MSDmotif: exploring protein sites and motifs

<p>Abstract</p> <p>Background</p> <p>Protein structures have conserved features – motifs, which have a sufficient influence on the protein function. These motifs can be found in sequence as well as in 3D space. Understanding of these fragments is essential for 3D structure prediction, modelling and drug-design. The Protein Data Bank (PDB) is the source of this information however present search tools have limited 3D options to integrate protein sequence with its 3D structure.</p> <p>Results</p> <p>We describe here a web application for querying the PDB for ligands, binding sites, small 3D structural and sequence motifs and the underlying database. Novel algorithms for chemical fragments, 3D motifs, ϕ/ψ sequences, super-secondary structure motifs and for small 3D structural motif associations searches are incorporated. The interface provides functionality for visualization, search criteria creation, sequence and 3D multiple alignment options. MSDmotif is an integrated system where a results page is also a search form. A set of motif statistics is available for analysis. This set includes molecule and motif binding statistics, distribution of motif sequences, occurrence of an amino-acid within a motif, correlation of amino-acids side-chain charges within a motif and Ramachandran plots for each residue. The binding statistics are presented in association with properties that include a ligand fragment library. Access is also provided through the distributed Annotation System (DAS) protocol. An additional entry point facilitates XML requests with XML responses.</p> <p>Conclusion</p> <p>MSDmotif is unique by combining chemical, sequence and 3D data in a single search engine with a range of search and visualisation options. It provides multiple views of data found in the PDB archive for exploring protein structures.</p

Status and future development of Heating and Current Drive for the EU DEMO

The European DEMO is a pulsed device with pulse length of 2 hours. The functions devoted to the heating and current drive system are: plasma breakdown, plasma ramp-up to the flat-top where fusion reactions occur, the control of the plasma during the flat-top phase, and finally the plasma ramp-down. The EU-DEMO project was in a Pre-Concept Design Phase during 2014-2020, meaning that in some cases, the design values of the device and the precise requirements from the physics point of view were not yet frozen. A total of 130 MW was considered for the all phases of the plasma: in the flat top, 30 MW is required for neoclassical tearing modes (NTM) control, 30 MW for burn control, and 70 MW for the control of thermal instability (TI), without any specific functions requested from each system, Electron Cyclotron (EC), Ion Cyclotron (IC), or Neutral Beam (NB) Injection. At the beginning of 2020, a strategic decision was taken, to consider EC as the baseline for the next phase (in 2021 and beyond). R&D on IC and NB will be risk mitigation measures. In parallel with progresses in Physics modelling, a decision point on the heating strategy will be taken by 2024. This paper describes the status of the R&D development during the period 2014-2020. It assumes that the 3 systems EC, IC and NB will be needed. For integration studies, they are assumed to be implemented at a power level of at least 50 MW. This paper describes in detail the status reached by the EC, IC and NB at the end of 2020. It will be used in the future for further development of the baseline heating method EC, and serves as starting point to further develop IC and NB in areas needed for these systems to be considered for DEMO

Status and future development of Heating and Current Drive for the EU DEMO

The European DEMO is a pulsed device with pulse length of 2 hours. The functions devoted to the heating and current drive system are: plasma breakdown, plasma ramp-up to the flat-top where fusion reactions occur, the control of the plasma during the flat-top phase, and finally the plasma ramp-down. The EU-DEMO project was in a Pre-Concept Design Phase during 2014-2020, meaning that in some cases, the design values of the device and the precise requirements from the physics point of view were not yet frozen. A total of 130 MW was considered for the all phases of the plasma: in the flat top, 30 MW is required for neoclassical tearing modes (NTM) control, 30 MW for burn control, and 70 MW for the control of thermal instability (TI), without any specific functions requested from each system, Electron Cyclotron (EC), Ion Cyclotron (IC), or Neutral Beam (NB) Injection. At the beginning of 2020, a strategic decision was taken, to consider EC as the baseline for the next phase (in 2021 and beyond). R&D on IC and NB will be risk mitigation measures. In parallel with progresses in Physics modelling, a decision point on the heating strategy will be taken by 2024. This paper describes the status of the R&D development during the period 2014-2020. It assumes that the 3 systems EC, IC and NB will be needed. For integration studies, they are assumed to be implemented at a power level of at least 50 MW. This paper describes in detail the status reached by the EC, IC and NB at the end of 2020. It will be used in the future for further development of the baseline heating method EC, and serves as starting point to further develop IC and NB in areas needed for these systems to be considered for DEMO

Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND-study)

Background: Recent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications. The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas. Methods/design. Multicenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma 3 cm, located between 115 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane i

SalmoNet, an integrated network of ten Salmonella enterica strains reveals common and distinct pathways to host adaptation

Salmonella enterica is a prominent bacterial pathogen with implications on human and animal health. Salmonella serovars could be classified as gastro-intestinal or extra-intestinal. Genome-wide comparisons revealed that extra-intestinal strains are closer relatives of gastro-intestinal strains than to each other indicating a parallel evolution of this trait. Given the complexity of the differences, a systems-level comparison could reveal key mechanisms enabling extra-intestinal serovars to cause systemic infections. Accordingly, in this work, we introduce a unique resource, SalmoNet, which combines manual curation, high-throughput data and computational predictions to provide an integrated network for Salmonella at the metabolic, transcriptional regulatory and protein-protein interaction levels. SalmoNet provides the networks separately for five gastro-intestinal and five extra-intestinal strains. As a multi-layered, multi-strain database containing experimental data, SalmoNet is the first dedicated network resource for Salmonella. It comprehensively contains interactions between proteins encoded in Salmonella pathogenicity islands, as well as regulatory mechanisms of metabolic processes with the option to zoom-in and analyze the interactions at specific loci in more detail. Application of SalmoNet is not limited to strain comparisons as it also provides a Salmonella resource for biochemical network modeling, host-pathogen interaction studies, drug discovery, experimental validation of novel interactions, uncovering new pathological mechanisms from emergent properties and epidemiological studies. SalmoNet is available at http://salmonet.org

Social Relationships and Mortality Risk: A Meta-analytic Review

In a meta-analysis, Julianne Holt-Lunstad and colleagues find that individuals' social relationships have as much influence on mortality risk as other well-established risk factors for mortality, such as smoking