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The composition of ions plays a crucial role for the fundamental plasma properties in the terrestrial magnetosphere. We investigate the oxygen‐to‐hydrogen ratio in the near‐Earth magnetosphere from −10 RE < XGSE < 10 RE. The results are based on seven years of ion flux measurements in the energy range ∼10 keV to ∼955 keV from the RAPID and CIS instruments on board the Cluster satellites. We find that (1) hydrogen ions at ∼10 keV show only a slight correlation with the geomagnetic conditions and interplanetary magnetic field changes. They are best correlated with the solar wind dynamic pressure and density, which is an expected effect of the magnetospheric compression; (2) ∼10 keV O+ ion intensities are more strongly affected during disturbed phase of a geomagnetic storm or substorm than >274 keV O+ ion intensities, relative to the corresponding hydrogen intensities; (3) In contrast to ∼10 keV ions, the >274 keV O+ions show the strongest acceleration during growth phase and not during the expansion phase itself. This suggests a connection between the energy input to the magnetosphere and the effective energization of energetic ions during growth phase; (4) The ratio between quiet and disturbed times for the intensities of ion ionospheric outflow is similar to those observed in the near‐Earth magnetosphere at >274 keV. Therefore, the increase of the energetic ion intensity during disturbed time is likely due to the intensification and the effective acceleration of the ionospheric source. In conclusion, the energization process in the near‐Earth magnetosphere is mass dependent and it is more effective for the heavier ions. Key Points Response of the O+ and H+ to the geomagnetic and solar wind changes The strongest energetic O+ acceleration is during growth phase O+ at lower energies is strongly affected by storms and substorms

Key Points The glucose-phosphorylating enzyme glucokinase has a crucial role in glucose homeostasis as 'glucose sensor' of the insulin-producing pancreatic β-cells and as a regulatory step in the conversion of glucose to glycogen, as well as in gluconeogenesis in the liver. Autosomal dominant activating or inactivating mutations of glucokinase in humans and rodents cause hyperinsulinism and diabetes, respectively. The activating point mutations are clustered at a location in the enzyme structure that is distinct from the substrate binding site, which suggests that glucokinase has an allosteric activator site. These and other observations highlighted glucokinase as a potential drug target. Glucokinase activators (GKAs) have been discovered recently that stimulate the enzyme allosterically by lowering its glucose S 0.5 (the concentration of glucose that allows half-maximal activity of the enzyme) and Hill coefficient (n H ) and increasing its catalytic constant ( k cat ). At present, approximately 100 patents on low molecular-weight compounds with GKA characteristics have been disclosed by the pharmaceutical industry. GKAs lower blood glucose levels in normal laboratory animals and humans by stimulating insulin release and enhancing hepatic glucose uptake. GKAs lower blood glucose in animal models of type 2 diabetes and in humans with type 2 diabetes. An assessment of the current status of basic and clinical GKA-related research indicates that this new class of anti-diabetic drugs shows promise for monotherapy or combination drug therapy of type 2 diabetes. The glucose-phosphorylating enzyme glucokinase acts as a glucose sensor of the insulin-producing pancreatic islet β-cells, controls the conversion of glucose to glycogen in the liver and also regulates hepatic glucose production, and is therefore a potential therapeutic target for the treatment of type 2 diabetes. Here, Matschinsky discusses the physiological roles of glucokinase and the most recent progress in the development of pharmacological glucokinase activators. Glucokinase, a unique isoform of the hexokinase enzymes, which are known to phosphorylate D -glucose and other hexoses, was identified during the past three to four decades as a new, promising drug target for type 2 diabetes. Glucokinase serves as a glucose sensor of the insulin-producing pancreatic islet β-cells, controls the conversion of glucose to glycogen in the liver and regulates hepatic glucose production. Guided by this fundamental knowledge, several glucokinase activators are now being developed, and have so far been shown to lower blood glucose in several animal models of type 2 diabetes and in initial trials in humans with the disease. Here, the scientific basis and current status of this new approach to diabetes therapy are discussed.

The JUpiter ICy moons Explorer (JUICE) of the European Space Agency will investigate Jupiter and its icy moons Europa, Ganymede, and Callisto, with the aim to better understand the origin and evolution of our Solar System and the emergence of habitable worlds around gas giants. The Particle Environment Package (PEP) on board JUICE is designed to measure neutrals and ions and electrons at thermal, suprathermal, and radiation belt energies (eV to MeV). In the vicinity of Callisto, PEP will characterize the plasma environment, the outer parts of Callisto's atmosphere and ionosphere and their interaction with Jupiter's dynamic magnetosphere. Roughly 20 Callisto flybys with closest approaches between 200 and 5,000 km altitude are planned over the course of the JUICE mission. In this article, we review the state of the art regarding Callisto's ambient environment and magnetospheric interaction with recent modeling efforts for Callisto's atmosphere and ionosphere. Based on this review, we identify science opportunities for the PEP observations to optimize scientific insight gained from the foreseen JUICE flybys. These considerations will inform both science operation planning of PEP and JUICE and they will guide future model development for Callisto's atmosphere, ionosphere, and their interaction with the plasma environment. Key Points Particle Environment Package (PEP) on JUpiter ICy moons Explorer (JUICE) will provide in situ and remote measurements of Callisto's atmosphere and its space environment during ∼20 flybys We investigate operation plans and instrument capabilities to optimize science return from PEP observations The interactions of the atmosphere with the space environment and surface are complex and must be further analyzed in preparation for JUICE

A system of Majorana zero modes with random infinite-range interactions—the Sachdev-Ye-Kitaev (SYK) model—is thought to exhibit an intriguing relation to the horizons of extremal black holes in two-dimensional anti–de Sitter space. This connection provides a rare example of holographic duality between a solvable quantum-mechanical model and dilaton gravity. Here, we propose a physical realization of the SYK model in a solid-state system. The proposed setup employs the Fu-Kane superconductor realized at the interface between a three-dimensional topological insulator and an ordinary superconductor. The requisite N Majorana zero modes are bound to a nanoscale hole fabricated in the superconductor that is threaded by N quanta of magnetic flux. We show that when the system is tuned to the surface neutrality point (i.e., chemical potential coincident with the Dirac point of the topological insulator surface state) and the hole has sufficiently irregular shape, the Majorana zero modes are described by the SYK Hamiltonian. We perform extensive numerical simulations to demonstrate that the system indeed exhibits physical properties expected of the SYK model, including thermodynamic quantities and two-point as well as four-point correlators, and discuss ways in which these can be observed experimentally.

Parkinson's Disease is a progressive neurodegenerative disorder marked by motor fluctuations in later disease stages that complicate treatment with levodopa. Traditional approaches to dosing often fail to capture the complex and dynamic nature of these fluctuations. In this study, we present the PD9™ algorithm, a novel approach to continuous motor state monitoring using data from a wrist-worn inertial measurement unit sensor. The algorithm provides minute-by-minute assessments of motor state severity on a unified scale quantifying bradykinesia, dyskinesia, and ON states. Data collected from 67 patients over 55,482 min were analyzed to assess levodopa response cycles. Across 218 identified levodopa cycles, the algorithm revealed reproducible patterns of symptom development based on the motor state at the time of levodopa administration. In particular, levodopa doses administered during non-ideal motor states (e.g., during dyskinesia) highlighted the limitations of fixed, empirically determined dosing regimens and underscore the need for individualized therapy, based on motor state. These findings demonstrate how AI-enabled continuous monitoring could help realize a more personalized treatment of Parkinson's disease and improve patient outcomes.

Dirac and Weyl semimetals form an ideal platform for testing ideas developed in high-energy physics to describe massless relativistic particles. One such quintessentially field-theoretic idea of the chiral anomaly already resulted in the prediction and subsequent observation of the pronounced negative magnetoresistance in these novel materials for parallel electric and magnetic fields. Here, we predict that the chiral anomaly occurs—and has experimentally observable consequences—when real electromagnetic fields E and B are replaced by strain-induced pseudo-electromagnetic fields e and b . For example, a uniform pseudomagnetic field b is generated when a Weyl semimetal nanowire is put under torsion. In accordance with the chiral anomaly equation, we predict a negative contribution to the wire resistance proportional to the square of the torsion strength. Remarkably, left- and right-moving chiral modes are then spatially segregated to the bulk and surface of the wire forming a “topological coaxial cable.” This produces hydrodynamic flow with potentially very long relaxation time. Another effect we predict is the ultrasonic attenuation and electromagnetic emission due to a time-periodic mechanical deformation causing pseudoelectric field e . These novel manifestations of the chiral anomaly are most striking in the semimetals with a single pair of Weyl nodes but also occur in Dirac semimetals such as Cd3As2 and Na3Bi and Weyl semimetals with unbroken time-reversal symmetry.

Recent studies have shown that low energy ions constitute a significant part of the total ion population in the Earth's magnetosphere. In this study, we have used a comprehensive data set with measurements of cold (total energy less than 70 eV) ion velocity and density to determine their source. This data set is derived from Cluster satellite measurements combined with solar wind and interplanetary magnetic field measurements and geomagnetic indices. By using the guiding center equation of motion, we were able to calculate the trajectories and thus determine the source region of the cold ions. Our results show that the polar cap region is the primary source for cold ions. We also found that the expansion and contraction of the polar cap as a consequence of changes in solar wind parameters were correlated with the source region size and intensity of the cold ion outflow. Elevated outflow fluxes near the nightside auroral zone and the dayside cusps during disturbed conditions suggest that energy and particle precipitation from the magnetosphere or directly from the solar wind can enhance the outflow of cold ions from the ionosphere. Key Points The primary source of the cold ions in magnetotail is the polar cap regions Elevated fluxes on polar cap during disturbed geomagnetic periods are found Size and intensity of the source region varies with geomagnetic activity

Second-order nonlinear spectroscopy has proven to be a powerful tool in elucidating key chemical and structural characteristics at a variety of interfaces. However, the presence of interfacial potentials may lead to complications regarding the interpretation of second harmonic and vibrational sum frequency generation responses from charged interfaces due to mixing of absorptive and dispersive contributions. Here, we examine by means of mathematical modeling how this interaction influences second-order spectral lineshapes. We discuss our findings in the context of reported nonlinear optical spectra obtained from charged water/air and solid/liquid interfaces and demonstrate the importance of accounting for the interfacial potential-dependent χ (3) term in interpreting lineshapes when seeking molecular information from charged interfaces using second-order spectroscopy. Charged interfaces are important in chemical systems, but the influence of charge on vibrational sum frequency spectra has only recently been considered. Here the authors show the importance of accounting for the interfacial potential-dependent χ (3) term in interpreting spectral lineshapes from charged interfaces.

Background This study aimed to evaluate the safety of raw vegetable products present on the German market regarding toxin-producing Bacillus cereus sensu lato ( s.l. ) group bacteria. Results A total of 147 B. cereus s.l. group strains isolated from cucumbers, carrots, herbs, salad leaves and ready-to-eat mixed salad leaves were analyzed. Their toxinogenic potential was assessed by multiplex PCR targeting the hemolysin BL ( hbl ) component D ( hblD ), non-hemolytic enterotoxin ( nhe ) component A ( nheA ), cytotoxin K-2 ( cytK-2 ) and the cereulide ( ces ) toxin genes. In addition, a serological test was used to detect Hbl and Nhe toxins. On the basis of PCR and serological results, none of the strains were positive for the cereulide protein/genes, while 91.2, 83.0 and 37.4% were positive for the Hbl, Nhe and CytK toxins or their genes, respectively. Numerous strains produced multiple toxins. Generally, strains showed resistance against the β-lactam antibiotics such as penicillin G and cefotaxim (100%), as well as amoxicillin/clavulanic acid combination and ampicillin (99.3%). Most strains were susceptible to ciprofloxacin (99.3%), chloramphenicol (98.6%), amikacin (98.0%), imipenem (93.9%), erythromycin (91.8%), gentamicin (88.4%), tetracycline (76.2%) and trimethoprim/sulfamethoxazole combination (52.4%). The genomes of eight selected strains were sequenced. The toxin gene profiles detected by PCR and serological test mostly agreed with those from whole-genome sequence data. Conclusions Our study showed that B. cereus s.l. strains encoding toxin genes occur in products sold on the German market and that these may pose a health risk to the consumer if present at elevated levels. Furthermore, a small percentage of these strains harbor antibiotic resistance genes. The presence of these bacteria in fresh produce should, therefore, be monitored to guarantee their safety.

We study the effect of the magnetosonic Mach number on the position of the bow shock (BS) at Mars. The magnetosonic Mach number is calculated from solar wind data obtained by the ACE satellite upstream of Earth and extrapolated to Mars during two intervals, starting in 2005 and 2007, when Mars and Earth were close to opposition. An increased Mach number is observed to cause the Martian BS to move to lower altitudes and the variation in the terminator altitude is proportional to the Mach number change. When the Mach number is lowered, the BS flares more. We also compare our results to previous studies at Venus. The variation in BS altitude with magnetosonic Mach number is found to be very similar to the variation of the Venusian BS, which has previously been shown to decrease linearly in altitude with increasing Mach number.