Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “Phase 1”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,801 records · Page 100
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Printable Fiber Reinforced Cement Composites – Feasibility Study

Additive manufacturing is enabling the manufacturability of structures with previously unattainable complexity or functionality, and there is growing interest in additive manufacturing of “printed” concrete structures. The focus of this Phase 1 Technical Collaboration (TC) project was to evaluate feasibility of printing hybrid cement composite structures reinforced with textile carbon fibers (tCF). This project leverages other (non-IACMI) projects on cement formulation and printing process development, as well as on the production process for tCF. This project’s primary focus was to explore cement composite mix design with textile carbon fibers to be manufactured by MonteFibre (TC partner) and evaluate suitable fiber-matrix interface or sizing for cement composites working with Michelman (TC Partner). This project supports IACMI’s goal of reducing the cost and embodied energy of carbon fiber composites. Cost is one of the fundamental challenges to carbon fiber reinforced cement composites. Cement is an extremely inexpensive material (approximately $\$$0.05/lb). Adding 1 wt% of conventional carbon fiber to cement quadruples its cost. Therefore, the need to use low-cost carbon fiber and ensure that the additional cost of the carbon fiber has a greater cost benefit to the final product. This was the first preliminary evaluation to integrate tCF reinforcement in cement composites, and such potential tCF utilization should significantly reduce materials cost. Cement composite production is energy and emissions intensive, thus by strengthening it less material will be required. Hence, the embodied energy and production time of the resulting structures will be reduced. Additionally, integrating these new materials into additive processes can enable selective use of the material in high load or stress areas. It is noteworthy that past work in this field of fiber reinforced cement composites did not consider the optimization of fiber-matrix interface using suitable sizing. Carbon fiber reinforcement offers potential added benefits of thermal conductivity (which affects cure rate) and flow behavior that could provide opportunities for site specific utilization of carbon fiber on hybrid cement structures (e.g. use the fiber reinforcement on outer surfaces to enhance strength and modulus and then infiltrating the internal structures with conventional concrete). MonteFibre was the industry lead and planned on supplying the tCF for this project. However, during the short Phase-1 duration of this project, MonteFibre was unable to produce tCF for this project due to manufacturing plant being off-line throughout the course of the project. The project team decided to pursue an alternate option which involved demonstrating printable concrete with steel fibers by the ORNL lead, Dr. Brian Post. The University of Tennessee collaboration team focused on evaluating the suitable chemical sizing for carbon fibers working with Michelman and also developed methods for material characterization of cement-based composites to evaluate the material response for compression, shear, flexure, and tension. The two milestones for University of Tennessee, Knoxville were realized related to identification of one sizing suitable for carbon fiber reinforced cement composite and developing data associated with mechanical behavior of unreinforced (neat) and carbon fiber reinforced cement composites. ORNL could not complete the task of carbon fiber reinforced printed cement composites due to the reasons mentioned earlier, but was able to replace tCF with steel fibers to demonstrate the feasibility of printing with fiber reinforced cement composites. The Project team reviewed possible sizing chemistry available in collaboration with Michelman for use on carbon fiber reinforcement in cement composites and concrete applications. Our initial goal was to identify a sizing most promising for formulation with textile carbon fibers (tCF) to deliver excellent mechanical properties in composite material state. Since tCF was not available for this project as originally envisioned, the team continued this task to identify a suitable sizing for carbon fiber applications by applying such sizing to lower cost carbon fibers currently available commercially from Zoltek called Panex fibers. At a future time this can be optimized for textile carbon fibers from Montefibre. The bulk of previous work on carbon fiber reinforced cement has neglected the importance of fiber-matrix adhesion on mechanical properties of the cement composite and identifying this missing link was an important accomplishment for future research. Tensile behavior of fiber reinforced concrete is important to evaluate in order to realize the dream of concrete products that do not need reinforcing steel. Important sample preparation and testing procedures were addressed in this study and it was concluded that substantial improvements in tensile behavior, without compromising compressive strength, and improved ductility can result from the use of carbon fiber reinforcement.

36 MATERIALS SCIENCE↗
DOE OSTI2020

CCE Phase 4: Mitigations and Protections

During the first three phases, the CCE Team identified any instances of unverified trust in the organization’s technologies, processes, and procedures, any or all of which could be used to adversely impact the system. In Phase 4, the primary goal is to remove the possibility of the end effect—that is, to develop means or mechanisms that will ensure an adversary cannot achieve their Objective (identified in Phase 1) via cyber means. Such measures are known as “protections.” In some cases, this may not be possible, or the implementation of protections may not be desirable due to other considerations. In such cases, means and mechanisms should be developed that focus on putting an organization in a better position to identify adversary activities directed against it, increasing the cost of cyber-enabled sabotage for the adversary (including making things more difficult for the adversary and attempting to lower the chances an adversary may succeed), or decreasing the recovery cost of a victim organization. These measures are known as “mitigations.”

99 GENERAL AND MISCELLANEOUS↗
NASA NTRS2002

Second Generation RLV Space Vehicle Concept

NASA has a long history of conducting development programs and projects in a consistent fashion. Systems Engineering within those programs and projects has also followed a given method outlined by such documents as the NASA Systems Engineering Handbook. The relatively new NASA Space Launch Initiative (SLI) is taking a new approach to developing a space vehicle, with innovative management methods as well as new Systems Engineering processes. With the program less than a year into its life cycle, the efficacy of these new processes has yet to be proven or disproven. At $776M for phase 1, SLI represents a major portion of the NASA focus; however, the new processes being incorporated are not reflected in the training provided by NASA to its engineers. The NASA Academy of Program and Project Leadership (APPL) offers core classes in program and project management and systems engineering to NASA employees with the purpose of creating a "knowledge community where ideas, skills, and experiences are exchanged to increase each other's capacity for strong leadership". The SLI program is, in one sense, a combination of a conceptual design program and a technology program. The program as a whole doesn't map into the generic systems engineering project cycle as currently, and for some time, taught. For example, the NASA APPL Systems Engineering training course teaches that the "first step in developing an architecture is to define the external boundaries of the system", which will require definition of the interfaces with other systems and the next step will be to "define all the components that make up the next lower level of the system hierarchy" where fundamental requirements are allocated to each component. Whereas, the SLI technology risk reduction approach develops architecture subsystem technologies prior to developing architectures. The higher level architecture requirements are not allowed to fully develop and undergo decomposition and allocation down to the subsystems before the subsystems must develop allocated requirements based on the highest level of requirements. In the vernacular of the project cycles prior to the mid 1990's, the architecture definition portion of the program appears to be at a generic Phase A stage, while the subsystems are operating at Phase B. Even the management structure of the SLI program is innovative in its approach to Systems Engineering and is not reflected in the APPL training modules. The SLI program has established a Systems Engineering office as an office separate from the architecture development or the subsystem technology development, while that office does have representatives within these other offices. The distributed resources of the Systems Engineering Office are co-located with the respective Project Offices. This template is intended to provide systems engineering as an integrated function at the Program Level. the program management of SLI and the MAT agree that "program/project managers and the systems engineering team must work closely together towards the single objective of delivering quality products that meet the customer needs". This paper will explore the differences between the methods being taught by NASA, which represent decades of ideas, and those currently in practice in SLI. Time will tell if the innovation employed by SLI will prove to be the model of the future. For now, it is suggested that the training of the present exercise the flexibility of recognizing the new processes employed by a major new NASA program.

Bailey, Michelle↗
DOE OSTI2015

V899 MON: AN OUTBURSTING PROTOSTAR WITH A PECULIAR LIGHT CURVE, AND ITS TRANSITION PHASES

We present a detailed study of V899 Mon (a new member in the FUors/EXors family of young low-mass stars undergoing outburst), based on our long-term monitoring of the source starting from 2009 November to 2015 April. Our optical and near-infrared photometric and spectroscopic monitoring recorded the source transitioning from its first outburst to a short-duration quiescence phase (<1 yr), and then returning to a second outburst. We report here the evolution of the outflows from the inner region of the disk as the accretion rate evolved in various epochs. Our high-resolution (R ∼ 37,000) optical spectrum could resolve interesting clumpy structures in the outflow traced by various lines. Change in far-infrared flux was also detected between two outburst epochs. Based on our observations, we constrained various stellar and envelope parameters of V899 Mon, as well as the kinematics of its accretion and outflow. The photometric and spectroscopic properties of this source fall between classical FUors and EXors. Our investigation of V899 Mon hints at instability associated with magnetospheric accretion being the physical cause of the sudden short-duration pause of the outburst in 2011. It is also a good candidate to explain similar short-duration pauses in outbursts of some other FUors/EXors sources.

79 ASTRONOMY AND ASTROPHYSICS↗
NASA NTRS2014

Asteroid Redirect Crewed Mission Nominal Design and Performance

In 2010, the President announced that, in 2025, the U.S. intended to launch a human mission to an asteroid [1]. This announcement was followed by the idea of a Capability Driven Framework (CDF) [2], which is based on the idea of evolving capabilities from less demanding to more demanding missions to multiple possible destinations and with increased flexibility, cost effectiveness and sustainability. Focused missions, such as a NASA inter-Center study that examined the viability and implications of sending a crew to a Near Earth Asteroid (NEA) [3], provided a way to better understand and evaluate the utility of these CDF capabilities when applied to an actual mission. The long duration of the NEA missions were contrasted with a concept described in a study prepared for the Keck Institute of Space Studies (KISS) [4] where a robotic spacecraft would redirect an asteroid to the Earth-Moon vicinity, where a relatively short duration crewed mission could be conducted to the captured asteroid. This mission concept was included in the National Aeronautics and Space Administration (NASA) fiscal year 2014 budget request, as submitted by the NASA Administrator [5]. NASA studies continued to examine the idea of a crewed mission to a captured asteroid in the Earth-Moon vicinity. During this time was an announcement of NASA's Asteroid Grand Challenge [6]. Key goals for the Asteroid Grand Challenge are to locate, redirect, and explore an asteroid, as well as find and plan for asteroid threats. An Asteroid Redirect Mission (ARM) study was being conducted, which supports this Grand Challenge by providing understanding in how to execute an asteroid rendezvous, capture it, and redirect it to Earth-Moon space, and, in particular, to a distant retrograde orbit (DRO). Subsequent to the returning of the asteroid to a DRO, would be the launch of a crewed mission to rendezvous with the redirected asteroid. This report examines that crewed mission by assessing the Asteroid Redirect Crewed Mission (ARCM) nominal design and performance costs associated with an Orion based crewed rendezvous mission to a captured asteroid in an Earth-Moon DRO. The ARM study includes two fundamental mission phases: 1) The Asteroid Redirect Robotic Mission (ARRM) and 2) the ARCM. The ARRM includes a solar electric propulsion based robotic asteroid return vehicle (ARV) sent to rendezvous with a selected near Earth asteroid, capture it, and return it to a DRO in the Earth-Moon vicinity. The DRO is selected over other possible asteroid parking orbits due to its achievability (by both the robotic and crewed vehicles) and by its stability (e.g., no orbit maintenance is required). After the return of the asteroid to the Earth-Moon vicinity, the ARCM is executed and carries a crew of two astronauts to a DRO to rendezvous with the awaiting ARV with the asteroid. The outbound and inbound transfers employ lunar gravity assist (LGA) flybys to reduce the Orion propellant requirement for the overall nominal mission, which provides a nominal mission with some reserve propellant for possible abort situations. The nominal mission described in this report provides a better understanding of the mission considerations as well as the feasibility of such a crewed mission, particularly with regard to spacecraft currently undergoing development, such as the Orion vehicle and the Space Launch System (SLS).

Condon, Gerald↗
DOE OSTI2018

Materials for Advanced Ultra-Supercritical (AUSC) Steam Turbines – AUSC Component Demonstration

The work by the United States Department of Energy (U.S. DOE)/Ohio Coal Development Office (OCDO) Advanced Ultra-Supercritical (AUSC) Steam Boiler and Turbine Materials Consortia from 2001 through September 2015 was primarily focused on lab scale and pilot scale materials testing. The field testing included air-cooled probes and steam-cooled “loops” that were installed into existing utility boilers to gain exposure of these materials to realistic conditions of high temperature and corrosion due to the constituents in the coal ash. Successful research and development resulted in identification of metallic alloy materials and fabrication processes suited for power generation applications with metal temperatures up to approximately 1472°F (800°C). These materials or alloys have shown, in extensive laboratory tests and shop fabrication studies, to have excellent applicability for high-efficiency low CO2 transformational power generation technologies. However, as valuable as these material field tests have been for obtaining information, their scale is significantly below that required to minimize the risk associated with a power company building a multi-billion-dollar AUSC power plant. To decrease the identified risk barriers to full-scale implementation of these advanced materials, the U.S. DOE/OCDO AUSC Steam Boiler and Turbine Materials Consortia identified the key areas of the technology that need to be tested at a larger scale. Based upon the recommendations and outcome of a Consortia-sponsored workshop with the U.S.’s leading utilities, a Component Test (ComTest) Program for AUSC was proposed. The AUSC ComTest program would define materials performance requirements, plan for overall advanced system integration, design critical component tests, fabricate components for testing from advanced materials, and carry out the tests. A Pre-FEED evaluation of the test facility including the evaluation of three potential sites has been completed and previously reported. This report describes the Front-End Engineering Design (FEED), Detailed Engineering and the Environmental Assessment of the ComTest project. A significant amount of work was accomplished during Phase 1 to identity the components, as well as the component size, that would be manufactured from advanced alloys such as INCONEL 740H or HAYNES 282 alloys. Pathways to supply these components for ComTest have been identified as well as any further development that would be required. Every project of this nature has challenges and this project was no exception. The greatest challenge has been the project cost. Largely due to the infrastructure and balance of plant equipment upgrades required for Youngstown Thermal, the estimated project cost for the “base case” project was greater than originally budgeted. The project team spent a significant amount of time exploring opportunities for reducing the project cost. These options included: • Youngstown Thermal was exploring building a Combined Heat and Power (CHP) unit at their facility. The Youngstown Thermal staff, supported by Thermal Engineering Group, worked with the project team to determine whether it was economically desirable to supply ComTest with steam and other utilities, which would be supplied by the CHP project. • The project team also evaluated opportunities to optimize the project scope to reduce cost, such as reducing project scope by eliminating the Superheater Outlet Header test. • Southern Company had offered two sites as possible host locations for ComTest. Both sites had infrastructure in place such as steam from an existing unit, natural gas, cooling water and ample electrical power that would be required to be added at the Youngstown Thermal site. Utilizing this existing infrastructure could reduce the project cost. An additional project challenge was the departure of Babcock and Wilcox from the project in September 2016. This project setback was overcome by GE Power’s willingness to assume the design of the ComTest superheater. Since the project could not proceed without the superheater, this was a very positive project development. The merger of the GE Power and Alstom Power steam turbine divisions created synergies leading to the conclusion that instead of building a small-scale turbine, a more practical and useful endeavor would be to validate the manufacturing technology and supplier readiness for fabricating and machining full scale steam turbine components. Consequently, in March 2017, GE Power decided that a steam turbine test would not be necessary as part of the ComTest demonstration. Removing the operational testing of the steam turbine from ComTest further reduced the total project cost. Additionally, there was an opportunity to move ComTest from Youngstown Thermal to one of the Southern Company sites and operate ComTest at supercritical steam conditions and test the steam turbine main stop/control valve at a temperature and pressure that would be representative of the conditions of a high pressure steam turbine inlet valve. The steam could also possibly be returned to the host boiler so there would be no economic penalty of using this steam for ComTest. Relocating the project could further reduce the project cost due to the infrastructure already in place, including high pressure natural gas and cooling water, and the potential for heat integration, allowing a reduction of operating costs. Due to these potential cost reductions, it was decided to move the project away from Youngstown Thermal in March 2017. As integrating ComTest at the Southern Company site was explored, an issue was raised regarding the integration of the ComTest cycle with the plant steam cycle. Steam would be supplied to ComTest at nominally ~3865 psia and 775°F. The steam would be heated with natural gas to 1400°F for the valve test and then cooled to 1000°F so that the steam would be returned to the host boiler at the same conditions as their high pressure steam turbine inlet. However, there were concerns raised that the addition of the energy (natural gas) to the steam could trigger a New Source Review on the unit. Southern Company did not want ComTest to cause this review, so condensing all of the steam exiting ComTest and returning it to the host steam cycle as condensate was explored to insure there would be no implication that ComTest was adding energy to the host plant’s steam cycle. Ultimately, Southern Company decided that they wanted to “decouple” ComTest from the operating unit, making ComTest self-supporting, similar to the Youngstown Thermal “base case.” Without the steam turbine, the project team reached a consensus that operating the ComTest Superheater and steam turbine valves at the typical pressure of a package boiler (~1000 psig) would not generate enough useful technical information to justify the cost of the test. Therefore, it was decided in the December 2017 project quarterly meeting to cancel the operational phase of ComTest. Throughout the engineering phase of ComTest, manufacturing and supply chain challenges were identified. When GE Power recommended dropping the steam turbine test from ComTest, they identified many important manufacturing issues that should be evaluated and demonstrated. Other challenges had been raised by the GE Power group designing the superheater as well as those engineering components such as pressure relief and steam turbine bypass valves. In the December 2017 meeting, the project team decided that it was more beneficial to the AUSC technology to pursue these manufacturing and supply chain issues as Phase 2 of the ComTest project. This report is organized in the following manner: • Section 2 discusses the ComTest project background and organization. • Section 3 discussed project management. • Section 4 discusses the design of the ComTest AUSC components – the Superheater, steam turbine and Superheater Outlet Header. • Section 5 discusses the implementation of ComTest at Youngstown Thermal and the Southern Company site. • Section 6 discusses the development of the AUSC Supply Chain • Section 7 discusses the recommended plan for Phase 2 of ComTest

01 COAL, LIGNITE, AND PEAT↗
DOE OSTI2017

Development of a New Structural Class of Broadly Acting HCV Non-Nucleoside Inhibitors Leading to the Discovery of MK-8876

Studies directed at developing a broadly acting non-nucleoside inhibitor of HCV NS5B led to the discovery of a novel structural class of 5-aryl benzofurans that simultaneously interact with both the palm I and palm II binding regions. An initial candidate was potent in vitro against HCV GT1a and GT1b replicons, and induced multi-log reductions in HCV viral load when orally dosed to chronic GT1 infected chimpanzees. However, in vitro potency losses against clinically relevant GT1a variants prompted a further effort to develop compounds with sustained potency across a broader array of HCV genotypes and mutants. Ultimately, a biology and medicinal chemistry collaboration led to the discovery of the development candidate MK-8876. MK-8876 demonstrated a pan-genotypic potency profile and maintained potency against clinically relevant mutants. It demonstrated moderate bioavailability in rats and dogs, but showed low plasma clearance characteristics consistent with once-daily dosing. Herein we describe the efforts which led to the discovery of MK-8876, which advanced into Phase 1 monotherapy studies for evaluation and characterization as a component of an all-oral direct-acting drug regimen for the treatment of chronic HCV infection.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Accelerating x-ray tracing for exascale systems using Kokkos

The upcoming exascale computing systems Frontier and Aurora will draw much of their computing power from GPU accelerators. The hardware for these systems will be provided by AMD and Intel, respectively, each supporting their own GPU programming model. The challenge for applications that harness one of these exascale systems will be to avoid lock-in and to preserve performance portability. We report here on our results of using Kokkos to accelerate a real-world application on NERSC's Perlmutter Phase 1 (using NVIDIA A100 accelerators) and Crusher, the testbed system for OLCF's Frontier (using AMD MI250X). By porting to Kokkos, we successfully ran the same X-ray tracing code on both systems and achieved speed-ups between 13 % and 66 % compared to the original CUDA code. Finally, these results are a highly encouraging demonstration of using Kokkos to accelerate production science code.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2019

Enhancing Photovoltaic Performance of Aromatic Ammonium-based Two-Dimensional Organic-Inorganic Hybrid Perovskites via Tuning CH···π Interaction

Phenethylammonium (PEA)-based 2D perovskite is an interesting example of 2D perovskites, serving as the gateway for further introduction of functional conjugated organic cations into 2D perovskites for a variety of applications, for example, photovoltaics. However, the efficiency of photovoltaic devices based on PEA 2D perovskites only achieved ≈7% for = 3, which was significantly lower than that achieved for other cation-based 2D perovskites. In this work, by introducing propyl ammonium (C3A) into the PEA-based 2D perovskites, the device efficiency is improved to ≈10% for 1:1 C3A:PEA-based 2D perovskites ( = 3). Further investigation reveals that tuning the CH···π interaction (between C3A and PEA or between two PEA molecules) can have multiple beneficial impacts on such modified 2D perovskites, including a) removal of undesirable n = 1 phase, b) lowering the density of trap states, and c) achieving larger crystalline grains. Additionally, after substitution with 50% C3A, other aromatic ammonium cation-based 2D perovskites ( = 3) also show similar efficiency enhancement in their photovoltaic devices, thus exhibiting the general applicability of this method. The results of this study highlight that the strategic tuning of non-covalent interactions (such as CH···π interaction) is a viable and important method to further develop 2D perovskites for photovoltaics.

14 SOLAR ENERGY↗
DOE OSTI2023

Ag Alloying in Cu 2– y Ag y Ba(Ge,Sn)Se 4 Films and Photovoltaic Devices

Trigonal Cu 2 BaGe 1–x Sn x Se 4 (CBGTSe) has recently gained interest as a potential photovoltaic absorber to target mitigation of antisite defect formation in Cu 2 ZnSn(S,Se) 4 . This study examines partial substitution of Cu by Ag as a potential approach to tune the properties of Ag-incorporated CBGTSe in the following aspects: 1) phase stability and crystal structure as a function of Ag content; 2) film morphology and grain structure; 3) charge carrier properties; 4) band positions; and 5) charge carrier kinetics and recombination. Up to 20% of Cu can be substituted by Ag in CBGTSe, while above 20% a phase mixture appears. Increasing Ag content induces larger average grain size and reduced hole carrier densities. In contrast, photoelectron spectroscopy and photoluminescence measurements reveal negligible impact of Ag substitution on ionization potential (≈5.4 eV) and electron affinity (≈3.7 eV). Also, Ag content offers negligible impact on carrier lifetimes (few ns). Consistent with these fundamental properties, solar cells based on two different Ag/(Ag + Cu) ratios (≈0% and ≈20%) show comparable power conversion efficiencies (≈2.7–2.8%). Finally, these results indicate that CBGTSe films and solar cells may be less sensitive to Ag substitution compared to Cu 2 ZnSn(S,Se) 4 , at least at the current level of absorber and device optimization.

14 SOLAR ENERGY↗
DOE OSTI2019

Influence of TiH{sub 2} on Interfacial Reaction Features Between Cubic Boron Nitride and Cu-Sn-Ti Active Filler Metals

Cubic boron nitride (CBN) grains are brazed by Cu-Sn-Ti filler metal in vacuum at 1223 K. Wetting behaviors, reaction layer features, and elemental distribution characteristics have been systematically investigated through scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD). The results show that when the TiH{sub 2} content is 5 wt pct, virtually no sharp-edged, partially coated, and uncoated CBN grains can be observed, indicating that adequate wetting could be achieved. Moreover, a continuous reaction layer with uniform thickness (1.30 μm) consisting of TiN, TiB{sub 2}, and TiB is obtained, which indicates that large numbers of TiN, TiB{sub 2}, and TiB compounds could have been formed at the interface. However, when the TiH{sub 2} content exceeds 5 wt pct, the thickness of the reaction layer is no longer significantly expanding and excessive Ti present in the matrix will lower the volume percentage of Cu{sub 3}Sn{sub 1} phase, which will reduce the bonding strength of the brazing samples. Wear tests indicate that the minimum weight loss also occurs at 5 wt pct TiH{sub 2}.

36 MATERIALS SCIENCE↗
DOE OSTI2019

Everolimus in combination with Imatinib overcomes resistance in Chronic myeloid leukaemia

Although Imatinib and other tyrosine kinase inhibitors (TKIs) have excellent results, the appearance of resistance is a problem in chronic myeloid leukaemia (CML). PI3K/AKT/mTOR pathway is activated by BCR-ABL playing a crucial rule in CML. This study aimed to evaluate the therapeutic potential of Everolimus, in CML models sensitive and resistant to Imatinib. We used one CML cell line sensitive to Imatinib (K562) and two resistant (K562-RC and K56-RD). Cell lines were treated with Everolimus alone and in combination with Imatinib. Cell viability was analysed by resazurin assay. Cell death and cell cycle were analysed by flow cytometry. Additionally, we also studied peripheral blood samples obtained from 52 patients under TKI treatment. Everolimus reduced cell line viability in sensitive (IC{sub 50} = 20 µM) and resistant models (K562-RC, IC{sub 50} = 25 µM; K562-RD, IC{sub 50} = 30 µM). This drug induced cell death by apoptosis and cell cycle arrest in G{sub 0}/G{sub 1} phase. Everolimus also reduced cell viability by increasing apoptosis of haematopoietic stem cells (CD34{sup +} cells) with low cytotoxicity to lymphocytes. Everolimus at 25 µM increased apoptotic cells 18.7% in CD34{sup +} cells and only 8% in lymphocytes. The response to Everolimus was influenced by TKI treatment, with a better response in samples from patients under 2nd and 3rd generation TKI and with less toxicity to lymphocytes. Our results reveal that Everolimus induce cell death in CML cells sensitive and resistant to Imatinib, with low cytotoxicity to normal cells, suggesting that Everolimus could be an alternative targeted therapeutic approach in CML patients, even in cases of Imatinib resistance.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Nonperturbative NN scattering in {sup 3}S{sub 1}–{sup 3}D{sub 1} channels of EFT(⁄π)

The closed-form T matrices in the {sup 3}S{sub 1}–{sup 3}D{sub 1} channels of EFT(⁄π) for NN scattering with the potentials truncated at order O(Q{sup 4}) are presented with the nonperturbative divergences parametrized in a general manner. The stringent constraints imposed by the closed form of the T matrices are exploited in the underlying theory perspective and turned into virtues in the implementation of subtractions and the manifestation of power counting rules in nonperturbative regimes, leading us to the concept of EFT scenario. A number of scenarios of the EFT description of NN scattering are compared with PSA data in terms of effective range expansion and {sup 3}S{sub 1} phase shifts, showing that it is favorable to proceed in a scenario with conventional EFT couplings and sophisticated renormalization in order to have large NN scattering lengths. The informative utilities of fine tuning are demonstrated in several examples and naturally interpreted in the underlying theory perspective. In addition, some of the approaches adopted in the recent literature are also addressed in the light of EFT scenario. -- Highlights: •Closed-form unitary T matrices for NN scattering are obtained in EFT(⁄π). •Nonperturbative properties inherent in such closed-form T matrices are explored. •Nonperturbative renormalization is implemented through exploiting these properties. •Unconventional power counting of couplings is shown to be less favored by PSA data. •The ideas about nonperturbative renormalization here might have wider applications.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2013

Berberine slows cell growth in autosomal dominant polycystic kidney disease cells

Highlights: •Berberine at appropriate doses slows cell proliferation in ADPKD cystic cells. •Reduction of cell growth by berberine occurs by inhibition of ERK and p70-S6 kinase. •Higher doses of berberine cause an overall cytotoxic effect. •Berberine overdose induces apoptotic bodies formation and DNA fragmentation. •Antiproliferative properties of this drug make it a new candidate for ADPKD therapy. -- Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary monogenic disorder characterized by development and enlargement of kidney cysts that lead to loss of renal function. It is caused by mutations in two genes (PKD1 and PKD2) encoding for polycystin-1 and polycystin-2 proteins which regulate different signals including cAMP, mTOR and EGFR pathways. Abnormal activation of these signals following PC1 or PC2 loss of function causes an increased cell proliferation which is a typical hallmark of this disease. Despite the promising findings obtained in animal models with targeted inhibitors able to reduce cystic cell growth, currently, no specific approved therapy for ADPKD is available. Therefore, the research of new more effective molecules could be crucial for the treatment of this severe pathology. In this regard, we have studied the effect of berberine, an isoquinoline quaternary alkaloid, on cell proliferation and apoptosis in human and mouse ADPKD cystic cell lines. Berberine treatment slows cell proliferation of ADPKD cystic cells in a dose-dependent manner and at high doses (100 μg/mL) it induces cell death in cystic cells as well as in normal kidney tubule cells. However, at 10 μg/mL, berberine reduces cell growth in ADPKD cystic cells only enhancing G{sub 0}/G{sub 1} phase of cell cycle and inhibiting ERK and p70-S6 kinases. Our results indicate that berberine shows a selected antiproliferative activity in cellular models for ADPKD, suggesting that this molecule and similar natural compounds could open new opportunities for the therapy of ADPKD patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Glutamine deprivation sensitizes human breast cancer MDA-MB-231 cells to TRIAL-mediated apoptosis

Tumor cell metabolism is a promising target for various cancer treatments. Apart from aerobic glycolysis, cancer cell growth is dependent on glutamine (Gln) supply, leading to their survival and differentiation. Therefore, we examined whether treatment with TNF-related apoptosis-inducing ligand (TRAIL) sensitizes MDA-MB-231 cells to apoptosis under Gln deprivation condition (TRAIL/Gln deprivation). Gln deprivation decreased cell proliferation as expected, but did not induce remarkable cell death. TRAIL/Gln deprivation, however, significantly increased growth inhibition and morphological shrinkage of MDA-MB-231 cells compared to those induced by treatment with either Gln deprivation or TRAIL alone. Moreover, TRAIL/Gln deprivation upregulated the apoptotic sub-G{sub 1} phase accompanied with a remarkable decrease of pro-caspase-3, pro-caspase-9, and anti-apoptotic xIAP, and Bcl-2. Increased cleavage of PARP and pro-apoptotic Bid protein expression suggests that TRAIL/Gln deprivation triggers mitochondrion-mediated apoptosis in MDA-MB-231 cells. Additionally, TRAIL/Gln deprivation upregulated the expression of endoplasmic reticulum (ER) stress markers such as ATF4 and phosphorylated eIF2α, thereby enhancing the C/EBP homologous protein (CHOP) protein level. Transient knockdown of CHOP partically reversed TRAIL/Gln deprivation-mediated apoptosis. Accordingly, TRAIL/Gln deprivation enhanced the expression of death receptor 5 (DR5) and transient knockdown of DR5 completely restored TRAIL/Gln deprivation-mediated apoptosis. Taken together, our results suggest that Gln deprivation conditions can be used for the development of new therapies for TRAIL-resistant cancers.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Coatomer subunit beta 2 (COPB2), identified by label-free quantitative proteomics, regulates cell proliferation and apoptosis in human prostate carcinoma cells

Highlights: • Our paper offered an available method to identified and confirm some differential expression of genes in prostate cancer. • Our paper provided us a common method to research the function of gene for prostate cancer. • Our paper helps us to identify a novel cancer related gene to explain for development of novel targeted drugs. Label-free quantitative proteomics has broad applications in the identification of differentially expressed proteins. Here, we applied this method to identify differentially expressed proteins (such as coatomer subunit beta 2 [COPB2]) and evaluated the functions and molecular mechanisms of these proteins in prostate cancer (PCA) cell proliferation. Proteins extracted from surgically resected PCA tissues and adjacent tissues of 3 patients were analyzed by label-free quantitative proteomics. The target protein was confirmed by bioinformatics and GEO dataset analyses. To investigate the role of the target protein in PCA, we used lentivirus-mediated small-interfering RNA (siRNA) to knockdown protein expression in the prostate carcinoma cell line, CWR22RV1 cells and assessed gene and protein expression by reverse transcription quantitative polymerase chain reaction and western blotting. CCK8 and colony formation assays were conducted to evaluate cell proliferation. Cell cycle distributions and apoptosis were assayed by flow cytometry. We selected the differentiation-related protein COPB2 as our target protein based on the results of label-free quantitative proteomics. High expression of COPB2 was found in PCA tissue and was related to poor overall survival based on a public dataset. Cell proliferation was significantly inhibited in COPB2-knockdown CWR22RV1 cells, as demonstrated by CCK8 and colony formation assays. Additionally, the apoptosis rate and percentage of cells in the G{sub 1} phase were increased in COPB2-knockdown cells compared with those in control cells. CDK2, CDK4, and cyclin D1 were downregulated, whereas p21 Waf1/Cip1 and p27 Kip1 were upregulated, affecting the cell cycle signaling pathway. COPB2 significantly promoted CWR22RV1 cell proliferation through the cell cycle signaling pathway. Thus, silencing of COPB2 may have therapeutic applications in PCA.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Hallmarks of Alzheimer disease are evolving relentlessly in Metropolitan Mexico City infants, children and young adults. APOE4 carriers have higher suicide risk and higher odds of reaching NFT stage V at ≤ 40 years of age

Highlights: • Exposures to fine particulate matter (PM{sub 2.5}) are associated with Alzheimer's disease(AD) risk. • AD starts in the brainstem of children. • AD hallmarks are present in 202/203 CDMX residents ages 11 months to 40 years. • APOE4 carriers have 4.92 times higher suicide odds versus APOE3. • Highly oxidative, ubiquitous nanoparticles are a plausible path into AD pathogenesis. Exposures to fine particulate matter (PM{sub 2.5}) and ozone (O{sub 3}) above USEPA standards are associated with Alzheimer's disease (AD) risk. Metropolitan Mexico City (MMC) residents have life time exposures to PM{sub 2.5} and O{sub 3} above USEPA standards. We investigated AD intra and extracellular protein aggregates and ultrastructural neurovascular pathology in 203 MMC residents age 25.36 ± 9.23 y. Immunohistochemical methods were used to identify AT8 hyperphosphorilated tau (Htau) and 4G8 (amyloid β 17-24). Primary outcomes: staging of Htau and amyloid, per decade and cumulative PM{sub 2.5} (CPM{sub 2.5}) above standard. Apolipoprotein E allele 4 (APOE4), age and cause of death were secondary outcomes. Subcortical pretangle stage b was identified in an 11month old baby. Cortical tau pre-tangles, neurofibrillary tangles (NFT) Stages I-II, amyloid phases 1–2, Htau in substantia nigrae, auditory, oculomotor, trigeminal and autonomic systems were identified by the 2nd decade. Progression to NFT stages III-V was present in 24.8% of 30–40 y old subjects. APOE4 carriers have 4.92 times higher suicide odds (p = 0.0006), and 23.6 times higher odds of NFT V (p < 0.0001) v APOE4 non-carriers having similar CPM{sub 2.5} exposure and age. Age (p = 0.0062) and CPM{sub 2.5} (p = 0.0178) were significant for developing NFT V. Combustion-derived nanoparticles were associated with early and progressive damage to the neurovascular unit. Alzheimer's disease starting in the brainstem of young children and affecting 99.5% of young urbanites is a serious health crisis. Air pollution control should be prioritised. Childhood relentless Htau makes a fundamental target for neuroprotective interventions and the first two decades are critical. We recommend the concept of preclinical AD be revised and emphasize the need to define paediatric environmental, nutritional, metabolic and genetic risk factor interactions of paramount importance to prevent AD. AD evolving from childhood is threating the wellbeing of our children and future generations.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2019

Options for low-global-warming-potential and natural refrigerants Part 2: Performance of refrigerants and systemic irreversibilities

There is growing interest in substituting existing refrigerants with low global warming potential (GWP) refrigerants, including naturally occurring fluids, to reduce the impact of human activities on climate change. In the Part I of the study, we examined 13 refrigerants from the perspective of the characteristic shape of their respective temperature–entropy (T–S) and the logarithm of the pressure versus inverse absolute temperature (log P vs. T –1 ) phase boundary. In Part 2, we are evaluating prospective low-GWP refrigerants in four distinct heat pump cycles using the First and Second Laws of thermodynamics. The essence of the study is to establish the performance of the low-GWP refrigerants when deployed in a heat pump system. Exergy analysis provides a true measure of lost work, or systemic inefficiencies, vividly quantifying areas of improvement and identifying the preferred cycle for a refrigerant. Here, the combined knowledge of the properties of the phase boundary on either side of the critical point, and exergy analysis of prospective cycles is necessary for a better perspective on discriminating among refrigerants as hydrochlorofluorocarbons are phased out and replacement refrigerants must be found.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Refine your search to explore more results.