Holistic evaluation of a machine learning-based timing calibration for PET detectors under varying data sparsity.

Modern PET scanners offer precise TOF information, improving the SNR of the reconstructed images. Timing calibrations are performed to reduce the worsening effects of the system components and provide valuable TOF information. Traditional calibration procedures often provide static or linear corrections, with the drawback that higher-order skews or event-to-event corrections are not addressed.

Augmented Whole-Body Scanning via Magnifying PET.

A novel technique, called augmented whole-body scanning via magnifying PET (AWSM-PET), that improves the sensitivity and lesion detectability of a PET scanner for whole-body imaging is proposed and evaluated. A Siemens Biograph Vision PET/CT scanner equipped with one or two high-resolution panel-detectors was simulated to study the effectiveness of AWSM-PET technology. The detector panels are located immediately outside the scanner's axial field-of-view (FOV).

A Putative Bacterial ABC Transporter Circumvents the Essentiality of Signal Peptidase.

Unlabelled: The type I signal peptidase of Staphylococcus aureus, SpsB, is an attractive antibacterial target because it is essential for viability and extracellularly accessible. We synthesized compound 103, a novel arylomycin-derived inhibitor of SpsB with significant potency against various clinical S. aureus strains (MIC of ~1 µg/ml).

Synthesis and evaluation of a series of 4-azaindole-containing p21-activated kinase-1 inhibitors.

A series of 4-azaindole-containing p21-activated kinase-1 (PAK1) inhibitors was prepared with the goal of improving physicochemical properties relative to an indole starting point. Indole 1 represented an attractive, non-basic scaffold with good PAK1 affinity and cellular potency but was compromised by high lipophilicity (clogD=4.4).

Structure-Guided Design of Group I Selective p21-Activated Kinase Inhibitors.

The p21-activated kinases (PAKs) play important roles in cytoskeletal organization, cellular morphogenesis, and survival and have generated significant attention as potential therapeutic targets for cancer. Following a high-throughput screen, we identified an aminopyrazole scaffold-based series that was optimized to yield group I selective PAK inhibitors. A structure-based design effort aimed at targeting the ribose pocket for both potency and selectivity led to much-improved group I vs II selectivity.