Variability of Quasilinear Diffusion Coefficients for Plasmaspheric Hiss

In the outer radiation belt, the acceleration and loss of high‐energy electrons is largely controlled by wave‐particle interactions. Quasilinear diffusion coefficients are an efficient way to capture the small‐scale physics of wave‐particle interactions due to magnetospheric wave modes such as plasmaspheric hiss. The strength of quasilinear diffusion coefficients as a function of energy and pitch angle depends on both wave parameters and plasma parameters such as ambient magnetic field strength, plasma number density, and composition. For plasmaspheric hiss in the magnetosphere, observations indicate large variations in the wave intensity and wave normal angle, but less is known about the simultaneous variability of the magnetic field and number density. We use in situ measurements from the Van Allen Probe mission to demonstrate the variability of selected factors that control the size and shape of pitch angle diffusion coefficients: wave intensity, magnetic field strength, and electron number density. We then compare with the variability of diffusion coefficients calculated individually from colocated and simultaneous groups of measurements. We show that the distribution of the plasmaspheric hiss diffusion coefficients is highly non‐Gaussian with large variance and that the distributions themselves vary strongly across the three phase space bins studied. In most bins studied, the plasmaspheric hiss diffusion coefficients tend to increase with geomagnetic activity, but our results indicate that new approaches that include natural variability may yield improved parameterizations. We suggest methods like stochastic parameterization of wave‐particle interactions could use variability information to improve modeling of the outer radiation belt

Attention-Based Machine Vision Models and Techniques for Solar Wind Speed Forecasting Using Solar EUV Images

Abstract: Extreme ultraviolet images taken by the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory make it possible to use deep vision techniques to forecast solar wind speed—a difficult, high‐impact, and unsolved problem. At a 4 day time horizon, this study uses attention‐based models and a set of methodological improvements to deliver an 11.1% lower RMSE and a 17.4% higher prediction correlation compared to the previous work testing on the period from 2010 to 2018. Our analysis shows that attention‐based models combined with our pipeline consistently outperform convolutional alternatives. Our study shows a large performance improvement by using a 30 min as opposed to a daily sampling frequency. Our model has learned relationships between coronal holes' characteristics and the speed of their associated high‐speed streams, agreeing with empirical results. Our study finds a strong dependence of our best model on the phase of the solar cycle, with the best performance occurring in the declining phase

Attention-Based Machine Vision Models and Techniques for Solar Wind Speed Forecasting Using Solar EUV Images

Abstract: Extreme ultraviolet images taken by the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory make it possible to use deep vision techniques to forecast solar wind speed—a difficult, high‐impact, and unsolved problem. At a 4 day time horizon, this study uses attention‐based models and a set of methodological improvements to deliver an 11.1% lower RMSE and a 17.4% higher prediction correlation compared to the previous work testing on the period from 2010 to 2018. Our analysis shows that attention‐based models combined with our pipeline consistently outperform convolutional alternatives. Our study shows a large performance improvement by using a 30 min as opposed to a daily sampling frequency. Our model has learned relationships between coronal holes' characteristics and the speed of their associated high‐speed streams, agreeing with empirical results. Our study finds a strong dependence of our best model on the phase of the solar cycle, with the best performance occurring in the declining phase

Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.

BackgroundT cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s.MethodsPatients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 1010 total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72.ResultsFourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14 weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48 weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had 111Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed.ConclusionThese findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity

Temporal variability of quasi-linear pitch-angle diffusion

This is the final version. Available on open access from Frontiers Media via the DOI in this recordData availability statement; The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://emfisis.physics.uiowa.edu/data/index; https://doi.org/10.17864/1947.212, Ensemble experiment data can be found at https://doi.org/10.25398/rd.northumbria.2126623.Kinetic wave-particle interactions in Earth’s outer radiation belt energize and scatter high-energy electrons, playing an important role in the dynamic variation of the extent and intensity of the outer belt. It is possible to model the effects of wave-particle interactions across long length and time scales using quasi-linear theory, leading to a Fokker-Planck equation to describe the effects of the waves on the high energy electrons. This powerful theory renders the efficacy of the wave-particle interaction in a diffusion coefficient that varies with energy or momentum and pitch angle. In this article we determine how the Fokker-Planck equation responds to the temporal variation of the quasi-linear diffusion coefficient in the case of pitch-angle diffusion due to plasmaspheric hiss. Guided by in-situ observations of how hiss wave activity and local number density change in time, we use stochastic parameterisation to describe the temporal evolution of hiss diffusion coefficients in ensemble numerical experiments. These experiments are informed by observations from three different example locations in near-Earth space, and a comparison of the results indicates that local differences in the distribution of diffusion coefficients can result in material differences to the ensemble solutions. We demonstrate that ensemble solutions of the Fokker-Planck equation depend both upon the timescale of variability (varied between minutes and hours), and the shape of the distribution of diffusion coefficients. Based upon theoretical construction of the diffusion coefficients and the results presented here, we argue that there is a useful maximum averaging timescale that should be used to construct a diffusion coefficient from observations, and that this timescale is likely less than the orbital period of most inner magnetospheric missions. We discuss time and length scales of wave-particle interactions relative to the drift velocity of high-energy electrons and confirm that arithmetic drift-averaging is can be appropriate in some cases. We show that in some locations, rare but large values of the diffusion coefficient occur during periods of relatively low number density. Ensemble solutions are sensitive to the presence of these rare values, supporting the need for accurate cold plasma density models in radiation belt descriptions.Natural Environment Research Council (NERC)Science and Technology Facilities Council (STFC)University of ExeterAlexander von Humboldt Postdoctoral Research Fellowshi

Disinhibition Mediates a Form of Hippocampal Long-Term Potentiation in Area CA1

The hippocampus plays a central role in memory formation in the mammalian brain. Its ability to encode information is thought to depend on the plasticity of synaptic connections between neurons. In the pyramidal neurons constituting the primary hippocampal output to the cortex, located in area CA1, firing of presynaptic CA3 pyramidal neurons produces monosynaptic excitatory postsynaptic potentials (EPSPs) followed rapidly by feedforward (disynaptic) inhibitory postsynaptic potentials (IPSPs). Long-term potentiation (LTP) of the monosynaptic glutamatergic inputs has become the leading model of synaptic plasticity, in part due to its dependence on NMDA receptors (NMDARs), required for spatial and temporal learning in intact animals. Using whole-cell recording in hippocampal slices from adult rats, we find that the efficacy of synaptic transmission from CA3 to CA1 can be enhanced without the induction of classic LTP at the glutamatergic inputs. Taking care not to directly stimulate inhibitory fibers, we show that the induction of GABAergic plasticity at feedforward inhibitory inputs results in the reduced shunting of excitatory currents, producing a long-term increase in the amplitude of Schaffer collateral-mediated postsynaptic potentials. Like classic LTP, disinhibition-mediated LTP requires NMDAR activation, suggesting a role in types of learning and memory attributed primarily to the former and raising the possibility of a previously unrecognized target for therapeutic intervention in disorders linked to memory deficits, as well as a potentially overlooked site of LTP expression in other areas of the brain

Individual Differences in Processing Speed and Working Memory Speed as Assessed with the Sternberg Memory Scanning Task

The Sternberg Memory Scanning (SMS) task provides a measure of processing speed (PS) and working memory retrieval speed (WMS). In this task, participants are presented with sets of stimuli that vary in size. After a delay, one item is presented, and participants indicate whether or not the item was part of the set. Performance is assessed by speed and accuracy for both the positive (item is part of the set) and the negative trials (items is not part of the set). To examine the causes of variation in PS and WMS, 623 adult twins and their siblings completed the SMS task. A non-linear growth curve (nLGC) model best described the increase in reaction time with increasing set size. Genetic analyses showed that WMS (modeled as the Slope in the nLGC model) has a relatively small variance which is not due to genetic variation while PS (modeled as the Intercept in the nLGC model) showed large individual differences, part of which could be attributed to additive genetic factors. Heritability was 38% for positive and 32% for negative trials. Additional multivariate analyses showed that the genetic effects on PS for positive and negative trials were completely shared. We conclude that genetic influences on working memory performance are more likely to act upon basic processing speed and (pre)motoric processes than on the speed with which an item is retrieved from short term memory

Long-term changes in habitat and trophic level of Southern Ocean squid in relation to environmental conditions

Long-term studies of pelagic nekton in the Southern Ocean and their responses to ongoing environmental change are rare. Using stable isotope ratios measured in squid beaks recovered from diet samples of wandering albatrosses Diomedea exulans, we assessed decadal variation (from 1976 to 2016) in the habitat (δ13C) and trophic level (δ15N) of five important Southern Ocean squid species in relation to indices of environmental conditions—Southern Oscillation Index (SOI) and Southern Annular Mode (SAM). Based on δ13C values, corrected for the Suess effect, habitat had changed over the last 50 years for Taonius sp. B (Voss), Gonatus antarcticus, Galiteuthis glacialis and Histioteuthis atlantica but not Moroteuthopsis longimana. By comparison, mean δ15N values were similar across decades for all five species, suggesting minimal changes in trophic levels. Both SAM and SOI have increased in strength and frequency over the study period but, of the five species, only in Taonius sp. B (Voss) did these indices correlate with, δ13C and δ15N values, indicating direct relationships between environmental conditions, habitat and trophic level. The five cephalopod species therefore changed their habitats with changing environmental conditions over the last 50 years but maintained similar trophic levels. Hence, cephalopods are likely to remain important prey for top predators in Southern Ocean food webs, despite ongoing climate change