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At least 1,369 records · Page 76
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Restricting electron flow at cytochrome b6f when downstream electron acceptors are severely limited

Abstract Photosynthetic organisms frequently experience abiotic stress that restricts their growth and development. Under such circumstances, most absorbed solar energy cannot be used for CO2 fixation and can cause the photoproduction of reactive oxygen species (ROS) that can damage the photosynthetic reaction centers of PSI and PSII, resulting in a decline in primary productivity. This work describes a biological “switch” in the green alga Chlamydomonas reinhardtii that reversibly restricts photosynthetic electron transport (PET) at the cytochrome b6f (Cyt b6f) complex when the capacity for accepting electrons downstream of PSI is severely limited. We specifically show this restriction in STARCHLESS6 (sta6) mutant cells, which cannot synthesize starch when they are limited for nitrogen (growth inhibition) and subjected to a dark-to-light transition. This restriction represents a form of photosynthetic control that causes diminished electron flow to PSI and thereby prevents PSI photodamage but does not appear to rely on a ΔpH. Furthermore, when electron flow is restricted, the plastid alternative oxidase (PTOX) becomes active, functioning as an electron valve that dissipates some excitation energy absorbed by PSII and allows the formation of a proton motive force (PMF) that would drive some ATP production (potentially sustaining PSII repair and nonphotochemical quenching [NPQ]). The restriction at the Cyt b6f complex can be gradually relieved with continued illumination. This study provides insights into how PET responds to a marked reduction in availability of downstream electron acceptors and the protective mechanisms involved.

Plant Sciences↗
DOE OSTI2021

Mechanistic Evaluation of Black Cohosh Extract-Induced Genotoxicity in Human Cells

Abstract Black cohosh extract (BCE) is marketed to women as an alternative to hormone replacement therapy for alleviating menopausal symptoms. Previous studies by the National Toxicology Program revealed that BCE induced micronuclei (MN) and a nonregenerative macrocytic anemia in rats and mice, likely caused by disruption of the folate metabolism pathway. Additional work using TK6 cells showed that BCE induced aneugenicity by destabilizing microtubules. In the present study, BCE-induced MN were confirmed in TK6 and HepG2 cells. We then evaluated BCE-induced DNA damage using the comet assay at multiple time points (0.5–24 h). Following a 0.5-h exposure, BCE induced significant, concentration-dependent increases in %tail DNA in TK6 cells only. Although DNA damage decreased in TK6 cells over time, likely due to repair, small but statistically significant levels of DNA damage were observed after 2 and 4 h exposures to 250 µg/ml BCE. A G1/S arrest in TK6 cells exposed to 125 µg/ml BCE (24 h) was accompanied by apoptosis and increased expression of γH2A.X, p-Chk1, p-Chk2, p53, and p21. Conditioning TK6 cells to physiological levels of folic acid (120 nM) did not increase the sensitivity of cells to BCE-induced DNA damage. BCE did not alter global DNA methylation in TK6 and HepG2 cells cultured in standard medium. Our results suggest that BCE induces acute DNA strand breaks which are quickly repaired in TK6 cells, whereas DNA damage seen at 4 and 24 h may reflect apoptosis. The present study supports that BCE is genotoxic mainly by inducing MN with an aneugenic mode of action.

Seo, Ji-Eun↗
DOE OSTI2015

Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome

Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot's syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. Lastly, the structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2020

Safeguarding the Grid: Diverse Resources for Resilience [In My View]

Reports on the vulnerability of the power grid. From wildfires, hurricanes, and floods to cyberattacks, the grid is vulnerable to natural and human-made disasters, which can cause widespread outages that last from hours to months and leave lasting economic impacts. Imagine a coastal region in the United States that has just been hit by a hurricane and lost all power. Besides the electricity infrastructure going out, communications networks, rail transportation, and gasoline pumps may also stop working after the emergency event, which often delays repair efforts to the grid. Unresponsive communications make it difficult to dispatch workers to repair the grid, and missing transportation links delay shipments of replacement equipment for the grid’s restoration.

cybersecurity↗
DOE OSTI2016

Impact of Data Placement on Resilience in Large-Scale Object Storage Systems

Distributed object storage architectures have become the de facto standard for high-performance storage in big data, cloud, and HPC computing. Object storage deployments using commodity hardware to reduce costs often employ object replication as a method to achieve data resilience. Repairing object replicas after failure is a daunting task for systems with thousands of servers and billions of objects, however, and it is increasingly difficult to evaluate such scenarios at scale on realworld systems. Resilience and availability are both compromised if objects are not repaired in a timely manner. In this work we leverage a high-fidelity discrete-event simulation model to investigate replica reconstruction on large-scale object storage systems with thousands of servers, billions of objects, and petabytes of data. We evaluate the behavior of CRUSH, a well-known object placement algorithm, and identify configuration scenarios in which aggregate rebuild performance is constrained by object placement policies. After determining the root cause of this bottleneck, we then propose enhancements to CRUSH and the usage policies atop it to enable scalable replica reconstruction. We use these methods to demonstrate a simulated aggregate rebuild rate of 410 GiB/s (within 5% of projected ideal linear scaling) on a 1,024-node commodity storage system. We also uncover an unexpected phenomenon in rebuild performance based on the characteristics of the data stored on the system.

Carns, Philip↗
DOE OSTI2023

Coarse-to-fine Task-driven Inpainting for Geoscience Images

The processing and recognition of geoscience images have wide applications. Most of existing researches focus on understanding the high-quality geoscience images by assuming that all the images are clear. However, in many real-world cases, the geoscience images might contain occlusions during the image acquisition. This problem actually implies the image inpainting problem in computer vision and multimedia. As far as we know, all the existing image inpainting algorithms learn to repair the occluded regions for a better visualization quality, they are excellent for natural images but not good enough for geoscience images, and they never consider the following geoscience task when developing inpainting methods. Here, this paper aims to repair the occluded regions for a better geoscience task performance and advanced visualization quality simultaneously, without changing the current deployed deep learning based geoscience models. Because of the complex context of geoscience images, we propose a coarse-to-fine encoder-decoder network with the help of designed coarse-to-fine adversarial context discriminators to reconstruct the occluded image regions. Due to the limited data of geoscience images, we propose a MaskMix based data augmentation method, which augments inpainting masks instead of augmenting original images, to exploit the limited geoscience image data. The experimental results on three public geoscience datasets for remote sensing scene recognition, cross-view geolocation and semantic segmentation tasks respectively show the effectiveness and accuracy of the proposed method. The code is available at: https://github.com/HMS97/Task-driven-Inpainting.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2019

A Stochastic Multi-Commodity Logistic Model for Disaster Preparation in Distribution Systems

In this paper, we propose a stochastic optimization approach for disaster preparation in distribution systems. For an upcoming storm, utilities should have a preparation plan that includes warehousing restoration supplies, securing staging sites (depots), and prepositioning crews and equipment. Pre-storm planning enables faster and more efficient post-disaster deploy ment of crews and equipment resources to damage locations. To assist utilities in making this important preparation, this paper develops a two-stage stochastic mixed integer linear program. The first stage determines the depots, number of crews in each site, and the amount of equipment. The second stage is the recourse action that deals with acquiring new equipment and assigning crews to repair damages in realized scenarios. The objective of the developed model is to minimize the costs of depots, crews, equipment, and penalty costs associated with delays in obtain ing equipment and restoration. We consider the uncertainties of damaged lines, number and type of equipment required, and expected repair times. The model is validated on modified IEEE 123-bus distribution test system.

24 POWER TRANSMISSION AND DISTRIBUTION↗
DOE OSTI2019

Insights into VdCmr1‐mediated protection against high temperature stress and UV irradiation in Verticillium dahliae

Summary The fungus Verticillium dahliae causes vascular wilt disease on more than 200 plant species worldwide. This fungus can survive for years in soil as melanized microsclerotia. We found that VdCmr1, a transcription factor, is required for the melanin production and increased survival following UV irradiation in V. dahliae but not for microsclerotia production or virulence. Here, we provided evidence how VdCmr1 protects against high temperature (HT) and UV irradiation in V. dahliae . The results indicate that VdCmr1 mediates entry to the diapause period in V. dahliae in response to HT and contributes to the expression of proteins to minimize protein misfolding and denaturation. VdCmr1 deletion results in the misregulation of DNA repair machinery, suggestive of reduced DNA repair capacity following UV irradiation and in correlation with the low survival rate of UV‐treated VdCmr1 mutants. We discovered a putative VdCmr1 ‐dependent gene cluster associated with secondary metabolism and stress responses. We also functionally characterized two VdCmr1‐responsive genes participating in HT and UV response. These results shed further light on the roles of VdCmr1 in protection from HT or UV irradiation, and the additional insights into the mechanisms of this protection may be useful to exploit for more effective disease control.

Fang, Yulin↗
DOE OSTI2015

Photobiological Origins of the Field of Genomic Maintenance

Abstract Although sunlight is essential for life on earth, the ultraviolet ( UV ) wavelengths in its spectrum constitute a major threat to life. Various cellular responses have evolved to deal with the damage inflicted in DNA by UV , and the study of these responses in model systems has spawned the burgeoning field of DNA repair. Although we now know of many types of deleterious alterations in DNA , the approaches for studying them and the early mechanistic insights have come in large part from pioneering research on the processing of UV ‐induced bipyrimidine photoproducts in bacteria. It is also notable that UV was one of the first DNA damaging agents for which exposure was directly linked to cancer; the sun‐sensitive syndrome, xeroderma pigmentosum, was the first example of a cancer‐prone hereditary disease involving a defect in DNA repair. We provide a short history of advances in the broad field of genomic maintenance as they have emerged from research in photochemistry and photobiology.

Ganesan, Ann↗
DOE OSTI2015

Differential effects of ambient or diminished CO 2 and O 2 levels on thylakoid membrane structure in light‐stressed plants

Summary Over‐reduction of the photosynthetic electron transport chain may severely damage the photosynthetic apparatus as well as other constituents of the chloroplast and the cell. Here, we exposed Arabidopsis leaves to saturating light either under normal atmospheric conditions or under CO 2 ‐ and O 2 ‐limiting conditions, which greatly increase excitation and electron pressures by draining terminal electron acceptors. The two treatments were found to have very different, often opposing, effects on the structure of the thylakoid membranes, including the width of the granal lumenal compartment. Modulation of the latter is proposed to be related to movements of ions across the thylakoid membrane, which alter the relative osmolarity of the lumen and stroma and affect the partitioning of the proton motive force into its electrical and osmotic components. The resulting changes in thylakoid organization and lumenal width should facilitate the repair of photodamaged photosystem II complexes in response to light stress under ambient conditions, but are expected to inhibit the repair cycle when the light stress occurs concurrently with CO 2 and O 2 depletion. Under the latter conditions, the changes in thylakoid structure are predicted to complement other processes that restrict the flow of electrons into the high‐potential chain, thus moderating the production of deleterious reactive oxygen species at photosystem I.

Tsabari, Onie↗
DOE OSTI2021

Initial Process Planning of a Hybrid Multi-Tasking Platform

Abstract Applications of hybrid technology are expanding from refurbishment and repair to low quantity, specialty part production, which are staple characteristics in medical implant, energy, and aerospace industry sectors, among others. This expansion has led to the development of the Mazak VC-500A/5X AM HWD, a wire fed laser cladding unit equipped with a standard 5 axis CNC. This unit is capable of building near net geometry of complex medium to large parts within a profitable timeframe, due to its comparatively high rate of deposition to that of a powder fed hybrid system. In this study, deposition and machining capabilities of the VC-500A/5X AM HWD are assessed through the production of three different test geometries by different process plans. Production of these test geometries is supported by an open loop sensor package primarily for monitoring machine health, data collection, and machine operator aid. The viability of extended deposition followed by machining is evaluated against a more cyclical strategy of reoccurring deposition and machining operations. Lastly, common defects in as-built geometries are evaluated and addressed through revisions to original process plans and toolpaths, indicating the need for continued innovation in hybrid manufacturing specific CAM/CAD software, as well as closed loop machine monitoring and quality control.

DeWitte, Lisa N.↗
DOE OSTI2013

A multimodality vascular imaging phantom of an abdominal aortic aneurysm with a visible thrombus

Purpose: With the continuous development of new stent grafts and implantation techniques, it has now become technically feasible to treat abdominal aortic aneurysms (AAA) with challenging anatomy using endovascular repair with standard, fenestrated, or branched stent-grafts. In vitro experimentations are very useful to improve stent-graft design and conformability or imaging guidance for stent-graft delivery or follow-up. Vascular replicas also help to better understand the limitation of endovascular approaches in challenging anatomy and possibly improve surgical planning or training by practicing high risk clinical procedures in the laboratory to improve outcomes in the operating room. Most AAA phantoms available have a very basic anatomy, which is not representative of the clinical reality. This paper presents a method of fabrication of a realistic AAA phantom with a visible thrombus, as well as some mechanical properties characterizing such phantom. Methods: A realistic AAA geometry replica of a real patient anatomy taken from a multidetector computed tomography (CT) scan was manufactured. To demonstrate the multimodality imaging capability of this new phantom with a thrombus visible in magnetic resonance (MR) angiography, CT angiography (CTA), digital subtraction angiography (DSA), and ultrasound, image acquisitions with all these modalities were performed by using standard clinical protocols. Potential use of this phantom for stent deployment was also tested. A rheometer allowed defining hyperelastic and viscoelastic properties of phantom materials. Results: MR imaging measurements of SNR and CNR values on T1 and T2-weighted sequences and MR angiography indicated reasonable agreement with published values of AAA thrombus and abdominal components in vivo. X-ray absorption also lay within normal ranges of AAA patients and was representative of findings observed on CTA, fluoroscopy, and DSA. Ultrasound propagation speeds for developed materials were also in concordance with the literature for vascular and abdominal tissues. Conclusions: The mimicked abdominal tissues, AAA wall, and surrounding thrombus were developed to match imaging features of in vivo MR, CT, and ultrasound examinations. This phantom should be of value for image calibration, segmentation, and testing of endovascular devices for AAA endovascular repair.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Determination of prescription dose for Cs-131 permanent implants using the BED formalism including resensitization correction

Purpose: The current widely used biological equivalent dose (BED) formalism for permanent implants is based on the linear-quadratic model that includes cell repair and repopulation but not resensitization (redistribution and reoxygenation). The authors propose a BED formalism that includes all the four biological effects (4Rs), and the authors propose how it can be used to calculate appropriate prescription doses for permanent implants with Cs-131. Methods: A resensitization correction was added to the BED calculation for permanent implants to account for 4Rs. Using the same BED, the prescription doses with Au-198, I-125, and Pd-103 were converted to the isoeffective Cs-131 prescription doses. The conversion factor F, ratio of the Cs-131 dose to the equivalent dose with the other reference isotope (F{sub r}: with resensitization, F{sub n}: without resensitization), was thus derived and used for actual prescription. Different values of biological parameters such as α, β, and relative biological effectiveness for different types of tumors were used for the calculation. Results: Prescription doses with I-125, Pd-103, and Au-198 ranging from 10 to 160 Gy were converted into prescription doses with Cs-131. The difference in dose conversion factors with (F{sub r}) and without (F{sub n}) resensitization was significant but varied with different isotopes and different types of tumors. The conversion factors also varied with different doses. For I-125, the average values of F{sub r}/F{sub n} were 0.51/0.46, for fast growing tumors, and 0.88/0.77 for slow growing tumors. For Pd-103, the average values of F{sub r}/F{sub n} were 1.25/1.15 for fast growing tumors, and 1.28/1.22 for slow growing tumors. For Au-198, the average values of F{sub r}/F{sub n} were 1.08/1.25 for fast growing tumors, and 1.00/1.06 for slow growing tumors. Using the biological parameters for the HeLa/C4-I cells, the averaged value of F{sub r} was 1.07/1.11 (rounded to 1.1), and the averaged value of F{sub n} was 1.75/1.18. F{sub r} of 1.1 has been applied to gynecological cancer implants with expected acute reactions and outcomes as expected based on extensive experience with permanent implants. The calculation also gave the average Cs-131 dose of 126 Gy converted from the I-125 dose of 144 Gy for prostate implants. Conclusions: Inclusion of an allowance for resensitization led to significant dose corrections for Cs-131 permanent implants, and should be applied to prescription dose calculation. The adjustment of the Cs-131 prescription doses with resensitization correction for gynecological permanent implants was consistent with clinical experience and observations. However, the Cs-131 prescription doses converted from other implant doses can be further adjusted based on new experimental results, clinical observations, and clinical outcomes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

WE-E-BRE-03: Biological Validation of a Novel High-Throughput Irradiator for Predictive Radiation Sensitivity Bioassays

Purpose: The large dose-response variation in both tumor and normal cells between individual patients has led to the recent implementation of predictive bioassays of patient-specific radiation sensitivity in order to personalize radiation therapy. This exciting new clinical paradigm has led us to develop a novel high-throughput, variable dose-rate irradiator to accompany these efforts. Here we present the biological validation of this irradiator through the use of human cells as a relative dosimeter assessed by two metrics, DNA double-strand break repair pathway modulation and intercellular reactive oxygen species production. Methods: Immortalized human tonsilar epithelial cells were cultured in 96-well micro titer plates and irradiated in groups of eight wells to absorbed doses of 0, 0.5, 1, 2, 4, and 8 Gy. High-throughput immunofluorescent microscopy was used to detect γH2AX, a DNA double-strand break repair mechanism recruiter. The same analysis was performed with the cells stained with CM-H2DCFDA that produces a fluorescent adduct when exposed to reactive oxygen species during the irradiation cycle. Results: Irradiations of the immortalized human tonsilar epithelial cells at absorbed doses of 0, 0.5, 1, 2, 4, and 8 Gy produced excellent linearity in γH2AX and CM-H2DCFDA with R2 values of 0.9939 and 0.9595 respectively. Single cell gel electrophoresis experimentation for the detection of physical DNA double-strand breaks in ongoing. Conclusions: This work indicates significant potential for our high-throughput variable dose rate irradiator for patient-specific predictive radiation sensitivity bioassays. This irradiator provides a powerful tool by increasing the efficiency and number of assay techniques available to help personalize radiation therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-686: Considerations About Dose Protraction Factor in TCP Calculations for Prostate VMAT Treatments

Purpose: Dose protraction factor should be considered in order to model the TCP calculations. Nevertheless, this study describes a brief discussion showing that the lack of its inclusion should not invalidate these calculations for prostate VMAT treatments. Methods: Dose protraction factor (G) modifies the quadratic term of the linear-quadratic expression in order to take into account the sublethal damage repair of protracting the dose delivery. If the delivery takes a short time (instantaneous), G = 1. For any other dose delivery pattern, G < 1. The Lea-Catcheside dose protraction factor for external beam radiotherapy contains terms depending of on the tissue specific repair parameter (λ) and the irradiation time (T). Expanding the exponential term using a Taylor’s series and neglecting terms of order (λT){sup 3}, the approximation leads to G = 1. The described situation occurs for 3DCRT techniques, where treatment times are about few minutes. For IMRT techniques, fraction times are prolonged compared to 3DCRT times. Wang et al. (2003) and Fowler et al. (2004) investigated the protraction effect with respect to IMRT treatments, reporting clinically significant loss in biological effect associated with IMRT delivery times. Results: Treatment times are noticeably reduced for prostate treatments using VMAT techniques. These times are comparable to 3DCRT times, leading to consider the previous approximation. Conclusion: Dose protraction factor can be approximated by G = 1 in TCP calculations for prostate treatments using VMAT techniques.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Simultaneous covalent and noncovalent hybrid polymerizations

Covalent and supramolecular polymers are two distinct forms of soft matter, composed of long chains of covalently and noncovalently linked structural units, respectively. We report a hybrid system formed by simultaneous covalent and supramolecular polymerizations of monomers. The process yields cylindrical fibers of uniform diameter that contain covalent and supramolecular compartments, a morphology not observed when the two polymers are formed independently. The covalent polymer has a rigid aromatic imine backbone with helicoidal conformation, and its alkylated peptide side chains are structurally identical to the monomer molecules of supramolecular polymers. In the hybrid system, covalent chains grow to higher average molar mass relative to chains formed via the same polymerization in the absence of a supramolecular compartment. Here, the supramolecular compartments can be reversibly removed and re-formed to reconstitute the hybrid structure, suggesting soft materials with novel delivery or repair functions.

36 MATERIALS SCIENCE↗
DOE OSTI2017

LungMAP: The Molecular Atlas of Lung Development Program

The National Heart, Lung, and Blood Institute is funding an effort to create a molecular atlas of the developing lung (LungMAP) to serve as a research resource and public education tool. The lung is a complex organ with lengthy development time driven by interactive gene networks and dynamic cross talk among multiple cell types to control and coordinate lineage specification, cell proliferation, differentiation, migration, morphogenesis, and injury repair. A better understanding of the processes that regulate lung development, particularly alveologenesis, will have a significant impact on survival rates for premature infants born with incomplete lung development and will facilitate lung injury repair and regeneration in adults. A consortium of four research centers, a data coordinating center, and a human tissue repository provides high-quality molecular data of developing human and mouse lungs. LungMAP includes mouse and human data for cross correlation of developmental processes across species. LungMAP is generating foundational data and analysis, creating a web portal for presentation of results and public sharing of data sets, establishing a repository of young human lung tissues obtained through organ donor organizations, and developing a comprehensive lung ontology that incorporates the latest findings of the consortium. The LungMAP website (www.lungmap.net) currently contains more than 6,000 high-resolution lung images and transcriptomic, proteomic, and lipidomic human and mouse data and provides scientific information to stimulate interest in research careers for young audiences. This paper presents a brief description of research conducted by the consortium, database, and portal development and upcoming features that will enhance the LungMAP experience for a community of users.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Archaeal Genome Guardians Give Insights into Eukaryotic DNA Replication and Damage Response Proteins

As the third domain of life, archaea, like the eukarya and bacteria, must have robust DNA replication and repair complexes to ensure genome fidelity. Archaea moreover display a breadth of unique habitats and characteristics, and structural biologists increasingly appreciate these features. As archaea include extremophiles that can withstand diverse environmental stresses, they provide fundamental systems for understanding enzymes and pathways critical to genome integrity and stress responses. Such archaeal extremophiles provide critical data on the periodic table for life as well as on the biochemical, geochemical, and physical limitations to adaptive strategies allowing organisms to thrive under environmental stress relevant to determining the boundaries for life as we know it. Specifically, archaeal enzyme structures have informed the architecture and mechanisms of key DNA repair proteins and complexes. With added abilities to temperature-trap flexible complexes and reveal core domains of transient and dynamic complexes, these structures provide insights into mechanisms of maintaining genome integrity despite extreme environmental stress. The DNA damage response protein structures noted in this review therefore inform the basis for genome integrity in the face of environmental stress, with implications for all domains of life as well as for biomanufacturing, astrobiology, and medicine.

59 BASIC BIOLOGICAL SCIENCES↗