(Acido)bacterial diversity in space and time

Recent technological achievements enabled microbiologists to fully grasp the vast diversity of microbial life that is resident in soils, highly complex matrices of alternating micro-habitats on very small scales. Since then, microbial community composition has been catalogued for many different terrestrial habitats. This triggered the investigation and definition of processes which shape these communities. In most cases, the environment determines community composition, and similar habitats may feature similar microbial communities despite being far apart. However, some habitats have been described as subjected to pronounced neutral processes, which are dispersal, ecological drift or speciation. The balance between these process types is now the subject of many studies looking at microbial communities. It is also clear that these processes need to be monitored on both temporal and spatial scales, as the two dimensions are inseparably interlinked. However, most microbial studies deal with only one aspect, but do not control for the other. In this work, the outcome of a highly sophisticated plot scale experiment is presented encompassing 358 sampling locations distributed between six intra-annual sampling points on a 10 m x 10 m unfertilized grassland site in the Swabian Alb. RNA was extracted from the A-horizon of each soil and the hypervariable region 3 of the ribosomal small subunit was amplified and sequenced with barcoded Illumina sequencing. Roughly 400 million eubacterial reads were obtained. The dataset was used to assess the population dynamics of Acidobacteria, as well as the spatio-temporal co-occurenze of functionally depending microorganism. Additionally, preliminary results motivated the assessment of common methods for the examination of rhizospheric communities. In combination, the diversity of bacterial communities in space and time was tested from different angles, reflecting different research question, and they all revealed a far more complex reality than previously thought

Flexibility of industrial product service systems: An assessment based on concept modelling

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Improving adaptive seamless designs through Bayesian optimization

We propose to use Bayesian optimization (BO) to improve the efficiency of the design selection process in clinical trials. BO is a method to optimize expensive black-box functions, by using a regression as a surrogate to guide the search. In clinical trials, planning test procedures and sample sizes is a crucial task. A common goal is to maximize the test power, given a set of treatments, corresponding effect sizes, and a total number of samples. From a wide range of possible designs, we aim to select the best one in a short time to allow quick decisions. The standard approach to simulate the power for each single design can become too time consuming. When the number of possible designs becomes very large, either large computational resources are required or an exhaustive exploration of all possible designs takes too long. Here, we propose to use BO to quickly find a clinical trial design with high power from a large number of candidate designs. We demonstrate the effectiveness of our approach by optimizing the power of adaptive seamless designs for different sets of treatment effect sizes. Comparing BO with an exhaustive evaluation of all candidate designs shows that BO finds competitive designs in a fraction of the time

Hybrid 240 Ton Off Highway Haul Truck: Quarterly Technical Status Report 19, DOE/AL68080-TSR19

This nineteenth quarterly status report for the Hybrid Off Highway Vehicle (OHV) project, DOE Award DE-FC04-02AL68080 presents the project status at the end of June 2007, and covers activities in the nineteenth project quarter, April 2007 – June 2007

Hybrid 240 Ton Off Highway Haul Truck: Quarterly Technical Status Report 18

This eighteenth quarterly status report for the Hybrid Off Highway Vehicle (OHV) project, DOE Award DE-FC04-02AL68080 presents the project status at the end of March 2007, and covers activities in the eighteenth project quarter, January 2007 – March 2007

Extensional equality preservation and verified generic programming

In verified generic programming, one cannot exploit the structure of concrete data types but has to rely on well chosen sets of specifications or abstract data types (ADTs). Functors and monads are at the core of many applications of functional programming. This raises the question of what useful ADTs for verified functors and monads could look like. The functorial map of many important monads preserves extensional equality. For instance, if $f, g : A \rightarrow B$ are extensionally equal, that is, $\forall x \in A, \ f \ x = g \ x$, then $map \ f : List \ A \rightarrow List \ B$ and $map \ g$ are also extensionally equal. This suggests that preservation of extensional equality could be a useful principle in verified generic programming. We explore this possibility with a minimalist approach: we deal with (the lack of) extensional equality in Martin-L\"of's intensional type theories without extending the theories or using full-fledged setoids. Perhaps surprisingly, this minimal approach turns out to be extremely useful. It allows one to derive simple generic proofs of monadic laws but also verified, generic results in dynamical systems and control theory. In turn, these results avoid tedious code duplication and ad-hoc proofs. Thus, our work is a contribution towards pragmatic, verified generic programming.Comment: Manuscript ID: JFP-2020-003

2D and 3D similarity landscape analysis identifies PARP as a novel off-target for the drug Vatalanib

Background Searching for two-dimensional (2D) structural similarities is a useful tool to identify new active compounds in drug-discovery programs. However, as 2D similarity measures neglect important structural and functional features, similarity by 2D might be underestimated. In the present study, we used combined 2D and three-dimensional (3D) similarity comparisons to reveal possible new functions and/or side-effects of known bioactive compounds. Results We utilised more than 10,000 compounds from the SuperTarget database with known inhibition values for twelve different anti-cancer targets. We performed all-against-all comparisons resulting in 2D similarity landscapes. Among the regions with low 2D similarity scores are inhibitors of vascular endothelial growth factor receptor (VEGFR) and inhibitors of poly ADP-ribose polymerase (PARP). To demonstrate that 3D landscape comparison can identify similarities, which are untraceable in 2D similarity comparisons, we analysed this region in more detail. This 3D analysis showed the unexpected structural similarity between inhibitors of VEGFR and inhibitors of PARP. Among the VEGFR inhibitors that show similarities to PARP inhibitors was Vatalanib, an oral “multi-targeted” small molecule protein kinase inhibitor being studied in phase-III clinical trials in cancer therapy. An in silico docking simulation and an in vitro HT universal colorimetric PARP assay confirmed that the VEGFR inhibitor Vatalanib exhibits off-target activity as a PARP inhibitor, broadening its mode of action. Conclusion In contrast to the 2D-similarity search, the 3D-similarity landscape comparison identifies new functions and side effects of the known VEGFR inhibitor Vatalanib

A Three-pronged View on Organizational Agility

The ability of organizations to sense and respond to changes–defined as organizational agility–is considered by senior executives among their top information technology (IT) concerns as an important ability for organizations on their quest toward sustained competitive advantage. However, every transformation toward agility also comes at a cost, requiring resource commitment and IT landscape changes. We present examples of successful and unsuccessful attempts at achieving agility while leveraging IT. Our presented cases focus on information systems development agility, customer agility, and entrepreneurial agility. Our findings suggest that agility is neither achieved easily, nor is a guarantor for success. Depending on the context and implementation of organizational agility, however, it can significantly improve process and product performance. We develop a three-pronged view consisting of a functional, temporal, and ambidextrous view to resolve these challenges. We end with three recommendations for practitioners that seek to shape their organization’s journey toward agility

A Three-pronged View on Organizational Agility

The ability of organizations to sense and respond to changes–defined as organizational agility–is considered by senior executives among their top information technology (IT) concerns as an important ability for organizations on their quest toward sustainedcompetitive advantage. However, every transformation toward agility also comes at a cost, requiring resource commitment and IT landscape changes. We present examples of successful and unsuccessful attempts at achieving agility while leveraging IT. Our presented cases focus on information systems development agility, customer agility, and entrepreneurial agility. Our findings suggest that agility is neither achieved easily, nor is a guarantor for success.Depending on the context and implementation of organizational agility, however, it can significantly improve process and product performance. We develop a three-pronged viewconsisting of a functional,temporal,andambidextrous viewtoresolve thesechallenges. We end with three recommendations for practitioners that seek to shape their organization’s journey toward agility