The Role of KRAS in Mechanosensing in Non-Small Cell Lung Cancer

Lung cancer is the number one cause of cancer related death worldwide, with more than 1.6 million fatalities each year. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers, with KRAS being one of the most prevalent oncogenic driver mutations. Therapeutic approaches for KRAS-mutated NSCLC have been extensively explored due to the US National Cancer Institute RAS Initiative, but methods of directly targeting KRAS or downstream effectors, such as MEK, still have poor results. Previous reports have shown that KRAS-mutated NSCLC activate distinct receptor tyrosine kinases (RTKs) depending on the epithelial or mesenchymal state. Epithelial-to-mesenchymal transition (EMT) is known to play a role in the metastasis and poor prognosis of cancer, and is induced by extracellular matrix (ECM) stiffness. Hallmarks of EMT include loss of E-Cadherin and increase in Vimentin. This research investigates the role of KRAS in EMT transition due to increased ECM stiffness in KRAS mutant NSCLC, and how this affects the efficacy of KRAS and MEK inhibition. To understand how KRAS mutations in NSCLC play a role in this stiffness induced EMT, experiments were performed to detect the gene and protein expression of EMT markers, as well as possible sources of mechanosensing, including primary cilia and receptor tyrosine kinases. We hypothesized that KRAS plays a role in activation of mechanosensors and directly correlates to EMT induced by increased mechanical forces. Results show when KRAS was inhibited and there was increased mechanical forces, either from stretch or substrate stiffness, there was a decreased activation of mechanosensors. KRAS inhibition also prevented the cells from undergoing stiffness-induced EMT. This supports our hypothesis that KRAS plays a key role in ECM stiffness induced EMT. Future studies include examining the mechanism behind this phenomenon and in vivo studies

Flower Bouquet

When we started working with flower shapes, we realized we could work with Gestalt\u27s principles of closure, continuation, and proximity. Starting with the concept of a flower vase this demonstrates Gestalt\u27s principle of proximity. Starting with the concept of a flower vase this demonstrates Gestalt\u27s principle of proximity. People group things together when they are close to each other and a flower bouquet is the perfect example of this. The second principle you see in our work is continuation. Continuation is the way our minds sees segments of a line as a continuous line. This is most commonly demonstrated in plaid where we see the lines of a color as one line. In our project this is used on the various flowers such as a circle on the orange flower, and the black and white fabric on the golden flower.https://digitalcommons.liberty.edu/theoryinaction_projects2020/1003/thumbnail.jp

Sensing Movement in Endotracheal Tubes

The objective of this project was to develop a device that would better secure endotracheal tubes (ETT), measure unwanted displacement, and notify caretakers when a dangerous amount of displacement has occurred. The project deliverables were as follows: a detailed design, a prototype, and a final demonstration of the prototype which shows successful ability to carry out the objectives stated above. The device needs to be small in size, expensive, flexible to allow for regular cleaning, yet strong enough to withstand stress. The final design consists of a small bite block holder and head straps to secure the device. The device also contains a sensor that detects voltage changes, which correlates to displacement, and sets off an auditory alarm when the ETT moves out of a pre-determined safety range. The prototype developed includes these attributes and provides an auditory and visual alarm in the event of unwanted ETT displacement. It is made of a flexible, durable, and non-toxic polyurethane material. Testing in the simulation laboratory revealed that the device was able to measure displacement accurately within a range of 2 mm and able to output an alarm when the ETT was moved out of the pre-determined safety range of 20 mm. In conclusion, the final prototype meets the objectives that were meant to be addressed in this project. Future plans include creating a wireless solution to increase portability, adding an exterior antimicrobial coating to decrease bacteria accumulation, and incorporating wall port electrical safety measures to ensure patient safety.https://scholarscompass.vcu.edu/capstone/1072/thumbnail.jp

The effectiveness of mobile app usage in facilitating weight loss: An observational study

Aim: With increasing rates of global obesity and associated health issues, there is an ever‐increasing need for weight management solutions to be more accessible. Mobile applications offer accessible support systems and have the potential to offer a viable and effective weight management solution as an alternative to traditional healthcare models. Objective: To evaluate the effectiveness of the SIMPLE mobile application for time‐restricted eating in achieving weight loss (WL). Methods: User data were analyzed between January 2021 and January 2023. In‐app activity was calculated as the proportion of active days over 12, 26 and 52 weeks. A day is considered active if it contains at least one in‐app action (e.g., logging weight, food, fasting, or physical activity). Users were categorized into four in‐app activity levels: inactive (in‐app activity <33%), medium activity (33%–66%), high activity (66%–99%), and maximal activity (100%). Weight change among in‐app activity groups was assessed at 12, 26, and 52 weeks. Results: Out of 53,482 users, a positive association was found between the use of the SIMPLE app and WL. Active app users lost more weight than their less active counterparts. Active users had a median WL of 4.20%, 5.04%, and 3.86% at 12, 26, and 52 weeks, respectively. A larger percentage of active users—up to 50.26%—achieved clinically significant WL (≥5%) when compared to inactive users. A dose‐response relationship between WL and app usage was found after adjusting for gender, age, and initial Body Mass Index; a 10% increase in app activity correlated with increased WL by 0.43, 0.66 and 0.69 kg at 12, 26, and 52 weeks, respectively. Conclusions: The study demonstrates that the SIMPLE app enables effective WL directly associated with the level of app engagement. Mobile health applications offer an accessible and effective weight management solution and should be considered when supporting adults to lose weight

Developing Effective Advocates during Doctoral Preparation: An Examination of Federal-Level Special Education Policy Internships

It is critically important for leadership personnel in special education to develop knowledge and skills in policy and advocacy. The Pew Charitable Trust initiated a survey to uncover resources and experiences impacting doctoral-level preparation at institutes of higher education. Results indicated that fewer than 30 percent of doctoral students were provided the opportunity for an internship experience. Thus, a large university located in the southeast United States created an internshipexperience reflective of current policies and trends within the field of special education. This article discusses interns’ responsibilities with reference to policy and politics, opportunities for mentorship, the development of personal contacts and networking, and the impact of each experience on the intern’s future role in special education teacher education and advocacy

The BAT AGN Spectroscopic Survey -- XVIII. Searching for Supermassive Black Hole Binaries in the X-rays

Theory predicts that a supermassive black hole binary (SMBHB) could be observed as a luminous active galactic nucleus (AGN) that periodically varies on the order of its orbital timescale. In X-rays, periodic variations could be caused by mechanisms including relativistic Doppler boosting and shocks. Here we present the first systematic search for periodic AGNs using $941$ hard X-ray light curves (14-195 keV) from the first 105 months of the Swift Burst Alert Telescope (BAT) survey (2004-2013). We do not find evidence for periodic AGNs in Swift-BAT, including the previously reported SMBHB candidate MCG+11$-$11$-$032. We find that the null detection is consistent with the combination of the upper-limit binary population in AGNs in our adopted model, their expected periodic variability amplitudes, and the BAT survey characteristics. We have also investigated the detectability of SMBHBs against normal AGN X-ray variability in the context of the eROSITA survey. Under our assumptions of a binary population and the periodic signals they produce which have long periods of hundreds of days, up to $13$% true periodic binaries can be robustly distinguished from normal variable AGNs with the ideal uniform sampling. However, we demonstrate that realistic eROSITA sampling is likely to be insensitive to long-period binaries because longer observing gaps reduce their detectability. In contrast, large observing gaps do not diminish the prospect of detecting binaries of short, few-day periods, as 19% can be successfully recovered, the vast majority of which can be identified by the first half of the survey.Comment: 17 pages, including 8 figures and 4 tables. Accepted for publication in Ap

BAT AGN spectroscopic survey - XV: the high frequency radio cores of ultra-hard X-ray selected AGN

We have conducted 22 GHz radio imaging at 1 arcsec resolution of 100 low-redshift AGN selected at 14–195 keV by the Swift-BAT. We find a radio core detection fraction of 96 per cent, much higher than lower frequency radio surveys. Of the 96 radio-detected AGN, 55 have compact morphologies, 30 have morphologies consistent with nuclear star formation, and 11 have sub-kpc to kpc-scale jets. We find that the total radio power does not distinguish between nuclear star formation and jets as the origin of the radio emission. For 87 objects, we use optical spectroscopy to test whether AGN physical parameters are distinct between radio morphological types. We find that X-ray luminosities tend to be higher if the 22 GHz morphology is jet-like, but find no significant difference in other physical parameters. We find that the relationship between the X-ray and core radio luminosities is consistent with the L_R/L_X ∼ 10⁻⁵ of coronally active stars. We further find that the canonical fundamental planes of black hole activity systematically overpredict our radio luminosities, particularly for objects with star formation morphologies

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The BAT AGN Spectroscopic Survey. XVIII. Searching for Supermassive Black Hole Binaries in X-Rays

Theory predicts that a supermassive black hole binary (SMBHB) could be observed as a luminous active galactic nucleus (AGN) that periodically varies on the order of its orbital timescale. In X-rays, periodic variations could be caused by mechanisms including relativistic Doppler boosting and shocks. Here we present the first systematic search for periodic AGNs using 941 hard X-ray light curves (14–195 keV) from the first 105 months of the Swift Burst Alert Telescope (BAT) survey (2004–2013). We do not find evidence for periodic AGNs in Swift-BAT, including the previously reported SMBHB candidate MCG+11−11−032. We find that the null detection is consistent with the combination of the upper-limit binary population in AGNs in our adopted model, their expected periodic variability amplitudes, and the BAT survey characteristics. We have also investigated the detectability of SMBHBs against normal AGN X-ray variability in the context of the extended ROentgen Survey with an Imaging Telescope Array (eROSITA) survey. Under our assumptions of a binary population and the periodic signals they produce, which have long periods of hundreds of days, up to 13% true periodic binaries can be robustly distinguished from normal variable AGNs with the ideal uniform sampling. However, we demonstrate that realistic eROSITA sampling is likely to be insensitive to long-period binaries because longer observing gaps reduce their detectability. In contrast, large observing gaps do not diminish the prospect of detecting binaries of short, few-day periods, as 19% can be successfully recovered, the vast majority of which can be identified by the first half of the survey