Life Sciences Commons^™

Structure-Activity Relationship Studies Of Dna Methyltransferase 1 Monovalent Degraders, Chao Qian, Youngeun Lee, Yulin Han, Yue Zhong, Jujun Zhou, Joel Hrit, Ling Xie, Qin Chen, H Ümit Kaniskan, Xian Chen, Scott Rothbart, Xiaodong Cheng, Yan Xiong, Jian Jin

Faculty, Staff and Student Publications

DNA methyltransferase 1 (DNMT1), which catalyzes maintenance methylation of hemimethylated DNA during DNA replication, is overexpressed in cancer. Recently, the first-in-class DNMT1-selective noncovalent small-molecule inhibitors, GSK3484862 and GSK3685032, were discovered. These inhibitors were also reported to degrade DNMT1. However, structure–activity relationship (SAR) studies of these monovalent DNMT1 degraders are lacking. Here, we report our SAR studies of this scaffold on degrading DNMT1, which led to the discovery of multiple lead degraders, including compound 4 (MS9024). Compound 4 potently and selectively degraded DNMT1 in multiple cancer cell lines in a concentration-, time-, and proteasome-dependent manner without altering DNMT1 transcription. Further mechanism-of-action …

Inhibition Of Histone Methyltransferase Ezh2 For Immune Interception Of Colorectal Cancer In Lynch Syndrome, Charles M Bowen, Fahriye Duzagac, Abel Martel-Martel, Laura Reyes-Uribe, Mahira Zaheer, Jacklyn Thompson, Nan Deng, Ria Sinha, Soham Mazumdar, Melissa W Taggart, Abhinav K Jain, Elena Tosti, Winfried Edelmann, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

Colorectal precancers in Lynch syndrome (LS) exhibit a distinct immune profile, presenting unique opportunities for developing immune-interception strategies to prevent carcinogenesis. Epigenetic modulation by EZH2 of immune-related genes is implicated in the carcinogenesis of different cancer types, including colorectal cancer. This study utilizes a mouse model of LS and ex vivo colonic organoids to assess the effects of the EZH2 inhibitor GSK503 on immune regulatory pathways, tumorigenesis, and epigenetic reprogramming. Our findings revealed that GSK503 significantly increased CD4+ and CD8+ T cells in both splenocytes and colonic mucosa of treated mice compared with controls. Additionally, a preventive dose of GSK503 …

The Persian-Period Archaeozoological Finds From Tel Ya‘Oz (Hebrew, Pp. 45*–47*), Moshe Sade

'Atiqot

The archaeozoological finds comprised the bones of domesticated sheep/goat and cattle, and mollusks.

Buildings Of The Persian, Hellenistic And Early Roman Periods At Khirbat Kabar, In The Northern Hebron Hills (Hebrew, Pp. 49*–71*; English Summary, Pp. 205–207), Yuval Baruch

'Atiqot

Two buildings were exposed. The northern building comprised rooms surrounding a central courtyard; the pottery finds from this building date from the Persian period, and chiefly, to the Hellenistic and Early Roman periods (first century BCE). Only two rooms survived of the southern building, which apparently opened to a courtyard. Many storage-jar sherds were found, seemingly in situ. On two of them, Aramaic letters were incised before firing. An Achaemenid-style conical glass seal was unearthed, depicting a hero or a ruler holding flanking lions. This building may have had an administrative or storage function. Three tombs were uncovered in proximity …

Drinking Vessels (Rytha) From Tel Ya‘Oz (Hebrew, Pp. 25*–37*; English Summary, Pp. 203–204), Irit Ziffer, Raz Kletter, Orit Segal

'Atiqot

Three drinking vessels (rytha) were found in the Persian-period building at Tel Ya‘oz: an almost complete human-headed rython and two animal heads, of a ram and a lion. The anthropomorphic rython is undoubtedly the most extraordinary of the three. It is a local adaptation of an Achaemenid vessel that was used at royal banquets. Its Egyptian appearance might suggest that is was created by an Egyptian working on the Levantine coast, or by a Levantine trained in Egyptian iconography.

Petrographic Analysis Of The Persian-Period Ceramic Assemblage From Tel Ya‘Oz (Hebrew, Pp. 39*–44*; English Summary, Pp. 204–205), Amir Gorzalczany

'Atiqot

Thirty-nine samples of Persian-period wares were selected for analysis, and five petrographic groups were identified. The overwhelming majority of the assemblage was of non-local provenance. Several ranges of import were discerned, and it seems that the import-trade-exchange patterns at the site were oriented overseas or toward the Phoenician coast.

A Persian-Period Building From Tel Ya‘Oz (Tell Ghaza) (Hebrew, Pp. 1*–24*; English Summary, P. 203), Orit Segal, Raz Kletter, Irit Ziffer

'Atiqot

Thirty-nine samples of Persian-period wares were selected for analysis, and five petrographic groups were identified. The overwhelming majority of the assemblage was of non-local provenance. Several ranges of import were discerned, and it seems that the import-trade-exchange patterns at the site were oriented overseas or toward the Phoenician coast.

Chemical Study Of Basaltic Hopper-Rubber (Olynthus) Mills From Naḥal Tut And ‘En Hofez (Pp. 197–200), Irena Segal

'Atiqot

Four basalt stones of hopper-rubber (Olynthus) mills were sampled for chemical analysis; two were found at Naḥal Tut and two, from ‘En Hofez. All were dated on the basis of stratigraphy to the second half of the fourth century BCE. The chemical examination established that the millstones from Naḥal Tut were manufactured in the area of Nisyros, in the Aegean region.

Naḥal Tut (Site Viii): A Fortified Storage Depot From The Late Fourth Century Bce (Pp. 131–189), Yardenna Alexandre

'Atiqot

Excavations at the site revealed a large building complex, comprising casemate walls built on bedrock around a large central courtyard with corner towers. It was a well-planned and well-fortified complex, located at a strategic point. The complex was occupied for a brief period of time, at the very end of the Persian (Achaemenid) period and the very beginning of the Hellenistic period (c. 350–325 BCE). It was destroyed by a violent destruction, which claimed human victims. The destruction was dated by a single bronze coin of Alexander III to 336–323 BCE. The pottery finds at the site were homogenous, including …

Petrographic Analysis Of The Pottery From Naḥal Tut (Pp. 191–195), Amir Gorzalczany

'Atiqot

Nine samples of Persian-period wares were selected for analysis. Five petrographic groups were identified, pointing to the presence of local wares, close-range imports from the Carmel shore and long-range imports from the Aegean area or western Cyprus. It seems that the trade or exchange patterns at Naḥal Tut Site VIII were oriented overseas

The Archaeozoological Finds From Tel Mikhal (Tel Michal) (Pp. 121–125), Moshe Sade

'Atiqot

Archaeozoological remains from the Middle Bronze Age and Persian period were discovered in the 1996 excavations at Tel Mikhal.

The Kurkar And Hamra Genesis Of The Northern Hill Of Tel Mikhal (Tel Michal) (Pp. 127–130), Eldad Barzilay

'Atiqot

The geological environment of the site is composed of mobile sand, kurkar, hamra and grumosols (swelling and cracking clay soils) sediments of the Quaternary Hefer formation.

The Flint Tools From Tel Mikhal (Tel Michal) (Pp. 117–119), Hamoudi Khalaily

'Atiqot

The Early Bronze Age is represented at Tel Mikhal by three Canaanean sickle blades and retouched blades, products of the Canaanean industry.

A Lead Amulet Of Nefertem From Tel Mikhal (Tel Michal) (Pp. 109–111), Amir Gorzalczany

'Atiqot

A lead amulet representing the Egyptian god Nefertem (nfrtm) was found at Tel Mikhal, very close to the edge of the northern hill, in a fill over what seems to have been a small circular Persian-period shrine

The Stone Anchor From Tel Mikhal (Tel Michal) (Pp. 113–115), Jacob Sharvit

'Atiqot

The anchor is a triangular shaped flat slab of limestone with rounded corners and one unfinished elliptical hole. It seems to belong to the ‘weight anchors’ group.

Persian-Period Metal Finds From Tel Mikhal (Tel Michal) (Pp. 93–107), Sariel Shalev, Kamil Sari

'Atiqot

More than 100 metal objects dating to the Persian period (fifth–fourth centuries BCE) were unearthed in the excavations at Tel Mikhal. The assemblage included weapons (arrowheads); tools and implements (e.g., knives, needles, nails and tacks); weights; jewelry (bracelets, fibulae, pins and spatulae); a Tanit figurine; and an Egyptian amulet. The arrowheads were of the Irano-Scytic type, made of tin-bronze. All the arrowheads were left as cast, without mechanical treatment. Among the tools and implements, nails form the largest group; they were made of unalloyed copper and tin-bronze. The ten fibulae found at the site were made of tin-bronze; all underwent …

Stamped Amphora Handles From Tel Mikhal (Tel Michal) (Pp. 89–91), Donald T. Ariel

'Atiqot

Three stamped amphora handles were recovered from the excavations at Tel Mikhal. Two are Rhodian, while the third is most likely the handle of a Samian amphora.

Petrographic Analysis Of Two Ballast Stones From Tel Mikhal (Tel Michal) (Pp. 67–69), Amir Gorzalczany

'Atiqot

Both ballast stones were reused in a Persian-period installation. Their analysis revealed that they were of plutonic material, thus pointing to a distant provenance, perhaps in the Cyprus area. The stones were probably loaded on a merchant ship on its way from the eastern Mediterranean to the Tel Mikhal anchorage.

Coins From Tel Mikhal (Tel Michal) (Pp. 71–88), Donald T. Ariel

'Atiqot

Thirty-eight coins were found in the excavation on the Northern Hill at Tel Mikhal, 33 were identified: 18 isolated coins, and 15 coins that formed part of a Persian-period hoard. The isolated coins are mainly of the Persian period, probably deriving from one phase of occupation that began in the second quarter of the fourth century BCE. The war between Ptolemy I and Antigonus possibly marks the end of the Persian stratum. The later numismatic evidence at the site indicates that the Northern Hill may have been occupied only during the Seleucid period. The hoard comprises Athenian-style tetradrachms, dating to …

Petrographic Analysis Of The Tel Mikhal (Tel Michal) Pottery (Pp. 57–65), Amir Gorzalczany

'Atiqot

Thirty-six vessels were submitted for petrographic analysis, most of them from the Persian period and several from Middle Bronze Age II. Several wasters from the kilns were analyzed as well. The results point to a large variety of pottery types in the Persian period, which were divided into three main groups: local products; short- to medium-range distance imports; and long-distance imports. These finds parallel those identified at other southern coastal sites, which show an overwhelming amount of imported pottery.

The Pottery From The Iaa Excavations At Tel Mikhal (Tel Michal) (Pp. 21–56), Lev Arie Kapitaikin

'Atiqot

Three main assemblages were identified in the pottery from the IAA excavations at Tel Mikhal: Persian coarse wares, imported pottery and pottery from three kilns (Area B1). The Persian wares, including mortaria, stands, kraters and jars, date to the later part of the Persian period (450–300 BCE). The imported Persian-period wares include decorated sherds of Cypriot or Eastern Greek origin, Attic pottery and undecorated imported vessels, such as amphorae and mortaria, dating to the last three quarters of the fourth century BCE. The pottery from Kiln 461 includes forms typical of the Persian period and miniature-sized (votive?) Persian-period vessels. Kilns …

The 1996 Excavations Along The Northern Hill At Tel Mikhal (Tel Michal) (Pp. 1–19), Amir Gorzalczany

'Atiqot

Excavations on the Northern Hill at Tel Mikhal revealed rich finds, in stark contrast with the poorly preserved and scant architectural remains. The earliest settlement here dates to prehistoric times, continuing into the Middle Bronze Age, when a ceramic industry operated at the site. In the Iron Age, settlement was sporadic, and mainly winepresses were unearthed. Toward the end of the Persian period, the area functioned as an industrial area for pottery production and a metal industry, as well as an area for storage and commerce. In the Hellenistic period, the site was also used for industry and storage. No …

Modeling The Relationship Between Calories And Activity Metrics: A Regression Analysis With Variable Selection, Felix Yeboah

Data Science and Data Mining

Physical activity monitors have become integral to daily routines, with wearable devices such as the Apple Watch and Fitbit offering continuous data on users’ physical activity. This study compares the measurement accuracy of these devices by examining how they record parameters relevant to fitness and health. Employing multiple linear regression, we modeled the relationship between calories expended and a set of explanatory variables, including heart rate, steps, distance, age, activity level, weight, and device type. Evaluation of all possible variable combinations identified heart rate, steps, distance, weight, and watch type as the most effective predictors of calorie expenditure. Although the …

Effect Of Routine Third Trimester Ultrasounds On Maternal Mental Health In Low-Risk Population In Utah, Claire Z. Zai, Priyanka R. Purohit, Emily M. Snyder, Bryson M. Mcadams, Daniela A. Betancourt-Martinez, Donna O. Van Beuge, Maria N. Easler, Makayla A. Muzinic, Carlos E. Angulo

Annual Research Symposium

Purpose: One in five pregnant women in the United States experience a maternal mental health condition. Within Utah from 2018-2022, during pregnancy, 22.7% of women experienced depression and 31.6% experienced anxiety, and 15.1% experienced postpartum depression. These data represent a prevalence higher than the national average. Third trimester ultrasound (TTUS) is not a standard of care performed in the United States currently. Previous TTUS research has mainly focused on the financial burden and birth outcomes rather than maternal mental health. Literature on first trimester ultrasound has demonstrated a notable impact on maternal mental health, but these outcomes within the third …

Force And Gait Mechanics At Reduced Body Weight On A Lower Body Positive Pressure Treadmill, Julia Paige Phillips, Eesha Gudiseva, Silvio Polly Da Costa Valladao, Thomas Andre

International Journal of Exercise Science

International Journal of Exercise Science 18(7): 239-250, 2025. Lower body positive pressure treadmills (LBPPT) have gained increasing attention due to their potential applications in sports training, rehabilitation, and biomechanics research. However, there is limited understanding of how differing body weight percentages influence gait and force production. This study aimed to investigate the relationship between force and gait parameters at different body weight percentages on a LBPPT. Twenty-seven healthy participants completed a series of walking, jogging, and running trials at three different body weight conditions: 100%, 90%, and 75%. Gait parameters, including cadence, stride length, stance time, and ground reaction force, …

Clinical Importance Of Phenytoin Monitoring To Reduce Phenytoin-Related Toxicity In Saudi Patients With Epilepsy, Ghidaa Alwaf, Hussam Younis, Mohammed Al-Hartani, Alaa H. Falemban, Et.Al.

Saudi Toxicology Journal

Background: Phenytoin toxicity can result from overdose, dosage changes, drug interac-tions, or physiological alterations. Symptoms range from nausea and confusion to severe cases involving coma and seizures, though fatalities are rare. To date, no literature has been found concerning phenytoin monitoring in Saudi epileptic patients. This study is the first to inves-tigate phenytoin monitoring for toxicity prevention, optimal dosing, and adverse effect management in Saudi epileptic patients. Methods: A two-month, randomized, open-label, prospective monitoring study was conducted in Saudi epileptic patients treated with phen-ytoin. The patients (n=40) were subdivided into two groups (monitored and unmonitored) to check the prevalence of …

The Employer/Employee Relationship: It’S More Than Just Hiring, Cheryl A. Burkhart-Kriesel

Cornhusker Economics

For some businesses this year, they may be thinking about hiring one or more new employees. This is a big decision. Initially, they may be thinking, “Can this business support another employee?” That could be the easy question. The harder questions could be, “How do I find a good employee, and then what do I need to do to retain them?”

These questions are at the top of the minds of businesses all across the country right now. The workplace environment is subtly changing with current trends impacting both employees and employers. In a recently published article by the …

Contribution Of Rare Chromosome 22q112 Copy Number Variants To Non-Syndromic Bicuspid Aortic Valve, Helene Digregorio, Sara Mansoorshahi, Steven G Carlisle, Catherina Tovar Pensa, Abi Watts, Courtney Mcneely, Anna Sabate-Rotes, Anji Yetman, Hector I Michelena, Julie F A De Backer, Laura Muiño Mosquera, Malenka M Bissell, Maria Grazia Andreassi, Ilenia Foffa, Dawn S Hui, Anthony Caffarelli, Yuli Y Kim, Rodolfo Citro, Margot De Marco, Justin T Tretter, Kim L Mcbride, Simon C Body, Dianna M Milewicz, Siddharth K Prakash, Ebav Investigators

Faculty, Staff and Student Publications

Background: Bicuspid aortic valve (BAV) is the most common congenital heart defect in adults, often leading to complications such as thoracic aortic aneurysms and aortic stenosis. While BAV is frequently associated with 22q11.2 deletion syndrome (22q11.2DS), the contribution of rare copy number variants (CNVs) in this region to non-syndromic BAV is less clear. This study is aimed to assess the role of rare 22q11.2 CNVs in patients with early-onset BAV (EBAV) and to determine whether these variants are linked to an increased risk of complications.

Methods: Whole genome microarray genotyping was conducted on 272 patients with BAV with early onset …

Efficacy And Safety Of Nivolumab Plus Ipilimumab In Patients With Metastatic Variant Histology (Non-Clear Cell) Renal Cell Carcinoma, Mohammad Jad Moussa, Jaanki Khandelwal, Nathaniel R Wilson, Kiran L Malikayil, Devaki Shilpa Surasi, Tharakeswara K Bathala, Yiyun Lin, Priya Rao, Pheroze Tamboli, Kanishka Sircar, Helen Ajufo, Khaled M Elsayes, Amishi Shah, Andrew C Johns, Sangeeta Goswami, Elshad Hasanov, Eric Jonasch, Pavlos Msaouel, Matthew T Campbell, Omar Alhalabi, Nizar M Tannir

Faculty, Staff and Student Publications

Background: Nivolumab plus ipilimumab (nivo/ipi) is a standard of care first-line (1 L) therapy for patients with metastatic clear-cell renal cell carcinoma (ccRCC), but its role in patients with metastatic, non-ccRCC has not been fully defined. We report a single-institution experience with nivo/ipi in non-ccRCC.

Methods: Between November 2017 and February 2024, 55 patients with metastatic non-ccRCC received nivo/ipi at MD Anderson Cancer Center. The tumor response was assessed by blinded radiologists using RECIST v1.1. The overall response rate (ORR), progression-free survival (PFS), PFS milestone, duration of response (DoR), and overall survival (OS) were determined. Next-generation sequencing (NGS) was performed …

A Comparison Between The Traditional And Novel Isometric Mid-Thigh Methods And The Relationship To Countermovement Jump Performance, Meir Magal, Jay R. Hoffman, Matan Amitay

International Journal of Exercise Science

International Journal of Exercise Science 18(3): 226-238, 2025. The isometric mid-thigh pull (IMTP) test using the traditional bar grip (BAR) is a reliable and effective measure of strength performance in different populations. In addition, IMTP performance has been linked to jump performance. Recent research has shown that the pelvic belt (PEL) IMTP method produces higher absolute and relative peak force values than the Bar IMTP method. However, limited scientific data has examined the PEL IMTP method performance data and its relationship to dynamic strength and sports performance. The study aimed to provide a more robust comparison between the BAR and …