Homozygous MTAP deletion occurs in ~15% of cancers, making them vulnerable to decreases in the concentration of S-adenosylmethionine (SAM). AG-270/S095033 is an oral, potent, reversible inhibitor of methionine adenosyltransferase 2 A (MAT2A), the enzyme primarily responsible for the synthesis of SAM. We report results from the first-in-human, phase 1 trial of AG-270/S095033 as monotherapy in patients with advanced malignancies (ClinicalTrials.
View Article and Find Full Text PDFCopper(I) complexes of isobutyl- () and isopropyl-substituted () proazaphosphatranes have been synthesized. Structural and computational studies of a series of monomeric complexes CuX (X = Cl, Br, I) and dimeric [CuCl] provide insight into the transannulation within and steric properties of the proazaphosphatrane ligand. These halide complexes are competent precatalysts in a model borylation reaction, and the silylamido complex CuN(TMS) catalyzes hydrosilylation of benzaldehyde under mild conditions.
View Article and Find Full Text PDFThe Particle Time of Flight (PTOF) diagnostic is a chemical vapor deposition diamond-based detector and is the only diagnostic for measuring nuclear bang times of low yield (<1013) shots on the National Ignition Facility. Recently, a comprehensive study of detector impulse responses revealed certain detectors with very fast and consistent impulse responses with a rise time of <50 ps, enabling low yield burn history measurements. At the current standoff of 50 cm, this measurement is possible with fast 14 MeV neutrons from deuterium-tritium (DT) fusion plasmas.
View Article and Find Full Text PDFPurpose: To summarize and categorize postulated mechanisms of immune checkpoint inhibitor (ICI)-mediated retinal and choroidal inflammation and discuss resulting implications for evaluation and management of these adverse reactions.
Design: Targeted literature review with interpretation and perspective Methods: We performed a review of selected literature describing immune-mediated retinal and choroidal adverse reactions associated with ICI therapy, synthesizing and categorizing the likely underlying pathogenic mechanisms. Based on these mechanistic categories, we provide perspective on a rational approach to the evaluation of patients with ICI-associated inflammatory disorders of the retina and choroid.
Purpose: To report the clinical presentation, treatment course, and outcome of a case of bilateral frosted branch angiitis (FBA) and neuroretinitis associated with acute Epstein-Barr virus (EBV) infection in a pediatric patient with Turner Syndrome.
Methods: Case report with multimodal ocular imaging and extensive systemic workup.
Results: A 16-year-old female with Turner syndrome presented with acute bilateral vision loss, hearing loss, and ataxia.