A compact setup for behavioral studies measuring limb acceleration.

Behavioral studies contribute largely to a broader understanding of human brain mechanisms and the process of learning and memory. An established method to quantify motor learning is the analysis of thumb activity. In combination with brain stimulation, the effect of various treatments on neural plasticity and motor learning can be assessed. So far, the setups for thumb abduction measurements employed consist of bulky amplifiers and digital-to-analog devices to record the data. We developed a compact hardware setup to measure acceleration data which can be integrated into a wearable, including a sensor board and a microcontroller board which can be connected to a PC via USB. Additionally, we provide two software packages including graphical user interfaces, one to communicate with the hardware and one to evaluate and process the data. This work demonstrates the construction and application of our setup at the example of thumb acceleration measurement with a custom made glove and its use for research. Using integrated circuits, the size of the measurement devices is reduced to this wearable. It is simple to construct and can be operated easily by non-technical staff.

Low energy magnetic stimulation of the phrenic nerve - a simulation study.

Peripheral magnetic stimulation is a promising assistive technique for rehabilitation. Today's magnetic stimulation devices, designed for transcranial stimulation, operate at currents of 6 kA and higher. This makes them expensive and bulky. Many motor neurons in peripheral nerves are more accessible, have large diameters, and require significantly lower field strengths for stimulation. In this work, we present a simulation environment to determine the threshold current required to trigger an action potential in phrenic nerve motor neurons for different coil geometries. An anatomical model was used for coil placement and realistic field calculations. The field distribution was calculated using the finite integration technique and then applied to a neuronal model to simulate the axon membrane dynamics. For general applicability, the coil-nerve distance and the axon diameter were varied. We show that the required current was approximately 1.3 kA for a nerve-coil distance of 35 mm, which corresponds to 20% of the available power of a commercial TMS device. By including the nearby vagus nerve in the simulations, we showed that accidental stimulation of this nerve is highly unlikely. Our results pave the way for the development of smaller, less complex, and more affordable stimulators and promise to increase the use of peripheral magnetic stimulators in clinical settings.

Optimal pulse configuration for peripheral inductive nerve stimulation.

Peripheral magnetic stimulation is a promising technique for several applications like rehabilitation or diagnose of neuronal pathways. However, most available magnetic stimulation devices are designed for transcranial stimulation and require high-power, expensive hardware. Modern technology such as rectangular pulses allows to adapt parameters like pulse shape and duration in order to reduce the required energy. Nevertheless, the effect of different temporal electromagnetic field shapes on neuronal structures is not yet fully understood. We created a simulation environment to find out how peripheral nerves are affected by induced magnetic fields and what pulse shapes have the lowest energy requirements. Using the electric field distribution of afigure-of-8coil together with an axon model in saline solution, we calculated the potential along the axon and determined the required threshold current to elicit an action potential. Further, for the purpose of selective stimulation, we investigated different axon diameters. Our results show that rectangular pulses have the lowest thresholds at a pulse duration of 20µs. For sinusoidal coil currents, the optimal pulse duration was found to be 40µs. Most importantly, with an asymmetric rectangular pulse, the coil current could be reduced from 2.3 kA (cosine shaped pulse) to 600 A. In summary, our results indicate that for magnetic nerve stimulation the use of rectangular pulse shapes holds the potential to reduce the required coil current by a factor of 4, which would be a massive improvement.

Development of the materials analysis and particle probe for Proto-MPEX.

The Prototype Material Plasma Exposure eXperiment (Proto-MPEX) is a linear plasma device being used in plasma source research and development (R&D) for the proposed MPEX. Once the R&D is completed, this device can also be used to perform plasma-material interaction studies. To perform these studies, a new materials analysis and particle probe (MAPP) has been constructed. The MAPP's components are a sample holder and manipulator and a custom vacuum chamber with ports to facilitate surface chemistry diagnostics. The MAPP's overall design enables rapid sample turnaround and in vacuo surface characterization. The surface analysis vacuum chamber has ports for x-ray photoelectron spectroscopy, thermal desorption spectroscopy, back-scatter ion scattering spectroscopy, forward-scatter ion scattering spectroscopy, and direct recoil spectroscopy. The sample manipulator and holder is a Lesker/UHV Multi-Centre Analytical Stage, which is used to place the samples in the exposure region of the Proto-MPEX or the analysis position in the MAPP vacuum chamber. The sample holder has a heating capability of up to 1200 °C for heated exposure and for desorption studies. In this work, we present the MAPP's design and the first tungsten sample exposure with ex situ analysis that shows a surface deposition layer on the exposed target, highlighting the need for additional in situ measurements on the Proto-MPEX.

Acute acral eruptions in children during the COVID-19 pandemic: Characteristics of 103 children and their family clusters.

BACKGROUND: A marked increase in frequency of acute acral eruptions (AAE) was observed in children during the COVID-19 pandemic in the spring period. OBJECTIVES: In this observational multicenter study, based on children with AAE, we aimed to assess the proportion of household members possibly infected by SARS-CoV-2. METHODS: We collected data from all children observed with AAE, prospectively from April 7, 2020 to June 22, 2020, and retrospectively since February 28, 2020. The primary outcome was the household infection rate, defined as the proportion of family clusters having at least one member with COVID-19 infection other than the child with AAE ("index child"). The definition of a case was based on characteristic clinical signs and a positive PCR or serology. RESULTS: The study included 103 children in 10 French departments and in Quebec. The median age was 13 years and the interquartile range [8-15], with a female-to-male ratio of 1/1.15. In children with AAE, all PCR tests were negative (n=18), and serology was positive in 2/14 (14.3%) cases. We found no significant anomalies in the lab results. A total of 66 of the 103 families (64.1%) of included children had at least one other infected member apart from the index child. The total number of household members was 292, of whom 119 (40.8%) were considered possibly infected by SARS-CoV-2. No index children or households exhibited severe COVID-19. DISCUSSION: Among the 103 households included, 64.1% had at least one infected member. Neither children with AAE nor their households showed severe COVID-19.

Microplastic ingestion by Atlantic chub mackerel (Scomber colias) in the Canary Islands coast.

In recent years, due to the increasing concerns about their negative impact on wildlife and possible toxicity to living organisms (including humans), microplastics have become the subject of intense investigations. In the ocean, microplastics can be easily ingested by numerous marine organisms because of their small size (<5 mm). The Northwest African upwelling system is an important fishery area, and the present study is the first one in the region to reveal the presence of microplastic particles in the digestive tract of Atlantic chub mackerel (Scomber colias). From the 120 examined fish gastrointestinal tracts, 78.3% contained some type of microplastics, 74.2% contained fibres, 17.5% plastic fragments, and 16.7% paint. More studies are needed on fish, but S. colias is a candidate for being a good indicator of microplastic contamination in the region.

ABCB1 and ABCG2 drug transporters are differentially expressed in non-small cell lung cancers (NSCLC) and expression is modified by cisplatin treatment via altered Wnt signaling.

BACKGROUND: Lung cancer (LC) is still the most common cause of cancer related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of all LC cases but is not a single entity. It is now accepted that, apart from the characteristic driver mutations, the unique molecular signatures of adeno- (AC) and squamous cell carcinomas (SCC), the two most common NSCLC subtypes should be taken into consideration for their management. Therapeutic interventions, however, frequently lead to chemotherapy resistance highlighting the need for in-depth analysis of regulatory mechanisms of multidrug resistance to increase therapeutic efficiency. METHODS: Non-canonical Wnt5a and canonical Wnt7b and ABC transporter expressions were tested in primary human LC (n = 90) resections of AC and SCC. To investigate drug transporter activity, a three dimensional (3D) human lung aggregate tissue model was set up using differentiated primary human lung cell types. Following modification of the canonical, beta-catenin dependent Wnt pathway or treatment with cisplatin, drug transporter analysis was performed at mRNA, protein and functional level using qRT-PCR, immunohistochemistry, immune-fluorescent staining and transport function analysis. RESULTS: Non-canonical Wnt5a is significantly up-regulated in SCC samples making the microenvironment different from AC, where the beta-catenin dependent Wnt7b is more prominent. In primary cancer tissues ABCB1 and ABCG2 expression levels were different in the two NSCLC subtypes. Non-canonical rhWnt5a induced down-regulation of both ABCB1 and ABCG2 transporters in the primary human lung aggregate tissue model recreating the SCC-like transporter pattern. Inhibition of the beta-catenin or canonical Wnt pathway resulted in similar down-regulation of both ABC transporter expression and function. In contrast, cisplatin, the frequently used adjuvant chemotherapeutic agent, activated beta-catenin dependent signaling that lead to up-regulation of both ABCB1 and ABCG2 transporter expression and activity. CONCLUSIONS: The difference in the Wnt microenvironment in AC and SCC leads to variations in ABC transporter expression. Cisplatin via induction of canonical Wnt signaling up-regulates ABCB1 and ABCG2 drug transporters that are not transporters for cisplatin itself but are transporters for drugs that are frequently used in combination therapy with cisplatin modulating drug response.

First results from the Thomson scattering diagnostic on proto-MPEX.

A Thomson scattering (TS) diagnostic has been successfully implemented on the prototype Material Plasma Exposure eXperiment (Proto-MPEX) at Oak Ridge National Laboratory. The diagnostic collects the light scattered by plasma electrons and spectroscopically resolves the Doppler shift imparted to the light by the velocity of the electrons. The spread in velocities is proportional to the electron temperature, while the total number of photons is proportional to the electron density. TS is a technique used on many devices to measure the electron temperature (Te) and electron density (ne) of the plasma. A challenging aspect of the technique is to discriminate the small number of Thomson scattered photons against the large peak of background photons from the high-power laser used to probe the plasma. A variety of methods are used to mitigate the background photons in Proto-MPEX, including Brewster angled windows, viewing dumps, and light baffles. With these methods, first results were measured from argon plasmas in Proto-MPEX, indicating Te ∼ 2 eV and ne ∼ 1 × 1019 m-3. The configuration of the Proto-MPEX TS diagnostic will be described and plans for improvement will be given.

Heat flux estimates of power balance on Proto-MPEX with IR imaging.

The Prototype Material Plasma Exposure eXperiment (Proto-MPEX) at Oak Ridge National Laboratory (ORNL) is a precursor linear plasma device to the Material Plasma Exposure eXperiment (MPEX), which will study plasma material interactions (PMIs) for future fusion reactors. This paper will discuss the initial steps performed towards completing a power balance on Proto-MPEX to quantify where energy is lost from the plasma, including the relevant diagnostic package implemented. Machine operating parameters that will improve Proto-MPEX's performance may be identified, increasing its PMI research capabilities.

Design of a digital holography system for PFC erosion measurements on Proto-MPEX.

A project has been started at ORNL to develop a dual-wavelength digital holography system for plasma facing component erosion measurements on prototype material plasma exposure experiment. Such a system will allow in situ real-time measurements of component erosion. Initially the system will be developed with one laser, and first experimental laboratory measurements will be made with the single laser system. In the second year of development, a second CO2 laser will be added and measurements with the dual wavelength system will begin. Adding the second wavelength allows measurements at a much longer synthetic wavelength.

Increased Wnt5a in squamous cell lung carcinoma inhibits endothelial cell motility.

BACKGROUND: Angiogenesis is important both in normal tissue function and disease and represents a key target in lung cancer (LC) therapy. Unfortunately, the two main subtypes of non-small-cell lung cancers (NSCLC) namely, adenocarcinoma (AC) and squamous cell carcinoma (SCC) respond differently to anti-angiogenic e.g. anti-vascular endothelial growth factor (VEGF)-A treatment with life-threatening side effects, often pulmonary hemorrhage in SCC. The mechanisms behind such adverse reactions are still largely unknown, although peroxisome proliferator activator receptor (PPAR) gamma as well as Wnt-s have been named as molecular regulators of the process. As the Wnt microenvironments in NSCLC subtypes are drastically different, we hypothesized that the particularly high levels of non-canonical Wnt5a in SCC might be responsible for alterations in blood vessel growth and result in serious adverse reactions. METHODS: PPARgamma, VEGF-A, Wnt5a, miR-27b and miR-200b levels were determined in resected adenocarcinoma and squamous cell carcinoma samples by qRT-PCR and TaqMan microRNA assay. The role of PPARgamma in VEGF-A expression, and the role of Wnts in overall regulation was investigated using PPARgamma knock-out mice, cancer cell lines and fully human, in vitro 3 dimensional (3D), distal lung tissue aggregates. PPARgamma mRNA and protein levels were tested by qRT-PCR and immunohistochemistry, respectively. PPARgamma activity was measured by a PPRE reporter system. The tissue engineered lung tissues expressing basal level and lentivirally delivered VEGF-A were treated with recombinant Wnts, chemical Wnt pathway modifiers, and were subjected to PPARgamma agonist and antagonist treatment. RESULTS: PPARgamma down-regulation and VEGF-A up-regulation are characteristic to both AC and SCC. Increased VEGF-A levels are under direct control of PPARgamma. PPARgamma levels and activity, however, are under Wnt control. Imbalance of both canonical (in AC) and non-canonical (in SCC) Wnts leads to PPARgamma down-regulation. While canonical Wnts down-regulate PPARgamma directly, non-canonical Wnt5a increases miR27b that is known regulator of PPARgamma. CONCLUSION: During carcinogenesis the Wnt microenvironment alters, which can downregulate PPARgamma leading to increased VEGF-A expression. Differences in the Wnt microenvironment in AC and SCC of NSCLC lead to PPARgamma decrease via mechanisms that differentially alter endothelial cell motility and branching which in turn can influence therapeutic response.

Pathogenic prions deviate PrP(C) signaling in neuronal cells and impair A-beta clearance.

The subversion of the normal function exerted by the cellular prion protein (PrP(C)) in neurons by pathogenic prions is assumed to have a central role in the pathogenesis of transmissible spongiform encephalopathies. Using two murine models of prion infection, the 1C11 neuronal cell line and neurospheres, we document that prion infection is associated with the constitutive activation of signaling targets normally coupled with PrP(C), including the Fyn kinase, the mitogen-associated protein kinases ERK1/2 and the CREB transcription factor. PrP(C)-dependent signaling overactivation in infected cells is associated with the recruitment of p38 and JNK stress-associated kinases. Downstream from CREB, prion-infected cells exhibit reduced activity of the matrix metalloprotease (MMP)-9. As MMP-9 catalyzes the degradation of the amyloid A-beta peptide, the decrease in MMP-9 activity in prion-infected cells causes a significant impairment of the clearance of A-beta, leading to its accumulation. By exploiting two 1C11-infected clones accumulating high or moderate levels of prions, we show that the prion-induced changes are correlated with the level of infectivity. Of note, a dose-dependent increase in A-beta levels was also found in the cerebrospinal fluid of mice inoculated with these infected clones. By demonstrating that pathogenic prions trigger increases in A-beta levels through the deviation of PrP(C) signaling, our data argue that A-beta may exacerbate prion-induced toxicity.

Advanced Thomson scattering system for high-flux linear plasma generator.

An advanced Thomson scattering system has been built for a linear plasma generator for plasma surface interaction studies. The Thomson scattering system is based on a Nd:YAG laser operating at the second harmonic and a detection branch featuring a high etendue (f/3) transmission grating spectrometer equipped with an intensified charged coupled device camera. The system is able to measure electron density (n(e)) and temperature (T(e)) profiles close to the output of the plasma source and, at a distance of 1.25 m, just in front of a target. The detection system enables to measure 50 spatial channels of about 2 mm each, along a laser chord of 95 mm. By summing a total of 30 laser pulses (0.6 J, 10 Hz), an observational error of 3% in n(e) and 6% in T(e) (at n(e) = 9.4 × 10(18) m(-3)) can be obtained. Single pulse Thomson scattering measurements can be performed with the same accuracy for n(e) > 2.8 × 10(20) m(-3). The minimum measurable density and temperature are n(e) < 1 × 10(17) m(-3) and T(e) < 0.07 eV, respectively. In addition, using the Rayleigh peak, superimposed on the Thomson scattered spectrum, the neutral density (n(0)) of the plasma can be measured with an accuracy of 25% (at n(0) = 1 × 10(20) m(-3)). In this report, the performance of the Thomson scattering system will be shown along with unprecedented accurate Thomson-Rayleigh scattering measurements on a low-temperature argon plasma expansion into a low-pressure background.

Suppression of tritium retention in remote areas of ITER by nonperturbative reactive gas injection.

A technique based on reactive gas injection in the afterglow region of the divertor plasma is proposed for the suppression of tritium-carbon codeposits in remote areas of ITER when operated with carbon-based divertor targets. Experiments in a divertor simulator plasma device indicate that a 4 nm/min deposition can be suppressed by addition of 1 Pa·m³ s⁻¹ ammonia flow at 10 cm from the plasma. These results bolster the concept of nonperturbative scavenger injection for tritium inventory control in carbon-based fusion plasma devices, thus paving the way for ITER operation in the active phase under a carbon-dominated, plasma facing component background.

High-resolution CT imaging of carotid artery atherosclerotic plaques.

BACKGROUND AND PURPOSE: Plaque morphologic features have been suggested as a complement to luminal narrowing measurements for assessing the risk of stroke associated with carotid atherosclerotic disease, giving rise to the concept of "vulnerable plaque." The purpose of this study was to evaluate the ability of multidetector-row CT angiography (CTA) to assess the composition and characteristics of carotid artery atherosclerotic plaques with use of histologic examination as the gold standard. MATERIALS AND METHODS: Eight patients with transient ischemic attacks who underwent carotid CTA and "en bloc" endarterectomy were enrolled in a prospective study. An ex vivo micro-CT study of each endarterectomy specimen was obtained, followed by histologic examination. A systematic comparison of CTA images with histologic sections and micro-CT images was performed to determine the CT attenuation associated with each component of the atherosclerotic plaques. A computer algorithm was subsequently developed that automatically identifies the components of the carotid atherosclerotic plaques, based on the density of each pixel. A neuroradiologist's reading of this computer analysis was compared with the interpretation of the histologic slides by a pathologist with respect to the types and characteristics of the carotid plaques. RESULTS: There was a 72.6% agreement between CTA and histologic examination in carotid plaque characterization. CTA showed perfect concordance for calcifications. A significant overlap between densities associated with lipid-rich necrotic core, connective tissue, and hemorrhage limited the reliability of individual pixel readings to identify these components. However, CTA showed good correlation with histologic examination for large lipid cores (kappa = 0.796; P < .001) and large hemorrhages (kappa = 0.712; P = .102). CTA performed well in detecting ulcerations (kappa = 0.855) and in measuring the fibrous cap thickness (R(2) = 0.77; P < .001). CONCLUSION: The composition of carotid atherosclerotic plaques determined by CTA reflects plaque composition defined by histologic examination.

Monitoring Alfvén cascades with interferometry on the JET Tokamak.

A microwave interferometry technique is applied for the first time for detecting a discrete spectrum of Alfvén cascade (AC) eigenmodes excited with fast ions in reversed magnetic shear plasmas of the Joint European Torus. The interferometry measurements of plasma density perturbations associated with ACs show an unprecedented frequency and time resolution superior to that obtained with external magnetic coils. The measurements of ACs are used for monitoring the evolution of the safety factor and density of rational magnetic surfaces in the region of maximum plasma current.

Cytotoxic necrotizing factor-2 of Escherichia coli alters the morphology of cultured hippocampal neurons.

Certain pathogenic strains of E. coli produce the cytotoxic necrotizing factors-1 or -2. Cytotoxic necrotizing factor-1 irreversibly activates the small GTPases of the Rho family Rho, Rac and Cdc42. Cytotoxic necrotizing factor-2 may have similar effects. Since the Rho proteins play an important role in the organization of the actin cytoskeleton and neuronal differentiation, we have investigated whether cytotoxic necrotizing factor-2 affects the morphology of cultured hippocampal neurons. The toxin indeed caused dendrite retraction and axon shortening. Within 4 h of application, cytotoxic necrotizing factor-2 induced a transient formation of short finger-like extensions. To study the role of the Rho proteins in the morphological changes caused by cytotoxic necrotizing factor-2, we transfected neurons with recombinant Rho proteins. Dominant-negative forms of Rac or Rho but not of Cdc42 prevented the formation of short extensions induced by cytotoxic necrotizing factor-2, indicating synergistic effects of Rac and Rho. In contrast, the retraction of dendrites induced by cytotoxic necrotizing factor-2 was only prevented by dominant-negative Rho. Analysis with pull-down assays showed that cytotoxic necrotizing factor-2 strongly activated Rac and Rho, whereas an effect on Cdc42 was not observed. Cytotoxic necrotizing factor-2 also diminished the total amount of Rac and Rho. The degradation of Rac was so pronounced that the increase in Rac activity was only transient. In organotypic cultures of the hippocampus, cytotoxic necrotizing factor-2 reduced the number of neurites per neuron, suggesting that neurons in the tissue context were also vulnerable. We conclude that cytotoxic necrotizing factor-2 has pronounced effects on neuronal morphology, which are due to activation of the GTPases Rho and Rac.

Biochemical characterization of atherosclerotic plaque constituents using FTIR spectroscopy and histology.

The behavior of vulnerable atherosclerotic plaques is believed to be closely related to plaque composition. There is a need for an effective in vivo technique for examining plaque constituent properties. In this study, Fourier transform infrared spectroscopy using attenuated total reflectance (FTIR-ATR) was used to assess and analyze the biochemical properties of human atherosclerotic plaques. FTIR spectra clearly revealed prominent spectral features corresponding to plaque constituents of interest: the 2930 cm(-1) and 2850 cm(-1) peaks (indicating the presence of lipids), the 1730 cm(-1) peak (lipid esters), the 1550 cm(-1) and 1650 cm(-1) peaks (fibrous tissues), and the 1100-1000 cm(-1) broad phosphate peak (calcification). Spectral data examined on a qualitative basis correlated well with both gross tissue anatomy and histologic features. Gross spatial mappings of tissue sections of both lipidic and calcified plaques were performed. Spectra from various regions of the plaques demonstrated the evolution of lipid peaks, fibrous tissue peaks, and the phosphate calcification band within the plaques. Histologic analysis corroborated the spectral findings in this study.