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Jackson, James

Publications and source records attributed to Jackson, James.

Potent and Selective Amidopyrazole Inhibitors of IRAK4 That Are Efficacious in a Rodent Model of Inflammation

IRAK4 is a critical upstream kinase in the IL-1R/TLR signaling pathway. Inhibition of IRAK4 is hypothesized to be beneficial in the treatment of autoimmune related disorders. A screening campaign identified a pyrazole class of IRAK4 inhibitors that were determined by X-ray crystallography to exhibit an unusual binding mode. SAR efforts focused on the identification of a potent and selective inhibitor with good aqueous solubility and rodent pharmacokinetics. Pyrazole C-3 piperidines were well tolerated, with N-sulfonyl analogues generally having good rodent oral exposure but poor solubility. N-Alkyl piperidines exhibited excellent solubility and reduced exposure. Pyrazoles possessing N-1 pyridine and fluorophenyl substituents were among the most active. Piperazine 32 was a potent enzyme inhibitor with good cellular activity. Compound 32 reduced the in vivo production of proinflammatory cytokines and was orally efficacious in a mouse antibody induced arthritis disease model of inflammation.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

The bones of the Milky Way

The very long and thin infrared dark cloud 'Nessie' is even longer than had been previously claimed, and an analysis of its Galactic location suggests that it lies directly in the Milky Way's mid-plane, tracing out a highly elongated bone-like feature within the prominent Scutum-Centaurus spiral arm. Re-analysis of mid-infrared imagery from the Spitzer Space Telescope shows that this infrared dark cloud (IRDC) is at least two and possibly as many as five times longer than had originally been claimed by Nessie's discoverers; its aspect ratio is therefore at least 300:1 and possibly as large as 800:1. A careful accounting for both the Sun's offset from the Galactic plane (∼25 pc) and the Galactic center's offset from the (l{sup II} , b{sup II} ) = (0, 0) position shows that the latitude of the true Galactic mid-plane at the 3.1 kpc distance to the Scutum-Centaurus Arm is not b = 0, but instead closer to b = –0.4, which is the latitude of Nessie to within a few parsecs. An analysis of the radial velocities of low-density (CO) and high-density (NH{sub 3}) gas associated with the Nessie dust feature suggests that Nessie runs along the Scutum-Centaurus Arm in position-position-velocity space, which means it likely forms a dense 'spine' of the arm in real space as well. The Scutum-Centaurus Arm is the closest major spiral arm to the Sun toward the inner Galaxy, and, at the longitude of Nessie, it is almost perpendicular to our line of sight, making Nessie the easiest feature to see as a shadow elongated along the Galactic plane from our location. Future high-resolution dust mapping and molecular line observations of the harder-to-find Galactic 'bones' should allow us to exploit the Sun's position above the plane to gain a (very foreshortened) view 'from above' the Milky Way's structure.

79 ASTRONOMY AND ASTROPHYSICS↗

Final Report

This multi-year grant partially supported the Infrared Space Observatory (ISO) data analysis and related activities of three Guest Investigators (Prof. Dan Clemens, Prof. Thomas Bania, and Prof. James Jackson) at Boston University for ten distinct ISO investigations. Support under this grant covered "Years 1 & 2" of the ISO activities at Boston University. "Year 3" activities support is currently in force under a separate JPL contract, with Prof. James Jackson as the Block Grant PI; "Year 4" support has been requested from JPL and that proposal is currently pending.

Clemens, Dan↗

Active faulting and block rotations in the western Transverse Ranges, California

This paper uses the results of five years of VLBI measurements in conjunction with data on slip vectors of major earthquakes and the dominant westerly trend of faults and blocks to argue that these data are consistent with the concept that rotations about vertical axes in the western Transverse Ranges in California continue at rates of several degrees per million years. It is suggested that rotations about vertical axes may occur in the western Transverse Ranges without these rotations necessarily being manifestations of continuous deformation at depth and that attempts to account for the relative motion of the Pacific and the North America plates by adding rates of slip on major faults are likely to fail.

Jackson, James↗

Real-time optical laboratory solution of parabolic differential equations

An optical laboratory matrix-vector processor is used to solve parabolic differential equations (the transient diffusion equation with two space variables and time) by an explicit algorithm. This includes optical matrix-vector nonbase-2 encoded laboratory data, the combination of nonbase-2 and frequency-multiplexed data on such processors, a high-accuracy optical laboratory solution of a partial differential equation, new data partitioning techniques, and a discussion of a multiprocessor optical matrix-vector architecture.

Casasent, David↗