130 research outputs found
Prediction of Combustion Noise in a Model Combustor Using a Network Model and a LNSE Approach
The reduction of pollution and noise emissions of modern aero engines represents a key concept to meet the requirements of the future air traffic. This requires an improvement in the understanding of combustion noise and its sources, as well as the development of accurate predictive tools. This is the major goal of the current study where the low-order thermo-acoustic network (LOTAN) solver and a hybrid computational fluid dynamics/computational aeroacoustics approach are applied on a generic premixed and pressurized combustor to evaluate their capabilities for combustion noise predictions. LOTAN solves the linearized Euler equations (LEE) whereas the hybrid approach consists of Reynolds-averaged NavierβStokes (RANS) mean flow and frequency-domain simulations based on linearized NavierβStokes equations (LNSE). Both solvers are fed in turn by three different combustion noise source terms which are obtained from the application of a statistical noise model on the RANS simulations and a post-processing of incompressible and compressible large eddy simulations (LES). In this way, the influence of the source model and acoustic solver is identified. The numerical results are compared with experimental data. In general, good agreement with the experiment is found for both the LOTAN and LNSE solvers. The LES source models deliver better results than the statistical noise model with respect to the amplitude and shape of the heat release spectrum. Beyond this, it is demonstrated that the phase relation of the source term does not affect the noise spectrum. Finally, a second simulation based on the inhomogeneous Helmholtz equation indicates the minor importance of the aerodynamic mean flow on the broadband noise spectrum.</jats:p
Reconstruction and control of a time-dependent two-electron wave packet
The concerted motion of two or more bound electrons governs atomic1 and molecular2,3 non-equilibrium processes including chemical reactions, and hence there is much interest in developing a detailed understanding of such electron dynamics in the quantum regime. However, there is no exact solution for the quantumthree-body problem, and as a result even the minimal system of two active electrons and a nucleus is analytically intractable4. This makes experimental measurements of the dynamics of two bound and correlated electrons, as found in the helium atom, an attractive prospect.However, although the motion of single active electrons and holes has been observed with attosecond time resolution5-7, comparable experiments on two-electron motion have so far remained out of reach. Here we showthat a correlated two-electron wave packet can be reconstructed froma 1.2-femtosecondquantumbeatamong low-lying doubly excited states in helium.The beat appears in attosecond transient-absorption spectra5,7-9 measured with unprecedentedly high spectral resolution and in the presence of an intensity-tunable visible laser field.Wetune the coupling10-12 between the two low-lying quantum states by adjusting the visible laser intensity, and use the Fano resonance as a phase-sensitive quantum interferometer13 to achieve coherent control of the two correlated electrons. Given the excellent agreement with large-scalequantum-mechanical calculations for thehelium atom, we anticipate thatmultidimensional spectroscopy experiments of the type we report here will provide benchmark data for testing fundamental few-body quantumdynamics theory in more complex systems. Theymight also provide a route to the site-specificmeasurement and control of metastable electronic transition states that are at the heart of fundamental chemical reactionsWe thank E. Lindroth for calculating the dipole moment (2p2|r|sp2,3+), and also A. Voitkiv, Z.-H. Loh, and R. Moshammer for helpful discussions. We acknowledge financial support by the Max-Planck Research Group Program of the Max-Planck Gesellschaft (MPG) and the European COST Action CM1204 XLIC. L. A. and F. M. acknowledge computer time from the CCC-UAM and Mare Nostrum supercomputer centers and financial support by the European Research Council under the ERC Advanced Grant no. 290853 XCHEM, the Ministerio de EconomΓa y Competitividad projects FIS2010-15127, FIS2013-42002-R and ERA-Chemistry PIM2010EEC-00751, and the European grant MC-ITN CORIN
Longitudinal studies that use data collected as part of usual care risk reporting biased results: a systematic review
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Ethics, politics and embodied imagination in crafting scientific knowledge
This article explores βresearch-as-craftβ as a sensitizing concept for disclosing the presence of ethics and politics, as well as embodiment and imagination, in the doing and representation of scientific activity. Routinely unnoticed, marginalized or suppressed in methodology sections of articles and methodology textbooks, research-as-craft gestures towards messy, tacit, uncertain, yet rarely thematized, practices that are central to getting science done. To acknowledge and address the significance of research-as-craft in knowledge production, we show how it relates to three forms of reflexivity β constitutive, epistemic and disruptive. Through this we demonstrate the craftiness that is required when struggling with the indeterminacy that is endemic to the production and communication of scientific knowledge. By showing how empirical situations require imaginative interpretation by embodied researchers, we argue that our conception of research-as-craft facilitates appreciation of scientific inquiry as an indexical activity that involves the crafted object and the researcher in an ethico-political process of co-constituting knowledge
Development of a kinetic metabolic model: application to Catharanthus roseus hairy root
A kinetic metabolic model describing Catharanthus roseus hairy root growth and nutrition was developed. The metabolic network includes glycolysis, pentose-phosphate pathway, TCA cycle and the catabolic reactions leading to cell building blocks such as amino acids, organic acids, organic phosphates, lipids and structural hexoses. The central primary metabolic network was taken at pseudo-steady state and metabolic flux analysis technique allowed reducing from 31 metabolic fluxes to 20 independent pathways. Hairy root specific growth rate was described as a function of intracellular concentration in cell building blocks. Intracellular transport and accumulation kinetics for major nutrients were included. The model uses intracellular nutrients as well as energy shuttles to describe metabolic regulation. Model calibration was performed using experimental data obtained from batch and medium exchange liquid cultures of C. roseus hairy root using a minimal medium in Petri dish. The model is efficient in estimating the growth rate
Salivary gland branching morphogenesis: a quantitative systems analysis of the Eda/Edar/NFΞΊB paradigm
<p>Abstract</p> <p>Background</p> <p>Ectodysplasin-A appears to be a critical component of branching morphogenesis. Mutations in mouse <it>Eda </it>or human <it>EDA </it>are associated with absent or hypoplastic sweat glands, sebaceous glands, lacrimal glands, salivary glands (SMGs), mammary glands and/or nipples, and mucous glands of the bronchial, esophageal and colonic mucosa. In this study, we utilized <it>Eda</it><sup><it>Ta </it></sup>(Tabby) mutant mice to investigate how a marked reduction in functional Eda propagates with time through a defined genetic subcircuit and to test the proposition that canonical NFΞΊB signaling is sufficient to account for the differential expression of developmentally regulated genes in the context of <it>Eda </it>polymorphism.</p> <p>Results</p> <p>The quantitative systems analyses do not support the stated hypothesis. For most NFΞΊB-regulated genes, the observed time course of gene expression is nearly unchanged in Tabby (<it>Eda</it><sup><it>Ta</it></sup>) as compared to wildtype mice, as is NFΞΊB itself. Importantly, a subset of genes is dramatically differentially expressed in Tabby (<it>Edar</it>, <it>Fgf8</it>, <it>Shh</it>, <it>Egf</it>, <it>Tgfa</it>, <it>Egfr</it>), strongly suggesting the existence of an alternative Eda-mediated transcriptional pathway pivotal for SMG ontogeny. Experimental and <it>in silico </it>investigations have identified C/EBPΞ± as a promising candidate.</p> <p>Conclusion</p> <p>In Tabby SMGs, upregulation of the Egf/TgfΞ±/Egfr pathway appears to mitigate the potentially severe abnormal phenotype predicted by the downregulation of Fgf8 and Shh. Others have suggested that the buffering of the phenotypic outcome that is coincident with variant Eda signaling could be a common mechanism that permits viable and diverse phenotypes, normal and abnormal. Our results support this proposition. Further, if branching epithelia use variations of a canonical developmental program, our results are likely applicable to understanding the phenotypes of other branching organs affected by <it>Eda </it>(<it>EDA</it>) mutation.</p
Maternal Wnt/Ξ²-Catenin Signaling Coactivates Transcription through NF-ΞΊB Binding Sites during Xenopus Axis Formation
Maternal Wnt/Ξ²-Catenin signaling establishes a program of dorsal-specific gene expression required for axial patterning in Xenopus. We previously reported that a subset of dorsally expressed genes depends not only on Wnt/Ξ²-Catenin stimulation, but also on a MyD88-dependent Toll-like receptor/IL1-receptor (TLR/IL1-R) signaling pathway. Here we show that these two signal transduction cascades converge in the nucleus to coactivate gene transcription in blastulae through a direct interaction between Ξ²-Catenin and NF-ΞΊB proteins. A transdominant inhibitor of NF-ΞΊB, ΞNIΞΊBΞ±, phenocopies loss of MyD88 protein function, implicating Rel/NF-ΞΊB proteins as selective activators of dorsal-specific gene expression. Sensitive axis formation assays in the embryo demonstrate that dorsalization by Wnt/Ξ²-Catenin requires NF-ΞΊB protein activity, and vice versa. Xenopus nodal-related 3 (Xnr3) is one of the genes with dual Ξ²-Catenin/NF-ΞΊB input, and a proximal NF-ΞΊB consensus site contributes to the regional activity of its promoter. We demonstrate in vitro binding of Xenopus Ξ²-Catenin to several XRel proteins. This interaction is observed in vivo upon Wnt-stimulation. Finally, we show that a synthetic luciferase reporter gene responds to both endogenous and exogenous Ξ²-Catenin levels in an NF-ΞΊB motif dependent manner. These results suggest that Ξ²-Catenin acts as a transcriptional co-activator of NF-ΞΊB-dependent transcription in frog primary embryonic cells
MRI of the temporo-mandibular joint: which sequence is best suited to assess the cortical bone of the mandibular condyle? A cadaveric study using micro-CT as the standard of reference
OBJECTIVE: To determine the best suited sagittal MRI sequence out of a standard temporo-mandibular joint (TMJ) imaging protocol for the assessment of the cortical bone of the mandibular condyles of cadaveric specimens using micro-CT as the standard of reference.
METHODS: Sixteen TMJs in 8 human cadaveric heads (mean age, 81 years) were examined by MRI. Upon all sagittal sequences, two observers measured the cortical bone thickness (CBT) of the anterior, superior and posterior portions of the mandibular condyles (i.e. objective analysis), and assessed for the presence of cortical bone thinning, erosions or surface irregularities as well as subcortical bone cysts and anterior osteophytes (i.e. subjective analysis). Micro-CT of the condyles was performed to serve as the standard of reference for statistical analysis.
RESULTS: Inter-observer agreements for objective (rβ=β0.83-0.99, Pβ<β0.01) and subjective (ΞΊβ=β0.67-0.88) analyses were very good. Mean CBT measurements were most accurate, and cortical bone thinning, erosions, surface irregularities and subcortical bone cysts were best depicted on the 3D fast spoiled gradient echo recalled sequence (3D FSPGR).
CONCLUSION: The most reliable MRI sequence to assess the cortical bone of the mandibular condyles on sagittal imaging planes is the 3D FSPGR sequence.
KEY POINTS: MRI may be used to assess the cortical bone of the TMJ. β’ Depiction of cortical bone is best on 3D FSPGR sequences. β’ MRI can assess treatment response in patients with TMJ abnormalities
Analysis of miRNA and mRNA Expression Profiles Highlights Alterations in Ionizing Radiation Response of Human Lymphocytes under Modeled Microgravity
BACKGROUND: Ionizing radiation (IR) can be extremely harmful for human cells since an improper DNA-damage response (DDR) to IR can contribute to carcinogenesis initiation. Perturbations in DDR pathway can originate from alteration in the functionality of the microRNA-mediated gene regulation, being microRNAs (miRNAs) small noncoding RNA that act as post-transcriptional regulators of gene expression. In this study we gained insight into the role of miRNAs in the regulation of DDR to IR under microgravity, a condition of weightlessness experienced by astronauts during space missions, which could have a synergistic action on cells, increasing the risk of radiation exposure.
METHODOLOGY/PRINCIPAL FINDINGS: We analyzed miRNA expression profile of human peripheral blood lymphocytes (PBL) incubated for 4 and 24 h in normal gravity (1 g) and in modeled microgravity (MMG) during the repair time after irradiation with 0.2 and 2Gy of \u3b3-rays. Our results show that MMG alters miRNA expression signature of irradiated PBL by decreasing the number of radio-responsive miRNAs. Moreover, let-7i*, miR-7, miR-7-1*, miR-27a, miR-144, miR-200a, miR-598, miR-650 are deregulated by the combined action of radiation and MMG. Integrated analyses of miRNA and mRNA expression profiles, carried out on PBL of the same donors, identified significant miRNA-mRNA anti-correlations of DDR pathway. Gene Ontology analysis reports that the biological category of "Response to DNA damage" is enriched when PBL are incubated in 1 g but not in MMG. Moreover, some anti-correlated genes of p53-pathway show a different expression level between 1 g and MMG. Functional validation assays using luciferase reporter constructs confirmed miRNA-mRNA interactions derived from target prediction analyses.
CONCLUSIONS/SIGNIFICANCE: On the whole, by integrating the transcriptome and microRNome, we provide evidence that modeled microgravity can affects the DNA-damage response to IR in human PBL
A Genome-Wide Association Study Identifies Susceptibility Variants for Type 2 Diabetes in Han Chinese
To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (Pβ=β8.54Γ10β10; odds ratio [OR]β=β1.57; 95% confidence interval [CI]β=β1.36β1.82), and serine racemase (SRR) (Pβ=β3.06Γ10β9; ORβ=β1.28; 95% CIβ=β1.18β1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (Pβ=β9.65Γ10β10; ORβ=β1.29, 95% CIβ=β1.19β1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations
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