On propagators and vertices of Landau gauge Yang-Mills theory

We calculate the three-point functions of pure Landau gauge QCD and investigate their influence on the propagators. As expected, the ghost-gluon vertex leads only to minor modifications, while the three-gluon vertex has a sizeable impact on the mid-momentum regime of the gluon propagator. We describe an effective model of the three-gluon vertex that includes contributions from the neglected two-loop diagrams and thus allows to obtain propagators in good agreement with lattice results. We also determine the three-gluon vertex from these propagators and find good agreement with lattice results as well. In turn, these results allow us to assess the effect of the missing two-loop diagrams in the gluon propagator equation. Finally, we present the first self-consistent calculation that includes all two-and three-point functions.Comment: 12 pages, 10 figs., contribution to "QCD-TNT-III: From quarks and gluons to hadronic matter: A bridge too far?", 2-6 Sept 2013, ECT*, Trento, Ital

Effective potential for SU(2) Polyakov loops and Wilson loop eigenvalues

We simulate SU(2) gauge theory at temperatures ranging from slightly below $T_c$ to roughly $2T_c$ for two different values of the gauge coupling. Using a histogram method, we extract the effective potential for the Polyakov loop and for the phases of the eigenvalues of the thermal Wilson loop, in both the fundamental and adjoint representations. We show that the classical potential of the fundamental loop can be parametrized within a simple model which includes a Vandermonde potential and terms linear and quadratic in the Polyakov loop. We discuss how parametrizations for the other cases can be obtained from this model.Comment: 16 pages, 39 figure

Heterologous biosynthesis, modifications and structural characterization of ruminococcin-A, a lanthipeptide from the gut bacterium ruminococcus gnavus E1, in escherichia coli

Ruminococcin A (RumA) is a lanthipeptide with high activity against pathogenic clostridia and is naturally produced by the strict anaerobic bacterium Ruminococcus gnavus E1, isolated from human intestine. Cultivating R. gnavus E1 is challenging, limiting high-quality production, further biotechnological development and therapeutic exploitation of RumA. To supply an alternative production system, the gene encoding RumA-modifying enzyme (RumM) and the gene encoding the unmodified precursor peptide (preRumA) were amplified from the chromosome of R. gnavus E1 and coexpressed in Escherichia coli. Our results show that the ruminococcin-A lanthionine synthetase RumM catalysed dehydration of threonine and serine residues and subsequently installed thioether bridges into the core structure of a mutant version of preRumA (preRumA*). These modifications were achieved when the peptide was expressed as a fusion protein together with GFP, demonstrating that a larger attachment to the N-terminus of the leader peptide does not obstruct in vivo processivity of RumM in modifying the core peptide. The leader peptide serves as a docking sequence which the modifying enzyme recognizes and interacts with, enabling its catalytic role. We further investigated RumM catalysis in conjunction with the formation of complexes observed between RumM and the chimeric GFP fusion protein. Results obtained suggested some insights into the catalytic mechanisms of class II lanthipeptide synthetases. Our data further indicated the presence of three thioether bridges, contradicting a previous report whose findings ruled out the possibility of forming a third ring in RumA. Modified preRumA* was activated in vitro by removing the leader peptide using trypsin and biological activity was achieved against Bacillus subtilis ATCC 6633. A production yield of 6 mg of pure modified preRumA* per litre of E. coli culture was attained and considering the size ratio of the leader-to-core segments of preRumA*, this amount would generate a final yield of approximately 1-2 mg of active RumA when the leader peptide is removed. The yield of our system exceeds that attainable in the natural producer by several thousand-fold. The system developed herein supplies useful tools for product optimization and for performing in vivo peptide engineering to generate new analogues with superior anti-infective properties.DFG, 325093850, Open Access Publizieren 2017 - 2018 / Technische Universität Berli

Bioprocess Development for Lantibiotic Ruminococcin-A Production in Escherichia coli and Kinetic Insights Into LanM Enzymes Catalysis

Ruminococcin-A (RumA) is a peptide antibiotic with post-translational modifications including thioether cross-links formed from non-canonical amino acids, called lanthionines, synthesized by a dedicated lanthionine-generating enzyme RumM. RumA is naturally produced by Ruminococcus gnavus, which is part of the normal bacterial flora in the human gut. High activity of RumA against pathogenic Clostridia has been reported, thus allowing potential exploitation of RumA for clinical applications. However, purifying RumA from R. gnavus is challenging due to low production yields (120 mg L–1 for the chimeric construct and >150 mg L–1 for RumM. The correlation observed between microscale and lab-scale bioreactor cultivations suggests that the process is robust and realistically applicable to industrial-scale conditions.DFG, 53182490, EXC 314: Unifying Concepts in CatalysisDFG, 414044773, Open Access Publizieren 2019 - 2020 / Technische Universität Berli

Sustainable energy for whom? Governing pro-poor, low-carbon pathways to development: lessons from solar PV in Kenya

Using a combination of insights from innovation studies, sociotechnical transitions theory and the STEPS pathways approach, this paper analyses the evolution of the Kenyan photovoltaics (PV) market. Considered by many to be an exemplar of private sector led development, the Kenyan PV market has witnessed the adoption of more than 300,000 solar home systems and over 100,000 solar portable lights. The notion of an entrepreneurially driven unsubsidised solar market has proved to be a powerful narrative amongst development actors who, paradoxically, have provided millions of dollars of funding to encourage the market’s development. We argue that this donor support has been critical to the success of the market, but not simply by helping to create an enabling environment in which entrepreneurs can flourish. Donor assistance has been critical in supporting a range of actors to build the elements of a PV innovation system by providing active protection for experimentation, network-building, and the construction of shared visions amongst actors throughout supply chains and amongst users.This analysis gives important clues for designing climate and development policies, with implications for the governance of energy access pathways that are inclusive of poor and marginalised groups in low income countries

Macroecology of methane-oxidizing bacteria: the β-diversity of pmoA genotypes in tropical and subtropical rice paddies

Studies addressing microbial biogeography have increased during the past decade, but research on microbial distribution patterns is still in its infancies, and many aspects are only poorly understood. Here, we compared the methanotroph community in paddy soils sampled in Indonesia, Vietnam, China and Italy, focusing on the distance-decay relationship. We used the pmoA gene as marker for methanotroph diversity in terminal restriction fragment length polymorphism, microarray and pyrosequencing approaches. We could observe a significant increase of -diversity with geographical distance across continents (12000km). Measured environmental parameters explained only a small amount of data variation, and we found no evidence for dispersal limitation. Thus, we propose historical contingencies being responsible for the observed patterns. Furthermore, we performed an in-depth analysis of type II methanotroph pmoA distribution at the sequence level. We used ordination analysis to project sequence dissimilarities into a three-dimensional space (multidimensional scaling). The ordination suggests that type II methanotrophs in paddy fields can be divided into five major groups. However, these groups were found to be distributed in all soils independent of the geographic origin. By including tropical field sites (Indonesia and Vietnam) into the analysis, we further observed the first paddy fields harbouring a methanotroph community depleted in type II methanotrophs

Type I error control in biomarker-stratified clinical trials

Biomarker-stratified clinical trials assess the biomarker signature of subjects and split them into subgroups so that treatment is of benefit to those who are likely to respond. Since multiple hypotheses are tested, it becomes important to control the type I error. Current methods control the false positive rate where one rejects the null hypothesis while in reality that was true. For two subgroups, the false positive rate is controlled across the two hypotheses as a Family Wise Error Rate (FWER) to an overall predetermined significance level

Adaptive enrichment in biomarker-stratified clinical trial design

In Phase II oncology trials, targeted therapies are being constantly evaluated for their efficacy in specific populations of interest. Such trials require designs that allow for stratification based on the participants' biomarker signature. One of the disadvantages of a targeted design (defined as enrichment in biomarker-positive sub-population) is that if the drug has at least some activity in the biomarker-negative subjects, then their effect in the biomarker-negative population may never be known. Jones and Holmgren (JH) have proposed a design to determine whether drug has activity only in target population or the general population. Their design is an enrichment adaptation based on two parallel Simon two-stage designs. Unfortunately, there are several pitfalls in the JH design: the issue of hypothesis testing is not properly addressed and the type I error, power calculations and expected sample size formulae are wrong too. We study the JH design in detail, appropriately control the type I and type II error probabilities that yield novel optimal designs. We also discuss various alternative Family Wise Error Rates (FWER) and the Individual Hypothesis (IH) error rates in the weak sense as well as the strong sense. For each option of the error controls, we search for designs over a 10 trillion search space and obtain optimal designs that minimise the expected sample size. For the particular example trial that JH consider, our optimal design requires 38% fewer subjects in comparison with the two parallel Simon two-stage design thereby offering substantial efficiency in terms of the expected sample size. In conclusion, our rectified design provides a robust framework for adaptive enrichment in biomarker-stratified Phase II trial design

2 MW peak power generation in fluorine co-doped Yb fiber prepared by powder-sinter technology

We report on the first, to the best of our knowledge, implementation of a fluorine co-doped large-mode-area REPUSIL fiber for high peak power amplification in an ultrashort-pulse master oscillator power amplifier. The core material of the investigated step-index fiber with high Yb-doping level, 52 µm core and high core-to-clad ratio of 1:4.2 was fabricated by means of the REPUSIL powder-sinter technology. The core numerical aperture was adjusted by fluorine codoping to 0.088. For achieving high beam quality and for ensuring a monolithic seed path, the LMA fiber is locally tapered. We demonstrate an Yb fiber amplifier with near-diffraction-limited beam quality of M2 = 1.3, which remains constant up to a peak power of 2 MW. This is a record for a tapered single core fiber. © 2020 Optical Society of Americ