Ion Loss Research Articles

Study of High-Energy Proton Irradiation Effects in Top-Gate Graphene Field-Effect Transistors

In this article, the effects of high-energy proton irradiation on top-gate graphene field-effect transistors (GFETs) were investigated by using 20 MeV protons. The basic electrical parameters of the top-gate GFETs were measured before and after proton irradiation with a fluence of 1 × 1011 p/cm2 and 5 × 1011 p/cm2, respectively. Decreased saturation current, increased Dirac sheet resistance, and negative drift in the Dirac voltage in response to proton irradiation were observed. According to the transfer characteristic curves, it was found that the carrier mobility was reduced after proton irradiation. The analysis suggests that proton irradiation generates a large net positive charge in the gate oxide layer, which induces a negative drift in the Dirac voltage. Introducing defects and increased impurities at the gate oxide/graphene interface after proton irradiation resulted in enhanced Coulomb scattering and reduced mobility of the carriers, which in turn affects the Dirac sheet resistance and saturation current. After annealing at room temperature, the electrical characteristics of the devices were partially restored. The results of the technical computer-aided design (TCAD) simulation indicate that the reduction in carrier mobility is the main reason for the degradation of the electrical performance of the device. Monte Carlo simulations were conducted to determine the ionization and nonionization energy losses induced by proton incidence in top-gate GFET devices. The simulation data show that the ionization energy loss is the primary cause of the degradation of the electrical performance.

Guiding-centre orbit-following simulations of charge exchange loss of NBI ions with the finite Larmor radius effect

Guiding-centre orbit-following simulations of the charge exchange (CX) loss of neutral beam injection (NBI) ions are presented. The finite Larmor radius (FLR) effect in the fast ion–neutral collision can be included in guiding-centre orbit-following simulations by using the gyroaverage method. It is proved that the neutralization probability of fast ions computed by using the gyroaverage method in the guiding-centre orbit simulation is roughly the same as that computed in the full-orbit simulation when the time step in the guiding-centre simulation is the order of the gyroperiod. The CX losses of NBI fast ions for two NBIs in the EAST tokamak have been simulated by the guiding-centre orbit-following code GYCAVA, and the FLR effect in the fast ion–neutral collision on CX losses has been numerically studied. The CX effect of the fast ion–neutral collision can significantly enhance NBI ion losses on EAST. The FLR effect in the fast ion–neutral collision can enhance the CX loss. Vertical asymmetry of localized heat loads induced by CX losses is found, which is related to the FLR effect of fast ions and the strong radial gradient of the neutral density near the plasma edge. Heat loads induced by CX losses are localized in the regions near the poloidal angle $\theta =-60^\circ$ , because the likelihood of exchanging charge is the largest at gyrophase $\xi ={\rm \pi}$ , and this leads to fast downwards moving neutrals. Fast ion loss fractions induced by CX increase with the neutral density increasing.

Evaluation of Red Cell Deformability in Sickle Cell Disease Patients, Sickle Cell Carriers, and Healthy Controls Using Lorrca-Derived Parameters

BACKGROUND Red blood cell (RBC) deformability plays a critical role in RBC elongation and viscosity, and when reduced, perfusion of peripheral tissues and oxygen delivery are impaired. Intracellular ATP maintains water and ion homeostasis in RBCs; reduced ATP leads to water and ion loss, dehydration and loss of RBC elasticity. RBC dehydration increases mean corpuscular hemoglobin concentration (MCHC) and also affects distribution of RBC width (RDW). Patients with sickle cell disease (SCD) have reduced RBC ATP, and markedly reduced RBC deformability when compared to healthy individuals. Here, we employed Laser-Optical Rotational Red Cell Analyzer (LORRCA, RR Mechatronics) to evaluate deformability in RBCs from patients with SCD (HbSS) compared to RBCs from sickle cell carriers (HbAS) and ethnic-matched healthy controls (HbAA). We further analyzed how these LORRCA-derived parameters correlate with ATP, MCHC, and RDW. METHODS We enrolled adult subjects (age ≥ 18 years) of African-descent, and not recently transfused (within 8 weeks) under protocol NCT03685721 approved by the NHLBI Institutional Review Board. Fresh whole blood in EDTA was processed on the same day of collection. Cells were counted and diluted in polyvinylpyrrolidone (PVP) solution before undergoing LORRCA assays including deformability, osmoscan, and oxygenscan (HbSS subjects). The deformability assay uses the elongation Index (EI) to measure the cells' ability to undergo deformation with increasing shear stress at 0.95, 3, and 30 Pascals (Pa). The osmoscan assay measures the deformability under continuous osmotic changes (0-600mOsm/kg) and has several parameters: O min (RBC fragility); El max (maximum deformability and membrane flexibility); O max (osmolality where EI max is achieved) and O hyper (intracellular viscosity and maximum deformability in the hypertonic region). The oxygenscan assay measures the oxygen pressure at the time when RBCs start to become rigid (point of sickling). Whole blood levels of ATP were measured using LC-MS/MS with LLOQ at 50.0 μg/mL and converted to intracellular concentrations by dividing by the hematocrit (as a fraction). Descriptive statistics and correlation (Spearman) of ATP, RDW, and MCHC with each LORRCA parameter were performed using R (v4.2.3) and Prism(v9). RESULTS We studied 156 subjects which comprised of 63 HbSS (33 males), 61 HbAS (23 males) and 32 HbAA (8 males) genotypes. The average age in years (range) in HbSS was 32 (18-58); in HbAS, 43 (18-70), and in HbAA, 38 (19-72). As shear stress and osmotic pressure increased, the mean EI and osmolality were significantly (p<0.001, unpaired two-sample t-test) lower in the HbSS cohort compared to HbAS and HbAA (Figure 1). There was no significant difference in the mean EI and osmolality between HbAA and HbAS with increasing shear stresses and osmotic pressures. As shear stress increased, the correlation of deformability with reduced ATP got significantly stronger in the HbSS cohort (r= -0.351 at 0.95 Pa to r=-0.401 at 30 Pa) but the trend was reversed for the HbAS and HbAA cohort (Table 1). Under increasing osmotic pressure, a significant correlation was found between reduced ATP and maximal deformability (EI Max) in HbSS (p=0.008) compared to HbAS (p=0.896) and HbAA (p=0.114). MCHC was significantly correlated with RBC hydration state (O Hyper) in all 3 genotypic groups (HbSS, HbAS and HbAA). Similarly, RDW correlated with maximal deformability (EI Max) under increasing osmotic pressure in all 3 cohorts. In the HbSS subjects, there was a significant positive correlation of ATP and RDW with point of sickling (oxygenscan); MCHC was negatively correlated but was not significant. CONCLUSION RBC deformability was reduced in HbSS patients compared to HbAS and HbAA under increasing shear stress and osmotic pressure. ATP levels showed significant correlation with RBC deformability as measured by LORRCA, particularly in patients with SCD, suggesting increasing ATP levels as an important therapeutic strategy in patients with SCD. In keeping with published data, our analyses showed that RBC volume and size as well as intracellular hemoglobin concentration can affect deformability.

Investigation of lithium-ion battery nonlinear degradation by experiments and model-based simulation

Understanding the lithium-ion battery (LIB) nonlinear degradation is essential for battery full-lifespan usage and management. In this study, LIBs are cycled under conditions of low-temperature and high-current charging respectively. By designing a multi-battery parallel aging experiment, the evolution process and changing regulation of lithium ions (Li-ions) loss are quantified. The amount of irreversible lithium loss caused by two side reactions, i.e., the side reaction of SEI film growth and irreversible lithium plating, within the full lifespan of LIBs is measured and analyzed, which reveals that irreversible lithium plating is the dominant reason causing the battery nonlinear degradation. With the quantitative results above, an electrochemical aging coupled model is established, which agrees well with the experimental nonlinear aging. Furthermore, a simulation of the battery secondary capacity diving is conducted, and the formation of the nonlinear aging mechanism is revealed. A porosity reduction theory is proposed, in which the capacity diving of the battery is caused by the exponential growth of irreversible lithium plating, while the exponential growth phenomenon is due to the positive feedback loop formed by the porosity reduction of the negative electrode and the irreversible lithium plating.

A Critical Analysis of Target Ionization and Projectile Electron Loss in Neutral– and Ion–Atom Collisions

Electron removal (target ionization and/or projectile electron loss) in neutral–atom collisions is theoretically studied for the impact of H0, He0 and He+ beams on noble gases (He, Ne and Ar). These reactions are investigated theoretically within the Continuum Distorted Wave-Eikonal Initial State model. New features have been included in the theoretical model: (i) a scaled projectile charge depending on its velocity and charge, (ii) a dynamic projectile-effective-charge depending on the momentum transfer, and (iii) a dynamic target-effective-charge depending on the kinematics of the emitted electron. The energy and angular spectra of emitted electrons from the target and from the projectile are calculated and compared with the available experimental data. Also, the influence of each one of the corrections on the resulting spectra will be studied.

Evaluating Ion Accumulation and Storage in Traveling Wave Based Structures for Lossless Ion Manipulations.

Structures for lossless ion manipulations (SLIM) technology has demonstrated high resolving power ion mobility separation and flexibility to integrate complex ion manipulations into a single experimental platform. To enable IMS separations, trapping/accumulating ions inside SLIM (or in-SLIM) prior to injection of a packet for separations provides ease of operation and reduces the need for dedicated ion traps external to SLIM. To fully characterize the ion accumulation process, we have evaluated the effect of TW amplitudes, ion collection times, and storage times on the "in-SLIM" accumulation process. The study utilized a SLIM module comprising 5 distinct tracks, each with a specific ion accumulation configuration. The effect of the TW conditions on the accumulation process was investigated for a 3-peptide mixture: kemptide, angiotensin II, and neurotensin at a TW speed of 106 m/s. The effect of ion accumulation time/collection time and storage time was investigated, in addition to TW amplitude. Overall, the signal of the analyte ions increased when the ion collection time increased from 49 to 163 ms but decreased when the ion collection time increased further to 652 ms due to the space charge effects. Ion losses were observed at high TW amplitudes (e.g., 15 Vp-p and 20 Vp-p). In addition, under space charge conditions (e.g., collection times of 163 and 652 ms), the signal of the analyte ions decreased with an increase in storage times for all TW amplitudes applied to the trapping region. For ion accumulation, the data indicate that gentler TW conditions must be utilized to minimize ion losses and fragments to benefit from the "in-SLIM" accumulation process. Wider SLIM tracks provided better performance than those with narrower tracks.

A hydrogen-vanadium rebalance cell based on ABPBI membrane operating at low hydrogen concentration to restore the capacity of VRFB

A hydrogen‑vanadium rebalance cell (HVRC) is developed to address the capacity degradation and hydrogen explosion risks in long-term operations of all‑vanadium liquid flow battery (VRFB). Different operating conditions was evaluated in this study to investigate the cell's performance focusing on low hydrogen concentrations (4 %). The HVRC achieved a stable rebalance process with a meager hydrogen stoichiometry ratio of 1.15 at 300 mA cm−2. The use of PFSA membranes was found to be problematic due to the contradictory issues of unstable battery operation without humidification and severe vanadium ion loss with humidification. Therefore, ABPBI membrane was used instead of PFSA membrane to reduce vanadium ion crossover and Pt catalyst corrosion. HVRC based on ABPBI membrane completed a 100 h stability test at 70 mA cm−2 with a stoichiometric ratio of hydrogen of 1.23. The vanadium ion crossover of ABPBI-HVRC was less than 1/6 that of PFSA-HVRC, and no significant platinum dissolution occurred during 100 h operation without humidification. The reliability of the ABPBI-HVRC in intermittent operation mode has also been verified. These results illustrate the HVRC offers a promising measure to eliminate safety issues and restore capacity in VRFB systems. Additionally, incorporating the ABPBI membrane in the HVRC holds greater promise for enhancing its stability.

LightGBM-Based Framework for Lithium-Ion Battery Remaining Useful Life Prediction Under Driving Conditions

The remaining useful life (RUL) degradation under driving conditions is complex. The features from incremental capacity-differential voltage (IC-DV) curves and electrochemical impedance spectroscopy (EIS) can be implemented to identify the battery degradation modes and predict RUL. This paper proposes a light gradient boosting machine (LightGBM) based framework with electro- chemical theory to achieve RUL prediction under driving conditions. The degradation modes are identified as loss of conductivity, loss of active material and loss of lithium ion, and the EIS is refined as ohmic resistance, charge transfer resistance, solid electrolyte interphase film resistance, and Warburg resistance. The LightGBM model is improved by the adaptive robust loss function to achieve multi-loss functions adaptive adjustment for different cases and limit the effect of measurement noise on gradients. Based on the perspective of multitask learning, the Pearson correlation is analyzed to design the sharing principle, which ensures full use of features and reduce experimental costs. The proposed framework is validated by the database under four vibration cases (static, X-axis, Y-axis, and Z-axis). Experimental results demonstrate that the proposed framework is capable of providing accurate and steady RUL prediction under driving conditions even with measurement noise. The proposed framework could guide periodic maintenance and stable operation to avoid risks.

Analysis of Toroidal Alfven Eigenmode-Induced Fast Ion Losses in Globus-M2 Spherical Tokamak

Analysis of Toroidal Alfven Eigenmode-Induced Fast Ion Losses in Globus-M2 Spherical Tokamak

Impact of Simulated Acid Rain on Soil Base Cations Dissolution between Eucalyptus Pure Plantations and Eucalyptus–Castanopsis fissa Mixed Plantations

The soils of Eucalyptus pure plantations and Eucalyptus–Castanopsis fissa mixed plantations were studied using soil column leaching experiments with acid solutions to mimic the effects of acid rain on the soils. This helped researchers learn more about how soil base ions react to acid deposition and their ability to protect the soil from excessive acidity under pure and mixed-species plantations. The results showed that acid rain leaching increased the leaching loss, desorption, and desorption rate of soil base ions while decreasing the soil pH value, adsorption, and adsorption rate of soil base ions. The soil pH value and the leaching loss ranges of K+, Na+, and Mg2+ were all greater in the pure plantations than in the mixed plantations, while the leaching range of Ca2+ was greater in the mixed plantation than in the pure plantations. In the two types of plantations, the adsorption rates of Ca2+ and Na+ in the mixed plantations were higher than in the pure plantations, while K+ and Mg2+ showed higher adsorption rates in the pure plantations than in the mixed plantations. Therefore, soil pH and base ions were greatly affected by the pH value of acid rain. Compared with the pure plantations, the establishment of Eucalyptus–Castanopsis fissa mixed plantations can slow soil acidification and leaching of K+, Na+, and Mg2+ and contribute to the adsorption of Ca2+ and Na+, which is beneficial for the soil nutrient fixation of Eucalyptus plantations. The mixed plantations were found to increase the exchange reaction between H+ and base ions, thereby improving the acid buffer performance of the soil. This, in turn, helped to mitigate the decline in soil fertility. Therefore, establishment of Eucalyptus–Castanopsis fissa mixed-species plantations can slow down the impact of acid rain on soil acidification in artificial plantation land to a certain extent and play an important role in optimizing the plantation structure of Eucalyptus stands and maintaining their productivity.

Fast and reliable characterization of egg triacylglycerol profiles using atmospheric solids analysis probe tandem mass spectrometry (ASAP-MS/MS) combined with chemometric tools

In this study, the potential of atmospheric solid analysis probe tandem mass spectrometry (ASAP-MS/MS) was assessed as a green and rapid method combined with gas chromatography with flame ionization detection (GC-FID) and chemometrics to determine the triacylglycerol (TAG) profile of eggs from various housing systems, including indoor, cage-free, free-range, organic, and enriched systems. The most abundant ions were identified using the product ion and neutral loss scan. The fatty acid composition, mainly unsaturated, palmitic, and stearic acids of eggs was influenced by the housing systems. The optimal conditions of ASAP-MS for cone voltage, desolvation gas temperature, and desolvation gas flow were determined to be 40 V, 600 °C, and 1100 L h−1, respectively. The main TAGs (50:2, 50:1, 52:4, 52:3, 52:2, 52:1, 54:4, 54:3, 54:2, 54:1) were observed in the mass range m/z 830–890. Notable differences were observed for TAGs 54:1 and 52:4, which were found in significantly higher levels on WE and CE. The proposed methodology enables rapid and efficient TAG profiling of egg yolks, providing a solid foundation for future research in this field.

Robust stellarator optimization via flat mirror magnetic fields

Stellarator magnetic configurations need to be optimized in order to meet all the required properties of a fusion reactor. In this work, it is shown that a flat-mirror quasi-isodynamic (QI) configuration (i.e. a QI configuration with sufficiently small radial variation of the mirror term) can achieve small radial transport of energy and good confinement of bulk and fast ions even if it is not very close to perfect omnigeneity, and for a wide range of plasma scenarios, including low β and small radial electric field. This opens the door to constructing better stellarator reactors. On the one hand, they would be easier to design, as they would be robust against error fields. On the other hand, they would be easier to operate since, both during startup and steady-state operation, they would require less auxiliary power, and the heat loads on plasma-facing components caused by fast ion losses would be reduced to acceptable levels.

Long-term study using of short stems with ceramic-on-metal bearing in hip replacement

Abstract Background Osteoarthritis is a disease that affects about 300 million people in the world. Surgery is indicated in cases where all other treatments have failed, in economic terms expenses are between 1 and 2.5% of the GDP of the most industrialized countries in the world. Hip prosthetic replacement surgery is the gold standard for patients affected by symptomatic osteoarthritis. The ceramic-on-metal (C-M) hybrid hard-on-hard bearing was initially launched on the market with the purpose of reducing adhesive and corrosion wear, loss of metal debris and ions and risk of fracture and squeaking. However, this bearing was withdrawn from the market, in the apprehension of local and systemic toxicity. The aim of this study is to evaluate the reliability and safety of ceramic-on-metal bearing at long term follow-up. Methods From 2 cohorts of patients suffering of hip osteoarthritis who underwent total hip arthroplasty using ceramic-on-metal bearing with two different short stems, 19 of the GROUP A and 25 of the GROUP B were suitable for this study. All compared clinically using the Harris Hip Score (HHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analogue scale (VAS), 12-item Short Form Health Survey (SF12P/M), and radiographically. The two groups were compared in terms of metal ions blood levels (chromium and cobalt), and finally all the implanted prostheses were compared with a healthy control group. Results All the implanted stems were well osseointegrated at a mean follow-up of 114 months. Radiographical and clinical scores performed well. Chromium and cobalt ion analysis revealed values below the safety threshold except for 3. No revision occurred. Conclusions Ceramic-on-metal bearing is safe and reliable at long term follow-up in association to short stems arthroplasty, if the implant is correctly positioned. Chromium and cobalt metal ions blood levels evaluation should be performed annually. Key messages • Metal ions evaluations is mandatory in patients with ceramic-on-metal bearing. • Ceramic-on-metal bearing is safe and reliable at long term follow-up, if the implant is correctly positioned.

Determination of the number of 235U target nuclei in the irregular target using a fission time projection chamber

Based on multiple measurements of ionization loss, the Time Projection Chamber (TPC) combines strong tracking ability with particle identification ability in a large momentum range, which is an important advantage of TPC detection technology over traditional ionization measurement technology. According to these two characteristics of TPC, applying it to the measurement of fission cross-section can greatly improve the measurement accuracy. During the measurement of the fission cross-section, the number of target nuclei is required to be accurately measured. So this paper introduces a method for measuring the number of 235U target nuclei using a fission TPC system. The measurement result agrees with the reference value, and relative error is around 1 %.

Ionoacoustic monitoring of relativistic heavy ion beams

The performance of ionoacoustic detectors is investigated with respect to application of high-precision range and energy loss measurements for relativistic heavy ions. The technique is based on the generation of a pressure wave when a microsecond-pulsed relativistic ion beam is stopped in a water container. The acoustic signal from individual ion pulses is registered by a piezoelectric detector and analyzed in the time/frequency domain to identify the location of pressure wave generation. The experiments were performed at the SIS18 synchrotron at GSI Helmholtzzentrum (Darmstadt, Germany) with Xe, Pb and U ions of energies between 200 MeV/u and 1 GeV/u. We show that the signal amplitude of the acoustic pressure pulse has a linear correlation with the beam intensity within a range of at least 104 to 109 particles/spill.By determining the delay time of the primary and reflected acoustic signal in the water reservoir, the ionoacoustic technique provides information on ion ranges of 1 % accuracy. By an energy-range calibration in combination with a simulation code such as FLUKA, the range data can be used to determine the beam energy. As demonstrated, inserting targets of known thickness in front of the detector is a simple approach for measuring the energy loss of relativistic ions. The advantage of the ionoacoustic technique is the rather simple experimental setup, the huge dynamic range, the information available online by means of only a single pulse and its radiation hardness. Ionoacoustic detectors have great potential as intensity and energy monitor for short-pulsed light and heavy ion beams at existing or future high-energy ion facilities.

Experiments in high-performance JET plasmas in preparation of second harmonic ICRF heating of tritium in ITER

The reference ion cyclotron resonance frequency (ICRF) heating schemes for ITER deuterium–tritium (D-T) plasmas at the full magnetic field of 5.3 T are second harmonic heating of T and 3He minority heating. The wave-particle resonance location for these schemes coincide and are central at a wave frequency of 53 MHz at 5.3 T. Experiments have been carried out in the second major D-T campaign (DTE2) at JET, and in its prior D campaigns, to integrate these ICRF scenarios in JET high-performance plasmas and to compare their performance with the commonly used hydrogen (H) minority heating. In 50:50 D:T plasmas, up to 35% and 5% larger fusion power and diamagnetic energy content, respectively, were obtained with second harmonic heating of T as compared to H minority heating at comparable total input powers and gas injection rates. The core ion temperature was up to 30% and 20% higher with second harmonic T and 3He minority heating, respectively, with respect to H minority heating. These are favourable results for the use of these scenarios in ITER and future fusion reactors. According to modelling, adding ICRF heating to neutral beam injection using D and T beams resulted in a 10%–20% increase of on-axis bulk ion heating in the D-T plasmas due to its localisation in the plasma core. Central power deposition was confirmed with the break-in-slope and fast Fourier transform analysis of ion and electron temperature in response to ICRF modulation. The tail temperature of fast ICRF-accelerated tritons, their enhancement of the fusion yield and time behaviour as measured by an upgraded magnetic proton recoil spectrometer and neutral particle analyser were found in agreement with theoretical predictions. No losses of ICRF-accelerated ions were observed by fast ion detectors, which was as expected given the high plasma density of n e ≈ 7–8 × 1019 m−3 in the main heating phase that limited the formation of ICRF-accelerated fast ion tails. 3He was introduced in the machine by 3He gas injection, and the 3He concentration was measured by a high-resolution optical penning gauge in the sub-divertor region. The DTE2 experiments with 3He minority heating were carried with a low 3He concentration in the range of 2%–4% given the fact that the highest neutron rates with 3He minority heating in D plasmas were obtained at low 3He concentrations of ∼2%, which also coincided with the highest plasma diamagnetic energy content. In addition to 3He introduced by 3He gas injection, an intrinsic concentration of 3He of the order of 0.2%–0.4% was measured in D-T plasmas before 3He was introduced in the device, which is attributed to the radioactive decay of tritium to 3He. According to modelling, even such low intrinsic concentrations of 3He lead to significant changes in ICRF power partitioning during second harmonic heating of T due to absorption of up to 30% of the wave power by 3He.

Internal fault diagnosis method for lithium batteries based on a failure physical model

Performance degradation of lithium-ion batteries is directly related to failure mechanisms such as loss of internal active lithium ions or active material. For in-service batteries, internal failures or degradation cannot be directly observed, and it is difficult to analyze and diagnose them through limited external characteristic measurements. To effectively diagnose lithium-ion batteries failure behaviors, an internal fault diagnosis method is proposed. Firstly, a failure physical model containing side reactions is established, aiming at studying the inherent relationship between the parameters of the failure physical model and internal faults. Then, a method of constructing parameter failure boundaries is proposed to diagnose whether aging failures including electrolyte decomposition, active particle rupture, SEI film growth, and lithium plating occur inside the battery by tracking and analyzing the evolution laws of the model parameters. Finally, abnormal batteries with faster capacity degradation in the same group are selected, and based on destructive characterization testing, the effectiveness and reliability of the proposed non-destructive internal fault diagnosis method are verified.

Rutin from Begonia roxburghii modulates iNOS and Sep A activity in treatment of Shigella flexneri induced diarrhoea in rats: An in vitro, in vivo and computational analysis

In developing countries, diarrhoea is a major issue of concern, where consistent use of antibiotics has resulted in several side effects along with development of resistance among pathogens against these antibiotics. Since natural products are becoming the treatment of choice, therefore present investigation involves mechanistic evaluation of antidiarrhoeal potential of Begonia roxburghii and its marker rutin against Shigella flexneri (SF) induced diarrhoea in rats following in vitro, in vivo and in silico protocols. The roots of the plant are used as vegetable in the North East India and are also used traditionally in treating diarrhoea. Phytochemically standardized ethanolic extract of B. roxburghii (EBR) roots and its marker rutin were first subjected to in vitro antibacterial evaluation against SF. Diarrhoea was induced in rats using suspension of SF and various diarrhoeagenic parameters were examined after first, third and fifth day of treatment at 100, 200 and 300 mg/kg, p.o. with EBR and 50 mg/kg, p.o. with rutin respectively. Additionally, density of SF in stools, stool water content, haematological and biochemical parameters, cytokine profiling, ion concentration, histopathology and Na+/K+–ATPase activity were also performed. Molecular docking and dynamics simulation studies of ligand rutin was studied against secreted extracellular protein A (Sep A, PDB: 5J44) from SF and Inducible nitric oxide synthase (iNOS, PDB: 1DD7) followed by network pharmacology. EBR and rutin demonstrated a potent antibacterial activity against SF and also showed significant recovery from diarrhoea (EBR: 81.29 ± 0.91% and rutin: 75.27 ± 0.89%) in rats after five days of treatment. EBR and rutin also showed significant decline in SF density in stools, decreased cytokine expression, potential antioxidant activity, cellular proliferative nature and recovered ion loss due to enhanced Na+/K+–ATPase activity, which was also supported by histopathology. Rutin showed a very high docking score of −11.61 and −9.98 kcal/mol against iNOS and Sep A respectively and their stable complex was also confirmed through dynamics, while network pharmacology suggested that, rutin is quite capable of modulating the pathways of iNOS and Sep A. Thus, we may presume that rutin played a key role in the observed antidiarrhoeal activity of B. roxburghii against SF induced diarrhoea.

SAT182 Effects Of An Orally Bioavailable Nonpeptide Parathyroid Hormone Receptor Type 1 (PTH1R) Antagonist In Rodent Models Of Primary Hyperparathyroidism (PHPT)

Abstract Disclosure: A.S. Antwan: Employee; Self; Crinetics Pharmaceuticals. E. Rico-Bautista: Employee; Self; Crinetics Pharmaceuticals. J. Pontillo: Employee; Self; Crinetics Pharmaceuticals. S. Wang: Employee; Self; Crinetics Pharmaceuticals. M. Johns: Employee; Self; Crinetics Pharmaceuticals. B. Ramms: Employee; Self; Crinetics Pharmaceuticals. M.A. Fowler: Employee; Self; Crinetics Pharmaceuticals. J.B. Nguyen: Employee; Self; Crinetics. A.A. Castellanos Gonzalez: Employee; Self; Crinetics. B. Fleck: Employee; Self; Crinetics Pharmaceuticals. K. Retting: Employee; Self; Crinetics Pharmaceuticals. D. Dalvie: Employee; Self; Crinetics Pharmaceuticals. S.F. Betz: Employee; Self; Crinetics Pharmaceuticals. S. Markison: Employee; Self; Crinetics Pharmaceuticals. Primary hyperparathyroidism (PHPT) is a condition resulting from an over-secretion of parathyroid hormone (PTH) from one or more overactive parathyroid glands. PTH is a peptide hormone that regulates blood calcium concentrations through effects on bone, intestines, and kidney. PTH acts on parathyroid hormone receptor type 1 (PTH1R) in the kidney to increase calcium reabsorption and block phosphate reabsorption. The loss of phosphate ions then causes an increase in ionized calcium in the blood and cAMP in the urine. At the bone, continuous PTH infusion stimulates osteoclast activity while inhibiting osteoblast activity, leading to breakdown of bone and release of calcium into the extracellular fluid. Conditions that cause excess PTH, such as PHPT, result in elevated concentrations of plasma calcium, increased bone loss, increased fracture risk, and higher susceptibility to kidney stone development. PHPT affects approximately 100,000 patients per year, but many patients are asymptomatic and remain undiagnosed. While a partial or total parathyroidectomy may be suitable for patients diagnosed with severe cases of PHPT, there are limited treatment options for those who do not meet the criteria or do not wish to undergo surgery. The goals for medicinal treatment are to normalize blood calcium levels and urinary calcium excretion, as well as increase bone mineral density to reduce fracture risk. Blocking PTH action directly via a potent PTH1R antagonist may provide an important new therapeutic mechanism to treat patients with PHPT. Using iterative medicinal chemistry and pharmacology, Crinetics has identified several potent and orally bioavailable PTH1R antagonists with good drug-like properties. Lead molecules were evaluated in vivo in preclinical rodent models for their ability to suppress the effects of excess PTH on serum calcium, bone turnover, and cAMP levels in the kidney. One of these compounds, ANT-5, was characterized as a potent negative allosteric modulator of both human and rat PTH1R. In rats, oral administration of ANT-5 dose-dependently suppressed PTH-induced hypercalcemia. ANT-5 also suppressed PTH-stimulated urinary cAMP in rats, indicating its ability to inhibit the actions of PTH in the kidney. We further evaluated the effect of ANT-5 in a rodent model of continuous PTH infusion-induced bone turnover. Once-daily oral administration of ANT-5 mitigated PTH-induced bone resorption, suggesting that inhibiting PTH1R may have beneficial clinical effects on bone density. The culmination of these studies has led to a subset of candidate molecules that are being evaluated in safety studies to identify the compound(s) suitable for evaluation in human clinical trials. Support: Crinetics Pharmaceuticals. Presentation: Saturday, June 17, 2023

Analysis of a cusped helicon plasma thruster discharge

Experiments and simulations are used to analyze a compact helicon plasma thruster with a cusp in its internal magnetic field. The former rely on a compensated Langmuir probe and a Faraday cup, while the latter employ a hybrid PIC/fluid transport model combined with a frequency-domain electromagnetic field model. Measurements serve to tune the anomalous transport parameters of the model and overall show the same trends as the numerical results, including a secondary peak of electron temperature downstream in the magnetic nozzle, where electron cyclotron resonance conditions for the 13.56 MHz excitation frequency are met. The cusp plays a central role in determining the plasma losses to the walls and the profile of electron temperature, which in turn defines the excitation and ionization losses. While losses to the rear wall are reduced, losses to the lateral wall are increased, which, together with the low production efficiency, limit the performance of the device.