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Sustained Human Background Exposure to Acrolein Evidenced by Monitoring Urinary Exposure Biomarkers
(2019)
Scope
This study investigates a potential correlation between the intake of heat-processed food and the excretion of the acrolein (AC) biomarkers N-acetyl-S-(3-hydroxypropyl)-l-cysteine (HPMA) and N-acetyl-S-(carboxyethyl)-l-cysteine (CEMA) based on two human studies.
Methods and Results
Human exposure to AC is monitored using the AC-related mercapturic acids HPMA and CEMA in the urine of a) non-smoking volunteers under defined living conditions and b) of non-smoking volunteers on unrestricted or vegan diet under free living conditions. Free living volunteers in part show markedly enhanced urinary excretions of HPMA and CEMA. The intake of heat-processed food does not influence AC-related biomarker excretion. Incidentally enhanced urinary exposure biomarker levels appear to suggest AC exposure possibly from open fire, barbecuing, or tobacco smoke. However, kinetics of urinary biomarkers related to tobacco and other potential smoke exposure, do not correlate with those observed for HPMA and CEMA.
Conclusion
This study is the first to convincingly show a sustained and substantial background exposure to AC in non-smoking humans, clearly independent from uptake of heat-processed foods. The data strongly point to endogenous AC generation by pathways of mammalian and/or microbial metabolism as yet not taken into consideration.
Water availability shapes edaphic and lithic cyanobacterial communities in the Atacama Desert
(2019)
In the Atacama Desert, cyanobacteria grow on various substrates such as soils (edaphic) and quartz or granitoid stones (lithic). Both edaphic and lithic cyanobacterial communities have been described but no comparison between both communities of the same locality has yet been undertaken. In the present study, we compared both cyanobacterial communities along a precipitation gradient ranging from the arid National Park Pan de Azúcar (PA), which resembles a large fog oasis in the Atacama Desert extending to the semiarid Santa Gracia Natural Reserve (SG) further south, as well as along a precipitation gradient within PA. Various microscopic techniques, as well as culturing and partial 16S rRNA sequencing, were applied to identify 21 cyanobacterial species; the diversity was found to decline as precipitation levels decreased. Additionally, under increasing xeric stress, lithic community species composition showed higher divergence from the surrounding edaphic community, resulting in indigenous hypolithic and chasmoendolithic cyanobacterial communities. We conclude that rain and fog water, respectively, cause contrasting trends regarding cyanobacterial species richness in the edaphic and lithic microhabitats.
Synapses are the fundamental structures that regulate the functionality of the neural circuit. The ability of the synapse to modulate its structure and function at a fast rate due to various sensory inputs provides the strength to the nervous system to incorporate new adaptations and behaviors in the animal. The synapses are very dynamic throughout the life of the animal starting from early development. Continuous events of formation and elimination of synapse, activation and inhibition of synaptic function are observed in almost all synapses. These processes occur at a high speed and require controlled cellular mechanisms. Imbalance in these processes results in defective nervous system and has been reported in many neurological disorders. Thus, it is important to understand the mechanisms that regulate process of synapse development maintenance and function.
Kinases and phosphatases are the key regulators of cellular mechanisms. Understanding the function of these molecules in the neuron will shed light on the molecular mechanisms of synaptic plasticity. Using Drosophila melanogaster larval neuromuscular junction as a model, Bulat et al. (2014) performed a large RNAi based screen targeting kinome and phosphatome of Drosophila to identify the essential kinases and phosphatases and found Myeloid leukemia factor-1 adaptor molecule (Madm) and Protein phosphatase 4 (PP4) as novel regulators of synapse development and maintenance. The function of these molecules in the nervous system has not been reported and hence I investigated on the role of Madm and PP4 in the regulation of synapse development, maintenance and function.
Myeloid leukemia factor-1 adaptor molecule (Madm), a ubiquitously expressing psuedokinase essentially functions to regulate synaptic growth, stability and function. Using a combination of genetic and high throughput imaging, I could demonstrate that Madm functions to regulate the synaptic growth and stability from the presynapse and synaptic organization form the postsynapse. Also, I could demonstrate that Madm functions in association with mTOR pathway to regulate synapse growth acting downstream of 4E-BP. In addition, using electrophysiology, we could demonstrate that Madm is essential for the basic synaptic transmission with an additive function of retrograde synaptic potentiation. In summary, I could demonstrate that Madm is a novel regulator of synaptic development, maintenance and function.
Protein phosphatase 4 (PP4), a ubiquitously expressing protein phosphatase is involved in the regulation of multiple aspects of the nervous system. I could demonstrate that PP4 is essential for the development of nervous system and the metamorphosis. Using genetics and imaging analysis, I could demonstrate that loss of PP4 results in the abnormal morphology of cell organelles. In addition, I could show that loss of PP4 results in defective brain development with poorly developed structures.
Altogether, in this study, I could demonstrate the importance of novel molecules, a pesudokinase Madm and protein phosphatases PP4 in the nervous system to regulate distinct aspects of the neuron.
Nachfolgend ist ein modularer Multilevel-Umrichter mit einer Mehrzahl von Einzelmodulen beschrieben, bei dem eine erste Gruppe von Modulen hintereinander zu einem geschlossenen Ring verschaltet sind und mindestens zwei Abgriffe jeweils zwischen zwei benachbarten Einzelmodulen des Rings angeordnet sind. An mindestens zwei Abgriffen ist je eine zweite weitere Gruppe von Modulen als von der Ringanordnung abzweigendes und einen Sternstrang bildendes Phasenmodul vorgesehen ist. Diese letztgenannten Gruppen von Modulen bilden an den Enden jeweils Anschlüsse oder Abgriffe. Die Module erlauben durch Schaltelemente ein Verschalten von Energiespeichern benachbarter Einzelmodule, wodurch zwischen zwei benachbarten Phasenanschlüssen eine Spannungsdifferenz bereitstellbar ist, die von einer Steuereinheit entsprechend eines Verlaufs eines mehrphasigen Drehfeldes regelbar ist. Ferner betrifft die vorliegende Erfindung ein Polyphasensystem und ein Verfahren zum effizienten Leistungsaustausch zwischen Modulen.
Wetted contacts play an important role in many fields. A prominent example in engineering is the lubricated contact between tool and workpiece in machining processes with cutting liquids. In such contacts, highly dynamic processes occur in the fluid at small length scales under extreme conditions regarding temperature, pressure, and shear. Experimental studies of these phenomena are generally not feasible. Thus, only little information on the actual processes in the contact zone is available. A tractable route for obtaining such information is molecular dynamics (MD) simulation. As input for these simulations, only a potential model that describes the interactions on the atomistic scale, is needed. On that basis also complex processes can be predicted. In the present work, a simple model potential was used, i.e. the Lennard-Jones truncated and shifted potential (LJTS), which was parameterized to describe the solids, the fluid, and their interactions. A novel method for determining fluid properties with non-equilibrium MD simulations was developed, which yields thermal, caloric and transport properties in a single simulation run. It can also be used for studying the influence of shear on these properties. With the new method, a comprehensive study of properties of the LJTS fluid was carried out. Furthermore, it was investigated how these fluid properties change near the solid-fluid interface and how these changes affect the conductive heat transfer between the solid and the fluid. Finally, a nanotribological process was studied, in which all these phenomena occur simultaneously.
Hamiltonian daemons allow the transfer of energy from systems with very fast degrees
of freedom to systems with slower ones across several orders of magnitude. They act on
small scales and can be regarded as micro-engines.
Such daemons were previously described in the classical as well as the quantum me-
chanical regime. In this thesis the semi-classical regime is examined, where quantum
phenomena occur as corrections to classical systems. Here, the focus is on numerical
simulations.
First some introductory models are examined. They are concerned with quantum
tunneling, since it occurs as an important quantum correction, as well as with the
capture and decay of bound states, since this represents the transition between the
dynamical phases of a daemon: adiabatic decoupling and downconversion.
The examinations are carried out using wave functions, as solutions to the Schrödinger
equation, and by means of Wigner functions in a quantum mechanical phase-space in
the framework of the Weyl-Wigner-Groenewold-Moyal formalism. For one these Wigner
functions are computed from the wave functions, but they are also obtained from a
numerical method based on the Moyal equation, which will be introduced here.
After developing this methodology, it is employed in the study of a daemon system
with a tilted washboard potential. The daemon behavior is studied with regards to
quantum corrections, especially in phase-space and concerning Kruskal’s theorem, which
describes the capture of phase-space flow via a time-dependent separatrix.
Lastly the semi-classically quantized phase-space will be discussed as a basis for a
combined description of both classical and quantum daemons. The behavior of the
energy spectrum in the deep quantum regime is explained by dynamical tunneling pro-
cesses.
Untersuchung der spektroskopischen und kinetischen Eigenschaften von Dihydroxysäure-Dehydratasen
(2019)
Eisen-Schwefel-Cluster sind wichtige Cofaktoren, die an der Redox- und Nicht-Redox-Katalyse beteiligt sind. Enzyme der Lyase-Familie wie Aconitase, Fumarase und DihydroxysäureDehydratase enthalten Cluster, die an drei Cystein-Liganden koordiniert sind. Das Eisenion, das an einen Nicht-Cysteinyl-Liganden koordiniert ist, wirkt als Lewis-Säure und interagiert mit dem Substrat über die Hydroxygruppe des dritten Kohlenstoffatoms und der Carboxygruppe. Das in dieser Arbeit untersuchte Enzym ist die Dihydroxysäure-Dehydratase (DHAD), welche an der Biosynthese der Aminosäuren Isoleucin, Leucin und Valin beteiligt ist. In dieser Arbeit wurden die kinetischen und spektroskopischen Eigenschaften von DHAD aus Streptococcus mutans, Streptococcus thermophilus, Saccharomyces cerevisiae und Escherichia coli untersucht. Zu diesem Zweck wurden ihre Gene kloniert und die Proteine in E. coli Zellen exprimiert. Nach der Proteinreinigung zeigten die UV-Vis-, ESR- und Mössbauer-Spektroskopie die Anwesenheit eines [2Fe-2S]2+-Clusters in der S. mutans DHAD, eines [4Fe-4S]2+-Cluster in E. coli DHAD und einer Mischung von [2Fe-2S]2+- und [4Fe-4S]2+ -Cluster in der S. cerevisiae DHAD. Darüber hinaus unterstützten die Ergebnisse der Sauerstoffstabilitätstests und des Eisen- und säurelabilen Sulfidgehalts die spektroskopischen Analysen. MössbauerSpektroskopie lieferte zusätzlich Information für das Vorhandensein eines nicht-cysteinyl-koordinierten Eisenions in den Clustern der S. mutans und in E. coli DHAD. Enzymaktivitätsmessungen mit dem Dinitrophenylhydrazin-Assay und den hier etablierten gekoppelten Assays mit NADH-abhängigen Ketoisovalerat-reduzierenden Dehydrogenasen wurden durchgeführt, um die spezifischen Aktivitäten und die kinetischen Parameter der DHAD zu bestimmen. Interaktionsstudien der S. mutans DHAD mit dem Substrat, dem Produkt, den substrat- und produktähnlichen Verbindungen mittels UV-Vis-, ESR-, Mössbauer- und FT-IR-Spektroskopie zeigten, dass nur das (2R)-Isomer des Substrats und 2-Ketosäuren (KIV, Kbut) mit dem Cluster der S. mutans DHAD interagierten. Das DHAD-Produkt (2-Ketoisovalerat) interagiert vermutlich über seine Enolform mit dem Cluster. Interessanterweise wurde starke Interaktion des Clusters mit der β-Mercaptogruppe von 3-Mercaptopropionat beobachtet. Diese Wechselwirkung wurde unabhängig durch Inhibitionsstudien verifiziert. Anschließend zeigte eine Gelfiltrationsanalyse die Reversibilität der Interaktionen. Insgesamt hat die vorliegende Arbeit unser Wissen über die biotechnologisch wichtigen DHAD-Enzyme erweitert.
Infobrief FBK 57/19
(2019)
Infobrief FBK 58/19
(2019)
Infobrief FBK 59/19
(2019)
The objective of current research on internal combustion engines
is to further reduce exhaust emissions while simultaneously
reducing fuel consumption. The resulting measures often mean
an increase in complexity of internal combustion engines, which
on one hand increases production cost and on the other hand
increases the susceptibility of the overall system to defects. It is
therefore necessary to develop technologies which can generate
an advantage for the consumer despite increasing complexity.
Within the scope of the project “High Efficiency Diesel Engine
Concept” (“Hocheffizientes Diesel-Motoren-Konzept” HDMK),
funded by the Federal Ministry of Economic Affairs and Energy
with TÜV Rheinland as project management organization
(funding code: 19U15003A), two engine concepts were
investigated and combined on a John Deere four-cylinder inline
engine.
On the one hand, a new cylinder activation concept ("3/4-
cylinder concept") was implemented with the aim of reducing
fuel consumption. On the other hand, a fully variable valve train
was developed for this engine, which both improves the
functionality of the 3/4-cylinder concept and can have a positive
influence on exhaust emissions through internal exhaust gas
recirculation.
A comparison of this engine concept with its series reference
based on measurement data showed a fuel economy advantage
of up to 5.2% in the low load field cycles of the DLG PowerMix.
The maximum fuel consumption benefit in the low load engine
regime exceeded 15% in some of the operating points.
As a final step, the engine was modified for the integration into
an existing and working tractor, maintaining the available
installation space of the powertrain.
Glycine constitutes the major neurotransmitter at inhibitory synapses of lower brain regions.
A rapid removal of glycine from the synaptic cleft and consequent recycling is crucial for
synaptic transmission in systems with high effort on temporal precision. This is mainly
achieved by glycine translocation via two glycine transporters (GlyTs), namely GlyT1 and
GlyT2. At inhibitory synapses, GlyT2 was found to be specifically expressed by neurons,
supplying the presynapse with glycine needed for vesicle filling. In contrast, GlyT1 is attributed
to astrocytes and primarily mediates the termination of synaptic transmission by glycine
removal from the synaptic cleft. Employing patch-clamp recordings from principal neurons of
the lateral superior olive (LSO) in acute brainstem slices of GlyT1b/c knockout (KO) mice and
wildtype (WT) littermates at postnatal day 20, I analyzed how postsynaptic responses are
changed in a GlyT1-depleted environment. During spontaneous vesicle release I found no
change of postsynaptic responses, contradicting my initial hypothesis of prolonged decay
times. Electrical stimulation of fibers of the medial nucleus of the trapezoid body (MNTB),
which are known to form fast, reliable and highly precise synapses with LSO principal neurons,
revealed that GlyT1 is involved in proper synaptic function during sustained, high frequent
synaptic transmission. Stimulation with 50 Hz led to a stronger decay time and latency
prolongation in GlyT1b/c KO, accelerating to 60% longer decay times and 30% longer latencies.
Additionally, a more pronounced frequency-dependent depression and fidelity decrease was
observed during stimulation with 200 Hz in GlyT1b/c KO, resulting in 67% smaller amplitudes
and only 25% of WT fidelity at the end of the challenge. Basic properties like readily releasable
pool, release probability, and quantal size (q) were not altered in GlyT1b/c KO, but
interestingly q decreased during 50 Hz and 100 Hz challenges to about 84%, which was not
observed in WT. I conclude that stronger accumulation of extracellular glycine due to GlyT1
loss leads to prolonged activation of postsynaptic glycine receptors (GlyRs). As a further
consequence, activation of presynaptic GlyRs in the vicinity of the synaptic cleft might be
enhanced, accompanied by a stronger occurrence of shunting inhibition. Furthermore, I
assume a GlyT1-dependent glycine shuttle, which is absent at GlyT1b/c KO synapses. This
could result in a diminished glycine supply to GlyT2 located at more distant sites, causing a
disturbed replenishment during periods with excess release of glycine. Conclusively, my study
reveals a contribution of astrocytes in fast and reliable synaptic transmission at the MNTB-LSO
synapse, which in turn is crucial for proper sound source localization.
Nachhaltigkeit und Digitalisierung sind zwei der großen Themen unserer
Zeit. In beiden Kontexten wird oft von Transformation gesprochen: Wirtschaft und Gesellschaft werden sich maßgeblich verändern. Deshalb sollten die beiden Trends Digitalisierung und Nachhaltigkeit zusammen betrachtet und ihre Zusammenhänge untersucht werden. Grundsätzlich
wird der Digitalisierung in der wissenschaftlichen Literatur ein Einfluss
auf die Erreichung einer nachhaltigen Zukunft attestiert – sowohl positiv
als auch negativ. Im Rahmen der Digitalisierungsforschung ist der Aspekt
der Nachhaltigkeit zumeist mehr Zusatz als Leitbild. Ob und inwiefern
eine digitale Transformation auch eine Nachhaltigkeitstransformation mit
sich bringt, bleibt in der Forschung also bisher weitestgehend unbeantwortet. Daher ist es unser Ziel, eine mögliche Wirkungskette aufzustellen,
die sowohl nachhaltigkeitsbezogene als auch Digitalisierungsaspekte vor
dem Hintergrund der Erreichung der Agenda 2030 integriert. Der Tenor
unserer Recherche: Digitalisierung wird von sich aus keine der großen
Nachhaltigkeitsherausforderungen lösen, sofern sie nicht in eine klare
Strategie eingebettet ist.
Using industrial robots for machining applications in flexible manufacturing
processes lacks a high accuracy. The main reason for the deviation is the
flexibility of the gearbox. Secondary Encoders (SE) as an additional, high precision
angle sensor offer a huge potential of detecting gearbox deviations. This paper
aims to use SE to reduce gearbox compliances with a feed forward, adaptive
neural control. The control network is trained with a second network for system
identification. The presented algorithm is capable of online application and optimizes
the robot accuracy in a nonlinear simulation.
Biological soil crusts (biocrusts) have been recognized as key ecological players in arid and semiarid regions at both local and global scales. They are important biodiversity components, provide critical ecosystem services, and strongly influence soil-plant relationships, and successional trajectories via facilitative, competitive, and edaphic engineering effects. Despite these important ecological roles, very little is known about biocrusts in seasonally dry tropical forests. Here we present a first baseline study on biocrust cover and ecosystem service provision in a human-modified landscape of the Brazilian Caatinga, South America's largest tropical dry forest. More specifically, we explored (1) across a network of 34 0.1 ha permanent plots the impact of disturbance, soil, precipitation, and vegetation-related parameters on biocrust cover in different stages of forest regeneration, and (2) the effect of disturbance on species composition, growth and soil organic carbon sequestration comparing early and late successional communities in two case study sites at opposite ends of the disturbance gradient. Our findings revealed that biocrusts are a conspicuous component of the Caatinga ecosystem with at least 50 different taxa of cyanobacteria, algae, lichens and bryophytes (cyanobacteria and bryophytes dominating) covering nearly 10% of the total land surface and doubling soil organic carbon content relative to bare topsoil. High litter cover, high disturbance by goats, and low soil compaction were the leading drivers for reduced biocrust cover, while precipitation was not associated Second-growth forests supported anequally spaced biocrust cover, while in old-growth-forests biocrust cover was patchy. Disturbance reduced biocrust growth by two thirds and carbon sequestration by half. In synthesis, biocrusts increase soil organic carbon (SOC) in dry forests and as they double the SOC content in disturbed areas, may be capable of counterbalancing disturbance-induced soil degradation in this ecosystem. As they fix and fertilize depauperated soils, they may play a substantial role in vegetation regeneration in the human-modified Caatinga, and may have an extended ecological role due to the ever-increasing human encroachment on natural landscapes. Even though biocrusts benefit from human presence in dry forests, high levels of anthropogenic disturbance could threaten biocrust-provided ecosystem services, and call for further, in-depth studies to elucidate the underlying mechanisms.
Was in der vorliegenden empirischen Analyse des Einzelfalls mit Blick auf eine umfassende organisationale Transformation als inhärent-emergenter Prozess beschrieben wird, ist gewiss ein Sonderfall: Nach dem Abbruch eines Beratungsprozesses treibt ein System seine Transformation autonom voran, ohne weitere Unterstützung einer Prozessberatung und stellt damit seine Selbstentwicklungsfähigkeit in einem transformativen Prozess der Organisationsentwicklung unter Beweis. Dies ist in der Organisationsentwicklung nicht die Regel und wird sehr wahrscheinlich auch nicht von anderen Organisationen als Modell aufgegriffen, auch nicht von Organisationen desselben Typs (familiengeführte mittelständische Organisationen). Dass ein Eintritt in eine radikale Transformation als autopoietischer Prozess wie hier überhaupt möglich ist, ist den spezifischen Eigenschaften einer Organisation und ihrer zentralen Entscheidungsakteure, besonderen, kontingent geprägten Ereignisketten sowie der aktuellen Konstellation der zweiten Führungsebene zuzuschreiben. Die hier vorgestellte Untersuchung entspricht daher einem „neuen und unbeschriebenen Fall“ (Hering/Jungmann, 2005: 621), einem „per se interessanten Fall“ (ebd.), der sich in keinen Forschungsstand einordnen lässt.
To exploit the whole potential of Additive Manufacturing (AM), a sound knowledge about the mechanical and especially cyclic properties of AM materials as well as their dependency on the process parameters is indispensable. In the presented work, the influence of chemical composition of the used powder on the fatigue behavior of Selectively Laser Melted (SLM) and Laser Deposition Welded (LDW) specimens made of austenitic stainless steel AISI 316L was investigated. Therefore, in each manufacturing process two variations of chemical composition of the used powder were utilized. For qualitative characterization of the materials cyclic deformation behavior, load increase tests (LITs) were performed and further used for the physically based lifetime calculation method (PhyBaLLIT), enabling an efficient determination of stress (S)–number of cycles to failure (Nf) curves (S–Nf), which show excellent correlation to additionally performed constant amplitude tests (CATs). Moreover, instrumented cyclic indentation tests (PhyBaLCHT) were utilized to characterize the materials’ defect tolerance in a comparably short time. All material variants exhibit a high influence of microstructural defects on the fatigue properties. Consequently, for the SLM process a higher fatigue lifetime at lower stress amplitudes could be observed for the batch with a higher defect tolerance, resulting from a more pronounced deformation induced austenite–α’-martensite transformation. In correspondence to that, the batch of LDW material with an increased defect tolerance exhibit a higher fatigue strength. However, the differences in defect tolerance between the LDW batches is only slightly influenced by phase transformation and seems to be mainly governed by differences in hardening potential of the austenitic microstructure. Furthermore, a significantly higher fatigue strength could be observed for SLM material in relation to LDW specimens, because of a refined microstructure and smaller microstructural defects of SLM specimens.
In this paper we present the results of the project “#Datenspende” where during the German election in 2017 more than 4000 people contributed their search results regarding keywords connected to the German election campaign.
Analyzing the donated result lists we prove, that the room for personalization of the search results is very small. Thus the opportunity for the effect mentioned in Eli Pariser’s filter bubble theory to occur in this data is also very small, to a degree that it is negligible. We achieved these results by applying various similarity measures to the result lists that were donated. The first approach using the number of common results as a similarity measure showed that the space for personalization is less than two results out of ten on average when searching for persons and at most four regarding the search for parties. Application of other, more specific measures show that the space is indeed smaller, so that the presence of filter bubbles is not evident.
Moreover this project is also a proof of concept, as it enables society to permanently monitor a search engine’s degree of personalization for any desired search terms. The general design can also be transferred to intermediaries, if appropriate APIs restrict selective access to contents relevant to the study in order to establish a similar degree of trustworthiness.