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One-Shot Klein Cutting Planes for Lipschitz Geodesically Convex Optimization in Hyperbolic Space
arXiv:2605.17540v4 Announce Type: replace Abstract: Motivated by the COLT 2023 open problem of Criscitiello, Mart\'inez-Rubio, and Boumal on deterministic first-order methods for Lipschitz geodesically convex optimization on Hadamard manifolds, we study hyperbolic space \[ \HH^d_{-\kappaC^2} =\{X\in\R^{d+1}:\ipL{X}{X}=-1,\ X_0>0\}, \qquad \ip{U}{V}_X=\kappaC^{-2}\ipL{U}{V}. For every geodesically convex $M$-Lipschitz function \[ f:\bar B_{\HH}(x_0,r)\to\R,\qquad s=\kappaC r, \] we give a...
Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer
Abstract BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1,2,3.
The Last Evolution, by John W Campbell Jr. (1932)
The Project Gutenberg EBook of The Last Evolution, by John Wood Campbell This eBook is for the use of anyone anywhere at no cost and with almost no restrictions whatsoever. You may copy it, give it away or re-use it under the terms of the Project Gutenberg License included with this eBook or online at www.gutenberg.org
Mutation-dependent responses to sleep and exercise in clonal haematopoiesis
Abstract Clonal haematopoiesis (CH) activates inflammation and increases the risk of atherosclerosis1,2. Whether lifestyle alters CH clone expansion or the phenotypic programming of CH mutant cells, thereby affecting atherosclerosis, is unknown. Here, in humans and mice and across mutations in Jak2, Tet2, Trp53 and Dnmt3a, we demonstrate mutation-dependent responses to sleep and exercise in CH and show that mutant cells are uniquely sensitive to lifestyle.
A prognostic human brain network for diffuse midline glioma
Abstract Diffuse midline gliomas (DMGs) are near-universally lethal tumours of the childhood central nervous system1,2. In animal models, DMGs form brain-wide integrated networks through neuron-to-glioma synapses3,4,5,6 and glioma-to-glioma gap junctional coupling3. This extensive connectivity robustly promotes the growth and invasion of DMG3,4,5,6,7,8,9 and other glial malignancies10,11,12 through paracrine mechanisms and direct neuron-to-glioma synapses.
A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases
Abstract Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor...
Structural basis for chaperone-guided assembly of RNA-induced silencing complex
Abstract The RNA-induced silencing complex (RISC), comprising an Argonaute (AGO) protein and a small RNA, is the central effector in RNA silencing. Small RNAs are loaded onto AGO as bulky duplexes in an HSP70- and HSP90-dependent process1,2,3, but the molecular mechanism remains poorly understood. Here we identify the human AGO–HSP90–p23 complex, which captures AGO in an RNA-free state, termed the AGO maturation complex (AMC).
A 5.3-million-year-old deep-sea whale necropolis in the Diamantina Zone
Abstract Whale falls are biodiversity oases at seabeds1,2,3,4,5,6, yet their record from the oceans has remained sparse and fragmentary6,7. Here we report the discovery of a vast whale necropolis in the Diamantina Zone (4,616- to 7,001-m depth), extending about 1,200 km along the sea floor of the southeastern Indian Ocean. This area has a deep and extensive accumulation comprising five modern natural whale-fall communities and 476 fossil cetaceans recorded.
How back is the U? Can Clemson rebound? Previewing...
Life in the ACC certainly isn't boring. In the past year alone, the conference has produced a long and awkward CFP rankings battle, an irate affiliate member, a thrilling national title game run, the strangest tiebreaker result imaginable, an out-of-nowhere 11-win season, the most disappointing team in the country, an epic pro-to-college face-plant, 18 of the 38 best games of the 2025 season, the No. 1 pick in the NFL draft (indirectly) and the most awkward possible move to nine-game...