We propose a theoretical method for the deterministic shaping of quantum light via photon number state selective interactions. Nonclassical states of light are an essential resource for high precision optical techniques that rely on photon correlations and noise reshaping. Notable techniques include quantum enhanced interferometry, ghost imaging, and generating fault tolerant codes for continuous variable optical quantum computing. We show that a class of nonlinear-optical resonators can transform many-photon wavefunctions to produce structured states of light with nonclassical noise statistics. The devices, based on parametric down conversion, utilize the Kerr effect to tune photon number dependent frequency matching, inducing photon number selective interactions. With a high amplitude coherent pump, the number selective interaction shapes the noise of a two-mode squeezed cavity state with minimal dephasing, illustrated with simulations. We specify the requisite material properties to build the device and highlight the remaining material degrees of freedom which offer flexible material design.

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.

Trace amines are a separate, independent group of biogenic amines, close in structure to classical monoamine neurotransmitters such as dopamine, serotonin and norepinephrine. G protein-coupled Trace Amine-Associated Receptors (TAAR) are mostly investigated for their involvement in the pathogenesis of neuropsychiatric disorders, but expression of TAAR family receptors is observed also in various populations of cells of the immune system. The review is focused on the basic information on the interaction of trace amines and their receptors with cells of the general immune system of humans and other mammals, as well as on data on TAARs role in the function of individual populations of myeloid and lymphoid cells. With further research on the regulatory role of the trace amine system in the pathogenesis of the immune response and determination of the biological mechanisms for their action it would be possible to develop new methods for treating diseases related to immune system dysfunctions.

A comprehensive theory is developed for the chiral optical response of two configurations of the N-oscillator Born-Kuhn model (NOBK): the helically stacked and the corner stacked models. In the helical NOBK model, there is always a chiral response regardless of the value of N, whereas in the corner NOBK, only configurations with even N demonstrate a chiral response. Generally, the magnitudes of optical rotatory dispersion (ORD) and circular dichroism (CD) increase with N when the parameters of each oscillator are fixed. In cases of weak coupling, the spectral shapes of ORD and CD remain invariant, while strong coupling significantly alters the spectral shapes. For large damping, the spectral amplitude becomes smaller, and the spectral features become broader. In the presence of small damping, strong coupling introduces degeneracy in the coupled oscillator system, leading to multiple spectral features in both ORD and CD across the entire spectral region. This simple model not only can help in the design of tunable chiral metamaterials but also enhance our understanding of chiro-optical responses in structures with different configurations.

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.

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.

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).

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).

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.

It is known that complexes based on natural polysaccharides are able to eliminate bone defects. Prolonged hyperglycemia means low bone regeneration and a chronic inflammatory response. The purpose of the study was to increase the efficiency of early bone formation in a cavity of critical size in diabetes mellitus in the experiment. The polyelectrolyte complex contains high molecular ascorbate of chitosan, chondroitin sulfate, sodium hyaluronate, heparin, adgelon serum growth factor, sodium alginate and amorphous nanohydroxyapatite (CH-SA-HA). Studies were conducted on 5 groups of white female Wistar rats: group 1 - regeneration of a bone defect in healthy animals under a blood clot; group 2 - regeneration of a bone defect under a blood clot in animals with diabetes mellitus; group 3 - bone regeneration in animals with diabetes mellitus after filling the bone cavity with a collagen sponge; group 4 - filling of a bone defect with a CH-SA-HA construct in healthy animals; Group 5 - filling of a bone defect CH-SA-HA in animals with diabetes mellitus. Implantation of the CH-SA-HA construct into bone cavities in type I diabetic rats can accelerate the rate of bone tissue repair. The inclusion of modifying polysaccharides and apatite agents in the construction may be a prospect for further improvement of the properties of implants.

Silicon-based photonic integrated circuit (PIC) is a research focus in producing high-density photonics. One of the potential applications of silicon PIC is the sensing and measurement system. In this work, we use the one-dimensional photonic crystal (1D-PhC) cavity design which and utilize it at the PIC level design. The 1D PhC design used as the compact model has the same characteristics as experimentally demonstrated in previous works. The compact model is made from the S-parameter extraction of the 1D-PhC device which is done by using Lumerical FDTD software. The PIC design integrates the 1D-PhC device as a sensing component with a PN-phase shifter (PN-PS) to function as a refractive index (RI) sensor calibration or tuning circuit. A custom design of PN-PS device is used by simulating and extracting the bias voltage-effective index (bias-Neff) data by using Lumerical DEVICE and MODE into the circuit simulator. The circuit-level simulation is done by using Lumerical Interconnect software. Finally, we show the GDSII layout design of the 1D-PhC based photonic sensor calibration circuit with an analysis of generic silicon PIC design rules. The designed PIC is applicable for the bio-sensing applications and photonic SOC component. This work also shows the promise of PIC design approach for further PIC development.

Protons are gaining increasing attention as neurotransmitters due to their extraordinary abilities to rapidly transfer electrical charge, mobilize cellular calcium and modulate ion channels. How all this is possible is currently the subject of in-depth studies and discussions concerning not only neurophysiology, but also biological materials for artificial intelligence. In this short review, some biochemical mechanisms are described by which protons, in combination with calcium, can initiate firing in sensory neurons and transmit impulse across synapses. Furthermore, mechanisms are put forward concerning how three neurotransmitters, glutamate, gamma-aminobutyric acid and acetylcholine, are able to generate protons. The results of the numerous experimental works taken into consideration indicate that protons can play a fundamental role both in the generation and in the transmission of the nerve impulse.

In this study novel recommendations are presented and substantiated for selecting the number of modes and optical thicknesses of flat lattice slabs that make up the microreliefs, which minimize the computational complexity of the rigorous coupled-wave analysis calculation of the diffraction efficiency (DE) of a sawtooth two-layer two-relief microstructure, while maintaining the specified reliability of the calculation results. The computational complexity can be controlled by allowing one or another level of oscillation of the DE curves depend on the angle of incidence of the radiation incident on the microstructure. In particular, the complexity of the multi-thousand DE calculations in the optimization process can be reduced by using the proposed methodology as well as increased computational complexity to certify the accuracy of the solution obtained as a result of implemented optimization.

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.

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.

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.

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.

Ultra-low radioactive titanium alloy is a promising material for the manufacture of low-background detectors, which are being developed for experiments in astroparticle physics and neutrino astrophysics. Structural titanium is manufactured on an industrial scale from titanium-sponge. The ultra-low-background titanium-sponge can be produced on an industrial scale with a contamination level of less than 1 mBq/kg of uranium and thorium isotopes. The pathways of contaminants during the industrial production of structural titanium have been analyzed. The measurements have been carried out using two methods: inductively coupled plasma spectroscopy (ICP-MS) and gamma-spectroscopy using high-purity germanium detectors (HPGe). It has been shown that the level of contamination with radioactive impurities does not increase during remelting of titanium-sponge and mechanical processing. We examined titanium-alloys samples obtained at different stages of titanium production, namely, an electrode compaction, a vacuum arc remelting with a consumable electrode (VAR), and a cold rolling of titanium-sheets. It has been found out that all studied samples will be a source of uranium and thorium contamination of the final titanium-alloys. It has been established that the only product allowed obtaining ultra-low-background titanium was the VT1-00 which is manufactured without master alloys addition..

Resource conflicts represent a significant global challenge in regions abundant with natural re-sources. Modelling the myriad factors driving natural resource-based conflicts (NRBCs), spanning environmental, health, socio-economic, and political dimensions, is a complex endeavor exacer-bated by data scarcity. Furthermore, existing quantitative studies often focus solely on large-scale conflicts. This article introduces a novel algorithm, the Spatially Explicit Fuzzy Logic-Adapted Model for Conflict Management (SEFLAME-CM), which integrates the local knowledge of stakeholders into spatial decision-making technologies to support sustainable peace efforts. The results are validated with spatial multi-criteria evaluation (SMCE) using spatial statistics. The Moran’s I scatter plots for the overall conflicts reveal significant values of 0.99 and 0.98 for both the SEFLAME-CM and SMCE, respectively, with significant spatial autocorrelation. While there re-mains room for improvement in enhancing the model's quality, SEFLAME-CM demonstrates its capacity to transparently model complex real-world problems. The findings underscore the im-perative for a holistic approach to addressing environmental degradation, socio-economic, and political drivers of resource conflicts at the community level. Our paper demonstrates the signif-icance of spatial information technologies and knowledge exchange between experts and local stakeholders in effectively managing resource conflicts. These insights should inform national policies and international interventions, ensuring that the complex underlying issues are ad-dressed while prioritizing the knowledge and needs of affected communities.

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

Background: biophysical stimulation therapy, and in particular Pulsed Electromagnetic Fields (PEMFs) and capacitively coupled electric fields (CCEFs) has significantly increased in the last twenty years. For this, it is necessary to have clear information regarding the efficacy, the therapeutic indication and the expected objectives. Methods: we conducted a narrative review taking into consideration different types of studies with different areas of application. The objective was to take into consideration and analyze the different fields of use and the relevant information present in the literature. Results: There is unanimous opinion regarding the usefulness of applying biophysical therapy on the bone compartment both in terms of the tissue healing process and the symptoms associated with this situation. Differently, but no less importantly, in the joint compartment positive opinions were observed mainly on the inflammatory and catabolic process, however, at present,we did not report evidence regarding cartilaginous tissue regeneration. Conclusion: the effectiveness of PEMFs and CCEFs on the bone healing process in the Orthopedic and Traumatology fields is consolidated evidence in the literature. We have also found positive results on symptoms and patient compliance with rehabilitation therapies. Therefore, notable application can be envisaged in the fields of Prosthetic Surgery and Sports Medicine.

An efficient design method is proposed for a compact common-mode rejection (CMR) filter utilizing dumbbell-shaped defected ground (DS-DG) structures and gap-coupled stub (GCS) resonators. A CMR filter for differential lines helps to improve the signal integrity of high-speed digital signals on printed circuit boards. The proposed CMR filter design is based on the equivalent circuit models, while the previous designs depended heavily on the DS-DG structure optimization using the EM simulations. The proposed CMR filter effectively reject the common-mode components with minimally affecting the differential signals. To prove the simplified design approach, a 5th-order Chebyshev band-stop filter has been designed with three DS-DG structures and two GCS resonators. From the simulated and measured results, it is found that the proposed CMR filter provides ~90% fractional frequency bandwidth with more than 20 dB of common-mode rejection ratio and less than 0.6 dB of insertion loss of the differential signal.

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.

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.

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.

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.

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.

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.

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.

The differential-equation of second order for space-time oscillation in flat tangential-spacetime of Minkowski-type can be written as an energy-equation. For this energy-equation the analogon of damping energy in two coupled Minkoswki-spacetimes with ftl can be calculated and formulated over Lamberts W-function or via Euler-equation.

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.

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.

Bat feces were reported in ancient Chinese medicine books to have the effect of reducing heat and improving eyesight, but the mechanism of vision improvement still needs further research. To this end, we used 2,2-diphenyl-1-picrylhydrazyl (DPPH) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) to analyze the antioxidant capacity of and the types of vitamins in bat feces. We hoped to screen the pharmacological components of bat feces, and to explain the role that these components may play in the treatment of visual deterioration. Our results found that bat feces had a good antioxidant capacity and mainly contain vitamins B1 (thiamine), B2 (riboflavin), B3 (nicotinamide), B3 (nicotinic acid), and B5 (pantothenic acid). Although these vitamins may help maintain the health of the optic nerve and cornea, the vitamin content of bat feces is low, but the heavy metal content is high, as shown using inductively coupled plasma mass spectrometry (ICP-MS) analysis. Therefore, we suggest that the use of bat feces as traditional Chinese medicine to improve vision should be strictly restricted.

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.

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.

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].

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.

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.

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.

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

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.