In Vivo, In Vitro, and In Silico Characterization of Peptoids as Antimicrobial Agents

Bacterial resistance to conventional antibiotics is a global threat that has spurred the development of antimicrobial peptides (AMPs) and their mimetics as novel anti-infective agents. While the bioavailability of AMPs is often reduced due to protease activity, the non-natural structure of AMP mimetics renders them robust to proteolytic degradation, thus offering a distinct advantage for their clinical application. We explore the therapeutic potential of N-substituted glycines, or peptoids, as AMP mimics using a multi-faceted approach that includes in silico, in vitro, and in vivo techniques. We report a new QSAR model that we developed based on 27 diverse peptoid sequences, which accurately correlates antimicrobial peptoid structure with antimicrobial activity. We have identified a number of peptoids that have potent, broad-spectrum in vitro activity against multi-drug resistant bacterial strains. Lastly, using a murine model of invasive S. aureus infection, we demonstrate that one of the best candidate peptoids at 4 mg/kg significantly reduces with a two-log order the bacterial counts compared with saline-treated controls. Taken together, our results demonstrate the promising therapeutic potential of peptoids as antimicrobial agents

The mammals of Angola

Scientific investigations on the mammals of Angola started over 150 years ago, but information remains scarce and scattered, with only one recent published account. Here we provide a synthesis of the mammals of Angola based on a thorough survey of primary and grey literature, as well as recent unpublished records. We present a short history of mammal research, and provide brief information on each species known to occur in the country. Particular attention is given to endemic and near endemic species. We also provide a zoogeographic outline and information on the conservation of Angolan mammals. We found confirmed records for 291 native species, most of which from the orders Rodentia (85), Chiroptera (73), Carnivora (39), and Cetartiodactyla (33). There is a large number of endemic and near endemic species, most of which are rodents or bats. The large diversity of species is favoured by the wide range of habitats with contrasting environmental conditions, while endemism tends to be associated with unique physiographic settings such as the Angolan Escarpment. The mammal fauna of Angola includes 2 Critically Endangered, 2 Endangered, 11 Vulnerable, and 14 Near-Threatened species at the global scale. There are also 12 data deficient species, most of which are endemics or near endemics to the countryinfo:eu-repo/semantics/publishedVersio

Charles Bonnet Syndrome:Evidence for a Generative Model in the Cortex?

Several theories propose that the cortex implements an internal model to explain, predict, and learn about sensory data, but the nature of this model is unclear. One condition that could be highly informative here is Charles Bonnet syndrome (CBS), where loss of vision leads to complex, vivid visual hallucinations of objects, people, and whole scenes. CBS could be taken as indication that there is a generative model in the brain, specifically one that can synthesise rich, consistent visual representations even in the absence of actual visual input. The processes that lead to CBS are poorly understood. Here, we argue that a model recently introduced in machine learning, the deep Boltzmann machine (DBM), could capture the relevant aspects of (hypothetical) generative processing in the cortex. The DBM carries both the semantics of a probabilistic generative model and of a neural network. The latter allows us to model a concrete neural mechanism that could underlie CBS, namely, homeostatic regulation of neuronal activity. We show that homeostatic plasticity could serve to make the learnt internal model robust against e.g. degradation of sensory input, but overcompensate in the case of CBS, leading to hallucinations. We demonstrate how a wide range of features of CBS can be explained in the model and suggest a potential role for the neuromodulator acetylcholine. This work constitutes the first concrete computational model of CBS and the first application of the DBM as a model in computational neuroscience. Our results lend further credence to the hypothesis of a generative model in the brain

Locking alleviation in the large displacement analysis of beam elements: the strain split method

This paper proposes a new locking alleviation technique for absolute nodal coordinate formulation (ANCF) beam and plate elements based on a strain split approach. The paper also surveys classical finite element (FE) and ANCF locking alleviation techniques discussed in the literature. Because ANCF beam elements, which allow for the cross-sectional stretch fully capture the Poisson effect, Poisson locking is an issue when such beam elements are considered. The two-dimensional fully parameterized ANCF beam element is primarily used in this investigation because such an element can serve as a good surrogate model for three-dimensional ANCF beams and plates as far as membrane, bending and transverse shearing behavior is concerned. In addition to proposing the strain split method (SSM) for ANCF locking alleviation, this work assesses the ANCF element performance in the cases of higher-order interpolation, enhanced assumed strain method, elastic line method, and the enhanced continuum mechanics approach, and demonstrates the design of the enhanced strain interpolation function by using the shape functions of higher-order ANCF elements. Additionally, a new higher-order ANCF two-dimensional beam element is proposed in order to compare its performance with other finite elements that require the use of other locking alleviation techniques proposed and reviewed in the paper. Finally, several numerical examples are shown to demonstrate the effectiveness of the locking alleviation methods applied to ANCF elements. The purpose of this investigation, apart from proposing a new locking alleviation technique, a new higher-order beam element, and comparing several existing locking alleviation techniques, is to show that dealing with locking in fully parameterized ANCF elements is feasible and that several methods exist to effectively improve the ANCF element performance without sacrificing important ANCF element properties and features including position vector gradient continuity. Because of the use of ANCF position vector gradients as nodal coordinates, complex stress-free initially-curved geometries can be systematically obtained. Such initially-curved geometries require special attention when attempting to solve locking problems, as will be discussed in this paper

HiGlass: web-based visual exploration and analysis of genome interaction maps

We present HiGlass, an open source visualization tool built on web technologies that provides a rich interface for rapid, multiplex, and multiscale navigation of 2D genomic maps alongside 1D genomic tracks, allowing users to combine various data types, synchronize multiple visualization modalities, and share fully customizable views with others. We demonstrate its utility in exploring different experimental conditions, comparing the results of analyses, and creating interactive snapshots to share with collaborators and the broader public. HiGlass is accessible online at http://higlass.io and is also available as a containerized application that can be run on any platform.National Institutes of Health (U.S.) (U01 CA200059)National Institutes of Health (U.S.) (R00 HG007583)National Institutes of Health (U.S.) (U54 HG007963