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Towards a THz Bloch laser
(2011)
The realisation of tunable THz laser sources working at room temperature would give
rise to further applications in this range of the electromagnetic spectrum. The THz
Bloch laser could therefore become the basis for a technological breakthrough. Beside
this practical relevance, the physics of the gain mechanism has been investigated
theoretically for a long time and the experimental implementation of a self-starting
laser still has not been achieved.
At the beginning of this thesis the basic principles of Bloch oscillations and the
related Bloch gain are described. The need of a superlattice structure to make Bloch
oscillations possible in a semiconductor material is discussed. In this context, the effect
of negative differential resistance and its influence on the field distribution due to Gunn
domains is explained. The latter lead to an inhomogeneous field which may suppress
the Bloch gain mechanism. The Krömer criterion is introduced and the concept of
field-pinning layers to improve the field homogeneity is deduced. Finally, the design of
the laser material is shown and different types of laser waveguides are compared.
In chapter 3 detailed recipes for the processing of samples are given. Different types of
contacts (ohmic and Schottky), the wafer bonding process required for double-metal
lasers and the application of different photoresists for different purposes are described.
An explanation of the formation of waveguides due to dry etching, wet etching
and ion implantation follows. Dry etching is an established technique in the field
of microstructure processing but the challenge of etching about 20 μm has led to
problems. The high etching depth also makes wet etching difficult but this method
could be improved due to a hard bake of the photoresist. The protection of critical
areas on the surface of the samples with photoresist during ion implantation was
increased by optimising the spin coating process. However, a full implantation of the
active layer between the waveguides was not achieved which was the reason for the
development of the hybrid technology. Here a prior wet etching of about 10 μm is
performed and the rest of the material is implanted.
The experimental setup is shown in chapter 4. An alternative method for the electrical
contacting with the help of a copper bar is introduced. This improves the current
distribution and the risk of an electrical breakdown during the measurements could
therefore be lowered. Devices for THz beam guidance and spectroscopic measurements
are shown and the method of biasing the samples with pulses below 100 ns and
determining the effective voltage applied to the sample is depicted. These short pulses
are required to prevent the samples heating up drastically due to high power.
Chapter 5 contains the current-voltage characterisation of several structures including
I-V-samples, Bloch laser samples and a quantum cascade laser. Different contacts
(ohmic and Schottky) and different techniques for the formation of the ridges have
been used in the processing of these samples (performed at the University of Frankfurt
in all cases) and their influence on the I-V-dependence is discussed. The properties of
the THz emission of the quantum cascade laser are in good agreement with published
results from lasers processed with the same material. Another important result of
this chapter is that the Bloch laser samples show unstable behaviour compared to the
quantum cascade structure even with short pulses (of about 10 ns) where the risk of an
electrical breakdown or the building of filaments is low. THz radiation emitted from
one of the Bloch laser samples could not be observed.
Two aspects that may have prevented the Bloch laser to emit are discussed in
chapter 6. The saturation of the gain for higher amplitudes of the THz wave is
investigated in single mode and multiple mode operation (the latter could occur due
to the Bloch gain being expected to be broadband). In both cases it is shown that
the saturation effect would limit the output power only to values clearly above the
detection limit. In the subsequent section the distribution of the electric field is
simulated with SILVACO software. Structures with transit layer lengths above the
Krömer criterion are compared with structures which include field-pinning layers. It is
shown that the latter are useful to avoid propagating Gunn domains as they build up
in similar structures without field-pinning layers. Nevertheless, the electric field inside
the superlattice regions is not stable. Beside spatial inhomogeneities also temporal
variations of the field magnitude are observed. The lack of a suitable field distribution
is expected to be the main reason for the samples not to work.
Only 3 of the 13 species so far comprised in Amphidium were retained in the genus: A lapponicum (Hedw.) Schimp., A. mougeotii (B.S.G.) Schimp. and A. tortuosum (Hornschuch) Cufodontis. Amphidium. sublapponicum (C. Müll.) Broth. is conspecific with A. lapponicum, A. cyathicarpum (Mont.) Broth., A. curvipes (C. Müll.) Broth. and A. californicum (C. Müll.) Broth. are synoymous with A. tortuosum. Amphidium brevifolium Broth., A. clastophyllum Broth. and A. papillosum Broth., all known only from the type locality, are sterile and differ vegetatively from all other species of the genus. They belong probably not to Amphidium. The types of Amphidium letestui Thér. & P. Varde, A. aloysii-sabaudiae Negri and A. remotidens (C. Müll.) Broth. could not be located.
Nematodes represent a diverse and ubiquitous group of metazoans in terrestrial environments. They feed on bacteria, fungi, plants, other nematodes or parasitize a variety of animals and hence may be considered as active members of many food webs. Deadwood is a structural component of forest ecosystems which harbors many niches for diverse biota. As fungi and bacteria are among the most prominent decomposing colonizers of deadwood, we anticipated frequent and diverse nematode populations to co-occur in such ecosystems. However, knowledge about their ability to colonize this habitat is still limited. We applied DNA-based amplicon sequencing (metabarcoding) of the 18S rRNA gene to analyze nematode communities in sapwood and heartwood of decaying logs from 13 different tree species. We identified 247 nematode ASVs (amplicon sequence variants) from 27 families. Most of these identified families represent bacterial and fungal feeders. Their composition strongly depended on tree species identity in both wood compartments. While pH and water content were the only wood properties that contributed to nematodes’ distribution, co-occurring fungal and prokaryotic (bacteria and archaea) α- and β-diversities were significantly related to nematode communities. By exploring thirteen different tree species, which exhibit a broad range of wood characteristics, this study provides first and comprehensive insights into nematode diversity in deadwood of temperate forests and indicates connectivity to other wood-inhabiting organisms.
Hintergrund: Der eigene Körper ist das zentrale Arbeitsinstrument eines*einer Tanzpädagog*in (TP) innerhalb der Bewegungsvermittlung. Bisher fehlen Erkenntnisse über die subjektive Wahrnehmung der eigenen berufsassoziierten Gesundheit und Zufriedenheit sowie die Identifizierung gesundheitsbelastender Berufsmerkmale.
Methodik: Im Rahmen einer fragebogenbasierten Querschnittserhebung wurde eine Kohorte von TP in Deutschland zur eigenen Gesundheit und generellen Berufszufriedenheit und belastenden Aspekten im Zusammenhang mit ihrer Berufsausübung untersucht. Zusätzlich wurden allgemeine anthropometrische und soziodemographische Merkmale erfasst. Neben der Betrachtung der Gesamtkohorte wurde auf geschlechtsspezifische Unterschiede getestet. In die statistische Analyse wurden n = 232 TP (m: 51/w: 181) im Alter von 43,1 ± 11,0 Jahren eingeschlossen.
Ergebnisse: Der allgemeine Gesundheitszustand wurde von 85,3 % der Befragten mit „befriedigend“ (26,1 %) bis „sehr gut“ (14,7 %) beurteilt. 59,2 % der Tanzpädagog*innen schätzten ihre Gesundheit „gut“ (35,3 %) bis „sehr gut“ ein. Es herrschte eine hohe Zufriedenheit mit der eigenen Berufsausübung für 80 % der Teilnehmenden. Die TP fühlten sich überwiegend in der Lage (trifft „voll & ganz“ bzw. „eher zu“), mit den physischen (75,7 %) und psychischen Berufsanforderungen (70,3 %) umzugehen. Als belastende Berufsmerkmale in der Eigenwahrnehmung können neben Zukunftsängsten (51,5 %) vor allem arbeitsorganisatorische (fehlende Zeit für Familie und Freunde bei 28,4 %) und ökonomische Aspekte (Einkommensunsicherheit bei 61,0 % und fehlende Altersabsicherung bei 65,7 %) herausgestellt werden.
Diskussion: Die Berufsausübung als TP geht mit einer hohen generellen Zufriedenheit und einem positiven Empfinden des eigenen Gesundheitszustandes einher. Eine Bestätigung dieser positiven Ergebnisse durch Verletzungs- und Erkrankungsstatistiken steht noch aus. Darüber hinaus wäre eine Verbesserung arbeitsorganisatorischer und ökonomischer Aspekte wünschenswert.
Motivated by the question of correctness of a specific implementation of concurrent buffers in the lambda calculus with futures underlying Alice ML, we prove that concurrent buffers and handled futures can correctly encode each other. Correctness means that our encodings preserve and reflect the observations of may- and must-convergence. This also shows correctness wrt. program semantics, since the encodings are adequate translations wrt. contextual semantics. While these translations encode blocking into queuing and waiting, we also provide an adequate encoding of buffers in a calculus without handles, which is more low-level and uses busy-waiting instead of blocking. Furthermore we demonstrate that our correctness concept applies to the whole compilation process from high-level to low-level concurrent languages, by translating the calculus with buffers, handled futures and data constructors into a small core language without those constructs.
Motivated by our experience in analyzing properties of translations between programming languages with observational semantics, this paper clarifies the notions, the relevant questions, and the methods, constructs a general framework, and provides several tools for proving various correctness properties of translations like adequacy and full abstractness. The presented framework can directly be applied to the observational equivalences derived from the operational semantics of programming calculi, and also to other situations, and thus has a wide range of applications.
Various concurrency primitives have been added to sequential programming languages, in order to turn them concurrent. Prominent examples are concurrent buffers for Haskell, channels in Concurrent ML, joins in JoCaml, and handled futures in Alice ML. Even though one might conjecture that all these primitives provide the same expressiveness, proving this equivalence is an open challenge in the area of program semantics. In this paper, we establish a first instance of this conjecture. We show that concurrent buffers can be encoded in the lambda calculus with futures underlying Alice ML. Our correctness proof results from a systematic method, based on observational semantics with respect to may and must convergence.
We investigate methods and tools for analyzing translations between programming languages with respect to observational semantics. The behavior of programs is observed in terms of may- and mustconvergence in arbitrary contexts, and adequacy of translations, i.e., the reflection of program equivalence, is taken to be the fundamental correctness condition. For compositional translations we propose a notion of convergence equivalence as a means for proving adequacy. This technique avoids explicit reasoning about contexts, and is able to deal with the subtle role of typing in implementations of language extensions.
We investigate methods and tools for analyzing translations between programming languages with respect to observational semantics. The behavior of programs is observed in terms of may- and mustconvergence in arbitrary contexts, and adequacy of translations, i.e., the reflection of program equivalence, is taken to be the fundamental correctness condition. For compositional translations we propose a notion of convergence equivalence as a means for proving adequacy. This technique avoids explicit reasoning about contexts, and is able to deal with the subtle role of typing in implementations of language extensions.
We investigate methods and tools for analysing translations between programming languages with respect to observational semantics. The behaviour of programs is observed in terms of may- and mustconvergence in arbitrary contexts, and adequacy of translations, i.e., the reflection of program equivalence, is taken to be the fundamental correctness condition. For compositional translations we propose a notion of convergence equivalence as a means for proving adequacy. This technique avoids explicit reasoning about contexts, and is able to deal with the subtle role of typing in implementations of language extensions.
We investigate methods and tools for analysing translations between programming languages with respect to observational semantics. The behaviour of programs is observed in terms of may- and mustconvergence in arbitrary contexts, and adequacy of translations, i.e., the reflection of program equivalence, is taken to be the fundamental correctness condition. For compositional translations we propose a notion of convergence equivalence as a means for proving adequacy. This technique avoids explicit reasoning about contexts, and is able to deal with the subtle role of typing in implementations of language extensions.
Motivated by the question of correctness of a specific implementation of concurrent buffers in the lambda calculus with futures underlying Alice ML, we prove that concurrent buffers and handled futures can correctly encode each other. Correctness means that our encodings preserve and reflect the observations of may- and must-convergence, and as a consequence also yields soundness of the encodings with respect to a contextually defined notion of program equivalence. While these translations encode blocking into queuing and waiting, we also describe an adequate encoding of buffers in a calculus without handles, which is more low-level and uses busy-waiting instead of blocking. Furthermore we demonstrate that our correctness concept applies to the whole compilation process from high-level to low-level concurrent languages, by translating the calculus with buffers, handled futures and data constructors into a small core language without those constructs.
Background: Eukaryotic gene expression is controlled by cis-regulatory elements (CREs), including promoters and enhancers, which are bound by transcription factors (TFs). Differential expression of TFs and their binding affinity at putative CREs determine tissue- and developmental-specific transcriptional activity. Consolidating genomic data sets can offer further insights into the accessibility of CREs, TF activity, and, thus, gene regulation. However, the integration and analysis of multi-modal data sets are hampered by considerable technical challenges. While methods for highlighting differential TF activity from combined chromatin state data (e.g., ChIP-seq, ATAC-seq, or DNase-seq) and RNA-seq data exist, they do not offer convenient usability, have limited support for large-scale data processing, and provide only minimal functionality for visually interpreting results.
Results: We developed TF-Prioritizer, an automated pipeline that prioritizes condition-specific TFs from multi-modal data and generates an interactive web report. We demonstrated its potential by identifying known TFs along with their target genes, as well as previously unreported TFs active in lactating mouse mammary glands. Additionally, we studied a variety of ENCODE data sets for cell lines K562 and MCF-7, including twelve histone modification ChIP-seq as well as ATAC-seq and DNase-seq datasets, where we observe and discuss assay-specific differences.
Conclusion: TF-Prioritizer accepts ATAC-seq, DNase-seq, or ChIP-seq and RNA-seq data as input and identifies TFs with differential activity, thus offering an understanding of genome-wide gene regulation, potential pathogenesis, and therapeutic targets in biomedical research.
Background Eukaryotic gene expression is controlled by cis-regulatory elements (CREs) including promoters and enhancers which are bound by transcription factors (TFs). Differential expression of TFs and their putative binding sites on CREs cause tissue and developmental-specific transcriptional activity. Consolidating genomic data sets can offer further insights into the accessibility of CREs, TF activity, and thus gene regulation. However, the integration and analysis of multi-modal data sets are hampered by considerable technical challenges. While methods for highlighting differential TF activity from combined ChIP-seq and RNA-seq data exist, they do not offer good usability, have limited support for large-scale data processing, and provide only minimal functionality for visual result interpretation.
Results We developed TF-Prioritizer, an automated java pipeline to prioritize condition-specific TFs derived from multi-modal data. TF-Prioritizer creates an interactive, feature-rich, and user-friendly web report of its results. To showcase the potential of TF-Prioritizer, we identified known active TFs (e.g., Stat5, Elf5, Nfib, Esr1), their target genes (e.g., milk proteins and cell-cycle genes), and newly classified lactating mammary gland TFs (e.g., Creb1, Arnt).
Conclusion TF-Prioritizer accepts ChIP-seq and RNA-seq data, as input and suggests TFs with differential activity, thus offering an understanding of genome-wide gene regulation, potential pathogenesis, and therapeutic targets in biomedical research.
In vivo inducible reverse genetics in patients' tumors to identify individual therapeutic targets
(2021)
High-throughput sequencing describes multiple alterations in individual tumors, but their functional relevance is often unclear. Clinic-close, individualized molecular model systems are required for functional validation and to identify therapeutic targets of high significance for each patient. Here, we establish a Cre-ERT2-loxP (causes recombination, estrogen receptor mutant T2, locus of X-over P1) based inducible RNAi- (ribonucleic acid interference) mediated gene silencing system in patient-derived xenograft (PDX) models of acute leukemias in vivo. Mimicking anti-cancer therapy in patients, gene inhibition is initiated in mice harboring orthotopic tumors. In fluorochrome guided, competitive in vivo trials, silencing of the apoptosis regulator MCL1 (myeloid cell leukemia sequence 1) correlates to pharmacological MCL1 inhibition in patients´ tumors, demonstrating the ability of the method to detect therapeutic vulnerabilities. The technique identifies a major tumor-maintaining potency of the MLL-AF4 (mixed lineage leukemia, ALL1-fused gene from chromosome 4) fusion, restricted to samples carrying the translocation. DUX4 (double homeobox 4) plays an essential role in patients’ leukemias carrying the recently described DUX4-IGH (immunoglobulin heavy chain) translocation, while the downstream mediator DDIT4L (DNA-damage-inducible transcript 4 like) is identified as therapeutic vulnerability. By individualizing functional genomics in established tumors in vivo, our technique decisively complements the value chain of precision oncology. Being broadly applicable to tumors of all kinds, it will considerably reinforce personalizing anti-cancer treatment in the future.
73Ge(n, γ ) cross sections were measured at the neutron time-of-flight facility n_TOF at CERN up to neutron energies of 300 keV, providing for the first time experimental data above 8 keV. Results indicate that the stellar cross section at kT = 30 keV is 1.5 to 1.7 times higher than most theoretical predictions. The new cross sections result in a substantial decrease of 73Ge produced in stars, which would explain the low isotopic abundance of 73Ge in the solar system.
Background: Platelet activating factor and tachykinins (substance P, neurokinin A, neurokinin B) are important mediators contributing to increased airway secretion in the context of different types of respiratory diseases including acute and chronic asthma. Leukotriene receptor antagonists are recommended as add-on therapy for this disease. The cys-leukotriene-1 receptor antagonist montelukast has been used in clinical asthma therapy during the last years. Besides its inhibitory action on bronchoconstriction, only little is known about its effects on airway secretions. Therefore, the aim of this study was to evaluate the effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity.
Methods: The effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity in the rat were assessed by quantification of secreted 35SO4 labelled mucus macromolecules using the modified Ussing chamber technique.
Results: Platelet activating factor potently stimulated airway secretion, which was completely inhibited by the platelet activating factor receptor antagonist WEB 2086 and montelukast. In contrast, montelukast had no effect on tachykinin induced tracheal secretory activity.
Conclusion: Cys-leukotriene-1 receptor antagonism by montelukast reverses the secretagogue properties of platelet activating factor to the same degree as the specific platelet activating factor antagonist WEB 2086 but has no influence on treacheal secretion elicited by tachykinins. These results suggest a role of montelukast in the signal transduction pathway of platelet activating factor induced secretory activity of the airways and may further explain the beneficial properties of cys-leukotriene-1 receptor antagonists.
The KER for electron capture of vibrational cooled HeH+ and H3 + ions at 20 keV from residual gas atoms has been measured in the Frankfurt Low Energy Storage Ring (FLSR). At a vacuum in the order of few 10-11 mbar, this residual gas consists to 99% of H2 molecules. For the identification of the recoil products of this reaction, a recoil spectrometer (with an MCP-detector with position and time sensitive read out) was installed at one of the focus points (IP) in the FLSR. The planned extension of this set up by a gas target to a full COLTRIMS reaction microscope will be discussed.
We investigate methods and tools for analysing translations between programming languages with respect to observational semantics. The behaviour of programs is observed in terms of may- and must-convergence in arbitrary contexts, and adequacy of translations, i.e., the reflection of program equivalence, is taken to be the fundamental correctness condition. For compositional translations we propose a notion of convergence equivalence as a means for proving adequacy. This technique avoids explicit reasoning about contexts, and is able to deal with the subtle role of typing in implementations of language extension.
Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0–T1: +3.37±2.17%), while non-responders further decreased in methylation (−2.00±1.28%; P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02–0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.