114 research outputs found
Theoretical linear approach to the combined man-manipulator system in manual control of an aircraft
An approach to the calculation of the dynamic characteristics of the combined man manipulator system in manual aircraft control was derived from a model of the neuromuscular system. This model combines the neuromuscular properties of man with the physical properties of the manipulator system which is introduced as pilot manipulator model into the manual aircraft control. The assumption of man as a quasilinear and time invariant control operator adapted to operating states, depending on the flight phases, of the control system gives rise to interesting solutions of the frequency domain transfer functions of both the man manipulator system and the closed loop pilot aircraft control system. It is shown that it is necessary to introduce the complete precision pilot manipulator model into the closed loop pilot aircraft transfer function in order to understand the well known handling quality criteria, and to derive these criteria directly from human operator properties
Doctor of Philosophy
dissertationSemiconductor nanocrystal quantum dots are a relatively recent area of study in materials science and engineering, but their unique, size-dependent properties have resulted in active growth over the past three decades. The motivation for this thesis has been exploiting the ability to tune the energy band gap and develop new families of geothermal reservoir tracers. While colloid transport in porous media has been studied extensively for groundwater systems, there is little existing research appropriate to high temperature geothermal systems. In this research, a multitiered approach is used to characterize quantum dot behavior at temperatures above 100 °C. First, a model system of cadmium selenide (CdSe) quantum dots is used to investigate fundamental aspects of nanocrystal growth and dissolution. Observing quantum dot dissolution and modeling the kinetic parameters yields critically important thermodynamic properties. These parameters are necessary for optimizing large-scale reactor conditions and design, and predicting fluid-phase quantum dot behavior. Insight into these thermodynamic properties provides the basis for experimentally studying transport in high temperature porous media that are surrogates for a geothermal reservoir. Core/shell quantum dots were pumped through Ottawa sand columns under a range of temperatures and salinities. Retardation and deposition were investigated as the principal transport parameters, while also considering the dynamics of quantum dot solubility and the interaction energy between quantum dots and the sand surfaces. Elevated temperatures increased the amount of quantum dot retention, following a multilayer deposition model. Finally, a novel method for detecting optically active species is introduced. Existing techniques for optical detection of quantum dots fail in turbid or high temperature environments. We demonstrate how the characteristic absorption - coupled with a long-wavelength overtone band - can be used to detect QDs in a variety of industrially relevant mixtures
Design of a Low Speed Wind Tunnel for Micrometeorology Research
Mechanical Engineerin
Epigenome-wide analysis of T-cell large granular lymphocytic leukemia identifies BCL11B as a potential biomarker
Background
The molecular pathogenesis of T-cell large granular lymphocytic leukemia (T-LGLL), a mature T-cell leukemia arising commonly from T-cell receptor αβ-positive CD8+ memory cytotoxic T cells, is only partly understood. The role of deregulated methylation in T-LGLL is not well known. We analyzed the epigenetic profile of T-LGLL cells of 11 patients compared to their normal counterparts by array-based DNA methylation profiling. For identification of molecular events driving the pathogenesis of T-LGLL, we compared the differentially methylated loci between the T-LGLL cases and normal T cells with chromatin segmentation data of benign T cells from the BLUEPRINT project. Moreover, we analyzed gene expression data of T-LGLL and benign T cells and validated the results by pyrosequencing in an extended cohort of 17 patients, including five patients with sequential samples.
Results
We identified dysregulation of DNA methylation associated with altered gene expression in T-LGLL. Since T-LGLL is a rare disease, the samples size is low. But as confirmed for each sample, hypermethylation of T-LGLL cells at various CpG sites located at enhancer regions is a hallmark of this disease. The interaction of BLC11B and C14orf64 as suggested by in silico data analysis could provide a novel pathogenetic mechanism that needs further experimental investigation.
Conclusions
DNA methylation is altered in T-LGLL cells compared to benign T cells. In particular, BCL11B is highly significant differentially methylated in T-LGLL cells. Although our results have to be validated in a larger patient cohort, BCL11B could be considered as a potential biomarker for this leukemia. In addition, altered gene expression and hypermethylation of enhancer regions could serve as potential mechanisms for treatment of this disease. Gene interactions of dysregulated genes, like BLC11B and C14orf64, may play an important role in pathogenic mechanisms and should be further analyzed.Open Access funding enabled and organized by Projekt DEAL. PJ was funded by IFORES and the Dr. Werner Jackstädt Stiftung. TL and ECdSP received funding from the Spanish Ministry of Science (Plan Nacional I + D+i PID2019-110183RB-C21); RK was supported by the DFG (KU1315/9-2).Peer Reviewed"Article signat per 17 autors/es:Patricia Johansson, Teresa Laguna, Julio Ossowski, Vera Pancaldi, Martina Brauser, Ulrich Dührsen, Lara Keuneke, Ana Queiros, Julia Richter, José I. Martín-Subero, Reiner Siebert, Brigitte Schlegelberger, Ralf Küppers, Jan Dürig, Eva M. Murga Penas, Enrique Carillo-de Santa Pau & Anke K. Bergmann"Postprint (published version
Development of Models to Simulate Tracer Tests for Characterization of Enhanced Geothermal Systems
A recent report found that power and heat produced from enhanced (or engineered) geothermal systems (EGSs) could have a major impact on the U.S energy production capability while having a minimal impact on the environment. EGS resources differ from high-grade hydrothermal resources in that they lack sufficient temperature distribution, permeability/porosity, fluid saturation, or recharge of reservoir fluids. Therefore, quantitative characterization of temperature distributions and the surface area available for heat transfer in EGS is necessary for the design and commercial development of the geothermal energy of a potential EGS site. The goal of this project is to provide integrated tracer and tracer interpretation tools to facilitate this characterization. This project was initially focused on tracer development with the application of perfluorinated tracer (PFT) compounds, non-reactive tracers used in numerous applications from atmospheric transport to underground leak detection, to geothermal systems, and evaluation of encapsulated PFTs that would release tracers at targeted reservoir temperatures. After the 2011 midyear review and subsequent discussions with the U.S. Department of Energy Geothermal Technology Program (GTP), emphasis was shifted to interpretive tool development, testing, and validation. Subsurface modeling capabilities are an important component of this project for both the design of suitable tracers and the interpretation of data from in situ tracer tests, be they single- or multi-well tests. The purpose of this report is to describe the results of the tracer and model development for simulating and conducting tracer tests for characterizing EGS parameters
VARDA (VARved sediments DAtabase) – providing and connecting proxy data from annually laminated lake sediments
Varved lake sediments provide long climatic records with high temporal resolution and low associated age uncertainty. Robust and detailed comparison of well-dated and annually laminated sediment records is crucial for reconstructing abrupt and regionally time-transgressive changes as well as validation of spatial and temporal trajectories of past climatic changes. The VARved sediments DAtabase (VARDA) presented here is the first data compilation for varve chronologies and associated palaeoclimatic proxy records. The current version 1.0 allows detailed comparison of published varve records from 95 lakes. VARDA is freely accessible and was created to assess outputs from climate models with high-resolution terrestrial palaeoclimatic proxies. VARDA additionally provides a technical environment that enables to explore the database of varved lake sediments using a connected data-model and can generate a state-of-the-art graphic representation of multi-site comparison. This allows to reassess existing chronologies and tephra events to synchronize and compare even distant varved lake records. Furthermore, the present version of VARDA permits to explore varve thickness data. In this paper, we report in detail on the data mining and compilation strategies for the identification of varved lakes and assimilation of high-resolution chronologies as well as the technical infrastructure of the database. Additional paleoclimate proxy data will be provided in forthcoming updates. The VARDA graph-database and user interface can be accessed online at https://varve.gfz-potsdam.de, all datasets of version 1.0 are available at http://doi.org/10.5880/GFZ.4.3.2019.003 (Ramisch et al., 2019)
Epigenome-wide analysis of T-cell large granular lymphocytic leukemia identifies BCL11B as a potential biomarker
Background: The molecular pathogenesis of T-cell large granular lymphocytic leukemia (T-LGLL), a mature T-cell leukemia arising commonly from T-cell receptor alpha beta-positive CD8(+) memory cytotoxic T cells, is only partly understood. The role of deregulated methylation in T-LGLL is not well known. We analyzed the epigenetic profile of T-LGLL cells of 11 patients compared to their normal counterparts by array-based DNA methylation profiling. For identification of molecular events driving the pathogenesis of T-LGLL, we compared the differentially methylated loci between the T-LGLL cases and normal T cells with chromatin segmentation data of benign T cells from the BLUEPRINT project. Moreover, we analyzed gene expression data of T-LGLL and benign T cells and validated the results by pyrosequencing in an extended cohort of 17 patients, including five patients with sequential samples. Results: We identified dysregulation of DNA methylation associated with altered gene expression in T-LGLL. Since T-LGLL is a rare disease, the samples size is low. But as confirmed for each sample, hypermethylation of T-LGLL cells at various CpG sites located at enhancer regions is a hallmark of this disease. The interaction of BLC11B and C14orf64 as suggested by in silico data analysis could provide a novel pathogenetic mechanism that needs further experimental investigation. Conclusions: DNA methylation is altered in T-LGLL cells compared to benign T cells. In particular, BCL11B is highly significant differentially methylated in T-LGLL cells. Although our results have to be validated in a larger patient cohort, BCL11B could be considered as a potential biomarker for this leukemia. In addition, altered gene expression and hypermethylation of enhancer regions could serve as potential mechanisms for treatment of this disease. Gene interactions of dysregulated genes, like BLC11B and C14orf64, may play an important role in pathogenic mechanisms and should be further analyzed
Biophysical mechanisms of endotoxin neutralization by cationic amphiphilic peptides
Bacterial endotoxins (lipopolysaccharides (LPS)) are strong elicitors of the human immune system by interacting with serum and membrane proteins such as lipopolysaccharide-binding protein (LBP) and CD14 with high specificity. At LPS concentrations as low as 0.3 ng/ml, such interactions may lead to severe pathophysiological effects, including sepsis and septic shock. One approach to inhibit an uncontrolled inflammatory reaction is the use of appropriate polycationic and amphiphilic antimicrobial peptides, here called synthetic anti-LPS peptides (SALPs). We designed various SALP structures and investigated their ability to inhibit LPS-induced cytokine secretion in vitro, their protective effect in a mouse model of sepsis, and their cytotoxicity in physiological human cells. Using a variety of biophysical techniques, we investigated selected SALPs with considerable differences in their biological responses to characterize and understand the mechanism of LPS inactivation by SALPs. Our investigations show that neutralization of LPS by peptides is associated with a fluidization of the LPS acyl chains, a strong exothermic Coulomb interaction between the two compounds, and a drastic change of the LPS aggregate type from cubic into multilamellar, with an increase in the aggregate sizes, inhibiting the binding of LBP and other mammalian proteins to the endotoxin. At the same time, peptide binding to phospholipids of human origin (e.g., phosphatidylcholine) does not cause essential structural changes, such as changes in membrane fluidity and bilayer structure. The absence of cytotoxicity is explained by the high specificity of the interaction of the peptides with LPS
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