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Zhao, Peng

Publications and source records attributed to Zhao, Peng.

At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Ignition Delay Times and CO Composition during Ethanol Combustion in Miniature Shock Tube

Ignition delay times and composition of CO were measured simultaneously in a miniature high repetition rate shock tube (HRRST) using chemiluminescence and tunable diode laser absorption spectroscopy. Mixtures of 1% ethanol with oxygen and balance argon were tested with equivalence ratios 0.5, 1, and 1.2, over pressure range of 1.6 to 1.8 bar, and temperature range of 1180 to 1400K. Ignition delay times in this range were compared with those in larger shock tubes using several different techniques. One method included using the Livengood-Wu integral (and improved estimates from measured pressure trace). Another method involved direct modeling of conditions in the miniature shock tube using the measured pressure trace. CO composition was measured in parallel with the ignition delay time experiments. Comparison was made with mechanisms in the literature. Experiments were also performed doping CO into the Ar bath gas and conducting two-line CO measurements using TDLAS before ignition. With proper calibration, this measurement is sensitive to temperature.

Sutar, Ashish↗
DOE OSTI2018

GDC-0084 inhibits cutaneous squamous cell carcinoma cell growth

Highlights: • GDC-0084 is a novel small-molecule PI3K/mTOR dual inhibitor. • GDC-0084 inhibits cutaneous squamous cell carcinoma (cSCC) cell survival/proliferation. • GDC-0084 induces apoptosis activation in cSCC cells. • GDC-0084 blocks PI3K-Akt-mTOR and DNA-PKcs signaling activation in cSCC cells. • Gastric gavage of GDC-0084 inhibits A431 xenograft tumor growth in SCID mice. GDC-0084 is a novel and potent small-molecule PI3K-mTOR dual inhibitor. The present study examined its potential activity in cutaneous squamous cell carcinoma (cSCC) cells. Our results show that GDC-0084 treatment at nanomole concentrations potently inhibited survival and proliferation of established (A431, SCC-13 and SCL-1 lines) and primary human cSCC cells. GDC-0084 induced apoptosis activation and cell cycle arrest in the cSCC cells. It was more efficient than other known PI3K-Akt-mTOR inhibitors in killing cSCC cells, but was non-cytotoxic to the normal human skin fibroblasts/keratinocytes. In A431 cells and primary cSCC cells, GDC-0084 blocked phosphorylation of key PI3K-Akt-mTOR components, including p85, Akt, S6K1 and S6. GDC-0084 also inhibited DNA-PKcs activation in cSCC cells. Significantly, restoring DNA-PKcs activation by a constitutively active-DNA-PKcs (S2056D) partially inhibited GDC-0084-induced cell death and apoptosis in A431 cells. In vivo, GDC-0084 daily gavage potently inhibited A431 xenograft tumor growth in mice. In GDC-0084-treated tumor tissues PI3K-Akt-mTOR and DNA-PKcs activation were significantly inhibited. In summary, GDC-0084 inhibits human cSCC cell growth in vitro and in vivo through blocking PI3K-Akt-mTOR and DNA-PKcs signalings.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Ultrafast extreme ultraviolet photoemission without space charge

Time- and Angle-resolved photoelectron spectroscopy from surfaces can be used to record the dynamics of electrons and holes in condensed matter on ultrafast time scales. However, ultrafast photoemission experiments using extreme-ultraviolet (XUV) light have previously been limited by either space-charge effects, low photon flux, or limited tuning range. In this article, we describe XUV photoelectron spectroscopy experiments with up to 5 nA of average sample current using a tunable cavity-enhanced high-harmonic source operating at 88 MHz repetition rate. The source delivers >1011 photons/s in isolated harmonics to the sample over a broad photon energy range from 18 to 37 eV with a spot size of 58 × 100 μm2. From photoelectron spectroscopy data, we place conservative upper limits on the XUV pulse duration and photon energy bandwidth of 93 fs and 65 meV, respectively. The high photocurrent, lack of strong space charge distortions of the photoelectron spectra, and excellent isolation of individual harmonic orders allow us to observe laser-induced modifications of the photoelectron spectra at the 10−4 level, enabling time-resolved XUV photoemission experiments in a qualitatively new regime.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

Crystal structure of EGFR T790M/C797S/V948R in complex with EAI045

Lung cancer is the leading cause of cancer deaths. Epidermal growth factor receptor (EGFR) kinase domain mutations are a common cause of non-small cell lung cancers (NSCLCs), a major subtype of lung cancers. Patients harboring most of these mutations respond well to the anti-EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib initially, but soon develop resistance to them in about half of the cases due to the emergence of the gatekeeper mutation T790M. The third-generation TKIs such as AZD9291, HM61713, CO-1686 and WZ4002 can overcome T790M through covalent binding to the EGFR kinase through Cys 797, but ultimately lose their efficacy upon emergence of the C797S mutation that abolishes the covalent bonding. Therefore to develop new TKIs to overcome EGFR drug-resistant mutants harboring T790M/C797S is urgently demanded. EAI001 and EAI045 are a new type of EGFR TKIs that bind to EGFR reversibly and not relying on Cys 797. EAI045 in combination with cetuximab is effective in mouse models of lung cancer driven by EGFR L858R/T790M and L858R/T790M/C797S. Here we report the crystal structure of EGFR T790M/C797S/V948R in complex with EAI045, and compare it to EGFR T790M/V948R in complex with EAI001. The complex structure reveals why EAI045 binds tighter to EGFR than does EAI001, and why EAI001 and EAI045 prefer binding to EGFR T790M. The knowledge may facilitate future drug development studies targeting this very important cancer target.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Kinetic modeling of ignition in miniature shock tube

The ignition delay times of toluene, n-heptane/iso-octane primary reference fuel blends, and toluene/n-heptane/iso-octane toluene primary reference fuel blends were studied in the miniature high repetition rate shock tube (HRRST). In the HRRST, the temperature and pressure change during the test time, complicating interpretation of ignition delay times. Two methods of chemical kinetic modeling were employed in order to account for the changing thermodynamic states in the HRRST. One was based on direct modeling using the pressure profile and the kinetic mechanism, and the other was based on a Livengood-Wu type approach using modeled constant volume ignition delay times. Two different kinetic mechanisms were used in modeling the data. Both methods showed agreement with experimental data over a range of temperatures, pressures, and blends. While overall agreement was fair, agreement was poorer for one of the mechanisms for the primary reference fuel blends. An evaluation of the ignition delay iso-contours from these mechanisms for representative HRRST experiment thermodynamic trajectories revealed that the HRRST measured IDTs are controlled by the high temperature chemistry and are more sensitive to temperature. Furthermore, the different performance of mechanisms is therefore attributed to their different high temperature reactivity.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

Insights on fuel performance in advanced compression ignition engines: combining engine thermodynamic trajectory and fuel ignition delay iso-contour

With the development of various low temperature engine combustion strategies, the behavior of gasoline-type fuels under compression ignition conditions has attracted extensive research interest. In this study, gasoline surrogates based on toluene primary reference fuel blends (TPRF) with different research and motor octane numbers (i.e., RON and MON) and fuel octane sensitivity (OS) have been strategically designed using a recently established surrogate model, and their combustion chemistry is further described using a well-validated kinetic mechanism. Based on a typical advanced compression ignition engine configuration, the crank angle corresponding to 50% total heat release (CA50) was utilized as an indicator of the overall fuel reactivity, and representative engine operating conditions have been selected based on the regime exhibited from the CA50 iso-contours. By combining the thermodynamic trajectory and ignition delay isocontours, useful insights on the fuel reactivity and sensitivity have been obtained to evaluate the fuel performance under various engine operating regimes with distinct chemistry, accounting for the effects of equivalence ratio and ratio of exhaust gas recirculation (EGR). This study provides useful insight on the different effects of engine operating conditions on a fuel’s performance following different engine trajectories, based on the different controlling fuel chemistry.

Tao, Mingyuan↗
DOE OSTI2018

Chemical Kinetic Modeling of Ignition in HRRST

In the high repetition rate miniature shock tube, HRRST, the temperature and pressure change during the test time, complicating interpretation of ignition delay times. In order to evaluate the use of the HRRST as a reliable means of high throughput- high temperature ignition delay testing and make better use of the acquired data for kinetic validation, several methods of modeling were employed in order to account for the changing thermodynamic states in the HRRST. One line of approach was based on direct chemical modeling using the pressure profile and detailed or simplified kinetic mechanism, and the other was based on a Livengood-Wu type approach using modeled constant volume or constant pressure ignition delay times. Additionally, the modeling approaches evaluated the distinction between results based on thermodynamic trajectories either assuming non-reactive adiabatic conditions or measured from actual ignition delay experiments. Several n-heptane/iso-octane primary reference fuel and toluene/n-heptane/iso-octane toluene primary reference fuel blends were experimentally evaluated and compared with both experimental results and chemical kinetic mechanisms.

Tao, Mingyuan↗
DOE OSTI2018

On the Interpretation and Correlation of High-Temperature Ignition Delays in Reactors with Varying Thermodynamic Conditions

Ignition delay time (IDT) is a useful global metric for fuel performance screening and a major target for kinetic modeling. Measurements of IDT are conceptually straightforward, however interpretation could be complicated, especially for systems with changing temperature and pressure. Some experimental conditions in the high repetition rate miniature shock tube (HRRST) exhibit complex temperature and pressure state histories. To better interpret and correlate IDTs, especially those obtained in reactors with varying thermodynamic conditions, an inverse Livengood-Wu (L-W) integral technique is applied to de-convolve the constant condition IDTs from measured IDTs in the HRRST using information on the varying state history. In this paper, the approximate problem is demonstrated using only the measured pressure history leading up to ignition, where the temperature history is estimated based on an isentropic assumption. The IDTs of several fuels were first measured in the HRRST including isooctane and acetone to represent those fuels without strong low temperature chemistry effects. Based on the measured pressure and approximated temperature history, measurements of IDTs in the HRRST compare very favorably with those measured using more conventional techniques, including conventionally sized shock tubes, via the inverse L-W correlation with relaxed Newton iteration and Genetic Algorithm (GA). Furthermore, this study demonstrates the feasibility of using a high throughput ignition testing facility, like the HRRST to extract the constant state IDT measured in regular shock tubes, assisted by the inverse L-W correlation. It is expected with an independent temperature measurement available in the future, IDTs in a broader range of thermodynamic conditions and effects of heat loss could be better resolved.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2017

Distinct roles of N- and O-glycans in cellulase activity and stability

Significance Glycosylation is a ubiquitous posttranslational modification of proteins wherein carbohydrates are appended to protein side chains, with myriad functions in molecular and cell biology. The enzymes that break down polysaccharides and other recalcitrant polymers in nature are often decorated with two canonical forms of glycosylation, N- and O-linked glycans, the roles of which are only partially understood in these key enzyme families with importance to both natural biomass turnover and industrial biotechnology. Here, we report that, depending on where they are attached, glycans play substantially different roles for the enzyme in thermal and proteolytic stability, substrate binding, and substrate turnover. Overall, these results provide fundamental insights into how glycans affect critical properties of biomass-degrading enzymes.

09 BIOMASS FUELS↗
DOE OSTI2017

Frog: Asynchronous Graph Processing on GPU with Hybrid Coloring Model

GPUs have been increasingly used to accelerate graph processing for complicated computational problems regarding graph theory. Many parallel graph algorithms adopt the asynchronous computing model to accelerate the iterative convergence. Unfortunately, the consistent asynchronous computing requires locking or atomic operations, leading to significant penalties/overheads when implemented on GPUs. As such, coloring algorithm is adopted to separate the vertices with potential updating conflicts, guaranteeing the consistency/correctness of the parallel processing. Common coloring algorithms, however, may suffer from low parallelism because of a large number of colors generally required for processing a large-scale graph with billions of vertices. We propose a light-weight asynchronous processing framework called Frog with a preprocessing/hybrid coloring model. The fundamental idea is based on Pareto principle (or 80-20 rule) about coloring algorithms as we observed through masses of realworld graph coloring cases. We find that a majority of vertices (about 80%) are colored with only a few colors, such that they can be read and updated in a very high degree of parallelism without violating the sequential consistency. Accordingly, our solution separates the processing of the vertices based on the distribution of colors. In this work, we mainly answer three questions: (1) how to partition the vertices in a sparse graph with maximized parallelism, (2) how to process large-scale graphs that cannot fit into GPU memory, and (3) how to reduce the overhead of data transfers on PCIe while processing each partition. Here, we conduct experiments on real-world data (Amazon, DBLP, YouTube, RoadNet-CA, WikiTalk and Twitter) to evaluate our approach and make comparisons with well-known non-preprocessed (such as Totem, Medusa, MapGraph and Gunrock) and preprocessed (Cusha) approaches, by testing four classical algorithms (BFS, PageRank, SSSP and CC). On all the tested applications and datasets, Frog is able to significantly outperform existing GPU-based graph processing systems except Gunrock and MapGraph. MapGraph gets better performance than Frog when running BFS on RoadNet-CA. The comparison between Gunrock and Frog is inconclusive. Frog can outperform Gunrock more than 1.04X when running PageRank and SSSP, while the advantage of Frog is not obvious when running BFS and CC on some datasets especially for RoadNet-CA.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2017

Deubiquitinase USP33 is negatively regulated by β-TrCP through ubiquitin-dependent proteolysis

Ubiquitin-mediated proteolysis regulates cellular levels of various proteins, and therefore plays important roles in controlling cell signaling and disease progression. The Skp1-Cul1-F-box ubiquitin ligase β-TrCP is recognized as an important negative regulator for numerous key signaling proteins. Recently, the deubiquitinases (DUBs) have turned out to be essential to regulate signaling pathways related to human diseases. However, whether β-TrCP is able to regulate the deubiquitinase family members remains largely unexplored. Here, we found that β-TrCP downregulated cellular levels of endogenous USP33. We also revealed that β-TrCP interacted with USP33 independently of the classic binding motif for β-TrCP, and mediated USP33 degradation via the ubiquitin proteasome pathway. Furthermore, we found that the WD40 motif of β-TrCP and 201–400 amino acid motif of USP33 are required for the interaction between β-TrCP and USP33. Consequently, β-TrCP attenuated USP33-mediated inhibition of cell proliferation and cell invasion. Taken together, our study clarified that the E3 ligase β-TrCP regulates cellular USP33 levels by the ubiquitin-proteasomal proteolysis. - Highlights: •β-TrCP downregulates protein levels of USP33. •β-TrCP promotes USP33 ubiquitination and degradation. • The effect of β-TrCP on USP33 is independent of DSG motif. • β-TrCP attenuates USP33-mediated suppression of cell proliferation and invasion.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Structural basis of mutant-selectivity and drug-resistance related to CO-1686

Non-small-cell lung cancers (NSCLCs) caused by activating mutations in the kinase domain of epidermal growth factor receptor (EGFR) initially respond to first-generation reversible drugs gefitinib and erlotinib. However, clinical efficacy is limited due to the development of drug-resistance that in more than half of the cases are driven by the secondary T790M mutation. CO-1686 is one of the third generation irreversible inhibitors that inhibits EGFR activating mutants, including those with concurrent T790M, while avoiding the off-target toxicity owing to inhibition of wild-type EGFR in treating EGFR mutation-positive NSCLCs. Despite the remarkable success, the experimentally determined structure of this agent in complex with EGFR T790M remains unknown. In this study, we determined crystal structures of EGFR T790M or L858R mutants covalently bound by CO-1686. Based on these structural data, we can explain why CO-1686 irreversibly inhibits EGFR and selectively prefers T790M, which may help improving this or similar compounds, and explain why EGFR L718Q and L844V mutations incur resistance to this agent.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

A kinetic modeling study on octane rating and fuel sensitivity under HCCI conditions

With the development of advanced compression ignition engines such as the homogeneous charge compression ignition (HCCI) and the reactivity controlled compression ignition (RCCI), the long existing research and motor octane rating for fuels, i.e., RON and MON, might be insufficient to describe the fuel reactivity and performance with these new combustion strategies due to their distinctive engine operation conditions. It is also noted that with the stringent regulation for CO2 emission, a detailed knowledge of fuel reactivity is urgently needed for the selection of novel alternative bio-fuels for transportation, and optimization of their engine performance in the future. It is therefore very important to understand the reactivity and sensitivity for general classes of fuels as a function of the operating conditions in these advanced combustion engines. In this modeling study, using validated kinetic mechanism for ignition, we have simulated the performance of different classes of fuels including hydrogen, alkanes (straight and branched), alcohols and potential bio-fuels under typical HCCI engine conditions using detailed chemical kinetics. The crank angle corresponding to 50% total heat release (CA50) is utilized as an indicator for the fuel reactivity. Iso-contours of CA50 are then plotted in the engine operating parameter coordinate, such as the intake temperature, and pressure. It is shown that CA50 value can vary significantly with different engine operating conditions, and that fuels with the same RON/MON even exhibit qualitatively different CA50 iso-contours in specific operating regimes, implying differences in the intrinsic reactivity of different classes of fuels, as well as the insufficiency of RON/MON as comprehensive metrics of fuel reactivity in advanced compression ignition (ACI) strategies. In addition, the operating regime with high and low sensitivity, as well as potential non-monotonic change in fuel reactivity, has been identified by the CA50 iso-contour map for all studied fuels.

Wu, Tong↗