Dynamics of warped accretion discs

Accretion discs are present around both stellar-mass black holes in X-ray binaries and supermassive black holes in active galactic nuclei. A wide variety of circumstantial evidence implies that many of these discs are warped. The standard Bardeen--Petterson model attributes the shape of the warp to the competition between Lense--Thirring torque from the central black hole and viscous angular-momentum transport within the disc. We show that this description is incomplete, and that torques from the companion star (for X-ray binaries) or the self-gravity of the disc (for active galactic nuclei) can play a major role in determining the properties of the warped disc. Including these effects leads to a rich set of new phenomena. For example, (i) when a companion star is present and the warp arises from a misalignment between the companion's orbital axis and the black hole's spin axis, there is no steady-state solution of the Pringle--Ogilvie equations for a thin warped disc when the viscosity falls below a critical value; (ii) in AGN accretion discs, the warp can excite short-wavelength bending waves that propagate inward with growing amplitude until they are damped by the disc viscosity. We show that both phenomena can occur for plausible values of the black hole and disc parameters, and briefly discuss their observational implications.Comment: 28 pages, 11 figure

Organoboranes in organic synthesis

Aryl ketonetrisylhydrazones were found to react with trialkylboranes, in the presence of base, to generate the corresponding aromatic alkanes in good to excellent yields. Alkyl aldehydetrisylhydrazones also participate under the same reaction conditions to produce aliphatic alcohols in good yields upon oxidation. The effects of the solvent and the aromatic leaving group were also examined. The Suzuki coupling of acid chlorides with trialkylboranes were also evaluated. Both aromatic and aliphatic acid chlorides were alkylated to generate the analogous ketone in good yields. The synthesis of a boronated 1,5-diarylpyrrazole was attempted. Evidence suggests the desired product was produced

Genetic and Pharmacologic Studies Towards Prevention of opioid use disorder

Endogenous opioids mediate both analgesic and affective responses to stress. While the mu opioid receptor (MOR) produces the reinforcing euphoric effects responsible for the high abuse potential of traditional opioid analgesics, the kappa opioid receptor (KOR) is hypothesized to mediate the dysphoric component of stress. With increasing rates of opioid addiction, extensive research efforts are focused on better understanding each of these systems and how they interact, with the goal of developing less addictive pain management strategies and better approaches to addiction treatment. With this in mind, we conducted both clinical and pre-clinical studies aimed at developing better treatment strategies for opioid use and the management of patients with opioid use disorder (OUD). First, we assessed a local cohort of patients with (OUD) for a collection of single nucleotide polymorphisms (SNPs) related to reward processing, with the goal of furthering efforts to develop a gene-based screening mechanism for OUD risk assessment. Second, we conducted preclinical assessments of the G protein-biased KOR agonist nalfurafine as a potential adjuvant medication for increasing the therapeutic efficacy of opioid-based analgesia. Genetic analysis of OUD patients identified two SNPs within the gene encoding the mu opioid receptor, one SNP within the gene encoding the serotonin 2B (5-HT2B) receptor, and one SNP within the gene encoding Regulator of G protein Signaling 2 (RGS2), with the frequency of each SNP varying significantly from that observed in reference populations of European descent. Preclinical investigations with nalfurafine use in mice demonstrated a greater analgesic synergy when co-administered with morphine than morphine co-administered with the unbiased KOR agonist U50,488. As G protein-biased KOR agonists are hypothesized to produce less dysphoria (a therapeutically limiting side effect of KOR agonists), they may present a viable method for reducing the dose of MOR-targeting analgesic necessary for adequate pain relief, thereby reducing the likelihood of developing OUD. Further research is necessary to identify any anti-therapeutic effects of co-administering these two classes of drugs, as well as the range of pain modalities for which this approach is efficacious