AstroGrid-D: Grid Technology for Astronomical Science

We present status and results of AstroGrid-D, a joint effort of astrophysicists and computer scientists to employ grid technology for scientific applications. AstroGrid-D provides access to a network of distributed machines with a set of commands as well as software interfaces. It allows simple use of computer and storage facilities and to schedule or monitor compute tasks and data management. It is based on the Globus Toolkit middleware (GT4). Chapter 1 describes the context which led to the demand for advanced software solutions in Astrophysics, and we state the goals of the project. We then present characteristic astrophysical applications that have been implemented on AstroGrid-D in chapter 2. We describe simulations of different complexity, compute-intensive calculations running on multiple sites, and advanced applications for specific scientific purposes, such as a connection to robotic telescopes. We can show from these examples how grid execution improves e.g. the scientific workflow. Chapter 3 explains the software tools and services that we adapted or newly developed. Section 3.1 is focused on the administrative aspects of the infrastructure, to manage users and monitor activity. Section 3.2 characterises the central components of our architecture: The AstroGrid-D information service to collect and store metadata, a file management system, the data management system, and a job manager for automatic submission of compute tasks. We summarise the successfully established infrastructure in chapter 4, concluding with our future plans to establish AstroGrid-D as a platform of modern e-Astronomy.Comment: 14 pages, 12 figures Subjects: data analysis, image processing, robotic telescopes, simulations, grid. Accepted for publication in New Astronom

Towards the integration and development of a cross-European research network and infrastructure:the DEterminants of DIet and Physical ACtivity (DEDIPAC) Knowledge Hub

To address major societal challenges and enhance cooperation in research across Europe, the European Commission has initiated and facilitated ‘joint programming’. Joint programming is a process by which Member States engage in defining, developing and implementing a common strategic research agenda, based on a shared vision of how to address major societal challenges that no Member State is capable of resolving independently. Setting up a Joint Programming Initiative (JPI) should also contribute to avoiding unnecessary overlap and repetition of research, and enable and enhance the development and use of standardised research methods, procedures and data management. The Determinants of Diet and Physical Activity (DEDIPAC) Knowledge Hub (KH) is the first act of the European JPI ‘A Healthy Diet for a Healthy Life’. The objective of DEDIPAC is to contribute to improving understanding of the determinants of dietary, physical activity and sedentary behaviours. DEDIPAC KH is a multi-disciplinary consortium of 46 consortia and organisations supported by joint programming grants from 12 countries across Europe. The work is divided into three thematic areas: (I) assessment and harmonisation of methods for future research, surveillance and monitoring, and for evaluation of interventions and policies; (II) determinants of dietary, physical activity and sedentary behaviours across the life course and in vulnerable groups; and (III) evaluation and benchmarking of public health and policy interventions aimed at improving dietary, physical activity and sedentary behaviours. In the first three years, DEDIPAC KH will organise, develop, share and harmonise expertise, methods, measures, data and other infrastructure. This should further European research and improve the broad multi-disciplinary approach needed to study the interactions between multilevel determinants in influencing dietary, physical activity and sedentary behaviours. Insights will be translated into more effective interventions and policies for the promotion of healthier behaviours and more effective monitoring and evaluation of the impacts of such intervention

Fuzzy Scalar Field Theory as Matrix Quantum Mechanics

We study the phase diagram of scalar field theory on a three dimensional Euclidean spacetime whose spatial component is a fuzzy sphere. The corresponding model is an ordinary one-dimensional matrix model deformed by terms involving fixed external matrices. These terms can be approximated by multitrace expressions using a group theoretical method developed recently. The resulting matrix model is accessible to the standard techniques of matrix quantum mechanics.Comment: 1+17 pages, 4 figures, minor improvements, version published in JHE

Neurofilament as a blood marker for diagnosis and monitoring of primary progressive aphasias

Objective: To assess the utility of serum neurofilament for diagnosis and monitoring of primary progressive aphasia (PPA) variants. Methods: We investigated neurofilament light chain (NF-L) levels in blood of 99 patients with PPA (40 with nonfluent variant PPA [nfvPPA], 38 with semantic variant PPA [svPPA], 21 with logopenic variant PPA [lvPPA]) and compared diagnostic performance with that reached by CSF NF-L, phosphorylated neurofilament heavy chain (pNF-H), b-amyloid (Ab(1)-42), tau, and phosphorylated tau. The longitudinal change of blood NF-L levels was measured and analyzed for correlation with functional decline and brain atrophy. Results: Serum NF-L is increased in PPA compared to controls and discriminates between nfvPPA/svPPA and lvPPA with 81% sensitivity and 67% specificity (cutoff 31 pg/mL). CSF NF-L, pNF-H, tau, phosphorylated tau, and Ab1-42 achieved similar performance, and pNF-H was the only marker for discrimination of nfvPPA from svPPA/lvPPA. In most patients with nfvPPA and svPPA, but not lvPPA, serum NF-L increased within follow-up. The increase correlated with functional decline and progression of atrophy of the left frontal lobe of all patients with PPAs and the right middle frontal gyrus of patients with nfvPPA and svPPA. Conclusions: Blood level of NF-L can aid the differential diagnosis of PPA variants, especially in combination with CSF pNF-H. Because serum NF-L correlates with functional decline and atrophy in the disease course, it qualifies as an objective disease status marker. Extended follow-up studies with cases of known neuropathology are imperative

Different CSF protein profiles in amyotrophic lateral sclerosis and frontotemporal dementia with C9orf72 hexanucleotide repeat expansion

Objectives: The hexanucleotide repeat expansion in the C9orf72 gene is the most common mutation associated with amyotrophic lateral sclerosis (C9-ALS) and frontotemporal dementia (C9-FTD). Until now, it is unknown which factors define whether C9orf72 mutation carriers develop ALS or FTD. Our aim was to identify protein biomarker candidates in the cerebrospinal fluid (CSF) which differentiate between C9-ALS and C9-FTD and might be indicative for the outcome of the mutation. Methods We compared the CSF proteome of 16 C9-ALS and 8 C9-FTD patients and 11 asymptomatic C9orf72 mutation carriers (CAR) by isobaric tags for relative and absolute quantitation. Eleven biomarker candidates were selected from the pool of differentially regulated proteins for further validation by multiple reaction monitoring and single-molecule array in a larger cohort (n=156). Results In total, 2095 CSF proteins were identified and 236 proteins were significantly different in C9-ALS versus C9-FTD including neurofilament medium polypeptide (NEFM) and chitotriosidase-1 (CHIT1). Eight candidates were successfully validated including significantly increased ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) levels in C9-ALS compared with C9-FTD and controls and decreased neuronal pentraxin receptor (NPTXR) levels in C9-FTD versus CAR. Conclusions: This study presents a deep proteomic CSF analysis of C9-ALS versus C9-FTD patients. As a proof of concept, we observed higher NEFM and CHIT1 CSF levels in C9-ALS. In addition, we also show clear upregulation of UCHL1 in C9-ALS and downregulation of NPTXR in C9-FTD. Significant differences in UCHL1 CSF levels may explain diverging ubiquitination and autophagy processes and NPTXR levels might reflect different synapses organisation processes

Serum neurofilament light chain in behavioral variant frontotemporal dementia

Objective To determine the association of serum neurofilament light chain (NfL) with functional deterioration and brain atrophy during follow-up of patients with behavioral variant frontotemporal dementia (bvFTD). Methods Blood NfL levels from 74 patients with bvFTD, 26 with Alzheimer disease (AD), 17 with mild cognitive impairment (MCI), and 15 healthy controls (Con) at baseline and follow-up were determined and analyzed for the diagnostic potential in relation to functional assessment (Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB], frontotemporal lobar degeneration-related CDR-SOB, Mini-Mental State Examination [MMSE]) and brain volumetry. Results At baseline, serum NfL level correlated with CSFNfL (bvFTD r = 0.706, p < 0.0001;AD/MCI r = 0.666, p = 0.0003). Highest serum levels were observed in bvFTD (p < 0 0.0001 vs Con and MCI, p = 0.0078 vs AD, respectively). Discrimination of bvFTD from Con/MCI/AD was possible with 91%/74%/74% sensitivity and 79%/74%/58% specificity. At follow-up, serum NfL increased in bvFTD and AD (p = 0.0039 and p = 0.0006, respectively). At baseline and follow-up, NfL correlated with functional scores of patients with bvFTD (e.g., CDR-SOB [baseline] r = 0.4157, p = 0.0006;[follow-up] r = 0.5629, p < 0.0001) and with atrophy in the gray and white matter of many brain regions including frontal and subcortical areas (e.g., frontal lobe: r = -0.5857, p < 0.0001;95% confidence interval -0.7415 to -0.3701). For patients with AD/MCI, NfL correlated with the functional performance as well (e.g., CDR-SOB [baseline] r = 0.6624, p < 0.0001;[follow-up] r = 0.5659, p = 0.0003) but not with regional brain volumes. Conclusions As serum NfL correlates with functional impairment and brain atrophy in bvFTD at different disease stages, we propose it as marker of disease severity, paving the way for its future use as outcome measure for clinical trials. Classification of evidence This study provides Class III evidence that for patients with cognitive problems, serum NfL concentration discriminates bvFTD from other forms of dementia

Towards the integration and development of a cross-European research network and infrastructure: the DEterminants of DIet and Physical ACtivity (DEDIPAC) Knowledge Hub

To address major societal challenges and enhance cooperation in research across Europe, the European Commission has initiated and facilitated `joint programming’. Joint programming is a process by which Member States engage in defining, developing and implementing a common strategic research agenda, based on a shared vision of how to address major societal challenges that no Member State is capable of resolving independently. Setting up a Joint Programming Initiative (JPI) should also contribute to avoiding unnecessary overlap and repetition of research, and enable and enhance the development and use of standardised research methods, procedures and data management. The Determinants of Diet and Physical Activity (DEDIPAC) Knowledge Hub (KH) is the first act of the European JPI `A Healthy Diet for a Healthy Life’. The objective of DEDIPAC is to contribute to improving understanding of the determinants of dietary, physical activity and sedentary behaviours. DEDIPAC KH is a multi-disciplinary consortium of 46 consortia and organisations supported by joint programming grants from 12 countries across Europe. The work is divided into three thematic areas: (I) assessment and harmonisation of methods for future research, surveillance and monitoring, and for evaluation of interventions and policies; (II) determinants of dietary, physical activity and sedentary behaviours across the life course and in vulnerable groups; and (III) evaluation and benchmarking of public health and policy interventions aimed at improving dietary, physical activity and sedentary behaviours. In the first three years, DEDIPAC KH will organise, develop, share and harmonise expertise, methods, measures, data and other infrastructure. This should further European research and improve the broad multi-disciplinary approach needed to study the interactions between multilevel determinants in influencing dietary, physical activity and sedentary behaviours. Insights will be translated into more effective interventions and policies for the promotion of healthier behaviours and more effective monitoring and evaluation of the impacts of such interventions