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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records

HPRT promotes proliferation and metastasis in head and neck squamous cell carcinoma through direct interaction with STAT3

Highlights: • The higher expression of HPRT in HNSCC tissue was related to poor prognosis of patients. • Overexpression of HPRT increased the gene expression of epithelial mesenchymal transition markers. • HPRT directly interacted with STAT3. • Knocking down HPRT significantly decreased tumour growth and enhanced the anticancer effect against HNSCC xenografts. Increasing effort has been put into finding novel molecular pathways to improve the efficiency of EGFR inhibitors against head and neck squamous cell cancer (HNSCC). In this study, we performed data mining and bioinformatically analysed RNA-Seq data downloaded from TCGA and confirmed that higher expression of HPRT in HNSCC tissue was related to poor prognosis of patients. Then, we conducted in vitro and in vivo loss- and gain-of-function experiments to demonstrate the role of HPRT in HNSCC cell lines. Overexpression of HPRT increased the gene expression of epithelial mesenchymal transition markers via direct interaction with STAT3. Knocking down HPRT significantly decreased tumour growth and enhanced the anticancer effect of EGFR inhibitors against HNSCC xenografts. In conclusion, HPRT is a binding partner of STAT3 that promotes EMT and proliferation. Our findings support HPRT as a promising prognostic indicator and potential therapeutic target for HNSCC.

60 APPLIED LIFE SCIENCES↗

Neck Muscle Coactivation Response to Varied Levels of Mental Workload During Simulated Flight Tasks

Objective To evaluate neck muscle coactivation across different levels of mental workload during simulated flight tasks. Background Neck pain (NP) is highly prevalent among military aviators. Given the complex nature within the flight environment, mental workload may be a risk factor for NP. This may induce higher levels of neck muscle coactivity, which over time may accelerate fatigue, increase neck discomfort, and affect flight task performance. Method Three counterbalanced mental workload conditions represented by simulated flight tasks modulated by interstimulus frequency and complexity were investigated using the Modifiable Multitasking Environment (ModME). The primary measure was a neck coactivation index to describe the neuromuscular effort of the neck muscles as a system. Additional measures included perceived workload (NASA TLX), subjective discomfort, and task performance. Participants ( n = 60; 30M, 30F) performed three test conditions over 1 hr each while seated in a simulated seating environment. Results Neck coactivation indices (CoA) and subjective neck discomfort corresponded with increasing level of mental workload. Average CoAs for low, medium, and high workloads were: .0278(SD = .0232), .0286(SD = .0231), and .0295(SD = .0228), respectively. NASA TLX mental, temporal, effort, and overall scores also increased with the level of mental workload assigned. For ModME task performance, the overall performance score, monitoring accuracy, and resource management accuracy decreased while reaction times increased with the increasing level of mental workload. Communication accuracy was lowest with the low mental workload but had higher reaction times relative to increasing workload. Conclusion Mental workload affects neck muscle coactivation during combinations of simulated flight tasks within a simulated helicopter seating environment. Application The results of this study provide insights into the physical response to mental workload. With increasing multisensory modalities within the work environment, these insights may assist the consideration of physical effects from cognitive factors.

Behavioral Sciences↗

Viscoelastic necking dynamics between attractive microgels

Hypothesis: Microgels can deform and interpenetrate and display colloid/polymer duality. The effective interaction of microgels in the collapsed state is governed by the interplay of polymer–solvent interfacial tension and bulk elasticity. A connecting neck is shown to mediate microgel interaction, but its temporal evolution has not been addressed. Here we hypothesize that the necking dynamics of attractive microgels exhibits liquid-like or solid-like behavior over different time and length scales. Experiments: We simulate the merging and pinching of attractive microgels with different crosslinking densities in explicit solvent using dissipative particle dynamics. The temporal coalescence dynamics of microgels is investigated and compared with simple liquid and polymeric droplets. We model the neck growth on long time scales using Maxwell model of polymer relaxation and compare the theoretical prediction with simulation data. The mechanical strength of the neck is characterized systematically via simulated pinch-off of microgels by steered molecular dynamics. Findings: We evidence a crossover in the coalescence dynamics reflecting the viscoelastic signature of microgels. In contrast to the common knowledge that viscoelastic materials respond elastically on short time scales, the early expansion of the microgel neck exhibits a linear behavior, similar to the viscous coalescence of liquid droplets. However, the late regime with arrested dynamics resembles sintering of solid particles. Through an analytical model relating microgel dynamics to neck growth, we show that the long-term behavior is governed by stress relaxation of the polymers in the neck region and predict an exponential decay in the rate of growth, which agrees favorably with the simulation. Different from coalescence, the thread thinning in microgel breakup primarily highlights its polymeric characteristics.

42 ENGINEERING↗

A macro-micro approach for identifying crystal plasticity parameters for necking and failure in nickel-based alloy haynes 282

Here, this work develops a two-scales macro-micro approach to address the challenge in calibrating crystal plasticity microstructural models when samples undergo necking prior to fracture. The crystal plasticity models are crucial for predicting the materials’ plastic deformation and failure at the microstructure level, identifying the materials’ intrinsic properties as well as investigating the microstructure-properties relationships. However, after necking occurs, the experimentally measured stress-strain curves fail to reflect the materials ‘true’ stress-strain behavior and cannot be directly fitted into crystal plasticity models. The proposed macro-micro approach employs a top-down strategy to address this challenge, which has been studied with experimental tests on precipitation-strengthened Ni-based superalloy Haynes® 282®. In this approach, a macro rate-dependent anisotropic plasticity model with Voce-type hardening and Rice-Tracey damage law is first utilized to model the deformation and failure of the tensile bar, and calibrated by matching the stress-strain curves, necking strain, and reduction of area. Especially, to match the testing results under different applied strain rates, the rate-sensitivity parameter m and saturation stress in the elasticity model are modified to incorporate dependence on the local strain rate. Then, the ‘true’ stress-strain behaviors are extracted from the necking zone of the macro-model, which are used to calibrate a micro-model with explicit microstructures and governed by an extended crystal plasticity law. The consistency between the micro-model and macro-model are enforced during calibration. The calibration outcomes from the crystal plasticity model elucidate the materials intrinsic properties for slip, hardening, and failure, which is vital for further investigations into the microstructure-properties relationship and for accurate prediction of the material behavior under various test and service conditions.

36 MATERIALS SCIENCE↗

Refinement and Validation of the Head and Neck Lymphedema and Fibrosis Symptom Inventory

Lymphedema and fibrosis (LEF) are common yet overlooked late effects of head and neck cancer and its therapy. Lack of reliable and valid measures of head and neck LEF is a critical barrier to the timely identification and management of head and neck LEF. To fill this gap, we developed and pilot tested a 64-item patient-reported outcome measure ( Lymphedema Symptom Intensity and Distress Survey-Head and Neck, LSIDS-H&N). This article aims to report the process of further validation and refinement of the tool.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Neck Rupture and Scission Neutrons in Nuclear Fission

Just before a nucleus undergoes fission, a neck is formed between the emerging fission fragments. It is widely accepted that this neck undergoes a rather violent rupture, despite the absence of unambiguous experimental evidence. The main difficulty in addressing the neck rupture and saddle-to-scission stages of fission is that both are highly nonequilibrium processes. Here, we present the first fully microscopic characterization of the scission mechanism, along with the spectrum and the spatial distribution of scission neutrons (SNs), and some upper limit estimates for the emission of charged particles. The spectrum of SNs has a distinct angular distribution, with neutrons emitted in roughly equal numbers in the equatorial plane and along the fission axis. They carry an average energy around 3±0.5 MeV for the fission of 236 U, 240 Pu, and 252 Cf, and a maximum of 16–18 MeV. We estimate a conservative lower bound of 9%–14% of the total emitted neutrons are produced at scission.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Exploring the Interaction Between Head-Supported Mass, Posture, and Visual Stress on Neck Muscle Activation

Objective Assess neck muscle activity for varying interactions between helmet, posture, and visual stress in a simulated “helo-hunch” posture. Background Military aviators frequently report neck pain (NP). Risk factors for NP include head-supported mass, awkward postures, and mental workload. Interactions between these factors could induce constant low-level muscle activation during helicopter flight and better explain instances of NP. Method Interactions between physical loading (helmet doffed/donned), posture (symmetric/asymmetric), and visual stress (low/high contrast) were studied through neck muscle electromyography (EMG), head kinematics, subjective discomfort, perceived workload, and task performance. Subjects ( n = 16) performed eight 30-min test conditions (varied physical loading, posture, and visual stress) while performing a simple task in a simulated “helo-hunch” seating environment. Results Conditions with a helmet donned had fewer EMG median frequency cycles (which infer motor unit rotation for rest/recovery, where more cycles are better) in the left cervical extensor and left sternocleidomastoid. Asymmetric posture (to the right) resulted in higher normalized EMG activity in the right cervical extensor and left sternocleidomastoid and resulted in less lateral bending compared with neutral across all conditions. Conditions with high visual stress also resulted in fewer EMG cycles in the right cervical extensor. Conclusion A complex interaction exists between the physical load of the helmet, postural stress from awkward postures, and visual stress within a simulated “helo-hunch” seating environment. Application These results provide insight into how visual factors influence biomechanical loading. Such insights may assist future studies in designing short-term administrative controls and long-term engineering controls.

Behavioral Sciences↗

Agent-based modeling to evaluate the effects of harvesting biomass and hunting on ring-necked pheasant ( Phasianus colchicus ) populations

As the US strives to divest from fossil fuels, dedicated energy crops have increased in popularity because of their potential to serve as a renewable source of transportation fuel and biomass-generated electricity. Whereas the impacts of crop agriculture on biodiversity have been well-documented, less is known about the potential impacts that growing bioenergy crops could have on wildlife. Here we look specifically at the ring-necked pheasant (Phasianus colchicus) and how pheasant populations may be influenced by growing and harvesting bioenergy crops. We explored effects of temporal harvest strategies at the field scale on biomass yield and pheasant population size. To investigate, we developed an agent-based model (ABM) that simulates ring-necked pheasants, tractors, hunters, and vegetation classes. One such vegetation class is land that is enrolled in a Conservation Reserve Program (CRP) plan specifically targeting pheasant conservation. Using this ABM, we assessed four different landscapes—corn-dominated, CRP-dominated, grassland-dominated, and mixed landscape—under strategies that varied the time of harvest. We also used ecological valuation to compare scenario outcomes from an economic perspective. We determined that biomass yield and pheasant population size were sensitive to harvesting times. Our scenarios totaled between ~$931,000 (minimum) and $3.8 million (maximum) over all landscapes, though on average harvesting in late spring generated the most value ($2.45 million) and harvesting in fall was a close second in terms of profitability ($2.39 million).

59 BASIC BIOLOGICAL SCIENCES↗

Risk and incidence of head and neck cancers in veterans living with HIV and matched HIV‐negative veterans

Background Persons living with HIV/AIDS have a higher incidence of virus‐related and tobacco/alcohol‐related cancers. This study is the first to estimate the effect of HIV versus HIV‐negative veterans on the risk of head and neck squamous cell carcinoma incidence in a large retrospective cohort study. Methods The authors constructed a retrospective cohort study using patient data from 1999 to 2016 from the National Veterans Administration Corporate Data Warehouse and the VA Central Cancer Registry. This cohort study included 45,052 veterans living with HIV/AIDS and 162,486 HIV‐negative patients matched by age, sex, and index visit (i.e., HIV diagnosis date or clinic visit date). The age‐standardized incidence rates and estimated adjusted hazard ratios were calculated with a Cox proportional hazards regression for oropharyngeal and nonoropharyngeal head and neck cancer squamous cell carcinoma (HNSCC). The authors also abstracted human papillomavirus (HPV) status from oropharyngeal HNSCC diagnosed after 2010. Results Veterans living with HIV/AIDS (VLWH) have 1.71 (95% confidence interval [CI], 1.36, 2.14) times the risk of oropharyngeal cancer and 2.06 (95% CI, 1.76, 2.42) times the hazard of nonoropharyngeal cancer compared with HIV‐negative veterans. VLWH with oropharyngeal squamous cell carcinoma (OPSCC) were more likely to be HPV‐positive ( N = 30 [81.1%]) than the HIV‐negative veterans with OPSCC ( N = 50 [67.6%]), although this difference was not significant ( p = .135). For nonoropharyngeal cancer, the increased risk of oral cavity cancer among VLWH drove the increased risk. Conclusions The study results suggest that HIV may play a role in virally mediated and nonvirally mediated HNSCC. As the HIV prevalence rises in the United States due to better survival and the incidence of HPV‐positive oropharyngeal HNSCC increases, the interaction between HPV and HIV becomes increasingly relevant.

Mazul, Angela L.↗

Health-Related Quality of Life Outcomes in Head and Neck Cancer: Results From a Prospective, Real-World Data Study With Brazilian Patients Treated With Intensity Modulated Radiation Therapy, Conformal and Conventional Radiation Techniques

To compare global health-related quality of life (HRQoL) and overall survival (OS) in patients with head and neck cancer treated with intensity modulated radiation therapy (IMRT), conformal radiation therapy (3DCRT) or conventional radiation therapy (2DRT).

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Prospective Phase 2 Study of Radiation Therapy Dose and Volume De-escalation for Elective Neck Treatment of Oropharyngeal and Laryngeal Cancer

The required elective nodal dose and volumes for head and neck intensity modulated radiation therapy have largely been extrapolated from conventional radiation therapy fields. In this prospective, dual-center, phase 2 study, we investigated the efficacy and tolerability of reduced elective nodal volume and dose in oropharyngeal and laryngeal squamous cell carcinoma.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Initial Feasibility and Clinical Implementation of Daily MR-Guided Adaptive Head and Neck Cancer Radiation Therapy on a 1.5T MR-Linac System: Prospective R-IDEAL 2a/2b Systematic Clinical Evaluation of Technical Innovation

This prospective study is, to our knowledge, the first report of daily adaptive radiation therapy (ART) for head and neck cancer (HNC) using a 1.5T magnetic resonance imaging-linear accelerator (MR-linac) with particular focus on safety and feasibility and dosimetric results of an online rigid registration-based adapt to position (ATP) workflow.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Attention Guided Lymph Node Malignancy Prediction in Head and Neck Cancer

Accurate lymph node (LN) malignancy classification is essential for treatment target identification in head and neck cancer (HNC) radiation therapy. Given the constraints imposed by relatively small sample sizes in real-world medical applications, to classify LN malignancy status accurately, we proposed an attention-guided classification (AGC) scheme that (1) incorporates human knowledge (ie, LN contours) into model training to guide model’s “learning” direction, alleviating the critical requirement of large training samples by deep learning approaches; and (2) does not require accurate delineation of LNs in the inference stage but can highlight the discriminative region nearby the LN, which is important for malignancy determination.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Pharmacological Inhibition of HSP90 Radiosensitizes Head and Neck Squamous Cell Carcinoma Xenograft by Inhibition of DNA Damage Repair, Nucleotide Metabolism, and Radiation-Induced Tumor Vasculogenesis

Recent preclinical studies suggest combining the HSP90 inhibitor AT13387 (Onalespib) with radiation (IR) against colon cancer and head and neck squamous cell carcinoma (HNSCC). These studies emphasized that AT13387 downregulates HSP90 client proteins involved in oncogenic signaling and DNA repair mechanisms as major drivers of enhanced radiosensitivity. Given the large array of client proteins HSP90 directs, we hypothesized that other key proteins or signaling pathways may be inhibited by AT13387 and contribute to enhanced radiosensitivity. Metabolomic analysis of HSP90 inhibition by AT13387 was conducted to identify metabolic biomarkers of radiosensitization and whether modulations of key proteins were involved in IR-induced tumor vasculogenesis, a process involved in tumor recurrence.

62 RADIOLOGY AND NUCLEAR MEDICINE↗