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Background Microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) tumours have a high response rate to immunotherapy. Antitumour activity and safety of serplulimab, a novel humanised anti-PD-1 monoclonal antibody, were evaluated in this phase II study. Methods In this ongoing, single-arm, open-label, phase II trial, patients with previously treated unresectable or metastatic MSI-H/dMMR solid tumours received intravenous serplulimab 3 mg/kg every 2 weeks for up to 52 cycles. The primary endpoint was objective response rate (ORR) assessed by an independent radiological review committee per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included additional efficacy measures, safety, and tolerability. Results As of 9 January 2021, 108 patients were enrolled, and 68 patients with confirmed MSI-H solid tumours were included in the main efficacy analysis population (MEAP). The median follow-up duration in the MEAP was 7.7 months, with an ORR of 38.2% (95% confidence interval, 26.7–50.8). Of the 108 patients, grade ≥3 treatment-emergent adverse events were reported in 53 (49.1%) patients; immune-related adverse events occurred in 52 (48.1%) patients. Conclusions Serplulimab demonstrates a durable antitumour effect and a manageable safety profile in previously treated patients with MSI-H solid tumours. Serplulimab is a promising tissue-agnostic treatment for previously treated MSI-H solid tumours. Trial registration NCT03941574.

Purpose: H3B-6545, a novel Selective ERα Covalent Antagonist (SERCA), inactivates both and wild-type and mutant ERα by targeting cysteine 530 and enforcing antagonist conformation. H3B-6545 demonstrated preclinical high activity in breast cancer models with constitutively active ESR1 mutations (Furman C, SABCS 2020) and clinical activity in pretreated women with ER+ breast cancer (Hamilton EP, ASCO 2021). Patients and Methods: The primary objective of the phase II is to estimate the objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), and secondary objectives include safety. Results: 94 pts were treated with 450 mg daily, the recommended phase II dose: 11 in the phase I and 83 in the phase II parts of the trial. Patients and tumor characteristics were presented previously (Hamilton EP, ASCO, 2021). As of March 31, 2021, grade (gr) 2 or higher adverse events (AE) reported in ≥10% were anemia (19%), nausea (17%), fatigue (16%), and diarrhea (12%). Laboratory gr 2 or higher abnormalities reported in ≥10% pts were creatinine clearance decrease (39%), hemoglobin decrease (38%), Lymphocytes decrease (37%), ALT increase (14%), AST increase (13%), bilirubin increase (12%), and creatinine increase (12%). AE of gr 1 sinus bradycardia (asymptomatic) was reported in 35% and gr 2 (symptomatic, no intervention needed) was reported in 5%. Gr 2 and 3 QTcF prolongation were reported in 2 and 3 pts, respectively. There were no treatment-related deaths. Efficacy estimates are presented in Table 1. CI: Confidence interval. N: total number of pts in full analysis set, used in PFS analysis. n: number of response-evaluable pts, used in ORR and CBR analysis. Efficacy estimates were consistent across the various subgroups. Responses were demonstrated in heavily pretreated pts, pts with visceral metastases, pts with constitutionally active ESR1 Y537S mutations, and in pts who received chemotherapy in the metastatic setting. Numerically higher response rate and longer PFS were observed in pts with ESR1 Y537s. Conclusions: H3B-6545 has a manageable safety profile and demonstrated single-agent anti-tumor activity in heavily pretreated ER+, HER2- mBC patients. Clinical activity was consistent across the various subgroups. Tumors harboring the constitutionally active ESR1 Y537S mutation may present higher ERα activity, and consequently enrich for luminal A traits and demonstrate greater lineage dependence on ERα. Table 1.Consistency of H3B-6545 activity across the key subgroupsEfficacyClinical CharacteristicORR % (95% CI)CBR % (95% CI)Median PFS mo (95% CI)Overall population (N=94, n=72)16.7 (8.9, 27.3)40.3 (28.9, 52.5)5.1 (3.2, 6.2)Liver and/or lung metastases (N=76, n=62)17.7 (9.2, 29.5)41.9 (29.5, 55.2)5.4 (1.8, 7.2)≥3 prior regimens (N=49, n=39)20.5 (9.3, 36.5)48.7 (32.4, 65.2)5.4 (3.5, 7.3)Prior chemotherapy (N=47, n=35)17.1 (6.6, 33.6)51.4 (34.0, 68.6)5.5 (3.6, 7.3)PgR+ (N=38, n=32)15.6 (5.3, 32.8)50.0 (31.9, 68.1)5.4 (2.0, 8.8)ESR1 clonal Y537S (N=10, n=10)30.0 (6.7, 65.2)60.0 (26.2, 87.8)7.3 (0.8, 11.2)ESR1 clonal D538G (N=19, n=17)0.0 (0.0, 19.5)35.3 (14.2, 61.7)5.4 (1.7, 7.2) Citation Format: Erika P Hamilton, Judy S Wang, Timothy Pluard, Aki Morikawa, E Claire Dees, Robert H Jones, Barbara Haley, Anne Armstrong, Adam L Cohen, Pamela Munster, Gail S Wright, Fadi Kayali, Lisa Cantagallo, Manav Korpal, Jenny Long, Jianjun Xiao, Benoit Destenaves, Lei Gao, Tarek Sahmoud, Antonio Gualberto, Dejan Juric. H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer - A phase II study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-17-10.

An accurate prediction of the hydrogen behaviors in the accident and management process is a crucial topic for both the hydrogen safety assessment and safety analysis in the confined enclosure like the containment of the nuclear power plant (NPP). Hence, the hydrogen behaviors including the transient light gas release, stratification and dissolution in the TH22 test facility for the NPP containment are analyzed and compared using the 3-D CFD code GASFLOW-MPI in this study. In this paper, the light gas helium is adopted as a substitute for the hydrogen in the calculations in accordance with the experiment. Firstly, the detached eddy simulation (DES) turbulence model, 3-D numerical model and experiment setup are introduced. Then, the hydrogen behaviors with the GASFLOW-MPI including the light gas release, stratification and dissolution are analyzed and validated with the experiment data. In addition, the velocity profiles, light gas concentrations, dimensionless numbers and temperature distributions are evaluated for the characteristics of the hydrogen behaviors. The results indicate that the calculation results agree well with the experiment data. Foremostly, the relative errors between the calculation results and experiment data during the phase of the dissolution of the light gas cloud are within 11.9%. Meanwhile, the relative errors of the time for the complete dissolution during the phase of the dissolution of the light gas cloud are within 5.0%. For the light gas release and stratification phase, the jet flow dominates as the Froude (Fr) number exceeds 10 during the time t = 600 s–800 s. Additionally, the time averaged centerline velocity and light gas concentration after the potential core region decay with a slop of 1/z which coincide with the theoretical jet limit. Lastly, the light gas concentrations and temperature distributions in all three phases are captured clearly with the GAFLOW-MPI. It demonstrates that the GASFLOW-MPI can accurately described the details of the related hydrogen behaviors in the accident and management process in the confined enclosure like the NPP. This paper can provide guidance for the numerical computation of the hydrogen safety issues in the confined space.

We conducted a phase I clinical trial of H3B-8800, an oral small molecule that binds Splicing Factor 3B1 (SF3B1), in patients with MDS, CMML, or AML. Among 84 enrolled patients (42 MDS, 4 CMML and 38 AML), 62 were red blood cell (RBC) transfusion dependent at study entry. Dose escalation cohorts examined two once-daily dosing regimens: schedule I (5 days on/9 days off, range of doses studied 1–40 mg, n = 65) and schedule II (21 days on/7 days off, 7–20 mg, n = 19); 27 patients received treatment for ≥180 days. The most common treatment-related, treatment-emergent adverse events included diarrhea, nausea, fatigue, and vomiting. No complete or partial responses meeting IWG criteria were observed; however, RBC transfusion free intervals >56 days were observed in nine patients who were transfusion dependent at study entry (15%). Of 15 MDS patients with missense SF3B1 mutations, five experienced RBC transfusion independence (TI). Elevated pre-treatment expression of aberrant transcripts of Transmembrane Protein 14C (TMEM14C), an SF3B1 splicing target encoding a mitochondrial porphyrin transporter, was observed in MDS patients experiencing RBC TI. In summary, H3B-8800 treatment was associated with mostly low-grade TAEs and induced RBC TI in a biomarker-defined subset of MDS.

Hydrogen energy is expanding world-widely in recent years, while hydrogen safety issues have drawn considerable attention. It is widely accepted that accidental hydrogen release in an open-air environment will disperse quickly, hence not causing significant hydrogen hazards. A hydrogen hazard is more likely to occur when hydrogen is accidentally released in a confined place, i.e. parking garages and tunnels. Prediction the main accident process, including the hydrogen release, dispersion, and combustion, is important for hydrogen safety assessment, and ensuring the safety installations during accidents. Hence, a postulated accident scenario induced by the operation of Thermal Pressure Relief Device in a tunnel is analysed for hydrogen fuel cell vehicles with GASFLOW-MPI in this study. GASFLOW-MPI is a well validated parallel CFD code focusing on the transport, combustion, and detonation of hydrogen. It solves compressible Navier-Stokes equations with a powerful all-speed Arbitrary-Lagrangian-Eulerian (ALE) method; hence can cover both the non-compressible flow during the hydrogen release and dispersion phases, and the compressible flow during deflagration and detonation. In this study, a 3D model of real-scaled tunnel is modelled, firstly. Then the hydrogen dispersion in the tunnel is calculated to evaluate the risk of Flame acceleration and the Deflagration-Detonation Transient (DDT). The case with jet fire is analysed with assuming that the hydrogen is ignited right after being injected forming a jet fire in the tunnel, the consequence of this case is limited considering the small hydrogen inventory. The detonation in the tunnel is calculated by assuming a strong ignition at the top of the tunnel at an unfavourable time and location. The pressure loads are calculated to evaluate the consequence of the hazard. The analysis shows that the GASFLOW-MPI is applicable at a widely range for tunnel accidents, meanwhile, the safety issues related to tunnel accidents is worthy further study considering the complexity of tunnels.

The liquid product from biomass direct pyrolysis is usually complex and difficult to effectively utilize. By combining hydrothermal conversion and low-temperature pyrolysis, the hemicellulose and cellulose of biomass can be transformed into value-added furfural and levoglucosan (LG), respectively. The effects of temperature during hydrothermal treatment (160–240 °C) and subsequent pyrolysis (340–400 °C) on the production of furfural and LG were investigated by using three typical agricultural wastes, namely corn stalk, peanut shells, and rice stalk. The maximum furfural yield of 4.2% was achieved upon hydrolysis of peanut shells at 200 °C. The hydrochar produced from peanut shells presented the highest LG yield of 7.3% (based on original biomass weight) for a pyrolysis temperature of 360 °C. Under this optimal condition, the total revenue from various products of the hybrid thermochemical process was estimated at $0.362 per kilogram of peanut shells, whereas furfural and LG account for 90% of the revenue.

A series of experiments were conducted to study the pressure and combustion characteristics of the high-pressure hydrogen during the occurrence of spontaneous ignition and the conversion from spontaneous ignition to a jet fire and explosion. Different initial conditions including release pressure (4–10 MPa), tube diameter (10/15 mm), and tube length (0.3/0.7/1.2/1.7/2.2/3 m) were tested. The variation of the pressure and flame signal inside and outside of the tube and the development of the jet flame were recorded. The experimental results revealed that the minimum ignition pressure required for self-ignition of hydrogen at different tube diameters decreased first and then increased with the extension of tubes. The minimum ignition pressure for tubes diameters of 10 mm and 15 mm is no more than 4 MPa and the length of the tubes is L = 1.7 m. The minimum release pressure required for spontaneous ignition of a tube D = 15 mm is always lower than that of a tube D = 10 mm at the same tube length. When the spontaneous ignition occurred, it did not absolutely trigger the jet fire. The transition from spontaneous ignition to a jet fire must go through the specific stages.

The main problem in on-site radiated emission test of EMU (Electric multiple unit) is the excess ambient electromagnetic noise due to the complex electromagnetic environment. In order to solve this problem, this paper proposed a novel approach for on-site radiated emission measurement test. A joint algorithm comprise blind source separation and adaptive signal processing is used to suppress the ambient electromagnetic noise. The normalized estimation of ambient electromagnetic noise is obtained by blind source separation algorithm, then the normalized estimation of ambient electromagnetic noise is used as the reference signal to adaptively cancel the ambient noise in the mixed electromagnetic noise, so the estimation of radiated noise of EMU is obtained. The simulation and experiment results showed that the proposed method can effectively suppress the ambient electromagnetic noise, thus realize the accurate measurement of the radiated emission of the EMU.

Catalytic hydrotreatment under supercritical ethanol conditions is an effective method for improving the performance of wood tar. In this study, the physicochemical properties of industrial wood ta...

To understanding the biomass pyrolysis process in depth, the pyrolysis mechanism of cellulose was investigated based on the combination of gas and liquid product releasing behavior with the structu...

Experiment and simulation were conducted to study the development process of jet fire and explosion induced by the high-pressure hydrogen spontaneous ignition. The pressurized hydrogen was released under different tube length and release pressure in the experiment. The overpressure generated by the leading shock and the light signal of the flame with different conditions were recorded. The propagation of the external jet flame was captured by a high-speed camera. Different parameters including velocity, temperature, and concentration distribution were analyzed based on the simulated results. It is revealed that the jet fire and explosion, which are induced by hydrogen self-ignition, must go through a series of specific stages of development, and this process has no significant correlation with pipe length and release pressure. This process consists of several stages, including the formation of the combustion zone downstream of the Mach disk; the flame chases the top of the jet along the shear layer; the flow velocity at the top of the jet decreases causing the ring vortex to disappear and the combustible gas to accumulate; the shear layer flame propagates to the top of the jet causing the explosion. Besides, the explosion will inevitably occur along with the jet fire, which is caused by the spontaneous ignition induced by the sudden release of high-pressure hydrogen and is developed in the open space.

Chemokine and chemokine receptors (CCRs) play a significant role in tumor infiltration of immune cells, tumor angiogenesis and distant metastasis. In this study, we explored the importance of CCRs in gastric cancer (GC) by analyzing the datasets from TCGA database. First, we analyzed the characteristics of the CCRs mutations. Then, we screened the differentially expressed CCRs and performed GO functional annotation and KEGG pathway analyses to explore their potential biological functions. Using multivariate Cox regression analyses, we constructed a prediction model based on four-CCRs (CCL15, CCL21, CCR3 and ACKR3) signature, and we found that the risk score of the model was an independent prognostic factor of GC. Next, a nomogram was constructed to assess the prognosis of GC patients. GSEA indicated that the high-risk group was significantly enriched in immune response and immune system process. Moreover, GSVA was employed to investigate the up- and down-regulated signaling pathways in the high- and low-risk groups. The correlation between risk score and immune-cell infiltration indicated that the four-CCRs signature might play a pivotal role in GC immune microenvironment. In conclusion, we revealed the potential molecular mechanisms of CCRs in GC and constructed a prediction model which might guide personalized treatment and prognosis for GC patients.

BACKGROUND: Existing research shows that long non-coding RNAs (lncRNAs) have important regulatory effects in gastric cancer (GC). In recent years, focally amplified lncRNA on chromosome 1 (FALEC) has been repeatedly reported to have carcinogenic effects in thyroid carcinoma, colorectal cancer, and endometrial cancer, etc. While the role and mechanism of FALEC during GC tumorigenesis remains unclear. METHODS: The levels of FALEC, microRNA-203b (miR-203b), and Recombinant Pim-3 Oncogene (PIM3) were confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell autophagy, proliferation, apoptosis, migration, and invasion were estimated using western blot, transmission electron microscopy (TEM), cell counting kit-8 (CCK-8), flow cytometer, and Transwell assays. The interaction between miR-203b and FALEC or PIM3 was verified using a dual-luciferase reporter assay. Moreover, the involvement of miR-203b and PIM3 in the regulatory effects of FALEC on GC was determined with rescue experiments. RESULTS: The results showed that FALEC and PIM3 were highly expressed, while miR-203b was lowly expressed, in GC. FALEC knockdown repressed GC cell proliferation, migration, and invasion, and promoted apoptosis and autophagy in vitro. Meanwhile, FALEC knockdown prevented growth and induced GC autophagy in vivo. This shows that FALEC upregulated PIM3 by sponging miR-203b in GC cells. Besides, FALEC induced the malignant behaviors of GC cells by regulating the miR-203b/PIM3 axis. CONCLUSIONS: The FALEC/miR-203b/PIM3 axis might be a promising therapeutic target for therapy in GC patients.

In the process of continuous development of the network, big data has been widely used and has received increasing attention and importance. Financial big data belongs to a brand-new field involved in the continuous development of Internet finance. In this context, internet finance presents a more obvious openness and diversity, which also makes it more dynamic in its development. But some risks will also be magnified by this. Therefore, in terms of the internet finance, it is necessary to focus on the implementation of risk control.

Ring resonators and Mach-Zehnder interference structures are promising candidates for compact optical filters and electro-optic modulators in the field of integrated photonics. Two types of ring-loaded Mach-Zehnder interferometers (MZIs) based on 3D direct laser writing are designed by finite-element simulation software. The model is composed of two Y-waveguides, Mach-Zehnder waveguide arm, and a micro-ring coupled with Mach-Zehnder waveguide arm side. The optimal radius of curvature of the two models and the spectral characteristics of the two models are calculated by numerical analysis. The optimal radii of curvature for the bend of Y-waveguides are 385 μm, the average free spectral ranges (FSRs) of are about 18 nm, and the average full widths at half maximum (FWHM) are about 1.4 nm and 3.2 nm, respectively, for the two MZI models. The numerical analysis results have practical reference value for the fabrication of resonator coupled Mach-Zehnder interferometer using 3D direct laser writing technology.

BackgroundPieces of evidences have shown the important regulatory effects of long non-coding RNAs (lncRNAs) in gastric cancer (GC). While it is not entirely clear for the role and mechanism of focally amplified lncRNA on chromosome 1 (FALEC) during GC tumorigenesis. MethodsThe levels of FALEC, microRNA-203b (miR-203b), and PIM3 were confirmed by qRT-PCR. And cell autophagy, proliferation, apoptosis, migration, and invasion were estimated using western blot for autophagy-related proteins, Transmission electron microscopy (TEM), CCK-8, flow cytometer, and Transwell assays in NCI-N87 cells and Xenograft tumor. Besides, the interaction between miR-203b and FALEC or PIM3 was verified using a dual-luciferase reporter assay. Moreover, the involvement of miR-203b and PIM3 in the regulatory effects of FALEC on GC was determined by rescue experiments. ResultsThe results proved that FALEC and PIM3 were highly expressed, while miR-203b was lowly expressed in GC. FALEC knockdown repressed GC cell proliferation, migration, and invasion, promoted apoptosis and autophagy in vitro. Meanwhile, FALEC knockdown prevented growth and induced GC autophagy in vivo. In mechanism, FALEC could upregulate PIM3 by sponging miR-203b in GC cells. Besides, FALEC induced the malignant behaviors of GC cells by regulating the miR-203b/PIM3 axis. Conclusions Therefore, FALEC/miR-203b/PIM3 axis might act as the promising therapeutic target for the therapy of GC patients.

Background Metastasis and recurrence, wherein circulating tumour cells (CTCs) play an important role, are the leading causes of death in colorectal cancer (CRC). Metastasis-initiating CTCs manage to maintain intravascular survival under anoikis, immune attack, and importantly shear stress; however, the underlying mechanisms remain poorly understood. Methods In view of the scarcity of CTCs in the bloodstream, suspended colorectal cancer cells were flowed into the cyclic laminar shear stress (LSS) according to previous studies. Then, we detected these suspended cells with a CK8+/CD45−/DAPI+ phenotype and named them mimic circulating tumour cells (m-CTCs) for subsequent CTCs related researches. Quantitative polymerase chain reaction, western blotting, and immunofluorescence were utilised to analyse gene expression change of m-CTCs sensitive to LSS stimulation. Additionally, we examined atonal bHLH transcription factor 8 (ATOH8) expressions in CTCs among 156 CRC patients and mice by fluorescence in situ hybridisation and flow cytometry. The pro-metabolic and pro-survival functions of ATOH8 were determined by glycolysis assay, live/dead cell vitality assay, anoikis assay, and immunohistochemistry. Further, the concrete up-and-down mechanisms of m-CTC survival promotion by ATOH8 were explored. Results The m-CTCs actively responded to LSS by triggering the expression of ATOH8, a fluid mechanosensor, with executive roles in intravascular survival and metabolism plasticity. Specifically, ATOH8 was upregulated via activation of VEGFR2/AKT signalling pathway mediated by LSS induced VEGF release. ATOH8 then transcriptionally activated HK2-mediated glycolysis, thus promoting the intravascular survival of colorectal cancer cells in the circulation. Conclusions This study elucidates a novel mechanism that an LSS triggered VEGF-VEGFR2-AKT-ATOH8 signal axis mediates m-CTCs survival, thus providing a potential target for the prevention and treatment of hematogenous metastasis in CRC.

During a severe accident involving a Nuclear Power Plant (NPP), a hydrogen-enriched stratification may occur in the dome of the containment. This is due to the gaseous density difference of a steam/hydrogen turbulent jet released from the break. This accident scenario is one of the high-ranking phenomena identified in the Phenomena Identification and Ranking Table (PIRT) for containment safety thermal hydraulics. In this work, the temporal evolution of the stratification erosion is analysed using the parallel CFD code GASFLOW-MPI with comparison to the experimental data from the THAI TH-20 benchmark, where helium is used as a hydrogen simulate. Identifying a suitable turbulence model is an important issue for a successful stratification erosion simulation due to turbulent mixing between the stratification and turbulent jet featured with the sharp velocity and density gradients. Three well-known turbulence models: 1. The classic k-e model, 2. Large Eddy Simulation (LES) model and 3. Detached Eddy Simulation (DES) model are employed to evaluate their performances. Due to the negative buoyancy effect resulting from the light gas layer, the jet gradually loses its initial momentum and cannot penetrate the stratified layer in depth. The interaction Froude (Fr) number which is used to categorize the mixing mechanism is close to 1 in this work, indicating that the erosion process of the stratified layer is dominated by both the molecular diffusion and the momentum transport. The experimental data measured at different heights in THAI TH-20 benchmark, from the pure air region at the lower containment region up into the large helium concentration gradient region, and further up to high helium concentration region at the top of the containment. The calculated results show that the LES and DES turbulence models can capture time histories of helium concentration at all of the sensor points accurately, while the k-e turbulence model predictions are always delayed due to its overestimating the turbulence mixing in the stratified layer. Moreover, compared with the k-e model, more detailed turbulent eddy structure is resolved by the LES model and DES model, whose frequency satisfies the negative −5/3 energy decay rate for a wide region of frequency. Therefore, the LES and DES models are recommended for the stratification erosion simulation. This can provide guidance for nuclear engineers analysing hydrogen distribution phenomena during severe accidents.

Hydrogen energy is one of the most promising candidates for clean and renewable energy in the coming future. Under the commission of safety study in hydrogen application, storage and transportation, CFD code analysis is always an important component in the engineering design workflow. Among the three stages of CFD analysis, the solver part has been well studied in the past two decades. However, the pre-processing and post-processing parts demand further study. The meshing process can be an important factor on the convergence speed and simulation reliability in hydrogen CFD study, which makes Cartesian mesh as an important choice in hydrogen safety codes However, traditional meshing process relies heavily on hand-based input card manipulation, which is inefficient and prone to human's improper manipulation. With the recent developments in codes like GASFLOW-MPI and FLACS, new functions have been added, which provide automatic mesh generation directly from the CAD geometry. In this work, the algorithm on automatic mesh generation will be further studied, which is more robust on the defective CAD geometries. In addition, application of the new evolving Virtual Reality technology will be implemented on the post-processing of the simulation result, which provides a better view in a real 3D environment. In the application part, three cases on a leaking hydrogen tank, a steam generator and a single car garage will be studied with regards to the validation of the new mesh generation approach. Finally, the Virtual Reality (VR) rendering performance will be studied based on the leaking hydrogen distribution in the single car garage. The work shows that the winding number based approach is an efficient and robust solution for the mesh generation of hydrogen CFD codes, and VR technology is a powerful tool for hydrogen safety simulation result rendering.

A hydrogen leak from a facility, which uses highly compressed hydrogen gas (714 bar, 800 K) during operation was studied. The investigated scenario involves supersonic hydrogen release from a 10 cm2 leak of the pressurized reservoir, turbulent hydrogen dispersion in the facility room, followed by an accidental ignition and burn-out of the resulting H2-air cloud. The objective is to investigate the maximum possible flame velocity and overpressure in the facility room in case of a worst-case ignition. The pressure loads are needed for the structural analysis of the building wall response. The first two phases, namely unsteady supersonic release and subsequent turbulent hydrogen dispersion are simulated with GASFLOW-MPI. This is a well validated parallel, all-speed CFD code which solves the compressible Navier-Stokes equations and can model a broad range of flow Mach numbers. Details of the shock structures are resolved for the under-expanded supersonic jet and the sonic-subsonic transition in the release. The turbulent dispersion phase is simulated by LES. The evolution of the highly transient burnable H2-air mixture in the room in terms of burnable mass, volume, and average H2-concentration is evaluated with special sub-routines. For five different points in time the maximum turbulent flame speed and resulting overpressures are computed, using four published turbulent burning velocity correlations. The largest turbulent flame speed and overpressure is predicted for an early ignition event resulting in 35–71 m/s, and 0.13–0.27 bar, respectively.

Fiber Bragg grating (FBG) sensors are popular sensing elements and have a wide application of strain monitoring in the area of structural health monitoring, medical and aerospace due to the features of electromagnetic interference resistance, high sensitivity and simplicity. Here, a simple intensity demodulation configuration based on a semiconductor ring laser is proposed for FBG dynamic strain sensing system. Due to the characteristics of semiconductor optical amplifier, it can act as the gain medium as well as light source. An arrayed waveguide grating module is adapted to be the wavelength demodulator. It is feasible for this configuration to respond when FBG is subjected to dynamic strains at a high frequency. Additionally, a simultaneous dual-channel interrogation system is in detail discussed. This interrogation scheme can be widely utilized in structure health monitoring because of its low insertion loss, high stability and low cost.

The effect of potassium in biomass on the catalytic activity of ZSM-5 zeolite in the fast pyrolysis of biomass was investigated using 2-methylfuran (2-MF) as the typical model compound. The mechanism of action of potassium was explored in detail, along with the physicochemical properties of ZSM-5, including crystallinity, pore structure, and surface acidity. The physicochemical properties of ZSM-5 deteriorated to varying degrees after being tainted with different potassium sources (KOH, K2CO3, KAc, and KCl). Compared with neutral KCl and strong alkali KOH, K2CO3, and KAc, with weaker alkalinity but larger crystal structure, exerted a larger influence on ZSM-5. Changes in ZSM-5 tainted with K2CO3 were the greatest, and crystallinity, surface area, acidity, and the corresponding yields of valuable aromatic hydrocarbons and gas products, all declined significantly, compared with raw ZSM-5. When the amount of K(CO32−) on ZSM-5 was less than 0.5 wt%, only minor (

Power-to-Gas technologies could play an important role in future energy systems, since they make it possible to store surplus electric energy from fluctuating renewable energy sources such as solar and wind. In Power-to-Gas concepts, the first step towards storage is the production of H2 by electrolysis, a possible further step is methanation. The Engler-Bunte-Institute, Fuel Technology at Karlsruhe Institute of Technology is conducting research on catalytic methanation in slurry bubble column reactors, which represent a highly load flexible reactor technology. To obtain experimental data at a semi-industrial scale a methanation pilot plant was built and commissioned. The plant is equipped with various safety valves, which may release the hazardous gases H2, CO and CH4 in the chemical reactor into the environment in the unintended case of overpressure, which may lead to a flammable and/or toxic cloud, threatening the safety of the workers and other humans near the plant. In this work, the safety evaluation of the accidental release in the methanation plant is performed using the numerical tool GASFLOW-MPI. Both toxicity and flammability of the hazardous gas cloud are analyzed and discussed. A local-global two-step simulation strategy, including a local computational model and a global computational model, is employed to calculate the hazardous gas dispersion efficiently and accurately. In the first step, a local detailed computational model with fine mesh is used to calculate the release mass flow through the exhaust tube and the complicated shock waves directly without any further assumption model such as the notional nozzle model. In the second step, a large-scale model with the relatively coarse mesh is chosen to efficiently predict the hazardous gas dispersion around the entire methanation plant. Moreover, the performances of two different types of exhaust pipes are compared and discussed, and the recommended exhaust pipe design is provided. The simulation results show that version B of the exhaust tubes is more recommendable from the viewpoint of safety.

Large bridges and industrial equipment may encounter natural disasters (earthquakes, tsunamis, etc.) and man-made effects during their service period. When they are subjected to these external influences, the structure may be deformed or even cracked, and the internal stress of the structure can also cause the occurrence of acoustic emission events. In this work, we report a fiber-optic acoustic emission sensing system using a semiconductor optical amplifier (SOA)-based fiber-ring laser source including a non-tunable fiber Fabry-Perot filter (NTFFPF) to demodulate dynamic signals from fiber Bragg grating (FBG) sensors. The shift in the FBG reflection spectrum caused by external strain is demodulated by the NTFFPF in the ring laser cavity, which ultimately produces an amplified output signal. The proposed system was used to detect the high-frequency acoustic emission signals generated by the piezoelectric buzzer. Experimental results show that this system can demodulate high-frequency acoustic emission signals with a good response and a high signal-to-noise ratio up to 21.6 dB. At the same time, acoustic emission signals generated by an ultrasonic vibrator with a frequency of 40 kHz are detected simultaneously with a FBG sensor and a piezoelectric sensor placed in the middle of a square aluminum plate. The angle-dependent acoustic emission measurement is performed by placing the ultrasonic vibrator at different angles from 0° to 90° in the radial direction of the FBG sensor. The results show that the sensor system can accurately detect the high-frequency acoustic emission signals on the aluminum plate and larger signal amplitude can be obtained when the angle between the ultrasonic vibrator and the FBG sensor axial is in the range of 0-60°. The fiber ring laser sensing system proposed in this paper has application prospects in many aspects, such as acoustic emission source location and ultrasonic detection.

Near-field electroluminescent refrigerators (NFERs) have potential applications in thermal management. The input electricity can manipulate the photons’ electrochemical potential to realize heat transfer from cold side to hot side. However, the coupled properties and the overall optimum performances of the NFER driven by actual power sources have not been studied. A model of solar cell powered NFER is conceptually proposed and optimally designed. The electrical coupling characteristics between the solar cell and the NFER are discussed. The operating region of the NFER’s input voltage is provided. The structure and the electrical parameters are optimized to obtain the maximum efficiency. The effects of the vacuum gap, the emitter’s thickness, and the solar irradiance on the optimum performances are analyzed. Making trade-offs between the efficiency and cooling heat flow rate, the optimum region of solar irradiance is determined. The proposed model and the parametric optimal analysis can provide a route for solar-driven refrigerators.

A non-invasive optical fiber pulse sensor is proposed and experimentally demonstrated. It comprises a simple structure in which a section of thin-core fiber is spliced into another single-mode fiber. And a silicone rubber device is designed to ensure that weak pulse signals are detected. To assess the availability of the optical fiber pulse sensor, a commercial photoplethysmograph is used to measure the pulse of the same subject as a control. The measurement results of the two methods are consistent. The fiber pulse sensor can show a segmented signal in individual pulses, which provides more physiological information. It also possesses the advantages of high sensitivity, simple signal acquisition and processing, easy fabrication, and thus is an ideal candidate for replacing traditional electrical sensor.

With the rapid development of photonic integrated circuit, waveguide-based electro-optic modulators are widely used in the fields of optical communication, optical signal processing and optical sensors. The Mach-Zehnder modulator is one of the most widely used device structures as a particular kind of optical switching element, which has the advantages of great accuracy and high sensitivity. We investigate two types of Mach-Zehnder modulators (using balanced and unbalanced interferometers) based on lithium niobate (LiNbO3) through theoretical and numerical analysis. The transmission characteristics of the balanced Mach-Zehnder modulator are numerically analyzed while the electric field is applied across the waveguide in one of the arms (or the two arms) of the interferometer, and the transmission characteristics of the unbalanced Mach-Zehnder modulator with different length differences between the two waveguide arms are studied. Numerical calculation results show that the transmission of the waveguide in the Mach-Zehnder structure changes sinusoidally, with alternately switching between port 2 and port 4. The theoretical results in the present work can provide some guidance for developing the practical optical modulator devices.

A time-frequency analytical method using a combined adaptive optimal-kernel with compressed sensing is proposed in this paper for analyzing the electromagnetic interference in railway GNSS system. The proposed method is applied to analyzing the liner-frequency-modulated signal and pantograph-catenary arc interference in GNSS system, the performance of the proposed representation is further verified by comparing with short-time Fourier transform and Wigner-Ville distribution.

A dynamic film model is developed in GASFLOW-MPI to study the thermal-hydraulic behaviour of the containment with external film cooling, i.e. the passive containment cooling system (PCCS). Former researches on PCCS are mainly conducted with lumped parameter computer codes, hence the CFD study coupling both sides of the containment is necessary. In this study, the dynamic film model of GASFLOW-MPI is validated with both a separate effect test EFFE (Experiments on Falling Film Evaporation) facility and an integral test facility. Firstly, the 2D model of the EFFE facility is built and analyzed in both dry cases and wet cases. The results agree well with the experimental data indicating that the dynamic film model of GASFLOW-MPI can provide reasonable predictions for both heat and mass transfer between the film and gas. Then the 3D model of the scaled down containment test facility is built with the cylindrical coordinate, and a mesh sensitivity analysis is conducted with one section of the 3D model. The 3D model results show that the steady state analysis of GASFLOW-MPI has good agreement with experimental data. Furthermore, GASFLOW-MPI manages to capture the thermal stratification in the containment which is underestimated in former research. The heat transfer analysis on both sides of the containment shell shows that the steam condensation in the dome contributes almost 50% to the total steam condensation, while the film evaporation in the cylinder part contributes about 90% for the heat removal of PCCS. This is the result of heat and mass transfer on both sides of the containment shell coupling with each other. The validation of these two cases indicates that the GASFLOW-MPI can provide reasonable predictions for the thermal hydraulics behavior on both sides of the containment when implementing PCCS. Further research will focus on transient analysis and the model for film coverage.

Due to the limited space on the train, the shielded cables were utilized to protect signal cables against influence by the disturbance from power cables which arranged in parallel with the signal cables. To reduce cable coupling, the cables are usually arranged close to train body. The influence of the body of the train should not be ignored. To analyze the coupling of shielded cables in the train, a hybrid method is proposed based on the circuit model. To solve the influence from the reflection of the train body, Green's function deduced from image theory is utilized. The current on the shielding layer is calculated by lumped circuit model, which is set up by admittance parameter matrix. And then, the coupling voltage on the core of shielded cable is given by using BTL function. Finally, a laboratory test case and a field test were investigated. Results of the proposed method were validated by measurement results.

In this paper, a non-tunable fiber Fabry–Perot filter (FFPF) is configured to demodulate dynamic strain signals in a multiplexed dynamic sensing system based on a fiber ring laser. A semiconductor optical amplifier (SOA) contained in the fiber ring laser cavity enables this system to implement multiplex operation because of the inhomogeneous broadening of the SOA source. The shift of the reflective spectrum of the fiber Bragg grating caused by external dynamic strain is demodulated by the FFPF in the laser cavity, which ultimately generates an amplified output. In the experiment, the sensing system can respond to dynamic strains at ultra-high frequencies up to megahertz, and an example for detection of ultrasonic signals in water has been successfully demonstrated. A dual-channel system for multiplexing demodulation is also discussed. This system presented here has a simple structure and a low cost, which makes it attractive for dynamic strain detection in structural health monitoring.

Window composting with inoculation or frequent turning is a superior way to improve traditional composting efficiency. However, the relationship between the innocent treatment in composting with inoculation or turning and microbial dynamics is unclear. Here, the impact of inoculation and turning for full scale composting on core bacterial community and their co-occurrence network as well as harmless level were compared by network analysis. Results showed that composts with both inoculation and turning had 46% increase of total organic carbon degradation compared to traditional composting and decreased the abundance of potential pathogens. The relative abundance of thermophilic bacteria and Galbibacter, Methylocaldum, Steroidobacter, etc. increased during composting with turning and inoculation. Luteimonas, Sphaerobacter, Turicibacter and Flavobacterium as core bacteria had significant difference between control and composting with enhanced innocent treatment efficiency. Network analysis suggested that turning increased the number of indigenous core bacteria and inoculation enhanced the interaction among key bacterial network.

287 Background: The best choice of second-line chemotherapy regimen for patients with advanced gastric cancer is still debated. Anti-VEGF target therapy is proven to be effective both in second and third line settings. Apatinib, a highly selective VEGFR2 inhibitor, has been demonstrated to be efficacious and well-tolerated for third line of treatment in gastric cancer. The aim of this study is to evaluate the safety and efficacy of apatinib in combination with irinotecan in the second line treatment of advanced gastric cancer. Methods: With the expectation of improving PFS to 4.4m, this investigator-initiated, single arm, multi-center, registered phase II prospective study was designed to enroll 62 eligible patients diagnosed with advanced gastric cancer. Each participant was expected to receive chemotherapy plus apatinib (irinotecan 1800mg/m2, d1, Q2W; apatinib 500mg po qd). The severity of side effects was established according to Common Terminology Criteria for Adverse Events (CTCAE),Version 4.0. Efficacy assessed every three cycles (6 weeks) during the study. The primary endpoint was PFS. The secondary endpoint was OS, ORR, and DCR. The tumor response was determined according to RECIST 1.1 criteria. Results: Baseline characteristics (FAS population): From March 2019 to April 2021, 31 patients from 4 centers in Guangdong province were enrolled. Among them, 28 are eligible for analysis. There are 16 females and 15 males, median age 55 years old. Safety: 82.4% patients reported adverse events (AEs). The incidence of grade 3-4 AEs was 52.9%. Main 3-4 AEs were neutropenia (32.4%), leucopenia (17.6%), anorexia (8.8%), hypoalbuminaemia (8.8%), thrombocytopenia (5.9%), nausea (5.9%). Efficacy: By Aug 31th, 2021, 28 patients were evaluable for response and survival, 1 of them achieved complete response (CR), 10 of them achieved partial response (PR), 8 achieved stable disease (SD), and 9 experienced progression disease (PD). The ORR is 35.48%, the DCR is 61.29%. Median PFS is 4.40m, median OS is 6.64m. Conclusions: Adding apatinib to irinotecan chemotherapy as the second line treatment would be well tolerant in patients with advanced gastric cancer. This indicated the combination could be a potential treatment option for patients with advanced gastric cancer. Clinical trial information: ChiCTR1900021377.

With the development of the computational capability, Computational Fluid Dynamics (CFD) is more and more widely used as the best estimate approach for the design and safety issues related to reactor thermal hydraulics. The conjugate condensation heat transfer is a widespread phenomenon in nuclear safety analysis, such as a key heat transfer process for Passive Containment Cooling Systems (PCCS) in advanced passive reactors. However, the uncertainty analysis of CFD predictions applied to reactor thermal hydraulics is still immature. In this work, the uncertainty quantification of the condensation heat transfer in COPAIN experiment was performed using a well-validated parallel CFD code GASFLOW-MPI. Six sources of uncertainty were considered here, including the inlet velocity/temperature/turbulent intensity, outlet pressure and condensation heat transfer coefficient, as well as the computational mesh size. For the first five uncertainty sources, the deterministic sampling method was employed in this work to reduce the required number of sampling points. Unlike the ensemble in the random sampling Monte Carlo method, the deterministic sampling method represents the probability density function with an ensemble that has the same statistical moments but contains much fewer samples. Two ensembles which were 2nd and 4th order statistical moments accuracy, respectively, were employed in this work and their performances were compared. The Richardson extrapolation method was used to quantify the uncertainty propagated from the computational mesh size. The contributions of each uncertainty source to the condensation heat flux and temperature distribution were also performed. The results of the uncertainty quantification are consistent well with the experimental data in COPAIN facility, suggesting that the deterministic sampling method and Richardson extrapolation method are powerful tools for uncertainty quantification of CFD calculations.

Hydrogen safety analysis is an important issue in the field of the nuclear severe accident. Fast, robust and accurate simulation of the complex hydrogen behavior in the nuclear containment is the first but critical step for hydrogen risk mitigation. GASFLOW-MPI is a widely used CFD numerical tool which provides the fast and reliable prediction, because of its parallel computational capability and well-validated models. However, due to its manual input-card based mesh generation, the whole meshing process is slow and lacks user friendliness. Therefore, a fast automatic mesh generation module is of importance and profit for practical industrial applications. Nowadays, Computer Aid Design (CAD) has become the formal standard for project design and preview. In this work, a mesh generation module is developed for GASFLOW-MPI, which directly uses the CAD file as the input for automatic mesh generation. The module exploits a voxelization-based method, which seeks to generate a Cartesian mesh by tracing rays directed into the geometry. The complexity of the mesh generation algorithm is also analyzed. Three models, including a toy problem, a steam generator compartment model, and a complex full scale reactor containment model are used to validate the new developed automated mesh generation module. The results show that meshes are generated at fast construction speed and well match the original CAD models.

Hydrogen fires may pose serious safety issues in vented compartments of nuclear reactor containment and fuel cell systems under hypothetical accidents. Experimental studies on vented hydrogen fires have been performed with the HYKA test facility at Karlsruhe Institute of Technology (KIT) within Work Package 4 (WP4) - hydrogen jet fire in a confined space of the European HyIndoor project. It has been observed that heat losses of the combustion products can significantly affect the combustion regimes of hydrogen fire as well as the pressure and thermal loads on the confinement structures. Dynamics of turbulent hydrogen jet fire in a vented enclosure was investigated using the CFD code GASFLOW-MPI. Effects of heat losses, including convective heat transfer, steam condensation and thermal radiation, have been studied. The unsteady characteristics of hydrogen jet fires can be successfully captured when the heat transfer mechanisms are considered. Both initial pressure peak and pressure decay were very well predicted compared to the experimental data. A pulsating process of flame extinction due to the consumption of oxygen and then self-ignition due to the inflow of fresh air was captured as well. However, in the adiabatic case without considering the heat loss effects, the pressure and temperature were considerably over-predicted and the major physical phenomena occurring in the combustion enclosure were not able to be reproduced while showing large discrepancies from the experimental observations. The effect of sustained hydrogen release on the jet fire dynamics was also investigated. It indicates that heat losses can have important implications and should be considered in hydrogen combustion simulations.

The condensation on containment shell drives the nearby gas downwards creating a natural convection in containments which plays a key role for long-term passive containment cooling. In late phase of accident where hydrogen and steam accumulate in containment, recovery of containment cooling can cause the loss of steam-inert status for the containment atmosphere leading to hydrogen risk in containment. This process is analyzed in this paper focusing on the natural convection driven by wall condensation, and its influence on hydrogen distribution. Firstly, both convective heat transfer model and condensation model are validated with two separate effect experiments. The analogy argument among monument, heat and mass transfer is adopted in GASFLOW-MPI to analysis monument, mass and energy transfer between structure surface and fluid. The simulation result shows good agreement with experiment data. Then a simplified containment model including two steam generator compartments and pressurizer compartment is built and analyzed with GASFLOW-MPI with a postulated accident condition. To avoid long time calculation, the initial condition is calculated with a methodology that is designed to estimate containment status during severe accident provided by EPRI. Two cases are simulated, one without steam injection, where the natural convection drives only by condensation. Other one considers the decay heat that is postulated as a constant steam injection to simulate the natural circulation in containments. Result shows that, during the containment cooling, a transient stratification will occur, leading to high concentration of steam in the dome while low concentration at bottom. This is because the condensed gas is driven downwards near containment shell, pushing steam-rich gas at bottom upwards. The stratification of steam results in a reverse stratification of hydrogen, with high concentration at bottom while low concentration in the dome. Combustibility cloud shows that there is still a stratification of combustibility in containment, though the hydrogen distribution is quite uniform at the end of computation. Therefore, the hydrogen risk should be concerned when implementing containment cooling, especially the local hydrogen concentrate happening at the bottom of containment.

Turbulent flow at a wide range of Mach numbers may occur during design based accidents (DBA) or severe accidents in nuclear power plants (NPPs), for instinct, incompressible gas mixing flow (subsonic), gas mixture critical flow (transonic) or detonation (supersonic). All of them need to be simulated in safety analysis of NPP containments, therefore we need the computer code to have the capability to simulate all-speed flow. GASFLOW-MPI is a well-developed parallel all-speed CFD software used to predict gas turbulent mixing, chemical combustion and other related thermal-hydraulic phenomena in containments of NPPs. In order to validate the all-speed turbulent flow capability of GASFLOW-MPI, four turbulent jet cases over a broad range of Mach number have been performed in this paper. The large eddy simulation (LES) turbulent model is employed to capture more details of turbulence and flow features in this study. The standard Smagorinsky sub-grid scale model is utilized to model the unresolved turbulent behaviors at sub-grid scale. Both the instantaneous and time-averaged flow fields are analyzed as well as turbulent statistics to compare with the experimental data sets. The simulation results are in good agreement with the experimental data sets available in the literature. The shear layer instability is observed in the instantaneous flow field which leads to the end of the potential core and then the centerline velocity begins to decay. The size of the potential core and the decay rate of the centerline velocity are consistent well with the experiments. The turbulence intensity in the fully developed region agree well with the experimental data and the velocity power spectrum reveals the -5/3 law. Simulation results show that the compressibility has a significant effect on a free shear layer growing rate which is consistent with the experiments. The complex shock wave structure is also captured exactly by the second-order total variation diminishing (TVD) scheme. GASFLOW-MPI code has been successfully validated using the experimental data of turbulent jet flow at the wide regime of Mach numbers.