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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 955 records · Page 53
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Induction of kidney-related gene programs through co-option of SALL1 in mole ovotestes

Changes in gene expression represent an important source of phenotypic innovation. Yet how such changes emerge and impact the evolution of traits remains elusive. Here, we explore the molecular mechanisms associated with the development of masculinizing ovotestes in female moles. By performing integrative analyses of epigenetic and transcriptional data in mole and mouse, we identified the co-option of SALL1 expression in mole ovotestes formation. Chromosome conformation capture analyses highlight a striking conservation of the 3D organization at the SALL1 locus, but an evolutionary divergence of enhancer activity. Interspecies reporter assays support the capability of mole-specific enhancers to activate transcription in urogenital tissues. Through overexpression experiments in transgenic mice, we further demonstrate the capability of SALL1 to induce kidney-related gene programs, which are a signature of mole ovotestes. Our results highlight the co-option of gene expression, through changes in enhancer activity, as a plausible mechanism for the evolution of traits.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Roles of Pin1 as a Key Molecule for EMT Induction by Activation of STAT3 and NF-κB in Human Gallbladder Cancer

Background: Despite developments in multidisciplinary treatment, the prognosis for advanced gallbladder cancer (GBC) still is poor because of its rapid progression. Epithelial–mesenchymal transition (EMT) plays a central role in promoting tumor invasion and metastasis in malignancies thorough signal transducer and activator of transcription-3 (STAT3) and nuclear factor κB (NF-κB) activation. Whereas Pin1 mediates STAT3 and NF-κB activation, the involvement of Pin1 in GBC progression is unclear. Methods: Factors regulating Pin1-related STAT3 and NF-κB activation were evaluated using surgical specimens collected from 76 GBC patients, GBC cells, and orthotopic GBC xenograft mice. Results: In the patients with GBC, high Pin1 expression in GBC was associated with aggressive tumor invasion and increased tumor metastasis, and was an independent factor for a poor prognosis. Pin1 expression was correlated with phosphorylation of STAT3(Ser727) and NF-κB-p65(Ser276), thereby activating STAT3 and NF-κB in GBC. Pin1-mediated STAT3 and NF-κB activation induced EMT in GBC. When Pin1 knockdown was performed in GBC cells, the phosphorylation of STAT3(Ser727) and NF-κB-p65(Ser276) was inhibited, and STAT3 and NF-κB activation was suppressed. Inactivation of STAT3 and NF-κB in Pin1-depleted cells decreased snail and zeb-2 expression, thereby reducing the rate of mesenchymal-like cells, suggesting that EMT was inhibited in GBC cells. PiB, a Pin1-specific inhibitor, inhibited EMT and reduced tumor cell invasion by inactivating STAT3 and NF-κB in vitro. Moreover, PiB treatment inhibited lymph node metastasis and intrahepatic metastasis in orthotopic GBC xenograft tumor in vivo. Conclusions: Pin1 accelerates GBC invasion and metastasis by activating STAT3 and NF-κB. Therefore, Pin1 inhibition by PiB is an excellent therapy for GBC by safely inhibiting its metastasis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Meiotic susceptibility for induction of sperm with chromosomal aberrations in patients receiving combination chemotherapy for Hodgkin lymphoma

Improvements in survival rates with gonad-sparing protocols for childhood and adolescence cancer have increased the optimism of survivors to become parents after treatment. Findings in rodents indicate that chromosomal aberrations can be induced in male germ cells by genotoxic exposures and transmitted to offspring and future generations with effects on development, fertility and health. Thus, there is a need for effective technologies to identify human sperm carrying chromosomal aberrations to assess the germ-line risks, especially for cancer survivors who have received genotoxic therapies. The time-dependent changes in the burden of sperm carrying structural chromosomal aberrations were assessed for the first time in a cancer setting, using the AM8 sperm FISH protocol which simultaneously detects abnormalities in chromosomal structure and number in sperm. Nine Hodgkin lymphoma (HL) patients provided 20 semen samples before, during, and after NOVP therapy (Novantrone, Oncovin, Velban and Prednisone) and radiation therapy that produced scattered gonadal doses from <0.05 to 0.6 Gy. Late meiosis was found to be the most sensitive to NOVP treatment for the production of sperm with chromosomal abnormalities, both in structure and number. Earlier stages of spermatogenesis were less sensitive and there was no evidence that therapy-exposed stem cells resulted in increased frequencies of sperm with abnormalities in chromosomal structure or number. This indicates that NOVP therapy may increase the risks for paternal transmission of chromosomal structural aberrations for sperm produced 32 to 45 days after a treatment with these drugs and implies that there are no excess risks for pregnancies conceived more than 6 months after this therapy. This clinical evaluation of the AM8 sperm FISH protocol indicates that it is a promising tool for assessing an individual’s burden of sperm carrying chromosomal structural aberrations as well as aneuploidies after cancer therapy, with broad applications in other clinical and environmental situations that may pose aneugenic or clastogenic risks to human spermatogenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

RAPID: The Development and Application of a Hybrid High Pressure Ion Chromatography and Inductively Coupled Plasma Mass Spectrometry Method for the Direct Analysis of Irradiated Materials

RAPID (Rapid Analysis of Post-Irradiation Debris) is an automated online separation–direct analysis method developed at Oak Ridge National Laboratory (ORNL) to measure both radioactive and stable fission isotopes by mass. Developed to measure the concentration and isotopic composition of over 40 elements down to the femtogram level, RAPID demonstrates the sensitivity, stability, and precision required to achieve accurate, low-level analyses of elements of non-natural origin. The application of the RAPID method to silica- and soil-based matrices achieved complete matrix exclusion and direct online analysis of the elementally separated analytes, yielding precise isotopic compositions. When combined with isotope dilution, this approach yielded elemental concentrations with low uncertainties, providing a rapid analytical method that encompasses group I and II metals, transition metals, refractory metals, platinum group metals, lanthanides, and actinides. The robustness, sensitivity, reproducibility, and numerous applications to a number of fields in nuclear measurements have been confirmed.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Beam breakup in a solid state powered linear induction accelerator

It has been proposed to use solid-state pulsed-power modules to power the new Scorpius accelerator. Since this highcurrent accelerator would have 360 gaps (more than five times the number of cells as present radiography LIAs), it is natural to be concerned about the beam-breakup (BBU) instability. Earlier calculations of this effect used a half-scale model of the accelerator to avoid the limitation to 200 gaps in the code. We have now updated the code to accommodate the extraordinary number of gaps in this proposed LIA. The results of these early simulations are presented here. They indicate that BBU can only be suppressed to the same level as in designs powered by conventional pulsed power, if the calculated cell impedance can truly be achieved in practice. The magnetic focusing field required for this is of the same order as the field required for a conventionally powered LIA only if the transverse impedance can indeed be constrained to the values obtained in some simulations of the cell.

42 ENGINEERING↗
DOE OSTI2020

Manufacturing Hybrid Copper-Aluminum Rotors for High Power Induction and Permanent Magnet Electric Motors: CRADA 475 [Abstract only]

General Motors Research & Development (GM R&D) and Pacific Northwest National Laboratory (PNNL) will develop an electric rotor manufacturing technology with the potential of making electric motors lighters and more efficient. This will be achieved by developing a solid phase joining method to effectively join the Copper shorting bars to Aluminum end cap.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗