Prototype air-water flow measurements in a tunnel chute

Air-water flows commonly occur in hydraulic structures such as spillway chutes and low-level outlets. In highvelocity flows, air entrainment is a dominant feature and must be considered for a sound design of these safety-relevant appurtenant structures. Most applied research and engineering design recommendations for such structures have been based upon laboratory scale air-water flow experiments. However, scale effects remain a common and complex issue in air-water flow research as they possibly affect the extrapolation of laboratory scale mass, momentum, and heat transfer processes to prototype scale and a validation from observations at prototype scale is generally missing. To tackle this challenge, we conducted measurements in high-velocity tunnel chute flows at the 225 m high Luzzone Dam in Switzerland. The mean flow velocities reached up to 38 m/s corresponding to Reynolds numbers up to 2.4×107. The measured void fraction and flow velocity profiles, as well as the bulk parameters mean void fraction and flow resistance agreed well with existing laboratory data and empirical equations with Reynolds numbers in the order of 105 to 106. However, microscopic air-water flow properties such as the droplet size showed significant scale effects, which requires further research

Image Registration for Quantitative Parametric Response Mapping of Cancer Treatment Response

AbstractImaging biomarkers capable of early quantification of tumor response to therapy would provide an opportunity to individualize patient care. Image registration of longitudinal scans provides a method of detecting treatment-associated changes within heterogeneous tumors by monitoring alterations in the quantitative value of individual voxels over time, which is unattainable by traditional volumetric-based histogram methods. The concepts involved in the use of image registration for tracking and quantifying breast cancer treatment response using parametric response mapping (PRM), a voxel-based analysis of diffusion-weighted magnetic resonance imaging (DW-MRI) scans, are presented. Application of PRM to breast tumor response detection is described, wherein robust registration solutions for tracking small changes in water diffusivity in breast tumors during therapy are required. Methodologies that employ simulations are presented for measuring expected statistical accuracy of PRM for response assessment. Test-retest clinical scans are used to yield estimates of system noise to indicate significant changes in voxel-based changes in water diffusivity. Overall, registration-based PRM image analysis provides significant opportunities for voxel-based image analysis to provide the required accuracy for early assessment of response to treatment in breast cancer patients receiving neoadjuvant chemotherapy

Universal Stress Proteins Are Important for Oxidative and Acid Stress Resistance and Growth of Listeria monocytogenes EGD-e In Vitro and In Vivo

Background: Pathogenic bacteria maintain a multifaceted apparatus to resist damage caused by external stimuli. As part of this, the universal stress protein A (UspA) and its homologues, initially discovered in Escherichia coli K-12 were shown to possess an important role in stress resistance and growth in several bacterial species. Methods and Findings: We conducted a study to assess the role of three homologous proteins containing the UspA domain in the facultative intracellular human pathogen Listeria monocytogenes under different stress conditions. The growth properties of three UspA deletion mutants (deltalmo0515, deltalmo1580 and deltalmo2673) were examined either following challenge with a sublethal concentration of hydrogen peroxide or under acidic conditions. We also examined their ability for intracellular survival within murine macrophages. Virulence and growth of usp mutants were further characterized in invertebrate and vertebrate infection models. Tolerance to acidic stress was clearly reduced in Δlmo1580 and deltalmo0515, while oxidative stress dramatically diminished growth in all mutants. Survival within macrophages was significantly decreased in deltalmo1580 and deltalmo2673 as compared to the wild-type strain. Viability of infected Galleria mellonella larvae was markedly higher when injected with deltalmo1580 or deltalmo2673 as compared to wild-type strain inoculation, indicating impaired virulence of bacteria lacking these usp genes. Finally, we observed severely restricted growth of all chromosomal deletion mutants in mice livers and spleens as compared to the load of wild-type bacteria following infection. Conclusion: This work provides distinct evidence that universal stress proteins are strongly involved in listerial stress response and survival under both in vitro and in vivo growth conditions

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Mining the human phenome using allelic scores that index biological intermediates

J. Kaprio ja M-L. Lokki työryhmien jäseniä.It is common practice in genome-wide association studies (GWAS) to focus on the relationship between disease risk and genetic variants one marker at a time. When relevant genes are identified it is often possible to implicate biological intermediates and pathways likely to be involved in disease aetiology. However, single genetic variants typically explain small amounts of disease risk. Our idea is to construct allelic scores that explain greater proportions of the variance in biological intermediates, and subsequently use these scores to data mine GWAS. To investigate the approach's properties, we indexed three biological intermediates where the results of large GWAS meta-analyses were available: body mass index, C-reactive protein and low density lipoprotein levels. We generated allelic scores in the Avon Longitudinal Study of Parents and Children, and in publicly available data from the first Wellcome Trust Case Control Consortium. We compared the explanatory ability of allelic scores in terms of their capacity to proxy for the intermediate of interest, and the extent to which they associated with disease. We found that allelic scores derived from known variants and allelic scores derived from hundreds of thousands of genetic markers explained significant portions of the variance in biological intermediates of interest, and many of these scores showed expected correlations with disease. Genome-wide allelic scores however tended to lack specificity suggesting that they should be used with caution and perhaps only to proxy biological intermediates for which there are no known individual variants. Power calculations confirm the feasibility of extending our strategy to the analysis of tens of thousands of molecular phenotypes in large genome-wide meta-analyses. We conclude that our method represents a simple way in which potentially tens of thousands of molecular phenotypes could be screened for causal relationships with disease without having to expensively measure these variables in individual disease collections.Peer reviewe

Air Demand of Low-Level Outlets for Large Dams

ISSN:0733-9429ISSN:1943-790

Air-Water Flow Patterns and Shockwave Formation in Low-Level Outlets

Reservoir dams play a significant role in society and the economy. Low-level outlets (LLOs) are key safety devices providing reservoir drawdown for maintenance and emergency purposes, sediment flushing, and release of environmental flow. High velocities and turbulence levels of the free-surface flow lead to air entrainment and air transport along the LLO tunnel, resulting in subatmospheric air pressures. In addition, shockwaves formed downstream of the gate may lead to a complete filling of the tunnel cross section, possibly resulting in slug flow and flow pulsations, which should be avoided for operational safety. In this study, physical model tests were performed to investigate the effects of gate opening and hydraulic head on shockwave patterns. Especially for large contraction Froude numbers, the shockwaves were strongly aerated, resulting in a complex air-water flow pattern. The results provide insights into the formation and propagation of shockwaves, contributing to an improved design of LLO tunnels.ISSN:0733-9429ISSN:1943-790

High-Velocity Air–Water Flow Measurements in a Prototype Tunnel Chute: Scaling of Void Fraction and Interfacial Velocity

Aeration occurs in many natural and human-made flows and must be considered in engineering design. In water infrastructure, air–water flows can be violent and of very high velocity. To date, most fundamental research and engineering design guidelines involving air–water flows have been based upon laboratory scale measurements with limited validation at prototype scale with larger Reynolds numbers. Herein, unique measurements were conducted in high-velocity air–water flows in the tunnel chute of the 225-m-high Luzzone arch Dam in Switzerland. For each of the two test series, an array of 16 double-tip conductivity probes was installed in the circular tunnel chute of 3 m diameter and slope of ≈37° measuring void fraction, bubble count rate, interfacial velocity, and droplet sizes for four different discharges of up to 15.9  m3/s corresponding to Reynolds numbers of up to 2.4 × 107 and mean flow velocities of up to 38  m/s. Void fraction and interfacial velocity distributions, as well as design parameters such as depth-averaged void fractions and flow resistance, compared well with previous laboratory studies and empirical equations. The droplet chord sizes exhibited scale effects, and care must be taken if air–water mass transfer and droplet momentum exchange processes are assessed at the laboratory scale.ISSN:0733-9429ISSN:1943-790

High-velocity air-water flows downstream of sluice gates including selection of optimum phase-detection probe

ISSN:0301-9322ISSN:1879-353