Integrating Numerical Models for Efficient Simulation of Compressor Valves

The motion of automatic, self-acting valves is a primary aspect in achieving superior compressor reliability and performance. Simulation of compressor valve mechanics involves a complex set of interactions that include characteristics of the compression chamber, thermodynamics, gas flow, valve motion, and pressure pulsations through the valve passages. One-dimensional (1D) lumped simulation models that encompass these interactions have been formulated and refined over the past several decades. During that same time period, finite element theory for fluid-structural-interaction (FSI) has been developed. Â FSI provides three-dimensional (3D) results across the entire fluid and solid domain and is well-suited for compressor simulation. However, the usage of FSI on real problems has not been adopted until much more recently, as sufficient computational resources became available. Still, the high computational expense and significant run times create a practical barrier to using FSI as a routine design tool. This paper presents techniques for integrating 1D-lumped models with 3D-FSI models. Methods to properly formulate the 1D-models are discussed. Once formulated, these 1D-models provide quick and accurate results that are used to narrow various design alternatives. Additionally, the 1D-models provide initial conditions for the higher resolution 3D-FSI models in critical regimes of operation. Lastly, experimental data is shown to confirm the techniques

Use of a continuous-flow bioreactor to evaluate nitrate reduction rate of Halomonas desiderata in cementitious environment relevant to nuclear waste deep repository

The redox level of repositories can influence the mobility of the waste components stored in them (i.e. radionuclides) and thus the related safety assessments. Microbial activity is known to impact the control of redox reactions, the mechanisms and kinetics of which must be evaluated. This study investigates the denitrification rates of a model bacterium Halomonas desiderata (Hd) in cementitious environment with alkaline and anoxic conditions comparable to those found in radioactive waste repository cells. The growth and the total oxidized nitrogen (TON) reduction rates of Hd was determined in a continuous bioreactor with several feeding solutions with or without solid cement paste. Temporary nitrite accumulation and reduced denitrification rates are correlated with diminished bacterial growth. When the system was fed by optimal culture medium supplemented with acetate and nitrate, the TON reduction rates varied between 0.082 mM TON/h and 0.063 mM TON/h, depending on whether solid cement paste was present in the reactor or not. When the culture medium was replaced with pure cement leachate, the reaction rates increased to 0.137 mM TON/h with solid cement paste and dropped to 0.023 mM TON/h without. In these conditions at pH 10, solid cement paste had no negative influence on Hd activity

Nitrate and nitrite bacterial reduction at alkaline pH and high nitrate concentrations, comparison of acetate versus dihydrogen as electron donors

This study assesses bacterial denitrification at alkaline pH, up to 12, and high nitrate concentration, up to 400 mM. Two types of electron donors organic (acetate) and inorganic (dihydrogen) were compared. With both types of electron donors, nitrite reduction was the key step, likely to increase the pH and lead to nitrite accumulation. Firstly, an acclimation process was used: nitrate was progressively increased in three cultures set at pH 9, 10, or 11. This method allowed to observe for the first time nitrate reduction up to pH 10 and 100 mM nitrate with dihydrogen, or up to pH 10 and 400 mM nitrate with acetate. Nitrate reduction kinetics were faster in the presence of acetate. To investigate further the impact of the type of electron donor, a transition from acetate to dihydrogen was tested, and the pH evolution was modelled. Denitrification with dihydrogen strongly increases the pH while with acetate the pH evolution depends on the initial pH. The main difference is the production of acidifying CO2 during the acetate oxidation. Finally, the use of long duration cultures with a highly alkaline pH allowed a nitrate reduction up to pH 11.5 with acetate. However, no reduction was possible in hydrogenotrophy as it would have increased the pH further. Instead, bacteria used organic matter from inoculum to reduce nitrate at pH 11.5. Therefore, considering bacterial denitrification in a context of alkaline pH and high nitrate concentration an organic electron donor such as acetate is advantageous

Adaptation of neutrophilic Paracoccus denitrificans to denitrification at highly alkaline pH

Bacterial denitrification is widely documented at neutral pH in order to improve the removal of nitrate in wastewater treatment processes. However, certain industrial contexts generate alkaline waste and effluent containing nitrate that must be denitrified. To obtain more information on denitrification at alkaline pH, this study evaluated the possibility of adapting a neutrophilic denitrifying strain, Paracoccus denitrificans, to alkaline pH. Firstly, P. denitrificans’ denitrifying activity was evaluated without acclimation in batch bioreactors at pH 7.0, 8.0, 9.0 and 10.0. Then, two acclimation methods using successive batch bioreactors and a continuous bioreactor allowed P. denitrificans to be gradually exposed to alkaline pH: from 8.5 to 11.2 in 26 and 72 days respectively. Results showed that P. denitrificans could grow and catalyse nitrate reduction (i) at pH 9.0 without acclimation, (ii) at pH 10.5 in successive batch cultures with progressively increasing pH and (iii) at pH 10.8 in continuously fed culture with a hydraulic retention time (HRT) of 8 days. It was shown that denitrification affected the pH despite the presence of carbonate buffering of the P. denitrificans growth medium. With acetate as an electron donor, the pH of a carbonate buffered medium tends towards pH 10 during the process of denitrification

Nitrate and nitrite reduction activity of activated sludge microcosm in a highly alkaline environment with solid cementitious material

Denitrification is a major biological process contributing to nitrate and nitrite reduction. However, this process remains poorly understood at alkaline pH although such conditions can be encountered in natural (e.g. soda lakes) or industrial environments (e.g. geological waste repositories with cementitious materials). To investigate the nitrate reduction (NR) rate for pH > 9.5 in a cementitious environment, several batch reactors were implemented, with cement leachate or with hardened cement paste (HCP). In the experiments carried out with cement leachate, NR dropped from 0.72 mM/h at pH 9.5 to 0.17 mM/h at pH > 11, while the concentration of nitrite increased. The NR was inhibited at pH close to 12, as was the nitrite reduction at pH above 11. In the reactor containing HCP, the NR rate was 0.75 mM/h at pH close to 10. Calcite precipitated on the HCP surface. Epifluorescence microscopy observations coupled with DNA labelling suggested the presence of microorganisms attached to the HCP surface. This was confirmed by biological growth coupled with NR activity after the transfer of the HCP into a new medium, considered to be sterile. The bacterial community analysis showed that the highly selective culture conditions led to the selection of two species: Halomonas sp. and a species known for its versatile metabolism and ability to form biofilms, i.e. Thauera sp

366 Combined exploratory immunophenotyping and transcriptomic tumor analysis in patients treated with OSE2101 vaccine in HLA-A2+ advanced non-small cell lung cancer (NSCLC) from the ATALANTE-1 trial

BackgroundOSE2101 (Tedopi®) is an anticancer vaccine with HLA-A2+ restricted modified epitopes targeting five tumor-associated antigens (TAAs) frequently expressed in lung cancer (CEA, HER2, MAGE2, MAGE3, P53). Step-1 results of the phase III, randomized, open-label ATALANTE-1 study comparing Tedopi® vs standard treatment (SoC) showed a favorable benefit/risk of Tedopi® over SoC (HR 0.71 for overall survival OS) in HLA-A2+ NSCLC patients in 2nd or 3rd line treatment after progression on immune checkpoint blockers (ICB).1 We analyze available tumor biopsies at initial diagnosis from some patients treated with Tedopi® to determine the expression of the 5 TAAs and to identify other tumor factors associated with long-term survival.MethodsTumor biopsies were available for 8 HLA-A2+ (blood test) stage IV NSCLC patients included in the trial. Primary (<12 weeks) and secondary (≥ 12 weeks) resistance to ICB were observed in 3 (38%) and 5 (62%) of patients. Best response to Tedopi® and OS were: 1 partial response (PR) (OS of 33 months), 3 stable disease (SD) (OS of 22, 26 and 41 mo.) and 4 disease progression (PD) (OS of 3, 4, 30 and 31 mo.). HLA-class I, PD-L1, CD8 T-cells, HER2, CEA and P53 tumor expression were evaluated by immunohistochemistry (IHC). NanoString gene expression profiling was performed using the Pan Cancer Immune gene set.ResultsHLA-class I was expressed in all tumor samples. IHC analysis revealed that P53, CEA and HER2 were expressed in 6/7, 5/7 and 0/7 patients, respectively. P53, CEA, HER2, MAGE2, and MAGE3 were detected at RNA level in 5/5 tested patients (table 1). IMMUNOSCORE® IC CD8/PDL1 analysis showed High/High, High/Low and Low/Low scores for 1/7, 1/7 and 5/7 patients, respectively. The High/High IMMUNOSCORE® with a pronounced CD8+ T-cell tumor infiltration was observed in the patient with PR. High percentage of tumor cells expressing P53 (69%–97%) and overexpression of genes associated with activated macrophages (TREM2, MARCO, SLC11A1, CHIT1, SERPINB2) were observed in the PR and SD patients. High IFN-gamma and Expanded Immune Gene Signature scores were observed in long-term survivor patients with secondary resistance to ICB, even after progressive disease.Abstract 366 Table 1Summary of clinical and translational dataCEACarcinoembryonic antigen; HER2: Human Epidermal Growth Factor Receptor-2; ICB: Immune checkpoint blocker; IHC: Immunohistochemistry; ND: Not determined; OS: Overall Survival; Patient ID: Patient identification; PDL1: Programmed death-ligand 1; PFS: Progression-free survival; ssGSEA: Single-sample Gene Set Enrichment Analysis. Blue bars = Length of overall survival; Green bars = Gene Signature upregulation; Red bars = Gene Signature downregulationConclusionsThis study shows that all HLA-A2+ patients (blood test), expressed HLA class I in the tumors at initial diagnosis. Transcriptomic data in the patients that benefited from Tedopi® showed activated macrophage pathway, high IFN-gamma and Expanded Immune Gene Signatures scores. These data will be validated on larger number of patients treated with Tedopi® after the step 2 analysis.AcknowledgementsWe thank Julie Le Boulicaut, François Montestruc and Constant Josse (eXYSTAT, Malakoff, France) for the statistical analysis, and HalioDx for the IHC and NanoString analysis.Trial RegistrationEudraCT number2015-003183-36; NCT number: NCT02654587ReferenceGiaccone, et al. Activity of OSE-2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (ICI): step 1 results of phase III ATALANTE-1 randomised trial. ESMO meeting 2020, abstract #1260MO.Ethics ApprovalThe study protocol and its related documents (including the patient information and informed consent form) received approval from the Institutional Review Board (IRB), and the Competent Authority prior to study initiation.ConsentEach patient gave his/her written informed consent prior to study enrolment

Gravitational waves: search results, data analysis and parameter estimation

The Amaldi 10 Parallel Session C2 on gravitational wave (GW) search results, data analysis and parameter estimation included three lively sessions of lectures by 13 presenters, and 34 posters. The talks and posters covered a huge range of material, including results and analysis techniques for ground-based GW detectors, targeting anticipated signals from different astrophysical sources: compact binary inspiral, merger and ringdown; GW bursts from intermediate mass binary black hole mergers, cosmic string cusps, core-collapse supernovae, and other unmodeled sources; continuous waves from spinning neutron stars; and a stochastic GW background. There was considerable emphasis on Bayesian techniques for estimating the parameters of coalescing compact binary systems from the gravitational waveforms extracted from the data from the advanced detector network. This included methods to distinguish deviations of the signals from what is expected in the context of General Relativity

A new 3MW ECRH system at 105 GHz for WEST

The aim of the WEST experiments is to master long plasma pulses (1000s) and expose ITER-like tungsten wall to deposited heat fluxes up to 10 MW/m$^2$. To increase the margin to reach the H-Mode and to control W-impurities in the plasma, the installation of an upgraded ECRH heating system, with a gyrotron performance of 1MW/1000s per unit, is planned in 2023. With the modifications of Tore Supra to WEST, simulations at a magnetic field B$_0$∼3.7T and a central density n$_{e0}$∼6 × 10$^{19}$ m$^{−3}$ show that the optimal frequency for central absorption is 105 GHz. For this purpose, a 105 GHz/1MW gyrotron (TH1511) has been designed at KIT in 2021, based on the technological design of the 140 GHz/1.5 MW (TH1507U) gyrotron for W7-X. Currently, three units are under fabrication at THALES. In the first phase of the project, some of the previous Tore Supra Electron Cyclotron (EC) system components will be re-installed and re-used whenever possible. This paper describes the studies performed to adapt the new ECRH system to 105 GHz and the status of the modifications necessary to re-start the system with a challenging schedule

Haploinsufficiency of ARFGEF1 is associated with developmental delay, intellectual disability, and epilepsy with variable expressivity

ADP ribosylation factor guanine nucleotide exchange factors (ARFGEFs) are a family of proteins implicated in cellular trafficking between the Golgi apparatus and the plasma membrane through vesicle formation. Among them is ARFGEF1/BIG1, a protein involved in axon elongation, neurite development, and polarization processes. ARFGEF1 has been previously suggested as a candidate gene for different types of epilepsies, although its implication in human disease has not been well characterized. International data sharing, in silico predictions, and in vitro assays with minigene study, western blot analyses, and RNA sequencing. We identified 13 individuals with heterozygous likely pathogenic variants in ARFGEF1. These individuals displayed congruent clinical features of developmental delay, behavioral problems, abnormal findings on brain magnetic resonance image (MRI), and epilepsy for almost half of them. While nearly half of the cohort carried de novo variants, at least 40% of variants were inherited from mildly affected parents who were clinically re-evaluated by reverse phenotyping. Our in silico predictions and in vitro assays support the contention that ARFGEF1-related conditions are caused by haploinsufficiency, and are transmitted in an autosomal dominant fashion with variable expressivity. We provide evidence that loss-of-function variants in ARFGEF1 are implicated in sporadic and familial cases of developmental delay with or without epilepsy

Extending the clinical spectrum of X-linked Tonne-Kalscheuer syndrome (TOKAS):new insights from the fetal perspective

INTRODUCTION: Tonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused by RLIM variations. Of the 41 patients reported, only 7 antenatal cases were described.METHOD: After the antenatal diagnosis of TOKAS by exome analysis in a family followed for over 35 years because of multiple congenital anomalies in five male fetuses, a call for collaboration was made, resulting in a cohort of 11 previously unpublished cases.RESULTS: We present a TOKAS antenatal cohort, describing 11 new cases in 6 French families. We report a high frequency of diaphragmatic hernia (9 of 11), differences in sex development (10 of 11) and various visceral malformations. We report some recurrent dysmorphic features, but also pontocerebellar hypoplasia, pre-auricular skin tags and olfactory bulb abnormalities previously unreported in the literature. Although no clear genotype-phenotype correlation has yet emerged, we show that a recurrent p.(Arg611Cys) variant accounts for 66% of fetal TOKAS cases. We also report two new likely pathogenic variants in RLIM, outside of the two previously known mutational hotspots.CONCLUSION: Overall, we present the first fetal cohort of TOKAS, describe the clinical features that made it a recognisable syndrome at fetopathological examination, and extend the phenotypical spectrum and the known genotype of this rare disorder.</p