Impact of Uncertainty Quantification on Design Decisions for a Hydraulic-Hybrid Powertrain Engine

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76707/1/AIAA-2006-2001-814.pd

A finite element analysis of beams on elastic foundation including shear and axial effects

A displacement finite element method for analyzing a beam on continuous elastic foundation is presented. A three-dimensional model which accounts for the effects of both the Filonenko-Borodich and Pasternak foundation models in a consistent and complete way is used. A variational principle is introduced with the slope field due to bending only and the displacement field approximated by independent quantities subjected to variation. Numerical examples illustrate the accuracy of the element, the importance of shear, axial and shear-axial interaction effects associated with continuous elastic foundation, and finally the application of the element to a rotor supported by two hydrodynamic journal bearings.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26944/1/0000510.pd

TERA-Seq: true end-to-end sequencing of native RNA molecules for transcriptome characterization

Direct sequencing of single, native RNA molecules through nanopores has a strong potential to transform research in all aspects of RNA biology and clinical diagnostics. The existing platform from Oxford Nanopore Technologies is unable to sequence the very 5′ ends of RNAs and is limited to polyadenylated molecules. Here, we develop True End-to-end RNA Sequencing (TERA-Seq), a platform that addresses these limitations, permitting more thorough transcriptome characterization. TERA-Seq describes both poly-and non-polyadenylated RNA molecules and accurately identifies their native 5′ and 3′ ends by ligating uniquely designed adapters that are sequenced along with the transcript. We find that capped, full-length mRNAs in human cells show marked variation of poly(A) tail lengths at the single molecule level. We report prevalent capping downstream of canonical transcriptional start sites in otherwise fully spliced and polyadenylated molecules. We reveal RNA processing and decay at single molecule level and find that mRNAs decay cotranslationally, often from their 5′ ends, while frequently retaining poly(A) tails. TERA-Seq will prove useful in many applications where true end-to-end direct sequencing of single, native RNA molecules and their isoforms is desirable

MIWI N-terminal arginines orchestrate generation of functional pachytene piRNAs and spermiogenesis

N-terminal arginine (NTR) methylation is a conserved feature of PIWI proteins, which are central components of the PIWI-interacting RNA (piRNA) pathway. The significance and precise function of PIWI NTR methylation in mammals remains unknown. In mice, PIWI NTRs bind Tudor domain containing proteins (TDRDs) that have essential roles in piRNA biogenesis and the formation of the chromatoid body. Using mouse MIWI (PIWIL1) as paradigm, we demonstrate that the NTRs are essential for spermatogenesis through the regulation of transposons and gene expression. The loss of TDRD5 and TDRKH interaction with MIWI results in attenuation of piRNA amplification. We find that piRNA amplification is necessary for transposon control and for sustaining piRNA levels including select, nonconserved, pachytene piRNAs that target specific mRNAs required for spermatogenesis. Our findings support the notion that the vast majority of pachytene piRNAs are dispensable, acting as self-serving genetic elements that rely for propagation on MIWI piRNA amplification. MIWI-NTRs also mediate interactions with TDRD6 that are necessary for chromatoid body compaction. Furthermore, MIWI-NTRs promote stabilization of spermiogenic transcripts that drive nuclear compaction, which is essential for sperm formation. In summary, the NTRs underpin the diversification of MIWI protein function

High-Throughput Experimental Studies to Identify miRNA Targets Directly, with Special Focus on the Mammalian Brain

We review the pertinent literature on methods used in high-throughput experimental identification of microRNA (miRNA) targets with emphasis on neurochemical studies. miRNAs are short regulatory noncoding RNAs that play important roles in the mammalian brain. The functions of miRNAs are related to their binding of RNAs including mRNAs. Since mammalian miRNAs tend to bind to target mRNAs via imperfect complementarity, understanding exactly which target mRNAs are recognized by which specific miRNAs is a challenge. Based on early experimental evidence, a set of binding rules for miRNAs has been described. These have focused on the 5\u27 seed region of miRNAs binding to the 3\u27 untranslated region of targeted mRNAs. Bioinformaticians have applied these algorithms for theoretical miRNA target prediction. To date, the different computational methods are not in agreement with each other and do not explain all miRNA targets as defined using high-throughput experimental methods. We consider these latter techniques which identify putative miRNA targets directly. Each experimental approach involves specific assumptions and potential technical pitfalls. Some of these direct experimental methods for miRNA target identification have used co-immunoprecipitation (RIP-Chip and others) and transfection-based experimental design. Topics related to experimentally identified miRNA targets are discussed, with special emphasis on studies pertinent to the mammalian brain

Modulation of Aub-TDRD interactions elucidates piRNA amplification and germplasm formation.

Aub guided by piRNAs ensures genome integrity by cleaving retrotransposons, and genome propagation by trapping mRNAs to form the germplasm that instructs germ cell formation. Arginines at the N-terminus of Aub (Aub-NTRs) interact with Tudor and other Tudor domain-containing proteins (TDRDs). Aub-TDRD interactions suppress active retrotransposons via piRNA amplification and form germplasm via generation of Aub-Tudor ribonucleoproteins. Here, we show that Aub-NTRs are dispensable for primary piRNA biogenesis but essential for piRNA amplification and that their symmetric dimethylation is required for germplasm formation and germ cell specification but largely redundant for piRNA amplification

Erratum: Corrigendum: Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution

International Chicken Genome Sequencing Consortium. The Original Article was published on 09 December 2004. Nature432, 695–716 (2004). In Table 5 of this Article, the last four values listed in the ‘Copy number’ column were incorrect. These should be: LTR elements, 30,000; DNA transposons, 20,000; simple repeats, 140,000; and satellites, 4,000. These errors do not affect any of the conclusions in our paper. Additional information. The online version of the original article can be found at 10.1038/nature0315

A Distributed Pool Architecture for Highly Constrained Optimization Problems in Complex Systems Design

Optimal design of complex engineering systems is challenging because numerous design variables and constraints are present. Dynamic changes in design requirements and lack of complete knowledge of subsystem requirements add to the complexity. We propose an enhanced distributed pool architecture to aid distributed solving of design optimization problems. The approach not only saves solution time but is also resilient against failures of some processors. It is best suited to handle highly constrained design problems, with dynamically changing constraints, where finding even a feasible solution (FS) is challenging. In our work, this task is distributed among many processors. Constraints can be easily added or removed without having to restart the solution process. We demonstrate the efficacy of our method in terms of computational savings and resistance to partial failures of some processors, using two mixed integer nonlinear programming (MINLP)-class mechanical design optimization problems