DSOM - Decision Support for Operations and Maintenance - Application to a USMC Base Centralized Energy System.

PNNL DSOM technology coordinates efficient steam plant operation with EMCS and SCADA systems, providing generation support and automated load shedding to meet peak demand limits saving over $1M in two years

Core modifications of GSK3335103 toward orally bioavailable αvβ6 inhibitors with improved synthetic tractability

The α β integrin has been identified as a target for the treatment of fibrotic diseases, based on the role it has in activating TGF-β , a protein implicated in the pathogenesis of fibrosis. However, the development of orally bioavailable α β inhibitors has proven challenging due to the zwitterionic pharmacophore required to bind to the RGD binding site. This work describes the design and development of a novel, orally bioavailable series of α β inhibitors, developing on two previously published α β inhibitors, GSK3008348 and GSK3335103. Strategies to reduce the basicity of the central ring nitrogen present in GSK3008348 were employed, while avoiding the synthetic complexity of the chiral, fluorine-containing quaternary carbon center contained in GSK3335103. Following initial PK studies, this series was optimized, aided by analysis of the physicochemical and in vitro PK properties, to deliver lead molecules ( )- and as potent and orally bioavailable α β inhibitors with improved synthetic tractability

Synthetic approaches to N- and 4-substituted 1,4-dihydro-3(2H)-isoquinolinone derivatives

Reaction of methyl-2-(2-formylphenyl)acetate with primary amines in a reductive amination/cyclisation process resulted in N-substituted 1,4-dihydro-3(2H)-isoquinolinones. With H 2NCH 2R sodium borohyride is a suitable reductant (11 examples), but H 2NCHR 1R 2 required a transfer hydrogenation using ammonium formate catalysed by palladium on carbon (9 examples). 4-Substituted-1,4-dihydro-3(2H)-isoquinolinones were synthesised by deprotonation (n-butyllithium) and addition of R 3CH 2Br (12 examples with R 3 = alkyl, Ar, CH[dbnd]CH 2, C[tbnd]CH). Modest diastereoselectivity was achieved with 1,4-dihydro-3(2H)-isoquinolinones derived from H 2NCHMeR 2 [R 2 = (η 5-C 5H 4)Co(η 4-C 4Ph 4) - max. dr = 1.9: 1], but use of H 2NCHMeFc (Fc = ferrocenyl) provided a new method of 1,4-dihydro-3(2H)-isoquinolinone N-deprotection with formic acid

2,5-Diketopiperazines as potent and selective oxytocin antagonists 1:identification, stereochemistry and initial SAR

This paper covers efforts to discover orally active potent and selective oxytocin antagonists. Screening pooled libraries identified a novel series of 2,5-diketopiperazine derivatives with antagonist activity at the human oxytocin receptor. We report the initial structure-activity relationship investigations and the determination of the stereochemistry of the most potent compounds

The Role of Assessment Feedback in Developing Academic Buoyancy

This research focuses on the everyday challenge in academic learning of assessment, and argues that academic buoyancy is a key factor in academic success. To scaffold students’ learning and effectively support academic buoyancy, there is arguably a need for a better understanding of: (i) what students find most and least useful in their assessment feedback; (ii) how students use feedback to approach future assessments; and (iii) how students respond to feedback in terms of what they think, feel and do. Key findings from survey responses of 91 undergraduate students were that students use their feedback more than anticipated and look for specific information to help their future performance. In addition, five indicators of academically buoyant behaviour were identified: an internal locus of control, understanding the grade, being forward looking, being improvement focused and being action orientated. These indicators suggested a distinction between students who were academically buoyant because they were constructive in their response to feedback, and those who appeared less so because they were not action orientated, but more focused on their emotional response. These findings have implications for the provision of assessment feedback in higher education and offer insight into opportunities for the development of academic buoyancy