Analytical Review of Court Cases Considered with the Participation of Antimonopoly Authorities

Analysis of the legal positions of arbitration courts in cases of violation of antimonopoly legislation regarding the consideration of issues: the statute of limitations for bringing to administrative responsibility, the grounds for refusing to provide state preference, the consideration of complaints about the actions of bidders/operators carried out during the mandatory procedures applied in the bankruptcy case.Objective: to develop uniform approaches in law enforcement practice in cases of violation of antitrust laws.

Time trade-off with someone to live for: impact of having significant others on time trade-off valuations of hypothetical health states

Background The TTO task involves giving up life years, i.e. living a shorter life, to avoid an undesirable health state. Despite being a hypothetical task, some respondents take other life factors into account when completing the task. This study explored the effect of having children and/or a partner on TTO valuations of hypothetical EQ-5D-5L health states in a valuation study of the general population. Methods The study used TTO data collected in a Norwegian EQ-5D-5L valuation study in 2019–2020, by one-to-one pc-assisted interviews following the EQ-VT protocol. We used regression modelling to determine the effect of significant others (having children or a partner) on disutility per health state from the TTO valuations. Results 430 respondents were included [mean age 43.8 (SD 15.9) years, 58% female, 48% with children, 68% with a partner, 25% with neither children nor partner]. Having children and/or a partner was associated with lowered willingness to trade life years translating to higher elicited health state utilities (p < 0.01). Conclusion Having significant others, or the lack of having significant others, was associated with respondents’ valuation of hypothetical health states using TTO, more so than traditional sampling variables such as age and sex. Inadequate representativeness in terms of having significant others could bias health state preference values in valuation studies.

Religious Peace building, the Problems, and Potentials Now and in the Foreseeable Federal Republic of Nepal

Introduction: There is debate whether most Nepali people still want Nepal to be a Hindu state. A significant number of opinions wish to see the country as secular, where people are respected with dignity without any discrimination where people can profess, practice, and protect their religions, whichever religion it may be. Methods: This paper is based on public opinion surveys through interviews and discussions with100 individuals, including key informant interviews with 25 religious leaders from different religions conducted between September 20019 and February 2020 and secondary data from various literature reviews. Results: The paper's finding reveals that the public's preference toward the Hindu state is not accepted in all sub-national levels; a secular state preference is evident in some of the sub-national levels, which cannot be undervalued. The mindsets of most of the elder populations interviewed still want Nepal to be the only Hindu state in the world, whereas the active young-age (youth) population is more inclusive and is happy with the secular nation. Conclusion: Understanding and implementing inclusive secular policies and practicing the preexistence principles of religious freedom by the political parties and incorporating the same in all government, semi-government and private sectors will ensure a secular and peaceful Nepal. Government authorities and other bureaucrats becoming more sensitive towards religious issues will create space for promoting peace.

Structural Water Stabilizes Protein Motifs in Liquid Protein Phase: The Folding Mechanism of Short β-Sheets Coupled to Phase Transition

Macromolecular associates, such as membraneless organelles or lipid-protein assemblies, provide a hydrophobic environment, i.e., a liquid protein phase (LP), where folding preferences can be drastically altered. LP as well as the associated phase change from water (W) is an intriguing phenomenon related to numerous biological processes and also possesses potential in nanotechnological applications. However, the energetic effects of a hydrophobic yet water-containing environment on protein folding are poorly understood. Here, we focus on small β-sheets, the key motifs of proteins, undergoing structural changes in liquid–liquid phase separation (LLPS) and also model the mechanism of energy-coupled unfolding, e.g., in proteases, during W → LP transition. Due to the importance of the accurate description for hydrogen bonding patterns, the employed models were studied by using quantum mechanical calculations. The results demonstrate that unfolding is energetically less favored in LP by ~0.3–0.5 kcal·mol−1 per residue in which the difference further increased by the presence of explicit structural water molecules, where the folded state was preferred by ~1.2–2.3 kcal·mol−1 per residue relative to that in W. Energetics at the LP/W interfaces was also addressed by theoretical isodesmic reactions. While the models predict folded state preference in LP, the unfolding from LP to W renders the process highly favorable since the unfolded end state has >1 kcal·mol−1 per residue excess stabilization.

Pharmacological modulation of AMPA receptors rescues specific impairments in social behavior associated with the A350V Iqsec2 mutation

In this study we tested the hypothesis that pharmacological modulation of glutamatergic neurotransmission could rescue behavioral deficits exhibited by mice carrying a specific mutation in the Iqsec2 gene. The IQSEC2 protein plays a key role in glutamatergic synapses and mutations in the IQSEC2 gene are a frequent cause of neurodevelopmental disorders. We have recently reported on the molecular pathophysiology of one such mutation A350V and demonstrated that this mutation downregulates AMPA type glutamatergic receptors (AMPAR) in A350V mice. Here we sought to identify behavioral deficits in A350V mice and hypothesized that we could rescue these deficits by PF-4778574, a positive AMPAR modulator. Using a battery of social behavioral tasks, we found that A350V Iqsec2 mice exhibit specific deficits in sex preference and emotional state preference behaviors as well as in vocalizations when encountering a female mouse. The social discrimination deficits, but not the impaired vocalization, were rescued with a single dose of PF-4778574. We conclude that social behavior deficits associated with the A350V Iqsec2 mutation may be rescued by enhancing AMPAR mediated synaptic transmission.

Precision medicine for the rescue of specific impairments in social behavior associated with the A350V Iqsec2 mutation

In this study we tested the hypothesis that precision medicine guided therapy targeting glutamatergic neurotransmission could rescue behavioral deficits exhibited by mice carrying a specific mutation in the Iqsec2 gene. The IQSEC2 protein plays a key role in glutamatergic synapses and mutations in the IQSEC2 gene are a frequent cause of neurodevelopmental disorders. We have recently reported on the molecular pathophysiology of one such mutation A350V and demonstrated that this mutation downregulates AMPA type glutamatergic receptors (AMPAR) in A350V mice. Here we sought to identify behavioral deficits in A350V mice and hypothesized that we could rescue these deficits by PF-4778574, a positive AMPAR modulator. We found that A350V Iqsec2 mice exhibit specific deficits in sex preference and emotional state preference behaviors as well as in vocalizations when encountering a female mouse. The social discrimination deficits, but not the impaired vocalization, were rescued with PF-4778574. We conclude that social behavior deficits associated with the A350V Iqsec2 mutation may be rescued by enhancing AMPAR mediated synaptic transmission.