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The DIII-D tokamak has elucidated crucial physics and developed projectable solutions for ITER and fusion power plants in the key areas of core performance, boundary heat and particle transport, and integrated scenario operation, with closing the core-edge integration knowledge gap being the overarching mission. New experimental validation of high-fidelity, multi-channel, non-linear gyrokinetic turbulent transport models for ITER provides strong confidence it will achieve Q ⩾ 10 operation. Experiments identify options for easing H-mode access in hydrogen, and give new insight into the isotopic dependence of transport and confinement. Analysis of 2,1 islands in unoptimized low-torque IBS demonstration discharges suggests their onset time occurs randomly in the constant β phase, most often triggered by non-linear 3-wave coupling, thus identifying an NTM seeding mechanism to avoid. Pure deuterium SPI for disruption mitigation is shown to provide favorable slow cooling, but poor core assimilation, suggesting paths for improved SPI on ITER. At the boundary, measured neutral density and ionization source fluxes are strongly poloidally asymmetric, implying a 2D treatment is needed to model pedestal fuelling. Detailed measurements of pedestal and SOL quantities and impurity charge state radiation in detached divertors has validated edge fluid modelling and new self-consistent ‘pedestal-to-divertor’ integrated modeling that can be used to optimize reactors. New feedback adaptive ELM control minimizes confinement reduction, and RMP ELM suppression with sustained high core performance was obtained for the first time with the outer strike point in a W-coated, compact and unpumped small-angle slot divertor. Advances have been made in integrated operational scenarios for ITER and power plants. Wide pedestal intrinsically ELM-free QH-modes are produced with more reactor-relevant conditions, Low torque IBS with W-equivalent radiators can exhibit predator-prey oscillations in T _e and radiation which need control. High- β _P scenarios with q _min > 2, q _95 –7.9, β _N > 4, β _T –3.3% and H _98y2 > 1.5 are sustained with high density ( $\bar n$ = 7E19 m ^−3 , f _G –1) for 6 τ _E , improving confidence in steady-state tokamak reactors. Diverted NT plasmas achieve high core performance with a non-ELMing edge, offering a possible highly attractive core-edge integration solution for reactors.

Thermal helium beam diagnostics using the line ratio spectroscopy method are widely used to infer temperature and density in fusion-relevant edge plasmas. These diagnostics consist of an observational system which measures emitted line radiation from either intrinsic or injected helium plasma impurities. These spectral features are then compared to the output of a collisional-radiative model to infer plasma parameters (Te, ne) from the observed helium radiation. In order to investigate the systematic uncertainties of such a diagnostic, we present the results of a Bayesian treatment of a helium collisional-radiative model (Schmitz et al., 2008) using synthetic data modeled after an existing system on the plasma experiment Wendelstein 7-X (Barbui et al. 2016). From this study, we present a new method for comprehensively combining measurement uncertainties with underlying atomic rate parameter uncertainties in the inference of plasma parameters. Finally, we also demonstrate the utility of this Bayesian approach in targeting sensitivities within the model, allowing determination of high-priority atomic data for future refinement and comparison between differing atomic models.

This paper presents a novel method for the parameter estimation and model selection for the reconstruction of indoor environments based on sparse observations. While most approaches for the reconstruction of indoor models rely on dense observations, we predict scenes of the interior with high accuracy in the absence of indoor measurements. We use a model-based top-down approach and incorporate strong but profound prior knowledge. The latter includes probability density functions for model parameters and sparse observations such as room areas and the building footprint. The floorplan model is characterized by linear and bi-linear relations with discrete and continuous parameters. We focus on the stochastic estimation of model parameters based on a topological model derived by combinatorial reasoning in a first step. A Gauss-Markov model is applied for estimation and simulation of the model parameters. Symmetries are represented and exploited during the estimation process. Background knowledge as well as observations are incorporated in a maximum likelihood estimation and model selection is performed with AIC/BIC. The likelihood is also used for the detection and correction of potential errors in the topological model. Estimation results are presented and discussed.

This paper introduces a novel method for the automatic derivation of building floorplans and indoor models. Our approach is based on a logical and stochastic reasoning using sparse observations such as building room areas. No further sensor observations like 3D point clouds are needed. Our method benefits from an extensive prior knowledge of functional dependencies and probability density functions of shape and location parameters of rooms depending on their functional use. The determination of posterior beliefs is performed using Bayesian Networks. Stochastic reasoning is complex since the problem is characterized by a mixture of discrete and continuous parameters that are in turn correlated by non-linear constraints. To cope with this kind of complexity, the proposed reasoner combines statistical methods with constraint propagation. It generates a limited number of hypotheses in a model-based top-down approach. It predicts floorplans based on a-priori localised windows. The use of Gaussian mixture models, constraint solvers and stochastic models helps to cope with the a-priori infinite space of the possible floorplan instantiations.

The acquisition of detailed information for buildings and their components becomes more and more important. However, an automatic reconstruction needs high-resolution measurements. Such features can be derived from images or 3D laserscans that are e.g. taken by unmanned aerial vehicles (UAV). Since this data is not always available or not measurable at the first for example due to occlusions we developed a reasoning approach that is based on sparse observations. It benefits from an extensive prior knowledge of probability density distributions and functional dependencies and allows for the incorporation of further structural characteristics such as symmetries. Bayesian networks are used to determine posterior beliefs. Stochastic reasoning is complex since the problem is characterized by a mixture of discrete and continuous parameters that are in turn correlated by nonlinear constraints. To cope with this kind of complexity, the implemented reasoner combines statistical methods with constraint propagation. It generates a limited number of hypotheses in a model-based top-down approach. It predicts substructures in building facades – such as windows – that can be used for specific UAV navigations for further measurements.

Background: The burgeoning interest in implant and regenerative dental care has led to a notable upsurge in the utilization of regenerative modalities. The intent of the present investigation was to evaluate the osteogenic ability of two different concentrated platelet groups at various concentrations in the human osteosarcoma MG–63 cell line. Materials and Methods: Blood samples from 21 volunteers with chronic periodontitis were collected which were then centrifuged in accordance with the protocols of Choukroun et al. and Miron et al. to produce leukocyte- and platelet-rich fibrin (L-PRF) and injectable platelet-rich fibrin (I-PRF), respectively. Following MG-63 cell culture, the osteogenic ability of 0, 4%, and 20% concentrations of both L-PRF and I-PRF were determined using the real-time polymerase chain reaction assay. Results: The results showed that 20% I-PRF (1.52 ± 0.24) and 4% L-PRF (1.42 ± 0.37) had the highest amount of bone morphogenetic protein 2 and osteocalcin, respectively. Conclusion: I-PRF appears to promote the initial differentiation of cells.

Chemical reactivity of the superheavy elements nihonium (Nh, element 113) and moscovium (Mc, element 115) has been studied by the gas-solid chromatography method using a new combined chromatography and detection setup. The Mc isotope, 288Mc, was produced in the nuclear fusion reaction of 48Ca ions with 243Am targets at the GSI Helmholtzzentrum Darmstadt, Germany. After isolating 288Mc ions in the gas-filled separator TASCA, adsorption of 288Mc and its decay product 284Nh on silicon oxide and gold surfaces was investigated. As a result of this work, the values of the adsorption enthalpy of Nh and Mc on the silicon oxide surface were determined for the first time, −∆HadsSiO2Mc=54−5+11 kJ/mol and −∆HadsSiO2Nh=58−3+8 kJ/mol (68% c.i.). The obtained −ΔHads values are in good agreement with results of advanced relativistic calculations. Both elements, Nh and Mc, were shown to interact more weakly with the silicon oxide surface than their lighter homologues Tl and Bi, respectively. However, Nh and Mc turned out to be more reactive than the neighbouring closed-shell and quasi-closed-shell elements copernicium (Cn, element 112) and flerovium (Fl, element 114), respectively. The established trend is explained by the influence of strong relativistic effects on the valence atomic orbitals of these elements.

Abstract Fluorescence‐based sensing is a promising method for detecting trace quantities (vapors) of chemical threats. However, direct detection at standard temperature and pressure of chemicals with low volatilities, such as the salts of illegal drugs, is difficult to achieve. Herein, the development of a testing platform designed to maximize the response from fluorescent material detection of low volatility analytes, using the salts of illicit drugs as exemplars, is described. The challenges encountered in detecting low‐volatility analytes are highlighted, and the hardware solutions employed to overcome them are detailed. The testing platform is composed of a swab heating unit, a sensing chamber, and optical components that enable detection of illicit drugs via a fluorescence quenching mechanism. The swab heating unit facilitates volatilization of the analytes, with the shape of the sensing chamber and its fabrication material optimized to maximize the interaction of the analyte with the sensing element, increasing sensitivity. The detection platform is able to detect trace amounts (down to 30 ng) of (±)‐3,4‐methylenedioxyamphetamine hydrochloride (MDA•HCl), along with other common illicit drug salts such as cocaine hydrochloride (cocaine•HCl), fentanyl•HCl, and methamphetamine•HCl (MA•HCl).

Trials in the Condamine-Balonne basin, Australia, compared 11 promising perennial pasture grass accessions (4 Bothriochloa, 2 Cenchrus, 2 Urochloa and 1 each of Digitaria, Eragrostis and Panicum species) against the best similar commercial cultivars on the basis of ease of establishment from seed, persistence once established, forage yield and ease of seed production. Accessions sown at a site were determined by prior experience with them on a range of soils. High quality seed was relatively easy to produce for both Urochloa species and for Eragrostis curvula CPI 30374 but problematic for the Bothriochloa spp. Once established, all accessions persisted for 3–5 years and most were well grazed, but adequate establishment was sometimes a problem with Panicum stapfianum and Bothriochloa ewartiana. The dry matter yield ratings of the non-commercial lines were similar to those of the commercial equivalents of the same species. While agronomically valuable, none of the promising new grasses was considered worthy of commercialization at this point because their strengths did not warrant the setting up of a seed-production business in competition with current commercial enterprises. Long-standing cultivars such as Gayndah buffel and Nixon sabi grass continued to exhibit their superior pasture qualities.Keywords: Herbicide tolerance, persistence, forage yield, establishment ease, commercialization, seed production.DOI: 10.17138/TGFT(3)15-26

Background: Sarcopenia is a muscle disease characterized by reduction of muscle strength and muscle mass. In RA, 25.9 to 43.3% of the patients present sarcopenia. The loss of muscle mass observed in RA patients occurs either by activation of catabolic pathways or by inhibition of anabolic pathways. Despite having a list of drugs capable of treating RA inflammation, their effect on muscle is unclear. Our objective was to evaluate the tofacitinib effect on the muscle mass of collagen-induced arthritis (CIA) mice., Methods: CIA was induced in male DBA/1J mice by subcutaneous injection of Type 2 Collagen plus Freund Adjuvant. Animals were randomized into 3 groups: CIA + tofacitinib; CIA + vehicle; and healthy controls. Treatment was administered twice a day, between days 18 and 45 after induction. Clinical score, edema, and body weight were evaluated during the experimental period. After euthanasia, tibiotarsal joints were collected for assessment of disease histopathological score, and tibialis anterior (TA) and gastrocnemius (GA) muscles were weighed to assess muscle mass. Muscle atrophy was evaluated by measurement of TA myofiber cross-sectional area (CSA). Protein expression was evaluated by western blot using GA homogenates. Serum inflammatory markers were evaluated by ELISA. Statistical analysis included ANOVA followed by Tukey's or with Kruskal-Wallis. The statistical difference was assumed for p < 0.05., Results: Tofacitinib treatment decreased arthritis severity by reducing clinical score, and hind paw edema in comparison with the vehicle group. Tofacitinib showed weight gain, higher TA and GA weights, and increased CSA compared to the vehicle group. On day 45, Tofacitinib presented increased muscle strength compared to the vehicle group, however, no difference was found in muscle fatigue. Pax7 expression was unchanged, while MyoD expression showed an increasing trend, and myogenin expression was significantly increased in Tofacitinib compared to vehicle and control groups. The treatment didn't modify Murf-1 expression. Tofacitinib mice showed decreased serum levels of TNF and increased IL-6 serum levels., Conclusion: Tofacitinib attenuated muscle loss in arthritic mice, increased muscle weight and muscle CSA. Activation of satellite cell regeneration, based on the increased expression of myogenin, is a potential mechanism involved in tofacitinib action against muscle loss., Competing Interests: Declarations Ethical approval This study was approved by the Research Ethics Committee of the Hospital de Clínicas de Porto Alegre (protocol number 18-0302). Patient and public involvement Not applicable. Conflict of interest Thales Hein da Rosa, Bárbara Bartikoski, Rafaela Cavalheiro do Espírito Santo, Mirian Farinon, Jordana Miranda de Souza Silva, Renata Ternus Pedo, Maria Luísa Gasparini, Thaís Karnopp, Leonardo Santos, Gustavo Chapacais, Andressa Di Domenico, Sofia Loch: None declared, Ricardo Xavier Grant/research support from Pfizer Grant 60289911., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background People living with HIV have higher sudden cardiac death (SCD) rates compared with the general population. Whether HIV infection is an independent SCD risk factor is unclear. Methods and Results This study evaluated participants from the Veterans Aging Cohort Study, an observational, longitudinal cohort of veterans with and without HIV infection matched 1:2 on age, sex, race/ethnicity, and clinical site. Baseline for this study was a participant's first clinical visit on or after April 1, 2003. Participants were followed through December 31, 2014. Using Cox proportional hazards regression, we assessed whether HIV infection, CD4 cell counts, and/or HIV viral load were associated with World Health Organization (WHO)-defined SCD risk. Among 144 336 participants (30% people living with HIV), the mean (SD) baseline age was 50.0 years (10.6 years), 97% were men, and 47% were of Black race. During follow-up (median, 9.0 years), 3035 SCDs occurred. HIV infection was associated with increased SCD risk (hazard ratio [HR], 1.14; 95% CI, 1.04-1.25), adjusting for possible confounders. In analyses with time-varying CD4 and HIV viral load, people living with HIV with CD4 counts <200 cells/mm 3 (HR, 1.57; 95% CI, 1.28-1.92) or viral load >500 copies/mL (HR, 1.70; 95% CI, 1.46-1.98) had increased SCD risk versus veterans without HIV. In contrast, people living with HIV who had CD4 cell counts >500 cells/mm 3 (HR, 1.03; 95% CI, 0.90-1.18) or HIV viral load <500 copies/mL (HR, 0.97; 95% CI, 0.87-1.09) were not at increased SCD risk. Conclusions HIV infection is associated with increased risk of WHO-defined SCD among those with elevated HIV viral load or low CD4 cell counts.

Neural stem cells (NSCs) in the adult mouse hippocampus occur in a specific neurogenic niche, where a multitude of extracellular signaling molecules converges to regulate NSC proliferation as well as fate and functional integration. However, the underlying mechanisms how NSCs react to extrinsic signals and convert them to intracellular responses still remains elusive. NSCs contain a functional endocannabinoid system, including the cannabinoid type-1 receptor (CB1). To decipher whether CB1 regulates adult neurogenesis directly or indirectly in vivo, we performed NSC-specific conditional inactivation of CB1 by using triple-transgenic mice. Here, we show that lack of CB1 in NSCs is sufficient to decrease proliferation of the stem cell pool, which consequently leads to a reduction in the number of newborn neurons. Furthermore, neuronal differentiation was compromised at the level of dendritic maturation pointing towards a postsynaptic role of CB1 in vivo. Deteriorated neurogenesis in NSC-specific CB1 knock-outs additionally resulted in reduced long-term potentiation in the hippocampal formation. The observed cellular and physiological alterations led to decreased short-term spatial memory and increased depression-like behavior. These results demonstrate that CB1 expressed in NSCs and their progeny controls neurogenesis in adult mice to regulate the NSC stem cell pool, dendritic morphology, activity-dependent plasticity, and behavior.

Research on the antiepileptic effects of (endo-)cannabinoids has remarkably progressed in the years following the discovery of fundamental role of the endocannabinoid (eCB) system in controlling neural excitability. Moreover, an increasing number of well-documented cases of epilepsy patients exhibiting multi-drug resistance report beneficial effects of cannabis use. Pre-clinical and clinical research has increasingly focused on the antiepileptic effectiveness of exogenous administration of cannabinoids and/or pharmacologically induced increase of eCBs such as anandamide (also known as arachidonoylethanolamide [AEA]). Concomitant research has uncovered the contribution of neuroinflammatory processes and peripheral immunity to the onset and progression of epilepsy. Accordingly, modulation of inflammatory pathways such as cyclooxygenase-2 (COX-2) was pursued as alternative therapeutic strategy for epilepsy. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide related to the centrally and peripherally present eCB AEA, and is a naturally occurring nutrient that has long been recognized for its analgesic and anti-inflammatory properties. Neuroprotective and anti-hyperalgesic properties of PEA were evidenced in neurodegenerative diseases, and antiepileptic effects in pentylenetetrazol (PTZ), maximal electroshock (MES) and amygdaloid kindling models of epileptic seizures. Moreover, numerous clinical trials in chronic pain revealed that PEA treatment is devoid of addiction potential, dose limiting side effects and psychoactive effects, rendering PEA an appealing candidate as antiepileptic compound or adjuvant. In the present study, we aimed at assessing antiepileptic properties of PEA in a mouse model of acute epileptic seizures induced by systemic administration of kainic acid (KA). KA-induced epilepsy in rodents is assumed to resemble to different extents human temporal lobe epilepsy (TLE) depending on the route of KA administration; intracerebral (i.c.) injection was recently shown to most closely mimic human TLE, while systemic KA administration causes more widespread pathological damage, both in brain and periphery. To explore the potential of PEA to exert therapeutic effects both in brain and periphery, acute and subchronic administration of PEA by intraperitoneal (i.p.) injection was assessed on mice with systemically administered KA. Specifically, we investigated: (i) neuroprotective and anticonvulsant properties of acute and subchronic PEA treatment in KA-induced seizure models, and (ii) temporal dynamics of eCB and eicosanoid (eiC) levels in hippocampus and plasma over 180 min post seizure induction in PEA-treated and non-treated KA-injected mice vs. vehicle injected mice. Finally, we compared the systemic PEA treatment with, and in combination with, pharmacological blockade of fatty acid amide hydrolase (FAAH) in brain and periphery, in terms of anticonvulsant properties and modulation of eCBs and eiCs. Here, we demonstrate that subchronic administration of PEA significantly alleviates seizure intensity, promotes neuroprotection and induces modulation of the plasma and hippocampal eCB and eiC levels in systemic KA-injected mice.

The endocannabinoid (eCB) system possesses neuromodulatory functions by influencing the release of various neurotransmitters, including γ-aminobutyric acid (GABA) and glutamate. A functional interaction between eCBs and the serotonergic system has already been suggested. Previously, we showed that cannabinoid type-1 (CB1) receptor mRNA and protein are localized in serotonergic neurons of the raphe nuclei, implying that the eCB system can modulate serotonergic functions. In order to substantiate the physiological role of the CB1 receptor in serotonergic neurons of the raphe nuclei, we generated serotonergic 5-hydroxytryptamine (5-HT) neuron-specific CB 1 receptor-deficient mice, using the Cre/loxP system with a tamoxifen-inducible Cre recombinase under the control of the regulatory sequences of the tryptophan hydroxylase 2 gene (TPH2-CreER (T2)), thus, restricting the recombination to 5-HT neurons of the central nervous system (CNS). Applying several different behavioral paradigms, we revealed that mice lacking the CB1 receptor in serotonergic neurons are more anxious and less sociable than control littermates. Thus, we were able to show that functional CB1 receptor signaling in central serotonergic neurons modulates distinct behaviors in mice.

Samples of whole seeds, isolated endosperms including the aleurone layer and isolated embryos with attached scutellum from an industrial scale barley malting process (variety Braemar) were analysed for their water soluble metabolites by gas chromatography-mass spectrometry (GC-MS). 73 known metabolites and about 350 unknown signals were detected. Principal component analysis (PCA) showed a time dependent shift of sample profiles. Whole seeds and endosperm samples showed very similar patterns with nearly all compounds rising until the end of germination. In the embryos a maximum concentration of compounds was reached after 72-96 h of malting. Most concentrations decreased afterwards. The kilning step, namely the drying and roasting of germinated seeds, induced variable effects of increases, stability or decreases of metabolites and thereby separated kilned samples from germinated seeds in the PCA. A second barley cultivar (Quench) underwent the same malting and analysis procedures and gave nearly identical results. Fructose, malate, myo-inositol and raffinose exhibited the potential to serve as markers for specific developmental stages of seeds in both varieties. Biological markers represent targets for industrial process control. Their potential application would meet the maltsters' demand to flatten variances in germination properties and to produce equal composed malt by directed malting management., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Virus-infected cells are eliminated by cytotoxic T lymphocytes, which recognize viral epitopes displayed on major histocompatibility complex class I molecules at the cell surface. Herpesviruses have evolved sophisticated strategies to escape this immune surveillance. During the lytic phase of EBV infection, the viral factor BNLF2a interferes with antigen processing by preventing peptide loading of major histocompatibility complex class I molecules. Here we reveal details of the inhibition mechanism of this EBV protein. We demonstrate that BNLF2a acts as a tail-anchored protein, exploiting the mammalian Asna-1/WRB (Get3/Get1) machinery for posttranslational insertion into the endoplasmic reticulum membrane, where it subsequently blocks antigen translocation by the transporter associated with antigen processing (TAP). BNLF2a binds directly to the core TAP complex arresting the ATP-binding cassette transporter in a transport-incompetent conformation. The inhibition mechanism of EBV BNLF2a is distinct and mutually exclusive of other viral TAP inhibitors.

Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I-restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL 49.5 proteins of the varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL 49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL 49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL 49.5 proteins block TAP as well, these data indicate that UL 49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL 49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL 49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL 49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL 49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL 49.5. Taken together, these results classify the UL 49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms.

Cytotoxic T lymphocytes eliminate infected cells upon surface display of antigenic peptides on major histocompatibility complex I molecules. To promote immune evasion, UL49.5 of several varicelloviruses interferes with the pathway of major histocompatibility complex I antigen processing. However, the inhibition mechanism has not been elucidated yet. Within the macromolecular peptide-loading complex we identified the transporter associated with antigen processing (TAP1 and TAP2) as the prime target of UL49.5. Moreover, we determined the active oligomeric state and crucial elements of the viral factor. Remarkably, the last two residues of the cytosolic tail of UL49.5 are essential for endoplasmic reticulum (ER)-associated proteasomal degradation of TAP. However, this process strictly requires additional signaling of an upstream regulatory element in the ER lumenal domain of UL49.5. Within this new immune evasion mechanism, we show for the first time that additive elements of a small viral factor and their signaling across the ER membrane are essential for targeted degradation of a multi-subunit membrane complex.

The inhibitory effect of the intravenous anaesthetic ketamine on CaCl2-induced contractions in the isolated K+-depolarized uterus of the rat in Ca2+-free medium was compared with that produced by papaverine, theophylline and the calcium entry blocker verapamil. Pre-incubation for 20 min with either ketamine (0.3 to 3 mM), papaverine (3 to 30 microM), theophylline (0.1 to 1 mM) or verapamil (3 to 30 nM) induced parallel, concentration-dependent rightward displacements of the dose-response curves to Ca2+ (0.04 to 22 mM). The antagonism was competitive, except that due to verapamil, the Schild plot for which yielded a slope which differed significantly from unity. The calculated pA2 values (+/- s.e.mean) were: ketamine 3.90 +/- 0.07; papaverine 5.55 +/- 0.05; theophylline 3.99 +/- 0.1 and verapamil 9.54 +/- 0.24. These drugs differed in their ability to relax the sustained contraction induced by Ca2+ (1 mM) in K+-depolarizing solution. Ketamine and verapamil relaxed the preparation in a concentration-dependent manner whereas theophylline and especially papaverine were less potent and induced only partial maximal relaxation. The t1/2 of the relaxant effect was significantly less for ketamine than for verapamil (5 and 22 min, respectively). Only ketamine produced a relaxation comparable to that obtained by washing the preparation with Ca2+-free solution (t1/2 = approx. 5 min). Prior exposure of the depolarized uterine strip to a low concentration of Ca2+ (0.22 mM) increased the potency of ketamine, but decreased that of papaverine and theophylline, in antagonizing Ca2+ induced contractions. In contrast, this procedure did not affect the potency of verapamil. 5 The inhibitory effects of these drugs, excluding those of verapamil, were completely reversed after washing the preparations with a high-potassium Ca2+-free solution, 3-5 times for about 30-60 min. 6 These experiments provide further evidence that the relaxant effect produced by ketamine on the rat isolated uterus is due to its ability to antagonize Ca2+ movements competitively and also show that there are marked differences between the nature of the relaxant effects of ketamine and those of papaverine, theophylline and verapamil.