In-house Tool Research Articles

Techno-economically-driven identification of ideal plant configurations for a new biomass-to-liquid process – A case study for Central-Europe

The conversion of agricultural waste materials such as bark or straw into 2nd generation biofuels constitutes an auspicious way to meet part of the future fuel demand in a sustainable way. The number of possible production routes is diverse, and the techno-economic analyses of these routes have been conducted in very different ways. The route involving gasification, gas purification, and a subsequent Fischer-Tropsch synthesis enables the production of hydrocarbons that achieve current fuel standards after upgrading in the existing refinery infrastructure. To evaluate a promising biomass-to-liquid process, a methodology is presented that incorporates economic constraints into the process design, allowing identification of a regionally optimal process design. The production costs of the new concepts are estimated by setting up a detailed flowsheet simulation in AspenPlus® based on experimental data from the successful demonstration runs of the EU-Project COMSYN. In addition, an existing techno-economic evaluation methodology incorporated into the in-house software tool TEPET (Techno-Economic Process Evaluation Tool) has been extended to evaluate the processes’ performance in different European regions and to include transportation and refining costs. The approach enables the identification of regional sweet spots shown on a map for Central-Europe, indicating production costs and favorable process design for each region. Furthermore, the results of an automated mapping for the optimal process design depending on the heat and electricity market are presented. The performed analyses show that the techno-economic evaluation tends to expand the technology in regions with low feedstock costs, while the optimal process design is defined by the regional heat and electricity market. In this work, net production costs of less than 1.12 €2019/lbiofuel were determined for regions in Hungary, Poland and Slovakia.

Verification and Validation of High-Fidelity Open-Source Simulation Tools for Supersonic Aircraft Aerodynamic Analysis

Abstract Small supersonic vehicle concepts used as research platforms to test new aerospace technologies, such as advanced propulsion systems or large sensor payloads, require major modifications to conventional, large-scale, manned, supersonic airframe design. High-fidelity numerical simulation of these concepts in academic settings often requires the use of in-house or available open-source tools instead of expensive commercial software or those with export-control restrictions. A verification and validation analysis of two widely-used open-source compressible-flow solvers, rhoCentralFoam (rCF) and su2, is performed for several flow problems relevant to the supersonic aerodynamics of small-scale, autonomous aircraft concepts. The one-dimensional shock tube problem, two-dimensional supersonic turbulent boundary layer, and three-dimensional delta wing are simulated with both solvers. The effects of flux scheme, flux limiters, and Courant–Friedrichs–Lewy (CFL) number on solution accuracy, stability, and solver speed are assessed. The solvers' limitations and their usefulness as supersonic aircraft design tools in a holistic sense are discussed.

Assessment of thermal fatigue induced by dryout front oscillation in printed circuit steam generator

A printed circuit steam generator (PCSG) is being considered as the component for pressurized water reactor (PWR) type small modular reactor (SMR) that can further reduce the physical size of the system. Since a steam generator in many PWR-type SMR generates superheated steam, it is expected that dryout front oscillation can potentially cause thermal fatigue failure due to cyclic thermal stresses induced by the transition in boiling regimes between convective evaporation and film boiling. To investigate the fatigue issue of a PCSG, a reference PCSG is designed in this study first using an in-house PCSG design tool. For the stress analysis, a finite element method analysis model is developed to obtain the temperature and stress fields of the designed PCSG. Fatigue estimation is performed based on ASME Boiler and pressure vessel code to identify the major parameters influencing the fatigue life time originating from the dryout front oscillation. As a result of this study, the limit on the temperature difference between the hot side and cold side fluids is obtained. Moreover, it is found that the heat transfer coefficient of convective evaporation and film boiling regimes play an essential role in the fatigue life cycle as well as the temperature difference.

Intra-fractional per-beam adaptive workflow to mitigate the need for a rotating gantry during MRI-guided proton therapy

The integration of real-time magnetic resonance imaging (MRI) guidance and proton therapy would potentially improve the proton dose steering capability by reducing daily uncertainties due to anatomical variations. The use of a fixed beamline coupled with an axial patient couch rotation would greatly simplify the proton delivery with MRI guidance. Nonetheless, it is mandatory to assure that the plan quality is not deteriorated by the anatomical deformations due to patient rotation. In this work, an in-house tool allowing for intra-fractional per-beam adaptation of intensity-modulated proton plans (BeamAdapt) was implemented through features available in RayStation. A set of three MRIs was acquired for two healthy volunteers (V 1, V 2): (1) no rotation/static, (2) rotation to the right and (3) left. V 1 was rotated by 15°, to simulate a clinical pediatric abdominal case and V 2 by 45°, to simulate an extreme patient rotation case. For each volunteer, a total of four intensity-modulated pencil beam scanning plans were optimized on the static MRI using virtual abdominal targets and two-three posterior-oblique beams. Beam angles were defined according to the angulations on the rotated MRIs. With BeamAdapt, each original plan was initially converted into separate plans with one beam per plan. In an iterative order, individual beam doses were non-rigidly deformed to the rotated anatomies and re-optimized accounting for the consequent deformations and the beam doses delivered so far. For evaluation, the final accumulated dose distribution was propagated back to the static MRI. Planned and adapted dose distributions were compared by computing relative differences between dose-volume histogram metrics. Absolute target dose differences were on average below 1% and organs-at-risk mean dose differences were below 3%. With BeamAdapt, not only intra-fractional per-beam proton plan adaptation coupled with axial patient rotation is possible but also the need for a rotating gantry during MRI guidance might be mitigated.

Hybrid Rocket Engine Design Optimization at Politecnico di Torino: A Review

Optimization of Hybrid Rocket Engines at Politecnico di Torino began in the 1990s. A comprehensive review of the related research activities carried out in the last three decades is here presented. After a brief introduction that retraces driving motivations and the most significant steps of the research path, the more relevant aspects of analysis, modeling and achieved results are illustrated. First, criteria for the propulsion system preliminary design choices (namely the propellant combination, the feed system and the grain design) are summarized and the engine modeling is presented. Then, the authors describe the in-house tools that have been developed and used for coupled trajectory and propulsion system design optimization. Both deterministic and robust-based approaches are presented. The applications that the authors analyzed over the years, starting from simpler hybrid powered sounding rocket to more complex multi-stage launchers, are then presented. Finally, authors’ conclusive remarks on the work done and their future perspective in the context of the optimization of hybrid rocket propulsion systems are reported.

Unusual Para-Substituent Effects on the Intramolecular Hydrogen Bond in Hydrazone-Based Switches: Insights from Chemical Landscape Analysis and DFT Calculations

Тhe adequacy of chemical property predictions strongly depends on the structure representation, including the proper treatment of the tautomeric and isomeric forms. A combination of an in-house developed open-source tool for automatic generation of tautomers, Ambit-Tautomer, based on H-atom shift rules and standard quantum chemical (DFT) calculations is used for a detailed investigation of the possible geometric isomers, conformers and tautomers of unsubstituted and para-substituted phenylhydrazones, systems with experimentally observed unusual para-substituent effects on the intramolecular hydrogen bond (IMHB) for E-isomers of the compounds. The computational results show that the energetically preferred E-isomers are characterized by stronger IMHBs than the corresponding Z-isomers. The HN–N=C–C=N molecular fragment in the E-configurations is less sensitive to the substitution effect than the HN–N=C–C=O fragment in the isomers with Z-configuration. A probable reason for this decreased sensitivity of E-isomers to phenyl ring substitution is the more efficient conjugation and charge distribution in the HN–N=C–C=N fragment.

The Potential of O’nyong-nyong Virus Strain SG650 Murine Monoclonal Antibodies for Detection of O’nyong-nyong and Chikungunya Viruses

O’nyong-nyong virus (ONNV) and Chikungunya virus (CHIKV) are antigenically related alphaviruses responsible for febrile illnesses common to the tropics and associated with relatively high morbidity and mortality. Murine monoclonal antibodies (mAbs) targeting alphaviruses like Chikungunya have been developed and used to make commercially available kits. However, few studies have been conducted to develop antibodies specific to ONNV and no commercial kits are available for use in endemic regions where outbreak potential is high. We demonstrate the potential of in-house generated monoclonal antibodies against ONNV to detect both ONNV and CHIKV. The objective of this study was to generate mAbs using hybridoma technology, characterize the developed mAbs, determine their specificity against selected alphaviruses and check their diagnostic potential using an indirect IgG enzyme-linked immunosorbent assay (ELISA) and focus neutralization assay (FRNT50). BALB/c mice were immunized with ONNV purified proteins from ONNV infectious culture fluid. After four rounds of booster injections, the mice were sacrificed, spleen cells harvested and fused with parental myeloma cells then cultured in selective media and the successful hybrid clones with antibody-producing ability purified to yield the desired mAbs. Five monoclonal antibodies targeting the ONNV E1 protein of isotypes IgG2a/kappa, IgG2b/kappa and IgM/kappa (P1B12, P1E9, P1G11, P1B4 and P1G6) demonstrated a potential to detect both ONNV and CHIKV isolates by indirect IgG ELISA but no potential for neutralization of the viruses by FRNT50. This study demonstrates the potential efficacy of in-house serological tools as an alternative in the absence of commercial assays in screening and diagnosis of ONN and CHIK viruses which are often co-circulating. It is our recommendation that this work may be pursued further to design and optimize ELISA assays, using the developed mAbs, for the detection of both ONN and CHIK viruses in the research laboratory set-up

A Transfer Entropy Based Approach for Fault Isolation in Industrial Robots

Abstract In this paper, we cast the problem of fault isolation in industrial robots as that of causal analysis within coupled dynamical processes and evaluate the related efficacy of the information-theoretic approach of transfer entropy. To create a realistic and exhaustive dataset, we simulate wear-induced failure by increasing friction coefficient on select axes within an in-house robotic simulation tool that incorporates an elastic gearbox model. The source axis of failure is identified as one which has the highest net transfer entropy across all pairs of axes. In an exhaustive simulation study, we vary the friction successively in each axis across three common industrial tasks: pick and place, spot welding, and arc welding. Our results show that transfer entropy-based approach is able to detect the axis of failure more than 80% of the time when the friction coefficient is 5% above the nominal value and always when friction coefficient is 10% above the nominal value. The transfer entropy approach is more than twice as accurate as cross-correlation, a classical time series analysis used to identify directional dependence among processes.

Efficient electrical characteristics estimation techniques for sub-20-nm FDSOI integrated circuits with nonrectangular gate patterning effects

In subwavelength lithography, printed patterns on the silicon wafer suffer from geometric distortions and differ from the original design. These nonrectangular patterns can seriously affect electrical characteristics and circuit performances. We extend the verification of location-dependent weighting method and further propose three single equivalent gate length (EGL) extraction methods for representing each nonrectangular gate (NRG) transistor with a single EGL model. These methods are applied to sub-20-nm fully depleted silicon on insulator (FDSOI) circuits to predict the postlithography performances. An in-house extreme ultraviolet lithography simulation tool is utilized for nonrectangular pattern simulation. Shape information is imported to TCAD to construct three-dimensional nonrectangular FDSOI transistor models. The accuracy of the location-dependent weighting method and EGL extraction methods is verified with TCAD circuit simulations. Preliminary simulation results indicate that weighting factors can improve the accuracy of electrical characteristics estimation, especially in leakage current analysis. On average, the EGLs extracted from off-state only data, and from data lumping both off- and on-states, respectively, can each predict SRAM electrical characteristics with overall error <1 % , or a factor of 5 accuracy improvement over the EGLs extracted without the weightings. These methods could be used to simulate large-scale sub-20-nm FDSOI circuits with NRG transistors caused by nonideal optical effects.

Hydrodynamic performances of wave energy converter arrays in front of a vertical wall

Wave power absorption with Wave Energy Converters (WECs) arrays in front of a vertical wall is predicted with an in-house transient wave-multibody numerical tool of ITU-WAVE which uses time marching scheme to solve a boundary integral equation for the analyses of hydrodynamic radiation and exciting forces. The perfect reflection of incident waves from a vertical wall is considered with method of images. Mean interaction factor, which can have constructive or destructive effect and determines the performances of WECs, is approximated with different array configurations. The vertical wall effect plays significant role over hydrodynamic parameters as the radiation and exciting forces show quite different behaviour in the case of WECs with and without vertical wall in an array system. The numerical results show that the performance and wave power absorption with WECs arrays in front of vertical wall are much greater compared to WECs arrays without vertical wall effect. This is mainly due to standing and nearly trapped waves between a vertical wall and WECs arrays in addition to strong interactions between WECs. The satisfactory agreements are obtained when the present ITU-WAVE numerical results for different hydrodynamic parameters in an array system are compared with other published analytical and numerical results.

Digital Form Finding Using Voronoi Pattern

Starting from funicular models, chain models and hanging membranes, the role of 3D physical models in optimized shape research is the basis of form-finding strategies. Advances in structural optimized shape design derive from the wide spread of special digital form-finding tools. The goal of this paper is to test and evaluate interdisciplinary approaches based on computational tools useful in the form finding of efficient structural systems. This work is aimed at designing an inverse hanging shape subdivided into polygonal voussoirs (Voronoi patterns) by relaxing a planar discrete and elastic system, loaded at each point and anchored along its boundary. The workflow involves shaping, discretization (from pre-shaped paneling to digital stereotomy) and structural analysis carried out using two modeling approaches, finite element and rigid block modeling, using an in-house software tool, LiABlock_3D (MATLAB®), to check the stress state and to evaluate the equilibrium stability of the final shell.

Investigation of Reynolds Number Effects on Aerodynamic Characteristics of a Transport Aircraft

The scale difference between the real flight vehicle and the experimental model results in the Reynolds number effect, which makes it unreliable to predict the aerodynamic characteristics of flight vehicles by wind tunnel testing. To understand the mechanism of Reynolds number effects on the aerodynamic characteristics of the supercritical wing that is commonly used in transport aircraft in more detail, surface pressure wind tunnel tests of a transport aircraft reference model with a wing-body configuration were conducted in the European Transonic Windtunnel (ETW) at different Reynolds numbers. There are 495 pressure taps in total equipped on the surface of the test model with the Mach numbers ranging from 0.6 to 0.86 and Reynolds number varying from 3.3 × 106 to 35 × 106. In addition, an in-house developed CFD tool that has been validated by extensive experimental data was used to correct the wing deformation effect of the test model and achieve detailed flow structures. The results show that the Reynolds number has a significant impact on the boundary layer displacement thickness, surface pressure distribution, shock wave position, and overall aerodynamic force coefficients of the transport aircraft in the presence of shock wave and the induced boundary layer separation. The wind tunnel data combined with flow fields achieved from CFD show that the essence of the Reynolds number effect on the aerodynamic characteristics of transport aircraft is the difference of boundary layer development, shock wave/boundary layer interaction, and induced flow separation at different Reynolds numbers.

Aspariginase-Triggered Hyperglycerimedia: An Analysis on Germline Regulatory Gene Variations in Adult Acute Lymphoblastic Leukemia Patients

Asparaginase (ASP) is considered as a backbone of successful treatment of acute lymphoblastic leukemia (ALL). Cell growth and division of malignant lymphoblasts are highly dependent on asparagine and glutamine. ASP depletes them from extracellular fluid which leads to apoptosis of lymphoblasts. Aside from the aimed antileukemic properties, asparaginase exposes patients to multiple adverse effects including severe hypertriglyceridemia which potentially hampers efficient leukemia therapy. Molecular background of ASP-induced hypertriglyceridemia and its regulators are not well known. We aimed to investigate constitutional genetic factors as biomarkers for hypertriglyceridemia following ASP therapy.We analyzed clinical and laboratory data recorded in The Finnish Hematology Registry (FHR) from 52 adult ALL patients treated at the Helsinki University Hospital, Department of Hematology in 2014-2016. Study subjects were selected for further analyses if germline whole exome sequencing (WES) had been performed, patients had received ASP and data on basic chemistry and lipids before and after ASP dosing were available. Sixteen patients fulfilled these criteria.The patients' germline DNA was extracted from a skin biopsy taken in conjunction with a bone marrow sampling. Roche MedExome kit was used to target the coding regions of the genome and sequencing was conducted using an Illumina HiSeq sequencer. The reads were processed and aligned to the GRCh37 human reference genome. SNVs and indels in the exome sequencing data were analyzed using an in-house developed analysis tool. Shared variants in patients with similar serum triglyceride level changes after ASP treatment were analyzed and variants in genes associated with lipid metabolism were selected as candidate target genes.Three patient groups were identified based on to the maximum triglyceride changes pre- and post ASP infusion (both clinical and exome data available, n=7, 5, and 4; respectively). Mean changes in the Groups 1-3 were 1.7, 8.4, and 72,7 mmol/L, respectively. Differences in patients' BMI or corticosteroids use did not explain the distribution. Hence, a germline determinant was hypothesized and a candidate gene analysis (xx known genes affecting lipid and ASP metabolisms) performed from patients' germline WES.Mean changes in the Groups 1-3 were 1.7, 8.4, and 72,7 mmol/L, respectively. Differences in patients' BMI or usage of corticosteroids did not explain the distribution. Hence, a germline determinant was hypothesized and candidate gene search performed on patients' germline WES.Four of the candidate variants in ATF5, NKX1-1, THEM4, and LPCAT2 were enriched in patients with ASP-induced hyperTG. None of the variants suggested here have been previously reported to be associated with ASP-induced hypertriglyceridemia, but another SNP in ATF5 has been linked to adverse outcome in ASP-treated patients. ATF5, a transcription factor, regulates asparagine synthetase biosynthesis and is also involved in the cell cycle and apoptosis regulation, in the cellular stress response and the ceramide pathway. NKX1-1 is a transcription factor and an essential regulator of organ development, and it is also probably associated with energy homeostasis. THEM4 is an acyl-CoA thioesterase and is probably involved in mitochondrial fatty acid metabolism as well as in AKT1 signaling and apoptosis. LPCAT2 is a member of the lysophospholipid acyltransferase family involved in the synthesis of phospholipids, but also in the biosynthesis of platelet-activating factor (PAF) in inflammatory conditions.Here, we present four candidate genes and variations in them possibly linking to ASP-induced hypertriglyceridemia in adult ALL patients. Prospective studies exploring the impact of these findings are called for.Figure 1. Patient groups (3) identified according to the maximum triglyceride changes pre (green dot) - and post (red dot) ASP infusion. [Display omitted] DisclosuresPorkka:Pfizer: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding.

Whole-Genome Mate Pair Sequencing Transforms Cytogenetic Analysis of Hematologic Malignancies: Development of a Targeted Panel to Detect Diagnostic/Prognostic Chromosomal Rearrangements and Copy Number Changes in AML

Acute myeloid leukemia (AML) is the most common form of acute leukemia affecting both children and adults. Once recognized as a single disease, the World Health Organization now groups AML into ten subtypes based on genetic abnormality. This is based on differences among recurrent genetic abnormalities with respect to response to therapy, relapse risk and overall survival. Currently most testing of AML patients occurs by karyotype analysis, FISH or RT-PCR. Here we describe a next generation sequencing approach to better classify and accurately detect abnormalities associated with AML.For the validation of whole genome mate pair sequencing (MPseq) targeted panel to test patients with AML, twenty-five abnormal and ten normal samples extracted from each sample type (peripheral blood (PB) and bone marrow (BM)) were run with the MPseq assay. Samples were chosen based on reported abnormalities previously tested by conventional karyotyping and/or FISH. The mate pair panel is designed to detect rearrangements involving genes ABL1, BCR, CBFB, CREBBP, DEK, KAT6A(MYST3), MECOM(EVI1), MLF1, MLL(KMT2A), MYH11, NPM1, NUP214(CAN), NUP98, PML, RARA, RPN1, RUNX1(AML1), RUNX1T1(ETO) and copy number changes on chromosomes 5, 7, 8, 13, 17, and 20. DNA was processed using the Illumina Nextera Mate Pair library preparation kit, multiplexed at 2 samples/lane and sequenced on the Illumina HiSeq. Data was aligned to the reference genome (GRCh38) using BIMA and abnormalities were identified using SVAtools, both in-house developed tools. A targeted analysis approach was utilized using a well-defined list of recurrent chromosomal abnormalities associated with known diagnostic and prognostic significance as well as targeted therapies in AML. The karyotype, FISH and MPseq results were compared to determine concordance.To test the limit of detection based on percent tumor, samples previously tested with FISH were diluted. Tumor percentage was determined by the abnormal FISH result and was diluted with a normal sample to mimic various percentages (100%, 50%, 25%, 10%, 5%, 2%). For both PB and BM specimens, the rearrangements were detected down to the 10% dilution and the copy number changes were detected down to 25%. Based on these cutoffs, all 50 abnormal samples (25 PB, 25 BM) used for the validation were 100% concordant with abnormalities targeted by the panel that were previously detected by FISH and/or karyotype. In addition, MPseq identified additional abnormalities not detected by karyotype or FISH and further characterized several complex abnormalities. One example includes a case with MLLT10/MLL(KMT2A) fusion detected by MPseq which was missed by the AML FISH panel because the rearrangement involved an insertional translocation. Another example is the identification of BCR/FGFR1 fusion in a case when AML FISH identified three copies of BCR.In conclusion, we validated a whole genome mate pair sequencing targeted panel to detect diagnostic/prognostic chromosomal rearrangements and copy number changes in patients with AML. Due to the limitations in detecting very low level abnormalities, MPseq would not be recommended for follow-up post therapy or minimal residual disease testing unless the coverage is increased with deeper sequencing. However, our validation study demonstrate the clinical utility of MPseq as a potential replacement assay to conventional FISH on diagnostic AML samples and highlight the increased diagnostic yield. Thus, MPseq represents a next generation sequencing technology that has the potential to revolutionize the diagnosis of hematologic malignancies and provide an opportunity to advance precision medicine. DisclosuresNo relevant conflicts of interest to declare.

Design and usability testing of an in-house developed performance feedback tool for medical students

BackgroundFeedback is essential in a self-regulated learning environment such as medical education. When feedback channels are widely spread, the need arises for a system of integrating this information in a single platform. This article reports on the design and initial testing of a feedback tool for medical students at Charité-Universitätsmedizin, Berlin, a large teaching hospital. Following a needs analysis, we designed and programmed a feedback tool in a user-centered approach. The resulting interface was evaluated prior to release with usability testing and again post release using quantitative/qualitative questionnaires.ResultsThe tool we created is a browser application for use on desktop or mobile devices. Students log in to see a dashboard of “cards” featuring summaries of assessment results, a portal for the documentation of acquired practical skills, and an overview of their progress along their course. Users see their cohort’s average for each format. Learning analytics rank students’ strengths by subject. The interface is characterized by colourful and simple graphics. In its initial form, the tool has been rated positively overall by students. During testing, the high task completion rate (78%) and low overall number of non-critical errors indicated good usability, while the quantitative data (system usability scoring) also indicates high ease of use. The source code for the tool is open-source and can be adapted by other medical faculties.ConclusionsThe results suggest that the implemented tool LevelUp is well-accepted by students. It therefore holds promise for improved, digitalized integrated feedback about students’ learning progress. Our aim is that LevelUp will help medical students to keep track of their study progress and reflect on their skills. Further development will integrate users’ recommendations for additional features as well as optimizing data flow.

Dosimetric Impact of Physician Style Variations in Contouring CTV for Postoperative Prostate Cancer: A Deep Learning—Based Simulation Study

Inter-observer variation is a significant problem in clinical target volume (CTV) segmentation in postoperative settings, where there is no gross tumor present. In this scenario, the CTV is not an anatomically established structure, but one determined by the physician based on the clinical guideline used, the preferred trade-off between tumor control and toxicity, their experience and training background, and other factors. This results in high inter-observer variability between physicians. This variability has been considered an issue, but the absence of multiple physician CTV contours for each patient and the significant amount of time required for dose planning based on each physician CTV have made it impractical to study its dosimetric consequences. In this study, we analyze the impact that variations in physician style have on dose to organs-at-risk (OAR) by simulating the clinical workflow via deep learning. For a given patient previously treated by one physician, we use deep learning–based tools to simulate how other physicians would contour the CTV and how the corresponding dose distributions would look for other physicians. To simulate multiple physician styles, we use a previously developed in-house CTV segmentation model that can produce physician style–aware segmentations. The corresponding dose distribution is predicted using another in-house deep learning tool, which, can predict dose within 3% of the prescription dose, on average, on the test data. For every test patient, four different physician style CTVs are considered, and four different dose distributions are analyzed. OAR dose metrics are compared, showing that even though physician style variations result in organs getting different doses, all the important dose metrics except maximum dose point are within the clinically acceptable limit.

Toxic effects of nanomaterials for health applications: How automation can support a systematic review of the literature?

Systematic reviews of the scientific literature can be an important source of information supporting the daily work of the regulators in their decision making, particularly in areas of innovative technologies where the regulatory experience is still limited. Significant research activities in the field of nanotechnology resulted in a huge number of publications in the last decades. However, even if the published data can provide relevant information, scientific articles are often of diverse quality, and it is nearly impossible to manually process and evaluate such amount of data in a systematic manner. In this feasibility study, we investigated to what extent open‐access automation tools can support a systematic review of toxic effects of nanomaterials for health applications reported in the scientific literature. In this study, we used a battery of available tools to perform the initial steps of a systematic review such as targeted searches, data curation and abstract screening. This work was complemented with an in‐house developed tool that allowed us to extract specific sections of the articles such as the materials and methods part or the results section where we could perform subsequent text analysis. We ranked the articles according to quality criteria based on the reported nanomaterial characterisation and extracted most frequently described toxic effects induced by different types of nanomaterials. Even if further demonstration of the reliability and applicability of automation tools is necessary, this study demonstrated the potential to leverage information from the scientific literature by using automation systems in a tiered strategy.

EmiRIT: a text-mining-based resource for microRNA information.

microRNAs (miRNAs) are essential gene regulators, and their dysregulation often leads to diseases. Easy access to miRNA information is crucial for interpreting generated experimental data, connecting facts across publications and developing new hypotheses built on previous knowledge. Here, we present extracting miRNA Information from Text (emiRIT), a text-miningbased resource, which presents miRNA information mined from the literature through a user-friendly interface. We collected 149 ,233 miRNA –PubMed ID pairs from Medline between January 1997 and May 2020. emiRIT currently contains ‘miRNA –gene regulation’ (69 ,152 relations), ‘miRNA disease (cancer)’ (12 ,300 relations), ‘miRNA –biological process and pathways’ (23, 390 relations) and circulatory ‘miRNAs in extracellular locations’ (3782 relations). Biological entities and their relation to miRNAs were extracted from Medline abstracts using publicly available and in-house developed text-mining tools, and the entities were normalized to facilitate querying and integration. We built a database and an interface to store and access the integrated data, respectively. We provide an up-to-date and user-friendly resource to facilitate access to comprehensive miRNA information from the literature on a large scale, enabling users to navigate through different roles of miRNA and examine them in a context specific to their information needs. To assess our resource’s information coverage, we have conducted two case studies focusing on the target and differential expression information of miRNAs in the context of cancer and a third case study to assess the usage of emiRIT in the curation of miRNA information. Database URL: https://research.bioinformatics.udel.edu/emirit/

Algorithm to derive progression-based lines of therapy from a real-world non-small cell lung cancer (NSCLC) dataset.

e21172 Background: Analysis of Real World Data (RWD) from Electronic Health Records (EHR) for applications such as Health Economics and Outcomes Research (HEOR) or regulatory submissions requires identification of the lines of therapy (LoT) patients have received. LoTs are typically not captured in EHR and must be manually abstracted. As the use of RWD increases, there is a growing need to create algorithms that can work on RWD to extract LoT information in an automated manner with high accuracy. We present here the results of such an algorithm created on NSCLC RWD. Methods: 10950 advanced NSCLC patients from the ConcertAI Oncology RWD database who had received anti-neoplastic treatment after advanced diagnosis were used to build and validate this algorithm. These data were further enriched by expert nurse curators to fill in missing oral drug information and identify progression events. We developed a progression-based LoT (pLoT) model that identified LoT changes in sync with tumor progressions. If patients received multiple regimens before progression they were captured as nested regimens within the LoT. The algorithm uses complex rules to define combination of drugs as regimens (combination rule), identify resumption of regimens (gap rule) or dropping of drugs from regimens as new lines and to handle noisiness in RWD etc. Results: The LoT model accurately captures line changes triggered by progression events as well as any nested regimen changes due to adverse events etc. Patient level validation of LoT was carried out by clinical experts using an in-house tool and found to be consistent with literature &amp; individual drug data. Cohort level analysis of top 3 combinations of therapies used in 1st &amp; 2nd line treatment between 2015-2020 (8200 patients) are shown in Table. Sensitivity analysis on the combination rule showed that this parameter can be changed between 28-33 days without significantly impacting the LoT output (&lt;1% impact). We use a 30 day combination rule as the default. Similarly, the gap rule parameter is quite robust and does not show significant variation between 45 – 90 days (&lt;2% impact). We use 63 days. Conclusions: We have developed a robust algorithm to derive pLoT on RWD at scale assuming availability of curated progression data which can be used to support use cases such as HEOR, clinical development and regulatory submissions. pLoT is better suited for outcomes analysis compared to regimen based LoT since it distinguishes changes in treatment due to progression events from changes due to toxicity, drug availability, etc., and allows analysis on a more homogeneous patient population relating to their past clinical experience. [Table: see text]

Preliminary uncertainty and sensitivity analysis of the Molten Salt Fast Reactor steady-state using a Polynomial Chaos Expansion method

In this work, we present the results of a preliminary uncertainty quantification and sensitivity analysis study of the Molten Salt Fast Reactor (MSFR) behavior at steady-state performed by applying a non-intrusive Polynomial Chaos Expansion (PCE) approach. An in-house high-fidelity multi-physics simulation tool is used as reactor reference model. Considering several thermal-hydraulics and neutronics parameters as stochastic inputs, with a limited number of samples we build a PCE meta-model able to reproduce he reactor response in terms of effective multiplication factor, maximum, minimum, and average salt temperatures, and complete salt temperature distribution. The probability density functions of the responses are constructed and analyzed, highlighting strengths and issues of the current MSFR design. The sensitivity study highlights the relative importance of each input parameter, thus providing useful indications for future research efforts. The analysis on the whole temperature field shows that the heat exchanger can be a critical component, so its design requires particular care.