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A Family of Rare Earth Molybdenum Bronzes: Oxides Consisting of PeriodicArrays of Interacting Magnetic Units. -The compounds LnMo 16O44 (Ln: Y, La-Lu) are synthesized from stoichiometric mixtures of Ln 2O3, Mo, and MoO3 (silica tubes, 700 C, 5 d) and characterized by powder and single crystal XRD, magnetic measurements, and DFT electronic structure calculations. All the compounds crystallize in the rhombohedral space group R3. The structure contains two types of distinct layers built from corner-sharing MoO 6 octahedra and corner-sharing MoO4 tetrahedra, enclosing eight-coordinate Ln ions. The structure of LnMo16O44 is distinguished by the presence of isolated Mo 8O36 units of ReO3-type, that are entirely surrounded by MoO4 tetrahedra. The La, Ce, Pr, and Gd compounds display paramagnetic behavior with weak antiferromagnetic interactions between the lanthanoids. The d-orbital occupation in a unique Mo 8O36 structural subunit leads to a magnetic transition at temperatures around 6.5 K. -(SCHNEEMEYER, L. F.; SIEGRIST*, T.; BESARA, T.; LUNDBERG, M.; SUN, J.; SINGH, D. J.; J. Solid State Chem. 227 (2015) 178-185, http://dx.

The family of rare earth molybdenum bronzes, reduced ternary molybdates of composition LnMo 16 O 44, was synthesized and a detailed structural study carried out. Bond valence sum (BVS) calculations clearly show that the molybdenum ions in tetrahedral coordination are hexavalent while the electron count in the primitive unit cell is odd. Yet, measurements show that the phases are semiconductors. The temperature dependence of the magnetic susceptibility of samples containing several different rare earth elements was measured. These measurements verified the presence of a 6.5 K magnetic phase transition not arising from the rare earth constituent, but likely associated with the unique isolated ReO 3 -type Mo 8 O 36 structural subunits in this phase. To better understand the behavior of these materials, electronic structure calculations were performed within density functional theory. Results suggest a magnetic state in which these structural moieties have an internal ferromagnetic arrangement, with small ~1/8 μB moments on each Mo. We suggest that the Mo 8 O 36 units behave like pseudoatoms with spin ½ derived from a single hole distributed over the eight Mo atoms that are strongly hybridized with the O atoms of the subunit.Interestingly, while the compound is antiferromagnetic, our calculations suggest that a field-stabilized ferromagnetic state, if achievable, will be a narrow band half-metal.

While Interleukin-2 (IL-2) has produced remarkable clinical efficacy in a fraction of cancer patients, its clinical use is limited by its narrow therapeutic index due to systemic and pleotropic activation of both inflammatory and suppressive lymphocytes. Numerous approaches to improve the specificity and activity profile of IL-2 are being evaluated. Using Tentarix’s propriety Tentacles™ platform, which is based on fully human stabilized antibody VH domains, we generated TNRX-257, a novel multispecific biologic that effectively blocks LAG3 while simultaneously delivering IL2Rγ/β agonism to LAG3+ cells in a highly conditional manner. LAG3 expression is restricted to antigen-experienced and tumor-reactive immune cells with little expression on peripheral PBMC or immune cells in normal tissues. TNRX-257 was designed to combine LAG3 inhibition with an IL2R agonist moiety to activate and expand LAG3+ tumor-reactive T cells in tumor microenvironment while enhancing their effector function and anti-tumor immunity with minimal systemic toxicity. TNRX-257 blocks the interaction of LAG3 with MHC-II and enhances TCR signaling with similar potency as Relatlimab. TNRX-257 also selectively induces pSTAT5 on LAG3+ immune cells with little activity on LAG3- immune cells, including resting human PBMCs. Moreover, the lower level of pSTAT5 (Emax) induced by TNRX-257 than IL-2 indicates TNRX-257 mediates its activity as a partial agonist, a phenotype that preserves stemness. TNRX-257 induces higher and preferential activation of CD8+ T cells over CD4+ T cells due to higher expression of LAG3 on CD8+ T cells than CD4+ T cells, particularly within the tumor microenvironment. Unlike an undirected IL-15 agonist that induced total CD8+ T cell proliferation, TNRX-257 selectively induced proliferation of LAG3+ CD8+ T cells in a human melanoma TIL stimulation assay without expansion of Tregs. TNRX-257 treatment also preserved the stem-like CD8+ population compared to the undirected IL-15 agonist. TNRX-257 showed in vitro and in vivo molecular stability, as well as good pharmacokinetic (PK) and pharmacodynamic (PD) properties. TNRX-257 induced robust anti-tumor efficacy when tested in early and established tumor models using melanoma A375-CMV-pp65 or colorectal cancer HT-29 cells in humanized mice. In contrast, the corresponding untargeted IL2Rγ/β Tentacle had no efficacy. Together, these data show that TNRX-257 has drug-like properties and elicits strong anti-tumor efficacy, supporting its clinical development. Citation Format: Rajesh K. Sharma, Jianying Dong, Natasha Del Cid, Yasamine Ghorbanian, Christina Carnevale, Christen Buetz, Matthew Lundberg, Glenn Capodagli, Jayd Hannah, Gavin Hong, Pricilla Walters, Arlene Sereno, Falene Chai, Abby Lin, James Furney, Wendy Zhang, Craig Pigott, Paul Kang, Michael Gallo, Margaret Karow, Stephen Demarest. TNRX-257, a novel multifunctional biologic effectively blocks LAG3 and conditionally delivers IL2Rg/b agonism to LAG3+ cells for robust anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2956.

<div class="section abstract"><div class="htmlview paragraph">Modern water injection systems typically deliver water separately from the primary fuel system using a discrete injector either through the intake port or directly to the cylinder. Recently, however, water dilution strategies using fully hydrous fuel systems have been receiving increased attention. Hydrous fuels are water and liquid fuel blends that are fully mixed prior to delivery to the combustion system. Removing water from naturally hydrous fuels such as ethanol requires large amounts of energy; consequently, it is possible to combine water injection with more economical production by leaving some amount of water in the fuel. This paper compares experimentally the water dilution effects on the combustion and emissions characteristics and overall engine performance when delivering the water through either a hydrous fuel blend or discrete port water injection.</div><div class="htmlview paragraph">A 2.4L 4-cylinder NA GDI engine was used in experimental testing. The engine was controlled using an aftermarket ECU interfaced with OEM components and a laboratory-grade wide-band oxygen sensor for equivalence ratio quantification and feedback. The results indicated that for brake measurements the type of water addition affects combustion sufficiently enough to be measured and quantified. ISFC reduction ranged between 0.5 and 2% for water injection and 0.5 and 3% for hydrous fuel. Combustion stability tended to be not strongly affected or degraded by water addition. Combustion analysis demonstrated retarded combustion timings and reduced peak pressures of up to 8.5% for all water dilution cases with the largest reductions at the highest speed and load points. Emissions effects showed mixed results that depended on both speed and type of water addition.</div></div>