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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 379 records · Page 21
All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

Deep Sequencing-guided Design of a High Affinity Dual Specificity Antibody to Target Two Angiogenic Factors in Neovascular Age-related Macular Degeneration

The development of dual targeting antibodies promises therapies with improved efficacy over mono-specific antibodies. Here, we engineered a Two-in-One VEGF/angiopoietin 2 antibody with dual action Fab (DAF) as a potential therapeutic for neovascular age-related macular degeneration. Crystal structures of the VEGF/angiopoietin 2 DAF in complex with its two antigens showed highly overlapping binding sites. To achieve sufficient affinity of the DAF to block both angiogenic factors, we turned to deep mutational scanning in the complementarity determining regions (CDRs). By mutating all three CDRs of each antibody chain simultaneously, we were able not only to identify affinity improving single mutations but also mutation pairs from different CDRs that synergistically improve both binding functions. Furthermore, insights into the cooperativity between mutations allowed us to identify fold-stabilizing mutations in the CDRs. The data obtained from deep mutational scanning reveal that the majority of the 52 CDR residues are utilized differently for the two antigen binding function and permit, for the first time, the engineering of several DAF variants with sub-nanomolar affinity against two structurally unrelated antigens. Here, the improved variants show similar blocking activity of receptor binding as the high affinity mono-specific antibodies against these two proteins, demonstrating the feasibility of generating a dual specificity binding surface with comparable properties to individual high affinity mono-specific antibodies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Specific absorbed fractions for a revised series of the UF/NCI pediatric reference phantoms: internal photon sources

Assessment of radiation absorbed dose to internal organs of the body from the intake of radionuclides, or in the medical setting through the injection of radiopharmaceuticals, is generally performed based upon reference biokinetic models or patient imaging data, respectively. Biokinetic models estimate the time course of activity localized to source organs. The time-integration of these organ activity profiles are then scaled by the radionuclide S-value, which defines the absorbed dose to a target tissue per nuclear transformation in various source tissues. S-values are computed using established nuclear decay information (particle energies and yields), and a parameter termed the specific absorbed fraction (SAF). The SAF is the ratio of the absorbed fraction—fraction of particle energy emitted in the source tissue that is deposited in the target tissue—and the target organ mass. While values of the SAF may be computed using patient-specific or individual-specific anatomic models, they have been more widely available through the use of computational reference phantoms. In this study, we report on an extensive series of photon SAFs computed in a revised series of the University of Florida and the National Cancer Institute pediatric reference phantoms which have been modified to conform to the specifications embodied in the ICRP reference adult phantoms of Publication 110 (e.g. organs modeled, organ ID numbers, blood contribution to elemental compositions). Following phantom anatomical revisions, photon radiation transport simulations were performed using MCNPX v2.7 in each of the ten phantoms of the series—male and female newborn, 1 year old, 5 year old, 10 year old, and 15 year old—for 60 different tissues serving as source and/or target regions. A total of 25 photon energies were considered from 10 keV to 10 MeV along a logarithm energy grid. Detailed analyses were conducted of the relative statistical errors in the Monte Carlo target tissue energy deposition tallies at low photon energies and over all energies for source–target combinations at large intra-organ separation distances. Based on these analyses, various data smoothing algorithms were employed, including multi-point weighted data smoothing, and log–log interpolation at low energies (1 keV and 5 keV) using limiting SAF values based upon target organ mass to bound the interpolation interval. The final dataset is provided in a series of ten electronic supplemental files in MS Excel format. Finally, the results of this study were further used as the basis for assessing the radiative component of internal electron source SAFs as described in our companion paper (Schwarz et al 2021) for this same pediatric phantom series.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2021

Specific absorbed fractions for a revised series of the UF/NCI pediatric reference phantoms: internal electron sources

Assessment of radiation absorbed dose to internal organs of the body from the intake of radionuclides, or in the medical setting through the injection of radiopharmaceuticals, is generally performed based upon reference biokinetic models or patient imaging data, respectively. Biokinetic models estimate the time course of activity localized to source organs. The time-integration of these organ activity profiles are then scaled by the radionuclide S-value, which defines the absorbed dose to a target tissue per nuclear transformation in various source tissues. S-values are computed using established nuclear decay information (particle energies and yields), and a parameter termed the specific absorbed fraction (SAF). The SAF is the ratio of the absorbed fraction—fraction of particle energy emitted in the source tissue that is deposited in the target tissue—and the target organ mass. While values of the SAF may be computed using patient-specific or individual-specific anatomic models, they have been more widely available through the use of computational reference phantoms. In this study, we report on an extensive series of photon SAFs computed in a revised series of the University of Florida and the National Cancer Institute pediatric reference phantoms which have been modified to conform to the specifications embodied in the ICRP reference adult phantoms of Publication 110 (e.g. organs modeled, organ ID numbers, blood contribution to elemental compositions). Following phantom anatomical revisions, photon radiation transport simulations were performed using MCNPX v2.7 in each of the ten phantoms of the series—male and female newborn, 1 year old, 5 year old, 10 year old, and 15 year old—for 60 different tissues serving as source and/or target regions. A total of 25 photon energies were considered from 10 keV to 10 MeV along a logarithm energy grid. Detailed analyses were conducted of the relative statistical errors in the Monte Carlo target tissue energy deposition tallies at low photon energies and over all energies for source–target combinations at large intra-organ separation distances. Based on these analyses, various data smoothing algorithms were employed, including multi-point weighted data smoothing, and log–log interpolation at low energies (1 keV and 5 keV) using limiting SAF values based upon target organ mass to bound the interpolation interval. The final dataset is provided in a series of ten electronic supplemental files in MS Excel format. Finally, the results of this study were further used as the basis for assessing the radiative component of internal electron source SAFs as described in our companion paper (Schwarz et al 2021) for this same pediatric phantom series.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2019

Impact of anharmonicity on the vibrational entropy and specific heat of UO 2

The impact of anharmonicity on the vibrational entropy and heat capacity of UO 2 has been discovered from 10 to 1200 K using inelastic neutron-scattering measurements of the phonon density of states (PDOS). Small changes in the PDOS are observed from 10 to 295 K, with more noticeable changes appearing in the 750- and 1200-K data. The specific heat determined from the PDOS measurements is in agreement with macroscopic specific heat measurements, and the overall impact of nondilation anharmonicity on the specific heat has been shown to be less than 2%. An analysis of the phonon measurements shows that the softening of acoustic phonons with temperature is consistent with the quasiharmonic approximation. The optical phonons deviate from the quasiharmonic prediction, with the low-energy optical phonons between approximately 20 and 50 meV softening more than expected, while the higher-energy optical phonons between approximately 50 and 80 meV have no appreciable softening over the temperature range measured. The observation of a small anharmonic specific heat contribution has been demonstrated to be the result of relatively large energy-dependent anharmonic effects which have opposite sign, leading to a total contribution near zero.

36 MATERIALS SCIENCE↗
DOE OSTI2014

TU-C-BRE-09: Performance Comparisons of Patient Specific IMRT QA Methodologies Using ROC Analysis

Purpose: To evaluate the ability of a selection of patient-specific QA methods to accurately classify IMRT plans as acceptable or unacceptable based on a multiple ion chamber (MIC) phantom. Methods: Twenty-four IMRT plans were selected (20 previously failed the institutional QA), and were measured on a MIC phantom to assess their dosimetric acceptability. These same plans were then measured using film (Kodak EDR2) and ion chamber (Wellhofer cc04), ArcCheck (Sun Nuclear), and MapCheck (Sun Nuclear) (delivered AP field-by-field, AP composite, and with original gantry angles). All gamma analyses were performed at 2%/2mm, 3%/3mm, and 5%/3mm. By using the MIC results as a gold standard, the sensitivity and specificity were calculated across a range of cut-off thresholds (% pixels passing for gamma analysis, and % dose difference for ion chamber), and were used to form ROC curves. Area under the curve (AUC) was used as a metric to quantify the performance of the various QA methods. Results: Grouping device’s AUC’s revealed two statistically significant different groups: ion chamber (AUC of 0.94), AP composite MapCheck (AUC of 0.85), ArcCheck (AUC of 0.84), and film (AUC of 0.82) were in the better performing group, while original gantry angles and AP field-by-field MapCheck (AUC of 0.65 and 0.66, respectively) matched less well with the gold standard results. Optimal cut-offs were also assessed using the ROC curves. We found that while often 90% of pixels passing is used as a criteria, the differing sensitivities of QA methods can lead to device and methodology-based optimal cutoff thresholds. Conclusion: While many methods exist to perform the same task of patient-specific IMRT QA, they utilize different strategies. This work has shown that there are inconsistencies in these methodologies in terms of their sensitivity and specificity to dosimetric acceptability. This work was supported by Public Health Service grants CA010953, CA081647, and CA21661 awarded by the National Cancer Institute, United States Department of Health and Human Services.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

TU-G-201-00: Imaging Equipment Specification and Selection in Radiation Oncology Departments

This session will update therapeutic physicists on technological advancements and radiation oncology features of commercial CT, MRI, and PET/CT imaging systems. Also described are physicists’ roles in every stage of equipment selection, purchasing, and operation, including defining specifications, evaluating vendors, making recommendations, and optimal and safe use of imaging equipment in radiation oncology environment. The first presentation defines important terminology of CT and PET/CT followed by a review of latest innovations, such as metal artifact reduction, statistical iterative reconstruction, radiation dose management, tissue classification by dual energy CT and spectral CT, improvement in spatial resolution and sensitivity in PET, and potentials of PET/MR. We will also discuss important technical specifications and items in CT and PET/CT purchasing quotes and their impacts. The second presentation will focus on key components in the request for proposal for a MRI simulator and how to evaluate vendor proposals. MRI safety issues in radiation Oncology, including MRI scanner Zones (4-zone design), will be discussed. Basic MR terminologies, important functionalities, and advanced features, which are relevant to radiation therapy, will be discussed. In the third presentation, justification of imaging systems for radiation oncology, considerations in room design and construction in a RO department, shared use with diagnostic radiology, staffing needs and training, clinical/research use cases and implementation, will be discussed. The emphasis will be on understanding and bridging the differences between diagnostic and radiation oncology installations, building consensus amongst stakeholders for purchase and use, and integrating imaging technologies into the radiation oncology environment. Learning Objectives: Learn the latest innovations of major imaging systems relevant to radiation therapy Be able to describe important technical specifications of CT, MRI, and PET/CT Understand the process of budget request, equipment justification, comparisons of technical specifications, site visits, vendor selection, and contract development.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Spatial Study 2021: Sensor-Based Time Series of Surface Water Temperature, Specific Conductance, Total Dissolved Solids, pH, and Dissolved Oxygen from across Multiple Watersheds in the Yakima River Basin, Washington, USA (v3)

This dataset supports a broader study examining the drivers of spatial variability in sediment respiration rates in the Yakima River Basin. The dataset provides two-hour time series hydrological and water chemistry sensor data, manual chamber open channel respiration data, handheld sensor water chemistry data, river substrate grain size photos, general environmental context photos, and field metadata (including qualitative information on instream and river corridor characteristics) collected during the same two-week period at 47 sites within multiple rivers throughout the Yakima River Basin in Washington, USA. Grain size photos can be used to improve estimates of channel substrate D50 data. Related sample-based water chemistry data are published separately at https://data.ess-dive.lbl.gov/datasets/doi:10.15485/1898914.This dataset is comprised of four main folders, one containing three sensor-specific subfolders and the others containing photographs. The SFA_SpatialStudy_2021_SensorData main data folder includes file-level metadata (FLMD), data dictionary (dd), installation methods, field metadata, Ultrameter water chemistry data, field data collection protocols, international generic sample number (IGSN) mapping file, and a readme file. The “Sensor_Manual_Specifications” subfolder contains pdf files from the manufacturer of each sensor with details on the sensor specifications. Each sensor subfolder (BarotrollAtm, MantaRiver, and MinidotManualChamber) contains a sensor data subfolder for timeseries data and a subfolder for plots and summary statistics. The BarotrollAtm Data subfolder contains In Situ Rugged BaroTROLL pressure and temperature data. The MantaRiver Data subfolder contains Eureka Manta+ 35B multisonde temperature, specific conductance, and pH data. The MinidotManualChamber Data subfolder contains PME MiniDOT Logger dissolved oxygen (mg/L and percent saturation) and temperature data. The folder SFA_SpatialStudy_2021_EnvironmentalContextPhotos contains environmental context photographs and videos. The folders SFA_SpatialStudy_2021_SedimentQuadratPhotos_Part1 and SFA_SpatialStudy_2021_SedimentQuadratPhotos_Part2 contain sediment quadrat photographs. All files are .csv, .pdf, .R, .jpg, .jpeg, .mp4, or .mov. This data package was originally published September 2022. It was updated January 2023 (modified files) and June 2024 (new and modified files). See the change history in data package readme for more details.We acknowledge the Yakama Nation as owners and caretakers of the lands where we collected these data. We thank the Confederated Tribes and Bands of the Yakama Nation Tribal Council and Yakama Nation Fisheries for working with us to facilitate sample collection and optimization of data usage according to their values and worldview.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2014

Vibrio chromosome-specific families

We have compared chromosome-specific genes in a set of 18 finished Vibrio genomes, and, in addition, also calculated the pan- and core-genomes from a data set of more than 250 draft Vibrio genome sequences. These genomes come from 9 known species and 2 unknown species. Within the finished chromosomes, we find a core set of 1269 encoded protein families for chromosome 1, and a core of 252 encoded protein families for chromosome 2. Many of these core proteins are also found in the draft genomes (although which chromosome they are located on is unknown.) Of the chromosome specific core protein families, 1169 and 153 are uniquely found in chromosomes 1 and 2, respectively. Gene ontology (GO) terms for each of the protein families were determined, and the different sets for each chromosome were compared. A total of 363 different “Molecular Function” GO categories were found for chromosome 1 specific protein families, and these include several broad activities: pyridoxine 5’ phosphate synthetase, glucosylceramidase, heme transport, DNA ligase, amino acid binding, and ribosomal components; in contrast, chromosome 2 specific protein families have only 66 Molecular Function GO terms and include many membrane-associated activities, such as ion channels, transmembrane transporters, and electron transport chain proteins. Thus, it appears that whilst there are many “housekeeping systems” encoded in chromosome 1, there are far fewer core functions found in chromosome 2. However, the presence of many membrane-associated encoded proteins in chromosome 2 is surprising.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2012

Specification and Design of Electrical Flight System Architectures with SysML

Modern space flight systems are required to perform more complex functions than previous generations to support space missions. This demand is driving the trend to deploy more electronics to realize system functionality. The traditional approach for the specification, design, and deployment of electrical system architectures in space flight systems includes the use of informal definitions and descriptions that are often embedded within loosely coupled but highly interdependent design documents. Traditional methods become inefficient to cope with increasing system complexity, evolving requirements, and the ability to meet project budget and time constraints. Thus, there is a need for more rigorous methods to capture the relevant information about the electrical system architecture as the design evolves. In this work, we propose a model-centric approach to support the specification and design of electrical flight system architectures using the System Modeling Language (SysML). In our approach, we develop a domain specific language for specifying electrical system architectures, and we propose a design flow for the specification and design of electrical interfaces. Our approach is applied to a practical flight system.

specifications↗
DOE OSTI2017

Model-based verification of I and C specifications - 184

In the field of nuclear I and C (Instrumentation and Control), the late detection of errors in the specifications and the design of I and C has a strong impact in terms of time and money. The early verification in the V cycle of I and C functions is a key issue to capture inconsistencies and errors before the implementation and on-site tests. EDF, in the framework of the collaborative project CONNEXION, has investigated methods based on simulation to formalize I and C requirements and to evaluate them at the conceptual and basic design phases. Behavioral models of the physic parts of the system and I and C functions, described as functional diagrams, are co-simulated in an integration environment based on the FMI (Functional Mockup Interface) standard. In this specific environment, test scenarios are performed on these models. These scenarios are defined on the basis of a high level model of the studied system that takes into account the states to cover (in normal and degraded situations). Requirements, once formalized, are translated into observers that evaluate their fulfillment during the simulations. Simulation logs are then a tool for the designer to analyze the causes of the possible non-fulfillment of requirements and to fix the corresponding errors in the specifications. The proposed methodology enables to detect errors in the specifications of I and C functions, to generate automatically functional test scenarios taking into account the coverage of the requirements and all the different operational modes of the system. (authors)

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
NASA NTRS1994

Initiating Formal Requirements Specifications with Object-Oriented Models

This paper reports results of an investigation into the suitability of object-oriented models as an initial step in developing formal specifications. The requirements for two critical system-level software modules were used as target applications. It was found that creating object-oriented diagrams prior to formally specifying the requirements enhanced the accuracy of the initial formal specifications and reduced the effort required to produce them. However, the formal specifications incorporated some information not found in the object-oriented diagrams, such as higher-level strategy or goals of the software.

requirements specifications↗
DOE OSTI2023

Structural and functional validation of a highly specific Smurf2 inhibitor

Smurf1 and Smurf2 are two closely related member of the HECT (homologous to E6AP carboxy terminus) E3 ubiquitin ligase family and play important roles in the regulation of various cellular processes. Both were initially identified to regulate transforming growth factor‐β and bone morphogenetic protein signaling pathways through regulating Smad protein stability and are now implicated in various pathological processes. Generally, E3 ligases, of which over 800 exist in humans, are ideal targets for inhibition as they determine substrate specificity; however, there are few inhibitors with the ability to precisely target a particular E3 ligase of interest. In this work, we explored a panel of ubiquitin variants (UbVs) that were previously identified to bind Smurf1 or Smurf2. In vitro binding and ubiquitination assays identified a highly specific Smurf2 inhibitor, UbV S2.4, which was able to inhibit ligase activity with high potency in the low nanomolar range. Orthologous cellular assays further demonstrated high specificity of UbV S2.4 toward Smurf2 and no cross‐reactivity toward Smurf1. Structural analysis of UbV S2.4 in complex with Smurf2 revealed its mechanism of inhibition was through targeting the E2 binding site. In summary, we investigated several protein‐based inhibitors of Smurf1 and Smurf2 and identified a highly specific Smurf2 inhibitor that disrupts the E2–E3 protein interaction interface.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Method for Accurate Determination of the Electron Contribution: Specific Heat of Ba 0.59 K 0.41 Fe 2 As 2

Twenty two years after the opening of the field of high temperature superconductivity by Georg Bednorz and Alex Müller a new addition to this class of materials, namely the iron-pnictides and chalcogenides, perplexes the scientific community. Making use of the accumulated wisdom, a great deal of their physics has been “mapped” in record time using all available measurement techniques. Among these, specific-heat has been proven a powerful and unique technique in the study of physical properties of bulk materials, especially of superconductors. We report here specific-heat measurements on the nearly optimally doped iconic iron-arsenide superconductor Ba 0.59 K 0.41 Fe 2 As 2 . We use a new method, based on direct comparisons of α-model expressions for the electron contribution with the measured total specific heat, to extract the electron contribution. It circumvents the need in the conventional analyses for an independent, necessarily approximate, determination of the lattice contribution, which is subtracted from the total to obtain the electron contribution, and it eliminates the consequent uncertainties in the electron contribution. For Ba 0.59 K 0.41 Fe 2 As 2 the electron density of states is comprised of contributions from two electron bands with superconducting-state energy gaps differing by a factor 3.8, with 77% coming from the band with the larger gap. The vortex-state specific heat suggests nodeless gaps. Comparison of the normal-state density of states with band-structure calculations shows an extraordinarily large effective mass enhancement, for which there is no precedent in simple metals and no theoretical explanation.

Conventional Analysis↗
DOE OSTI2019

Negative specific heat from non-planar interactions and small black holes in AdS/CFT

The gravity side of the gauge/gravity duality predicts the existence of small black holes with negative specific heat. A free theory of strings has a Hagedorn behavior, but it does not lead to negative specific heat. To understand such states one needs to consider a theory of interacting strings. In the dual gauge theory, the string interactions are related to non-planar diagrams. In this paper the simplest gauge matrix model of two free matrices, that has Hagedorn behavior is analyzed in detail. A simple double trace deformation of the Hamiltonian, proportional to square of the free Hamiltonian square with a negative sign that mimics a gravitational attraction is enough to produce states with negative specific heat perturbatively and one can still compute the equation of state relating the entropy and the energy. A more general argument based on non-planar interactions that are random and that grow faster in strength than the energy suggests that states with negative specific heat appear generically.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2019

Biochemical Properties and Catalytic Specificity of a Novel Neutral Serine Peptidase Secreted by Fungus Pyrenochaetopsis sp

The fungal genus Pyrenochaetopsis has received particular attention because of its different lifestyles, such as numerous plant pathogenic, saprophytic, and endophytic species. Its ability to infect plant cells relies heavily upon secreted peptidases. Here, we investigated the biochemical properties and catalytic specificity of a new serine peptidase secreted by the filamentous fungus Pyrenochaetopsis sp. We found that while this neutral serine peptidase displayed optimal activity at a pH of 7.0 and temperature of 45 °C, it tolerated a wide range of pH conditions and temperatures lower than 45 °C. Its peptidase activity was depressed by some metallic ions (such as aluminum, cobalt, and copper (II) chloride) and enhanced by others (such as sodium, lithium, magnesium, potassium, calcium, and manganese). Lastly, the enzyme showed the greatest specificity for non-polar amino acids, particularly leucine and isoleucine, and moderate specificity for basic and neutral polar amino acids. It displayed the least specificity for acidic residues.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

Highlights: •C-26 cancer cachexia causes a significant decrease in limb muscle absolute force. •C-26 cancer cachexia causes a significant decrease in limb muscle specific force. •C-26 cancer cachexia decreases fatigue resistance in the soleus muscle. •C-26 cancer cachexia prolongs time to peak twitch tension in limb muscle. •C-26 cancer cachexia prolongs one half twitch relaxation time in limb muscle. -- Abstract: Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. However, more recently, we provided evidence that during severe cancer cachexia muscle weakness in the diaphragm muscle cannot be entirely accounted for by the muscle atrophy. This indicates that muscle weakness is not just a consequence of muscle atrophy but that there is also significant contractile dysfunction. The current study aimed to determine whether contractile dysfunction is also present in limb muscles during severe Colon-26 (C26) carcinoma cachexia by studying the glycolytic extensor digitorum longus (EDL) muscle and the oxidative soleus muscle, which has an activity pattern that more closely resembles the diaphragm. Severe C-26 cancer cachexia caused significant muscle fiber atrophy and a reduction in maximum absolute force in both the EDL and soleus muscles. However, normalization to muscle cross sectional area further demonstrated a 13% decrease in maximum isometric specific force in the EDL and an even greater decrease (17%) in maximum isometric specific force in the soleus. Time to peak tension and half relaxation time were also significantly slowed in both the EDL and the solei from C-26 mice compared to controls. Since, in addition to postural control, the oxidative soleus is also important for normal locomotion, we further performed a fatigue trial in the soleus and found that the decrease in relative force was greater and more rapid in solei from C-26 mice compared to controls. These data demonstrate that severe cancer cachexia causes profound muscle weakness that is not entirely explained by the muscle atrophy. In addition, cancer cachexia decreases the fatigue resistance of the soleus muscle, a postural muscle typically resistant to fatigue. Thus, specifically targeting contractile dysfunction represents an additional means to counter muscle weakness in cancer cachexia, in addition to targeting the prevention of muscle atrophy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

In silico analysis of stomach lineage specific gene set expression pattern in gastric cancer

Highlights: •Identified stomach lineage specific gene set (SLSGS) was found to be under expressed in gastric tumors. •Elevated expression of SLSGS in gastric tumor is a molecular predictor of metabolic type gastric cancer. •In silico pathway scanning identified estrogen-α signaling is a putative regulator of SLSGS in gastric cancer. •Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. -- Abstract: Stomach lineage specific gene products act as a protective barrier in the normal stomach and their expression maintains the normal physiological processes, cellular integrity and morphology of the gastric wall. However, the regulation of stomach lineage specific genes in gastric cancer (GC) is far less clear. In the present study, we sought to investigate the role and regulation of stomach lineage specific gene set (SLSGS) in GC. SLSGS was identified by comparing the mRNA expression profiles of normal stomach tissue with other organ tissue. The obtained SLSGS was found to be under expressed in gastric tumors. Functional annotation analysis revealed that the SLSGS was enriched for digestive function and gastric epithelial maintenance. Employing a single sample prediction method across GC mRNA expression profiles identified the under expression of SLSGS in proliferative type and invasive type gastric tumors compared to the metabolic type gastric tumors. Integrative pathway activation prediction analysis revealed a close association between estrogen-α signaling and SLSGS expression pattern in GC. Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. In conclusion, our results highlight that estrogen mediated regulation of SLSGS in gastric tumor is a molecular predictor of metabolic type GC and prognostic factor in GC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Endurance exercise training induces fat depot-specific differences in basal autophagic activity

The purpose of this study was to uncover the effect of exercise training on the expression of autophagy marker proteins in epididymal white adipose tissue (eWAT), inguinal WAT (iWAT), and the stromal vascular fraction (SVF) collected from eWAT. Male Wistar rats aged 4–5 weeks were randomly divided into two groups, sedentary control (n = 7) and exercise-trained (n = 7). Rats in the exercise-trained group were exercised on a treadmill set at a 5° incline 5 days/week for 9 weeks. We determined that the expression levels of an autophagosome-associating form of microtubule-associated protein 1 light chain 3 (LC3)-II and of p62 were significantly higher in eWAT from exercise-trained than from control rats, while those of adipose-specific deletion of autophagy-related protein (ATG7) and lysosomal-associated membrane protein type 2A (LAMP2a) showed no difference between groups. However, in iWAT, the expression levels of LC3-II and ATG7 were significantly higher in exercise-trained than in control rats. The expression of p62 was highly correlated with that of peroxisome proliferator-activated receptor γ (PPARγ), a master regulator of adipogenesis and lipid metabolism, in both WAT types (eWAT, r = 0.856, P < 0.05; iWAT, r = 0.762, P < 0.05), whereas LC3-II and PPARγ levels were highly correlated in eWAT (r = 0.765, P < 0.05) but not in iWAT (r = −0.306, ns). In SVF, the expression levels of LC3II, ATG7, and LAMP2a were significantly higher in exercise-trained than in control rats. These results suggest that exercise training suppresses basal autophagy activity in eWAT, but that this activity is enhanced in iWAT and SVF collected from eWAT. Thus, the adaptation of basal autophagic activity following exercise training exhibits fat depot-specific differences. - Highlights: • Autophagy has been associated with obesity and associated diseases. • We examined exercise-associated rat white adipose tissue (WAT) autophagy markers. • Exercise increased autophagosome associated LC3-II in WAT. • Exercise-induced changes in p62 and ATG7 were WAT-type specific. • Exercise-induced basal autophagic activity shows fat depot-specific differences.

60 APPLIED LIFE SCIENCES↗