Activation and inhibition of retinal ganglion cells in response to epiretinal electrical stimulation: A computational modelling study

Objective. Retinal prosthetic devices aim to restore sight in visually impaired people by means of electrical stimulation of surviving retinal ganglion cells (RGCs). This modelling study aims to demonstrate that RGC inhibition caused by high-intensity cathodic pulses greatly influences their responses to epiretinal electrical stimulation and to investigate the impact of this inhibition on spatial activation profiles as well as their implications for retinal prosthetic device design. Another aim is to take advantage of this inhibition to reduce axonal activation in the nerve fibre layer. Approach. A three-dimensional finite-element model of epiretinal electrical stimulation was utilized to obtain RGC activation and inhibition threshold profiles for a range of parameters. Main results. RGC activation and inhibition thresholds were highly dependent on cell and stimulus parameters. Activation thresholds were 1.5, 3.4 and 11.3 mu A for monopolar electrodes with 5, 20 and 50 mu m radii, respectively. Inhibition to activation threshold ratios were mostly within the range 2-10. Inhibition significantly altered spatial patterns of RGC activation. With concentric electrodes and appropriately high levels of stimulus amplitudes, activation of passing axons was greatly reduced. Significance. RGC inhibition significantly impacts their spatial activation profiles, and therefore it most likely influences patterns of perceived phosphenes induced by retinal prosthetic devices. Thus this inhibition should be taken into account in future studies concerning retinal prosthesis development. It might be possible to utilize this inhibitory effect to bypass activation of passing axons and selectively stimulate RGCs near their somas and dendrites to achieve more localized phosphenes

Preload-based starling-like control for rotary blood pumps: Numerical comparison with pulsatility control and constant speed operation

In this study, we evaluate a preload-based Starling-like controller for implantable rotary blood pumps (IRBPs) using left ventricular end-diastolic pressure (PLVED) as the feedback variable. Simulations are conducted using a validated mathematical model. The controller emulates the response of the natural left ventricle (LV) to changes in PLVED. We report the performance of the preload-based Starling-like controller in comparison with our recently designed pulsatility controller and constant speed operation. In handling the transition from a baseline state to test states, which include vigorous exercise, blood loss and a major reduction in the LV contractility (LVC), the preload controller outperformed pulsatility control and constant speed operation in all three test scenarios. In exercise, preload-control achieved an increase of 54 in mean pump flow ((Q) over bar (P)) with minimum loading on the LV, while pulsatility control achieved only a 5 increase in flow and a decrease in mean pump speed. In a hemorrhage scenario, the preload control maintained the greatest safety margin against LV suction. PLVED for the preload controller was 4.9 mmHg, compared with 0.4 mmHg for the pulsatility controller and 0.2 mmHg for the constant speed mode. This was associated with an adequate mean arterial pressure (MAP) of 84 mmHg. In transition to low LVC, (Q) over bar (P) for preload control remained constant at 5.22 L/min with a PLVED of 8.0 mmHg. With regards to pulsatility control, (Q) over bar (P) fell to the nonviable level of 2.4 L/min with an associated PLVED of 16 mmHg and a MAP of 55 mmHg. Consequently, pulsatility control was deemed inferior to constant speed mode with a PLVED of 11 mmHg and a (Q) over bar (P) of 5.13 L/min in low LVC scenario. We conclude that pulsatility control imposes a danger to the patient in the severely reduced LVC scenario, which can be overcome by using a preload-based Starling-like control approach

Online estimation of respiratory mechanics in non-invasive pressure support ventilation: a bench model study.

An online algorithm for determining respiratory mechanics in patients using non-invasive ventilation (NIV) in pressure support mode was developed and embedded in a ventilator system. Based on multiple linear regression (MLR) of respiratory data, the algorithm was tested on a patient bench model under conditions with and without leak and simulating a variety of mechanics. Bland-Altman analysis indicates reliable measures of compliance across the clinical range of interest (± 11-18% limits of agreement). Resistance measures showed large quantitative errors (30-50%), however, it was still possible to qualitatively distinguish between normal and obstructive resistances. This outcome provides clinically significant information for ventilator titration and patient management

Characteristics of American coals in relation to their conversion into clean-energy fuels. Final report. [1150 samples of US coals]

To further characterize the Nation's coals, the Penn State Coal Sample Bank and Data Base were expanded to include a total of 1150 coal samples. The Sample Bank includes full-seam channel samples as well as samples of lithotypes, seam benches, and sub-seam sections. To the extent feasible and appropriate basic compositional data were generated for each sample and validated and computerized. These data include: proximate analysis, ultimate analysis, sulfur forms analysis, calorific value, maceral analysis, vitrinite reflectance analysis, ash fusion analysis, free-swelling index determination, Gray-King coke type determination, Hardgrove grindability determination, Vicker's microhardness determination, major and minor element analysis, trace element analysis, and mineral species analysis. During the contract period more than 5000 samples were prepared and distributed. A theoretical and experimental study of the pyrolysis of coal has been completed. The reactivity of chars, produced from all ranks of American coals, has been studied with regard to reactivity to air, CO/sub 2/, H/sub 2/ and steam. Another area research has concerned the catalytic effect of minerals and various cations on the gasification processes. Combustion of chars, low volatile fuels, coal-oil-water-air emulsions and other subjects of research are reported here. The products of this research can be found in 23 DOE Technical Research Reports and 49 published papers. As another mechanism of technology transfer, the results have been conveyed via more than 70 papers presented at a variety of scientific meetings. References to all of these are contained in this report

Somatic point mutations are enriched in non-coding RNAs with possible regulatory function in breast cancer

Non-coding RNAs (ncRNAs) form a large portion of the mammalian genome. However, their biological functions are poorly characterized in cancers. In this study, using a newly developed tool, SomaGene, we analyze de novo somatic point mutations from the International Cancer Genome Consortium (ICGC) whole-genome sequencing data of 1,855 breast cancer samples. We identify 1030 candidates of ncRNAs that are significantly and explicitly mutated in breast cancer samples. By integrating data from the ENCODE regulatory features and FANTOM5 expression atlas, we show that the candidate ncRNAs significantly enrich active chromatin histone marks (1.9 times), CTCF binding sites (2.45 times), DNase accessibility (1.76 times), HMM predicted enhancers (2.26 times) and eQTL polymorphisms (1.77 times). Importantly, we show that the 1030 ncRNAs contain a much higher level (3.64 times) of breast cancer-associated genome-wide association (GWAS) single nucleotide polymorphisms (SNPs) than genome-wide expectation. Such enrichment has not been seen with GWAS SNPs from other cancers. Using breast cell line related Hi-C data, we then show that 82% of our candidate ncRNAs (1.9 times) significantly interact with the promoter of protein-coding genes, including previously known cancer-associated genes, suggesting the critical role of candidate ncRNA genes in the activation of essential regulators of development and differentiation in breast cancer. We provide an extensive web-based resource ( https://www.ihealthe.unsw.edu.au/research ) to communicate our results with the research community. Our list of breast cancer-specific ncRNA genes has the potential to provide a better understanding of the underlying genetic causes of breast cancer. Lastly, the tool developed in this study can be used to analyze somatic mutations in all cancers.Narges Rezaie, Masroor Bayati, Mehrab Hamidi, Maedeh Sadat Tahaei, Sadegh Khorasani, Nigel H. Lovell, James Breen, Hamid R. Rabiee, Hamid Alinejad-Rokn