Conformational polymorphic changes in the crystal structure of the chiral antiparasitic drug praziquantel and interactions with calcium carbonate

Praziquantel is an antiparasitic drug used for decades. Currently, the praziquantel commercial preparation is a racemic mixture, in which only the levo-enantiomer possesses anthelmintic activity. The knowledge of its properties in the solid state and other chemical-physical properties is necessary for improving its efficacy and applications. Drug solid dispersions were prepared with calcium carbonate at 1:5 drug to excipient weight ratio by solvent evaporation method. Then, the modification of the crystal structure of the racemic polymorph of praziquantel in presence of calcium carbonate has been studied by means of several analytical techniques (DSC,TGA, XRD, SEM, FTIR, Raman spectroscopy and chiral liquid chromatography). This study has been completed with atomistic calculations based on empirical interatomic force fields and quantum mechanics methods applied to the crystal structure of praziquantel and of intermolecular interactions. The results evidenced that calcium carbonate provoked a conformational change in the praziquantel molecule yielding the formation of different polymorphs of praziquantel crystal. These alterations were not observed replacing calcium carbonate with colloidal silica as excipient in the solid dispersion

Cytotoxic Acetogenins from the Roots of Annona purpurea

Annona purpurea, known in Mexico as "cabeza de negro" or "ilama", belongs to the Annonaceae family. Its roots are employed in folk medicine in several regions of Mexico. Taking that information into account, a chemical and biological analysis of the components present in the roots of this species was proposed. Our results demonstrated that the dichloromethane (DCM) extract was exclusively constituted by a mixture of five new acetogenins named annopurpuricins A-E (1-5). These compounds have an aliphatic chain of 37 carbons with a terminal \u3b1,\u3b2 unsaturated \u3b3-lactone. Compounds 1 and 2 belong to the adjacent bis-THF (tetrahydrofuran) \u3b1-monohydroxylated type, while compounds 3 and 4 belong to the adjacent bis-THF \u3b1,\u3b1'-dihydroxylated type; only compound 5 possesses a bis-epoxide system. Complete structure analysis was carried out by spectroscopy and chemical methods. All compounds were evaluated for their antiproliferative activity on three human tumor cell lines (MSTO-211H, HeLa and HepG2). Compounds 1-4 inhibited significantly the growth of HeLa and HepG2 cells, showing GI50 values in the low/subnanomolar range, while 5 was completely ineffective under the tested conditions. The investigation of the mechanism of action responsible for cytotoxicity revealed for the most interesting compound 1 the ability to block the complex I activity on isolated rat liver mitochondria (RLM)

Event reconstruction for KM3NeT/ORCA using convolutional neural networks

The authors acknowledge the financial support of the funding agencies: Agence Nationale de la Recherche (contract ANR-15-CE31-0020), Centre National de la Recherche Scientifique (CNRS), Commission Europeenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), LabEx UnivEarthS (ANR-10-LABX-0023 and ANR-18-IDEX-0001), Paris Ile-de-France Region, France; Shota Rustaveli National Science Foundation of Georgia (SRNSFG, FR-18-1268), Georgia; Deutsche Forschungsgemeinschaft (DFG), Germany; The General Secretariat of Research and Technology (GSRT), Greece; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell'Universita e della Ricerca (MUR), PRIN 2017 program (Grant NAT-NET 2017W4HA7S) Italy; Ministry of Higher Education, Scientific Research and Professional Training, Morocco; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; The National Science Centre, Poland (2015/18/E/ST2/00758); National Authority for Scientific Research (ANCS), Romania; Ministerio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento (refs. PGC2018-096663-B-C41, -A-C42, -B-C43, -B-C44) (MCIU/FEDER), Severo Ochoa Centre of Excellence and MultiDark Consolider (MCIU), Junta de Andalucia (ref. SOMM17/6104/UGR), Generalitat Valenciana: Grisolia (ref. GRISOLIA/2018/119) and GenT (ref. CIDEGENT/2018/034) programs, La Caixa Foundation (ref. LCF/BQ/IN17/11620019), EU: MSC program (ref. 713673), Spain.The KM3NeT research infrastructure is currently under construction at two locations in the Mediterranean Sea. The KM3NeT/ORCA water-Cherenkov neutrino detector off the French coast will instrument several megatons of seawater with photosensors. Its main objective is the determination of the neutrino mass ordering. This work aims at demonstrating the general applicability of deep convolutional neural networks to neutrino telescopes, using simulated datasets for the KM3NeT/ORCA detector as an example. To this end, the networks are employed to achieve reconstruction and classification tasks that constitute an alternative to the analysis pipeline presented for KM3NeT/ORCA in the KM3NeT Letter of Intent. They are used to infer event reconstruction estimates for the energy, the direction, and the interaction point of incident neutrinos. The spatial distribution of Cherenkov light generated by charged particles induced in neutrino interactions is classified as shower- or track-like, and the main background processes associated with the detection of atmospheric neutrinos are recognized. Performance comparisons to machine-learning classification and maximum-likelihood reconstruction algorithms previously developed for KM3NeT/ORCA are provided. It is shown that this application of deep convolutional neural networks to simulated datasets for a large-volume neutrino telescope yields competitive reconstruction results and performance improvements with respect to classical approaches.French National Research Agency (ANR) ANR-15-CE31-0020Centre National de la Recherche Scientifique (CNRS), Commission Europeenne (FEDER fund)European Union (EU)Institut Universitaire de France (IUF)LabEx UnivEarthS ANR-10-LABX-0023 ANR-18-IDEX-0001Shota Rustaveli National Science Foundation of Georgia FR-18-1268German Research Foundation (DFG)Greek Ministry of Development-GSRTIstituto Nazionale di Fisica Nucleare (INFN)Ministry of Education, Universities and Research (MIUR) Research Projects of National Relevance (PRIN)Ministry of Higher Education, Scientific Research and Professional Training, MoroccoNetherlands Organization for Scientific Research (NWO)National Science Centre, Poland 2015/18/E/ST2/00758National Authority for Scientific Research (ANCS), RomaniaMinisterio de Ciencia, Innovacion, Investigacion y Universidades PGC2018-096663-B-C41 A-C42 B-C43 B-C44Severo Ochoa Centre of ExcellenceJunta de Andalucia SOMM17/6104/UGRGeneralitat Valenciana: Grisolia GRISOLIA/2018/119 CIDEGENT/2018/034La Caixa Foundation LCF/BQ/IN17/11620019EU: MSC program 71367

Correlated long-range mixed-harmonic fluctuations measured in pp, p+Pb and low-multiplicity Pb+Pb collisions with the ATLAS detector

For abstract see published article

Performance of top-quark and W -boson tagging with ATLAS in Run 2 of the LHC

The performance of identification algorithms (“taggers”) for hadronically decaying top quarks and W bosons in pp collisions at √s=13 TeV recorded by the ATLAS experiment at the Large Hadron Collider is presented. A set of techniques based on jet shape observables are studied to determine a set of optimal cut-based taggers for use in physics analyses. The studies are extended to assess the utility of combinations of substructure observables as a multivariate tagger using boosted decision trees or deep neural networks in comparison with taggers based on two-variable combinations. In addition, for highly boosted top-quark tagging, a deep neural network based on jet constituent inputs as well as a re-optimisation of the shower deconstruction technique is presented. The performance of these taggers is studied in data collected during 2015 and 2016 corresponding to 36.1 fb −1 for the tt ¯ and γ+jet and 36.7 fb −1 −1 for the dijet event topologies

In situ calibration of large-radius jet energy and mass in 13 TeV proton–proton collisions with the ATLAS detector

The response of the ATLAS detector to largeradius jets is measured in situ using 36.2 fb−1 of √s = 13 TeV proton–proton collisions provided by the LHC and recorded by the ATLAS experiment during 2015 and 2016. The jet energy scale is measured in events where the jet recoils against a reference object, which can be either a calibrated photon, a reconstructed Z boson, or a system of well-measured small-radius jets. The jet energy resolution and a calibration of forward jets are derived using dijet balance measurements. The jet mass response is measured with two methods: using mass peaks formed by W bosons and top quarks with large transverse momenta and by comparing the jet mass measured using the energy deposited in the calorimeter with that using the momenta of charged-particle tracks. The transversemomentum and mass responses in simulations are found to be about 2–3% higher than in data. This difference is adjusted for with a correction factor. The results of the different methods are combined to yield a calibration over a large range of transverse momenta (pT). The precision of the relative jet energy scale is 1–2% for 200 GeV < pT < 2 TeV, while that of the mass scale is 2–10%. The ratio of the energy resolutions in data and simulation is measured to a precision of 10–15% over the same pT range

Measurements of the charge asymmetry in top-quark pair production in the dilepton final state at s √ =8 TeV with the ATLAS detector

Measurements of the top-antitop quark pair production charge asymmetry in the dilepton channel, characterized by two high-pT leptons (electrons or muons), are presented using data corresponding to an integrated luminosity of 20.3  fb−1 from pp collisions at a center-of-mass energy s√=8  TeV collected with the ATLAS detector at the Large Hadron Collider at CERN. Inclusive and differential measurements as a function of the invariant mass, transverse momentum, and longitudinal boost of the tt¯ system are performed both in the full phase space and in a fiducial phase space closely matching the detector acceptance. Two observables are studied: AℓℓC based on the selected leptons and Att¯C based on the reconstructed tt¯ final state. The inclusive asymmetries are measured in the full phase space to be AℓℓC=0.008±0.006 and Att¯C=0.021±0.016, which are in agreement with the Standard Model predictions of AℓℓC=0.0064±0.0003 and Att¯C=0.0111±0.0004

Evidence for electroweak production of W±W±jj in pp collisions at s√=8 TeV with the ATLAS detector

This Letter presents the first study of W±W±jj, same-electric-charge diboson production in association with two jets, using 20.3  fb−1 of proton-proton collision data at s√=8  TeV recorded by the ATLAS detector at the Large Hadron Collider. Events with two reconstructed same-charge leptons (e±e±, e±μ±, and μ±μ±) and two or more jets are analyzed. Production cross sections are measured in two fiducial regions, with different sensitivities to the electroweak and strong production mechanisms. First evidence for W±W±jj production and electroweak-only W±W±jj production is observed with a significance of 4.5 and 3.6 standard deviations, respectively. The measured production cross sections are in agreement with standard model predictions. Limits at 95% confidence level are set on anomalous quartic gauge couplings

Search for three-jet resonances in pp collisions at √s=7 TeV

This is a Pre-Print version of the Article - Copyright @ 2011 APSA model-independent search for three-jet hadronic resonance production in pp collisions at a center-of-mass energy of 7 TeV has been conducted by the CMS Collaboration at the LHC, using a data sample corresponding to an integrated luminosity of 35 inverse picobarns. Events with high jet multiplicity and a large scalar sum of jet transverse momenta are analyzed. The number of expected standard model background events is found to be in good agreement with the observed events. Limits are set on a model describing the production of R-parity-violating supersymmetric gluino pairs, and gluino masses in the range of 200 to 280 GeV/c^2 are excluded at a 95% confidence level for the first time.This work is supported by the FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF andWCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTD (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

Search for vectorlike B quarks in events with one isolated lepton, missing transverse momentum, and jets at √s = 8 TeV with the ATLAS detector

A search has been performed for pair production of heavy vectorlike down-type (B) quarks. The analysis explores the lepton-plus-jets final state, characterized by events with one isolated charged lepton (electron or muon), significant missing transverse momentum, and multiple jets. One or more jets are required to be tagged as arising from b quarks, and at least one pair of jets must be tagged as arising from the hadronic decay of an electroweak boson. The analysis uses the full data sample of pp collisions recorded in 2012 by the ATLAS detector at the LHC, operating at a center-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 20.3 fb −1 . No significant excess of events is observed above the expected background. Limits are set on vectorlike B production, as a function of the B branching ratios, assuming the allowable decay modes are B → Wt/Zb/Hb. In the chiral limit with a branching ratio of 100% for the decay B → Wt, the observed (expected) 95% C.L. lower limit on the vectorlike B mass is 810 GeV (760 GeV). In the case where the vectorlike B quark has branching ratio values corresponding to those of an SU(2) singlet state, the observed (expected) 95% C.L. lower limit on the vectorlike B mass is 640 GeV (505 GeV). The same analysis, when used to investigate pair production of a colored, charge 5/3 exotic fermion T 5/3 , with subsequent decay T 5/3 → Wt, sets an observed (expected) 95% C.L. lower limit on the T 5/3 mass of 840 GeV (780 GeV)