Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel 2-substituted-5-(4-chloro-2-phenoxy)phenyl-1,3,4-oxadiazole derivatives, ligands of GABAA/benzodiazepine receptor complex: Design, synthesis, radioligand binding assay, and pharmacological evaluation

Agonists of Benzodiazepine (BZD) receptor are exhaustively used in the control of muscle spasms, seizure, anxiety, and insomnia. BZDs have some unwanted effects; therefore, the development of new BZD receptor agonists with better efficacy and fewer unwanted effects is one of the subjects of interest. In this study, based on the pharmacophore/receptor model of the BZD binding site of GABAA receptors, a series of new 2-substituted-5-(4-chloro-2-phenoxy)phenyl-1,3,4-oxadiazole derivatives (6a-f) were designed. Energy minima conformers of the designed compounds and diazepam were well matched in conformational analysis and showed proper interaction with the BZD-binding site of the GABAA receptor model (α1β2ϒ2) in docking studies. The designed compounds were synthesized in acceptable yield and evaluated for their in vitro affinity to the benzodiazepine receptor of rat brains by radioligand receptor binding assay. The results demonstrated that the affinities of most of the novel compounds were even higher than diazepam. The novel compound 6a with the best affinity in radioligand receptor binding assay (Ki=0.44 nM and IC50= 0.73±0.17 nM) had considerable hypnotic activity and weak anticonvulsant and anxiolytic effects with no negative effect on memory in animal models. Flumazenil as a selective benzodiazepine receptor antagonist was able to prevent hypnotic and anticonvulsant effects of 6a indicating the role of BZD receptors in these effects.
COBWEB THEORY, MARKET STABILITY, AND PRICE EXPECTATIONS

Contributors to cobweb theory include many leading economists of the twentieth century. From early beginnings in 1930, cobweb theory played a key role in evolving perceptions of market stability arising from recursive linear models with endogenous dynamics. The focal point of this evolution in cobweb theory is the transition from naive to adaptive to rational price expectations. After a review of the prehistory, this paper examines the first wave of linear cobweb theory initiated by Jan Tinbergen, Henry Schultz, and Umberto Ricci and proceeds to consider the evolution of price expectations in the second wave of cobweb models associated with endogenous cycles in commodity markets. The role of modern cobweb theory in discussions about the stability of market equilibrium and the connection to processes with rational expectations is assessed.
Diet of Free Ranging American Mink (Neovison vison) in Denmark

Simple Summary This study is the first to compare the diets of captive-born (escaped farm mink) and wild-born mink. This study aimed to evaluate the diets of captive-born and wild-born mink and compare the diets of mink on mainland Denmark and the seasonal variations in diet. The stomachs of 243 wild-born and 114 captive-born mink were analyzed. No significant differences were found between the diets of captive-born mink and wild-born mink from the two populations (mainland Denmark and Bornholm). Significantly more empty stomachs were found during spring than during the summer and autumn. Primarily, the diets of the mink consisted of fish, voles, birds, and crustaceans. Abstract Non-native American mink (Neovison vison) is a widely spread predator in Denmark. The feral population in mainland Denmark consists of captive-born mink that escaped from fur farms and wild mink born in nature, whereas the population on Bornholm is almost all wild-born mink. In this study, the diets of feral mink in mainland Denmark and on the island of Bornholm are analyzed. The aim of this study was to examine (1) whether the diet of the larger captive-born mink differs from that of the smaller wild-born mink, (2) assess the regional variations between the diets of mink in mainland Denmark and on Bornholm, and (3) investigate the seasonal variation in the diet composition of mink. The stomach contents of 364 mink (243 wild-born and 114 captive-born) culled in the years 2019–2022 were analyzed. Of these, 203 mink were from mainland Denmark, and 154 were from Bornholm. No significant differences were found between the diets of captive-born mink and wild-born mink or the mink found in mainland Denmark and on the island of Bornholm. Significantly more empty stomachs were found during spring than during the summer and autumn, suggesting a bottleneck in the diet during spring.
VAMP-Based Iterative Equalization for Index-Modulated Multicarrier FTN Signaling

The spectrally efficient multicarrier faster-than-Nyquist (MFTN) signaling provides an efficient and robust solution for enhancing transmission rate and resisting channel impairments. In this paper, an evolutionary non-orthogonal physical waveform is proposed for simultaneously achieving high spectral and energy efficiency via combining MFTN signaling with index modulation (IM). Exploiting the implicit transmission of IM, the inactivated subcarriers alleviate the inherent two-dimensional interferences imposed by time-frequency packing in MFTN. Then, we develop a pair of iterative equalization algorithms based on vector approximate message passing (VAMP). For the first time-domain equalization (TDE), an extended constellation set is constructed for uniformly characterizing the activated and inactivated subcarriers. To further reducing the computational complexity, we establish a subcarrier-based segment-wise frequency-domain received signal model and accordingly develop low-complexity VAMP-based frequency-domain equalization (FDE) combined with interference elimination. Corroborated by simulations, the novel MFTN-IM waveform achieves superior bit error rate (BER) performance over benchmark waveforms in the high signal noise ratio (SNR) regions. Interestingly, while the proposed VAMP-TDE outperforms the proposed VAMP-FDE in BER performance, the latter is more competitive in balancing demodulation performance and computational complexity.
A widening authority–legitimacy gap in EU regulatory governance? An experimental study of the European Medicines Agency’s legitimacy in health security regulation

ABSTRACT Agencification in the EU stretches the confines of the European regulatory state to the maximum by extending to policy domains that were formerly the exclusive terrain of national institutions. Although the challenge to legitimize EU-level agencies is widely acknowledged, scant empirical research has been done on the conditions under which EU-level epistemic authority prevails or fails. To fill this gap, we examine whether EU agencies are perceived as more legitimate when the scientific nature of their regulatory outputs is made explicit and whether they start facing grave legitimacy challenges when national-level stakeholders signal disapproval with their scientific recommendations. We draw on a survey experiment with Dutch local politicians to study their legitimacy perceptions about the European Medicines Agency (EMA) and its mandate to authorize vaccines in view of cross-border health security risks. Our data suggest that the EMA is regarded as a highly legitimate agency and that disapproval by national-level politicians and citizens does not undermine its epistemic authority in the eyes of local decision-makers. This study contributes to the scholarship on non-majoritarian institutions’ legitimation imperatives by introducing novel research avenues and analytical tools to continue rigorous empirical testing of the well-established theoretical and normative claims.
Elevated Initial Serum Phosphate Levels Predict Higher Mortality and Impaired Neurological Outcome in Cardiac Arrest Patients with Return of Spontaneous Circulation

Purpose: Although a moderate proportion of cardiac arrest (CA) patients achieve a return of spontaneous circulation (ROSC), few survive to discharge, mostly with poor neurological development. As serum phosphate levels were described as elevated after cardiopulmonary resuscitation (CPR), we asked whether these elevations would predict a higher risk of mortality and impaired neurological outcome in CA patients following ROSC. Methods: Initial serum phosphate levels, survival, and neurologic status at discharge of 488 non-traumatic CA patients treated at a single German hospital after achieving ROSC were analyzed. The cut-off value of phosphate for mortality prediction was determined using the receiver operator characteristic (ROC) curve, and patients were divided accordingly for comparison. Results were validated by analyzing phosphate levels in a multi-centric cohort containing 3299 CA patients from the eICU database of the United States. Results: In the German cohort, ROC analysis showed a 90% specificity for phosphate levels >2.7 mmol/L to predict mortality (AUC: 0.76, p < 0.0001), and phosphate level elevations were associated with higher in-hospital mortality (crude odds ratio 3.04, 95% CI 2.32 to 4.08). Patients with initial phosphate levels >2.7 mmol/L had significantly higher mortality in both analyzed collectives (p < 0.0001). Similarly, patients from the German cohort who initially had higher phosphate levels also showed a higher proportion of impaired neurological status at discharge and morphological signs of brain injury. Conclusions: In CA patients following ROSC, initial serum phosphate levels >2.7 mmol/L predict higher mortality and impaired neurological outcome. Our data suggests that phosphate determination might improve the preciseness of the overall and neurologic prognostication in patients after CPR following ROSC.
Rounding off the cow: Challenges and successes in an interdisciplinary physics course for life science students

We describe a 4-yr project designing, teaching, and assessing an interdisciplinary algebra-based physics course for undergraduate biology students. We addressed the needs of this cohort through careful selection of topics and rich biological applications, while also attending to deeper pedagogical concerns (students’ conceptual understanding, epistemological stance, and ability to connect meaning and mathematics). The course provided biology/physics connections that students value, and their work indicated an ability to understand and integrate physics in biological contexts. We offer strategies, suggestions, and some cautionary tales for faculty contemplating or already engaged in similar endeavors.
A stochastic Monte Carlo approach to modelling of real star cluster evolution — I. The model

A new approach is outlined to follow the individual formation and evolution of hard tbree­ body binaries in an evolving equal point mass star cluster. The single stars are treated as a conducting gas sphere with a standard anisotropic gaseous model, binary formation and subsequent hardening by close encounters, and relaxation (dynamical friction) of the binaries with the single stars by a Monte Carlo technique. The results agree very well with the standard theoretical models and with a direct N -body simulation. It is argued that the method can be extended to generate an efficient, cheap and realistic model of large star clusters.
The Conjunction fallacy: Causality vs. event probability

Under certain conditions people give a conjunction of events a higher probability than one of its constituents. This finding has been called the ‘conjunction fallacy’ (Tversky and Kahneman, 1983). One such condition is when the conjunction includes a possible cause and an outcome (called ‘causal conjunctions’) because the strength of the causal link biases the probability judgment. In the present experiment we investigated whether this finding could be replicated and whether it could be reasonably attributed to causality or might be attributed alternatively to the single event probabilities, as has been suggested by Yates and Carlson (1986). 120 subjects read short texts each describing two diseases. These texts varied with respect to the probability of disease A and the probability of disease B (high or low), and the causal relation between the two diseases (yes or no). Ss judged the conjunctive probabilities that a person suffered from both diseases. Causality showed neither an effect upon the judged probability of conjunctions nor upon the frequency of conjunction fallacies. The single event probabilities, on the other hand, had significant effects: conjunction fallacies occured most often when the text included a combination of high and low event probability. Our results support the assumption that (a) causality is not sufficient to induce the conjunction fallacy, and (b) single event probabilities have a major influence on conjunctive probability judgments. The mental model approach is suggested as a theoretical framework that might allow the integrative and systematic examination of causal reasoning processes.
In Vitro and In Silico Studies of Neolignans from Magnolia grandiflora L. Seeds against Human Cannabinoids and Opioid Receptors

Magnolia grandiflora L. (Magnoliaceae) is a plant of considerable medicinal significance; its flowers and seeds have been used in various traditional remedies. Radioligand binding assays of n-hexane seeds extract showed displacement of radioligand for cannabinoid (CB1 and CB2) and opioid δ (delta), κ (kappa), and µ (mu) receptors. Bioactivity-guided fractionation afforded 4-O-methylhonokiol (1), magnolol (2), and honokiol (3), which showed higher binding to cannabinoid rather than opioid receptors in radioligand binding assays. Compounds 1–3, together with the dihydro analog of 2 (4), displayed selective affinity towards CB2R (Ki values of 0.29, 1.4, 1.94, and 0.99 μM, respectively), compared to CB1R (Ki 3.85, 17.82, 14.55, and 19.08 μM, respectively). An equal mixture of 2 and 3 (1:1 ratio) showed additive displacement activity towards the tested receptors compared to either 2 or 3 alone, which in turn provides an explanation for the strong displacement activity of the n-hexane extract. Due to the unavailability of an NMR or X-ray crystal structure of bound neolignans with the CB1 and CB2 receptors, a docking study was performed to predict ligand–protein interactions at a molecular level and to delineate structure-activity relationships (SAR) of the neolignan analogs with the CB1 and CB2 receptors. The putative binding modes of neolignans 1–3 and previously reported related analogs (4, 4a, 5, 5a, 6, 6a, and 6b) into the active site of the CB1 and CB2 receptors were assessed for the first time via molecular docking and binding free-energy (∆G) calculations. The docking and ∆G results revealed the importance of a hydroxyl moiety in the molecules that forms strong H-bonding with Ser383 and Ser285 within CB1R and CB2R, respectively. The impact of a shift from a hydroxyl to the methoxy group on experimental binding affinity to CB1R versus CB2R was explained through ∆G data and the orientation of the alkyl chain within the CB1R. This comprehensive SAR, influenced by the computational study and the observed in vitro displacement binding affinities, has indicated the potential of magnolia neolignans for developing new CB agonists for potential use as analgesics, anti-inflammatory agents, or anxiolytics.
Modelling of a nanosecond surface discharge actuator

Surface dielectric barrier discharges (SDBDs) can modify the boundary layer of a flow and are studied as a possible means to control the flow over an airfoil. In SDBDs driven by sinusoidal voltages in the 1–10 kHz range, momentum is transferred from ions to the neutral gas, as in a corona discharge (ion wind), and the resulting electrohydrodynamic force can generate a flow of several m s−1 in the boundary layer along the surface. In this paper we are interested in a different regime of SDBDs where nanosecond voltage pulses are applied between the electrodes. Recent experiments by the group of Starikovskii have demonstrated that such discharges are able to modify a flow although no significant ion wind can be detected. A two-dimensional self-consistent numerical model of the discharge and gas dynamics in conditions similar to those of these experiments has been developed. The model couples fluid discharge equations with compressible Navier–Stokes equations including momentum and thermal transfer from the plasma to the neutral gas. This is a difficult multi-scale problem and special care has been taken to accurately solve the equations over a large simulation domain and at a relatively low computational cost. The results show that under the conditions of the simulated experiments, fast gas heating takes place in the boundary layer, leading to the generation of a ‘micro’ shock wave, in agreement with the experiments.
On the simulation of the director field of a nematic liquid crystal

Abstract A numerical method for the analysis of the static and dynamic behaviour of the director field, n, of a nematic liquid crystal is presented, where the equivalence of n and – n is taken into account. The occurrence of defects characteristic of nematics is studied for a hybrid cell, and for a material with a negative anisotropic susceptibility subject to an external field. Typical director configurations with defects are displayed graphically for some two dimensional arrangements and, in addition, the resulting pictures corresponding to an observation between crossed polarizer and analyser have been computed.
Changes in Body Composition and Motor Fitness of Young Female Volleyball Players in an Annual Training Cycle

Background: Modern volleyball requires a high level of motor preparation, specific body build and optimal body composition. Objectives: The aim of this study was to determine changes in body build, body composition and motor skills in young volleyball female players during an annual training cycle. Methods: The research group was comprised of 36 female athletes aged 14–16 years, who were monitored throughout a whole season using a longitudinal study design. Body composition was estimated by bioelectrical impedance analysis. Motor fitness was assessed with the following tests: vertical jumping tests (based on one-handed and two-handed reach, standing vertical jump and running vertical jump), standing long jump and 2 kg medicine ball throw. Measurements were carried out at the beginning of the preparatory period, after its completion, in the middle of the start period, at the end of the start period and during transition periods. Results: The study showed significant changes in body composition and motor fitness level during the annual training cycle. These changes differ in subsequent periods of the macrocycle. The most pronounced changes occurred after the preparatory period and concerned increases in fat-free mass, total water content and cell mass. A significant reduction in fat content was also noted at this point. Conclusions: Systematic monitoring of morpho-functional changes in young female volleyball players over extended periods provides them a chance to maintain their optimal fitness level.
Alterations in Serum Concentration of Soluble CD163 within Five Study Days from ICU Admission Are Associated with In-Hospital Mortality of Septic Patients—A Preliminary Study

Background: CD163, a cell membrane surface molecule specifically expressed by macrophages with an anti-inflammatory phenotype, participates in innate immunity. The purpose of the study was to evaluate the clinical utility of sCD163 in septic patients in comparison to other parameters associated with infections, mainly PCT, CRP and IL-18. Methods: Serum samples were obtained from 40 septic patients on the ICU admission day, 3rd and 5th study days. The control group consisted of 30 healthy volunteers from whom the specimen was collected once. An enzyme-linked immunosorbent assay (ELISA) was used to determine the concentrations of sCD163 and IL-18. CRP and PCT records, among others, were provided by the hospital. Results: Septic shock was associated with the highest concentrations of sCD163 and IL-18. Admission values of sCD163 significantly contributed to mortality prediction in septic patients. Conclusions: The concentration of sCD163 determined on the ICU admission day may potentially be utilized in estimation of the odds of death among septic patients.
Human and Livestock Surveillance Revealed the Circulation of Rift Valley Fever Virus in Agnam, Northern Senegal, 2021

The mosquito-borne disease caused by the Rift Valley Fever Virus (RVFV) is a viral hemorrhagic fever that affects humans and animals. In 1987, RVFV emerged in Mauritania, which caused the first RVFV outbreak in West Africa. This outbreak was shortly followed by reported cases in humans and livestock in Senegal. Animal trade practices with neighboring Mauritania suggest northern regions of Senegal are at high risk for RVF. In this study, we aim to conduct a molecular and serological survey of RVFV in humans and livestock in Agnam (northeastern Senegal) by RT-PCR (reverse transcription real-time polymerase chain reaction) and ELISA (Enzyme-Linked Immunosorbent Assay), respectively. Of the two hundred fifty-five human sera, one (0.39%) tested RVFV IgM positive, while fifty-three (20.78%) tested positive for RVFV IgG. For animal monitoring, out of 30 sheep recorded and sampled over the study period, 20 (66.67%) showed seroconversion to RVFV IgG antibodies, notably during the rainy season. The presence of antibodies increased significantly with age in both groups (p < 0.05), as the force of RVF infection (FOI), increased by 16.05% per year for humans and by 80.4% per month for livestock sheep. This study supports the usefulness of setting up a One Health survey for RVF management.
Comparison of Different Antiviral Regimens in the Treatment of Patients with Severe COVID-19: A Retrospective Cohort

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disorders, with disease severity ranging from asymptomatic to critical manifestations. The current retrospective study compared the efficacies of different antiviral regimens used in patients suffering from severe COVID-19 disease from 19 January 2020 to December 2021 in a single center in Saudi Arabia. In total, 188 patients were enrolled in the current study, including 158 patients treated with different antiviral regimens, and 30 who did not receive any antiviral treatment. Different antiviral regimens, including favipiravir, remdesivir, oseltamivir, favipiravir/remdesivir, and favipiravir/oseltamivir were adopted. The effects of using different antivirals and antibiotics on the survival rate were evaluated, as well as the presence of comorbidities. Among all severely affected patients, 39/188 (20.7%) survived. Both age and comorbidities, including diabetes and hypertension, were significantly correlated with high case fatality following SARS-CoV-2 infection. Remdesivir alone and the combination of favipiravir and remdesivir increased the survival rate. Surprisingly, both imipenem and linezolid helped in the deterioration of disease outcome in the patients. A negative correlation was detected between increased mortality and the use of favipiravir and the use of either imipenem or linezolid. Among the compared antiviral regimens used in the treatment of severe COVID-19, remdesivir was found to be an effective antiviral that reduces COVID-19 case fatality. Antibiotic treatment using imipenem and/or linezolid should be carefully re-evaluated.
Use of the Kalman filter for inference in state-space models with unknown noise distributions

The Kalman filter is frequently used for state estimation in state-space models when the standard Gaussian noise assumption does not apply. A problem arises, however, in that inference based on the incorrect Gaussian assumption can lead to misleading or erroneous conclusions about the relationship of the Kalman filter estimate to the true (unknown) state. This paper shows how inequalities from probability theory associated with the probabilities of convex sets have potential for characterizing the estimation error of a Kalman filter in such a non-Gaussian (distribution-free) setting.