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At least 19 records

Information-incorporated gene network construction with FDR control

Abstract Motivation Large-scale gene expression studies allow gene network construction to uncover associations among genes. To study direct associations among genes, partial correlation-based networks are preferred over marginal correlations. However, FDR control for partial correlation-based network construction is not well-studied. In addition, currently available partial correlation-based methods cannot take existing biological knowledge to help network construction while controlling FDR. Results In this paper, we propose a method called Partial Correlation Graph with Information Incorporation (PCGII). PCGII estimates partial correlations between each pair of genes by regularized node-wise regression that can incorporate prior knowledge while controlling the effects of all other genes. It handles high-dimensional data where the number of genes can be much larger than the sample size and controls FDR at the same time. We compare PCGII with several existing approaches through extensive simulation studies and demonstrate that PCGII has better FDR control and higher power. We apply PCGII to a plant gene expression dataset where it recovers confirmed regulatory relationships and a hub node, as well as several direct associations that shed light on potential functional relationships in the system. We also introduce a method to supplement observed data with a pseudogene to apply PCGII when no prior information is available, which also allows checking FDR control and power for real data analysis. Availability and implementation R package is freely available for download at https://cran.r-project.org/package=PCGII.

59 BASIC BIOLOGICAL SCIENCES↗

Improving Peptide-Level Mass Spectrometry Analysis via Double Competition

A critical statistical task in the analysis of shotgun proteomics data involves controlling the false discovery rate (FDR) among the reported set of discoveries. This task is most commonly solved at the peptide-spectrum match (PSM) level by using target-decoy competition (TDC), in which a set of observed spectra are searched against a database containing a mixture of real (target) and decoy peptides. The PSM-level procedure can be adapted to the peptide level by selecting the top-scoring PSM per peptide prior to FDR estimation. Here, we investigate both PSM-level and peptide-level FDR control methods and come to two conclusions. First, although the TDC procedure is provably correct under certain assumptions, we observe that one of these assumptions - that incorrect PSMs are independent of one another - is frequently violated. Hence, we empirically demonstrate that TDC-based PSM-level FDR estimates can be liberally biased. Further, we propose that researchers avoid PSM-level results and instead focus on peptide-level analysis. Second, we investigate three ways to carry out peptide level TDC and show that the most common method ("PSM-only") offers the lowest statistical power in practice. The most powerful method, peptide-level FDR with PSM competition ("PSM-and-peptide"), carries out competition first at the PSM level and then again at the peptide level. In our experiments, this approach yields an average increase of 17% more discovered peptides at a1% FDR threshold relative to the PSM-only method.

59 BASIC BIOLOGICAL SCIENCES↗

Comparing Top-Down Proteoform Identification: Deconvolution, PrSM Overlap, and PTM Detection

Generating top-down tandem mass spectra (MS/MS) for complex mixtures of proteoforms has become possible through improvements in fractionation, on-line separation, dissociation, and mass analysis. The algorithms to match tandem mass spectra to sequences have undergone a parallel evolution, with both spectral alignment and peak matching being paired with diverse methods for scoring proteoform-spectral matches (PrSMs). This study assesses state-of-the-art algorithms for top-down identification through three distinct challenges. The first is identifying a large yield of PrSMs while controlling false discovery rate (FDR) in identifying thousands of proteoforms from complex cell lysates via four software workflows: ProSight Proteome Discoverer, TopPIC, Informed Proteomics, and pTop. The second is the deconvolution of data from both Thermo Orbitrap-class and Bruker maXis Q-TOF instruments to produce consistent precursor charge and mass determinations while generating fragment mass lists to optimize identification. The third attempts to detect diverse post-translational modifications (PTMs) in proteoforms from cow milk and human ovarian tissue. The data demonstrate that existing software suites produce admirable sensitivity, in some cases identifying a third of collected tandem mass spectra with FDR controlled below 2%; the overlap in these PrSMs, however, illustrates real value in searching data with multiple search engines. Differences among identification workflows seem to result from each search algorithm incorporating its own deconvolution algorithm. By transmitting deconvolution data from multiple deconvolution routes (Thermo Xtract, Bruker Auto MSn, Mascot Distiller, TopFD, and FLASHDeconv) to the downstream TopPIC search algorithm, we were able to detect common causes of deconvolution disagreement. The detection of PTMs was very inconsistent among search algorithms, with some workflows suggesting as little as 1% of PrSMs from cow’s milk were singly-phosphorylated while other workflows found that 18% of PrSMs were singly-phosphorylated. Taken together, these results make a strong argument for top-down researchers to adopt a standard practice of analyzing each MS/MS experiment with at least two different search engines.

59 BASIC BIOLOGICAL SCIENCES↗

Target–decoy false discovery rate estimation using Crema

Assigning statistical confidence estimates to discoveries produced by a tandem mass spectrometry proteomics experiment is critical to enabling principled interpretation of the results and assessing the cost/benefit ratio of experimental follow-up. The most common technique for computing such estimates is to use target-decoy competition (TDC), in which observed spectra are searched against a database of real (target) peptides and a database of shuffled or reversed (decoy) peptides. TDC procedures for estimating the false discovery rate (FDR) at a given score threshold have been developed for application at the level of spectra, peptides, or proteins. Although these techniques are relatively straightforward to implement, it is common in the literature to skip over the implementation details or even to make mistakes in how the TDC procedures are applied in practice. Here we present Crema, an open-source Python tool that implements several TDC methods of spectrum-, peptide- and protein-level FDR estimation. Crema is compatible with a variety of existing database search tools and provides a straightforward way to obtain robust FDR estimates.

59 BASIC BIOLOGICAL SCIENCES↗

Accurate Identification of Deamidation and Citrullination from Global Shotgun Proteomics Data Using a Dual-Search Delta Score Strategy

While proteins with deamidated/citrullinated amino acids play critical roles in the pathogenesis of many human diseases, identifying these modifications in complex biological samples has been an ongoing challenge. Herein we present a method to accurately identify these modifications from shotgun proteomics data from a deep proteome profiling study of human pancreatic islets obtained by laser capture microdissection. All MS/MS spectra were searched against database by MSGF+ twice with or without a +0.9840 Da mass shift on amino acids asparagine, glutamine, and arginine (NQR) as a dynamic modification. Consequently, for each spectrum the resulting two peptide-to-spectrum matches (PSM) with their respective MSGF+ scores were used for Delta Score calculation. It was observed that all PSMs with positive Delta Score values were clustered with mass errors around 0 ppm, while PSMs with negative Delta Score values were distributed nearly equally within the defined mass error range (20 ppm) for database searching. To estimate false discovery rate (FDR), a “pseudo-decoy” approach was applied whether datasets were searched against a database with a “real modification” mass shift (+0.9840 Da) and a “mock modification” mass shift (+1.0227 Da). FDR was controlled to ~2% with a Delta Score filter greater than zero. Manual inspection of spectra showed that PSMs with positive Delta Score value contained deamidated/citrullinated fragments in their MS/MS spectra. Finally, the results demonstrated that in-situ deamidated/citrullinated peptides can be accurately identified from shotgun tissue proteomics data by the Dual-search Delta Score Strategy.

59 BASIC BIOLOGICAL SCIENCES↗

Chemoproteogenomic stratification of the missense variant cysteinome

Abstract Cancer genomes are rife with genetic variants; one key outcome of this variation is widespread gain-of-cysteine mutations. These acquired cysteines can be both driver mutations and sites targeted by precision therapies. However, despite their ubiquity, nearly all acquired cysteines remain unidentified via chemoproteomics; identification is a critical step to enable functional analysis, including assessment of potential druggability and susceptibility to oxidation. Here, we pair cysteine chemoproteomics—a technique that enables proteome-wide pinpointing of functional, redox sensitive, and potentially druggable residues—with genomics to reveal the hidden landscape of cysteine genetic variation. Our chemoproteogenomics platform integrates chemoproteomic, whole exome, and RNA-seq data, with a customized two-stage false discovery rate (FDR) error controlled proteomic search, which is further enhanced with a user-friendly FragPipe interface. Chemoproteogenomics analysis reveals that cysteine acquisition is a ubiquitous feature of both healthy and cancer genomes that is further elevated in the context of decreased DNA repair. Reference cysteines proximal to missense variants are also found to be pervasive, supporting heretofore untapped opportunities for variant-specific chemical probe development campaigns. As chemoproteogenomics is further distinguished by sample-matched combinatorial variant databases and is compatible with redox proteomics and small molecule screening, we expect widespread utility in guiding proteoform-specific biology and therapeutic discovery.

Desai, Heta (ORCID:0000000343621707)↗

Inference for Nonparanormal Partial Correlation via Regularized Rank-Based Nodewise Regression

Abstract Partial correlation is a common tool in studying conditional dependence for Gaussian distributed data. However, partial correlation being zero may not be equivalent to conditional independence under non-Gaussian distributions. In this paper, we propose a statistical inference procedure for partial correlations under the high-dimensional nonparanormal (NPN) model where the observed data are normally distributed after certain monotone transformations. The NPN partial correlation is the partial correlation of the normal transformed data under the NPN model, which is a more general measure of conditional dependence. We estimate the NPN partial correlations by regularized nodewise regression based on the empirical ranks of the original data. A multiple testing procedure is proposed to identify the nonzero NPN partial correlations. The proposed method can be carried out by a simple coordinate descent algorithm for lasso optimization. It is easy-to-implement and computationally more efficient compared to the existing methods for estimating NPN graphical models. Theoretical results are developed to show the asymptotic normality of the proposed estimator and to justify the proposed multiple testing procedure. Numerical simulations and a case study on brain imaging data demonstrate the utility of the proposed procedure and evaluate its performance compared to the existing methods. Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

97 MATHEMATICS AND COMPUTING↗

A Pilot Study of Whole-Blood Transcriptomic Analysis to Identify Genes Associated with Repetitive Low-Level Blast Exposure in Career Breachers

Repetitive low-level blast exposure is one of the major occupational health concerns among US military service members and law enforcement. This study seeks to identify gene expression using microRNA and RNA sequencing in whole-blood samples from experienced breachers and unexposed controls. We performed experimental RNA sequencing using Illumina’s HiSeq 2500 Sequencing System, and microRNA analysis using NanoString Technology nCounter miRNA expression panel in whole-blood total RNA samples from 15 experienced breachers and 14 age-, sex-, and race-matched unexposed controls. We identified 10 significantly dysregulated genes between experienced breachers and unexposed controls, with FDR corrected <0.05: One upregulated gene, LINC00996 (long intergenic non-protein coding RNA 996); and nine downregulated genes, IGLV3-16 (immunoglobulin lambda variable 3-16), CD200 (CD200 molecule), LILRB5 (leukocyte immunoglobulin-like receptor B5), ZNF667-AS1 (ZNF667 antisense RNA 1), LMOD1 (leiomodin 1), CNTNAP2 (contactin-associated protein 2), EVPL (envoplakin), DPF3 (double PHD fingers 3), and IGHV4-34 (immunoglobulin heavy variable 4-34). The dysregulated gene expressions reported here have been associated with chronic inflammation and immune response, suggesting that these pathways may relate to the risk of lasting neurological symptoms following high exposures to blast over a career.

59 BASIC BIOLOGICAL SCIENCES↗

Navier-Stokes Analysis of the Flowfield Characteristics of an Ice Contaminated Aircraft Wing

An analytical study was performed as part of the NASA Lewis support of a National Transportation Safety Board (NTSB) aircraft accident investigation. The study was focused on the performance degradation associated with ice contamination on the wing of a commercial turbo-prop-powered aircraft. Based upon the results of an earlier numerical study conducted by the authors, a prominent ridged-ice formation on the subject aircraft wing was selected for detailed flow analysis using 2-dimensional (2-D), as well as, 3-dimensional (3-D) Navier-Stokes computations. This configuration was selected because it caused the largest lift decrease and drag increase among all the ice shapes investigated in the earlier study. A grid sensitivity test was performed to find out the influence of grid spacing on the lift, drag, and associated angle-of-attack for the maximum lift (C(sub lmax)). This study showed that grid resolution is important and a sensitivity analysis is an essential element of the process in order to assure that the final solution is independent of the grid. The 2-D results suggested that a severe stability and control difficulty could have occurred at a slightly higher angle-of-attack (AOA) than the one recorded by the Flight Data Recorder (FDR). This stability and control problem was thought to have resulted from a decreased differential lift on the wings with respect to the normal loading for the configuration. The analysis also indicated that this stability and control problem could have occurred whether or not natural ice shedding took place. Numerical results using an assumed 3-D ice shape showed an increase of the angle at which this phenomena occurred of about 4 degrees. As it occurred with the 2-D case, the trailing edge separation was observed but started only when the AOA was very close to the angle at which the maximum lift occurred.

Chung, J.↗

Cortical proteins may provide motor resilience in older adults

Motor resilience proteins may be a high value therapeutic target that offset the negative effects of pathologies on motor function. This study sought to identify cortical proteins associated with motor decline unexplained by brain pathologies that provide motor resilience. We studied 1226 older decedents with annual motor testing, postmortem brain pathologies and quantified 226 proteotypic peptides in prefrontal cortex. Twenty peptides remained associated with motor decline in models controlling for ten brain pathologies (FDR < 0.05). Higher levels of nine peptides and lower levels of eleven peptides were related to slower decline. A higher motor resilience protein score based on averaging the levels of all 20 peptides was related to slower motor decline, less severe parkinsonism and lower odds of mobility disability before death. Cortical proteins may provide motor resilience. Targeting these proteins in further drug discovery may yield novel interventions to maintain motor function in old age.

Buchman, Aron↗

Characterizing the Joint Effect of Diverse Test-Statistic Correlation Structures and Effect Size on False Discovery Rates in a Multiple-Comparison Study of Many Outcome Measures

In their 2009 Annals of Statistics paper, Gavrilov, Benjamini, and Sarkar report the results of a simulation assessing the robustness of their adaptive step-down procedure (GBS) for controlling the false discovery rate (FDR) when normally distributed test statistics are serially correlated. In this study we extend the investigation to the case of multiple comparisons involving correlated non-central t-statistics, in particular when several treatments or time periods are being compared to a control in a repeated-measures design with many dependent outcome measures. In addition, we consider several dependence structures other than serial correlation and illustrate how the FDR depends on the interaction between effect size and the type of correlation structure as indexed by Foerstner s distance metric from an identity. The relationship between the correlation matrix R of the original dependent variables and R~, the correlation matrix of associated t-statistics is also studied. In general R~ depends not only on R, but also on sample size and the signed effect sizes for the multiple comparisons.

Feiveson, Alan H.↗

Spread spectrum time domain reflectometry (SSTDR) and frequency domain reflectometry (FDR) cable inspection using machine learning

Cables are initially qualified for nuclear power plant use for 40 years. As plants extend their operating license to 60 and 80 years, justification for continued cable use must shift to a condition-based approach since it is cost prohibitive to completely replace cables that are likely still capable of performing their design function. The Pacific Northwest National Laboratory (PNNL) Accelerated and Real Time Experimental Nodal Analysis (ARENA) cable motor test bed was used to test the response of a commercial spread spectrum time domain reflectometry (SSTDR) system, a laboratory instrument software-controlled SSTDR, and a vector network analyzer-based frequency domain reflectometry (FDR) system to various cable anomalies. The three instrument systems were able to interrogate cables over a range of frequency bandwidths that can be helpful for human data analysis. Data were subjected to supervised and unsupervised machine learning (ML) analyses to distinguish normal undamaged cable responses from anomalous cable responses. Both supervised and unsupervised ML approaches produced encouraging results with an undamaged/anomalous prediction accuracy from 0.69% to 0.87%. Recommendations for further development and field implementation include increased and more balanced sample sets particularly including more training data.

SSTDR, FDR, Reflectometry, Machine Learning, ARENA↗

Reconstruction of the 1994 Pittsburgh Airplane Accident Using a Computer Simulation

On September 8, 1994, a Boeing 737-300 passenger airplane was on a downwind approach to the Pittsburgh International Airport at an altitude of 5000 feet above ground level (6000 feet MSL). While in a shallow left turn onto a downwind approach heading, the airplane crossed into the vortex trail of a Boeing 727 flying in the same approach pattern about 4 miles ahead. The B-737 airplane rolled and turned sharply to the left, exited the vortex wake and plunged into the ground. Weather was not a factor in the accident. The airplane was equipped with a 11+ channel digital Flight Data Recorder (FDR) and a multiple channel Cockpit Voice Recorder (CVR). Both recorders were recovered from the crash site and provided excellent data for the development of an accident scenario. Radar tracking of the two airplanes as well as the indicated air speed (IAS) perturbations clearly visible on the B-737 FDR recordings indicate that the upset was apparently initiated by the airplane's crossing into the wake of the B-727 flying ahead in the same traffic pattern. A 6 degree-of-freedom simulation program for the B-737 airplane using MATLAB and SIMULINK was constructed. The simulation was initialized at the stabilized flight conditions of the airplane about 13 seconds prior to its entry into the vortex trail of the B-727 airplane. By assuming a certain combination of control inputs, it was possible to produce a simulated motion that closely matched that recorded on the FDR.

Parks, Edwin K.↗

Progress in ITER ECE diagnostic design and integration

The ITER electron cyclotron emission (ECE) diagnostic system has primary roles in providing measurements of the core electron temperature profile and the electron temperature fluctuation associated with the neoclassical tearing modes. The ITER ECE system includes a radial and oblique line-of-sight. Four 43-meter long low-loss transmission lines (TLs) are designed to transmit millimeter wave power in the frequency range of 70–1000 GHz in both X- and O-mode polarization from the port plug to the ECE instrumentation room in the diagnostic building. The measurement instrumentation includes two Fourier transform spectrometer (FTS) systems and two radiometer systems. The Indian Domestic Agency (IN-DA) and United States Domestic Agency share the responsibility. The IN-DA scope excluding instrumentation and control has passed its preliminary design review and is progressing towards the final design review (FDR). In parallel, the diagnostic integration in different areas is ongoing. Furthermore, several captive components for the TLs have passed FDR and will be manufactured for installation in the tokamak building soon. A peer review meeting has been held on the prototype hot calibration source, and its integration and new thermal analysis in the diagnostic shield module are continuing. A prototype TL is being tested. A prototype polarizing Martin-Puplett type FTS, operating in the frequency range 70–1000 GHz, features an in-vacuo fast scanning mechanism and a cryo-cooled dual-channel THz detector system. Its performance has been assessed in detail against ITER requirements.

47 OTHER INSTRUMENTATION↗

PROACTIVE Focus Area 4: Structured Decision Metrics Analysis (Final Report)

A structured decision metrics analysis was developed as one of the tasks under PROACTIVE’s Focus Area 4 (FA4) and used structured decision metrics for processes, items, and facilities (PIF) to determine the efficacy of an M&V system in meeting treaty goals and technical objectives. The method starts with the functional decomposition of a “treaty” with the M&V system overlaid on it. A Functional Decomposition Rubric (FDR) for each PIF is used to determine a score ranging from 0 (weak) to 4 (strong) for assurance, security, and burden. The individual scores are combined to provide an overall Verification System Score (VSS) which assesses the overall verification system’s suitability given goals; scores for each step of the process are also given. The outcome of the evaluation is to identify needs or modifications to the enterprise model, verification system, or proposed testbed capabilities. VeriScore was used to evaluate FA4’s Spiral 0 exercise; those results are included in this report. The VeriScore and FDR framework can also be used in a non-treaty environment, as any goal/objective/method structure will work, thus expanding its applicability beyond traditional arms control structures.

99 GENERAL AND MISCELLANEOUS↗

The ARENA Test Bed – A Versatile Resource for I&C Development and Validation

The Accelerated and Real-time Experimental Nodal Assessment (ARENA) Test Bed at the Pacific Northwest National Laboratory (PNNL) is a versatile resource for development and validation of instrumentation and control (I&C) technologies. This capability was created to facilitate in-situ testing of nuclear electrical cables in various simulated operational environments. Using cable trays, a control box, and selected test components, low voltage cables can be staged to experience local adverse environments such as elevated temperature and water immersion. Cable condition can be continuously monitored over time to track the effect of local stresses using nondestructive assessment tools. A heads-up display (ARENA TV) plots key data in real-time for users. The ARENA Test Bed has recently been used to evaluate the potential for spread spectrum time domain reflectometry (SSTDR) to monitor thermal aging of a portion of live cable powering a three-phase motor. The arrangement provided the opportunity to directly compare the performance of the novel online SSTDR method with offline results from the more standard frequency domain reflectometry (FDR) method. The ability of SSTDR and FDR to identify the presence of water in immersed shielded and unshielded cables and to detect ground faults was also assessed. A digital twin is being developed to track and predict FDR signals from a thermally aging conceptual cable region to compare with measured signals from the ARENA physical counterpart. The test bed concept addresses an important need in nuclear I&C monitoring tool development. New tools and techniques can be developed in the test bed and validated versus known methods and physical measurements. Digital twins and machine learning engines can be populated with measured data in a controlled environment that would not be readily available in the actual nuclear power plant. Proposed monitoring strategies can be confirmed for effectiveness through objective evaluation. It is anticipated that the PNNL ARENA Test Bed will be a valuable resource in advancing nuclear plant instrumentation.

nuclear electrical cables, ARENA Test Bed, conditi↗

Impact of Porcine Arterivirus, Influenza B, and Their Coinfection on Antiviral Response in the Porcine Lung

Interferon (IFN) cytokines induce an autonomous antiviral state in cells of the infected site to restrict virus spreading and critically regulate overall antiviral response. The antiviral state leads to host protection through expression of hundreds of IFN-stimulated genes that restrict viral infection through multiple mechanisms, for example, directly in viral genome degradation and indirectly through cellular metabolic inhibition. Young pigs were split into four treatment groups: control, porcine reproductive and respiratory syndrome virus (PRRSV, also known as porcine arterivirus) infected, influenza B virus (IBV) infected, and IBV/PRRSV coinfection. Lung tissue was collected at 3, 5, and 7 days post infection (dpi) for control, PRRSV and IBV/PRRSV coinfection, and at 3 and 5 dpi for IBV. Transcriptomic analysis, using usegalaxy.org tools, was performed against the S.scrofa 11.1 reference genome. Differentially expressed gene (DEG) analysis was carried out using DeSeq2 based on the model treatment + dpi + treatment:dpi + E. Downstream analysis examined the interaction of DEG at each dpi for over-enriched gene ontology (G.O.) terms and pathways. Comparisons of the infected groups vs. the controls yielded a total of (n = 1412) DEGs for the PRRSV group and (n = 1578) for the IBV/PRRSV group across all timepoints. The IBV group had (n = 64) total DEGs across 3 and 5 dpi. Expression data were considered statistically significant based on false discovery rate (FDR) ⫹ 0.1. Venn diagram comparisons of the DEGs across dpi showed that groups shared only 16 DEGs at 3 dpi, no DEGs were shared at 5 dpi, and for 7 dpi, only the PRRSV and IBV/PRRSV groups were compared and shared a total of 43 DEGs. Across the comparisons, differential expression was observed in antiviral genes such as IRF1, MX1, and OAS2. The IBV and IBV/PRRSV groups showed higher expression of antiviral genes at earlier dpi than the PRRSV group. Additionally, downregulated genes from the comparisons clustered around Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways effecting lung development and cellular integrity. Early expression of host IFN and antiviral genes may lead to viral RNA degradation, and assembly and transcription inhibition in the IBV infections. In comparison, expression of antiviral genes in the PRRSV group decreased across time. The decrease may explain why PRRSV infections persist, while IBV clears. Moreover, all infected groups showed prolonged upregulation in neutrophil degranulation pathway activity, possibly exacerbating symptomatic lung lesion pathology seen in these respiratory infections.

59 BASIC BIOLOGICAL SCIENCES↗

An Experimental and Numerical Study of Icing Effects on the Performance and Controllability of a Twin Engine Aircraft

In September 1997 the National Transportation Safety Board (NTSB) requested assistance from the NASA Lewis Research Center (LeRC) Icing Branch in the investigation of an aircraft accident that was suspected of being caused by ice contamination. In response to the request NASA agreed to perform an experimental and computational study. The main activities that NASA performed were LERC Icing Research Tunnel (IRT) testing to define ice shapes and 2-D Navier-Stokes analysis to determine the performance degradation that those ice shapes would have caused. An IRT test was conducted in January 1998. Most conditions for the test were based upon raw and derived data from the Flight Data Recorder (FDR) recovered from the accident and upon the current understanding of the Meteorological conditions near the accident. Using a two-dimensional Navier-Stokes code, the flow field and resultant lift and drag were calculated for the wing section with various ice shapes accreted in the IRT test. Before the final calculations could be performed extensive examinations of geometry smoothing and turbulence were conducted. The most significant finding of this effort is that several of the five-minute ice accretions generated in the IRT were found by the Navier-Stokes analysis to produce severe lift and drag degradation. The information generated by this study suggests a possible scenario for the kind of control upset recorded in the accident. Secondary findings were that the ice shapes accreted in the IRT were mostly limited to the protected pneumatic boot region of the wing and that during testing, activation of the pneumatic boots cleared most of the ice.

Reehorst, A.↗