Van Allen Probes show that the inner radiation zone contains no MeV electrons: ECT/MagEIS data

Abstract We present Van Allen Probe observations of electrons in the inner radiation zone. The measurements were made by the Energetic Particle, Composition, and Thermal Plasma/Magnetic Electron Ion Spectrometer (MagEIS) sensors that were designed to measure electrons with the ability to remove unwanted signals from penetrating protons, providing clean measurements. No electrons \u3e900 keV were observed with equatorial fluxes above background (i.e., \u3e0.1 el/(cm2 s sr keV)) in the inner zone. The observed fluxes are compared to the AE9 model and CRRES observations. Electron fluxes \u3c200 keV exceeded the AE9 model 50% fluxes and were lower than the higher-energy model fluxes. Phase space density radial profiles for 1.3 ≤ L* \u3c 2.5 had mostly positive gradients except near L*~2.1, where the profiles for μ = 20–30 MeV/G were flat or slightly peaked. The major result is that MagEIS data do not show the presence of significant fluxes of MeV electrons in the inner zone while current radiation belt models and previous publications do

Outer Van Allen Radiation Belt Response to Interacting Interplanetary Coronal Mass Ejections

We study the response of the outer Van Allen radiation belt during an intense magnetic storm on 15-22 February 2014. Four interplanetary coronal mass ejections (ICMEs) arrived at Earth, of which the three last ones were interacting. Using data from the Van Allen Probes, we report the first detailed investigation of electron fluxes from source (tens of kiloelectron volts) to core (megaelectron volts) energies and possible loss and acceleration mechanisms as a response to substructures (shock, sheath and ejecta, and regions of shock-compressed ejecta) in multiple interacting ICMEs. After an initial enhancement induced by a shock compression of the magnetosphere, core fluxes strongly depleted and stayed low for 4 days. This sustained depletion can be related to a sequence of ICME substructures and their conditions that influenced the Earth's magnetosphere. In particular, the main depletions occurred during a high-dynamic pressure sheath and shock-compressed southward ejecta fields. These structures compressed/eroded the magnetopause close to geostationary orbit and induced intense and diverse wave activity in the inner magnetosphere (ULF Pc5, electromagnetic ion cyclotron, and hiss) facilitating both effective magnetopause shadowing and precipitation losses. Seed and source electrons in turn experienced stronger variations throughout the studied interval. The core fluxes recovered during the last ICME that made a glancing blow to Earth. This period was characterized by a concurrent lack of losses and sustained acceleration by chorus and Pc5 waves. Our study highlights that the seemingly complex behavior of the outer belt during interacting ICMEs can be understood by the knowledge of electron dynamics during different substructures.Peer reviewe

The Response of Earth's Electron Radiation Belts to Geomagnetic Storms : Statistics From the Van Allen Probes Era Including Effects From Different Storm Drivers

A statistical study was conducted of Earth's radiation belt electron response to geomagnetic storms using NASA's Van Allen Probes mission. Data for electrons with energies ranging from 30 keV to 6.3 MeV were included and examined as a function of L-shell, energy, and epoch time during 110 storms with SYM-H 1 MeV also revealed a marked increase in likelihood of a depletion at all L-shells through the outer belt (3.5 1-MeV electrons throughout the outer belt, while storms driven by full CMEs and stream interaction regions are most likely to produce an enhancement of MeV electrons at lower (L similar to 4.5) L-shells, respectively. CME sheaths intriguingly result in a distinct enhancement of similar to 1-MeV electrons around L similar to 5.5, and on average, CME sheaths and stream interaction regions result in double outer belt structures.Peer reviewe

Weapons Make the Man (Larger): Formidability Is Represented as Size and Strength in Humans

In order to determine how to act in situations of potential agonistic conflict, individuals must assess multiple features of a prospective foe that contribute to the foe's resource-holding potential, or formidability. Across diverse species, physical size and strength are key determinants of formidability, and the same is often true for humans. However, in many species, formidability is also influenced by other factors, such as sex, coalitional size, and, in humans, access to weaponry. Decision-making involving assessments of multiple features is enhanced by the use of a single summary variable that encapsulates the contributions of these features. Given both a) the phylogenetic antiquity of the importance of size and strength as determinants of formidability, and b) redundant experiences during development that underscore the contributions of size and strength to formidability, we hypothesize that size and strength constitute the conceptual dimensions of a representation used to summarize multiple diverse determinants of a prospective foe's formidability. Here, we test this hypothesis in humans by examining the effects of a potential foe's access to weaponry on estimations of that individual's size and strength. We demonstrate that knowing that an individual possesses a gun or a large kitchen knife leads observers to conceptualize him as taller, and generally larger and more muscular, than individuals who possess only tools or similarly mundane objects. We also document that such patterns are not explicable in terms of any actual correlation between gun ownership and physical size, nor can they be explained in terms of cultural schemas or other background knowledge linking particular objects to individuals of particular size and strength. These findings pave the way for a fuller understanding of the evolution of the cognitive systems whereby humans – and likely many other social vertebrates – navigate social hierarchies

Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

Objective: Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods: In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results: More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions: The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients

Genetic Deletion of Laminin Isoforms β2 and γ3 Induces a Reduction in Kir4.1 and Aquaporin-4 Expression and Function in the Retina

Glial cells such as retinal Müller glial cells are involved in potassium ion and water homeostasis of the neural tissue. In these cells, inwardly rectifying potassium (Kir) channels and aquaporin-4 water channels play an important role in the process of spatial potassium buffering and water drainage. Moreover, Kir4.1 channels are involved in the maintenance of the negative Müller cell membrane potential. The subcellular distribution of Kir4.1 and aquaporin-4 channels appears to be maintained by interactions with extracellular and intracellular molecules. Laminins in the extracellular matrix, dystroglycan in the membrane, and dystrophins in the cytomatrix form a complex mediating the polarized expression of Kir4.1 and aquaporin-4 in Müller cells.The aim of the present study was to test the function of the β2 and γ3 containing laminins in murine Müller cells. We used knockout mice with genetic deletion of both β2 and γ3 laminin genes to assay the effects on Kir4.1 and aquaporin-4. We studied protein and mRNA expression by immunohistochemistry, Western Blot, and quantitative RT-PCR, respectively, and membrane currents of isolated cells by patch-clamp experiments. We found a down-regulation of mRNA and protein of Kir4.1 as well as of aquaporin-4 protein in laminin knockout mice. Moreover, Müller cells from laminin β2 and γ3 knockout mice had reduced Kir-mediated inward currents and their membrane potentials were more positive than those in age-matched wild-type mice.These findings demonstrate a strong impact of laminin β2 and γ3 subunits on the expression and function of both aquaporin-4 and Kir4.1, two important membrane proteins in Müller cells

The global structure and time evolution of dayside magnetopause surface eigenmodes

Theoretical work and recent observations suggest that the dayside magnetopause may support its own eigenmode, consisting of propagating surface waves which reflect at the northern and southern ionospheres. These magnetopause surface eigenmodes (MSEs) are a potential source of magnetospheric ultralow‐frequency (ULF) waves with frequencies less than 2 mHz. Here we use the Space Weather Modeling Framework to study the magnetospheric response to impulsive solar wind dynamic pressure increases. Waves with 1.8 mHz frequency are excited whose global properties are largely consistent with theoretical predictions for MSE and cannot be explained by other known ULF wave modes. These simulation results lead to two key findings: (1) MSE can be sustained in realistic magnetic field geometries with nonzero flow shear and finite current layer thickness at the magnetopause and (2) MSE can seed the growth of tailward propagating surface waves via the Kelvin‐Helmholtz instability.Key PointsDayside ULF response to pulse consistent with magnetopause surface eigenmodeMagnetopause surface eigenmodes are a potential source of ULF waves below 2 mHzMagnetopause surface eigenmodes seed tailward propagating surface wave growthPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111803/1/grl52799.pd

Associations of lumbar scoliosis with presentation of suspected early axial spondyloarthritis

Objective: Scoliosis may impact the mechanical loading and cause secondary changes of the sacroiliac joints and lumbar spine. Our goal was to look how lumbar scoliosis modify the clinical and imaging-study in patients with recent-onset inflammatory back pain (IBP) suggesting axial spondyloarthritis (axSpA).Methods: Baseline weight-bearing lumbar-spine radiographs obtained in the DESIR cohort of patients aged 18-50 years and having IBP for at least 3 months but less than 3 years suggesting axSpA were studied. After training on scoliosis detection based on Cobb's angle>10 degrees plus Nash-Moe grade >= 1, readers blinded to patient data measured spine lumbar scoliosis, sacral horizontal angle, lumbosacral angle and lumbar lordosis on the radiograph of the lumbar and scored sacroiliitis on the radiograph of the pelvis. Baseline MRIs T1 and STIR of the lumbar spine and sacroiliac joints were evaluated for respectively degenerative changes and signs of axSpA.Results: Of the 360 patients (50.8% females) 88.7% had lumbar pain and 69.3% met ASAS criteria for axSpA. Mean Cobb's angle was 3.2 degrees +/- 5.0 degrees and 28 (7.7%) patients had lumbar scoliosis. No statistical differences were observed for radiographic sacroiliitis, MRI sacroiliitis, modified Stoke Ankylosing Spondylitis Spinal Score, Pfirmmann score, high-intensity zone, protrusion, extrusion, MODIC score between patients with and without scoliosis. In both groups, degenerative changes by MRI were rare and predominated at L4-L5 and L5-S1.Conclusion: In patients with early IBP suggesting axSpA, lumbar scoliosis was not associated with inflammatory or degenerative changes. (C) 2019 Elsevier Inc. All rights reserved.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Efficient Photodynamic Therapy against Gram-Positive and Gram-Negative Bacteria Using THPTS, a Cationic Photosensitizer Excited by Infrared Wavelength

The worldwide rise in the rates of antibiotic resistance of bacteria underlines the need for alternative antibacterial agents. A promising approach to kill antibiotic-resistant bacteria uses light in combination with a photosensitizer to induce a phototoxic reaction. Concentrations of 1, 10 and 100µM of tetrahydroporphyrin-tetratosylat (THPTS) and different incubation times (30, 90 and 180min) were used to measure photodynamic efficiency against two Gram-positive strains of S.aureus (MSSA and MRSA), and two Gram-negative strains of E.coli and P.aeruginosa. We found that phototoxicity of the drug is independent of the antibiotic resistance pattern when incubated in PBS for the investigated strains. Also, an incubation with 100µM THPTS followed by illumination, yielded a 6lg (≥99.999%) decrease in the viable numbers of all bacteria strains tested, indicating that the THPTS drug has a high degree of photodynamic inactivation. We then modulated incubation time, photosensitizer concentration and monitored the effect of serum on the THPTS activity. In doing so, we established the conditions to obtain the strongest bactericidal effect. Our results suggest that this new and highly pure synthetic compound should improve the efficiency of photodynamic therapy against multiresistant bacteria and has a significant potential for clinical applications in the treatment of nosocomial infections