Kinetic Interaction Research Articles

Pore configuration control in hybrid azolate ultra-microporous frameworks for sieving propylene from propane.

Developing porous adsorbents for the complete sieving of propylene/propane mixtures represents an alternative method to energy-intensive cryogenic distillation processes. However, the similar physical properties of these molecules and the inherent trade-off among adsorption capacity, selectivity, diffusion kinetic and host-guest binding interactions in molecular sieving adsorbents makes their separation challenging. Here we report the separation of propylene/propane mixtures through a crystalline porous material (HAF-1) that features channels and shrinkage throats-the latter defined as narrower channels that connect the main channels and a molecular pocket-where the throat aperture is between the kinetic diameters of propylene and propane. Single-crystal X-ray diffraction and computational simulation reveal that the shrinkage channels and hanging molecular pockets are key to ensure high sieving efficiency and high propylene adsorption capacity. Dynamic breakthrough experiments show that HAF-1 enables the achievement of high-purity (≥99.7%) propylene with a productivity of 33.9 l kg-1 by just one adsorption-desorption circle from propylene/propane mixtures.

An exactly solvable model for RNA polymerase during the elongation stage

We consider a Markovian model for the kinetics of RNA Polymerase (RNAP) which provides a physical explanation for the phenomenon of cooperative pushing during transcription elongation observed in biochemical experiments onEscherichia coliand yeast RNAP. To study how backtracking of RNAP affects cooperative pushing we incorporate into this model backward (upstream) RNAP moves. With a rigorous mathematical treatment of the model we derive conditions on the mutual static and kinetic interactions between RNAP under which backtracking preserves cooperative pushing. This is achieved by exact computation of several key properties in the steady state of this model, including the distribution of headway between two RNAP along the DNA template and the average RNAP velocity and flux.

Damping of Strong GHz Waves near Magnetars and the Origin of Fast Radio Bursts

We investigate how a fast radio burst (FRB) emitted near a magnetar would propagate through its surrounding dipole magnetosphere at radii r = 107–109 cm. First, we show that a GHz burst emitted in the O-mode with luminosity L ≫ 1040 erg s−1 is immediately damped for all propagation directions except a narrow cone along the magnetic axis. Then, we examine bursts in the X-mode. GHz waves propagating near the magnetic equator behave as magnetohydrodynamic (MHD) waves if they have L ≫ 1040 erg s−1. The waves develop plasma shocks in each oscillation and dissipate at r∼3×108L42−1/4 cm. Waves with lower L or propagation directions closer to the magnetic axis do not obey MHD. Instead, they interact with individual particles and require a kinetic description. The kinetic interaction quickly accelerates particles to Lorentz factors 104–105 at the expense of the wave energy, which again results in strong damping of the wave. In either propagation regime, MHD or kinetic, the dipole magnetosphere surrounding the FRB source acts as a pillow absorbing the radio burst and reradiating the absorbed energy in X-rays. These results constrain the origin of observed FRBs. We argue that the observed FRBs avoid damping because they are emitted by relativistic outflows from magnetospheric explosions, so that the GHz waves do not need to propagate through the outer equilibrium magnetosphere surrounding the magnetar.

Investigation into the linearity of the Roche c 702 carbamazepine assay.

Carbamazepine is an anticonvulsant drug which is monitored in patients due to toxic side effects. At Manchester University NHS Foundation Trust (MFT), carbamazepine is measured using Roche's Kinetic Interaction of Microparticles in Solution (KIMS) method on the c 702 platform. The assay has an upper limit of linearity of 20mg/L. Samples with concentrations above this limit should be identified and manually diluted. However, a poor EQA return from UK NEQAS for Tox and TDM Distribution 456 has highlighted an issue with the Roche KIMS assay. Sample A of the distribution had a carbamazepine concentration of 36mg/L but was underreported by several Roche users. This indicated that the assay was not consistently identifying high concentration samples which required a dilution. In this investigation, fresh frozen plasma was spiked with carbamazepine concentrations ranging from 15 to 40mg/L. The spiked samples and EQA material were analysed at two clinical laboratories using the Roche KIMS assay. Samples spiked with concentrations 20-30mg/L were not consistently identified for dilution by the analyser. This was observed at both hospital sites. Spike samples and EQA with concentrations >30mg/L were correctly identified at both sites. The manual dilution policy has been changed at MFT, so all samples with a carbamazepine level ≥15mg/L will be manually diluted. The problem was reported to Roche who are investigating the issue further. We would suggest that other laboratories look at validating their dilution protocols.

B-299 Comparison of a Recently FDA-Cleared Urine Benzodiazepine Screening Assay with β-Glucuronidase Hydrolysis to Liquid Chromatography-Mass Spectrometry

Abstract Background Benzodiazepines are a class of prescribed psychoactive drugs that act as a depressant on the central nervous system. Over the last decade, the fast-acting sedative effects of these drugs have led to misuse, therefore making detection important for monitoring proper drug compliance. Immunoassays on urine samples are commonly used as a screening method and the results are confirmed using high-performance liquid chromatography/tandem mass spectrometry (LC-MS/MS). The metabolites of benzodiazepine in urine are predominantly excreted as glucuronides which may lead to false negative results when utilizing immunoassay-based methods. The purpose of this study was to compare a new generation of benzodiazepine reagent, that includes a β-glucuronidase enzyme to increase sensitivity, to LC-MS/MS. Secondly, the positivity rate was compared before and after the increased sensitivity screening assay was implemented. Methods Validation of benzodiazepine II assay was performed on an automated chemistry analyzer (Roche Diagnostics, cobas c502), utilizing a kinetic interaction of microparticles in a solution (KIMS) method. A total of thirty urine samples that screened positive on the benzodiazepine II assay and thirty samples that screened negative, were compared with LC-MS/MS. The LC-MS/MS panel included α- hydroxytriazolam, 7- aminoclonazepam, nordiazepam, temazepam, oxazepam, lorazepam, and α-hydroxyalprazolam. The lower limit of quantitation was 40 ng/mL for all compounds except α-hydroxyalprazolam which was 60 ng/mL. The cutoff concentration for the benzodiazepine II assay was 200 ng/mL. Three months of data was also collected before and after converting to the new generation of benzodiazepine assay. Results Conclusions The addition of β-glucuronidase to the benzodiazepine II assay allowed for high sensitivity when detecting urine benzodiazepine metabolites. With the increased sensitivity, almost a doubling of positivity rate was observed. The overall high diagnostic accuracy of the test makes it a reliable screening method for urine benzodiazepine detection.

B-287 Comparing a Recently FDA-Cleared Free Phenytoin Assay to a Laboratory Developed Test

Abstract Background Phenytoin is an anti-convulsant drug that is commonly prescribed to epileptic patients to control seizures. The drug circulates in two forms: protein-bound (90%), and the free, biologically active form (10%). In certain circumstances, such as protein-binding disruption, hypoalbuminemia, and drug-drug interactions, the total phenytoin serum concentration may not accurately reflect active phenytoin levels. Therefore, a free phenytoin level (i.e. non-protein bound) may be indicated. Until recent FDA-clearance, we utilized an in-house, laboratory-development test (LDT) to deliver these needed results. The purpose of this study was to validate the FDA-cleared assay and compare its performance characteristics to a free phenytoin LDT. Methods Validation of the FDA-cleared assay was performed on an automated chemistry analyzer (Roche Diagnostics, cobas c502), utilizing a kinetic interaction of microparticles in a solution (KIMS) method. Both the FDA and LDT assay used the same free phenytoin reagent, however the calibrators and pipetting parameters for each assay were different. FDA assay used a six-point calibration at concentrations of: 0, 2.5, 5, 10, 20, 40 µg/mL (Preciset TDM I Calibrators), whereas the LDT assay used a six-point calibration at concentrations of: 0.0, 0.5, 1.0, 2.0, 3.0, 4.0 µg/mL (cobas FP Free Phenytoin Calibrators). The following performance characteristics were determined for the FDA-cleared assay and compared to the current LDT: analytical measurement range, precision, accuracy, and maximum dilution. Free forms of the drug were obtained as a filtrate through centrifugation using a molecular weight cut-off filter (30 kDa, Millipore), spun at 3600 rpm for twenty minutes. Results Conclusions The FDA-cleared free phenytoin assay is suitable for use in the clinical laboratory producing similar results to our LDT. Switching to the FDA-cleared assay reduces the regulatory burden and eliminates the need for transferring reagent into open channel cassettes and manual dilutions.

B-262 Validation of a point-of-care lateral flow immunoassay for urine drug testing prior to application in an outpatient rapid access addiction medicine clinic

Abstract Background Point-of-care (POC) urine drug testing is a useful adjunct to self-reporting in rapid access addiction medicine settings to immediately guide patient management. However, available POC immunoassays have limitations including cross-reactivity with unrelated compounds or low sensitivity that may cause false results. Here, we assessed the performance of a multi-drug test panel by comparing against gold-standard liquid chromatography tandem mass spectrometry (LC-MS/MS) testing. Methods 102 residual urine specimens were assayed using a competitive lateral flow immunoassay (LFA) for 10 drugs: 2-ethylene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP, methadone metabolite), buprenorphine, morphine, hydromorphone, oxycodone, fentanyl, cocaine, methamphetamine, amphetamine, and benzodiazepines (BTNX Rapid ResponseTM Multi-Drug Panel). Results were compared to those obtained by LC-MS/MS (n=67, 66%) or kinetic interaction of microparticles in solution automated immunoassay (KIMS) (Roche Diagnostics, n=35, 33%). Broad spectrum LC-MS/MS results were reviewed in entirety for discordant cases, particularly in false positives to identify the presence of any known cross-reacting compounds. Results Of 10 drugs evaluated, four demonstrated ≥95% agreement with LC-MS/MS or KIMS immunoassay (EDDP, buprenorphine, oxycodone, methamphetamine). Fentanyl demonstrated the highest false negative rate of 44% (LFA cut-off: 10 ng/mL) followed by amphetamines (22%, cut-off: 1000 ng/mL). Morphine and hydromorphone demonstrated false positive rates of 14% and 18%, respectively, with most cases likely due to cross-reacting opiate or opioid metabolites. Benzodiazepines (target: Oxazepam) demonstrated false positive and negative rates of 13% and 24%, respectively. Conclusions To our knowledge, this is the first study to evaluate the performance of the BTNX multi-drug test panel against definitive testing in urine samples. While good concordance was observed for most drugs, high rates of discordant results for fentanyl and others emphasize the need for confirmatory testing by methods with higher sensitivity and specificity. Careful consideration prior to implementation would be essential, including physician education, interpretative comments, and training resources.

A perturbative multi-mode model with finite parallel electric field for fast-ion-driven Alfvén eigenmodes

Abstract Alfvén eigenmodes are of great interest in any fusion device as they can be excited by fast ions in the plasma. If the modes grow to large amplitudes, they can cause transport and redistribution of the fast ions, thus limiting fusion performance. To save computational resources, the resonant kinetic interaction between the fast-particle species and the modes is often modelled by MHD-kinetic hybrid codes. Here, we present such a hybrid model which is applicable to three-dimensional magnetic fields, accounts for a finite parallel electric field and multiple MHD modes present at the same time. The model extends the one previously implemented in the CKA-EUTERPE code allowing for a better estimate of the damping due to the parallel electric field and nonlinear mode-mode interaction. The capabilities of our model are illustrated by applying the code to model nonlinear frequency chirping and fast-ion profile flattening.

Low oxygen adsorption energy barrier architectures to facilitate microenvironmental photocatalytic disinfection in Wei River

Photocatalytic disinfection is an eco-friendly strategy that uses solar energy to purify bacteria-contaminated water. However, improvements in photocatalysts tend to focus on thermodynamics while neglecting kinetic interactions that involve oxygen. Here, we propose the MOF-on-MOF heterojunction NR-HKUST-1@Cu/ZIF-8 (NH@CZ) for kinetic photocatalytic disinfection; the heterojunction reduced bacterial load by nearly 8-log within 20 min. The NH@CZ structure exhibits a high specific surface area with Cu2O8 and CuN4 sites that provide substantial oxygen storage capacity and binding sites. In vitro experiments demonstrated the effective delivery of oxygen to photocatalytic reactions via NH@CZ, leading to enhanced superoxide radical (·O2-) generation. Experimental analysis and theoretical calculations confirm that the formation of heterojunctions in NH@CZ provides an efficient pathway for oxygen reduction by reducing the energy barrier associated with oxygen adsorption. Mechanistic studies show that reactive oxygen species (ROS) disrupt bacterial cell membranes, resulting in the release of cellular contents (e.g., potassium ions and macromolecular proteins) and subsequent cell death. Furthermore, the oxygen-carrying NH@CZ killed all microorganisms in Wei River water samples within 45 min. The MOF-on-MOF heterojunction offers a promising pathway to enhance ROS generation and provides valuable insights into advances in water disinfection technology.

Comparison of vancomycin assays in patients undergoing hemodialysis

Vancomycin is a glycopeptide antibiotic mainly excreted by glomerular filtration. Therefore, patients undergoing hemodialysis tend to accumulate its crystalline degradation product, which has been associated with cross-reaction in commercial immunoassays. The aim of this study was to assess the performance of two commercial immunoassays for measuring vancomycin levels in patients undergoing hemodialysis. This method-comparison study enrolled patients undergoing hemodialysis at two hospitals in Porto Alegre, Brazil. Vancomycin serum concentrations measured by Chemiluminescent Microparticle Assay (CMIA) and measured by Kinetic Interaction of Microparticles in Solution (KIMS) were compared with Liquid Chromatography coupled with Tandem Mass Spectrometry (LC-MS/MS). A total of 64 samples from 42 patients and 54 samples from 23 patients were included in CMIA and KIMS groups. Both measurements were highly correlated with LC-MS/MS, with Spearman rank correlation coefficient r = 0.840 (p < 0.001) and r = 0.926 (p < 0.001), respectively. No deviation of linearity was observed (p = 0.81 and p = 0.49, respectively). The mean difference between CMIA and LC-MS/MS was -1.19 μg/mL and between KIMS and LC-MS/MS was -2.28 μg/mL. LC-MS/MS measured levels were, on average, 2.64 % higher than CMIA and 8.81 % higher than KIMS. CMIA and KIMS revealed accurate commercial methods to measure vancomycin serum concentrations in patients undergoing hemodialysis.

Effect of methanol-water mixtures on the oxidation of n-heptane at low to intermediate temperatures: Experimental and numerical study

Methanol is widely recognized as a carbon-neutral fuel. This work used synchrotron vacuum ultraviolet photoionization mass spectrometry (SVUV-PIMS) to study the oxidation process of water/methanol/n-heptane mixes in a jet-stirred reactor (JSR) at a pressure of 1 atm, equivalence ratios (ϕ) of 1 and a temperature range of 500–1100 K. The results of the experiment indicate that the inhibition of n-heptane's oxidation at low temperatures (500–740K) is the primary manifestation of the action of methanol/water mixtures on n-heptane oxidation. The strong interactions among the components of water/methanol/n-heptane mixtures at low temperatures are primarily between methanol and n-heptane. The higher the methanol content, the greater the strength of inhibition of n-heptane oxidation. This inhibitory effect primarily results from the competition of methanol with ˙OH radicals. It is noteworthy that the chemical kinetic interactions between methanol-water mixtures and n-heptane not only manifest changes in the ˙OH radical pools but are also associated with the intermolecular chemical kinetic interactions between peroxyalkyl radicals (ROO˙) and CH3OH.

40Ar diffusion in phlogopite: [formula omitted] atomistic calibration and implications for Ar–melt–solid kinetic interactions and ascent dynamics of mantle xenoliths and kimberlites

40Ar/39Ar ages of phlogopite from kimberlite-hosted mantle xenoliths are commonly older than the kimberlite eruption, despite the fact that argon is supposed not to be retained by phlogopite at temperatures above hydrothermally-derived Ar closure temperatures (<500°C). Combining Molecular Dynamics (MD) with Nudged Elastic Band (NEB) and Transition State Theory (TST), we investigate 40Ar−PVT (Pressure−Volume−Temperature) relationships in pristine, defect-free, phlogopite and show that 40Ar diffusivity is several orders of magnitude slower than existing estimates with a strong effect of pressure on diffusion rates and retention of 40Ar at mantle conditions. These results imply to fundamentally revise residence- and transit-time estimates based on Ar kinetics in phlogopite assuming simple diffusive relaxation during upwelling. When accounting for pressure, 40Ar retention trends in phlogopite predict substantially slower kimberlite ascent rates than documented by independent chronometers, indicating that 40Ar resetting during ascent in phlogopite does not result from simple decompression-driven diffusive relaxation. We argue that 40Ar remobilization probably involves secondary structural–textural modifications induced by reaction-driven recrystallization or rim overgrowth. These findings have far-reaching consequences in terms of argon isotopic mobility at mantle depths as well as for dating and tracing metasomatic events during crust−mantle interactions in the evolution of the subcontinental mantle.

Effects of Plasma Ions/Radicals on Kinetic Interactions in Nanowall Deposition: A Review

Recent advances in the growth of carbon nanowalls (CNWs) and vertical graphene nanosheets using various plasma‐enhanced chemical vapor deposition (PECVD) methods are reviewed in this article. Growth methods are classified into hot‐ and cold‐wall reactors equipped with diverse plasma generation systems, and their respective characteristics are summarized, with particular attention to the behavior of reactive species, such as ions and radicals, generated within the plasma. Recent progress in this research domain is outlined for each method, and an organized account of the chemical kinetic phenomena occurring within the plasma is provided. Finally, future perspectives are discussed. Fundamental data are obtained through real‐time in situ measurements of ions and radicals, and the construction of a database from these data offers microscopic insights that significantly enhance processing outcomes for macroscopically controlling the mechanical shapes and chemical properties of CNWs.

Modeling and Optimizing Biocontrol in Wines: pH as a Modulator of Yeast Amensalism Interaction

The control of spoilage yeasts in wines is crucial to avoid organoleptic deviations in wine production. Traditionally, sulfur dioxide (SO2) was used to control them; nevertheless, SO2 influence on human health and its use is criticized. Biocontrol emerges as an alternative in wine pre-fermentation, but there is limited development in its applicability. Managing kinetics is relevant in the microbial interaction process. pH was identified as a factor affecting the interaction kinetics of Wickerhamomyces anomalus killer biocontrol on Zygosaccharomyces rouxii. Mathematical modeling allows insight into offline parameters and the influence of physicochemical factors in the environment. Incorporating submodels that explain manipulable factors (pH), the process can be optimized to achieve the best-desired outcomes. The aim of this study was to model and optimize, using a constant and a variable pH profile, the interaction of killer biocontrol W. anomalus vs. Z. rouxii to reduce the spoilage population in pre-fermentation. The evaluated biocontrol was W. anomalus against the spoilage yeast Z. rouxii in wines. The kinetic interactions of yeasts were studied at different pH levels maintained constant over time. The improved Ramón-Portugal model was adopted using the AMIGO2 toolbox for Matlab. A static optimization of a constant pH profile was performed using the Monte Carlo method, and a dynamic optimization was carried out using a method based on Fourier series and orthogonal polynomials. The model fit with an adjusted R2 of 0.76. Parametric analyses were consistent with the model behavior. Variable vs. constant optimization achieved a lower initial spoilage population peak (99% less) and reached a lower final population (99% less) in a reduced time (100 vs. 140 h). These findings reveal that control with a variable profile would allow an early sequential inoculation of S. cerevisiae. The models explained parameters that are difficult to quantify, such as general inhibitor concentration and toxin concentration. Also, the models indicate higher biocontrol efficiency parameters, such as toxin emission or sensitivity to it, and lower fitness of the contaminant, at pH levels above 3.7 during biocontrol. From a technological standpoint, the study highlights the importance of handling variable profiles in the controller associated with the pH management actuators in the process without incurring additional costs.

Synergy of atom doping and defect construction in marigold-like Zn3In2S6 for improved photocatalytic hydrogen production

Atom doping and defect construction are effective strategies to enhance the performance of photocatalysts. Herein, zirconium (Zr) doping and sulfur vacancies (Vs) are introduced on marigold-like Zn3In2S6 (Zr-ZIS-Vs) by controlling the amount of sulfur precursors and ZrCl4 via a one-pot hydrothermal process. Remarkably, the optimized Zr-ZIS-Vs catalyst exhibits excellent photocatalytic activity, giving a photocatalytic hydrogen evolution rate of 9.44 mmol g−1 h−1, which is 10.73, 4.39 and 2.37 times higher than pure Zn3In2S6 (ZIS, 0.88 mmol g−1 h−1), Zn3In2S6 with sulfur vacancies alone (ZIS-Vs, 2.15 mmol g−1 h−1), and Zn3In2S6 with Zr doping alone (Zr-ZIS, 3.98 mmol g−1 h−1). The apparent quantum efficiency (AQE) of Zr-ZIS-Vs achieves 27.15 % and 4.90 % at λ = 370 and 456 nm, respectively. Experimental results and theoretical simulations reveal the behavioral mechanisms of the deletion of S atoms and the tendency of Zr to replace In, indicating that the defective and reference strategies can narrow the band gap, provide abundant active sites, enhance the effective transport and separation of photogenerated carriers, and modulate the transfer of active sites to empirical site S atoms to achieve the synergistic thermodynamic and kinetic interactions, which effectively enhances the performance of photocatalytic hydrogen production.

Control of curing kinetic and strong interaction between resins network and boehmite nanoparticles: Dynamic‐mechanical and curing kinetics study

AbstractIn this study, two characteristics of boehmite nanoparticles (BNs) were used to improve the dynamic‐mechanical properties of pure unsaturated polyester resin (Neat UP). (1) Boehmite's ability to target free radical control in the radical curing reaction of UP resin, and (2) adsorption of alkyd chains and creation of attractive interactions with the resin network. X‐ray diffraction (XRD), Fourier‐transform infrared spectroscopy (FT‐IR), and field‐emission scanning electron microscopy (FESEM) analysis were used to identify the synthesis of particles. The results of FESEM analysis showed that the average particle size was 80–100 nm. TGA was used to investigate the thermal properties of the Neat UP and UP resin containing 0.3 wt% BNs (UP 0.3 BNs). The results of the dynamic‐mechanical analysis showed that the elastic modulus of the UP 0.3 BNs composite increased by 42% compared to the Neat UP. To investigate the significant increase observed in the dynamic‐mechanical properties, the curing kinetics were investigated by differential scanning calorimetry (DSC). Investigating the activation energy in terms of the conversion degree showed earlier dominance of the diffusion phenomenon in the UP 0.3 BNs composite. Investigating the diffusion factors provided by Vyazovkin–Sbirrazzouli showed a significant decrease in K and ED in the UP 0.3 BNs composite (−10.5, 19 kJ/mol) compared to the Neat UP resin (−9.5, 40 kJ/mol).Highlights Targeted control of free radicals increases network regularity of the UP/BNs. Impressive improvement of mechanical properties of UP/BNs compared to Neat UP. Increasing diffusion phenomenon dominance of UP/BNs system compared to Neat UP.

Electrochemical and Plasmonic Detection of Myocardial Infarction Using Microfluidic Biochip Incorporated with Mesoporous Nanoscaffolds.

This paper reports a microfluidic device for the electrochemical and plasmonic detection of cardiac myoglobin (cMb) and cardiac troponin I (cTnI) with noticeable limits of detection (LoD) as low as a few picograms per milliliter (pg/mL) ranges, achieved in a short detection time. The device features two working electrodes, each with a mesoporous Ni3V2O8 nanoscaffold grafted with reduced graphene oxide (rGO) that improves the interaction of diffusing analyte molecules with the sensing surface by providing a high surface area and reaction kinetics. Electrochemical studies reveal sensitivities as high as 9.68 μA ng/mL and a LoD of 2.0 pg/mL for cTnI, and 8.98 μA ng/mL and 4.7 pg/mL for cMb. Additionally, the surface plasmon resonance (SPR) studies demonstrate a low-level LoD of 8.8 pg/mL for cMb and 7.3 pg/mL for cTnI. The dual-modality sensor enables dynamic tracking of kinetic antigen-antibody interactions during sensing, self-verification through providing signals of two modes, and reduced false readout. This study demonstrates the complementary nature of the electrochemical and SPR modes in biosensing, with the electrochemical mode being highly sensitive and the SPR mode providing superior tracking of molecular recognition behaviors. The presented sensor represents a significant innovation in cardiovascular disease management and can be applied to monitor other clinically important biomolecules.

Antibody fragments targeting the extracellular domain of follicular stimulating hormone receptor for contraception in male dogs and cats

The increased LH levels resulting from the absence of negative feedback after castration has been linked to long-term health issues. A need exists for an alternative contraceptive agent that functions without interfering the LH pathways. This study aimed to develop antibody fragments against the follicular-stimulating hormone receptor (anti-FSHr) using phage-display technology and evaluate its effects on Sertoli cell functions. Phage clones against the extracellular domain of dog and cat FSHr selected from an antibody fragment phagemid library were analyzed for binding kinetics by surface plasmon resonance. Sertoli cells were isolated from testes of adult animals (five dogs and five cats). Efficacy test was performed by treating Sertoli cell cultures (SCCs) with anti-FSHr antibody fragments compared with untreated in triplicates. Expressions of androgen binding protein (ABP), inhibin subunit beta B (IHBB) and vascular endothelial growth factor A (VEGFA) mRNA in SCCs were quantified by RT-qPCR. The results demonstrated that the molecular weight of the purified dog and cat anti-FSHr antibody fragment was 25 kDa and 15 kDa, respectively. Based on protein molecular weight, the antibody fragment of dogs and cats was therefore, so-called single-chain variable fragments (scFv) and nanobody (nb), respectively. The binding affinity with dissociation constant (KD) was 2.32 × 10−7 M and 2.83 × 10−9 M for dog and cat anti-FSHr antibody fragments, respectively. The cross-binding kinetic interactions between the dog anti-FSHr scFv and the cat ECD of FSHr could not be fitted to the curves to determine the binding kinetics. However, the cross-binding affinity KD between the cat anti-FSHr nb and the dog ECD FSHr was 1.75 × 10−4 M. The mRNA expression of ABP, IHBB and VEGFA in SCCs was less (P < 0.05) in both dogs (12.26, 4.07 and 5.11 folds, respectively) and cats (39.53, 14.07 and 20.29 folds, respectively) treated with anti-FSHr antibody fragments, indicating the Sertoli cell functions were suppressed. In conclusion, this study demonstrated the establishment of species-specific antibody fragments against FSHr in SCCs for dogs and cats. The fragment proteins illustrate potential to be developed as non-surgical contraceptive agent targeting FSHr in companion animals.

Is there a fast track (“Darmstrasse”) for fluids in the small intestine? Evidence from magnetic resonance imaging

BackgroundThe transit and distribution pattern of fluids in the small intestine is a key parameter for the dissolution and absorption of drugs. Although some information is known about the small intestinal water content after administration of fluid volumes and meals, the intestinal transit of orally ingested fluids and solutions has been barely investigated. The aim of this three-arm, cross-over, 9-subject human study was to investigate the transit of orally ingested water in the small intestine under fasting and postprandial conditions using MRI. To identify the ingested water, manganese gluconate, which can be identified with T1-weighted MRI sequences, was added as a marker. Using Horos (DICOM software), quantification of the distribution of Mn2+ ions in the gastrointestinal tract in fasted versus fed state (standard meal by FDA guidance and a light meal) was possible. The distribution and approximate wetted intestinal length was very similar in the fasting and postprandial states, suggesting rapid transport of water ingested after a meal through the chyme-filled small intestine in continuation of the “Magenstrasse” (stomach road). In some subjects, manganese gluconate reached deeper parts of the small intestine even more quickly in the postprandial state than in the fasting arm of the study. A deeper understanding of the behaviour of solutes in the gastrointestinal tract is fundamental to a mechanistic explanation for the kinetic interaction between food and drug intake (food effects).

Electromagnetic Signatures of Mirror Stars

Mirror stars are a generic prediction of dissipative dark matter (DM) models, including minimal atomic DM and twin baryons in the mirror twin Higgs model. Mirror stars can capture regular matter from the interstellar medium through extremely suppressed kinetic mixing interactions between the regular and the dark photon. This accumulated “nugget” will draw heat from the mirror star core and emit highly characteristic X-ray and optical signals. In this work, we devise a general parameterization of mirror star nugget properties that is independent of the unknown details of mirror star stellar physics, and use the Cloudy spectral synthesis code to obtain realistic and comprehensive predictions for the thermal emissions from optically thin mirror star nuggets. We find that mirror star nuggets populate an extremely well-defined and narrow region of the Hertzsprung–Russell diagram that only partially overlaps with the white dwarf population. Our detailed spectral predictions, which we make publicly available, allow us to demonstrate that optically thin nuggets can be clearly distinguished from white dwarf stars by their continuum spectrum shape, and from planetary nebulae and other optically thin standard sources by their highly exotic emission-line ratios. Our work will enable realistic mirror star telescope searches, which may reveal the detailed nature of DM.