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During evolution, humans are acclimatized to the stresses of natural radiation and circadian rhythmicity. Radiosensitivity of mammalian cells varies in the circadian period and adaptive radioprotection can be induced by pre-exposure to low-level radiation (LDR). It is unclear, however, if clock proteins participate in signaling LDR radioprotection. Herein, we demonstrate that radiosensitivity is increased in mice with the deficient Period 2 gene (Per2def) due to impaired DNA repair and mitochondrial function in progenitor bone marrow hematopoietic stem cells and monocytes. Per2 induction and radioprotection are also identified in LDR-treated Per2wt mouse cells and in human skin (HK18) and breast (MCF-10A) epithelial cells. LDR-boosted PER2 interacts with pGSK3β(S9) which activates β-catenin and the LEF/TCF mediated gene transcription including Per2 and genes involved in DNA repair and mitochondrial functions. This study demonstrates that PER2 plays an active role in LDR adaptive radioprotection via PER2/pGSK3β/β-catenin/Per2 loop, a potential target for protecting normal cells from radiation injury.

131I-metaiodobenzylguanidine (131I-mIBG) is a targeted radiation therapy developed for the treatment of advanced neuroblastoma. We have previously shown that this patient cohort can be used to predict absorbed dose associated with early 131I exposure, 72 h after treatment. We now expand these studies to identify gene expression differences associated with 131I-mIBG exposure 15 days after treatment. Total RNA from peripheral blood lymphocytes was isolated from 288 whole blood samples representing 59 relapsed or refractory neuroblastoma patients before and after 131I-mIBG treatment. We found that several transcripts predictive of early exposure returned to baseline levels by day 15, however, selected transcripts did not return to baseline. At 72 h, all 17 selected pathway-specific transcripts were differentially expressed. Transcripts CDKN1A (P < 0.000001), FDXR (P < 0.000001), DDB2 (P < 0.000001), and BBC3 (P < 0.000001) showed the highest up-regulation at 72 h after 131I-mIBG exposure, with mean log2 fold changes of 2.55, 2.93, 1.86 and 1.85, respectively. At day 15 after 131I-mIBG, 11 of the 17 selected transcripts were differentially expressed, with XPC, STAT5B, PRKDC, MDM2, POLH, IGF1R, and SGK1 displaying significant up-regulation at 72 h and significant down-regulation at day 15. Interestingly, transcripts FDXR (P = 0.01), DDB2 (P = 0.03), BCL2 (P = 0.003), and SESN1 (P < 0.0003) maintained differential expression 15 days after 131I-mIBG treatment. These results suggest that transcript levels for DNA repair, apoptosis, and ionizing radiation-induced cellular stress are still changing by 15 days after 131I-mIBG treatment. Our studies showcase the use of biodosimetry gene expression panels as predictive biomarkers following early (72 h) and late (15 days) internal 131I exposure. Our findings also demonstrate the utility of our transcript panel to differentiate exposed from non-exposed individuals up to 15 days after exposure from internal 131I.

Curcumin, a natural polyphenol derived from the spice turmeric (Curcuma longa), contains antioxidant, anti-inflammatory, and anti-cancer properties. However, curcumin bioavailability is inherently low due to poor water solubility and rapid metabolism. Here, we further refined for use curcumin incorporated into "biomimetic" nanolipoprotein particles (cNLPs) consisting of a phospholipid bilayer surrounded by apolipoprotein A1 and amphipathic polymer scaffolding moieties. Our cNLP formulation improves the water solubility of curcumin over 30-fold and produces nanoparticles with ~350 µg/mL total loading capacity for downstream in vitro and in vivo applications. We found that cNLPs were well tolerated in AG05965/MRC-5 human primary lung fibroblasts compared to cultures treated with curcumin solubilized in DMSO (curDMSO). Pre-treatment with cNLPs of quiescent G0/G1-phase MRC-5 cultures improved cell survival following 137Cs gamma ray irradiations, although this finding was reversed in asynchronously cycling log-phase cell cultures. These findings may be useful for establishing cNLPs as a method to improve curcumin bioavailability for administration as a radioprotective and/or radiomitigative agent against ionizing radiation (IR) exposures in non-cycling cells or as a radiosensitizing agent for actively dividing cell populations, such as tumors.

Glioblastoma multiforme (GBM) remains the top challenge to radiotherapy with only 25% one-year survival after diagnosis. Here, we reveal that co-enhancement of mitochondrial fatty acid oxidation (FAO) enzymes (CPT1A, CPT2 and ACAD9) and immune checkpoint CD47 is dominant in recurrent GBM patients with poor prognosis. A glycolysis-to-FAO metabolic rewiring is associated with CD47 anti-phagocytosis in radioresistant GBM cells and regrown GBM after radiation in syngeneic mice. Inhibition of FAO by CPT1 inhibitor etomoxir or CRISPR-generated CPT1A-/-, CPT2-/-, ACAD9-/- cells demonstrate that FAO-derived acetyl-CoA upregulates CD47 transcription via NF-κB/RelA acetylation. Blocking FAO impairs tumor growth and reduces CD47 anti-phagocytosis. Etomoxir combined with anti-CD47 antibody synergizes radiation control of regrown tumors with boosted macrophage phagocytosis. These results demonstrate that enhanced fat acid metabolism promotes aggressive growth of GBM with CD47-mediated immune evasion. The FAO-CD47 axis may be targeted to improve GBM control by eliminating the radioresistant phagocytosis-proofing tumor cells in GBM radioimmunotherapy.

Fused deposition modeling (FDM), a type of additive manufacturing is widely used for complex mold design, single‐part tool manufacturing, and prototyping. The FDM process, especially with fiber‐reinforced filament, induces intricate changes that influence microstructure and properties, highlighting the necessity for a thorough understanding to maximize FDM utilization. This study comprehensively examines microstructural changes and mechanical attributes in polyamide (PA) and carbon fiber‐reinforced polyamide (CF‐PA) before and after FDM printing. Through various characterization techniques including X‐ray diffraction, thermal gravimetric, differential scanning calorimetry, tensile testing, micro‐Computed Tomography (μ‐CT), and fractography, insightful perspectives were obtained. Results reveal substantial fiber breakage, resulting in a 33.03% decrease in the average fiber length from filament to printed parts. X‐ray μ‐CT scans illustrated a more pronounced fiber alignment in CF‐PA filament than in the CF‐PA printed sample. TG analysis confirms approximately 20 wt.% CF content in the filament, with negligible residue in pure PA filament and samples. DSC shows enhanced thermal stability with CF reinforcement, while XRD confirms amorphous behavior in filament and printed parts. Tensile tests reveal anisotropic properties in FDM samples. The addition of short CFs increases Young's modulus but decreases strength. Examination of fractured surfaces reveals different failure modes for filament and printed coupons. [ABSTRACT FROM AUTHOR]

3D digitization methods have become essential tools in cultural heritage practice. Methods like laser scanning and photogrammetry are being widely applied for the conservation of priceless objects and for enabling audience engagement with history. Such data have value as a new wave of multisensory museum practice ripples through the sector and could provide a perfect use for the enormous corpus of 3D data in cultural heritage. This paper documents such an application, where laser scanning has been used in conjunction with 3D printing to re-present the Chichester Roman tablet, an object of key importance in early Romano-British history, to new audiences. It details the process used to digitize the tablet and recreate different versions of its missing text and its state of preservation. It describes how such data can play a role beyond just documentation. Discussed is how such approaches enrich families' engagement in cultural heritage and how such material can used as didactic material in higher education. [ABSTRACT FROM AUTHOR]

Combining existing knowledge of museum exhibition visitor experience with concepts of User Experience (UX), a model for Museum Exhibition User Experience (MEUX) is presented. The model was developed from research interviews and surveys with UK museum professionals and presents the museum exhibition experience from both museum and visitor perspectives. Its use as an evaluation tool for visitor experience is explored at Oxford University Museum of Natural History (OUMNH). In comparing results with those from staff, a disconnect emerged between museum and visitor preferences on motivations for visiting and what outcomes emerge from visits. The incorporation of the theoretical MEUX model into museum practice enables holistic conceptualization of the visitor experience through the pragmatic and hedonic qualities of an exhibition. With the development of further evaluation tools, this framework and methodology accurately captures institutional and visitor preferences and can evaluate how the development decisions of museums influence and impact the visitor experience. [ABSTRACT FROM AUTHOR]

We report on effects of low-dose exposures of accelerated protons delivered at high-dose rate (HDR) or a simulated solar-particle event (SPE) like low-dose rate (LDR) on immediate DNA damage induction and processing, survival and in vitro transformation of low passage NFF28 apparently normal primary human fibroblasts. Cultures were exposed to 50, 100 and 1,000 MeV monoenergetic protons in the Bragg entrance/plateau region and cesium-137 γ rays at 20 Gy/h (HDR) or 1 Gy/h (LDR). DNA double-strand breaks (DSB) and clustered DNA damages (containing oxypurines and abasic sites) were measured using transverse alternating gel electrophoresis (TAFE) and immunocytochemical detection/scoring of colocalized γ-H2AX pS139/53BP1 foci, with their induction being linear energy transfer (LET) dependent and dose-rate sparing observed for the different damage classes. Relative biological effectiveness (RBE) values for cell survival after proton irradiation at both dose-rates ranged from 0.61–0.73. Transformation RBE values were dose-rate dependent, ranging from ∼1.8–3.1 and ∼0.6–1.0 at low doses (≤30 cGy) for HDR and LDR irradiations, respectively. However peak transformation frequencies were significantly higher (1.3–7.3-fold) for higher doses of 0.5–1 Gy delivered at SPE-like LDR. Cell survival and transformation frequencies measured after low-dose 500 MeV/n He-4, 290 MeV/n C-12 and 600 MeV/n Si-28 ion irradiations also showed an inverse dose-rate effect for transformation at SPE-like LDR. This work demonstrates the existence of inverse dose-rate effects for proton and light-ion-induced postirradiation cell survival and in vitro transformation for space mission-relevant doses and dose rates. [ABSTRACT FROM AUTHOR]

131I-metaiodobenzylguanidine (131I-mIBG) is a targeted radiation therapy developed for the treatment of advanced neuroblastoma. We have previously shown that this patient cohort can be used to predict absorbed dose associated with early 131I exposure, 72 h after treatment. We now expand these studies to identify gene expression differences associated with 131I-mIBG exposure 15 days after treatment. Total RNA from peripheral blood lymphocytes was isolated from 288 whole blood samples representing 59 relapsed or refractory neuroblastoma patients before and after 131I-mIBG treatment. We found that several transcripts predictive of early exposure returned to baseline levels by day 15, however, selected transcripts did not return to baseline. At 72 h, all 17 selected pathway-specific transcripts were differentially expressed. Transcripts CDKN1A (P < 0.000001), FDXR (P < 0.000001), DDB2 (P < 0.000001), and BBC3 (P < 0.000001) showed the highest up-regulation at 72 h after 131I-mIBG exposure, with mean log2 fold changes of 2.55, 2.93, 1.86 and 1.85, respectively. At day 15 after 131I-mIBG, 11 of the 17 selected transcripts were differentially expressed, with XPC, STAT5B, PRKDC, MDM2, POLH, IGF1R, and SGK1 displaying significant up-regulation at 72 h and significant down-regulation at day 15. Interestingly, transcripts FDXR (P = 0.01), DDB2 (P = 0.03), BCL2 (P = 0.003), and SESN1 (P < 0.0003) maintained differential expression 15 days after 131I-mIBG treatment. These results suggest that transcript levels for DNA repair, apoptosis, and ionizing radiation-induced cellular stress are still changing by 15 days after 131I-mIBG treatment. Our studies showcase the use of biodosimetry gene expression panels as predictive biomarkers following early (72 h) and late (15 days) internal 131I exposure. Our findings also demonstrate the utility of our transcript panel to differentiate exposed from non-exposed individuals up to 15 days after exposure from internal 131I. [ABSTRACT FROM AUTHOR]

ABSTRACT The impact of broaching and uncemented implantation on bone density during total hip arthroplasty (THA) remains unclear. Previous studies have typically examined extracted bone sections, which may not directly correlate with outcomes in human hip systems. This study aimed to evaluate bone density changes resulting from broaching and uncemented implantation using micro‐computed tomography (μCT) on cadaveric samples. An in‐house density calibration phantom (DCP) was developed by validating the densities of polymer inserts through mass and volume measurements. Its performance was then evaluated using lamb bone in comparison with a commercial DCP (QRM‐50124). The sensitivity of density predictions to μCT scan parameters was also evaluated with the lamb bone. Additionally, density predictions from medical‐CT and μCT scans were compared using the in‐house DCP. Finally, uncemented THA procedures were performed on three cadaveric femurs, each undergoing three μCT scans at various surgical stages to assess changes in bone density. The density predictions obtained using the in‐house DCP achieved an accuracy of ±0.097 g/cc compared to QRM‐50124, with a precision of ±0.052 g/cc. The sensitivity to changes in μCT scan parameters was ±0.022 g/cc. Notably, density predictions from medical‐CT and μCT scans were similar, particularly in cortical bone. Broaching and implantation led to an average increase in bone density of 0.137 g/cc, which was attributed to the accumulation of bone debris around the bone‐implant interface. This accumulation raised the bone volume fraction, ranging from 3.31% to 20.69%, which acts as an autograft. These measurements have been made for the first time using a µCT and an in‐house DCP. [ABSTRACT FROM AUTHOR]