placed in the graphene structure and improve the catalytic activity due to the structural defects, surface charges, increased electron transfers, and the high absorption. In this mechanism, O2 dissolved in water absorbs onto the positive charged C in doped graphenes to create oxygenated radicals, which enables the degradation of antibiotic molecules. Light irradiation increases the amounts of radicals and rate of antibiotic removal. The results have shown that the hollow cubic Chitosan-derived graphene has shown the best performance due to the doping of N, S, and P. The Boswellia-derived grapheme shows the highest surface area, but lower catalytic performance, which indicates the more effective role of doping in the catalytic activity. The effect of oxygen and light were also studied to accelerate the degradation process.

Despite the uptake of tobacco smoking declining in the UK, smoking is still the leading cause of preventable poor health and premature death. While improved approaches to smoking cessation are necessary, encouraging and assisting smokers to switch by using substantially less toxic non-tobacco nicotine products may be a possible option. To date few studies have investigated the rates of smoking cessation and smoking reduction associated with the free provision of electronic-cigarettes (e-cigarette) to smokers. In this study the Blu Pro e-cigarette was given to smokers for use in place of tobacco for 90 days. The rates of smoking abstinence and daily smoking patterns were assessed at baseline 30 days, 60 days and 90 days. The response rate was 87%. After 90 days, the complete abstinence rate was 36.5% from 0% at baseline. Frequency of daily smoking reduced from 88.7% to 17.5% (P<0.001) and median consumption of cigarettes/day from 15 to 5 (P<0.001). Median days per month participants smoked also dropped from 30 to 13 after 90-days (P<0.001). On the basis of these results there may be value in smoking cessation services and other services ensuring that smokers are provided with e-cigarettes at zero or minimal costs for at least a short period of time.

Considering Games with the broad definition proposed by Juul (Juul, 2010), consequences outside of the magic circle can be negotiated. This definition opens up the possibility to define serious games, games developed with an utilitarian goal in mind, in addition to fun. The entertaining and utilitarian objectives may however be contradictory, leading serious games to be, more often than not, less than optimal in at least one of the two dimensions. Another way to play with the boundaries of games is to consider pervasive games, which include alternate reality games, and crossmedia games (Montola, 2005). We question here the limit between game, play and toy in the context of a mixed reality serious game. ‘Pangu’ is a game designed for bachelor students, with biochemistry as the utilitarian objective, and the origin of life as a game theme. The students are asked to play the game on their smartphone, which in turn ask them to build molecules with a tangible balls-and-sticks model typically used in chemistry classes. Pictures taken from the models allow users to ‘scan’ these models and progress in the game. The use of the game was observed in four opportunities. An unanticipated observation is that, in addition to expected behaviors, some students used briefly the models like a toy rather than in the context of the game. It is therefore tempting to speculate that the pervasive nature of the game is blurring the game/non game boundary and, in the context of this serious game, opens a door for fun.

Primary importance is devoted to Fault Detection and Diagnosis (FDI) of electrical machine and drive systems in modern industrial automation. The widespread use of Machine Learning techniques has made it possible to replace traditional motor fault detection techniques with more efficient solutions that are capable of early fault recognition by using large amounts of sensory data. However, the detection of concurrent failures is still a challenge in the presence of disturbing noises or when the multiple faults cause overlapping features. The contribution of this work is to propose a novel methodology using multi-label classification method for simultaneously diagnosing multiple faults and evaluating the fault severity under noisy conditions. Performance of various multi-label classification models are compared. Current and vibration signals are acquired under normal and fault conditions. The applicability of the proposed method is experimentally validated under diverse fault conditions such as unbalance and misalignment.

Consciousness is usually perceived as a state of being aware of one’s environment as well as self. Despite its omnipresence in our life, understanding this concept is challenging. This has given rise to several theories attempting to explain the nature of consciousness, as well as hard and soft problems of consciousness. In fact, the boundaries of consciousness defined by these theories are a topic of continued discussion, particularly in light of the recent advances in artificial intelligence (AI). Some of these theories consider consciousness as a simple integration of information while others purport the need for an agency in the process of integration for an entity to be considered conscious. Some theories consider consciousness as a graded entity and some equate consciousness with content of awareness. In this work, major theories of consciousness are reviewed and compared, focusing on awareness, attention, and sense of self. These findings are interpreted in relation to AI in order to ascertain what makes AI distinct from natural intelligence.

Consciousness is usually interpreted as a state of being aware of one’s environment as well as self, while awareness is understood as knowledge of something. Despite their semantic differences, in philosophy, these terms are often used interchangeably, as is the case of the hard problem of consciousness proposed by Chalmers, which in fact is the hard problem of awareness. Trilogy paradigm of consciousness (or simply “trilogy”) offers a new paradigm where consciousness is the result of a unique interaction between awareness and the decision-making process. By conferring the input of awareness to the decision-making process, a new mental function of awareness-based choice selection (ABCS) or true free will emerges. Likewise, application of the power of decision-making to the process of awareness gives rise to discretionary selection of information for awareness (DSIA) or intentional attention. The intertwined actions of ABCS and DSIA comprise “I” which is the faculty of our consciousness and is what sets natural intelligence (NI) apart from artificial intelligence (AI). Based on trilogy, mind is an unconscious compilation of all mental function excluding ABCS and DSIA that are the essence of consciousness. As humans, we are a union of “I,” our minds, and our bodies.

Lead halide perovskite has become a promising candidate for high-performance photodetector (PD) applications due to its attractive optical and electrical properties such as high optical absorption coefficient, high carrier mobility, and long carrier diffusion length. However, the presence of highly toxic lead in these devices has limited their practical applications and even hindered their progress toward commercialization. Therefore, the scientific community has been committed to searching for low-toxic and stable perovskite-type alternative materials. Lead-free double perovskite materials, which are still in the preliminary stage of exploration, have achieved inspiring results in recent years. In this review, we mainly focused on two types of lead-free double perovskite based on different Pb substitution strategies, including A2M(I)M(Ⅲ)X6 and A2M(IV)X6. We reviewed the research progress and prospects of lead-free double perovskite photodetectors in the past three years. And more importantly, from the perspective of optimizing inherent defects in materials and improving device performance, we proposed some feasible pathways and made an encouraging perspective for the future development of lead-free double perovskite photodetectors.

Endometriosis occurs when endometrial-like tissue grows outside the uterine cavity, leading to pelvic pain, infertility, and increased risk of ovarian cancer. The present study describes the optimization and characterization of cellular spheroids as building blocks for Kenzan scaffold-free method biofabrication and proof-of-concept models of endometriosis and the endometriotic microenvironment. The spheroid building blocks must be a specific diameter (~500 m), compact, round, and smooth to withstand Kenzan biofabrication. Under optimized spheroid conditions for biofabrication, the endometriotic epithelial-like cell line, 12Z, expressed high levels of estrogen-related genes and secreted high amounts of endometriotic inflammatory factors that were independent of TNF stimulation. Heterotypic spheroids, composed of 12Z and T-HESC, an immortalized endometrial stromal cell line, self-assembled into a biologically relevant pattern, consisting of epithelial cells on the outside of the spheroids and stromal cells in the core. 12Z spheroids were biofabricated into large three-dimensional constructs alone, with HEYA8 spheroids, or as heterotypic spheroids with T-HESC. These three-dimensional biofabricated constructs containing multiple monotypic or heterotypic spheroids represent the first scaffold-free biofabricated in vitro models of endometriosis and the endometriotic microenvironment. These efficient and innovative models will allow us to study the complex interactions of multiple cell types within a biologically relevant microenvironment.

In Philadelphia chromosome positive B-cell (Ph+) acute lymphoblastic leukemia (LLA), growing evidence has ac-cumulated about the efficacy of low-intensity and chemo-free regimens. Our objective was to analyze all recent trials evaluating these treatments and to compare them in terms of efficacy. We applied the Shiny method, an artificial intelligence technique, to analyze Kaplan-Meier curves and reconstruct patient-level data. Reconstructed patient data were then evaluated through standard survival statistics and subjected to indirect head-to-head treatment comparisons. The endpoint was progression-free survival (PFS). Based on 848 reconstructed patients, 9 trials were analyzed. The survival data from these trials were pooled into three types of treatments: i) treatments based on ty-rosine kinase inhibitors (TKIs) combined with reduced-intensity chemotherapy (denoted as TKICHE); ii) TKIs as-sociated to steroids with no chemotherapy (TKISTE); iii) chemotherapy-free combinations of blinatumomab plus TKIs (TKIBLI). According to the Shiny method, the three PFS curves were reported in a single Kaplan-Meier graph and subjected to survival statistics. In terms of PFS, TKIBLI ranked first, TKICHE second, and TKISTE third; the differences between these three regimens were statistically significant. This multi-treatment Kaplan-Meier graph, generated through the Shiny method, summarized the current evidence on these treatments in both qualitative and quantitative terms.

Pancakes are fast food snacks that are generally made with the basic ingredients of wheat flour, which is an imported commodity and detrimental for people who are allergic to gluten. To reduce the use of wheat, alternative raw materials derived from local commodities are used, such as modified cassava flour (mocaf), arrowroot flour, and suweg flour. The experiment was carried out by mixing mocaf flour, arrowroot flour, and suweg flour to produce composite flour with a ratio of 70:15:15 (CF1), 70:20:10 (CF2), and 70:20:5 (CF3). The result showed that the ratio of mocaf flour, arrowroot flour, and suweg flour had a significant effect on pasting temperature, peak viscosity, hold viscosity, breakdown viscosity, setback, L*, a*, hue, whiteness, ∆E, as well as swelling volume and solubility on the characteristics of the composite flour It also had a significant effect on the texture characteristics of hardness, adhesiveness, chewiness, color characteristics L*, a*, whiteness, ∆E, and preference for the flavor of gluten-free pancake products. It is known that the best formulation for the resulting pancake product is P1, with the addition of a 70% ratio of mocaf flour, 15% ratio of arrowroot tuber flour, and 15% ratio of suweg flour.

Background: Free-living amoebas (FLA), also amebas, are eukaryotic and mitochondrial microorganisms that are capable of growing in any environment, aquatic or terrestrial. These free-living amoebas are mostly non-pathogenic to humans. However, there exist some highly pathogenic species, such as Acanthamoeba — mainly T-4 genotype —, Naegleria fowleri (known as brain-eating amoeba), and Balamuthia mandrillaris. They can be called "brain-eating amoebas” because of their ability to cause substantial destruction of brain tissue. There is no standard treatment; immunological processes which predispose humans to acquire and infection and, then, a disease are unknown. In addition, there are other species of free-living amoebas such as, Sappinea pedata, Vermamoeba vermiformes, Vanellas sp,Vahlkampfia sp., and, more recently, Paravahlkampfia francinae, which is less virulent and aggressive than the first three mentioned above. Methods: All CSF samples were evaluated in our laboratory under the microscope. Monoxenic and axenic cultures were negative as well as the presence of cysts or exponential growth. PCR was negative using the FLA primers. Results: Under close observation of sterile CSF, we can see mobile forms of non-human cells. None of the observed forms has the morphotype of Acanthamoeba, Naegleria sp. or Balamuthia mandrillaris. Conclusions: Due to these findings, we know these structures can be observed in the CSF and many of them do not form cysts as others do. In addition, these microorganisms are uncultivable in conventional medium culture to FLA and impossible to detect even when using molecular tools such as PCR, using the primers for EUK A/B or 18s RNAr gene as a target.

Structural information of biological macromolecules is crucial and necessary to deliver predictions about the effects of mutations—whether polymorphic or deleterious (i.e., disease causing), wherein, thermodynamic parameters, namely, folding and binding free energies potentially serve as effective biomarkers. It may be emphasized that the effect of a mutation depends on various factors, including the type of protein (globular, membrane or intrinsically disordered protein) and the structural context to which it occurs. Such information may positively aid drug-design. Furthermore, due to the intrinsic plasticity of proteins, even mutations involving radical change of the structural and physico-chemical properties of the amino acids (native vs. mutant) can still have minimal effects of protein thermodynamics. However, if a mutation causes significant perturbation of either folding or binding free energies, it is quite likely to be deleterious. Mitigating such effects is a promising alternative to the traditional approaches of designing inhibitors. This can be done by structure-based in silico screening of small molecules for which binding to the dysfunctional protein restores its wild type thermodynamics. In this review we emphasize on the effects of mutations on two important biophysical characteristics, stability and binding affinity, and how structures can be used for structure-based drug design to mitigate the effects of disease-causing variants on the above biophysical characteristics.

Considering that the electric refrigeration temperature range of 0.94BNT-0.06BT ceramic materials is 100~140˚C, the electric refrigeration performance of the 0.94BNT-0.06BT ceramic material system was modified by LiNbO3 doping to reduce the cooling temperature. As a result, the refrigeration temperature range of the 0.94BNT-0.06BT ceramic material system was lowered to 25~80 ˚C, achieving its cooling effect near room temperature, and in this temperature range, the adiabatic temperature changes ∆T&gt;0.6K.

Complementary and alternative treatment approaches are becoming more common among children with chronic conditions. The pravelance of CAM use among US adults was estimated to be around 42% in 2015, and around 44% to 50% among adults with neurologic disorders. Studies report children with chronic illnesses such as cancer, asthma, attention-deficit/hyperactivity disorder (ADHD), genetic disorders, and other neurodevelopmental disorders are treated with complementary and alternative treatments at higher rates. Dietary therapies are gaining increasing popularity in the mainstream population, due to the heavy media involvement. Although, majority of “fad” diets do not have enough supporting evidence, some dietary therapies have been utilized for decades and have numerous published studies. The objective of this review is to describe the dietary interventions used in children with the specific chronic conditions, to evaluate their efficacy based on published data, and to encourage pharmacist involvement in the management and care of such patients.

There is evidence that behavioral risk factors such as western type diet, and life style can predispose to oxidative stress, deficiency in antioxidant status, hyperglycemia, dyslipidemia and increase in inflammation in tissues of various organs: beta cells of the pancreas, LDL receptors in the hepatocytes, endothelium, neurons, osteocytes and gut. Further studies indicate that diets rich in antioxidant flavonoids, omega-3 fatty acids and fiber in foods were inversely associated whereas western-type foods were positively associated with risk of mortality due to cardiovascular diseases (CVDs). One important cause for beneficial effects of diet may be certain foods and nutrients such as vegetables, fruits and whole grains that are rich in fiber and flavonoids, known to produce liters og molecular hydrogen in the gut. It seems that, high-fiber diets, prebiotic and probiotics can produce greater hydrogen, which acts as an antioxidant and may inhibit free radical generation. Recent studies indicate that molecular hydrogen can inhibit hydroxyl and nitrosyl radicals and can directly act as antioxidant in the cells and tissues, which can cause marked decline in oxidative stress and inflammation leading to significant decline in CVDs and metabolic diseases. Clinical and experimental studies indicate that hydrogen therapy such as hydrogen rich water can provide benefits in the management of CVDs and metabolic diseases. Larger studies are necessary to verify the role of hydrogen administration in CVDs.

Aryl chlorides and bromides in the presence of NHC palladium hydroxo dimers of the type [{Pd(µ-OH)Cl(NHC)}2] (where NHC = IPr, SIPr, IMes, SIMes) undergo an efficient and selective Sonogashira cross-coupling with terminal acetylenes. For the coupling of 4-chlorotoluene with phenylacetylene TON = 560000 was observed. The procedure enables high-throughput and selective synthesis of a broad spectrum of unsymmetrically substituted 1,2-diarylacetylenes. Nearly a quantitative amount of HCl was detected within cross-coupling products. Water plays the role of the base and is regenerated in the process so that it does not have to be used in stoichiometric amounts (relative to the limiting reactant). Generation of the active Pd(0) complex proceeds via ethanol oxidation.

: In Philadelphia chromosome positive B-cell (Ph+) acute lymphoblastic leukemia (LLA), growing evidence has accumulated about the efficacy of low-intensity and chemo-free regimens. Our objective was to analyse all recent trials evaluating these treatments and to compare them in terms of efficacy. We applied the Shiny method, an artificial intelligence technique, to analyse Kaplan-Meier curves and reconstruct patient-level data. Reconstructed patient data were then evaluated through standard survival statistics and subjected to indirect head-to-head treatment comparisons. The endpoint was progression-free survival (PFS). Based on 562 reconstructed patients, 8 trials were analyzed. The survival data from these trials were pooled into three types of treatment: i) treatments based on tyrosine kinase inhibitors (TKIs) combined with reduced-intensity chemotherapy (denoted as TKICHE); ii) TKIs associated to steroids with no chemotherapy (TKISTE); iii) chemotherapy-free combinations of blinatumomab plus TKIs (TKIBLI). According to the Shiny method, the three PFS curves were reported in a single Kaplan-Meier graph and subjected to survival statistics. In terms of PFS, TKIBLI ranked first, TKICHE second, and TKISTE third; the differences between these three regimens were statistically significant. In conclusion, the multi-treatment Kaplan-Meier graph generated in this study has effectively summarized the current evidence on these treatments in comparative terms.

Customs law and procedures are important part of the trade system in Jordan. They regulate the flow of goods across the borders. The purpose of this paper is to examine Jordan's import regime by analyzing customs law, rules of origin, free trade zones, and tariffs reform.

Abstract: Power generation using dielectric elastomer (DE) artificial muscle is attracting attention because of its light weight, low cost, and high efficiency. Since this method is a system that produces electricity without emitting carbon dioxide nor using rare earths, it would contribute to the goal of environmental sustainability. In this paper, the background of DEs, the associated high-efficient wave energy generation (WEG) systems that we developed using DEs, as well as the latest development of its material are summarized. By covering the challenges we face and the achievements that we’ve reached, we can discuss the opportunities to build the foundation of a recycled energy society through the usage of these WEGs. On the other hand, to make these possibilities commercially successful, the advantages of DEs need to be integrated with traditional technologies. To achieve this, we also consider the method of using DEs alone and a system used in combination with an oscillating water column. Finally, the current status and future of DEGs are discussed.

This study comprehensively evaluates the DNA/RNA Defend Pro (DRDP) sample collection buffer designed to inactivate and stabilize patient samples. The primary objectives encompassed assessing DRDP's efficacy in ensuring sample stability, facilitating extraction-free polymerase chain reaction (PCR), and ensuring compatibility with rapid antigen testing.Ninety-five diagnostic nasopharyngeal swab samples tested for influenza A/B, RSV A/B, and/or SARS-CoV-2 were diluted 1/10 with DRDP and anonymized. Stability testing involved incubating 31 positive samples at 4 °C, 20 °C, and 37 °C for 7 days, with regular extraction-free nucleic acid amplification testing (NAAT).Results demonstrated that DRDP guaranteed viral RNA stability at all temperatures for influenza, SARS-CoV-2 and RSV showing stability up to 7 days at 4 °C. DRDP-diluted samples exhibited robust compatibility with direct PCR, as 72 out of 88 samples positive for cobas Liat also tested positive for direct PCR. Non-concordant results could be explained by the 200-fold lower input in the extraction-free NAAT.Compared to NAAT, rapid antigen testing demonstrated lower sensitivity, as expected, while maintaining perfect specificity. Clear cutoffs between positive and negative rapid antigen testing results were observed in both cobas Liat and direct PCR analyses, validating DRDP's compatibility with these techniques. In conclusion, DRDP is an effective stabilizing medium compatible with direct PCR and rapid antigen testing and shows great potential for optimizing diagnostic processes, particularly in resource-limited or time-sensitive scenarios.

Graphene oxide was synthesized by a one-step environmentally friendly mechanochemistry process directly from graphite and characterized by Raman, FT-IR and UV/vis spectroscopies, Atomic Force Microscopy, X-ray Diffraction, Scanning Electron Microscopy, Energy-Dispersive X-ray Spectroscopy and Thermogravimetric Analysis. Spectroscopic analysis shows that the functional groups and oxygen content of the synthesized material are comparable with those of graphene oxide synthesized by other previously reported methods (Hummers). Thermogravimetric analysis reveals thermal stability up to 400 °C.

A novel method proposed in the production of Calophyllum inophyllum biodiesel has been investigated experimentally. In this study, we report the results of biodiesel processing with electromagnetic induction technology. The method used is to compare the results of Calophyllum inophyllum biodiesel processing between conventional, microwave and electromagnetic induction. The degumming, transesterification, and esterification process of the 3 methods are measured by stopwatch to obtain time comparison data. Characteristics of viscosity, density, and Fatty Acid Metil Ester (FAME) were obtained from testing of a Gas Chromatography-mass Spectrometry (GCMS) at the Polytechnic Chemistry Laboratory of the State of Malang. The results show that the biodiesel produced by this method satisfies the biodiesel standards and their characteristics are better than the biodiesel produced by conventional and microwave methods. The electromagnetic induction method also offers a fast and easy route to produce biodiesel with the advantage of increasing the reaction rate and improving the separation process compared to other methods. This advanced technology has the potential to significantly increase biodiesel production with considerable potential to reduce production time and costs.

This study was conducted to evaluate the yield and quality parameters of milk from 60 indigenous South African goats of different genotypes namely Nguni, Boer and Non- descript reared under a free ranging system. Milk yield and quality parameters (milk fat, protein, lactose, solid non-fat and minerals) from Nguni (10), Boer (10) and Non-descript (10) goats was measured and analysed per week at each stage of lactation. Result showed that, Nguni goats produced (1.2±0.09, 1.3±0.11 and 1.2±0.07 litres per day) more milk (P ˂ 0.05) at early, mid and late stages of lactation than Boer (0.6±0.10, 1.0±0.17 and 0.6±0.09 litres per day) and Non-descript (0.3±0.10, 0.3±0.12 and 0.3±0.09 litres per day) goats, respectively. The mean value of milk fat, protein and lactose content from Nguni goat was (3.98, 3.54 and 5.31); Boer goat (2.9, 3.59 and 5.04) and Non-descript goat (4.05, 3.39 and 5.02), respectively. There was significant effect (P ˂ 0.05) of genotypes on milk fat, milk magnesium and sodium contents of Nguni, Boer and Non-descript goats. It could be concluded that, Nguni goat produced more milk than Boer and Non-descript goats, but the Non-descript goat had higher mean percentage of milk fat compared to Nguni and Boer goats.

Explaining the emergence of behavior and understanding on the basis of neuronal mechanisms is still elusive. One renowned proposal is the Free Energy Principle (FEP), which uses an information-theoretic framework derived from thermodynamic considerations to describe how behavior and understanding would emerge. FEP starts from a whole organism approach, based on mental states and phenomena, mapping them into the neuronal substrate. An alternative approach, the Energy Homeostasis Principle (EHP), initiates a similar explanatory effort, but starting from single neuron phenomena and building up to the whole organism’s behavior and understanding. In this work, we develop the EHP as an alternative but complementary vision to FEP and try to explain how behavior and understanding would emerge from the local requirements of the neurons. Based on EHP and a strict naturalist approach that sees living beings as physical and deterministic systems, we explain scenarios where learning would emerge without the need for volition or goals. Given these starting points, we state several considerations of how we see the nervous system, particularly the role of function, purpose, and the conception of goal-oriented behaviors. We problematize these conceptions, giving an alternative teleology-free framework in which behavior and, ultimately, understanding would still emerge. We reinterpret neural processing explaining basic learning situations up to simple anticipatory behavior. Finally, we end the work with an evolutionary perspective of how this non-goal-oriented behavior appears. We acknowledge that in the current form of our proposal, we are still far from explaining the emergence of understanding. Still, we set the ground for an alternative neuron-based framework to ultimately explain understanding.

The aim of this study (first analytical approach) was to obtain data on the fatty acid composition of gluten-free foods (bakery products) for celiac people. The study included 35 different products (snacks, biscuits, bakery products, pasta, flours, etc.) from several manufacturers. After extraction and esterification, the fatty acid content was determined by GC-MS. The monounsaturated fatty acids (MUFAs) are the major constitutes (57%) of the fatty acids pool followed by saturated fatty acids (SFAs) (30%) and polyunsaturated fatty acid (13%). Only fifteen, of the thirty-five gluten free samples analyzed, provide adequate energy intake, while in eleven samples, saturated fatty acids take more energy than that recommended by EFSA. It has emerged that local producers generally use the finest raw materials (olive oil, etc.) compared to the industries which, as has been pointed out, in many cases use palm and palm kernel oils although gluten free commercial products are high added value foods, expensive and intended for a particularly sensitive public.

Background User fee exemption for maternal and child health care service policy was introduced with a focus on providing free caesarean sections (CS) in Nigeria from 2011 to 2015. This policy had a positive impact on access to facility-based delivery, but its effect on socioeconomic and geographical inequality remains unclear. This study’s main objective is to examine access to birth by CS in the context of free maternal health care. Specifically, the study examines socio-demographic and geographical inequality in access to birth by CS among women who gave birth between 2011 and 2015 under the free maternal health care policy using a population-based survey data obtained from two of the six main regions of the country. Methods Data were obtained from 1227 women who gave birth during the period the policy was in operation selected using cluster random sampling between May and August 2016. Adjusted and unadjusted binary logistic regression models were used to examine whether there is socio-demographic and geographical inequality in access to birth by caesarean section. Results The overall caesarean section rate of 6.1% was found but varies by income (14.1% in monthly income of over $150 versus 4.9% in income of $150 and below), education (11.8% in women with higher education versus 3.9% among women with secondary education and less) and place of residence (7.8% in urban areas versus 3.6% in rural areas). Women who earn a monthly income of $150 or less were 48% less likely to have a birth by CS compared to those who earn more. Compared to women who were educated to tertiary level, women who had secondary education or less were 54% less likely to have birth by caesarean section. Conclusion This study shows that inequality in access to CS persists despite the implementation of free maternal health care services. Given the poor access to facilities with capabilities to offer CS in most rural areas, free maternal healthcare policy is not enough to make birth by CS universally accessible to all pregnant women in Nigeria.

An imbalance in any metabolic system can be traced to its homeostasis. When homeostatic environment is not attainable then there will be a response from the body. A new shift has emerged, “the negative feedback effect of high fructose consumption;” more pain than gain. The human metabolic system daily combat fructose sugar metabolism which emanates from high consumption. This inadvently lead to a chronological series of complications arising from the feedback. These feedbacks play pivotal roles in skeletal muscle damage and other body frameworks, it also fosters toxic advanced glycation end products (AGEs), factors that impose and inflict damaging effects to the body`s energy currency and serious threat to health. These damages are missed or overlooked because of early nonspecific physiological symptoms. High level of fructose has both long- and short-term effects on human metabolic processes. These effects which are majorly through the production of reactive oxygen species (ROS) and other free radicals, are felt in the disruption of biomolecules such as causing DNA mutation, lipid peroxidation etc. these effects in turn lead to various diseases such as cancer, diabetes, atherosclerosis, and other health issues. In this review, we will focus on the damaging effects this sugar has on human health and the present solutions being applied. We will also look at the next step in combatting and controlling these negative feedbacks.

Background: Traditional omic analysis relies on p-value and fold change as selection criteria. There is an ongoing debate on their effectiveness in delivering systemic and robust interpretation, due to their dependence on assumptions of conformity with various parametric distributions.Here, we propose a threshold-free selection method based on robust, non-parametric statistics, ensuring independence from the statistical distribution properties and broad applicability. Such methods could adapt to different initial data distributions, contrary to statistical techniques based on fixed thresholds. Methods: Our work extends the Rank Products methodology with a neutral selection method of high information-extraction capacity. We introduce the calculation of the RP distribution’s entropy to isolate the features of interest by their contribution to the distribution’s information content. The aim is a methodology performing threshold-free identification of the differentially expressed features, which are highly informative about the phenomenon under scrutiny. Conclusions: Applying the proposed method on microarray (transcriptomic and DNA methylation) and RNAseq count data of varying sizes and noise presence, we observe robust convergence for the different parameterisations to stable cutoff points. Functional analysis through BioInfoMiner and EnrichR was used to evaluate the information potency of the resulting feature lists. Overall, the derived functional terms provide a systemic description highly compatible with the results of traditional statistical hypothesis testing techniques. The methodology behaves consistently across different data types. The feature lists are compact and information-rich, indicating phenotypic aspects specific to the tissue and biological phenomenon i nvestigated. Selection by information content measures efficiently addresses problems, emerging from arbitrary thresholding, thus facilitating the full automation of the analysis.

Resection of malignant lesions in the oral and maxillofacial area causes functional and morphological defects. To recover from these defects, reconstruction surgery is needed such as a primary closure or a flap. There are advantages and disadvantages to the method of using the primary closure and the flap, and the choice of procedure is entirely up to a surgeon. The purpose of this study is to evaluate availability of primary closure in patients. For 10 years from January 2010 to May 2020, patients who recovered using flaps after removing malignant lesions from the oral cavity and those who closed the lesion using primary closure were investigated. The investigation was conducted by searching the database of the hospital. There were 85 patients who removed malignant lesions in the oral and maxillofacial area, and among them 16 patients closed the soft tissue defects using primary closure. Operation time, histologic types, stages, wound status, and period of hospitalization according to the patients' medical records were investigated retrospectively. Between the staging and the primary closure, statistically significant differences were observed between stage I and stage II patients in 13 patients using the primary closure. (P=0.046). Statistically significant differences were identified between operation time and primary closure, with an average of 4.02 hours (P=0.015). The average period of hospitality for patients who underwent primary closure was 13.4 days, compared to 26.7 days for those who underwent flap surgery. This difference was statistically significant (P=0.0003). This study evaluated the use of primary closure in patients who underwent resection of malignant lesions in the oral and maxillofacial area. Although the majority of patients underwent reconstruction with flaps, our results showed that primary closure can be a viable option for certain patients with early-stage lesions. Therefore, oral and maxillofacial surgeons should carefully consider various evaluation criteria and select appropriate reconstruction methods to optimize functional and aesthetic outcomes for each patient.

Keywords: free radicals; oxidative stress; hepatocellular carcinoma; anti-oxidants; kaempferol

This paper summarizes some works exploiting the ate-type addition of electron-withdrawing monomers to hydrogenosiloxane groups so as to generate new silicone materials. Two types of monomers were oligomerized onto silicone backbones, namely unsaturated phosphonate and sulfone monomers. Phosphonated silicones are thermally more resistant than conventional silicones and can be transformed into amphiphilic polymers after selective ester hydrolysis. Sulfoned silicones generate solid supramolecular elastomers thanks to the strong pseudo-ionic interactions in play between sulfone groups. Rheology and modulated DSC show a solid/viscoelastic transition around 175°C, which allows using these thermoplastic materials on a larger scale than conventional silicone urea copolymers. These results open new avenues in the generation of silicone block- and grafted-copolymers with unique functionality and properties.