Power converters with coupled inductors are very promising due to the high efficiency and high voltage gain. Apart from the aforementioned advantages, the boost-flyback converter reduces the voltage stress on the semiconductors. However, to obtain good performance with high voltage gains, the controller must include two control loops (current and voltage), and a compensation ramp. One of the most used control techniques for power converters is the peak current-mode control with compensation ramp. However, in the case of a boost-flyback converter there is no mathematical expression in the literature, to compute the slope of the compensation ramp. In this paper, a formula to compute the slope of the compensation ramp is proposed in such a way that a stable period-1 orbit is obtained. This formula is based on the values of the circuit parameters, such as inductances, capacitances, input voltage, switching frequency and includes some assumptions related to internal resistances, output voltages, and some other electrical properties related with the physical construction of the circuit. The formula is verified numerically using the saltation matrix and experimentally using a test circuit.

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

In power systems there are complex transformer structures, whose accurate analysis is not possible using the techniques available today. This paper presents a systematic data driven analysis method for coupled inductors of arbitrary complexity. The method first establishes a winding matrix N mapping the windings to the limbs of the transformer. A permeance matrix P is created from the reluctance network of the magnetic core. A generalized inductance matrix L mapping currents in the transformer windings to the induced voltages is generated based on the winding (N) and permeance (P) matrices. The inductance matrix representation of a coupled inductor is then transformed to an admittance matrix, which can be integrated to the nodal analysis of the electrical circuit surrounding the coupled inductor. The method presented is validated by simulations with real transformer structures using electromagnetic transient program (EMTP/ATP).

Background: COVID-19 is a disease of the elderly as 95% of deaths related to COVID-19 occur in people over 60 years of age. Despite the urgent need for a preventive treatment there are currently no serious leads, other than the vaccination. Objective: To find a preventive treatment of COVID-19 in elderly patients. Design: Retrospective case-control study. Setting: Robertsau Geriatric Hospital of the University Hospitals of Strasbourg, France. Patients: 179 elderly patients who had been in contact with the SARS-CoV-2, of whom 89 had tested RT-PCR-positive (COVID-pos) for the virus and 90 had tested RT-PCR-negative (COVID-neg). Measurements: Treatments within 15 days prior to RT-PCR (including antihypertensive drugs, antipsychotics, antibiotics, nonsteroidal anti-inflammatory drugs, proton pump inhibitors (PPIs), paracetamol, anticoagulant, oral antidiabetics (OADs), corticosteroids, immunosuppressants), comorbidities, symptoms, laboratory values, and clinical outcome were all collected using the electronic patient record. Results: COVID-pos patients more frequently had a history of diabetes (P=.016) and alcoholism (P=.023), a lower leukocyte count (P=.014) and a higher mortality rate– 29.2% versus 14.4% – (P=.014) when compared to COVID-neg patients. Patients on PPIs were 2.3 times less likely (odds ratio [OR] = 0.4381, 95% confidence interval [CI] [0.2331, 0.8175], P=.0053) to develop COVID-19 infection, compared to those not on PPIs. No other treatment decreased or increased this risk. COVID-19 patients on antipsychotics (P=.0013) and OADs (P=.0166) were less likely to die. Limitations: retrospective study. Conclusion: PPIs treatment lowered the risk of development of COVID-19 infection, and antipsychotics and OADs decreased the risk of mortality in geriatric patients. If further studies confirm this finding, PPIs could be used preventatively in the elderly in this pandemic context. Moreover, OADS and antipsychotics should be tested in clinical trials.

Energy demand has exponentially increased with the increase in the world population and ur-banization. Renewable energy is clean, renewable, and environmentally friendly. Hydrogen production through Proton Exchange Membrane (PEM) electrolyzer is an efficient way to produce renewable energy. The efficiency and energy consumption of the PEM electrolyzer depends on the feed water quality. In this report, we study the effect of pH, TDS, and conductivity on hydrogen production as well as energy consumption during the process. pH values (3, 7, 9), TDS values (300ppm, 600ppm, 900ppm), and conductivity values (30mS/cm, 70mS/cm, 100mS/cm) were studied to understand and optimize the hydrogen production using PEM electrolyzer. The in-vestigations showed that hydrogen production is significantly affected by pH, total dissolved solids, and conductivity, and the best levels of each variable were identified by extensive testing. The findings show both the scientific significance of proton exchange electrolysis in meeting the growing energy demands of society as well as the importance of knowing the influence that di-verse conditions have on the creation of hydrogen. Our research, in general, contributes to the expanding body of scientific knowledge on the topic of the effective production of hydrogen and offers useful insights for the continuation of investigation in this field.

In this article, a novel hybrid welding process called plasma-TIG coupled arc welding was proposed to improve the efficiency and quality of welding by utilizing the full advantage of plasma and TIG welding processes. The two arcs of plasma and TIG were pulled into each other into one coupled arc under the effect of Lorentz force and plasma flow force during welding experiments. The arc behavior of coupled arc was studied by means of it’s arc profile, arc pressure and arc force conditions. The coupled arc pressure distribution measurements were performed. The effects of welding conditions on coupled arc pressure were evaluated and the maximum coupled arc pressure was improved compared with single-plasma arc and single-TIG arc. It was found that the maximum arc pressure was mainly determined by plasma arc current and plasma gas flow. According to the results, the proposed coupled arc welding process have both advantages of plasma arc and TIG method, and it has a broad application prospect.

This paper presents a microgrid distributed energy resources (DERs) for a rural standalone system. It is made up of solar photovoltaic (solar PV) system, battery energy storage system (BESS), and wind turbine coupled to permanent magnet synchronous generator (WT-PMSG). The DERs are controlled by maximum power point tracking (MPPT) based proportional intergral (PI) controllers for both maximum power tracking and error feedback compensation. The MPPT uses the perturb and observe (P&O) algorithm for tracking the maximum power point of the DERs. The PI gains are tuned using the Ziegler-Nichol’s method. The developed system was built and simulated in MATLAB/Simulink under two conditions - constant load, and step load changes. The controllers enabled the BESS to charge even during conditions of varying load and other environmental factors such as change of irradiance and wind speed. The reference was tracked very well by the output voltage of the DC grid. This is a useful research for electrifying the rural islanded areas, too far from the grid.

The performance of ground heat exchangers systems depends on the knowledge of the thermal parameters of the ground like thermal conductivity, thermal capacity and diffusivity. The knowledge of these parameters often requires quite accurate experimental analysis, known under the name of Thermal Response Test (TRT). In this paper, after a general analysis of the various available types of TRT and the study of the theoretical basics of the method, the perspective of the definition of a simplified routine method of analysis based on the combination of a particular version of TRT and the routine geotechnical tests for the characterization of soil stratigraphy and of the ground characteristics, mandatory before the construction of a new buildings, even if limited to quite short drilling depth (lower than 30 m). The idea of developing TRT in connection with geotechnical test activity has the objective of promoting a widespread use of in-situ experimental analysis and of reducing TRT costs and time duration of the experimental analysis. The considerations exposed in the present paper lead to reconsider a particular variety of the TRT in particular the version known as Thermal Response Test while Drilling (TRTWD).

SARS-CoV-2 mRNA vaccination can entail chronic fatigue/dis-autonomy tentatively termed post-acute COVID-19 vaccination syndrome (PACVS). We explored receptor autoantibodies and interleukin-6 (IL-6) as somatic correlates of PACVS. Blood markers determined before and six months after first-time SARS-CoV-2-vaccination of healthy controls (N = 89, 71 females, mean/ median age 39/ 49 years) were compared with corresponding values of PACVS-affected persons (N= 191, 159 females, mean/median age: 40/39 years) exhibiting chronic fatigue/dis-autonomy (≥ three symptoms for ≥ five months after last SARS-CoV-2 mRNA vaccination) not due to SARS-CoV-2 infection and/or confounding diseases/medications. Normal vaccination response encompassed decreases of 11 receptor-antibodies (by 25 - 50 %, p < 0.0001), increases in two receptor-antibodies (by 15 - 25 %, p < 0.0001) and normal IL-6. In PACVS, serological vaccination-response appeared significantly (p < 0.0001) altered, allowing discrimination from normal post-vaccination state (sensitivity = 90%, p &lt; 0.0001) by increased angiotensin II type 1 receptor antibodies (cut-off ≤ 10.7 U/ml, ROC-AUC = 0.824 ± 0.027), decreased alpha-2B adrenergic receptor antibodies (cut-off ≥ 25.2 U/ml, ROC-AUC = 0.828 ± 0.025) and increased IL-6 (cut-off ≤ 2.3 pg/ml, ROC-AUC = 0.850 ± 0.022). PACVS is thus indicated as a somatic syndrome delineated/detectable by diagnostic blood markers

In this paper, firstly, some questionable formulas and conceptual oversights of previous reduced sigma set unscented transformation (UT) methods are revised through theoretical analysis. Then the revised UT methods based Kalman filters are used in a GPS/INS tightly-coupled system. The Kalman filter flows are the kind of square-root, since the square-root unscented Kalman filters (SRUKFs) can guarantee the stability of the system. By using the reduced sigma set SRUKFs (which contain simplex sigma set square-root unscented Kalman filter (S-SRUKF), spherical simplex sigma set square-root unscented Kalman filter (SS-SRUKF) and minimum sigma set square-root unscented Kalman filter (M-SRUKF)), the computation cost is greatly saved compared with the standard SRUKF, while the accuracy of the GPS/INS tightly-coupled system still maintained. The structure of the GPS/INS tightly-coupled system is in the form of error state, and the time updates of the state and the state covariance of SRUKFs are directly estimated without using UT, thus the computational time is also greatly saved. The pseudo-satellite is introduced to aid the system when the observation information is deficient, for example, when the GPS signal is deficient in the maneuver environment. By using the pseudo-satellite, the optimal performance of the system is guaranteed. Experiment of unmanned aerial vehicle (UAV) showed that the pseudo-satellite aided mechanism worked well.

Unavoidable exposure to radiosensitive normal tissues around cancerous tumor during the radiotherapy can cause side effects such as self-limited acute toxicities, mild chronic symptoms, or severe organ dysfunction. Nevertheless, clinical use of currently available radiation protective agents is limited because of their generic cytotoxicity. A study on radiation protective effect of delphinidin was conducted with proton-beam-exposed human colon cells (CCD-18Co). The measurement in changes of survival fractions of CCD-18Co with/without delphinidin administration at different radiation doses were measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The changes in expression of reactive oxygen species (ROS) and in activities of antioxidant enzymes were measured by colorimetric assays using pertinent assay kits. The measurement of pro-apoptosis/pro-survival protein expressions using Western blot assay and the measurement of DNA damage using comet assay were also fulfilled to evaluate the molecular level of radiation damages in CCD-18Co cells. The experimental results revealed that the pre-administration of delphinidin regulated antioxidant enzymes, reduced ROS, decreased DNA damage, regulated pro-apoptosis/pro-survival proteins, and eventually reduced apoptosis of CCD-18Co cells. In conclusion, it is claimed that delphinidin is nontoxic natural radiation protective compound, and thus delphinidin can be used to protect normal colon tissues during the proton beam therapy.

By using the new recently proposed extended rational methods, we set some solitary and multi wave solutions of the coupled Higgs system in the present study. Some new families of hyperbolic and trigonometric solutions of the coupled Higgs equations are successfully obtained. Some solutions are real as some are complex valued functions. Particular forms of some solutions derived by choice of some parameters are demonstrated in three dimensional spaces. The complex valued solutions are also depicted by plotting both real and complex component.

The current pneumonia epidemic could evolve into a pandemic on a global scale if not effectively contained. The COVID-19 virus possesses a 61-amino acid open reading frame resembling SARS-CoV virulence factor - ORF6 peptide. The isoleucine content is 15.9% in ORF6 of SARS-CoV versus 16.4% of that in SARS-CoV-2. Given the proton affinity in the carbonyl oxygen in isoleucine, augmented proton traffic can enhance proton-ion antiport and prompt cell swelling. Calorie restriction has been confirmed in animal studies to extend lifespan, and its underlying mechanism is not fully known. As the content of essential amino acids in the open reading frame of SARS-CoV-2 reaches 57.4%, a starch/vitamin diet served for short period of time does not give rise to essential amino acids and halts virion production, which could be adopted as prophylactic approach of many viral infections. Plant-based diet or fasting/boiled rice water can also minimize the intake of essential amino acids or all amino acids respectively. Furthermore, several proteins of SARS-CoV-2 possess high valine plus glycine content which is implicated in heart disease, justifying the aforementioned approaches.

In this research paper, a novel high step up dc-dc converter with a coupled inductor and voltage doubler circuits is proposed. The converter achieves a high step up voltage gain with an appropriate duty ratio and low voltage stress on the power switches. Also, the energy which is stored in the leakage inductor of the coupled inductor can be recycled to the output. The operating principles and the steady state analysis of the proposed converter are discussed in detail. Finally, a prototype circuit of the proposed converter is implemented in the laboratory in order to verify the performance of the proposed converter.

This article deals with the conformable double Laplace transforms and their some properties with examples and also the existence Condition for the conformable double Laplace transform is studied. Finally, in order to obtain the solution of nonlinear fractional problems, we present a modified conformable double Laplace that we call conformable double Laplace decomposition methods (CDLDM). Then, we apply it to solve, Regular and singular conformable fractional coupled burgers equation illustrate the effectiveness of our method some examples are given.

Reversible protonic ceramic cells (rPCCs) combine two different operation regimes, fuel cell and electrolysis cell modes, which allow reversible chemical-to-electrical energy conversion at reduced temperatures with high efficiency and performance. Here we present novel technological and materials science approaches, enabling a rPCC with symmetrical functional electrodes to be prepared using a single sintering step. The response of the cell fabricated on the basis of P–N–BCZD|BCZD|PBN–BCZD (where BCZD = BaCe_0.5Zr_0.3Dy_0.2O_3–δ, PBN = Pr_1.9Ba_0.1NiO_4+δ, P = Pr₂O₃, N = Ni) is studied at different temperatures and water vapor partial pressures (pH₂O) by means of volt-ampere measurements, electrochemical impedance spectroscopy and distribution of relaxation times analyses. The obtained results demonstrate that symmetrical electrodes exhibit classical mixed-ionic/electronic conducting behavior with no hydration capability at 750 °C; therefore, increasing the pH₂O values in both reducing and oxidizing atmospheres leads to some deterioration of their electrochemical activity. At the same time, the electrolytic properties of the BCZD membrane are improved, positively affecting the rPCC’s efficiency. The electrolysis cell mode of the rPCC is found to be more appropriate than the fuel cell mode under highly humidified atmospheres, since its improved performance is determined by the ohmic resistance, which decreases with pH₂O increasing.

Abstract: Nonlinear spectrum distortions are caused by the peculiarities of the operation of charge-coupled device elements (CCD), in which the signal exposition time (TINT) is one of the significant parameters. A change of TINT on a CCD leads to a nonlinear distortion of the resulting spectrum. Nonlinear distortion of the spectrum, in its turn, leads to errors in determining the central wavelength of Fiber Bragg Gratings (FBG) and spectrally sensitive sensors, which, in general, negatively affects the accuracy of measuring systems. The paper proposes an algorithm for correcting nonlinear distortions of the spectrum obtained on a spectrum analyzer using CCD as a receiver. It is shown that preliminary calibration of the optical spectrum analyzer with subsequent mathematical processing of the signal makes it possible to make corrections in the resulting spectrum, thereby leveling the errors caused by measurements at different TINT.

Lately Silicon Carbide (SiC) and Galium Nitride (GaN) based high frequency power conversion has gained immense popularity which stems from relatively low switching energy, robustness to high temperature operation, wide-band gap and superior thermal limits. While this aspect inherently results in a high-density power stage design, the design of adjoining passive components, particularly magnetics, needs careful attention. This is especially true if the compatibility of core and winding options and their performance is limited with the use of higher switching frequency. In this regard, this paper presents a brief review of existent research conducted in materials, optimization and integration of magnetics for single and three phase applications, ranging from filters, resonant inductors to isolation transformers. Design knobs pertaining to medium voltage (MV) applications, low-voltage (LV) applications, e-mobility sector such as more electric aircrafts (MEAs) and electric vehicles (EVs) are discussed. Guidelines for magnetics design are summarized for each application with a projected roadmap on future trend for magnetics.

We have developed IrO_x/M-SnO₂ (M = Nb, Ta, and Sb) anode catalysts, IrO_x nanoparticles uniformly dispersed on M-SnO₂ supports with fused-aggregate structures, which make it possible to evolve oxygen efficiently, even with a reduced amount of noble metal (Ir) in proton exchange membrane water electrolysis. Polarization properties of IrO_x/M-SnO₂ catalysts for the oxygen evolution reaction (OER) were examined at 80 °C in both 0.1 M HClO₄ solution (half cell) and a single cell with a Nafion^® membrane (thickness = 50 μm). While all catalysts exhibited similar OER activities in the half cell, the cell potential (E_cell) of the single cell was found to decrease with the increasing apparent conductivities (σ_{app, catalyst}) of these catalysts: an E_cell of 1.61 V (voltage efficiency of 92%) at 1 A cm^-2 was achieved in a single cell by the use of an IrO_x/Sb-SnO₂ anode (highest σ_{app, catalyst}) with a low Ir-metal loading of 0.11 mg_Ir cm^-2 and Pt supported on graphitized carbon black (Pt/GCB) as the cathode, with 0.35 mg_Pt cm⁻². In addition to the reduction of the ohmic loss in the anode catalyst layer, the increased electronic conductivity contributed to decreasing the OER overpotential due to the effective utilization of the IrO_x nanocatalysts on the M-SnO₂ supports, which is an essential factor in improving the performance with low noble metal loadings.

Taste signaling is a complex process that is linked to obesity and its associated metabolic syndromes. The sweet taste is mediated through a heterodimeric G protein coupled receptor (GPRC) in a species-specific manner and at multi-tissue specific levels. The sweet receptor recognizes a large number of ligands with structural and functional diversities to modulate different amplitudes of downstream signaling pathway(s). The human sweet-taste receptor has been extremely difficult to study by biophysical methods due to inadequate methods for producing large homogeneous quantities of the taste-receptor protein and a lack of reliable in vitro assays to precisely measure productive ligand binding modes leading to activity upon their interactions with the receptor protein. We report a multimodal high throughput assays to monitor ligand binding, receptor stability and conformational changes to model the molecular interactions between ligand-receptor. We applied saturation transfer difference nuclear magnetic resonance spectroscopy (STD-NMR) complemented by differential scanning calorimetry (DSC), circular dichroism (CD) spectroscopy, and intrinsic fluorescence spectroscopy (IF) to characterize binding interactions. Our method using complementary NMR and biophysical analysis is advantageous to study the mechanism of ligand binding and signaling processes in other GPCRs.

Background: In the heart, aldosterone (Aldo) binds the mineralocorticoid receptor (MR) to exert damaging, adverse remodeling-promoting effects. We recently showed that G protein-coupled receptor (GPCR)-kinase (GRK)-5 blocks the cardiac MR by directly phosphorylating it, thereby repressing its transcriptional activity. MR antagonist (MRA) drugs block the cardiac MR reducing morbidity and mortality of advanced human heart failure. Non-steroidal MRAs, such as finerenone, may provide better cardio-protection against Aldo than classic, steroidal MRAs, like spironolactone and eplerenone. Herein, we sought to investigate potential differences between finerenone and eplerenone at engaging GRK5-dependent cardiac MR phosphorylation and subsequent blockade. Methods: We used the cardiomyocyte cell line H9c2 and neonatal rat ventricular myocytes (NRVMs). Results: GRK5 phosphorylates the MR in H9c2 cardiomyocytes in response to finerenone but not to eplerenone. Unlike eplerenone, finerenone alone potently and efficiently suppresses cardiac MR transcriptional activity, thus displaying inverse agonism. GRK5 is necessary for finerenone`s inverse agonism, since GRK5 genetic deletion renders finerenone incapable of blocking cardiac MR transcriptional activity. Eplerenone alone does not fully suppress cardiac MR basal activity regardless of GRK5 expression levels. Finally in NRVMs, GRK5 is necessary for the anti-apoptotic and anti-fibrotic effects of both finerenone and eplerenone against Aldo, as well as for the higher efficacy and potency of finerenone at blocking Aldo-induced apoptosis and fibrosis. Conclusions: Finerenone, but not eplerenone, induces GRK5-dependent cardiac MR inhibition, which underlies, at least in part, its higher potency and efficacy, compared to eplerenone, as an MRA in the heart. GRK5 acts as a co-repressor of the cardiac MR and is essential for efficient MR antagonism in the myocardium.

Molecular overtone transitions provide optical frequency transitions sensitive to variation in the proton-to-electron mass ratio (μ = m_p/m_e). However, robust molecular state preparation presents a challenge critical for achieving high precision. Here, we characterize infrared and optical-frequency broadband laser cooling schemes for TeH⁺, a species with multiple electronic transitions amenable to sustained laser control. Using rate equations to simulate laser cooling population dynamics, we estimate the fractional sensitivity to μ attainable using TeH⁺. We find that laser cooling of TeH⁺ can lead to significant improvements on current μ variation limits.

Despite all efforts, the treatment of breast cancer (BC) cannot be considered to be a success story. The advances in surgery, chemotherapy and radiotherapy have not been sufficient. Indeed, the accumulated experience clearly indicates that new perspectives and non-main stream approaches are needed to better characterize the etiopathogenesis and treatment of this disease. This contibution deals with how the new pH-centric anticancer paradigm plays a fundamental role in reaching a more integral understanding of the etiology, etiopathogenesis and treatment of this multifactorial disease. For the first time the armamentarium available for the treatment of the different types and phases of BC is approached here from a Unitarian perspective based upon the hydrogen ion dynamics of cancer. The wide-ranged pH-related molecular, biochemical and metabolic model is able to embrace most the fields and subfields of breast cancer pathology. This single and integrated approach allows to advance a unidirectional program to treatment. Further efforts in this line are likely to first improve the therapeutics of each subtype of this tumor, then every phase of the disease and finally every individual patient.

Abstract: We review the development and application of an organic polymer-gel capable of producing fixed, three-dimensional fluorescent images of complex radiation fields. The gel consists for more than 99% of γ-ray-polymerized (~15% conversion) tertiary-butyl acrylate (TBA) containing ~100 ppm of a fluorogenic compound, e.g. maleimido-pyrene (MPy). The radio-fluorogenic effect depends on copolymerization of the MPy into growing chains of TBA on radiation-induced polymerization. This converts the maleimido residue, which quenches the pyrene fluorescence, into a succinimido moeity (SPy), which doesn't. The intensity of the fluorescence is proportional to the yield of free-radicals formed and hence to the local dose deposited. Because the SPy moieties are built into the cross-linked polymer matrix the image is fixed. The method of preparing the gel and imaging the radiation-induced fluorescence are presented and discussed. The effect is illustrated with fluorescent images of the energy deposited in the gel by beams of X-rays, electrons and protons as well as a radioactive isotope.

Protein is the proteios building block of life. Evolutionarily, its sequence is not as conserved as its structure, making it more reasonable for protein structure, instead of protein sequence, to be the descriptor of protein function. Yet, in the National Center for Biotechnology Information (NCBI) database, the number of experimentally identified protein sequences is in great excess of that of experimentally determined protein structures inside the almost-half-a-century old Protein Data Bank (PDB). For instance, GPR151 is an proton-sensing G-protein coupled receptor (GPCR) originally identified as homologous to galanin receptors. As of March 19, 2020, GPR151’s structure has not been experimentally determined and deposited in PDB yet. Thus, an ab initio modelling approach was employed here to build a three-dimensional structure of GPR151. Overall, the ab initio GPR151 model presented herein constitutes the first structural hypothesis of GPR151 to be experimentally tested in future with previously published, currently ongoing and future GPR151 studies.

Gut microbiota and its metabolites like short chain fatty acids (SCFAs) are linked with pathology of Alzheimer’s disease (AD)- a debilitating public health problem in older adults. However, strategies to beneficially modulate gut microbiota and its sensing signaling pathways remain largely unknown. Here, we screened, validated and established the agonists of free fatty acid receptor 2 (FFAR2) signaling, which senses beneficial signals from SCFAs produced by microbiota in the gut. We demonstrated that inhibition of FFAR2 signaling increases amyloid-beta (Aβ) stimulated neuronal toxicity. Thus, we screened FFAR2 agonists, using in-silico library of more than 144,000 natural compounds, and 15 compounds were selected based on binding with FFAR2 agonist sites. Further, cell culture toxicity and FFAR2 stimulatory experiments demonstrated that Fenchol (a natural compound commonly present in basil) was potent FFAR2 agonist in neuronal cells. Interestingly, we also demonstrated that Fenchol protects Aβ-stimulated neurodegeneration in FFAR2 dependent manner. In addition, Fenchol reduced AD like phenotypes such as Aβ-accumulation and, learning and memory behaviors in Caenorhabditis (C.) elegans. Fenchol increased Aβ-clearance by increasing proteasome/lysosome activity and reduced senescence in neuronal cells. These results demonstrated that the inhibition of FFAR2 signaling promotes Aβ-induced neurodegeneration, while activating it by Fenchol as a natural agonist reverse it by promoting Aβ-clearance and reducing cellular senescence; thus stimulation of FFAR2 signaling can be a therapeutic approach to prevent/ treat AD.

Vibrational overtones in deeply bound molecules are sensitive probes for variation of the proton-to-electron mass ratio μ. In nonpolar molecules, these overtones may be driven as two-photon transitions. Here, we present procedures for experiments with O₂⁺, including state-preparation through photoionization, a two-photon probe, and detection. We calculate transition dipole moments between all X²П_g vibrational levels and those of the A²П_u excited electronic state. Using these dipole moments, we calculate two-photon transition rates and AC-Stark-shift systematics for the overtones. We estimate other systematic effects and statistical precision. Two-photon vibrational transitions in O₂⁺ provide multiple routes to improved searches for μ variation.

The mineralocorticoid hormone aldosterone regulates sodium and potassium homeostasis but also adversely modulates the maladaptive process of cardiac adverse remodeling post-myocardial infarction. Through activation of its mineralocorticoid receptor (MR), a classic steroid hormone receptor/transcription factor, aldosterone promotes inflammation and fibrosis of the heart, the vasculature, and the kidneys. This is why MR antagonists reduce morbidity and mortality of heart disease patients and are part of the mainstay pharmacotherapy of advanced human heart failure. A plethora of animal studies using cell type–specific targeting of the MR gene have established the importance of MR signaling and function in cardiac myocytes, vascular endothelial and smooth muscle cells, renal cells, and macrophages. In terms of its signaling properties, the MR is distinct from nuclear receptors in that it has, in reality, two physiological hormonal agonists: not only aldosterone but also cortisol. In fact, in several tissues, including in the myocardium, cortisol is the primary hormone activating the MR. There is a considerable amount of evidence indicating that the effects of the MR in each tissue expressing it depend on tissue- and ligand-specific engagement of molecular co-regulators that either activate or suppress its transcriptional activity. Identification of these co-regulators for every ligand that interacts with the MR in the heart (and in other tissues) is of utmost importance therapeutically, since it can not only help elucidate fully the pathophysiological ramifications of the cardiac MR`s actions but also help design and develop novel better MR antagonist drugs for heart disease therapy. Among the various proteins the MR interacts with are molecules involved in cardiac G protein-coupled receptor (GPCR) signaling. This results in a significant amount of crosstalk between GPCRs and the MR, which can affect the latter`s activity dramatically in the heart and in other cardiovascular tissues. This review summarizes the current experimental evidence for this GPCR-MR crosstalk in the heart and discusses its pathophysiological implications for cardiac adverse remodeling as well as for heart disease therapy. Novel findings revealing non-conventional roles of GPCR signaling molecules, specifically of GPCR-kinase (GRK)-5, in cardiac MR regulation are also highlighted.

Addition of the bulky redox-active diphosphine 1,8-bis(diphenylphosphino)naphthalene (dppn) to [Fe2(CO)6(-edt)] (1) (edt = 1,2-ethanedithiolate) affords [Fe2(CO)4(2-dppn)(-edt)] (3) as the major product, together with small amounts of a P-C bond cleavage product [Fe2(CO)5{1-PPh2(1-C10H7)}(-edt)] (2). The redox properties of 3 have been examined by cyclic voltammetry and it has been tested as a proton-reduction catalyst. It undergoes a reversible reduction at E1/2 = –2.18 V and exhibits two overlapping reversible oxidations at E1/2 = –0.08 V and E1/2 = 0.04 V. DFT calculations show that while the HOMO is metal-centred (Fe-Fe -bonding), the LUMO is primarily ligand-based but also contains an antibonding Fe-Fe contribution, highlighting the redox-active nature of the diphosphine. It is readily protonated upon addition of strong acids to afford two isomeric hydride complexes and catalyzes the electrochemical reduction of protons at Ep = –2.00 V in the presence of CF3CO2H. The catalytic current indicates that it is one of the most efficient diiron electrocatalysts for the reduction of protons, albeit operating at quite negative potential.

This paper presents a demonstration of the feasibility of fabricating micro-cantilever harvesters with extended stress distribution and enhanced bandwidth by exploiting an M-shaped two-degrees-of-freedom design. The measured mechanical response of the fabricated device displays the predicted dual resonance peak behavior with the fundamental peak at the intended frequency. This design has the features of high energy conversion efficiency in a miniaturized environment where the available vibrational energy varies in frequency. It makes such a design suitable for future large volume production of integrated self powered sensors nodes for the Internet-of-Things.

With reference to our earlier published views on large nuclear gravitational constant , nuclear elementary charge and strong coupling constant , in this paper, we present simple relations for nuclear stability range, binding energy of isotopes and magic proton numbers.

Current numerical methods for simulating biophysical processes in aquatic environments are typically constructed in a grid-based Eulerian framework or as an individual-based model in a particle-based Lagrangian framework. Often, the biogeochemical processes and physical (hydrodynamic) processes occur at different time and space scales, and changes in biological processes do not affect the hydrodynamic conditions. Therefore, it is possible to develop an alternative strategy to grid-based approaches for linking hydrodynamic and biogeochemical models that can significantly improve computational efficiency for this type of linked biophysical model. In this work, we utilize a new technique which links hydrodynamic effects and biological processes through a property-carrying particle model (PCPM) in a Lagrangian/Eulerian framework. The model is tested in idealized cases and its utility is demonstrated in a practical application to Sandusky Bay. Results show the integration of Lagrangian and Eulerian approaches allows for a natural coupling of mass transport (represented by particle movements and random walk) and biological processes in water columns which is described by a nutrient-phytoplankton-zooplankton-detritus (NPZD) biological model. This method is far more efficient than traditional tracer based Eulerian biophysical models for 3-D simulation, particularly for a large domain and/or ensemble simulations.

The available magnetic field strength for high resolution NMR in persistent superconducting magnets has recently improved from 23.5 to 28 Tesla, increasing the proton resonance frequency from 1 to 1.2 GHz. For magic-angle spinning (MAS) NMR, this is expected to improve resolution, provided the sample preparation results in homogeneous broadening. We compare two-dimensional (2D) proton detected MAS NMR spectra of four membrane proteins at 950 and 1.2 GHz. We find a consistent improvement in resolution that scales superlinearly with the increase in magnetic field for three of the four examples. In 3D and 4D spectra, which are now routinely acquired, this improvement indicates the ability to resolve at least 2 and 2.5 times as many signals, respectively.

G protein-coupled receptors (GPCRs) are expressed essentially on all cells, facilitating cellular responses to external stimuli, and are involved in nearly every biological process. Several members of this family play significant roles in the regulation of adipogenesis and adipose me-tabolism. However, the expression and functional significance of a vast number of GPCRs in adipose tissue are unknown. We used a high-throughput RT-PCR panel to determine the expres-sion of the entire repertoire of non-sensory GPCRs in mouse white, and brown adipose tissue and assess changes in their expression during adipogenic differentiation of murine adipocyte cell line, 3T3-L1. In addition, the expression of GPCRs in subcutaneous adipose tissues from lean, obese, and diabetic human subjects was evaluated by re-analyzing RNA-sequencing data. We detected a total of 292 and 271 GPCRs in mouse white and brown adipose tissue, respectively. There is a significant overlap in the expression of GPCRs between the two adipose tissue depots but several GPCRs are specifically expressed in one of the two tissue types. Adipogenic differ-entiation of 3T3-L1 cells had a profound impact on the expression of several GPCRs. RNA se-quencing of subcutaneous adipose from healthy human subjects detected 255 GPCRs and obesity significantly changed the expression of several GPCRs in adipose tissue. Finally, we report sev-eral highly expressed GPCRs with no known role in adipose biology whose expression was sig-nificantly altered during adipogenic differentiation and/or in the diseased human subjects. These GPCRs could play an important role in adipose metabolism and serve as a valuable translational resource for obesity and metabolic research.

Ensuring a protection scheme in DC distribution is more difficult to achieve against pole-to-ground fault than in AC distribution system because of the absence of zero crossing points and low line impedance. To complement the major obstacle of limiting the fault current, several compositions have been proposed related to mechanical switching and solid-state switching. Among them, solid-state circuit breakers(SSCBs) are considered a possible solution to limit fast fault current. However, they may cause problems in circuit complexity, reliability and cost-related troubles due to the use of multiple power semiconductor devices and additional circuit configuration to commutate current. This paper proposes the SSCB with a coupled inductor(SSCB-CI) which has symmetrical configuration. The circuit is comprised of passive components like commutation capacitors, a CI and damping resistors. Thus, proposed SSCB-CI offers the advantages of simple circuit configuration and fewer utilized power semiconductor devices than another typical SSCBs in LVDC microgrid. For analysis, six operation states are described for the voltage across main switches and fault current. The effectiveness of the SSCB-CI against a short-circuit fault is proved via simulation and experimental results in a lab-scale prototype.

G protein-coupled receptors (GPCRs) serve prominent roles in melanocyte lineage physiology, with an impact at all stages of development, as well as on mature melanocyte functions. GPCR ligands are present in the skin and regulate melanocyte homeostasis, including pigmentation. The role of GPCRs in the regulation of pigmentation and, consequently, protection against external aggression, such as ultraviolet radiation, has long been established. However, evidence of new functions of GPCRs directly in melanomagenesis has been highlighted in recent years. GPCRs are coupled, through their intracellular domains, to heterotrimeric G proteins, which induce cellular signaling through various pathways. Such signaling modulates essential cellular processes of melanomagenesis, such as proliferation and migration. GPCR-associated signaling in melanoma can be activated by the binding of paracrine factors to their receptors or directly by activating mutations. In this review, we present melanoma-associated alterations of GPCRs and their downstream signaling and discuss the various preclinical models used to evaluate new therapeutic approaches against GPCR activity in melanoma. Recent striking advances in our understanding of the structure, function, and regulation of GPCRs will undoubtedly broaden treatment options in melanoma in the future.

The genome of Vibrio cholerae contains three structural genes for the NhaP-type cation-proton antiporter paralogues, Vc-NhaP1, 2 and 3 mediating exchange of K+ and or Na+ for protons across the membrane. Based on phenotype analysis of chromosomal Vc-NhaP1, 2 and 3 triple deletion mutants we suggested that Vc-NhaP paralogues might play a role in the Acid Tolerance Response (ATR) of V. cholerae as it passes through the gastric acid barrier of the stomach. Comparison of the biochemical properties of Vc-NhaP isoforms revealed that Vc-NhaP2 is the most active among all three paralogues. Therefore, Vc-NhaP2 antiporter is a plausible therapeutic target for developing novel inhibitors targeting these ion exchangers. Our structural and mutational analysis of Vc-NhaP2 identified a putative cation binding pocket formed by antiparallel extended regions of two transmembrane segments (TMSs V/XII) along with TMS VI. Molecular Dynamics (MD) simulations suggested that the flexibility of TMS-V/XII is crucial for the intra-molecular conformational events in Vc-NhaP2. In this study, we developed some putative Vc-NhaP2 inhibitors from Amiloride analogs (AAs). Amiloride is a potent inhibitor of human Na+/H+ exchanger-1 (NHE1). Based on the pharmacokinetic properties and potential binding affinity scores we chose six AAs showing high binding affinity scores to Vc-NhaP2. In silico, the six AAs interacted with the functionally important amino acid residues located in TMSs III, IV, V, VI, VIIII and IX either from the cytoplasmic side (three AAs) or the periplasmic side (three AAs) of Vc-NhaP2. Four AAs were modified to reduce their toxicity profile compared to the original AAs. Molecular docking of the modified AAs revealed promising binding. The four selected drugs interacted with functionally important amino acid residues located on the cytoplasmic side of TMS VI, the extended chain region of TMS V and TMS XII and the loop region between TMSs VIIII and IX. Molecular dynamics simulations revealed that binding of the selected drugs destabilized the Vc-NhaP2 and altered the flexibility of functionally important TMS VI.

In this study, we describe quark confinement in terms of linear interaction potentials and solve the problem of the net spin of a proton. The three quarks in a proton are assumed to revolve around a common center, and their masses are determined assuming they are Dirac particles. On the basis of these assumptions, the magnetic moment of a proton can be derived. Moreover, the rotation of the quarks is considered, in which an electrical current induces a magnetic field. Thus, the scalar product of the magnetic moment and field describes the linear interaction potential between the quarks, and the mass of the proton can be obtained. The proton mass predicted by this physical model is consistent with experimental values, and no numerical or fitting calculations are required. Furthermore, using the newly derived spins and angular momentum of the three quarks, we derived the net spin of a proton. Additionally, we predicted the mass of a pi-meson from the same model, which agrees with the experimental values.

Membranes based on sulfonated synditoactic polystyrene were thoroughly characterized by contrast variation SANS over a wide Q-range in dry and hydrated states. The film samples were prepared by solid-state sulfonation that allowed a uniform sulfonation of only the amorphous phase while preserving the crystallinity of the membrane. The samples were loaded with different guest molecules in either the amorphous (fullerenes) or the crystalline (toluene) regions, in order to vary the neutron contrast or to reproduce the conditions enabling an increased resistance of the membranes to chemical decomposition. The use of uni-axially deformed film samples and contrast variation with different H2O/D2O mixtures allowed for the identification and characterization of different structural levels with sizes between nm and μm, which form and evolve in the membrane morphology in dry and hydrated states and produce scattering features on different detection sectors and at different detection distances after the sample, depending on their size and orientation.

36 years after the publication of the important article by Busa and Nuccitelli on the variability of intracellular pH (pH_i) and the interdependence of pH_i and intracellular Ca²⁺ concentration ([Ca²⁺]_i), little research has been carried out on pH_i and calcium signaling. Moreover, the results appear to be contradictory. Some authors claim that the increase in [Ca²⁺]_i is due to a reduction in pH_i, others that it is caused by an increase in pH_i. The reasons for these conflicting results have not yet been discussed and clarified in an exhaustive manner. Variations in pH_i have a significant impact on the increase in [Ca²⁺]_i and hence on some of the basic biochemical mechanisms of calcium signaling. This paper focuses on the possible triggering role of protons, highlighting the mechanisms potentially involved and the open issues that could be clarified by research.

The relative force strengths of the Coulomb forces, gravitational forces, dark matter forces, weak forces and strong forces are compared for the dark matters, leptons, quarks, and normal matters (p and n baryons) in terms of the 3-D quantized space model. The quark confinement and asymptotic freedom are explained by the CC merging to the A(CC=-5)₃ state. The proton with the (EC,LC,CC) charge configuration of p(1,0,-5) is p(1,0) + A(CC=-5)₃. The A(CC=-5)₃ state has the 99.6% of the proton mass. The three quarks in p(1,0,-5) are asymptotically free in the EC and LC space of p(1,0) and are strongly confined in the CC space of A(CC=-5)₃. This means that the lepton beams in the deep inelastic scattering interact with three quarks in p(1,0) by the EC interaction and weak interaction. Then, the observed spin is the partial spin of p(1,0) which is 32.6 % of the total spin (1/2) of the proton. The A(CC=-5)₃ state has the 67.4 % of the proton spin. This explains the proton spin crisis. The EC charge distribution of the proton is the same to the EC charge distribution of p(1,0) which indicates that three quarks in p(1,0) are mostly near the proton surface. From the EC charge distribution of neutron, the 2 lepton system (called as the koron) of the koron is, for the first time, reported in the present work.

Emergence of multi drug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis poses a serious threat to TB control as the available treatment options are less effective in these cases. Therefore, new strategies are required for identification of new drugs and drug targets. The M. tuberculosis dihydrodipicolinate synthase is a putative drug target with no potent inhibitor. Here in this study, we have used a comprehensive computational approach to identify small molecule inhibitors and validated them in vitro. As similar structures tend to have similar functions, therefore 3 approaches, namely, (a) known inhibitor-based approach, (b) substrate analogues, (c) product analogues were used for compound screening from various chemical libraries. The fourth approach we have taken is fragment library screening.In vitro studies revealed that β-hydroxypyruvic acid tartronic acid are inhibitors of Mtb-rDapA with maximum inhibition 48% and 51% at 500µM concentrations respectively. We have also observed that β-hydroxypyruvic acid is a time dependent inhibitor of Mtb-rDapA. Further, thermal shift assays showed that β-hydroxypyruvic acid interacts with Mtb-rDapA and the thermal stability of Mtb-rDapA shifted by 3˚C. Among the product analogues of Mtb-DapA, dipicolinic acid showed to bind to Mtb-rDapB shifting thermal stability of Mtb-rDapB by 0.5˚C in binding. Additionally, we have designed a new approach by combining substrate and product analogues to achieve better inhibitions. In vitro assays validated that this combination approach increased maximum inhibition up to 100%. We envision that these compounds would serve as potent leads for tuberculosis drug discovery.

Production of electricity using hydro-kinetic tidal turbines has many challenges that must to be overcome to ensure reliable, economic and practical solutions. Energy from flowing water is converted by a system comprising: the turbine rotor blades, a gearbox, an electrical generator, control systems, power electronics, export cables, and a connection to the electricity grid. To date these have often been modelled using simulations of independent systems, lacking bi-directional, real-time, coupling. This approach leads to critical effects being missed. Turbulence in the flow, results in large velocity fluctuations around the blades, causing rapid variation in the shaft torque and generator speed, and consequently in the voltage seen by the power electronics and consequently the export power quality. The resulting poor quality power may be unacceptable to the grid. Conversely, grid frequency and voltage changes can also cause the generator speed to change, resulting in changes to the shaft speed and torque and consequently changes to the lift and drag forces acting on the blades. Clearly, fully integrated, bi-directional, models are needed. Here we present two fully coupled models which use different approaches to model the hydrodynamics of rotor blades. The first model uses Blade Element Momentum Theory (BEMT), resulting in an efficient tool for turbine designers. The second model also uses BEMT combines this with an actuator line model of the blades coupled to an unsteady computational fluid dynamics (CFD) simulation. This simulation, implemented in OpenFOAM, uses an energy balance to compute the shaft speed. Both the BEMT and CFD models are coupled to an Open Modellica model of the electro-mechanical system. Both models have been used to simulate the performance of a 1.2m diameter, scale model, of a three bladed horizontal axis tidal turbine tested in the University of Edinburgh FloWave Ocean Energy Research Facility. The turbulent flow around the blades and the mechanical-electrical variables during the stable period of operation are analysed. Time series and tabulated average values of mechanical thrust, power, torque, and rotational speed as well as electrical variables of generator power, electromagnetic torque, voltage and current are presented for the coupled system simulation. The relationship between the mechanical and electrical variables and the results from both tidal turbine approaches are discussed. Our comparison shows that while the BEMT model provides an effective design tool (leading to slightly more conservative designs), the CFD/BEMT simulations provide more accurate predictions of the blade loads which can be especially important in assessing fatigue on the blades (though at an increased computational cost).

A formulation of nonequilibrium thermo field dynamics has been performed using the nonequilibrium statistical operator method by D.N. Zubarev. Generalized transfer equations for a consistent description of kinetics and hydrodynamics of the dense quantum-field system with strongly coupled states are derived.

Abstract: It is assumed that upon SARS-CoV-2 infection granulocytes can undergo potentially destructive oxidative burst. Therefore, the aim of this study was to evaluate some parameters of redox and inflammatory signaling in granulocytes of recovered and of deceased COVID-19 pa-tients. Granulocytes were isolated from the blood of 32 COVID-19 patients on admission to the hospital (16 survived and 16 died within a week). The levels of proteins (immunoassay), eico-sanoids (UPLC-MS) and antioxidants activity (spectrophotometry) were examined. Enhanced activation of Nrf2 and NFκB and the levels of heme oxygenase and proinflammatory cytokines where found in granulocytes of all COVID-19 patients, while Cu,Zn-SOD and Mn-SOD activities were decreased, especially in deceased patients. Moreover, in patients who died increased levels of pro-inflammatory eicosanoids (PGE2 and TXB2) and decreased of anti-inflammatory (15d-PGJ2 and 5-HETE) were observed. However TXB2 was decreased, and IL-2 and IL-10 levels were in-creased in survivors, if compared both to healthy subjects and deceased patients, who did not change their cytokine generation. Therefore, it seems that by triggering transcription factors granulocytes activate redox signaling, leading to the production of pro-inflammatory eicosanoids, while reducing cellular antioxidant capacity via SOD, they express altered response to COVID-19, which might result in the onset of the vicious cycle of systemic oxidative stress in deceased patients.

A coupled stratospheric chemistry-meteorology model was developed by combining the Canadian operational weather prediction model Global Environmental Multiscale (GEM) with a comprehensive stratospheric photochemistry model from the Belgian Assimilation System for Chemical ObsErvations (BASCOE). The coupled model was called GEM-BACH for GEM-Belgian Atmospheric CHemistry. The coupling was made across a chemical interface that preserves time splitting while being modular, allowing GEM to run with or without chemistry. An evaluation of the coupling was performed by comparing the coupled model, refreshed by meteorological analyses every 6 hours, against the standard offline chemical transport model (CTM) approach. Results show that the dynamical meteorological consistency between meteorological analysis times far outweighs the error created by the jump resulting from the meteorological analysis increments at regular time intervals, irrespective whether a 3D-Var or 4D-Var meteorological analysis is used. GEM-BACH forecast refreshed by meteorological analyses every 6 hours were compared against independent measurements of temperature, long-lived species, ozone and water vapor. The comparison showed a relatively good agreement throughout the stratosphere except for an upper-level warm temperature bias and an ozone deficit of nearly 15%. Arguments in favor of using the same horizontal resolution for chemistry, meteorology, and meteorological analysis increments are also presented. In particular, the coupled model simulation during an ozone hole event gives better ozone concentrations than a 4D-Var chemical assimilation at a lower resolution.

It is shown that the termination of the channeling of the fundamental radiation mode in the waveguide can be observed upon heating of an optical integrated circuit based on proton exchange channel waveguides formed in a lithium niobate single crystal. This process is reversible, but restoration of waveguide performance takes tens of minutes. The effect of the waveguide disappearance is observed upon rapid heating (5 °C/min) from a low temperature (minus 40 °C). This effect can lead to a temporary failure of navigation systems using fiber optic gyroscopes with modulators based on a lithium niobate crystal

Intrinsically disordered proteins mediate crucial biological functions through their interactions with other proteins. Mutual synergistic folding (MSF) occurs when all interacting proteins are disordered, folding into a stable structure in the course of the complex formation. In these cases, the folding and binding processes occur in parallel, lending the resulting structures uniquely heterogeneous features. Currently there are no dedicated classification approaches that would take into account the particular biological and biophysical properties of MSF complexes. Here we present a scalable clustering-based classification scheme, built on redundancy-filtered features that describe the sequence and structure properties of the complexes, and the role of the interaction, which is directly responsible for structure formation. Using this approach, we define six major types of MSF complexes, corresponding to biologically meaningful groups. Hence, the presented method also shows that differences in binding strength, subcellular localization, and regulation are encoded in the sequence and structural properties of proteins. While current structure classification methods can also handle complex structures, we show that the developed scheme is fundamentally different, and since it takes into account defining features of MSF complexes, it serves as a better representation of structures arising through this specific interaction mode.

Understanding the ionic channel network of proton exchange membranes, which dictate fuel cell performance, is crucial when developing proton exchange membrane fuel cells. However, itis difficult to characterize due to complicated nano structure and differing changes to their structure with different amounts of water uptake. Electrostatic force microscopy (EFM) can map surface charge distribution as nano special resolution by measuring the electrostatic force between a vibrating conductive tip and a charged surface under an applied voltage, . In this study, the ionic channel network of a proton exchange membrane is analyzed using EFM. A mathematical approximation model of the ionic channel network is first derived, to explain changes in force gradient on the surface using EFM. The phase lag of dry and wet Nafion under stepwise changes to bias voltage is then measured. Based on the model, variations in the ionic channel network of Nafion with different amounts of water uptake are analyzed numerically. The mean surface charge density of both membranes, which is connected with the ionic channel network, is calculated using the model. The results show that the difference between the mean surface charge of the dry and wet membranes is consistent with the variation in their proton conductivity.

The evolutionary conserved STING-cGAS pathway represents one of the most important cytosolic DNA sensing systems that is activated in response to viral invasion and/or damaged integrity of the nuclear envelope. The key outcome of this pathway is the production of IFN, which subsequently stimulates hundreds of genes. In oncology, the situation is a complex one since this pathway may serve either anti- or pro-oncogenic roles in a context-dependent fashion. The prevailing understanding is that when the innate immune response is activated by sensing cytosolic DNA, such as from ruptured micronuclei, it results in the production of interferon which attracts cytotoxic cells to destroy tumors. However, in tumor cells that have adjusted to significant chromosomal instability, particularly in relapsed, treatment-resistant cancers, the cGAS–STING pathway often supports cancer progression. In these cells, the pathway initiates a non-canonical nuclear factor κB transcriptional response, fostering the epithelial-to-mesenchymal transition (EMT). Here, we review this intricate pathway in conjunction with cancer progression and development of new treatment modalities.

A separate group consists of compounds that are able to simultaneously interact with both orthosteric and allosteric sites, which are classified as bitopic GPCR ligands [74, 76-81]. They have two pharmacophores, one of which binds with high affinity to the orthosteric site, while the other, with lower affinity, binds to the allosteric site. If these sites are spatially separated in the receptor, then the pharmacophores in the bitopic ligand must be connected with a flexible linker, the length of which exactly corresponds to the distance between the orthosteric and allosteric sites. At the same time, it is important that the linker does not significantly affect the conformational rearrangements in the receptor caused by its activation by orthosteric and (or) allosteric agonists [74, 79].

Recently, more wind turbine systems are being installed in deep waters far from the coast. Several concepts of floating wind turbine systems (FWTSs) are developed, among which the semisubmersible platform, due to its applicability in different water depths, good hydrodynamic performance, and facility in the installation process, constitutes the most explored technology compared to the others. However, a significant obstacle to the industrialization of this technology is a design of a cost-effective FWTS, which can be achieved by optimizing the geometry, size and weight of the floating platform, along with the mooring system. This is only possible by selecting a method capable of accurately analyzing the FWTS coupled hydro-aero-structural dynamics at each design stage. Accordingly, this paper aims at providing a detailed overview of the most common coupled numerical and physical methods, including their basic assumptions, formulations, limitations, and costs, used for analyzing the dynamics of FWTSs, mainly those supported by a semisubmersible, to assist the choice of the most suitable method at each design phase of FWTSs. Finally, the article discusses possible future research to address challenges in modeling FWTSs dynamics that persist to date.

In order to enhance the gain of antenna suitable for the airplane mounted platform, a conformal tightly coupled antenna array is investigated in this paper. Especially, three-dimensional (3-D) inkjet printing technique is used to implement the conformal property. The printing of antenna substrate and radiation layer is implemented by combining the fused deposition modelling and microdroplet injection molding technologies based on the existing 3-D printer. Here, through a unique combination of 3-D and 2-D inkjet printing of dielectric material and metallic ink, respectively, we demonstrate a monolithically integrated to a nonplanar antenna for the first time. Antenna measurements show that the complete characterization of this new process in terms of minimum feature sizes and achievable conductivities. This antenna configuration offers a high-gain performance with low-cost and rapid fabrication technique by using 3-D printing. The voltage standing wave ratio and radiation patterns are tested after adding the newly designed feed structure. Results shown the design process much efficient. Both antenna element and the array with good properties, which are in very good agreement with the specially mounted platform.

Reliable information on transition matrix elements of various property operators between molecular electronic states is of crucial importance for predicting spectroscopic, electric, magnetic and radiative properties of molecules. The finite-field technique is a simple and rather accurate tool for evaluating transition matrix elements of first-order properties in the frames of the Fock space relativistic coupled cluster approach. We formulate and discuss the extension of this technique to the case of transitions between the electronic states associated with different sectors of the Fock space. Pilot applications to the evaluation of transition dipole moments between the closed-shell-like states (vacuum sector) and those dominated by single excitations of the Fermi vacuum (the $1h1p$ sector) in heavy atoms (Xe, Hg) and simple molecules of heavy element compounds (I${}_2$, TlF) are reported.

The paper is focused on numerical modeling of multi-strand cable lines placed in free air. Modeling is carried out within the framework of the so-called multi-physics approach using commercial software. The paper describes in detail the steps undertaken to develop realistic, reliable numerical models of power engineering cables, taking into account their geometries and heat exchange conditions. The results might be of interest to the designers of multi-strand cable systems.

At present there is a renewed interest in theories of ”modified” gravity. Here, under a more drastic modification enforced by Galilei group, we obtain a completely new gravitational structure, and which exists in addition to the already available general relativity of today. Correlated with this, we show that in addition, there is a new ”modified” quantum mechanics, in as much as it exists as an independent and new ”pure” non-relativistic quantum me- chanics, and which has no relativistic counterpart. This is in addition to the present quantum mechanics, where the relativistic and non-relativistic structures are counterparts of each other. The above holds, firstly due to the correlation between Galilei group and quantum mechanics. These math- ematical conclusions are consolidated by the fact that there exists a physical Majorana interaction between each neutron- proton pairs in nuclei. Galilei invariance of Majorana exchange in Majorana interaction, shows that the mass here is of pure gravitational nature, and which is immune to the other three forces. This makes an amazing connection between the gravitational force and the quantum mechanics. This pure gravitational mass would man- ifest itself as dark matter of the universe. It is our new modified gravity that generates the dark matter.

Purpose: To report the early clinical outcomes of combining intensity‐modulated radiation therapy (IMRT) and intensity‐modulated proton therapy (IMPT) in comparison with IMRT alone in treating the oropharynx cancer (OPC) patients. Materials and Methods: The medical records of 148 OPC patients were retrospectively reviewed, who underwent definitive radiotherapy (RT) with concurrent systemic therapy, from January 2016 till December 2019 at Samsung Medical Center. During the 5.5 weeks’ RT course, the initial 16 (or 18) fractions were delivered by IMRT in all patients, and the subsequent 12 (or 10) fractions were either by IMRT in 81 patients (IMRT only) or by IMPT in 67 (IMRT/IMPT combination), respectively, based on comparison of adaptive re-plan profiles and availability of equipment. Propensity‐score matching (PSM) was done on 76 patients (38 from each group) for comparative analyses. Results: With the median follow‐up of 24.7 months, there was no significant difference in overall survival and progression free survival between groups, both before and after PSM. Before PSM, IMRT/IMPT combination group experienced grade ≥3 acute toxicities less frequently: mucositis in 37.0% and 13.4% (p<0.001); and analgesic quantification algorithm (AQA) in 37.0% and 19.4% (p=0.019), respectively. The same trends were observed after PSM: mucositis in 39.5% and 15.8% (p=0.021); and AQA in 47.4% and 21.1% (p=0.016), respectively. In multivariate logistic regression, grade ≥3 mucositis was significantly less frequent in IMRT/IMPT combination group, both before and after PSM (p=0.027 and 0.024, respectively). AQA score ≥3 was also less frequent in IMRT/IMPT combination group, both before and after PSM (p=0.085 and 0.018, respectively). Conclusions: In treating the OPC patients, with comparable early oncologic outcomes, more favorable acute toxicity profiles were achieved following IMRT/IMPT combination than IMRT alone.

We present a method to turn results of model-based optimisations into resilient and comprehensible control strategies. Our approach is to define priority lists for all available technologies in a district energy system. Using linear discriminant analysis and the results of the optimisations, these are then assigned to discrete time steps using a set of possible steering parameters. In contrast to the model-based optimisations, the deduced control strategies do not need perfect foresight but solely rely on data about the present. Our result indicate that the results of the control strategies obtained using the proposed method are comparable to the results of the linear optimisations, in our case in terms of emissions and prices.

In this study, we focus on the effects of fuel bed representation and fire heat and smoke distribution in a coupled fire-atmosphere simulation platform for two landscape-scale fires: the 2018 Camp Fire and the 2021 Caldor Fire. The fuel bed representation in the coupled fire-atmosphere simulation platform WRF-Fire currently includes only surface fuels. Thus, we enhance the model by adding canopy fuel characteristics and heat release, for which a method to calculate the heat generated from canopy fuel consumption is developed and implemented in WRF-Fire. Furthermore, the current WRF-Fire heat and smoke distribution in the atmosphere is replaced with a heat-conserving Truncated Gaussian (TG) function and its effects are evaluated. The simulated fire perimeters of case studies are validated against semi-continuous, high-resolution fire perimeters derived from NEXRAD radar observations. Furthermore, simulated plumes of the two fire cases are compared to NEXRAD radar reflectivity observations followed by buoyancy analysis using simulated temperature and vertical velocity fields. The results show that while the improved fuel bed and the TG heat release scheme have small effects on the simulated fire perimeters of the wind-driven Camp Fire, they affect the propagation direction of the plume-driven Caldor Fire, leading to better-matching fire perimeters with the observations. However, the improved fuel bed representation together with the TG heat smoke release scheme leads to more realistic plume structure in comparison to the observations in both fires. The buoyancy analysis also depicts more realistic fire-induced temperature anomalies and atmospheric circulation when the fuel bed is improved.

In this paper, we investigate the accuracy and robustness of three classes of methods for solving two-phase incompressible flows on a staggered grid. Here, the unsteady two-phase flow equations are simulated by finite volumes and penalty methods using implicit and monolithic approaches (such as the augmented Lagrangian and the fully coupled methods), where all velocity components and pressure variables are solved simultaneously (as opposed to segregated methods). The interface tracking is performed with a Volume-of-Fluid (VOF) method, using the Piecewise Linear Interface Construction (PLIC) technique. The home code Fugu is used for implementing the various methods. Our target application is the simulation of two-phase flows at high density and viscosity ratios, which are known to be challenging to simulate. The resulting strategies of monolithic approaches will be proven to be considerably better suited for these two-phase cases, they also allow to use larger time step than segregated methods.

To assess cognitive impairment and affective symptoms and their association with damage to normal-appearing white matter (NAWM) in patients with clinically isolated syndrome (CIS), we compared neuropsychological test scores between patients with CIS and healthy controls, and examined correlations between these and proton magnetic resonance spectroscopy (1H-MRS) outcomes in patients with CIS. Forty patients with CIS and 40 healthy participants were tested with the set of neuropsychological tests, the Beck Depression Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS). Single-voxel 1H-MRS was performed on frontal and parietal NAWM of patients with CIS to assess ratios of N-acetyl-aspartate (NAA) to creatine (Cr), myo-inositol (mI), and choline (Cho), as well as mI/Cr and Cho/Cr ratios. Patients with CIS had lower cognitive performance, higher scores for the BDI and anxiety subscale of HADS than healthy controls. There were significant correlations between the following neuropsychological tests and metabolic ratios in the frontal NAWM: Stroop Color-Word Test and Cho/Cr, Symbol Digit Modalities Test and mI/Cr as well as NAA/mI, Go/no-go reaction time and NAA/Cho as well as NAA/mI, Californian Verbal Learning Test and NAA/Cr. BDI scores were related to frontal NAA/mI and parietal NAA/Cr and Cho/Cr ratios, whereas HADS-depression scores were associated with frontal NAA/Cr and NAA/mI, and parietal NAA/Cr and Cho/Cr ratios. HADS-anxiety correlated with parietal NAA/Cr ratio. This study suggests that neurochemical changes in the NAWM assessed with single-voxel 1H-MRS are associated with cognitive performance and affective symptoms in patients with CIS.

Fatty acids (FFAs) are important biological molecules that serve as a major energy source and are key components of biological membranes. Besides, FFAs play important roles in metabolic regulation and contribute to the development and progression of metabolic disorders like diabetes. Recent studies have shown that FFAs can act as important ligands of G-protein coupled receptors (GPCRs) on the surface of cells and impact key physiological processes. Free fatty acid activated receptors include FFAR1 (GPR40), FFAR2 (GPR43), FFAR3 (GPR41) and FFAR4 (GPR120). FFAR2 and FFAR3are activated by short chain fatty acids like acetate, propionate and butyrate whereas FFAR1 and FFAR4 are activated by medium and long chain fatty acids like palmitate, oleate, linoleate and others. FFARs have generated considerable attention over the last few years and have become attractive pharmacological targets in the treatment of type 2 diabetes and metabolic syndrome. Several lines of evidence point to their importance in the regulation of whole-body metabolic homeostasis including adipose metabolism. Here we summarize our current understanding of the physiological functions of FFAR isoforms in adipose biology and explore the prospect of FFAR based therapies to treat patients with obesity and Type 2 Diabetes.

We examine data assimilation coupling between meteorology and chemistry in the stratosphere from both weak and strong coupling strategies. The study was performed with the Canadian operational weather prediction Global Environmental Multiscale (GEM) model coupled online with the photochemical stratospheric chemistry developed at the Belgian Institute for Space Aeronomy, described in Part I. Here, the Canadian Meteorological Centre’s operational variational assimilation system was extended to include errors of chemical variables and cross-covariances between meteorological and chemical variables in a 3D-Var configuration, and we added the adjoint of tracer advection in the 4D-Var configuration. Our results show that the assimilation of limb sounding observations from the MIPAS instrument on board Envisat can be used to anchor the AMSU-A radiance bias correction scheme. Also, the added value of limb sounding temperature observations on meteorology and transport is shown to be significant. Weak coupling data assimilation with ozone-radiation interaction is shown to give comparable on meteorology whether a simplified linearized or comprehensive ozone chemistry scheme is used. Strong coupling data assimilation, using static error cross-covariances between ozone and temperature in a 3D-Var context, produced inconclusive results with the approximations we used. We have also conducted the assimilation of long-lived species observations using 4D-Var to infer winds. Our results showed the added value of assimilating several long-lived species, and an improvement in the zonal wind in the Tropics within the troposphere and lower stratosphere. 4D-Var assimilation also induced a correction of zonal wind in the surf zone and a temperature bias in the lower tropical stratosphere

In order to clarify the nature of the halogen bond (XB), we considered the prototype noble gas – dihalogen molecule (Ng-X2) systems, focusing on the nature, range and strength of the interaction. We exploited data gained from molecular beam scattering experiments with the measure of interference effects to obtain a suitable formulation of the interaction potential, with the support of high-level ab initio calculations, and charge displacement analysis. The essential interaction components involved in the Ng-X2 adducts have been characterized, pointing at their critical balance in the definition of the XB. Particular emphasis is devoted to the energy stability of the orientational Ng-X2 isomers, the barrier for the X2 hindered rotation, and the influence of the X2 electronic state. The present integrated study returns reliable force fields for molecular dynamics simulations in Ng-X2 complexes that can be extended to systems with increasing complexity and whose properties depend on the selective formation of XB.

Novel molecular pinball machines of the plasma membrane control cytosolic Ca²⁺ levels that regulate plant metabolism. [https://youtu.be/zABg7LiBk88] Essential components involve: 1. an auxin-activated proton pump; 2. arabinogalactan glycoproteins (AGPs); 3. Ca²⁺ channels; 4. auxin-efflux “PIN” proteins. Typical pinball machines release pinballs that trigger various sound and visual effects. However, in plants “proton pinballs” eject Ca²⁺ bound by paired glucuronic acid residues of numerous glycomodules in periplasmic AGP-Ca²⁺. Freed Ca²⁺ ions flow down the electrostatic gradient through open Ca²⁺ channels into the cytosol thus activating numerous Ca²⁺-dependent activities.Clearly cytosolic Ca²⁺ levels depend on activity of the proton pump, the state of Ca²⁺ channels and size of the periplasmic AGP-Ca²⁺ capacitor: Proton pump activation is a major regulatory focal point tightly controlled by the supply of auxin: auxin efflux carriers conveniently known as “PIN” proteins [null mutants are pin-shaped!] pump auxin from cell to cell. Mechanosensitive Ca²⁺ channels and their activation by reactive oxygen species (ROS) are yet another factor regulating cytosolic Ca²⁺.Cell expansion also triggers proton pump/pinball activity by mechanotransduction of wall stress via Hechtian adhesion thus forming a Hechtian oscillator that underlies cycles of wall plasticity and oscillatory growth.Finally, Ca²⁺ homeostasis of plants depends on cell surface external storage as source of dynamic Ca²⁺, unlike the internal ER storage source of animals where the added regulatory complexities ranging from vitamin D to parathormone contrast with the elegant simplicity of plant life. This paper summarises a sixty year Odyssey.

Here we are concerning with two problems of a coupled system of random and stochastic nonlinear differential equations with two coupled systems of nonlinear nonlocal random and stochastic integral conditions. The existence of solutions will be studied. The sufficient condition for the uniqueness of the solution will be given. The continuous dependence of the unique solution on the nonlocal conditions will be proved.

Generalized relativistic pseudopotentials (GRPP) of atomic cores implying the use of different potentials for atomic electronic shells with different principal quantum numbers give rise to accurate and reliable relativistic electronic structure models of atoms, molecules, clusters, and solids. These models readily incorporate the effects of Breit electron-electron interactions and one-loop quantum electrodynamics effects. Here we report the computational procedure for evaluating one-electron integrals of GRPP over contracted Gaussian functions. This procedure was implemented in a library of routines named LIBGRPP, which can be integrated into existing quantum chemistry software, thus enabling the application of various methods to solve the many-electron problem with GRPPs. Pilot applications to electronic transitions in the ThO and UO2 molecules using the new library and intermediate-Hamiltonian Fock space relativistic coupled cluster method are presented. The results clearly demonstrate that rather economical tiny-core GRPP models can exceed in accuracy relativistic all-electron models defined by Dirac-Coulomb and Dirac-Coulomb-Gaunt Hamiltonians.

Accurate and efficient determination of excited-state polarizabilities (α) is an open problem both experimentally and computationally. Following our previous work, [Phys. Chem. Chem. Phys. 2023, 25, 2131−2141], where one can employ simple ground-state density-based functions from the information-theoretic approach (ITA) to accurately and efficiently predict the macromolecular polarizabilities, we aim to predict the lowest excited-state polarizabilities in this work. The philosophy is to use density-based functions to depict the excited-state polarizabilities. As a proof-of-principle application, employing 2-(2′-hydroxyphenyl)benzimidazole and its derivatives as model systems, we have verified that either with the ground-state (S0) or excited-state (S1) densities as input, ITA quantities can be strongly correlated with the excited-state polarizabilities. When the transition densities are considered, both S0 and S1 polarizabilities are in good relationships with some ITA quantities. Furthermore, excitation and emission energies can be predicted based on multivariant linear regression equations of ITA quantities.

Phase synchronization of weakly coupled limit cycle oscillators are related to the stability of the zero solution of the reduced-order dynamics of phase differences, represented by a systems of differential equations on a hypertorus. Using Rantzer's density function, a dual form of Lyapunov function, we propose a method to certify almost global stability of an equilibrium on a hypertorus. We show that the proposed method can certify robustness of phase synchronization of all-to-all and weakly coupled limit cycle oscillators with respect to disturbances in phases. The method leverages sum of squares polynomial optimization to construct the certification function.

Heterogeneous distribution of delivery or treatment modalities within the tumor mass is a crucial limiting factor for a vast range of theranostic applications. Understanding the interactions between a nanomaterial and the tumor microenvironment will help to overcome challenges associated with tumor heterogeneity as well as the clinical translation of nanotheranostic materials. This study aims to evaluate the influence of protein surface adsorption on gold nanoparticle (GNP) biodistribution using high resolution Computed Tomography (CT) preclinical imaging in C57BL/6 mice harboring Lewis Lung Carcinoma (LLC) tumors. LLC provides a valuable model for study due to its highly heterogenous nature which makes drug delivery to the tumor challenging. By controlling the adsorption of proteins on the GNP surface, we hypothesize that we can influence the intratumoral distribution pattern and particle retention. We performed an in vitro study to evaluate the uptake of GNPs by LLC cells and an in vivo study to assess and quantify the GNP biodistribution by injecting concentrated GNPs citrate stabilized or passivated with Bovine Serum Albumin (BSA) intratumorally into LLC solid tumors. Quantitative CT and Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) results both confirm the presence of particles in the tumor 9 days post-injection (n=8 mice/group). Significant difference is highlighted between citrate-GNP and BSA-GNP groups (**p < 0.005, Tukey’s multiple comparisons test), confirming the protein corona of GNPs modifies intratumoral distribution and retention of the particles. In conclusion, our investigations show that the surface passivation of GNPs influences the mechanism of cellular uptake and intratumoral distribution in vivo highlighting the spatial heterogeneity of the solid tumor.

The fault diagnosis of the gearbox is primarily based on the analysis of the harmonic response. However, the generation mechanism of the harmonic response of the gear pair is still not distinctly explained in a healthy gearbox. Therefore, this paper is dedicated to establishing a dynamic model of the gearbox for this issue. In this model, the contact force of the bearing and the meshing stiffness of the gear pair are determined by the Hertz theory and the potential energy method, then the shaft motion is used as the connection to establish the coupling relationship between the gear pair and the bearing. After this dynamic model is confirmed by experiments and existing models, the coupling relationship inside the gearbox and the harmonic response of the gear pair are studied using this model. The result demonstrates that a closed control loop is formed due to the vibration transmission between the gear pair, the bearing and the shaft, and there is a strong coupled vibration between the gear pair and the bearing in the gearbox. Due to the generation of the center distance error, misalignment angle and disorganized meshing process of the gear pair, the meshing stiffness is altered, which excites the harmonic response of the gear pair. When the speed of the gearbox is increased, although the vibration amplitude of the gearbox is increased, the system predominantly vibrates at the fundamental frequency, and the harmonic of the gear pair is also shifted to the low frequency band.

It is extremely fascinating and astonishing that the gravitational field on the surface of a neutron star is with a relativistic mass density of 2.65*10¹⁶~5.87*10¹⁸kgm^-3 which can be larger than the mass density of the neutron star (~10¹⁷kgm^-3).Therefore, it is the author’s first intuitional imagining that this field could directly convert into mass. In so strong a gravitational field, electron and proton could be produced directly from graviton–photon collision. The gravitational field exists in everywhere in our universe. No vacuum that the region of a space is “empty” does exist. A particle is clearly always being acted on by the gravitational field. The quantum vacuum fluctuation and vacuum polarization need be re-understood with the interaction between photon and gravitational field. Therefore, the gravitational field is naturally one of the foundations of modern physics.

We performed a systematic review and meta-analysis to evaluate the role of gastric acid suppressant use on outcomes of tyrosine kinase inhibitors (TKIs) and oral chemotherapy. We identified all researches evaluating the effect of GAS use on patients receiving oral chemotherapy or TKIs for solid tumors. The pooled hazard ratios (HRs) and 95% confidence interval (95% CI) for overall survival (OS) and progression-free survival (PFS) were calculated with fixed-effects or random-effects model. The study population included n=16 retrospective studies and 372,418 patients. Series concerned gastrointestinal tract tumors (n=5 studies), renal cell carcinomas (RCC, n=3 studies), non-small cell lung cancers (NSCLC, n=5 studies), and soft tissue sarcomas or mixed histologies solid tumors in n=3 studies. The pooled HRs for OS and PFS were 1.31 (95% CI: 1.20–1.43; P<01) and 1.3 (95%CI 1.07-1.57; P<0.01) for GAS and no GAS users, respectively. Only studies of EGFR mutated NSCLC patients receiving TKIs and those with colorectal cancer receiving oral chemotherapy showed a significant correlation between GAS and poor survival. Our study supports the evidence of a possible negative impact of concomitant GAS therapy on survival outcomes of patients receiving oral anti-cancer drugs.

The sustainable metabolic engineering (SME) concept was defined by Stalidzans and Dace as an approach for the selection of most sustainable metabolic engineering designs taking the economic, environmental and social components of sustainability into account. In the centre of sustainability calculations is a genome scale metabolic model that provides full balance of all incoming and outgoing metabolic fluxes at steady state. Therefore, sustainability indicators are assigned for each exchange reaction enabling calculation of sustainability features of consumption or production of each metabolite. The further development of the SME concept depends on its implementation at the computational level to acquire applicable results – sustainable production strain designs. This study proposes for the first time a workflow and tools of SME implementation using constraint based stoichiometric modelling, genome scale metabolic models and growth coupled product synthesis approach. For SME application demonstration purposes, a relatively simple engineering task has been carried out. The most sustainable designs have been identified using Escherichia coli as chassis organism, glucose as a substrate and gene deletions as metabolic engineering tool. A growth coupled production design tool has been used to reduce the variability of sustainability. The 10 000 most sustainable designs were producing succinate as the main product with the number of deleted genes ranging from two to ten. A big number of similar designs has been identified due to the combinatorial explosion of different alternative combinations of gene deletion sets that result in interruption of the same metabolic pathways with the same impact on the metabolism.

G-protein coupled receptors (GPCRs), one of the largest superfamilies of cell-surface receptors, are heptahelical integral membrane proteins that play critical roles in virtually every organ system. G-protein-coupled receptors operate in membranes rich in cholesterol, with an imbalance in cholesterol level within the vicinity of GPCR transmembrane domains affecting the structure and/or function of many GPCRs, a phenomenon that has been linked to several diseases. These effects of cholesterol could result in indirect changes by altering the mechanical properties of the lipid environment or direct changes by binding to specific sites on the protein. There are a number of studies and reviews on how cholesterol modulates class A GPCRs, however, this area of study is yet to be explored for class C GPCRs, which are characterized by a large extracellular region and often form constitutive dimers. This review highlights specific sites of interaction, functions, and structural dynamics involved in the cholesterol recognition of the class C GPCRs. We summarize recent data from some typical family members to explain the effects of membrane cholesterol on the structural features and functions of Class C GPCRs and speculate on their corresponding therapeutic potential.

Leaf mechanical wounding triggers a rapid, within minutes, release of a blend of volatile organic compounds (VOCs). Wounding-induced VOC blend is mainly composed of oxygenated ubiquitous stress volatiles such as methanol and volatile products of lipoxygenase (LOX) pathway (mainly C5 and C6 alcohols and aldehydes and their derivatives), but also includes multiple minor VOCs that collectively act as infochemicals inducing defences in non-damaged plant leaves, neighbouring plants and attracting herbivore enemies. Till present, interspecific variability of the rate of induction and magnitude of wounding-induced emissions, and the extent to which plant structural traits and physiological activity alter these emissions are poorly known. Particularly scarce is the information of the induced emissions in tropical agricultural plant species despite their economic importance and large area of cultivation at regional to global scales. We chose five tropical crops with varying photosynthetic activity and leaf structural characteristics: Abelmoschus esculentus, Amaranthus cruentus, Amaranthus hybridus, Solanum aethiopicum and Telfairia occidentalis to characterize the kinetics and magnitude of wounding-induced emissions, hypothesizing that the induced emission response is greater and faster in physiologically more active species with greater photosynthetic activity than in less active species. Rapid highly repeatable leaf wounds (12-mm cuts) were generated by a within-leaf-chamber cutting knife. Wounding-induced VOC emissions were measured continuously with a proton-transfer reaction time-of-flight mass spectrometer and gas-chromatography mass spectrometry was used to separate isomers. Twenty-three ion VOCs and twelve terpenoid molecule structures were identified, whereas ubiquitous stress volatiles methanol (on average 40% of total emissions), hexenal (24%), and acetaldehyde (11%) were the main compounds across the species. Emissions of low-weight oxygenated compounds (LOC, 70% of total), and LOX products (29%) were positively correlated across species, but minor VOC components, monoterpenoids and benzenoids were negatively correlated with LOC and LOX, indicating a reverse relationship between signal specificity and strength. There was a large interspecific variability in the rate of induction and emission magnitude, but the hypothesis of a stronger emission response in physiologically more active species was only partly supported. In addition, the overall emission levels were somewhat lower with different emission blend compared to the data reported for wild species, as well as different shares for the VOCs in the blend. The study demonstrates that wounding-dependent emissions from tropical agricultural crops can significantly contribute to atmospheric volatiles, and these emissions cannot be predicted based on current evidence of wild plant model systems.

The elimination of superoxide radical anions (O2•−) by 5-amino-2-hydroxybenzoic acid (mesalazine, 5-ASA), 4-amino-2-hydroxybenzoic acid (4-ASA), and related compounds used for ulcerative colitis treatment was investigated using cyclic voltammetry and electron spin resonance (ESR) analyses aided by density functional theory (DFT) calculations. Quasi-reversible O2/O2•− redox was found to be modified by the compounds, suggesting that an acid-base reaction in which a hydroperoxyl radical (HO2•) is formed from O2•− occurs. However, the deprotonated 5-ASA anion can eliminate O2•− through proton-coupled electron transfer (PCET), forming a radical product. This electron transfer (ET) was confirmed by ESR analysis. The 4-aminophenol moiety in 5-ASA plays an important role in the PCET involving two proton transfers and one ET based on -conjugation. The electrochemical and DFT results indicated that O2•− elimination by 5-ASA proceeds efficiently viathrough the PCET mechanism after deprotonation of the 1-carboxyl group. Thus, 5-ASA may act as an anti-inflammatory agent in the alkali intestine through PCET-based O2•− elimination.

Adrenergic receptor β3 (ADRβ3) is a member of the rhodopsin-like G protein-coupled receptor family. The binding of the ligand to ADRβ3 activates adenylate cyclase and increases cAMP in the cells. ADRβ3 is highly expressed in white and brown adipocytes and controls key regulatory pathways of lipid metabolism. Trp64Arg (W64R) polymorphism in the ADRβ3 has been associated with the early development of type 2 diabetes mellitus, lower resting metabolic rate, abdominal obesity, and insulin resistance. It is unclear how the substitution of W64R affects the functioning of ADRβ3. This study was initiated to functionally characterize this obesity-linked variant of ADRβ3. We evaluated in detail the expression, subcellular distribution, and post-activation behavior of the WT and W64R ADRβ3 using a single cell quantitative fluorescence microscopy. When expressed in HEK 293 cells, ADRβ3 shows a typical distribution displayed by other GPCRs with a predominant localization at the cell surface. Unlike Adrenergic receptor β2 (ADRβ2), agonist induced desensitization of ADRβ3 does not involve loss of cell surface expression. WT and W64R variant of ADRβ3 displayed comparable biochemical properties and there was no significant impact of the substitution of Tryptophan with Arginine on the expression, cellular distribution, signaling, and post-activation behavior of ADRβ3. The obesity-linked W64R variant of ADRβ3 is indistinguishable from the WT ADRβ3 in terms of expression, cellular distribution, signaling, and post-activation behavior.

The naturally occurring dipeptide carnosine (β alanyl L histidine) specifically attenuates tumor growth. Here, we asked whether other small imidazole containing compounds also affect viability of tumor cells without affecting non-malignant cells, and whether formation of histamine is involved. Patient-derived fibroblasts and glioblastoma cells were treated with carnosine, L alanyl L histidine (LA-LH), ß alanyl L alanine, L histidine, histamine, imidazole, β alanine and L alanine. Cell viability was assessed by cell-based assays and microscopy. The intracellular release of L histidine and formation of histamine was investigated by High Performance Liquid Chromatography coupled Mass Spectrometry. Whereas carnosine and LA LH inhibited tumor cell growth with minor effects on fibroblasts, L-histidine, histamine and imidazole affected viability in both cell types. Compounds without imidazole moiety did not diminish viability. In the presence of LA LH but not in the presence of carnosine a significant rise of intracellular amounts of histidine was detected in all cells. Formation of histamine was not detectable in the presence of carnosine, LA LH or histidine. In conclusion, the imidazole moiety of carnosine contributes to its anti-neoplastic effect, which is also seen in the presence of histidine and LA LH. Despite histamine had a strong effect on cell viability, formation of histamine is not responsible for the effects on cell viability of carnosine, LA LH and histidine.

Talbot effect is a self-imaging or lensless imaging phenomenon of a periodic grating illuminated by a collimated light beam at regular distances from the grating. Research on the Talbot effect has recently made significant strides thanks to the quick development of optical superlattices. The emergence of various applications of this effect in fields such as optics, acoustics, X-ray, plasmonics, and information processing has led to the increasing importance of obtaining a Talbot carpet with the use of different structures. In this paper, we investigate the Talbot effect that originates from the tunneling effect between an ensemble of vertically coupled cylindrical quantum dots (QDs). The Talbot carpet can be manipulated by changing the parameters of the QD system. In the current paper, two modified Pöschl-Teller potentials were used to model the QDs ensemble. The exciton’s lifetime and tunneling time’s dependence on the first QD’s potential half-width is found for a fixed value of the external electric field. The nonlinear changes in the refractive index and absorption spectrum dependent on the tunneling effect are obtained. Afterward, the Talbot carpet formation is investigated, particularly the dependences of the formed periodic wavefront’s visibility on medium length, coupling field’s strength, and tunneling parameter. Finally, we have observed the intensity distribution of the diffraction field at Talbot half-distance.

The Multi-Level Model (=MLM) was suggested by A. Levichev as a description of quarks and gluons. The review recalls MLM-terminology while MLM-findings (for quarks and leptons) are compared to the theoretical and experimental data as accepted by the Standard Model (=SM). MLM is based on Segal’s compact space-time U(2) and on the sequence of embeddings: U(2) into U(3), U(2) into U(4), etc. These groups were called the levels (of matter): U(2) - the 0th (that is, our mundane world), U(3) - the 1st, U(4) - the 2nd, etc. Such a convention matches the SM-quarks' generations list. Each SM-quark is viewed either as a sunken proton, or as a captured proton. The MLM-proton is elementary and indestructible (hence no need for confinement). For MLM-quarks, in terms of the notion of a ruling group, flavor and color are defined mathematically. The number of colors (and of flavors) is level-dependent. For levels U(3) through U(6) the correspondence with the SM-quarks is established. Three new quarks and two new leptons are predicted. The SM-puzzle of quark and lepton generations is solved. Using the Han-Nambu scheme, the notion of the quark’s electric charge is expressed in terms of color charges. The original part of the review suggests studying the proton’s properties (like mass, shape and inner pressure) on the ba-sis of its wave function.

Space-time evolution is briefly explained by using the 3-dimensional quantized space model (TQSM) based on the 4-dimensional (4-D) Euclidean space. The energy (E=cDtDV), charges (|q|= cDt) and absolute time (ct) are newly defined based on the 4-D Euclidean space. The big bang is understood by the space-time evolution of the 4-D Euclidean space but not by the sudden 4-D Minkowski space-time creation. The big bang process created the matter universe with the positive energy and the partner anti-matter universe with the negative energy from the CPT symmetry. Our universe is the matter universe with the negative charges of electric charge (EC), lepton charge (LC) and color charge (CC). This first universe is made of three dark matter -, lepton -, and quark - primary black holes with the huge negative charges which cause the Coulomb repulsive forces much bigger than the gravitational forces. The huge Coulomb forces induce the inflation of the primary black holes, that decay to the super-massive black holes. The dark matter super-massive black holes surrounded by the normal matters and dark matters make the galaxies and galaxy clusters. The spiral arms of galaxies are closely related to the decay of the 3-D charged normal matter black holes to the 1-D charged normal matter black holes. The elementary leptons and quarks are created by the decay of the normal matter charged black holes, that is caused by the Coulomb forces much stronger than the gravitational forces. The Coulomb forces are very weak with the very small Coulomb constants (k₁(EC) = k_dd(EC) ) for the dark matters and very strong with the very big Coulomb constants (k₂(EC) = k_nn(EC)) for the normal matters because of the non-communication of the photons between the dark matters and normal matters. The photons are charge dependent and mass independent. But the dark matters and normal matters have the similar and very weak gravitational forces because of the communication of the gravitons between the dark matters and normal matters. The gravitons are charge independent and mass dependent. Note that the three kinds of charges (EC, LC and CC) and one kind of mass (m) exist in our matter universe. The dark matters, leptons and quarks have the charge configurations of (EC), (EC,LC) and (EC,LC,CC), respectively. Partial masses of elementary fermions are calculated, and the proton spin crisis is explained. The charged black holes are not the singularities.

Abstract: Elimination of superoxide radical anion (O2•−) by tocopherols (TOH), and related compounds was investigated on the basis of cyclic voltammetry and in situ electrolytic electron spin resonance spectral measurements in N,N-dimethylformamide (DMF) with the aid of density functional theory (DFT) calculations. Quasi-reversible O2/O2•− redox was modified by the presence of TOHs, suggesting that the electrogenerated O2•− was eliminated by α-, β-, γ-TOH through proton-coupled electron transfer (PCET), but not by δ-TOH. The structure–activity correlation of α-, β-, γ-, and δ-TOH characterized by methyl group on the 6-chromanol ring was experimentally confirmed, where the methyl group promotes the PCET mechanism. Furthermore, comparative analyses using some related chemical analogues suggested that methoxyl group of the 6-chromanol ring is required for a successful electron transfer (ET) to O2•− through the PCET. The electrochemical and DFT results in dehydrated DMF suggested that the PCET mechanism involves preceding proton transfer (PT) forming hydroperoxyl radical followed by a concerted PCET (ET–PT). The O2•− elimination by TOH proceeds efficiently along the net PCET mechanism involving one ET and two PTs.

The proton conductivity, phase composition and mechanical properties of (1-x)CsH2PO4–x fluoropolymer electrolytes (x-mass fraction, x=0-0.3) have been investigated firstly and discussed. UPTFE and PVDF-based polymers (F2M, F42, SKF26) with the high mechanical properties and thermal stability have been chosen as a fluoropolymer additive. According the XRD data, a monoclinic CsH2PO4 (P21/m) phase is retained in all compositions of the polymer electrolytes studied. The conductivity of (1-x)CsH2PO4-x fluoropolymer in the high-temperature phase decreases by approximately one order of magnitude compared with the pure CsH2PO4 for x~0.15-0.20. The size and shape of CsH2PO4 particles and their distribution have been shown to affect significantly the proton conductivity and mechanical properties of the membranes. The thin-film composite systems were produced by various methods of the obtaining salt particles, their mixing and applying to a polymer matrix. The uniform distribution of particles in the polymer systems with the size of ~300 nm was achieved by a pretreatment of the suspension in a bead mill. CsH2PO4-based mechanically strong membranes with the thickness ~50–100 μm were obtained for the soluble fluoropolymers (F2M, F42, SKF26). With an increase in the mass fraction of the polymer the ability of the membranes to resist the plastic deformation and the mechanical strength increases and comparable to the best low temperature membranes. The proton-conducting membranes (1-x)CsH2PO4 – x fluoropolymer with the optimal combination of the conductivity, mechanical and hydrophobic properties are promising for use in solid acid fuel cells.

Abstract: Scavenging of electrogenerated superoxide radical anion (O2•−) by pyrogallol (PyH3) was investigated on the basis of cyclic voltammetry and in situ electrolytic electron spin resonance spectrum in N,N-dimethylformamide with the aid of density functional theory (DFT) calculations. Quasi-reversible dioxygen/O2•− redox coupe was modified by the presence of PyH3, suggesting that O2•− was scavenged by PyH3 through proton-coupled electron transfer (PCET) involving two proton transfer and one electron transfer. The DFT calculation suggested that the formation of hydrogen bond (HB) complex and the subsequent concerted-two-proton coupled electron transfer (2PCET) characterized by catechol moiety in PyH3 is plausible mechanism which embodies the superior kinetics of the O2•− scavenging by PyH3 as shown in the electrochemical results. Furthermore, it was clarified that three hydroxyl groups of PyH3 promote the formation of prereactive HB complex, in comparative analyses using related compounds, resulting the promotion of the O2•− scavenging.

The cross-kingdom stress hormone abscisic acid (ABA) and its mammalian receptors LANCL1 and LANCL2 regulate cardiomyocyte response to hypoxia by activating NO generation. Over-expression of LANCL1/2 increases transcription, phosphorylation and activity of eNOS and im-proves cell vitality after hypoxia/reoxygenation via the AMPK/PGC-1α axis. The aim of this study was to investigate whether the ABA/LANCL system also affects mitochondrial oxidative metab-olism and structural proteins. The effect of ABA and of the silencing or overexpression of LANCL1 and LANCL2 were investigated in H9c2 rat cardiomyoblasts on mitochondrial function, cell cycle and expression of cytoskeletal, contractile and ion channel proteins. Overexpression or silencing of LANCL1/2 significantly increased, or conversely decreased, mitochondrial number, oxphos complex I, proton gradient, glucose and palmitate-dependent respiration, transcription of uncoupling proteins, expression of proteins involved in cytoskeletal, contractile and electrical functions. These effects, and LANCL1/2-dependent NO generation, are mediated by the tran-scription factor ERRα, upstream of the AMPK/PGC1-α axis and transcriptionally controlled by the LANCL1/2-ABA system. The ABA-LANCL1/2 hormone-receptors system controls fundamental aspects of cardiomyocyte physiology via an ERRα/AMPK/PGC-1α signaling axis and ABA-mediated targeting of this axis could improve cardiac function and resilience to hypoxic and dysmetabolic conditions.

Object-level Simultaneous Localization and Mapping (SLAM) has gained popularity in recent years since it can provide a means for intelligent robot-to-environment interactions. However, most of these methods assume that the distribution of the errors is gaussian. This assumption is not valid under many circumstances. Further, these methods use a delayed initialization of the objects in the map. During this delayed period, the solution relies on the motion model provided by an Inertial Measurement Unit (IMU). Unfortunately, the errors tend to accumulate quickly due to the dead-reckoning nature of these motion models. Finally, the current solutions depend on a set of salient features on the object’s surface and not the object’s shape. This research proposes an accurate object-level solution to the SLAM problem with a 4.1 to 13.1 cm error in the position (0.005 to 0.021 of the total path). The developed solution is based on Rao-blackwellized Particle Filtering (RBPF) that does not assume any predefined error distribution for the parameters. Further, the solution relies on the shape and thus can be used for objects that lack texture on their surface. Finally, the developed tightly coupled IMU/camera solution is based on an undelayed initialization of the objects in the map.

Comparisons of power flows and efficiencies in two structurally quite similar cylindrical series-parallel planetary gear systems (PGSs) were performed in three separate parts of this paper. Each of these single degree of freedom (DoF) systems consists of three different 2KH subsystems connected in series-parallel. The main goal was to prove that apart from complex, structurally and dynamically coupled PGSs, there are also complex and only structurally coupled PGSs, in which the phenomenon of power flow circulation inside closed loops does not occur. Such a half-coupled type of PGS is herein called pseudo-coupled. Therefore, Part I discusses in detail the geometry, kinematics and statics of coupled PGSs in order to determine power flow paths. A comparison of the directions of power flow in both types of PGSs can be made in Part II after determining the power flow paths in the second planetary gear in a similar way. The directions of power flow in both types of PGSs were determined in a relatively simple way, thanks to the distinction between active and passive torques and thus active and passive shafts of individual subsystems. The efficiency comparison made in Part III will show whether power circulation has an influence on the efficiency value, at least in these two types of PGSs.

A simple mathematical interaction function, with the limit value w = e2π/e, derived as a basis for modelling emergent properties of nanoparticles, nanodrops and liquids, has been further developed. A correlation between physical systems of uniform particles and fundamental properties of natural numbers leads to a model, which acts as a bridge between properties of macroscopic systems and fundamental physical constants. The four fundamental coupling constants, and the masses of fundamental elementary particles, including the Higgs and Z bosons, are derived by using this interaction function. A proposal for the mass of the electron neutrino is given. Finally, the nuclear binding interaction is modeled with the interaction function. Only the experimental values of the Planck constant h and the speed of light c are needed for the model.

In this research the possibility of using pH change to measure proton conductivity of proton exchange membranes (PEM) or else known as polymer electrolyte membranes are tested with using an experimental setup prepared by using pH meters. PEMs are an important part of the fuel cells and proton conductivity of the PEMs are one of the most important properties of the PEMs. Also, proton conductivity is the one of the biggest limiting factors of fuel cells thus it is important to measure the proton conductivity of the PEMs while trying new polymers or new types of membranes. But as current measurement methods do not have a standard and can be separated into mainly two different measurement methods which are Electron Impedance Spectroscopy (EIS) and Ion Exchange Capacity (IEC). EIS gives clearer results, but it needs an impedance analyzer machine, platinum electrodes and setup so this cannot be possible for every researcher due to its economical aspect. For IEC it is basically a titration method to see acid groups in the polymer or polymer matrix which are directly responsible for proton conductivity so this can show an indirect measurement of proton conductivity. But as for this one drawback are firstly this one is an indirect measurement and secondly needs overnight bath in solution can take long times. So, the possibility of using pH can be easier and both from time and economical aspect if it can be proven the give a direct relationship between pH change and proton conductivity.

The knowledge of COVID-19 impact on the human body has increased rapidly. Although many people recover from COVID-19, some continue to experience persistent symptoms that have been identified as Long COVID. This condition can have a severe impact on quality of life, and it remains a significant concern for medical professionals and researchers. One of the key components of the SARS-CoV-2 virus that enables it to enter human cells is the spike (S) protein. Recent studies have revealed a complex network of interactions between G proteins, spike (S) protein, and the Renin-Angiotensin System (RAS) may be responsible, at least in part, for long COVID. SARS-CoV-2 can also affect the brain, leading to neurological symptoms such as confusion, memory loss, and fatigue. Increasing evidence suggests that COVID-19 is not just a respiratory illness since it is likely that the virus could influence signal transduction pathways such as G-protein-coupled receptor (GPCR), among others, in the brain, either directly or indirectly, affecting neural functions. These interactions with the spike (S) protein and RAS, alongside the brain, are complex and require deep research to understand their implications for Long COVID-19 manifestation fully. While recent research has shed light on the complex interactions between G proteins, spike (S) protein, the brain, and the angiotensin system, this article explores these interconnected pathways and their implications for long COVID-19 manifestations. The present review summarises current research on different molecular mechanisms in Long COVID pathophysiology and may help identify possible targets or new strategies for the diagnosis and treatment.

The purpose of this study is to identify the steps involved in fabricating silica/chitosan composite membranes and their suitability in fuel cell application. It also intends to identify the physical characteristics of chitosan composite membranes, including their degree of water absorption, proton conductivity, methanol permeability, and functional groups. In this investigation, composite membranes were fabricated using the solution casting method with chitosan content of 5 g and silica variations dosage of 2% and 4% while stirring at a constant speed for 2h. According to the findings, the analysis of composite membranes produced chitosan membranes that were successfully modified with silica. The optimum membrane was found to be 4% s-SiO2 from the Sol-gel method with composite membrane's optimal condition of 0.234 cm/s proton conductivity, water uptake of 56.21%, and reduced methanol permeability of 0.99 × 10 -7 cm2/s in the first 30 minutes and 3.31 × 10-7 in the last 150 minutes. Maintaining lower water uptake capacity at higher silica content is still a challenge that needs to be addressed. However, the fabricated membranes showed exceptional results in terms of proton conductivity and methanol permeability.

The blended perfluorinated sulfonic acid ionomers are prepared to have equivalent weight (EW) ~1000, 980, and 830. The catalyst layers (CLs) using blended PFSA ionomers with different side chain lengths and EWs are investigated, compared to the CLs utilizing single ionomers. The IEC results indicate that the blended ionomers have the targeted EWs. As a result, it is found that the blended ionomers exhibit higher ion conductivity than the single ionomers at all temperatures due to higher water uptake of the blended ionomers. Even though they have a similar EW, it implies that the blended ionomers have bulk structure to form competent free volume. The blended ionomers with short side chain (SSC) and low EW can help reduce the activation energy due to the enhanced hydrophobic and hydrophilic segregation. In addition, it is observed that the catalyst layers using the blended ionomer form more porous microstructure to help reduce the resistance of oxygen transport and attributes to lower mass transfer loss. This effect is significantly revealed in the fuel cell operation at not the lower temperature (70 °C) and full humidification (100%) but the elevated temperature (80 °C) and lower relative humidity (50 and 75%). The blended ionomer-based catalyst layers with higher water uptake and porous CL structure result in higher fuel cell performance and better mass transport than the single ionomer-based catalyst layers.

Bis-benzimidazole derivative (BBM) molecule, consisting of two 2-(2’-Hydroxyphenyl) benzim-idazole (HBI) halves, has been synthesized and successfully utilized as a ratiometric fluorescence sensor for the sensitive detection of Cu2+ based on enol-keto excited state intramolecular proton transfer (ESIPT). In this study, we strategically implement femtosecond stimulated Raman spec-troscopy and several time-resolved electronic spectroscopies, aided by quantum chemical calcula-tions to investigate the detailed primary photodynamics of BBM molecule. The results demonstrate that the ESIPT from BBM-enol* to BBM-keto* was observed in only one of HBI halves with a time constant of 300 fs, after that, the rotation of the dihedral angle between two HBI halves generate a planarized BBM-keto* isomer in 3 ps, leading to dynamics red shift of BBM-keto* emission.

Objectives: We aimed to clarify the endoscopic and clinicopathological features of raspberry-shaped gastric lesions (RSGLs) and to establish an endoscopic diagnostic algorithm for RSGLs. Methods: We collected RSGLs from an endoscopic database at our hospital between May 2009 and August 2021. All RSGLs were histopathologically classified and compared based on their endoscopic and clinicopathological characteristics. Results: Sixty-five RSGLs in 54 patients were classified into five histopathological types: gastric adenocarcinoma of foveolar type (GA-FV, n = 43), gastric adenocarcinoma of fundic-gland type (GA-FG, n = 2), gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM, n = 4), hyperplastic polyp (HP, n = 12), and proton pump inhibitor-related lesion (PPI-L, n = 4). All RSGLs exhibited polygonal or curved marginal crypt epithelium (MCE). GA-FV lesions had homogenously reddish (95%) and irregular microvascular (MV) pattern (91%). GA-FG lesions were heterogeneously reddish with a submucosal tumor shape (100%) and had a regular MV pattern (50%). GA-FGM lesions were homogenously reddish (75%) and occasionally had a submucosal tumor shape (50%) with an irregular MV pattern (75%). HP and PPI-L were homogeneously reddish (93%), with linear or dotted MCE (81%) and a regular MV pattern (100%). Conclusion: Our diagnostic algorithm for RSGLs constructed using endoscopic features might be useful for the endoscopic differential diagnosis of RSGLs.

We used an ultrasensitive, broadband optomechanical ultrasound sensor to study the acoustic signals produced by pressurized nitrogen escaping from a variety of small syringes. Harmonically related jet tones extending into the MHz region were observed for a certain range of flow (i.e., Reynolds number), in qualitative agreement with historical studies on gas jets emitted from pipes/orifices of much larger dimensions. For higher turbulent flow rates, we observed broadband ultrasonic emission in the ~ 0 – 5 MHz range, likely limited on the upper end by attenuation in air. These observations are made possible by the broadband, ultrasensitive response (for air-coupled ultrasound) of our optomechanical devices. Aside from their theoretical interest, our results could have practical implications for the non-contact monitoring and detection of early-stage leaks in pressured fluid systems.

Consciousness is a special type of interaction between subjects exchanging by lingua quanta (phonemes). A set of lingua quanta composes a thesaurus placed on the edge of chaos. Its library is a memory, modification of which is due to tuning of memristive neural elements scattered in the brain volume. The memristive neural model takes into consideration two types of neurons - excitatory and inhibitory and the current leakage, all at the body temperature, T = 309 K. At such temperatures only heavy ions like hydrogen ions - protons can pass robustly through the water medium of the brain. The robust ion transport is proton water wires supported by the Grotthuss mechanism. Final aims of the ions are the gap junctions (electric synapses) linking nearest neurons. Following these observations, a model of excitable nervous tissue is constructed. Namely, a difference mapping on the basis of sigmoid curves can reproduce chaotic modes of neural activity proved by positive values of the Lyapunov exponent. The edge of chaos is placed near the bifurcation boundary dividing the chaos and the periodic convulsive activity typical at the epileptic discharges. In this region the self-sustained spiral waves occur. An intermittent activity of the competing excitatory and inhibitory neurons is observed on the edge of chaos. The intermittent electrical activity of neural tissues is demonstrated by records both from different literature issues and records made by the author together with DR. A. Dudkin on slices of CA1 field of the hippocampus.

Depression is one of the most severe sequelae of COVID-19, with major depressive disorder often characterized by disruption in white matter (WM) connectivity , stemming from changes in brain myelination. This study aimed to quantitatively assess brain myelination in clinically diagnosed post-COVID depression using recently proposed MRI method, macromolecular proton fraction (MPF) mapping. The study involved 63 recovered COVID-19 patients (52 mild, 11 moderate, 2 severe) at 13.5±10.0 months post-recovery, with matched controls without prior COVID-19 history (n=19). A post-COVID depression group (PCD, n=25) was identified based on psychiatric diagnosis, while a comparison group (noPCD, n=38) included participants with neurological COVID-19 complications, excluding clinical depression. Fast MPF mapping revealed extensive demyelination in PCD patients, particularly in juxtacortical WM (predominantly occipital lobe and medial surface), WM tracts (inferior fronto-occipital fasciculus (IFOF), posterior thalamic radiation, external capsule, sagittal stratum, tapetum), and grey matter (GM) structures (hippocampus, putamen, globus pallidus, and amygdala). The noPCD group also displayed notable demyelination but with less magnitude and propagation. Multiple regression analysis highlighted IFOF demyelination as the primary predictor of PCD presence and severity according to Hamilton scores. The number of post-COVID symptoms was a significant predictor of PCD presence while the number acute of symptoms was a significant predictor of PCD severity. This study, for the first time, reveals extensive demyelination in numerous WM and GM structures in PCD, outlining IFOF demyelination as a key biomarker.

The ability to control the flow of quantum information deterministically is useful for scaling up quantum computation. In this paper, we demonstrate a controllable quantum switchboard which directs the teleportation protocol to one of two targets, fully dependent on the sender’s choice. The quantum switchboard additionally acts as a optimal quantum cloning machine. We also provide a physical implementation of the proposal using a coupled-cavity array. The proposed switchboard can be utilized for the efficient routing of quantum information in a large quantum network.

Recent advancements in the study of the protein complex photosystem II have clarified the sequence of events leading to the formation of oxygen during the S3->S4->S0 tran-sition, wherein the inorganic Mn4Ca(µ-O)6(OHx)4 cluster finishes photo-catalyzing the water splitting reaction (Greife et al, Nature 2023, 617, 623-628; Bhowmick et al, Nature 2023, 617, 629-636) . During this final step a tyrosine radical (TyrZ), stable for a couple of milliseconds, oxidizes a cluster bound oxygen while the hydrogen bonding patterns of nearby waters shift a proton away. A treatment of this redox reaction within the context of accepted transition state theories predicts rate constants that are significantly higher than experimentally recovered values (10^12s^-1 versus 10^3s^-1). In an effort to understand this disparity, temperature dependent experiments have revealed large entropic con-tributions to the rates with only a moderate energy of activation. We suggest that the entropic source may be related to the observed proton rearrangements, and further possible near isoenergetic variations in the nearby extended h-bonding network de-laying the realization of an ‘ideal’ transition state. In the following we explore this re-lation in the context of Eyring’s transition state theory and Marcus’ electron transfer theory, and evaluate their compatibility with the experimental evidence.