Using local states to drive the sampling of global conformations in proteins

Conformational changes associated with protein function often occur beyond the time scale currently accessible to unbiased molecular dynamics (MD) simulations, so that different approaches have been developed to accelerate their sampling. Here we investigate how the knowledge of backbone conformations preferentially adopted by protein fragments, as contained in precalculated libraries known as structural alphabets (SA), can be used to explore the landscape of protein conformations in MD simulations. We find that (a) enhancing the sampling of native local states in both metadynamics and steered MD simulations allows the recovery of global folded states in small proteins; (b) folded states can still be recovered when the amount of information on the native local states is reduced by using a low-resolution version of the SA, where states are clustered into macrostates; and (c) sequences of SA states derived from collections of structural motifs can be used to sample alternative conformations of preselected protein regions. The present findings have potential impact on several applications, ranging from protein model refinement to protein folding and design.The computer resources, technical expertise, Red Española de Supercomputación, Cristian Micheletti, Michael Sadowski and Katarzyna Maksimia

Exploiting the WH/ZH symmetry in the search for New Physics

We suggest to isolate the loop-induced gluon-initiated component ($gg\to ZH$) for associated $ZH$ production by using the similarity of the Drell-Yan-like component for $ZH$ production to the $WH$ process. We argue that the cross-section ratio of the latter two processes can be predicted with high theoretical accuracy. Comparing it to the experimental $ZH/WH$ cross-section ratio should allow to probe for New Physics in the $gg\to ZH$ component at the HL-LHC. We consider typical BSM scenarios in order to exemplify the effect they would have on the proposed observable.Comment: 22 pages, 10 figures. v2: Minor changes; matches published versio

Una procedura per la valutazione dei limiti di utilizzo di O-Ring sottoposti ad intensi fasci di neutroni

Si presenta una procedura per la previsione della durata di utilizzo di O-ring in materiale polimerico impiegati nei bersagli per la produzione di fasci di ioni radioattivi. Si sono dapprima condotte prove di tenuta a vuoto e analisi a elementi finiti di un O-ring di riferimento operante con diversi livelli di interferenza con la cava, identificando la precompressione limite per la tenuta e la corrispondente pressione di contatto con la cava. Si sono poi effettuate prove di trazione e di Compression Set su campioni di O-ring in EPDM, preventivamente sottoposti a diversi livelli di irraggiamento in campi misti di neutroni e gamma, analizzando l’effetto della dose assorbita sul comportamento meccanico del materiale e sulle corrispondenti proprietà resistenziali, e definendo opportune leggi costitutive. Si sono infine simulate le progressive modifiche di comportamento della guarnizione indotte dall’irraggiamento, prevedendone la durata in esercizio in termini di tenuta e di resistenza strutturale

Fatigue behavior and cyclic damage of peek short fiber reinforced composites

Fatigue strength and failure mechanisms of short fiber reinforced (SFR) PEEK have been investigated in the past by several research groups. However some relevant aspects of the fatigue behavior of these materials, like cyclic creep and fatigue damage accumulation and modeling, have not been studied yet, in particular in presence of both fillers and short fibers as reinforcement. In the present research these aspects were considered by carrying out uni-axial fatigue tests in load control (cycle ratio R = 0) on neat PEEK and PEEK based composites reinforced either with short carbon fibers only or with addition of fillers (graphite and PTFE). For each material stress-life curves were obtained and compared. Fatigue fracture surfaces were analyzed to identify failure mechanisms in presence of different reinforcement types. The evolution of cyclic creep strain was also monitored as a function of the number of cycles, thus allowing investigation on the correlation between cyclic creep parameters and fatigue life. The evolution of cyclic damage with loading cycles was then compared by defining a damage parameter related to the specimen stiffness reduction observed during the tests. Progressive cyclic damage evolution of short fiber reinforced PEEK composites presented significantly different patterns depending on applied stress level and on the presence of different reinforcement typologies. In order to reproduce the different fatigue damage kinetics and stages of progressive damage accumulation observed experimentally, a cyclic damage model was finally developed and implemented into a finite element code by which a satisfactory agreement between numerical prediction and experimental data at different stress levels for each examined material

Development of Hydro-Meteorological Hazard Early Warning System in Indonesia

This paper discusses the result of the development of a hydro-meteorological hazard early warning system (H-MHEWS) that combines weather prediction from Weather Research and Forecasting (WRF) and the hydrometeorological hazard index from the National Disaster Management Authority (BNPB), Indonesia. In its current development phase, the hazards that H-MHEWS predicts are floods, landslides, and extreme weather events. Potential hazard indices are obtained by using an overlay approach and resampling so that the data have a 100-m spatial resolution. All indices are classified into 4 status categories: “No alert”, “Advisory”, “Watch”, and “Warning”. Flood potential is produced by overlaying rainfall prediction at 3-hour intervals with the flood index. Landslide potential is produced by overlaying rainfall prediction with the landslide index. Extreme weather potential is divided into 3 categories, i.e. heavy rain, strong winds, and extreme ocean waves. The whole prediction is dynamic, following weather predictions at 3-hour intervals. The hazard prediction results will trigger a ‘Warning' alert in case of emergency status. This alert will be set up in a notification system to make it easier for the user to identify the most dangerous hydrometeorological hazard events

Coevolved mutations reveal distinct architectures for two core proteins in the bacterial flagellar motor

Switching of bacterial flagellar rotation is caused by large domain movements of the FliG protein triggered by binding of the signal protein CheY to FliM. FliG and FliM form adjacent multi-subunit arrays within the basal body C-ring. The movements alter the interaction of the FliG C-terminal (FliGC) "torque" helix with the stator complexes. Atomic models based on the Salmonella entrovar C-ring electron microscopy reconstruction have implications for switching, but lack consensus on the relative locations of the FliG armadillo (ARM) domains (amino-terminal (FliGN), middle (FliGM) and FliGC) as well as changes during chemotaxis. The generality of the Salmonella model is challenged by the variation in motor morphology and response between species. We studied coevolved residue mutations to determine the unifying elements of switch architecture. Residue interactions, measured by their coevolution, were formalized as a network, guided by structural data. Our measurements reveal a common design with dedicated switch and motor modules. The FliM middle domain (FliMM) has extensive connectivity most simply explained by conserved intra and inter-subunit contacts. In contrast, FliG has patchy, complex architecture. Conserved structural motifs form interacting nodes in the coevolution network that wire FliMM to the FliGC C-terminal, four-helix motor module (C3-6). FliG C3-6 coevolution is organized around the torque helix, differently from other ARM domains. The nodes form separated, surface-proximal patches that are targeted by deleterious mutations as in other allosteric systems. The dominant node is formed by the EHPQ motif at the FliMMFliGM contact interface and adjacent helix residues at a central location within FliGM. The node interacts with nodes in the N-terminal FliGc α-helix triad (ARM-C) and FliGN. ARM-C, separated from C3-6 by the MFVF motif, has poor intra-network connectivity consistent with its variable orientation revealed by structural data. ARM-C could be the convertor element that provides mechanistic and species diversity.JK was supported by Medical Research Council grant U117581331. SK was supported by seed funds from Lahore University of Managment Sciences (LUMS) and the Molecular Biology Consortium

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente