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Rhabdomyosarcoma (RMS) is the most common soft tissue cancer in children. Treatment outcomes, particularly for relapsed/refractory or metastatic disease, have not improved in decades. The current lack of novel therapies and low tumor mutational burden suggest that chimeric antigen receptor (CAR) T-cell therapy could be a promising approach to treating RMS. Previous work identified FGF receptor 4 (FGFR4, CD334) as being specifically upregulated in RMS, making it a candidate target for CAR T cells. We tested the feasibility of an FGFR4-targeted CAR for treating RMS using an NSG mouse with RH30 orthotopic (intramuscular) tumors. The first barrier we noted was that RMS tumors produce a collagen-rich stroma, replete with immunosuppressive myeloid cells, when T-cell therapy is initiated. This stromal response is not seen in tumor-only xenografts. When scFV-based binders were selected from phage display, CARs targeting FGFR4 were not effective until our screening approach was refined to identify binders to the membrane-proximal domain of FGFR4. Having improved the CAR, we devised a pharmacologic strategy to augment CAR T-cell activity by inhibiting the myeloid component of the T-cell-induced tumor stroma. The combined treatment of mice with anti-myeloid polypharmacy (targeting CSF1R, IDO1, iNOS, TGFbeta, PDL1, MIF, and myeloid misdifferentiation) allowed FGFR4 CAR T cells to successfully clear orthotopic RMS tumors, demonstrating that RMS tumors, even with very low copy-number targets, can be targeted by CAR T cells upon reversal of an immunosuppressive microenvironment., (©2022 The Authors; Published by the American Association for Cancer Research.)

Enhanced aquifer recharge (EAR) is defined as any engineered structure or enhanced natural feature designed to convey stormwater, surface water or wastewater directly into an aquifer (e.g. aquifer storage and recovery (ASR) wells) or into the vadose zone eventually percolating to an aquifer (e.g. spreading basins, dry well, etc.; USEPA 2021). Identifying the storage and flow capabilities of complex aquifers can improve the efficacy of many conceptual site models (CSM) for sites considered for ASR projects. In a karst setting, the EAR process may be able to take advantage of natural surficial features and the increased storage capacity of karst aquifers to improve recharge to groundwater. However, the suitability for an EAR project in a karst setting depends on the maturity of the karst and its preceding epikarst. The focus of flow within the epikarst causes enlargement of fractures and karst conduits. Thus, the storage and transmissivity within the karst vary greatly. Electrical resistivity imaging (ERI) is a well-known geophysical tool for mapping fractures and sinkholes, typical in karst settings. Locating enhanced water conveyance structures of a karst aquifer can improve the design and operation of an EAR site. This study investigated the hydraulic connection between shallow and deep groundwater using ERI to identify potential flow pathways and to improve our understanding of the storage mechanisms of the epikarst. The results presented in this paper validate the effectiveness of ERI in characterizing karst/epikarst and delineating soil, bedrock and local faults and fractures in the subsurface., Competing Interests: Conflict of interest statement. Todd Halihan has a financial interest in Aestus, LLC. An approved management plan is on file in OSU’s Office of University Research Compliance.

Use of thinner oxides to improve the operating speed of a complementary metal-oxidesemiconductor (CMOS) device causes serious gate leakage problems. Leakage current of the dielectric analysis method has I-V , C-V , and charge pumping, but the procedure is very complicated. In this premier work, we analyzed the leakage current of metal insulator semiconductor (MIS) capacitors with different initiators through low-frequency noise (LFN) measurement with simplicity and high sensitivity. The LFN measurement results show a correlation between power spectral density ( S IG ) and gate leakage current ( I G ). MIS capacitors of hafnium zirconium silicate (HZS, (HfZrO₄) 1- x (SiO₂) x ) were used for the experiments with varying SiO₂ ratio ( x = 0, 0.1, 0.2) of hafnium zirconium oxide (HZO, HfZrO₄). As the SiO₂ ratio increased, the leakage current decreased according to J-V measurement. Further, the C-V measurement confirmed that the oxide-trapped charge ( N ot ) increased with increasing SiO₂ ratio. Finally, the LFN measurement method revealed that the cause of leakage current reduction was trap density reduction of the insulator.

Restoration and reconnection of floodplain systems provide multiple societal and ecosystem benefits, while providing municipalities the opportunity to attempt alternative approaches to maintain infrastructure protection and function. In some restored floodplains, treated wastewater effluent discharge is redirected over land instead of directly into rivers to allow natural flow and infiltration, to facilitate restoration designs such as levee setback, and to provide additional freshwater to floodplain ecosystems. However, indirect discharge of treated effluent over land may pose risks to surface and groundwater when pollutants like excess nutrients enter the floodplain and undergo transformation. We investigated the consequences for groundwater and surface water quality when effluent was redirected as open water channels over a floodplain surface. In this study, seasonal floodplain nutrient concentrations in groundwater and surface water were observed for more than 5 years as a floodplain and wastewater treatment plant underwent a major restoration project that included river-floodplain reconnection with levee setback and redirection of effluent discharge from a river channel to open flow across the restored floodplain. Nutrient loading to the surrounding floodplain groundwater and surface water was observed, but based on measures of hydrological connectivity, groundwater flow paths, and biogeochemistry, nutrients from the effluent moved within the floodplain with minimal effect to the surrounding floodplain water quality. We did not find evidence of substantial additional processing that could replace advanced nutrient treatment in this system, however we did observe evidence of diverse nutrient processes that may support enhanced retention if treatment channels were designed to enhance these processes. We suggest that indirect discharge of high quality treated effluent in a restored floodplain is a viable alternative to direct discharge into a river when groundwater flow directs that discharge to habitats where minimal nutrient sensitivity is expected.