Designing and optimizing a micromanipulator-controlled surgical tool for reproducible nerve crush injuries in mice

Poster presented at the 2017 Health Sciences Research Day which was organized and sponsored by the University of Missouri School of Medicine Research Council and held on November 9, 2017.Introduction: Recurrent laryngeal nerve (RLN) injury, even if temporary, is a devastating complication of anterior cervical surgical procedures, resulting in debilitating dysphonia and dysphagia. During surgery, injury can be imparted by stretching, crushing, cauterizing, and/or transecting the laryngeal nerves. The injury can be temporary or permanent, depending on the severity and mechanism of insult. Treatment of the injury is generally palliative in nature and includes feeding tubes, voice and swallowing therapy, and diet modifications. The underlying pathophysiology of RLN is not completely understood. To effectively investigate various treatment strategies in mouse models, we need to improve the current translational animal model by standardizing the widely-used manual nerve crush techniques that apply variable force and may unintentionally add traction injuries. To control for these potential confounds, we are developing a micromanipulator-controlled surgical tool that (1) reliably applies a calibrated crush force injury, and (2) minimizes secondary injuries, such as traction, induced by manual methods

Reinforcement Learning Agents acquire Flocking and Symbiotic Behaviour in Simulated Ecosystems

In nature, group behaviours such as flocking as well as cross-species symbiotic partnerships are observed in vastly different forms and circumstances. We hypothesize that such strategies can arise in response to generic predator-prey pressures in a spatial environment with range-limited sensation and action. We evaluate whether these forms of coordination can emerge by independent multi-agent reinforcement learning in simple multiple-species ecosystems. In contrast to prior work, we avoid hand-crafted shaping rewards, specific actions, or dynamics that would directly encourage coordination across agents. Instead we test whether coordination emerges as a consequence of adaptation without encouraging these specific forms of coordination, which only has indirect benefit. Our simulated ecosystems consist of a generic food chain involving three trophic levels: apex predator, mid-level predator, and prey. We conduct experiments on two different platforms, a 3D physics engine with tens of agents as well as in a 2D grid world with up to thousands. The results clearly confirm our hypothesis and show substantial coordination both within and across species. To obtain these results, we leverage and adapt recent advances in deep reinforcement learning within an ecosystem training protocol featuring homogeneous groups of independent agents from different species (sets of policies), acting in many different random combinations in parallel habitats. The policies utilize neural network architectures that are invariant to agent individuality but not type (species) and that generalize across varying numbers of observed other agents. While the emergence of complexity in artificial ecosystems have long been studied in the artificial life community, the focus has been more on individual complexity and genetic algorithms or explicit modelling, and less on group complexity and reinforcement learning emphasized in this article. Unlike what the name and intuition suggests, reinforcement learning adapts over evolutionary history rather than a life-time and is here addressing the sequential optimization of fitness that is usually approached by genetic algorithms in the artificial life community. We utilize a shift from procedures to objectives, allowing us to bring new powerful machinery to bare, and we see emergence of complex behaviour from a sequence of simple optimization problems

Electrostatic considerations affecting the calculated HOMO-LUMO gap in protein molecules.

A detailed study of energy differences between the highest occupied and lowest unoccupied molecular orbitals (HOMO-LUMO gaps) in protein systems and water clusters is presented. Recent work questioning the applicability of Kohn-Sham density-functional theory to proteins and large water clusters (E. Rudberg, J. Phys.: Condens. Mat. 2012, 24, 072202) has demonstrated vanishing HOMO-LUMO gaps for these systems, which is generally attributed to the treatment of exchange in the functional used. The present work shows that the vanishing gap is, in fact, an electrostatic artefact of the method used to prepare the system. Practical solutions for ensuring the gap is maintained when the system size is increased are demonstrated. This work has important implications for the use of large-scale density-functional theory in biomolecular systems, particularly in the simulation of photoemission, optical absorption and electronic transport, all of which depend critically on differences between energies of molecular orbitals.Comment: 13 pages, 4 figure

Electrical manipulation of spin states in a single electrostatically gated transition-metal complex

We demonstrate an electrically controlled high-spin (S=5/2) to low-spin (S=1/2) transition in a three-terminal device incorporating a single Mn2+ ion coordinated by two terpyridine ligands. By adjusting the gate-voltage we reduce the terpyridine moiety and thereby strengthen the ligand-field on the Mn-atom. Adding a single electron thus stabilizes the low-spin configuration and the corresponding sequential tunnelling current is suppressed by spin-blockade. From low-temperature inelastic cotunneling spectroscopy, we infer the magnetic excitation spectrum of the molecule and uncover also a strongly gate-dependent singlet-triplet splitting on the low-spin side. The measured bias-spectroscopy is shown to be consistent with an exact diagonalization of the Mn-complex, and an interpretation of the data is given in terms of a simplified effective model.Comment: Will appear soon in Nanoletter

Physicochemical analysis of rotavirus segment 11 supports a 'modified panhandle' structure and not the predicted alternative tRNA-like structure (TRLS)

.Rotaviruses are a major cause of acute gastroenteritis, which is often fatal in infants. The viral genome consists of 11 double-stranded RNA segments, but little is known about their cis-acting sequences and structural elements. Covariation studies and phylogenetic analysis exploring the potential structure of RNA11 of rotaviruses suggested that, besides the previously predicted "modified panhandle" structure, the 5' and 3' termini of one of the isoforms of the bovine rotavirus UKtc strain may interact to form a tRNA-like structure (TRLS). Such TRLSs have been identified in RNAs of plant viruses, where they are important for enhancing replication and packaging. However, using tRNA mimicry assays (in vitro aminoacylation and 3'- adenylation), we found no biochemical evidence for tRNA-like functions of RNA11. Capping, synthetic 3' adenylation and manipulation of divalent cation concentrations did not change this finding. NMR studies on a 5'- and 3'-deletion construct of RNA11 containing the putative intra-strand complementary sequences supported a predominant panhandle structure and did not conform to a cloverleaf fold despite the strong evidence for a predicted structure in this conserved region of the viral RNA. Additional viral or cellular factors may be needed to stabilise it into a form with tRNA-like properties

Coincidence of a Novel KCNJ11 Missense Variant R365H With a Paternally Inherited 6q24 Duplication in a Patient With Transient Neonatal Diabetes

OBJECTIVE—Neonatal diabetes is a heterogeneous group of disorders with diabetes manifestation in the first 6 months of life. The most common etiology in permanent neonatal diabetes is mutations of the ATP-sensitive K+ channel subunits; in transient neonatal diabetes, chromosome 6q24 abnormalities are the most common cause

Eliciting a predatory response in the eastern corn snake (Pantherophis guttatus) using live and inanimate sensory stimuli: implications for managing invasive populations

North America's Eastern corn snake (Pantherophis guttatus) has been introduced to several islands throughout the Caribbean and Australasia where it poses a significant threat to native wildlife. Invasive snake control programs often involve trapping with live bait, a practice that, as well as being costly and labour intensive, raises welfare and ethical concerns. This study assessed corn snake response to live and inanimate sensory stimuli in an attempt to inform possible future trapping of the species and the development of alternative trap lures. We exposed nine individuals to sensory cues in the form of odour, visual, vibration and combined stimuli and measured the response (rate of tongue-flick [RTF]). RTF was significantly higher in odour and combined cues treatments, and there was no significant difference in RTF between live and inanimate cues during odour treatments. Our findings suggest chemical cues are of primary importance in initiating predation and that an inanimate odour stimulus, absent of simultaneous visual and vibratory cues, is a potential low-cost alternative trap lure for the control of invasive corn snake populations

Social Network Evolution during Long-term Migration: A comparison of three case studies in the South Wales region

Ten years after Poland joined the European Union (EU), a sizable number of the once considered short-term migrants that entered the United Kingdom (UK) post-2004 have remained. From the literature, it is known that when initially migrating, social networks, composed of family and friends, are used to facilitate migration. Later, migrants’ social networks may evolve to include local, non-ethnic members of the community. Through these networks, migrants may access new opportunities within the local economy. They also serve to socialise newcomers in the cultural modalities of life in the destination country. However, what if migrants’ social networks do not evolve or evolve in a limited manner? Is cultural integration still possible under these conditions? Using data collected from three case studies in the South Wales region –Cardiff, Merthyr Tydfil & Llanelli- from 2008-2012, the aim of this article is to compare Polish migrants’ social network usage, or lack thereof, over time. This comparison will be used to understand how these social networks can be catalysts and barriers for cultural integration. The findings point to the migrants’ varied use of their local social networks, which is dependent upon their language skill acquisition and their labour market mobility in the destination country

Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis

Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials