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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 1,009 records · Page 56
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

MWA Versus RFA for Perivascular and Peribiliary CRLM: A Retrospective Patient- and Lesion-Based Analysis of Two Historical Cohorts

PurposeTo retrospectively analyse the safety and efficacy of radiofrequency ablation (RFA) versus microwave ablation (MWA) in the treatment of unresectable colorectal liver metastases (CRLM) in proximity to large vessels and/or major bile ducts.Method and MaterialsA database search was performed to include patients with unresectable histologically proven and/or {sup 18}F–FDG–PET avid CRLM who were treated with RFA or MWA between January 2001 and September 2014 in a single centre. All lesions that were considered to have a peribiliary and/or perivascular location were included. Univariate logistic regression analysis was performed to assess the distribution of patient, tumour and procedure characteristics. Multivariate logistic regression was used to correct for potential confounders.ResultsTwo hundred and forty-three patients with 774 unresectable CRLM were ablated. One hundred and twenty-two patients (78 males; 44 females) had at least one perivascular or peribiliary lesion (n = 199). Primary efficacy rate of RFA was superior to MWA after 3 and 12 months of follow-up (P = 0.010 and P = 0.022); however, after multivariate analysis this difference was non-significant at 12 months (P = 0.078) and vanished after repeat ablations (P = 0.39). More CTCAE grade III complications occurred after MWA versus RFA (18.8 vs. 7.9 %; P = 0.094); biliary complications were especially common after peribiliary MWA (P = 0.002).ConclusionFor perivascular CRLM, RFA and MWA are both safe treatment options that appear equally effective. For peribiliary CRLM, MWA has a higher complication rate than RFA, with similar efficacy. Based on these results, it is advised to use RFA for lesions in the proximity of major bile ducts.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Prophylactic Temporary Occlusion of the Cystic Artery Using a Fibered Detachable Coil During {sup 90}Y Radioembolization

PurposeTo address the feasibility of prophylactic temporary occlusion of the cystic artery using a detachable coil during {sup 90}Y radioembolization.Materials and MethodsFrom January 2012 to October 2016, nine patients underwent temporary occlusion of the cystic artery during {sup 90}Y radioembolization. Based on the planning hepatic angiography, a detachable coil was deployed into the cystic artery, which arose from a more distal level (e.g., right anterior hepatic artery) than its usual origin, but the proximal 1 cm was left inside the microcatheter. {sup 90}Y microspheres were infused proximal to the cystic artery where the 99mTc-MAA had been infused, and then the coil was retrieved. Afterward, the patients underwent PET/CT imaging. Medical records were reviewed, and the differences in the uptake of 99mTc-MAA and {sup 90}Y microspheres in the gallbladder were evaluated using Wilcoxon’s signed-rank test.ResultsTemporary placement of a detachable coil was feasible in all cases. On the angiograms obtained after detachable coil placement, the distal cystic artery and gallbladder were partially identifiable in eight of the nine (88.8%) patients, but fully restored after the removal of the coils in all cases. The proportional uptake of 99mTc-MAA (mean, 4.35%) and {sup 90}Y (mean, 0.90%) in the gallbladder was significantly different due to the temporary occlusion of the cystic artery (p = 0.004). No clinical complications were identified for three months after the procedure.ConclusionTemporary occlusion of the cystic artery using a detachable coil appeared to be feasible and effective in reducing {sup 90}Y uptake in the gallbladder.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Histologic Analysis with the Newly Designed Exoskeleton Seal{sup ®} Stent-Graft in the Porcine Abdominal Aorta

Purpose: To investigate the technical feasibility of a novel exoskeleton Seal{sup ®} stent-graft and analyze early histologic changes in the porcine abdominal aorta. Materials and Methods: Six pigs received an abdominal stent-graft (Group I), and six received an iliac branch stent-graft (Group II). Groups were subdivided as follows: Group Ia, which received three bifurcated main-body stent-grafts; Group Ib, which received three bifurcated main-body stent-grafts with both iliac graft-stents; Group IIa, which received three simple uni-iliac tapered stent-grafts; and Group IIb, which received three uni-iliac tapered tapered stent-grafts with right straight limb and left branched limb. Statistical analyses were performed with the Wilcoxon signed-rank test and mixed-model regression analysis. Results: The primary technical success rate (< 24 h) was 83% because of two acute thromboses in the lumen of the stented abdominal aorta immediately after stent-graft placement. At 4 weeks, late thrombosis occurred in two pigs. Higher mean neointimal hyperplasia areas (23.5% vs. 16.2%; P = .047), neointimal hyperplasia thicknesses (545.5 μm vs. 422.2 μm; P = .001), and degrees of collagen deposition (2.71 vs. 2.33; P = .002) were observed at the bare-metal stent-graft compared with the proximal exoskeleton portion of the stent-graft, with no significant differences between the patent and occluded groups or among the four types of stent-grafts. Conclusions: The exoskeleton stent-graft demonstrates 66% of patency rate during 1-month follow-up due to four cases of thromboses; however, the endothelialization on the junction of proximal graft showed no significant differences between the patent and occluded groups. Further studies should investigate long-term outcomes with prolonged neointimal hyperplasia.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Endovascular Neck Stabilization Before EVAR for Infrarenal Aortic Aneurysm in Chronic Aortic Dissection

Background: Endovascular treatment of infrarenal abdominal aortic aneurysm (AAA) with proximal chronic aortic dissection is challenging as a false and true lumen at the level of the infra-renal neck does not allow a sufficient landing zone. We describe staged endovascular neck stabilization prior to standard endovascular aortic repair (EVAR) for AAA with chronic aortic dissection. Technique: To create a stable proximal neck (PN) by closing entry tears, thereby resulting in total false lumen thrombosis (FLT) prior to standard EVAR. Case 1 false lumen fenestrations were present at the descending aorta, the right renal artery orifice and PN. After closing the entry tear by thoracic EVAR, an aortic cuff was placed in the true lumen of the PN and renal stenting for the right renal artery was performed. After 2 months, total FLT was achieved, and EVAR was performed. Case 2 false lumen fenestrations were present at the descending, super celiac aorta and PN. After closing the entry by TEVAR, aortic cuffs were placed at infrarenal aorta to close residual entries. After 1 month of achieving total FLT, EVAR was performed. Both cases had no type 1 endoleak during follow-up. Conclusion: The endovascular neck stabilization is a useful treatment option that facilitates standard EVAR for AAA in chronic aortic dissection.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

Structural features promoting dioxygen production by Dechloromonas aromatica chlorite dismutase

Chlorite dismutase (Cld) is a heme enzyme capable of rapidly and selectively decomposing chlorite (ClO{sub 2}{sup -}) to Cl{sup -} and O{sub 2}. The ability of Cld to promote O{sub 2} formation from ClO{sub 2}{sup -} is unusual. Heme enzymes generally utilize ClO{sub 2}{sup -} as an oxidant for reactions such as oxygen atom transfer to, or halogenation of, a second substrate. The X-ray crystal structure of Dechloromonas aromatica Cld co-crystallized with the substrate analogue nitrite (NO{sub 2}{sup -}) was determined to investigate features responsible for this novel reactivity. The enzyme active site contains a single b-type heme coordinated by a proximal histidine residue. Structural analysis identified a glutamate residue hydrogen-bonded to the heme proximal histidine that may stabilize reactive heme species. A solvent-exposed arginine residue likely gates substrate entry to a tightly confined distal pocket. On the basis of the proposed mechanism of Cld, initial reaction of ClO{sub 2}{sup -} within the distal pocket generates hypochlorite (ClO{sup -}) and a compound I intermediate. The sterically restrictive distal pocket probably facilitates the rapid rebound of ClO{sup -} with compound I forming the Cl{sup -} and O{sub 2} products. Common to other heme enzymes, Cld is inactivated after a finite number of turnovers, potentially via the observed formation of an off-pathway tryptophanyl radical species through electron migration to compound I. Three tryptophan residues of Cld have been identified as candidates for this off-pathway radical. Finally, a juxtaposition of hydrophobic residues between the distal pocket and the enzyme surface suggests O{sub 2} may have a preferential direction for exiting the active site.

36 MATERIALS SCIENCE↗
DOE OSTI2018

Lifshitz Transitions In Multi-band Hubbard Models for Topological Superconductivity in Complex Quantum Matter

How the macroscopic quantum coherence can resist to the decoherence attacks of high temperature is a major challenge for the science of the twenty-first century. Superstripes 2017 conference held in Ischia on June 2017 has been focused on the new physics of high-T{sub c} superconductors made of complex quantum matter. Today, the standard model of high-T{sub c} superconductivity which grabs the physics of complex quantum matter is the multi-band Hubbard model where the dome of T{sub c} occurs by driving the chemical potential in the proximity of a topological Lifshitz transition. The multi-gap superconductivity in the T{sub c} dome is driven by exchange interaction between a first condensate in the BEC-BCS crossover which coexists with second BCS condensates. The proximity to Lifshitz transitions in correlated electronic systems gives the ubiquitous arrested phase separation observed in all high-temperature superconductors. Non-Euclidean filamentary hyperbolic geometry is needed for the space description of superstripe textures produced by the coexistence of short-range CDW puddles, hole-poor SDW puddles, and self-organized dopant-rich puddles. A road map to room-temperature superconductors in particular organic compounds made of superlattices of quantum wires driven by Fano resonances with one of the condensates in the BEC-BCS crossover has been proposed.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2013

Determining HPGe Total Detection Efficiency Using γ–γ Coincidence

Abstract Both the peak and total detection efficiencies are generally needed in order to calculate sample activity from a gamma spectroscopic measurement, except in the case of isotope specific calibration. This is particularly true when the sample is in close proximity to the detector and corrections for cascade summing effects are required to avoid significant inaccuracy in the result. These corrections use the total detection efficiency to correct for summing-in and summing-out events, and the extent of the correction depends on both the geometry and the gamma cascade for the isotope in question. Experimentally determining the total efficiency is a labor intensive endeavor requiring multiple measurements with a set of single-gamma-emitting standards. Modeling the total efficiency vs. energy may be less time consuming, but is also likely to produce less confidence in the final result. Pacific Northwest National Laboratory's Radiation Detection and Nuclear Sciences group has constructed a low background 14-crystal HPGe array for sample measurement; in all measurements, samples will be in close proximity to the germanium crystals. This close geometry and the sheer number efficiency calibrations required for the system have led us to investigate methods to simplify the efficiency calibration procedure. One method we are developing uses the Y-Y coincidence plane to isolate Compton scattering event populations, allowing experimental determination of total detection efficiency values from the measurement of a single mixed isotope standard. A description of the analysis and experimental results of this method are presented.

low background HPGe High Purity Germanium detector↗
DOE OSTI2020

Natively oxidized amino acid residues in the spinach PS I-LHC I supercomplex

Reactive oxygen species (ROS) production is an unavoidable byproduct of electron transport under aerobic conditions. Photosystem II (PS II), the cytochrome b 6 /ƒ complex and Photosystem I (PS I) are all demonstrated sources of ROS. It has been proposed that PS I produces substantial levels of a variety of ROS including O$_{2}^{·-}$, 1 O 2 , H 2 O 2 and, possibly, ∙OH, however, the site(s) of ROS production within PS I has been the subject of significant debate. We hypothesize that amino acid residues close to the sites of ROS generation will be more susceptible to oxidative modification than distant residues. In this study, we have identified oxidized amino acid residues in spinach PS I which was isolated from field-grown spinach. The modified residues were identified by high-resolution tandem mass spectrometry. As expected, many of the modified residues lie on the surface of the complex. However, a well-defined group of oxidized residues, both buried and surface-exposed, lead from the chl a’ of P 700 to the surface of PS I. These residues (PsaB: 609 F, 611 E, 617 M, 619 W, 620 L, and PsaF: 139 L, 142 A, 143 D) may identify a preferred route for ROS, probably 1 O 2 , to egress the complex from the vicinity of P 700 . Additionally, two buried residues located in close proximity to A1B (PsaB: 712 H and 714 S) were modified, which may be consistent with A 1B being a source of O$_{2}^{·-}$. Surprisingly, no oxidatively modified residues were identified in close proximity to the 4Fe-FS clusters F X , F A or F B . These cofactors had been identified as a principal targets for ROS damage in the photosystem. Finally, a large number of residues located in the hydrophobic cores of Lhca1-Lhca4 are oxidatively modified. These appear to be the result of 1 O 2 production by the distal antennae for the photosystem.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Subsurface Grain Morphology Reconstruction by Differential Aperture X-ray Microscopy

A multistep, non-destructive grain morphology reconstruction methodology that is applicable to near-surface volumes is developed and tested on synthetic grain structures. This approach probes the subsurface crystal orientation using differential aperture x-ray microscopy on a sparse grid across the microstructure volume of interest. Resulting orientation data are clustered according to proximity in physical and orientation space and used as seed points for an initial Voronoi tessellation to (crudely) approximate the grain morphology. Curvature-driven grain boundary relaxation, simulated by means of the Voronoi implicit interface method, progressively improves the reconstruction accuracy. The similarity between bulk and readily accessible surface reconstruction error provides an objective termination criterion for boundary relaxation.

36 MATERIALS SCIENCE↗
DOE OSTI2018

Predictions on the modes of decay of odd Z superheavy isotopes within the range 105≤Z≤135

The decay modes of 1051 odd Z superheavy nuclei within the range 105 ≤Z≤ 135, and their daughter nuclei are studied by comparing the alpha decay half-lives with the spontaneous fission half-lives. The alpha decay half-lives are calculated using the Coulomb and proximity potential model for deformed nuclei (CPPMDN) proposed by Santhosh et al. (2011) and the spontaneous fission half-lives are obtained with the shell-effect dependent formula of Santhosh et al. (Santhosh and Nithya, 2016). For a theoretical comparison, the alpha decay half-lives are also computed with the Coulomb and proximity potential model (CPPM), Viola–Seaborg–Sobiczewski semi-empirical relation (VSS), Universal curve of Poenaru et al. (UNIV), the analytical formula of Royer, and the Universal decay law of Qi et al. (UDL). The predicted decay modes and half-lives were compared with the available experimental results. The proton and neutron separation energies are calculated to identify those nuclei, which decay through proton and neutron emission. From the entire study of odd Z superheavy elements, it is seen that among 1051 nuclei, 233 nuclei exhibit proton emission and 18 nuclei exhibit neutron emission. 56 nuclei are stable against alpha decay with negative Q value for the decay. 92 nuclei show alpha decay followed by spontaneous fission and 9 nuclei show alpha decay followed by proton emission. 39 nuclei decay through full alpha chain and 595 nuclei decay through spontaneous fission. We hope that the study will be very useful for the future experimental investigations in this field.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2014

Visualizations of coherent center domains in local Polyakov loops

Quantum Chromodynamics exhibits a hadronic confined phase at low to moderate temperatures and, at a critical temperature T{sub C}, undergoes a transition to a deconfined phase known as the quark–gluon plasma. The nature of this deconfinement phase transition is probed through visualizations of the Polyakov loop, a gauge independent order parameter. We produce visualizations that provide novel insights into the structure and evolution of center clusters. Using the HMC algorithm the percolation during the deconfinement transition is observed. Using 3D rendering of the phase and magnitude of the Polyakov loop, the fractal structure and correlations are examined. The evolution of the center clusters as the gauge fields thermalize from below the critical temperature to above it are also exposed. We observe deconfinement proceeding through a competition for the dominance of a particular center phase. We use stout-link smearing to remove small-scale noise in order to observe the large-scale evolution of the center clusters. A correlation between the magnitude of the Polyakov loop and the proximity of its phase to one of the center phases of SU(3) is evident in the visualizations. - Highlights: • We produce visualizations of center clusters in Polyakov loops. • The evolution of center clusters with HMC simulation time is examined. • Visualizations provide novel insights into the percolation of center clusters. • The magnitude and phase of the Polyakov loop are studied. • A correlation between the magnitude and center phase proximity is evident.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2025

Elucidating the factors controlling the methanol synthesis from CO 2 on ZnPd-ZnO/TiO 2 catalysts prepared by direct/inverse impregnation

The direct hydrogenation of CO 2 to methanol over supported ZnPd intermetallic catalysts remains a challenge due to the complex nature of the active sites, which are highly dependent on both the dispersion of ZnPd intermetallics and their proximity to ZnO. This study investigates the effect of the Pd and Zn incorporation order on methanol synthesis over TiO 2 -supported ZnPd catalysts. Catalysts were prepared via direct (Pd/Zn), inverse (Zn/Pd), and co-impregnation (Pd+Zn) methods using anatase TiO 2 as the support. Comprehensive characterization by XRD, HRTEM, CO-DRIFTS and XPS revealed that the formation of small and crystalline intermetallic β-ZnPd particles and their interaction with ZnO/ZnO x depends on the sequence of Pd and Zn incorporation. It was found that, under the reaction conditions, the ZnO x species plays a critical role in facilitating the formation of the intermetallic ZnPd through the interactions between Pd and ZnO x . In addition, ZnO x species have also been shown to modulate key catalytic properties, such as CO 2 activation and methanol selectivity. Specifically, the ZnPd/Pd surface ratio, determined by Pd dispersion and proximity to ZnO/ZnO x , was shown to determine the methanol production from CO 2 directly or via a CO intermediate. The Pd/Zn catalyst showed superior selectivity due to the in-situ formation of intermetallic species facilitated by Pd-ZnO x interactions.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2016

Chemical and isotope compositions of shallow groundwater in areas impacted by hydraulic fracturing and surface mining in the Central Appalachian Basin, Eastern United States

Here, hydraulic fracturing of shale deposits has greatly increased the productivity of the natural gas industry by allowing it to exploit previously inaccessible reservoirs. Previous research has demonstrated that this practice has the potential to contaminate shallow aquifers with methane (CH 4 ) from deeper formations. This study compares concentrations and isotopic compositions of CH 4 sampled from domestic groundwater wells in Letcher County, Eastern Kentucky in order to characterize its occurrence and origins in relation to both neighboring hydraulically fractured natural gas wells and surface coal mines. The studied groundwater showed concentrations of CH 4 ranging from 0.05 mg/L to 10 mg/L, thus, no immediate remediation is required. The δ 13 C values of CH 4 ranged from 66‰ to 16‰, and δ 2 H values ranged from –286‰ to –86‰, suggesting an immature thermogenic and mixed biogenic/thermogenic origin. The occurrence of CH 4 was not correlated with proximity to hydraulically fractured natural gas wells. Generally, CH 4 occurrence corresponded with groundwater abundant in Na + , Cl – , and HCO 3 – , and with low concentrations of SO 4 –2 . The CH 4 and SO 4 –2 concentrations were best predicted by the oxidation/reduction potential of the studied groundwater. CH 4 was abundant in more reducing waters, and SO 4 –2 was abundant in more oxidizing waters. Additionally, groundwater in greater proximity to surface mining was more likely to be oxidized. This, in turn, might have increased the likelihood of CH 4 oxidation in shallow groundwater.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2020

The rhizosphere and cropping system, but not arbuscular mycorrhizae, affect ammonia oxidizing archaea and bacteria abundances in two agricultural soils

Arbuscular mycorrhizal fungi (AMF) form symbioses with roots that can enhance plant nutrition. While AMF have been shown to have a role in soil nitrogen (N) cycling, it is unclear whether AMF affect N cycling microbes such as ammonia-oxidizing bacteria (AOB) and archaea (AOA), which convert ammonium into nitrite in the first step of nitrification. In this study, we examined the effects of AMF on AOA and AOB abundances within the corn rhizosphere and bulk soil of conventional (corn-soybean rotation with inorganic fertilizer) and diversified (cornsoybean- oats/alfalfa-oats rotation with composted manure) systems. We hypothesized that AMF would decrease AOA and AOB abundances in a cropping-system dependent manner, possibly due to competition for ammonium. We grew corn deficient or proficient in AMF symbiosis in microcosms for 10 weeks. At the end of the experiment, both soils planted with the AMF-proficient corn genotype had higher ammonium and lower nitrate pool sizes compared to the same soils planted with the AMF-deficient corn genotype. Likewise, total plant N was higher in the AMF-proficient genotype compared to the AMF-deficient genotype. Despite changes in soil inorganic N pool sizes, AOA and AOB abundances were unaffected by plant AMF-proficiency. Instead, AOA abundance was greater in the rhizosphere than in the bulk soil regardless of cropping system, and AOB abundance was greater in the conventional than the diversified cropping system soil regardless of proximity to the root. These data indicate that 1) AMF did not affect AOA or AOB abundance in these N-rich soils but other factors such as root proximity and inorganic fertilization did and 2) AOA and AOB have differing ecological niches within rhizosphere and bulk soil that should be considered when managing for nitrogen losses.

Wattenburger, Cassandra↗
DOE OSTI2011

SAP-like domain in nucleolar spindle associated protein mediates mitotic chromosome loading as well as interphase chromatin interaction

Highlights: {yields} The SAP-like domain in NuSAP is a functional DNA-binding domain with preference for dsDNA. {yields} This SAP-like domain is essential for chromosome loading during early mitosis. {yields} NuSAP is highly dynamic on mitotic chromatin, as evident from photobleaching experiments. {yields} The SAP-like domain also mediates NuSAP-chromatin interaction in interphase nucleoplasm. -- Abstract: Nucleolar spindle associated protein (NuSAP) is a microtubule-stabilizing protein that localizes to chromosome arms and chromosome-proximal microtubules during mitosis and to the nucleus, with enrichment in the nucleoli, during interphase. The critical function of NuSAP is underscored by the finding that its depletion in HeLa cells results in various mitotic defects. Moreover, NuSAP is found overexpressed in multiple cancers and its expression levels often correlate with the aggressiveness of cancer. Due to its localization on chromosome arms and combination of microtubule-stabilizing and DNA-binding properties, NuSAP takes a special place within the extensive group of spindle assembly factors. In this study, we identify a SAP-like domain that shows DNA binding in vitro with a preference for dsDNA. Deletion of the SAP-like domain abolishes chromosome arm binding of NuSAP during mitosis, but is not sufficient to abrogate its chromosome-proximal localization after anaphase onset. Fluorescence recovery after photobleaching experiments revealed the highly dynamic nature of this NuSAP-chromatin interaction during mitosis. In interphase cells, NuSAP also interacts with chromatin through its SAP-like domain, as evident from its enrichment on dense chromatin regions and intranuclear mobility, measured by fluorescence correlation spectroscopy. The obtained results are in agreement with a model where NuSAP dynamically stabilizes newly formed microtubules on mitotic chromosomes to enhance chromosome positioning without immobilizing these microtubules. Interphase NuSAP-chromatin interaction suggests additional functions for NuSAP, as recently identified for other nuclear spindle assembly factors with a role in gene expression or DNA damage response.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes

Highlights: Black-Right-Pointing-Pointer cAMP blocks cell death induced by TNF and actinomycin D in cultured hepatocytes. Black-Right-Pointing-Pointer cAMP blocks NF-{kappa}B activation induced by TNF and actinomycin D. Black-Right-Pointing-Pointer cAMP blocks DISC formation following TNF and actinomycin D exposure. Black-Right-Pointing-Pointer cAMP blocks TNF signaling at a proximal step. -- Abstract: Tumor necrosis factor {alpha} (TNF) is a pleiotropic proinflammatory cytokine that plays a role in immunity and the control of cell proliferation, cell differentiation, and apoptosis. The pleiotropic nature of TNF is due to the formation of different signaling complexes upon the binding of TNF to its receptor, TNF receptor type 1 (TNFR1). TNF induces apoptosis in various mammalian cells when the cells are co-treated with a transcription inhibitor like actinomycin D (ActD). When TNFR1 is activated, it recruits an adaptor protein, TNF receptor-associated protein with death domain (TRADD), through its cytoplasmic death effector domain (DED). TRADD, in turn, recruits other signaling proteins, including TNF receptor-associated protein 2 (TRAF2) and receptor-associated protein kinase (RIPK) 1, to form a complex. Subsequently, this complex combines with FADD and procaspase-8, converts into a death-inducing signaling complex (DISC) to induce apoptosis. Cyclic AMP (cAMP) is a second messenger that regulates various cellular processes such as cell proliferation, gene expression, and apoptosis. cAMP analogues are reported to act as anti-apoptotic agents in various cell types, including hepatocytes. We found that a cAMP analogue, dibutyryl cAMP (db-cAMP), inhibits TNF + ActD-induced apoptosis in rat hepatocytes. The protein kinase A (PKA) inhibitor KT-5720 reverses this inhibitory effect of cAMP on apoptosis. Cytoprotection by cAMP involves down-regulation of various apoptotic signal regulators like TRADD and FADD and inhibition of caspase-8 and caspase-3 cleavage. We also found that cAMP exerts its affect at the proximal level of TNF signaling by inhibiting the formation of the DISC complex upon the binding of TNF to TNFR1. In conclusion, our study shows that cAMP prevents TNF + ActD-induced apoptosis in rat hepatocytes by inhibiting DISC complex formation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Transcriptional regulation of PCFT by KLF4, HNF4α, CDX2 and C/EBPα: Implication in its site-specific expression in the small intestine

Highlights: ► We examined transcription factors that may regulate PCFT expression in the intestine. ► PCFT promoter activity is basically induced by KLF4. ► KLF4-induced PCFT promoter activity is enhanced by HNF4α synergistically. ► CDX2 and C/EBPα suppress PCFT promoter activity induced by KLF4 and HNF4α. -- Abstract: Proton-coupled folate transporter (PCFT), which is responsible for the intestinal uptake of folates and analogs, is expressed only in the proximal region in the small intestine. The present study was to examine its transcriptional regulation, which may be involved in such a unique expression profile and potentially in its alteration, using dual-luciferase reporter assays in human embryonic kidney (HEK) 293 cells. The luciferase activity derived from the reporter construct containing the 5′-flanking sequence of −1695/+96 of the human PCFT gene was enhanced most extensively by the introduction of Krüppel-like factor 4 (KLF4). The KLF4-induced luciferase activity was further enhanced by hepatocyte nuclear factor 4α (HNF4α) synergistically. To the contrary, caudal-type homeobox transcription factor 2 (CDX2) and CCAAT/enhancer-binding protein α (C/EBPα) extensively suppressed the luciferase activity induced by KLF4 alone and also that induced by KLF4 and HNF4α. Western blot analysis using the rat small intestine indicated uniform expression of KLF4 along the intestinal tract, proximal-oriented expression of HNF4α, distal-oriented expression of CDX2 and C/EBPα. These results suggest that the activity of PCFT promoter is basically induced by KLF4 and the gradiented expression profile of PCFT may be at least in part accounted for by those of HNF4α, CDX2 and C/EBPα.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Regulation of channel function due to physical energetic coupling with a lipid bilayer

Highlights: • Lipid membrane regulation of membrane protein functions has been addressed. • Energetics behind ion channel-membrane coupling phenomena has been investigated. • Charge based interactions stabilize peptide–lipid complex. • Screened Coulomb interaction model explains the energetics. • Van der Waals and electrostatic forces drive peptides and lipids to close proximity. - Abstract: Regulation of membrane protein functions due to hydrophobic coupling with a lipid bilayer has been investigated. An energy formula describing interactions between lipid bilayer and integral ion channels with different structures, which is based on the screened Coulomb interaction approximation, has been developed. Here the interaction energy is represented as being due to charge-based interactions between channel and lipid bilayer. The hydrophobic bilayer thickness channel length mismatch is found to induce channel destabilization exponentially while negative lipid curvature linearly. Experimental parameters related to channel dynamics are consistent with theoretical predictions. To measure comparable energy parameters directly in the system and to elucidate the mechanism at an atomistic level we performed molecular dynamics (MD) simulations of the ion channel forming peptide–lipid complexes. MD simulations indicate that peptides and lipids experience electrostatic and van der Waals interactions for short period of time when found within each other’s proximity. The energies from these two interactions are found to be similar to the energies derived theoretically using the screened Coulomb and the van der Waals interactions between peptides (in ion channel) and lipids (in lipid bilayer) due to mainly their charge properties. The results of in silico MD studies taken together with experimental observable parameters and theoretical energetic predictions suggest that the peptides induce ion channels inside lipid membranes due to peptide–lipid physical interactions. This study provides a new insight helping better understand of the underlying mechanisms of membrane protein functions in cell membrane leading to important biological implications.

60 APPLIED LIFE SCIENCES↗