Hardware Coupled Nonliear Oscillators as a Model of Retina

An electronic circuit consisting of coupled nonlinear oscillators⁴＇⁵ simulates the spatiotemporal processing in retina. Complex behavior recorded in vivo from ganglion cells in the cat retina 6 in response to flickering light spots is matched by setting the coupling parameters in the hardware oscillators. An electronic neuron (c-neuron) is composed of four coupled oscillators: three representing the light driven generator potential of the ganglion cell, the other representing membrane spiking. A 1-D ring of e-neurons reflects the connectivity in the retina: strong neighborhood excitation, and wider inhibition. E-neurons, like retinal ganglion cells, exhibit spontaneous spiking. Driving more than one e-neuron with a sinusoidally modulated input increases regularity in the e-neurons responses, as is found in the retina. We encoded c-neuron activity into single-bit spike trains and found chaotic spontaneous oscillations using close return histograms. The model's behavior gives a new understanding of neurophysiological findings.Whitehall (S93-24); Air Force Office of Scientific Research (F49620-92-J-0499, F49620-92-J-0334); Office of Naval Research (N00014-89-J-1377, N00014-95-I-0409); MIT Undergraduate Research Oppurtunities Progra

Northward field excursions in Saturn’s magnetotail and their relationship to magnetospheric periodicities

We present results from an investigation of Cassini encounters with Saturn’s magnetotail current sheet, using magnetic field and plasma data. In the first of two intervals shown, small periodic changes in the north-south component of the magnetic field are matched by periodic density enhancements associated with the plasma sheet center. In the second interval, a large plasmoid signature is observed set against a background of small-scale current sheet motions. We interpret the quasi-periodic small field deflections and density enhancements as large-scale wave-like motion of the current sheet. We stress that plasmoid signatures are of a clearly different character and occur much less frequently

PT Invariant Complex E (8) Root Spaces

We provide a construction procedure for complex root spaces invariant under antilinear transformations, which may be applied to any Coxeter group. The procedure is based on the factorisation of a chosen element of the Coxeter group into two factors. Each of the factors constitutes an involution and may therefore be deformed in an antilinear fashion. Having the importance of the E(8)-Coxeter group in mind, such as underlying a particular perturbation of the Ising model and the fact that for it no solution could be found previously, we exemplify the procedure for this particular case. As a concrete application of this construction we propose new generalisations of Calogero-Moser Sutherland models and affine Toda field theories based on the invariant complex root spaces and deformed complex simple roots, respectively

AI is a viable alternative to high throughput screening: a 318-target study

High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Balancing neurotrophin pathway and sortilin function: its role in human disease

Neurotensin receptor-3 or sortilin is a vacuolar protein sorting 10 protein domain (Vps10p) has been firstly discovered in the human brain, it acts as receptor or co-receptor of the cell and traffics different proteins within the cell. Sortilin deregulation contributes to the development of several diseases, including neurological diseases and cancer. On the other hand, neurotrophins which are a family of proteins essential for the nervous system development, function and plasticity. The first discovered member is the nerve growth factor; other members are brain-derived growth factor, neurotrophin-3 and neurotrophin-4. Nerve growth factor and brain-derived growth factor are the common neurotrophins that have a role in cancer. Neurotrophins initiate their signals through interaction with tyrosine receptor kinases TrkA, TrkB, and TrkC; each member has an affinity for a specific receptor to stimulate cell survival, while the interaction with p75NTR initiates cell apoptosis pathway by forming a complex with sortilin and neurotrophin precursors. A number of therapeutic approaches are emerging to target the neurotrophins pathway as well as sortilin

Bone Health Improvement Protocol

Introduction. Metabolic bone disease is a malady that causessignificant morbidity and mortality to a patient who has sustaineda fragility fracture. There is currently no protocol toprevent secondary fragility fracture at our institution. The objectiveof this study was to create an appropriate protocol forimplementing clinical pathways for physicians to diagnose andtreat osteoporosis and fragility fractures by educating patients. Methods. A multidisciplinary team created an appropriateprotocol that could be implemented in an inpatient setting.A thorough literature review was conducted to evaluatepotential barriers and efficacious methods of protocol design. Results. A bone health improvement protocol was developed.Any patient over the age of 50 who sustains a fracture from lowenergy trauma, such as a fall from standing or less, should beconsidered to place into this protocol. These patients receivededucation on metabolic bone disease, a prescription for highdose vitamin D therapy, and laboratory testing to determinethe etiology of their metabolic bone disease. Continuity of careof these patients with their primary care provider was providedfor further management of their metabolic bone disease andevaluation of their disease after discharged from the hospital. Conclusion. Comprehensive secondary prevention should consistof osteoporosis assessment and treatment together with afall risk assessment. With this protocol, secondary fragility fracturespotentially could be prevented. KS J Med 2017;10(3):62-66

State space modeling of time-varying contemporaneous and lagged relations in connectivity maps

Most connectivity mapping techniques for neuroimaging data assume stationarity (i.e., network parameters are constant across time), but this assumption does not always hold true. The authors provide a description of a new approach for simultaneously detecting time-varying (or dynamic) contemporaneous and lagged relations in brain connectivity maps. Specifically, they use a novel raw data likelihood estimation technique (involving a second-order extended Kalman filter/smoother embedded in a nonlinear optimizer) to determine the variances of the random walks associated with state space model parameters and their autoregressive components. The authors illustrate their approach with simulated and blood oxygen level-dependent functional magnetic resonance imaging data from 30 daily cigarette smokers performing a verbal working memory task, focusing on seven regions of interest (ROIs). Twelve participants had dynamic directed functional connectivity maps: Eleven had one or more time-varying contemporaneous ROI state loadings, and one had a time-varying autoregressive parameter. Compared to smokers without dynamic maps, smokers with dynamic maps performed the task with greater accuracy. Thus, accurate detection of dynamic brain processes is meaningfully related to behavior in a clinical sample