Despite decades of research, little is known about the cellular targets and the mode of action of the vast majority of antimalarial drugs. We recently demonstrated that the cellular thermal shift ...assay (CETSA) protocol in its two variants: the melt curve and the isothermal dose-response, represents a comprehensive strategy for the identification of antimalarial drug targets. CETSA enables proteome-wide target screening for unmodified antimalarial compounds with undetermined mechanisms of action, providing quantitative evidence about direct drug-protein interactions. The experimental workflow involves treatment of P. falciparum-infected erythrocytes with a compound of interest, heat exposure to denature proteins, soluble protein isolation, enzymatic digestion, peptide labeling with tandem mass tags, offline fractionation, and liquid chromatography-tandem mass spectrometry analysis. Methodological optimizations necessary for the analysis of this intracellular parasite are discussed, including enrichment of parasitized cells and hemoglobin depletion strategies to overcome high hemoglobin abundance in the host red blood cells. We outline an effective data processing workflow using the mineCETSA R package, which enables prioritization of drug-target candidates for follow-up studies. The entire protocol can be completed within 2 weeks.
Certification from the American Board of Neurological Surgeons (ABNS) is the gold standard for certification of neurosurgeons practicing in the U.S. This text is the most up-to-date board review ...guide for neurosurgeons. It features actual cases, over 300 high-quality illustrations and images, clinical overviews, and a Q and A that mimics the ABNS exam format. Uniquely qualified as esteemed experts in organized neurosurgery as well as past or present Directors of the ABNS, the editors have compiled a book of remarkable depth and scope. With contributions from top neurosurgeons in each subspecialty, this text will prepare neurosurgeons for the rigorous ABNS exams. This indispensable book will help neurosurgeons and neurosurgical residents prepare thoroughly for written and oral board examinations, and benefit board- certified neurosurgeons who need to fulfill MOC requirements. Thieme eNeurosurgery is the worlds most comprehensive neurosurgical resource online. For a free trial, go to: http://thieme.com/eneurotrial
We present a measurement of neutrino oscillation parameters with the Super-Kamiokande detector using atmospheric neutrinos from the complete pure-water SK I-V (April 1996-July 2020) data set, ...including events from an expanded fiducial volume. The data set corresponds to 6511.3 live days and an exposure of 484.2 kiloton-years. Measurements of the neutrino oscillation parameters \(\Delta m^2_{32}\), \(\sin^2\theta_{23}\), \(\sin^2 \theta_{13}\), \(\delta_{CP}\), and the preference for the neutrino mass ordering are presented with atmospheric neutrino data alone, and with constraints on \(\sin^2 \theta_{13}\) from reactor neutrino experiments. Our analysis including constraints on \(\sin^2 \theta_{13}\) favors the normal mass ordering at the 92.3% level.
We report the first measurement of the atmospheric neutrino-oxygen neutral-current quasielastic (NCQE) cross section in the gadolinium-loaded Super-Kamiokande (SK) water Cherenkov detector. In June ...2020, SK began a new experimental phase, named SK-Gd, by loading 0.011% by mass of gadolinium into the ultrapure water of the SK detector. The introduction of gadolinium to ultrapure water has the effect of improving the neutron-tagging efficiency. Using a 552.2 day data set from August 2020 to June 2022, we measure the NCQE cross section to be 0.74 \(\pm\) 0.22(stat.) \(^{+0.85}_{-0.15}\) (syst.) \(\times\) 10\(^{-38}\) cm\(^{2}\)/oxygen in the energy range from 160 MeV to 10 GeV, which is consistent with the atmospheric neutrino-flux-averaged theoretical NCQE cross section and the measurement in the SK pure-water phase within the uncertainties. Furthermore, we compare the models of the nucleon-nucleus interactions in water and find that the Binary Cascade model and the Liege Intranuclear Cascade model provide a somewhat better fit to the observed data than the Bertini Cascade model. Since the atmospheric neutrino-oxygen NCQE reactions are one of the main backgrounds in the search for diffuse supernova neutrino background (DSNB), these new results will contribute to future studies - and the potential discovery - of the DSNB in SK.
Cosmic-ray muons that enter the Super-Kamiokande detector cause hadronic showers due to spallation in water, producing neutrons and radioactive isotopes. Those are a major background source for ...studies of MeV-scale neutrinos and searches for rare events. Since 2020, gadolinium was introduced in the ultra-pure water in the Super-Kamiokande detector to improve the detection efficiency of neutrons. In this study, the cosmogenic neutron yield was measured using data acquired during the period after the gadolinium loading. The yield was found to be \((2.76 \pm 0.02\,\mathrm{(stat.) \pm 0.19\,\mathrm{(syst.)}}) \times 10^{-4}\,\mu^{-1} \mathrm{g^{-1} cm^{2}}\) at 259 GeV of average muon energy at the Super-Kamiokande detector.
The Cellular Thermal Shift Assay (CETSA) has recently emerged as a promising method to directly monitor functional modulations of protein interaction states in intact cells and tissue samples. Recent ...data support that the mass spectrometry–coupled proteome-wide implementation of CETSA (MS-CETSA) generates stringent information on a wide range of different interaction classes and is uniquely well suited to study the modulation of protein interaction states in cellular processes and during drug action. To expand the mechanistic insight of CETSA shifts, and to complement information from CETSA experiments, we outline how the integration of MS-CETSA with other proteomics techniques can provide a new platform for detailed, comprehensive, and interactive studies of the functional modulations of proteomes in situ.
We report a search for cosmic-ray boosted dark matter with protons using the 0.37 megaton\(\times\)years data collected at Super-Kamiokande experiment during the 1996-2018 period (SKI-IV phase). We ...searched for an excess of proton recoils above the atmospheric neutrino background from the vicinity of the Galactic Center. No such excess is observed, and limits are calculated for two reference models of dark matter with either a constant interaction cross-section or through a scalar mediator. This is the first experimental search for boosted dark matter with hadrons using directional information. The results present the most stringent limits on cosmic-ray boosted dark matter and exclude the dark matter-nucleon elastic scattering cross-section between \(10^{-33}\text{ cm}^{2}\) and \(10^{-27}\text{ cm}^{2}\) for dark matter mass from 10 MeV/\(c^2\) to 1 GeV/\(c^2\).
Phys.Rev.D 108 (2023) 9, 092009 We report an updated measurement of the $\nu_{\mu}$-induced, and the first
measurement of the $\bar{\nu}_{\mu}$-induced coherent charged pion production
cross section ...on $^{12}C$ nuclei in the T2K experiment. This is measured in a
restricted region of the final-state phase space for which $p_{\mu,\pi} > 0.2$
GeV, $\cos(\theta_{\mu}) > 0.8$ and $\cos(\theta_{\pi}) > 0.6$, and at a mean
(anti)neutrino energy of 0.85 GeV using the T2K near detector. The measured
$\nu_{\mu}$ CC coherent pion production flux-averaged cross section on $^{12}C$
is $(2.98 \pm 0.37 (stat.) \pm 0.31 (syst.) \substack{ +0.49 \\ -0.00 }
\mathrm{ (Q^2\,model)}) \times 10^{-40}~\mathrm{cm}^{2}$. The new measurement
of the $\bar{\nu}_{\mu}$-induced cross section on $^{12}{C}$ is $(3.05 \pm 0.71
(stat.) \pm 0.39 (syst.) \substack{ +0.74 \\ -0.00 } \mathrm{(Q^2\,model)})
\times 10^{-40}~\mathrm{cm}^{2}$. The results are compatible with both the NEUT
5.4.0 Berger-Sehgal (2009) and GENIE 2.8.0 Rein-Sehgal (2007) model
predictions.
We report the first search result for the flux of astrophysical electron antineutrinos for energies O(10) MeV in the gadolinium-loaded Super-Kamiokande (SK) detector. In June 2020, gadolinium was ...introduced to the ultra-pure water of the SK detector in order to detect neutrons more efficiently. In this new experimental phase, SK-Gd, we can search for electron antineutrinos via inverse beta decay with efficient background rejection and higher signal efficiency thanks to the high efficiency of the neutron tagging technique. In this paper, we report the result for the initial stage of SK-Gd with a \(22.5\times552\) \(\rm kton\cdot day\) exposure at 0.01% Gd mass concentration. No significant excess over the expected background in the observed events is found for the neutrino energies below 31.3 MeV. Thus, the flux upper limits are placed at the 90% confidence level. The limits and sensitivities are already comparable with the previous SK result with pure-water (\(22.5 \times 2970 \rm kton\cdot day\)) owing to the enhanced neutron tagging.
AbstractThis paper investigates the effect of the SiC and triplex thermal aging treatment (TTAT) on the mechanical behavior of compound bars. The bars were fabricated by varying the SiC (2, 4 and 6 ...wt. %) in Al6061. Initially, bars were tested for hardness and compression strength in homogenized conditions. It is observed that as SiC is increased in the matrix, mechanical properties have improved. The bars with composite cores exhibited better properties as compared to bars with composite casing. For the bar having a composite core, with 2 wt. % SiC, the compression strength was 530.70 MPa, for the 4 wt.% SiC core it was 589.35 MPa and for the 6 wt.% SiC it was 691.88 MPa. Failure was progressive, with noticeable signs of failure, and the load-bearing ability was found to be fairly stable up to nearly 218 kN. Later, the bar with a 6 wt. % SiC core was subjected to TTAT, and surface hardness, compression strength, and interfacial shear strength were found to have increased by 11.2, 3.2 and 11.11%, respectively. SiC are the hard particles; reinforcing them in a soft matrix induces strain in the lattice and thus enhances the hardness of the composite. During aging, the diffusion of alloy atoms is blocked by the generated dislocations present around the SiC particles. Hence, the bars with a higher quantity of SiC in the composite core can be used for high load-bearing structural applications due to their superior mechanical properties as an alternative to the simple composite bars with the same SiC quantity.
