Ab-initio Electronic Structure Method for Substitutional Disorder Applied to Iron-Based Superconductors

An ab-initio electronic structure method for substitutionally disordered real materials is developed within a pseudopotential density functional theory approach. The method is validated against exact diagonalization and for simple disordered CuZn alloys. The developed method is applied to iron-based superconductors. In particular, band renormalization effects due to various chemical substitutions in BaFe₂As₂ are investigated and their Cooper pair breaking effects are compared

Computational Methods for the Identification and Characterization of Non-Coding RNAs in Bacteria

In recent years the complexity even of bacterial transcriptomes became more and more evident. The important role of so-called non-coding RNAs (ncRNA), which do not encode proteins, is increasingly recognized as they fulfill a variety of functions, such as the regulation of cellular processes or catalysis of other molecules. Therefore, the characterization of an organism's ncRNA repertoire has become an essential part of systems biology studies. In this context novel high-throughput technologies in the field of DNA and RNA sequencing allow for the investigation of genomes and transcriptomes in unprecedented detail. These methodologies produce vast amounts of data that have to be analysed comparatively in order to elucidate variations between different organisms or environmental conditions. For these tasks efficient computational methods are needed that integrate genomic and transcriptomic data from multiple data sets in an automated and reproducible manner. In addition, these approaches have to facilitate the genomic localization of ncRNA elements and their detailed annotation e.g., with respect to promoter regions or transcription start sites as well as their functional characterization such as the prediction of their targets of regulation. In this dissertation I have made a number of contributions that address these challenges. The computer program nocoRNAc was developed, which predicts ncRNAs in bacterial genomes and characterizes them with respect to multiple properties such as transcription start and end points, secondary structure and potential interaction partners. nocoRNAc has been applied in the context of a comprehensive time series expression study of the antibiotics producing bacterium Streptomyces coelicolor, which was cultivated under different environmental conditions. During this study the importance of ncRNAs as potential regulators became evident. For the analysis of high-resolution genomic and transcriptomic data from multiple organisms the SuperGenome concept was developed. The approach was applied in the context of whole-genome alignment visualization and served as the basis for an algorithm for the comparative detection of transcription start sites in bacterial genomes utilizing RNA-seq data. The application to multiple strains of the human pathogen Campylobacter jejuni allowed for the global characterization of this organism's transcriptome and led to the detection of several novel ncRNAs, among them a previously uncharacterized CRISPR locus, which represents an adaptive bacterial immune system. Studying pathogens can also be of historic relevance. The emerging field of paleogenetics focuses on the reconstruction and analysis of genomes of ancient organisms, whose DNA has been extracted from archaeological samples, such as bones. In this dissertation I present computational methods for the reconstruction and characterization of ancient bacterial genomes, which have been applied to study the evolution of Mycobacterium leprae, the bacterium causing leprosy. Overall, the algorithms and tools developed in this dissertation and the insights that have been gained by their application contribute to the understanding of the structure and organization of bacterial genomes and transcriptomes and will help to elucidate the basic mechanisms that drive their evolution.Forschungsergebnisse vergangener Jahre konnten zeigen wie komplex die Struktur und Regulation selbst bakterieller Transkriptome sein kann. Auch die wichtige Rolle nicht-kodierender RNAs (ncRNA), die nicht in Proteine translatiert werden, wird dabei immer deutlicher. Diese Moleküle erfüllen in der Zelle verschiedenste Aufgaben wie zum Beispiel die Regulation von Stoffwechselprozessen. Daher ist die Charakterisierung der ncRNA-Gene eines Organismus immer mehr zu einem unverzichtbaren Teil von Systembiologie-Projekten geworden. Hierbei erlauben moderne Hochdurchsatzverfahren im Bereich der DNA- und RNA-Sequenzierung das im hohen Maße detaillierte Studium von Genomen und Transkriptomen. Die daraus resultierenden Daten müssen einer vergleichenden Analyse unterzogen werden, um Variationen des Transkriptoms zwischen verschiedenen Organismen und Umweltbedingungen untersuchen zu können. Hierfür werden effiziente Computerprogramme benötigt, die in der Lage sind genomische und transkriptomische Daten zu kombinieren und entsprechende Analysen automatisiert und reproduzierbar durchzuführen. Zudem müssen diese Ansätze nicht-kodierende Elemente im genomischen Kontext lokalisieren und annotieren können. In dieser Dissertation präsentiere ich Computerprogramme zur Lösung dieser Aufgaben. So wurde das Programm nocoRNAc entwickelt, welches ncRNAs in bakteriellen Genomen detektiert und diese bezüglich verschiedener Eigenschaften charakterisiert. Dazu gehören zum Beispiel Berechnung von Transkriptionsstart- und endpunkten, Sekundärstruktur und möglicher Interaktionspartner. nocoRNAc wurde im Rahmen einer umfangreichen Transkriptomstudie über das antibiotikaproduzierende Bakterium Streptomyces coelicolor verwendet, wodurch die Relevanz von ncRNAs als mögliche Regulatoren gezeigt werden konnte. Für die komparative Analyse hoch aufgelöster Genom- und Transkriptomdaten multipler Organismen wurde in dieser Dissertation das SuperGenom-Konzept entwickelt, welches bei der vergleichenden Visualisierung multipler Genome Anwendung fand. Zudem diente es als Grundlage für eine neue Methode zur Bestimmung von Transkriptionsstartpunkten in bakteriellen Genomen. Bei der Anwendung auf das für Menschen pathogene Bakterium Campylobacter jejuni konnte das Transkriptom dieses Organismus auf globaler Ebene charakterisiert werden. Zudem wurden mehrere bislang unbekannte ncRNAs identifiziert, darunter ein zuvor noch uncharakterisierter CRISPR-Lokus. Hierbei handelt es sich um ein adaptives bakterielles Immunsystem. Das Studium von Pathogenen kann auch von historischem Interesse sein. Das aufstrebende Feld der Paläogenetik befasst sich mit der Rekonstruktion und Analyse von Genomen alter, mitunter längst ausgestorbener Organismen. In dieser Dissertation werden neue Methoden zur automatischen Rekonstruktion und Charakterisierung alter bakterieller Genome eingeführt, welche zur Erforschung der Evolution von Mycobacterium leprae verwendet wurden, dem Verursacher von Lepra. Die Algorithmen und Werkzeuge, welche in dieser Dissertation entwickelt wurden, sowie die Erkenntnisse, die damit gewonnen werden konnten, stellen einen wertvollen Beitrag zum Verständnis bakterieller Genome und Transkriptome dar und werden weiterhin dazu beitragen deren grundlegende evolutionäre Mechanismen zu verstehen

High-Resolution Transcriptome Maps Reveal Strain-Specific Regulatory Features of Multiple Campylobacter jejuni Isolates

Campylobacter jejuni is currently the leading cause of bacterial gastroenteritis in humans. Comparison of multiple Campylobacter strains revealed a high genetic and phenotypic diversity. However, little is known about differences in transcriptome organization, gene expression, and small RNA (sRNA) repertoires. Here we present the first comparative primary transcriptome analysis based on the differential RNA–seq (dRNA–seq) of four C. jejuni isolates. Our approach includes a novel, generic method for the automated annotation of transcriptional start sites (TSS), which allowed us to provide genome-wide promoter maps in the analyzed strains. These global TSS maps are refined through the integration of a SuperGenome approach that allows for a comparative TSS annotation by mapping RNA–seq data of multiple strains into a common coordinate system derived from a whole-genome alignment. Considering the steadily increasing amount of RNA–seq studies, our automated TSS annotation will not only facilitate transcriptome annotation for a wider range of pro- and eukaryotes but can also be adapted for the analysis among different growth or stress conditions. Our comparative dRNA–seq analysis revealed conservation of most TSS, but also single-nucleotide-polymorphisms (SNP) in promoter regions, which lead to strain-specific transcriptional output. Furthermore, we identified strain-specific sRNA repertoires that could contribute to differential gene regulation among strains. In addition, we identified a novel minimal CRISPR-system in Campylobacter of the type-II CRISPR subtype, which relies on the host factor RNase III and a trans-encoded sRNA for maturation of crRNAs. This minimal system of Campylobacter, which seems active in only some strains, employs a unique maturation pathway, since the crRNAs are transcribed from individual promoters in the upstream repeats and thereby minimize the requirements for the maturation machinery. Overall, our study provides new insights into strain-specific transcriptome organization and sRNAs, and reveals genes that could modulate phenotypic variation among strains despite high conservation at the DNA level

A seventeenth-centuryMycobacterium tuberculosisgenome supports a Neolithic emergence of theMycobacterium tuberculosiscomplex

BACKGROUND: Although tuberculosis accounts for the highest mortality from a bacterial infection on a global scale, questions persist regarding its origin. One hypothesis based on modern Mycobacterium tuberculosis complex (MTBC) genomes suggests their most recent common ancestor followed human migrations out of Africa approximately 70,000 years before present. However, studies using ancient genomes as calibration points have yielded much younger dates of less than 6000 years. Here, we aim to address this discrepancy through the analysis of the highest-coverage and highest-quality ancient MTBC genome available to date, reconstructed from a calcified lung nodule of Bishop Peder Winstrup of Lund (b. 1605-d. 1679). RESULTS: A metagenomic approach for taxonomic classification of whole DNA content permitted the identification of abundant DNA belonging to the human host and the MTBC, with few non-TB bacterial taxa comprising the background. Genomic enrichment enabled the reconstruction of a 141-fold coverage M. tuberculosis genome. In utilizing this high-quality, high-coverage seventeenth-century genome as a calibration point for dating the MTBC, we employed multiple Bayesian tree models, including birth-death models, which allowed us to model pathogen population dynamics and data sampling strategies more realistically than those based on the coalescent. CONCLUSIONS: The results of our metagenomic analysis demonstrate the unique preservation environment calcified nodules provide for DNA. Importantly, we estimate a most recent common ancestor date for the MTBC of between 2190 and 4501 before present and for Lineage 4 of between 929 and 2084 before present using multiple models, confirming a Neolithic emergence for the MTBC

A systematic survey for eruptive young stellar objects using mid-infrared photometry

Accretion in young stellar objects (YSOs) is at least partially episodic, i.e. periods with high accretion rates ('bursts') are interspersed by quiescent phases. These bursts manifest themselves as eruptive variability. Here we presenta systematic survey for eruptive YSOs aiming to constrain the frequency of accretion bursts. We compare mid-infrared photometry from Spitzer and WISE separated by ~5 yr for two samples of YSOs, in nearby star-forming regions and in the Galactic plane, each comprising about 4000 young sources. All objects for which the brightness at 3.6 and 4.5 μm is increased by at least 1 mag between the two epochs may be eruptive variables and burst candidates. For these objects, we carry out follow-up observations in the near-infrared. We discover two new eruptive variables in the Galactic plane which could be FU Ori-type objects, with K-band amplitudes of more than 1.5 mag. One object known to undergo an accretion burst, V2492 Cyg, is recovered by our search as well. In addition, the young star ISO-Oph-50, previously suspected to be an eruptive object, is found to be better explained by a disc with varying circumstellar obscuration. In total, the number of burst events in a sample of 4000 YSOs is 1-4. Assuming that all YSOs undergo episodic accretion, this constraint can be used to show that phases of strong accretion (>10-6Mâ?? yr-1) occur in intervals of about 104 yr, most likely between 5000 and 50 000 yr. This is consistent with the dynamical time-scales for outflows, but not with the separations of emission knots in outflows, indicating that episodic accretion could either trigger or stop collimated large-scale outflows. © 2013 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society

X-ray view of IC348 in the light of an updated cluster census

We study the properties of the coronae of the low-mass stars in the young (~2-3Myr), nearby (~310pc) open cluster IC348 combining X-ray and optical/infrared data. The four existing Chandra observations of IC348 are merged, thus providing a deeper and spatially more complete X-ray view than previous X-ray studies of the cluster. We have compiled a comprehensive catalog of IC348 members taking into account recent updates to the cluster census. Our data collection comprises fundamental stellar parameters, infrared excess indicating the presence of disks, Halpha emission as a tracer of chromospheric emission or accretion and mass accretion rates. We have detected 290 X-ray sources in four merged Chandra exposures, of which 187 are associated with known cluster members. Only four of the X-ray sources are brown dwarfs (spectral type M6 and later). The detection rate is highest for diskless Class III stars and increases with stellar mass. This may be explained with higher X-ray luminosities for higher mass and later evolutionary stage that is evident in the X-ray luminosity functions. In particular, we find that for the lowest examined masses (0.1-0.25 Msun) there is a difference between the X-ray luminosity functions of accreting and non-accreting stars (classified on the basis of their Halpha emission strength) as well as those of disk-bearing and diskless stars (classified on the basis of the slope of the spectral energy distribution). These differences disappear for higher masses. This is related to our finding that the L_x/L_bol ratio is non-constant across the mass/luminosity sequence of IC348 with a decrease towards lower luminosity stars. Our analysis of an analogous stellar sample in the Orion Nebula Cluster suggests that the decline of L_x/L_ bol for young stars at the low-mass end of the stellar sequence is likely universal.Comment: Accepted for publication in Astronomy & Astrophysic

Accretion in Evolved and Transitional Disks in Cep OB2: Looking for the Origin of the Inner Holes

We present accretion rates for a large number of solar-type stars in the Cep OB2 region, based on U band observations. Our study comprises 95 members of the ~4 Myr-old cluster Tr 37 (including 20 "transition" objects; TO), as well as the only CTTS in the ~12 Myr-old cluster NGC 7160. The stars show different disk morphologies, with the majority of them having evolved and flattened disks. The typical accretion rates are about one order of magnitude lower than in regions aged 1-2 Myr, and we find no strong correlation between disk morphology and accretion rates. Although half of the TO are not accreting, the median accretion rates of normal CTTS and accreting "transition" disks are similar (~3 10^{-9} and 2 10^{-9} Msun/yr, respectively). Comparison with other regions suggests that the TO observed at different ages do not necessarily represent the same type of objects, which is consistent with the fact that the different processes that can lead to reduced IR excess/inner disk clearing (e.g., binarity, dust coagulation/settling, photoevaporation, giant planet formation) do not operate on the same timescales. Accreting TO in Tr 37 are probably suffering strong dust coagulation/settling. Regarding the equally large number of non-accreting TO in the region, other processes, like photoevaporation, the presence of stellar/substellar companions, and/or giant planet formation may account for their "transitional" SEDs and negligible accretion rates.Comment: 37 pages, 5 figures, 6 tables Accepted by Ap

Theoretical spectra of photoevaporating protoplanetary discs: An atlas of atomic and low-ionisation emission lines

We present a calculation of the atomic and low-ionisation emission line spectra of photoevaporating protoplanetary discs. Line luminosities and profiles are obtained from detailed photoionisation calculations of the disc and wind structures surrounding young active solar-type stars. The disc and wind density and velocity fields were obtained from the recently developed radiation-hydrodynamic models of Owen et al., that include stellar X-ray and EUV irradiation of protoplanetary discs at various stages of clearing, from primordial sources to inner hole sources of various hole sizes. Our models compare favourably with currently available observations, lending support to an X-ray driven photoevaporation model for disc dispersal. In particular, we find that X-rays drive a warm, predominantly neutral flow where the OI 6300A line can be produced by neutral hydrogen collisional excitation. Our models can, for the first time, provide a very good match to both luminosities and profiles of the low-velocity component of the OI 6300A line and other forbidden lines observed by Hartigan et al., which covered a large sample of T-Tauri stars. We find that the OI 6300A and the NeII 12.8um lines are predominantly produced in the X-ray-driven wind and thus appear blue-shifted by a few km/s for some of the systems when observed at non-edge-on inclinations. We note however that blue-shifts are only produced under certain conditions: X-ray luminosity, spectral shape and inner hole size all affect the location of the emitting region and the physical conditions in the wind. We caution therefore that while a blueshifted line is a tell-tale sign of an outflow, the lack of a blueshift should not be necessarily interpreted as a lack of outflow.Comment: 18 pages, 7 figures, accepted to be published in MNRAS - changes in the revised version: reference list update

A Near-Infrared Spectroscopic Survey of Class I Protostars

We present the results of a near-IR spectroscopic survey of 110 Class I protostars observed from 0.80 microns to 2.43 microns at a spectroscopic resolution of R=1200. We find that Class I objects exhibit a wide range of lines and the continuum spectroscopic features. 85% of Class I protostars exhibit features indicative of mass accretion, and we found that the veiling excess, CO emission, and Br Gamma emission are closely related. We modeled the spectra to estimate the veiling excess (r_k) and extinction to each target. We also used near-IR colors and emission line ratios, when available, to also estimate extinction. In the course of this survey, we observed the spectra of 10 FU Orionis-like objects, including 2 new ones, as well as 3 Herbig Ae type stars among our Class I YSOs. We used photospheric absorption lines, when available, to estimate the spectral type of each target. Although most targets are late type stars, there are several A and F-type stars in our sample. Notably, we found no A or F class stars in the Taurus-Auriga or Perseus star forming regions. There are several cases where the observed CO and/or water absorption bands are deeper than expected from the photospheric spectral type. We find a correlation between the appearance of the reflection nebula, which traces the distribution of material on very large scales, and the near-IR spectrum, which probes smaller scales. The spectra of the components of spatially resolved protostellar binaries tend to be very similar. In particular both components tend to have similar veiling and H_2 emission, inconsistent with random selection from the sample as a whole. There is a strong correlation between [Fe II] and H_2 emission, supporting previous results showing that H_2 emission in the spectra of young stars is usually shock excited by stellar winds.Comment: 89 pages, 13 figures, 7 Table