Detection of subthreshold pulses in neurons with channel noise

Neurons are subject to various kinds of noise. In addition to synaptic noise, the stochastic opening and closing of ion channels represents an intrinsic source of noise that affects the signal processing properties of the neuron. In this paper, we studied the response of a stochastic Hodgkin-Huxley neuron to transient input subthreshold pulses. It was found that the average response time decreases but variance increases as the amplitude of channel noise increases. In the case of single pulse detection, we show that channel noise enables one neuron to detect the subthreshold signals and an optimal membrane area (or channel noise intensity) exists for a single neuron to achieve optimal performance. However, the detection ability of a single neuron is limited by large errors. Here, we test a simple neuronal network that can enhance the pulse detecting abilities of neurons and find dozens of neurons can perfectly detect subthreshold pulses. The phenomenon of intrinsic stochastic resonance is also found both at the level of single neurons and at the level of networks. At the network level, the detection ability of networks can be optimized for the number of neurons comprising the network.Comment: 14 pages, 9 figure

A dynamically cold disk galaxy in the early Universe

The extreme astrophysical processes and conditions that characterize the early Universe are expected to result in young galaxies that are dynamically different from those observed today. This is because the strong effects associated with galaxy mergers and supernova explosions would lead to most young star-forming galaxies being dynamically hot, chaotic and strongly unstable. Here we report the presence of a dynamically cold, but highly star-forming, rotating disk in a galaxy at redshift ($z$) 4.2, when the Universe was just 1.4 billion years old. Galaxy SPT-S J041839-4751.9 is strongly gravitationally lensed by a foreground galaxy at $z = 0.263$, and it is a typical dusty starburst, with global star-forming and dust properties that are in agreement with current numerical simulations and observations of its galaxy population. Interferometric imaging at a spatial resolution of about 60 pc reveals a ratio of rotational-to-random motions of $V/\sigma = 9.7\pm 0.4$, which is at least four times larger than expected from any galaxy evolution model at this epoch, but similar to the ratios of spiral galaxies in the local Universe. We derive a rotation curve with the typical shape of nearby massive spiral galaxies, which demonstrates that at least some young galaxies are dynamically akin to those observed in the local Universe, and only weakly affected by extreme physical processes.Comment: Published in Nature on 12 August 2020. The published version is available at http://www.nature.com/articles/s41586-020-2572-

Detecting low-mass haloes with strong gravitational lensing I: the effect of data quality and lensing configuration

This paper aims to quantify how the lowest halo mass that can be detected with galaxy-galaxy strong gravitational lensing depends on the quality of the observations and the characteristics of the observed lens systems. Using simulated data, we measure the lowest detectable NFW mass at each location of the lens plane, in the form of detailed sensitivity maps. In summary, we find that: (i) the lowest detectable mass Mlow decreases linearly as the signal-to-noise ratio (SNR) increases and the sensitive area is larger when we decrease the noise; (ii) a moderate increase in angular resolution (0.07′′ versus 0.09′′) and pixel scale (0.01′′ versus 0.04′′) improves the sensitivity by on average 0.25 dex in halo mass, with more significant improvement around the most sensitive regions; (iii) the sensitivity to low-mass objects is largest for bright and complex lensed galaxies located inside the caustic curves and lensed into larger Einstein rings (i.e rE ≥ 1.0′′). We find that for the sensitive mock images considered in this work, the minimum mass that we can detect at the redshift of the lens lies between 1.5 × 108 and 3 × 109 M☉. We derive analytic relations between Mlow, the SNR and resolution and discuss the impact of the lensing configuration and source structure. Our results start to fill the gap between approximate predictions and real data and demonstrate the challenging nature of calculating precise forecasts for gravitational imaging. In light of our findings, we discuss possible strategies for designing strong lensing surveys and the prospects for HST, Keck, ALMA, Euclid and other future observations

Earthquake Forecast via Neutrino Tomography

We discuss the possibility of forecasting earthquakes by means of (anti)neutrino tomography. Antineutrinos emitted from reactors are used as a probe. As the antineutrinos traverse through a region prone to earthquakes, observable variations in the matter effect on the antineutrino oscillation would provide a tomography of the vicinity of the region. In this preliminary work, we adopt a simplified model for the geometrical profile and matter density in a fault zone. We calculate the survival probability of electron antineutrinos for cases without and with an anomalous accumulation of electrons which can be considered as a clear signal of the coming earthquake, at the geological region with a fault zone, and find that the variation may reach as much as 3% for $\bar \nu_e$ emitted from a reactor. The case for a $\nu_e$ beam from a neutrino factory is also investigated, and it is noted that, because of the typically high energy associated with such neutrinos, the oscillation length is too large and the resultant variation is not practically observable. Our conclusion is that with the present reactor facilities and detection techniques, it is still a difficult task to make an earthquake forecast using such a scheme, though it seems to be possible from a theoretical point of view while ignoring some uncertainties. However, with the development of the geology, especially the knowledge about the fault zone, and with the improvement of the detection techniques, etc., there is hope that a medium-term earthquake forecast would be feasible.Comment: 6 pages, 4 figures, 1 tabl

The Earth Effect in the MSW Analysis of the Solar Neutrino Experiments

We consider the Earth effect in the MSW analysis of the Homestake, Kamiokande, GALLEX, and SAGE solar neutrino experiments. Using the time-averaged data and assuming two-flavor oscillations, the large-angle region of the combined fit extends to much smaller angles (to $\sin^22\theta \simeq 0.1$) than when the Earth effect is ignored. However, the additional constraint from the Kamiokande II day-night data excludes most of the parameter space sensitive to the Earth effect independent of astrophysical uncertainties, and leaves only a small large-angle region close to maximal mixing at 90\% C.L. The nonadiabatic solution remains unaffected by the Earth effect and is still preferred. Both theoretical and experimental uncertainties are included in the analysis.Comment: (11 pages, Revtex 3.0 (can be changed to Latex), 3 postscript figures included, UPR-0570T

Treating Solar Model Uncertainties: A Consistent Statistical Analysis of Solar Neutrino Models and Data

We describe how to consistently incorporate solar model uncertainties, along with experimental errors and correlations, when analyzing solar neutrino data to derive confidence limits on parameter space for proposed solutions of the solar neutrino problem. Our work resolves ambiguities and inconsistencies in the previous literature. As an application of our methods we calculate the masses and mixing angles allowed by the current data for the proposed MSW solution using both Bayesian and frequentist methods, allowing purely for solar model flux variations, to compare with previous work. We consider the effects of including metal diffusion in the solar models and also discuss implications for future experiments.Comment: 29 pages (incl figs), latex, 6 figures (appended as separate uuencoded file. To embed figures in text, uncomment 6 \epsfysize lines which appear before bibliography), CWRU-P5-94, CfPA-94-TTH-29, Fermilab-Pub-94/176-

Behavior of QQ-Plots and Genomic Control in Studies of Gene-Environment Interaction

Genome-wide association studies of gene-environment interaction (GxE GWAS) are becoming popular. As with main effects GWAS, quantile-quantile plots (QQ-plots) and Genomic Control are being used to assess and correct for population substructure. However, in GE work these approaches can be seriously misleading, as we illustrate; QQ-plots may give strong indications of substructure when absolutely none is present. Using simulation and theory, we show how and why spurious QQ-plot inflation occurs in GE GWAS, and how this differs from main-effects analyses. We also explain how simple adjustments to standard regression-based methods used in GE GWAS can alleviate this problem

Factor structure and construct validity of the Adult Social Care Outcomes Toolkit for Carers (ASCOT-Carer)

Background: The ASCOT-Carer is a self-report instrument designed to measure social care-related quality of life (SCRQoL). This article presents the psychometric testing and validation of the ASCOT-Carer four response-level interview (INT4) in a sample of unpaid carers of adults who receive publicly-funded social care services in England. Methods: Unpaid carers were identified through a survey of users of publicly-funded social care services in England. 387 carers completed a face-to-face or telephone interview. Data on variables hypothesised to be related to SCRQoL (for example, characteristics of the carer, cared-for person and care situation) and measures of carer experience, strain, health-related quality of life and overall QoL were collected. Relationships between these variables and overall SCRQoL score were evaluated through correlation, ANOVA and regression analysis to test the construct validity of the scale. Internal reliability was assessed using Cronbach’s alpha and feasibility by the number of missing responses. Results: The construct validity was supported by statistically significant relationships between SCRQoL and scores on instruments of related constructs, as well as with characteristics of the carer and care recipient in univariate and multivariate analyses. A Cronbach’s alpha of 0.87 (7 items) indicates that the internal reliability of the instrument is satisfactory and a low number of missing responses (<1%) indicates a high level of acceptance. Conclusions: The results provide evidence to support the construct validity, factor structure, internal reliability and feasibility of the ASCOT-Carer INT4 as an instrument for measuring social care-related quality of life of unpaid carers who care for adults with a variety of long-term conditions, disability or problems related to old age

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability