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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 433 records · Page 24
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Electron and hole partial specific resistances: a framework to understand contacts to solar cells

In order to understand how contacts influence the performance of solar cells, we previously developed and presented the concept of partial specific resistances: for each contact of a solar cell, we defined voltage-dependent specific resistances to electrons and to holes. Although the connection between these partial specific resistances and the cell performance metrics at open circuit (iV oc and V oc ) is straightforward, the relationship becomes more complex when current flows out of the cell, in particular at the maximum power point. In the present work, we investigate the dependence of these hole and electron specific resistances on implied voltage. We show that the shapes of these curves-and not simply the resistance values at the maximum power point, which do not correspond to the same injection level in every cell-dictate the cell efficiency.

Onno, Arthur↗
DOE OSTI2019

Selection and characterization of ssDNA aptamers specifically recognizing pathogenic Vibrio alginolyticus

Abstract Vibrio alginolyticus ( V. alginolyticus ) is a major opportunistic pathogen to both marine animals and humans, which has also caused heavy economic losses to mariculture. The aim of this study was to develop highly specific aptamers for V. alginolyticus . Single‐stranded DNA (ssDNA) aptamers with high binding affinity to viable V. alginolyticus were generated by Systematic Evolution of Ligands by Exponential Enrichment (SELEX) and identified by flow cytometric analysis in this study. The selected aptamers showed high specificity for V. alginolyticus and low apparent binding for other bacteria. The aptamers formed distinct stem‐loop structures, which could form the basis of aptamers’ specific binding to the target V. alginolyticus . Aptamer VA2 and VA8 showed particularly high binding affinity constant (K d ) of 14.31 ± 4.26 and 90.00 ± 13.51 nM, respectively. The aptamers produced no cytotoxic effects in vitro and in vivo. ssDNA aptamers were successfully selected against the viable bacteria pathogen V. alginolyticus by SELEX. The aptamers selected in this study could be not only applied as specific chemical molecular probes for studying V. alginolyticus pathogenesis to Trachinotus ovatus , but also developing rapid convenient diagnosis assay for V. alginolyticus infection, even when applied to the complex sample matrix, such as food and environment samples.

Yu, Qing↗
DOE OSTI2022

OSCA1 is an osmotic specific sensor: a method to distinguish Ca 2+ -mediated osmotic and ionic perception

Genetic mutants defective in stimulus-induced Ca 2+ increases have been gradually isolated, allowing the identification of cell-surface sensors/receptors, such as the osmosensor OSCA1. However, determining the Ca 2+ -signaling specificity to various stimuli in these mutants remains a challenge. For instance, less is known about the exact selectivity between osmotic and ionic stresses in the osca1 mutant. Here, we have developed a method to distinguish the osmotic and ionic effects by analyzing Ca 2+ increases, and demonstrated that osca1 is impaired primarily in Ca 2+ increases induced by the osmotic but not ionic stress. We recorded Ca 2+ increases induced by sorbitol (osmotic effect, OE) and NaCl/CaCl 2 (OE + ionic effect, IE) in Arabidopsis wild-type and osca1 seedlings. Here we assumed the NaCl/CaCl 2 total effect (TE) = OE + IE, then developed procedures for Ca 2+ imaging, image analysis and mathematic fitting/modeling, and found osca1 defects mainly in OE. The osmotic specificity of osca1 suggests that osmotic and ionic perceptions are independent. The precise estimation of these two stress effects is applicable not only to new Ca 2+ -signaling mutants with distinct stimulus specificity but also the complex Ca 2+ signaling crosstalk among multiple concurrent stresses that occur naturally, and will enable us to specifically fine tune multiple signal pathways to improve crop yields.

Arabidopsis↗
DOE OSTI2014

Specific recommendations for accurate and direct use of PET-CT in PET guided radiotherapy for head and neck sites

Purpose: To provide specific experience-based guidance and recommendations for centers wishing to develop, validate, and implement an accurate and efficient process for directly using positron emission tomography-computed tomography (PET-CT) for the radiotherapy planning of head and neck cancer patients. Methods: A PET-CT system was modified with hard-top couch, external lasers and radiotherapy immobilization and indexing devices and was subject to a commissioning and quality assurance program. PET-CT imaging protocols were developed specifically for radiotherapy planning and the image quality and pathway tested using phantoms and five patients recruited into an in-house study. Security and accuracy of data transfer was tested throughout the whole data pathway. The patient pathway was fully established and tested ready for implementation in a PET-guided dose-escalation trial for head and neck cancer patients. Results: Couch deflection was greater than for departmental CT simulator machines. An area of high attenuation in the couch generated image artifacts and adjustments were made accordingly. Using newly developed protocols CT image quality was suitable to maintain delineation and treatment accuracy. Upon transfer of data to the treatment planning system a half pixel offset between PET and CT was observed and corrected. By taking this into account, PET to CT alignment accuracy was maintained below 1 mm in all systems in the data pathway. Transfer of structures delineated in the PET fusion software to the radiotherapy treatment planning system was validated. Conclusions: A method to perform direct PET-guided radiotherapy planning was successfully validated and specific recommendations were developed to assist other centers. Of major concern is ensuring that the quality of PET and CT data is appropriate for radiotherapy treatment planning and on-treatment verification. Couch movements can be compromised, bore-size can be a limitation for certain immobilization techniques, laser positioning may affect setup accuracy and couch deflection may be greater than scanners dedicated to radiotherapy. The full set of departmental commissioning and routine quality assurance tests applied to radiotherapy CT simulators must be carried out on the PET-CT scanner. CT image quality must be optimized for radiotherapy planning whilst understanding that the appearance will differ between scanners and may affect delineation. PET-CT quality assurance schedules will need to be added to and modified to incorporate radiotherapy quality assurance. Methods of working for radiotherapy and PET staff will change to take into account considerations of both parties. PET to CT alignment must be subject to quality control on a loaded and unloaded couch preferably using a suitable emission phantom, and tested throughout the whole data pathway. Data integrity must be tested throughout the whole pathway and a system included to verify that delineated structures are transferred correctly. Excellent multidisciplinary team communication and working is vital, and key staff members on both sides should be specifically dedicated to the project. Patient pathway should be clearly devised to optimize patient care and the resources of all departments. Recruitment of a cohort of patients into a methodology study is valuable to test the quality assurance methods and pathway.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

SU-E-I-40: New Method for Measurement of Task-Specific, High-Resolution Detector System Performance

Purpose: Although generalized linear system analytic metrics such as GMTF and GDQE can evaluate performance of the whole imaging system including detector, scatter and focal-spot, a simplified task-specific measured metric may help to better compare detector systems. Methods: Low quantum-noise images of a neuro-vascular stent with a modified ANSI head phantom were obtained from the average of many exposures taken with the high-resolution Micro-Angiographic Fluoroscope (MAF) and with a Flat Panel Detector (FPD). The square of the Fourier Transform of each averaged image, equivalent to the measured product of the system GMTF and the object function in spatial-frequency space, was then divided by the normalized noise power spectra (NNPS) for each respective system to obtain a task-specific generalized signal-to-noise ratio. A generalized measured relative object detectability (GM-ROD) was obtained by taking the ratio of the integral of the resulting expressions for each detector system to give an overall metric that enables a realistic systems comparison for the given detection task. Results: The GM-ROD provides comparison of relative performance of detector systems from actual measurements of the object function as imaged by those detector systems. This metric includes noise correlations and spatial frequencies relevant to the specific object. Additionally, the integration bounds for the GM-ROD can be selected to emphasis the higher frequency band of each detector if high-resolution image details are to be evaluated. Examples of this new metric are discussed with a comparison of the MAF to the FPD for neuro-vascular interventional imaging. Conclusion: The GM-ROD is a new direct-measured task-specific metric that can provide clinically relevant comparison of the relative performance of imaging systems. Supported by NIH Grant: 2R01EB002873 and an equipment grant from Toshiba Medical Systems Corporation.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2014

TU-C-BRE-06: Effect of Implementing In-House Treatment Couch Model On Patient Specific QA for Pinnacle SmartArc Treatment Plans

Purpose: Failure to model the treatment couch during VMAT QA planar dose calculation may Result in discrepancies between measured and calculated dose. These discrepancies are due to beam attenuation by the treatment couch that is not included in dose calculation. This work evaluates effects of accounting for this attenuation on patient specific VMAT QA results using an in-house created Varian Exact couch model in Pinnacl Methods: Patient specific VMAT QA results for 13 Pinnacle SmartArc plans generated for treatment on a Varian iX accelerator were studied. These plans included 3 treatment sites (7 H'N, 5 brain, 1 prostate). A Pinnacle model for Varian Exact couch was created in-house to replace the CT simulator couch. Composite arc planar doses were calculated with no couch present (NC) and with the Exact couch model (CM) in place for each plan. QA measurements were taken using IBA Matrixx Evolution ion chamber array set up in IBA MultiCube and were compared to each planar dose. Gamma passing criteria of both 3%/3mm and 2%/2mm tolerances were used. Results: Over all treatment sites, increases in gamma passing rates from NC to CM ranged from -0.4% to +27.3% at 3%/3mm and +0.1% to +30.5% at 2%/2mm. Mean increases in passing rates were +3.7% and +5.3% for 3%/3mm and 2%/2mm tolerances, respectively. Site-specific mean increases (NC to CM) in gamma passing rates were +4.4%, +3.4%, +0.4% (3%/3mm tolerance) and +6.9%, +3.7%, and +2.9% at (2%/2mm tolerance) for H'N, brain, and prostate, respectively. Conclusion: Results support use of a couch model when generating planar dose for patient specific VMAT QA analysis. The improvements were most noticeable at 2%/2mm tolerance and for the H'N and brain sites. Eliminating treatment couch beam attenuation as a source of discrepancy in QA measurements may improve the ability to recognize otherwise masked delivered dose errors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-D-304-06: Measurement of LET in Patient-Specific Proton Therapy Treatment Fields Using Optically Stimulated Luminescence Detectors

Purpose: To investigate the use of optically stimulated luminescence (OSL) detectors (OSLDs) for measurements of dose-averaged linear energy transfer (LET) in patient-specific proton therapy treatment fields. Methods: We used Al{sub 2}O{sub 3}:C OSLDs made from the same material as commercially available nanoDot OSLDs from Landauer, Inc. We calibrated two parameters of the OSL signal as functions of LET in therapeutic proton beams: the ratio of the ultraviolet and blue emission intensities (UV/blue ratio) and the OSL curve shape. These calibration curves were created by irradiating OSLDs in passively scattered beams of known LET (0.96 to 3.91 keV/µm). The LET values were determined using a validated Monte Carlo model of the beamline. We then irradiated new OSLDs with the prescription dose (16 to 74 cGy absorbed dose to water) at the center of the spread-out Bragg peak (SOBP) of four patient-specific treatment fields. From readouts of these OSLDs, we determined both the UV/blue ratio and OSL curve shape parameters. Combining these parameters with the calibration curves, we were able to measure LET using the OSLDs. The measurements were compared to the theoretical LET values obtained from Monte Carlo simulations of the patient-specific treatments fields. Results: Using the UV/blue ratio parameter, we were able to measure LET within 3.8%, 6.2%, 5.6% and 8.6% of the Monte Carlo value for each of the patient fields. Similarly, using the OSL curve shape parameter, LET measurements agreed within 0.5%, 11.0%, 2.5% and 7.6% for each of the four fields. Conclusion: We have demonstrated a method to verify LET in patient-specific proton therapy treatment fields using OSLDs. The possibility of enhancing biological effectiveness of proton therapy treatment plans by including LET in the optimization has been previously shown. The LET verification method we have demonstrated will be useful in the quality assurance of such LET optimized treatment plans. DA Granville received financial support from the Natural Sciences and Engineering Research Council of Canada.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-J-72: Dosimetric Study of Cone-Beam CT-Based Radiation Treatment Planning Using a Patient-Specific Stepwise CT-Density Table

Purpose: To assess dose calculation accuracy of cone-beam CT (CBCT) based treatment plans using a patient-specific stepwise CT-density conversion table in comparison to conventional CT-based treatment plans. Methods: Unlike CT-based treatment planning which use fixed CT-density table, this study used patient-specific CT-density table to minimize the errors in reconstructed mass densities due to the effects of CBCT Hounsfield unit (HU) uncertainties. The patient-specific CT-density table was a stepwise function which maps HUs to only 6 classes of materials with different mass densities: air (0.00121g/cm3), lung (0.26g/cm3), adipose (0.95g/cm3), tissue (1.05 g/cm3), cartilage/bone (1.6g/cm3), and other (3g/cm3). HU thresholds to define different materials were adjusted for each CBCT via best match with the known tissue types in these images. Dose distributions were compared between CT-based plans and CBCT-based plans (IMRT/VMAT) for four types of treatment sites: head and neck (HN), lung, pancreas, and pelvis. For dosimetric comparison, PTV mean dose in both plans were compared. A gamma analysis was also performed to directly compare dosimetry in the two plans. Results: Compared to CT-based plans, the differences for PTV mean dose were 0.1% for pelvis, 1.1% for pancreas, 1.8% for lung, and −2.5% for HN in CBCT-based plans. The gamma passing rate was 99.8% for pelvis, 99.6% for pancreas, and 99.3% for lung with 3%/3mm criteria, and 80.5% for head and neck with 5%/3mm criteria. Different dosimetry accuracy level was observed: 1% for pelvis, 3% for lung and pancreas, and 5% for head and neck. Conclusion: By converting CBCT data to 6 classes of materials for dose calculation, 3% of dose calculation accuracy can be achieved for anatomical sites studied here, except HN which had a 5% accuracy. CBCT-based treatment planning using a patient-specific stepwise CT-density table can facilitate the evaluation of dosimetry changes resulting from variation in patient anatomy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-D-204-01: A Methodology Based On Machine Learning and Quantum Clustering to Predict Lung SBRT Dosimetric Endpoints From Patient Specific Anatomic Features

Purpose: To develop a data-mining methodology based on quantum clustering and machine learning to predict expected dosimetric endpoints for lung SBRT applications based on patient-specific anatomic features. Methods: Ninety-three patients who received lung SBRT at our clinic from 2011–2013 were retrospectively identified. Planning information was acquired for each patient, from which various features were extracted using in-house semi-automatic software. Anatomic features included tumor-to-OAR distances, tumor location, total-lung-volume, GTV and ITV. Dosimetric endpoints were adopted from RTOG-0195 recommendations, and consisted of various OAR-specific partial-volume doses and maximum point-doses. First, PCA analysis and unsupervised quantum-clustering was used to explore the feature-space to identify potentially strong classifiers. Secondly, a multi-class logistic regression algorithm was developed and trained to predict dose-volume endpoints based on patient-specific anatomic features. Classes were defined by discretizing the dose-volume data, and the feature-space was zero-mean normalized. Fitting parameters were determined by minimizing a regularized cost function, and optimization was performed via gradient descent. As a pilot study, the model was tested on two esophageal dosimetric planning endpoints (maximum point-dose, dose-to-5cc), and its generalizability was evaluated with leave-one-out cross-validation. Results: Quantum-Clustering demonstrated a strong separation of feature-space at 15Gy across the first-and-second Principle Components of the data when the dosimetric endpoints were retrospectively identified. Maximum point dose prediction to the esophagus demonstrated a cross-validation accuracy of 87%, and the maximum dose to 5cc demonstrated a respective value of 79%. The largest optimized weighting factor was placed on GTV-to-esophagus distance (a factor of 10 greater than the second largest weighting factor), indicating an intuitively strong correlation between this feature and both endpoints. Conclusion: This pilot study shows that it is feasible to predict dose-volume endpoints based on patient-specific anatomic features. The developed methodology can potentially help to identify patients at risk for higher OAR doses, thus improving the efficiency of treatment planning. R01-184173.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-E-16: A Specific Training Package for Medical Physicists in Support to Nuclear and Radiological Emergency Situations

Purpose: To provide the professional medical physicists with adequate competencies and skills in order to help them get prepared to support Nuclear or Radiological Emergency (NRE) situations. Methods: Although clinical medical physicists working have in-depth knowledge in radiation dosimetry, including dose reconstruction and dose measurements, they are usually not involved in NRE situations. However, in a few instances where medical physicists were involved in NREs, it appeared that many lacked specific knowledge and skills that are required in such situations. This lack of specific knowledge and skills is probably due to the fact that most current medical physics curricula do not include a specific module on this topic. As a response to this finding, the IAEA decided to initiate a project to develop a specific training package to help prepare medical physicists to support NRE situations. The training package was developed with the kind support of the Government of Japan and in collaboration with Fukushima Medical University (FMU) and the National Institute of Radiological Sciences (NIRS). Results: The first International Workshop to test the training package was held in Fukushima, Japan in June 2015. It consisted of lectures, demonstrations, simulation, role play, and practical sessions followed by discussions. The training was delivered through 14 modules which were prepared with the support of 12 lecturers. A knowledge assessment test was done before the workshop, followed by the same test done at the end of the Workshop, to assess the knowledge acquired during the training. Conclusion: The Workshop was successfully implemented. The overall rating of the workshop by the participants was excellent and all participants reported that they acquired a good understanding of the main issues that are relevant to medical physics support in case of NRE situations. They are expected to disseminate the knowledge to other medical physicists in their countries.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2016

SU-G-TeP2-13: Patient-Specific Reduction of Range Uncertainties in Proton Therapy by Proton Radiography with a Multi-Layer Ionization Chamber

Purpose: The conversion from Hounsfield units (HU) to stopping powers is a major source of range uncertainty in proton therapy (PT). Our contribution shows how proton radiographs (PR) acquired with a multi-layer ionization chamber in a PT center can be used for accurate patient positioning and subsequently for patient-specific optimization of the conversion from HU to stopping powers. Methods: A multi-layer ionization chamber was used to measure the integral depth-dose (IDD) of 220 MeV pencil beam spots passing through several anthropomorphic phantoms. The whole area of interest was imaged by repositioning the couch and by acquiring a 45×45 mm{sup 2} frame for each position. A rigid registration algorithm was implemented to correct the positioning error between the proton radiographs and the planning CT. After registration, the stopping power map obtained from the planning CT with the calibration curve of the treatment planning system was used together with the water equivalent thickness gained from two proton radiographs to generate a phantom-specific stopping power map. Results: Our results show that it is possible to make a registration with submillimeter accuracy from proton radiography obtained by sending beamlets separated by more than 1 mm. This was made possible by the complex shape of the IDD due to the presence of lateral heterogeneities along the path of the beam. Submillimeter positioning was still possible with a 5 mm spot spacing. Phantom specific stopping power maps obtained by minimizing the range error were cross-verified by the acquisition of an additional proton radiography where the phantom was positioned in a random but known manner. Conclusion: Our results indicate that a CT-PR registration algorithm together with range-error based optimization can be used to produce a patient-specific stopping power map. Sylvain Deffet reports financial funding of its PhD thesis by Ion Beam Applications (IBA) during the confines of the study and outside the submitted work. Francois Vander Stappen reports being employed by Ion Beam Applications (IBA) during the confines of the study and outside the submitted work.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

MO-DE-207B-03: Improved Cancer Classification Using Patient-Specific Biological Pathway Information Via Gene Expression Data

Purpose: To develop an efficient, pathway-based classification system using network biology statistics to assist in patient-specific response predictions to radiation and drug therapies across multiple cancer types. Methods: We developed PICS (Pathway Informed Classification System), a novel two-step cancer classification algorithm. In PICS, a matrix m of mRNA expression values for a patient cohort is collapsed into a matrix p of biological pathways. The entries of p, which we term pathway scores, are obtained from either principal component analysis (PCA), normal tissue centroid (NTC), or gene expression deviation (GED). The pathway score matrix is clustered using both k-means and hierarchical clustering, and a clustering is judged by how well it groups patients into distinct survival classes. The most effective pathway scoring/clustering combination, per clustering p-value, thus generates various ‘signatures’ for conventional and functional cancer classification. Results: PICS successfully regularized large dimension gene data, separated normal and cancerous tissues, and clustered a large patient cohort spanning six cancer types. Furthermore, PICS clustered patient cohorts into distinct, statistically-significant survival groups. For a suboptimally-debulked ovarian cancer set, the pathway-classified Kaplan-Meier survival curve (p = .00127) showed significant improvement over that of a prior gene expression-classified study (p = .0179). For a pancreatic cancer set, the pathway-classified Kaplan-Meier survival curve (p = .00141) showed significant improvement over that of a prior gene expression-classified study (p = .04). Pathway-based classification confirmed biomarkers for the pyrimidine, WNT-signaling, glycerophosphoglycerol, beta-alanine, and panthothenic acid pathways for ovarian cancer. Despite its robust nature, PICS requires significantly less run time than current pathway scoring methods. Conclusion: This work validates the PICS method to improve cancer classification using biological pathways. Patients are classified with greater specificity and physiological relevance as compared to current gene-specific approaches. Focus now moves to utilizing PICS for pan-cancer patient-specific treatment response prediction.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Sci-Thur PM - Colourful Interactions: Highlights 06: Patient-specific calibration of cone-beam computed tomographic (CBCT) image sets for on-line dose tracking and plan assessment

Purpose: To develop a radiotherapy dose tracking and plan evaluation technique using cone-beam computed tomography (CBCT) images. Methods: We developed a patient-specific method of calibrating CBCT image sets for dose calculation. The planning CT was first registered with the CBCT using deformable image registration (DIR). A scatter plot was generated between the CT numbers of the planning CT and CBCT for each slice. The CBCT calibration curve was obtained by least-square fitting of the data, and applied to each CBCT slice. The calibrated CBCT was then merged with original planning CT to extend the small field of view of CBCT. Finally, the treatment plan was copied to the merged CT for dose tracking and plan evaluation. The proposed patient-specific calibration method was also compared to two methods proposed in literature. To evaluate the accuracy of each technique, 15 head-and-neck patients requiring plan adaptation were arbitrarily selected from our institution. The original plan was calculated on each method’s data set, including a second planning CT acquired within 48 hours of the CBCT (serving as gold standard). Clinically relevant dose metrics and 3D gamma analysis of dose distributions were compared between the different techniques. Results: Compared to the gold standard of using planning CTs, the patient-specific CBCT calibration method was shown to provide promising results with gamma pass rates above 95% and average dose metric agreement within 2.5%. Conclusions: The patient-specific CBCT calibration method could potentially be used for on-line dose tracking and plan evaluation, without requiring a re-planning CT session.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

Supplemental material for paper "Radiosonde-to-Space (R2S) atmospheric specifications: Bridging observations and models for infrasound propagation"

This document describes the supplemental materials for the paper: TITLE: "Radiosonde-to-Space (R2S) atmospheric specifications: Bridging observations and models for infrasound propagation" DOI: xxxxxxxxxxx JOURNAL: TBD Written by Loring Schaible, September 17, 2025 This folder contains eight subfolders, each for a specific date and UTC time (in format YYYY-MM-DD_HH). All eight of these dates are exemplified and described in the manuscript. Within each folder is six documents. As an example, consider the folder "2022-12-31_00". The six files are comprised of: - Two text files (extension .txt) that describe the atmospheric specifications of Albuquerque, NM. One is the G2S model, the other is the R2S model. "G2S_2022-12-31_00.txt" "R2S_2022-12-31_00.txt" - Two text files (extension .dat) that contain the ground arrivals predicted by infraGA using the parameters described in the manuscript. One each for the two atmospheric specification models above, G2S and R2S. "G2S_2022-12-31_00.arrivals.dat" "R2S_2022-12-31_00.arrivals.dat" - Two image files (extension .png) that illustrate the predicted arrivals contained in the two files above. One image shows all arrivals as either black (G2S) or red (R2S). The other image shows the same but with arrivals common to both models in gray. "2022-12-31_00_Arrivals.png" "2022-12-31_00_DifArrivals.png"

Schaible, Loring Pratt [Sandia National Laboratori↗
DOE OSTI2013

Specific Mutations in H5N1 Mainly Impact the Magnitude and Velocity of the Host Response in Mice

Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators is not well-understood. By analyzing a collection of mouse lung samples infected by A/Vietnam/1203/2004 (H5N1; VN1203) influenza, we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that infection concentrations and four specific mutations in VN1203 mainly impact on the magnitude and velocity of the host response kinetics, rather than on specific sets of genes up- and down-regulated. We observed similar kinetic effects using A/California/04/2009 (H1N1)-infected samples, and we show that these effects correlate with mice morbidity and viral titer measurements. Speed and extent of changes in the host response between days 1 and 2 post-infection were attenuated for each VN1203 mutant compared to the wild-type, except for PB1-F2 deletion at a high dose, which was associated with high virulence. This indicates that the host response in that time frame is critical and that immunomodulatory therapeutics should specifically be applied during the early days post-infection.

Environmental Molecular Sciences Laboratory↗
DOE OSTI2013

Abdominal-B and caudal inhibit the formation of specific neuroblasts in the Drosophila tail region

The central nervous system of Drosophila melanogaster consists of fused segmental units (neuromeres), each generated by a characteristic number of neural stem cells (neuroblasts). In the embryo, thoracic and anterior abdominal neuromeres are almost equally sized and formed by repetitive sets of neuroblasts, whereas the terminal abdominal neuromeres are generated by significantly smaller populations of progenitor cells. Here we investigated the role of the Hox gene Abdominal-B in shaping the terminal neuromeres. We show that the regulatory isoform of Abdominal-B (Abd-B.r) not only confers abdominal fate to specific neuroblasts (e.g. NB6-4) and regulates programmed cell death of several progeny cells within certain neuroblast lineages (e.g. NB3-3) in para-segment 14, but also inhibits the formation of a specific set of neuroblasts in para-segment 15 (including NB7-3). We further show that Abd-B.r requires cooperation of the ParaHox gene caudal to unfold its full competence concerning neuroblast inhibition and specification. Thus, our findings demonstrate that combined action of Abdominal-B and caudal contributes to the size and composition of the terminal neuromeres by regulating both the number and lineages of specific neuroblasts.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Odor exposure during imprinting periods increases odorant-specific sensitivity and receptor gene expression in coho salmon ( Oncorhynchus kisutch )

ABSTRACT Pacific salmon are well known for their homing migrations; juvenile salmon learn odors associated with their natal streams prior to seaward migration, and then use these retained odor memories to guide them back from oceanic feeding grounds to their river of origin to spawn several years later. This memory formation, termed olfactory imprinting, involves (at least in part) sensitization of the peripheral olfactory epithelium to specific odorants. We hypothesized that this change in peripheral sensitivity is due to exposure-dependent increases in the expression of odorant receptor (OR) proteins that are activated by specific odorants experienced during imprinting. To test this hypothesis, we exposed juvenile coho salmon, Oncorhynchus kisutch, to the basic amino acid odorant l-arginine during the parr–smolt transformation (PST), when imprinting occurs, and assessed sensitivity of the olfactory epithelium to this and other odorants. We then identified the coho salmon ortholog of a basic amino acid odorant receptor (BAAR) and determined the mRNA expression levels of this receptor and other transcripts representing different classes of OR families. Exposure to l-arginine during the PST resulted in increased sensitivity to that odorant and a specific increase in BAAR mRNA expression in the olfactory epithelium relative to other ORs. These results suggest that specific increases in ORs activated during imprinting may be an important component of home stream memory formation and this phenomenon may ultimately be useful as a marker of successful imprinting to assess management strategies and hatchery practices that may influence straying in salmon.

Dittman, Andrew H. (ORCID:000000016482359X)↗
DOE OSTI2016

Structure of Type IIL Restriction-Modification Enzyme MmeI in Complex with DNA Has Implications for Engineering New Specificities

The creation of restriction enzymes with programmable DNA-binding and -cleavage specificities has long been a goal of modern biology. The recently discovered Type IIL MmeI family of restriction-and-modification (RM) enzymes that possess a shared target recognition domain provides a framework for engineering such new specificities. However, a lack of structural information on Type IIL enzymes has limited the repertoire that can be rationally engineered. We report here a crystal structure of MmeI in complex with its DNA substrate and an S-adenosylmethionine analog (Sinefungin). The structure uncovers for the first time the interactions that underlie MmeI-DNA recognition and methylation (5’-TCCRAC-3’; R = purine) and provides a molecular basis for changing specificity at four of the six base pairs of the recognition sequence (5’-TCCRAC-3’). Surprisingly, the enzyme is resilient to specificity changes at the first position of the recognition sequence (5’-TCCRAC-3’). Collectively, the structure provides a basis for engineering further derivatives of MmeI and delineates which base pairs of the recognition sequence are more amenable to alterations than others.

59 BASIC BIOLOGICAL SCIENCES↗