Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide, with roughly 41% of CRC cases harboring a KRAS mutation. There have been significant advances with the advent of KRAS-targeted therapies; however, acquired resistance to KRAS-targeted treatments has occurred in other cancers, with mechanisms including increased HER family expression among other receptor tyrosine kinases. HER3, a member of the HER family that is kinase impaired, has been shown to be a resistance mechanism upon inhibition of the HER family and downstream targets including RAS/MEK/ERK and PI3K/AKT. Our study examines whether HER3 and mutant KRAS are viable co-targets. We find that KRAS mutations tend to co-occur with HER3 alterations in a large panel of cancers and in CRCs. Our results show that both total and activated HER3 levels increase in CRC patient derived organoids and cell lines after treatment with KRASG12D targeted agents, indicating that HER3 could be a potential adaptive response mechanism to KRAS-targeted therapy. Further, we found that genetic knock-down of KRAS and HER3 resulted in a statistically significant reduction in growth of CRC cells compared to single knockdown of either KRAS or HER3. We observed that kinase impaired HER3 binding partners, as assessed by immunoprecipitation, is cell dependent with EGFR binding HER3 in one cell line. After co-treating CRC cells with pan-HER inhibitors in combination with MRTX1133, a KRASG12D inhibitor, synergistic and additive effects in reduction in cell growth were observed in a drug-dependent manner. Finally, we found that co-targeting KRASG12D mutant cells with a KRASG12D inhibitor and a HER3 antibody-drug conjugate further reduced cell viability. We posit that co-targeting both KRASG12D and HER3, whether directly or indirectly, is a potential therapeutic strategy in CRC patients.
Greater Caribbean manatee (Trichechus manatus manatus) pool recordings from the Caribbean Manatee Conservation Center in Bayamon, Puerto Rico including location and depth of recordings as well as recordings from the natural protected habitat of Laguna del Condado, San Juan, Puerto Rico which includes the GPS coordinates in the recording title. All recordings obtained using omnidirectional hydrophones with H1 recorder (Model SQ26-H1; Cetacean Research Technology, 2007) and are in .wav format.
The Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) rating method was developed in head and neck cancer populations to describe severity of aspiration and residue. The purpose of this study was to assess criterion validity of DIGEST in a post-stroke cohort. In this retrospective analysis, 2 raters (using version 2 criteria) performed DIGEST rating on recordings of modified barium swallow studies (MBSS) from 88 post-stroke patients that were extracted from a larger de-identified database. Modified Barium Swallow Study Impairment Profile (MBSImP) scores and Functional Oral Intake Scale (FOIS) scores were used to determine criterion validity. Inter-rater and intra-rater reliability for overall DIGEST grade were substantial (ƙ=0.69 and 0.73, respectively), however inter-rater reliability for efficiency were only moderately reliable (ƙ=0.52). Reliability for MBSImP scoring was excellent for Pharyngeal Total (PT) scores (ICC=0.81-0.93). Overall DIGEST grades were significantly associated with PT scores in the expected direction (τ=0.51, p<0.0001), and there was no association between Oral Total (OT) and DIGEST grade (τ=-0.02, p=0.077). Pairwise comparisons using PT scores indicated significant differentiation between DIGEST grades 0 from all other grades (p<0.0001), with overlap in intermediate grades (p=0.106-0.713). Functional Oral Intake Scale (FOIS) scores were significantly associated with DIGEST grade in the anticipated direction (τ=-0.43, p<0.0001). Expected psychometrics and acceptable reliability for DIGEST grading were shown in this post-stroke cohort. A larger dataset would clarify mid-grade differentiation and potential influence of oral phase impairments in this sub-population.
Data associated withs studies carried out in the Biomedical Ultrasonics and Cavitation Laboratory (PI: Haworth) associated with NIH grant R01HL148451. These studies focus on the development of a perfluorocarbon emulsion for use in ultrasound-mediated oxygen scavenging. The studies also assess the risk of gas embolization using a Langendorff preparation for a rat work heart model.
Data from a project studying Cincinnati's gas streetlights. Table S1 contains latitude and longitude information for all natural gas streetlights identified within the Cincinnati city limits. These data can also be viewed at https://www.google.com/maps/d/edit?mid=1oEm033LLFl0KN3wIYVYyjkjUUCmxsF0&usp=sharing
Table S2 contains methane emission rates measured from a subset of natural gas streetlights in Cincinnati. Measurements were made by Dr. Amy Townsend-Small and her students.
Seniors at the University of Cincinnati in the College of Engineering and Applied Science have an opportunity to complete a senior design capstone course. Seniors in the Mechanical Engineering program work with external clients on real industrial problems of practical importance. Selected senior design capstone reports are chosen for publication in Scholar@UC. More information on all senior design reports is at: https://libraries.uc.edu/libraries/ceas/services/senior-design-reports.html.
The overuse of plastic containers in greenhouse and nursery production surpasses the amount being recycled. A solution to this issue involves a shift in the materials used for making containers. Specifically, containers employed for plant growth are single-use due to the higher costs associated with reusing them in production. Due to chemicals used during the growing process recycling containers is challenging. Transitioning to eco-friendly alternatives holds the promise of positively impacting the environment and curbing plastic waste generated in growing containerized plants. This research delves into the types of plastics currently utilized, their purposes, and the recycling processes involved. This is compared to new eco-friendly container options, analyzing their advantages and disadvantages. The significance of this study is exploring potential materials for manufacturing containers in greenhouse and nursery production. The result of this paper finds alternatives to plastic, fostering sustainability and reducing reliance on plastic for containers, thereby contributing to a more sustainable industry.
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