Experimental Comparison of Cycle Modifications to a Multi-Stage Two-Evaporator Transcritical CO2 Refrigeration Cycle

With increasing awareness of the adverse effects of carbon emissions on the environment, researchers within the heating, ventilation, air conditioning, and refrigeration (HVAC&R) community have been pushing for lower global warming potential (GWP) and natural working fluids as well as systems that are more efficient than the higher-GWP systems they replace. One such working fluid is carbon dioxide (CO2). While CO2 has the advantages of being low-cost, non-flammable, and possessing a high volumetric heat capacity, it has a high critical pressure associated with a low critical temperature, thus often necessitating transcritical operation that requires significant compressor input power. As such, numerous cycle modifications have been proposed that enable the transcritical CO2 cycle to match, and in some cases surpass, the coefficient of performance (COP) of existing hydrofluorocarbon (HFC) cycles under the same operating conditions. This work provides an experimental comparison of four cycle architectures that utilize the same compressors and heat exchangers. This enables a meaningful comparison of these modifications, consisting of open economization with an evaporator bypass, as well as both electronic expansion valve (EXV) and ejector expansion strategies, along with a pump applied between the gas cooler outlet and the ejector motive nozzle inlet for control and increased recoverable pressure differential. Experimental parametric studies were conducted, and comparisons of architecture costs and benefits are presented. Design recommendations are provided along with future work

Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase

Metabolic networks are interconnected and influence diverse cellular processes. The protein-metabolite interactions that mediate these networks are frequently low affinity and challenging to systematically discover. We developed mass spectrometry integrated with equilibrium dialysis for the discovery of allostery systematically (MIDAS) to identify such interactions. Analysis of 33 enzymes from human carbohydrate metabolism identified 830 protein-metabolite interactions, including known regulators, substrates, and products as well as previously unreported interactions. We functionally validated a subset of interactions, including the isoform-specific inhibition of lactate dehydrogenase by long-chain acyl-coenzyme A. Cell treatment with fatty acids caused a loss of pyruvate-lactate interconversion dependent on lactate dehydrogenase isoform expression. These protein-metabolite interactions may contribute to the dynamic, tissue-specific metabolic flexibility that enables growth and survival in an ever-changing nutrient environment

Collateral deletion of the mitochondrial AAA+ ATPase ATAD1 sensitizes cancer cells to proteasome dysfunction

The tumor suppressor gene PTEN is the second most commonly deleted gene in cancer. Such deletions often include portions of the chromosome 10q23 locus beyond the bounds of PTEN itself, which frequently disrupts adjacent genes. Coincidental loss of PTEN-adjacent genes might impose vulnerabilities that could either affect patient outcome basally or be exploited therapeutically. Here, we describe how the loss of ATAD1, which is adjacent to and frequently co-deleted with PTEN, predisposes cancer cells to apoptosis triggered by proteasome dysfunction and correlates with improved survival in cancer patients. ATAD1 directly and specifically extracts the pro-apoptotic protein BIM from mitochondria to inactivate it. Cultured cells and mouse xenografts lacking ATAD1 are hypersensitive to clinically used proteasome inhibitors, which activate BIM and trigger apoptosis. This work furthers our understanding of mitochondrial protein homeostasis and could lead to new therapeutic options for the hundreds of thousands of cancer patients who have tumors with chromosome 10q23 deletion

Mutations in GRK2 cause Jeune syndrome by impairing Hedgehog and canonical Wnt signaling

Abstract Mutations in genes affecting primary cilia cause ciliopathies, a diverse group of disorders often affecting skeletal development. This includes Jeune syndrome or asphyxiating thoracic dystrophy (ATD), an autosomal recessive skeletal disorder. Unraveling the responsible molecular pathology helps illuminate mechanisms responsible for functional primary cilia. We identified two families with ATD caused by loss‐of‐function mutations in the gene encoding adrenergic receptor kinase 1 (ADRBK1 or GRK2). GRK2 cells from an affected individual homozygous for the p.R158* mutation resulted in loss of GRK2, and disrupted chondrocyte growth and differentiation in the cartilage growth plate. GRK2 null cells displayed normal cilia morphology, yet loss of GRK2 compromised cilia‐based signaling of Hedgehog (Hh) pathway. Canonical Wnt signaling was also impaired, manifested as a failure to respond to Wnt ligand due to impaired phosphorylation of the Wnt co‐receptor LRP6. We have identified GRK2 as an essential regulator of skeletogenesis and demonstrate how both Hh and Wnt signaling mechanistically contribute to skeletal ciliopathies

A product of observation, pedagogy, and cybernetic curriculum design

This paper, co-authored by undergraduate students and their instructor part of an educational psychology seminar, describes a participatory curriculum design approach for preservice teacher education that focuses on the use of the principles of second-order cybernetics to teach about teaching and learning. Using elements of an Open Source Educational Processes framework, our Spring ESEPSY2309 section created project-based collective hive minds of preservice teachers, relying on a cybernetic approach at the crossroads of Gregory Bateson and Gordon Pask's theories. The classroom community used four innovative tool-mediated pillars to guide collaborative activity: 1) Live-chatting using the Reddit social media platform, 2) observation of the lives, strategies, and practices used by teachers and students in their own social networks through Soundcloud podcasting to expand their own perceptions of pedagogies and best practices that they could employ in their careers, 3) open-ended paper writing, exploring sources beyond the object language provided by the textbook through extensive dyadic conversations with the instructor, and 4) training in the use of the Alice 3 game creation tool for block programming enabling the accumulation of competence in designing classroom systems that may treat students these undergraduates would soon teach as active historical agents in learning environments, combining skills from varied subjects into transdisciplinary educational experiences. We showcase outcomes of our class projects using a narrative inquiry to describe podcast episodes, a topic network analysis to illustrate the expansive nature of Open Source writing activity, and a visual depiction of our class Alice 3 games