Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “Repair”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

Multimodality Imaging Approach towards Primary Aortic Sarcomas Arising after Endovascular Abdominal Aortic Aneurysm Repair: Case Series Report

Primary aortic neoplasms are rare. Aortic sarcoma arising after endovascular aneurysm repair (EVAR) is a scarce subset of primary aortic malignancies, reports of which are infrequent in the published literature. The diagnosis of aortic sarcoma is challenging due to its non-specific clinical presentation, and the prognosis is poor due to delayed diagnosis, rapid proliferation, and propensity for metastasis. Post-EVAR, aortic sarcomas may mimic other more common aortic processes on surveillance imaging. Radiologists are rarely knowledgeable about this rare entity for which multimodality imaging and awareness are invaluable in early diagnosis. A series of three pathologically confirmed cases are presented to display the multimodality imaging features and clinical presentations of aortic sarcoma arising after EVAR.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Use of Suture-Mediated Closure Device in Percutaneous Direct Carotid Puncture During Chimney-Thoracic Endovascular Aortic Repair

BackgroundInsertion of a carotid chimney graft during thoracic endovascular aortic repair (Ch-TEVAR) is a recognized technique to extend the proximal landing zone into the aortic arch in the treatment of thoracic aortic disease. Conventional technique requires surgical exposure of the carotid artery for insertion of the carotid chimney graft.MethodologyWe describe our experience in the use of a suture-mediated closure device in percutaneous Ch-TEVAR in four patients.ResultsSuccessful hemostasis was achieved in all four patients. No complications related to the carotid puncture were recorded.ConclusionWe conclude that using suture-mediated closure device for carotid closure appears feasible and deserves further studies as a potential alternative to conventional surgical approach.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Early- and Mid-term Results of the Chimney Technique in the Repair of Aortic Arch Pathologies

PurposeTo examine the safety, feasibility, and mid-term efficacy of the chimney technique for aortic arch pathologies.MethodsFrom February 2011 to December 2014, a total of 35 patients (30 men; mean age 54.3 ± 14.1 years) with aortic arch pathologies underwent thoracic endovascular aortic repair combined with chimney stents. The indication was a proximal landing zone <1.5 cm. Follow-up was performed at 3, 6, and 12 months and then yearly thereafter.ResultsA total of 36 chimney stents were deployed (innominate artery, n = 1; left common carotid artery, n = 9; right subclavian artery, n = 1; left subclavian artery, n = 25). The technical success rate was 94.3 % (33/35). Immediate type Ia endoleaks (ELIa) were observed in two patients (8.6 %, 2/35). Twenty-five patients were successfully followed-up for a median period of 29.3 months (range, 6–48 months). One patient died due to aortic dissection aneurysm rupture at 36 months (mortality rate of 4 %, 1/25). Three late ELIa were observed and no reinterventions were performed. The overall incidence of ELIa was 20 % (5/25). During follow-up, the patency rate for chimney stents was 92 % (23/25).ConclusionOur limited experience demonstrates that the chimney technique is a viable and relatively safe treatment for patients with challenging thoracic aortic pathologies at least in the mid-term follow-up period.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Factors Affecting Optimal Aortic Remodeling After Thoracic Endovascular Aortic Repair of Type B (IIIb) Aortic Dissection

PurposeThe purpose of this study was to determine factors associated with entire aortic remodeling after thoracic endovascular aortic repair (TEVAR) in patients with type B dissection.Materials and MethodsThe patients with type B (IIIb) dissections who underwent TEVAR from 2006 to 2013 with minimum of 2 years of follow-up computed tomography data were retrospectively reviewed. Based on the status of false lumen remodeling of entire aorta, patients were divided into three groups: complete regression, total thrombosis, and inadequate regression with patent abdominal false lumen.ResultsA total of 90 patients (72 males, 18 females; mean age 56.6 ± 16.4 years) were included and divided into the complete regression (n = 22), total thrombosis (n = 18), and inadequate regression (n = 50) groups. Multivariate logistic regression analysis indicated that dissection extension to iliac arteries, increased preoperative number of dissection tear over abdominal aorta, and decreased preoperative abdominal aorta bifurcation true lumen ratio, as compared between the inadequate and complete regression groups, were associated with a persistent false lumen (odds ratio = 33.33, 2.304, and 0.021; all, p ≤ 0.012). Comparison of 6, 12, and 24 months postoperative data revealed no significant differences at any level, suggesting that the true lumen area ratio might not change after 6 months postoperatively.ConclusionsIncreased preoperative numbers of dissection tear around the abdominal visceral branches, dissection extension to the iliac arteries, and decreased preoperative true lumen area ratio of abdominal aorta are predictive of entire aortic remodeling after TEVAR in patients with type B dissection.Level of EvidenceIII.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Fusion Imaging to Guide Thoracic Endovascular Aortic Repair (TEVAR): A Randomized Comparison of Two Methods, 2D/3D Versus 3D/3D Image Fusion

Purpose: To compare the accuracy of two-dimensional (2D) versus three-dimensional (3D) image fusion for thoracic endovascular aortic repair (TEVAR) image guidance. Materials and Methods: Between December 2016 and March 2018, all eligible patients who underwent TEVAR were prospectively included in a single-center study. Image fusion methods (2D/3D or 3D/3D) were randomly assigned to guide each TEVAR and compared in terms of accuracy, dose area product (DAP), volume of contrast medium injected, fluoroscopy time and procedure time. Results: Thirty-two patients were prospectively included; 18 underwent 2D/3D and 14 underwent 3D/3D TEVAR. The 3D/3D method allowed more accurate positioning of the aortic mask on top of the fluoroscopic images (proximal landing zone error vector: 1.7 ± 3.3 mm) than was achieved by the 2D/3D method (6.1 ± 6.1 mm; p = 0.03). The 3D/3D image fusion method was associated with significantly lower DAP than the 2D/3D method (50.5 ± 30.1 Gy cm{sup 2} for 3D/3D vs. 99.5 ± 79.1 Gy cm{sup 2} for 2D/3D; p = 0.03). The volume of contrast medium injected was significantly lower for the 3D/3D method than for the 2D/3D method (50.6 ± 22.9 ml vs. 98.4 ± 47.9 ml; p = 0.002). Conclusion: Higher image fusion accuracy and lower contrast volume and irradiation dose were observed for 3D/3D image fusion than for 2D/3D during TEVAR. Level of Evidence: II, Randomized trial.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Experimental Validation of the Earthquake Resistance of a Full-Scale Model of RBMK-1000 Graphite Stack with Post-Repair Characteristics

In providing justification for the operational safety of RBMK-1000 power units with graphite stack distortion, earthquake resistance tests were performed on a full-scale model of RBMK graphite stack under seismic platform conditions. The tests were performed for three mutually perpendicular axes of the model successively for seismic loads corresponding to magnitudes 6, 7 and 8 on the MSK-64 scale. The tests confirmed the earthquake resistance of the graphite stack for prescribed loads. The results were used to verify the FEMGR code (Kurchatov Institute) and the LEGAK-DF finite-element software system (RFYaTs – VNIIEF) for purposes of computational validation of the earthquake resistance of the post-repair restored RMBK-1000 core.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2018

Bioenergetic consequences of compromised mitochondrial DNA repair in the mouse heart

Highlights: • Loss of mitochondrial DNA repair compromises bioenergetic efficiency. • Impairments in bioenergetic efficiency result from ETS stoichiometry shifts. • Bioenergetic flux in Polg{sup m/m} mitochondria favors accelerated electron leak. The progeroid phenotype of mitochondrial DNA (mtDNA) mutator mice has been nebulously attributed to general mitochondrial ‘dysfunction’, though few studies have rigorously defined the bioenergetic consequences of accumulating mtDNA mutations. Comprehensive mitochondrial diagnostics was employed to interrogate the bioenergetic properties of isolated cardiac mitochondria from mtDNA mutator mice and wild type littermates. Assessment of respiratory flux in conjunction with parallel measurements of mitochondrial free energy all point to the cause of respiratory flux limitations observed in mtDNA mutator mouse mitochondria being due to impairments within the energy transduction step catalyzed by the electron transport system in which NADH/NAD{sup +} free energy is transduced to the proton motive force (ΔP). The primary bioenergetic consequence of this limitation appears to be hyper-reduction of NAD(P)H/NAD(P){sup +} redox poise across multiple substrate conditions, particularly evident at moderate to high respiration rates. This hyper-reduced phenotype appears to result from specific reductions in both complex I and complex IV expression, presumably due to compromised mtDNA integrity. Translation of these findings to the working heart would suggest that the primary biological consequence of accumulated mtDNA damage is accelerated electron leak driven by an increase in electron redox pressure for a given rate of oxygen consumption.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Epigenetic alteration of mismatch repair genes in the population chronically exposed to arsenic in West Bengal, India

Highlights: • The present study highlights the association of MMR pathway with arsenic exposure. • Evaluation of the methylation status of key MMR genes. • Epigenetic repression of MLH1 and MSH2 due to promoter hypermethylation. • Significant down regulation of H3K36me3-the mismatch recognition moiety. • Impaired MMR pathway might increase susceptibility towards DNA damage and cancer. Arsenic exposure and its adverse health outcome, including the association with cancer risk are well established from several studies across the globe. The present study aims to analyze the epigenetic regulation of key mismatch repair (MMR) genes in the arsenic-exposed population.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2014

Influence of Double-Strand Break Repair on Radiation Therapy-Induced Acute Skin Reactions in Breast Cancer Patients

Purpose: Curative radiation therapy (RT)-induced toxicity poses strong limitations for efficient RT and worsens the quality of life. The parameter that explains when and to what extent normal tissue toxicity in RT evolves would be of clinical relevance because of its predictive value and may provide an opportunity for personalized treatment approach. Methods and Materials: DNA double-strand breaks and repair were analyzed by microscopic γ-H2AX foci analysis in peripheral lymphocytes from 38 healthy donors and 80 breast cancer patients before RT, a 2 Gy challenge dose of x-ray exposed in vitro. Results: The actual damage (AD) at 0.25, 3, and 6 hours and percentage residual damage (PRD) at 3 and 6 hours were used as parameters to measure cellular radiosensitivity and correlated with RT-induced acute skin reactions in patients stratified as non-overresponders (NOR) (Radiation Therapy Oncology Group [RTOG] grade <2) and overresponders (OR) (RTOG grade ≥2). The results indicated that the basal and induced (at 0.25 and 3 hours) γ-H2AX foci numbers were nonsignificant (P>.05) between healthy control donors and the NOR and OR groups, whereas it was significant between ORs and healthy donors at 6 hours (P<.001). There was a significantly higher PRD in OR versus NOR (P<.05), OR versus healthy donors (P<.001) and NOR versus healthy donors (P<.01), supported further by the trend analysis (r=.2392; P=.0326 at 6 hours). Conclusions: Our findings strongly suggest that the measurement of PRD by performing γ-H2AX foci analysis has the potential to be developed into a clinically useful predictive assay.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

ZRBA1, a Mixed EGFR/DNA Targeting Molecule, Potentiates Radiation Response Through Delayed DNA Damage Repair Process in a Triple Negative Breast Cancer Model

Purpose: ZRBA1 is a combi-molecule designed to induce DNA alkylating lesions and to block epidermal growth factor receptor (EGFR) TK domain. Inasmuch as ZRBA1 downregulates the EGFR TK-mediated antisurvival signaling and induces DNA damage, we postulated that it might be a radiosensitizer. The aim of this study was to further investigate the potentiating effect of ZRBA1 in combination with radiation and to elucidate the possible mechanisms of interaction between these 2 treatment modalities. Methods and Materials: The triple negative human breast MDA-MB-468 cancer cell line and mouse mammary cancer 4T1 cell line were used in this study. Clonogenic assay, Western blot analysis, and DNA damage analysis were performed at multiple time points after treatment. To confirm our in vitro findings, in vivo tumor growth delay assay was performed. Results: Our results show that a combination of ZRBA1 and radiation increases the radiation sensitivity of both cell lines significantly with a dose enhancement factor of 1.56, induces significant numbers of DNA strand breaks, prolongs higher DNA damage up to 24 hours after treatment, and significantly increases tumor growth delay in a syngeneic mouse model. Conclusions: Our data suggest that the higher efficacy of this combination could be partially due to increased DNA damage and delayed DNA repair process and to the inhibition of EGFR. The encouraging results of this combination demonstrated a significant improvement in treatment efficiency and therefore could be applicable in early clinical trial settings.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

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↗
DOE OSTI2021

Developing a Peptide That Inhibits DNA Repair by Blocking the Binding of Artemis and DNA Ligase IV to Enhance Tumor Radiosensitivity

Artemis and DNA Ligase IV are 2 critical elements in the nonhomologous end joining pathway of DNA repair, acting as the nuclease and DNA ligase, respectively. Enhanced cellular radiosensitivity by inhibition of either protein contributes to a promising approach to develop molecular targeted radiosensitizers. The interaction between Artemis and DNA Ligase IV is required for the activation of Artemis as nuclease at 3’overhang DNA; thus, we aim to generate an inhibitory peptide targeting the interaction between Artemis and DNA Ligase IV for novel radiosensitizer development.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Down-regulation of ERK1/2 and AKT-mediated X-ray repair cross-complement group 1 protein (XRCC1) expression by Hsp90 inhibition enhances the gefitinib-induced cytotoxicity in human lung cancer cells

Gefitinib (Iressa{sup R}, ZD1839) is a selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that blocks growth factor-mediated cell proliferation and extracellular signal-regulated kinases 1/2 (ERK1/2) and AKT signaling activation. It has been shown that inhibition of Hsp90 function can enhance antitumor activity of EGFR-TKI. XRCC1 is an important scaffold protein in base excision repair, which could be regulated by ERK1/2 and AKT pathways. However, the role of ERK1/2 and AKT-mediated XRCC1 expression in gefitinib alone or combination with an Hsp90 inhibitor-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. In this study, gefitinib treatment decreased XRCC1 mRNA and protein expression through ERK1/2 and AKT inactivation in two NSCLC cells, A549 and H1975. Knocking down XRCC1 expression by transfection with small interfering RNA of XRCC1 enhanced the cytotoxicity and cell growth inhibition of gefitinib. Combining treatment of gefitinib with an Hsp90 inhibitor resulted in enhancing the reduction of XRCC1 protein and mRNA levels in gefitinib-exposed A549 and H1975 cells. Compared to a single agent alone, gefitinib combined with an Hsp90 inhibitor resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells. Furthermore, transfection with constitutive active MKK1 or AKT vectors rescued the XRCC1 protein level as well as the cell survival suppressed by an Hsp90 inhibitor and gefitinib. These findings suggested that down-regulation of XRCC1 can enhance the sensitivity of gefitinib for NSCLC cells. - Highlights: • Gefitinib treatment decreased XRCC1 mRNA and protein expression in NSCLC cells. • Knocking down XRCC1 expression enhanced the cytotoxic effect of gefitinib. • Gefitinib combined with an Hsp90 inhibitor resulted in synergistically cytotoxicity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Mechanism of Rad26-assisted rescue of stalled RNA polymerase II in transcription-coupled repair

Transcription-coupled repair is essential for the removal of DNA lesions from the transcribed genome. The pathway is initiated by CSB protein binding to stalled RNA polymerase II. Mutations impairing CSB function cause severe genetic disease. Yet, the ATP-dependent mechanism by which CSB powers RNA polymerase to bypass certain lesions while triggering excision of others is incompletely understood. Here we build structural models of RNA polymerase II bound to the yeast CSB ortholog Rad26 in nucleotide-free and bound states. This enables simulations and graph-theoretical analyses to define partitioning of this complex into dynamic communities and delineate how its structural elements function together to remodel DNA. We identify an allosteric pathway coupling motions of the Rad26 ATPase modules to changes in RNA polymerase and DNA to unveil a structural mechanism for CSB-assisted progression past less bulky lesions. Our models allow functional interpretation of the effects of Cockayne syndrome disease mutations.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Dynamic conformational switching underlies TFIIH function in transcription and DNA repair and impacts genetic diseases

Transcription factor IIH (TFIIH) is a protein assembly essential for transcription initiation and nucleotide excision repair (NER). Yet, understanding of the conformational switching underpinning these diverse TFIIH functions remains fragmentary. TFIIH mechanisms critically depend on two translocase subunits, XPB and XPD. To unravel their functions and regulation, we build cryo-EM based TFIIH models in transcription- and NER-competent states. Using simulations and graph-theoretical analysis methods, we reveal TFIIH’s global motions, define TFIIH partitioning into dynamic communities and show how TFIIH reshapes itself and self-regulates depending on functional context. Our study uncovers an internal regulatory mechanism that switches XPB and XPD activities making them mutually exclusive between NER and transcription initiation. By sequentially coordinating the XPB and XPD DNA-unwinding activities, the switch ensures precise DNA incision in NER. Mapping TFIIH disease mutations onto network models reveals clustering into distinct mechanistic classes, affecting translocase functions, protein interactions and interface dynamics.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Molecular architecture and functional dynamics of the pre-incision complex in nucleotide excision repair

Nucleotide excision repair (NER) is vital for genome integrity. Yet, our understanding of the complex NER protein machinery remains incomplete. Combining cryo-EM and XL-MS data with AlphaFold2 predictions, we build an integrative model of the NER pre-incision complex(PInC). Here TFIIH serves as a molecular ruler, defining the DNA bubble size and precisely positioning the XPG and XPF nucleases for incision. Using simulations and graph theoretical analyses, we unveil PInC’s assembly, global motions, and partitioning into dynamic communities. Remarkably, XPG caps XPD’s DNA-binding groove and bridges both junctions of the DNA bubble, suggesting a novel coordination mechanism of PInC’s dual incision. XPA rigging interlaces XPF/ERCC1 with RPA, XPD, XPB, and 5' ssDNA, exposing XPA’s crucial role in licensing the XPF/ERCC1 incision. Mapping disease mutations onto our models reveals clustering into distinct mechanistic classes, elucidating xeroderma pigmentosum and Cockayne syndrome disease etiology.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Enhanced self-repairing capability of sol-gel derived SrTiO{sub 3}/nano Al{sub 2}O{sub 3} composite films

SrTiO{sub 3}/nano Al{sub 2}O{sub 3} inorganic nanocomposites were prepared by using a conventional sol-gel spin coating process. For comparison, SrTiO{sub 3} films doped by equivalent amount of sol-Al{sub 2}O{sub 3} have also been investigated. Aluminum deposited by using vacuum evaporation was used as the top electrode. The nanocomposites exhibited a significantly enhanced dielectric strength of 506.9 MV/m, which was increased by 97.4% as compared with the SrTiO{sub 3} films doped with sol-Al{sub 2}O{sub 3}. The leakage current maintained of the same order of microampere until the ultimate breakdown of the nanocomposites. The excellent electrical performances are ascribed to the anodic oxidation reaction in origin, which can repair the internal and/or surface defects of the films.

36 MATERIALS SCIENCE↗