A point process framework for modeling electrical stimulation of the auditory nerve

Model-based studies of auditory nerve responses to electrical stimulation can provide insight into the functioning of cochlear implants. Ideally, these studies can identify limitations in sound processing strategies and lead to improved methods for providing sound information to cochlear implant users. To accomplish this, models must accurately describe auditory nerve spiking while avoiding excessive complexity that would preclude large-scale simulations of populations of auditory nerve fibers and obscure insight into the mechanisms that influence neural encoding of sound information. In this spirit, we develop a point process model of the auditory nerve that provides a compact and accurate description of neural responses to electric stimulation. Inspired by the framework of generalized linear models, the proposed model consists of a cascade of linear and nonlinear stages. We show how each of these stages can be associated with biophysical mechanisms and related to models of neuronal dynamics. Moreover, we derive a semi-analytical procedure that uniquely determines each parameter in the model on the basis of fundamental statistics from recordings of single fiber responses to electric stimulation, including threshold, relative spread, jitter, and chronaxie. The model also accounts for refractory and summation effects that influence the responses of auditory nerve fibers to high pulse rate stimulation. Throughout, we compare model predictions to published physiological data and explain differences in auditory nerve responses to high and low pulse rate stimulation. We close by performing an ideal observer analysis of simulated spike trains in response to sinusoidally amplitude modulated stimuli and find that carrier pulse rate does not affect modulation detection thresholds.Comment: 1 title page, 27 manuscript pages, 14 figures, 1 table, 1 appendi

Carbon Black Exposure Induces Alterations in Mitochondrial Morphology in Human Lung Cells: A Software-Based Quantitative Analysis

Nanoparticulates of pure carbon, carbon black (CB), are a common atmospheric pollutant in industrialized and heavily populated areas. They are produced primarily via combustion of fossil fuels, and represent a significant health hazard. They are known to worsen asthma and bronchitis when inhaled and to cause inflammation, heart dysfunction, and oxidative stress when incorporated into other organs. The key focal point of this work was to examine markers of stress signaling and cellular dysfunction when human bronchial epithelial cells (16HBE14o-) were exposed to CB particles ranging in size from 70 nm and averaging 130 nm in diameter. BrdU incorporation and DAPI staining studies revealed a 24-hour CB exposure (25 ug/ml and higher) to reduce rates of cell division and to significantly elevate percentages of cells exhibiting apoptotic nuclear morphology. Chronic exposure (24 days) of cells to low doses of CB (5 ug/ml) revealed a significant impact upon both cell division and survival. A central marker for stress signaling in these lung cells was elevation of reactive oxygen species, which rose within 12 hours of CB exposure, consistent with stress signals that induce mitochondrial apoptosis. Sirtuin 1, a stress regulated protein deacetylase in the cytosol, whose levels are known to be destabilized by ROS elevation in stressed cells, displayed no significant change following CB exposure at varied doses. Analysis of mitochondrial dynamics via fluorescence microscopy revealed clear changes in organization and morphology. HBE cells were treated with varying doses of CB, fixed, and analyzed via immunocytochemistry. Mitochondria were labelled using a Tom20 antibody conjugate (Alexa488), while microtubules were assessed with phalloidin (Alexa594). Using software developed in MatLab, mitochondria were analyzed for changes in mitochondrial size and localization. Significant changes were identified with regard to an increase in mitochondrial size, and strong trends were observed in an increased localization preference for the perinuclear region. A discussion of the link between elevated ROS levels and mitochondrial behavior will be discussed

Innovation in Rangeland Monitoring: Annual, 30 M, Plant Functional Type Percent Cover Maps for U.S. Rangelands, 1984-2017

Innovations in machine learning and cloud‐based computing were merged with historical remote sensing and field data to provide the first moderate resolution, annual, percent cover maps of plant functional types across rangeland ecosystems to effectively and efficiently respond to pressing challenges facing conservation of biodiversity and ecosystem services. We utilized the historical Landsat satellite record, gridded meteorology, abiotic land surface data, and over 30,000 field plots within a Random Forests model to predict per‐pixel percent cover of annual forbs and grasses, perennial forbs and grasses, shrubs, and bare ground over the western United States from 1984 to 2017. Results were validated using three independent collections of plot‐level measurements, and resulting maps display land cover variation in response to changes in climate, disturbance, and management. The maps, which will be updated annually at the end of each year, provide exciting opportunities to expand and improve rangeland conservation, monitoring, and management. The data open new doors for scientific investigation at an unprecedented blend of temporal fidelity, spatial resolution, and geographic scale

The place of strategic environmental assessment in the privatised electricity industry

The private sector has given relatively little attention to the emergence of strategic environmental assessment (SEA); even recently privatised utilities, where SEA might be deemed particularly appropriate, and whose activities are likely to fall within the scope of the European Union SEA Directive, have shown less interest than might be expected. However, the global trend towards the privatisation of state-owned enterprises makes the adaptation of SEA towards these industries all the more pressing. This paper addresses the place that SEA might take within the electricity sector, taking the privatised UK electricity industry as an example. Particular challenges are posed by the radical restructuring of the industry, designed to introduce competitive behaviour, making the development of comprehensive SEA processes problematic, and requiring SEA to be placed in the context of corporate environmental policy and objectives.</p

Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

Background: A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. &lt;p/&gt;Methods: Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). &lt;p/&gt;Results: 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m2. MTD was 10 mg/m2; DLTs at 12 (2/4 patients) and 10 mg/m2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and Cmax from 1--10 mg/m2. Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. &lt;p/&gt;Conclusions: TP300 had predictable hematologic toxicity, and diarrhea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage

Integrating Evolutionary and Functional Tests of Adaptive Hypotheses: A Case Study of Altitudinal Differentiation in Hemoglobin Function in an Andean Sparrow, \u3ci\u3eZonotrichia capensis\u3c/i\u3e

In air-breathing vertebrates, the physiologically optimal blood-O2 affinity is jointly determined by the prevailing partial pressure of atmospheric O2, the efficacy of pulmonary O2 transfer, and internal metabolic demands. Consequently, genetic variation in the oxygenation properties of hemoglobin (Hb) may be subject to spatially varying selection in species with broad elevational distributions. Here we report the results of a combined functional and evolutionary analysis of Hb polymorphism in the rufouscollared sparrow (Zonotrichia capensis), a species that is continuously distributed across a steep elevational gradient on the Pacific slope of the Peruvian Andes. We integrated a population genomic analysis that included all postnatally expressed Hb genes with functional studies of naturally occurring Hb variants, as well as recombinant Hb (rHb) mutants that were engineered through site-directed mutagenesis. We identified three clinally varying amino acid polymorphisms: Two in the αA-globin gene, which encodes the α-chain subunits of the major HbA isoform, and one in the αD-globin gene, which encodes the α-chain subunits of the minor HbD isoform. We then constructed and experimentally tested single- and double-mutant rHbs representing each of the alternative αA-globin genotypes that predominate at different elevations. Although the locusspecific patterns of altitudinal differentiation suggested a history of spatially varying selection acting on Hb polymorphism, the experimental tests demonstrated that the observed amino acid mutations have no discernible effect on respiratory properties of the HbA or HbD isoforms. These results highlight the importance of experimentally validating the hypothesized effects of genetic changes in protein function to avoid the pitfalls of adaptive storytelling

The under-ice microbiome of seasonally frozen lakes

Compared to the well-studied open water of the “growing” season, under-ice conditions in lakes are characterized by low and rather constant temperature, slow water movements, limited light availability, and reduced exchange with the surrounding landscape. These conditions interact with ice-cover duration to shape microbial processes in temperate lakes and ultimately influence the phenology of community and ecosystem processes. We review the current knowledge on microorganisms in seasonally frozen lakes. Specifically, we highlight how under-ice conditions alter lake physics and the ways that this can affect the distribution and metabolism of auto- and heterotrophic microorganisms. We identify functional traits that we hypothesize are important for understanding under-ice dynamics and discuss how these traits influence species interactions. As ice coverage duration has already been seen to reduce as air temperatures have warmed, the dynamics of the under-ice microbiome are important for understanding and predicting the dynamics and functioning of seasonally frozen lakes in the near future

Investigation relative to the Roentgen Satellite (ROSAT)

Reports include: High Resolution Observations of the Central Region of M31; The X-ray Emission of Low-X-ray-Luminosity Early-Type Galaxies: Gas Versus Compact Sources; Interaction Between Cluster Gas and Radio Features of Cygnus A; Hot Gas and Dark Halos in Early-Type Galaxies; A Gravitational Lens in X-rays - 0957+461; How Massive are Early-Type Galaxies?; Three Crab-Like SNR in the Large Magellanic Cloud; and Soft X-ray Emission from Boundary Layers in Cataclysmic Variables. Papers submitted to the Astrophysical Journal are attached

The Gliese 86 Binary System: A Warm Jupiter Formed in a Disk Truncated at ≈2 au

© 2022. The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/Gliese 86 is a nearby K dwarf hosting a giant planet on a ≈16 day orbit and an outer white dwarf companion on a ≈century-long orbit. In this study we combine radial velocity data (including new measurements spanning more than a decade) with high angular resolution imaging and absolute astrometry from Hipparcos and Gaia to measure the current orbits and masses of both companions. We then simulate the evolution of the Gl 86 system to constrain its primordial orbit when both stars were on the main sequence; the closest approach between the two stars was then about 9 au. Such a close separation limited the size of the protoplanetary disk of Gl 86 A and dynamically hindered the formation of the giant planet around it. Our measurements of Gl 86 B and Gl 86 Ab’s orbits reveal Gl 86 as a system in which giant planet formation took place in a disk truncated at ≈2 au. Such a disk would be just big enough to harbor the dust mass and total mass needed to assemble Gl 86 Ab’s core and envelope, assuming a high disk accretion rate and a low viscosity. Inefficient accretion of the disk onto Gl 86 Ab, however, would require a disk massive enough to approach the Toomre stability limit at its outer truncation radius. The orbital architecture of the Gl 86 system shows that giant planets can form even in severely truncated disks and provides an important benchmark for planet formation theory.Peer reviewe