The Charité Grid Portal: User-friendly and Secure Access to Grid-based Resources and Services

The Charité Grid Portal combines portal components from different groups and projects to provide domain researchers a gateway to Grid-based biomedical applications. Trusted users can securely access and employ Grid resources and services. In this paper, five portal components are presented: (1) The credential management administrates the user-credentials and authenticates them to the Grid. (2) The brain imaging data analysis (FSL) submits workflows to the Grid as part of Medical Image processing. (3) The integrated web services of Generic Workflow Execution Service (GWES) manage workflows executed by users in the Grid. (4) The data management component provides secure and efficient data management in a Grid environment, and enables high-speed data transports between user and Grid. (5) The lung sound analysis application provides twofold-pseudonymization before data-transferred to the Grid. The implementation as standardized portlets allows easy integration of specific components into different Grid portals such as the VO specific MediGRID and PneumoGrid portals.     

Variable echo time imaging for detecting the short T2* components of the sciatic nerve: a validation study

Objective

The aim of this study was to develop and validate an MRI protocol based on a variable echo time (vTE) sensitive to the short T2* components of the sciatic nerve.

Materials and methods

15 healthy subjects (M/F: 9/6; age: 21–62) were scanned at 3T targeting the sciatic nerve at the thigh bilaterally, using a dual echo variable echo time (vTE) sequence (based on a spoiled gradient echo acquisition) with echo times of 0.98/5.37 ms. Apparent T2* (aT2*) values of the sciatic nerves were calculated with a mono-exponential fit and used for data comparison.

Results

There were no significant differences in aT2* related to side, sex, age, and BMI, even though small differences for side were reported. Good-to-excellent repeatability and reproducibility were found for geometry of ROIs (Dice indices: intra-rater 0.68–0.7; inter-rater 0.70–0.72) and the related aT2* measures (intra-inter reader ICC 0.95–0.97; 0.66–0.85) from two different operators. Side-related signal-to-noise-ratio non-significant differences were reported, while contrast-to-noise-ratio measures were excellent both for side and echo.

Discussion

Our study introduces a novel MR sequence sensitive to the short T2* components of the sciatic nerve and may be used for the study of peripheral nerve disorders.

     

Ca2+ Signalling Induced by NGF Identifies a Subset of Capsaicin-Excitable Neurons Displaying Enhanced Chemo-Nociception in Dorsal Root Ganglion Explants from Adult pirt-GCaMP3 Mouse

Nociceptors sense hazards via plasmalemmal cation channels, including transient receptor potential vanilloid 1 (TRPV1). Nerve growth factor (NGF) sensitises TRPV1 to capsaicin (CAPS), modulates nociceptor excitability and induces thermal hyperalgesia, but cellular mechanisms remain unclear. Confocal microscopy was used to image changes in intracellular Ca²⁺ concentration ([Ca²⁺]_i) across neuronal populations in dorsal root ganglia (DRG) explants from pirt-GCaMP3 adult mice, which express a fluorescent reporter in their sensory neurons. Raised [Ca²⁺]_i was detected in 84 neurons of three DRG explants exposed to NGF (100 ng/mL) and most (96%) of these were also excited by 1 μM CAPS. NGF elevated [Ca²⁺]_i in about one-third of the neurons stimulated by 1 μM CAPS, whether applied before or after the latter. In neurons excitable by NGF, CAPS-evoked [Ca²⁺]_i signals appeared significantly sooner (e.g., respective lags of 1.0 ± 0.1 and 1.9 ± 0.1 min), were much (>30%) brighter and lasted longer (6.6 ± 0.4 vs. 3.9 ± 0.2 min) relative to those non-responsive to the neurotrophin. CAPS tachyphylaxis lowered signal intensity by ~60% but was largely prevented by NGF. Increasing CAPS from 1 to 10 μM nearly doubled the number of cells activated but only modestly increased the amount co-activated by NGF. In conclusion, a sub-population of the CAPS-sensitive neurons in adult mouse DRG that can be excited by NGF is more sensitive to CAPS, responds with stronger signals and is further sensitised by transient exposure to the neurotrophin.     

A Versatile Toolkit for Semi-Automated Production of Fluorescent Chemokines to Study CCR7 Expression and Functions

Chemokines guide leukocyte migration in different contexts, including homeostasis, immune surveillance and immunity. The chemokines CCL19 and CCL21 control lymphocyte and dendritic cell migration and homing to lymphoid organs. Thereby they orchestrate adaptive immunity in a chemokine receptor CCR7-dependent manner. Likewise, cancer cells that upregulate CCR7 expression are attracted by these chemokines and metastasize to lymphoid organs. In-depth investigation of CCR7 expression and chemokine-mediated signaling is pivotal to understand their role in health and disease. Appropriate fluorescent probes to track these events are increasingly in demand. Here, we present an approach to cost-effectively produce and fluorescently label CCL19 and CCL21 in a semi-automated process. We established a versatile protocol for the production of recombinant chemokines harboring a small C-terminal S6-tag for efficient and site-specific enzymatic labelling with an inorganic fluorescent dye of choice. We demonstrate that the fluorescently labeled chemokines CCL19-S6^Dy649P1 and CCL21-S6^Dy649P1 retain their full biological function as assessed by their abilities to mobilize intracellular calcium, to recruit β-arrestin to engaged receptors and to attract CCR7-expressing leukocytes. Moreover, we show that CCL19-S6^Dy649P1 serves as powerful reagent to monitor CCR7 internalization by time-lapse confocal video microscopy and to stain CCR7-positive primary human and mouse T cell sub-populations.     

Intercomparison of ocean colour band-ratio algorithms for chlorophyll concentration in the Subtropical Front east of New Zealand

This study intercompared the performance of eight band-ratio chlorophyll-a algorithms which together can be used to process measurements from the ocean colour satellite sensors CZCS, OCTS, SeaWiFS, MODIS, MERIS, and GLI. The study area included Subtropical, Subtropical Front and Subantarctic waters east of New Zealand, and Case 1 waters of the New Zealand northeast continental shelf. Over 170 co-incident measurements of spectral normalised water-leaving radiance and near-surface concentration of chlorophyll-a were made on nine research voyages between 1998 and 2000. The studentised bootstrap method was used to identify statistically significant bias in algorithm products relative to in situ measurements. The band-ratio algorithms used by CZCS, OCTS and SeaWiFS missions systematically underestimated chlorophyll-a concentration in the offshore regions by between 21% and 45%, but showed no systematic bias in the continental shelf waters. The band-ratio algorithms applicable to the MODIS and MERIS sensors had no clear bias with respect to in situ measurements in offshore waters, but had a positive bias of 20% over the continental shelf. The proposed GLI band-ratio algorithm led to estimates that were negatively biased with respect to in situ measurement offshore (− 30%), and positively biased over the continental shelf (20%). The results were consistent with unusually high values of absorption in the blue part of the spectrum (443-490 nm) compared to the green part (∼ 550 nm) by phytoplankton pigments in the offshore waters, and high chlorophyll-specific absorption over the continental shelf.     

Representing von Neumann–Morgenstern Games in the Situation Calculus

Sequential von Neumann–Morgernstern (VM) games are a very general formalism for representing multi-agent interactions and planning problems in a variety of types of environments. We show that sequential VM games with countably many actions and continuous utility functions have a sound and complete axiomatization in the situation calculus. This axiomatization allows us to represent game-theoretic reasoning and solution concepts such as Nash equilibrium. We discuss the application of various concepts from VM game theory to the theory of planning and multi-agent interactions, such as representing concurrent actions and using the Baire topology to define continuous payoff functions.     

On Task Scheduling Accuracy: Evaluation Methodology and Results

Many heuristics based on the directed acyclic graph (DAG) have been proposed for the static scheduling problem. Most of these algorithms apply a simple model of the target system that assumes fully connected processors, a dedicated communication sub-system and no contention for the communication resources. Only a few algorithms consider the network topology and the contention for the communication resources. This article evaluates the accuracy of task scheduling algorithms and thus the appropriateness of the applied models. An evaluation methodology is proposed and applied to a representative set of scheduling algorithms. The obtained results show a significant inaccuracy of the produced schedules. Analyzing these results is important for the development of more appropriate models and more accurate scheduling algorithms.     

Preparation and characterization of LaCrO3 and Cr2O3 methane combustion catalysts supported on LaAl11O18- and Al2O3-coated monoliths

A series of LaAl₁₁O₁₈- and Al₂O₃-supported LaCrO₃ and Cr₂O₃ combustion catalysts was prepared. Different active phase–support combinations were prepared and applied to cordierite monoliths. The washcoat materials were aged in flowing humid air at temperatures between 1100°C and 1400°C, after which they were characterized by BET, XRD, TPR, and EDS. The monolith catalysts were evaluated in methane combustion. The presence of an active phase retarded sintering of the Al₂O₃ support, whereas the active phase slightly decreased the thermal stability of LaAl₁₁O₁₈. X-ray measurements revealed extensive interaction between support and active phase in the washcoat materials. A substituted perovskite, LaCr_1−xAl_xO₃, is proposed to be formed in nearly all samples containing both lanthanum and chromium. The accessibility of chromium decreased rapidly after aging. The activities of the Al₂O₃-supported catalysts were higher than of those supported on LaAl₁₁O₁₈, which was related to the higher surface area of the former.