Homiletics: Outlines on the Nassau Pericopes

Outlines on the Nassau Pericope

Anti-plasmodial polyvalent interactions in Artemisia annua L. aqueous extract – possible synergistic and resistance mechanisms

Artemisia annua hot water infusion (tea) has been used in in vitro experiments against P. falciparum malaria parasites to test potency relative to equivalent pure artemisinin. High performance liquid chromatography (HPLC) and mass spectrometric analyses were employed to determine the metabolite profile of tea including the concentrations of artemisinin (47.5±0.8 mg L-1), dihydroartemisinic acid (70.0±0.3 mg L-1), arteannuin B (1.3±0.0 mg L-1), isovitexin (105.0±7.2 mg L-1) and a range of polyphenolic acids. The tea extract, purified compounds from the extract, and the combination of artemisinin with the purified compounds were tested against chloroquine sensitive and chloroquine resistant strains of P. falciparum using the DNA-intercalative SYBR Green I assay. The results of these in vitro tests and of isobologram analyses of combination effects showed mild to strong antagonistic interactions between artemisinin and the compounds (9-epi-artemisinin and artemisitene) extracted from A. annua with significant (IC50 <1 μM) anti-plasmodial activities for the combination range evaluated. Mono-caffeoylquinic acids, tri-caffeoylquinic acid, artemisinic acid and arteannuin B showed additive interaction while rosmarinic acid showed synergistic interaction with artemisinin in the chloroquine sensitive strain at a combination ratio of 1:3 (artemisinin to purified compound). In the chloroquine resistant parasite, using the same ratio, these compounds strongly antagonised artemisinin anti-plasmodial activity with the exception of arteannuin B, which was synergistic. This result would suggest a mechanism targeting parasite resistance defenses for arteannuin B’s potentiation of artemisinin

Software Training in HEP

The long-term sustainability of the high-energy physics (HEP) research software ecosystem is essential to the field. With new facilities and upgrades coming online throughout the 2020s, this will only become increasingly important. Meeting the sustainability challenge requires a workforce with a combination of HEP domain knowledge and advanced software skills. The required software skills fall into three broad groups. The first is fundamental and generic software engineering (e.g., Unix, version control, C++, and continuous integration). The second is knowledge of domain-specific HEP packages and practices (e.g., the ROOT data format and analysis framework). The third is more advanced knowledge involving specialized techniques, including parallel programming, machine learning and data science tools, and techniques to maintain software projects at all scales. This paper discusses the collective software training program in HEP led by the HEP Software Foundation (HSF) and the Institute for Research and Innovation in Software in HEP (IRIS-HEP). The program equips participants with an array of software skills that serve as ingredients for the solution of HEP computing challenges. Beyond serving the community by ensuring that members are able to pursue research goals, the program serves individuals by providing intellectual capital and transferable skills important to careers in the realm of software and computing, inside or outside HEP

Software Training in HEP

The long-term sustainability of the high-energy physics (HEP) research software ecosystem is essential to the field. With new facilities and upgrades coming online throughout the 2020s, this will only become increasingly important. Meeting the sustainability challenge requires a workforce with a combination of HEP domain knowledge and advanced software skills. The required software skills fall into three broad groups. The first is fundamental and generic software engineering (e.g., Unix, version control, C++, and continuous integration). The second is knowledge of domain-specific HEP packages and practices (e.g., the ROOT data format and analysis framework). The third is more advanced knowledge involving specialized techniques, including parallel programming, machine learning and data science tools, and techniques to maintain software projects at all scales. This paper discusses the collective software training program in HEP led by the HEP Software Foundation (HSF) and the Institute for Research and Innovation in Software in HEP (IRIS-HEP). The program equips participants with an array of software skills that serve as ingredients for the solution of HEP computing challenges. Beyond serving the community by ensuring that members are able to pursue research goals, the program serves individuals by providing intellectual capital and transferable skills important to careers in the realm of software and computing, inside or outside HEP

Functional Characterization of the Plasmodium falciparum Chloroquine-Resistance Transporter (PfCRT) in Transformed Dictyostelium discoideum Vesicles

Chloroquine (CQ)-resistant Plasmodium falciparum malaria has been a global health catastrophe, yet much about the CQ resistance (CQR) mechanism remains unclear. Hallmarks of the CQR phenotype include reduced accumulation of protonated CQ as a weak base in the digestive vacuole of the erythrocyte-stage parasite, and chemosensitization of CQ-resistant (but not CQ-sensitive) P. falciparum by agents such as verapamil. Mutations in the P. falciparum CQR transporter (PfCRT) confer CQR; particularly important among these mutations is the charge-loss substitution K→T at position 76. Dictyostelium discoideum transformed with mutant PfCRT expresses key features of CQR including reduced drug accumulation and verapamil chemosensitization.We describe the isolation and characterization of PfCRT-transformed, hematin-free vesicles from D. discoideum cells. These vesicles permit assessments of drug accumulation, pH, and membrane potential that are difficult or impossible with hematin-containing digestive vacuoles from P. falciparum-infected erythrocytes. Mutant PfCRT-transformed D. discoideum vesicles show features of the CQR phenotype, and manipulations of vesicle membrane potential by agents including ionophores produce large changes of CQ accumulation that are dissociated from vesicular pH. PfCRT in its native or mutant form blunts the ability of valinomycin to reduce CQ accumulation in transformed vesicles and decreases the ability of K(+) to reverse membrane potential hyperpolarization caused by valinomycin treatment.Isolated vesicles from mutant-PfCRT-transformed D. discoideum exhibit features of the CQR phenotype, consistent with evidence that the drug resistance mechanism operates at the P. falciparum digestive vacuole membrane in malaria. Membrane potential apart from pH has a major effect on the PfCRT-mediated CQR phenotype of D. discoideum vesicles. These results support a model of PfCRT as an electrochemical potential-driven transporter in the drug/metabolite superfamily that (appropriately mutated) acts as a saturable simple carrier for the facilitated diffusion of protonated CQ

Measurement of exclusive pion pair production in proton–proton collisions at √s=7 TeV with the ATLAS detector

The exclusive production of pion pairs in the process pp→ ppπ+π- has been measured at s=7TeV with the ATLAS detector at the LHC, using 80μb-1 of low-luminosity data. The pion pairs were detected in the ATLAS central detector while outgoing protons were measured in the forward ATLAS ALFA detector system. This represents the first use of proton tagging to measure an exclusive hadronic final state at the LHC. A cross-section measurement is performed in two kinematic regions defined by the proton momenta, the pion rapidities and transverse momenta, and the pion–pion invariant mass. Cross-section values of 4.8±1.0(stat)-0.2+0.3(syst)μb and 9±6(stat)-2+2(syst)μb are obtained in the two regions; they are compared with theoretical models and provide a demonstration of the feasibility of measurements of this type

Search for resonant WZ production in the fully leptonic final state in proton–proton collisions at √s=13 TeV with the ATLAS detector

A search for a WZ resonance, in the fully leptonic final state (electrons or muons), is performed using 139&nbsp;fb - 1 of data collected at a centre-of-mass energy of 13&nbsp;TeV by the ATLAS detector at the Large Hadron Collider. The results are interpreted in terms of a singly charged Higgs boson of the Georgi–Machacek model, produced by WZ fusion, and of a Heavy Vector Triplet, with the resonance produced by WZ fusion or the Drell–Yan process. No significant excess over the Standard Model prediction is observed and limits are set on the production cross-section times branching ratio as a function of the resonance mass for these processes

Measurement of the H → γ γ and H → ZZ∗ → 4 cross-sections in pp collisions at √s = 13.6 TeV with the ATLAS detector

The inclusive Higgs boson production cross section is measured in the di-photon and the Z Z∗ → 4 decay channels using 31.4 and 29.0 fb−1 of pp collision data respectively, collected with the ATLAS detector at a centre of-mass energy of √s = 13.6 TeV. To reduce the model dependence, the measurement in each channel is restricted to a particle-level phase space that closely matches the chan nel’s detector-level kinematic selection, and it is corrected for detector effects. These measured fiducial cross-sections are σfid,γ γ = 76+14 −13 fb, and σfid,4 = 2.80 ± 0.74 fb, in agreement with the corresponding Standard Model predic tions of 67.6±3.7 fb and 3.67±0.19 fb. Assuming Standard Model acceptances and branching fractions for the two chan nels, the fiducial measurements are extrapolated to the full phase space yielding total cross-sections of σ (pp → H) = 67+12 −11 pb and 46±12 pb at 13.6 TeV from the di-photon and Z Z∗ → 4 measurements respectively. The two measure ments are combined into a total cross-section measurement of σ (pp → H) = 58.2±8.7 pb, to be compared with the Stan dard Model prediction of σ (pp → H)SM = 59.9 ± 2.6 p

Measurement of the nuclear modification factor of b-jets in 5.02 TeV Pb+Pb collisions with the ATLAS detector

This paper presents a measurement of b-jet production in Pb+Pb and pp collisions at √sNN = 5.02 TeV with the ATLAS detector at the LHC. The measurement uses 260 pb−1 of pp collisions collected in 2017 and 1.4 nb−1 of Pb+Pb collisions collected in 2018. In both collision systems, jets are reconstructed via the anti-kt algorithm. The b-jets are identified from a sample of jets containing muons from the semileptonic decay of b-quarks using template fits of the muon momentum relative to the jet axis. In pp collisions, b-jets are reconstructed for radius parameters R = 0.2 and R = 0.4, and only R = 0.2 jets are used in Pb+Pb collisions. For comparison, inclusive R = 0.2 jets are also measured using 1.7 nb−1 of Pb+Pb collisions collected in 2018 and the same pp collision data as the b-jet measurement. The nuclear modification factor, RAA, is calculated for both b-jets and inclusive jets with R = 0.2 over the transverse momentum range of 80–290 GeV. The nuclear modification factor for b-jets decreases from peripheral to central collisions. The ratio of the b-jet RAA to inclusive jet RAA is also presented and suggests that the RAA for b-jets is larger than that for inclusive jets in central Pb+Pb collisions. The measurements are compared with theoretical calculations and suggest a role for mass and colour-charge effects in partonic energy loss in heavy-ion collisions