Although there are a large number of databases available for regulatory elements, bottleneck has been created by the lack of bioinformatics tools for predicting types of mechanisms underlying actions of regulatory elements. To reduce the gap, we developed ARabidopsis Transcription regulatory Factor Domain-domain interaction Analysis Tool- Liquid-liquid phase separation (LLPS), Oligomerization, GO analysis (ART FounDATion-LOG), a useful toolkit for protein-nucleic acid interactions (PNI) and protein-protein interactions (PPI) analysis based on domain-domain interaction (DDI). LLPS, protein oligomerization, structural properties of protein domains, and protein modifications are major components in orchestrating spatio-temporal dynamics of PPI and PNI. Our goal is to integrate PPI/PNI information into development of prediction model for identifying important genetic variants in peach. The program unified inter-database relational keys by protein domains for facilitating inference from the model species. Key advantage of the program lies in the integrated information of related features: LOG, structural characterization of domain (e.g. domain linker, intrinsically disordered regions, DDI, domain-motif (peptide) interaction, beta-sheet and transmembrane helices), and post-translational modification. We provided simple tests to demonstrate how to use the program. The program may be applied to other eukaryotic organisms. The program codes and data are freely available for download at and https://sourceforge.net/projects/artfoundation-log/.

In biology molecules and macromolecules like sugars, proteins, DNA, and RNA are of utter importance. Detecting their presence as well as their conformation is still a challenge in many cases. It is well known that the vibrational states of such molecules lie from the infrared to the TeraHertz range. Spectroscopy can be used to detect such compounds and probe their conformation. Still, terahertz spectroscopy on biosample is a challenge for two main reasons: water absorption; and the small size of the samples. The sample volume is smaller than the cube of the TeraHertz wavelength; the light matter interactions are thus extremely reduced. In this paper, we present the design, fabrication, characterization and the first typical uses of a biophotonic device aiming at increasing light matter interaction to enable terahertz spectroscopy of minute samples on a broad band (0.2–2 THz). We demonstrate time domain spectroscopy experiments on few µl samples showing the validity of our approach.

SRC homology 3 (SH3) domains are critical interaction modules that orchestrate the assembly of protein complexes involved in diverse biological processes. They facilitate transient protein-protein interactions by selectively interacting with proline-rich motifs (PRMs). A database search revealed 298 SH3 domains in 221 human proteins. Multiple sequence alignment of human SH3 domains is useful for phylogenetic analysis and determination of their selectivity towards PRM-containing peptides (PRPs). However, a more precise functional classification of SH3 domains is achieved by constructing a phylogenetic tree only from PRM-binding residues and using existing SH3-PRP structures and biochemical data to determine the specificity within each of the 10 families for particular PRPs. In addition, the C-terminal proline-rich domain of the RAS activator SOS1 covers 13 of the 14 recognized proline-rich consensus sequence motifs, encompassing differential PRP pattern selectivity among all SH3 families. To evaluate binding capabilities and affinities, we conducted fluorescence dot blot and polarization experiments using 25 representative SH3 domains and various PRPs derived from SOS1. Our analysis has identified 45 interacting pairs with binding affinities ranging from 0.2 to 125 micromolar out of 300 tested and potential new interactors of SOS1. Furthermore, it establishes a framework to bridge the gap between SH3 and PRP interactions and provides predictive insights into potential interactions of SH3 domains with PRMs based on sequence specifications. This novel framework has the potential to enhance the understanding of protein networks mediated by SH3-PRM interactions and be utilized as a general approach for other domain-peptide interactions.

Beginning in 2012, our understanding of human papillomavirus (HPV) subcellular trafficking has undergone a drastic paradigm shift. Work from multiple laboratories has revealed that HPV has evolved a unique means to deliver its viral genome (vDNA) to the cell nucleus, relying on a myriad of host cell proteins and processes. The major breakthrough finding from these recent endeavors was the realization of L2-dependent utilization of cellular sorting factors for the retrograde transport of vDNA away from degradative endo/lysosomal compartments to the Golgi, prior to mitosis-dependent nuclear accumulation of L2/vDNA. An overview of current models of HPV entry, subcellular trafficking, and the role of L2 during initial infection is provided below, highlighting unresolved questions and gaps in knowledge.

Rhotekin is an effector protein for small GTPase Rho. This protein consists of a Rho binding domain (RBD), a pleckstrin homology (PH) domain, proline-rich regions and a C-terminal PDZ-binding motif. We and other groups have identified various binding partners for Rhotekin and proposed their possible physiological roles. However, functions of Rhotekin per se are largely unknown and information about its physiological roles are fragmentary. In this review, we summarize known features of Rhotekin in neuronal tissues and cancer cells. We also describe characteristics of binding partners for Rhotekin and predicted roles of their interaction.

Phosphatase and tensin homologue (PTEN) and SH2-containing-inositol-5’-phosphatase 2 (SHIP2) are structurally and functionally similar. They both consist of a Phosphastase (Ptase) domain and an adjacent C2 domain, and both proteins dephosphorylate phosphoinositol-tri(3,4,5)phosphate, PI(3,4,5)P3; PTEN at the 3-phophate and SHIP2 at the 5-phosphate. Therefore, they play pivotal roles in the PI3K/Akt pathway. Here, we investigate the role of the C2 domain in membrane interactions of PTEN and SHIP2, using molecular dynamics simulations and free energy calculations. It is generally accepted that for PTEN the C2 domain interacts strongly with anionic lipids and therefore significantly contributes to membrane recruitment. In contrast, for the C2 domain in SHIP2 we previously found much weaker binding affinity for anionic membranes. Our simulations confirm the membrane anchor role of the C2 domain in PTEN, as well as its necessity for the Ptase domain in gaining its productive membrane binding conformation. In contrast, we identified that the C2 domain in SHIP2 undertakes neither of these roles, which are generally proposed for C2 domains. Our data support a model in which the main role of the C2 domain in SHIP2 is to introduce allosteric interdomain changes that enhance catalytic activity of the Ptase domain.

Antimicrobial Peptides (AMPs), as immune effectors synthesized by a variety of organisms, not only constitute a robust defense mechanism against a broad spectrum of pathogens in the host, but also show promising applications as effective antimicrobial agents. Notably, insects are significant reservoirs of natural AMPs. However, the complex array of variations in types, quantities, antimicrobial activities, production pathways of AMPs, and evolution of AMPs across insect species presents a significant challenge for immunity system understanding and AMP applications. This review covers insect AMP discoveries, classification, common properties, and mechanisms of action. Additionally, we summarize the types, quantities, and activities of im-mune-related AMPs in each model insect. We also conducted the first comprehensive investigation into the diversity, distribution, and evolution of 20 types of AMPs in model insects, employing phylogenetic analysis to describe their evolutionary relationships and shed light on conserved and distinctive AMP families. Furthermore, we summarize the regulatory pathways of AMP production through classical signaling pathways and additional pathways associated with Nitric Oxide, insulin-like signaling, and hormones. This review advances our understanding of AMP as guardians in insect immunity system and also unlocks a gateway to insect AMP resources, facilitating the use of AMPs to address food safety concerns.

Antimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their clinical application has been hindered by their vulnerability to protease degradation and toxicity towards mammalian cells. To overcome these challenges, our study aims to develop a method to enhance the stability and safety of AMPs, applicable to effective drug-device combination products. KR12 antimicrobial peptide was chosen and in order to further enhance its delivery and efficacy, HIV TAT protein-derived cell-penetrating peptide (CPP) was fused to form CPP-KR12. A new product, CPP-KR12@Si, was developed by forming silica nanoparticles with self-entrapped CPP-KR12 peptide using the biomimetic silica precipitability due to its cationic nature. Peptide delivery from CPP-KR12@Si to bacteria and cells was delivered at a slightly delayed rate with improved stability against trypsin treatment and a reduction in cytotoxicity over CPP-KR12. Finally, the antimicrobial potential of CPP-KR12@Si/bone graft substitute (BGS) combination product was demonstrated, which is coated with CPP-KR12 in the form of nanoparticles on the surface of BGS. Self-entrapped AMP in silica nanoparticles is a safe and effective AMP delivery method that will be useful for developing a drug/device combination product for tissue regeneration.

Pin1 is a peptidyl-prolyl isomerase responsible for isomerizing phosphorylated S/T-P motifs. Pin1 has two domains that each have a distinct ligand binding site, but only its PPIase domain has catalytic activity. Vast evidence supports interdomain allostery of Pin1, with binding of a ligand to its regulatory WW domain impacting activity in the PPIase domain. Many diverse studies have made mutations in Pin1 in order to elucidate interactions that are responsible for ligand binding, isomerase activity, and interdomain allostery. Here, we summarize these mutations and their impact on Pin1’s structure and function.

Cell junction that is usually associated with dynamic cytoskeletons is essential for a wide range of cellular activities such as cell migration, cell communication, barrier function and signal transduction. Real-time observation of cell junction facilitates understanding of the mechanisms by which cell junction regulate relevant cellular activities. In this study, we examined the binding capacity of a modified tridecapeptide from Cx43 to cell junction protein ZO-1 and sought to create a fluorescent peptide that could be used to label cell junction. To introduce the fluorescent peptide into the cells, a cell-penetrating peptide was linked to the modified tridecapeptide and synthesized. The binding of the modified tridecapeptide was tested using pull down and immunoprecipitation assay. The ability of the peptide to label cell junction was assessed by adding it to fixed or cultured Caco-2 cells. Testing assay revealed that the Cx43-derived peptide can bind to ZO-1. Besides, the peptide was able to label cell junction of fixed cell, although no obvious cell junction labeling was observed clearly in living cells, probably due to the inadequate affinity. These results indicate that a peptide-based strategy for labeling cell junction may be feasible, and efforts to improve its affinity are warranted in the future.

The Chromogranin A (CgA)-derived peptide Catestatin (CST: hCgA352-372) is highly conserved (>90% in 90% species) in mammalian species. The highest-evolved primates show 58.8% similarity with the lowest-evolved monotremes. CST was initially identified as a physiological brake in catecholamine secretion by inhibiting nicotinic-cholinergic signaling. CST also inhibits desensitization of catecholamine secretion, indicating that CST can act both as a cholinergic antagonist (short-term) and as a cholinergic agonist (long-term). The long-term effect sustains catecholamine secretion during stressful situations. CST is now established as a pleiotropic hormone: it affects the cardiovascular system by lowering blood pressure and cardiac contractility, enhancing baroreflex sensitivity, increasing heart rate variability, and promoting angiogenesis; and it increases insulin sensitivity by reducing inflammation, inhibiting hepatic glucose production, attenuating endoplasmic reticulum stress, and inducing glycogen production. The present review will highlight the important direct and indirect effects of CST, CST1-15 (aka cateslytin), D-CST1-15 (where L-amino acids were changed to D-amino acids), and human variants of CST (Gly364Ser-CST and Pro370Leu-CST) on microbial growth inhibition and their potential as therapy for antibiotic-resistant pathogenic microbes.

Oral immunization with the choleric toxin (CT) elicits a high level of protection against its enterotoxin activities and can control cholera in endemic settings. However, the complete B-cell epitope map of the CT responsible for protection remains to be clarified. Here, we have mapped the B-cell linear epitopes of the three chains of the CT protein (CTP) prepared by Spot synthesis. The immunoreactivity of sera from mice immunized with an oral, inactivated vaccine (Schankol†™) was measured against membrane-bound peptides for mapping. Results: Eighteen IgG epitopes were identified; eight in the CTA, three in the CTB, and seven in the protein P. Three epitopes, TQTGFVRHDDGYVST (aa 66-77, Vc/TxA-3), KNGAIFQVE VPGSQN (aa 64-78, Vc/TxB-11), and LNDEHK (aa 90-95, Vc/TxP-16), were chosen to synthesize a multiple antigen peptide that was used to coat ELISA plates to screen immunized mouse sera as a test for an in vitro diagnostics for cholera. Conclusion: Vaccination with inactive CT-generated antibodies against multiple linear epitopes and the selected epitopes can be used to construct immunological reagents for rapid serological diagnosis of cholera with high sensitivity and specificity.

The high transmissibility and replication of SARS-CoV-2 have been attributed to enhanced protein functions which are dependent on protein folding. Our in silico study endeavored to scrutinize SARS-CoV-2 ORF1ab by analyzing the conserved folding patterns of its transcribed proteins. Accordingly, the findings indicated that SARS-CoV-2 ORF1ab shares domain-specific fold-fingerprints with a spectrum of unrelated organisms. Closer observation revealed slight changes in folding patterns engendered with small variation in the intrinsic amino acid sequence. By correlating with the evolvability-potential of RNA-viruses and COVID-19 pandemic, we hypothesize that SARS-CoV-2 could undergo fast recombination with the host, SARS-CoV-2 minor variants and other viral species resulting in a reservoir of SARS-CoV-2 quasispecies. It is highly possible that natural selection will cause a future emergence of evolved SARS-CoV-2-descendants. Nonetheless, we hope that this insightful study will assist in elucidating SARS-CoV-2 protein functionalities, development of vaccines, and the possibility and nature of future emergence.

Melanocortins play crucial roles in regulating the stress response, inflammation, and skin pigmentation. In this review, we focus on the melanocortin 1 receptor (MC1R), a G protein-coupled receptor primarily known for regulating skin pigmentation and exhibiting anti-inflammatory effects. First, we provide an overview of the structure, signaling pathways, and related diseases of MC1R. Next, we discuss the potential therapeutic use of synthetic peptides and small molecule modulators of MC1R, highlighting the development of various drugs that enhance stability through amino acid sequence modifications and small molecule drugs to overcome limitations associated with peptide characteristics. Notably, MC1R-targeted drugs have applications beyond skin pigmentation-related diseases, which predominantly affect MC1R in melanocytes. These drugs can also be useful in treating inflammatory diseases with MC1R expression present in various cells. Our review underscores the potential of MC1R-targeted drugs to treat a wide range of diseases and encourages further research in this area.

Various peptides or non-structural amino acids are recognized by their specific target proteins and perform biological role in various pathways in vivo. Understanding the interactions between target protein and peptides (or non-structural amino acids) provides key information on the molecular interactions, which can be potentially translated to the development of novel drugs. However, it is experimentally challenging to determine the crystal structure of protein-peptide complexes. To obtain structural information on substrate recognition of peptide-recognizing enzyme, X-ray crystallographic studies were performed using triglycine (Gly-Gly-Gly) as main-chain of peptide. The crystal structure of Parengyodontium album Proteinase K in complex with triglcyine was determined at 1.4 Å resolution. Two different bound conformations of triglycine were observed at the substrate recognition site. The triglycine backbone forms stable interactions with β5-α4 and α5-β6 loops of main-chain. One of the triglycine-binding conformations was identical with the binding mode of a peptide-based inhibitor from a previously reported crystal structure of Proteinase K. Triglycine has potential application X-ray crystallography to identify substrate recognition sites in peptide binding enzymes.

In archaea, the interaction of HerA helicase and NurA nuclease is required for 3' end resection during DNA double-stranded break repair, and its disruption results in unfaithful DNA repair. Interactions transpire by the four conserved domains, including the N-terminal HAS domain (HerA-ATP synthase), which serves as a binding site for the exonuclease NurA. As a HerA hexamer between its two subunits, the conserved C-terminal brace extension functions as an adjacent brace. DBD serves as a location for DNA binding, which causes the DNA strands to be propelled into the HerA pocket to begin unwinding. The putative pore entrance is made up of four helix coils, which provide a suitable charged surface for guiding DNA into the pore. The crystal structure of the complex HerA-NurA allows for the identification of key residues for protein-protein interaction. This allows us to predict that most archaeal HerA orthologs will be able to interact with one another. Archaeal HerA is a homo-hexameric assembly featuring a DNA-binding domain that is conserved. It also features distinctive ATP and NurA binding domains. Following the structure and sequence conservation criteria, we find one HerA ortholog in Pyrobaculum calidifontis and multiple HerA paralogs, but the role of none is established yet.Interestingly, orthologous HerA is part of an Mre11-Rad50 gene neighborhood while paralogous HerA is not, which could be misleading. As a result, it sought to describe the criteria that may be used as a possible fingerprint for identifying orthologous genes, as well as the cloning procedures and tactics that would aid in the confirmation of the HerA helicase in P. calidifontis. Their confirmation is based on PCR cloning and characterization following HerA construct creation.

Lipoxygenases are non-heme iron-containing enzymes that catalyze the oxidation of polyunsaturated fatty acids, resulting in the production of lipid hydroperoxides, which are precursors of inflammatory lipid mediators. The enzymes are widely distributed in humans, other eukaryotes, and cyanobacteria. Lipoxygenases hold promise as therapeutic targets for several human diseases, including cancer and inflammation-related disorders. Inhibitors of lipoxygenase have potential applications in pharmaceuticals, cosmetics, and food. Bioactive peptides are short amino acid sequences embedded within parent proteins, which can be released by enzymatic hydrolysis, microbial fermentation, and gastrointestinal digestion. A wide variety of bioactivities have been documented for protein hydrolysates and peptides derived from different biological sources. Recent findings indicate that protein hydrolysates and peptides derived from both edible and non-edible bioresources can act as lipoxygenase inhibitors. In this review, we explore current knowledge on the production of anti-lipoxygenase protein hydrolysates and peptides from millet grains, chia seeds, insects, milk proteins, fish feed, velvet antler blood, fish scales, and feather keratins. We delve into the anti-lipoxygenase activities and modes of action of these protein hydrolysates and peptides, while also highlighting the strengths and shortcomings of previous research. Additionally, we propose potential research directions and areas of improvement that can propel the discovery of anti-lipoxygenase peptides in the near future.

The field of domain adaptation, particularly in cross-domain sentiment classification, leverages labeled data from a source domain alongside unlabeled or sparsely labeled data from a target domain. The objective is to enhance performance in the target domain by mitigating the discrepancies in data distributions. Traditional methods in this area have focused on identifying and differentiating between pivotal sentiment words (shared across domains) and domain-specific sentiment words. In our work, we introduce a novel framework called Sentiment Domain Adapter (SDA), which incorporates a Category Attention Network (CAN) alongside a Convolutional Neural Network (CNN). This approach treats pivotal and domain-specific words as part of a collective category of attributes, which SDA learns to discern automatically, thereby enhancing domain adaptation. Additionally, SDA seeks to provide interpretative insights by learning these category attributes. Our model's optimization targets three main goals: (1) supervised classification accuracy, (2) minimizing the disparity in category feature distribution, and (3) maintaining domain invariance. Evaluations on three benchmark datasets for sentiment analysis affirm that SDA surpasses several established baselines.

In gravitational theory and astrophysical dynamics, singular initial value problems (IVPs) are frequently encountered. Finding the solutions to this class of IVPs can be challenging due to their complex nature. This study strives to circumvent the complexity by proposing a numerical method for solving such problems. The approach proposed in the current research seeks solutions to the IVP by partitioning the domain [0,L] of the problem into two intervals and solving the problem on each domain. The study seeks a closed-form solution to the IVP in the interval containing the singular point. A linearization technique and piecewise partitioning of the domain not containing the singularity are applied to the nonlinear IVP. The resulting linearized differential equation is solved using the Chebyshev spectral collocation method. Some examples are presented to illustrate the efficiency of the proposed method. Numerical analysis of the solution and residual errors are shown to ascertain convergence and accuracy. The results suggest that the technique gives accurate convergent solutions using a few collocation points.

Sea cucumber peptides are small molecular peptides with biological function obtained from fresh sea cucumber as feedstock, which were hydrolyzed by protease, separated ,and purified. As the main product of sea cucumber refinement, it more accurately expresses the nutritional effect of sea cucumber and has a wide range of potential applications. It has been demonstrated that sea cucumber has a certain value-added effect on bone mineral density regulation, but the differences in bone mineral density regulation of extracts from different parts of sea cucumber and the techniques contributing to the efficient isolation of bone sea cucumber peptides have not been reported. Firstly, the aim of this study was to reveal the differences in osteogenic activities of enzymatic peptides from three major parts of sea cucumber: the body wall, the egg protein, and the intestinal protein. Then, the bone-enhancing sea cucumber peptides were isolated based on the characteristics of the dif-ferences in molecular weight distribution, hydrophilicity, and ionisation degree of sea cucumber, and to explore the possible mechanisms of their action. The findings indicated that sea cucumber peptides extracted from three distinct sites exhibited a dose-dependent enhancement of osteoblast proliferation and differentiation. Upon evaluating the three methods of sea cucumber peptide separation based on molecular weight distribution, hydrophilicity, and ionization, it was observed that the fraction isolated by hydrophobicity and

Abstract: Carbohydrates form the major source of energy in Asian diets. A lower carbohydrate diet became the recommended golden standard for healthy lifestyle. However, the effects of low-carbohydrates diet on health in apparently healthy individuals have been poorly studied, especially in relation to insulin resistance syndrome (IRS). A total of 120 healthy weight participants with no previous history of a major medical condition and an average BMI of ≤ 25kg/m2 were recruited. Self-reported dietary intake and objective physical activity by accelerometry were tracked for seven days. Participants were divided into three categories according to their dietary intake of carbohydrates. Blood samples were collected for metabolic markers analysis. HOMA of insulin resistance (HOMA-IR), β-cell function (HOMA-B) and C-peptide were used to evaluate glucose homeostasis. The consumption of low carbohydrates (less than 45% of total energy) significantly correlated with higher HOMA-IR, Lower HOMA-β % compared to moderate carbohydrate intake (between 45% to 65%). However, only the HOMA-β % was significantly influenced by carbohydrates intake. Moreover, low carbohydrates intake was significantly associated with elevated C-peptide secretion. The substitution of carbohydrates with other macronutrients, such as fat and proteins in the Atkins/ketogenic diet, resulted in a pronounced induction of IRS-related inflammatory markers; FGF2, IP-10, IL-6, IL-17A, MDC and reduction of IL-13. Overall, the presented data highlight, for the first time, that low carbohydrate intake results in significant glucose homeostasis imbalance that may be driven by a heightened state of inflammatory response.

Amyloid β-peptide (Aβ) oligomerization is believed to contribute to the neuronal dysfunction in Alzheimer disease (AD). Despite decades of research, many details of Aβ oligomerization in neurons still need to be revealed. Förster Resonance Energy Transfer (FRET) is a simple but effective way to study molecular interactions. Here we use a confocal microscope with a sensitive Airyscan detector for FRET detection. By live cell FRET imaging, we detect Aβ42 oligomerization in primary neurons. The neurons were incubated with fluorescently labelled Aβ42 in the cell culture medium for 24 hours. Aβ42 were internalized and oligomerized into the lysosomes/late endosomes in a concentration-dependent manner. Both the cellular uptake and intracellular oligomerization of Aβ42 were significantly higher than for Aβ40. These findings provide a better understanding of Aβ42 oligomerization in neurons.

During December 2019, a novel coronavirus named as 2019-nCoV, has emerged in Wuhan, China. The human to human transmission of this virus has also been established. Untill now the virus has infected more than seven thousand people and has spread to fifteen countries. The World Health Organization (WHO) has declared 2019-nCoV as global health emergency due to its outburst well beyond China. There is need to develop some vaccines or therapeutics to control or prevent 2019-nCoV infections. The bottleneck with current conventional approaches is that these require longer time for vaccine development. However, computer assisted approaches help us to produce effective vaccine in short time compared with conventional methods. In this study, bioinformatics analysis was used to predict B cell and T cell epitopes of surface glycoprotein of 2019-nCoV that could be suitable to trigger significant immune response. The sequence of surface glycoprotein was collected from the database and analyzed to identify the immunogenic epitope. Both B cell and T cell epitopes were analyzed so the predicted epitopes can stimulate both cellular and humoral immune responses. We predicted 13 B cell and 05 T cell epitopes that later on were joined with GPGPG linker to make a single peptide. This computational approach to design a multi epitope peptide vaccine against emerging 2019-nCoV allows us to find novel immunogenic epitopes against the antigen targets of surface 2019-nCoV surface glycoprotein. This multi epitope peptide vaccine may prove effective to combat 2019-nCoV infections.

After screening nearly 1000 synthetic peptides, a synthetic peptide termed JAL-AK22 (KYEGHWYPEKPYKGSGFRCIHI) derived from the BoxA domain in Tob1 protein was found to activate both unfolded and folded proMMP-7. In addition, JAL-AK22 showed auto-proteolytic activity. Interestingly, the smaller derivative of JAL-AK22 termed JAL-TA9 (YKGSGFRMI) also possessed auto-proteolytic activity and cleaved 2 fragment peptides (MMP18-33 and MMP18-40) derived from the prodomain of proMMP-7 under physiological conditions. These proteolytic activities were inhibited by AEBSF, a serine protease inhibitor. Our results demonstrate that a small synthetic peptide consisting of only 9 amino acids has serine protease-like activity and activates proMMP-7 by cleaving the prodomain region. We thus propose calling small peptides possessing with protease-like activity Catalytides (catalytic peptides). We expect that our findings will stimulate the development of novel Catalytides and related applications.

Leucokinins (LKs) constitute a family of neuropeptides identified in numerous insects and many other invertebrates. The LKs act on G-protein coupled receptors that display only distant relations to other known receptors. In adult Drosophila, 26 neurons/neurosecretory cells of three main types express LK. The four brain interneurons are of two types, and these are implicated in several important functions in the fly’s behavior and physiology, including feeding, sleep-metabolism interactions, state-dependent memory formation, as well as modulation of gustatory sensitivity and nociception. The 22 neurosecretory cells (ABLKs) of the abdominal neuromeres coexpress LK and a diuretic hormone (DH44), and together these regulate water and ion homeostasis and associated stress, as well as food intake. In Drosophila larvae, LK neurons modulate locomotion, escape responses, and aspects of ecdysis behavior. A set of lateral neurosecretory cells, ALKs, in the brain express LK in larvae, but inconsistently so in adults. These ALKs coexpress three other neuropeptides and regulate water and ion homeostasis, feeding and drinking, but the specific role of LK is not yet known. This review summarizes Drosophila data on embryonic lineages of LK neurons, functional roles of individual LK neuron types, interactions with other peptidergic systems, and orchestrating functions of LK.

Growth factors, chemokines and cytokines guide tissue regeneration after injuries. However, their applications as recombinant proteins are almost non-existent due to the difficulty of maintaining their bioactivity in the protease-rich milieu of injured tissues in humans. Safety concerns have ruled out their systemic administration. The vascular system provides a natural platform for circumvent the limitations of the local delivery of protein-based therapeutics. Tissue selectivity in drug accumulation can be obtained as organ-specific molecular signatures exist in the blood vessels in each tissue, essentially forming a postal code system (“vascular zip codes”) within the vasculature. These target-specific “vascular zip codes” can be exploited in regenerative medicine as the angiogenic vasculature forming in the regenerating tissues has a unique molecular signature. The identification of vascular homing peptides capable of finding these unique “vascular zip codes” after their systemic administration provides an opportunity for the target-specific delivery of therapeutics to tissue injuries. Therapeutic proteins can be “packaged” together with homing peptides by expressing them as multi-functional recombinant proteins. These multi-functional recombinant proteins provide an example how molecular engineering gives a compound an ability to home to regenerating tissue and enhance its therapeutic potential. Regenerative medicine has been dominated by the locally applied therapeutic approaches despite these therapies are not moving to clinical medicine with success. There might be a time to change the paradigm towards systemically administered, target organ-specific therapeutic molecules in future drug discovery and development for regenerative medicine

Effective control of domain walls or magnetic textures in antiferromagnets promises to enable robust, fast, and non-volatile memories. The lack of net magnetic moment in antiferromagnets implies the need for creative ways to achieve such a manipulation. Here, we investigate changes in magnetic force microscopy (MFM) imaging and in magnon-related mode in Raman spectroscopy of virgin NiO films under a microwave pump. After the MFM and Raman studies, a combined action of broadband microwave (0.01-20 GHz, power scanned from −20 to 5 dBm) and magnetic field (up to 3 kOe) were applied to virgin epitaxial (111) NiO and (100) NiO films grown on (0001) Al2O3 and (100) MgO substrates, following which the MFM and Raman studies were repeated. We observed a suppression of the magnon-related Raman mode subsequent to the microwave exposure. Based on MFM imaging, this effect appears to be caused by the suppression of large antiferromagnetic domain walls due to the possible excitation of antiferromagnetic spin oscillations localized within the antiferromagnetic domain walls.

Federated Distillation (FD) has recently attracted increasing attention for its efficiency in aggregating multiple diverse local models trained from statistically heterogeneous data of distributed clients. Existing FD methods generally treat these models equally by merely computing the average of their output soft predictions for some given input distillation sample, which does not take the diversity across all local models into account, thus leading to degraded performance of the aggregated model, especially when some local models learn little knowledge about the sample. In this paper, we propose a new perspective that treats the local data in each client as a specific domain and design a novel domain knowledge aware federated distillation method, dubbed DaFKD, that can discern the importance of each model to the distillation sample, and thus is able to optimize the ensemble of soft predictions from diverse models. Specifically, we employ a domain discriminator for each client, which is trained to identify the correlation factor between the sample and the corresponding domain. Then, to facilitate the training of the domain discriminator while saving communication costs, we propose sharing its partial parameters with the classification model. Extensive experiments on various datasets and settings show that the proposed method can improve the model accuracy by up to $6.02\%$ compared to state-of-the-art baselines.

This paper aims to provide an overview of the complete process in the development of a Domain-Specific Language (DSL). It explains the construction steps such as preliminary research, language implementation, and evaluation. Moreover, it provides details for different key components which are commonly found in the DSLs such as the abstraction layer, DSL metamodel, and the applications. It also explains the general limitations related to the Domain-Specific Languages for Workflows.

(1) Purpose: This work aims at developing a generalizable MRI reconstruction model in the meta-learning framework. The standard benchmarks in meta-learning are challenged by learning on diverse task distributions. The proposed network learns the regularization function in a variational model and reconstructs MR images with various under-sampling ratios or patterns that may or may not be seen in the training data by leveraging a heterogeneous dataset. (2) Methods: We propose an unrolling network induced by learnable optimization algorithms (LOA) for solving our nonconvex nonsmooth variational model for MRI reconstruction. In this model, the learnable regularization function contains a task-invariant common feature encoder and task-specific learner represented by a shallow network. To train the network we split the training data into two parts: training and validation, and introduce a bilevel optimization algorithm. The lower-level optimization trains task-invariant parameters for the feature encoder with fixed parameters of the task-specific learner on the training dataset, and the upper-level optimizes the parameters of the task-specific learner on the validation dataset. (3) Results: The PSNR increases 1.5 dB on average compared to the network trained through conventional supervised learning on the seen CS ratios. We test the result of quick adaption on the unseen tasks after meta-training, the average PSNR arises 1.22 dB compared to the conventional learning procedure that is directly trained on the unseen CS ratios in the meanwhile saving half of the training time. The average PSNR arises 1.87 dB for unseen sampling patterns comparing to conventional learning; (4) Conclusion: We proposed a meta-learning framework consisting of the base network architecture, design of regularization, and bi-level optimization-based training. The network inherits the convergence property of the LOA and interpretation of the variational model. The generalization ability is improved by the designated regularization and bilevel optimization-based training algorithm.

In this paper, a technique of image watermarking using multiple images as watermarks is presented. The technique is based on transform domain functions including discrete wavelet transform (DWT), discrete cosine transform (DCT) and singular value decomposition (SVD) with an image as the host signal i.e. the watermarks will be used as proofs of the authenticity of the host image. The technique is executed by performing multilevel DWT followed by applying DCT and SVD to both the host and watermark. Multiple watermarks are used for the insurance of better security level. The scheme is immune to common image processing operations & some attacks and exhibits PSNR of 108.3781dB, normalized cross correlation (NCC) over 0.99 and normalized correlation (NC) over 0.99.

Six Half-ring with varying linewidth from 120nm to 370nm were connected in series on five corners. The magnetization reversal processes were investigated by the measurement of anisotropic magnetoresistances (AMR). The number of switching jumps in the AMR loops, from zero to five, varied with the longitudinal applied field. These discrete jumps result from domain wall nucleating and depinning on the corners. The larger external field applied the fewer number of jumps in the MR curve. This reproducible and particular-respondence of domain wall device in pattern of half-ring wire might be the new promising magnetoelectronic devices.

In Korea, the underground silo structure for low- and intermediate-level radioactive waste disposal facilities has been constructed and operated since 2014. Large-scale earthquakes occurred in 2016 and 2017, respectively, in Gyeongju and Pohang areas near the underground silo structures, and interest in the stability of the underground silo increased significantly. In this paper, one-dimensional free field analyses have been carried out before the three-dimensional silo dynamic analyses subjected to earthquake loadings. As an additional study, a new form of finite element equilibrium equation is derived in terms of relative motions, which is essentially the same equation as that expressed in terms of total motions where the base shear force is applied for earthquake load. The accuracy of conventional finite element solutions is evaluated by directly comparing them with closed-form solutions by frequency domain analysis such as SHAKE91.

The healing of osteochondral defects (OCD) resulting from injury, osteochondritis, or osteoarthritis in middle- and old-age individuals, bearing lesions in the cartilage and bone, pain, and loss of joint function, presents challenges to the clinical practitioners because of non-regenerative cartilage and the limitations of current therapies. Bioactive peptide-based osteochondral (OC) tissue regeneration is becoming more popular because it does not have the immunogenicity, misfolding, or denaturation problems associated with original proteins. Periodically, reviews are published on the regeneration of bone and cartilage; however, none of them address the simultaneous healing of these tissues in the complicated heterogeneous environment of the OC interface. As regulators of cell adhesion, proliferation, differentiation, angiogenesis, immunomodulation, and antibacterial activity, potential therapeutic strategies for OC defects utilizing bone and cartilage-specific peptides should be examined and investigated. Therefore, the main goal of this review is to study how they contribute to the healing of OC defects, either alone or in conjunction with other peptides and biomaterials.

Staphylococcus aureus(S. aureus) is associated with mastitis in dairy cows, this study investigates the therapeutic effect of maggot antimicrobial peptides on S. aureus induced mastitis in mice. The maggot AMP was isolated and purified, tested for antimicrobial activity, and used to treat a pathological model of rat mastitis. The concentration of 1.5mg/（Kg. BW）AMP was selected as intramammary treatment in S. aureus-induced mastitis in mice. The mice were divided into four groups of 30 mice each: group I (healthy control), group II (disease control), group III (AMP), and group IV (ciprofloxacin). To evaluate the therapeutic efficacy of maggot AMP in mastitis induced by S. aureus based on clinical presentation, mammary gland structure, bacterial load, histopathology, and cure. During the 7-day treatment period, all the mice in Group II died in the afternoon of the fifth day, and the clinical signs of the mice in Group III began to improve on the third day, as evidenced by the gradual recovery of the mice's mental status, dietary intake, and water intake. During the treatment period, the bacterial load count of Group III was significantly lower than that of Group II but higher than that of Group IV, while the bacterial load count of Group III gradually decreased and approached that of Group IV from the fifth to the seventh day. The levels of TNF-α in groups III and IV were significantly lower than those in group II, suggesting that maggot AMP has a certain inhibitory effect on TNF-α. Treatment with AMP@ 1.5 mg/(Kg. BW) showed restoration of clinical signs, reduced bacterial load, and lower TNF-α levels in mice, leading to significant improvement in histopathological changes as compared to disease controls. The final cure rate was 40% for mice in Group III compared to 70% for mice in Group IV, compared to all mice in Group II that died. From this study, it can be concluded that maggot AMP can be used as a potential alternative treatment option to antibiotics for the treatment of bovine mastitis.

In this work we developed two new polyfunctional hybrid systems, in which the presence of Fc redox "antennas" on peptide scaffolds allows a modulation of their electronic properties. Specifically, we synthesized two helical hexapeptides containing four Aib (α-amionoisobutyric acid) and two L-Dap (2,3-diamino propionic acid) residues. L-Dap side chains were then functionalized with Fc moieties. The structures of the two 310 helical peptides, namely Z-Aib-L-Dap(Fc)-Aib-Aib- L-Dap(Fc)-Aib-NH-iPr and Z-Aib-L-Dap(Fc)-Aib- L-Dap(Fc)-Aib-Aib-NH-iPr, were investigated by X-ray diffraction, 2D-NMR, CD and IR spectroscopies. Due to the helical conformation, in Z-Aib-L-Dap(Fc)-Aib-Aib- L-Dap(Fc)-Aib-NH-iPr the Fc groups are located on the same face of the helix, in Z-Aib-L-Dap(Fc)-Aib- L-Dap(Fc)-Aib-Aib-NH-iPr on opposite faces. Surprisingly, two bands were found in DPV for Z-Aib- L-Dap(Fc)-Aib- L-Dap(Fc)-Aib-Aib-NH-iPr, indicating electrostatic interaction between the Fc groups despite their longer reciprocal distance with respect to that in Z-Aib- L-Dap(Fc)-Aib-Aib- L-Dap(Fc)-Aib-NH-iPr. CD experiments at different concentrations evidenced aggregation for Z-Aib- L-Dap(Fc)-Aib-L-Dap(Fc)-Aib-Aib-NH-iPr even at high dilution, thus suggesting that the Fc-Fc electrostatic interaction could be of intermolecular nature.

The emergence of multi-drug resistant bacteria has severely increased the burden on the global health system, and such pathogen infections are considered a great threat to human well-being. Antimicrobial peptides, due to their potent antimicrobial activity and low possibility of inducing resistance, are increasingly becoming the focus of much interest. Herein, a novel dermaseptin peptide, named Dermaseptin-SS1 (SS1), was identified from a skin secretion-derived cDNA library of the South/Central American tarsier leaf frog, Phyllomedusa tarsius, using a ‘shotgun’ cloning strategy. Chemically-synthesised peptide SS1 was found to be broadly effective against Gram-negative bacteria with low haemolytic activity in vitro. A designed synthetic analogue of SS1, named peptide 14V5K, showed a lower salt sensitivity with more rapid bacteria-killing compared to SS1. Both peptides employed the membrane-targeting mechanism to kill Escherichia coli. The antiproliferative activity of SS1 and its analogues, against lung cancer cell lines, was found to be significant.

Immune checkpoint blockade therapy has shown successful clinical outcomes in multiple human cancers. In dogs, several types of tumors resemble human tumors in many respects. Therefore, several groups have developed the anti-dog programmed cell death ligand 1 (dPD-L1) monoclonal antibodies (mAbs) and showed efficacy in several canine tumors. To examine the abundance of dPD-L1 in canine tumors, anti-dPD-L1 diagnostic mAbs for immunohistochemistry are required. In this study, we immunized the peptide in the dPD-L1 intracellular domain, and established anti-dPD-L1 mAbs, L1Mab-352 (mouse IgG1, kappa) and L1Mab-354 (mouse IgG1, kappa). In enzyme-linked immunosorbent assay, L1Mab-352 and L1Mab-354 showed high binding affinity to the dPD-L1 peptide, and the dissociation constants (KD) were determined as 6.9 ×10-10 M and 7.2 ×10-10 M, respectively. Furthermore, L1Mab-352 and L1Mab-354 were applicable for the detection of dPD-L1 in immunohistochemical analysis in paraffin-embedded dPD-L1-expressed cells. These results indicated that L1Mab-352 and L1Mab-354 are useful for detecting dPD-L1 in immunohistochemical analysis.

Prospects for predicting the fragmentation of polypeptide chains during their enzymatic hydrolysis using proteolysis models are considered. The opening of the protein substrate during proteolysis and the exposure of its internal peptide bonds for a successful enzymatic attack, the so-called demasking process, were taken into account. The two-step model of proteolysis was used, including the parameters of peptide bond demasking and hydrolysis rate constants for various peptide bonds. Herein, we presented an algorithm for calculating the concentrations of peptide fragments depending on the hydrolysis time or the degree of hydrolysis. The intermediate peptide fragments with two or one internal specific bonds were considered. The fragmentation of β-lactoglobulin (b-LG) with trypsin was predicted, and the calculated concentration curves for peptide fragments were compared with the experimental dependences of concentrations on the degree of hydrolysis. Numerical parameters characterizing the kinetic curves were proposed for the intermediate and final peptide fragments, and they were used to compare the calculated and experimental dependences. The predicted distribution of peptide fragments corresponded to the experimental data on the peptide release during proteolysis of b-LG by trypsin.

Background: Biomarker development, improvement, and clinical implementation in the context of kidney disease has been a central focus of biomedical research for decades. To this point, only serum creatinine and urinary albumin excretion are well accepted biomarkers in kidney disease. With their known blind spot in early stages of kidney impairment and diagnostic limitations there is a need for better and more specific biomarkers. With the rise of large-scale analysis of thousands of peptides in serum or urine samples using mass spectrometry techniques hopes for biomarker development were high. Advances in proteomic research have led to the discovery of an increasing amount of potential proteomic biomarkers and identification of candidate biomarkers for clinical implementation in the context of kidney disease management. In this review we focus on urinary peptide and especially peptidomic biomarkers emerging from recent research and underline the role of those with the highest potential for clinical implementation. Methods: The Web of Science database (all databases) was searched on October 17th, 2020, using the search terms “marker*” OR biomarker* AND “renal disease” OR “kidney disease” AND “proteome*” OR “peptid*” AND “urin*”. English, full-text original articles on humans published within the last 5 years were included which were cited at least 5 times per year. Studies based on animal models, renal transplant studies, metabolite studies, studies on miRNA and studies on exosomal vesicles were excluded focusing on urinary peptide biomarkers. Results: The described search led to the identification of 3668 articles and application of inclusion and exclusion criteria as well as abstract and consecutive full-text analysis of 3 independent authors to a final number of 62 studies for this manuscript. The 62 manuscripts encompassed 8 established single peptide biomarkers and several proteomic classifiers including CKD273 and IgAN237. Discussion: This review provides a summary of recent evidence on single peptide urinary biomarkers in CKD while emphasizing the increasing role of proteomic biomarker research with new research on established and new proteomic biomarkers. Lessons learned from the last 5 years in this review might encourage future studies hopefully resulting in routine clinical applicability of new biomarkers.

Antimicrobial peptides (AMPs) are considered as promising alternatives to conventional antibiotics in order to overcome the growing problems of antibiotic resistance. Computational prediction approaches receive an increasing interest to identify and design the best candidate AMPs prior to the in-vitro tests. In this study, we focused on the linear cationic peptides with non-hemolytic activity, which are downloaded from the Database of Antimicrobial Activity and Structure of Peptides (DBAASP). Referring to the MIC (Minimum inhibition concentration) values, we have assigned a positive label to a peptide if it shows antimicrobial activity; otherwise the peptide is labeled as negative. Here, we focused on the peptides showing antimicrobial activity against Gram-negative and against Gram-positive bacteria separately, and we created two datasets accordingly. Ten different physico-chemical properties of the peptides are calculated and used as features in our study. Following data exploration and data preprocessing steps, a variety of classification algorithms are used with 100-fold Monte Carlo Cross Validation to build models and to predict the antimicrobial activity of the peptides. Among the generated models, Random Forest has resulted in the best performance metrics for both Gram-negative dataset (Accuracy: 0.98, Recall: 0.99, Specificity: 0.97, Precision: 0.97, AUC: 0.99, F1: 0.98) and Gram-positive dataset (Accuracy: 0.95, Recall: 0.95, Specificity: 0.95, Precision: 0.90, AUC: 0.97, F1: 0.92) after outlier elimination is applied. This prediction approach might be useful to evaluate the antibacterial potential of a candidate peptide sequence before moving to the experimental studies.

Human cytomegalovirus (HCMV) tegument protein pp150 is essential for the completion of final steps in virion maturation. Earlier studies indicated that three pp150nt (N terminal one-third of pp150) conformers cluster on each triplex (Tri1, Tri2A and Tri2B) and extend towards small capsid proteins atop nearby major capsid proteins forming a net-like layer of tegument densities that enmesh and stabilize HCMV capsids. Based on this atomic detail, we designed several peptides targeting pp150nt. Our data show significant reduction in virus growth upon treatment with one of these peptides (pep-CR2) with an IC50 of 1.33 μM. Based on 3D modeling, pep-CR2 specifically interferes with the pp150-capsid binding interface. Cells pre-treated with pep-CR2 and infected with HCMV sequester pp150 in the nucleus indicating a mechanistic disruption of pp150 loading onto capsids and subsequent nuclear egress. To enhance the in-vivo inhibitory potential and bioavailability of pep-CR2, we conjugated it with a carrier molecule (elastin like polypeptide (ELP)). The ELP-pep-CR2 conjugate was expressed in E.coli and purified. Upon treatment with ELP-pep-CR2, HCMV showed significant titer reductions with no significant impact on cell viability. These results indicate that CR2 of pp150 is amenable to targeting by a peptide inhibitor and can be developed into an effective antiviral.

Human Rhinovirus (HRV) is the most common cause of upper respiratory infections and exacerbations of asthma. In this work, we selected 14 peptides (6 from HRV A and 8 from HRV C) encompassing potential CD4 T cell epitopes. Peptides were selected for being highly conserved in HRV A and C serotypes and predicted to bind to multiple HLA II molecules. We found positive T cell recall responses by IFNγ-ELISPOT assays to 8 peptides, validating 7 of them (3 from HRV A and 4 from HRV C) as CD4 T cell epitopes through intracellular cytokine staining assays. Additionally, we verified their promiscuous binding to multiple HLA II molecules by quantitative binding assays. According to their experimental HLA II binding profile, the combination of all these 7 epitopes could be presented and recognized by > 95 % of the world population. We actually determined IFNγ responses to a pool encompassing these CD4 T cell epitopes by intracellular cytokine staining, finding positive responses in 29 out of 30 donors. The CD4 T cell epitopes identified in this study could be key to monitor HRV infections and to develop peptide-based vaccines against most HRV A and C serotypes.

Lassa virus (LASV) is responsible for a type of acute viral haemorrhagic fever referred to as Lassa fever. Lack of adequate treatment and preventive measures against LASV resulted in a high mortality rate in its endemic regions. In this study, a multi-epitope vaccine was designed using immunoinformatics as a prophylactic agent against the virus. Following a rigorous assessment, the vaccine was built using T-cell (N_CTL=8 and N_HTL=6) and B-cell (N_LBL=4) epitopes from each LASV-derived protein with suitable linkers and adjuvant. The physicochemistry, immunogenic potency and safeness of the designed vaccine (~68 kDa) were assessed. In addition, chosen CTL and HTL epitopes of our vaccine showed 97.37% worldwide population coverage. Besides, disulphide engineering also improved the stability of the chimeric vaccine. Molecular docking of our vaccine protein with toll-like receptor (TLR2) showed binding efficiency followed by dynamic simulation for stable interaction. Furthermore, higher levels of cell-mediated immunity and rapid antigen clearance were suggested by immune simulation and repeated-exposure simulation, respectively. Finally, the optimized codons were used in in silico cloning to ensure higher expression within E. coli K12 bacterium. With further assessment both in vitro and in vivo, we believe that our proposed peptide-vaccine would be potential immunogen against Lassa fever.

In this work we demonstrate the proof-of-concept of real-time discrimination between patches of serine or isoleucine monomers in the primary structure of custom-engineered, macro-dipole-like peptides, at uni-molecular level. We employed single-molecule recordings to examine the ionic current through the α-hemolysin (α-HL) nanopore, when hydrophilic serine or hydrophobic isoleucine residues, flanked by segments of oppositely charged arginine and glutamic amino acids functioning as a voltage-dependent ‘molecular brake’ on the peptide, were driven at controllable rates across the nanopore. The observed differences in the ionic currents blockades through the nanopore, visible at time resolutions corresponding to peptide threading through the α-HL’s constriction region, was explained by a simple model of the volumes of electrolyte excluded by either amino acid species, as groups of three serine or isoleucine monomers transiently occupy the α-HL. To provide insights into the conditions ensuring optimal throughput of peptide readout through the nanopore, we probed the sidedness-dependence of peptide association to and dissociation from the electrically and geometrically asymmetric α-HL.

The threat of antimicrobial resistance to society is compounded by a relative lack of new clinically effective licensed therapies reaching patients over the past three decades. This has been particularly problematic within antifungal drug development leading to a rise in fungal infection rates and associated mortality. This paper highlights the potential of an ultrashort peptide, (naphthalene-2-ly)-acetyl-diphenylalanine-dilysine-OH (NapFFKK-OH), encompassing hydrogel-forming and antifungal properties within a single peptide motif, thus overcoming formulation (e.g. solubility, drug loading) issues associated with many current employed highly hydrophobic antifungals. A range of fungal susceptibility (colony counts) and cell cytotoxicity (MTS cell viability, LIVE/DEAD staining® with fluorescent microscopy, haemolysis) assays were employed. Scanning electron microscopy confirmed the nanofibrous architecture of our self-assembling peptide, existing as a hydrogel at concentrations of 1% w/v and above. Broad-spectrum activity was demonstrated against a range of fungi clinically relevant to infection (Aspergillus niger, Candida glabrata, Candida albicans, Candida parapsilosis and Candida dubliniensis) with greater than 4 log10 CFU/mL reduction at concentrations of 0.5% w/v and above. We hypothesise antifungal activity is due to targeting of anionic components present within fungal cell membranes resulting in membrane disruption and cell lysis. NapFFKK-OH demonstrated reduced toxicity against mammalian cells (NCTC 929, ARPE-19) suggesting increased selectivity for fungal cells. However, further studies relating to safety for systemic administration is required, given the challenges toxicity has presented in the wider context of antimicrobial peptide drug development. Overall this study highlights the promise of NapFFKK-OH hydrogels, particularly as a topical formulation for the treatment of fungal infections relating to the skin and eyes, or as a hydrogel coating for the prevention of biomaterial related infection.

In today’s world face detection is the most important task. Due to the chromosomes disorder sometimes a human face suffers from different abnormalities. For example, one eye is bigger than the other, cliff face, different chin-length, variation of nose length, length or width of lips are different, etc. For computer vision currently this is a challenging task to detect normal and abnormal face and facial parts from an input image. In this research paper a method is proposed that can detect normal or abnormal faces from a frontal input image. This method used Fast Fourier Transformation (FFT) and Discrete Cosine Transformation of frequency domain and spatial domain analysis to detect those faces.

Recent advancements in machine learning have ushered in innovative techniques for augmenting datasets, particularly through contrastive learning in the computer vision domain. This study pioneers the application of contrastive learning for sentiment analysis, introducing a novel approach termed EmoConLearn. By fine-tuning contrastive learning embeddings, EmoConLearn significantly surpasses BERT-based embeddings in sentiment analysis accuracy, as evidenced by our evaluations on the DynaSent dataset. This research further delves into the efficacy of EmoConLearn across various domain-specific datasets, highlighting its versatility. Additionally, we investigate upsampling strategies to mitigate class imbalance, further enhancing EmoConLearn's performance in sentiment analysis benchmarks.

Rice blast fungus (Magnaporthe oryzae) causes massive yield losses annually worldwide. The fungus secreted bunch of effector proteins target different rice cellular compartments to facilitate its infection. However, most of intensively studied effectors are small secreted proteins with high presence/absence polymorphism in the fungus, and effectors conserved among different species were rarely investigated. In this study, we identified MoPce1, a CAP/PR domain containing protein common in different species, as an important virulence factor from a screening of 145 putative core effectors (PCE). MoPCE1 is required for pathogenicity but not the asexual development. Ectopic expression of MoPCE1sp in ZH11 background compromised the plant resistance. We also found that MoPce1 lacks the conserved cysteine residuals in CAP domain, and is BIC-localized in invasive hyphae and nuclei-localized when ectopically expressed in tobacco leaves and rice protoplasts. These results suggested that MoPce1 may bind novel ligand(s) rather than sterol. Indeed, we found that MoPce1 could interact with OsDi19-5, a transcription factor in rice. We inferred from these results that MoPce1 is required for pathogenicity by suppressing the immune response in rice, likely through the interaction with OsDi19-5.

The earthquake alert of the early warning systems is based on the delay that the S waves have in reference to the P waves and on the interpretation of the P waves’ specific parameters. One of the most used parameters for estimating the moment magnitude of an earthquake is the characteristic period measured in the first 3 seconds of the appearance of the P wave. The typical method determines the characteristic period in the time domain, based on the velocity wave and the displacement wave. In the present work, we present a method for estimating the frequency of the characteristic period. This method includes zero padding of the P wave sequence, conversion of the extended sequence from the time domain to the frequency domain, the identification of local frequency maxima and the calculation of the weighted average of the frequency based on the identified maxima. Tests conducted on synthetic signals, as well as standard deviation evaluation tests for simultaneous recordings on several stations, reveal better performance to the usual method.

Neuronal PAS domain protein 2 (NPAS2) is a hemeprotein comprising a basic helix-loop-helix domain (bHLH) and two heme-binding sites, the PAS-A and PAS-B domains. This protein acts as a pyridine nucleotide-dependent and gas-responsive CO-dependent transcription factor and is encoded by a gene whose expression fluctuates with circadian rhythmicity. NPAS2 can heterodimerize with ARNTL in the activating limb of the transcriptional/translational feedback loop operating the circadian clock circuitry. NPAS2 can functionally substitute for the core transcription factor and histone/protein acetylase CLOCK in the molecular clockwork endowing central oscillators in the suprachiasmatic nuclei of hypothalamus as well as in peripheral oscillators in the cell of other body tissues, such as the liver and kidney.

Lipases have tremendous potential for industrial use, particularly, those mostly active against water-insoluble substrates, such as triglycerides composed of long-chain fatty acids. However, in most cases, mutants often need to be constructed to achieve optimal performance for such substrates. Protein engineering techniques have been reported as strategies for improving lipase characteristics by introducing specific mutations in the cap domain of esterases or in the lid domain of lipases, or through lid domain swapping. Here, we have improved the lipase character of a lipase, retrieved from the Marine Metagenomics MarRef Database and assigned to the Actinoalloteichus genus (WP_075743487.1), through site-directed mutagenesis and by substituting its lid domain (FRGTEITQIKDWLTDA) by the one of Rhizopus delemar (previously Rhizopus oryzae) lipase (FRGTNSFRSAITDIVF). Results demonstrated that the redesigned mutants gain activity against bulkier triglycerides such as glyceryl tridecanoate and tridodecanoate, olive oil, coconut oil, and palm oil. The absence of a residue in the new lid, present in the original lid, appears to be a key aspect to the increase in lipase character, although full activity recovery is only obtained with lid swapping.

The inherent dependency of deep learning models to labeled data is a well-known problem and one of the barriers that slows down the integration of such methods into different fields of applied sciences and engineering, in which experimental and numerical methods can easily generate a colossal amount of unlabeled data. This paper proposes an unsupervised domain adaptation methodology that mimics the peer review process to label new observations in a different domain from the training set. The approach evaluates the validity of a hypothesis using domain knowledge acquired from the training set through a similarity analysis, exploring the projected feature space to examine the class centroid shifts. The methodology is tested on a binary classification problem, where synthetic images of cubes and cylinders in different orientations are generated. The methodology improves the accuracy of the object classifier from 60% to around 90% in the case of a domain shift in physical feature space without human labeling.

We employ another approach to quantize electromagnetic fields in the coordinate space, instead of the mode (or Fourier) space, such that local features of photons can be efficiently, physically, and more intuitively described. To do this, coordinate-ladder operators are defined from mode-ladder operators via the unitary transformation of systems involved in arbitrary inhomogeneous dielectric media. Then, one can expand electromagnetic field operators through the coordinate-ladder operators weighted by non-orthogonal and spatially-localized bases, which are propagators of initial quantum electromagnetic (complex-valued) field operators. Here, we call them QEM-CV-propagators. However, there are no general closed form solutions available for them. This inspires us to develop a quantum finite-difference time-domain (Q-FDTD) scheme to numerically time evolve QEM-CV-propagators. In order to check the validity of the proposed Q-FDTD scheme, we perform computer simulations to observe the Hong-Ou-Mandel effect resulting from the destructive interference of two photons in a 50/50 quantum beam splitter.

Ontology is a formalized representation of the problem area (PrA). Representation of the PrA in the form of an domain ontology is often used in the process of development of intelligent software systems and used as a knowledge base. The process of building an ontology is complex and requires an expert in the PrA. A large number of researchers are working to solve this problem. The basis of our approach is the use of a pipeline of different linguistic methods of text analysis. The set of rules developed by us is used to build an ontology based on the content analysis of a text resource. This article describes the method of building a domain ontology based on the linguistic analysis of content of text resources, presents an example of the proposed approach, and also presents the architecture of our pipeline.

OBJECTIVES: To assess the predictive value of serum trypsin and Trypsinogen Activation Peptide (TAP) for the severity of AP by means of a single center cohort study as well as a systematic review of the current literature. METHODS: The literature search was conducted using Medline (PubMed), EMBASE and the Cochrane Central Register. A total of 142 patients with acute pancreatitis (AP) were included in the cohort study and parameters of the revised Atlanta criteria of 2012 and the APACHE II were assessed. RESULTS: The review showed promising results for the predictive value of serum trypsinogen-2, but conflicting results for serum TAP and trypsin. In the cohort study, patients were observed for 4 days after diagnosis of AP: 9 patients had severe AP, 35 patients had moderate AP and 81 patients had mild AP. The ratio of the geometric mean of severe vs mild AP for trypsin was 0.72 (95% CI: 0.51-1.00), p=0.053 and for TAP 0.74 (95% CI: 0.54-1.01), p=0.055 respectively. CONCLUSION: The cohort study showed an inverse correlation of serum levels of TAP and trypsin with severity of AP. Serum TAP and trypsin have an inferior predictive value of severity of AP compared to the clinical APACHE II score.

A wide variety of bioactive peptides have been identified in the central nervous system and several peripheral tissues in the ascidian Ciona intestinalis type A (Ciona robusta). However, hemocyte endocrine peptides have yet to be explored. Here, we report a novel 14-amino acid peptide, CiEMa, that is predominant in the granular hemocytes and unilocular refractile granulocytes of Ciona. RNA-seq and qRT-PCR revealed the high CiEma expression in the adult pharynx and stomach. Immunohistochemistry further revealed the highly concentrated CiEMa in the hemolymph of the pharynx and epithelial cells of the stomach, suggesting biological roles in the immune response. Notably, bacterial lipopolysaccharide stimulation of isolated hemocytes for 1-4 hours resulted in increased CiEMa secretion. Furthermore, CiEMa-stimulated pharynx exhibited mRNA upregulation of the growth factor (Fgf3/7/10/22), vanadium binding proteins (CiVanabin1 and CiVanabin3), and forkhead and homeobox transcription factors (Foxl2, Hox3, and Dbx), but not antimicrobial peptides (CrPap-a and CrMam-a) or immune-related genes (Tgfbtun3, Tnfa, and Il17-2). Collectively, these results suggest that CiEMa plays roles in signal transduction involving tissue development or repair in the immune response, rather than in the direct regulation of immune-response genes. The present study identified a novel Ciona hemocyte peptide, CiEMa, providing insights into the molecular and functional diversity of the immune response in chordates.

China faces a persistent deficiency in feed protein resources. Enhancing the utilization efficiency of indigenous feed protein resources emerges as a viable strategy to alleviate the current deficit in protein feed supply. Corn gluten meal (CGM), characterized by high proportion of crude protein and glutamine, is predominantly employed in animal feed. Nonetheless, the water-insolubility of CGM protein hampers its protein bioavailability when utilized as feed material. This study aimed to augment protein bioavailability, liberate glutamine peptides from CGM, and produce gluta-mine-enriched CGM fermented feed. We executed a co-fermentation protocol using Bacillus subtilis A5, Lactobacillus 02002, and acid protease to generate the CGM fermented feed. Subsequent in vivo experiment with broilers were conducted to assess the efficacy of the fermented product. Findings revealed that the soluble protein, glutamine, small peptides, and lactic acid contents in the fer-mented feed increased by 69.1%, 700%, 47.6%, and 125.9%, respectively. Incorporating CGM fermented feed into the diet markedly enhanced the growth performance and intestinal health of broilers, positively modulated the cecal microbiota structure, and augmented the population of beneficial bacteria, specifically Lactobacillus. These results furnish both experimental and theoretical foundations for deploying CGM fermented feed as an alternative protein feed resource.

Background: The number of people with type 2 diabetes is increasing daily, and therefore effective therapy is needed to successfully regulate glycemia and reduce the risk of associated complications. Recently, an oral formulation of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide has become available. Therefore, the aim of our study was to compare the effectiveness of the new oral formulation and the existing injectable formulation of semaglutide in terms of glycemic and body weight control in a real-world setting. Patients and methods: This was a single-center retrospective observational study conducted at the Rijeka Clinical Hospital Centre. A total of 106 patients with inadequately controlled type 2 diabetes (HbA1 ≥ 7%) on different oral or basal insulin supported oral therapy were recruited from the diabetes outpatient clinic, and data from electronic medical records were retrospectively collected and analyzed from May 2021 to November 2022. All subjects were GLP-1 RA naive and consequently prescribed 0.5 or 1.0 mg once weekly injectable semaglutide (IS) or 7 mg or 14 mg once daily oral semaglutide (OS) for at least 6 months. Glycated hemoglo-bin (HbA1c), body weight, and body mass index (BMI) were assessed prior to semaglutide administration and after a 6-month follow-up period. The primary endpoint was the change from baseline in HbA1c, and sec-ondary endpoints were the change in body weight and the proportion of participants with a reduction in body weight of ≥ 5% and ≥ 10%, respectively, 6 months after the initiation of semaglutide treatment. Results: At 6-month follow-up, no significant difference was observed between the two formulations in terms of HbA1c reduction (IS -1.1% vs OS -1.4%, p=0.126) and weight loss (IS -6.50 kg vs OS -5.90 kg, p=0.714). Exactly the same proportion of participants in both groups achieved a weight loss of ≥ 5% (56.7%, n=30). A weight loss ≥ 10% was observed in 20.7% (n=11) of participants administered IS and 15.1% (n=8) of participants adminis-tered OS, respectively (p=0.454). Conclusion: In a real-world setting, oral semaglutide as add-on therapy to ongoing antihyperglycemic treatment in patients with inadequately controlled type 2 diabetes who had not previously received GLP-1 RA demonstrated the same effectiveness as injectable semaglutide in terms of gly-cemic control and weight loss after 6 months of treatment.

Antimicrobial peptides (AMPs) can directly kill Gram-positive bacteria, Gram-negative bacteria, mycobacteria, fungi, enveloped viruses and parasites. At sublethal concentrations some AMPs and also conventional antibiotics can stimulate bacteria response to increase their resilience, also called the hormetic response. That can include stimulation of growth, mobility, and biofilm production. Here, we have discovered AMPs that stimulate the growth of certain mycobacteria. Peptide 14 for example showed growth stimulating effect on M. tuberculosis, M. bovis, M. avium subsp. paratuberculosis (MAP), M. marinum, M. avium-intracellulare, M. celatum and M. abscessus. The effect was more pronounced at low bacterial inocula. The peptides induce a faster transition from the lag phase to the log phase and keep the bacteria longer in the log phase before entering the stationary phase compared to non treated control. In some cases, an increase in the division rate was observed. An initial screen using MAP and a collection of 75 peptides revealed 13 peptides with a hormetic effect. For M. tuberculosis a collection of 25 artificial peptides were screened and 9 were found to reduce the time to positivity (TTP), improving growth. A screen of 43 naturally occurring peptides, 11 fragments of naturally occurring peptides and 5 designed peptides, all taken from the APD3, identified a further 44 peptides that also lowered TTP by at least 5%. Lasioglossin LL-III (Bee) and Ranacyclin E (Frog) were the most active natural peptides, the human cathelicidin LL37 fragment GF-17 and a porcine cathelicidin protegrin-1 fragment was the most active fragment of naturally occurring peptides. Peptide 14 showed growth-stimulating activity between 50 ng/ml and 10 µg/ml whereas the stability-optimised peptide 14D had a narrow activity range of 0.1 - 1 µg/ml. Peptides identified in this study are now part of novel products improving the diagnosis of mycobacteria in humans and animals.

CC chemokine receptor 6 (CCR6) is a member of the G protein-coupled receptor (GPCR) family that is highly expressed in B lymphocytes, effector and memory T cells, regulatory T cells, and immature dendritic cells. CCR6 has been revealed to have important functions in many pathological conditions, such as cancer, intestinal bowel disease, psoriasis, and autoimmune diseases. The only CCR6 chemokine ligand, CC motif chemokine ligand 20 (CCL20), is also involved in pathogenesis by interacting with CCR6. The CCL20/CCR6 axis is drawing attention as an attractive therapeutic target for various diseases. In this study, we developed novel monoclonal antibodies (mAbs) against human CCR6 (hCCR6) using the peptide immunization method, which are applicable to flow cytometry and immunohistochemistry. The established anti-hCCR6 mAb, clone C6Mab-19 (mouse IgG1, kappa), reacted with hCCR6-overexpressed Chinese hamster ovary-K1 (CHO/hCCR6), HepG2 (human liver carcinoma), and HuH-7 (human differentiated hepatoma) cells in flow cytometry. The dissociation constant (KD) of C6Mab-19 was determined as 3.0 × 10−10 M for CHO/hCCR6, 6.9 × 10−10 M for HepG2, and 1.8 × 10−10 M for HuH-7. Thus, C6Mab-19 could bind to exogenously and endogenously expressed hCCR6 with extremely high affinity. Furthermore, C6Mab-19 could stain formalin-fixed paraffin-embedded lymph node tissues from a patient with non-Hodgkin lymphoma by immunohistochemistry. Therefore, C6Mab-19 is suitable for detecting hCCR6-expressing cells and tissues, and could be useful for pathological analysis and diagnosis.

Plant diseases are among the major factors affecting plant productivity. Biological control of plant diseases is preferred over chemical control as it is environment-friendly, cost-effective, and sustainable. Among many microbes capable of providing biological control of plant diseases, probiotic Bacillus species are most promising as they can survive in adverse conditions, provide plants with a wide range of benefits including protection from phytopathogens. Wheat blast caused by Magnaporthe oryzae Triticum pathotype (MoT) has emerged as a potential threat to global wheat production. Due to unreliability of fungicides and limited cultivar resistance, we aimed to screen and identify potential antagonist bacteria collected from internal tissues of rice and wheat seeds to determine their in vitro and in vivo inhibitory effects against MoT. Dual culture and seedling assays were performed to evaluate the efficacy of probiotic bacteria. Out of 170 bacterial isolates, three bacteria (BTS-3, BTS-4, and BTLK6A) were screened as potential antagonists against MoT in vitro. Artificial inoculation at the seedling stage showed that the isolates BTS-4, BTS–3, and BTLK6A reduced 89, 88, and 85% of wheat blast disease severity, respectively, compared to mock-inoculated control. The bacterial isolates were identified as Bacillus subtilis (BTS-3) and B. velezensis (BTS-4 and BTLK6A) through genome phylogeny. The whole genome sequence of these three bacterial strains decoded a number of orthologs to intrinsic genes of antimicrobial peptides, antioxidant defense enzymes, cell wall degrading enzymes, compounds involved in the induction of systemic resistance (ISR) in host plants, and volatile compounds to make them promising biologicals to control MoT in wheat. Combined data of in vitro and in vivo along with genome analysis suggest that Bacillus spp. suppress the destructive wheat blast disease likely through antibiosis and ISR in the host plants. Further field evaluation and characterization of antimicrobial compounds are needed for a better understanding of the mode of action and practical recommendation of these bacteria for wheat blast control in the farmers’ fields.

Advanced derivatives of the CXCR4 antagonist EPI-X4 have shown therapeutic efficacy upon topical administration in animal models of asthma and dermatitis. Here, we studied plasma stability of the EPI-X4 lead compounds WSC02 and JM#21, using mass spectrometry to monitor the chemical integrity of the peptides and a functional fluorescence-based assay that determines peptide function in a CXCR4-antibody competition assay. Although mass spectrometry revealed a very rapid disappearance of both peptides in human plasma within seconds, the functional assay revealed a significantly higher half-life of 9 minutes for WSC02 and 6 minutes for JM#21, respectively. Further analyses demonstrated that WSC02 and JM#21 interact with low molecular weight plasma components and serum albumin. Albumin binding is mediated by the formation of a disulfide bridge between Cys10 in the EPI-X4 peptides and Cys34 in albumin. These covalently linked albumin-peptide complexes have a higher stability in plasma as compared to the non-bound peptides and retain the ability to bind and antagonize CXCR4. Remarkably, chemically synthesized albumin-EPI-X4 conjugates coupled by non-breakable bonds have a drastically increased plasma stability of over 2 hours. Thus, covalent coupling of EPI-X4 to albumin in vitro before administration or in vivo post administration may significantly increase the pharmacokinetic properties of the new class of CXCR4 antagonists.

The association of the APOE4 (vs APOE3) isoform with an increased risk of Alzheimer’s Disease (AD) is unequivocal, but the underlying mechanisms remain incompletely elu-cidated. A prevailing hypothesis incriminates the impaired ability of APOE4 to clear neurotoxic amyloid-β peptides (Aβ) from the brain as the main mechanism linking apolipoprotein isoform to disease aetiology. APOE protein mediates lipid transport both within the brain and from the brain to the periphery, suggesting that lipids may be potential co-factors in APOE4-associated physiopathology. The present study reveals several alterations in pathways of lipid homeostasis in the brains of mice expressing the human APOE4 versus APOE3 isoform. Carriers of APOE4 had deficient cholesterol turnover, an imbalance in the ratio of specific classes of phospholipids, lower levels of phosphatidylethanolamines bearing poly-unsaturated fatty acids and an overall eleva-tion in levels of monounsaturated fatty acids. These modifications in lipid homeostasis were related with increased production of Aβ peptides as well as augmented levels of tau and phosphorylated tau in primary neuronal cultures. This suite of AP-OE4-associated anomalies in lipid homeostasis and neurotoxic protein levels may be related to the accrued risk for AD in APOE4 carriers and provides novel insights into potential strategies for therapeutic intervention.

Gap junctions (GJ) and connexins play integral roles in cellular physiology and have been found to be involved in multiple pathophysiological states from cancer to cardiovascular disease. Studies over the last 60 years have demonstrated the utility of altering GJ signaling pathways in experimental models, which has led to them being attractive targets for therapeutic intervention. A number of different mechanisms have been proposed to regulate GJ signaling, including channel blocking, enhancing channel open state, and disrupting protein-protein interactions. The primary mechanism for this has been through the design of numerous peptides as therapeutics, that are either currently in early development or are in various stages of clinical trials. Despite over 25 years of research into connexin targeting peptides, the overall mechanisms of action are still poorly understood. In this overview, we discuss published connexin targeting peptides, their reported mechanisms of action and the potential for these molecules in the treatment of disease.

Sexually transmitted infections (STIs) such as Gonorrhea is associated with serious morbidity and mortality rates in the world considering the multiple virulence factors possessed. The disease is manifested as salpingitis, pelvic inflammatory disease (PID), and bacteremia and is controlled by macrophages, dendritic cells, neutrophils, T cells, epithelial cells and cytokines. Dihydroliponamide acetyltransferase, a component of the mitochondrial pyruvate complex can be used as immunogenic target. Recent changes in the strain allowed the bacteria to acquire resistance against antibiotics.Vaccination remains an alternative to prevention against the disease. This study predicts an effective epitope-based vaccine against dihydrolipoamide acetyltransferase of Neisseria Gonorrhea using immunoinformatics approaches. Sequences retrieved from NCBI were passed on several prediction tests to analyze for possible B-cell, T-cell MHC class I epitopes and class II. Two epitopes showed high binding affinity for B-cells, while thirteen epitopes showed high binding affinity for MHCI and forty-five for MHCII. A population coverage of 100% for combined MHC I and II dictates the huge number of individuals who will benefit from formulating the vaccine. We recommend invivo and invitro studies to prove our prediction results.

By manipulating the various physico-chemical properties of amino acids, design of peptides with specific self-assembling properties has been emerging since more than a decade. In this context, short peptides possessing detergent properties (so-called “peptergents”) have been developed to self-assemble into well-ordered nanostructures that can stabilize membrane proteins for crystallization. In this study, the peptide with “peptergency” properties, called ADA8 extensively described by Zhang et al., is studied by molecular dynamics for its self-assembling properties in different conditions. In water, it spontaneously forms beta sheets with a β barrel-like structure. We next simulated the interaction of this peptide with a membrane protein, the bacteriorhodopsin, in the presence or absence of a micelle of dodecylphosphocholine. According to the literature, the peptergent ADA8 is thought to generate a belt of β structures around the hydrophobic helical domain that could help stabilize purified membrane proteins. Molecular dynamics is here used to challenge this view and to provide further molecular details for the replacement of detergent molecules around the protein. To our best knowledge, this is the first molecular mechanism proposed for ''peptergency''. In addition, our calculation approach should serve as a predicting tool for the design of beta peptergent with diverse amphipathic properties.

Autosomal dominant isolated foveal hypoplasia (FVH1) is a rare condition of foveal hypoplasia (FH) that lacks any other ocular manifestations. FVH1 is associated with hypomorphic mutations in the PAX6 gene. We report our findings in 17 patients with PAX6 mutations associated with FVH1 or FH with aniridia and corneal opacities. Patients with three mutations, p.V78E, p.V83F and p.R128H, in the C-terminal subdomain of the paired domain (CTS) consistently had severe FH. Luciferase assays indicated that the transcriptional activities of these mutations were significantly reduced comparable to that with truncation mutation of p.G65Rfs*5. Patients with p.P20S in the N-terminal subdomain of the paired domain, and a patient with p.N365K in the proline-serine-threonine-rich domain (PSTD) had mild FH. A patient with p.Q255L in the homeodomain had severe FH. The P20S and Q255L mutants did not affect the transcriptional activity. Mutant N365K had a retained DNA binding activity but a reduced transcriptional activity due to a low PSTD transactivation. These findings demonstrated that mutations associated with FVH1 underlie a functional divergence between DNA binding ability and transcriptional activity. Broadly distributed mutations in the PAX6 gene, not limited to the CST region, were responsible for FVH1.

Peptides are promising drug development frameworks thanks to their high target selectivity, tolerability and relatively low production cost. However, despite the fact that several thousand potentially therapeutic peptides reported, only sixty have arrived at the market. This concerning low proportion is partially explained by undesired properties such as peptide-induced hemolytic activity. Hence, we aim to get a better insight into the chemical space of hemolytic peptides using a novel approach based on network science and interactive data mining as an alternative to design more effective peptide drugs with low hemolytic activity. Metadata networks (METNs) were used to characterize and find general patterns associated to hemolytic peptides, whereas Half-Space Proximal Networks (HSPNs), created using five different two-way dissimilarity measures, represented the hemolytic peptide space. Then, using the best candidate HSPNs, we extracted various scaffolds that capture information of almost all the chemical space but avoiding peptide overrepresentation. Such scaffolds can have many applications, such as training accurate ML-based prediction models, constructing one-class multi-query similarity searching models and characterizing the diversity of hemolytic peptides using a manageable set of peptides. Finally, by means of an alignment-free approach, we reported 47 putative hemolytic motifs, which might provide hints about the mechanisms of hemolysis and can also be used as toxic signatures when developing novel peptide-based drugs.

Liver related diseases are the 3rd leading causes (9.3%) of mortality in type 2 diabetes mellitus (T2DM) in Japan. T2DM is closely associated with nonalcoholic fatty liver disease (NAFLD) which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. There are no established pharmacotherapies for NASH patients with T2DM. Though vitamin E is established as a 1st line agent in NASH without T2DM, its efficacy was recently denied in NASH with T2DM. The effects of pioglitazone on NASH histology with T2DM have extensively been established, but several concerns exist such as body weight gain, fluid retention, cancer incidence, and bone fracture. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium/glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH　(LEAN study, LEAD trial, and E-LIFT study). Among a variety of SGLT2 inhibitors, dapagliflozin have already entered phase 3 trials (DEAN study). A key clinical question is what kinds of anti-diabetic drugs are the most appropriate for the treatment of NASH to prevent progression of hepatic fibrosis resulting in HCC/liver-related mortality without increasing risk at cardiovascular or renal events. The combination therapies such as glucagon receptor agonist/GLP-1 or gastrointestinal peptide /GLP-1 will be under development. This review focuses on antidiabetic agents and future perspectives on the view of the treatment of NAFLD with T2DM.

The log data generated during the operation of a software system contains information about the system, and using logs for anomaly detection can detect system failures in a timely manner. Most of the existing log anomaly detection methods are specific to a particular system, have cold start problems, and are sensitive to updates in log format. In this paper, we propose a log anomaly detection method LogBD based on pre-training model and domain adaptation, which uses the pre-training model BERT to learn the semantic information of logs, and can solve the problems caused by multiple meaning words and log statement updates. An anomaly detection method LogBD based on distance to determine anomalies is constructed based on domain adaptation, using TCN networks to extract common features of different system logs and map them to the same hypersphere space. Finally, experiments are conducted on two publicly available datasets to evaluate the method, and the experimental results show that the method can better solve the log instability problem and has some improvement in the cross-system log anomaly detection effect.

Eukaryotic cells contain membranes with various curvatures, from the near-plane plasma membrane to the highly curved membranes of organelles, vesicles, and membrane protrusions. These curvatures are generated and sustained by curvature-inducing proteins, peptides, and lipids, and describing these mechanisms is an important scientific challenge. In addition to that, some molecules can sense membrane curvature and a thereby be trafficked to specific locations. The description of curvature-sensing is another fundamental challenge. Curved lipid membranes and their interplay with membrane-associated proteins can be investigated with molecular dynamics (MD) simulations, given the right tools. Various methods for simulating curved membranes with MD are discussed here, including tools for setting up simulation of vesicles, and methods for sustaining membrane curvature. The latter are divided into methods that exploit scaffolding virtual beads, methods that use curvature-inducing molecules, and methods applying virtual forces. The variety of simulation tools allow the researcher to closely match the conditions of experimental studies of membrane curvatures.

We are of the opinion that during the design of a binary classifier one ought to consider adding an “I don’t know” answer. We provide the case for the introduction of this third category when a human needs to make a decision based on the answer from a binary classifier. We discuss the costs and potential benefits of its introduction. Colloquially, we have used the term “I don’t know”, but formally we refer to it as NotAvailable. A procedure to define NotAvailable predictions in binary classifiers, called all leave-one-out models (ALOOM), is presented as proof of the concept. Furthermore, we discuss the potential benefits of applying ALOOM in real life applications.

It is widely, but not universally, believed that the lipids of the plasma membrane are not uniformly distributed, but that "rafts'' of sphingolipids and cholesterol float in a "sea'' of unsaturated lipids. The physical origin of such heterogeneities is often attributed to a phase coexistence between the two different domains. We argue that this explanation is untenable for several reasons. Further we note that the results of recent experiments are inconsistent with this picture. However they are quite consistent with an alternate explanation, namely that the plasma membrane is an emulsion of the two kinds of regions. To show this, we briefly review a simplified version of this theory and its phase diagram. We also explicate the dependence of the predicted domain size on four physical parameters. Among them are the spontaneous curvature of the membrane and its bending modulus and surface tension. Taking values of the latter two from experiment, we obtain domain sizes for several different cell types that vary from 58 to 88 nm.

Domain walls were studied for permalloy wires with different depth trenches (500 nm wide, 30 nm thick, 7.5 µm long, the depth of the trench was 0, 4, 5, 8, 10, 12 and 15nm). Permalloy (Ni80Fe20) wires were fabricated by electron beam lithography and Ar ion milling. When the depth of trench is smaller than 12 nm, the switching field (Hs) is increasing with the deeper trench. However, the depth of trench is bigger than half depth of thickness, the Hs is decreasing with the deeper trench. We believed that Hs increased as the trench depth increased was because the magnetic diploes force increased between the magnetic poles on two sides of the trench. The domains of the wires were divided by the trenches and the domain walls were pinned on the trenches these were confirmed by magnetic force microscopy images.

This algorithm is designed to perform Discrete Fourier Transforms (DFT) to convert temporal data into spectral data. This algorithm obtains the Fourier Transforms by studying the Coefficient of Determination of a series of artificial sinusoidal functions with the temporal data, and normalizing the variance data into a high-resolution spectral representation of the time-domain data with a finite sampling rate. What is especially beneficial about this DFT algorithm is that it can produce spectral data at any user-defined resolution.

Plastic contamination of small dimensions (

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in cattle raised in North America. At the feedlot, cattle are subject to metaphylactic treatment with macrolides to prevent BRD, a practice that may promote antimicrobial resistance and has resulted in an urgent need for novel strategies. Mannheimia haemolytica is one of the major bacterial agents of BRD. The inhibitory effects of two amphipathic, α-helical (PRW4, WRL3) and one β-sheet (WK2) antimicrobial peptides were evaluated against multidrug-resistant (MDR) M. haemolytica isolated from Alberta feedlots. WK2 was not cytotoxic against bovine turbinate (BT) cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. All three peptides inhibited M. haemolytica, with WK2, being the most efficacious against multiple isolates. At 8-16 µg/ml, WK2 was bactericidal against Mh 330 in broth and at 32 µg/ml in the presence of BT cells, reduced the population by 3 logs CFU/ml without causing cytotoxic effects. The membrane integrity of Mh 330 was examined using NPN (1-N-phenylnaphthylamine), and ONPG (o-Nitrophenyl β-D-galactopyranoside) with both the inner and outer membranes being compromised. Thus, WK2 may be a viable alternative to the use of macrolides as part of BRD prevention and treatment strategies.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that acts on the pancreas to increase insulin and decrease glucagon secretion. Albuminuria is the pivotal marker for diabetic nephropathy, which is the leading microvascular complication of diabetes mellitus. Most of the previous studies mainly focused on the clinical trials of the therapeutic renal protective effect after administration of GLP-1 receptor agonists (GLP-1 RAs), not prior to administration. Therefore, this study aimed to investigate the association between fasting plasma GLP-1 levels and albuminuria before GLP-1 RA administration. A cross-sectional study was designed to evaluate the association between fasting plasma GLP-1 levels and albuminuria in patients with type 2 diabetes mellitus (T2DM). A total of 68 T2DM participants were analyzed from the data at Wonkwang University Hospital in Iksan, Korea. Logistic regression analysis was performed to evaluate the odds ratio (OR) and 95% confidence interval (CI) of the incidence of albuminuria between the GLP-1 low group (Group L) and the high group (Group H). The OR (95% CI) for the incidence of albuminuria comparing the Group L with the Group H of fasting plasma GLP-1 levels was 3.410 (1.160-10.023), p = 0.026 after adjustment for age, gender, fasting plasma glucose, HbA1c, C-peptide, the use of ACE inhibitors or ARBs, SGLT-2 inhibitors, and DPP-4 inhibitors. As a continuous variable, the OR (95% CI) for the incidence of albuminuria associated with the reduction of each 1 pmol/L in fasting plasma GLP-1 levels was 1.673 (1.173-1.870), p = 0.018, after full adjustment. This study showed the negative association between fasting plasma GLP-1 levels and the incidence of albuminuria in Korean patients with T2DM, before GLP-1 RA administration. This result suggests that endogenous GLP-1 may play a role in attenuating albuminuria.

In our previous work, we demonstrated the potential of the amphiphilic cyclic peptide [W4R4] as a promising antimicrobial agent. The extensive data accumulated on the antimicrobial activity of this peptide and its homologs presented an opportunity to unravel the molecular mechanisms governing their action and establish crucial structure-activity relationships (SAR). To achieve this, we employed a comprehensive approach involving peptide synthesis, in vitro biological testing, and molecular modeling to systematically analyze the SAR of a series of cyclic peptides derived from the [W4R4] scaffold. Minimal modifications were introduced to the original peptide by incorporating either one aromatic hydrophobic residue (W) or one polar positively charged residue (R) while maintaining the sequential W/R arrangement. Additionally, we introduced an "intermediate" substitution by incorporating 2,5-diketopiperazine (DKP), possessing both aromatic and polar properties, into the macrocycle [W4R4] between the W and R residues. Notably, this study marked the first synthesis and evaluation of the [W4R4(DKP)] peptide. Structural, dynamic, hydrophobic, and membrane-binding properties of four cyclic peptides ([W4R4], [W5R4], [W4R5], [W4R4(DKP)]) were explored using molecular dynamics simulations within a DOPC/DOPG lipid bilayer that mimics the bacterial membrane. The results obtained revealed distinct SAR profiles for all peptides, enabling the establishment of correlations between their antimicrobial activity and structural/dynamic parameters. These parameters included the degree of conformational plasticity, the depth of immersion into the bi-layer, and the population of the membrane binding mode characterized by the embedding of the hydrophobic peptide pattern into the acyl chain region of lipids. In particular, the peptide [W4R5] exhibited an optimal "activity/binding to the bacterial membrane" pattern. This work highlights the significance of our multidisciplinary approach in efficiently deciphering finely regulated SAR profiles for a series of homologous peptides with diverse activities. Furthermore, this research provides a solid foundation for the rational design of novel antimicrobial peptides.

Regulatory T cell master transcription factor, Forkhead box P3 (Foxp3) has been detected in cancer cells, but its role in breast tumor pathogenesis remains controversial. Here we assessed Foxp3 tumor intrinsic effects in experimental breast cancer using a Foxp3 binder peptide (P60) that impairs Foxp3 nuclear translocation. Cisplatin upregulated Foxp3 expression in HER2+ and triple negative breast cancer (TNBC) cells. Foxp3 inhibition with P60 enhanced chemosensitivity and reduced cell survival and migration in human and murine breast tumor cells. We also developed an adenoviral vector encoding P60 (Ad.P60) that efficiently transduced breast tumor cells, reduced cell viability and migration, and improved the cytotoxic response to cisplatin. Conditioned medium from transduced breast tumor cells contained lower levels of IL-10 and improved the activation of splenic lymphocytes. Intratumor administration of Ad.P60 in breast tumor-bearing mice significantly reduced tumor infiltration of Tregs, delayed tumor growth and inhibited the development of spontaneous lung metastases. Our results suggest that Foxp3 exerts protumoral intrinsic effects in breast cancer cells, and that gene therapy-mediated blockade of Foxp3 could constitute a therapeutic strategy to improve the response of these tumors to standard treatment.

The protein extract of Ulva australis hydrolyzed with alcalase and flavourzyme investigated multi-functional properties, including total antioxidant capacity (TAC), collagenase inhibitory and antibacterial activities. The #5 fraction (SP5) and #7 fraction (SP7) of U. australis hydrolysate from cation-exchange chromatography showed significantly high TAC, collagenase inhibitory and antibacterial effects against Propionibacterium acnes, and only Q3 fraction from anion-exchange chromatography showed high multi-functional activities. The eight peptides among 42 peptides identified by MALDI-TOF/MS and Q-TOF/MS/MS were selected from the results to screen molecular docking on target proteins, and were synthesized. Thr-Gly-Thr-Trp (TGTW) showed ABTS [2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)] radical scavenging activity. Effect TAC as Trolox equivalence was dependent on the concentration of TGTW. The Asn-Arg-Asp-Tyr (NRDY) and Arg-Asp-Arg-Phe (RDRF) possessing collagenase inhibitory activity increased according to the increase of concentration and the IC50 values of them were 0.95 mM and 0.84 mM, respectively. Peptides, RDRF and His-Ala-Val-Tyr (HAVY) showed anti-P. acnes effects with IC50 values of 8.57 mM and 13.23 mM, respectively. These results suggest that the U. australis hydrolysate could be a resource for the application of effective nutraceuticals and cosmetics.

Background and Objectives: A novel synthetic self-assembling peptide, PuraStat, has been introduced as a hemostatic agent. This case series aimed to evaluate the clinical efficacy of PuraStat for gastrointestinal bleeding during emergency endoscopy. Cases: Twenty-five patients with gastrointestinal bleeding who had undergone emergency endoscopy with PuraStat between August 2021 and December 2022 were retrospectively examined. Six patients were receiving antithrombotic agent, and ten patients with refractory gastrointestinal bleeding had undergone at least one endoscopic hemostatic procedure. The breakdown of bleeding was gastroduodenal ulcer/erosion in 12 cases, bleeding after gastroduodenal or colorectal endoscopic resection in 4 cases, rectal ulcer in 2 cases, postoperative anastomotic ulcer in 2 cases, and gastric cancer, diffuse antral vascular ectasia, small intestinal ulcer, colonic diverticular bleeding, and radiation proctitis in each case. The method of hemostasis was only PuraStat application in six cases, and hemostasis in combination with high-frequency hemostatic forceps, hemostatic clip, argon plasma coagulation, and hemostatic agents (i.e. thrombin) in the remaining cases. Rebleeding was observed in three cases. Hemostatic efficiency was observed in 23 cases (92%). Conclusions: PuraStat has the expected hemostatic effect on gastrointestinal bleeding during emergency endoscopy. The use of PuraStat should be considered in emergency endoscopic hemostasis of gastrointestinal bleeding.

Ion-complementary self-assembling peptides have been studied in many fields for their distinct advantages mainly due to their self-assembly properties. However, their shortcomings, such as insufficient specific activity and poor mechanical properties, also limited their application. For better and wider application of this kind of promising biomaterials, ion-complementary self-assembling peptides can be modified with their self-assembly properties not being destroyed to the greatest extent. The modification strategies were reviewed by taking RADA16-Ⅰ as an example. For the insufficient specific activity, RADA16-Ⅰ can be structurally modified with active motifs derived from the active domain of the extracellular matrix or other related active factors. For weak mechanical properties, materials with strong mechanical properties or materials that can undergo chemical crosslinking were used to mix with RADA16-Ⅰto enhance the mechanical properties of RADA16-Ⅰ. To improve the performance of RADA16-Ⅰ as drug carriers, appropriate adjustment of the RADA16-Ⅰ sequence and/ or modification of the RADA16-Ⅰ-related delivery system with polymer materials or specific molecules can be considered to achieve sustained and controlled release of specific drugs or active factors. The modification strategies reviewed in this paper may provide some references for the further basic research and clinical application of ion-complementary self-assembling peptides and their derivatives.

Ferulic acid (FA) is known for its excellent antioxidant properties that can provide a lot of health benefits. One of its drawbacks is being unstable under UVA light that limits its potency. In this study, new peptides LW2 (QNKRFYFRKNQ) and CW2 (a cyclic form of LW2) have been designed based on bovine serum albumin site ⅡA conformation. UVA irradiation experiment was performed to investigate the protective ability of these peptides towards FA against UVA damage. The percentage of FA remaining under UV irradiation by the protection of CW2 and LW2 was 83%, 76% respectively. The results showed the importance of the cationic residues and hydrophobic residues included in the peptide sequences. Moreover, the cyclic rigid structure showed more protecting ability over that of the linear counterpart.

Active films based on carboxymethyl chitosan incorporated corn peptide were developed. Physicochemical properties of the films, including thickness, opacity, moisture content, color, mechanical properties, water vapor permeability, and oil resistance, were measured. Biological activities of the films, including the antioxidant and antibacterial activities, were characterized in terms of 2, 2-diphenyl-1-picrylhydrazyl free radical scavenging activity, reducing power, the total antioxidant activity, and the filter disc inhibition zone method. The results indicated that the incorporation of corn peptide caused interactions between carboxymethyl chitosan and corn peptide in Maillard reaction and gave rise to the films light yellow appearance. Compared with the Control, the degree of glycosylation, browning intensity, thickness, opacity, tensile strength, antioxidant activity, and antibacterial activity of films were increased, but the elongation, vapor permeability, and oil resistance of films were decreased. The films based on corn peptide and carboxymethyl chitosan can potentially be applied to food packaging.

A facile solid-phase synthetic method for incorporating the imidazoline ring motif, a surrogate for a trans peptide bond, into bioactive peptides is reported. The example described is the synthesis of an imidazoline peptidomimetic analog of an insect pyrokinin neuropeptide via a cyclization reaction of an iminium salt generated from the preceding amino acid and 2,4-diaminopropanoic acid (Dap).

Quantum leaps advances in the single-molecule investigative science have been made possible over the past decades through the implication of nanopores, as versatile components on dedicated biosensors. Here, we employed the nanopore-tweezing technique to capture amino acid-functionalized, peptide-nucleic acids (PNA) with -hemolysin-based nanopores, and correlate the ensuing stochastic fluctuations of the ionic current through the nanopore with the composition and order of bases in the PNAs primary structure. We demonstrate that while the system enables detection of distinct bases on homopolymeric PNA or triplet bases on heteropolymeric strands, it also reveals rich insights into the conformational dynamics of the entrapped PNA within the nanopore, relevant for perfecting the recognition capability single-molecule sequencing.

In a large variety of organisms, antimicrobial peptides (AMPs) are primary defences against pathogens. BP100 (KKLFKKILKYL-NH2), a short, synthetic, and cationic AMP, is active against bacteria and displays low toxicity towards eukaryotic cells. BP100 acquires an α-helical conformation upon interaction with membranes and increases membrane permeability. Despite the volume of information available, the mechanism of action of BP100, the selectivity of its biological effects, and its applications are far from consensual. In this work, we synthesized a fluorescent BP100 analog containing naphthalimide linked to its N-terminal end, Napht-BP100 (Napht-AAKKLFKKILKYL-NH2). The fluorescence properties of naphthalimides, especially their spectral sensitivity to microenvironment changes, are well established, and their biological activities against different types of cells are known. A wide variety of techniques were used to demonstrate that a-helical Napht-BP100 was bound and permeabilized POPC and POPG LUV. Napht-BP100, different from that observed for BP100, was bound to, and permeabilized POPC LUV. With zwitterionic (POPC) and negatively charged (POPG) containing LUVs, membrane surface high peptide/lipid ratios triggered complete disruption of the liposomes in a detergent-like manner. This disruption was driven by charge neutralization, lipid aggregation, and membrane destabilization. Napht-BP100 also interacted with double-stranded DNA, indicating that this peptide could also affect other cellular processes in addition to membrane destabilization. Napht-BP100 showed superior antibacterial activity, increased hemolytic activity compared to BP100, and may constitute an efficient antimicrobial agent for dermatological use. By conjugating BP100 and naphthalimide antimicrobial properties, Napht-BP100 was bound more efficiently to the bacterial membrane and could destabilize the membrane and enter the cell by interacting with its cytoplasm- exposed DNA.

In this report, we demonstrate that it is possible to design epitope-based peptide vaccine candidates to counteract the novel China coronavirus (2019-nCoV) by using an approach similar to the one used in cancer neoantigen vaccination therapy. We identified multiepitope peptide vaccine candidates against 2019-nCov that can potentially trigger both CD4⁺ and CD8⁺ T cell immune response with increased efficiency due to the presence of CD4⁺ and CD8⁺ T cell epitopes and a cathepsin-sensitive linker. Furthermore, we suggest that the peptide design strategy should incorporate population-specific HLA alleles in order to optimize binding specificity of the peptides. We refer to this as populationalized vaccinomics.

Development of novel anti-cancer peptides requires a rapid screening process which can be accelerated by using appropriate in vitro tumor models. Breast carcinoma tissue is a three dimensional (3D) microenvironment, which contains a hypoxic center surrounded by dense proliferative tissue. Biochemical clues provided by such 3D cell mass cannot be recapitulated in conventional 2D culture systems. In this experiment, we evaluate the efficacy of the sandalwood peptide, cyclosaplin on established in vitro 3D silk breast cancer model using invasive MDA-MB-231 cell line. The anti-proliferative effect of the peptide on 3D silk tumor model is monitored by alamar blue assay, with conventional 2D culture as control. The proliferation rate, glucose consumed, LDH, and MMP-9 activity of Human breast cancer cells are higher in 3D constructs compared to 2D. A higher concentration of drug is required to achieve 50% cell death in 3D culture than 2D cultures. The cyclosaplin treated MDA-MB-231 cells showed significant decrease in MMP-9 activity in 3D constructs. Microscopic analysis revealed the formation of cell clusters evenly distributed in the scaffolds. The drug treated cells were less in number, smaller and showed unusual morphology. Overall, these findings indicate the role of cyclosaplin as a promising anti-cancer therapeutics.

2017 was an excellent year in terms of new drugs (chemical entities and biologics) approved by the FDA, with a total of forty-six. In turn, one of the highlights was the number of peptides (six) included in this list. Here, the six peptides are analysed in terms of chemical structure, synthetic strategy used for their production, source, biological target, and mode of action.

Smart sensors based on graphene field effect transistor and biologically receptors are regarded as a promising nanomaterial that could be the basis for future generations of selective real-time monitoring of target analytes and smaller electronics. So the purpose of this paper is to provide details a real-time and selective explosive sensor based on GFETs and PDA-based lipid membranes coupled with biologically inspired TNT peptide receptors. Following an introduction, this paper describes the way of fabrication of the GFETs device by investigation methods for transferring graphene sheet from Cu substrates to target substrates, which is functionalized by the TNT peptide receptors, in order to offer a system which has the capability of answering the presence of related target molecules. Field effet transistor was fabricated using graphene as a channel and monitored by the source-drain current and back-gate voltage curves in the measurement. The transport property changed compared to that of the FET made by intrinsic graphene, that is, the Dirac point position moved from positive Vg to negative Vg, indicating the transition of graphene from p-type to n-type after annealing in TNT, and GFET sensor show good sensitivity and selectivity response.

This paper presents a novel approach for accurate counting and localization of tropical plants in aerial images that is able to work in new visual domains in which the available data is not labeled. Our approach uses deep learning and domain adaptation, designed to handle domain shift between the training and test data, which is a common challenge in this agricultural applications. This method uses a source dataset with annotated plants and a target dataset without annotations, and adapts a model trained on the source dataset to the target dataset using unsupervised domain alignment and pseudolabeling. The experimental results show the effectiveness of this approach for plant counting in aerial images of pineapples under significative domain shift, achieving a reduction up to 97% in the counting error when compared to the supervised baseline.

In this paper, we propose and demonstrate a network analysis optical frequency domain reflectometer (NA-OFDR) for distributed temperature measurements at high spatial (down to 3 cm) and temperature resolution. The system makes use of a frequency-stepped, continuous-wave (cw) laser, whose output light is modulated using a vector network analyzer. The latter is also used to demodulate the amplitude of the beat signal obtained by coherently mixing the Rayleigh backscattered light with a local oscillator. The system is capable of high measurand resolution (50 mK at 3-cm spatial resolution), thanks to the high sensitivity of coherent Rayleigh scattering to temperature. Furthermore, compared to the conventional optical-frequency domain reflectometry (OFDR), the proposed system does not rely on the use of a tunable laser, therefore it is less prone to limitations related to the laser coherence or sweep nonlinearity. Two configurations are analyzed, both numerically and experimentally, based on either a double sideband or single sideband modulated probe light. The results confirm the validity of the proposed approach.

This work introduces a new architecture for a time-domain feedback-based beamformer designed to meet real-time processing demands. The primary goal of this design is to locate reflective sources by estimating their direction of arrival (DOA) and signal range. Incorporating a feedback mechanism in this architecture is a unique aspect that refines localization precision. We conduct an in-depth analysis highlighting their respective benefits and limitations to compare the effectiveness of time-domain feedback beamforming against conventional time-domain methods. Our evaluation of the proposed architecture, based on critical performance indicators such as peak-to-sidelobe ratio, mainlobe width, and directivity factor, demonstrates its ability to improve beamformer effectiveness significantly.

A parallel shallow water flow model is introduced in this paper. The explicit-time finite volume approach is adopted to solve the 2D shallow water equations on an unstructured triangular mesh. The proposed scheme is second-order accurate in temporal and spatial terms using the two-stage Runge-Kutta and the monotone upwind scheme for conservation law (MUSCL) methods, respectively. Based on Message Passing Interface (MPI) and OpenACC, a multi-GPU model is presented with the METIS library to produce the domain decomposition. A CUDA-aware MPI library through GPUDirect for peer-to-peer (P2P) transfer between two GPUs and overlapping computation and MPI communication are used to speed up MPI memory exchange and the performance of the code. A 2D circular dam break test with wet and dry downstream beds and grid resolutions of about 2 million cells is considered to verify the accuracy of the code, and good results were achieved compared to the numerical simulations of published studies. Compared with the multi-CPU version of the 6-core CPU, maximum speedups of 56.18 and 331.51 were obtained using the single-GPU and multi-GPU versions, respectively. Results indicate that acceleration performance improves as the mesh resolution increases.

Tropical cyclones (TC) are dangerous weather events and accurate monitoring and forecasting can provide significant early warning to reduce loss of life and property. However, the study of tropical cyclone intensity remains challenging, both in terms of theory and forecasting. ERA5 reanalysis is benchmark data set for tropical cyclone studies, yet the maximum wind speed error is very large (68 kts) and still 19 kts after simple linear correction even in the better sampled North Atlantic. Here, we develop an adaptive learning approach to correct the intensity in the ERA5 reanalysis, by optimising the inputs to overcome the problems because of the poor data quality and updating the features to improve the generalisability of the deep learning-based model. Specifically, we use TC knowledge to increase the representativeness of the inputs so that the general features can be learned with deep neural networks in the sample space, and then use domain adaptation to update the general features from the known domain with historical storms to the specific features for the unknown domain of new storms. This approach can reduce the error to only 6 kts which is within the uncertainty of the best track data in IBTrACS in the North Atlantic. The method may have wide applicability, such as extending it to the correction of intensity estimation from satellite imagery and intensity prediction from dynamical models.

The cytoskeleton is a master organizer of cell cortex, organelles positioning and membrane trafficking. Therefore, playing a decisive role in establishment of apico-basal polarity. Septins are critical cytoskeleton components which function in apico-basal polarity remain weakly investigated. Here, using 3D culture system, we demonstrate that septin9 localizes at basolateral membrane (BM). Its depletion induces an inverted polarity phenotype, decreasing -catenin at BM and increasing the expression of the transforming growth factor (TGF) and the epithelial-to-mesenchymal transition (EMT) markers. Similar effects were observed upon deleting its two polybasic domains, and the mutant become cytoplasmic and apical. The cysts with an inverted polarity phenotype display an invasive phenotype, with src and cortactin accumulating at the peripheric membrane. Inhibition of TGF-receptor and RhoA rescues the polarized phenotype. Although the cysts from overexpressed-septin 9, overgrowth and present a filled lumen. Both phenotypes correspond to tumor features. This suggests that septin 9 expression and assembly through the two PB domains are essential for establishing and maintaining apico-basal polarity against tumor development through a mechanism involving TGF-dependent EMT and RhoA activity.

We demonstrate that the conductivity of graphene on thin-film polymer substrates can be accurately determined by reflection-mode air-plasma-based THz time-domain spectroscopy (THz-TDS). The phase uncertainty issue associated with reflection measurements is discussed, and our implementation is validated by convincing agreement with graphene electrical properties extracted from more conventional transmission-mode measurements. Both the reflection and transmission THz-TDS measurements reveal strong nonlinear and instantaneous conductivity depletion across an ultra-broad bandwidth under relatively high incident THz electrical field strengths.