Consequences of converting graded to action potentials upon neural information coding and energy efficiency

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ~50% in generator potentials, to ~3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation

A multiscale approach to estimating topographically correlated propagation delays in radar interferograms

When targeting small amplitude surface deformation, using repeat orbit Interferometric Synthetic Aperture Radar (InSAR) observations can be plagued by propagation delays, some of which correlate with topographic variations. These topographically-correlated delays result from temporal variations in vertical stratification of the troposphere. An approximate model assuming a linear relationship between topography and interferometric phase has been used to correct observations with success in a few studies. Here, we present a robust approach to estimating the transfer function, K, between topography and phase that is relatively insensitive to confounding processes (earthquake deformation, phase ramps from orbital errors, tidal loading, etc.). Our approach takes advantage of a multiscale perspective by using a band-pass decomposition of both topography and observed phase. This decomposition into several spatial scales allows us to determine the bands wherein correlation between topography and phase is significant and stable. When possible, our approach also takes advantage of any inherent redundancy provided by multiple interferograms constructed with common scenes. We define a unique set of component time intervals for a given suite of interferometric pairs. We estimate an internally consistent transfer function for each component time interval, which can then be recombined to correct any arbitrary interferometric pair. We demonstrate our approach on a synthetic example and on data from two locations: Long Valley Caldera, California, which experienced prolonged periods of surface deformation from pressurization of a deep magma chamber, and one coseismic interferogram from the 2007 Mw 7.8 Tocapilla earthquake in northern Chile. In both examples, the corrected interferograms show improvements in regions of high relief, independent of whether or not we pre-correct the data for a source model. We believe that most of the remaining signals are predominately due to heterogeneous water vapor distribution that requires more sophisticated correction methods than those described here

Southern San Andreas-San Jacinto fault system slip rates estimated from earthquake cycle models constrained by GPS and interferometric synthetic aperture radar observations

We use ground geodetic and interferometric synthetic aperture radar satellite observations across the southern San Andreas (SAF)-San Jacinto (SJF) fault systems to constrain their slip rates and the viscosity structure of the lower crust and upper mantle on the basis of periodic earthquake cycle, Maxwell viscoelastic, finite element models. Key questions for this system are the SAF and SJF slip rates, the slip partitioning between the two main branches of the SJF, and the dip of the SAF. The best-fitting models generally have a high-viscosity lower crust (η = 10^(21) Pa s) overlying a lower-viscosity upper mantle (η = 10^(19) Pa s). We find considerable trade-offs between the relative time into the current earthquake cycle of the San Jacinto fault and the upper mantle viscosity. With reasonable assumptions for the relative time in the earthquake cycle, the partition of slip is fairly robust at around 24–26 mm/a for the San Jacinto fault system and 16–18 mm/a for the San Andreas fault. Models for two subprofiles across the SAF-SJF systems suggest that slip may transfer from the western (Coyote Creek) branch to the eastern (Clark-Superstition hills) branch of the SJF from NW to SE. Across the entire system our best-fitting model gives slip rates of 2 ± 3, 12 ± 9, 12 ± 9, and 17 ± 3 mm/a for the Elsinore, Coyote Creek, Clark, and San Andreas faults, respectively, where the large uncertainties in the slip rates for the SJF branches reflect the large uncertainty in the slip rate partitioning within the SJF system

The severity of pandemic H1N1 influenza in the United States, from April to July 2009: A Bayesian analysis

Background: Accurate measures of the severity of pandemic (H1N1) 2009 influenza (pH1N1) are needed to assess the likely impact of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with confidence. Also, detection of severe cases may be more likely, resulting in overestimation of the severity of an average case. We sought to estimate the probabilities that symptomatic infection would lead to hospitalization, ICU admission, and death by combining data from multiple sources. Methods and Findings: We used complementary data from two US cities: Milwaukee attempted to identify cases of medically attended infection whether or not they required hospitalization, while New York City focused on the identification of hospitalizations, intensive care admission or mechanical ventilation (hereafter, ICU), and deaths. New York data were used to estimate numerators for ICU and death, and two sources of data - medically attended cases in Milwaukee or self-reported influenza-like illness (ILI) in New York - were used to estimate ratios of symptomatic cases to hospitalizations. Combining these data with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic patients who died (symptomatic case-fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR), overall and by age category. Evidence, prior information, and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated an sCFR of 0.048% (95% credible interval [CI] 0.026%-0.096%), sCIR of 0.239% (0.134%-0.458%), and sCHR of 1.44% (0.83%-2.64%). Using self-reported ILI, we obtained estimates approximately 7-96lower. sCFR and sCIR appear to be highest in persons aged 18 y and older, and lowest in children aged 5-17 y. sCHR appears to be lowest in persons aged 5-17; our data were too sparse to allow us to determine the group in which it was the highest. Conclusions: These estimates suggest that an autumn-winter pandemic wave of pH1N1 with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with the greatest impact in children aged 0-4 and adults 18-64. These estimates of impact depend on assumptions about total incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the total proportion of the population symptomatically infected were lower than assumed.published_or_final_versio

Pathogenesis of lassa fever in cynomolgus macaques

<p>Abstract</p> <p>Background</p> <p>Lassa virus (LASV) infection causes an acute and sometimes fatal hemorrhagic disease in humans and nonhuman primates; however, little is known about the development of Lassa fever. Here, we performed a pilot study to begin to understand the progression of LASV infection in nonhuman primates.</p> <p>Methods</p> <p>Six cynomolgus monkeys were experimentally infected with LASV. Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease.</p> <p>Results</p> <p>Dendritic cells were identified as a prominent target of LASV infection in a variety of tissues in all animals at day 7 while Kupffer cells, hepatocytes, adrenal cortical cells, and endothelial cells were more frequently infected with LASV in tissues of terminal animals (days 13.5-17). Meningoencephalitis and neuronal necrosis were noteworthy findings in terminal animals. Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers.</p> <p>Conclusion</p> <p>The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.</p

Upper Plate And Subduction Interface Deformation Models In The 2022 Revision Of The Aotearoa New Zealand National Seismic Hazard Model

As part of the 2022 revision of the Aotearoa New Zealand National Seismic Hazard Model (NZ NSHM 2022), deformation models were constructed for the upper plate faults and subduction interfaces that impact ground-shaking hazard in New Zealand. These models provide the locations, geometries, and slip rates of the earthquake-producing faults in the NZ NSHM 2022. For upper plate faults, two deformation models were developed: a geologic model derived directly from the fault geometries and geologic slip rates in the NZ Community Fault Model version 1.0 (NZ CFM v.1.0); and a geodetic model that uses the same faults and fault geometries and derives fault slip-deficit rates by inverting geodetic strain rates for back slip on those specified faults. The two upper plate deformation models have similar total moment rates, but the geodetic model has higher slip rates on low-slip-rate faults, and the geologic model has higher slip rates on higher-slip-rate faults. Two deformation models are developed for the Hikurangi–Kermadec subduction inter-face. The Hikurangi–Kermadec geometry is a linear blend of the previously published interface models. Slip-deficit rates on the Hikurangi portion of the deformation model are updated from the previously published block models, and two end member models are developed to represent the alternate hypotheses that the interface is either frictionally locked or creeping at the trench. The locking state in the Kermadec portion is less well constrained, and a single slip-deficit rate model is developed based on plate convergence rate and coupling considerations. This single Kermadec realization is blended with each of the two Hikurangi slip-deficit rate models to yield two overall Hikurangi–Kermadec deformation models. The Puysegur subduction interface deformation model is based on geometry taken directly from the NZ CFM v.1.0, and a slip-deficit rate derived from published geodetic plate convergence rate and interface coupling estimates

Effective Post-Exposure Treatment of Ebola Infection

Ebola viruses are highly lethal human pathogens that have received considerable attention in recent years due to an increasing re-emergence in Central Africa and a potential for use as a biological weapon. There is no vaccine or treatment licensed for human use. In the past, however, important advances have been made in developing preventive vaccines that are protective in animal models. In this regard, we showed that a single injection of a live-attenuated recombinant vesicular stomatitis virus vector expressing the Ebola virus glycoprotein completely protected rodents and nonhuman primates from lethal Ebola challenge. In contrast, progress in developing therapeutic interventions against Ebola virus infections has been much slower and there is clearly an urgent need to develop effective post-exposure strategies to respond to future outbreaks and acts of bioterrorism, as well as to treat laboratory exposures. Here we tested the efficacy of the vesicular stomatitis virus-based Ebola vaccine vector in post-exposure treatment in three relevant animal models. In the guinea pig and mouse models it was possible to protect 50% and 100% of the animals, respectively, following treatment as late as 24 h after lethal challenge. More important, four out of eight rhesus macaques were protected if treated 20 to 30 min following an otherwise uniformly lethal infection. Currently, this approach provides the most effective post-exposure treatment strategy for Ebola infections and is particularly suited for use in accidentally exposed individuals and in the control of secondary transmission during naturally occurring outbreaks or deliberate release

Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates

Ebola virus (EBOV) is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV) is particularly robust, as it can also confer protection when administered as a postexposure treatment. A concern that has been raised regarding the replication-competent VSV vectors that express EBOV glycoproteins is how these vectors would be tolerated by individuals with altered or compromised immune systems such as patients infected with HIV. This is especially important as all EBOV outbreaks to date have occurred in areas of Central and Western Africa with high HIV incidence rates in the population. In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVΔG/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). All six animals showed no evidence of illness associated with the VSVΔG/ZEBOVGP vaccine, suggesting that this vaccine may be safe in immunocompromised populations. While one goal of the study was to evaluate the safety of the candidate vaccine platform, it was also of interest to determine if altered immune status would affect vaccine efficacy. The vaccine protected 4 of 6 SHIV-infected macaques from death following ZEBOV challenge. Evaluation of CD4+ T cells in all animals showed that the animals that succumbed to lethal ZEBOV challenge had the lowest CD4+ counts, suggesting that CD4+ T cells may play a role in mediating protection against ZEBOV

Coding Efficiency of Fly Motion Processing Is Set by Firing Rate, Not Firing Precision

To comprehend the principles underlying sensory information processing, it is important to understand how the nervous system deals with various sources of perturbation. Here, we analyze how the representation of motion information in the fly's nervous system changes with temperature and luminance. Although these two environmental variables have a considerable impact on the fly's nervous system, they do not impede the fly to behave suitably over a wide range of conditions. We recorded responses from a motion-sensitive neuron, the H1-cell, to a time-varying stimulus at many different combinations of temperature and luminance. We found that the mean firing rate, but not firing precision, changes with temperature, while both were affected by mean luminance. Because we also found that information rate and coding efficiency are mainly set by the mean firing rate, our results suggest that, in the face of environmental perturbations, the coding efficiency is improved by an increase in the mean firing rate, rather than by an increased firing precision