Analysis and simplification of chemical kinetics mechanisms with CSP-based techniques

The computational singular perturbation (CSP) method is exploited to build a comprehensive framework for analysis and simplification of chemical kinetic models. The necessity for both smart post-process tools, able to perform rational diagnostics on large numerical simulations of reactive flows, and affordable reduced kinetic mechanisms, to make the simulations feasible, is the driving force behind this work. The ultimate goal is to improve the understanding of the fundamentals of chemically reacting flows. The CSP method is a suitable candidate for extracting physical insights from reactive flows dynamics that can be employed for both the generation of simplified kinetic schemes and the calculation of smart and compact diagnostic observables. Among them, the tangential stretching rate (TSR) is an estimate of the system’s driving chemical timescale that can be profitably employed for characterising the reactive flow dynamics in terms of combustion regimes and role of transport with respect to kinetics. The potentials of TSR are extensively highlighted, starting from prototypical combustion models, such as batch reactor and unsteady laminar flamelet, and getting to real-life usage on 3-dimensional direct numerical simulation datasets. The CSP mathematical foundations are then employed for mechanism simplification purposes, where small and accurate kinetic mechanisms are sought after. An existing CSP-based simplification algorithm is improved, aiming at the minimisation of the required user knowledge, which becomes a critical feature of the algorithm when dealing with new fuels. Practical applications of the revised algorithm are shown and discussed. Finally, the focus is shifted from the quest for tight accuracy in the simplified mechanisms towards a much broader question regarding confidence in detailed kinetic schemes. Uncertainty in the kinetic model parameters, such as Arrhenius coefficients, can jeopardize the efforts spent in the reduction challenge. A new, uncertainty-aware, robust CSP simplification strategy is proposed, discussed and employed, and its robustness demonstrated in a test case involving an uncertain -in its Arrhenius pre-exponential coefficients- kinetic scheme

Deformable Linear Objects Manipulation With Online Model Parameters Estimation

Manipulating deformable linear objects (DLOs) is a challenging task for a robotic system due to their unpredictable configuration, high-dimensional state space and complex nonlinear dynamics. This letter presents a framework addressing the manipulation of DLOs, specifically targeting the model-based shape control task with the simultaneous online gradient-based estimation of model parameters. In the proposed framework, a neural network is trained to mimic the DLO dynamics using the data generated with an analytical DLO model for a broad spectrum of its parameters. The neural network-based DLO model is conditioned on these parameters and employed in an online phase to perform the shape control task by estimating the optimal manipulative action through a gradient-based procedure. In parallel, gradient-based optimization is used to adapt the DLO model parameters to make the neural network-based model better capture the dynamics of the real-world DLO being manipulated and match the observed deformations. To assess its effectiveness, the framework is tested across a variety of DLOs, surfaces, and target shapes in a series of experiments. The results of these experiments demonstrate the validity and efficiency of the proposed methodology compared to existing methods

Model identification in reactor-based combustion closures using sparse symbolic regression

info:eu-repo/semantics/publishe

RT-DLO: Real-Time Deformable Linear Objects Instance Segmentation

Deformable Linear Objects (DLOs) such as cables, wires, ropes, and elastic tubes are numerously present both in domestic and industrial environments. Unfortunately, robotic systems handling DLOs are rare and have limited capabilities due to the challenging nature of perceiving them. Hence, we propose a novel approach named RT-DLO for real-time instance segmentation of DLOs. First, the DLOs are semantically segmented from the background. Afterward, a novel method to separate the DLO instances is applied. It employs the generation of a graph representation of the scene given the semantic mask where the graph nodes are sampled from the DLOs center-lines whereas the graph edges are selected based on topological reasoning. RT-DLO is experimentally evaluated against both DLO-specific and general-purpose instance segmentation deep learning approaches, achieving overall better performances in terms of accuracy and inference time

Evaluation of in vivo labelled dendritic cell migration in cancer patients

BACKGROUND: Dendritic Cell (DC) vaccination is a very promising therapeutic strategy in cancer patients. The immunizing ability of DC is critically influenced by their migration activity to lymphatic tissues, where they have the task of priming naïve T-cells. In the present study in vivo DC migration was investigated within the context of a clinical trial of antitumor vaccination. In particular, we compared the migration activity of mature Dendritic Cells (mDC) with that of immature Dendritic Cells (iDC) and also assessed intradermal versus subcutaneous administration. METHODS: DC were labelled with (99m)Tc-HMPAO or (111)In-Oxine, and the presence of labelled DC in regional lymph nodes was evaluated at pre-set times up to a maximum of 72 h after inoculation. Determinations were carried out in 8 patients (7 melanoma and 1 renal cell carcinoma). RESULTS: It was verified that intradermal administration resulted in about a threefold higher migration to lymph nodes than subcutaneous administration, while mDC showed, on average, a six-to eightfold higher migration than iDC. The first DC were detected in lymph nodes 20–60 min after inoculation and the maximum concentration was reached after 48–72 h. CONCLUSIONS: These data obtained in vivo provide preliminary basic information on DC with respect to their antitumor immunization activity. Further research is needed to optimize the therapeutic potential of vaccination with DC

FDG PET/CT Response Evaluation in Malignant Pleural Mesothelioma Patients Treated with Talc Pleurodesis and Chemotherapy

Purpose: Talc pleurodesis (TP) is employed worldwide for the management of persistent pneumothorax or pleural effusion, particularly of malignant origin. However, there are very little available data on 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F FDG PET/CT) response evaluation in malignant pleural mesothelioma (MPM) patients treated with TP and chemotherapy

Role of the repeat expansion size in predicting age of onset and severity in RFC1 disease

RFC1 disease, caused by biallelic repeat expansion in RFC1, is clinically heterogeneous in terms of age of onset, disease progression and phenotype. We investigated the role of the repeat size in influencing clinical variables in RFC1 disease. We also assessed the presence and role of meiotic and somatic instability of the repeat. In this study, we identified 553 patients carrying biallelic RFC1 expansions and measured the repeat expansion size in 392 cases. Pearson's coefficient was calculated to assess the correlation between the repeat size and age at disease onset. A Cox model with robust cluster standard errors was adopted to describe the effect of repeat size on age at disease onset, on age at onset of each individual symptoms, and on disease progression. A quasi-poisson regression model was used to analyse the relationship between phenotype and repeat size. We performed multi-variate linear regression to assess the association of the repeat size with the degree of cerebellar atrophy. Meiotic stability was assessed by Southern blotting on first-degree relatives of 27 probands. Finally, somatic instability was investigated by optical genome mapping on cerebellar and frontal cortex and unaffected peripheral tissue from four post-mortem cases. A larger repeat size of both smaller and larger allele was associated with an earlier age at neurological onset (smaller allele HR=2.06, p<0.001; larger allele HR=1.53, p<0.001) and with a higher hazard of developing disabling symptoms, such as dysarthria or dysphagia (smaller allele HR=3.40, p<0.001; larger allele HR=1.71, p=0.002) or loss of independent walking (smaller allele HR=2.78, p<0.001; larger allele HR=1.60; p<0.001) earlier in disease course. Patients with more complex phenotypes carried larger expansions (smaller allele: complex neuropathy RR=1.30, p=0.003; CANVAS RR=1.34, p<0.001; larger allele: complex neuropathy RR=1.33, p=0.008; CANVAS RR=1.31, p=0.009). Furthermore, larger repeat expansions in the smaller allele were associated with more pronounced cerebellar vermis atrophy (lobules I-V β=-1.06, p<0.001; lobules VI-VII β=-0.34, p=?0.005). The repeat did not show significant instability during vertical transmission and across different tissues and brain regions. RFC1 repeat size, particularly of the smaller allele, is one of the determinants of variability in RFC1 disease and represents a key prognostic factor to predict disease onset, phenotype, and severity. Assessing the repeat size is warranted as part of the diagnostic test for RFC1 expansion.Funding: This work was supported by Medical Research Council (MR/T001712/1), Fondazione Cariplo (grant n. 2019-1836), the Inherited Neuropathy Consortium, and Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia, project ID 1751723). R. Currò was supported by the European Academy of Neurology (EAN) Research Fellowship 2021. H. Houlden and M.M. Reilly thank the MRC, the Wellcome Trust, the MDA, MD UK, Ataxia UK, The MSA Trust, the Rosetrees Trust and the NIHR UCLH BRC for grant support. F. Taroni thanks the Fondazione Regionale per la Ricerca Biomedica (CP 20/2018 (Care4NeuroRare) and the Italian Ministry of Health (RC) for grant support. D. Pareyson thanks the Italian Ministry of Health (RRC) for grant support. F.M. Santorelli thanks Ricerca Corrente 2022 Ministero della Salute 5X1000 for grant support. M. Synofzik thanks the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) and the European Joint Programme on Rare Diseases for grant support. P.F. Chinnery the Medical Research Council Mitochondrial Biology Unit, the Medical Research Council (MRC) International Centre for Genomic Medicine in Neuromuscular Disease, the Leverhulme Trust (RPG-2018-408), the Medical Research Council, the Alzheimer's Society Project, and the NIHR Cambridge Biomedical Research for grant support. Acknowledgements: We thank the patients and relatives who participated in this study

Optical Genome Mapping Enables Detection and Accurate Sizing of RFC1 Repeat Expansions

A recessive Short Tandem Repeat expansion in RFC1 has been found to be associated with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), and to be a frequent cause of late onset ataxia and sensory neuropathy. The usual procedure for sizing these expansions is based on Southern Blotting (SB), a time-consuming and a relatively imprecise technique. In this paper, we compare SB with Optical Genome Mapping (OGM), a method for detecting Structural Variants (SVs) based on the measurement of distances between fluorescently labelled probes, for the diagnosis of RFC1 CANVAS and disease spectrum. The two methods are applied to 17 CANVAS patients' blood samples and resulting sizes compared, showing a good agreement. Further, long-read sequencing is used for two patients to investigate the agreement of sizes with either SB or OGM. Our study concludes that OGM represents a viable alternative to SB, allowing for a simpler technique, a more precise sizing of the expansion and ability to expand analysis of SV in the entire genome as opposed to SB which is a locus specific method

Road traffic pollution and childhood leukemia: a nationwide case-control study in Italy

Background The association of childhood leukemia with traffic pollution was considered in a number of studies from 1989 onwards, with results not entirely consistent and little information regarding subtypes. Aim of the study We used the data of the Italian SETIL case-control on childhood leukemia to explore the risk by leukemia subtypes associated to exposure to vehicular traffic. Methods We included in the analyses 648 cases of childhood leukemia (565 Acute lymphoblastic–ALL and 80 Acute non lymphoblastic-AnLL) and 980 controls. Information on traffic exposure was collected from questionnaire interviews and from the geocoding of house addresses, for all periods of life of the children. Results We observed an increase in risk for AnLL, and at a lower extent for ALL, with indicators of exposure to traffic pollutants. In particular, the risk was associated to the report of closeness of the house to traffic lights and to the passage of trucks (OR: 1.76; 95% CI 1.03–3.01 for ALL and 6.35; 95% CI 2.59–15.6 for AnLL). The association was shown also in the analyses limited to AML and in the stratified analyses and in respect to the house in different period of life. Conclusions Results from the SETIL study provide some support to the association of traffic related exposure and risk for AnLL, but at a lesser extent for ALL. Our conclusion highlights the need for leukemia type specific analyses in future studies. Results support the need of controlling exposure from traffic pollution, even if knowledge is not complete

Prognostic and Predictive Role of Body Composition in Metastatic Neuroendocrine Tumor Patients Treated with Everolimus: A Real-World Data Analysis

Neuroendocrine tumors (NETs) are rare neoplasms frequently characterized by an up- regulation of the mammalian rapamycin targeting (mTOR) pathway resulting in uncontrolled cell proliferation. The mTOR pathway is also involved in skeletal muscle protein synthesis and in adipose tissue metabolism. Everolimus inhibits the mTOR pathway, resulting in blockade of cell growth and tumor progression. The aim of this study is to investigate the role of body composition in- dexes in patients with metastatic NETs treated with everolimus. The study population included 30 patients with well-differentiated (G1-G2), metastatic NETs treated with everolimus at the IRCCS Romagnolo Institute for the Study of Tumors (IRST) “Dino Amadori”, Meldola (FC), Italy. The body composition indexes (skeletal muscle index [SMI] and adipose tissue indexes) were assessed by measuring on a computed tomography (CT) scan the cross-sectional area at L3 at baseline and at the first radiological assessment after the start of treatment. The body mass index (BMI) was assessed at baseline. The median progression-free survival (PFS) was 8.9 months (95% confidence interval [CI]: 3.4–13.7 months). The PFS stratified by tertiles was 3.2 months (95% CI: 0.9–10.1 months) in patients with low SMI (tertile 1), 14.2 months (95% CI: 2.3 months-not estimable [NE]) in patients with intermediate SMI (tertile 2), and 9.1 months (95% CI: 2.7 months-NE) in patients with high SMI (tertile 3) (p = 0.039). Similarly, the other body composition indexes also showed a statistically significant difference in the three groups on the basis of tertiles. The median PFS was 3.2 months (95% CI: 0.9–6.7 months) in underweight patients (BMI 18.49 kg/m2) and 10.1 months (95% CI: 3.7–28.4 months) in normal-weight patients (p = 0.011). There were no significant differences in terms of overall survival. The study showed a correlation between PFS and the body composition indexes in patients with NETs treated with everolimus, underlining the role of adipose and muscle tissue in these patients