The detector description is an essential component that is used to analyze data resulting from particle collisions in high energy physics experiments. We will present a generic detector description ...toolkit and describe the guiding requirements and the architectural design for such a toolkit, as well as the main implementation choices. The design is strongly driven by easy of use; developers of detector descriptions and applications using them should provide minimal information and minimal specific code to achieve the desired result. The toolkit will be built reusing already existing components from the ROOT geometry package and provides missing functional elements and interfaces to offer a complete and coherent detector description solution. A natural integration to Geant4, the detector simulation program used in high energy physics, is provided.
Objectives
Antioxidant and anti‐inflammatory properties of naringenin could confer hepatoprotective effects.
Methods
Chang cells in culture media were maintained at 37°C and treated with increased ...concentrations of glucose (5.5–50 mm) and/or naringenin (25–100 µm), respectively, for 24 h. The cells were harvested and carbonyl proteins, antioxidant enzymes and proteins measured in cell lysates. Sprague Dawley rats were divided into 5 groups (n = 7) and orally treated daily for 56 days with 3.0 ml/kg per body weight (BW) distilled water (group 1), 60 mg/kg BW of naringenin (groups 2 and 4), respectively. Groups 3, 4 and 5 were given single 60 mg/kg per BW intraperitoneal injections of streptozotocin or insulin (2.0 IU/kg BW bid), (group 5 only).
Key findings
Cell viability was significantly decreased in response to increased hyperglycaemia but naringenin dose‐dependently, significantly reversed this compared to controls, respectively. However, antioxidant enzyme activities were reduced due to increased and reduced oxidative stress, respectively. Naringenin further significantly reduced hepatic oxidative stress and nuclear factor erythroid 2‐related factor 2 (Nrf2) protein expression and liver : body weight ratios in diabetic compared to controls rats.
Conclusions
Naringenin confers hepatoprotective antioxidant effects by initially preventing upregulation of Nrf2 protein expression and its downstream antioxidant enzymes.
Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease caused by a CAG repeat expansion in the
gene. Though the ATXN3 protein is expressed ubiquitously throughout the CNS, regional ...pathology in SCA3 patients is observed within select neuronal populations and more recently within oligodendrocyte-rich white matter tracts. We have previously recapitulated these white matter abnormalities in an overexpression mouse model of SCA3 and demonstrated that oligodendrocyte maturation impairments are one of the earliest and most progressive changes in SCA3 pathogenesis. Disease-associated oligodendrocyte signatures have recently emerged as significant contributors to several other neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, and Parkinson's disease, but their role in regional vulnerability and disease progression remains unexplored. Here, we are the first to comparatively assess myelination in human tissue in a region-dependent manner. Translating these findings to SCA3 mouse models of disease, we confirmed endogenous expression of mutant
leads to regional transcriptional dysregulation of oligodendrocyte maturation markers in Knock-In models of SCA3. We then investigated the spatiotemporal progression of mature oligodendrocyte transcriptional dysregulation in an overexpression SCA3 mouse model and how it relates to the onset of motor impairment. We further determined that regional reduction in mature oligodendrocyte cell counts in SCA3 mice over time parallels the onset and progression of brain atrophy in SCA3 patients. This work emphasizes the prospective contributions of disease-associated oligodendrocyte signatures to regional vulnerability and could inform timepoints and target regions imperative for biomarker assessment and therapeutic intervention in several neurodegenerative diseases.
Naringenin possesses many pharmacological effects and may modulate metformin disposition. The purpose of this study was to evaluate the role of naringenin on hepatic expression of organic cation ...transporter 1 (OCT1) protein and its associated effects on metformin‐associated hyperlactataemia in diabetes. Forty‐nine male Sprague Dawley rats randomly assigned to seven groups (n = 7) were orally treated daily with 3.0 mL/kg body‐weight (BW) of distilled water (group 1) or 60 mg/kg BW of naringenin (groups 2 and 5) or 250 mg/kg BW of metformin (groups 3 and 6), respectively, dissolved in distilled water. Similarly, group 7 was given metformin and naringenin. Groups 4, 5, 6 and 7 were administered intraperitoneally with streptozotocin at a single dose of 60 mg/kg BW to induce diabetes. Glucose tolerance tests were performed. The animals were killed after 8 weeks of treatment, blood was collected, and livers excised for further biochemical analysis. Lowered body‐weight, increased polydipsia and reduced hepatic glycogen concentrations were observed in diabetic rats compared to controls. Naringenin only significantly decreased plasma lactate levels, while metformin only or with naringenin significantly increased plasma lactate levels in diabetic compared to non‐treated diabetic animals. Metformin only but not naringenin significantly increased plasma lactate levels in non‐diabetic compared to control rats. Furthermore, naringenin with or without metformin but not metformin only significantly increased hepatic organic cation transporter 1 (OCT1) expression in diabetic compared to non‐treated diabetic rats. Contrastingly, metformin only but not naringenin significantly increased hepatic OCT1 expression in non‐diabetic rats compared to controls. Diabetic rats treated with metformin exhibited significantly increased plasma metformin concentrations compared to non‐diabetic but naringenin significantly dropped this parameter. Conversely, hepatic metformin concentrations were significantly lower in diabetic rats treated with metformin compared to non‐diabetic rats but significantly increased when naringenin was added. These results suggest that naringenin ameliorated hyperglycaemia‐induced reduction in hepatic OCT1 expression leading to metformin accumulation and increased lactic acid production.
To evaluate whether circulating microparticles (MPs) derived from three cell subtypes (platelets, total leukocytes or monocytes) obtained from multiple sclerosis (MS) patients were modulated ...depending on the clinical status and to investigate the effect of treatments on MP levels.
The MP counts were assessed with flow cytometry.
The platelet-derived MP level was higher in untreated MS patients than controls. Relapsing-remitting patients showed the highest levels in the three subtypes of MP while secondary progressive patients presented similar levels to those of healthy controls. Treatments had significant effects increasing the three subtypes of MP counts.
We suggest that MPs play a role in MS pathogenesis, reflecting disease status with an increment of their shedding during inflammatory periods and turning to baseline during chronic progressive degeneration.
Human studies, in combination with animal and cellular models, support glial cells as both major contributors to neurodegenerative diseases and promising therapeutic targets. Among glial cells, ...oligodendrocytes and Schwann cells are the myelinating glial cells of the central and peripheral nervous system, respectively. In this review, we discuss the contributions of these central and peripheral myelinating glia to the pathomechanisms of polyglutamine (polyQ) spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, and 17. First, we highlight the function of oligodendrocytes in healthy conditions and how they are disrupted in polyQ SCA patients and diseased model systems. We then cover the role of Schwann cells in peripheral nerve function and repair as well as their possible role in peripheral neuropathy in polyQ SCAs. Finally, we discuss potential polyQ SCA therapeutic interventions in myelinating glial.
The bright future of particle physics at the Energy and Intensity frontiers poses exciting challenges to the scientific software community. The traditional strategies for processing and analysing ...data are evolving in order to (i) offer higher-level programming model approaches and (ii) exploit parallelism to cope with the ever increasing complexity and size of the datasets. This contribution describes how the ROOT framework, a cornerstone of software stacks dedicated to particle physics, is preparing to provide adequate solutions for the analysis of large amount of scientific data on parallel architectures. The functional approach to parallel data analysis provided with the ROOT TDataFrame interface is then characterised. The design choices behind this new interface are described also comparing with other widely adopted tools such as Pandas and Apache Spark. The programming model is illustrated highlighting the reduction of boilerplate code, composability of the actions and data transformations as well as the capabilities of dealing with different data sources such as ROOT, JSON, CSV or databases. Details are given about how the functional approach allows transparent implicit parallelisation of the chain of operations specified by the user. The progress done in the field of distributed analysis is examined. In particular, the power of the integration of ROOT with Apache Spark via the PyROOT interface is shown. In addition, the building blocks for the expression of parallelism in ROOT are briefly characterised together with the structural changes applied in the building and testing infrastructure which were necessary to put them in production.
PODIO is a C++ library that supports the automatic creation of event data models (EDMs) and efficient I/O code for HEP experiments. It is developed as a new EDM Toolkit for future particle physics ...experiments in the context of the AIDA2020 EU programme. Experience from LHC and the linear collider community shows that existing solutions partly suffer from overly complex data models with deep object-hierarchies or unfavorable I/O performance. The PODIO project was created in order to address these problems. PODIO is based on the idea of employing plain-old-data (POD) data structures wherever possible, while avoiding deep object-hierarchies and virtual inheritance. At the same time it provides the necessary high-level interface towards the developer physicist, such as the support for inter-object relations and automatic memory-management, as well as a Python interface. To simplify the creation of efficient data models PODIO employs code generation from a simple yaml-based markup language. In addition, it was developed with concurrency in mind in order to support the use of modern CPU features, for example giving basic support for vectorization techniques.
CernVM is a Virtual Software Appliance capable of running physics applications from the LHC experiments at CERN. It aims to provide a complete and portable environment for developing and running LHC ...data analysis on any end-user computer (laptop, desktop) as well as on the Grid, independently of Operating System platforms (Linux, Windows, MacOS). The experiment application software and its specific dependencies are built independently from CernVM and delivered to the appliance just in time by means of a CernVM File System (CVMFS) specifically designed for efficient software distribution. The procedures for building, installing and validating software releases remains under the control and responsibility of each user community. We provide a mechanism to publish pre-built and configured experiment software releases to a central distribution point from where it finds its way to the running CernVM instances via the hierarchy of proxy servers or content delivery networks. In this paper, we present current state of CernVM project and compare performance of CVMFS to performance of traditional network file system like AFS and discuss possible scenarios that could further improve its performance and scalability.
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