The GRAVITY+ Project: Towards All-sky, Faint-Science, High-Contrast Near-Infrared Interferometry at the VLTI

The GRAVITY instrument has been revolutionary for near-infrared interferometry by pushing sensitivity and precision to previously unknown limits. With the upgrade of GRAVITY and the Very Large Telescope Interferometer (VLTI) in GRAVITY+, these limits will be pushed even further, with vastly improved sky coverage, as well as faint-science and high-contrast capabilities. This upgrade includes the implementation of wide-field off-axis fringe-tracking, new adaptive optics systems on all Unit Telescopes, and laser guide stars in an upgraded facility. GRAVITY+ will open up the sky to the measurement of black hole masses across cosmic time in hundreds of active galactic nuclei, use the faint stars in the Galactic centre to probe General Relativity, and enable the characterisation of dozens of young exoplanets to study their formation, bearing the promise of another scientific revolution to come at the VLTI.Comment: Published in the ESO Messenge

Risk Budgeting Portfolios Under a Modern Optimization and Machine Learning Lens

The mean-variance optimization framework has been the traditional approach to decide portfolio allocations based on return-risk trade-offs. However, it faces practical drawbacks, including sensitivity to estimated input parameters and concentration of portfolio risk. Risk budgeting portfolio optimization is a popular risk-based asset allocation technique where risk budgets are assigned to each assets' risk contribution, and equalizing all risk budgets in the portfolio is known as risk parity strategy. Unlike mean-variance, the risk parity strategy provides a balanced risk concentration in the portfolio and does not require expected asset return estimates as input. However, its performance can depend on the selected asset universe. Furthermore, its mathematical formulation imposes some computational challenges due to the non-convex structure. In this thesis, the risk budgeting problem is studied with modern optimization and machine learning approaches to enhance the portfolio model and address the aforementioned challenges. The second chapter introduces regime-switching risk parity portfolios with two primary components: regime modeling and prediction with supervised learning methods and identifying a regime-based strategy to improve the performance of a nominal risk parity portfolio. In the third chapter, we formulate a multi-period risk parity portfolio optimization problem in a transaction cost environment with a model predictive control approach. We provide a successive convex program algorithm that provides faster and more robust solutions. Lastly, we present an end-to-end portfolio allocation method by embedding the risk budget optimization problem as an implicit layer in a neural network. This approach combines prediction and optimization tasks in a single decision-making pipeline and constructs dynamic risk budgeting portfolios. Furthermore, we introduce a novel asset selection property with stochastic gates that protects the risk budgeting portfolio against the unprofitable assets

Examination of empathy-like behaviour in nicotine-preferring rat lines

Aim: Addiction is an important global health issue, impacting also addicts environment and society. Empathy plays crucial role in establishing successful social relationships and is a fundamental component of social life. The aim of this study is to investigate how nicotine preferring (NP) strain and oral forced nicotine administration affects empathy-like behaviour in rats, with gender differences. Materials and Methods: Sprague-Dawley NP rats (10 males/10 females) and wild-type control rats (10 males/10 females) were used. Behavioural tests were administered to all rats before and after oral forced nicotine administration. The behavioural tests were completed in the fourth week of nicotine administration. Anxiety levels that could affect empathy-like behaviour were evaluated with open field, elevated plus maze tests and with blood cortisol levels. Oxytocin receptor and arginine vasopressin (AVP) levels, which have been shown to be related to empathy-like behaviour, were examined in the prefrontal cortex and amygdala regions using the enzyme-linked immunoassay method. Results: It was observed that males from the NP strain showed less empathy-like behaviour than all other groups, and nicotine administration did not cause a significant change in the results. Higher levels of locomotor activity (LA) were found in control females than in all other groups. Blood nicotine and corticosterone levels were higher in NP rats. No significant differences were found in AVP and oxytocin receptor levels in the prefrontal cortex and amygdala. Conclusions: It was found that coming from an addicted strain particularly reduces empathy-like behaviour in males

Design, synthesis, and biological evaluation of some novel naphthoquinone-glycine/beta-alanine anilide derivatives as noncovalent proteasome inhibitors

A series of novel noncovalent glycine/beta- alanine anilide derivatives possessing 2-chloronaphthoquinone structure as a pharmacophoric unit were designed, synthesized, and evaluated for their antiproliferative and antiproteasomal activities against MCF- 7 cell line, in vitro. According to biological activity results, all the target compounds showed antiproliferative activity in the range of IC50 = 7.10 +/- 0.10-41.08 +/- 0.14 mu M and most of them exhibited inhibitory efficacy with varying ratios against the three catalytic subunits (beta 1, beta 2, and beta 5) presenting caspase- like (C -L), trypsin- like (T -L) and chymotrypsin- like (ChT- L) activities of proteasome. The antiproteasomal activity evaluations revealed that compounds preferentially inhibited the beta 5 subunit compared with beta 1 and beta 2 subunits of the proteasome. Among the compounds, compounds 7 and 9 showed the highest antiproliferative activity with an IC50 value of 7.10 +/- 0.10 and 7.43 +/- 0.25 mu M, respectively. Additionally, compound 7 displayed comparable potency to PI -083 lead compound in terms of beta 5 antiproteasomal activity with an inhibition percentage of 34.67 at 10 mu M. This compound showed an IC50 value of 32.30 +/- 0.45 mu M against beta 5 subunit. Furthermore, molecular modeling studies of the most active compound 7 revealed key interactions with beta 5 subunit. The results suggest that this class of compounds may be beneficial for the development of new potent proteasome inhibitors.Tuerkiye Bilimsel ve Teknolojik Arastirma KurumuTuerkiye Bilimsel ve Teknolojik Arastirma Kurum