Targeted protein degradation (TPD) is an emerging therapeutic strategy that would benefit from new chemical entities with which to recruit a wider variety of ubiquitin E3 ligases to target proteins for proteasomal degradation. Here we describe a TPD strategy involving the recruitment of FBXO22 to induce degradation of the histone methyltransferase and oncogene NSD2. UNC8732 facilitates FBXO22-mediated degradation of NSD2 in acute lymphoblastic leukemia cells harboring the NSD2 gain-of-function mutation p.
View Article and Find Full Text PDFTargeted protein degradation (TPD) is an emerging therapeutic strategy that would benefit from new chemical entities with which to recruit a wider variety of ubiquitin E3 ligases to target proteins for proteasomal degradation. Here, we describe a TPD strategy involving the recruitment of FBXO22 to induce degradation of the histone methyltransferase and oncogene NSD2. UNC8732 facilitates FBXO22-mediated degradation of NSD2 in acute lymphoblastic leukemia cells harboring the NSD2 gain of function mutation p.
View Article and Find Full Text PDFThe adapted DIRAC experiment at the CERN PS accelerator observed for the first time long-lived hydrogenlike π^{+}π^{-} atoms, produced by protons hitting a beryllium target. A part of these atoms crossed the gap of 96 mm between the target and a 2.1 μm thick platinum foil, in which most of them dissociated.
View Article and Find Full Text PDFThe observation of hydrogenlike πK atoms, consisting of π^{-}K^{+} or π^{+}K^{-} mesons, is presented. The atoms are produced by 24 GeV/c protons from the CERN PS accelerator, interacting with platinum or nickel foil targets. The breakup (ionization) of πK atoms in the same targets yields characteristic πK pairs, called "atomic pairs," with small relative momenta Q in the pair center-of-mass system.
View Article and Find Full Text PDFIt is known that, in spite of meeting appropriate clinical criteria for spinal cord stimulation (SCS) and having undergone flawless procedures, a significant number of patients who fail the therapy continues to exist. It is the purpose of this article to focus on the development of psychosocial indicators of success for SCS, if any. Referring to specialist literature authors present a review of what is known, what is not known, and what remains controversial on this topic.
View Article and Find Full Text PDFWe report the first observation of a charm-strange meson D(+)(sJ)(2632) at a mass of 2632.5+/-1.7 MeV/c(2) in data from SELEX, the charm hadro-production experiment E781 at Fermilab.
View Article and Find Full Text PDFWe observe a signal for the doubly charmed baryon Xi(+)(cc) in the charged decay mode Xi(+)(cc)-->Lambda(+)(c)K-pi(+) in data from SELEX, the charm hadroproduction experiment at Fermilab. We observe an excess of 15.9 events over an expected background of 6.
View Article and Find Full Text PDFWe report new precision measurements of the lifetimes of the Lambda(+)(c) and D0 from SELEX, the charm hadroproduction experiment at Fermilab. Based upon 1630 Lambda(+)(c) and 10 210 D0 decays we observe lifetimes of tau[Lambda(+)(c)] = 198.1+/-7.
View Article and Find Full Text PDFWe report the first observation of the Cabibbo-suppressed charm baryon decay Ξ_{c}^{+}→pK^{-}π^{+}. We observe 150±22±5 events for the signal. The data were accumulated using the SELEX spectrometer during the 1996-1997 fixed target run at Fermilab, chiefly from a 600 GeV/c Σ^{-} beam.
View Article and Find Full Text PDFThe aim of this paper is to focus on a medical issue which is not held in due consideration in Italy. In chronic pain control and management, specialists may advise at various times drugs, physical therapies, behavioral modification techniques, and not demolitive antinociceptive procedures. Quite often patients do not follow medical prescriptions as one should expect, especially if they are not inpatients.
View Article and Find Full Text PDFThe MMPI scores, the PPI and the MPQ of seven multi-operated patients for chronic pain complaints of non malignant origin were studied. The results of the analysis performed in this group of surgically treated patients point out that there is a strong evidence of relationship between personality traits and the persistence of pain.
View Article and Find Full Text PDF