Ladderane Natural Products: From the Ground Up

The ladderane family of natural products are well known for their linearly concatenated cyclobutane skeletal structure. Owing to their unique carbocyclic framework, several chemical syntheses have been reported since their discovery in 2002. The focus of this review is to showcase the novel tactics that have been used to generate the ladderane core and the challenges that are associated with the synthesis of these unusual and complex natural products.     

Hybridorubrins A–D: Azaphilone Heterodimers from Stromata of Hypoxylon fragiforme and Insights into the Biosynthetic Machinery for Azaphilone Diversification

The diversity of azaphilones in stromatal extracts of the fungus Hypoxylon fragiforme was investigated and linked to their biosynthetic machineries by using bioinformatics. Nineteen azaphilone-type compounds were isolated and characterized by NMR spectroscopy and mass spectrometry, and their absolute stereoconfigurations were assigned by using Mosher ester analysis and electronic circular dichroism spectroscopy. Four unprecedented bis-azaphilones, named hybridorubrins A–D, were elucidated, in addition to new fragirubrins F and G and various known mitorubrin derivatives. Only the hybridorubrins, which are composed of mitorubrin and fragirubrin moieties, exhibited strong inhibition of Staphylococcus aureus biofilm formation. Analysis of the genome of H. fragiforme revealed the presence of two separate biosynthetic gene clusters (BGCs) hfaza1 and hfaza2 responsible for azaphilone formation. While the hfaza1 BGC likely encodes the assembly of the backbone and addition of fatty acid moieties to yield the (R)-configured series of fragirubrins, the hfaza2 BGC contains the necessary genes to synthesise the widely distributed (S)-mitorubrins. This study is the first example of two distant cross-acting fungal BGCs collaborating to produce two families of azaphilones and bis-azaphilones derived therefrom.     

Optimization of thin film solid phase microextraction and data deconvolution methods for accurate characterization of organic compounds in produced water

The continued rise in the extraction of unconventional oil and gas across the globe poses many questions about how to manage these relatively new waste‐streams. Produced water, the primary waste by‐product, contains a diverse number of anthropogenic additives together with the numerous hydrocarbons extracted from the well. Due to potential environmental hazards, it is critical to characterize the chemical composition of this type of waste before proper disposal or remediation/reuse. In this work, a thin film solid phase microextraction approach was developed and optimized to characterize produced water. The thin film device consisted of hydrophilic‐lipophilic balance particles embedded in polydimethylsiloxane and immobilized on a carbon mesh surface. These devices were chosen to provide broad extraction coverage and high reusability. Various parameters were evaluated to ensure reproducible results while minimizing analyte loss. This optimized protocol, consisting of a 15 min extraction followed by a short (3 s) rinsing step, enabled the reproducible analysis of produced water without any sample pretreatment. Extraction efficiency was suitable for both produced water additives and hydrocarbons. The developed approach was able to tentatively identify a total of 201 compounds from produced water samples, by using one‐dimensional gas chromatography hyphenated to mass spectrometry and data deconvolution.     

Biocompatible Lipid‐Coated Persistent Luminescent Nanoparticles for In Vivo Imaging of Dendritic Cell Migration

Dendritic cell (DC)‐based vaccines for immunotherapy have already achieved promising results in the last decade. To further improve current treatment protocols and enhance the therapeutic outcome, noninvasive in vivo tracking of DCs remains of crucial importance. Persistent luminescent nanoparticles (PLNPs) are inorganic materials which show an afterglow for hours after the optical excitation has ceased. If the afterglow is in the near‐infrared, the emission of injected particles can be tracked in vivo. However, stability and toxicity issues limit the use of bare PLNPs for biological applications. Therefore, appropriate surface functionalization is needed to improve their biocompatibility. In this study, it is demonstrated that near‐infrared light emitting LiGa₅O₈:Cr³⁺ nanoparticles can be functionalized with a biocompatible lipid coating which provides them with outstanding stability in biological media. In vitro experiments show efficient uptake, absence of cytotoxicity even at very high particle concentrations, and no adverse effects on the maturation potential of DCs. DCs labeled with lipid‐coated LiGa₅O₈:Cr³⁺ nanoparticles injected in mice can be imaged over days, confirming efficient in vivo migration to the popliteal lymph node. Together the results show that lipid coated LiGa₅O₈:Cr³⁺ nanoparticles possess excellent possibilities for further use in research and development of DC based vaccines.     

Economical,Green, and Safe Route Towards Substituted Lactones by Anodic Generation of Oxycarbonyl Radicals

A new electrochemical methodology has been developed for the generation of oxycarbonyl radicals under mild and green conditions from readily available hemioxalate salts. Mono‐ and multi‐functionalised γ‐butyrolactones were synthesised through exo‐cyclisation of these oxycarbonyl radicals with an alkene, followed by the sp³–sp³ capture of the newly formed carbon‐centred radical. The synthesis of functionalised valerolactone derivatives was also achieved, demonstrating the versatility of the newly developed methodology. This represents a viable synthetic route towards pharmaceutically important fragments and further demonstrates the practicality of electrosynthesis as a green and economical method to activate small organic molecules.     

Versatile image-based measurements of granular flows and water wave propagation in experiments of tsunamis generated by landslides

Landslides falling into water bodies can generate destructive waves, which can be classified as tsunamis. An experimental facility to study this phenomenon has been set up. It consists of a landslide generator releasing gravel at high-speed into a wave basin. A non-intrusive system has been designed ad-hoc to be able to measure the high velocity and the geometry of the landslide as well as the generated waves characteristics. The measurement system employs the treatment of images captured by a high-speed camera which records the launched granular material illuminated by a laser sheet. A grid of laser sheets marks the basin water surface. The water has been filled by a small amount of kaolin to properly reflect the laser light at water surface. Thus, by filming with high definition cameras the perturbed water surface and successively processing the resulting images, it has been possible to measure the generated waves. The measurement framework employs a versatile camera calibration technique which allows accurate measurements in presence of: (1) high lens distortions; (2) pronounced non-parallelism condition between camera sensor and plane of measurement coincident with the laser sheet. The maximum resolution of the measurement tool is 0.01 mm, while the maximum uncertainty due to systematic error has been estimated to be 15% for the worst-case scenario. This work improves the suitability of image-based measuring systems in granular flows and free surface hydraulics experiments.     

Unconventional Secondary Structure Mimics: Ladder‐Rungs

Secondary structures tend to be recognizable because they have repeating structural motifs, but mimicry of these does not have to follow such well‐defined patterns. Bioinformatics studies to match side‐chain orientations of a novel hydantoin triazole chemotype ( 1 ) to protein‐protein interfaces revealed it tends to align well across parallel and antiparallel sheets, like rungs on a ladder. One set of these overlays was observed for the protein‐protein interaction uPA?uPAR. Consequently, chemotype 1 was made with appropriate side‐chains to mimic uPA at this interface. Biophysical assays indicate these compounds did in fact bind uPAR, and elicit cellular responses that affected invasion, migration, and wound healing.     

Expectations and fairness in a simple bargaining experiment

We evaluate two competing hypotheses that try to account for robust violations of the predictions of game theory in Ultimatum bargaining experiments. One popular hypothesis is that the subjects are motivated by considerations of fairness that are not modelled by traditional theory. The alternative hypothesis is that the subjects do not have common knowledge of the rationality, beliefs and motives of other players. Each hypothesis can explain existing data. We design several experiments to discriminate between these two hypotheses. The results provide strong support for the alternative hypothesis.     

A Discrete Wavelet Transform without edge effects using wavelet extrapolation

The Discrete Wavelet Transform (DWT) is of considerable practical use in image and signal processing applications. For example, significant compression can be achieved through the use of the DWT. A fundamental problem with the DWT, however, is the treatment of finite length data sequences. Commonly used techniques such as circular convolution and symmetric extension can produce undesirable edge effects which propagate into the interior of the transformed data as the number of DWT iterations increases. In this paper, we develop a DWT applicable to Daubechies’ orthogonal wavelets which does not exhibit edge effects. The underlying idea is to extrapolate the data at the boundaries by determining the coefficients of a best fit polynomial through data points in the vicinity of the boundary. This approach can be regarded as a solution to the problem of orthogonal wavelets on an interval. However, it has the advantage that it does not involve the explicit construction of boundary wavelets. The extrapolated DWT is designed to be well conditioned and to produce a critically sampled output. The methods we describe are equally applicable to biorthogonal wavelet bases.