An Alcohol Dehydrogenase from the Short-Chain Dehydrogenase/Reductase Family of Enzymes for the Lactonization of Hexane-1,6-diol

Biocatalytic production of lactones, and in particular ϵ-caprolactone (CL), have gained increasing interest as a greener route to polymer building blocks, especially through the use of Baeyer–Villiger monooxygenases (BVMOs). Despite several advances in the field, BVMOs, however, still suffer several practical limitations. Alcohol dehydrogenase (ADH)-mediated lactonization of diols in turn has received far less attention and very few enzymes have been identified for the conversion of diols to lactones, with horse-liver ADH (HLADH) remaining the catalyst of choice. Screening of a diverse panel of ADHs, AaSDR-1, a member of the short-chain dehydrogenase/reductase family, was found to produce ϵ-caprolactone from hexane-1,6-diol. Moreover, cofactor regeneration by an NADH oxidase eliminated the requirement of co-substrates, yielding water as the sole by-product. Despite lower turnover frequencies as compared to HLADH, higher selectivity was found for the production of CL, with HLADH forming significant amounts of 6-hydroxyhexanoic acid and adipic acid through aldehyde dehydrogenation/oxidation of the gem-diol intermediates. Also, CL yield were shown to be dependent on buffer choice, as structural elucidation of a Tris adduct confirmed the buffer amine to react with aliphatic aldehydes forming a Schiff-base intermediate which through further ADH oxidation, forms a tricyclic acetal product.     

Mammalian-Cell-Driven Polymerisation of Pyrrole

A model cancer cell line was used to initiate polymerisation of pyrrole to form the conducting material polypyrrole. The polymerisation was shown to occur through the action of cytosolic exudates rather than that of the membrane redox sites that normally control the oxidation state of iron as ferricyanide or ferrocyanide. The data demonstrate for the first time that mammalian cells can be used to initiate synthesis of conducting polymers and suggest a possible route to detection of cell damage and/or transcellular processes through in situ and amplifiable signal generation.     

The Multifunctional Sactipeptide Ruminococcin C1 Displays Potent Antibacterial Activity In Vivo as Well as Other Beneficial Properties for Human Health

The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from Clostridium perfringens with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest.     

MicroRNA Profiling of B Cell Subsets from Systemic Lupus Erythematosus Patients Reveals Promising Novel Biomarkers

MicroRNAs control the differentiation and function of B cells, which are considered key elements in the pathogenesis of systemic lupus erythematosus (SLE). However, a common micro(mi)RNA signature has not emerged since published data includes patients of variable ethnic background, type of disease, and organ involvement, as well as heterogeneous cell populations. Here, we aimed at identifying a miRNA signature of purified B cells from renal and non-renal severe SLE patients of Latin American background, a population known to express severe disease. Genome-wide miRNA expression analyses were performed on naive and memory B cells and revealed two categories of miRNA signatures. The first signature represents B cell subset-specific miRNAs deregulated in SLE: 11 and six miRNAs discriminating naive and memory B cells of SLE patients from healthy controls (HC), respectively. Whether the miRNA was up or down-regulated in memory B cells as compared with naive B cells in HC, this difference was abolished in SLE patients, and vice versa. The second signature identifies six miRNAs associated with specific pathologic features affecting renal outcome, providing a further understanding for SLE pathogenesis. Overall, the present work provided promising biomarkers in molecular diagnostics for disease severity as well as potential new targets for therapeutic intervention in SLE.     

Behavioral Evidence for Olfactory-Based Location of Honeybee Colonies by the Scarab <Emphasis Type="Italic">Oplostomus haroldi</Emphasis>

The Afro-tropical scarab Oplostomus haroldi (Witte) is a pest of honeybees in East Africa with little information available on its chemical ecology. Recently, we identified a female-produced contact sex pheromone, (Z)-9-pentacosene, from the cuticular lipids that attracted males. Here, we investigated the kairomonal basis of host location in O. haroldi. We used coupled gas chromatography/electroantennographic detection (GC/EAD) and GC/mass spectrometry to identify antennally-active compounds from volatiles collected from honeybee colonies. Antennae of both sexes of the beetle consistently detected seven components, which were identified as 3-hydroxy-2-butanone, 2,3-butanediol, butyl acetate, isopentyl acetate, butyl butyrate, hexyl acetate, and methyl benzoate. In olfactometer bioassays, both sexes responded to the full seven-component synthetic blend over solvent controls, but chose honeybee colony odors over the blend. These findings suggest that the seven compounds are components of a kairomone from honeybee colonies used by O. haroldi.     

Multilayer hybrid visualizations to support 3D GIS

In this paper, we present a unique hybrid visualization system for spatial data. Although some existing 3D GIS systems offer 2D views they are typically isolated from the 3D view in that they are presented in a separate window. Our system is a novel hybrid 2D/3D approach that seamlessly integrates 2D and 3D views of the same data. In our interface, multiple layers of information are continuously transformed between the 2D and 3D modes under the control of the user, directly over a base terrain. In this way, our prototype system is able to depict 2D and 3D views within the same window. This has advantages, since 2D and 3D visualizations can each be easier to interpret in different contexts.In this work we develop this concept of a hybrid visualization by presenting a comprehensive set of capabilities within our distinctive system. These include new facilities such as: hybrid landmark, 3D point, and chart layers, the grouping of multiple hybrid layers, layer painting, the merging of layer controls and consistent zooming functionality.     

Feature-based statistical analysis of combustion simulation data

We present a new framework for feature-based statistical analysis of large-scale scientific data and demonstrate its effectiveness by analyzing features from Direct Numerical Simulations (DNS) of turbulent combustion. Turbulent flows are ubiquitous and account for transport and mixing processes in combustion, astrophysics, fusion, and climate modeling among other disciplines. They are also characterized by coherent structure or organized motion, i.e. nonlocal entities whose geometrical features can directly impact molecular mixing and reactive processes. While traditional multi-point statistics provide correlative information, they lack nonlocal structural information, and hence, fail to provide mechanistic causality information between organized fluid motion and mixing and reactive processes. Hence, it is of great interest to capture and track flow features and their statistics together with their correlation with relevant scalar quantities, e.g. temperature or species concentrations. In our approach we encode the set of all possible flow features by pre-computing merge trees augmented with attributes, such as statistical moments of various scalar fields, e.g. temperature, as well as length-scales computed via spectral analysis. The computation is performed in an efficient streaming manner in a pre-processing step and results in a collection of meta-data that is orders of magnitude smaller than the original simulation data. This meta-data is sufficient to support a fully flexible and interactive analysis of the features, allowing for arbitrary thresholds, providing per-feature statistics, and creating various global diagnostics such as Cumulative Density Functions (CDFs), histograms, or time-series. We combine the analysis with a rendering of the features in a linked-view browser that enables scientists to interactively explore, visualize, and analyze the equivalent of one terabyte of simulation data. We highlight the utility of this new framework for combustion science; however, it is applicable to many other science domains.     

Hierarchical streamline bundles

Effective 3D streamline placement and visualization play an essential role in many science and engineering disciplines. The main challenge for effective streamline visualization lies in seed placement, i.e., where to drop seeds and how many seeds should be placed. Seeding too many or too few streamlines may not reveal flow features and patterns either because it easily leads to visual clutter in rendering or it conveys little information about the flow field. Not only does the number of streamlines placed matter, their spatial relationships also play a key role in understanding the flow field. Therefore, effective flow visualization requires the streamlines to be placed in the right place and in the right amount. This paper introduces hierarchical streamline bundles, a novel approach to simplifying and visualizing 3D flow fields defined on regular grids. By placing seeds and generating streamlines according to flow saliency, we produce a set of streamlines that captures important flow features near critical points without enforcing the dense seeding condition. We group spatially neighboring and geometrically similar streamlines to construct a hierarchy from which we extract streamline bundles at different levels of detail. Streamline bundles highlight multiscale flow features and patterns through clustered yet not cluttered display. This selective visualization strategy effectively reduces visual clutter while accentuating visual foci, and therefore is able to convey the desired insight into the flow data.     

Estimation and vicarious validation of urban vegetation abundance by spectral mixture analysis

Both moderate and high spatial resolution imagery can be used to quantify abundance and distribution of urban vegetation for urban landscape management and to provide inputs to physical process models. Estimation of vegetation fraction from Landsat ETM+ and Quickbird allows for operational monitoring and reconnaissance at moderate resolution with calibration and vicarious validation at higher resolution. Establishing a linear correspondence between ETM-derived vegetation fraction and Quickbird-derived vegetation fraction facilitates the validation task by extending the spatial scale from 30 × 30 m to a more manageable 2.8 × 2.8 m. A comparative analysis indicates that urban reflectance can be accurately represented with a three component linear mixture model for both Landsat ETM+ and Quickbird imagery in the New York metro area. The strong linearity of the Substrate Vegetation Dark surface (SVD) mixture model provides consistent estimates of illuminated vegetation fraction that can be used to constrain physical process models that require biophysical inputs related to vegetation abundance. When Quickbird-derived 2.8 m estimates of vegetation fraction are integrated to 30 m scales and coregistered to Landsat-derived 30 m estimates, median estimates agree with the integrated fractions to within 5% for fractions > 0.2. The resulting Quickbird-ETM+ scatter distribution cannot be explained with estimate error alone but is consistent with a 3% to 6% estimation error combined with a 17 m subpixel registration ambiguity. The 3D endmember fraction space obtained from ETM+ imagery forms a ternary distribution of reflectance properties corresponding to distinct biophysical surface types. The SVD model is a reflectance analog to Ridd's V–I–S land cover model but acknowledges the fact that permeable and impermeable surfaces cannot generally be distinguished on the basis of broadband reflectance alone. We therefore propose that vegetation fraction be used as a proxy for permeable surface distribution to avoid the common erroneous assumption that all nonvegetated surfaces along the gray axis are completely impermeable. Comparison of mean vegetation fractions to street tree counts in New York City shows a consistent relationship between minimum fraction and tree count. However, moderate and high resolution areal estimates of vegetation fraction provide complementary information because they image all illuminated vegetation, including that not counted by the in situ street tree inventory.     

The ethics of NHS computing: A terminal case

Value in the British National Health Service have shifted away from patient care towards financial control. However, in the quest for efficiency, huge amounts of NHS money have been wasted on computer system which failed. In this paper, I draw on a case study to explore some of the ethical issues which underlie this kind of waste of resources. Issues include the gap between public pronouncements and personal experience, the chaos of which lies behind the facade of rationality, and the systematic silencing of people, usually women, who question the viability of computer systems which are created for private gain rather than public service.