Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline**

Bedaquiline is a crucial medicine in the global fight against tuberculosis, yet its high price places it out of reach for many patients. Herein, we describe improvements to the key industrial lithiation-addition sequence that enable a higher yielding and therefore more economical synthesis of bedaquiline. Prioritization of mechanistic understanding and multi-lab reproducibility led to optimized reaction conditions that feature an unusual base-salt pairing and afford a doubling of the yield of racemic bedaquiline. We anticipate that implementation of these improvements on manufacturing scale will be facile, thereby substantially increasing the accessibility of this essential medication.     

Efficient approximation of random fields for numerical applications

This article is dedicated to the rapid computation of separable expansions for the approximation of random fields. We consider approaches based on techniques from the approximation of non‐local operators on the one hand and based on the pivoted Cholesky decomposition on the other hand. Especially, we provide an a posteriori error estimate for the pivoted Cholesky decomposition in terms of the trace. Numerical examples are provided to validate and quantify the presented methods. Copyright © 2015 John Wiley & Sons, Ltd.     

On the complexity of SNP block partitioning under the perfect phylogeny model

Recent technologies for typing single nucleotide polymorphisms (SNPs) across a population are producing genome-wide genotype data for tens of thousands of SNP sites. The emergence of such large data sets underscores the importance of algorithms for large-scale haplotyping. Common haplotyping approaches first partition the SNPs into blocks of high linkage-disequilibrium, and then infer haplotypes for each block separately. We investigate an integrated haplotyping approach where a partition of the SNPs into a minimum number of non-contiguous subsets is sought, such that each subset can be haplotyped under the perfect phylogeny model. We show that finding an optimum partition is -hard even if we are guaranteed that two subsets suffice. On the positive side, we show that a variant of the problem, in which each subset is required to admit a perfect path phylogeny haplotyping, is solvable in polynomial time.     

What is a Logic Translation?

We study logic translations from an abstract perspective, without any commitment to the structure of sentences and the nature of logical entailment, which also means that we cover both proof- theoretic and model-theoretic entailment. We show how logic translations induce notions of logical expressiveness, consistency strength and sublogic, leading to an explanation of paradoxes that have been described in the literature. Connectives and quantifiers, although not present in the definition of logic and logic translation, can be recovered by their abstract properties and are preserved and reflected by translations under suitable conditions. In memoriam Joseph Goguen     

Radiation damage to alkyl chain monolayers on semiconductor substrates investigated by electron spectroscopy

Monolayers of alkyl chains, attached through direct Si-C bonds to Si(111), via phosphonates to GaAs(100) surfaces, or deposited as alkyl-silane monolayers on SiO2, are investigated by ultraviolet and inverse photoemission spectroscopy and X-ray absorption spectroscopy. Exposure to ultraviolet radiation from a He discharge lamp, or to a beam of energetic electrons, leads to significant damage, presumably associated with radiation- or electron-induced H-abstraction leading to carbon-carbon double-bond formation in the alkyl monolayer. The damage results in an overall distortion of the valence spectrum, in the appearance of (occupied) states above the highest occupied molecular orbital of the alkyl molecule, and in a characteristic (unoccupied state) pi resonance at the edge of the carbon absorption peak. These distortions present a serious challenge for the interpretation of the electronic structure of the monolayer system. We show that extrapolation to zero damage at short exposure times eliminates extrinsic features and allows a meaningful extraction of the density of state of the pristine monolayer from spectroscopy measurements.     

Preparation of indoles from alpha-aminonitriles: A short synthesis of FGIN-1-27

Alpha-Aminonitriles derived from 2-aminocinnamic acid esters and amides can be cyclized under basic conditions to furnish substituted indole-3-acetic acid derivatives in quantitative yield. The reaction provides a simple access to a class of biologically active compounds.     

Carnap,Goguen, and the Hyperontologies: Logical Pluralism and Heterogeneous Structuring in Ontology Design

This paper addresses questions of universality related to ontological engineering, namely aims at substantiating (negative) answers to the following three basic questions: (i) Is there a ‘universal ontology’?, (ii) Is there a ‘universal formal ontology language’?, and (iii) Is there a universally applicable ‘mode of reasoning’ for formal ontologies? To support our answers in a principled way, we present a general framework for the design of formal ontologies resting on two main principles: firstly, we endorse Rudolf Carnap’s principle of logical tolerance by giving central stage to the concept of logical heterogeneity, i.e. the use of a plurality of logical languages within one ontology design. Secondly, to structure and combine heterogeneous ontologies in a semantically well-founded way, we base our work on abstract model theory in the form of institutional semantics, as forcefully put forward by Joseph Goguen and Rod Burstall. In particular, we employ the structuring mechanisms of the heterogeneous algebraic specification language HetCasl for defining a general concept of heterogeneous, distributed, highly modular and structured ontologies, called hyperontologies. Moreover, we distinguish, on a structural and semantic level, several different kinds of combining and aligning heterogeneous ontologies, namely integration, connection, and refinement. We show how the notion of heterogeneous refinement can be used to provide both a general notion of sub-ontology as well as a notion of heterogeneous equivalence of ontologies, and finally sketch how different modes of reasoning over ontologies are related to these different structuring aspects.