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Societal effects of transdisciplinary sustainability research – How can they be strengthened during the research process?
No full textTransdisciplinary sustainability research aims to mitigate or to solve complex societal problems and advance the production of scientific knowledge. Reflexive approaches to transdisciplinary research processes are outlined to systematically strengthen the potential for societal effectiveness. So far, it is rare to find empirically based analyses of the links between the quality of the research process and the methods applied on the one hand and the effects achieved on the other.
This paper thus addresses the issue of heightening the societal effects of transdisciplinary sustainability research. The objective is to explore ways of consciously promoting societal effectiveness in transdisciplinary research. We argue that these possibilities evolve at the intersection between the general project framework and an adaptive shaping of transdisciplinary research processes. A reflexive approach of this kind proactively considers the dynamics of interests and concerns, roles and responsibilities, the collaboration culture within a project, and the connectivity to the context of action addressed. Its deployment presupposes an appreciation of the basic conditions, i.e. the historical development of the respective problem, the heterogeneity of actors involved, the general environment and, finally, the funding conditions
From Metastable to Coherent Sets – time-discretization schemes
Get PDFGiven a time-dependent stochastic process with trajectories x(t) in a space \Omega, there may be sets such that the corresponding trajectories only very rarely cross the boundaries of these sets. We can analyze such a process in terms of metastability or coherence. Metastable sets M are defined in space M \subset \Omega, coherent sets M(t) \subset \Omega are defined in space and time. Hence, if we extend the space \Omega by the time-variable t, coherent sets are metastable sets in \Omega \times [0,\infty). This relation can be exploited, because there already exist spectral algorithms for the identification of metastable sets. In this article we show that these well-established spectral algorithms (like PCCA+) also identify coherent sets of non-autonomous dynamical systems. For the identification of coherent sets, one has to compute a discretization (a matrix T) of the transfer operator of the process using a space-time-discretization scheme. The article gives an overview about different time-discretization schemes and shows their applicability in two different fields of application
Stacking fault reduction during annealing in Cu-poor CuInSe2 thin film solar cell absorbers analyzed by in situ XRD and grain growth modeling
No full textBuried wurtzite structures composed by stacking faults of the {111} planes in zinc-blende and {112} planes in chalcopyrite structures can result in barriers for charge carrier transport. A precise understanding of stacking fault annihilation mechanisms is therefore crucial for the development of effective deposition processes. During co-evaporation of Cu(In,Ga)Se2—a photovoltaic absorber material showing record efficiencies of up to 22.9% for thin film solar cells—a reduction of stacking faults occurs at the transition from a Cu-poor to a Cu-rich film composition, parallel to grain growth, which is suggesting that the two phenomena are coupled. Here, we show by in situ synchrotron X-ray diffraction during annealing of Cu-poor CuInSe2 thin films that stacking faults can be strongly reduced through annealing, without passing through a Cu-rich film composition. We simulate the evolution of the X-ray diffraction stacking fault signal with a simple numerical model of grain growth driven by stacking fault energy and grain boundary curvature. The results support the hypothesis that the stacking fault reduction can be explained by grain growth. The model is used to make predictions on annealing times and temperatures required for stacking fault reduction and could be adapted for polycrystalline thin films with similar morphology
Markov State Models in drug design
No full textStarting from the lock-and-key model [1], models of ligand–target binding have been extended to acknowledge the role of conformational flexibility. In current models, the targets are assumed to fluctuate between several different confor- mations. In the conformational selection model [2], one of these conformations is the active state, i.e. the conformation which is assumed in complex with the ligand. e ligand then “selects” this conformation from the ensemble and stabi- lizes it by forming a complex. By contrast, in the induced-fit model [3], the active conformation is not sampled by the apo-target. Instead, the receptor and the lig- and form an unspecific encounter complex. is weak complex then triggers a conformational rearrangement in the receptor, which leads to the fully formed complex. While examples of mechanisms have been found [4–7], most binding processes fall somewhere in between these two extremes.
e conformational selection and the induced-fit model neglect the confor- mational dynamics of the ligand, which is justified if the ligand is either rigid or its dynamics is fast compared to the dynamics of the target. However, this is not always a valid assumption. In particular, peptides and peptidomimetics exhibit a complex and often slow conformational dynamics. It is increasingly recognized that the flexibility of the target and the ligand and their mutual inter- action are crucial factors in the ligand-binding process. us, to systematically vary the thermodynamic and kinetic properties of a drug molecule, not only bind- ing affinities but also dynamics need to be taken into account.
Experimentally, it is difficult to characterize the full conformational ensem- ble and its dynamics. However, an increase in computer power combined with improved algorithms has rendered molecular dynamics (MD) simulations as use- ful tools in structure-based drug design [8]. With progress in distributed com- puting [9], special purpose computers [10], and graphics processing unit (GPU) devices [11], trajectories of several tens in microseconds are now accessible on a routine basis.
A visual inspection of these trajectories is sometimes not feasible, due to the shear size of the data set, and almost always unrewarding, because it does not yield a quantitative description of the system.1 While statistical analyses of the trajectory for the stationary properties of the system have been used routinely for decades, methods which yield a model of the dynamics have matured only recently. Markov State Models (MSMs) [12–17], in which the dynamics is approx- imated as a Markovian jump process between distinct microstates, are the most widely used dynamic models. MSMs have been used to improve ensemble dock- ing, to optimize a specific conformation in a ligand, to identify cryptic allosteric sites, and to characterize ligand-binding processes as well as inactive-to-active transitions in signaling proteins. We do not aim at a comprehensive survey of the literature on this subject, nor do we focus on specific results. Our goal is to explain the different ways in which MSMs can be helpful in structure-based design
Molecular dynamics of open systems: construction of a mean-field particle reservoir
Get PDFThe simulation of open molecular systems requires explicit or implicit reservoirs of energy and particles. Whereas full atomistic resolution is desired in the region of interest, there is some freedom in the implementation of the reservoirs. Here, we construct a combined, explicit reservoir by interfacing the atomistic region with regions of point-like, non-interacting particles (tracers) embedded in a thermodynamic mean field. The tracer molecules acquire atomistic resolution upon entering the atomistic region and equilibrate with this environment, while atomistic molecules become tracers governed by an effective mean-field potential after crossing the atomistic boundary. The approach is extensively tested on thermodynamic, structural, and dynamic properties of liquid water. Conceptual and numerical advantages of the procedure as well as new perspectives are highlighted and discussed
Whole Genome Shotgun Sequencing Based Taxonomic Profiling Methods for Comparative Study of Microbial Communities
No full textMicroorganisms, typically occurring as large, species diverse communities, are a ubiquitous part of nature. These communities are a vital part of their environment, influencing it through various layers of interaction. Host-associated microbial communities are particularly scrutinized for their influence on the host’s health. Additionally, there is a growing interest in microbial communities due to their role in livestock, agriculture, waste treatment, mining, and biotechnology. Metagenomics is a relatively young scientific field that aims to study such microbial communities based on genetic material recovered directly from an environment. Advances in DNA sequencing have enabled us to perform taxonomic profiling, i.e. to identify microbial species quantitatively and qualitatively at increasing depth.
In whole genome shotgun sequencing (WGS), environmental DNA is taken directly from an environment and sequenced after being fragmented, without PCR amplification. Taxonomic profiling methods based on such sequencing data introduce less PCR bias compared to their amplicon based counterparts such as 16S-rDNA based profiling methods. However, the challenges posed by the enormous and redundancy of databases and the high degree homology among reference genomes of microorganisms put WGS methods at a disadvantage. In this thesis, we will present and discuss two separate computational methods that address both challenges.
The first method is a taxonomic profiler that leverages coverage landscapes created by mapping sequencing reads across reference genomes to address the challenge posed by homologous regions of genomes. By carefully evaluating the coverage profile of reference genomes we drop spurious references from consideration. This filtration strategy results in more uniquely mapping reads to the remaining reference genomes improving both the resolution and accuracy of the taxonomic profiling process. We have also shown that this method improves the quality of relative abundances assigned to each detected member organism.
The second method is a distributed read mapper which addresses the issue of large and frequently changing databases by systematically partitioning it into smaller bins. It significantly reduces the time, and computational resources required to build indices from such large databases by orders of magnitudes and updates can be performed very quickly in a few minutes compared to days in earlier methods. To achieve a competitive mapping speed while maintaining many small indices, we implemented a novel, fast and lightweight filtering data structure called interleaved bloom filter. With that, we are able to achieve the described improvements in the index building and updating time without compromising the read-mapping speed
Approaches to Obtaining Fluorinated α-Amino Acids
No full textFluorine does not belong to the pool of chemical elements that nature uses to build organic matter. However, chemists have exploited the unique properties of fluorine and produced countless fluoro-organic compounds without which our everyday lives would be unimaginable. The incorporation of fluorine into amino acids established a completely new class of amino acids and their properties, and those of the biopolymers constructed from them are extremely interesting. Increasing interest in this class of amino acids caused the demand for robust and stereoselective synthetic protocols that enable straightforward access to these building blocks. Herein, we present a comprehensive account of the literature in this field going back to 1995. We place special emphasis on a particular fluorination strategy. The four main sections describe fluorinated versions of alkyl, cyclic, aromatic amino acids, and also nickel-complexes to access them. We progress by one carbon unit increments. Special cases of amino acids for which there is no natural counterpart are described at the end of each section. Synthetic access to each of the amino acids is summarized in form of a table at the end of this article with the aim to make the information easily accessible to the reader
Rate-independent damage in thermoviscoelastic materials with inertia
No full textAbstract We present a model for rate-independent, unidirectional, partial damage in visco-
elastic materials with inertia and thermal effects. The damage process is modeled by means
of an internal variable, governed by a rate-independent flow rule. The heat equation and
the momentum balance for the displacements are coupled in a highly nonlinear way. Our
assumptions on the corresponding energy functional also comprise the case of the Ambrosio–
Tortorelli phase-field model (without passage to the brittle limit). We discuss a suitable weak
formulation and prove an existence theorem obtained with the aid of a (partially) decoupled
time-discrete scheme and variational convergence methods. We also carry out the asymptotic
analysis for vanishing viscosity and inertia and obtain a fully rate-independent limit model
for displacements and damage, which is independent of temperature
Identifying Conformational-Selection and Induced-Fit Aspects in the Binding-Induced Folding of PMI from Markov State Modeling of Atomistic Simulations
No full textUnstructured proteins and peptides typically fold during binding to ligand proteins. A challenging problem is to identify the mechanism and kinetics of these binding-induced folding processes in experiments and atomistic simulations. In this Article, we present a detailed picture for the folding of the inhibitor peptide PMI into a helix during binding to the oncoprotein fragment 25–109Mdm2 obtained from atomistic, explicit-water simulations and Markov state modeling. We find that binding-induced folding of PMI is highly parallel and can occur along a multitude of pathways. Some pathways are induced-fit-like with binding occurring prior to PMI helix formation, while other pathways are conformational-selection-like with binding after helix formation. On the majority of pathways, however, binding is intricately coupled to folding, without clear temporal ordering. A central feature of these pathways is PMI motion on the Mdm2 surface, along the binding groove of Mdm2 or over the rim of this groove. The native binding groove of Mdm2 thus appears as an asymmetric funnel for PMI binding. Overall, binding-induced folding of PMI does not fit into the classical picture of induced fit or conformational selection that implies a clear temporal ordering of binding and folding events. We argue that this holds in general for binding-induced folding processes because binding and folding events in these processes likely occur on similar time scales and do exhibit the time-scale separation required for temporal ordering
DREAM-Yara: an exact read mapper for very large databases with short update time
No full textMotivation
Mapping-based approaches have become limited in their application to very large sets of references since computing an FM-index for very large databases (e.g. >10 GB) has become a bottleneck. This affects many analyses that need such index as an essential step for approximate matching of the NGS reads to reference databases. For instance, in typical metagenomics analysis, the size of the reference sequences has become prohibitive to compute a single full-text index on standard machines. Even on large memory machines, computing such index takes about 1 day of computing time. As a result, updates of indices are rarely performed. Hence, it is desirable to create an alternative way of indexing while preserving fast search times.
Results
To solve the index construction and update problem we propose the DREAM (Dynamic seaRchablE pArallel coMpressed index) framework and provide an implementation. The main contributions are the introduction of an approximate search distributor via a novel use of Bloom filters. We combine several Bloom filters to form an interleaved Bloom filter and use this new data structure to quickly exclude reads for parts of the databases where they cannot match. This allows us to keep the databases in several indices which can be easily rebuilt if parts are updated while maintaining a fast search time. The second main contribution is an implementation of DREAM-Yara a distributed version of a fully sensitive read mapper under the DREAM framework.
Availability and implementation:
https://gitlab.com/pirovc/dream_yara