Capturing the ‘ome’ : the expanding molecular toolbox for RNA and DNA library construction

All sequencing experiments and most functional genomics screens rely on the generation of libraries to comprehensively capture pools of targeted sequences. In the past decade especially, driven by the progress in the field of massively parallel sequencing, numerous studies have comprehensively assessed the impact of particular manipulations on library complexity and quality, and characterized the activities and specificities of several key enzymes used in library construction. Fortunately, careful protocol design and reagent choice can substantially mitigate many of these biases, and enable reliable representation of sequences in libraries. This review aims to guide the reader through the vast expanse of literature on the subject to promote informed library generation, independent of the application

Self-consistent thermodynamic description of silicate liquids, with application to shock melting of MgO periclase and MgSiO 3 perovskite

We develop a self-consistent thermodynamic description of silicate liquids applicable across the entire mantle pressure and temperature regime. The description combines the finite strain free energy expansion with an account of the temperature dependence of liquid properties into a single fundamental relation, while honouring the expected limiting behaviour at large volume and high temperature. We find that the fundamental relation describes well previous experimental and theoretical results for liquid MgO, MgSiO 3 , Mg 2 SiO 4 and SiO 2 . We apply the description to calculate melting curves and Hugoniots of solid and liquid MgO and MgSiO 3 . For periclase, we find a melting temperature at the core–mantle boundary (CMB) of 7810 ± 160 K , with the solid Hugoniot crossing the melting curve at 375 GPa, 9580 K , and the liquid Hugoniot crossing at 470 GPa, 9870 K . For complete shock melting of periclase we predict a density increase of 0.14 g cm −3 and a sound speed decrease of 2.2 km s −1 . For perovskite, we find a melting temperature at the CMB of 5100 ± 100 K with the perovskite section of the enstatite Hugoniot crossing the melting curve at 150 GPa, 5190 K , and the liquid Hugoniot crossing at 220 GPa, 5520 K . For complete shock melting of perovskite along the enstatite principal Hugoniot, we predict a density increase of 0.10 g cm −3 , with a sound speed decrease of 2.6 km s −1 .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75103/1/j.1365-246X.2009.04142.x.pd

Effect of decision parameter efficiency on target reliability

Target reliability forms the basis of most modern design standards and is intended to represent an optimal balance of safety and risk of failure. Previous research noted discrepancies between target reliability obtained using generic and case-specific cost optimization for SLS cases. The source of the discrepancies was identified as the efficiency of the decision parameter at increasing reliability. This research extends the investigation to cases of ULS failures and found similar discrepancies. Generic cost optimization assumes a linear dependence between the decision parameter and the structural resistance. Where the dependence of resistance on the decision parameter is superlinear, the generic was found to under-predict target reliability by up to 15%. A factor is proposed to adjust generically-obtained ULS target reliability to be more appropriate to specific ULS cases. The factor accounts for the efficiency of the decision parameter, the case-specific cost of safety and parameter variation. The adjustment factor represents a first step towards mapping generic to case-specific target reliability in the ideal of promoting safer and more cost-effective structures

Structural reliability of existing rc beams strengthened with UHPFRC tensile layers

A methodology for reliability analysis of reinforced concrete (RC) beams strengthened with ultra high-performance fibre reinforced concrete (UHPFRC) tensile layers is presented. The proposed methodology includes stochastic stress-block analysis of a section, assuming a perfect bond between the RC beam and the UHPFRC layer. Annual reliability analysis of the RC beam before and after the strengthening operation is conducted. Deterioration induced by chloride corrosion is incorporated into the analysis via a chloride induced corrosion model based on Fick’s law of diffusion and described stochastically to account for the epistemic uncertainty in the time to corrosion initiation and rate of corrosion. A plot for determining the required thickness of the UHPFRC tensile layer to upgrade to the required reliability level is also given, considering the time from construction to when the strengthening operation is conducted. The proposed approach is easy to apply for routine practice

Liquid State Physics of the MgO-SiO2 System at Deep Mantle Pressures.

As the primary medium through which planetary differentiation occurs, silicate liquids are key in the study of the thermal and chemical evolution of Earth. First principles molecular dynamics simulations were used to study the liquid state physics of the MgO - SiO2 join at pressure and temperature conditions relevant to the deep interiors of Earth-like planets, with special focus on the variation of liquid state thermodynamics and structure with pressure, temperature and composition. We find the structure of liquids to change continuously upon compression, and to differ markedly from that of the respective isochemical crystalline polymorphs. Si-O coordination increases from four to six upon two-fold compression in all compositions considered, with the increase strongly delayed in pure silica. Changes in liquid structure is expressed in the liquid state thermodynamic properties. A density crossover along the forsterite melting curve is found within the stability field of the mineral, a feature which a melting curve computed through the Lindemann criterion from the mean squared atomic displacements in forsterite is unable to reproduce. Composition dependent structural differences within the liquid are expressed as a liquid immiscibility field at low pressure in high silica compositions. Using our first principles molecular dynamics results, we develop a self-consistent thermodynamic description of liquid state thermodynamics, which also accounts for the thermal electronic contribution to the free energy, relevant to silicate liquids over a large range of pressures and temperature. With liquid state thermodynamics thus self-consistently constrained, we investigate the high pressure melting of MgO periclase and MgSiO3 perovskite. By calculating theoretical solid and liquid Hugoniot loci, we predict the changes in density and sound velocity which would be expected during shock melting of periclase and enstatite. We also apply the thermodynamic description to the thermodynamics of mixing along the extent of the binary. At low pressure the enthalpy of mixing is notably pressure dependent, primarily due to the disappearance of a maximum at high silica compositions with an increase in pressure. The structural mechanism responsible for liquid immiscibility is identified, and found to be stable only at low pressure.Ph.D.GeologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/60828/1/dekoker_1.pd

Combining accelerometer data and contextual variables to evaluate the risk of driver behaviour

Telemetry devices are generating and transferring increasingly more data, with notable potential for decision makers. In this paper we consider the accelerometer and speed data produced by in-vehicle data recorders as a proxy for driver behaviour. Instead of extracting harsh events to cope with the large volumes of data, we discretise the data into a tractable and finite risk space. This novel methodology allows us to track both acceptable and non-acceptable driving behaviour, and calculate a more comprehensive risk model using the envelope of the data, and nota priorithresholds. We show how thresholds suggested in literature can characterise some driving behaviour as good, even though our empirical evidence has not even registered such extreme driving behaviour. We demonstrate the model using accelerometer data from 124 vehicles over a one month period. Three rules, each a combination of accelerometer and/or speed data, are applied to the risk space to derive person-specific scores that are comparable among the individuals. The results show that the scoring is useful to identify specific risk groups. The proposed model is also dynamic in that it dynamically adjusts to the observed records, instead of data having to abide by a limited model specification.http://www.elsevier.com/locate/trf2017-08-31hb2016Industrial and Systems Engineerin

The effects of lithospheric thickness and density structure on Earth's stress field

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89572/1/j.1365-246X.2011.05248.x.pd

Minimally invasive classification of pediatric solid tumors using reduced representation bisulfite sequencing of cell-free DNA : a proof-of-principle study

In the clinical management of pediatric solid tumors, histological examination of tumor tissue obtained by a biopsy remains the gold standard to establish a conclusive pathological diagnosis. The DNA methylation pattern of a tumor is known to correlate with the histopathological diagnosis across cancer types and is showing promise in the diagnostic workup of tumor samples. This methylation pattern can be detected in the cell-free DNA. Here, we provide proof-of-concept of histopathologic classification of pediatric tumors using cell-free reduced representation bisulfite sequencing (cf-RRBS) from retrospectively collected plasma and cerebrospinal fluid samples. We determined the correct tumor type in 49 out of 60 (81.6%) samples starting from minute amounts (less than 10 ng) of cell-free DNA. We demonstrate that the majority of misclassifications were associated with sample quality and not with the extent of disease. Our approach has the potential to help tackle some of the remaining diagnostic challenges in pediatric oncology in a cost-effective and minimally invasive manner. Translational relevance: Obtaining a correct diagnosis in pediatric oncology can be challenging in some tumor types, especially in renal tumors or central nervous system tumors. Furthermore, the diagnostic odyssey can result in anxiety and discomfort for these children. By applying a novel technique, reduced representation bisulfite sequencing on cell-free DNA (cf-RRBS), we show the feasibility of obtaining the histopathological diagnosis with a minimally invasive test on either plasma or cerebrospinal fluid. Furthermore, we were able to derive the copy number profile or tumor subtype from the same assay. Given that primary tumor material might be difficult to obtain, in particular in critically ill children or depending on the tumor location, and might be limited in terms of quantity or quality, our assay could become complementary to the classical tissue biopsy in difficult cases