A Genome-Wide Analysis of FRT-Like Sequences in the Human Genome

Efficient and precise genome manipulations can be achieved by the Flp/FRT system of site-specific DNA recombination. Applications of this system are limited, however, to cases when target sites for Flp recombinase, FRT sites, are pre-introduced into a genome locale of interest. To expand use of the Flp/FRT system in genome engineering, variants of Flp recombinase can be evolved to recognize pre-existing genomic sequences that resemble FRT and thus can serve as recombination sites. To understand the distribution and sequence properties of genomic FRT-like sites, we performed a genome-wide analysis of FRT-like sites in the human genome using the experimentally-derived parameters. Out of 642,151 identified FRT-like sequences, 581,157 sequences were unique and 12,452 sequences had at least one exact duplicate. Duplicated FRT-like sequences are located mostly within LINE1, but also within LTRs of endogenous retroviruses, Alu repeats and other repetitive DNA sequences. The unique FRT-like sequences were classified based on the number of matches to FRT within the first four proximal bases pairs of the Flp binding elements of FRT and the nature of mismatched base pairs in the same region. The data obtained will be useful for the emerging field of genome engineering

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

In Silico Prediction and Analysis of Caenorhabditis EF-hand Containing Proteins

Calcium (Ca+2) is a ubiquitous messenger in eukaryotes including Caenorhabditis. Ca+2-mediated signalling processes are usually carried out through well characterized proteins like calmodulin (CaM) and other Ca+2 binding proteins (CaBP). These proteins interact with different targets and activate it by bringing conformational changes. Majority of the EF-hand proteins in Caenorhabditis contain Ca+2 binding motifs. Here, we have performed homology modelling of CaM-like proteins using the crystal structure of Drosophila melanogaster CaM as a template. Molecular docking was applied to explore the binding mechanism of CaM-like proteins and IQ1 motif which is a ∼25 residues and conform to the consensus sequence (I, L, V)QXXXRXXXX(R,K) to serve as a binding site for different EF hand proteins. We made an attempt to identify all the EF-hand (a helix-loop-helix structure characterized by a 12 residues loop sequence involved in metal coordination) containing proteins and their Ca+2 binding affinity in Caenorhabditis by analysing the complete genome sequence. Docking studies revealed that F165, F169, L29, E33, F44, L57, M61, M96, M97, M108, G65, V115, F93, N104, E144 of CaM-like protein is involved in the interaction with IQ1 motif. A maximum of 170 EF-hand proteins and 39 non-EF-hand proteins with Ca+2/metal binding motif were identified. Diverse proteins including enzyme, transcription, translation and large number of unknown proteins have one or more putative EF-hands. Phylogenetic analysis revealed seven major classes/groups that contain some families of proteins. Various domains that we identified in the EF-hand proteins (uncharacterized) would help in elucidating their functions. It is the first report of its kind where calcium binding loop sequences of EF-hand proteins were analyzed to decipher their calcium affinities. Variation in Ca+2-binding affinity of EF-hand CaBP could be further used to study the behaviour of these proteins. Our analyses postulated that Ca+2 is likely to be key player in Caenorhabditis cell signalling

Genetic Rearrangements Can Modify Chromatin Features at Epialleles

Analogous to genetically distinct alleles, epialleles represent heritable states of different gene expression from sequence-identical genes. Alleles and epialleles both contribute to phenotypic heterogeneity. While alleles originate from mutation and recombination, the source of epialleles is less well understood. We analyze active and inactive epialleles that were found at a transgenic insert with a selectable marker gene in Arabidopsis. Both converse expression states are stably transmitted to progeny. The silent epiallele was previously shown to change its state upon loss-of-function of trans-acting regulators and drug treatments. We analyzed the composition of the epialleles, their chromatin features, their nuclear localization, transcripts, and homologous small RNA. After mutagenesis by T-DNA transformation of plants carrying the silent epiallele, we found new active alleles. These switches were associated with different, larger or smaller, and non-overlapping deletions or rearrangements in the 3′ regions of the epiallele. These cis-mutations caused different degrees of gene expression stability depending on the nature of the sequence alteration, the consequences for transcription and transcripts, and the resulting chromatin organization upstream. This illustrates a tight dependence of epigenetic regulation on local structures and indicates that sequence alterations can cause epigenetic changes at some distance in regions not directly affected by the mutation. Similar effects may also be involved in gene expression and chromatin changes in the vicinity of transposon insertions or excisions, recombination events, or DNA repair processes and could contribute to the origin of new epialleles

Ultrasonic intensification as a tool for enhanced microbial biofuel yields

peer-reviewedUltrasonication has recently received attention as a novel bioprocessing tool for process intensification in many areas of downstream processing. Ultrasonic intensification (periodic ultrasonic treatment during the fermentation process) can result in a more effective homogenization of biomass and faster energy and mass transfer to biomass over short time periods which can result in enhanced microbial growth. Ultrasonic intensification can allow the rapid selective extraction of specific biomass components and can enhance product yields which can be of economic benefit. This review focuses on the role of ultrasonication in the extraction and yield enhancement of compounds from various microbial sources, specifically algal and cyanobacterial biomass with a focus on the production of biofuels. The operating principles associated with the process of ultrasonication and the influence of various operating conditions including ultrasonic frequency, power intensity, ultrasonic duration, reactor designs and kinetics applied for ultrasonic intensification are also described

Performance of the upgraded PreProcessor of the ATLAS Level-1 Calorimeter Trigger

The PreProcessor of the ATLAS Level-1 Calorimeter Trigger prepares the analogue trigger signals sent from the ATLAS calorimeters by digitising, synchronising, and calibrating them to reconstruct transverse energy deposits, which are then used in further processing to identify event features. During the first long shutdown of the LHC from 2013 to 2014, the central components of the PreProcessor, the Multichip Modules, were replaced by upgraded versions that feature modern ADC and FPGA technology to ensure optimal performance in the high pile-up environment of LHC Run 2. This paper describes the features of the newMultichip Modules along with the improvements to the signal processing achieved.ANPCyTYerPhI, ArmeniaAustralian Research CouncilBMWFW, AustriaAustrian Science Fund (FWF)Azerbaijan National Academy of Sciences (ANAS)SSTC, BelarusNational Council for Scientific and Technological Development (CNPq)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Natural Sciences and Engineering Research Council of CanadaCanada Foundation for InnovationNational Natural Science Foundation of China (NSFC)Departamento Administrativo de Ciencia, Tecnología e Innovación ColcienciasMinistry of Education, Youth & Sports - Czech Republic Czech Republic GovernmentCzech Republic GovernmentDNRF, DenmarkDanish Natural Science Research CouncilCentre National de la Recherche Scientifique (CNRS)CEA-DRF/IRFU, FranceFederal Ministry of Education & Research (BMBF)Max Planck SocietyGreek Ministry of Development-GSRTRGC and Hong Kong SAR, ChinaIsrael Science FoundationBenoziyo Center, IsraelIstituto Nazionale di Fisica Nucleare (INFN)Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of ScienceCNRST, MoroccoRCN, NorwayPortuguese Foundation for Science and TechnologyMNE/IFA, RomaniaMES of RussiaMESTD, SerbiaMSSR, SlovakiaSlovenian Research Agency - SloveniaMIZS, SloveniaSpanish GovernmentSRC, SwedenWallenberg Foundation, SwedenSNSF Geneva, SwitzerlandMinistry of Science and Technology, TaiwanMinistry of Energy & Natural Resources - TurkeyScience & Technology Facilities Council (STFC)United States Department of Energy (DOE)National Science Foundation (NSF)BCKDF, CanadaCANARIE, CanadaCRC, CanadaEuropean Research Council (ERC)European Union (EU)French National Research Agency (ANR)German Research Foundation (DFG)Alexander von Humboldt FoundationGreek NSRF, GreeceBSF-NSF, IsraelGerman-Israeli Foundation for Scientific Research and DevelopmentLa Caixa Banking Foundation, SpainCERCA Programme Generalitat de Catalunya, SpainPROMETEO, SpainGenT Programmes Generalitat Valenciana, SpainGoran Gustafssons Stiftelse, SwedenRoyal Society of LondonLeverhulme TrustNRC, CanadaCERNANID, ChileChinese Academy of SciencesMinistry of Science and Technology, ChinaSRNSFG, GeorgiaHGF, GermanyNetherlands Organization for Scientific Research (NWO) Netherlands GovernmentMinistry of Science and Higher Education, PolandNCN, PolandNRCKI, Russia FederationJINRDST/NRF, South AfricaSERI, Geneva, SwitzerlandCantons of Bern and Geneva, SwitzerlandCompute Canada, CanadaHorizon 2020Marie Sklodowska-Curie ActionsEuropean Cooperation in Science and Technology (COST)EU-ESF, Greec

Dijet Resonance Search with Weak Supervision Using root S=13 TeV pp Collisions in the ATLAS Detector

This Letter describes a search for narrowly resonant new physics using a machine-learning anomaly detection procedure that does not rely on signal simulations for developing the analysis selection. Weakly supervised learning is used to train classifiers directly on data to enhance potential signals. The targeted topology is dijet events and the features used for machine learning are the masses of the two jets. The resulting analysis is essentially a three-dimensional search A → BC, for mA ∼ OðTeVÞ, mB; mC ∼ Oð100 GeVÞ and B, C are reconstructed as large-radius jets, without paying a penalty associated with a large trials factor in the scan of the masses of the two jets. The full run 2 ffiffi s p ¼ 13 TeV pp collision dataset of 139 fb−1 recorded by the ATLAS detector at the Large Hadron Collider is used for the search. There is no significant evidence of a localized excess in the dijet invariant mass spectrum between 1.8 and 8.2 TeV. Cross-section limits for narrow-width A, B, and C particles vary with mA, mB, and mC. For example, when mA ¼ 3 TeV and mB ≳ 200 GeV, a production cross section between 1 and 5 fb is excluded at 95% confidence level, depending on mC. For certain masses, these limits are up to 10 times more sensitive than those obtained by the inclusive dijet search. These results are complementary to the dedicated searches for the case that B and C are standard model boson

Observation of electroweak production of two jets and a Z-boson pair

Electroweak symmetry breaking explains the origin of the masses of elementary particles through their interactions with the Higgs field. Besides the measurements of the Higgs boson properties, the study of the scattering of massive vector bosons with spin 1 allows the nature of electroweak symmetry breaking to be probed. Among all processes related to vector-boson scattering, the electroweak production of two jets and a Z-boson pair is a rare and important one. Here we report the observation of this process from proton–proton collision data corresponding to an integrated luminosity of 139 fb−1 recorded at a centre-of-mass energy of 13 TeV with the ATLAS detector at the Large Hadron Collider. We consider two different final states originating from the decays of the Z-boson pair: one containing four charged leptons and another containing two charged leptons and two neutrinos. The hypothesis of no electroweak production is rejected with a statistical significance of 5.7σ, and the measured cross-section for electroweak production is consistent with the Standard Model prediction. In addition, we report cross-sections for inclusive production of a Z-boson pair and two jets for the two final states

Search for long-lived neutral particles produced in pp collisions at √s = 13 TeV decaying into displaced hadronic jets in the ATLAS inner detector and muon spectrometer

A search is presented for pair production of long-lived neutral particles using 33     fb − 1 of √ s = 13     TeV proton–proton collision data, collected during 2016 by the ATLAS detector at the LHC. This search focuses on a topology in which one long-lived particle decays in the ATLAS inner detector and the other decays in the muon spectrometer. Special techniques are employed to reconstruct the displaced tracks and vertices in the inner detector and in the muon spectrometer. One event is observed that passes the full event selection, which is consistent with the estimated background. Limits are placed on scalar boson propagators with masses from 125 GeV to 1000 GeV decaying into pairs of long-lived hidden-sector scalars with masses from 8 GeV to 400 GeV. The limits placed on several low-mass scalars extend previous exclusion limits in the range of proper lifetimes c τ from 5 cm to 1 m