Tacrine is a centrally active non-competitive reversible acetylcholinesterase inhibitor. It also exerts antagonising activity against -methyl-D-aspartate receptors. Tacrine was approved for the treatment of Alzheimer's disease in 1993, but was withdrawn from clinical use in 2013 because of its hepatotoxicity and gastrointestinal side effects.
View Article and Find Full Text PDFHigh-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.
View Article and Find Full Text PDFA search for the exclusive hadronic decays W^{±}→π^{±}γ, W^{±}→K^{±}γ, and W^{±}→ρ^{±}γ is performed using up to 140 fb^{-1} of proton-proton collisions recorded with the ATLAS detector at a center-of-mass energy of sqrt[s]=13 TeV. If observed, these rare processes would provide a unique test bench for the quantum chromodynamics factorization formalism used to calculate cross sections at colliders. Additionally, at future colliders, these decays could offer a new way to measure the W boson mass through fully reconstructed decay products.
View Article and Find Full Text PDFThe effect of 3D printing parameters by Fused Filament Fabrication (FFF) on the translucency of polylactic acid (PLA) parts was investigated. Six different printing parameters were studied: object orientation, layer height, nozzle temperature, fan speed, extrusion multiplier, and printing speed. The commercially available Plasty Mladeč PLA filament and the Original Prusa MK4 3D printer were used for the experiments.
View Article and Find Full Text PDFThis Letter presents results from a combination of searches for Higgs boson pair production using 126-140 fb^{-1} of proton-proton collision data at sqrt[s]=13 TeV recorded with the ATLAS detector. At 95% confidence level (CL), the upper limit on the production rate is 2.9 times the standard model (SM) prediction, with an expected limit of 2.
View Article and Find Full Text PDFThis Letter presents the first study of the energy dependence of diboson polarization fractions in WZ→ℓνℓ^{'}ℓ^{'}(ℓ,ℓ^{'}=e,μ) production. The dataset used corresponds to an integrated luminosity of 140 fb^{-1} of proton-proton collisions at a center-of-mass energy of 13 TeV recorded by the ATLAS detector. Two fiducial regions with an enhanced presence of events featuring two longitudinally polarized bosons are defined.
View Article and Find Full Text PDFThis study aimed to characterize the mechanical properties of native human ligamentum flavum (LF) and correlate them with histopathological changes. Mechanical property gradients across the cranial, medial, and caudal regions of LF were mapped and compared with histological sections. We also compared lumbar spinal stenosis (LSS) samples with disc herniation (DH) samples as reference material to identify differences in mechanical properties and histopathological features.
View Article and Find Full Text PDFStatistical combinations of searches for charginos and neutralinos using various decay channels are performed using 139 fb^{-1} of pp collision data at sqrt[s]=13 TeV with the ATLAS detector at the Large Hadron Collider. Searches targeting pure-wino chargino pair production, pure-wino chargino-neutralino production, or Higgsino production decaying via standard model W, Z, or h bosons are combined to extend the mass reach to the produced supersymmetric particles by 30-100 GeV. The depth of the sensitivity of the original searches is also improved by the combinations, lowering the 95% C.
View Article and Find Full Text PDFMaternal-fetal microchimerism is a fascinating phenomenon in which maternal cells migrate to the tissues of the offspring during both pregnancy and breastfeeding. These cells primarily consist of leukocytes and stem cells. Remarkably, these maternal cells possess functional potential in the offspring and play a significant role in shaping their immune system development.
View Article and Find Full Text PDFBackground: Allogeneic stem cell transplant (allo-SCT) is a mainstay of treatment for acute myeloid leukemia (AML). Its success depends largely on response of donor T lymphocytes against leukemia cells, known as graft-vs-leukemia (GvL) effect. A key potential driver of GvL is immune response to mutation-derived neoantigens.
View Article and Find Full Text PDFA combination of searches for a new resonance decaying into a Higgs boson pair is presented, using up to 139 fb^{-1} of pp collision data at sqrt[s]=13 TeV recorded with the ATLAS detector at the LHC. The combination includes searches performed in three decay channels: bb[over ¯]bb[over ¯], bb[over ¯]τ^{+}τ^{-}, and bb[over ¯]γγ. No excess above the expected Standard Model background is observed and upper limits are set at the 95% confidence level on the production cross section of Higgs boson pairs originating from the decay of a narrow scalar resonance with mass in the range 251 GeV-5 TeV.
View Article and Find Full Text PDFHiggsinos with masses near the electroweak scale can solve the hierarchy problem and provide a dark matter candidate, while detecting them at the LHC remains challenging if their mass splitting is O(1 GeV). This Letter presents a novel search for nearly mass-degenerate Higgsinos in events with an energetic jet, missing transverse momentum, and a low-momentum track with a significant transverse impact parameter using 140 fb^{-1} of proton-proton collision data at sqrt[s]=13 TeV collected by the ATLAS experiment. For the first time since LEP, a range of mass splittings between the lightest charged and neutral Higgsinos from 0.
View Article and Find Full Text PDFWe tested the effect of substituents at the (1) C3´, C3´N, (2) C10, and (3) C2-meta-benzoate positions of taxane derivatives on their activity against sensitive versus counterpart paclitaxel-resistant breast (MCF-7) and ovarian (SK-OV-3) cancer cells. We found that (1) non-aromatic groups at both C3´ and C3´N positions, when compared with phenyl groups at the same positions of a taxane derivative, significantly reduced the resistance of ABCB1 expressing MCF-7/PacR and SK-OV-3/PacR cancer cells. This is, at least in the case of the SB-T-1216 series, accompanied by an ineffective decrease of intracellular levels in MCF-7/PacR cells.
View Article and Find Full Text PDFAngular correlations between heavy quarks provide a unique probe of the quark-gluon plasma created in ultrarelativistic heavy-ion collisions. Results are presented of a measurement of the azimuthal angle correlations between muons originating from semileptonic decays of heavy quarks produced in 5.02 TeV Pb+Pb and pp collisions at the LHC.
View Article and Find Full Text PDFObjectives: To characterize the genetic basis of azithromycin resistance in Escherichia coli and Salmonella collected within the EU harmonized antimicrobial resistance (AMR) surveillance programme in 2014-18 and the Danish AMR surveillance programme in 2016-19.
Methods: WGS data of 1007 E. coli [165 azithromycin resistant (MIC > 16 mg/L)] and 269 Salmonella [29 azithromycin resistant (MIC > 16 mg/L)] were screened for acquired macrolide resistance genes and mutations in rplDV, 23S rRNA and acrB genes using ResFinder v4.
CD19 CAR T-cell (CAR-T) therapy is commonly administered to patients with relapsed or refractory large B-cell lymphomas (LBCL), but salvage or bridging therapy can sometimes lead to a complete response (CR) prior to infusion. Limited studies have assessed the outcomes of patients infused in CR. A total of 134 patients with LBCL in CR prior to CAR-T infusion were identified from the CIBMTR registry, with median prior lines of therapy of 3 (range 2-9).
View Article and Find Full Text PDFBackground: Interleukin-6 (IL-6) is a multifunctional cytokine that controls the immune response, and its role has been described in the development of autoimmune diseases. Signaling via its cognate IL-6 receptor (IL-6R) complex is critical in tumor progression and, therefore, IL-6R represents an important therapeutic target.
Methods: An albumin-binding domain-derived highly complex combinatorial library was used to select IL-6R alpha (IL-6Rα)-targeted small protein binders using ribosome display.
Background: Programmed cell death 1 (PD-1) belongs to immune checkpoint proteins ensuring negative regulation of the immune response. In non-small cell lung cancer (NSCLC), the sensitivity to treatment with anti-PD-1 therapeutics, and its efficacy, mostly correlated with the increase of tumor infiltrating PD-1 lymphocytes. Due to solid tumor heterogeneity of PD-1 populations, novel low molecular weight anti-PD-1 high-affinity diagnostic probes can increase the reliability of expression profiling of PD-1 tumor infiltrating lymphocytes (TILs) in tumor tissue biopsies and in vivo mapping efficiency using immune-PET imaging.
View Article and Find Full Text PDFCrimean-Congo haemorrhagic fever orthonairovirus (CCHFV) is a negative-sense, single-stranded RNA virus with a segmented genome and the causative agent of a severe Crimean-Congo haemorrhagic fever (CCHF) disease. The virus is transmitted mainly by tick species in Hyalomma genus but other ticks such as representatives of genera Dermacentor and Rhipicephalus may also be involved in virus life cycle. To improve our understanding of CCHFV adaptation to its tick species, we compared nucleotide composition and codon usage patterns among the all CCHFV strains i) which sequences and other metadata as locality of collection and date of isolation are available in GenBank and ii) which were isolated from in-field collected tick species.
View Article and Find Full Text PDFThis Letter presents the first study of Higgs boson production in association with a vector boson (V=W or Z) in the fully hadronic qqbb final state using data recorded by the ATLAS detector at the LHC in proton-proton collisions at sqrt[s]=13 TeV and corresponding to an integrated luminosity of 137 fb^{-1}. The vector bosons and Higgs bosons are each reconstructed as large-radius jets and tagged using jet substructure techniques. Dedicated tagging algorithms exploiting b-tagging properties are used to identify jets consistent with Higgs bosons decaying into bb[over ¯].
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