Affordances, the opportunity for action offered by the environment to an agent, are vital for meaningful behavior and exist in every interaction with the environment. Regarding its temporal mechanism, some studies suggest that affordance perception is an automated process that is independent from the visual context and bodily interaction with the environment, while others argue that it is modulated by the visual and motor context in which affordances are perceived. We aims to resolve this debate by examining affordance automaticity from the perspective of sensorimotor time windows. We replicated a previous study on affordance perception in which participants actively moved through doors of different width in VR environments. To investigate the impact of different forms of bodily interactions with an environment, i.e., the movement context (physical vs. joystick movement), we used the identical virtual environment from Djebbara and colleagues (2019) but displayed it on a 2D screen with participants moving through different wide doors using the laptop keyboard. We compared components of the event-related potential (ERP) from the continuously recorded electroencephalogram (EEG) that were previously reported to be related to affordance perception of architectural transitions (passable and impassable doors). Comparing early sensory and later motor-related ERPs, our study replicated ERPs reflecting early affordance perception but found differences in later motor-related components. It indicates a shift from automated perception of affordances during early sensorimotor time windows to movement context dependence of affordance perception at later stages suggesting that affordance perception is a dynamic and flexible process that changes over sensorimotor stages.

Endometrial cancer is the most prevalent gynaecological cancer globally. Its association with obesity and metabolic diseases is a key aetiology, increasingly among younger females. Early diagnosis and improved treatment decisions are crucial for these women whose outcomes could be improved by discovering new biomarkers. We took a new approach to extracellular vesicle (EV) biomarker discovery - profiling the proteome of enriched EVs isolated directly from frozen biobanked endometrial cancers. Nine tissue pools, each generating collagenase-digested tissue and matched small EVs, were analysed using label-free proteomics. Three clinical subgroups: Endometrioid low BMI (body mass index), Endometrioid high BMI, and Serous, irrespective of BMI, were compared to identify shared secreted proteins, proteins associated with histological subtype, and proteins related to BMI. EVs were enriched for common EV markers and large secreted proteins. Cell lysates were enriched in mitochondrial and blood proteins. EV protein profiles were most different between the high BMI subgroup and the others, highlighting a significant influence of comorbidities on the intra-tumoural EV secretome. Proteins differentially abundant between subgroups in tissues were strikingly not also differential in the matched EVs. This work has identified secreted proteins implicated in the complex pathophysiology of endometrial cancer and pinpointed candidate biomarkers for diagnosis.

One of the most important management measures in foals is colostrum feeding in the first few hours after birth. The quality and quantity of colostrum play a pivotal role in the health of the foal. Low intake or intake of low-quality colostrum is one of the most significant factors leading to septicemia. Among the leading factors in producing low-quality colostrum are induced pregnancy and the early birth of the foal. A 14-day-old foal was referred with symptoms of lethargy, severe heartburn, lateral landing, dilatation of the ventricular space, and hypothermia. In the history obtained, the mother’s labour was induced by the veterinarian. One hour after referral, the foal died. Based on the laboratory and autopsy results, the cause of death was septicemia and peritonitis. Keyword(s): Colostrum - foal - septicemia - Salmonella.

Plasmonic gratings provide an advantageous platform for fluorescence sensing due to their compatibility with functionalization techniques, imaging detection, and the potential for signal enhancement. Among traditional fluorescence detection methods, microscopes are commonly used tools. The interaction between dye fluorescence processes and the plasmonic modes of the grating strongly depends on the measurement configuration and is influenced by the dispersion and spectral characteristics of the plasmonic modes. In our study, we investigated the angular behavior of the fluorescence emission from ATTO700 dye by varying the collection angle using a standard optical microscope coupled with a spectrometer. Our results show a clear dependence of fluorescence emission in terms of spectral shape on the collection angle that can be attributed to plasmonic mode dispersion.

The paper suggests a compound control that combines nonlinear flatness, active disturbance rejection control (ADRC), and sliding mode control (SMC). By employing the differential flatness methodology, the standard under-actuated wheeled mobile robot model is converted into a fully actuated one. Utilizing this model as a basis, a sliding feedback controller is suggested to address the issue of uncertainties associated with wheel slip and wind. However, as the uncertainties increase, a higher control input is required, resulting in an undesired chattering phenomenon. To reduce chattering in SMC, a boundary layer surrounding the switching surface is employed, and a continuous law is implemented within the boundary. The boundary layer width plays an important role in improving robustness and eliminating chatter. Indeed, increasing the thickness of the boundary layer significantly reduces chattering, but it may lead to a loss of robustness performance achieved by the discontinuous control provided by SMC. To resolve this problem, active disturbance rejection control is combined with boundary layer sliding mode control. When utilizing the ADRC method, the lumped uncertainties are estimated via an extended state observer and eliminated within the feedback loop. The newly obtained feedback control combines the advantages of boundary layer SMC and ADRC to achieve practical control and robust tracking performance. The stability properties exhibited by the closed-loop system are rigorously established through the application of Lyapunov theory. In conclusion, a series of simulations has been conducted to compare and evaluate the efficiency of the presented robust tracking controller against other existing control methods.

Objective: This research study aims to assess the status of cervical vestibular evoked myogenic potentials (cVEMP) in patients diagnosed with cervical discopathy and experiencing different types of vertigo. Cervical discopathy is a common condition characterized by disc degeneration and herniation in the cervical spine. Vertigo, a symptom of vestibular dysfunction, can be caused by various factors including cervical discopathy. However, the relationship between cervical discopathy and different types of vertigo remains unclear. Design: The study will recruit a sample of patients diagnosed with cervical discopathy, and presenting with different types of vertigo. The cVEMP test will be conducted to evaluate the vestibular function specifically related to the cervical disc status. The cVEMP test involves measuring the muscular responses of the sternocleidomastoid muscle in response to auditory stimuli. Result: The primary outcomes of this study include the assessment of cVEMP parameters such as peak-to-peak amplitudes and latencies in patients with cervical discopathy and various types of vertigo. These parameters will be compared with a control group of individuals without cervical discopathy or vertigo. Additionally, the study will explore potential correlations between cVEMP findings and clinical symptoms and characteristics related to cervical discopathy. Conclusion: The results of this research will provide valuable insights into the vestibular function associated with cervical discopathy and different types of vertigo. The findings may contribute to the understanding of the pathophysiology of vertigo in patients with cervical discopathy and help develop targeted management strategies. Ultimately, this study aims to improve the diagnosis and treatment of patients experiencing vertigo associated with cervical spine disorders.

For measuring the planar microstrip patch antenna in millimeter-wave frequency range, the transition is usually required to connect to the waveguide interface of frequency extender then a vector network analyzer. The conventional solution is a two-stages transition by a waveguide-to-coaxial transition as a first stage and an end-launch adaptor as the second. Some works had proposed a directly transition from a waveguide interface to a planar microstrip interface. But the transitions of in-line structure will easily scattering that will affect the measured results, and the vertical structure will encounter the trade-off from the size of back cavity and the bandwidth performance. In this paper, a vertical type, waveguide-to-microstrip (W2ML) transition structure is proposed by the adoption of an aperture-stacked microstrip patch antenna (ASMPA) to have the performance of ultra-wide bandwidth and miniaturize the size. In addition, the characteristic of ASMPA W2ML transition can easily been by one-kit de-embedding method that only THRU calibration kit with time gating process is required. The consistency of the simulated result compared to the measured-calculated result exhibit the effectiveness of the proposed ASMPA W2ML transition for measuring a real planar microstrip patch antenna in millimeter-wave band.

In this scholarly analysis, we aim to address the inaccuracies and unsupported claims presented in the paper “Math. Meth. Appl. Sci. 2023;1–3,”’authored by Elsayed M. E. Zayed and Shoukry El-Ganaini. Their paper [1] asserts that the authors of “Math Meth Appl Sci. 2021;44:2682–2691”employed the Khater method to solve the nonlinear fractional Cahn–Allen equation. It is imperative to emphasize that this claim lacks validity. Contrarily, upon a meticulous examination of our own work [2], we find that Mostafa M. A. Khater, Ahmet Bekir, Dianchen Lu, and Raghda A. M. Attia employed the modified Khater method, a robust computational technique recently introduced by Prof. Mostafa M. A. Khater. This assertion is substantiated by a substantial body of Prof. Mostafa M. A. Khater’s work (as cited in references [3–6]). These findings unmistakably contradict the assertions made in “Math. Meth. Appl. Sci. 2023, ”which erroneously claim the utilization of the Khater method. It is also of utmost importance to address the implications of these inaccuracies. The claims put forth by Zayed and El-Ganaini not only misrepresent the actual methodology used but also erroneously question the authorship of the modified Khater method, implying that it does not originate from Prof. Mostafa M. A. Khater. To counter this assertion, we emphasize Prof. Khater’s extensive publication history, which indisputably demonstrates his scholarly contributions employing the modified Khater method in the years 2018 and 2019 (as thoroughly documented in references [3–6]). In summary, our analysis underscores the discrepancies and ethical concerns within the aforementioned paper, asserting that it not only misrepresents the methodology employed but also inaccurately questions the ownership of the modified Khater method. This casts doubt on the integrity of the authors’ claims, suggesting an unwarranted attempt to appropriate the contributions of another researcher.

A document by Ahmed Alanzi. Click on the document to view its contents.

65-year-old man was referred to the Oral Medicine Department by his General Dental Practitioner for investigation of a swelling in the anterior maxilla, which had been present for 6 weeks and associated with mobility in the upper central incisors

The existing ripeness detection algorithm for strawberries suffers from low detection accuracy and high detection error rate. Considering these problems, we propose an improvement method based on YOLOv5, which firstly reconfigures the feature extraction network by replacing ordinary convolution with hybrid depth deformable convolution. In the second step, a double cooperative attention mechanism is constructed to improve the representation of strawberry features in complex environments. Finally, cross-scale feature fusion is proposed to fully integrate the multiscale target features. The method was tested on the strawberry ripeness dataset, the mAP reached 95.6 percentage points, the FPS reached 76, and the model size was 7.44M. The mAP and FPS are 8.4 and 1.3 percentage points higher respectively than the baseline network. The model size is reduced by 6.28M. This method is superior to many state-of-the-art algorithms in terms of detection speed and accuracy. The system can accurately identify the ripeness of strawberries in complex environments, which could provide technical support for automated picking robots.

This manuscript is devoted to a derivative-free parametric iterative step to obtain roots simultaneously for both nonlinear systems and equations. We prove that when it is added to an arbitrary scheme, it doubles the convergence order of the original procedure and defines a new algorithm that obtains several solutions simultaneously. Different numerical experiments are carried out to check the behaviour of the iterative methods by changing the value of the parameter and the initial guesses. Also, it is perform a numerical example where the dynamical planes are carried out to see and compare the basins of attraction.

An easy-to-implement noise estimation method for tuning state estimators is proposed. It outperforms benchmark methods in terms of accuracy or computational cost both in theory and in a case study. We assume parametric uncertainty in the process model, which we transform into noise statistics using the generalized unscented transformation (GenUT). While most other methods estimate only the noise covariance, we also estimate the mean. Our tuning method is suitable for input-output models, demonstrated through a case study involving process simulators and industrial data. We present a theoretical analysis of our method, which is based on splitting one large GenUT to two smaller GenUTs. This results in two theorems: i) mean approximations for the two systems are equal and ii) covariance approximations are similar under certain mild conditions. These theorems confirm the validity of our method, and we discuss their potential to realize a numerically stable GenUT for high-dimensional systems.

ABSTRACT OBJECTIVE: To detect serum placental growth factor levels and uterine artery doppler pulsatility index for predicting pre-eclampsia and assess their association with the severity of pre-eclampsia. DESIGN: Prospective observational study SETTING: Tertiary care centre POPULATION: All antenatal women from 11 to 13+6weeks gestation attending antenatal clinic during study period. METHODS: This involved 160 antenatal women, from 11-13+6 weeks gestation. Serum PlGF levels and UA doppler mean P.I measured and patients were followed up upto delivery and observed for the development of pre-eclampsia and its severity. MAIN OUTCOME MEASURES: PIGF Value cut-off was 40.33pg/ml with the sensitivity of 97.5 % and Specificity was 98.3%. For the PI Value of 1.85 the sensitivity was found to be 74.4% and Specificity was found to be 92.5%. RESULTS: Mean serum PlGF levels for pre-eclampsia patients was 25.09pg/ml and for normotensive patients mean PlGF level was 65.05pg/ml. Mean UA doppler P.I for pre-eclampsia patients was 2.02 and for normotensive patients was 1.39. Mean PI value increased with increasing severity of preeclampsia. CONCLUSION: Early recognition of women will help initiation of prophylactic measures and enhanced surveillance. First trimester UA Doppler with serum PlGF together with maternal characteristics can be used as a reliable screening test for preeclampsia prediction and to reduce feto-maternal morbidity KEYWORDS: uterine artery (UA) doppler pulsality index (P.I), placental growth factor levels(PlGF), pre-eclampsia, eclampsia

This research explores the effects of thermal and solute buoyancy forces on the unsteady boundary-layer (BL) stream through an upright porous flat plate with heat generation. The investigated fluid is viscid, impermeable, and electrically conductive. Thermo and solute buoyancy forces cause the mechanisms of thermal and material transfer. The nonlinear time-dependent partial differential equations (PDEs) about continuity, momentum, energy, and concentration are examined through suitable modifications. After mathematical modeling, an explicit finite difference method (EFDM) is used to solve a group of nonlinear dimensionless PDEs and appropriate boundary conditions. The detailing of the EFDM procedure due to the considered model is well-stated step by step. The validity of EFDM coding is conducted by reproducing similar previously available results. The mathematical formulation, stability, and convergence explored are also recognized. Searching for an appropriate uniform meshing and steady state condition is performed carefully. The existence of the pertinent parameters in this finite difference modeling is also checked. The thermo-physical consequences of inflowing physical values (buoyancy force and heat generation) on the velocity, temperature, and concentration distribution are scrutinized. The deviations in local and average skin friction coefficients, heat, and material transfer rates are also examined for physical curiosity in engineering research. The above-illustrated model equations are numerically simulated using LAHEY FORTRAN 95 v6.2. For graphical representation, Tecplot 365, and for data analysis, Microsoft Excel 2023 are used. The significant finding of this research reveals that the fluid velocity upsurges as the buoyancy intensifies, and the rising temperature generation enhances the thermal-material transport rates. The observed behavior is attributed to the thermal buoyancy force, which produces a pressure gradient. To compare the current modeling result, we correlate these findings to those of other research available in the literature.

Objective: This qualitative study investigated perspectives on causes of eating disorders as experienced by those caring for affected individuals with an eating disorder in New Zealand. Method: Participants were nine carers of affected individuals, recruited from an online survey, who consented to semi-structured qualitative interviews. Inductive thematic analysis was undertaken to identify themes from the data. Results: The overall theme informed by the data was ‘It’s complicated’, reflecting carer perspectives that eating disorder causes were complex and multifactorial. This theme was supported by sub-themes of; ‘it’s like Swiss cheese’; ‘it came out of the blue’ and ‘in hindsight maybe…’. Most participants indicated potential eating disorder causes had not been formally explored with treatment teams, although carers had reflected on possible causality across the treatment journey. Conclusion: All participants expressed uncertainty when reflecting on what factor(s) may have caused an eating disorder in their family member. Participants reflected that causes were likely a complex combination of environmental, social, psychological and biological influences. Future research would benefit from data analysis of dyads of carers and affected individuals who identify significant recovery from the eating disorder, in order to reflect back upon possible causes without the demands of treatment or continuing eating disorder symptomatology.

Phostensin (PTS) encoded by KIAA1949 is a scaffold protein. It can bind to protein phosphatase 1 (PP1), F-actin, Eps 15 homology domain-containing protein 1 (EHD1) and EHD4. PTS contains both PP1-binding and actin-binding motifs. Most EHD-binding proteins contain a consensus motif, Asn-Pro-Phe (NPF) motif, which interacts with the C-terminal EH domain of EHD proteins. Nevertheless, the NPF motif is absent in PTS. The binding motif for PTS to associate with EHD1 (or EHD4) remains unknown. Here, we used structure-function, far western blotting and GST pull-down assays to investigate this issue and identified that PTS-α binds to EHD1 (or EHD4) through the region of residues 60-80 which contains a consensus motif, 64ILV(X) 4(L/V)RL 74S. This novel motif was also found in the vacuolar protein sorting 35 (vps35) of retromer, an EHD1-associating complex and regulating retrograde trafficking, Replacement of 64ILV(X) 4(L/V)RL 74S with 64AAA(X) 4(L/V)RL 74S or with 64ILV(X) 4AEA 74A significantly reduces the binding efficiency of PTS-α to either EHD1 or EHD4. Overexpression of the PTS-β in 293T cells attenuated the endocytic trafficking of transferrin. However, this attenuation of transferrin in endocytic trafficking was disrupted when 293T cells overexpressed the mutant PTS-β with a defective EHD-binding motif, suggesting that PTS-β can regulate the endocytic recycling via associating with EHD1 or EHD4.

Organisms from all kingdoms of life release membrane vesicles, which are tiny and spherical structures made of a lipid bilayer. Membrane vesicles carry out a number of functions, such as forming new cell membranes, removing waste products from the cell, and transporting lipids and other substances from parent to recipient cells. The payloads often contained in the vesicles are sorted via the endosomal sorting complex required for transport (ESCRT) pathway in a stepwise manner. Alterations to this endomembrane system reduces formation of vesicles and aberrant endosomal compartments. Furthermore, in pathogenic fungi, the deletion of ESCRT genes negatively effects virulence and growth, suggesting the ESCRT pathway has links to disease. However, only a few fungal species have to date been evaluated for the ESCRT pathway. In this review, we evaluate recent developments in the ESCRT pathway of fungi that infect plant hosts and its role in pathogenesis. This will provide an overview of EV-mediated cell-cell communication during host-pathogen interactions.

Understanding and predicting population responses to climate change is a crucial challenge. A key component of population responses to climate change are cases in which focal biological rates (e.g. population growth rates) change in response to climate change due to non-compensatory effects of changes in the underlying components (e.g. birth and death rates) determining the focal rates. We refer to these responses as non-compensatory climate change effects. As differential responses of biological rates to climate change have been documented in a variety of systems and arise at multiple levels of organization within and across species, non-compensatory effects may be nearly ubiquitous. Yet, how non-compensatory climate change responses combine and scale to influence the demographics of populations is often unclear and requires mapping them to the birth and death rates underlying population change. We provide a flexible framework for incorporating non-compensatory changes in upstream rates within and among species and mapping their consequences for additional downstream rates across scales to their eventual effects on population growth rates. Throughout we provide specific examples and potential applications of the framework. We hope this framework helps to enhance our understanding of and unify research on population responses to climate change.

The relationship between biodiversity and ecosystem function (BEF) captivates ecologists, but the factors responsible for the direction of this relationship remain unclear. While higher ecosystem functioning at higher biodiversity levels (‘positive BEF’) is not universal in nature, negative BEF relationships seem puzzlingly rare. Here, we develop a dynamical consumer-resource model inspired by microbial decomposer communities in pitcher plant leaves to investigate BEF. We manipulate microbial diversity via controlled colonization and measure their function as total ammonia production. We test how niche partitioning among bacteria and other ecological processes influence BEF in the leaves. We find that a negative BEF can emerge from reciprocal interspecific inhibition in ammonia production causing a negative complementarity effect, or from competitive hierarchies causing a negative selection effect. Absent these factors, a positive BEF was the typical outcome. Our findings provide a potential explanation for the rarity of negative BEF in empirical data.

In the Arctic tundra, recurrent periods of food scarcity force predators to rely on a wide variety of resources. In particular most predators use ungulate carcasses as an alternative food supply, especially in winters when live preys are scarce. As important and localized resource patches, carrion promotes co-occurrence of different individuals, and its use by predators is likely to be affected by interspecific competition. Here, we studied how interspecific competition and resource availability impact winter use of carrion by Arctic and red foxes in low Arctic Fennoscandia. We predicted that presence of red foxes limits Arctic foxes' use of carrion, and that the outcome of competition for carrion depends on the availability of alternative food resources, such as rodents. We monitored Arctic and red fox presence at experimentally supplied carrion using camera traps, between 2006 and 2021 in late winter. Using a multi-species dynamic occupancy model at a week-to-week scale, we evaluated use of carrion by foxes, while accounting for the presence of competitors, rodent availability and supplemental feeding provided to Arctic foxes. Competition primarily affected carrion use by increasing both species' probability to leave occupied carcasses to a similar extent, suggesting a symmetrical avoidance. Rodent abundance was associated with an increase in the probability of colonizing carrion for both species. For Arctic foxes, however, this increase was only observed in carcasses unoccupied by red foxes, showing greater avoidance when alternative preys are available. Contrary to expectations, we did not find strong signs of asymmetric competition for carrion in winter. Our results suggest that interactions for resources at a short time scale are not necessarily aligned with interactions at the scale of the population. In addition, we found that competition for carcasses depends on the availability of other resources, suggesting that interactions between predators depend on the ecological context.

Aim: Cancer treatment long-term complications for men include testicular dysfunction and possible infertility. Nonetheless, the evidence for this risk for various chemotherapies is insufficient. This is the case with bleomycin, which, aside from its well-studied lung toxicity, has received little research attention for its effect on male reproduction. This systematic review sought evidence for the effects of bleomycin-cancer treatment on testicular function and fertility. Methods: PubMed and Web of Science were searched using specific search terms, and seven animal studies met all inclusion criteria and provided an analysis of bleomycin gonadotoxicity. Results: Overall, the results suggest that bleomycin is gonadotoxic. It has the same effect on the nuclear DNA integrity of rodent sperm as it does on cancer cells. Bleomycin-induced changes in rodent testis histopathology are most noticeable at seminiferous tubule structure level. Bleomycin also significantly decreases rodents´ seminal conventional parameters and testosterone levels, the latter of which is consistent with increased induced degeneration of Leydig cells. Seminiferous tubule necrosis and alterations in tunica albuginea thickness in rodent testis are signs of a bleomycin-induced inflammatory process similar to the pulmonary one. Conclusion: More research, particularly human research, is required to provide strong evidence on how bleomycin affects human testicular function, including hormone function; and whether is gonadotoxic, whether it has a transient or permanent effect; how it may affect offspring; and how it can be reduced. Despite this, the current findings have important implications for clinicians in counseling patients about fertility risk and guiding requirements for fertility preservation strategies.

Background and Purpose: Various plant-derived compounds can activate immune responses against bacterial infections, and this property contributes to them being developed as effective and safe adjuvants for vaccines. In this study, the potential adjuvant effects of a galactolipid-enriched fraction generated from the medicinal plant Crassocephalum rabens (designated CRA) were evaluated. Experimental Approaches: Heat shock protein 60 of periodontal disease pathogen Actinobacillus actinomycetemcomitans (AaHSP60) was taken as an antigen and mixed with CRA. The AaHSP60/CRA mixture was then injected subcutaneously into the BALB/c mice. Titers and affinity of specific antibodies were measured by ELISA. Cytokine profiles in mouse serum or culture media of AaHSP60/CRA-treated splenocytes were analyzed by cytokine multiplex assay and ELISA kits. B cell differentiation and macrophage activation were determined by phenotyping. Key Results: CRA dramatically enhanced specific antibody titers and induced Ig class switch as shown by increases in the IgG2a, IgG2b and IgG3 proportions of total Ig in mouse serum. Furthermore, CRA-induced anti-AaHSP60 antibodies had cross-reactivity to other bacterial HSP60s. Cell based and animal results showed that CRA triggered IL-21 and B cell activating factor (BAFF) release that led to B cell differentiation. CRA also enhanced cell proliferation, uptake ability, and antigen presentation in mouse phagocytes. Conclusion and Implications: CRA served as a vaccine adjuvant that enhance mouse immunity against pathogenic antigens. CRA strengthened the activation and capabilities of phagocytes and B cells. Therefore, CRA may be a promising adjuvant for bacterial vaccines including periodontal disease.

Background and Purpose: The classical theory of receptor action has been used for decades as a powerful tool to estimate molecular determinants of ligand-induced receptor activation (i.e. affinity and efficacy) from experimentally observable biological responses. However, it is also a well-recognized fact that the receptor-binding and activation mechanisms, and the parameters thereof, described in the classical theory contradict with the modern view of receptor activation based on allosteric principles. Experimental Approach: We used mathematical analysis, along with some numerical simulations, to answer the key question as to what extent the classical theory is compatible -if at all- with the modern understanding of receptor activation. Key Results: Here, we showed conclusively that 1) receptor activation equations based on allosteric principles contain the logic of the classical theory in disguise, and therefore, 2) estimates of “intrinsic efficacy” () obtained by means of classical techniques (i.e. null methods or fitting the operational model to concentration-response data) are equivalent to the allosteric coupling factors that represent the molecular efficacy of ligands. Conclusion and Implications: Thus, we conclude that despite the right criticisms it has received so far, the classical theory may continue to be useful in estimating ligand efficacy from experimental data, if used properly. Here, we also provide rigorous criteria for the proper use of the theory. These findings not only have implications on ligand classification, but also resolve some long lasting discussions in the field of bias agonism in GPCR, which requires reasonable estimates of relative ligand efficacies at different signalling pathways.