SEARCH · Engineering Papers

Results for “Maintainability”

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.

SourceResearch connectionFrom yearThrough year

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

At least 811 records · Page 45

All sources NASA NTRS DOE OSTI

DOE OSTI2012

Dose optimization with first-order total-variation minimization for dense angularly sampled and sparse intensity modulated radiation therapy (DASSIM-RT)

Purpose: A new treatment scheme coined as dense angularly sampled and sparse intensity modulated radiation therapy (DASSIM-RT) has recently been proposed to bridge the gap between IMRT and VMAT. By increasing the angular sampling of radiation beams while eliminating dispensable segments of the incident fields, DASSIM-RT is capable of providing improved conformity in dose distributions while maintaining high delivery efficiency. The fact that DASSIM-RT utilizes a large number of incident beams represents a major computational challenge for the clinical applications of this powerful treatment scheme. The purpose of this work is to provide a practical solution to the DASSIM-RT inverse planning problem. Methods: The inverse planning problem is formulated as a fluence-map optimization problem with total-variation (TV) minimization. A newly released L1-solver, template for first-order conic solver (TFOCS), was adopted in this work. TFOCS achieves faster convergence with less memory usage as compared with conventional quadratic programming (QP) for the TV form through the effective use of conic forms, dual-variable updates, and optimal first-order approaches. As such, it is tailored to specifically address the computational challenges of large-scale optimization in DASSIM-RT inverse planning. Two clinical cases (a prostate and a head and neck case) are used to evaluate the effectiveness and efficiency of the proposed planning technique. DASSIM-RT plans with 15 and 30 beams are compared with conventional IMRT plans with 7 beams in terms of plan quality and delivery efficiency, which are quantified by conformation number (CN), the total number of segments and modulation index, respectively. For optimization efficiency, the QP-based approach was compared with the proposed algorithm for the DASSIM-RT plans with 15 beams for both cases. Results: Plan quality improves with an increasing number of incident beams, while the total number of segments is maintained to be about the same in both cases. For the prostate patient, the conformation number to the target was 0.7509, 0.7565, and 0.7611 with 80 segments for IMRT with 7 beams, and DASSIM-RT with 15 and 30 beams, respectively. For the head and neck (HN) patient with a complicated target shape, conformation numbers of the three treatment plans were 0.7554, 0.7758, and 0.7819 with 75 segments for all beam configurations. With respect to the dose sparing to the critical structures, the organs such as the femoral heads in the prostate case and the brainstem and spinal cord in the HN case were better protected with DASSIM-RT. For both cases, the delivery efficiency has been greatly improved as the beam angular sampling increases with the similar or better conformal dose distribution. Compared with conventional quadratic programming approaches, first-order TFOCS-based optimization achieves far faster convergence and smaller memory requirements in DASSIM-RT. Conclusions: The new optimization algorithm TFOCS provides a practical and timely solution to the DASSIM-RT or other inverse planning problem requiring large memory space. The new treatment scheme is shown to outperform conventional IMRT in terms of dose conformity to both the targetand the critical structures, while maintaining high delivery efficiency.

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2013

A study of IMRT planning parameters on planning efficiency, delivery efficiency, and plan quality

Purpose: To improve planning and delivery efficiency of head and neck IMRT without compromising planning quality through the evaluation of inverse planning parameters.Methods: Eleven head and neck patients with pre-existing IMRT treatment plans were selected for this retrospective study. The Pinnacle treatment planning system (TPS) was used to compute new treatment plans for each patient by varying the individual or the combined parameters of dose/fluence grid resolution, minimum MU per segment, and minimum segment area. Forty-five plans per patient were generated with the following variations: 4 dose/fluence grid resolution plans, 12 minimum segment area plans, 9 minimum MU plans, and 20 combined minimum segment area/minimum MU plans. Each plan was evaluated and compared to others based on dose volume histograms (DVHs) (i.e., plan quality), planning time, and delivery time. To evaluate delivery efficiency, a model was developed that estimated the delivery time of a treatment plan, and validated through measurements on an Elekta Synergy linear accelerator. Results: The uncertainty (i.e., variation) of the dose-volume index due to dose calculation grid variation was as high as 8.2% (5.5 Gy in absolute dose) for planning target volumes (PTVs) and 13.3% (2.1 Gy in absolute dose) for planning at risk volumes (PRVs). Comparison results of dose distributions indicated that smaller volumes were more susceptible to uncertainties. The grid resolution of a 4 mm dose grid with a 2 mm fluence grid was recommended, since it can reduce the final dose calculation time by 63% compared to the accepted standard (2 mm dose grid with a 2 mm fluence grid resolution) while maintaining a similar level of dose-volume index variation. Threshold values that maintained adequate plan quality (DVH results of the PTVs and PRVs remained satisfied for their dose objectives) were 5 cm{sup 2} for minimum segment area and 5 MU for minimum MU. As the minimum MU parameter was increased, the number of segments and delivery time were decreased. Increasing the minimum segment area parameter decreased the plan MU, but had less of an effect on the number of segments and delivery time. Our delivery time model predicted delivery time to within 1.8%. Conclusions: Increasing the dose grid while maintaining a small fluence grid allows for improved planning efficiency without compromising plan quality. Delivery efficiency can be improved by increasing the minimum MU, but not the minimum segment area. However, increasing the respective minimum MU and/or the minimum segment area to any value greater than 5 MU and 5 cm{sup 2} is not recommended because it degrades plan quality.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2014

SU-E-T-524: Web-Based Radiation Oncology Incident Reporting and Learning System (ROIRLS)

Purpose: Describe a Web-based Radiation Oncology Incident Reporting and Learning system that has the potential to improve quality of care for radiation therapy patients. This system is an important facet of continuing effort by our community to maintain and improve safety of radiotherapy.Material and Methods: The VA National Radiation Oncology Program office has embarked on a program to electronically collect adverse events and near miss data of radiation treatment of over 25,000 veterans treated with radiotherapy annually. Software used for this program is deployed on the VAs intranet as a Website. All data entry forms (adverse event or near miss reports, work product reports) utilize standard causal, RT process step taxonomies and data dictionaries defined in AAPM and ASTRO reports on error reporting (AAPM Work Group Report on Prevention of Errors and ASTROs safety is no accident report). All reported incidents are investigated by the radiation oncology domain experts. This system encompasses the entire feedback loop of reporting an incident, analyzing it for salient details, and developing interventions to prevent it from happening again. The operational workflow is similar to that of the Aviation Safety Reporting System. This system is also synergistic with ROSIS and SAFRON. Results: The ROIRLS facilitates the collection of data that help in tracking adverse events and near misses and develop new interventions to prevent such incidents. The ROIRLS electronic infrastructure is fully integrated with each registered facility profile data thus minimizing key strokes and multiple entries by the event reporters. Conclusions: OIRLS is expected to improve the quality and safety of a broad spectrum of radiation therapy patients treated in the VA and fulfills our goal of Effecting Quality While Treating Safely The Radiation Oncology Incident Reporting and Learning System software used for this program has been developed, conceptualized and maintained by TSG Innovations Inc. and is deployed on the VA intranet as a Website. The Radiation Oncology Incident Reporting and Learning System software used for this program has been developed, conceptualized and maintained by TSG Innovations Inc. and is deployed on the VA intranet as a Website.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

TH-C-BRD-11: Robustness of Pencil Beam Scanning Proton Therapy for Pelvic Cancer Under Anatomical Changes

Purpose: Pencil beam scanning (PBS) proton therapy provides excellent dosimetric benefits in pelvic cancer treatment, yet day-to-day anatomical variations in pelvic region tend to cause range uncertainties. This study evaluates the dosimetric robustness under anatomical changes for three PBS intensity-modulated proton therapy (IMPT), IMPT using worstcase robust optimization (thereafter ‘Robust IMPT’), and single-field uniform dose (SFUD), in cervical cancer treatment. Methods: IMPT, Robust IMPT, and SFUD plans using the same beam directions and the same prescription (Rx) were generated on computed tomography (CT) images acquired on the simulation day. The dose from each plan was then recomputed on CT images acquired in subsequent two to five weeks using the same protocol. The weekly CTs were registered to the planning CT based on bony anatomy. Target coverage was considered adequate on each weekly CT if dose to 99% of the internal target volume (D-ITV99%) reached at least 95% of the Rx dose. Statistical analysis was then performed on the 21 weekly CT images available for the 7 enrolled patients. Results: Statistically, IMPT was unable to maintain target coverage (mean D-ITV99% = 90.5% Rx, p = 0.004), and SFUD was able to maintain target coverage (mean D-ITV99% = 98.0% Rx, p = 0.0064), in the weeks following simulation. Robust IMPT was able to improve the robustness of IMPT significantly (p < 0.0001), though its maintenance of target coverage was not statistically significant by the 95% Rx criteria (mean D-ITV99% = 96.0%, p = 0.1677). Conclusion: During the multi-week treatment course with anatomical variations, SFUD is robust in terms of maintaining target coverage while IMPT is not. The worst-case optimized Robust IMPT, assuming ±3.5% range uncertainties, improves the robustness of IMPT under anatomical changes significantly, even though it was not designed to account for anatomical changes by mechanism.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

Tailoring automatic exposure control toward constant detectability in digital mammography

Purpose: The automatic exposure control (AEC) modes of most full field digital mammography (FFDM) systems are set up to hold pixel value (PV) constant as breast thickness changes. This paper proposes an alternative AEC mode, set up to maintain some minimum detectability level, with the ultimate goal of improving object detectability at larger breast thicknesses. Methods: The default “OPDOSE” AEC mode of a Siemens MAMMOMAT Inspiration FFDM system was assessed using poly(methyl methacrylate) (PMMA) of thickness 20, 30, 40, 50, 60, and 70 mm to find the tube voltage and anode/filter combination programmed for each thickness; these beam quality settings were used for the modified AEC mode. Detectability index (d′), in terms of a non-prewhitened model observer with eye filter, was then calculated as a function of tube current-time product (mAs) for each thickness. A modified AEC could then be designed in which detectability never fell below some minimum setting for any thickness in the operating range. In this study, the value was chosen such that the system met the achievable threshold gold thickness (T{sub t}) in the European guidelines for the 0.1 mm diameter disc (i.e., T{sub t} ≤ 1.10 μm gold). The default and modified AEC modes were compared in terms of contrast-detail performance (T{sub t}), calculated detectability (d′), signal-difference-to-noise ratio (SDNR), and mean glandular dose (MGD). The influence of a structured background on object detectability for both AEC modes was examined using a CIRS BR3D phantom. Computer-based CDMAM reading was used for the homogeneous case, while the images with the BR3D background were scored by human observers. Results: The default OPDOSE AEC mode maintained PV constant as PMMA thickness increased, leading to a reduction in SDNR for the homogeneous background 39% and d′ 37% in going from 20 to 70 mm; introduction of the structured BR3D plate changed these figures to 22% (SDNR) and 6% (d′), respectively. Threshold gold thickness (0.1 mm diameter disc) for the default AEC mode in the homogeneous background increased by 62% in going from 20 to 70 mm PMMA thickness; in the structured background, the increase was 39%. Implementation of the modified mode entailed an increase in mAs at PMMA thicknesses >40 mm; the modified AEC held threshold gold thickness constant above 40 mm PMMA with a maximum deviation of 5% in the homogeneous background and 3% in structured background. SDNR was also held constant with a maximum deviation of 4% and 2% for the homogeneous and the structured background, respectively. These results were obtained with an increase of MGD between 15% and 73% going from 40 to 70 mm PMMA thickness. Conclusions: This work has proposed and implemented a modified AEC mode, tailored toward constant detectability at larger breast thickness, i.e., above 40 mm PMMA equivalent. The desired improvement in object detectability could be obtained while maintaining MGD within the European guidelines achievable dose limit. (A study designed to verify the performance of the modified mode using more clinically realistic data is currently underway.)

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-D-304-01: Development of An Applicator for Treating Shallow and Moving Tumors with Respiratory-Gated Spot-Scanning Proton Therapy Using Real-Time Image Guidance

Purpose: To develop a method for treating shallow and moving tumors (e.g., lung tumors) with respiratory-gated spot-scanning proton therapy using real-time image guidance (RTPT). Methods: An applicator was developed which can be installed by hand on the treatment nozzle. The mechanical design was considered such that the Bragg peaks are placed at the patient surface while a sufficient field of view (FOV) of fluoroscopic X-rays was maintained during the proton beam delivery. To reduce the treatment time maintaining the robustness of the dose distribution with respect to motion, a mini-ridge filter (MRF) was sandwiched between two energy absorbers. The measurements were performed to obtain a data for beam modeling and to verify the spot position-invariance of a pencil beam dose distribution. For three lung cancer patients, treatment plans were made with and without the MRF and the effects of the MRF were evaluated. Next, the effect of respiratory motion on the dose distribution was investigated. Results: To scan the proton beam over a 14 x 14 cm area while maintaining the φ16 cm of fluoroscopic FOV, the lower face of the applicator was set 22 cm upstream of the isocenter. With an additional range variance of 2.2 mm and peak-to-peak distance of 4 mm of the MRF, the pencil beam dose distribution was unchanged with the displacement of the spot position. The quality of the treatment plans was not worsened by the MRF. With the MRF, the number of energy layers was reduced to less than half and the treatment time by 26–37%. The simulation study showed that the interplay effect was successfully suppressed by respiratory-gating both with and without MRF. Conclusions: The spot-scanning proton beam was successfully delivered to shallow and moving tumors within a sufficiently short time by installing the developed applicator at the RTPT nozzle.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-T-551: Monitor Unit Optimization in Stereotactic Body Radiation Therapy for Stage I Lung Cancer

Purpose: The study aims to reduce the monitor units (MUs) in the stereotactic body radiation therapy (SBRT) treatment for lung cancer by adjusting the optimizing parameters. Methods: Fourteen patients suffered from stage I Non-Small Cell Lung Cancer (NSCLC) were enrolled. Three groups of parameters were adjusted to investigate their effects on MU numbers and organs at risk (OARs) sparing: (1) the upper objective of planning target volume (UOPTV); (2) strength setting in the MU constraining objective; (3) max MU setting in the MU constraining objective. Results: We found that the parameters in the optimizer influenced the MU numbers in a priority, strength and max MU dependent manner. MU numbers showed a decreasing trend with the UOPTV increasing. MU numbers with low, medium and high priority for the UOPTV were 428±54, 312±48 and 258±31 MU/Gy, respectively. High priority for UOPTV also spared the heart, cord and lung while maintaining comparable PTV coverage than the low and medium priority group. It was observed that MU numbers tended to decrease with the strength increasing and max MU setting decreasing. With maximum strength, the MU numbers reached its minimum while maintaining comparable or improved dose to the normal tissues. It was also found that the MU numbers continued to decline at 85% and 75% max MU setting but no longer to decrease at 50% and 25%. Combined with high priority for UOPTV and MU constraining objectives, the MU numbers can be decreased as low as 223±26 MU/Gy. Conclusion:: The priority of UOPTV, MU constraining objective in the optimizer impact on the MU numbers in SBRT treatment for lung cancer. Giving high priority to the UOPTV, setting the strength to maximum value and the max MU to 50% in the MU objective achieves the lowest MU numbers while maintaining comparable or improved OAR sparing.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2015

TU-EF-204-09: A Preliminary Method of Risk-Informed Optimization of Tube Current Modulation for Dose Reduction in CT

Purpose: X-rays from CT scans can increase cancer risk to patients. Lifetime Attributable Risk of Cancer Incidence for adult patients has been investigated and shown to decrease as patient age. However, a new risk model shows an increasing risk trend for several radiosensitive organs for middle age patients. This study investigates the feasibility of a general method for optimizing tube current modulation (TCM) functions to minimize risk by reducing radiation dose to radiosensitive organs of patients. Methods: Organ-based TCM has been investigated in literature for eye lens dose and breast dose. Adopting the concept in organ-based TCM, this study seeks to find an optimized tube current for minimal total risk to breasts and lungs by reducing dose to these organs. The contributions of each CT view to organ dose are determined through simulations of CT scan view-by-view using a GPU-based fast Monte Carlo code, ARCHER. A Linear Programming problem is established for tube current optimization, with Monte Carlo results as weighting factors at each view. A pre-determined dose is used as upper dose boundary, and tube current of each view is optimized to minimize the total risk. Results: An optimized tube current is found to minimize the total risk of lungs and breasts: compared to fixed current, the risk is reduced by 13%, with breast dose reduced by 38% and lung dose reduced by 7%. The average tube current is maintained during optimization to maintain image quality. In addition, dose to other organs in chest region is slightly affected, with relative change in dose smaller than 10%. Conclusion: Optimized tube current plans can be generated to minimize cancer risk to lungs and breasts while maintaining image quality. In the future, various risk models and greater number of projections per rotation will be simulated on phantoms of different gender and age. National Institutes of Health R01EB015478.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

An investigation of kV CBCT image quality and dose reduction for volume-of-interest imaging using dynamic collimation

Purpose: The focus of this work was to investigate the improvements in image quality and dose reduction for volume-of-interest (VOI) kilovoltage-cone beam CT (CBCT) using dynamic collimation. Methods: A prototype iris aperture was used to track a VOI during a CBCT acquisition. The current aperture design is capable of 1D translation as a function of gantry angle and dynamic adjustment of the iris radius. The aperture occupies the location of the bow-tie filter on a Varian On-Board Imager system. CBCT and planar image quality were investigated as a function of aperture radius, while maintaining the same dose to the VOI, for a 20 cm diameter cylindrical water phantom with a 9 mm diameter bone insert centered on isocenter. Corresponding scatter-to-primary ratios (SPR) were determined at the detector plane with Monte Carlo simulation using EGSnrc. Dose distributions for various sizes VOI were modeled using a dynamic BEAMnrc library and DOSXYZnrc. The resulting VOI dose distributions were compared to full-field distributions. Results: SPR was reduced by a factor of 8.4 when decreasing iris diameter from 21.2 to 2.4 cm (at isocenter). Depending upon VOI location and size, dose was reduced to 16%–90% of the full-field value along the central axis plane and down to 4% along the axis of rotation, while maintaining the same dose to the VOI compared to full-field techniques. When maintaining constant dose to the VOI, this change in iris diameter corresponds to a factor increase of approximately 1.6 in image contrast and a factor decrease in image noise of approximately 1.2. This results in a measured gain in contrast-to-noise ratio by a factor of approximately 2.0. Conclusions: The presented VOI technique offers improved image quality for image-guided radiotherapy while sparing the surrounding volume of unnecessary dose compared to full-field techniques.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2024

Data Citation Explorer (DCE) v1.0

Increases in sequencing capacity, combined with rapid accumulation of publications and associated data resources, have increased the complexity of maintaining associations between literature and genomic data. As the volume of literature and data have exceeded the capacity of manual curation, automated approaches to maintaining and confirming associations among these resources have become necessary. Here we present the Data Citation Explorer (DCE), which discovers literature incorporating genomic data whether or not provenance was clearly indicated. This service provides advantages over manual curation methods including consistent resource coverage, metadata enrichment, documentation of new use cases, and identification of conflicting metadata. The service reduces labor costs associated with manual review, improves the quality of genome metadata maintained by the U.S. Department of Energy Joint Genome Institute (JGI), and increases the number of known publications that incorporate its data products. The DCE facilitates an understanding of JGI impact, improves credit attribution for data generators, and can encourage data sharing by allowing scientists to see how reuse amplifies the impact of their original studies.

Parker, Charles↗

DOE OSTI2018

Opportunities for Joint Water–Energy Management: Sensitivity of the 2010 Western U.S. Electricity Grid Operations to Climate Oscillations

The 2016 SECURE Water Act report’s natural water availability benchmark, combined with the 2010 level of water demand from an integrated assessment model, is used as input to drive a large-scale water management model. The regulated flow at hydropower plants and thermoelectric plants in the Western U.S. electricity grid (WECC) is translated into potential hydropower generation and generation capacity constraints. The impact on reliability (unserved energy, reserve margin) and cost (production cost, carbon emissions) of water constraints on 2010-level WECC power system operations is assessed using an electricity production cost model (PCM). Use of the PCM reveals the changes in generation dispatch that reflect the inter-regional interdependencies in water-constrained generation and the ability to use other generation resources to meet all electricity loads in the WECC. August grid operational benchmarks show a range of sensitivity in production cost (-8 to +11%) and carbon emissions (-7 to 11%). The reference reserve margin threshold of 15% above peak load is maintained in the scenarios analyzed, but in 5 out of 55 years unserved energy is observed when normal operations are maintained. There is 1 chance in 10 that a year will demonstrate unserved energy in August, which defines the system’s historical performance threshold to support impact, vulnerability, and adaptation analysis. For seasonal and longer term planning, i.e., multi-year drought, we demonstrate how the Water Scarcity Grid Impact Factor and climate oscillations (ENSO, PDO) can be used to plan for joint water-electricity management to maintain grid reliability.

adaptation↗

DOE OSTI2022

A Positive Low Cloud–Sea Surface Temperature Feedback in the East Asian Marginal Seas during El Niño Mature Winters and Their Following Spring

During the winter and subsequent spring of an El Niño year, the East Asian marginal sea (EAMS) exhibits positive sea surface temperature anomalies (SSTAs) and fewer low clouds, while the western North Pacific experiences negative SSTAs. In this study, we suggest that the positive SSTAs in EAMS are maintained by a positive low cloud–SST feedback. In neutral winters and springs, the EAMS is covered by low clouds, which have a cooling effect on surface temperatures. During an El Niño year, a western North Pacific anomalous anticyclone is established, and along its northwestern flank, there are favorable conditions for convergence of moisture and weaker surface latent heat flux over the EAMS. Once a positive SSTA has been established, a further reduction of turbulent mixing results in less low cloud and enhanced solar heating of the ocean mixed layer; this reinforces and maintains both the positive SSTA and the lack of low cloud via a positive feedback mechanism. Further, the concurrent increase of low cloud–SST feedback and anticyclone circulation strengths is evident in the coupled-model simulations from phase 6 of the Coupled Model Intercomparison Project. Furthermore, sensitivity experiments, performed with the atmospheric components of Community Earth System Model (CESM2), reveal that a positive SSTA helps to maintain the western North Pacific anomalous anticyclone. Four pacemaker-coupled experiments by CESM2, with sea surface temperature in the equatorial Pacific restored to the observational anomalies plus the model climatology and altered low cloud feedback over EAMS, suggest that the low cloud–SST feedback results in more than the maintenance of a positive SSTA over the EAMS: the positive feedback is also a previously overlooked mechanism for the maintenance of the western North Pacific anomalous anticyclone.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2011

Effects of temperature on the transmission of Yersinia Pestis by the flea, Xenopsylla Cheopis , in the late phase period

Background: Traditionally, efficient flea-borne transmission of Yersinia pestis, the causative agent of plague, was thought to be dependent on a process referred to as blockage in which biofilm-mediated growth of the bacteria physically blocks the flea gut, leading to the regurgitation of contaminated blood into the host. This process was previously shown to be temperature-regulated, with blockage failing at temperatures approaching 30°C; however, the abilities of fleas to transmit infections at different temperatures had not been adequately assessed. We infected colony-reared fleas of Xenopsylla cheopis with a wild type strain of Y. pestis and maintained them at 10, 23, 27, or 30°C. Naïve mice were exposed to groups of infected fleas beginning on day 7 post-infection (p.i.), and every 3-4 days thereafter until day 14 p.i. for fleas held at 10°C, or 28 days p.i. for fleas held at 23-30°C. Transmission was confirmed using Y. pestis-specific antigen or antibody detection assays on mouse tissues. Results: Although no statistically significant differences in per flea transmission efficiencies were detected between 23 and 30°C, efficiencies were highest for fleas maintained at 23°C and they began to decline at 27 and 30°C by day 21 p.i. These declines coincided with declining median bacterial loads in fleas at 27 and 30°C. Survival and feeding rates of fleas also varied by temperature to suggest fleas at 27 and 30°C would be less likely to sustain transmission than fleas maintained at 23°C. Fleas held at 10°C transmitted Y. pestis infections, although flea survival was significantly reduced compared to that of uninfected fleas at this temperature. Median bacterial loads were significantly higher at 10°C than at the other temperatures. Conclusions: Our results suggest that temperature does not significantly effect the per flea efficiency of Y. pestis transmission by X. cheopis, but that temperature is likely to influence the dynamics of Y. pestis flea-borne transmission, perhaps by affecting persistence of the bacteria in the flea gut or by influencing flea survival. Whether Y. pestis biofilm production is important for transmission at different temperatures remains unresolved, although our results support the hypothesis that blockage is not necessary for efficient transmission.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2026

EvoDiffMol: evolutionary diffusion framework for 3D molecular design with optimized properties

Designing molecules with specific target properties remains a fundamental challenge in computational chemistry. While existing approaches show promise, most rely on simplified representations like SMILES strings or 2D graphs that lack essential three-dimensional geometric information. We present EvoDiffMol, a computational framework that integrates evolutionary algorithms with three-dimensional diffusion models for property-driven molecular generation. The method operates through adaptive evolutionary optimization, where population-based selection guides the generation process toward desired property landscapes. EvoDiffMol supports both unconstrained molecular design and scaffold-constrained generation that preserves fixed substructures while optimizing complementary regions. Comprehensive evaluation demonstrates exceptional performance, achieving the highest drug-likeness score (0.94) among all compared state-of-the-art methods while maintaining excellent validity, uniqueness, and novelty. Beyond single property optimization, the framework demonstrates flexible multi-property optimization capabilities, simultaneously controlling multiple molecular descriptors including synthetic accessibility, lipophilicity, topological polar surface area, and clinically relevant ADMET properties such as cardiotoxicity (hERG) and intestinal permeability (Caco-2). This adaptability spans from simple descriptors to practical pharmaceutical endpoints without requiring complete model retraining. The framework achieves precise control over target property values, generating molecules with properties closely matching specified targets for both single and multiple descriptors. Scaffold-constrained experiments preserve fixed molecular cores while maintaining effective property optimization. The three-dimensional representation offers advantages in maintaining structural validity during iterative optimization, with potential for geometry-aware applications in materials science and drug discovery.

3D molecular generation↗

DOE OSTI2013

Conformational Coupling between Receptor and Kinase Binding Sites through a Conserved Salt Bridge in a Signaling Complex Scaffold Protein

Bacterial chemotaxis is one of the best studied signal transduction pathways. CheW is a scaffold protein that mediates the association of the chemoreceptors and the CheA kinase in a ternary signaling complex. The effects of replacing conserved Arg62 of CheW with other residues suggested that the scaffold protein plays a more complex role than simply binding its partner proteins. Although R62A CheW had essentially the same affinity for chemoreceptors and CheA, cells expressing the mutant protein are impaired in chemotaxis. Using a combination of molecular dynamics simulations (MD), NMR spectroscopy, and circular dichroism (CD), we addressed the role of Arg62. Here we show that Arg62 forms a salt bridge with another highly conserved residue, Glu38. Although this interaction is unimportant for overall protein stability, it is essential to maintain the correct alignment of the chemoreceptor and kinase binding sites of CheW. Computational and experimental data suggest that the role of the salt bridge in maintaining the alignment of the two partner binding sites is fundamental to the function of the signaling complex but not to its assembly. We conclude that a key feature of CheW is to maintain the specific geometry between the two interaction sites required for its function as a scaffold.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2018

Different culture media modulate growth, heterogeneity, and senescence in human mammary epithelial cell cultures

The ability to culture normal human mammary epithelial cells (HMEC) greatly facilitates experiments that seek to understand both normal mammary cell biology and the many differences between normal and abnormal human mammary epithelia. To maximize in vivo relevance, the primary cell culture conditions should maintain cells in states that resemble in vivo as much as possible. Towards this goal, we compared the properties of HMEC strains from two different reduction mammoplasty tissues that were grown in parallel using different media and culture conditions. Epithelial organoids were initiated into three different media: two commonly used serum-free-media, MCDB 170-type (e.g. MEGM) and WIT-P, and a low stress media, M87A. Growth, lineage heterogeneity, p16 protein expression, and population doublings to senescence were measured for each culture condition. MCDB 170 caused rapid senescence and loss of heterogeneity within 2 to 3 passages, but some cultures went through the 1 to 2 month process of selection to generate clonal finite post-selection post-stasis cells. WIT-P caused impressive expansion of luminal cells in 2nd passage followed by their near complete disappearance by passage 4 and senescence shortly thereafter. M87A supported as much as twice the number of population doublings compared to either serum-free medium, and luminal and myoepithelial cells were present for as many as 8 passages. Thus, of the three media compared, WIT-P and MCDB 170 imposed rapid senescence and loss of lineage heterogeneity, phenotypes consistent with cells maintained in high-stress conditions, while M87A supported cultures that maintained multiple lineages and robust growth for up to 60 population doublings. In conjunction with previous studies examining the molecular properties of cultures grown in these media, we conclude that M87A medium is most able to support long-term culture of multiple lineages similar to in vivo conditions, thereby facilitating investigations of normal HMEC biology relevant to the mammary gland in situ.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2019

Polysaccharide-based liquid storage and transport media for non-refrigerated preservation of bacterial pathogens

The preservation of biological samples for an extended time period of days to weeks after initial collection is important for the identification, screening, and characterization of bacterial pathogens. Traditionally, preservation relies on cold-chain infrastructure; however, in many situations this is impractical or not possible. Thus, our goal was to develop alternative bacterial sample preservation and transport media that are effective without refrigeration or external instrumentation. The viability, nucleic acid stability, and protein stability of Bacillus anthracis Sterne 34F2, Francisella novicida U112, Staphylococcus aureus ATCC 43300, and Yersinia pestis KIM D27 (pgm-) was assessed for up to 28 days. Xanthan gum (XG) prepared in PBS with L-cysteine maintained more viable F . novicida U112 cells at elevated temperature (40°C) compared to commercial reagents and buffers. Viability was maintained for all four bacteria in XG with 0.9 mM L-cysteine across a temperature range of 22–40°C. Interestingly, increasing the concentration to 9 mM L-cysteine resulted in the rapid death of S . aureus . This could be advantageous when collecting samples in the built environment where there is the potential for Staphylococcus collection and stabilization rather than other organisms of interest. F . novicida and S . aureus DNA were stable for up to 45 days upon storage at 22°C or 40°C, and direct analysis by real-time qPCR, without DNA extraction, was possible in the XG formulations. XG was not compatible with proteomic analysis via LC-MS/MS due to the high amount of residual Xanthomonas campestris proteins present in XG. Our results demonstrate that polysaccharide-based formulations, specifically XG with L-cysteine, maintain bacterial viability and nucleic acid integrity for an array of both Gram-negative and Gram-positive bacteria across ambient and elevated temperatures.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2022

Maximizing Strength: The Stimuli and Mediators of Strength Gains and Their Application to Training and Rehabilitation

Abstract Spiering, BA, Clark, BC, Schoenfeld, BJ, Foulis, SA, and Pasiakos, SM. Maximizing strength: the stimuli and mediators of strength gains and their application to training and rehabilitation. J Strength Cond Res 37(4): 919–929, 2023—Traditional heavy resistance exercise (RE) training increases maximal strength, a valuable adaptation in many situations. That stated, some populations seek new opportunities for pushing the upper limits of strength gains (e.g., athletes and military personnel). Alternatively, other populations strive to increase or maintain strength but cannot perform heavy RE (e.g., during at-home exercise, during deployment, or after injury or illness). Therefore, the purpose of this narrative review is to (a) identify the known stimuli that trigger gains in strength; (b) identify the known factors that mediate the long-term effectiveness of these stimuli; (c) discuss (and in some cases, speculate on) potential opportunities for maximizing strength gains beyond current limits; and (d) discuss practical applications for increasing or maintaining strength when traditional heavy RE cannot be performed. First, by conceptually deconstructing traditional heavy RE, we identify that strength gains are stimulated through a sequence of events, namely: giving maximal mental effort, leading to maximal neural activation of muscle to produce forceful contractions, involving lifting and lowering movements, training through a full range of motion, and (potentially) inducing muscular metabolic stress. Second, we identify factors that mediate the long-term effectiveness of these RE stimuli, namely: optimizing the dose of RE within a session, beginning each set of RE in a minimally fatigued state, optimizing recovery between training sessions, and (potentially) periodizing the training stimulus over time. Equipped with these insights, we identify potential opportunities for further maximizing strength gains. Finally, we identify opportunities for increasing or maintaining strength when traditional heavy RE cannot be performed.

Sport Sciences↗