STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts.

Unlabelled: Phosphoinositide 3-kinase α (PIK3CA) is one of the most mutated genes across cancers, especially breast, gynecologic, and head and neck squamous cell carcinoma tumors. Mutations occur throughout the gene, but hotspot mutations in the helical and kinase domains predominate. The therapeutic benefit of isoform-selective PI3Kα inhibition was established with alpelisib, which displays equipotent activity against the wild-type and mutant enzyme.

Review Paper: Residual Stresses in Deposited Thin-Film Material Layers for Micro- and Nano-Systems Manufacturing.

This review paper covers a topic of significant importance in micro- and nano-systems development and manufacturing, specifically the residual stresses in deposited thin-film material layers and methods to control or mitigate their impact on device behavior. A residual stress is defined as the presence of a state of stress in a thin-film material layer without any externally applied forces wherein the residual stress can be compressive or tensile. While many material properties of deposited thin-film layers are dependent on the specific processing conditions, the residual stress often exhibits the most variability.

Spatial equity implications and neighborhood indicators of ridehailing trip frequency and vehicle miles traveled in the phoenix metro region.

Early optimism for ridehailing services to complement existing public transit services and offer individuals another shared mobility service with reduced travel costs and improved travel times have largely proven to be unsubstantiated. This unwelcomed outcome, in part due to the popularity of ridehailing services among wealthier populations and restrictions on the less-expensive ridesharing service in some urban settings, has likely instead resulted in heightened disparities in access to this on-demand mobility option for historically-marginalized populations and under-resourced communities. This hypothesis is examined by estimating the macro-level socioeconomic and built environment determinants of ridehailing pick-ups and drop-offs in the Phoenix metro region with spatial lag of X modeling.

Recent Advances in Reactive Ion Etching and Applications of High-Aspect-Ratio Microfabrication.

This paper reviews the recent advances in reaction-ion etching (RIE) for application in high-aspect-ratio microfabrication. High-aspect-ratio etching of materials used in micro- and nanofabrication has become a very important enabling technology particularly for bulk micromachining applications, but increasingly also for mainstream integrated circuit technology such as three-dimensional multi-functional systems integration. The characteristics of traditional RIE allow for high levels of anisotropy compared to competing technologies, which is important in microsystems device fabrication for a number of reasons, primarily because it allows the resultant device dimensions to be more accurately and precisely controlled.

Coho salmon spawner mortality in western US urban watersheds: bioinfiltration prevents lethal storm water impacts.

Adult coho salmon return each autumn to freshwater spawning habitats throughout western North America. The migration coincides with increasing seasonal rainfall, which in turn increases storm water run-off, particularly in urban watersheds with extensive impervious land cover. Previous field assessments in urban stream networks have shown that adult coho are dying prematurely at high rates (>50%).

The role of elective perioperative dialysis in nondialysis renal failure patients.

Background: Patients with renal insufficiency represent a difficult group. They show an increased morbidity and mortality after heart surgery. Nondialysis chronic kidney disease patients show higher mortality than patients receiving chronic dialysis.

Effect of mannose chain length on targeting of glucocerebrosidase for enzyme replacement therapy of Gaucher disease.

Recombinant human glucocerebrosidase (imiglucerase, Cerezyme) is used in enzyme replacement therapy for Gaucher disease. Complex oligosaccharides present on Chinese hamster ovary cell-expressed glucocerebrosidase (GCase) are enzymatically remodeled into a mannose core, facilitating mannose receptor-mediated uptake into macrophages. Alternative expression systems could be used to produce GCase containing larger oligomannose structures, offering the possibility of an improvement in targeting to macrophages.

AAV vector-mediated correction of brain pathology in a mouse model of Niemann-Pick A disease.

Niemann-Pick A disease (NPA) is a fatal lysosomal storage disorder caused by a deficiency in acid sphingomyelinase (ASM) activity. The lack of functional ASM results in cellular accumulation of sphingomyelin and cholesterol within distended lysosomes throughout the brain. In this study, we investigated the potential of AAV-mediated expression of ASM to correct the brain pathology in an ASM knockout (ASMKO) mouse model of NPA.