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Wei, Liu

Publications and source records attributed to Wei, Liu.

At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Preclinical evaluation of PSMA expression in response to androgen receptor blockade for theranostics in prostate cancer

Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a promising yet not curative approach in castration-resistant (CR) prostate cancer (PC). Rational combination therapies may improve treatment efficacy. Here, we explored the effect of androgen receptor blockade (ARB) on PSMA expression visualized by PET and its potential additive effect when combined with 177 Lu-PSMA RLT in a mouse model of prostate cancer. Mice bearing human CRPC (C4-2 cells) xenografts were treated with 10 mg/kg enzalutamide (ENZ), with 50 mg/kg bicalutamide (BIC), or vehicle (control) for 21 days. PSMA expression was evaluated by 68 Ga-PSMA11 PET/CT and quantified by flow cytometry of tumor fine needle aspirations before treatment and on days 23, 29, 34, and 39 post-therapy induction. For the RLT combination approach, mice bearing C4-2 tumors were treated with 10 mg/kg ENZ or vehicle for 21 days before receiving either 15 MBq (84 GBq/μmol) 177 Lu-PSMA617 or vehicle. DNA damage was assessed as phospho-γH2A.X foci in tumor biopsies. Reduction of tumor volume on CT and survival were used as study endpoints. Tumor growth was delayed by ARB while 68 Ga-PSMA11 uptake increased up to 2.3-fold over time when compared to controls. ABR-induced upregulation of PSMA expression was confirmed by flow cytometry. Phospho-γH2A.X levels increased 1.8- and 3.4-fold at 48 h in response to single treatment ENZ or RLT and ENZ+RLT, respectively. Despite significantly greater DNA damage and persistent increase of PSMA expression at the time of RLT, no additional tumor growth retardation was observed in the ENZ+RLT group (vs. RLT only, p = 0.372 at day 81). Median survival did not improve significantly when ENZ was combined with RLT. ARB-mediated increases in PSMA expression in PC xenografts were evident by 68 Ga-PSMA11 PET imaging and flow cytometry. 177 Lu-PSMA617 effectively decreased C4-2 tumor size. Furthermore, while pre-treatment with ARB increased DNA damage significantly, it did not result in synergistic effects when combined with RLT.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

ATR inhibition facilitates targeting of leukemia dependence on convergent nucleotide biosynthetic pathways

It is known that leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) reduces the output of both de novo and salvage pathways by regulating the activity of their respective rate-limiting enzymes, ribonucleotide reductase (RNR) and deoxycytidine kinase (dCK), via distinct molecular mechanisms. Quantification of nucleotide biosynthesis in ATR-inhibited acute lymphoblastic leukemia (ALL) cells reveals substantial remaining de novo and salvage activities, and could not eliminate the disease in vivo. However, targeting these remaining activities with RNR and dCK inhibitors triggers lethal replication stress in vitro and long-term disease-free survival in mice with B-ALL, without detectable toxicity. Thus the functional interplay between alternative nucleotide biosynthetic routes and ATR provides therapeutic opportunities in leukemia and potentially other cancers.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Tritium Control and Capture in Salt-Cooled Fission and Fusion Reactors: Status, Challenges, and Path Forward

Three advanced nuclear power systems use liquid salt coolants that generate tritium and thus face the common challenges of containing and capturing tritium to prevent its release to the environment. The fluoride salt–cooled high-temperature reactor (FHR) uses clean fluoride salt coolants and the same graphite-matrix coated-particle fuel as high-temperature gas-cooled reactors. Molten salt reactors (MSRs) dissolve the fuel in a fluoride or chloride salt with release of fission product tritium into the salt. In most FHR and MSR systems, the baseline salts contain lithium where isotopically separated 7 Li is proposed to minimize tritium production from neutron interactions with the salt. The Chinese Academy of Sciences plans to start operation of a 2-MW(thermal) molten salt test reactor by 2020. For high-magnetic-field fusion machines, the use of lithium enriched in 6 Li is proposed to maximize tritium generation—the fuel for a fusion machine. Advances in superconductors that enable higher power densities may require the use of molten lithium salts for fusion blankets and as coolants. Recent technical advances in these three reactor classes have resulted in increased government and private interest and the beginning of a coordinated effort to address the tritium control challenges in 700°C liquid salt systems. In this paper, we describe characteristics of salt-cooled fission and fusion machines, the basis for growing interest in these technologies, tritium generation in molten salts, the environment for tritium capture, models for high-temperature tritium transport in salt systems, alternative strategies for tritium control, and ongoing experimental work. Several methods to control tritium appear viable. Finally, limited experimental data are the primary constraint for designing efficient cost-effective methods of tritium control.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2014

National Alliance for Advanced Biofuels and Bio-Products Final Technical Report

The main objective of NAABB was to combine science, technology, and engineering expertise from across the nation to break down critical technical barriers to commercialization of algae-based biofuels. The approach was to address technology development across the entire value chain of algal biofuels production, from selection of strains to cultivation, harvesting, extraction, fuel conversion, and agricultural coproduct production. Sustainable practices and financial feasibility assessments ununderscored the approach and drove the technology development.

09 BIOMASS FUELS↗
DOE OSTI2013

OBSERVATION OF A MORETON WAVE AND WAVE-FILAMENT INTERACTIONS ASSOCIATED WITH THE RENOWNED X9 FLARE ON 1990 MAY 24

Using Big Bear Solar Observatory film data recently digitized at NJIT, we investigate a Moreton wave associated with an X9 flare on 1990 May 24, as well as its interactions with four filaments F1-F4 located close to the flaring region. The interaction yields interesting insight into physical properties of both the wave and the filaments. The first clear Moreton wavefront appears at the flaring-region periphery at approximately the same time as the peak of a microwave burst and the first of two {gamma}-ray peaks. The wavefront propagates at different speeds ranging from 1500-2600 km s{sup -1} in different directions, reaching as far as 600 Mm away from the flaring site. Sequential chromospheric brightenings are observed ahead of the Moreton wavefront. A slower diffuse front at 300-600 km s{sup -1} is observed to trail the fast Moreton wavefront about one minute after the onset. The Moreton wave decelerates to {approx}550 km s{sup -1} as it sweeps through F1. The wave passage results in F1's oscillation which is featured by {approx}1 mHz signals with coherent Fourier phases over the filament, the activation of F3 and F4 followed by gradual recovery, but no disturbance in F2. Different height and magnetic environment together may account for the distinct responses of the filaments to the wave passage. The wavefront bulges at F4, whose spine is oriented perpendicular to the upcoming wavefront. The deformation of the wavefront is suggested to be due to both the forward inclination of the wavefront and the enhancement of the local Alfven speed within the filament channel.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2013

Effectiveness of robust optimization in intensity-modulated proton therapy planning for head and neck cancers

Purpose: Intensity-modulated proton therapy (IMPT) is highly sensitive to uncertainties in beam range and patient setup. Conventionally, these uncertainties are dealt using geometrically expanded planning target volume (PTV). In this paper, the authors evaluated a robust optimization method that deals with the uncertainties directly during the spot weight optimization to ensure clinical target volume (CTV) coverage without using PTV. The authors compared the two methods for a population of head and neck (H and N) cancer patients. Methods: Two sets of IMPT plans were generated for 14 H and N cases, one being PTV-based conventionally optimized and the other CTV-based robustly optimized. For the PTV-based conventionally optimized plans, the uncertainties are accounted for by expanding CTV to PTV via margins and delivering the prescribed dose to PTV. For the CTV-based robustly optimized plans, spot weight optimization was guided to reduce the discrepancy in doses under extreme setup and range uncertainties directly, while delivering the prescribed dose to CTV rather than PTV. For each of these plans, the authors calculated dose distributions under various uncertainty settings. The root-mean-square dose (RMSD) for each voxel was computed and the area under the RMSD-volume histogram curves (AUC) was used to relatively compare plan robustness. Data derived from the dose volume histogram in the worst-case and nominal doses were used to evaluate the plan optimality. Then the plan evaluation metrics were averaged over the 14 cases and were compared with two-sided paired t tests. Results: CTV-based robust optimization led to more robust (i.e., smaller AUCs) plans for both targets and organs. Under the worst-case scenario and the nominal scenario, CTV-based robustly optimized plans showed better target coverage (i.e., greater D{sub 95%}), improved dose homogeneity (i.e., smaller D{sub 5%}- D{sub 95%}), and lower or equivalent dose to organs at risk. Conclusions: CTV-based robust optimization provided significantly more robust dose distributions to targets and organs than PTV-based conventional optimization in H and N using IMPT. Eliminating the use of PTV and planning directly based on CTV provided better or equivalent normal tissue sparing.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

PLASMOID EJECTIONS AND LOOP CONTRACTIONS IN AN ERUPTIVE M7.7 SOLAR FLARE: EVIDENCE OF PARTICLE ACCELERATION AND HEATING IN MAGNETIC RECONNECTION OUTFLOWS

Where particle acceleration and plasma heating take place in relation to magnetic reconnection is a fundamental question for solar flares. We report analysis of an M7.7 flare on 2012 July 19 observed by SDO/AIA and RHESSI. Bi-directional outflows in forms of plasmoid ejections and contracting cusp-shaped loops originate between an erupting flux rope and underlying flare loops at speeds of typically 200-300 km s{sup -1} up to 1050 km s{sup -1}. These outflows are associated with spatially separated double coronal X-ray sources with centroid separation decreasing with energy. The highest temperature is located near the nonthermal X-ray loop-top source well below the original heights of contracting cusps near the inferred reconnection site. These observations suggest that the primary loci of particle acceleration and plasma heating are in the reconnection outflow regions, rather than the reconnection site itself. In addition, there is an initial ascent of the X-ray and EUV loop-top source prior to its recently recognized descent, which we ascribe to the interplay among multiple processes including the upward development of reconnection and the downward contractions of reconnected loops. The impulsive phase onset is delayed by 10 minutes from the start of the descent, but coincides with the rapid speed increases of the upward plasmoids, the individual loop shrinkages, and the overall loop-top descent, suggestive of an intimate relation of the energy release rate and reconnection outflow speed.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2013

PTV-based IMPT optimization incorporating planning risk volumes vs robust optimization

Purpose: Robust optimization leads to intensity-modulated proton therapy (IMPT) plans that are less sensitive to uncertainties and superior in terms of organs-at-risk (OARs) sparing, target dose coverage, and homogeneity compared to planning target volume (PTV)-based optimized plans. Robust optimization incorporates setup and range uncertainties, which implicitly adds margins to both targets and OARs and is also able to compensate for perturbations in dose distributions within targets and OARs caused by uncertainties. In contrast, the traditional PTV-based optimization considers only setup uncertainties and adds a margin only to targets but no margins to the OARs. It also ignores range uncertainty. The purpose of this work is to determine if robustly optimized plans are superior to PTV-based plans simply because the latter do not assign margins to OARs during optimization. Methods: The authors retrospectively selected from their institutional database five patients with head and neck (H and N) cancer and one with prostate cancer for this analysis. Using their original images and prescriptions, the authors created new IMPT plans using three methods: PTV-based optimization, optimization based on the PTV and planning risk volumes (PRVs) (i.e., 'PTV+PRV-based optimization'), and robust optimization using the 'worst-case' dose distribution. The PRVs were generated by uniformly expanding OARs by 3 mm for the H and N cases and 5 mm for the prostate case. The dose-volume histograms (DVHs) from the worst-case dose distributions were used to assess and compare plan quality. Families of DVHs for each uncertainty for all structures of interest were plotted along with the nominal DVHs. The width of the 'bands' of DVHs was used to quantify the plan sensitivity to uncertainty. Results: Compared with conventional PTV-based and PTV+PRV-based planning, robust optimization led to a smaller bandwidth for the targets in the face of uncertainties {l_brace}clinical target volume [CTV] bandwidth: 0.59 [robust], 3.53 [PTV+PRV], and 3.53 [PTV] Gy (RBE){r_brace}. It also resulted in higher doses to 95% of the CTV {l_brace}D{sub 95%}: 60.8 [robust] vs 59.3 [PTV+PRV] vs 59.6 [PTV] Gy (RBE){r_brace}, smaller D{sub 5%} (doses to 5% of the CTV) minus D{sub 95%} {l_brace}D{sub 5%}- D{sub 95%}: 13.2 [robust] vs 17.5 [PTV+PRV] vs 17.2 [PTV] Gy (RBE){r_brace}. At the same time, the robust optimization method irradiated OARs less {l_brace}maximum dose to 1 cm{sup 3} of the brainstem: 48.3 [robust] vs 48.8 [PTV+PRV] vs 51.2 [PTV] Gy (RBE); mean dose to the oral cavity: 22.3 [robust] vs 22.9 [PTV+PRV] vs 26.1 [PTV] Gy (RBE); maximum dose to 1% of the normal brain: 66.0 [robust] vs 68.0 [PTV+PRV] vs 69.3 [PTV] Gy (RBE){r_brace}. Conclusions: For H and N cases studied, OAR sparing in PTV+PRV-based optimization was inferior compared to robust optimization but was superior compared to PTV-based optimization; however, target dose robustness and homogeneity were comparable in the PTV+PRV-based and PTV-based optimizations. The same pattern held for the prostate case. The authors' data suggest that the superiority of robust optimization is not due simply to its inclusion of margins for OARs, but that this is due mainly to the ability of robust optimization to compensate for perturbations in dose distributions within target volumes and normal tissues caused by uncertainties.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Dynamically accumulated dose and 4D accumulated dose for moving tumors

Purpose: The purpose of this work was to investigate the relationship between dynamically accumulated dose (dynamic dose) and 4D accumulated dose (4D dose) for irradiation of moving tumors, and to quantify the dose uncertainty induced by tumor motion. Methods: The authors established that regardless of treatment modality and delivery properties, the dynamic dose will converge to the 4D dose, instead of the 3D static dose, after multiple deliveries. The bounds of dynamic dose, or the maximum estimation error using 4D or static dose, were established for the 4D and static doses, respectively. Numerical simulations were performed (1) to prove the principle that for each phase, after multiple deliveries, the average number of deliveries for any given time converges to the total number of fractions (K) over the number of phases (N); (2) to investigate the dose difference between the 4D and dynamic doses as a function of the number of deliveries for deliveries of a 'pulsed beam'; and (3) to investigate the dose difference between 4D dose and dynamic doses as a function of delivery time for deliveries of a 'continuous beam.' A Poisson model was developed to estimate the mean dose error as a function of number of deliveries or delivered time for both pulsed beam and continuous beam. Results: The numerical simulations confirmed that the number of deliveries for each phase converges to K/N, assuming a random starting phase. Simulations for the pulsed beam and continuous beam also suggested that the dose error is a strong function of the number of deliveries and/or total deliver time and could be a function of the breathing cycle, depending on the mode of delivery. The Poisson model agrees well with the simulation. Conclusions: Dynamically accumulated dose will converge to the 4D accumulated dose after multiple deliveries, regardless of treatment modality. Bounds of the dynamic dose could be determined using quantities derived from 4D doses, and the mean dose difference between the dynamic dose and 4D dose as a function of number of deliveries and/or total deliver time was also established.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

SDO/AIA DETECTION OF SOLAR PROMINENCE FORMATION WITHIN A CORONAL CAVITY

We report the first analyses of SDO/AIA observations of the formation of a quiescent polar crown prominence in a coronal cavity. The He II 304 A (log T{sub max} {approx} 4.8 K) data show both the gradual disappearance of the prominence due to vertical drainage and lateral transport of plasma followed by the formation of a new prominence 12 hr later. The formation is preceded by the appearance of a bright emission 'cloud' in the central region of the coronal cavity. The peak brightness of the cloud progressively shifts in time from the Fe XIV 211 A channel, through the Fe XII 193 A channel, to the Fe IX 171 A channel (log T{sub max} {approx} 6.2, 6.1, 5.8 K, respectively) while simultaneously decreasing in altitude. Filter ratio analysis estimates the initial temperature of the cloud to be approximately log T {approx} 6.25 K with evidence of cooling over time. The subsequent growth of the prominence is accompanied by darkening of the cavity in the 211 A channel. The observations imply prominence formation via in situ condensation of hot plasma from the coronal cavity, in support of our previously proposed process of magnetothermal convection in coronal magnetic flux ropes.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2012

Influence of a strong laser field on Coulomb explosion and stopping power of energetic H{sub 3}{sup +} clusters in plasmas

The influence of a high-intensity laser field on the Coulomb explosion and stopping power for a swift H{sub 3}{sup +} cluster ion in a plasma target is studied by means of the molecular dynamic (MD) method based on the linearized Vlasov-Poisson theory. Excitations of the plasma are described by the classical plasma dielectric function. In the presence of the laser field, the general expressions for the induced potential in the target and the interaction force among the ions within the cluster are derived. Based on the numerical solution of the equations of motion for the constituent ions, the Coulomb explosion patterns and the cluster's stopping power are discussed for a range of laser parameters. Numerical results show that the laser field affects the correlation between the ions and contributes to weaken the wake effect and the stopping power as compared to the laser-free case. On the other hand, the stopping power ratio of H{sub 3}{sup +} cluster is higher than the situation of dicluster of H{sub 2}{sup +} due to the vicinage effect in the cluster.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗