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Overcoming acquired drug resistance remains a core challenge in the clinical management of human cancer, including in urothelial carcinoma of the bladder (UCB). Cancer stem-like cells (CSC) have been implicated in the emergence of drug resistance but mechanisms and intervention points are not completely understood. Here, we report that the proinflammatory COX2/PGE2 pathway and the YAP1 growth-regulatory pathway cooperate to recruit the stem cell factor SOX2 in expanding and sustaining the accumulation of urothelial CSCs. Mechanistically, COX2/PGE2 signaling induced promoter methylation of let-7, resulting in its downregulation and subsequent SOX2 upregulation. YAP1 induced SOX2 expression more directly by binding its enhancer region. In UCB clinical specimens, positive correlations in the expression of SOX2, COX2, and YAP1 were observed, with coexpression of COX2 and YAP1 particularly commonly observed. Additional investigations suggested that activation of the COX2/PGE2 and YAP1 pathways also promoted acquired resistance to EGFR inhibitors in basal-type UCB. In a mouse xenograft model of UCB, dual inhibition of COX2 and YAP1 elicited a long-lasting therapeutic response by limiting CSC expansion after chemotherapy and EGFR inhibition. Our findings provide a preclinical rationale to target these pathways concurrently with systemic chemotherapy as a strategy to improve the clinical management of UCB.Significance: These findings offer a preclinical rationale to target the COX2 and YAP1 pathways concurrently with systemic chemotherapy to improve the clinical management of UCB, based on evidence that these two pathways expand cancer stem-like cell populations that mediate resistance to chemotherapy. Cancer Res; 78(1); 168–81. ©2017 AACR.

Supplemental Table S1. Relative expression of stem cell-related genes using RT2 profile PCR array.

Supplemental information includes Supplemental Figure S1. The characterization of SOX2 as an oncogene in bladder cancer, Supplemental Figure S2. Stem cell-related molecules associated with SOX2 expression, Supplemental Figure S3. CD24+/CD133+ as a potential marker for SOX2-expressing CSCs, Supplemental Figure S4. COX2/PGE2 signaling pathway in regulating SOX2, Supplemental Figure S5. The association of PGE2 expression with apoptosis in YAP1-LV or YAP1-sh cells, Supplemental Figure S6. Correlation among SOX2, YAP1, and COX2 expression in human UCB samples, Supplemental Figure S7. CSC expansion following CDDP treatment suppressed by combination treatment with verteporfin and celecoxib, Supplemental Figure S8. The EGFR-regulated YAP1 expression via PI3K signaling in basal-type UCB, and Supplementary Materials and Methods.

We report an improved calculation of the electron backscattering coefficients (BSCs) for beryllium, molybdenum and tungsten at electron energies of 0.1–100 keV based on an up-to-date Monte Carlo simulation method with different input of energy loss function (ELF) data. The electron inelastic cross-section is derived from the relativistic dielectric functional formalism, where the full Penn’s algorithm is applied for the extension of the ELF from the optical limit of $$q \to 0$$ q → 0 into the $$\left( {q,\omega } \right)$$ q , ω -plane. We have found that the accuracy of energy loss function may affect largely the calculated BSC. We also show that this has close relationship with the f- and ps-sum rules.

The double-peaked distribution of particle deposition at divertor targets has been observed in various tokamaks, and is considered a potential approach for mitigating divertor particles and heat load in future fusion reactors. Recently, the systematical analysis of the double-peaked distribution behavior during EAST experiments shows that the appearance of the double-peaked profile is related to the line-average density and heating power. In order to understand general trends and related mechanisms, the influences of the upstream density (n e,sep) and power in the scrape-off layer (P SOL) on the double-peaked density profile are investigated by SOLPS-ITER simulations with full drifts and currents. It is found that the n e peak near the strike point is mainly contributed by the strong ionization source close to the target, and the n e peak in the far-SOL region is caused by the synergetic effects of poloidal and radial E × B drifts along the SOL. The double-peaked distribution is affected by the P SOL and impurity seeding by increasing or decreasing the whole profile of the electron temperature at the target (T et). When the peak value of T et (T et,peak) is fixed, the density peak in the far-SOL is increased for higher n e,sep by reducing the T et in the far-SOL region on the lower-field side under unfavorable B T and by the upstream-extended ionization source due to the geometry effect on the high-field side under favorable B T. Statistical analysis of the simulated results shows that the scaling expression of the peak ratio is ∼ T e t , p e a k − ( 1.4 ∼ 2.1 ) n e , s e p 1.6 ∼ 1.8 . In addition to the upper boundary found in the analysis of EAST experiments, a lower boundary of the region where the double-peaked feature appears on the P SOL-n e,sep plane is identified by simulations and preliminarily confirmed according to the measurements in several EAST discharges.

The beam emission spectroscopy (BES) system that shares the collection optics with the core charge exchange recombination spectroscopy (cCXRS) has recently been upgraded on EAST. The enhanced system aims at the simultaneous measurements of the neutral beam emission from the co-current and counter-current neutral beam injection (NBI) as well as the active charge exchange line (Dα, n = 3→2, 656.1 nm) from the interaction of the main ions and the injected neutral beam. The operating spectral band of the system is 656.1 ± 6 nm, with respect to the maximum Doppler shift and stark splitting induced by the highest energy of 80 keV for deuterium beam. Strong edge Dα line is effectively suppressed by one curved chromate strip (˜3% transmission and ˜83 μm width) on the fused silica. Main ion Dα emission and beam emission spectra are acquired simultaneously without any saturation of the signal on the detector. In this paper, an overview of the upgraded spectrometer will be shown and the first experimental results are presented.

Molecular dynamics (MD) methods have been employed to study the formation and growth of helium (He) bubble in bulk tungsten (W) from the atomic-level perspective. The primary variables examined are: irradiation temperature up to 2100 K, He concentration up to 10000 appm in order to study the effects of temperature and He concentration on micro-structural evolution, especially the He evolution. He atoms whose number ranged from 40 to 160 are randomly added to the tetrahedral interstice or octahedral interstice in the W matrix. The results show that the average size of He-V clusters increases with increasing in the temperature and He concentration in general. It is found that the He/V ratios of He-V clusters are mainly ranged from 1.5 to 4 after their nucleation with high He/V ratio more than 6. And the He/V ratio may be influenced greatly by the nearby He-V clusters. This is to be studied in the further work to understand how the He-V clusters interact in bulk W. These results can also provide input parameters to larger scale simulations methods, such as in kinetic Monte Carlo methods and rate theory.

The design of the China Fusion Engineering Test Reactor (CFETR) involves a complex system structure and intricate constraints, and the design work will be performed by a great number of geographically distributed groups. To support consistent design work effectively, the CFETR Integration Design Platform (CIDP) is being developed [IEEE Trans. Plasma Sci. 45 (2017) 512; Fusion Eng. Des. 123 (2017) 87]. CIDP is envisioned as a design center, where all design work can be performed and related design data and documents can be managed. The functions of CIDP are realized by hardware supporting a GPU-based design cloud and three software systems, which are a data management system for data and document management, a task management system for coordinating the design work and an integrated design framework to provide the unified environment for the implementation of detailed design work. The architecture and the detailed implementation of CIDP are given in this article.

Phase Contrast Imaging (PCI) diagnostic has been developed on HL-2 A tokamak. The chord integral density fluctuations of plasma can be obtained by measuring the phase shift of CO2 laser which has a wavelength of 10.6 μm after passing through plasma. The 32-channel detector array enables PCI to diagnose density fluctuations with wavenumbers ranging from 2 cm−1 to 15 cm−1. The temporal resolution of PCI is better than 2 μs which makes it suitable for broadband turbulence research. Calibration by the sound source confirms that PCI is able to discriminate a wide range of wavenumbers. The plasma density fluctuations measured by PCI on HL-2 A is presented for the first time. Comparison of MHD instability investigations with magnetic probe data shows the reliability of this PCI diagnostic.

Background Desmoplastic small round-cell tumor (DSCRT) in adults is an extremely rare (age-adjusted incidence 0.3 per million) and aggressive sarcoma with limited data for optimal management. Patients and methods Retrospective analysis of patients with DSCRT diagnosis (2010-2020) was performed following Institutional Review Board approval. The follow-up period was from pathological diagnosis to the last patient contact. Endpoints were type of response and duration of response. Results In the current analysis, first-line treatment in all cases was vincristine, anthracycline, and cyclophosphamide alternating with ifosfamide and etoposide (VAC-IE) with 100% response for a mean duration of 9.8 (range=5-12) months. Patients received 1-4 subsequent lines of therapy. All patients received temozolomide with irinotecan (50% partial response, duration 8-9 months). Two patients that underwent consolidative cytoreductive surgery with hyperthermic intraperitoneal chemotherapy had a longer survival (30.6 vs. 11.2 months). Patients suffered 100% mortality with a median survival was 17.8 (range=11.2-30.6) months. Conclusion While aggressive multimodality treatment is always warranted for DSCRT, the options are limited by the multicentric presentation, short-lived initial response and lack of established subsequent therapy portending a poor prognosis. Consolidative cytoreductive surgery following first-line therapy may improve survival.

PURPOSE Prostate cancer (PCa) becomes resistant to androgen ablation through adaptive upregulation of the androgen receptor in response to the low-testosterone microenvironment. Bipolar androgen therapy (BAT), defined as rapid cycling between high and low serum testosterone, disrupts this adaptive regulation in castration-resistant PCa (CRPC). METHODS The TRANSFORMER (Testosterone Revival Abolishes Negative Symptoms, Fosters Objective Response and Modulates Enzalutamide Resistance) study is a randomized study comparing monthly BAT (n = 94) with enzalutamide (n = 101). The primary end point was clinical or radiographic progression-free survival (PFS); crossover was permitted at progression. Secondary end points included overall survival (OS), prostate-specific antigen (PSA) and objective response rates, PFS from randomization through crossover (PFS2), safety, and quality of life (QoL). RESULTS The PFS was 5.7 months for both arms (hazard ratio [HR], 1.14; 95% CI, 0.83 to 1.55; P = .42). For BAT, 50% decline in PSA (PSA50) was 28.2% of patients versus 25.3% for enzalutamide. At crossover, PSA50 response occurred in 77.8% of patients crossing to enzalutamide and 23.4% to BAT. The PSA-PFS for enzalutamide increased from 3.8 months after abiraterone to 10.9 months after BAT. The PFS2 for BAT→enzalutamide was 28.2 versus 19.6 months for enzalutamide→BAT (HR, 0.44; 95% CI, 0.22 to 0.88; P = .02). OS was 32.9 months for BAT versus 29.0 months for enzalutamide (HR, 0.95; 95% CI, 0.66 to 1.39; P = .80). OS was 37.1 months for patients crossing from BAT to enzalutamide versus 30.2 months for the opposite sequence (HR, 0.68; 95% CI, 0.36 to 1.28; P = .225). BAT adverse events were primarily grade 1-2. Patient-reported QoL consistently favored BAT. CONCLUSION This randomized trial establishes meaningful clinical activity and safety of BAT and supports additional study to determine its optimal clinical integration. BAT can sensitize CRPC to subsequent antiandrogen therapy. Further study is required to confirm whether sequential therapy with BAT and enzalutamide can improve survival in men with CRPC.

INTRODUCTION AND OBJECTIVE:The link between biofilm and the risk of prostate cancer has become the center of attention recently. Understanding the role that microbiome play in the pathogenesis of p...

One of the major challenges for the Gigawatt-class Chinese Fusion Engineering Testing Reactor (CFETR) is to efficiently handle huge power fluxes on plasma-facing components , especially the divertor targets. This work investigates the effects of two candidate radiation impurity species, argon (Ar) and neon (Ne), with two different divertor geometries (baseline and long leg divertor geometry) on the reduction of steady-state power load to divertor targets in CFETR by using the SOLPS-ITER code package with full drifts and kinetic description of neutrals. The modeling results show clearly that increasing the seeding rate of Ar or Ne with fixed fueling gas D2 injection rate reduces the target electron temperature and heat flux density for the baseline divertor geometry, which can be reduced further by higher D2 injection rate. With a high impurity seeding rate, partial detachment with steady-state power load at the divertor target below the engineering limit of 10 MW m−2 is demonstrated. In addition, the radiation efficiency for Ar is better than that for Ne. Increasing the divertor leg length reduces the electron temperature and heat load at the targets. This modeling, therefore, suggests that a long leg divertor design with Ar seeding impurity is appropriate to meet the CFETR divertor requirements.

For the future fusion reactor, where no intrinsic radiative impurity, like carbon, is allowed to exist, impurity seeding is an indispensable way to exhaust the power across the separatrix. Meanwhile, the impurity concentration has to be limited in order to avoid significant dilution of the fuel in core plasma. For CFETR phase II with a fusion power ∼1 GW, the radiative divertor with argon seeding is studied by SOLPS simulation. Under a high radiative power fraction ∼80% of the power across the separatrix, a density scan is performed for different deuterium ion density at the core-edge boundary. The divertor plasma is fully detached and impurity radiation is concentrated in the divertor region. The relationship between the electron density ne, effective charge Zeff and radiated power Prad are well fitted to the Matthew law, which is considered helpful to find a consistent operation scenario by further core-edge integrated modeling for CFETR phase II.

Space allocation is important in the design of a fusion reactor, where numerous components operate under complex conditions, including a strong magnetic field, high-energy neutron irradiation, and a wide temperature range (4.5 K at the magnet and ∼300–500℃ at the blanket). To ensure the consistency of the China Fusion Engineering Test Reactor (CFETR) design, multi-component interference checks and distance measurements must be routinely performed. In this paper, a space analysis module is developed on the CFETR Integration Design Platform to provide the space analysis function for both rigid and deformed components (using the Representative-Triangles method). The example of the space allocation of a vacuum vessel (VV) and a thermal shield (TS) is demonstrated. The deformation due to heating under the bake-out condition is considered (during operation, heating and swelling due to radiation also cause deformation). With the input from the component design module, the space analysis can be well-performed for both rigid models and thermal deformation results (under the simplified boundary condition). Through iteration between the component design modules and the space analysis module, a preliminary designed clearance of 40 mm between the VV and TS is insufficient owing to the deformation during bake out, and the optimized clearance increases by a factor of two.

China fusion engineering test reactor (CFETR) is a tokamak fusion experimental device under design to bridge the research and development gaps between international thermonuclear experimental reactor and demonstration. Helium cooled ceramic breeder (HCCB) blanket is the candidate blanket concepts for CFETR. A blanket with S-shaped lithium zone and cooling pipes reduces the space of helium manifold and is beneficial to tritium breeding. The neutronics analyses of the HCCB blanket have been performed with the Monte Carlo code monte carlo N particle transport code and nuclear cross section data from the fusion evaluated nuclear data library-3.1b data library. The tritium breeding ratio without port is 1.22 and meets the requirements of tritium self-sufficiency, as well as, the nuclear heating power of 214 MW is achieved and the global energy multiplication factor is 1.33. The shielding performance was shown to meet the design limit. The aim of the analysis is to provide the reference for the design and optimization of CFETR blanket system.

Since tungsten is considered as the optional divertor target material for the future fusion devices, e.g., China Fusion Engineering Test Reactor (CFETR), it is crucial to have a good screening of the tungsten impurity to keep a low core tungsten concentration. In this paper, based on the two-point model, possible divertor plasma parameters are predicted in high recycling regime for CFETR. Further analysis of tungsten ionization lengths shows that when target temperature is low enough (less than 15 eV), the increase of upstream density may cause an increase of ionization length, and thus a degradation of divertor tungsten screening effect may happen. The 2-D simulations of tungsten transport are then performed by using Osm-Eirene-Divimp edGE [onion skin model (OSM)-EIRENE-DIVvertor IMPurities (DIVIMP)] code package. The target plasma parameters, in the region of those predicted by the two-point model, are set as input in OSM-EIRNEN to generate the background plasma. DIVIMP code is used to further simulate the tungsten impurity transport process. The results reveal that although the decrease of target plasma temperature may reduce the tungsten impurity prompt redeposition rate, the benefit of a lower erosion rate can make compensation. Therefore, to control the core tungsten concentration, lower target plasma temperature is preferred in high recycling regime.

A space-resolved extreme ultraviolet (EUV) spectrometer has been used to observe the spatial distribution and temporal behavior of core impurity emissions at the experimental advanced superconducting tokamak (EAST), evaluating the effects of resonant magnetic perturbations (RMPs) on impurity concentration. The vertical profiles of impurity emissions from the 0 ≤ Z ≤ 450 mm range results in spectra in the wavelength range of 30 A $\le \lambda \le 500\,{\mathring {\mathrm {A}}}$ . Line emissions of impurity carbon, lithium, and iron were observed for C VI (33.7 A, 2p–1s), Li III (135 A, 2p–1s), and Fe XXIII (132.9 A, 1s22s2p–1s22s2), respectively, whereas the unresolved transition array (UTA) of tungsten in the wavelength range of $\lambda = 48$ to 70 A is monitored to study tungsten behavior with RMP. It is clearly observed that the intensities of C VI, Li III, Fe XXIII, and W-UTA emissions are reduced by the application of RMP fields, during stages of edge-localized modes (ELMs). In addition, the reduction in Fe and W emissions with $n = 1$ and 2 (n: toroidal mode number) RMP is more significant than that of carbon and lithium emissions, i.e., ~50% to 70% for Fe XXIII and W-UTA, and ~30% for C VI and Li III. Considering that the changes in $n_{e}$ and $T_{e}$ cannot account for the impurity emissions mitigation, the EUV measurements may indicate that RMP can significantly and selectively decrease the impurity accumulation in the core region with slight effects on the main plasma. Spatial distributions of impurity emissions are also measured for different impurity species using the EUV spectrometer, confirming the space-resolved diagnostic’s feasibility to study RMP effects on core impurity concentration.

Chronic arsenic exposure is associated with the development of urothelial carcinoma of the bladder (UCB). To elucidate the contribution of arsenic exposure to urothelial cancer stem cell (CSC) generation, we established an in vitro stepwise malignant model transformed by chronically exposing human urothelial cells to arsenic. Using this model, we found that chronic arsenic exposure endows urothelial cells with malignant stemness properties including increased expression of stemness-related factors such as SOX2, sphere formation, self-renewal, invasion and chemoresistance. SOX2 was gradually and irreversibly overexpressed in line with acquired sphere-forming and self-renewal abilities. Following gene set enrichment analyses of arsenic-exposed and arsenic-unexposed cells, we found COX2 as an enriched gene for oncogenic signature. Mechanistically, arsenic-induced COX2/PGE2 increases SOX2 expression that eventually promotes malignant stem cell generation and repopulation. In urine samples from 90 subjects exposed to arsenic and 91 control subjects, we found a significant linear correlation between SOX2 and COX2 expression and the potential of SOX2 and COX2 expression as urinary markers to detect subjects exposed to arsenic. Furthermore, the combination marker yielded a high sensitivity for UCB detection in a separate cohort. Finally, our in vitro model exhibits basal-type molecular features and dual inhibition of EGFR and COX2 attenuated stem cell enrichment more efficiently than an EGFR inhibitor alone. In conclusion, the COX2/PGE2-SOX2 axis promotes arsenic-induced malignant stem cell transformation. In addition, our findings indicate the possible use of SOX2 and COX2 expression as urinary markers for the risk stratification and detection of UCB.

Overcoming acquired drug resistance remains a core challenge in the clinical management of human cancer, including in urothelial carcinoma of the bladder (UCB). Cancer stem-like cells (CSC) have been implicated in the emergence of drug resistance but mechanisms and intervention points are not completely understood. Here, we report that the proinflammatory COX2/PGE2 pathway and the YAP1 growth-regulatory pathway cooperate to recruit the stem cell factor SOX2 in expanding and sustaining the accumulation of urothelial CSCs. Mechanistically, COX2/PGE2 signaling induced promoter methylation of let-7, resulting in its downregulation and subsequent SOX2 upregulation. YAP1 induced SOX2 expression more directly by binding its enhancer region. In UCB clinical specimens, positive correlations in the expression of SOX2, COX2, and YAP1 were observed, with coexpression of COX2 and YAP1 particularly commonly observed. Additional investigations suggested that activation of the COX2/PGE2 and YAP1 pathways also promoted acquired resistance to EGFR inhibitors in basal-type UCB. In a mouse xenograft model of UCB, dual inhibition of COX2 and YAP1 elicited a long-lasting therapeutic response by limiting CSC expansion after chemotherapy and EGFR inhibition. Our findings provide a preclinical rationale to target these pathways concurrently with systemic chemotherapy as a strategy to improve the clinical management of UCB. Significance: These findings offer a preclinical rationale to target the COX2 and YAP1 pathways concurrently with systemic chemotherapy to improve the clinical management of UCB, based on evidence that these two pathways expand cancer stem-like cell populations that mediate resistance to chemotherapy. Cancer Res; 78(1); 168–81. ©2017 AACR.

The linear mercury diffusion pump is proposed as the primary pump for sustaining the continuous working of KALPUREX (Karlsruhe liquid metal based pumping process for fusion reactor exhaust gases), which is considered as the exhaust pumping solution for reducing the tritium inventory in future fusion reactor with the fuel cycle based on the Direct Internal Recycling (DIR) concept. In this work, a preliminary simulation study of the linear mercury diffusion pump (LDP) is performed based on the Direct Simulation Monte Carlo (DSMC) method. While the dsmcFoam solver in the OpenFOAM platform is used, the inlet model named by fixed mass-flow-rate (FixedMFR) model is developed to control the mass flow rate into the pump, in accord with the condition of the experiment in 1950s. The simulated pumping speeds are in reasonable agreement with the experimental results when the pressure is in the range of 1 × 10−2 ~ 2 × 10−2 Pa, which implies that the DSMC model can be used for simulating the performance of the LDP. It should be noted that in the preliminary DSMC model, the mesh size is too large. Due to the large mesh size, the expansion of the mercury vapor steam is overestimated and the pumping speed is underestimated. Further work is required to find a proper way to generate the computational mesh for predicting the pumping performance of the LDP accurately and effectively.

Tungsten (W) as plasma facing material (PFM) has been used in ITER divertor. Many experiments indicate that due to helium (He) ion irradiation the thermal conductivities (TCs) of W can be significantly reduced. In this work, the lattice thermal transport property is studied based on the non-equilibrium molecular dynamics (NEMD) method. Firstly, the Kapitza resistance of grain boundaries (GBs) in W is obtained. It can be confirmed that the Kapitza resistance is positively correlated with GB energies, which reflect the lattice distortion degree in a sense. The result indicates that the distortion energy may play a key role in the thermal properties. Further simulation is performed to study the thermal resistance of GBs with nano He bubble. When the number of He atoms in bubble is less than a value, the thermal resistances are stable and change little. It implies that the effect of GBs is more significant than He bubble to block phonons diffusion. With the number of He atoms increasing, the property of heat conduction deteriorates further because the coupling of He bubble and GBs change the lattice distortion degree.

An integration design platform is built for the CFETR design. By a project lifecycle management (PLM) system, the platform could provide the function to coordinate the progress among different task groups distributed in China. The PLM system manages many kinds of documents, like the project description and scientific target, the sub-system requirement, design reports and critical data; and distributes them to corresponding users in time. Two systems complementary to PLM system are developed: (1) an engineering CAD/CAE design management, builds a link between the PLM system and the detailed designs, it receives general tasks from the PLM system and assigns them to designers, then returns detailed report and data to the PLM; (2) a integrated design framework to provide the environment for detailed design work, two sub-framework for physical and engineering design are integrated via a unified graphic user interface. Furthermore, the platform is built based on an advanced GPU-based design cloud system, which provides a remote design environment for widely distributed working forces, and meanwhile keeps the data centralized management. The integration design platform is still under development to support the system engineering for CFETR.

The development of CFETR integration design platform is in progress to accelerate the CFETR design in consideration of both core physics and engineering practicability. Within the engineering framework of CFETR integration design platform, the neutronics interface module has been implemented. This work presents the parameter study on helium cooled ceramic breeder blanket neutronics with the neutronics interface module of the CFETR integration design platform. The parameterized 3-D neutronic model of CFETR was set in the first place. Afterwards, the workflow of neutronic analyses was established. The concerned geometry and composition parameters of breeder blanket were selected as input and the tritium breeding ratio was selected as target. And, then, the workflow was abstracted as the mathematical model in the form of the so called response surface based on sufficient MCNP simulations. With the workflow or response surface model, the estimation and optimization of target parameter could be achieved. Finally, a set of local optimal parameters was proposed for CFETR helium cooled ceramic breeder blanket.

The ramp up scenario design, which considers of both physics and engineering constrains, plays an important part in fusion device design. A workflow of ramp up design, which includes Tokamak Simulation Code (TSC), ONETWO and ANSYS, has been developed on CFETR Integrated Design Platform. According to the 0-D design, the 1.5 D code TSC is used to build a ramp up scenario describing all parameters evolutions, targeting the design goals and attempting to remain in all constrains. In TSC simulation, the deposited power and driven current of auxiliary heating are calculated by ONETWO. The plasma current and PF coil currents are then used as input of ANSYS, to analysis the 3D eddy current and electromagnetic force in the main structural components. An example case of CFETR ramp up, with ohmic heating during the current ramp up phase and 57 MW of neutral beam and 10 MW of electron cyclotron at the flattop, is given in this article to show the function of the workflow. Under the unified environment for both physics and engineering design provided by CFETR integrated design platform, the present workflow will make the ramp up design more efficient.

China fusion engineering test reactor (CFETR) is now in the conceptual design phase. The main objective of CFETR is demonstration of fusion energy with 50 ~ 200 MW fusion power, fuel cycle of T self-sustained and steady-state operation with duty cycle of 0.3 ~ 0.5. The design of CFETR involves complex system structure, and there are complex constrains between physics and engineering. Between optimization of performance parameters and design of main structure and key components, numerous data exchange and iterative optimization are necessary for optimal design of subsystems. To do the optimization design, the CFETR integration design platform is under development. The main technical schemes for it include: a physical design platform and various engineering design modules are developed, then a global framework integrates them by standard interfaces and communication technologies; and a standard material and design criterion database unifies the reference data for the integration platform. The detailed study will be presented in this paper.

BACKGROUND Small cell carcinoma (SCC) of the prostate is a rare, aggressive disease. Evidence is limited; however, the current standard of care is chemotherapy. The benefit of local treatment modalities is unknown. METHODS We queried the National Cancer Database identifying all SCC/neuroendocrine cases of the prostate, excluding those with unknown nodal or metastatic status, unknown treatment, or those not receiving chemotherapy. Overall survival (OS) was calculated using Kaplan-Meier curves. Multivariable Cox proportional hazards model was used to identify factors associated with survival. A further subgroup analysis was performed on the utility of local therapy on survival in the nonmetastatic setting. RESULTS Our final cohort included 657 patients with a median age of 68. Most patients had positive lymph nodes (60.1%) and metastatic disease (70.0%). Median survival was 12 months (95% confidence interval [95% CI], 11.1-13.3 months) with a median follow-up of 11.8 months. Metastatic disease, age greater than or equal to 70, omission of androgen deprivation therapy (ADT), and lower income (P

e16522 Background: Cisplatin-based neoadjuvant chemotherapy is the standard of care for muscle invasive bladder cancer (MIBC) in cisplatin-eligible patients. This systematic review and meta-analysis provide an updated efficacy and safety comparison between the two most commonly used cisplatin-based regimens; dose-dense (dd) or conventional MVAC versus GC. Methods: We searched different databases for studies comparing MVAC versus GC in the neoadjuvant setting. Outcomes of interest included overall survival, downstaging to pT≤1, pathologic complete response (pCR), recurrence, and toxicity. Meta-analysis was conducted using the random-effects model. Results: We identified 24 studies from inception to March 2020; among them 17 were peer reviewed and 7 were only reported as abstracts in national or international meetings, including a phase 3, randomized-controlled clinical trial. Among peer-reviewed published studies, efficacy outcomes such as OS, downstaging and pCR were comparable between conventional MVAC and GC for MIBC. If including non-peer-reviewed studies, dd-MVAC was associated with favorable efficacy compared to GC in terms of downstaging (OR 1.45; 95% CI 1.15–1.82), and OS at longest follow-up (OR 0.63; 95% CI 0.44–0.81). However, GC was associated with a better safety profile in terms of febrile neutropenia (OR 0.32; 95% CI 0.13–0.80), anemia (OR 0.32; 95% CI 0.18–0.54), nausea and vomiting (OR 0.27; 95% CI 0.12–0.65) compared to dd-MVAC. Compared to MVAC, patients receiving GC had an increased risk of developing grade 3–4 thrombocytopenia (OR 4.70; 95% CI 1.59–13.89) and a lower risk of nausea and vomiting (OR 0.05; 95% CI 0.01-0.31). Certainty in the estimates was very low for most outcomes. Conclusions: Among peer-reviewed published studies, efficacy and safety outcomes were comparable between conventional MVAC and GC for MIBC. However, If including non-peer-reviewed studies, this analysis showed higher efficacy with dd-MVAC. A phase III randomized trial comparing the two regimens is needed to guide clinical practice

A tomographic reconstruction method is developed for the visible light imaging diagnostic system of Experimental Advanced Superconducting Tokamak (EAST) to provide the emissive profile on the poloidal cross section of the divertor region. Weight matrix is calculated by a ray tracing method according to the optical path of the visible light imaging diagnostic system in the delicate three-dimensional grid model of EAST first wall to avoid the influence of complex structures of the divertor region. The Philips-Tikhonov regularization algorithm with second-order correction is adopted to calculate the emissive profile. The phantom tests are performed and the effectiveness of the method is confirmed with signal to noise ratio (SNR) at 50. The method is applied to the experimental images detected by the visible light imaging diagnostic and clear peaks are identified in the reconstructed emission profiles, which is in consistent with the radiation belts observed in the experimental images.

The China Fusion Engineering Test Reactor (CFETR) integrated system code contains three parts: a zero dimensional code, a physics platform and an engineering platform. We use the zero dimensional code to identify a set of preliminary physics and engineering parameters for CFETR, which is used as input to initiate multi-dimension studies using the physics and engineering platform for design, verification and validation. Effective data exchange between the zero dimensional code and the physical platform is critical for the optimization of CFETR design. For example, in evaluating the impact of impurity radiation on core performance, an open field line code is used to calculate the impurity transport from the first-wall boundary to the pedestal. The impurity particle in the pedestal are used as boundary conditions in a transport code for calculating impurity transport in the core plasma and the impact of core radiation on core performance. Comparison of the results from the multi-dimensional study to those from the zero dimensional code is used to further refine the controlled radiation model. The data transfer between the zero dimensional code and the physical platform, including data iteration and validation, and justification for performance parameters will be presented in this paper.

China Fusion Engineering Test Reactor (CFETR) is now in conceptual design phase. CFETR is proposed as a good complement to ITER for demonstrating of fusion energy. Divertor is a crucial component which faces the plasmas and handles huge heat power for CFETR and future fusion reactor. To explore an effective way for heat exhaust, various methods to reduce the heat flux to divertor target should be considered for CFETR. In this work, the effect of extended out divertor leg on the peak heat flux is studied. The magnetic configuration of the long leg divertor is obtained by EFIT and Tokamak Simulation Code (TSC), while a hypothetical geometry is assumed to extend the out divertor leg as long as possible inside vacuum vessel. A SOLPS simulation is performed to study peak heat flux of the long leg divertor for CFETR. D2 gas puffing is used and increasing of the puffing rate means increase of plasma density. Both peak heat flux onto inner and outer targets are below 10 MW/m2 is achieved. A comparison between the peak heat flux between long leg and conventional divertor shows that an attached–detached regime transition of out divertor occurs at lower gas puffing gas puffing rate for long leg divertor. While for the inner divertor, even the configuration is almost the same, the situation is opposite.

The system code is under developing aiming to integrate the design of engineering and physics for China fusion engineering testing reactor. The system code comprises the engineering design platform and the physics design platform. The integration platform is developed to handle the data exchange and workflow interaction of submodules and to integrate the engineering platform and the physics platform together. In this paper, a methodology of developing the integration platform of system code with Java, OPTIMUS, and MySQL is presented. We develop the GUI of the integration platform with the help of Java JRE System library, such as AWT and Swing. Second, we choose EXCEL and TXT documents as the carrier of system data. Then, OPTIMUS is employed to establish the core workflow of the system code. Finally, the relational database software, MySQL, is chose to create user database, material database, criterion database, and manipulate record database. Besides that, the workflow of a vacuum vessel module is described in this paper as an instance.

A system code for integrated simulation and optimization is being developed for China Fusion Engineering Test Reactor (CFETR). The main function of CFETR system code is to achieve consistent physical objectives with achievable engineering parameters. As one of the most important works for tokamak, many aspects must be considered in the divertor design, such as high-heat loads removal, particle pumping, electromagnetic forces sustaining, remote handling compatibility, and so on. Inevitably, it is difficult to ensure all parameters are optimum due to the fact that some divertor parameters may be conflicting or highly interdependent. An underdeveloped divertor module code could address these issues. The purposes of developing such a module code are to explore key elements of the divertor system, simplify the design process, and determine the main engineering parameters by iteration of a self-consistent workflow. The divertor module code incorporates submodules with input and output ports, material and criterion databases, and simulation and optimization CAE tool-box, including CATIA, ANSYS, and OPTIMUS. This paper presents a typical design workflow for divertor module and a simplified simulation case to validate the feasibility of this workflow.

Molecular dynamics (MD) methods have been employed to study the point defects production induced by helium (He) plasma exposure and He bubbles interactions in bulk tungsten (W) from the atomic-level perspective. The primary variables examined are: simulation temperature ranging between 300 K and 2300 K, He concentration ranging between 741 appm and 2963 appm in order to study the effects of temperature and He concentration on micro-structural evolution, especially the Frenkel pairs number evolution; for the He bubble, radius up to around 1.25 nm, the He/V ratio up to around 3. In this work, the Frenkel pairs production induced by He aggregation and the volume change of bubble because of the He bubbles interactions are obtained. The results show that the number of Frenkel pairs produced generally increases as the temperature and He concentration increase, but it may reach a saturation with a higher He concentration. It is also found that the equilibrium He/V ratios of He-V bubbles are mainly ranged from 1.6 to 1.9. In addition, we observed that the He atoms in smaller bubble may be trapped into the larger bubble in the cases of their distance below 2 lattice parameters. Due to the decrease in number of He atoms, the He/V ratio of small bubble would decrease. These results can also contribute to the understanding for nucleation and growth of He bubbles in bulk W that are observed by the experiment techniques.