A 2 MV Van de Graaff accelerator as a tool for planetary and impact physics research

Investigating the dynamical and physical properties of cosmic dust can reveal a great deal of information about both the dust and its many sources. Over recent years, several spacecraft (e.g., Cassini, Stardust, Galileo, and Ulysses) have successfully characterised interstellar, interplanetary, and circumplanetary dust using a variety of techniques, including in situ analyses and sample return. Charge, mass, and velocity measurements of the dust are performed either directly (induced charge signals) or indirectly (mass and velocity from impact ionisation signals or crater morphology) and constrain the dynamical parameters of the dust grains. Dust compositional information may be obtained via either time-of-flight mass spectrometry of the impact plasma or direct sample return. The accurate and reliable interpretation of collected spacecraft data requires a comprehensive programme of terrestrial instrument calibration. This process involves accelerating suitable solar system analogue dust particles to hypervelocity speeds in the laboratory, an activity performed at the Max Planck Institut fu?r Kernphysik in Heidelberg, Germany. Here, a 2 MV Van de Graaff accelerator electrostatically accelerates charged micron and submicron-sized dust particles to speeds up to 80 km s(-1). Recent advances in dust production and processing have allowed solar system analogue dust particles (silicates and other minerals) to be coated with a thin conductive shell, enabling them to be charged and accelerated. Refinements and upgrades to the beam line instrumentation and electronics now allow for the reliable selection of particles at velocities of 1-80 km s(-1) and with diameters of between 0.05 μm and 5 μm. This ability to select particles for subsequent impact studies based on their charges, masses, or velocities is provided by a particle selection unit (PSU). The PSU contains a field programmable gate array, capable of monitoring in real time the particles' speeds and charges, and is controlled remotely by a custom, platform independent, software package. The new control instrumentation and electronics, together with the wide range of accelerable particle types, allow the controlled investigation of hypervelocity impact phenomena across a hitherto unobtainable range of impact parameters.     

Axiomatizing the Monodic Fragment of

As we can show that the two-variable monadic fragment of thefull first-order extension of the propositional branching time logic is not recursively enumerable, we show in thisarticle that the monodic fragment of can be axiomatized.     

JavAdaptor—Flexible runtime updates of Java applications

Software is changed frequently during its life cycle. New requirements come, and bugs must be fixed. To update an application, it usually must be stopped, patched, and restarted. This causes time periods of unavailability, which is always a problem for highly available applications. Even for the development of complex applications, restarts to test new program parts can be time consuming and annoying. Thus, we aim at dynamic software updates to update programs at runtime. There is a large body of research on dynamic software updates, but so far, existing approaches have shortcomings either in terms of flexibility or performance. In addition, some of them depend on specific runtime environments and dictate the program's architecture. We present JavAdaptor , the first runtime update approach based on Java that (a) offers flexible dynamic software updates, (b) is platform independent, (c) introduces only minimal performance overhead, and (d) does not dictate the program architecture. JavAdaptor combines schema changing class replacements by class renaming and caller updates with Java HotSwap using containers and proxies. It runs on top of all major standard Java virtual machines. We evaluate our approach's applicability and performance in non‐trivial case studies and compare it with existing dynamic software update approaches. Copyright © 2012 John Wiley & Sons, Ltd.     

Long‐Range Domain Structure and Symmetry Engineering by Interfacial Oxygen Octahedral Coupling at Heterostructure Interface

In epitaxial thin film systems, the crystal structure and its symmetry deviate from the bulk counterpart due to various mechanisms such as epitaxial strain and interfacial structural coupling, which is accompanyed by a change in their properties. In perovskite materials, the crystal symmetry can be described by rotations of sixfold coordinated transition metal oxygen octahedra, which are found to be altered at interfaces. Here, it is unraveled how the local oxygen octahedral coupling at perovskite heterostructural interfaces strongly influences the domain structure and symmetry of the epitaxial films resulting in design rules to induce various structures in thin films using carefully selected combinations of substrate/buffer/film. Very interestingly it is discovered that these combinations lead to structure changes throughout the full thickness of the film. The results provide a deep insight into understanding the origin of induced structures in a perovskite heterostructure and an intelligent route to achieve unique functional properties.     

Hyperinsulinemic Hypoglycemia Associated with a CaV1.2 Variant with Mixed Gain- and Loss-of-Function Effects

The voltage-dependent L-type calcium channel isoform Ca_V1.2 is critically involved in many physiological processes, e.g., in cardiac action potential formation, electromechanical coupling and regulation of insulin secretion by beta cells. Gain-of-function mutations in the calcium voltage-gated channel subunit alpha 1 C (CACNA1C) gene, encoding the Ca_V1.2 α₁-subunit, cause Timothy syndrome (TS), a multisystemic disorder that includes autism spectrum disorders and long QT (LQT) syndrome. Strikingly, TS patients frequently suffer from hypoglycemia of yet unproven origin. Using next-generation sequencing, we identified a novel heterozygous CACNA1C mutation in a patient with congenital hyperinsulinism (CHI) and associated hypoglycemic episodes. We characterized the electrophysiological phenotype of the mutated channel using voltage-clamp recordings and in silico action potential modeling experiments. The identified Ca_V1.2^L566P mutation causes a mixed electrophysiological phenotype of gain- and loss-of-function effects. In silico action potential modeling supports that this mixed electrophysiological phenotype leads to a tissue-specific impact on beta cells compared to cardiomyocytes. Thus, CACNA1C variants may be associated with non-syndromic hyperinsulinemic hypoglycemia without long-QT syndrome, explained by very specific electrophysiological properties of the mutated channel. We discuss different biochemical characteristics and clinical impacts of hypoglycemia in the context of CACNA1C variants and show that these may be associated with significant morbidity for Timothy Syndrome patients. Our findings underline that the potential of hypoglycemia warrants careful attention in patients with CACNA1C variants, and such variants should be included in the differential diagnosis of non-syndromic congenital hyperinsulinism.     

基于ZigBee无线通信的汽车倾斜度测量的应用

引言ZigBee是一种新的无线局域网传输标准,它是基于IEEE802.15.4协议基础的一个通信标准。IEEE802.15.4定义了协议的物理层和媒体介质访问控制层(MAC),而ZigBee定义了网络层、安全层和应用层,见图1。这样,     

Topical Capsaicin in Poly(lactic-co-glycolic)acid (PLGA) Nanoparticles Decreases Acute Itch and Heat Pain

Background: Capsaicin, the hot pepper agent, produces burning followed by desensitization. To treat localized itch or pain with minimal burning, low capsaicin concentrations can be repeatedly applied. We hypothesized that alternatively controlled release of capsaicin from poly(lactic-co-glycolic acid) (PLGA) nanoparticles desensitizes superficially terminating nociceptors, reducing burning. Methods: Capsaicin-loaded PLGA nanoparticles were prepared (single-emulsion solvent evaporation) and characterized (size, morphology, capsaicin loading, encapsulation efficiency, in vitro release profile). Capsaicin-PLGA nanoparticles were applied to murine skin and evaluated in healthy human participants (n = 21) for 4 days under blinded conditions, and itch and nociceptive sensations evoked by mechanical, heat stimuli and pruritogens cowhage, β-alanine, BAM8-22 and histamine were evaluated. Results: Nanoparticles (loading: 58 µg capsaicin/mg) released in vitro 23% capsaicin within the first hour and had complete release at 72 h. In mice, 24 h post-application Capsaicin-PLGA nanoparticles penetrated the dermis and led to decreased nociceptive behavioral responses to heat and mechanical stimulation (desensitization). Application in humans produced a weak to moderate burning, dissipating after 3 h. A loss of heat pain up to 2 weeks was observed. After capsaicin nanoparticles, itch and nociceptive sensations were reduced in response to pruritogens cowhage, β-alanine or BAM8-22, but were normal to histamine. Conclusions: Capsaicin nanoparticles could be useful in reducing pain and itch associated with pruritic diseases that are histamine-independent.     

SARS-CoV-2 Infection Dysregulates Cilia and Basal Cell Homeostasis in the Respiratory Epithelium of Hamsters

Similar to many other respiratory viruses, SARS-CoV-2 targets the ciliated cells of the respiratory epithelium and compromises mucociliary clearance, thereby facilitating spread to the lungs and paving the way for secondary infections. A detailed understanding of mechanism involved in ciliary loss and subsequent regeneration is crucial to assess the possible long-term consequences of COVID-19. The aim of this study was to characterize the sequence of histological and ultrastructural changes observed in the ciliated epithelium during and after SARS-CoV-2 infection in the golden Syrian hamster model. We show that acute infection induces a severe, transient loss of cilia, which is, at least in part, caused by cilia internalization. Internalized cilia colocalize with membrane invaginations, facilitating virus entry into the cell. Infection also results in a progressive decline in cells expressing the regulator of ciliogenesis FOXJ1, which persists beyond virus clearance and the termination of inflammatory changes. Ciliary loss triggers the mobilization of p73⁺ and CK14⁺ basal cells, which ceases after regeneration of the cilia. Although ciliation is restored after two weeks despite the lack of FOXJ1, an increased frequency of cilia with ultrastructural alterations indicative of secondary ciliary dyskinesia is observed. In summary, the work provides new insights into SARS-CoV-2 pathogenesis and expands our understanding of virally induced damage to defense mechanisms in the conducting airways.     

Electron Transfer in a Bio-Photoelectrode Based on Photosystem I Multilayer Immobilized on the Conducting Glass

A film of ~40 layers of partially oriented photosystem I (PSI) complexes isolated from the red alga Cyanidioschyzon merolae formed on the conducting glass through electrodeposition was investigated by time-resolved absorption spectroscopy and chronoamperometry. The experiments were performed at a range of electric potentials applied to the film and at different compositions of electrolyte solution being in contact with the film. The amount of immobilized proteins supporting light-induced charge separation (active PSI) ranged from ~10%, in the absence of any reducing agents (redox compounds or low potential), to ~20% when ascorbate and 2,6-dichlorophenolindophenol were added, and to ~35% when the high negative potential was additionally applied. The origin of the large fraction of permanently inactive PSI (65–90%) was unclear. Both reducing agents increased the subpopulation of active PSI complexes, with the neutral P700 primary electron donor, by reducing significant fractions of the photo-oxidized P700 species. The efficiencies of light-induced charge separation in the PSI film (10–35%) did not translate into an equally effective generation of photocurrent, whose internal quantum efficiency reached the maximal value of 0.47% at the lowest potentials. This mismatch indicates that the vast majority of the charge-separated states in multilayered PSI complexes underwent charge recombination.