Tissue Doppler Imaging (TDI) is a non-invasive, echocardiographic imaging technique that measures myocardial motion velocity throughout the cardiac cycle using Doppler principles. While conventional Doppler techniques assess blood flow velocity by sensing high-frequency, low amplitude signals from small, fast-moving blood cells, TDI uses the same Doppler principles to instead measure high-amplitude, lower-velocity signals of myocardial tissue. Methods A literature review was conducted to survey and review studies investigating the limitations, strengths, physical principles, novel methods, applications in diseased states, and prognostic capabilities of TDI. These articles were further screened for inclusion, and those deemed ineligible or irrelevant to the scope of the review were discarded. In total, 19 studies were included in the qualitative synthesis. Results TDI is shown to be an effective method for detailed quantification of cardiac function. It provides an early means of diagnosing cardiac dysfunction and is a valid prognostic indicator for various forms of heart disease. TDI's versatility and precision allows clinicians to predict the clinical course of disease, leading to early intervention and the selection of targeted care management plans for many cardiac pathologies. Despite imaging limitations like angle dependence and incapacity for passive and active motion differentiation, further investigation continues to reveal novel TDI methodologies that advance the scope of this imaging technique.

Nobel Prize-winning physicist Sir Roger Penrose and Stuart Hameroff, a renowned American physician and scientist, have put forward an innovative theory that the human brain has a quantum mechanism located in the microtubular protein system within neurons, known as the "Orch OR" theory. According to the researchers, this mechanism is responsible for the brain's non-computational actions such as consciousness and free will. This theory has been criticized by several researchers from both the biological and physical sides. The purpose of this paper is to examine whether there is a possible basis for this theory in the philosophy of science.

This is a report on a dynamic autonomous magnetic interaction which does not depend on polarities resulting in short ranged repulsion involving one or more inertial bodies and a new class of bound state based on this interaction. Both effects are new to the literature, found so far. Experimental results are generalized and reported qualitatively. Working principles of these effects are provided within classical mechanics and found consistent with observations and simulations. The effects are based on the interaction of a rigid and finite inertial body (an object having mass and moment of inertia) endowed with a magnetic moment with a cyclic inhomogeneous magnetic field which does not require to have a local minimum. Such a body having some DoF involved in driven harmonic motion by this interaction can experience a net force in the direction of the weak field regardless of its position and orientation or can find stable equilibrium with the field itself autonomously. The former is called polarity free magnetic repulsion and the latter magnetic bound state. Experiments show that a bound state can be obtained between two free bodies having magnetic dipole moment. Various schemes of trapping bodies having magnetic moments by rotating fields are realized as well as rotating bodies trapped by a static dipole field in presence of gravity. Also, a special case of bound state called bipolar bound state between free dipole bodies is investigated.

The study aimed to explore the correlation among Angiopoietin-1, (Ang-1) and Angiopoietin-2, (Ang-2) concentrations and the Angiopoietin-2/Angiopoietin-1 ratio, (Ang-2/Ang-1) with clinical outcomes, potentially serving as disease severity and survival biomarkers. A study at AHEPA University Hospital involved 90 COVID-19 adult patients, with 30 hospitalized in intensive care and 30 in ward units and 30 asymptomatic non-hospitalized individuals as controls. Estimated endothelial dysfunction markers related to angiogenesis were measured, and statistical analysis was performed using IBM SPSS Statistics software, version 29. There was a statistically significant difference only between outpatient and hospitalized patients (non-ICU -ICU groups) for the Ang-1 and Ang-2 indexes. The Ang-2/Ang-1 ratio has differed significantly among all individual patient groups. A ROC analysis was conducted to find an optimal threshold for distinguishing (outpatients – non-ICU) and (non-ICU –ICU) groups. It was based on Youden's Index and was 0.1122 and 0.3825, respectively. The Ang-1, Ang-2 levels, and Ang-2/Ang-1 ratio were analysed as indicators for severity in COVID-19 patients. The Ang-2/Ang-1 ratio demonstrated more excellent prognostic and diagnostic utility than individual biomarker levels. Monitoring the Ang-2/Ang-1 ratio can identify COVID-19 patients at risk and assist clinicians in tailoring treatment strategies for improved outcomes.

Persons who inject drugs (PWIDs) represent an important reservoir of hepatitis C virus (HCV) infection, hence therapeutic communities (TCs) are promising points of care for the identification and treatment of HCV-infected PWIDs. We evaluated the effectiveness and efficacy of an HCV micro-elimination program targeting PWIDs in the context of a drug-free TC applying Cascade of Care (CoC) evaluation by calculating frequencies of infection diagnosis, confirmation, treatment and achievement of a sustained virological response (SVR). We also evaluated the risk of reinfection of PWIDs achieving HCV eradication, by collecting follow-up virologic information of previously recovered individuals and eventual relapse in drug use, assuming the latter as a potential source of reinfection. We considered all PWIDs (aged 18+ years) residing in the San Patrignano TC at the beginning of the observation period (Jan/2018–Mar/2022) or admitted thereafter, assessing for HCV and HIV serology and viral load by standard laboratory procedures. Ongoing infections were treated with direct acting antivirals (DAA), according to the current national guidelines. Out of the 792 individuals tested on admission, 503 (63.5%) were found to be seropositive for antibodies against HCV. 481 of these 503 individuals (95.6%) underwent HCV-RNA testing. Out of the 331 participants positive for HCV-RNA, 225 were ultimately prescribed a DAA treatment with a Sustained Viral Response (SVR), which was achieved by 222 PWIDs (98.7%). 186 of 222 PWIDs (83.8%) with SVR remained HCV-free on follow-up (with a median follow-up of 2.73 years after SVR ascertainment). The CoC model in our TC proved efficient in implementing HCV micro-elimination, as well as in preventing reinfection and promoting retention in care of individuals, which aligns with the therapeutic goals of addiction treatment.

Vulnerable carotid plaques are responsible for 20% of the ischemic strokes. The identification of those asymptomatic carotid plaques that will become symptomatic is essential but remains unclear. Our main goal was to investigate whether the amount of the peri-carotid adipose tissue, estimated by the extra-media thickness (EMT) is associated with the atherosclerotic characteristics at the carotid bifurcation in patients with PAD. An observational, prospective, single-center, longitudinal study was conducted. 177 patients performed carotid Doppler-ultrasound. The following data was collected: EMT, intima-media thickness (IMT), presence of carotid plaques, area of the highest plaque, and grade of internal carotid stenosis. From each carotid bifurcation a right and left EMT was determined. We analyzed both the mean EMT (calculated as the mean between the right and the left EMT) and the EMT ipsilateral to the carotid bifurcation. The presence of carotid plaques was associated with a higher mean EMT, [Median=1.14; IQR=0.66 versus Median=0.97; IQR=0.40; p=.001]. A positive correlation was found between mean EMT and IMT (right: ρ=.20; p=.010; left: ρ=.21; p=.007) and between mean EMT and area of the largest carotid plaque (right: ρ=.17; p=.036; left: ρ=.22; p=.004). Left carotid stenosis ≥ 70% was associated with higher mean EMT. [Median=1.55; IQR=0.68 versus Median=1.00; IQR=0.46; p=.019]. Patients with “acute culprit” carotid stenosis had a higher ipsilateral EMT [Left ipsilateral EMT: Median=1.46; IQR=0.63; “non-acute”: Median=0.94; IQR=0.43; p=.009; Right ipsilateral EMT: Median=2.25; IQR=0.62; “non-acute”: Median=1.00; IQR=0.51; p=.015]. This difference was not found in the contra-lateral EMT. Six months after the neurologic event, EMT ipsilateral to an “acute culprit” carotid stenosis decreased (p=.036). The amount of peri-carotid adipose tissue, estimated with EMT was associated with atherosclerosis at the carotid arteries. In particularly EMT could be a non-invasive marker of “acute culprit” carotid stenosis, easily determined in clinical practice. These findings may have implications in personalized medicine, for the determination of the best treatment approach.

The three-dimensional printing of scaffolds is an interesting alternative to the traditional techniques of periodontal regeneration. This technique uses computer assisted design and manufacturing after CT scan. After 3D modelling, individualized scaffolds are printed by extrusion, selective laser sintering, stereolithography, or powder bed inkjet printing. These scaffolds can be made of one or several materials such as natural polymers, synthetic polymers, or bioceramics. They can be monophasic or multiphasic and tend to recreate the architectural structure of the periodontal tissue. In order to enhance the bioactivity and have a higher regeneration, the scaffolds can be embedded with stem cells and/or growth factors. This new technique could enhance a complete periodontal regeneration. This review summarizes the application of 3D printed scaffolds in periodontal regeneration. The process, the materials and designs, the key advantages and prospects of 3D bioprinting are highlighted, providing new ideas for tissue regeneration.

Renewable resources gain increasing interest as source for environmentally benign biomaterials, such as drug encapsulation/release compounds, and scaffolds for tissue engineering in regenerative medicine. Being the second largest naturally abundant polymer, the interest in lignin valorization for biomedical utilization is rapidly growing. Depending on resource and isolation procedure, lignin shows specific antioxidant and antimicrobial activity. Today, efforts in research and industry are directed toward lignin utilization as renewable macromolecular building block for the preparation of polymeric drug encapsulation and scaffold materials. Within the last five years, remarkable progress has been made in isolation, functionalization and modification of lignin and lignin-derived compounds. However, literature so far mainly focuses lignin-derived fuels, lubricants and resins. The purpose of this review is to summarize the current state of the art and to highlight the most important results in the field of lignin-based materials for potential use in biomedicine (reported in 2014–2018). Special focus is drawn on lignin-derived nanomaterials for drug encapsulation and release as well as lignin hybrid materials used as scaffolds for guided bone regeneration in stem cell-based therapies.

The effective treatment for chronic wounds constitute one of the most common worldwide health care problem due to the presence of high levels of proteases, free radicals and exudates in the wound, which constantly activate the inflammatory system avoiding the tissue regeneration. In this study, we describe a multifunctional bioactive and resorbable membrane with in-built antioxidant agent for the continuous quenching of free radicals as well as to control inflammatory response helping to promote the wound healing process. To reach that goal synthesized statistical copolymers of N-vinylcaprolactam (V) and 2-hydroxyethyl methacrylate (H) have been conjugated with catechol bearing hydrocaffeic acid (HCA) molecules. The natural polyphenol (catechol) is the key molecule responsible for the mechanism of adhesion of mussels, and provides the functionalized polymer conjugate a continuous antioxidant response, antiinflammatory effect, UV screen and bioadhesion in the moist environment of the human body, all of them key features in the wound healing process. Therefore, these novel mussel-inspired materials have an enormous potential of application and can act very positively, favoring and promoting the healing effect in chronic wounds.

The development of potent antiviral agents is of utmost importance to combat the global burden of viral infections. Traditional antiviral drug development involves targeting specific viral proteins, which may lead to the emergence of resistant strains. To explore alternative strategies, we investigated the antiviral potential of antimicrobial peptidomimetic compounds. In this study, we evaluated the antiviral potential of short anthranilamide-based peptidomimetic compounds 1-17 against two viruses: Murine Hepatitis Virus 1 (MHV-1-single stranded RNA virus) which is a surrogate of human coronaviruses and Herpes Simplex Virus 1 (HSV-1-double stranded DNA virus). The half-maximal inhibitory concentration (IC50) values of these compounds were determined in vitro to assess their potency as antiviral agents. Compounds 11 and 14 displayed the most potent inhibitory effect with IC50 values of 2.38μM, and 6.3μM against MHV-1 while compounds 9 and 14 showed IC50 values of 14.8μM and 13μM, against HSV-1. Multiple antiviral assessments and microscopic images obtained through transmission electron microscopy (TEM) collectively demonstrated that these compounds exert a direct influence on the viral envelope. Based on this outcome, it can be concluded that peptidomimetic compounds could offer a new approach for the development of potent antiviral agents.

A human brain can communicate with another one’s brain using quantum entanglement. Similar particles can entangle without interaction. Sensory communication between two individuals from far distances is still not known. Former studies primarily have been performed regarding brain neurons' quantum behavior. The test was performed on two individuals far from each other. These individuals were put under the same music on the basis of brain neuroplasticity property. By activating the brain reward system, aligned thinking was time scheduled in these individuals’ brains. On the basis of entanglement, compressed information was sent and received between these two individuals.

Quantum cryptography is the field of cryptography that explores the quantum properties of matter. Its aim is to develop primitives beyond the reach of classical cryptography or to improve on existing classical implementations. Although much of the work in this field has been dedicated to quantum key distribution (QKD), some important steps were made towards the study and development of quantum oblivious transfer (QOT). It is possible to draw a comparison between the application structure of both QKD and QOT primitives. Just as QKD protocols allow quantum-safe communication, QOT protocols allow quantum-safe computation. However, the conditions under which QOT is actually quantum-safe have been subject to a great amount of scrutiny and study. In this review article, we survey the work developed around the concept of oblivious transfer in the area of theoretical quantum cryptography, with an emphasis on some proposed protocols and their security requirements. We review the impossibility results that daunt this primitive and discuss several quantum security models under which it is possible to prove QOT security.

Hydrogenases are iron-sulfur enzymes that catalyze proton reduction and H₂ oxidation with outstanding efficiency. They are considered blueprints for the design of transition metal complexes, e.g. as heterogenous catalysts in the context of H₂ production from water. Moreover, hydrogenases are biological model systems for metal hydride chemistry and proton-coupled electron transfer. Depending on the composition of the active site cofactor, [NiFe]-hydrogenases are distinguished from [FeFe]-hydrogenases. The former binds a hetero bimetallic nickel/iron site, embedded in the protein by four cysteine ligands. The later, by contrast, carries a homo bimetallic iron/iron site attached to the protein by only a single cysteine. Carbon monoxide and cyanide ligands (CO/CN) at the active site facilitated detailed investigations of hydrogenase catalysis by infrared spectroscopy, owing to strong signals and redox-dependent frequency shifts. However, the details of proton transfer have not been addressed experimentally.We found that specific redox state transitions in [NiFe]- and [FeFe]-hydrogenase can be triggered by visible light to record extremely sensitive ‘light-minus-dark’ infrared difference spectra monitoring key amino acid residues as shown in the ToC figure. As these transitions are coupled to protonation changes, our data allowed investigating dynamic hydrogen-bonding changes that go well beyond the resolution of protein crystallography. In [NiFe]-hydrogenase, photolysis of the bridging hydride ligand in the ‘Ni-C’ state was followed by rapid accumulation of the ‘Ni-SI_a’ state and/or ‘Ni-L’ state. Infrared difference spectra in various isotopic media clearly indicated the formation of a protonated cysteine residue as well as hydrogen-bonding changes involving the COOH group of a glutamic acid residue and a ‘dangling water’ molecule. These findings are in excellent agreement with crystallographic analyses of [NiFe]-hydrogenase in the Ni-R state and allowed devising a molecular precise model of catalytic proton transfer. In [FeFe]-hydrogenase, an external redox dye was used to accumulate the ‘Hred’ state over the oxidized resting state ‘Hox’. Infrared difference spectra of wild-type enzyme and numerous amino acid variants indicated hydrogen-bonding changes involving the COOH groups of two glutamic acid residues. Moreover, we noted the deprotonation of an arginine residue. Crystallographic analyses of [FeFe]-hydrogenase in the Hox state failed to explain the rapid proton transfer due to a ‘breach’ in the succession of residues. To this end, our findings facilitated a molecular precise model of ‘discontinued’ proton transfer.The comparison of catalytic proton transfer in bimetallic hydrogenases emphasizes the role of the outer coordination sphere. We suggest that the stable protonation of a nickel-ligating cysteine in [NiFe]-hydrogenase has a crucial influence on the preferred direction of proton flow and catalysis (i.e., H₂ oxidation). On the contrary, proton transfer in [FeFe]-hydrogenase involves an adjacent cysteine as a relay group that promotes both proton release and proton uptake. We presume that this causes the notable bidirectionality of [FeFe]-hydrogenase. These observations must guide the design of biomimetic compounds for the production or consumption of H₂.

This study investigates the long-term stability of the Suomi National Polar-orbiting Partnership (S-NPP) Visible Infrared Imaging Radiometer Suite (VIIRS) moderate-resolution Thermal Emissive Bands (M TEBs; M12 – M16) covering a period from February 2012 to August 2020. It also assesses inter-sensor consistency of the VIIRS M TEBs among three satellites-S-NPP, NOAA-20, and NOAA-21 over eight months spanning from March 18 to November 30, 2023. The field of interesting is limited to the ocean surface between 60°S and 60°N, specifically under clear-sky conditions. Taking radiative transfer modeling (RTM) as the transfer reference, we employed the Community Radiative Transfer Model (CRTM) to simulate VIIRS TEB brightness temperature (BTs), incorporating European Centre for Medium-range Weather Forecasts (ECMWF) reanalysis data as inputs. Our results reveal two key findings. Firstly, the reprocessed S-NPP VIIRS TEBs exhibit a robust long-term stability, as demonstrated through analyses of the observation minus background BT differences (O-B ∆BTs) between VIIRS measurements (O) and CRTM simulations (B). The drifts of the O-B BT differences are consistently less than 0.105 K/Decade across all S-NPP VIIRS M TEB bands. Notably, observations from VIIRS M14 and M16 stand out with drifts well within 0.04 K/Decade, reinforcing their exceptional reliability for climate change studies. Secondly, excellent inter-sensor consistency among these three VIIRS instruments is confirmed through the double-difference analysis method (O-O). This method relies on the O-B BT differences obtained from daily data. The mean inter-VIIRS O-O BT differences remain within 0.08 K for all M TEBs, except for M13. Even in the case of M13, the O-O BT differences between NOAA-21 and NOAA-20/S-NPP have values of 0.312 K and 0.234 K, respectively, which are comparable to the 0.2 K difference between some TEBs among VIIRS and MODIS. These disparities are primarily attributed to the significant differences in the Spectral Response Function (SRF) of NOAA-21 compared to NOAA-20 and S-NPP. Our study confirms the RTM-based TEB quality evaluation method’s versatility and effectiveness in assessing long-term sensor stability and inter-sensor consistency. The double-difference approach effectively mitigates uncertainties and biases inherent to CRTM simulations, establishing itself a robust mechanism for assessing inter-sensor consistency. In addition, we’ve observed that, except for M13, M12 always exhibits larger spatial variations of O-O BT differences with greater uncertainties compared to the other M TEBs. The influence of solar contribution through sea surface reflection on the Top of Atmosphere (TOA) radiance measurements during daytime in M12 should not be underestimated.

Incretin effect helps in regulating glucose homeostasis and maintaining glycaemic control within the human body. This effect is achieved by the two naturally occurring incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Such hormones released by specialized entero-endocrine cells of the gastrointestinal tract cause insulin augmentation after food consumption. However, incretin effects are impaired in type 2 diabetic, primarily attributed to the deterioration of GLP-1 function along with decreased GLP-1 receptor expression. Targeting this hormone has, therefore, become an important therapeutic approach to treat this diabetic condition. Native GLP-1’s brief half-life and rapid proteolytic degradation have generated significant enthusiasm in uncovering the long-acting GLP-1 receptor (GLP-1R) agonists to manage type 2 diabetes. These synthetic peptides mimic the natural GLP-1 to activate GLP-1R and effectively exert various physiological benefits in terms of weight management, blood pressure, lipid profile, obesity and major adverse cardiovascular event. This review paper provides insights into the structure, function and expression of GLP-1 and its receptor. It also summarizes existing literature regarding different types of GLP-1 receptor agonists, their effects on blood pressure and how they exert their actions. While animal models have contributed significantly to this area of study, the scarcity of human studies is noted, indicating a need for more investigation in this domain. Expanding research in humans will help in comprehending the impact of GLP-1 receptor agonists on blood pressure regulation and their underlying mechanisms.

Yerba maté, an herbal tea derived from Ilex paraguariensis, has previously been reported to be protective against obesity-related and other cardiometabolic disorders. Using high-resolution respirometry and reverse-phase high-performance liquid chromatography, the effects of four weeks of yerba maté consumption on mitochondrial efficiency and cellular redox status in skeletal muscle, adipose, and liver, tissues highly relevant to whole body metabolism, were explored in healthy adult mice. Yerba maté treatment increased mitochondrial oxygen consumption in adipose, but not in other tissues examined. Yerba maté increased ATP concentration in skeletal muscle and decreased ATP concentration in adipose. Combined with observed changes in oxygen consumption, these data yielded a significantly higher ATP:O2, a measure of mitochondrial efficiency, in muscle and a significantly lower ATP:O2 in adipose, which were consistent with yerba maté-induced weight loss. Yerba maté treatment also altered the hepatic glutathione (GSH)/glutathione disulfide (GSSG) redox potential to a more reduced redox state, suggesting potential protective effects against oxidative stress and preservation of cellular function. Together, these data indicate beneficial, tissue-specific effects of yerba maté supplementation on mitochondrial bioenergetics and redox states in healthy mice that are protective against obesity.

An exposition of entropy applications to highlight some potential entropic applications to artificial intelligence and knowledge transfer. Entropy is a basic idea in artificial intelligence that is applied to many different tasks, such as reinforcement learning, data compression, and decision-making. By quantifying uncertainty and information content, it helps artificial intelligence models provide predictions and decisions that are well-informed. Therefore, this paper shines on spotlighting the significance of entropy to attract the attention of artificial intelligence research community to entropy as a powerful tool to advance artificial intelligence.The significance of knowledge transfer (KT), particularly intergenerational knowledge transfer (IGT), in knowledge management is also covered in this paper. To quantify the complexity of knowledge distribution inside an organisation and assess the efficacy of knowledge transfer (KT) initiatives, the notion of knowledge entropy (KE) is presented. Additionally, the KT model—which is based on the conceptions of tacitness and information content—is introduced. It combines personalisation and codification methodologies. Future research directions are offered alongside a few difficult open problems.

Recently, the use of drones/unmanned aerial vehicles (UAVs) has notably increased due to their broad commercial spread and low cost. The wide diffusion of drones increases the hazards of their misuse in illegitimate actions such as drug smuggling and terrorism. Thus, the surveillance and automated detection of drones are crucial for safeguarding restricted regions or special zones from illegal drone interventions. One of the most challenging issues in drone detection in surveillance videos is the apparent similarity of drones and birds against complex backgrounds. In this work, an automated image-based drone-detection system utilizing an advanced deep-learning-based object-detection method known as you only look once (YOLOv5) is introduced for protecting restricted regions or special zones from unlawful drone interventions. Due to the lack of sufficient data, transfer learning was utilized to pretrain the object-detection method to increase the performance. The experiments showed outstanding results, and an average precision of 94.7% was accomplished.

We study the brain segmentation by dividing the brain into multiple tissues. Given possible brain segmentation by deep, machine learning can be efficiently exploited to expedite the segmentation process in the clinical practice. To accomplish segmentation process, a MRI and tissues transfer using generative adversarial networks is proposed. Given the better result, we propose the transfer model using GAN. For the case of the brain tissues, white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF) are segmented. Empirical results show that this proposed model significantly improved segmentation results compared to the stat-of-the-art results. Furthermore, a dice coefficient (DC) metric is used to evaluate the model performance.

Caveolin-1 (Cav-1) is 22 kDa caveolae protein, acts as a scaffold within caveolar membranes. It interacts with alpha subunits of G-protein and thereby regulates their activity. Earlier studies reported elevated or up-regulated levels of caveolin-1 in the serum of prostate cancer patients. Secreted Cav-1 promotes angiogenesis, cell proliferation and anti-apoptotic activities in prostate cancer patients. Cav-1 upregulation is mainly related to prostate cancer metastasis. Keeping above facts in view, the present study was designed to explore Cav-1 as a target for prostate cancer therapy using computational approach. Molecular docking, structural base molecular modelling and molecular dynamics simulations were performed to investigate Cav-1 inhibitors. A predictive model was generated and validated to establish a stable structure. ZINC database of biogenic compounds was used for induced fit docking (IFD) and high throughput virtual screening. The H-bond interactions of the compounds with active site residues of Cav-1 were estimated by IFD and 100 ns long molecular dynamic simulations. The reported compounds showed significant binding and thus can be considered as potent therapeutic inhibitors of Cav-1. This study provides a valuable insight into biochemical interactions of Cav-1 for therapeutic applications and warrants for experimental validation of the predicted ‘active(s)’.

The capability of radially polymerized bio-dendrimers and hyperbranched polymers for medical applications is well established. Among them, perhaps the most important are those that involve interactions with the regenerative mechanisms of cells. Dendritic polymers due to their distinctive architecture may play a multitude of roles such as protein biomimicry (collagen, elastin, hydroxy apatite production), gene and drug delivery (cell differentiation, antimicrobial protection), surface chemistry and charge modulation (adhesion to cells and tissues), polymer cross-linking (eye, skin and internal organ wound healing). The review highlights all the different categories of hard and soft tissues that may be remediated with their contribution. The reader will be also exposed to the incorporation methods to established biomaterials such as scaffolds, the functionalization strategies, and the synthetic paths for the assembly from biocompatible building blocks and natural metabolites.

Cardiovascular diseases are the leading cause of death worldwide. Cardiovascular diseases complication can give rise to myocardial infarction which produces cell death by blockage of blood flow, leading to loss of heart function. Current treatments directed at heart repair have several disadvantages such as the lack of donors for heart transplantation or the use of non-bioactive inert materials for replacement of the damage tissue. New treatment strategies involve stimulation of heart tissue regeneration with the use of bioactive materials like chitosan, in combination with cells and biochemical factors. Chitosan scaffolds have the necessary proprieties of biocompatibility, porosity, and biodegradation, that imitates the heart extracellular matrix. Chitosan scaffolds physical proprieties, such as electrical conductivity and mechanical proprieties, can be improved by different preparation techniques and by the functionalization with other materials.

The retina is a complex and fragile photosensitive part of the central nervous system which is prone to degenerative diseases leading to permanent vision loss. No proven treatment strategies exist to treat or reverse the degenerative conditions. Recent investigations demonstrate that cell transplantation therapies to replace the dysfunctional retinal pigment epithelial (RPE) cells and or the degenerating photoreceptors (PRs) are viable options to restore vision. Pluripotent stem cells, retinal progenitor cells and somatic stem cells are the main cell sources used for cell transplantation therapies. The success of retinal transplantation based on cell suspension injection is hindered by limited cell survival and lack of cellular integration. Recent advances in material science helped to develop strategies to grow cells as intact monolayers or as sheets on biomaterial scaffolds for transplantation into the eyes. Such implants are found to be more promising than the bolus injection approach. Tissue engineering techniques are specifically designed to construct biodegradable or non-degradable polymer scaffolds to grow cells as a monolayer and construct implantable grafts. The engineered cell construct along with the extracellular matrix formed, can hold the cells in place to enable easy survival, better integration and improved visual function. This article reviews the advances in the use of scaffolds for transplantation studies in animal models and its application in current clinical trials.

Vascular inflammation is recognized as the primary trigger of acute coronary syndrome (ACS). However, current noninvasive methods are not capable of accurately detecting coronary inflammation. Epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT), in addition to their role as an energy reserve system, have been found to contribute to the development and progression of coronary artery calcifica-tion, inflammation, and plaque vulnerability. They also participate in the vascular re-sponse during ischemia, sympathetic stimuli, and arrhythmia. As a result, the evalua-tion of EAT and PCAT using imaging techniques such as computed tomography (CT), cardiac magnetic resonance (CMR), and nuclear imaging has gained significant atten-tion. PCAT-CT attenuation, which measures the average CT attenuation in Hounsfield units (HU) of the adipose tissue, reflects adipocyte differentiation/size and leukocyte infiltration. It is emerging as a marker of tissue inflammation and has shown prognos-tic value in coronary artery disease (CAD), being associated with plaque development, vulnerability, and rupture. In patients with acute myocardial infarction (AMI), an in-flammatory pericoronary microenvironment promoted by dysfunctional EAT/PCAT has been demonstrated, and more recently, it has been associated with plaque rupture in non-ST-segment elevation myocardial infarction (NSTEMI). Endothelial dysfunc-tion, known for its detrimental effects on coronary vessels and its association with plaque progression, is bidirectionally linked to PCAT. PCAT modulates the secretory profile of endothelial cells in response to inflammation and also plays a crucial role in regulating vascular tone in the coronary district. Consequently, dysregulated PCAT has been hypothesized to contribute to type 2 myocardial infarction with non-obstructive coronary arteries (MINOCA) and coronary vasculitis. Recently, quan-titative measures of EAT derived from coronary CT angiography (CCTA) have been included in artificial intelligence (AI) models for cardiovascular risk stratification. These models have shown incremental utility in predicting major adverse cardiovas-cular events (MACE) compared to plaque characteristics alone. Therefore, the analysis of PCAT and EAT, particularly through PCAT-CT attenuation, appears to be a safe, valuable, and sufficiently specific noninvasive method for accurately identifying cor-onary inflammation and subsequent high-risk plaque. These findings have been sup-ported by biopsy and in vivo evidence. Although speculative, these pieces of evidence open the door to a fascinating new strategy in cardiovascular risk stratification. The incorporation of PCAT and EAT analysis, mainly through PCAT-CT attenuation, could potentially lead to improved risk stratification and guide early targeted primary pre-vention and intensive secondary prevention in patients at higher risk of cardiac events.

The canonical decomposition of a bipartite graph is a new decompositionmethod that involves three operators, parallel, series and K+S. The class of weak bisblit graphs is totally decomposable with respect of these operators, and the class of bicographs is totally decomposable with respect of parallel and series operators. We prove in this paper that the class of bipartite (P_6,C_6)-free graphs is exactly the class of bipartite graphs that are totally decomposable with respect of parallel and K+S operators. We simplify the recognition algorithm of weak-bisplit graphs to adepte with bipartite (P_6,C_6)-free graphs. As a result of this adapted algorithm, we prsent efficient solutions in this class of graphs for two optimization graph problems, the first is the maximm balanced bi-clique problem and the the second is the maximum independent set problem.

Spatial crowdsourcing emerges as a new computing paradigm that enables mobile users to accomplish spatio- temporal tasks in order to solve human-intrinsic problems. Existing crowdsourcing systems critically use centralized servers for interacting with workers and making task assignment decisions. These systems are hence susceptible to issues such as the single point of failure and the lack of operational transparency. Prior work, therefore, turns to blockchain-based decentralized crowdsourcing systems, yet still suffers from problems of lacking efficient task assignment scheme, requiring a deposit to an untrusted system, low block generation speed, and high transaction fees. To address these issues, we design a blockchain-based decentralized framework for spatial crowdsourcing, which we call SC-EOS. Our system does not rely on any trusted servers, while providing efficient and user-customizable task assignment, low monetary cost, and fast block generation. More importantly, it frees users from making a deposit into an untrusted system. Our framework can also be extended and applied to generic crowdsourcing systems. We implemented the proposed system on the EOS blockchain. Trace-driven evaluations involving real users show that our system attains the comparable task assignment performance against a clairvoyant scheme. It also achieves 10× cost savings than an Ethereum-based implementation.

The free energy principle states that self-organization occurs through minimization of free energy, which is a measure of potential thermodynamic work. By minimizing free energy, the organism happens to also minimize surprise over its boundary, promoting chances of survival. We discuss the ethical implications of the cognitive goal in detail from an empirical point of view, highlighting the principle of least action as a physical basis of Occam's razor, the universality of the free energy principle, and its explanation of natural selection. We explain that the free energy principle extends to groups of organisms and helps us understand group-scale adaptations and selection in biology. The free energy principle applies to all scales of organization in the organism from single cells to the entire nervous system. When this principle is taken to its logical extremes of modeling groups, populations and ecosystems, we uncover a new, evolutionarily sensible path at explaining puzzling aspects of human motivation and judgement, including ethical decisions. To minimize free energy, populations have to act to maximize gathering of information, while building effective models at mitigating changes to its dynamic structure. The free energy principle thus provides a naturalistic explanation of some of our deepest ethical intuitions, and valuable principles of social behavior. We interpret the cognitive goal that corresponds to the principle as seeking a dynamic, fruitful, yet peaceful activity that sustains the organism. This state of mind is interestingly similar to the Buddhist intuition of mental equanimity; the organism's final goal is to be at peace and harmony with the environment. Another immediately relevant aspect is that assemblies must form to promote symbiotic, synergistic, positive feedback loops, which coincides with the findings of ecologists. Therefore, ethics naturally emerges in self-organizing systems. Assemblies of organisms must ultimately unite in macro-minds to achieve the greatest reduction in free energy, as well as building technological extensions of themselves to improve their capacity to do such, therefore the principle also predicts a post-singularity world-mind composed mostly of artificial intelligence.

A series of novel sulfonylurea benzothiazoline were designed by splicing active groups and bioisosterism. A solvent-free synthetic route was developed for the sulfonylurea benzothiazoline derivatives via the cyclization and carbamylation. All the compounds were characterized by IR, 1H-NMR, 13C-NMR, HRMS. The biological activity tests indicated the compounds could protect maize against the injury caused by chlorsulfuron to some extent. The molecular docking result showed that the new compound competed with chlorosulfuron to bind with the herbicide target enzyme active site to attain detoxification.

Anti-interferon (IFN)-γ autoantibodies are linked to varicella-zoster virus (VZV) infection. Given the elevated risks of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKi), we aimed to examine the relationship between anti-IFN-γ autoantibodies with HZ development in JAKi-treated patients. In twenty-four RA patients with new-onset HZ and forty-two without HZ, serum titers of anti-IFN-γ autoantibodies, plasma levels of IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IFN-γ inducible protein-10 (IP-10) were measured by ELISA. Significantly lower MCP-1 levels were observed in patients with HZ compared to those without (median, 98.21pg/ml, interquartile range (IQR) 77.63-150.30pg/ml versus 142.3pg/ml, IQR 106.7-175.6pg/ml, p<0.05). There was no significant difference in anti-IFN-γ titers, IFN-γ levels, or IP-10 levels between patients with and without HZ. Three of 24 patients with HZ had severe HZ with multi-dermatomal involvement. Anti-IFN-γ titers were significantly higher in patients with severe HZ than in those with non-severe HZ (median 24.8ng/ml, IQR 21.0-38.2ng/ml versus 10.5ng/ml, IQR 9.9-15.0ng/ml, p<0.005). In conclusion, patients with HZ had significantly lower MCP-1 levels than those without HZ, and patients with severe HZ had significantly higher titers of anti-IFN-γ than those with non-severe HZ. Given small sample size, our results need further validation in future studies.

The evaluation of nanostructured biomaterials and medicines is associated with 2D cultures that provide insight into the biological mechanisms at the molecular level, while critical aspects of the tumor microenvironment (TME) are provided by the study of animal xenograft models. More realistic models that can histologically reproduce human tumors are provided by tissue engineering methodologies of co-culturing cells of varied phenotypes, to provide 3D tumor spheroids that recapitulate the dynamic TME in 3D matrices. The novel approaches of 3D tumor models are combined with tumor tissue engineering (TTE) scaffolds including hydrogels, bioprinted materials, decellularized tissues, fibrous and nanostructured matrices. This review focuses on the use of nanostructured materials in cancer therapy and regeneration, and the development of realistic models for studying TME molecular and immune characteristics. Tissue regeneration is an important aspect of TTE scaffolds for restoring the normal function of the tissues, while providing cancer treatment. Thus, this article reports recent advancements on the development of 3D TTE models for antitumor drug screening, studying of tumor metastasis, and tissue regeneration. Also, this review identifies the great opportunities of 3D TTE scaffolds in the evaluation of the immunological mechanisms and processes involved in the application of immunotherapies.

Nano/micron-sized bioactive glass (BG) particles are attractive candidates for both soft and hard tissue engineering. They can chemically bond to the host tissues, enhance new tissue formation, activate cell proliferation, stimulate the genetic expression of proteins, and trigger unique an-ti-bacterial, anti-inflammatory, and anti-cancer functionalities. Recently, composites based on bi-opolymers and BG particles have been developed with various state-of-the-art techniques for tis-sue engineering. Gelatin, a semi-synthetic biopolymer, has attracted the attention of researchers because it is derived from the most abundant protein in the body, viz., collagen. It is a polymer that can be dissolved in water and processed to acquire different configurations, such as hydro-gels, fibers, films, scaffolds, etc. Searching "bioactive glass gelatin" in the tile on Scopus renders 80 highly relevant articles published in the last ~10 years, which signifies the importance of such composites. First, this review addresses the basic concepts of soft and hard tissue engineering, in-cluding the healing mechanisms and limitations ahead. Then, current knowledge on gelatin/BG composites including composition, processing and properties is summarized and discussed both for soft and hard tissue applications. This review explores physical, chemical and mechanical features and ion-release effects of such composites concerning osteogenic and angiogenic respons-es in vivo and in vitro. Additionally, recent developments of BG/gelatin composites using 3D/4D printing for tissue engineering are presented. Finally, the perspectives and current challenges in developing desirable composites for the regeneration of different tissues are outlined.

Objectives: The promising specific growth regulators are employed tissue culture of the bamboo species. The specific natural hardening mixture supports the acclimatization and adaptation of the protected cultivation. The bamboo species contribute to the carbon sequestration and stabilization of the environment. Findings: The growth regulator 2, 4-D encourages callus induction and growth regulators NAA + TDZ, BAP + Kinetin + Gelrite, BAP + Kinetin + Coconut water + myo-inositol, NAA and TDZ impose plant regeneration in the Bambusa species. The growth regulator of 2,4-D, 2,4-D + Kinetin, 2,4-D + BA, 2,4-D + BAP and 2,4-D + NAA + BAP produces callus induction in the Dendrocalamus species. The growth regulator of TDZ, BA and IBA + Coumarin + Putrescine, BAP + GA3, NAA + Kinetin, BA + IBA, BA + Kinetin + NAA, NAA + Kinetin, Kinetin + IAA has facilitated shoot regeneration in the Dendrocalamus species with the specific period. The growth regulator of BA and TDZ; BAP + TDZ, IBA + Coumarin + Putrescine, BAP + GA3, NAA + Kinetin, BA + IBA, BA + Kinetin + NAA, NAA + Kinetin, Kinetin + IAA develops root regeneration with unambiguous time in the Dendrocalamus species. The growth regulator of BAP and Kinetin + BAP imposes shoot regeneration and IBA and IBA + Coumarin + sucrose conducts root regeneration in the edible bamboo. The natural hardening materials of cocopeat, vermicompost, perlite, cow dung, FYM, compost, soil & garden soil and humus soil, perlite, and FYM recommend in the acclimatization and adaptation of the Bambusa species and Dendrocalamus species respectively. Novelty: The standard growth regulators and hardening mixtures impose tissue culture, acclimatization and adaptation in the bamboo species. The bamboo species involves in managing carbon sequestration, biogeochemical cycle and the environment.

The natural hosts regarding Orthohantaviruses are rodents, soricomorphs and bats, and it is well known they may cause serious or even fatal diseases among humans worldwide. The virus is persistent among animals and it is shed via urine, saliva and feces, throughout the entirety of their lives. We aim to identify the effectiveness regarding hantavirus detection from rodent tissue samples and urine originating from naturally infected rodents. Initially, animals were trapped at five distinct locations throughout the Transdanubian region in Hungary. Lung, liver, kidney and urine samples were obtained from 163 perished animals. All organs and urine were tested using nested reverse transcriptase-polymerase chain reaction (nRT-PCR). Furthermore, sera were examined for IgG antibodies against DOBV and PUUV viruses by Western Blot assay. IgG antibodies against hantaviruses and/or nucleic acid were detected in 25 (15.3%) cases. Among Apodemus, Myodes, and Microtus rodent species, DOBV, PUUV, TULV were all clearly identified. The virus nucleic acid was detected most effectively from the kidney (100%), while only 55% of screened lung tissues were positive. Interestingly, only 3 out of 20 rodent urine samples were positive regarding nRT-PCR. Moreover, five rodents were seropositive without detectable virus nucleic acid from any of the tested organs.

The recent legalization of Cannabis sativa L. in many regions has revealed a need for effective propagation and biotechnologies for the species. Micropropagation affords researchers and producers methods to rapidly propagate insect/disease/virus free clonal plants, store germplasm, and forms the basis for other biotechnologies. Despite this need, research in the area is limited due to the long history or prohibitions and restrictions. Existing literature has multiple limitation: many publications use hemp as a proxy for drug-type Cannabis when it is well established that there is significant genotype specificity, studies using drug-type cultivars are predominantly op-timized using a single cultivar, most protocols have not been replicated by independent groups, and some attempts demonstrate a lack of reproducibility across genotypes. Due to culture decline and other problems the multiplication phase of micropropagation (stage 2) has not been fully developed in many reports. This review will provide a brief background on the history and botany of Cannabis as well as a comprehensive and critical summary of Cannabis tissue culture. Special attention will be paid to current challenges faced by researchers, the limitations of existing Cannabis micropropagation studies, and recent developments and future directions of Cannabis tissue culture technologies.

Development encompasses processes that occur at multiple length-scales, includ- ing gene regulatory interactions, cell movements and reorganisation, cell signalling and growth. It is essential that the timing of events in all of these different processes are coordinated to generate well patterned tissues and organs. However, how the timing of intrinsic cell state changes is coordinated with events at the multi-tissue and whole organism level is unknown. Here, we argue that an important mechanism which accounts for integration of timing across levels of organisation is provided by tissue tectonics: i.e. how morphogenetic events driving tissue shape change result in the relative displacement of signalling and responding tissues and coordinate devel- opmental timing across scales. In doing so, tissue tectonics provides a mechanism by which the cell specification events intrinsic to cells can be modulated by the temporal exposure to extracellular signals. This exposure is in turn regulated by higher-order properties of the embryo such as their physical properties, rates of growth and the combination of dynamic cell behaviours impacting tissue morphogenesis. Tissue tec- tonics creates a downward flow of information from higher to lower levels of biological organisation, providing an instance of downward causation in development.

The BRAFV600E mutation, found in approximately 50% of melanoma cases, is associated with aggressive tumor behavior and poor prognosis. This study aimed to assess its impact on immunogenic cell death (ICD), a pivotal cytotoxic process triggering anti-tumor immune responses. Through comprehensive in silico analysis of The Cancer Genome Atlas data, we explored the association between the BRAFV600E mutation, immune subtype dynamics, and tumor mutation burden (TMB). Our findings revealed that the mutation correlated with a lower TMB, indicating a reduced generation of immunogenic neoantigens. Investigation into immune subtypes reveals an exacerbation of immunosuppression mechanisms in BRAFV600E-mutated tumors. To assess the response to ICD inducers, including doxorubicin and Me-ALA-based photodynamic therapy (PDT), compared to the non-ICD inducer cisplatin, we used distinct melanoma cell lines with wild-type BRAF (SK-MEL-2) and BRAFV600E mutation (SK-MEL-28, A375). We demonstrated a differential response to PDT between the WT and BRAFV600E cell lines. Further transcriptomic analysis revealed upregulation of IFNAR1, IFNAR2, and CXCL10 genes associated with the BRAFV600E mutation, suggesting their involvement in ICD. Using a gene reporter assay, we showed that PDT robustly activated the IFN-1 pathway through cGAS-STING signaling. Collectively, our results underscore the complex interplay between the BRAFV600E mutation and immune responses, emphasizing a putative correlation between tumors carrying the mutation and their responsiveness to therapies inducing the IFN-1 pathway, such as the ICD inducer PDT, possibly mediated by the elevated expression of IFNAR1/2 receptors.

Caused by age or trauma, collapsed connective tissue can cause nerve entrapment and damage within the tarsal tunnel. Tarsal tunnel syndrome is relatively underdiagnosed. This study presents an intervention targeting damaged tissues surrounding the nerves and replacing the structural cushioning with a Wharton’s jelly tissue allograft. The eight selected patients from four clinical sites had tarsal tunnel-related defects. Patient outcomes were tracked on a 90-day calendar utilizing the Numeric Pain Rating Scale (NPRS) and the Western Ontario and McMaster University Arthritis Index (WOMAC). All patients had failed standard care practices for at least six weeks. Each patient received a Wharton’s jelly tissue allograft to sites around the affected tarsal tunnel. No patients experienced adverse reactions. Percent change calculated from the initial application to the 90-day follow-up showed an improvement of 59.43% in NPRS and a 37.58% improvement in WOMAC. This study provides evidence that WJ allograft applications are safe, minimally invasive, and efficacious for patients who have failed standard care treatments for tissue defects associated with Tarsal Tunnel syndrome. Limitations include the small cohort size and nonblinded nature. The results of this study warrant further research to confirm the efficacy, optimal dose, protocol, and durability of Wharton's jelly.

During last decades, production and consumption of small ruminant milk has been increased. As a result of it, sheep and goat farming has been developing and scientists are focused on these animal researches both clinical and feeding strategies. By the evolutionary challenges and adaptations, colostrum has a crucial role of immune complementation for litter. As a result of these challenges and adaptations neonatal life is especially more important in ruminants because of it affects their whole life and future of livestock. Passive immune transfer is the main mechanism that explained by biological evolution between dam and lamb and also it is effected by factors up to dam and up to the litter. Today importance of passive immune transfer is well known for the future of livestock economy and animal welfare. In the literature, researchers are focused on correlation between colostrum quality (especially immunoglobulin amounts) and blood serum levels of newborns. Aims of present review are to discuss datas of recent studies, point out different effecting factors in colostrum quality and passive immune transfer, enlighten and give new ideas to researchers.

Transformers are increasing replacing older generation of deep neural networks due to their success in a wide range of application. The dominant approach of using transformers is to pre-train them on a large training dataset and then fine-tune them on a downstream task. However, as transformers becoming larger, the fine-tuning approach is become an infeasible approach for transfer learning. In this short survey, we list a few recent methods that makes using transformers based on transfer learning more efficient.

Graph neural networks (GNNs) build on the success of deep learning models by extending them for use in graph spaces. Transfer learning has proven extremely successful for traditional deep learning problems: resulting in faster training and improved performance. Despite the increasing interest in GNNs and their use cases, there is little research on their transferability. This research demonstrates that transfer learning is effective with GNNs, and describes how source tasks and the choice of GNN impact the ability to learn generalisable knowledge. We perform experiments using real-world and synthetic data within the contexts of node classification and graph classification. To this end, we also provide a general methodology for transfer learning experimentation and present a novel algorithm for generating synthetic graph classification tasks. We compare the performance of GCN, GraphSAGE and GIN across both the synthetic and real-world datasets. Our results demonstrate empirically that GNNs with inductive operations yield statistically significantly improved transfer. Further we show that similarity in community structure between source and target tasks support statistically significant improvements in transfer over and above the use of only the node attributes.

Three-dimensional transfer functions (3D TFs) are generally assumed to fully describe the transfer behavior of optical topography measuring instruments such as coherence scanning interferometers in the spatial frequency domain. Therefore, 3D TFs are supposed to be independent of the surface under investigation resulting in a clear separation of surface properties and transfer characteristics. In this paper we show that the 3D TF of an interference microscope differs depending on whether the object is specularly reflecting or consists of point scatterers. In addition to the 3D TF of a point scatterer, we will derive an analytical expression for the 3D TF corresponding to specular surfaces and demonstrate this as being most relevant in practical applications of coherence scanning interferometry (CSI). We additionally study the effects of temporal coherence and disclose, that in conventional CSI temporal coherence effects dominate. However, narrowband light sources are advantageous if high spatial frequency components of weak phase objects are to be resolved, whereas for low-frequency phase objects of higher amplitude the temporal coherence is less affecting. Finally, we present an approach that explains the different transfer characteristics of coherence peak and phase detection in CSI signal analysis.

When a microgrid is grid-tied to a distribution system, it can provide surplus power generation to the distribution system, if any abnormality or interruption occurs in the distribution system, the microgrid can operate in standalone mode to isolate the impact of the abnormality or interruption. However, if the microgrid can not collect enough information from the distribution system, it may cause the failure of generation transferring of distribution feeders, or even further influence the stability of the distribution system. In this paper, a strategy for the resilient control of a microgrid is proposed. It can solve the above-mentioned problem, reduce the duration of the outage of loads. This strategy is experimented in the microgrid in the Institute of Nuclear Energy Research (INER), the reliability is also analyzed to evaluate the unavailability of the microgrid in INER, and it is verified that the proposed strategy can reduce the duration of the outage of loads, and hence the reliability of a microgrid can be upgraded.

Gastric cancer is an aggressive disease with increasing global incidence in recent years. Human epidermal growth receptor 2 (HER2) is overexpressed in approximately 10-20% of gastric cancers. The implementation of targeted therapy against HER2 as part of the standard of care treatment in metastatic disease has improved the prognosis of this subset of patients. However, gastric cancer still has high mortality rates and urgently requires new treatment strategies. The combination of immunotherapy with HER2-targeted therapies has shown synergistic effects in preclinical models, being the rationale behind exploring this combination in clinical trials in locally advanced and metastatic settings. Additionally, the irruption of antibody-drug conjugates and other novel HER2-targeted agents has led to the development of numerous clinical trials showing promising results. This review presents the molecular mechanisms supporting the use of HER2-targeted drugs in combination with immunotherapy and provides an overview of the therapeutic scenario of HER2-positive disease. We focus on the role of immunotherapy but also summarize emerging therapies and combinations under clinical research that may change the standard treatment in HER-2 positive disease in the future.

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

Accurate transfer learning of clinical outcomes, e.g., of the effects and side effects of drugs or other interventions, from one cellular context to another (in-vitro versus ex-vivo versus in-vivo, or across tissues), between cell-types, developmental stages, omics modalities or species, is considered tremendously useful. Ultimately, it may avoid most drug development failing in translation, despite large investments in the preclinical stages, which includes animal experiments requiring careful justification. Thus, when transferring a prediction task from a source (model) domain to a target domain, what counts is the high quality of the predictions in the target domain, requiring molecular states or processes common to both source and target that can be learned by the predictor, reflected by latent variables. These latent variables may form a compendium of knowledge that is learned in the source, to enable predictions in the target; usually, there are few, if any, labeled target training samples to learn from. Transductive learning then refers to the learning of the predictor in the source domain, transferring its outcome label calculations to the target domain, considering the same task. Inductive learning considers cases where the target predictor is performing a different yet related task as compared to the source predictor, making some labeled target data necessary. Often, there is also a need to first map the variables in the input/feature spaces (e.g. of gene names to orthologs) and/or the variables in the output/outcome spaces (e.g. by matching of labels). Transfer across omics modalities also requires that the molecular information flow connecting these modalities is sufficiently conserved. Only one of the methods for transfer learning we reviewed offers an assessment of input data, suggesting that transfer learning is unreliable in certain cases. Moreover, source domains feature their very own particularities, and transfer learning should consider these, e.g., as differences in pharmacokinetics, drug clearance or the microenvironment. In light of these general considerations, we here discuss and juxtapose various recent transfer learning approaches, specifically designed (or at least adaptable) to predict clinical (human in-vivo) outcomes based on molecular data, towards finding the right tool for a given task, and paving the way for a comprehensive and systematic comparison of the suitability and accuracy of transfer learning of clinical outcomes.

In this paper, we revisit a modified version of the classical Whitehead's theory of gravity in which all possible bilinear forms are considered to define the corresponding metric. Although, this is a linear theory that fails to give accurate results for the most sophisticated predictions of general relativity, such as gravity waves, it can still provide a convenient framework to analyze some new phenomena in the Solar System. In particular, recent development in the accurate tracking of spacecraft and the ephemerides of planetary positions have revealed certain anomalies in relation with our standard paradigm for celestial mechanics. Among them the so-called flyby anomaly and the anomalous increase of the astronomical unit play a prominent role. In the first case the total energy of the spacecraft changes during the flyby and a secular variation of the semi-major axis of the planetary orbits is found in the second anomaly. For this to happen it seems that a net energy and angular momentum transfer is taken place among the orbiting and the central body. We evaluate the total transfer per revolution for a planet orbiting the Sun in order to predict the astronomical unit anomaly in the context of Whitehead's theory. This could lead to a more deeply founded hypothesis for an extended gravity model.

Phagocytosis (and endocytosis) is an unusual cellular process which results in the formation of a novel subcellular organelle, the phagosome. This phagosome contains not only the internalised target of phagocytosis, but also the external medium, creating a new border between extracellular and intracellular environments. The boundary at the plasma membrane is, of course, tightly controlled and exploited in ionic cell signalling events. Although there has been much work on the control of phagocytosis by ions, notable Ca2+ ions influxing across the plasma membrane, increasing our understanding of the mechanism enormously, very little work has been done exploring the phagosome/cytosol boundary. In this paper, we have explored the changes in the intra-phagosomal Ca2+ ion content which occur during phagocytosis and phagosome formation in human neutrophils. Measuring Ca2+ ion concentration in the phagosome is potentially prone to artefacts as the intra-phagosomal environment experiences changes in pH and oxidation. However, by excluding such artefacts, we conclude that there are open Ca2+ channels on the phagosome, which allow Ca2+ ions to ‘drain’ into the surrounding cytosol. This conclusion was confirmed by monitoring the translocation of intracellularly expressed YFP-tagged C2 domain of PKC-γ. This approach marked regions of membrane at which Ca2+ influx occurred, the earliest being the phagocytic cup, and then the whole cell. This paper therefore presents data which has novel implications for understanding phagocytic Ca2+ signalling events, such as peri-phagosomal Ca2+ hotspots, and other phenomena.

Formation of the excited doublet (D) and quartet (Q) states of free radicals under their photoexcitation is discussed. Relative positions of D and Q states are compared to the positions of photoexcited states of organic molecules (Jablonsky diagram). A number of representative cases of the detected by emission or absorption excited is presented. A special case of the population lowest Q-state in some radicals of is discoursed. Spin-statistical factor in the reactions of Q and D is debated.

One of the most popular techniques for determining electrical properties of material is the free-space measurement technique. With the potential for new applications requiring efficient, accurate and broadband material measurement systems using higher millimeter-wave and terahertz frequencies, the free-space measurement method has received renewed interest. This is mainly due to its simplicity, favorable properties as a non-destructive method, and it allows transmission and reflection measurements without any physical contact with the sample. This paper reviews and discusses state- of-the-art free space material measurement systems, starting with the different measurement techniques available for material characterization, their important concepts, post-processing in determining their properties, and progress towards expanding their use at higher frequencies. Also, this paper reviews dielectric material characterization using the free space method focusing on their application extension towards the higher frequencies. Besides, the algorithms for conversion methods and usage of lens in free space material measurement system was discussed in this paper. Finally, a future perspective on the outlook of this free space method is presented prior to the conclusion.

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

We explore the class of positive integers n that admit idempotent factorizations n=pq such that lambda(n) divides (p-1)(q-1), where lambda(n) is the Carmichael lambda function. Idempotent factorizations with p and q prime have received the most attention due to their cryptographic advantages, but there are an infinite number of n with idempotent factorizations containing composite p and/or q. Idempotent factorizations are exactly those p and q that generate correctly functioning keys in the RSA 2-prime protocol with n as the modulus. While the resulting p and q have no cryptographic utility and therefore should never be employed in that capacity, idempotent factorizations warrant study in their own right as they live at the intersection of multiple hard problems in computer science and number theory. We present some analytical results here. We also demonstrate the existence of maximally idempotent integers, those n for which all bipartite factorizations are idempotent. We show how to construct them, and present preliminary results on their distribution.

Using insights from cybernetics and an information-based understanding of biological systems, a precise, scientifically inspired, definition of free-will is offered and the essential requirements for an agent to possess it in principle are set out. These are: a) there must be a self to self-determine; b) there must be a non-zero probability of more than one option being enacted; c) there must be an internal means of choosing among options (which is not merely random, since randomness is not a choice). For (a) to be fulfilled, the agent of self-determination must be organisationally closed (a `Kantian whole'). For (c) to be fulfilled: d) options must be generated from an internal model of the self which can calculate future states contingent on possible responses; e) choosing among these options requires their evaluation using an internally generated goal defined on an objective function representing the overall `master function' of the agent and f) for `deep free-will', at least two nested levels of choice and goal (d-e) must be enacted by the agent. The agent must also be able to enact its choice in physical reality. The only systems known to meet all these criteria are living organisms, not just humans, but a wide range of organisms. The main impediment to free-will in present-day artificial robots, is their lack of being a Kantian whole. Consciousness does not seem to be a requirement and the minimum complexity for a free-will system may be quite low and include relatively simple life-forms that are at least able to learn.

Regenerative Medicine and Tissue Engineering are interdisciplinary fields that combine cell biology, material science, and bioengineering to develop therapies for tissue repair and regeneration. This field has made significant advances in recent years, particularly in the use of stem cells and biomaterials. Advancements in cell-based therapies have involved the use of cells to repair or replace damaged tissues and organs. Tissue engineering involves using scaffolds and growth factors to promote tissue regeneration. However, a major challenge in this field is the formation of adhesions, which can cause complications, such as intestinal obstruction and chronic pain. Adhesion barriers are used to prevent adhesion of tissues and organs during recovery, thereby reducing the risk of complications. Anti-adhesion materials, such as polysaccharides, proteins, and synthetic polymers, are used to create a physical barrier between tissues and prevent adhesion. These materials can be used alone or in combination, but their effectiveness varies.

Ovarian tissue cryopreservation (OTC) or testicular tissue cryopreservation (TTC) are effective and often the only options for fertility preservation in female or male patients due to oncological, medical, or social aspects. While TTC and resumption of spermatogenesis, either in vivo or in vitro, has still be considered an experimental approach in humans, OTC and autotransplantation has been applied increasingly to preserve fertility with more than 200 live births worldwide. However, the cryopreservation of reproductive cells followed by the resumption of gametogenesis, either in vivo or in vitro, may interfere with sensitive and highly regulated cellular processes. In particular, the epigenetic profile, which includes not just reversible modifications of the DNA itself but also post-translational histone modifications, small non-coding RNAs, gene expression and availability, and storage of related proteins or transcripts, have to be considered in this context. Due to complex reprogramming and maintenance mechanisms of the epigenome in germ cells, growing embryos, and offspring, OTC and TTC are carried out at very critical moments early in the life cycle. Given this background, the safety of OTC and TTC taking into account the epigenetic profile has to be clarified. Cryopreservation of mature germ cells (including Metaphase II oocytes and mature spermatozoa collected via ejaculation or more invasively after testicular biopsy) or embryos has been used successfully for many years in Medically Assisted Reproduction (MAR). However, tissue freezing followed by in vitro or in vivo gametogenesis has become more attractive in the past, while few human studies have analysed the epigenetic effects, with most data deriving from animal studies. In this review, we highlight the potential influence of the cryopreservation of immature germ cells and subsequent in vivo or in vitro growth and differentiation on the epigenetic profile in humans and animals.

Inflammation plays a key role in the development and progression of type-2 diabetes (T2D), a disease characterised by peripheral insulin resistance and systemic glucolipotoxicity. Visceral adipose tissue (AT) is the main source of inflammation early in disease course. Macrophages are innate immune cells that populate all peripheral tissues, including AT. Dysregulated AT macrophage (ATM) responses to microenvironmental changes are at the root of aberrant inflammation and development of insulin resistance, locally and systemically. The inflammatory activation of macrophages is regulated at multiple levels: cell surface receptor stimulation, intracellular signalling, transcriptionally and metabolically. This review will cover the main mechanisms involved in AT inflammation and insulin resistance in T2D. First, we will describe the physiological and pathological changes in AT that lead to inflammation and insu- lin resistance. We will next focus on the transcriptional and metabolic mechanisms described that lead to the activation of ATMs. We will discuss more novel metabolic mechanisms that influence macrophage polarisation in other disease or tissues contexts that may be relevant to future work in insulin resistance and T2D.

The results of the most recent investigation of triterpenoid-based antiviral agents effective namely in the HIV-1 and HSV-1 treatment were reviewed and summarized. Several key historical achievements are included to stress consequences and continuity in this research. Most of the agents studied belong into a series of compound derived from betulin or betulinic acid, and their synthetic derivative called bevirimat. A termination of clinical trials of bevirimat in the Phase IIb initiated a search for more successful compounds partly derived from bevirimat or designed independently of bevirimat structure. Surprisingly, a majority of bevirimat mimics are derivatives of betulinic acid, while other plant triterpenoids, such as ursolic acid, oleanolic acid, glycyrrhetinic acid or other miscellaneous triterpenoids, are relatively rarely involved in a search for novel antiviral agent. Therefore, this review article is divided into three parts based on the leading triterpenoid core structure.

Diabetes mellitus (DM) poses a significant challenge to global health, with its prevalence projected to rise dramatically by 2045. This narrative review explores the bidirectional relationship between periodontitis (PD) and type 1 diabetes mellitus (T1DM), focusing on cellular and molecular mechanisms derived by the interplay between oral microbiota and the host immune response. A comprehensive search of literature published between 2008 and 2023 was conducted to elucidate the association between these two diseases. Preclinical and clinical evidence suggests a bidirectional relationship, with individuals with T1DM exhibiting heightened susceptibility to periodontitis, and vice versa. The review includes recent findings from human clinical studies, revealing variations in oral microbiota composition in T1DM patients, including increases in certain pathogenic species such as Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, along with shifts in microbial diversity and abundance. Molecular mechanisms underlying this association involve oxidative stress and dysregulated host immune responses, mediated by inflammatory cytokines such as IL-6, IL-8, and MMPs. Furthermore, disruptions in bone turnover markers, such as RANKL and OPG, contribute to periodontal complications in T1DM patients. While preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population.

Brazil, Russia, China, India, and the Republic of South Africa (BRICS) represent developing economies facing different energy and economic development challenges. The current study aims to forecast energy consumption in BRICS at aggregate and disaggregate levels using the annual time series data set from 1992 to 2019 and to compare results obtained from a set of models. The time-series data are from the British Petroleum (BP-2019) Statistical Review of World Energy. The forecasting methodology bases on a novel Fractional-order Grey Model (FGM) with different order parameters. This study contributes to the literature by comparing the forecasting accuracy and the forecasting ability of the FGM(1,1) with traditional ones, like standard GM(1,1) and ARIMA(1,1,1) models. Also, it illustrates the view of BRICS's nexus of energy consumption at aggregate and disaggregates levels using the latest available data set, which will provide a reliable and broader perspective. The Diebold-Mariano test results confirmed the equal predictive ability of FGM(1,1) for a specific range of order parameters and the ARIMA(1,1,1) model and the usefulness of both approaches for energy consumption efficient forecasting.

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.

Crohn's disease is a non-specific inflammatory bowel disease, which is a chronic condition that affects the ileum and/or large intestine. At the same time, it can also involve any other part of the human body, that is, from the mouth to the anus. The symptoms are very bothersome and cause a significant reduction in quality of life and sometimes even crippling permanent damage to the gastrointestinal tract, which requires enteral or parenteral nutrition for life. The purpose of this study was to investigate tissue metalloproteinases as markers of recurrent Crohn's disease. The experimental groups included 31 patients and 10 patients with normal Crohn's disease, ranging in age from 23-70 years, with a mean age of 40.4. Collected tissues were frozen and then fragmented tissues were homogenized with Ripa Lysis buffer on ice. The supernatant was collared and four metalloproteinases - MMP 3, MMP 7, MMP 8 and MMP 9 - were an-alized by Enzyme-linked Immunosorbent Assay using SEA101HU, SEA102Hu, SEA103Hu and SEA553Hu kits (Cloud-Clone Corp., Kata, TX, USA). All chemical analyses were performed in triplicate. Metalloproteinase content was expressed as mean ± standard deviation. Metalloproteinase 3 and metalloproteinase 8) significantly influenced the possibility of Crohn recurrence

Pulse oximetry is the current standard for detecting drops in arterial blood oxygen saturation (SpO₂) associated with obstructive sleep apnea and hypopnea events in polysomnographic (PSG) testing. In cases of hypoxic challenge, such as occurs during apneic events, regulatory mechanisms restrict blood flow to the skin to preferentially maintain SpO₂ for more vital organs. As a result, a measure related to skin tissue oxygenation is likely to be more sensitive to inadequate breathing during sleep than pulse oximetry. Energy Conversion Monitoring (ECM) provides a method for measuring skin tissue oxygen-dependent energy conversion and, as such, is promising for more sensitively detecting sleep disordered breathing (SDB) events compared to pulse oximetry. We hypothesized that ECM would detect hypoxia occurring with SDB events associated with drops in SpO₂ but also would detect hypoxic challenge occurring with SDB events not associated with drops in SpO₂ (hypopneas defined by a drop in nasal pressure occurring in conjunction with an arousal, respiratory-related arousals, and primary snoring). Primary snoring is of particular interest with respect to the potential of ECM because it is statistically associated with co-morbidities of SDB, such as hypertension, but is not considered pathological because of the lack of a proximal measure of pathology occurring with PSG. In this article we review ECM technology and methodology, present preliminary data indicating that it detects hypoxia occurring in the skin during SDB events that is not detected as blood desaturation by pulse oximetry, and make the case that it is a promising tool for identifying pathology occurring at the mild end of the SDB spectrum.

The aim of the study was to evaluate the influence of transduser design and its elements, and their materials on temperature in deeper layers of tissues measurement results. A digital modeling was performed to evaluate the influence of the properties of transduser design elements. Experimental research was carried out. Revealed that the accuracy, similar to that of an invasive method using needle probes, can be achieved by measuring the temperature in deeper muscle layers using the proposed transducer.

Background: Hepatic erythrophagocytosis is augmented in NASH and amplifies inflammation and fibrosis. Although various pro-phagocytic signals have been identified on erythrocytes of NASH patients, the role of bound thrombospondin-1 (TSP-1), which acts as an “eat-me” signal, arginase-1, which regulates the levels of nitric oxide in erythrocytes, and phosphatidylethano-lamine (PE) which can amplify erythrophagocytosis and hepatic inflammation have not been explored. Hence, we sought to investigate the levels of arginase-1 and TSP-1 in erythrocyte lysate and PE in erythrocyte membranes of NASH patients. Methods: Twenty-four patients and 14 healthy controls participated in our study. The levels of TSP-1 and arginase were quantified by ELISA in erythrocyte lysates, and the levels of PE in erythrocyte membranes by thin layer chro-matography. Results: Erythrocytes of NAFLD patients exhibit lower levels of arginase-1 and TSP-1 (p<0.01). Erythrocyte-bound TSP-1 levels correlated with the levels of erythrocyte surface CD47. Phosphatidylethanolamine was increased in erythrocytes of NASH patients and was accompanied by increased release, indicating exposure. Conclusion: Our results imply reduced TSP-1 binding by erythrocytes which could allow free TSP-1 molecules to act on macrophages, enhancing erythrophagocytosis. Increased PE which could amplify inflammation after efferocytosis, while downregulation of arginase-1 could lead to defective efferocytosis.

Early detection of neurological conditions is critical for timely diagnosis and treatment. Identifying cellular-level changes is essential for implementing therapeutic interventions prior to symptomatic disease onset. However, monitoring brain tissue directly through biopsies is invasive and high-risk. Bodily fluids such as blood or cerebrospinal fluid contain information in many forms, including proteins and nucleic acids. Particularly, cell-free DNA (cfDNA) has potential as a versatile neurological biomarker. Yet, our knowledge of cfDNA released by brain tissue and how cfDNA changes in response to deleterious events within the brain is incomplete. Mapping changes in cfDNA to specific cellular events is difficult in vivo, where many tissues contribute to circulating cfDNA. Organoids are tractable systems for examining specific changes consistently in a human background. However, few studies have investigated cfDNA released from organoids. Here, we examined cfDNA isolated from cerebral organoids. We found that cerebral organoids release quantities of cfDNA sufficient for downstream analysis with droplet-digital PCR and whole-genome sequencing. Further, gene ontology analysis of genes aligning with sequenced cfDNA fragments revealed association with terms related to neurodevelopment and autism spectrum disorder. We conclude that cerebral organoids hold promise as tools for the discovery of cfDNA biomarkers related to neurodevelopmental and neurological disorders.

Complex-structured polymeric microparticles hold significant promise as advance in next-generation medicine mostly due to demand from developing targeted drug delivery. However, the conventional methods for producing these microparticles of defined size, shape and sophisticated composition often face challenges in scalability, reliance on specialized components such as micro-patterned templates, or have limited control over particle size distribution and cargo release kinetics. In this study, we introduce a novel and reliably scalable approach for manufacturing microparticles of defined structures and sizes with variable parameters. The concept behind this method involves the deposition of a specific number of polymer layers on a substrate with low surface energy. Each layer can serve as either the carrier for cargo or a programmable shell-former with predefined permeability. Subsequently, this layered structure is precisely cut into desired-sized blanks using a laser. The manufacturing process is completed by applying of heat to the substrate what results on sealing the edges of the blanks. The combination of the high surface tension of the molten polymer and the low surface energy of the substrate enables the formation of discrete particles, each possessing semi-spherical or other designed geometries determined by their internal composition. Such anisotropic microparticles are envisaged versatile applications.

Surrogate model based optimization method is widely-used to accelerate the design and optimization process~\cite{marler2004survey}. The input of regression model used in the surrogate model are numbers, which requires users to parametrize the geometries. In this paper, a new parameterization-free surrogate model is introduced and its corresponding uncertainty quantification and sensitivity analysis method are discussed. The input of new surrogate model methods is surface mesh of simulation domain. \Gls{gnns} is used to extract geometric information, and \Gls{cnns} is used to predict contours. This framework bypasses parameterization,as a consequence, uncertainties introduced by manual parameterization is reduced. However, such changes compared with conventional surrogate model methods impose great challenge on uncertainties quantification and sensitivity analysis. Uncertainties quantification in this paper means the error bar of prediction results, which is calculated by Gaussian Process Regression method in current surrogate method. In this paper, a new quantification method achieved by Kullback-Leibler divergence (KLD) is introduced. And the sensitivity analysis is conducted by Automatic Differentiation, which gives a Jacobian matrix of inputs. The method and analysis mentioned above are demonstrated by a low-pressure steam turbine rotator and its exhaust system.

The mechanisms of natural oscillations and resonance are described, considering the peculiarities of the transformation of elastic and kinetic energy in the implementation of the law of conservation of energy in local and integral volumes of the body, using the concept of mechanics based on the concepts of space, time and energy. When describing the motion in the Lagrange form, the elastic deformation energy of the particles is determined by the quadratic invariant of the tensor, whose components are the partial derivatives of Euler variables with respect to Lagrange variables. The increment of the invariant due to elastic deformation is represented as the sum of two scalars, one of which depends on the average value of the relative lengths of the edges of the particles in the form of an infinitesimal parallelepiped, the second is equal to the standard deviation of these lengths from the average value. It is shown that each of the scalars can be represented in the form of two dimensionless kinematic parameters of elastic energy, which participate in different ways in the implementation of the law of conservation of energy. One part of the elastic energy passes into kinetic energy and participates in the implementation of the law of conservation of energy for the body as a whole, considering external forces. The second part is not converted into kinetic energy but changes the deformed state of the particles in accordance with the equations of motion while maintaining the same level of the part of the elastic energy of the particles used for this. The kinematic parameters differ from the volume density of the corresponding types of energy by a factor equal to the elastic modulus, which is directly proportional to the density and heat capacity of the material and inversely proportional to the volume compression coefficient. Transverse, torsional, and longitudinal vibrations are considered free and under resonance conditions. The mechanisms of transformation of forced vibrations into their own after the termination of external influences and resonance at the superposition of free and forced vibrations with the same or similar frequency are considered. The formation of a new free wave at each cycle with an increase in the amplitude, which occurs mainly due to internal energy sources, and not external forces, is justified.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes.

Adipose tissue has acquired considerable importance due to its role in maintaining body homeostasis. Beyond storing energy, adipose tissue is essential in numerous processes of energy metabolism, food intake, endocrine and immunological functions as well as neromodulatory functions by secreting hormones that participate in the regulation of homeostasis and being responsive to soluble proteins secreted by other tissues. An imbalance of these functions will generate structural and functional changes in the adipose tissue, favouring the secretion of deleterious adipocytokines that benefit a pro-inflammatory state, allowing the development of metabolic and cardiovascular diseases. Obesity is a disease that has increased rapidly in recent decades and is caused by environmental, hormonal, and genetic factors, which probably work in combination. Environmental factors that contribute to the increase in obesity include decreased physical activity, associated with increased screen time, increased accessibility and consumption of foods rich in fats and sugars. Weight loss should be recommended for all obese patients and overweight patients with comorbidities. For many patients who need to lose weight for medical reasons, the initial goal is to lose 5-10% of their body weight in the first 6 months. A common theme worldwide has been the development of professional guidelines for the control and treatment of obesity and in Chile, the Chilean Society of Metabolic and Bariatric Surgery led the process of adopting the adult obesity clinical practice guideline, which establishes changes in the approach to managing obesity as a chronic disease, with an emphasis on multifactorial lifestyle interventions that include dietary changes, increased physical activity, and behavioural modifications. Pharmacotherapy, medical devices, and bariatric surgery are other options for patients who need additional interventions, so the objective of this review is to know the pathophysiological mechanisms of obesity from its origin to the current treatments available for treatment.

We previously showed that feeding mice a diet containing 1% mantle tissue decreased food consumption, leading to death. We also isolated and identified toxic substances in the mantle tissue. In the present study, we investigated the characteristics and stability of mantle tissue toxicity. Treatment of mantle tissue with 1 mM HCl, 1 mM NaOH, 1 mM dithiothreitol, and 1 mM H2O2 and heating did not reduce the toxicity of mantle tissue in mice. These results suggest that mantle toxins are stable in tissues, particularly when exposed to acidic and digestive enzymes. We examined whether mantle tissue exhibited acute toxicity. Diets containing 1% and 20% mantle extract showed similar levels of toxicity, demonstrating that feeding of mantle tissue does not lead to acute toxicity. Finally, we examined the toxicity of the mantle tissue against small intestinal tissue. Chronic feeding of mantle tissue to mice changed the color of the small intestine. Real-time PCR analysis showed that mantle tissue feeding caused changes of inflammation and endoplasmic reticulum stress markers in the small intestine. These results suggest that feeding of mantle tissue causes toxicity after causing initial damage to the small intestinal tissue.

Lack of reliable information on PTC industry in Sri Lanka is hampering the advancement of the technology. Hence, this study attempted to assess the current status of PTC industry in Sri Lanka in order to ascertain the type and the level of interventions needed to broaden the horizons of the industry. Data of last 05 years were collected through qualitative research methods including a questionnaire-based survey, personal interviews, etc. and personal interviews to identify product diversity, R&D, available facilities, production capacity, and markets. Information was analyzed qualitatively using descriptive statistical software to assess the current status, and identify gaps, challenges and opportunities. COVID pandemic and the economic crisis had a heavy toll on the PTC industry. Six major challenges experienced by business owners were identified as increasing capacity, opportunities to build market linkages, demand fluctuations, issues relating to awareness and insufficient support given by the government. Proper identification and screening of mother plants, determining the production capacities and marketing, knowledgeable and skilled human resources, were identified as important contributory factors for success. Development strategies identified mainly include instinctive decision making and government support. Embracing the significant trade achievements through resource reallocation, prioritization and improvisation processes at individual, family group, inter-organizational levels and across these levels need to be regulated through a responsible authority. These interpretations and recommendations of this research can be utilized both by the policy makers and public and private sector organizations for decision making purposes targeting commercial scale advancements.

Fabry disease (FD) is a X-linked inheritable storage disease caused by deficiency of al-pha-galactosidase causing lysosomal overload of sphingolipids. FD cardiomyopathy is character-ized by left ventricular (LV) hypertrophy and should be considered in differential diagnosis with all the other causes of LV hypertrophy. An early diagnosis of FD is very important because the enzyme replacement therapy (ERT) may change the fate of patients by blocking both cardiac and systemic involvement and improving prognosis. Diagnosis may be relatively easy in young patients with the typical signs ans symptoms of FD, but in male patients with late onset of disease and in females, diagnosis may be very challenging. Morphological and functional aspects are not specific for FD, which cannot be diagnosed or excluded by echocardiography. Cardiac magnetic resonance (CMR) with tissue characterization capability, is the preferred technique for the differential diagnosis of LV hypertrophy. The finding of decreased myocardial T1 value in LV hypertrophy is very specific for FD. Late gadolinium enhancement (LGE) is found in late stage of disease but it is useful to predict the cardiac response to ERT and to stratify the prognosis.

In most Eukaryotes, ubiquitin either exists as free monoubiquitin or as a molecule that is covalently linked to other proteins. These two forms cycle between each other and due to the concerted antagonistic activity of ubiquitylating and deubiquitylating enzymes, an intracellular ubiquitin equilibrium is maintained that is essential for normal biological function. However, measuring the level and ratio of these forms of ubiquitin has been difficult and time consuming. In this paper, we have adapted a simple immunoblotting technique to monitor ubiquitin content and equilibrium dynamics in different developmental stages and tissues of Drosophila. Our data show that the level of total ubiquitin is distinct in different developmental stages, lowest at the larval-pupal transition and in three days old adult males, and highest in first instar larvae. Interestingly, the ratio of free mono-ubiquitin remains within 30-50% range of the total throughout larval development, but peaks to 70-80% at the larval-pupal and the pupal-adult transitions. It stays within the 70-80% range in adults. In developmentally and physiologically active tissues, the ratio of free ubiquitin is similarly high, most likely reflecting a high demand for ubiquitin availability. We also used this method to demonstrate the disruption of the finely tuned ubiquitin equilibrium by the abolition of proteasome function or the housekeeping deubiquitylase, Usp5. Our data support the notion that the ubiquitin equilibrium is regulated by tissue- and developmental stage-specific mechanisms.

Using machine learning or deep learning to solve the problem of garbage recognition and classification is an important application in computer vision, but due to the incomplete establishment of garbage datasets and the poor performance of complex network models on smart terminal devices, the existing garbage classification models The effect is not good.This paper presents a waste classification and identification method base on transfer learning and lightweight neural network. By migrating the lightweight neural network MobileNetV2 and rebuild it, The reconstructed network is used for feature extraction, and the extracted features are introduced into the SVM to realize the identification of 6 types of garbage. The model was trained and verified by using 2527 pieces of garbage labeled data in the TrashNet dataset, which ultimately resulted in a classification accuracy of 98.4% of the method, which proves that the method can effectively improve the classification accuracy and time and overcome the problem of weak data and less labeling. The over-fitting phenomenon encountered by small data sets in deep learning makes the model robust.

Contactless charging is evolving fast in many domains and applications such as the electrical vehicles (EV). The principle consists of transferring energy between two systems without having any electrical connection between them. This power transfer can be realized by emitting a magnetic field for Inductive Power Transfer (IPT). In the automotive domain, the application of contactless charging to supply power to the vehicle while driving is one of the solutions envisaged to solve the limited autonomy range of EV and reduced its cost but the system must comply with existing standards (e.g., allocated frequency range and radiated electromagnetic emissions), as summarized in this paper.

Conventional text style transfer (TST) methodologies primarily utilize style classifiers to segregate the content and stylistic elements of text for effective style transformation. Despite the pivotal role of these classifiers, their influence on TST techniques remains largely unexplored. This study embarks on a detailed exploration of the limitations inherent in style classifiers within current TST frameworks. We reveal that these classifiers often inadequately comprehend sentence syntax, leading to diminished performance in TST models. In response, we introduce the Syntax-Enhanced Style Transfer (SEST) model, a groundbreaking approach incorporating a syntax-sensitive style classifier. This classifier ensures that the extracted style representations robustly encapsulate syntax nuances, enhancing TST effectiveness. Rigorous evaluations across diverse TST benchmarks demonstrate that SEST significantly surpasses contemporary models in performance. Additionally, our case studies highlight SEST's proficiency in producing syntactically coherent sentences that aptly retain original content.

In this review, photoinduced electron transfer processes in specifically designed assembled ar-chitectures have been investigated on the basis of recent results reported from our laboratories. A convenient and useful way to study these kinds of systems has been described in order to under-stand the rules that drive to a light induced charge separation and its subsequent decay to the ground state, also with the aim of offering a tutorial for young researchers. Assembled systems of covalent or supramolecular nature have been presented and some functional multicomponent systems for the conversion of light energy into chemical energy have been discussed.

The paper concludes the first research on mouth-based Emotion Recognition (ER), adopting a Transfer Learning (TL) approach. Transfer Learning results paramount for mouth-based emotion ER, because a few data sets are available, and most of them include emotional expressions simulated by actors, instead of adopting a real-world categorization. Using TL we can use fewer training data than training a whole network from scratch, thus more efficiently fine-tuning the network with emotional data and improving the convolutional neural network accuracy in the desired domain. The proposed approach aims at improving the Emotion Recognition dynamically, taking into account not only new scenarios but also modified situations with respect to the initial training phase, because the image of the mouth can be available even when the whole face is visible only in an unfavourable perspective. Typical applications include automated supervision of bedridden critical patients in an healthcare management environment, or portable applications supporting disabled users having difficulties in seeing or recognizing facial emotions. This work takes advantage from previous preliminary works on mouth-based emotion recognition using CNN deep-learning, and has the further benefit of testing and comparing a set of networks on large data sets for face-based emotion recognition well known in literature. The final result is not directly comparable with works on full-face ER, but valorizes the significance of mouth in emotion recognition, obtaining consistent performances on the visual emotion recognition domain.

Quaking aspen (Populus tremuloides Michx.) is an important deciduous species in western U.S. forests. Existing maps of aspen distribution are based on Landsat imagery and often miss small stands (&lt;0.09 ha or 30 m²), which rapidly regrow when managed or following disturbance. In this study, we present methods for deriving a new regional map of aspen forests using one year of Sentinel-1 (S1) and Sentinel-2 (S2) imagery in Google Earth Engine. We assessed the annual phenology of aspen in the Southern Rockies and leveraged the frequent temporal resolution of S1 and S2 to create ecologically relevant seasonal composites. Additionally, we derived spectral indices and radar textural features targeting the canopy structure, moisture, and chlorophyll content. Using spatial block cross-validation and Random Forests, we assessed the accuracy of different scenarios and selected the best performing set of features for classification. Comparisons were then made with existing landcover products across the study region. The resulting map improves on existing landcover products in both accuracy (average F1-score = 93.1%) and detection of smaller forest patches. These methods enable accurate mapping at spatial and temporal scales relevant to forest management for one of the most widely distributed tree species in North America.

Diamidophosphate has been identified as a possible prebiotic compound used in the precursor membranes of the first ‘life’. Compounds such as these will be helpful in developing novel biomimetic approaches in synthetic chemistry. Thermochemical data for this type of compounds are not available. Hess’ law and estimates from calorimetric measurements used by Wakefield in the 1970s for other amido phosphates have been used to estimate the thermochemical values for the diamido and monoamido-phosphoric acid. Enthalpy of formation at 298.15 ^oC is calculated as – 821.9 kJ/mol and the free energy of formation calculated as -813.5 kJ/mol for the diamidophosphoric acid. The calculated enthalpy of formation of monoamidic phosphoric acid is -1117.1 kJ/mol and its free energy of formation is - -1105 kJ/mol.

Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of regulation of efficient virus replication. In this study, we comprehen-sively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182 are reproducibly deregulated dur-ing productive infection. These miRNAs are predicted to regulate a great number of potential tar-gets involved in different cellular processes and have only 33 shared targets. Among these, mem-bers of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus.

This review provides insight into the role that obesity, but especially mediators of the adipose tissue, have in both renal disease and transplantation. In particular, we focus on the functions of leptin and adiponectin, inflammatory mediators with widely known clinical implications, as well as on the role of arachidonic acid-derived eicosanoid metabolites. These latter compounds, epoxyeicosatrienoic (EETs) and hydroxyeicosatetraenoic (HETEs) acids, which modulate the liberation of cytokines in the adipose tissue, are generated in the epoxygenase pathway of arachidonic biotransformation via CYP450 enzymes. There is accumulating evidence suggesting that EETs and HETEs may have a critical role in the onset and outcome of chronic kidney disease and renal transplantation. Finally, we also discuss the reported effect that the presence of genetic variants in leptin, adiponectin, EETs and HETEs-related genes may cause in renal patients and recipients. The levels of cytokines of the adipose tissue and related compounds play a remarkable role in both renal disease and transplant. Accordingly, novel therapeutic strategies are being developed based on the modulation of their concentrations in patients with various diseases.

Nanocellulose is cellulose in the form of nanostructures, i.e. features not exceeding 100 nm at least in one dimension. These nanostructures include nanofibrils, e.g. in bacterial cellulose; nanofibers, e.g. in electrospun matrices; nanowhiskers and nanocrystals. These structures can be further assembled into bigger 2D and 3D nano-, micro- and macro-structures, such as nanoplatelets, membranes, films, microparticles and porous macroscopic matrices. There are four main sources of nanocellulose: bacteria (Gluonacetobacter), plants (trees, shrubs, herbs), algae (Cladophora) and animals (Tunicata). Nanocellulose has emerged for a wide range of industrial, technology and biomedical applications, e.g. for adsorption, ultrafiltration, packaging, conservation of historical artifacts, thermal insulation and fire retardation, energy extraction and storage, acoustics, sensorics, controlled drug delivery, and particularly for tissue engineering. Nanocellulose is promising for use in scaffolds for engineering of blood vessels, neural tissue, bone, cartilage, liver, adipose tissue, urethra and dura mater, for repairing connective tissue and congenital heart defects, and for constructing contact lenses and protective barriers. This review is focused on applications of nanocellulose in skin tissue engineering and wound healing as a scaffold for cell growth, for delivering cells into wounds, and as a material for advanced wound dressings coupled with drug delivery, transparency and sensorics. Potential cytotoxicity and immunogenicity of nanocellulose are also discussed.

The purpose of this paper is to propose a novel transfer learning regularization method based on knowledge distillation. Recently, transfer learning methods have been used in various fields. However, the problems such as knowledge loss still occur during the process of transfer learning to a new target dataset. To solve these problems, there are various regularization methods based on knowledge distillation techniques. In this paper, we propose a transfer learning regularization method based on feature map alignment used in the field of knowledge distillation. The proposed method is composed of two attention based submodules: self-pixel attention (SPA) and global channel attention (GCA). The self-pixel attention submodule utilizes both the feature maps of the source and target models, so that it provides an opportunity to jointly consider the features of the target and the knowledge of the source. The global channel attention submodule determines the importance of channels through all layers, unlike the existing methods that calculate these only within a single layer. Accordingly, transfer learning regularization is performed by considering both the internal of each single layer and the depth of the entire layer. Consequently, the proposed method using both of these submodules showed overall improved classification accuracy than the existing methods in classification experiments on commonly used dataset.

We aimed to investigate the clinical results following poor-quality embryo transfer and the parameters to foresee the prognosis. In this study, 2123 cycles that had day 3 and day 5 single-fresh embryo with a poor-quality embryo transfers and a good-quality embryo transfers were compared. The cycles according to transfer day were evaluated by conducting a subgroup analysis. The correlation between all the obtained demographic characteristics, controlled ovarian stimulation parameters and cycle results were analysed. Clinical pregnancy was established in 53 patients that underwent transfer in the poor-quality embryo group (14.9%). Of these patients, 36 had live birth (live birth rate per clinical pregnancy 67.9%). In cleavage-stage embryos, live birth rates per clinical pregnancy were higher in poor-quality blastocyst transfer. When analysing the factors affecting live births in poor-quality embryo group, as the total gonadotropin dose increases, the probability of live birth decreases, as in the probability of hCG positivity. In conclusion; although the probability of pregnant is low, when clinical pregnancy is established, there is a high chance of having a live birth after poor-quality embryo transfers. This could be regarded as an acceptable option in cycles when only poor-quality embryos were available.

Indoor localization (IL) is a significant topic of study with several practical applications. The area of IL has evolved greatly in recent years due to the introduction of numerous technologies such as WiFi, Bluetooth, cameras, and other sensors. Despite the growing interest in this field, there are numerous challenges and drawbacks that must be addressed to develop more accurate and sustainable systems for IL and its real-life applications. This review study gives an in-depth look into IL, covering the most promising artificial intelligence-based and hybrid strategies that have shown excellent potential in overcoming some of the limitations of classic methods. In addition, the paper investigates the significance of high-quality datasets and evaluation metrics in the design and assessment of IL algorithms. Furthermore, this overview study emphasizes the crucial role that machine learning techniques, such as deep learning and transfer learning, play in the advancement of IL. A focus on the importance of IL and the various technologies, methods, and techniques that are being used to improve it. Finally, The survey highlights the need for continued research and development to create more accurate and scalable techniques that can be applied across a range of industries, such as evacuation-egress routes, hazard-crime detection, smart occupancy-driven energy reduction and asset tracking and management.

Demand for development of the convergence industry, research studies on electrical conductivity, thermal characteristics, semiconductors, motors, and batteries using special materials have come to the fore. Meanwhile, molybdenum (Mo) exhibits relatively small inorganic qualities, and the thermal conductivity rate is applied to various fields. In this study, in-depth characteristics were considered regarding the concentration of thermal characteristics, IR car terminal characteristics, and IR ve-hicles. This study calculated each phase temperature of the molybdenum sputtered specimens in the steady state according to the heat transfer theory. When the molybdenum-sputtered fabric’s metal layer pointed to the outside air, the heat transfer rate (Q) was high at 5748.3W, In contrast, if the molybdenum sputtered film’s metal layer of the pointed toward the heat source, the heat transfer rate (Q) was low at 187.1W. As a result of measuring the IR transmittance, the infrared transmit-tance of the molybdenum sputtering-treated sample was significantly reduced compared to the untreated sample. In the case of untreated samples, the transmittance ranged from 92.7 to 42.0%. When only the cross part was treated with molybdenum sputtering and the molybdenum surface was directed toward the IR irradiator, the IR transmittance was 66.8~0.7%. It is believed that the molybdenum sputtering polyamide samples produced in this study can be applied to multifunc-tional military wear, biosignal detection sensors, semiconductor products, batteries, etc., by utilizing excellent electrical properties, stealth functions, IR blocking properties, and lightness for infrared thermal imaging detectors.

Skin cancer is an uncommon but serious malignancy. Dermoscopic images examination and biopsy are required for cancer detection. Deep learning (DL) is extremely effective in learning characteristics and predicting malignancies. However, DL requires a large number of images to train. Image augmentation and transferring learning were employed to overcome the lack of images issue. In this study we divided images into two categories: benign and malignant. To train and test our models, we used the public ISIC 2020 database. Melanoma is classified as malignant in the ISIC 2020 dataset. Along with categorization, the dataset was studied to demonstrate variation. The performance of three top pretrained models was then benchmarked in terms of training and validation accuracy. Three optimizers were employed to optimize the loss: RMSProp, SGD, and ADAM. Using ResNet, VGG16, and MobileNetV2, we obtained training accuracy of 98.73%, 99.12%, and 99.76%, respectively. Using these three pretrained models, we attained a validation accuracy of 98.39%.

The organo-catalyzed enantioselective benzylation reaction of α-trifluoromethoxy indanones afforded α-benzyl-α-trifluoromethoxy indanones with a tetrasubstituted stereogenic carbon center in excellent yield with moderate enantioselectivity (up to 57% ee). Cinchona alkaloid-based chiral phase transfer catalysts were found to be effective for this transformation, and both enantiomers of α-benzyl-α-trifluoromethoxy indanones were accessed, depended on the use of cinchonidine and cinchonine-derived catalyst. The method was extended to the enantioselective allylation reaction of α-trifluoromethoxy indanones to give the allylation products in moderate yield with good enantioselectivity (up to 76% ee).

Transfer factor is the name given to material derived from activated lymphocytes that is probably composed of a complex of a peptide and a short segment of RNA and which has the reported ability to transfer specific T cell immunity to uncommitted lymphocytes. Many independent groups around the world reported isolating transfer factors between 1955 and 1990 and demonstrating their ability to transfer passive immunity from one animal or individual to another, often within 24 hours of inoculation. Such activity is potentially revolutionary both in making T cell vaccines readily manufacturable and also because the existence of transfer factors would undermine the basic assumptions of the clonal selection theory, which currently dominates immunological theory. Unfortunately, lack of the microanalytical and synthetic techniques required to properly identify transfer factors, combined with safety factors associated with it derivation from blood sources susceptible to HIV and prion infections, put an end to transfer factor research after 1990. This paper reviews the evidence supporting transfer factor activity and suggests that this potentially revolutionary concept be resurrected and subjected to renewed scrutiny in light of CRISPR-Cas mechanisms and because of its potential to make possible T cell vaccination and provide a novel basis for understanding immunological function.

Background: Multidrug-resistant bacteria present resistance mechanisms against β-lactam antibiotics, such as Extended-Spectrum Beta-lactamases (ESBL) and Metallo-β-lactamases enzymes (MBLs) operon encoded in Gram-negative species. Likewise, Gram-positive bacteria have evolved other mechanisms through mec genes, which encode modified penicillin-binding proteins (PBP2). This study aimed to determine the presence and spread of β-lactam antibiotic resistance genes and the microbiome circulating in Quito’s Public Transport (QTP). Methods: A total of 29 station turnstiles were swabbed to extract the surface environmental DNA. PCRs were performed to detect the presence of 13 antibiotic resistance genes and to identify 16S rDNA barcoding, followed by clone analysis, Sanger sequencing and BLAST search. Results: ESBL genes blaTEM-1 and blaCTX-M-1 and MBL genes blaOXA-181 and mecA were detected along QPT stations. Two subvariants were found for blaTEM-1, blaCTX-M-1, and blaOXA-181. Almost half of the circulating bacteria found at QPT stations were common human microbiota species including those classified by the WHO as pathogens of critical and high-priority surveillance. Conclusions: β-lactam antibiotic resistance genes are widely spread throughout QPT. This is the first report of blaOXA-181 in environmental samples in Ecuador. Moreover, we detected a new putative variant of this gene. Some commensal coagulase-negative bacteria may have a role as mecA resistance reservoirs

In the paper it is demonstrated that a valid path to a contradiction in complex number theory exists. In the path use is made of Euler’s identity and simple trigonometry. Each step can be easily verified.

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

We focus on macromolecules which are modelled as sequentially growing dual scale-free networks. The dual networks are built by replacing star-like units of the primal treelike scale-free networks through rings, which are then transformed in a small-world manner up to the complete graphs. In this respect, the parameter γ describing the degree distribution in the primal treelike scale-free networks regulates the size of the dual units. The transition towards the networks of complete graphs is controlled by the probability p of adding link between non-neighbouring nodes of the same initial ring. The relaxation dynamics of the polymer networks is studied in the framework of generalized Gaussian structures by using the full eigenvalue spectrum of the Laplacian matrix. The dynamical quantities on which we focus here are the averaged monomer displacement and the mechanical relaxation moduli. For several intermediate values of the parameter’s set (γ, p) we encounter for these dynamical properties regions of constant in-between slope.

Thermodynamics of protein-ligand interactions seems to be associated to a narrow range of Gibbs Free Energy. As a consequence, a linear enthalpy-entropy relationship showing an apparent Enthalpy-Entropy compensation (EEC) is frequently observed associated to the study of protein-ligand interactions. This EEC affects negatively the design and discovery of new and more efficient drugs capable of binding protein-targets with a higher affinity. Originally attributed to experimental errors, compensation between H and TS values is a real observable fact, although its molecular origin has remained obscure and controversial. Herein we show the results of a data search of G values of 2558 protein-ligand interactions and 3025 “in vivo” ligand concentrations from the Protein Data Bank bind Database and the Metabolome Data Base (2020). These results, together with the mechano-statistical interpretation of the thermodynamic properties leads to the conclusion that the EEC has no basis in statistical thermodynamics. It can be plausibly explained as a consequence of the narrow range of G associated to protein-ligand interactions. The Gaussian distribution of the G values matches very well with that of ligands. These results suggest the hypothesis that the set of G values for the protein-ligand interactions is the result of the evolution of proteins. The conformation versatility of present proteins and the exchange of thousands (even millions) of minute amounts of energy with the environment may have functioned as a homeostatic mechanism to make G of proteins adaptive to changes in availability of ligands, and therefore achieve the maximum regulatory capacity of the protein function. Finally, a plausible strategy to avoid the EEC is suggested.

3D metal nanostructures are often the basis of several applications such as in catalysis, plasmonics, medical diagnosis, therapy, drug screening, ophthalmologic, and biomedical applications. Porous gold nanoparticles (PGNs) are intensively investigated due to their outstanding morphological as well as advantageous optical properties. Unfortunately, the thermal stability of these open-porous structures is poor, i.e. even as a result of low-temperature annealing (150$^\circ$C in air), their porosity disappears and they lose their favorable optical properties. In order to preserve their beneficial properties, a thin metal oxide coating can be applied. Changing the coating's thickness and/or composition, the optical response of the PGNs can also be tuned in a wide wavelength region. Moreover, these nanoparticles can be synthesized also in support-free form, which makes them more attractive from an application point of view. This review article summarizes some of the preparation modes of these complex nanostructures (fixed and support-free), as well as their thermal stability and optical responses.

The stick-free flight stability is an old-fashioned and non-progressive issue; nevertheless, it is still existent, and of significant importance to the design of aircraft whose control system is reversible. The problem’s existence necessitates a deep assessment of stick-free flight stability throughout the aircraft design. Up to now, this problem has been addressed using either analytical approaches, which are only related to the static stability evaluation, or performing flight tests. In this study, the problem is handled in its entirety, from static and dynamic flight stability assessment to design criteria with a comprehensive perspective. Moreover, it is also exhibited that contrary to what has been generally proposed in the literature, limiting the problem of stick-free flight stability through static stability assessment is far from the main challenge. As a brief scope, the derivation of the control surface dynamics, a stick-free trim algorithm, and assessment rationale of the stick-free static and dynamic flight stability using a simulation approach are proposed. As a consequence, the aim is to set a broad understanding for designers related to this phenomenon and add adjunct design criteria in the design optimization process by approaching it in terms of modeling, simulation, and flight test perspective.

Expression of Krüppel–like factor 15 (KLF15), a stress induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed KLF15 and glucocorticoid receptor (GR) cooperatively transactivate the BoHV-1 immediate early transcription unit 1 (IEtu1), herpes sim-plex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoter. The IEtu1 promoter drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 ex-pression and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1 productive infection and KLF15 steady state protein levels were increased at late stages of productive infection. KLF15 was primarily localized to the nucleus following in-fection of cultured cells with HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then infected with HSV-1, promoter activity was significantly increased. The ICP0 gene and to a lesser extent bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast, BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 pro-moter activity. Collectively, these studies revealed HSV-1 and BoHV-1 productive infection in-creased KLF15 steady state protein levels, which correlated with increased virus production.

Background: Sarcoma may show similarities to malignant melanoma in terms of morphologic and immunohistochemical aspects, hence making it difficult to differentiate between these two neoplasms during the diagnostic process. This systematic review aims to summarize available evidence on cases of sarcoma that were initially diagnosed as melanoma. Methods: A comprehensive search was conducted including MEDLINE/Pubmed, EMBASE and SCOPUS through March 2023. We included case series and case reports of sarcoma patients that were initially diagnosed as malignant melanoma. PRISMA guidelines were followed. Results: Twenty-three case reports and four case series with a total of 34 patients were included. The clinical presentation was heterogeneous, and the most involved anatomical regions were lower limbs (24%), head/neck (24%) and upper limbs (21%). IHC positivity was reported for S100 (69%), HMB45 (63%), MelanA (31%) and MiTF (3%). The main reasons for second assessment were unusual presentation (48%) and uncertain diagnosis (28%). EWSR1 translocation was investigated in 17/34 patients (50%) and found positive in 16/17 (94%). The final diagnosis was clear cell sarcoma (50%) or other soft tissue sarcomas (50%). Conclusions: Melanoma and some histotypes of sarcoma share many similarities. In case of atypical lesions, a second diagnosis should be considered, and ESWR1 translocation should be investigated.

Materials based on Mg2+-containing phosphates are gaining great relevance in the field of bone tissue repair via regenerative medicine methods. Magnesium ions, together with condensed phosphate ions, play a significant role in the process of bone remodeling, affecting the early stage of bone regeneration through active participation in the process of osteosynthesis. Here we pro-vide a comprehensive overview of the usage of biomaterials based on magnesium phosphate and magnesium calcium phosphate in bone reconstruction. The role of magnesium ions in angiogene-sis, an important process associated with osteogenesis, is considered. Finally, the biological properties of magnesium phosphates for bone regeneration are summarized. They show promis-ing results in terms of use as bone replacement material.