First measurements of an imaging heavy ion beam probe at the ASDEX Upgrade tokamak.

The imaging heavy ion beam probe (i-HIBP) diagnostic has been successfully commissioned at ASDEX Upgrade. The i-HIBP injects a primary neutral beam into the plasma, where it is ionized, leading to a fan of secondary (charged) beams. These are deflected by the magnetic field of the tokamak and collected by a scintillator detector, generating a strike-line light pattern that encodes information on the density, electrostatic potential, and magnetic field of the plasma edge. The first measurements have been made, demonstrating the proof-of-principle of this diagnostic technique. A primary beam of 85/87Rb has been used with energies ranging between 60 and 72 keV and extracted currents up to 1.5 mA. The first signals have been obtained in experiments covering a wide range of parameter spaces, with plasma currents (Ip) between 0.2 and 0.8 MA and on-axis toroidal magnetic field (Bt) between 1.9 and 2.7 T. Low densities appear to be critical for the performance of the diagnostic, as signals are typically observed only when the line integrated density is below 2.0-3.0 × 1019 m-2 in the central interferometer chord, depending on the plasma shape. The strike line moves as expected when Ip is ramped, indicating that current measurements are possible. Additionally, clear dynamics in the intensity of the strike line are often observed, which might be linked to changes in the edge profile structure. However, the signal-to-background ratio of the signals is hampered by stray light, and the image guide degradation is due to neutron irradiation. Finally, simulations have been carried out to investigate the sensitivity of the expected signals to plasma density and temperature. The results are in qualitative agreement with the experimental observations, suggesting that the diagnostic is almost insensitive to fluctuations in the temperature profile, while the signal level is highly determined by the density profile due to the beam attenuation.

Jejunal arteriovenous malformation and multiple acquired extrahepatic portosystemic shunts in a juvenile dog, presenting with melena.

A juvenile dog referred with a 1-month history of persistent melena and severe anaemia, was diagnosed with a jejunal arteriovenous malformation, and multiple acquired extrahepatic portosystemic shunts. A midline coeliotomy was performed, the jejunal arteriovenous malformation was localised intraoperatively and was successfully removed via an enterectomy. Histopathology confirmed a true arteriovenous malformation. Despite the initial improvement, the patient developed seizure episodes secondary to hepatic encephalopathy 8 months after surgery. Fifteen months after surgery, the owner opted for euthanasia due to the ongoing seizure episodes. Post-mortem histologic examination of the liver showed features consistent with portal vein hypoplasia. A congenital arteriovenous malformation should be considered as a differential diagnosis in juvenile patients with a chronic history of haemorrhage from the gastrointestinal tract. In addition, acquired portosystemic shunts may occur in patients with portal vein hypoplasia and jejunal arteriovenous malformations.

High-heat flux ball-pen probe head in ASDEX-Upgrade.

A new high heat flux ball-pen probe head installed on the midplane manipulator is currently being used in ASDEX-Upgrade (AUG). The probe was designed to withstand high heat fluxes making possible the investigation of the plasma edge under harsh conditions, such as low power H-mode. Composed of seven pins (four Langmuir probes, mounted in two Mach probe pairs, and three ball-pen probes), the new probe head allows us to measure several plasma parameters simultaneously and with high temporal resolution. A novel method to correct the sheath potential dynamically accounting for the total secondary electron emission is introduced together with applications to obtain the electron temperature and plasma potential profiles. The total secondary electron emission yield is obtained from particle in cell simulations in AUG condition and probe realistic impact angle with respect to the magnetic field. Finally, the probe capability to investigate turbulence around the separatrix of AUG is discussed.

In search of Kipling's six honest serving men in upper limb rehabilitation: within participant case-crossover experiment nested within a web-based questionnaire.

PURPOSE: In search of Kipling's six honest serving men in upper limb rehabilitation after stroke, we sought to investigate clinicians' perspective of when and where to begin therapy, how much and what therapy to provide, and who and why (or not) to provide therapy.Materials & methods: Within-participant case cross-over experiments were nested within an anonymous web-based questionnaire (21 questions, three cases). Graph theory-based voting to produce ranked ordered lists and mixed-effect logistic regression were performed. RESULTS: In total, 225 Australian stroke clinicians responded: 53% occupational therapists, 61% working in acute/inpatient stroke setting. Most respondents indicated they did not have a protocol/expectation regarding when (62%), how much (84%) or what (60%) therapy to provide in their setting. Respondents ranked 24-h to 7-days post-stroke as the optimal time to commence therapy, and 30- to 60-min per day as the optimal dose to provide. Within-participant experiments demonstrated that greater motor recovery as time progressed increased the odds of offering therapy, while lack of motor recovery, shoulder pain, neurological decline and sole therapist reduced the odds. CONCLUSION: We need to develop an evidence base concerning Kipling's six honest serving men and equip clinicians with clinical decision-making skills aligned with this focus.IMPLICATIONS FOR REHABILITATIONMost clinicians did not have access to a protocol / clinical pathway which defines when, how much and what upper limb therapy to provide after stroke, which may be improved by providing individual clinicians with organisational support to make therapy decisions.To improve the personalisation of upper limb rehabilitation in clinical practice, we need to understand when and where after stroke to begin therapy, how much and what therapy to provide, as well as who and why (clinical decision-making) to provide therapy.Clinicians perceive clinical trials as successful if the therapy can demonstrate recovery that is greater than a minimal clinical important difference (MCID).

Self-adaptive diagnostic of radial fast-ion loss measurements on the ASDEX Upgrade tokamak (invited).

A poloidal array of scintillator-based Fast-Ion Loss Detectors (FILDs) has been installed in the ASDEX Upgrade (AUG) tokamak. While all AUG FILD systems are mounted on reciprocating arms driven externally by servomotors, the reciprocating system of the FILD probe located just below the midplane is based on a magnetic coil that is energized in real-time by the AUG discharge control system. This novel reciprocating system allows, for the first time, real-time control of the FILD position including infrared measurements of its probe head temperature to avoid overheating. This considerably expands the diagnostic operational window, enabling unprecedented radial measurements of fast-ion losses. Fast collimator-slit sweeping (up to 0.2 mm/ms) is used to obtain radially resolved velocity-space measurements along 8 cm within the scrape-off layer. This provides a direct evaluation of the neutral beam deposition profiles via first-orbit losses. Moreover, the light-ion beam probe (LIBP) technique is used to infer radial profiles of fast-ion orbit deflection. This radial-LIBP technique is applied to trapped orbits (exploring both the plasma core and the FILD stroke near the wall), enabling radial localization of internal plasma fluctuations (neoclassical tearing modes). This is quantitatively compared against electron cyclotron emission measurements, showing excellent agreement. For the first time, radial profiles of fast-ion losses in MHD quiescent plasmas as well as in the presence of magnetic islands and edge localized modes are presented.

Design and simulation of an imaging neutral particle analyzer for the ASDEX Upgrade tokamak.

An Imaging Neutral Particle Analyzer (INPA) diagnostic has been designed for the ASDEX Upgrade (AUG) tokamak. The AUG INPA diagnostic will measure fast neutrals escaping the plasma after charge exchange reactions. The neutrals will be ionized by a 20 nm carbon foil and deflected toward a scintillator by the local magnetic field. The use of a neutral beam injector (NBI) as an active source of neutrals will provide radially resolved measurements, while the use of a scintillator as an active component will allow us to cover the whole plasma along the NBI line with unprecedented phase-space resolution (<12 keV and 8 cm) and a fast temporal response (up to 1 kHz with the high resolution acquisition system and above 100 kHz with the low resolution one), making it suitable to study localized fast-ion redistributions in phase space.

Diurnal Fe(II)/Fe(III) cycling and enhanced O2 production in a simulated Archean marine oxygen oasis.

The oxygenation of early Earth's atmosphere during the Great Oxidation Event, is generally accepted to have been caused by oceanic Cyanobacterial oxygenic photosynthesis. Recent studies suggest that Fe(II) toxicity delayed the Cyanobacterial expansion necessary for the GOE. This study investigates the effects of Fe(II) on two Cyanobacteria, Pseudanabaena sp. PCC7367 and Synechococcus sp. PCC7336, in a simulated shallow-water marine Archean environment. A similar Fe(II) toxicity response was observed as reported for closed batch cultures. This toxicity was not observed in cultures provided with continuous gaseous exchange that showed significantly shorter doubling times than the closed-culture system, even with repeated nocturnal addition of Fe(II) for 12 days. The green rust (GR) formed under high Fe(II) conditions, was not found to be directly toxic to Pseudanabaena sp. PCC7367. In summary, we present evidence of diurnal Fe cycling in a simulated shallow-water marine environment for two ancestral strains of Cyanobacteria, with increased O2 production under anoxic conditions.

Advanced ASDEX Upgrade pellet guiding system design.

Cryogenic pellet injection will be the prime candidate to fuel future fusion power plants. In order to harvest optimum fueling performance, it is essential to inject pellets from the magnetic high field side of the tokamak. The pellet launching system of the tokamak ASDEX Upgrade injects cryogenic hydrogen pellets with a speed of up to 1000 m/s from the magnetic high field side via curved guiding tubes. Pellets passing the guiding tube are sliding on a gas cushion, generated by the Leidenfrost effect. The actual track has a rectangular cross section and is composed of a series of ellipses in order to generate the required 270° looping type turn; the path length is 17 m. The last part of this track is marked by strong geometrical constraints from the vacuum vessel port. The previous design was composed of a sequence of three sections of ellipses too, tangentially constant but discontinuous with regard to the curvature. It had been in operation for almost 20 years. Its steps in the curvature are supposed to limit the system performance. A novel and advanced geometry concept, adopting a method well-known from civil engineering (e.g., for the railroad track design), has been applied to develop an improved design. It relies on clothoid shape sections keeping the track curvatures continuous and, thus, provides a smooth transition between all the elements. The new design presented improves the pellet launching system performance on ASDEX Upgrade and provides knowledge for an advanced design of pellet guiding tubes in future fusion devices.

Transgenerational transduction of MPTP-induced alterations in a Parkinson's disease mouse model.

Susceptibility to Parkinson's disease (PD) increases more than threefold in first-degree relatives of PD patients. Using a mouse model, we investigated in a proof-of-principle approach whether toxin exposure of F0 affects the F1 generation. We provide first evidence that disturbance of the nigrostriatal pathway can be transferred to the next generation.

Ion temperature measurement techniques using fast sweeping retarding field analyzer (RFA) in strongly intermittent ASDEX Upgrade tokamak plasmas.

This manuscript presents a new method of interpreting the ion temperature (Ti) measurement with a retarding field analyzer (RFA) that accounts for the intermittent/turbulent nature of the scrape off layer (SOL) plasmas in tokamaks. Fast measurements and statistical methods are desirable for an adequate description of random fluctuations caused by such intermittent events as edge localized modes (ELMs) and blobs. We use a RFA that can sweep its current-voltage (I-V) characteristics with up to 10 kHz. The RFA uses an electronics compensation stage to subtract the capacitive pickup due to the finite connecting cable capacitance, which greatly improves the signal-to-noise ratio. In the 10 kHz case, a single I-V characteristic is obtained in time, which is an order of magnitude faster than the ELM cycle. The fast sweeping frequency allows us to reconstruct the Ti probability density function (PDF), which we use as the Ti representation. The boundary conditions that we place on the I-V characteristics when calculating the Ti values impact the resulting Ti PDF. If the boundaries are insensitive to the plasma fluctuations, then the most probable Ti value of the PDF (20 eV-25 eV) is similar to the Ti value obtained via the classical conditional averaging method (20 eV-27 eV). However, if the boundary conditions follow the fluctuations, then the PDF-based method gives a substantially higher most probable Ti value (35 eV-60 eV). Overall, we show that a fast sweeping RFA diagnostic should be used in intermittent SOL plasmas to reconstruct the PDF for accurate Ti measurements.

[Epidemiology and prevention of heat-related adverse health effects on elderly people]. / Epidemiologie und Prävention hitzebedingter Gesundheitsschäden älterer Menschen.

Heat waves increase the morbidity and mortality in Germany, particularly of older patients in need of care. Due to climate change the number of heat waves in Germany will increase threefold by the end of the century. In addition, the proportion of patients at risk will grow due to demographic change. Therefore, the Government and the Federal States have developed recommendations for heat action plans, in which the medical profession should also participate in the prevention of heat-related damage to health. Physicians and their team should first become acquainted with the topic. In addition, they should inform patients at risk and their relatives of the risks and preventive measures. In the summer a critical check of drugs is also needed because medications impair cooling mechanisms in heat waves, the pharmacokinetics can change and unwanted side effects of drugs occur more frequently. Lastly, due to their central position in the healthcare system, physicians should participate in the coordination of a good nursing care and intensification of social contacts during heat waves.

Structural determinants of the interaction between influenza A virus matrix protein M1 and lipid membranes.

Influenza A virus is a pathogen responsible for severe seasonal epidemics threatening human and animal populations every year. One of the ten major proteins encoded by the viral genome, the matrix protein M1, is abundantly produced in infected cells and plays a structural role in determining the morphology of the virus. During assembly of new viral particles, M1 is recruited to the host cell membrane where it associates with lipids and other viral proteins. The structure of M1 is only partially known. In particular, structural details of M1 interactions with the cellular plasma membrane as well as M1-protein interactions and multimerization have not been clarified, yet. In this work, we employed a set of complementary experimental and theoretical tools to tackle these issues. Using raster image correlation, surface plasmon resonance and circular dichroism spectroscopies, we quantified membrane association and oligomerization of full-length M1 and of different genetically engineered M1 constructs (i.e., N- and C-terminally truncated constructs and a mutant of the polybasic region, residues 95-105). Furthermore, we report novel information on structural changes in M1 occurring upon binding to membranes. Our experimental results are corroborated by an all-atom model of the full-length M1 protein bound to a negatively charged lipid bilayer.

High resolution gamma-ray spectrometer with MHz capabilities for runaway electron studies at ASDEX Upgrade.

A new gamma-ray spectrometer with MHz capabilities has been developed to measure the bremsstrahlung emission spectrum in the gamma-ray energy band generated by MeV range runaway electrons in disruption experiments at ASDEX Upgrade. Properties of the runaway electrons are inferred from the measured bremsstrahlung spectrum by a deconvolution technique, particularly with regard to their maximum energy. Changes induced to the runaway electron velocity space are unambiguously observed both in massive gas injection and resonant magnetic perturbation experiments with the detector.

First measurements of a scintillator based fast-ion loss detector near the ASDEX Upgrade divertor.

A new reciprocating scintillator based fast-ion loss detector has been installed a few centimeters above the outer divertor of the ASDEX Upgrade tokamak and between two of its lower Edge Localized Modes (ELM) mitigation coils. The detector head containing the scintillator screen, Faraday cup, calibration lamp, and collimator systems are installed on a motorized reciprocating system that can adjust its position via remote control in between plasma discharges. Orbit simulations are used to optimize the detector geometry and velocity-space coverage. The scintillator image is transferred to the light acquisition systems outside of the vacuum via a lens relay (embedded in a 3D-printed titanium holder) and an in-vacuum image guide. A charge coupled device camera, for high velocity-space resolution, and an 8 × 8 channel avalanche photo diode camera, for high temporal resolution (up to 2 MHz), are used as light acquisition systems. Initial results showing velocity-space of neutral beam injection prompt losses and fast-ion losses induced by a (2, 1) neoclassical tearing mode are presented.

Correction to: The SAMHD1-mediated block of LINE-1 retroelements is regulated by phosphorylation.

[This corrects the article DOI: 10.1186/s13100-018-0116-5.].

Glypican-2 levels in cerebrospinal fluid predict the status of adult hippocampal neurogenesis.

Adult hippocampal neurogenesis is a remarkable form of brain plasticity through which new neurons are generated throughout life. Despite its important roles in cognition and emotion and its modulation in various preclinical disease models, the functional importance of adult hippocampal neurogenesis in human health has not been revealed because of a lack of tools for monitoring adult neurogenesis in vivo. Therefore, we performed an unbiased proteomics screen to identify novel proteins expressed during neuronal differentiation using a human neural stem cell model, and we identified the proteoglycan Glypican-2 (Gpc2) as a putative secreted marker of immature neurons. Exogenous Gpc2 binds to FGF2 and inhibits FGF2-induced neural progenitor cell proliferation. Gpc2 is enriched in neurogenic regions of the adult brain. Its expression is increased by physiological stimuli that increase hippocampal neurogenesis and decreased in transgenic models in which neurogenesis is selectively ablated. Changes in neurogenesis also result in changes in Gpc2 protein level in cerebrospinal fluid (CSF). Gpc2 is detectable in adult human CSF, and first pilot experiments with a longitudinal cohort indicate a decrease over time. Thus, Gpc2 may serve as a potential marker to monitor adult neurogenesis in both animal and human physiology and disease, warranting future studies.

Fast piezoelectric valve offering controlled gas injection in magnetically confined fusion plasmas for diagnostic and fuelling purposes.

In magnetically confined fusion plasmas controlled gas injection is crucial for plasma fuelling as well as for various diagnostic applications such as active spectroscopy. We present a new, versatile system for the injection of collimated thermal gas beams into a vacuum chamber. This system consists of a gas pressure chamber, sealed by a custom made piezo valve towards a small capillary for gas injection. The setup can directly be placed inside of the vacuum chamber of fusion devices as it is small and immune against high magnetic fields. This enables gas injection close to the plasma periphery with high duty cycles and fast switch on/off times ≲ 0.5 ms. In this work, we present the design details of this new injection system and a systematic characterization of the beam properties as well as the gas flowrates which can be accomplished. The thin and relatively short capillary yields a small divergence of the injected beam with a half opening angle of 20°. The gas box is designed for pre-fill pressures of 10 mbar up to 100 bars and makes a flowrate accessible from 1018 part/s up to 1023 part/s. It hence is a versatile system for both diagnostic as well as fuelling applications. The implementation of this system in ASDEX Upgrade will be described and its application for line ratio spectroscopy on helium will be demonstrated on a selected example.