The pressure distribution at the ballast–tie interface of conventional railroad track plays a key role in overall track support. Loads exceeding the strength of the ballast or tie can contribute to degradation of track quality. In this study, matrix-based tactile surface sensors (MBTSS) were used to study the load distribution at the ballast–tie interface. MBTSS allows for fine-scale pressure distributions to be measured unobtrusively and in a dynamic load environment. In this application, the loads imparted by individual ballast particles can be measured. Laboratory ballast box testing and in-track testing were conducted at the Transportation Technology Center. Ballast gradation at the interface was varied for both laboratory and in-track testing. Laboratory results indicated that under nominal heavy axle loads, average peak ballast–tie pressures ranged from 284 psi (1,960 kPa) on sand to 1,450 psi (10,000 kPa) on new ballast. In-track testing found that six of the 10 ties tested showed higher pressures adjacent to the rail and not directly underneath it. In both cases, the contact area was shown to increase under an increasing applied load, in part because of additional ballast particles being engaged as the tie deflects. The high peak pressures observed in the laboratory and the variability of pressure distribution along the tie observed in-track significantly varied from the ballast–tie pressure distribution recommended by the American Railway Engineering and Maintenance-of-Way Association's Manual for Railway Engineering. Ballast–tie interface characterization has implications for tie structural design, ballast degradation, and under-tie pad design.

One of the more critical failure modes of concrete crossties in North America is the degradation of the concrete surface at the crosstie rail seat, also known as rail seat deterioration (RSD). Loss of material beneath the rail can lead to wide gage, cant deficiency, reduced clamping force of the fastening system, and an increased risk of rail rollover. Previous research conducted at the University of Illinois at Urbana–Champaign (UIUC) identified five primary failure mechanisms associated with RSD: abrasion, crushing, freeze–thaw damage, hydroabrasive erosion, and hydraulic pressure cracking. Because the magnitude and distribution of load applied to the rail seat affects four of these five failure mechanisms, effectively addressing RSD requires an understanding of the factors affecting rail seat load distribution. As part of a larger study aimed at improving concrete crossties and fastening systems, UIUC researchers are attempting to characterize the loading environment at the rail seat by using matrix-based tactile surface sensors (MBTSS). This instrumentation technology has been implemented in both laboratory and field environments and has provided valuable insight into the distribution of a single load over consecutive crossties. This paper focuses on the analysis of data gathered from MBTSS experiments designed to explore the effect of manufactured RSD on the load distribution and pressure magnitude at the rail seat. The knowledge gained from these experiments will be integrated with associated research conducted at UIUC to form the framework for a mechanistic design approach for concrete crossties and fastening systems.

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The primary purpose of our work was to characterize the effects of the nuclear receptor TLX (NR2E1) in triple-negative breast cancer (TNBC) in order to evaluate its potential therapeutic value in a subtype of breast cancer that has proven particularly challenging to treat, primarily due to the lack of targeted modes of intervention. Unfortunately, breast cancer continues to be the second deadliest form of cancer among women in the United States. Considering the substantial public health implications, development of new therapeutic strategies for highly aggressive breast cancer subtypes, such as TNBC, is imperative. While the function of nuclear receptors such as the estrogen and androgen receptors has been extensively characterized in cancers of the breast and prostate respectively, due in part to their amenable nature to ligand modulation, it is likely that other nuclear receptors may represent therapeutic targets for these malignancies. Indeed, probing of available clinical datasets demonstrated that nuclear receptor TLX is most highly expressed in basal and estrogen receptor (ER)-negative breast cancer patients, and that ER-negative patients with higher TLX expression had increased relapse-free and overall survival. Therefore, we hypothesized that TLX could influence the pathophysiology of TNBC. Utilizing a stable overexpression model in the TNBC cell lines, MDA-MB-231 and MDA-MB-468, we have shown that TLX can inhibit critical oncogenic properties in the in vitro setting, including proliferation, migration and invasion. Furthermore, xenograft and lung colonization studies demonstrated that TLX continued to exert anti-oncogenic effects in the in vivo environment. In agreement with these results, transcriptomic analysis of TLX-overexpressing cells and xenograft tumors showed that TLX can regulate genes and pathways that are known to play crucial roles in the growth and metastatic dissemination of cancer. As previously published works have identified several putative TLX ligands, our findings demonstrating that TLX functions as an anti-cancer factor in TNBC provides a strong rationale for future research aimed at therapeutically targeting this nuclear receptor. Citation Format: Adam T. Nelczyk, Hashni E. Vidana Gamage, Liqian Ma, Michael T. McHenry, Madeline A. Henn, Mohammed Kadiri, Yu Wang, Anasuya Das Gupta, Natalia Krawczynska, Sisi He, Michael J. Spinella, Erik R. Nelson. Nuclear receptor TLX inhibits cancer cell intrinsic properties required for triple-negative breast cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 820.