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International audience; Cannabis exposure during the perinatal period results in varied and significant consequences in affected offspring. The prevalence of detrimental outcomes of perinatal cannabis exposure is likely to increase in tandem with the broadening of legalization and acceptance of the drug. As such, it is crucial to highlight the immediate and protracted consequences of cannabis exposure on pre-and post-natal development. Here, we identify lasting changes in neurons' learning flexibility (synaptic plasticity) and epigenetic misregulation in animal models of perinatal cannabinoid exposure (using synthetic cannabinoids or active components of the cannabis plant) in addition to significant alterations in social behavior and executive functions. These findings are supported by epidemiological data indicating similar behavioral outcomes throughout life in human offspring exposed to cannabis during pregnancy. Further, we indicate important lingering questions regarding accurate modeling of perinatal cannabis exposure as well as the need for sex-and agedependent outcome measures in future studies.

Since the first proton collisions at the CERN Intersecting Storage Rings (ISR) hadron colliders have defined the energy frontier. Noteworthy are the conversion of the Super Proton Synchrotron (SPS) into a proton-antiproton collider, the Tevatron proton-antiproton collider, as well as the abandoned SSC in the United States, and early forward-looking studies of even higher-energy colliders. Hadron colliders are likely to determine the pace of particle-physics progress also during the next hundred years. Discoveries at past hadron colliders were essential for establishing the so-called Standard Model of particle physics. The world’s present flagship collider, the Large Hadron Collider (LHC), including its high-luminosity upgrade (HL-LHC), is set to operate through the second half of the 2030’s. Further increases of the energy reach during the 21st century require another, still more powerful hadron collider. Three options for a next hadron collider are presently under investigation. The Future Circular Collider (FCC) study, hosted by CERN, is designing a 100 TeV collider, to be installed inside a new 100 km tunnel in the Lake Geneva basin. A similar 100-km collider, called Super proton-proton Collider (SppC), is being pursued by CAS- IHEP in China. In either machine, for the first time in hadron storage rings, synchrotron radiation damping will be significant, with a damping time of the order of 1 hour. In parallel, the synchrotron-radiation power emitted inside the cold magnets becomes an important design constraint. One important difference between FCC and SppC is the magnet technol- ogy. FCC uses 16 Tesla magnets based on Nb3Sn superconductor, while SppC magnets shall be realized with cables made from iron-based high- temperature superconductor. Initially the SppC magnets are assumed to provide a more moderate dipole field of 12 T, but they can later be pushed to a final ultimate field of 24 T. A third collider presently under study is the High-Energy LHC (HE-LHC), which is a higher energy collider in the existing LHC tunnel, exploiting the FCC magnet technology in order to essentially double the LHC energy at significantly higher luminosity.

Background: Biological interpretation of genomic summary data such as those resulting from GWAS and eQTL studies is one of the major bottlenecks in medical genomics research, calling for efficient and integrative tools to resolve this problem. Results: We introduce eXploring Genomic Relations (XGR), an open source tool designed for precision interpretation of genomic summary data enabling downstream knowledge discovery. Targeting users of varying computational skills, XGR utilises prior biological knowledge and relationships in a highly integrated but easily accessible way to make user-input genomic summary datasets more interpretable. We show how by incorporating ontology, annotation, and systems biology network-driven approaches, XGR generates more informative results than conventional analyses. We apply XGR to genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) summary data to explore the genomic landscape of the activated innate immune response and common immunological diseases. We provide genomic evidence for a disease taxonomy supporting the concept of a disease spectrum from autoimmune to autoinflammatory disorders. We also show how XGR can define SNP modulated gene networks and pathways that are shared and distinct between diseases, how it achieves functional, phenotypic and epigenomic annotations of genes and variants, and how it enables exploring annotation-based relationships between genetic variants. Conclusions: XGR provides a single integrated solution to enhance interpretation of genomic summary data for downstream biological discovery. XGR is released as an R package and web-app, freely available at http://galahad.well.ox.ac.uk/XGR.

Glasgow Mathematical Journal, 56 (1) ISSN:1469-509X ISSN:0017-0895

January 1974: In the dark of the electron microscope room, Paola Bonfante started up and looked again at the greenish screen; she was indeed looking at a round body very similar to a bacterium. Unexpectedly, this faint body was inside the cytoplasm of a mycorrhizal symbiotic fungus, which was inside the root cells of a plant.

Background: The posterior fusiform gyrus lies in a surgically challenging region. Several approaches have been described to access this anatomical area. The paramedian supracerebellar transtentorial (SCTT) approach benefits from minimal disruption of normal neurovascular tissue. The aim of this study was to demonstrate its application to access the posterior fusiform gyrus. Methods: Three brains and six cadaveric heads were examined. A stepwise dissection of the SCTT approach to the posterior fusiform gyrus was performed. Local cortical anatomy was studied. The operability score was applied for comparative analysis on surgical anatomy. Results: The major posterior landmark used to identify the fusiform gyrus with respect to the medial occipitotemporal gyrus was the collateral sulcus, which commonly bifurcated at its caudal extent. Compared with other surgical approaches addressed to access the region, SCTT demonstrated the best operability in terms of maneuverability arc. Favorable tentorial anatomy is the only limiting factor. Conclusions: The supracerebellar transtentorial approach is able to provide access to the posterior fusiform gyrus via a minimally disruptive, anatomic, microsurgical corridor. © 2016, Springer-Verlag Wien.

The computing power available nowadays to the average Monte-Carlo-code user is sufficient to perform large-scale neutron transport simulations, such as full-core burnup or high-fidelity multiphysics. In practice however, software limitations in the majority of the available Monte Carlo codes result in a low efficiency when running in High Performance Computing (HPC) environments, the main issues being inadequate memory utilization and poor scalability. The traditional parallel processing scheme based of splitting particle histories among processes requires domain replication across nodes, and therefore the memory demand for each computing node does not scale, and a memory bottleneck appears for large-scale problems. The scalability of this approach usually limits the resources that can be used efficiently to a small number of nodes/processors. Consequently, massively parallel execution is not viable with particle-based parallelism, at least not by itself. In this work we propose a Spatial Domain Decomposition (SDD) approach to develop an efficient and scalable Monte Carlo neutron transport algorithm. Breaking down the geometry into subdomains, a distributed memory scheme can be used to reduce the in-node memory demand, allowing the simulation of large-scale memory-intensive problems. Additionally, with an efficient neutron tracking algorithm the overall speedup can be significantly improved.

The instanton partition functions of 5d super Yang–Mills are built using elements of the representation theory of quantum algebra: Gaiotto state, intertwiner, vertex operator. This algebra is also known under the names of Ding–Iohara–Miki and quantum toroidal algebra. Exploiting the explicit action of the algebra on the partition function, we prove the regularity of the 5d qq-characters. These characters provide a solution to the Schwinger–Dyson equations, and they can also be interpreted as a quantum version of the Seiberg–Witten curve.

Abstract More than half of all known proteins, and almost all membrane and extra-cellular proteins have oligosaccharide structures or glycans attached to them. Defects in glycosylation pathways are directly involved in at least 30 severe human diseases. A multiple center cross-sectional study (China, Croatia, and Scotland) was carried out to investigate the possible association between hypertension and IgG glycosylation. A hydrophilic interaction chromatography of fluorescently labeled glycans was used to analyze N-glycans attached to IgG in plasma samples from a total of 4757 individuals of Chinese Han, Croatian, and Scottish ethnicity. Five glycans (IgG with digalactosylated glycans) significantly differed in participants with prehypertension or hypertension compared to those with normal blood pressure, while additional 17 glycan traits were only significantly differed in participants with hypertension compared to those of normal blood pressure. These glycans were also significant correlated with systolic blood pressure (SBP) or diastolic blood pressure (DBP). The present study demonstrated for the 1st time an association between hypertension and IgG glycome composition. These findings suggest that the individual variation in N-glycosylation of IgG contributes to pathogenesis of hypertension, presumably via its effect on pro- and/or anti-inflammatory pathways. Supplemental Digital Content is available in the text

Background: Abiraterone acetate became a referral treatment for metastatic castration-resistant prostate cancer (mCRPC) in a post-docetaxel setting despite a remarkable percentage of cardiovascular adverse events (AEs). As a consequence, the evaluation of cardiovascular safety in patients at risk should be mandatory. We aimed to assess the cardiovascular safety of abiraterone acetate in a real-world series of mCRPC patients treated at our institution. Materials and Methods: We retrospectively included mCRPC patients with at least 1 active cardiovascular comorbidity or risk factor according to the European Society of Cardiology (ESC) guidelines and who started treatment with abiraterone acetate from April 2011 to July 2012. Cardiac assessment with electrocardiogram and echocardiogram was performed at baseline and at treatment discontinuation. AEs were defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Statistical analyses were performed by descriptive statistics as appropriate. Results: We included 51 patients of whom 18% had an ESC score risk for a major cardiovascular event ≥4%. At a median follow-up of 36 months, no cardiac AEs (rhythm abnormalities or left ventricular function decrease) were observed. The most frequent grade 1-2 AE reported was fluid retention (18%) followed by hypertension and asthenia (16%). The most frequent grade 3-4 AEs were asthenia and pruritus/rash. No patients discontinued abiraterone because of toxicity. Conclusions: Abiraterone acetate showed a favorable safety profile in mCRPC patients with cardiovascular comorbidities or risk factors in a post-docetaxel setting, but further studies are needed to confirm our findings and to explore other settings of disease.