The Gut Microbiome and Trimethylamine N-Oxide: Implications for Chronic Disease Risk and Dietary Regulation

The leading causes of death in the United States include many chronic diseases with modifiable risk factors including ischemic heart diseases. Gut microbiota-dependent trimethylamine N-oxide (TMAO) synthesis has been implicated in cardiovascular disease risk in recent years. New evidence may also implicate TMAO involvement in other chronic diseases including diabetes mellitus and chronic kidney disease. The role of diet in TMAO synthesis has also been of considerable interest, as certain dietary precursors are known to modulate circulating TMAO. The gut microbiome is indeed susceptible to diet-induced change which may modulate the risk for chronic disease. Plant-based diets are considered by many to be beneficial for gut health and may play a protective role by reducing TMAO synthesis. This review discusses the purported role of TMAO and the mechanisms by which TMAO may contribute to atherosclerosis and chronic disease risk. The role of diet in chronic disease is also discussed with emphasis on utilizing clinical nutrition to reduce the burden of disease

Mighty Lak\u27a Rose

https://digitalcommons.library.umaine.edu/mmb-me/1149/thumbnail.jp

Skin Barrier Function and Its Importance at the Start of the Atopic March

Atopic dermatitis can be due to a variety of causes from nonatopic triggers to food allergy. Control of egress of water and protection from ingress of irritants and allergens are key components of cutaneous barrier function. Current research suggests that a degraded barrier function of the skin allows the immune system inappropriate access to environmental allergens. Epidermal aeroallergen exposure may allow sensitization to allergen possibly initiating the atopic march. Further research into connections between epidermal barrier function and possible allergen sensitization will be important to undertake. Future clinical trials focused on skin barrier protection may be of value as a possible intervention in prevention of the initiation of the atopic march

Early Pollen Sensitization in Children Is Dependent upon Regional Aeroallergen Exposure

Introduction. Aeroallergen sensitization occurs at an earlier age than previously noted. The purpose of this paper was to identify which pollens cause early sensitization in young children presenting with rhinitis symptoms. Methods. This paper was a retrospective analysis of skin test results from 2- to 8-year-old patients presenting with a history consistent with allergic rhinitis. Patients were tested to aeroallergens common to the Great Basin along with a histamine and saline control. Pollen counts were obtained from a Reno, NV-certified counting station. Results. 123 children less than 8 years of age were identified. Over 50% of these children were sensitized to at least one aeroallergen. Chemopodaciae, timothy, alfalfa, black walnut, olive, mountain cedar and willow were predominating sensitizing aeroallergens of the Great Basin Region. Pollen counts were notable for a early spring peak for the tree season, grass season in May and weed season in August. Pollen levels continued to November at low levels. Discussion. Aeroallergens causing early sensitization differed from those which had predominately been reported in other regions of the United States. Pediatric allergists should consider performing a local review of sensitizing aeroallergens in their region to assist with identification and management of allergic rhinitis in their youngest patients. Please make style changes as appropriate

Nonlinear Saturation of g-modes in Proto-Neutron Stars: Quieting the Acoustic Engine

According to Burrows et al.'s acoustic mechanism for core-collapse supernova explosions, the primary, l=1, g-mode in the core of the proto-neutron star is excited to an energy of ~ 10^{50} ergs and damps by the emission of sound waves. Here we calculate the damping of the primary mode by the parametric instability, i.e., by nonlinear, 3-mode coupling between the low-order primary mode and pairs of high-order g-modes. We show that the primary mode is strongly coupled to highly resonant, neutrino damped pairs with n>10; such short wavelength interactions cannot be resolved in the simulations. We find that the parametric instability saturates the primary mode energy at ~10^{48} ergs, well below the energy needed to drive an explosion. We therefore conclude that acoustic power is unlikely to be energetically significant in core-collapse supernova explosions.Comment: 6 pages, 3 figures, fixed minor typos, matches version published in MNRAS Letter

Techniques for applying reinforcement learning to routing and wavelength assignment problems in optical fiber communication networks

We propose a novel application of reinforcement learning (RL) with invalid action masking and a novel training methodology for routing and wavelength assignment (RWA) in fixed-grid optical networks and demonstrate the generalizability of the learned policy to a realistic traffic matrix unseen during training. Through the introduction of invalid action masking and a new training method, the applicability of RL to RWA in fixed-grid networks is extended from considering connection requests between nodes to servicing demands of a given bit rate, such that lightpaths can be used to service multiple demands subject to capacity constraints. We outline the additional challenges involved for this RWA problem, for which we found that standard RL had low performance compared to that of baseline heuristics, in comparison with the connection requests RWA problem considered in the literature. Thus, we propose invalid action masking and a novel training method to improve the efficacy of the RL agent. With invalid action masking, domain knowledge is embedded in the RL model to constrain the action space of the RL agent to lightpaths that can support the current request, reducing the size of the action space and thus increasing the efficacy of the agent. In the proposed training method, the RL model is trained on a simplified version of the problem and evaluated on the target RWA problem, increasing the efficacy of the agent compared with training directly on the target problem. RL with invalid action masking and this training method outperforms standard RL and three state-of-the-art heuristics, namely, k shortest path first fit, first-fit k shortest path, and k shortest path most utilized, consistently across uniform and nonuniform traffic in terms of the number of accepted transmission requests for two real-world core topologies, NSFNET and COST - 239. The RWA runtime of the proposed RL model is comparable to that of these heuristic approaches, demonstrating the potential for real-world applicability. Moreover, we show that the RL agent trained on uniform traffic is able to generalize well to a realistic nonuniform traffic distribution not seen during training, thus outperforming the heuristics for this traffic. Visualization of the learned RWA policy reveals an RWA strategy that differs significantly from those of the heuristic baselines in terms of the distribution of services across channels and the distribution across links

Collective Dynamics Differentiates Functional Divergence in Protein Evolution

Protein evolution is most commonly studied by analyzing related protein sequences and generating ancestral sequences through Bayesian and Maximum Likelihood methods, and/or by resurrecting ancestral proteins in the lab and performing ligand binding studies to determine function. Structural and dynamic evolution have largely been left out of molecular evolution studies. Here we incorporate both structure and dynamics to elucidate the molecular principles behind the divergence in the evolutionary path of the steroid receptor proteins. We determine the likely structure of three evolutionarily diverged ancestral steroid receptor proteins using the Zipping and Assembly Method with FRODA (ZAMF). Our predictions are within ∼2.7 Å all-atom RMSD of the respective crystal structures of the ancestral steroid receptors. Beyond static structure prediction, a particular feature of ZAMF is that it generates protein dynamics information. We investigate the differences in conformational dynamics of diverged proteins by obtaining the most collective motion through essential dynamics. Strikingly, our analysis shows that evolutionarily diverged proteins of the same family do not share the same dynamic subspace, while those sharing the same function are simultaneously clustered together and distant from those, that have functionally diverged. Dynamic analysis also enables those mutations that most affect dynamics to be identified. It correctly predicts all mutations (functional and permissive) necessary to evolve new function and ∼60% of permissive mutations necessary to recover ancestral function

Radiotherapy Optimal Design: An Academic Radiotherapy Treatment Design System

Optimally designing radiotherapy and radiosurgery treatments to increase the likelihood of a successful recovery from cancer is an important application of operations research. Researchers have been hindered by the lack of academic software that supports head-to-head comparisons of different techniques, and this article addresses the inherent difficulties of designing and implementing an academic treatment planning system. In particular, this article details the algorithms and the software design of Radiotherapy optimAl Design (RAD)