Updates in the use of cannabis for insomnia.

Purpose Of Review: This review aims to summarize recent updates in the area of cannabis use for insomnia.

Recent Findings: Cannabis products have continued to become more potent, particularly in regard to delta-9- tetrahydrocannabinol (THC) concentration. Additionally, the use of cannabis has continued to become more accepted with less legal restrictions.

New pharmacologic agents for insomnia and hypersomnia.

Purpose Of Review: Insomnia and hypersomnia are conditions with multifactorial causes that can be difficult to treat. There have been recent developments and changes in the treatment of both conditions, including the addition of some agents that have a novel mechanism of action. This review summarizes recent changes and highlights pertinent updates.

On Not Knowing What We Don't Know to Knowing What We Don't Know: Obstructive Sleep Apnea in the Transgender Community.

Earl DC, Brown LK. On not knowing what we don’t know to knowing what we don’t know: obstructive sleep apnea in the transgender community. 2019;15(10):1393–1395.

Discovery of human cell selective effector molecules using single cell multiplexed activity metabolomics.

Discovering bioactive metabolites within a metabolome is challenging because there is generally little foreknowledge of metabolite molecular and cell-targeting activities. Here, single-cell response profiles and primary human tissue comprise a response platform used to discover novel microbial metabolites with cell-type-selective effector properties in untargeted metabolomic inventories. Metabolites display diverse effector mechanisms, including targeting protein synthesis, cell cycle status, DNA damage repair, necrosis, apoptosis, or phosphoprotein signaling.

The use of fluorescently-tagged apoptolidins in cellular uptake and response studies.

The apoptolidins are glycomacrolide microbial metabolites reported to be selectively cytotoxic against tumor cells. Using fluorescently tagged active derivatives we demonstrate selective uptake of these four tagged glycomacrolides in cancer cells over healthy human blood cells. We also demonstrate the utility of these five fluorescently tagged glycomacrolides in fluorescent flow cytometry to monitor cellular uptake of the six glycomacrolides and cellular response.

Fluorescent probes of the apoptolidins and their utility in cellular localization studies.

Apoptolidin A has been described among the top 0.1% most-cell-selective cytotoxic agents to be evaluated in the NCI 60 cell line panel. The molecular structure of apoptolidin A consists of a 20-membered macrolide with mono- and disaccharide moieties.

Atomistic simulations of liquid crystal mixtures of alkoxy substituted phenylpyrimidines 2PhP and PhP14.

We study liquid crystal mixtures of alkoxy substituted phenylpyrimidines 2-[4-(butyloxy)phenyl]-5-(octyloxy)pyrimidine (2PhP) and 2-[4-(tetradecyloxy)phenyl]-5-(tetradecyloxy)pyrimidine (PhP14) using molecular dynamics simulations at the all atom level. The molecular length of PhP14 is 1.8 times that of 2PhP, resulting in an interesting binary mixture phase diagram.

Solvent-shift Monte Carlo: a cluster algorithm for solvated systems.

We present a cluster algorithm for the efficient simulation of solvated systems that we term solvent-shift Monte Carlo (SSMC). The algorithm involves a conformational change in a solvated solute molecule of interest, followed by a concerted movement of solvent particles about a rotation axis. The method satisfies detailed balance and can be applied to existing schemes to sample conformational space, where an axis or plane of rotation can be defined.

The effect of dielectric properties of sintering additives on microwave sintered silicon nitride ceramics.

Silicon nitride requires the use of susceptive additives for microwave liquid phase sintering due to the material's low dielectric loss. In this article, we report the effect of complex dielectric properties of two compositions of sintering aids on 2.45 GHz microwave sintered Si3N4 with respect to power absorption, temperature distribution and densification behavior.

Self-assembled chiral superstructures composed of rigid achiral molecules and molecular scale chiral induction by dopants.

We explore the phase behavior of a rigid achiral bent-core model system. Nematic and smectic phases form at higher densities, whereas micelles and columns composed of chiral clusters of these molecules self-assemble at lower densities. No nucleation mechanism requiring transient chirality is possible in the formation of these chiral superstructures due to the rigid achiral nature of the substituents.

Perspective: after a century of criticizing premedical education, are we missing the point?

Ever since Abraham Flexner formalized the idea of premedical education in 1910, medical educators have argued about how best to prepare students for medical school. This back-and-forth about the premedical years has focused almost exclusively on the range and content of the required course work; noticeably absent from the debate is consideration of the ways in which the experience of the premedical years-including the curricular and noncurricular demands placed on students-shape the moral education of the next generation of physicians. The authors review the century-long conversation about premedical education, highlighting the themes of that discussion and the important aspects of being a "premed" that have not been a part of the conversation.

Monte Carlo simulations.

A description of Monte Carlo methods for simulation of proteins is given. Advantages and disadvantages of the Monte Carlo approach are presented. The theoretical basis for calculating equilibrium properties of biological molecules by the Monte Carlo method is presented.

Modeling microscopic swimmers at low Reynolds number.

The authors employ three numerical methods to explore the motion of low Reynolds number swimmers, modeling the hydrodynamic interactions by means of the Oseen tensor approximation, lattice Boltzmann simulations, and multiparticle collision dynamics. By applying the methods to a three bead linear swimmer, for which exact results are known, the authors are able to compare and assess the effectiveness of the different approaches. They then propose a new class of low Reynolds number swimmers, generalized three bead swimmers that can change both the length of their arms and the angle between them.

Markov chains of infinite order and asymptotic satisfaction of balance: application to the adaptive integration method.

Adaptive Monte Carlo methods can be viewed as implementations of Markov chains with infinite memory. We derive a general condition for the convergence of a Monte Carlo method whose history dependence is contained within the simulated density distribution. In convergent cases, our result implies that the balance condition need only be satisfied asymptotically.

Quantifying influenza vaccine efficacy and antigenic distance.

We introduce a new measure of antigenic distance between influenza A vaccine and circulating strains. The measure correlates well with efficacies of the H3N2 influenza A component of the annual vaccine between 1971 and 2004, as do results of a theory of the immune response to influenza following vaccination. This new measure of antigenic distance is correlated with vaccine efficacy to a greater degree than are current state of the art phylogenetic sequence analyses or ferret antisera inhibition assays.

Parallel tempering: theory, applications, and new perspectives.

We review the history of the parallel tempering simulation method. From its origins in data analysis, the parallel tempering method has become a standard workhorse of physicochemical simulations. We discuss the theory behind the method and its various generalizations.

Glassy dynamics in the adaptive immune response prevents autoimmune disease.

The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self-antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens.

Induced and spontaneous deracemization in bent-core liquid crystal phases and in other phases doped with bent-core molecules.

Recently discovered chiral properties of several bent-core smectic liquid crystal phases are summarized and discussed in detail under the assumption that typical bent-core molecules may exist in chiral conformational states and are achiral only on average. Results of atomistic computer simulations are presented which indicate the existence of strongly chiral conformational states for typical bent-core mesogens. A theory is developed which describes a possible shift of equilibrium between left- and right-handed conformations in a macroscopically chiral phase.

Evolvability is a selectable trait.

Concomitant with the evolution of biological diversity must have been the evolution of mechanisms that facilitate evolution, because of the essentially infinite complexity of protein sequence space. We describe how evolvability can be an object of Darwinian selection, emphasizing the collective nature of the process. We quantify our theory with computer simulations of protein evolution.

Calculations of helical twisting powers from intermolecular torques.

We present a Monte Carlo molecular simulation method that calculates the helical twisting power of a chiral molecule by sampling intermolecular torques. The approach is applied to an achiral nematic liquid crystalline system, composed of Gay-Berne particles, that is doped with chiral molecules. Calculations are presented for six chiral dopant molecules and the results show a good correlation with the sign and magnitude of experimentally determined helical twisting powers.