Neurotensin(8–13) analogs as dual NTS1 and NTS2 receptor ligands with enhanced effects on a mouse model of Parkinson's disease

: The modulatory interactions between neurotensin (NT) and the dopaminergic neurotransmitter system in the brain suggest that NT may be associated with the progression of Parkinson's disease (PD). NT exerts its neurophysiological effects by interactions with the human NT receptors type 1 (hNTS1) and 2 (hNTS2). Therefore, both receptor subtypes are promising targets for the development of novel NT-based analogs for the treatment of PD. In this study, we used a virtually guided molecular modeling approach to predict the activity of NT(8-13) analogs by investigating the docking models of ligands designed for binding to the human NTS1 and NTS2 receptors. The importance of the residues at positions 8 and/or 9 for hNTS1 and hNTS2 receptor binding affinity was experimentally confirmed by radioligand binding assays. Further in vitro ADME profiling and in vivo studies revealed that, compared to the parent peptide NT(8-13), compound 10 exhibited improved stability and BBB permeability combined with a significant enhancement of the motor function and memory in a mouse model of PD. The herein reported NTS1/NTS2 dual-specific NT(8-13) analogs represent an attractive tool for the development of therapeutic strategies against PD and potentially other CNS disorders

AN ANALYSIS OF STUDENT SATISFACTION WITH THE ORGANIZATION OF HYBRID TEACHING IN THE DEPARTMENT OF HEALTH ECONOMICS

The PURPOSE of this research is for a survey to be conducted among the students of the Faculty of Public Health “Prof. Tzekomir Vodenicharov, МD, DSc” at Medical University – Sofia to study whether they are satisfied with how hybrid teaching has been organized in the Department of Health Economics. MATERIALS AND METHODS: An anonymous questionnaire survey was conducted. Out of all students who were invited to participate, 309 joined. The questionnaire was distributed through the Google Forms platform from June to October 2022. Chi-Quadrant analysis was used in order to find relationships between categorical variables. RESULTS: the result shows a statistically significant connection between the students who are studying different specialties in the FPH and their satisfaction with the organization of the hybrid classes carried out by the Department (p <0.001). From the participants’ responses, it is clear that the implementation of hybrid form of teaching (in-person classes for practical training and online classes for theoretical study) carried out through open educational resources and implementing innovative teaching methodology is preferred by the students. CONCLUSION: The scientific evidence arising from our empirical research can aid in the development of guidelines for practical improvement of the hybrid teaching organization in disciplines taught in the Department. The conclusions drawn presuppose continuous research with proper methodologies applied

The Lick AGN Monitoring Project 2011: Dynamical Modeling of the Broad-Line Region

We present models of the H$\beta$-emitting broad-line region (BLR) in seven Seyfert 1 galaxies from the Lick AGN (Active Galactic Nucleus) Monitoring Project 2011 sample, drawing inferences on the BLR structure and dynamics as well as the mass of the central supermassive black hole. We find that the BLR is generally a thick disk, viewed close to face-on, with preferential emission back toward the ionizing source. The dynamics in our sample range from near-circular elliptical orbits to inflowing or outflowing trajectories. We measure black hole masses of $\log_{10}(M_{\rm BH}/M_\odot) = 6.48^{+0.21}_{-0.18}$ for PG 1310$-$108, $7.50^{+0.25}_{-0.18}$ for Mrk 50, $7.46^{+0.15}_{-0.21}$ for Mrk 141, $7.58^{+0.08}_{-0.08}$ for Mrk 279, $7.11^{+0.20}_{-0.17}$ for Mrk 1511, $6.65^{+0.27}_{-0.15}$ for NGC 4593, and $6.94^{+0.14}_{-0.14}$ for Zw 229$-$015. We use these black hole mass measurements along with cross-correlation time lags and line widths to recover the scale factor $f$ used in traditional reverberation mapping measurements. Combining our results with other studies that use this modeling technique, bringing our sample size to 16, we calculate a scale factor that can be used for measuring black hole masses in other reverberation mapping campaigns. When using the root-mean-square (rms) spectrum and using the line dispersion to measure the line width, we find $\log_{10}(f_{{\rm rms},\sigma})_{\rm pred} = 0.57 \pm 0.19$. Finally, we search for correlations between $f$ and other AGN and BLR parameters and find marginal evidence that $f$ is correlated with $M_{\rm BH}$ and the BLR inclination angle, but no significant evidence of a correlation with the AGN luminosity or Eddington ratio.Comment: 26 pages, 14 figures. Accepted for publication in Ap

The Lick AGN Monitoring Project 2011: Spectroscopic Campaign and Emission-Line Light Curves

In the Spring of 2011 we carried out a 2.5 month reverberation mapping campaign using the 3 m Shane telescope at Lick Observatory, monitoring 15 low-redshift Seyfert 1 galaxies. This paper describes the observations, reductions and measurements, and data products from the spectroscopic campaign. The reduced spectra were fitted with a multicomponent model in order to isolate the contributions of various continuum and emission-line components. We present light curves of broad emission lines and the AGN continuum, and measurements of the broad H-beta line widths in mean and root-mean square (rms) spectra. For the most highly variable AGNs we also measured broad H-beta line widths and velocity centroids from the nightly spectra. In four AGNs exhibiting the highest variability amplitudes, we detect anticorrelations between broad H-beta width and luminosity, demonstrating that the broad-line region "breathes" on short timescales of days to weeks in response to continuum variations. We also find that broad H-beta velocity centroids can undergo substantial changes in response to continuum variations; in NGC 4593 the broad H-beta velocity shifted by ~250 km/s over a one-month duration. This reverberation-induced velocity shift effect is likely to contribute a significant source of confusion noise to binary black hole searches that use multi-epoch quasar spectroscopy to detect binary orbital motion. We also present results from simulations that examine biases that can occur in measurement of broad-line widths from rms spectra due to the contributions of continuum variations and photon-counting noise.Comment: 33 pages, 28 figures, accepted for publication in ApJ Supplement Serie

The Lick AGN Monitoring Project 2011: Reverberation Mapping of Markarian 50

The Lick AGN Monitoring Project 2011 observing campaign was carried out over the course of 11 weeks in Spring 2011. Here we present the first results from this program, a measurement of the broad-line reverberation lag in the Seyfert 1 galaxy Mrk 50. Combining our data with supplemental observations obtained prior to the start of the main observing campaign, our dataset covers a total duration of 4.5 months. During this time, Mrk 50 was highly variable, exhibiting a maximum variability amplitude of a factor of 4 in the U-band continuum and a factor of 2 in the H-beta line. Using standard cross-correlation techniques, we find that H-beta and H-gamma lag the V-band continuum by tau_cen = 10.64(-0.93,+0.82) and 8.43(-1.28,+1.30) days, respectively, while the lag of He II 4686 is unresolved. The H-beta line exhibits a symmetric velocity-resolved reverberation signature with shorter lags in the high-velocity wings than in the line core, consistent with an origin in a broad-line region dominated by orbital motion rather than infall or outflow. Assuming a virial normalization factor of f=5.25, the virial estimate of the black hole mass is (3.2+-0.5)*10^7 solar masses. These observations demonstrate that Mrk 50 is among the most promising nearby active galaxies for detailed investigations of broad-line region structure and dynamics.Comment: Accepted for publication in ApJ Letters. 6 pages, 4 figure

A Social Sciences and Humanities research agenda for transport and mobility in Europe: key themes and 100 research questions

Transport and mobility systems need to be transformed to meet climate change goals and reduce negative environmental and social effects. Despite EU policies having targeted such problems for more than three decades, transitions have been slow and geographically uneven. For effective change to happen, transport and mobility research needs fresh perspectives and better integration of knowledge from the Social Sciences and Humanities. Based on a Horizon Scanning approach, which allowed for a great deal of openness and variety in scholarly viewpoints, this paper presents a novel research agenda consisting of 8 themes and 100 research questions that may contribute to achieving environmentally sustainable mobility transitions within Europe. This research agenda highlights the need to not only support technological solutions for low-carbon mobility, but the importance of transformative policies that include new processes of knowledge production, civic participation and epistemic justice. We contend that the agenda points to the need for further research on the dynamics of science-society interactions

The Lick AGN Monitoring Project 2011: Dynamical Modeling of the Broad Line Region in Mrk 50

We present dynamical modeling of the broad line region (BLR) in the Seyfert 1 galaxy Mrk 50 using reverberation mapping data taken as part of the Lick AGN Monitoring Project (LAMP) 2011. We model the reverberation mapping data directly, constraining the geometry and kinematics of the BLR, as well as deriving a black hole mass estimate that does not depend on a normalizing factor or virial coefficient. We find that the geometry of the BLR in Mrk 50 is a nearly face-on thick disk, with a mean radius of 9.6(+1.2,-0.9) light days, a width of the BLR of 6.9(+1.2,-1.1) light days, and a disk opening angle of 25\pm10 degrees above the plane. We also constrain the inclination angle to be 9(+7,-5) degrees, close to face-on. Finally, the black hole mass of Mrk 50 is inferred to be log10(M(BH)/Msun) = 7.57(+0.44,-0.27). By comparison to the virial black hole mass estimate from traditional reverberation mapping analysis, we find the normalizing constant (virial coefficient) to be log10(f) = 0.78(+0.44,-0.27), consistent with the commonly adopted mean value of 0.74 based on aligning the M(BH)-{\sigma}* relation for AGN and quiescent galaxies. While our dynamical model includes the possibility of a net inflow or outflow in the BLR, we cannot distinguish between these two scenarios.Comment: Accepted for publication in ApJ. 8 pages, 6 figure

Stability of the broad-line region geometry and dynamics in Arp 151 over seven years

KH acknowledges support from STFC grant ST/M001296/1.The Seyfert 1 galaxy Arp 151 was monitored as part of three reverberation mapping campaigns spanning 2008−2015. We present modeling of these velocity-resolved reverberation mapping datasets using a geometric and dynamical model for the broad line region (BLR). By modeling each of the three datasets independently, we infer the evolution of the BLR structure in Arp 151 over a total of seven years and constrain the systematic uncertainties in non-varying parameters such as the black hole mass. We find that the BLR geometry of a thick disk viewed close to face-on is stable over this time, although the size of the BLR grows by a factor of 2. The dynamics of the BLR are dominated by inflow and the inferred black hole mass is consistent for the three datasets, despite the increase in BLR size. Combining the inference for the three datasets yields a black hole mass and statistical uncertainty of log10(MBH/M⊙) = 6.82(^+0.09_−0.09) with a standard deviation in individual measurements of 0.13 dex.PostprintPeer reviewe