Character sums for primitive root densities

It follows from the work of Artin and Hooley that, under assumption of the generalized Riemann hypothesis, the density of the set of primes $q$ for which a given non-zero rational number $r$ is a primitive root modulo $q$ can be written as an infinite product $\prod_p \delta_p$ of local factors $\delta_p$ reflecting the degree of the splitting field of $X^p-r$ at the primes $p$, multiplied by a somewhat complicated factor that corrects for the `entanglement' of these splitting fields. We show how the correction factors arising in Artin's original primitive root problem and some of its generalizations can be interpreted as character sums describing the nature of the entanglement. The resulting description in terms of local contributions is so transparent that it greatly facilitates explicit computations, and naturally leads to non-vanishing criteria for the correction factors. The method not only applies in the setting of Galois representations of the multiplicative group underlying Artin's conjecture, but also in the GL$_2$-setting arising for elliptic curves. As an application, we compute the density of the set of primes of cyclic reduction for Serre curves.Comment: 23 pages. This version is to appear in the Mathematical Proceedings of the Cambridge Philosophical Societ

Utilization and control of ecological interactions in polymicrobial infections and community-based microbial cell factories

Microbial activities are most often shaped by interactions between co-existing microbes within mixed-species communities. Dissection of the molecular mechanisms of species interactions within communities is a central issue in microbial ecology, and our ability to engineer and control microbial communities depends, to a large extent, on our knowledge of these interactions. This review highlights the recent advances regarding molecular characterization of microbe-microbe interactions that modulate community structure, activity, and stability, and aims to illustrate how these findings have helped us reach an engineering-level understanding of microbial communities in relation to both human health and industrial biotechnology

Indexing the Pseudomonas specialized metabolome enabled the discovery of poaeamide B and the bananamides

Pseudomonads are cosmopolitan microorganisms able to produce a wide array of specialized metabolites. These molecules allow Pseudomonas to scavenge nutrients, sense population density and enhance or inhibit growth of competing microorganisms. However, these valuable metabolites are typically characterized one-molecule–one-microbe at a time, instead of being inventoried in large numbers. To index and map the diversity of molecules detected from these organisms, 260 strains of ecologically diverse origins were subjected to mass-spectrometry-based molecular networking. Molecular networking not only enables dereplication of molecules, but also sheds light on their structural relationships. Moreover, it accelerates the discovery of new molecules. Here, by indexing the Pseudomonas specialized metabolome, we report the molecular-networking-based discovery of four molecules and their evolutionary relationships: a poaeamide analogue and a molecular subfamily of cyclic lipopeptides, bananamides 1, 2 and 3. Analysis of their biosynthetic gene cluster shows that it constitutes a distinct evolutionary branch of the Pseudomonas cyclic lipopeptides. Through analysis of an additional 370 extracts of wheat-associated Pseudomonas, we demonstrate how the detailed knowledge from our reference index can be efficiently propagated to annotate complex metabolomic data from other studies, akin to the way in which newly generated genomic information can be compared to data from public databases

MS/MS networking guided analysis of molecule and gene cluster families

The paper introduces the concepts of molecular families (MFs) and gene cluster families (GCFs). We define MFs as structurally related molecules based on their mass spectral fragmentation patterns, whereas GCFs are biosynthetic gene clusters that show similar gene cluster organization with a high degree of sequence similarity. We use MS/MS networking as a tool to map the molecular network of more than 60 organisms, most of which are unsequenced, and locate their nonribosomal peptide MFs. These MFs from unsequenced organisms are then connected to GCFs of publicly available genome sequences of closely related organisms

Cyclized NDGA modifies dynamic α-synuclein monomers preventing aggregation and toxicity.

Growing evidence implicates α-synuclein aggregation as a key driver of neurodegeneration in Parkinson's disease (PD) and other neurodegenerative disorders. Herein, the molecular and structural mechanisms of inhibiting α-synuclein aggregation by novel analogs of nordihydroguaiaretic acid (NDGA), a phenolic dibenzenediol lignan, were explored using an array of biochemical and biophysical methodologies. NDGA analogs induced modest, progressive compaction of monomeric α-synuclein, preventing aggregation into amyloid-like fibrils. This conformational remodeling preserved the dynamic adoption of α-helical conformations, which are essential for physiological membrane interactions. Oxidation-dependent NDGA cyclization was required for the interaction with monomeric α-synuclein. NDGA analog-pretreated α-synuclein did not aggregate even without NDGA-analogs in the aggregation mixture. Strikingly, NDGA-pretreated α-synuclein suppressed aggregation of naïve untreated aggregation-competent monomeric α-synuclein. Further, cyclized NDGA reduced α-synuclein-driven neurodegeneration in Caenorhabditis elegans. The cyclized NDGA analogs may serve as a platform for the development of small molecules that stabilize aggregation-resistant α-synuclein monomers without interfering with functional conformations yielding potential therapies for PD and related disorders

The influence of different contract types on the effectiveness of owner-contractor relationships in construction projects

The nature of working relationship between owner and contractor in engineering and construction projects is considered to have a major effect on the project performance. This research focuses on factors that may influence owner-contractor relationship effectiveness. Literature suggests that different types of contract, being one of these factors, tend to influence owner-contractor relationships. The aim of this research was is to clarify the role of different contract types on owner-contractor relationship effectiveness in industrial construction projects. A Q-methodology based study was performed to reveal the subjective perceptions of the project managers on the relative influence of various contract aspects and of other influencing factors of owner-contractor relationships. The influence of contract types on the relationships for project-specific situations was investigated by a project evaluation study. In this study, the relationship quality of four different projects was evaluated, using a relationship maturity assessment matrix. The research results show that contract type is not the tool to influence relationship effectiveness. The only contract aspects, which are identified as instrumental to improve the relationship, are contact aspects related to project structure specifying roles and responsibilities, and contract aspects about targeted criteria for performance.Management of TechnologyTechnology, Strategy and EntrepreneurshipTechnology, Policy and Managemen