Engineering topics

Young, K. S.

Publications and source records attributed to Young, K. S..

4 records

DOE OSTI2022

Unconventional isoquinoline-based SERMs elicit fulvestrant-like transcriptional programs in ER+ breast cancer cells

Estrogen receptor alpha (ERα) is a ligand-dependent master transcriptional regulator and key driver of breast cancer pathology. Small molecule hormones and competitive antagonists favor unique ERα conformational ensembles that elicit ligand-specific transcriptional programs in breast cancer and other hormone-responsive tissues. By affecting disparate ligand binding domain structural features, unconventional ligand scaffolds can redirect ERα genomic binding patterns to engage novel therapeutic transcriptional programs. To improve our understanding of these ERα structure-transcriptional relationships, we develop a series of chemically unconventional antagonists based on the antiestrogens elacestrant and lasofoxifene. High-resolution x-ray co-crystal structures show that these molecules affect both classical and unique structural motifs within the ERα ligand binding pocket. They show moderately reduced antagonistic potencies on ERα genomic activities but are effective anti-proliferative agents in luminal breast cancer cells. Interestingly, they favor a 4-hydroxytamoxifen-like accumulation of ERα in breast cancer cells but lack uterotrophic activities in an endometrial cell line. Importantly, RNA sequencing shows that the lead molecules engage transcriptional pathways similar to the selective estrogen receptor degrader fulvestrant. This advance shows that fulvestrant-like genomic activities can be achieved without affecting ERα accumulation in breast cancer cells.

60 APPLIED LIFE SCIENCES↗

NASA NTRS2016

Quantification of ln-Flight Physical Changes: Anthropometry and Neutral Body Posture

Currently, NASA does not have sufficient in-flight anthropometric data to assess the impact of changes in body shape and size. For developing future planetary and reduced-gravity suits, NASA needs to quantify the impacts of microgravity on anthropometry and body posture to ensure optimal crew performance, fit, and comfort. To obtain data on these changes, circumference, length, height, breadth, and depth for body segments (chest, waist, bicep, thigh, calf) from astronauts for preflight, in-flight, and post-flight conditions needs to be collected. Once these data have been collected, pre-flight, in-flight, and post-flight anthropometric values will be compared, yielding microgravity factors. The neutral body posture (NBP) will also be measured, to determine body posture (joint angle) changes between subjects throughout the duration of a mission. Data collection, starting with Increments 37/38, is still in progress but has been completed for 6 out of 9 subjects. NASA suit engineers and NASA's Extravehicular Activity (EVA) Project Office have identified that suit fit in microgravity could become an issue. It has been noted that crewmembers often need to adjust their suit sizing once they are in orbit. This adjustment could be due to microgravity effects on anthropometry and postural changes, and is necessary to ensure optimal crew performance, fit, and comfort in space. To date, the only data collected to determine the effects of microgravity on physical human changes were collected during Skylab 4, the Apollo-Soyuz Test Project (ASTP), Space Shuttle mission STS-57, and a recent HRP study on seated height changes due to spinal elongation (Spinal Elongation, Master Task List [MTL] #221). The Skylab 4, ASTP, and the STS-57 studies found that, according to photographs, a distinct NBP exists. The still photographs showed a distinguishable posture with the arms raised and the shoulders abducted; in addition, the knees are flexed, with noticeable hip flexion, and the foot is plantar flexed [1,2]. This combination is considered to be the standard set of body joint angles for an NBP in microgravity. A recent simulated microgravity NBP study [3] showed individual variability and inconsistencies in defining NBP. This variation may be influenced by spinal growth, and other potential anthropometry factors such as spinal curvature, age, and gender. Data on the variation of this posture data is required for all kinds of space device designs (such as suits, habitat, and mobility aids). The method proposed in this study considers the dynamic nature of body movement and will use a measurement technique to continually monitor posture and develop a probability likelihood of the neutral posture and how the NBP postures are affected by anthropometry. Additionally, Skylab studies found that crewmembers experienced a stature growth of up to 3 percent. The data included 3 crewmembers and showed that a biphasic stature growth occurs once the crewmember enters into weightlessness. However, the HRP Spinal Elongation study showed that crewmembers could experience about a 6 percent growth in seated height and a 3 percent stature growth, when exposed to microgravity. The results of that study prove that not all anthropometric measurements have the same microgravity percent growth factor. For EVA and suit engineers to properly update the sizing protocol for microgravity, they need additional anthropometric data from space missions. Hence, this study is aimed at gathering additional in-flight anthropometric measurements, such as length, depth, breadth, and circumference, to determine the changes to body shape and size caused by microgravity effects. It is anticipated that by recording the potential changes to body shape and size, NASA will develop a better suit sizing protocol for the International Space Station and other space missions. In essence, this study will help NASA quantify the impacts of microgravity on anthropometry to ensure optimal crew performance, fit, and comfort. This study will use standard anthropometry data collection techniques, 3D laser scanning, digital still photography, and video data, and perform photogrammetric analyses to determine the changes that occur to the body shape and size, and to NBP, when the human body is exposed to a microgravity environment.

Young, K. S.↗

NASA NTRS2014

Quantification of In-flight Physical Changes: Anthropometry and Neutral Body Posture

Currently, NASA does not have sufficient in-flight anthropometric data gathered to assess the impact of physical body shape and size changes on suit sizing. For developing future planetary and reduced gravity suits, NASA needs to quantify the impacts of microgravity on anthropometry, body posture, and neutral body postures (NBP) to ensure optimal crew performance, fit, and comfort. To obtain these impacts, anthropometric data, circumference, length, height, breadth, and depth for body segments (i.e. chest, waist, bicep, thigh, calf) from astronauts for pre, in-, and postflight conditions needs to be collected. Once this data has been collected, a comparison between pre, in-, and postflight anthropometric values will be analyzed, yielding microgravity factors. The NBP will be used to determined body posture (joint angle) changes between subjects throughout the duration of a mission. Data collection, starting with Increments 37/38, is still in progress with the completion of 3 out of 12 subjects. NASA suit engineers and NASA's Extravehicular Activity (EVA) Project Office have identified that suit fit in microgravity could become an issue. It has been noted that crewmembers often need to adjust their suit sizing once they are in orbit. This adjustment could be due to microgravity effects on anthropometry and postural changes, and is necessary to ensure optimal crew performance, fit, and comfort in space. To date, the only data collected to determine the effects of microgravity on physical human changes have been during Skylab, STS-57, and a recent HRP study on seated height changes due to spinal elongation (Spinal Elongation, Master Task List [MTL] #221). The Skylab and the STS-57 studies found that there is a distinct neutral body posture (NBP) based on photographs. The still photographs showed that there is a distinguishable posture with the arms raised and the shoulder abducted; and, in addition, the knees were flexed with noticeable hip flexion and the foot plantar flexed [1,2]. This is the one standard set of body joint angles for a NBP in microgravity. A recent simulated microgravity NBP study [3] has shown an individual variability and inconsistencies in defining NBP. This variation may be influenced by spinal growth, the type of suit fit, and other potential anthropometry factors such as spinal curvature, age, and gender. The variation aspect of this essential data is required for all kinds of space device designs (e.g. suits, habitat, mobility aids, etc.). The method proposed considers the dynamic nature of body movement and will use a measurement technique to continually monitor posture and develop a probability likelihood of the natural posture and how the NBP postures are affected by anthropometry. Additionally, Skylab studies found that crewmembers experienced a stature growth of up to 3%. The data included 3 crewmembers that showed that there is a bi-phasic stature growth once the crew enters into weightlessness. However, the Spinal Elongation study identified that the crewmembers could experience about a 6% growth in seated height and a 3% stature growth, when exposed to microgravity. The results prove that not all anthropometric measurements have the same microgravity percent growth factor. For EVA and suit engineers to properly update the sizing protocol for microgravity, they need additional anthropometric data from space missions. Hence, this study is aimed to gather additional in-flight anthropometric measurements, such as length, depth, breadth, and circumference, to determine the changes to body shape and size due to microgravity effects. It is anticipated that by recording the potential changes to body shape and size, a better suit sizing protocol will be developed for ISS and other space missions. In essence, this study will help NASA quantify the impacts of microgravity on anthropometry to ensure optimal crew performance, fit, and comfort. This study will use simplistic data collection techniques, 3D laser scanning, digital still, and video data, and perform photogrammetric analyses to determine the changes that occur to the body shape, size, and NBP when exposed to a microgravity environment.

Young, K. S.↗

NASA NTRS2011

The Effects of Microgravity on Seated Height (Spinal Elongation)

ABSTRACT Many physiological factors, such as spinal elongation, fluid shifts, bone atrophy, and muscle loss, occur during an exposure to a microgravity environment. Spinal elongation is just one of the factors that can also affect the safety and performance of a crewmember while in space. Spinal elongation occurs due to the lack of gravity/compression on the spinal column. This allows for the straightening of the natural spinal curve. There is a possible fluid shift in the inter-vertebral disks that may also result in changes in height. This study aims at collecting the overall change in seated height for crewmembers exposed to a microgravity environment. During previous Programs, Apollo-Soyuz Test Project (ASTP) and Skylab, spinal elongation data was collected from a small number of subjects in a standing posture but were limited in scope. Data from these studies indicated a quick increase in stature during the first few days of weightlessness, after which stature growth reached a plateau resulting in up to a 3% increase of the original measurement [1-5]. However, this data was collected only for crewmembers in standing posture and not in a seated posture. Seated height may have a different effect than standing height due to a change in posture as well as due to a compounded effect of wearing restraints and a potential compression of the gluteal area. Seated height was deemed as a critical measurement in the design of the Constellation Program s (CxP) Crew Exploration Vehicle (CEV), called Orion which is now the point-of-departure vehicle for the Multi-Purpose Crew Vehicle (MPCV) Program; therefore a better understanding of the effects of microgravity on seated height is necessary. Potential changes in seated height that may not have impacted crew accommodation in previous Programs will have significant effects on crew accommodation due to the layout of seats in the Orion.. The current and existing configuration is such that the four crewmembers are stacked two by two with the commander and pilot seats on the top and the two remaining seats underneath, thereby limiting the amount of clearance for the crewmembers seated in the bottom seat. The inner mold line of these types of vehicles are fixed due to other design constraints; therefore, it is essential that all seats incorporate additional clearance to account for adequate spinal growth thereby ensuring that the crew can safely ingress the seat and be strapped in prior to its return to earth. If there is not enough clearance to account for spinal growth deltas between seats then there is the potential that crewmembers will not be able to comfortably and safely fit into their seats. The crewmember in the bottom stacked seat may even have negative clearance with the seat above him or her which could lead to potential ingress/egress issues or potentially injury of the crewmember during landing. These impacts are specific to these types of vehicles with stacked seat configuration. Without proper knowledge of the amount of spinal elongation, or growth, which occurs due to microgravity and space flight, the design of future vehicle(s) or suits may cause injury, discomfort, and limit crew accommodation and crew complements. The experiment primarily aimed to collect seated height data for subjects exposed to microgravity environments, and feed new information regarding the effect of elongation of the spine forward into the design of the Orion. The data collected during the experiment included, two seated height measurement and two digital pictures of seated height pre-, in-, and post-flight. In addition to seated height, crewmembers had an optional task of collecting stature , standing height. Seated height data was obtained from 29 crewmembers that included 8 ISS increment crew (2 females and 6 males) and 21 Shuttle crew (1 female, 20 males), and whose mean age was 48 years ( 4 years). This study utilized the last six Shuttle flights, STS-128 to STS-134. The results show that partipating crewmembers experienced growth up to 6% in seated height and up to 3% in stature. Based on the worst case statistical analysis of the subject data, the recommended seated height growth of 6% will be provided to the designers as the necessary seated height adjustment.

Young, K. S.↗