The ALICE Off-Line Strategy: A Successful Migration to OO

The ALICE Experiment has chosen to start developing its software directly in OO, using the services of the ROOT system, which is ALICE's official candidate for the common LHC framework. This had lead to the definition of a complete environment (AliRoot) where the software developed by the different experimental groups is being integrated. Different test-benches for I/O and Simulation have been set up based on real production code. This allows early assessment of technology, both software and hardware in a realistic production environment. Different codes, such as GEANT3, GEANT4 and FLUKA, or the reconstruction algorithms by the physicists developing the detectors, have been easily integrated in the framework, that has shown to be both evolutive and modular.The ALICE Collaboration has adopted this setup and we are now successfully migrating the users into it. This talk describes the AliRoot environment and its future evolution

ROOT, an object oriented data analysis framework

ROOT is an object-oriented framework aimed at solving the data analysis challenges of high-energy physics. Here we discuss the main components of the framework. We begin with an overview describing the framework's organization, the interpreter CINT, its automatic interface to the compiler and linker ACLiC, and an example of a first interactive session. The subsequent sections cover histogramming and fitting. Then, ROOT's solution to storing and retrieving HEP data, building and managing of ROOT files, and designing ROOT trees. Followed by a description of the collection classes, the GUI classes, how to add your own classes to ROOT, and PROOF, ROOT's parallel processing facility

A new subtype of frontotemporal lobar degeneration with FUS pathology

Frontotemporal dementia (FTD) is a clinical syndrome with a heterogeneous molecular basis. The neuropathology associated with most FTD is characterized by abnormal cellular aggregates of either transactive response DNA-binding protein with Mr 43 kDa (TDP-43) or tau protein. However, we recently described a subgroup of FTD patients, representing around 10%, with an unusual clinical phenotype and pathology characterized by frontotemporal lobar degeneration with neuronal inclusions composed of an unidentified ubiquitinated protein (atypical FTLD-U; aFTLD-U). All cases were sporadic and had early-onset FTD with severe progressive behavioural and personality changes in the absence of aphasia or significant motor features. Mutations in the fused in sarcoma (FUS) gene have recently been identified as a cause of familial amyotrophic lateral sclerosis, with these cases reported to have abnormal cellular accumulations of FUS protein. Because of the recognized clinical, genetic and pathological overlap between FTD and amyotrophic lateral sclerosis, we investigated whether FUS might also be the pathological protein in aFTLD-U. In all our aFTLD-U cases (n = 15), FUS immunohistochemistry labelled all the neuronal inclusions and also demonstrated previously unrecognized glial pathology. Immunoblot analysis of protein extracted from post-mortem aFTLD-U brain tissue demonstrated increased levels of insoluble FUS. No mutations in the FUS gene were identified in any of our patients. These findings suggest that FUS is the pathological protein in a significant subgroup of sporadic FTD and reinforce the concept that FTD and amyotrophic lateral sclerosis are closely related condition

Developments in ROOT I/O and trees

For the last several months the main focus of development in the ROOT I/O package has been code consolidation and performance improvements. Access to remote files is affected both by bandwidth and latency. We introduced a pre-fetch mechanism to minimize the number of transactions between client and server and hence reducing the effect of latency. We will review the implementation and how well it works in different conditions (gain of an order of magnitude for remote file access). We will also review new utilities, including a faster implementation of TTree cloning (gain of an order of magnitude), a generic mechanism for object references, and a new entry list mechanism tuned both for small and large number of selections. In addition to reducing the coupling with the core module and becoming its owns library (libRIO) (as part of the general restructuration of the ROOT libraries), the I/O package has been enhanced in the area of XML and SQL support, thread safety, schema evolution, TTreeFormula, and many other areas. We will also discuss various ways, ROOT will be able to benefit from multi-core architecture to improve I/O performances

The Usage of ROOT for Online Monitoring in the ALICE DATE System

Presentation for CHEP2000Data Acquisition systems for HEP applications need constant monitoring (online and offline) of their data streams to accomplish several tasks: quality checking, tuning, statistics, pre-analysis. Monitoring tasks can and should use the same tools as data analysis products (conventions, libraries, environments) to reduce training, installation, development and support efforts and -at the same time - to strengthen the liaison between the online and the offline worlds. The ALICE DATE Data Acquisition system available today for R&D and for test beams is fully integrated with the ROOT environment. A simple DAQ-oriented approach and a more complex OO-based model have been developed to allow a variety of programming paradigms and to validate the complete life cycle of monitoring tools, both for online and offline environments

Highlights of the 2009 scientific sessions of the European Society of Cardiology.

Nebivolol is a third-generation beta-adrenergic receptor antagonist (beta-blocker) with high selectivity for beta(1)-adrenergic receptors. In addition, it causes vasodilatation via interaction with the endothelial L-arginine/nitric oxide (NO) pathway. This dual mechanism of action underlies many of the haemodynamic properties of nebivolol, which include reductions in heart rate and blood pressure (BP), and improvements in systolic and diastolic function. With respect to BP lowering, the NO-mediated effects cause a reduction in peripheral vascular resistance and an increase in stroke volume with preservation of cardiac output. Flow-mediated dilatation and coronary flow reserve are also increased during nebivolol administration. Other haemodynamic effects include beneficial effects on pulmonary artery pressure, pulmonary wedge pressure, exercise capacity and left ventricular ejection fraction. In addition, nebivolol does not appear to have adverse effects on lipid metabolism and insulin sensitivity like traditional beta-blockers. The documented beneficial haemodynamic effects of nebivolol are translated into improved clinical outcomes in patients with hypertension or heart failure. In patients with hypertension, the incidence of bradycardia with nebivolol is often lower than that with other currently available beta-blockers. This, along with peripheral vasodilatation and NO-induced benefits such as antioxidant activity and reversal of endothelial dysfunction, should facilitate better protection from cardiovascular events. In addition, nebivolol has shown an improved tolerability profile, particularly with respect to events commonly associated with beta-blockers, such as fatigue and sexual dysfunction. Data from SENIORS (Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure) showed that significantly fewer nebivolol versus placebo recipients experienced the primary endpoint of all-cause mortality or cardiovascular hospitalization. The benefits of nebivolol therapy were shown to be cost effective. Thus, nebivolol is an effective and well tolerated agent with benefits over and above those of traditional beta-blockade because of its effects on NO release, which give it unique haemodynamic effects, cardioprotective activity and a good tolerability profile

Rates of lobar atrophy in asymptomatic MAPT mutation carriers.

IntroductionThe aim of this study was to investigate the rates of lobar atrophy in the asymptomatic microtubule-associated protein tau (MAPT) mutation carriers.MethodsMAPT mutation carriers (n = 14; 10 asymptomatic, 4 converters from asymptomatic to symptomatic) and noncarriers (n = 13) underwent structural magnetic resonance imaging and were followed annually with a median of 9.2 years. Longitudinal changes in lobar atrophy were analyzed using the tensor-based morphometry with symmetric normalization algorithm.ResultsThe rate of temporal lobe atrophy in asymptomatic MAPT mutation carriers was faster than that in noncarriers. Although the greatest rate of atrophy was observed in the temporal lobe in converters, they also had increased atrophy rates in the frontal and parietal lobes compared to noncarriers.DiscussionAccelerated decline in temporal lobe volume occurs in asymptomatic MAPT mutation carriers followed by the frontal and parietal lobe in those who have become symptomatic. The findings have implications for monitoring the progression of neurodegeneration during clinical trials in asymptomatic MAPT mutation carriers

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis