17 research outputs found

    The Perception of Distance on a Real Geographic Slope

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    Ooi, Wu, and He (2001) have shown that for objects resting on flat, horizontal surfaces, those that appear in the lower sector of the visual field are perceived as close to the observer and objects located near the visual horizon are perceived as further from the observer. Researchers have hypothesized that observers utilize the angle subtended between the horizon and the line of sight to the target object as information for distance.In a previous investigation Hajnal, Bunch, and Kelty-Stephen (2014) showed that an object’s physical angle of declination below the horizon is not uniquely utilized when making distance estimates to objects placed on a sloped surface. In that experiment a flat, horizontal surface was visible in the background when viewing objects placed on the sloped surface. To further investigate the possible utility of the angular declination below the horizon hypothesis we have replicated the findings of the previous study on a natural hillside where a flat, horizontal surface is not visible in the background. This setup has allowed us to evaluate whether observers rely on the same information to perceive distance on ramps versus real hills. The present research may have implications for the hypothesis which claims that perceived effort influences space perception (Proffitt, 2006a, 2006b) in addition to optical variables

    Chronic kidney disease and arrhythmias: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

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    Patients with chronic kidney disease (CKD) are predisposed to heart rhythm disorders, including atrial fibrillation (AF)/atrial flutter, supraventricular tachycardias, ventricular arrhythmias, and sudden cardiac death (SCD). While treatment options, including drug, device, and procedural therapies, are available, their use in the setting of CKD is complex and limited. Patients with CKD and end-stage kidney disease (ESKD) have historically been under-represented or excluded from randomized trials of arrhythmia treatment strategies,1 although this situation is changing.2 Cardiovascular society consensus documents have recently identified evidence gaps for treating patients with CKD and heart rhythm disorders [...

    The Hospitality of the Commons: A Collaborative Reflection on a SoTL Conference

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    This is a large-scale, multi-author collaborative autoethnographic study exploring the concept of building a tangible teaching commons on the example of the Scholarship of Teaching and Learning (SoTL) Commons Conference. The project organizers sought to provide a big tent and extended an invitation to attendees to respond to a series of writing prompts about their conference experience. Collaborative writing took place asynchronously over an approximately 60-day period following the close of the conference and generated ≈ 20,000 words. This corpus became the basis for a three-stage emergent coding process, conducted by the four-member steering commit-tee, which led to the identification of three primary themes from the collective experiences of the 2023 SoTL Commons Conference attendees: SoTL as pedagogy, SoTL as a community of scholars, and SoTL as scholarship. Despite some limitations to what the sense of commons represents, the project highlighted the respondents’ spirit of appreciative inquiry, a signature mindset of SoTL and engaged participants who were new to the field. We argue that it acted as a form of academic hospitality itself; enabling the sharing of practice, deepening of reflection, strengthening of research skills, fostering of social connections, and, by extension, the advancement of the field as a community of scholars

    Recombinant human sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDHS) is expressed at high yield as an active homotetramer in baculovirus-infected insect cells

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    The sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDHS) isoform is a promising contraceptive target because it is specific to male germ cells, essential for sperm motility and male fertility, and well suited to pharmacological inhibition. However, GAPDHS is difficult to isolate from native sources and recombinant expression frequently results in high production of insoluble enzyme. We chose to use the Bac-to-Bac baculovirus-insect cell system to express a His-tagged form of human GAPDHS (Hu his-GAPDHS) lacking the proline-rich N-terminal sequence. This recombinant Hu his-GAPDHS was successfully produced in Spodoptera frugiperda 9 (Sf9) cells by infection with recombinant virus as a soluble, enzymatically active form in high yield, >35mg/L culture. Biochemical characterization of the purified enzyme by mass spectrometry and size exclusion chromatography confirmed the presence of the tetrameric form. Further characterization by peptide ion matching mass spectrometry and Edman sequencing showed that unlike the mixed tetramer forms produced in bacterial expression systems, human his-GAPDHS expressed in baculovirus-infected insect cells is homotetrameric. The ability to express and purify active human GAPDHS as homotetramers in high amounts will greatly aid in drug discovery efforts targeting this enzyme for discovery of novel contraceptives and three compounds were identified as inhibitors of Hu his-GAPDHS from a pilot screen of 1120 FDA-approved compounds

    The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer

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    Oncogenic KRAS mutations and inactivation of the APC tumor suppressor co-occur in colorectal cancer (CRC). Despite efforts to target mutant KRAS directly, most therapeutic approaches focus on downstream pathways, albeit with limited efficacy. Moreover, mutant KRAS alters the basal metabolism of cancer cells, increasing glutamine utilization to support proliferation. We show that concomitant mutation of Apc and Kras in the mouse intestinal epithelium profoundly rewires metabolism, increasing glutamine consumption. Furthermore, SLC7A5, a glutamine antiporter, is critical for colorectal tumorigenesis in models of both early- and late-stage metastatic disease. Mechanistically, SLC7A5 maintains intracellular amino acid levels following KRAS activation through transcriptional and metabolic reprogramming. This supports the increased demand for bulk protein synthesis that underpins the enhanced proliferation of KRAS-mutant cells. Moreover, targeting protein synthesis, via inhibition of the mTORC1 regulator, together with Slc7a5 deletion abrogates the growth of established Kras-mutant tumors. Together, these data suggest SLC7A5 as an attractive target for therapy-resistant KRAS-mutant CRC
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