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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 199 records · Page 11

Cognitively defined Alzheimer's dementia subgroups have distinct atrophy patterns

We sought to determine structural magnetic resonance imaging (MRI) characteristics across subgroups defined based on relative cognitive domain impairments using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and to compare cognitively defined to imaging-defined subgroups. We used data from 584 people with Alzheimer's disease (AD) (461 amyloid positive, 123 unknown amyloid status) and 118 amyloid-negative controls. We used voxel-based morphometry to compare gray matter volume (GMV) for each group compared to controls and to AD-Memory. There was pronounced bilateral lower medial temporal lobe atrophy with relative cortical sparing for AD-Memory, lower left hemisphere GMV for AD-Language, anterior lower GMV for AD-Executive, and posterior lower GMV for AD-Visuospatial. Formal asymmetry comparisons showed substantially more asymmetry in the AD-Language group than any other group (p = 1.15 × 10 -10 ). For overlap between imaging-defined and cognitively defined subgroups, AD-Memory matched up with an imaging-defined limbic predominant group. MRI findings differ across cognitively defined AD subgroups.

60 APPLIED LIFE SCIENCES↗

Characterizing hole trap production due to proton irradiation in germanium cross-strip detectors

We present an investigation into the effects of high-energy proton damage on charge trapping in germanium cross-strip detectors with the goal of accomplishing three important measurements. First, we calibrated and characterized the spectral resolution of a spare COSI-balloon detector in order to determine the effects of intrinsic trapping, finding that electron trapping due to impurities dominates over hole trapping in the undamaged detector. Second, we performed two rounds of proton irradiation of the detector in order to quantify, for the first time, the rate at which charge traps are produced by proton irradiation. We find that the product of the hole trap density and cross-sectional area, [nσ] h , follows a linear relationship with the proton fluence, F p , with a slope of (5.4 ± 0.4) x 10 -11 cm/p + . Third, by utilizing our measurements of physical trapping parameters, we performed calibrations which corrected for the effects of trapping and mitigated degradation to the spectral resolution of the detector.

79 ASTRONOMY AND ASTROPHYSICS↗

Characterizing peak electricity demand for U.S. households: an assessment of end-use loads and demand factors

Understanding household peak electricity demand is critical to evaluate the technical need for electrical infrastructure upgrades. This study characterizes peak loads for existing and new equipment using metered data from a convenience sample of 11,940 U.S. dwellings from four sources, including 911 from two sources with end-use metering. After standardized data cleaning and labeling, we derived descriptive statistics for key metrics, such as maximum demand and demand factors, and developed predictive models relating 60- to 15-min demand for the National Electrical Code (NEC). Mean 15-min maximum demand was 9.7 kW (median 9.0 kW; IQR 7.0–11.5 kW, 95% CI 9.6–9.8 kW), indicating spare capacity in 98% of homes with hypothetical 100 A panels. Maximum demand increased with floor area and number of high-demand loads. Dwelling maximum demand was driven by higher-power, longer-duration heating appliances and vehicle charging, while most user-operated appliances contributed little. Demand factors are used to account for how most devices contribute less than their rated power to maximum demand. Existing load mean demand factors (28%; median 10%; IQR 0–58%; CI 28–29%) were higher than those for new loads (21%; median 7%; IQR 0–35%; CI 20–21%), because new loads changed the timing and magnitude of maximum demand. New high-demand loads had higher than average demand factors (40–60%). Whole dwelling demand factors support the NEC's 40% assumption, but they challenge its conservative 100% treatment of new HVAC. We propose a data-driven 50% demand factor for new equipment, which would align with metered data, improve affordability, and modernize electrical codes.

Appliances↗

Discovery and characterization of a selective IKZF2 glue degrader for cancer immunotherapy

Malignant tumors can evade destruction by the immune system by attracting immune-suppressive regulatory T cells (Treg) cells. The IKZF2 (Helios) transcription factor plays a crucial role in maintaining function and stability of Treg cells, and IKZF2 deficiency reduces tumor growth in mice. Here we report the discovery of NVP-DKY709, a selective molecular glue degrader of IKZF2 that spares IKZF1/3. We describe the recruitment-guided medicinal chemistry campaign leading to NVP-DKY709 that redirected the degradation selectivity of cereblon (CRBN) binders from IKZF1 toward IKZF2. Selectivity of NVP-DKY709 for IKZF2 was rationalized by analyzing the DDB1:CRBN:NVP-DKY709:IKZF2(ZF2 or ZF2-3) ternary complex X-ray structures. Exposure to NVP-DKY709 reduced the suppressive activity of human Treg cells and rescued cytokine production in exhausted T-effector cells. In vivo, treatment with NVP-DKY709 delayed tumor growth in mice with a humanized immune system and enhanced immunization responses in cynomolgus monkeys. NVP-DKY709 is being investigated in the clinic as an immune-enhancing agent for cancer immunotherapy.

59 BASIC BIOLOGICAL SCIENCES↗

Mineral Recovery Enhanced Desalination (MRED) process: An innovative technology for desalinating hard brackish water

Desalination of water containing high concentrations of calcium, dissolved carbon dioxide, sulfate, silica and other sparingly soluble salts is difficult because of the scaling potential. An innovative pre-treatment scheme was investigated at bench scale that selectively removes these constituents and produces a soft water to enable desalination with high feed water recovery. The process first removes dissolved carbon dioxide by air stripping at low pH. Magnesium is removed by precipitation at high pH. Calcium is removed by ion exchange (IX), and sulfate is removed by nanofiltration (NF). Cation regenerant from IX, containing calcium, and concentrate from NF, containing sulfate, is combined to precipitate gypsum. Concentrate from the desalination process consisting of a concentrated NaCl solution is used to regenerate the IX resins. The selective precipitation, IX, and NF processes were tested in laboratory experiments and produced magnesium hydroxide and gypsum at greater than 90% and 95% purity respectively. A process model was developed to calculate process performance, mass and liquid flow rates. Finally, the MRED process offers the following benefits: 1) greater recovery of brackish feedwater by a desalination process, 2) recovery of marketable commodities and 3) reduction in the volume and mass of waste products from the treatment process.

42 ENGINEERING↗

Gene drive by Fusarium SKC1 is dependent on its competing allele

The Fusarium verticillioides SKC1 gene driver is transmitted to offspring in a biased manner through spore killing. The mechanism that allows SKC1 to kill non-SKC1 offspring while sparing others is poorly understood. Here we report that gene drive by SKC1 is dependent on SKC1's competing allele. We propose that SKC1's competing allele influences the ability of a genome defense process to detect SKC1, and we provide evidence that this genome defense process is meiotic silencing by unpaired DNA (MSUD). Furthermore, our findings suggest that the successful deployment of gene drivers to control pathogenic fungi will require researchers to consider how competing alleles influence the ability of gene drivers to be detected by genome defense processes.

59 BASIC BIOLOGICAL SCIENCES↗

First ITER CS module test results

The ITER Central Solenoid (CS) is under fabrication by the US ITER organization and its subcontractors. US ITER will supply seven modules to ITER IO, six of which will be assembled in a stack that forms the ITER Central Solenoid, with one as a spare. The first module fabrication has been completed by General Atomics (GA) at their facility and has begun testing including high voltage testing, Paschen testing in the vacuum and then testing at 4.5 K and up to 40 kA in order to demonstrate compliance of the coil to ITER requirements. In the paper we present the Test Plan and results of the CS Module performance tests, especially at 40 kA current. Herein, AC losses, joint resistances and hydraulic characteristics of the coil are all measured. Displacements of the coil height and hoop strain of the CS Module are also measured to verify structural and mechanical characteristics of the coil along with cooldown shrinkage of the coil. This information is used for verification of the stack behavior of CS in ITER operation. The test results and preliminary analyses results are presented, compared to expectations, and discussed. All measured parameters suggest that the CS module will perform well in ITER machine.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Normal Tissue Response of Combined Temporal and Spatial Fractionation in Proton Minibeam Radiation Therapy

Proton minibeam radiation therapy, a spatial fractionation concept, widens the therapeutic window. By reducing normal tissue toxicities, it allows a temporally fractionated regime with high daily doses. However, an array shift between daily fractions can affect the tissue-sparing effect by decreasing the total peak-to-valley dose ratio. Therefore, combining temporal fractions with spatial fractionation raises questions about the impact of daily applied dose modulations, reirradiation accuracies, and total dose modulations.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Establishment of Microbeam Radiation Therapy at a Small-Animal Irradiator

Microbeam radiation therapy is a preclinical concept in radiation oncology. It spares normal tissue more effectively than conventional radiation therapy at equal tumor control. The radiation field consists of peak regions with doses of several hundred gray, whereas doses between the peaks (valleys) are below the tissue tolerance level. Widths and distances of the beams are in the submillimeter range for microbeam radiation therapy. A similar alternative concept with beam widths and distances in the millimeter range is presented by minibeam radiation therapy. Although both methods were developed at large synchrotron facilities, compact alternative sources have been proposed recently.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Quality of Life: A Prospective Randomized Trial of Palliative Volumetric Arc Therapy Versus 3-Dimensional Conventional Radiation Therapy

Volumetric arc therapy (VMAT) is a radiation therapy (RT) technique that spares normal tissues from high and intermediate RT doses but increases the volume of tissues receiving low doses of RT compared with 3-dimensional conformal RT (3DCRT). We hypothesized that palliative VMAT would reduce the detriment to patient quality of life (QOL) compared with palliative 3DCRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Combined Preoperative Hypofractionated Radiotherapy With Doxorubicin-Ifosfamide Chemotherapy in Marginally Resectable Soft Tissue Sarcomas: Results of a Phase 2 Clinical Trial

There is no standard treatment for marginally resectable soft tissue sarcomas (STSs) of the extremities and trunk wall, and current approaches produce unsatisfactory results. We hypothesized that the combination of doxorubicin-ifosfamide (AI) chemotherapy and 5 × 5 Gy hypofractionated radiotherapy can generate a higher ratio of limb-sparing or conservative surgeries with negative microscopic margins (R0) and acceptable treatment toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

COVID-19 Vaccine-Induced Radiation Recall Phenomenon

Radiation recall phenomenon (RRP) is an uncommon, late occurring, acute inflammatory skin reaction that emerges in localized areas coincident with previously irradiated radiation therapy (RT) treatment fields. RRP has been known to be triggered by a number of chemotherapy agents. To the best of our knowledge, this report is the first description of RRP after administration of the Pfizer-BioNTech vaccine for COVID-19, or any other currently available vaccine against COVID-19. Acute skin reactions were observed in 2 RT patients with differing timelines of RT and vaccinations. In both cases however, the RRP presented within days of the patient receiving the second dose of vaccine. For each RT course, the treatment planning dosimetry of the radiation fields was compared with the area of the observable RRP. RRP developed within the borders of treatment fields where prescription dose constraints were prioritized over skin sparing. Our observation is currently limited to 2 patients. The actual incidence of RRP in conjunction with Pfizer-BioNTech vaccine or any other vaccine against COVID-19 is unknown. For patients with cancer being treated with radiation with significant dose to skin, consideration should be given to the probability of RRP side effects from vaccinations against COVID-19.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Quantification of Oxygen Depletion During FLASH Irradiation In Vitro and In Vivo

Delivery of radiation at ultrahigh dose rates (UHDRs), known as FLASH, has recently been shown to preferentially spare normal tissues from radiation damage compared with tumor tissues. However, the underlying mechanism of this phenomenon remains unknown, with one of the most widely considered hypotheses being that the effect is related to substantial oxygen depletion upon FLASH, thereby altering the radiochemical damage during irradiation, leading to different radiation responses of normal and tumor cells. Testing of this hypothesis would be advanced by direct measurement of tissue oxygen in vivo during and after FLASH irradiation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Strategies for Motion Robust Proton Therapy With Pencil Beam Scanning for Esophageal Cancer

Proton therapy of esophageal cancer is superior to photon radiation therapy in terms of normal tissue sparing. However, respiratory motion and anatomical changes may compromise target dose coverage owing to density changes, geometric misses, and interplay effects. Here we investigate the combined effect on clinical target volume (CTV) coverage and compare proton therapy with intensity modulated radiation therapy (IMRT).

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Fractionated Low-Dose Radiation Induces Long-Lasting Inflammatory Responses in the Hippocampal Stem Cell Niche

Despite major technical advances in hippocampus-sparing radiation therapy, radiation-induced injury to the neural stem cell compartment may affect neurocognitive functions. In the brain, glial cells modulate neuronal functions and are major mediators of neuroinflammation. In a preclinical mouse model with fractionated low-dose radiation (LDR), the complex response to radiation-induced injury was analyzed in the hippocampal stem cell compartment over a period of 6 months.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Rapid Access Palliative Radiation Therapy Clinics: The Evidence Is There, but Where Are the Clinics? An Australian and New Zealand Perspective

First developed in Canada in the 1990s, Rapid Access Palliative Radiation Therapy (RAPRT) clinics have subsequently spread internationally to expedite treatment for near end-of-life patients, sparing them the need for multiple visits to the department. A “classical” RAPRT clinic is herein defined as “a dedicated clinic specifically established to enable (ideally) same day consultation, planning for, and delivery of palliative radiation treatment.” The aim of this work was to determine the current status of these clinics in Australia and New Zealand (ANZ).

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Synchrotron Microbeam Radiation Therapy for the Treatment of Lung Carcinoma: A Preclinical Study

In the past 3 decades, synchrotron microbeam radiation therapy (S-MRT) has been shown to achieve both good tumor control and normal tissue sparing in a range of preclinical animal models. However, the use of S-MRT for the treatment of lung tumors has not yet been investigated. This study is the first to evaluate the therapeutic efficacy of S-MRT for the treatment of lung carcinoma, using a new syngeneic and orthotopic mouse model.

62 RADIOLOGY AND NUCLEAR MEDICINE↗