Use of Energy Consumption during Milling to Fill a Measurement Gap in Hybrid Additive Manufacturing

Coupling additive manufacturing (AM) with interlayer peening introduces bulk anisotropic properties within a build across several centimeters. Current methods to map high resolution anisotropy and heterogeneity are either destructive or have a limited penetration depth using a nondestructive method. An alternative pseudo-nondestructive method to map high-resolution anisotropy and heterogeneity is through energy consumption during milling. Previous research has shown energy consumption during milling correlates with surface integrity. Since surface milling of additively manufactured parts is often required for post-processing to improve dimensional accuracy, an opportunity is available to use surface milling as an alternative method to measure mechanical properties and build quality. The variation of energy consumption during the machining of additive parts, as well as hybrid AM parts, is poorly understood. In this study, the use of net cutting specific energy was proposed as a suitable metric for measuring mechanical properties after interlayer ultrasonic peening of 316 stainless steel. Energy consumption was mapped throughout half of a cuboidal build volume. Results indicated the variation of net cutting specific energy increased farther away from the surface and was higher for hybrid AM compared to as-printed and wrought. The average lateral and layer variation of the net cutting specific energy for printed samples was 81% higher than the control, which indicated a significantly higher degree of heterogeneity. Further, it was found that energy consumption was an effective process signature exhibiting strong correlations with microhardness. Anisotropy based on residual strains were measured using net cutting specific energy and validated by hole drilling. The proposed technique contributes to filling part of the measure gap in hybrid additive manufacturing and capitalizes on the preexisting need for machining of AM parts to achieve both goals of surface finish and quality assessment in one milling operation

Accelerated Sizing of a Power Split Electrified Powertrain

Component sizing generally represents a demanding and time-consuming task in the development process of electrified powertrains. A couple of processes are available in literature for sizing the hybrid electric vehicle (HEV) components. These processes employ either time-consuming global optimization techniques like dynamic programming (DP) or near-optimal techniques that require iterative and uncertain tuning of evaluation parameters like the Pontryagin's minimum principle (PMP). Recently, a novel near-optimal technique has been devised for rapidly predicting the optimal fuel economy benchmark of design options for electrified powertrains. This method, named slope-weighted energy-based rapid control analysis (SERCA), has been demonstrated producing results comparable to DP, while limiting the associated computational time by near two orders of magnitude. In this paper, sizing parameters for a power split electrified powertrain are considered that include the internal combustion engine size, the two electric motor/generator sizes, the transmission ratios, and the final drive ratio. The SERCA approach is adopted to rapidly evaluate the fuel economy capabilities of each sizing option in various driving missions considering both type-approval drive cycles and real-world driving profiles. While screening out for optimal sizing options, the implemented methodology includes drivability criteria along with fuel economy potential. Obtained results will demonstrate the agility of the developed sizing tool in identifying optimal sizing options compared to state-of-the-art sizing tools for electrified powertrains

A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis

Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intraindividual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available

Acute kidney injury in patients hospitalized with COVID-19

© 2020 International Society of Nephrology The rate of acute kidney injury (AKI) associated with patients hospitalized with Covid-19, and associated outcomes are not well understood. This study describes the presentation, risk factors and outcomes of AKI in patients hospitalized with Covid-19. We reviewed the health records for all patients hospitalized with Covid-19 between March 1, and April 5, 2020, at 13 academic and community hospitals in metropolitan New York. Patients younger than 18 years of age, with end stage kidney disease or with a kidney transplant were excluded. AKI was defined according to KDIGO criteria. Of 5,449 patients admitted with Covid-19, AKI developed in 1,993 (36.6%). The peak stages of AKI were stage 1 in 46.5%, stage 2 in 22.4% and stage 3 in 31.1%. Of these, 14.3% required renal replacement therapy (RRT). AKI was primarily seen in Covid-19 patients with respiratory failure, with 89.7% of patients on mechanical ventilation developing AKI compared to 21.7% of non-ventilated patients. 276/285 (96.8%) of patients requiring RRT were on ventilators. Of patients who required ventilation and developed AKI, 52.2% had the onset of AKI within 24 hours of intubation. Risk factors for AKI included older age, diabetes mellitus, cardiovascular disease, black race, hypertension and need for ventilation and vasopressor medications. Among patients with AKI, 694 died (35%), 519 (26%) were discharged and 780 (39%) were still hospitalized. AKI occurs frequently among patients with Covid-19 disease. It occurs early and in temporal association with respiratory failure and is associated with a poor prognosis

A Domain-Agnostic Approach for Characterization of Lifelong Learning Systems

Despite the advancement of machine learning techniques in recent years, state-of-the-art systems lack robustness to "real world" events, where the input distributions and tasks encountered by the deployed systems will not be limited to the original training context, and systems will instead need to adapt to novel distributions and tasks while deployed. This critical gap may be addressed through the development of "Lifelong Learning" systems that are capable of 1) Continuous Learning, 2) Transfer and Adaptation, and 3) Scalability. Unfortunately, efforts to improve these capabilities are typically treated as distinct areas of research that are assessed independently, without regard to the impact of each separate capability on other aspects of the system. We instead propose a holistic approach, using a suite of metrics and an evaluation framework to assess Lifelong Learning in a principled way that is agnostic to specific domains or system techniques. Through five case studies, we show that this suite of metrics can inform the development of varied and complex Lifelong Learning systems. We highlight how the proposed suite of metrics quantifies performance trade-offs present during Lifelong Learning system development - both the widely discussed Stability-Plasticity dilemma and the newly proposed relationship between Sample Efficient and Robust Learning. Further, we make recommendations for the formulation and use of metrics to guide the continuing development of Lifelong Learning systems and assess their progress in the future.Comment: To appear in Neural Network

Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses

A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis

Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intraindividual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs

Locus for severity implicates CNS resilience in progression of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and is a common cause of chronic neurological disability in young adults(1,2). Here, to provide insight into the potential mechanisms involved in progression, we conducted a genome-wide association study of the age-related MS severity score in 12,584 cases and replicated our findings in a further 9,805 cases. We identified a significant association with rs10191329 in the DYSF-ZNF638 locus, the risk allele of which is associated with a shortening in the median time to requiring a walking aid of a median of 3.7 years in homozygous carriers and with increased brainstem and cortical pathology in brain tissue. We also identified suggestive association with rs149097173 in the DNM3-PIGC locus and significant heritability enrichment in CNS tissues. Mendelian randomization analyses suggested a potential protective role for higher educational attainment. In contrast to immune-driven susceptibility(3), these findings suggest a key role for CNS resilience and potentially neurocognitive reserve in determining outcome in MS