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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 631 records · Page 35
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Urinary levels of triclosan and triclocarban in several Asian countries, Greece and the USA: Association with oxidative stress

Highlights: • Triclosan and triclocarban were analyzed in 430 urine samples collected from 9 countries. • Triclosan concentrations as high as 1600 ng/mL were found in urine. • Age and gender related differences in triclosan levels were minimal. • TCC levels were marginally correlated with the oxidative stress marker, 8OHdG. Triclosan (TCS) and Triclocarban (TCC) are widely used as antimicrobial preservatives in personal care products (PCPs). Because of their potential for endocrine disrupting effects, human exposure to these chemicals is a concern. Biomonitoring studies of human exposure to TCS and TCC have shown widespread exposure of populations in western European countries and the USA. However, exposure to TCC and TCS by populations in Asian countries is less well known. In this study, concentrations of TCS and TCC were determined in human urine collected from seven Asian countries (China, India, Korea, Kuwait, Japan, Saudi Arabia, and Vietnam), and Greece and the USA. A total of 430 urine samples were analyzed for TCS and TCC, of which 355 (83%) and 82 (19%), respectively, contained measurable levels of these chemicals. The overall geometric mean [GM] concentrations of TCS and TCC, were 1.36 and 0.03 ng/mL, respectively. The highest mean concentration of TCS was found in urine from China (100 ng/mL) and the lowest concentration was found in urine from Vietnam (2.34 ng/mL). We also analyzed urinary 8-OHdG, a marker of oxidative stress, to elucidate the association with TCS and TCC levels for samples from Saudi Arabia (n=130) and a positive correlation between Ln-transformed TCC levels and 8-OHdG was found, although this was not statistically significant. This is the first study to report urinary levels of TCS and TCC in several Asian countries, especially for Vietnam, Kuwait, and Japan.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Mechanism of co-seismic water level change following four great earthquakes – insights from co-seismic responses throughout the Chinese mainland

In this study, we analyze the co-seismic groundwater level responses to four great earthquakes recorded by China's network of groundwater monitoring wells. The large number of operational wells (164 wells for the 2007 Mw 8.5 Sumatra earthquake, 245 wells for the Mw 7.9 Wenchuan earthquake, 228 wells for the Mw 9.0 Tohoku earthquake and 223 wells for 2012 Mw 8.6 Sumatra earthquake) and co-seismic responses provide an opportunity to test hypotheses on mechanisms for co-seismic water level changes. Overall, the co-seismic water level responses are complex over large spatial scales, and there is great variability both in the sign and amplitude of water level responses in the data set. As shown in previous studies, permeability change, rather than static strain, is a more plausible mechanism to explain most of the co-seismic responses. However, we find through tidal analysis of water level responses to solid Earth tide that only one third of these wells that showed a sustained post-seismic response can be explained by earthquake-induced permeability change in aquifers, and these wells had sustained (>30 days) water level changes. Lastly, wells that did not show sustained changes are more likely affected by permeability changes only immediately adjacent to the wellbore.

58 GEOSCIENCES↗
DOE OSTI2026

Spectroscopy and dynamics of the v = 1 levels derived from the OH(D) stretching modes in the I‾∙HDO complex using CW and time-resolved, resonant two-photon infrared excitation of the cryogenically cooled ions

The vibrational energy levels of the two isotopomers adopted by the I‾∙HDO ion-molecule complex occur such that the OH(D) stretching fundamentals span its dissociation energy, thus enabling a spectroscopic investigation of the dynamics displayed by a system prepared in the vicinity of the dissociation threshold. This regime is explored using infrared photoexcitation of the mass-selected complexes cooled in a cryogenic radiofrequency (Paul) ion trap. Survey spectra are obtained at modest resolution using two-color, IR-IR photodissociation with nanosecond lasers to establish the level structure and unimolecular decay dynamics of the v = 1 and 2 levels of the bound OH(D) oscillator. The v = 1 levels are prepared by fixed frequency excitation in the trap and the absorption spectra arising from this excited state are probed by photofragmentation of the complex with a second pulsed IR laser after a variable delay time (0 to 20 ms). The transitions to levels above the dissociation threshold for I‾ + HDO formation are observed to be sharp (~5 cm -1 FWHM). At low pressure, the bound OD (v = 1) population relaxes very slowly (~3 ms), consistent with resonant fluorescence in the IR. The collisional quenching rate constants of this level by the He buffer gas were estimated to be on the order 3 x 10 -12 cm 3 /s based on a crude Stern-Volmer analysis. Here, the rotational fine structure and linewidths (≲0.01 cm -1 FWHM) arising from transitions of the non-bonded OH stretch fundamental of the OD-bound isotopomer that lies just above the dissociation energy are determined using single photon photodissociation by excitation of the 10 K ions with a single-frequency, CW IR laser in the ion trap.

Cryogenic ion infrared spectroscopy↗
DOE OSTI2011

High-Risk Prostate Cancer With Gleason Score 8-10 and PSA Level {<=}15 ng/ mL Treated With Permanent Interstitial Brachytherapy

Purpose: With widespread prostate-specific antigen (PSA) screening, there has been an increase in men diagnosed with high-risk prostate cancer defined by a Gleason score (GS) {>=}8 coupled with a relatively low PSA level. The optimal management of these patients has not been defined. Cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) were evaluated in brachytherapy patients with a GS {>=}8 and a PSA level {<=}15 ng/mL with or without androgen-deprivation therapy (ADT). Methods and Materials: From April 1995 to October 2005, 174 patients with GS {>=}8 and a PSA level {<=}15 ng/mL underwent permanent interstitial brachytherapy. Of the patients, 159 (91%) received supplemental external beam radiation, and 113 (64.9%) received ADT. The median follow-up was 6.6 years. The median postimplant Day 0 minimum percentage of the dose covering 90% of the target volume was 121.1% of prescription dose. Biochemical control was defined as a PSA level {<=}0.40 ng/mL after nadir. Multiple parameters were evaluated for impact on survival. Results: Ten-year outcomes for patients without and with ADT were 95.2% and 92.5%, respectively, for CSS (p = 0.562); 86.5% and 92.6%, respectively, for bPFS (p = 0.204); and 75.2% and 66.0%, respectively, for OS (p = 0.179). The median post-treatment PSA level for biochemically controlled patients was <0.02 ng/mL. Multivariate analysis failed to identify any predictors for CSS, whereas bPFS and OS were most closely related to patient age. Conclusions: Patients with GS {>=}8 and PSA level {<=}15 ng/mL have excellent bPFS and CSS after brachytherapy with supplemental external beam radiotherapy. The use of ADT did not significantly impact bPFS, CSS, or OS.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Results of a Phase 2 Study Examining the Effects of Omitting Elective Neck Irradiation to Nodal Levels IV and V{sub b} in Patients With N{sub 0-1} Nasopharyngeal Carcinoma

Purpose: To evaluate the patterns of nodal failure and toxicity in clinically negative necks of N{sub 0-1} nasopharyngeal carcinoma (NPC) patients who were treated with intensity modulated radiation therapy (IMRT) but did not receive elective neck irradiation (ENI) to level IV and V{sub b} nodes. Methods and Materials: We conducted a phase 2 prospective study in N{sub 0-1} NPC patients treated with IMRT. ENI included the retropharyngeal nodes and levels II to V{sub a} but omitted levels IV and V{sub b} in clinically negative necks. Patterns of nodal failure, regional control (RC), and late toxicity were evaluated. Results: Between 2001 and 2008, a total of 212 patients (128 N{sub 0} and 84 N{sub 1}) were enrolled in the study. Seven patients (4 in-field and 3 out-of-field) developed nodal failure. One patient (0.5%) developed nodal failure at level V{sub b}, but no patients developed nodal failure at level IV. The 5-year RC rates of the entire group, N{sub 0} patients and N{sub 1} patients were 95.6%, 98.2%, and 91.3%, respectively. Fifteen patients (7.1%) developed distant metastases. The 5-year distant failure-free survival (DFFS) and overall survival (OS) rates were 91.4% and 89.8%, respectively. The rates of grade 2 or greater skin dystrophy, subcutaneous fibrosis and xerostomia were 6.2%, 16.6%, and 17.9%, respectively. Conclusions: The rate of out-of-field nodal failure when omitting ENI to levels IV and V{sub b} in clinically negative necks of patients with N{sub 0-1} NPC was extremely low; therefore, a further phase 3 study is warranted.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

A discontinuous Galerkin conservative level set scheme for interface capturing in multiphase flows

The accurate conservative level set (ACLS) method of Desjardins et al. [O. Desjardins, V. Moureau, H. Pitsch, An accurate conservative level set/ghost fluid method for simulating turbulent atomization, J. Comput. Phys. 227 (18) (2008) 8395–8416] is extended by using a discontinuous Galerkin (DG) discretization. DG allows for the scheme to have an arbitrarily high order of accuracy with the smallest possible computational stencil resulting in an accurate method with good parallel scaling. This work includes a DG implementation of the level set transport equation, which moves the level set with the flow field velocity, and a DG implementation of the reinitialization equation, which is used to maintain the shape of the level set profile to promote good mass conservation. A near second order converging interface curvature is obtained by following a height function methodology (common amongst volume of fluid schemes) in the context of the conservative level set. Various numerical experiments are conducted to test the properties of the method and show excellent results, even on coarse meshes. The tests include Zalesak’s disk, two-dimensional deformation of a circle, time evolution of a standing wave, and a study of the Kelvin–Helmholtz instability. Finally, this novel methodology is employed to simulate the break-up of a turbulent liquid jet.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2012

High-resolution infrared studies of the v 10 , v 11 , v 14 , and v 18 levels of [1.1.1]propellane

This paper is a continuation of earlier work for which the high resolution infrared spectrum of [1.1.1]propellane was measured and its k and l structure resolved for the first time. Here we present results from an analysis of more than 16,000 transitions involving three fundamental bands v 10 (E'-A1'), v 11 (E'-A1'), v 14 (A2''-A1') and two difference bands (v 10 - v 18 ) (E'-E'') and (v 11 -v 18 ) (E'-E"). Additional information about v18 was also obtained from the difference band (v 15 +v 1 8)-v 18 (E'-E") and the binary combination band (v 15 +v 18 ) (E'-A1'). Through the use of the ground state constants reported in an earlier paper [1], rovibrational constants have been determined for all the vibrational states involved in these bands. The rovibrational parameters for the v 18 (E'') state were obtained from combination-differences and showed no need to include interactions with other states. The v 10 (E') state analysis was also straight-forward, with only a weak Coriolis interaction with the levels of the v 14 (A2'') state. The latter levels are much more affected by a strong Coriolis interaction with the levels of the nearby v 11 (E') state and also by a small but significant interaction with another state, presumably the v16(E'') state, that is not directly observed. Gaussian calculations (B3LYP/cc-pVTZ) computed at the anharmonic level aided the analyses by providing initial values for many of the parameters. These theoretical results generally compare favorably with the final parameter values deduced from the spectral analyses. Finally, evidence was obtained for several level crossings between the rotational levels of the v 11 and v 14 states and, using a weak coupling term corresponding to a Δk = ±5, Δl = ∓1 matrix element, it was possible to find transitions from the ground state that, combined with transitions to the same upper state, give a value of C 0 = 0.1936519(4) cm -1 . This result, combined with the value of B 0 = 0.28755833(14) cm-1 reported earlier [1], yields a value of 1.586282(3) Å for the length of the novel axial CC bond in propellane.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2014

Fraction of the theoretical specific energy achieved on pack level for hypothetical battery chemistries

In valuing new active materials chemistries for advanced batteries, the theoretical specific energy is commonly used to motivate research and development. A packaging factor is then used to relate the theoretical specific energy to the pack-level specific energy. As this factor is typically assumed constant, higher theoretical specific energies are judged to result in higher pack-level specific energies. Here, to test this implicit assumption, we calculated the fraction of the theoretical specific energy achieved on the pack level for hypothetical cell chemistries with various open-circuit voltages and theoretical specific energies using a peer-review bottom-up battery design model. The pack-level specific energy shows significant dependence on the open-circuit voltage and electrochemical impedance due to changes in the quantity of inactive materials required. At low-valued average open-circuit voltages, systems with dramatically different theoretical specific energies may result in battery packs similar in mass and volume. The fraction of the theoretical specific energy achieved on the pack level is higher for the lower theoretical specific energy systems mainly because the active materials mass dominates the pack mass. Finally, low-valued area-specific impedance is shown to be critical for chemistries of high theoretical specific energy and low open-circuit voltage to achieve higher pack-level specific energies.

25 ENERGY STORAGE↗
DOE OSTI2021

Structure of high-lying levels populated in the 96 Y → 96 Zr β decay

The nature of the high-lying final levels of the 96 Y gs β decay, one of the three most important contributors to the high-energy reactor antineutrino spectrum, has been investigated in high-resolution γ-ray spectroscopy following the β decay as well as in a campaign of inelastic photon scattering experiments. The comprehensive approach establishes 1 - levels associated with the Pygmy Dipole Resonance as high-lying final levels in the β decay. Branching ratios extracted from β decay complement photon scattering and allow the absolute E1 excitation strength to be determined for levels populated in both reactions. The combined data represents a comprehensive approach to the wavefunction of the 1 - levels below the Qβ value, which are investigated in the Quasiparticle Phonon Model. The calculations reveal that the components populated in β decay contribute only with small amplitudes to the complex wavefunction of these 1 - levels. A comparison of the β decay results to data from total absorption γ -ray spectroscopy demonstrates a good agreement between both measurements.

Pygmy dipole resonance↗
DOE OSTI2010

Temporal study of acetaminophen (APAP) and S-adenosyl-L-methionine (SAMe) effects on subcellular hepatic SAMe levels and methionine adenosyltransferase (MAT) expression and activity

Acetaminophen (APAP) is the leading cause of drug induced liver failure in the United States. Previous studies in our laboratory have shown that S-adenosyl methionine (SAMe) is protective for APAP hepatic toxicity. SAMe is critical for glutathione synthesis and transmethylation of nucleic acids, proteins and phospholipids which would facilitate recovery from APAP toxicity. SAMe is synthesized in cells through the action of methionine adenosyltransferase (MAT). This study tested the hypothesis that total hepatic and subcellular SAMe levels are decreased by APAP toxicity. Studies further examined MAT expression and activity in response to APAP toxicity. Male C57BL/6 mice (16-22 g) were treated with vehicle (Veh; water 15 ml/kg ip injections), 250 mg/kg APAP (15 ml/kg, ip), SAMe (1.25 mmol/kg) or SAMe administered 1 h after APAP injection (SAMe and SAMe + APAP). Hepatic tissue was collected 2, 4, and 6 h after APAP administration. Levels of SAMe and its metabolite S-adenosylhomocysteine (SAH) were determined by HPLC analysis. MAT expression was examined by Western blot. MAT activity was determined by fluorescence assay. Total liver SAMe levels were depressed at 4 h by APAP overdose, but not at 2 or 6 h. APAP depressed mitochondrial SAMe levels at 4 and 6 h relative to the Veh group. In the nucleus, levels of SAMe were depressed below detectable limits 4 h following APAP administration. SAMe administration following APAP (SAMe + APAP) prevented APAP associated decline in mitochondrial and nuclear SAMe levels. In conclusion, the maintenance of SAMe may provide benefit in preventing damage associated with APAP toxicity.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2011

A possible mechanism for 2,2',4,4',5,5'-hexachlorobiphenyl-mediated decrease in serum thyroxine level in mice

Serum total thyroxine (T{sub 4}) level was markedly decreased, without significant increases in the levels of hepatic T{sub 4}-UDP-glucuronosyltransferase (T{sub 4}-UGT) and serum thyroid-stimulating hormone, 3 days after treatment with 2,2',4,4',5,5'-hexachlorobiphenyl (CB153) (100 mg/kg, ip) in both 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-sensitive C57BL/6 and TCDD-resistant DBA/2 mice. Likewise, in either strain of mice, no CB153-mediated changes in the binding levels of [{sup 125}I]T{sub 4} to serum proteins, such as transthyretin, albumin, and thyroxine binding globulin, were observed, while in CB153-pretreated C57BL/6 mice, but not in CB153-pretreated DBA/2 mice, the levels of biliary [{sup 125}I]T{sub 4} and [{sup 125}I]T{sub 4}-glucuronide at 90-120 min after injection of [{sup 125}I]T{sub 4} slightly increased, as compared with those in the corresponding control mice. Concerning tissue distribution of [{sup 125}I]T{sub 4}, liver-selective increases in the [{sup 125}I]T{sub 4} accumulation by CB153-pretreatment were observed in both C57BL/6 and DBA/2 mice, and the hepatic levels of [{sup 125}I]T{sub 4} in the C57BL/6 and DBA/2 mice became more than 44% and 34% of the [{sup 125}I]T{sub 4} dosed, respectively. The present findings indicated that the CB153-mediated decreases in the level of serum total T{sub 4} in C57BL/6 and DBA/2 mice occur mainly through an increase in the accumulation of T{sub 4} in the liver.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Dioxin exposure reduces the steroidogenic capacity of mouse antral follicles mainly at the level of HSD17B1 without altering atresia

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent ovarian toxicant. Previously, we demonstrated that in vitro TCDD (1 nM) exposure decreases production/secretion of the sex steroid hormones progesterone (P4), androstenedione (A4), testosterone (T), and 17β-estradiol (E2) in mouse antral follicles. The purpose of this study was to determine the mechanism by which TCDD inhibits steroidogenesis. Specifically, we examined the effects of TCDD on the steroidogenic enzymes, atresia, and the aryl hydrocarbon receptor (AHR) protein. TCDD exposure for 48 h increased levels of A4, without changing HSD3B1 protein, HSD17B1 protein, estrone (E1), T or E2 levels. Further, TCDD did not alter atresia ratings compared to vehicle at 48 h. TCDD, however, did down regulate the AHR protein at 48 h. TCDD exposure for 96 h decreased transcript levels for Cyp11a1, Cyp17a1, Hsd17b1, and Cyp19a1, but increased Hsd3b1 transcript. TCDD exposure particularly lowered both Hsd17b1 transcript and HSD17B1 protein. However, TCDD exposure did not affect levels of E1 in the media nor atresia ratings at 96 h. TCDD, however, decreased levels of the proapoptotic factor Bax. Collectively, these data suggest that TCDD exposure causes a major block in the steroidogenic enzyme conversion of A4 to T and E1 to E2 and that it regulates apoptotic pathways, favoring survival over death in antral follicles. Finally, the down‐regulation of the AHR protein in TCDD exposed follicles persisted at 96 h, indicating that the activation and proteasomal degradation of this receptor likely plays a central role in the impaired steroidogenic capacity and altered apoptotic pathway of exposed antral follicles. -- Highlights: ► TCDD disrupts steroidogenic enzymes in mouse antral follicles. ► TCDD particularly affects the HSD17B1 enzyme in mouse antral follicles. ► TCDD does not affect atresia ratings in mouse antral follicles. ► TCDD decreases levels of the proapoptitic factor Bax in mouse antral follicles. ► TCDD down regulates the AHR protein in mouse antral follicles.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Comparative effects of parathion and chlorpyrifos on extracellular endocannabinoid levels in rat hippocampus: Influence on cholinergic toxicity

Parathion (PS) and chlorpyrifos (CPF) are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). Endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) can modulate neurotransmission by inhibiting neurotransmitter release. We proposed that differential inhibition of eCB-degrading enzymes (fatty acid amide hydrolase, FAAH, and monoacylglycerol lipase, MAGL) by PS and CPF leads to differences in extracellular eCB levels and toxicity. Microdialysis cannulae were implanted into hippocampus of adult male rats followed by treatment with vehicle (peanut oil, 2 ml/kg, sc), PS (27 mg/kg) or CPF (280 mg/kg) 6–7 days later. Signs of toxicity, AChE, FAAH and MAGL inhibition, and extracellular levels of AEA and 2AG were measured 2 and 4 days later. Signs were noted in PS-treated rats but not in controls or CPF-treated rats. Cholinesterase inhibition was extensive in hippocampus with PS (89–90%) and CPF (78–83%) exposure. FAAH activity was also markedly reduced (88–91%) by both OPs at both time-points. MAGL was inhibited by both OPs but to a lesser degree (35–50%). Increases in extracellular AEA levels were noted after either PS (about 2-fold) or CPF (about 3-fold) while lesser treatment-related 2-AG changes were noted. The cannabinoid CB1 receptor antagonist/inverse agonist AM251 (3 mg/kg, ip) had no influence on functional signs after CPF but markedly decreased toxicity in PS-treated rats. The results suggest that extracellular eCBs levels can be markedly elevated by both PS and CPF. CB1-mediated signaling appears to play a role in the acute toxicity of PS but the role of eCBs in CPF toxicity remains unclear. - Highlights: • Chlorpyrifos and parathion both extensively inhibited hippocampal cholinesterase. • Functional signs were only noted with parathion. • Chlorpyrifos and parathion increased hippocampal extracellular anandamide levels. • 2-Arachidonoylglycerol levels were lesser affected. • The CB1 antagonist AM251 had no effect on chlorpyrifos but reduced parathion toxicity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Oxidative DNA damage and repair in children exposed to low levels of arsenic in utero and during early childhood: Application of salivary and urinary biomarkers

The present study aimed to assess arsenic exposure and its effect on oxidative DNA damage and repair in young children exposed in utero and continued to live in arsenic-contaminated areas. To address the need for biological specimens that can be acquired with minimal discomfort to children, we used non-invasive urinary and salivary-based assays for assessing arsenic exposure and early biological effects that have potentially serious health implications. Levels of arsenic in nails showed the greatest magnitude of difference between exposed and control groups, followed by arsenic concentrations in saliva and urine. Arsenic levels in saliva showed significant positive correlations with other biomarkers of arsenic exposure, including arsenic accumulation in nails (r = 0.56, P < 0.001) and arsenic concentration in urine (r = 0.50, P < 0.05). Exposed children had a significant reduction in arsenic methylation capacity indicated by decreased primary methylation index and secondary methylation index in both urine and saliva samples. Levels of salivary 8-OHdG in exposed children were significantly higher (∼ 4-fold, P < 0.01), whereas levels of urinary 8-OHdG excretion and salivary hOGG1 expression were significantly lower in exposed children (∼ 3-fold, P < 0.05), suggesting a defect in hOGG1 that resulted in ineffective cleavage of 8-OHdG. Multiple regression analysis results showed that levels of inorganic arsenic (iAs) in saliva and urine had a significant positive association with salivary 8-OHdG and a significant negative association with salivary hOGG1 expression. - Highlights: • The effects of arsenic exposure in utero and through early childhood were studied. • Arsenic-exposed children had a reduction in arsenic methylation capacity. • Exposed children had more DNA damage, observed as elevated salivary 8-OHdG. • Lower salivary hOGG1 in exposed children indicated impairment of 8-OHdG repair. • Salivary and urinary 8-OHdG levels were discordant.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism

It's known that blood leptin level is reduced in intrauterine growth retardation (IUGR) fetus, and placental leptin is the major source of fetal blood leptin. This study aimed to investigate the decreased fetal blood leptin level by prenatal caffeine exposure (PCE) and its underlying placental mechanisms. Pregnant Wistar rats were intragastrically administered caffeine (30–120 mg/kg day) from gestational day 9 to 20. The level of fetal serum leptin and the expression of placental leptin-related genes were analyzed. Furthermore, we investigated the molecular mechanism of the reduced placental leptin's expression by treatment with caffeine (0.8–20 μM) in the BeWo cells. In vivo, PCE significantly decreased fetal serum leptin level in caffeine dose-dependent manner. Meanwhile, placental mRNA expression of adenosine A2a receptor (Adora2a), cAMP-response element binding protein (CREB), a short-type leptin receptor (Ob-Ra) and leptin was reduced in the PCE groups. In vitro, caffeine significantly decreased the mRNA expression of leptin, CREB and ADORA2A in concentration and time-dependent manners. The addition of ADORA2A agonist or adenylyl cyclase (AC) agonist reversed the inhibition of leptin expression induced by caffeine. PCE induced a lower level of fetal blood leptin, which the primary mechanism is that caffeine inhibited antagonized Adora2a and AC activities to decreased cAMP synthesis, thus inhibited the expression of the transcription factor CREB and target gene leptin in the placenta. Meantime, the reduced transportation of maternal leptin by placental Ob-Ra also contributed to the reduced fetal blood leptin. Together, PCE decreased fetal blood leptin mainly via reducing the expression and transportation of leptin in the placenta. - Highlights: • Caffeine reduced fetal blood leptin level. • Caffeine inhibited placental leptin production and transport. • Caffeine down-regulated placental leptin expression via antagonizing ADORA2. • Caffeine inhibited placental leptin transport via decreased OB-Ra expression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Ski protein levels increase during in vitro progression of HPV16-immortalized human keratinocytes and in cervical cancer

We compared the levels of the Ski oncoprotein, an inhibitor of transforming growth factor-beta (TGF-β) signaling, in normal human keratinocytes (HKc), HPV16 immortalized HKc (HKc/HPV16), and differentiation resistant HKc/HPV16 (HKc/DR) in the absence and presence of TGF-β. Steady-state Ski protein levels increased in HKc/HPV16 and even further in HKc/DR, compared to HKc. TGF-β treatment of HKc, HKc/HPV16, and HKc/DR dramatically decreased Ski. TGF-β-induced Ski degradation was delayed in HKc/DR. Ski and phospho-Ski protein levels are cell cycle dependent with maximal Ski expression and localization to centrosomes and mitotic spindles during G2/M. ShRNA knock down of Ski in HKc/DR inhibited cell proliferation. More intense nuclear and cytoplasmic Ski staining and altered Ski localization were found in cervical cancer samples compared to adjacent normal tissue in a cervical cancer tissue array. Overall, these studies demonstrate altered Ski protein levels, degradation and localization in HPV16-transformed human keratinocytes and in cervical cancer. - Highlights: • Ski oncoprotein levels increase during progression of HPV16-transformed cells. • Ski and phospho-Ski protein levels are cell cycle dependent. • Ski knock-down in HPV16-transformed keratinocytes inhibited cell proliferation. • Cervical cancer samples overexpress Ski.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2010

MicroRNA-15a fine-tunes the level of Delta-like 1 homolog (DLK1) in proliferating 3T3-L1 preadipocytes

Delta like 1 homolog (Dlk1) exists in both transmembrane and soluble molecular forms, and is implicated in cellular growth and plays multiple roles in development, tissue regeneration, and cancer. Thus, DLK1 levels are critical for cell function, and abnormal DLK1 expression can be lethal; however, little is known about the underlying mechanisms. We here report that miR-15a modulates DLK1 levels in preadipocytes thus providing a mechanism for DLK1 regulation that further links it to cell cycle arrest and cancer since miR-15a is deregulated in these processes. In preadipocytes, miR-15a increases with cell density, and peaks at the same stage where membrane DLK1{sup M} and soluble DLK1{sup S} are found at maximum levels. Remarkably, miR-15a represses the amount of all Dlk1 variants at the mRNA level but also the level of DLK1{sup M} protein while it increases the amount of DLK1{sup S} supporting a direct repression of DLK1 and a parallel effect on the protease that cleaves off the DLK1 from the membrane. In agreement with previous studies, we found that miR-15a represses cell numbers, but additionally, we report that miR-15a also increases cell size. Conversely, anti-miR-15a treatment decreases cell size while increasing cell numbers, scenarios that were completely rescued by addition of purified DLK1{sup S}. Our data thus imply that miR-15a regulates cell size and proliferation by fine-tuning Dlk1 among others, and further emphasize miR-15a and DLK1 levels to play important roles in growth signaling networks.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Impacts of Observational Constraints Related to Sea Level on Estimates of Climate Sensitivity

Reduced complexity climate models are necessary tools for quantifying decision-relevant uncertainties, given their flexibility, computational efficiency, and suitability for large-ensemble frameworks necessary for statistical estimation using resampling techniques (e.g. Markov chain Monte Carlo—MCMC). Here we document a new version of the simple, open-source, global climate model Hector, coupled with a one-dimensional diffusive heat and energy balance model (Diffusion Ocean Energy balance CLIMate model; DOECLIM) and a sea-level change module (Building blocks for Relevant Ice and Climate Knowledge; BRICK) that also represents contributions from thermal expansion, glaciers and ice caps, and polar ice sheets. We apply a Bayesian calibration approach to quantify model uncertainties surrounding 39 model parameters with prescribed radiative forcing, using observational information from global surface temperature, ocean heat uptake, and sea-level change. Furthermore, we find sea-level change as an observational constraint sharpens inference for the upper tail of posterior climate sensitivity estimates (the 97.5 percentile is tightened from 6.5 K to 5.3 K). The addition of sea-level change as an observational constraint also has implications for probabilistic projections of global surface temperature (the 97.5 percentile for RCP8.5 2100 temperature decreases 0.3 K) and sea-level rise (the 97.5 percentile for RCP8.5 2100 sea level decreases 0.5 m).

54 ENVIRONMENTAL SCIENCES↗