Stereo-electronic control of reaction selectivity in short-chain dehydrogenases : decarboxylation, epimerization, and dehydration

Sugar nucleotide?modifying enzymes of the short-chain dehydrogenase/reductase type use transient oxidation?reduction by a tightly bound nicotinamide cofactor as a common strategy of catalysis to promote a diverse set of reactions, including decarboxylation, single- or double-site epimerization, and dehydration. Although the basic mechanistic principles have been worked out decades ago, the finely tuned control of reactivity and selectivity in several of these enzymes remains enigmatic. Recent evidence on uridine 5'-diphosphate (UDP)glucuronic acid decarboxylases (UDP-xylose synthase, UDPapiose/UDP-xylose synthase) and UDP-glucuronic acid-4epimerase suggests that stereo-electronic constraints established at the enzyme?s active site control the selectivity, and the timing of the catalytic reaction steps, in the conversion of the common substrate toward different products. The mechanistic idea of stereo-electronic control is extended to epimerases and dehydratases that deprotonate the Ca of the transient ketohexose intermediate. The human guanosine 5'-diphosphate (GDP)-mannose 4,6-dehydratase was recently shown to use a minimal catalytic machinery, exactly as predicted earlier from theoretical considerations, for the 0-elimination of water from the keto-hexose species

S(C)ENTINEL - monitoring automated vehicles with olfactory reliability displays

Overreliance in technology is safety-critical and it is assumed that this could have been a main cause of severe accidents with automated vehicles. To ease the complex task of per- manently monitoring vehicle behavior in the driving en- vironment, researchers have proposed to implement relia- bility/uncertainty displays. Such displays allow to estimate whether or not an upcoming intervention is likely. However, presenting uncertainty just adds more visual workload on drivers, who might also be engaged in secondary tasks. We suggest to use olfactory displays as a potential solution to communicate system uncertainty and conducted a user study (N=25) in a high-fidelity driving simulator. Results of the ex- periment (conditions: no reliability display, purely visual reliability display, and visual-olfactory reliability display) comping both objective (task performance) and subjective (technology acceptance model, trust scales, semi-structured interviews) measures suggest that olfactory notifications could become a valuable extension for calibrating trust in automated vehicles

Practical observations on the performance of bare silica in hydrophilic interaction compared with C18 reversed-phase liquid chromatography

The kinetic performance of a bare silica and C18 phase prepared from the same sub-2. μm and 3.5. μm base materials were compared in the HILIC and RP mode using both charged and neutral solutes. The HILIC column was characterised using the neutral solute 5-hydroxymethyluridine, the weak base cytosine, and the strong base nortriptyline, the latter having sufficient retention also in the RP mode to allow comparison of performance. Naphthalene was also used as a simple neutral substance to evaluate the RP column alone. The retention factors of all substances were adjusted to give similar values (k'. ~. 5.5) at their respective optimum linear velocities. Reduced van Deemter b-coefficients (determined by curve fitting and by the peak parking method, using a novel procedure involving switching to a dummy column) were significantly lower in HILIC for all substances compared with those found under RP conditions. Against expectation, c-coefficients were always lower in RP when compared with HILIC using sub-2. μm particles. While measurement of these coefficients is complicated by retention shifts caused by the influence of high pressure and by frictional heating effects, broadly similar results were obtained on larger particle (3.5. μm) phases. The mechanism of the separations was further investigated by examining the effect of buffer concentration on retention. It was concluded that HILIC can sometimes show somewhat inferior performance to RP for fast analysis at high mobile phase velocity, but clearly shows advantages when high column efficiencies, using longer columns at low flow velocity, are employed. The latter result is attributable to the lower viscosity of the mobile phase in HILIC and the reduced pressure requirement as well as the lower b-coefficients. © 2014 David V. McCalley

Curation of characterized glycoside hydrolases of Fungal origin

Fungi produce a wide range of extracellular enzymes to break down plant cell walls, which are composed mainly of cellulose, lignin and hemicellulose. Among them are the glycoside hydrolases (GH), the largest and most diverse family of enzymes active on these substrates. To facilitate research and development of enzymes for the conversion of cell-wall polysaccharides into fermentable sugars, we have manually curated a comprehensive set of characterized fungal glycoside hydrolases. Characterized glycoside hydrolases were retrieved from protein and enzyme databases, as well as literature repositories. A total of 453 characterized glycoside hydrolases have been cataloged. They come from 131 different fungal species, most of which belong to the phylum Ascomycota. These enzymes represent 46 different GH activities and cover 44 of the 115 CAZy GH families. In addition to enzyme source and enzyme family, available biochemical properties such as temperature and pH optima, specific activity, kinetic parameters and substrate specificities were recorded. To simplify comparative studies, enzyme and species abbreviations have been standardized, Gene Ontology terms assigned and reference to supporting evidence provided. The annotated genes have been organized in a searchable, online database called mycoCLAP (Characterized Lignocellulose-Active Proteins of fungal origin). It is anticipated that this manually curated collection of biochemically characterized fungal proteins will be used to enhance functional annotation of novel GH genes

Impact of macro-structural reforms on the productivity growth of regions: distance to the frontier matters

Using a panel of 265 regions from 24 OECD countries from 1997 to 2007, we explore the impact of nation-wide macroeconomic and structural policies on the productivity growth of subnational regions. We find that average relationships between nation-wide policies and regional productivity growth can hide strong differentiated effects according to the distance to the frontier: relaxing employment protection legislation on temporary contracts, lowering barriers to trade and investment and increasing trade openness enhances productivity growth in lagging regions, whereas reducing barriers to entrepreneurship or higher levels of government debt has a positive effect on regions closer to the productivity frontier

Abundance analysis of prime B-type targets for asteroseismology I. Nitrogen excess in slowly-rotating beta Cephei stars

We present the results of a detailed NLTE abundance study of nine beta Cephei stars, all of them being prime targets for theoretical modelling: gamma Peg, delta Cet, nu Eri, beta CMa, xi1 CMa, V836 Cen, V2052 Oph, beta Cep and DD (12) Lac. The following chemical elements are considered: He, C, N, O, Mg, Al, Si, S and Fe. Our abundance analysis is based on a large number of time-resolved, high-resolution optical spectra covering in most cases the entire oscillation cycle of the stars. Nitrogen is found to be enhanced by up to 0.6 dex in four stars, three of which have severe constraints on their equatorial rotational velocity, \Omega R, from seismic or line-profile variation studies: beta Cep (\Omega R~26 km/s), V2052 Oph (\Omega R~56 km/s), delta Cet (\Omega R < 28 km/s) and xi1 CMa (\Omega R sin i < 10 km/s). The existence of core-processed material at the surface of such largely unevolved, slowly-rotating objects is not predicted by current evolutionary models including rotation. We draw attention to the fact that three stars in this subsample have a detected magnetic field and briefly discuss recent theoretical work pointing to the occurrence of diffusion effects in beta Cephei stars possibly capable of altering the nitrogen surface abundance. On the other hand, the abundances of all the other chemical elements considered are, within the errors, indistinguishable from the values found for OB dwarfs in the solar neighbourhood. Despite the mild nitrogen excess observed in some objects, we thus find no evidence for a significantly higher photospheric metal content in the studied beta Cephei stars compared to non-pulsating B-type stars of similar characteristics.Comment: Accepted for publication in A&A, 21 pages, 7 figure

Nanoscale crystallinity modulates cell proliferation on plasma sprayed surfaces

Calcium phosphate coatings have been applied to the surface of metallic prostheses to mediate hard and soft tissue attachment for more than 40 years. Most coatings are formed of high purity hydroxyapatite, and coating methods are often designed to produce highly crystalline surfaces. It is likely however, that coatings of lower crystallinity can facilitate more rapid tissue attachment since the surface will exhibit a higher specific surface area and will be considerably more reactive than a comparable highly crystalline surface. Here we test this hypothesis by growing a population of MC3T3 osteoblast-like cells on the surface of two types of hip prosthesis with similar composition, but with differing crystallinity. The surfaces with lower crystallinity facilitated more rapid cell attachment and increased proliferation rate, despite having a less heterogeneous surface topography. This work highlights that the influence of the crystallinity of HA at the nano-scale is dominant over macroscale topography for cell adhesion and growth. Furthermore, crystallinity could be easily adjusted by without compromising coating purity. These findings could facilitate designing novel coated calcium phosphate surfaces that more rapidly bond tissue following implantation

Policy Issues in NEG Models: Established Results and Open Questions

This paper provides a non-technical overview of NEG models dealing with policy issues. Considered policy measures include alternative categories of public expenditure, international tax competition, unilateral actions of protection/liberalisation, and trade agreements. The implications of public intervention in two-region NEG models are discussed by unfolding the impact of policy measures on agglomeration/dispersion forces. Results are described in contrast with those obtained in standard non-NEG theoretical models. The high degree of abstraction limits the applicability of NEG models to real world policy issues. We discuss in some detail two extensions of NEG models to reduce this applicability gap: the cases of multi-regional frameworks and firm heterogeneity

Hearing instruments for unilateral severe-to-profound sensorineural hearing loss in adults

Objectives: A systematic review of the literature and meta-analysis was conducted to assess the nature and quality of the evidence for the use of hearing instruments in adults with a unilateral severe-to-profound sensorineural hearing loss. Design: The PubMed, EMBASE, MEDLINE, Cochrane, CINAHL and DARE databases were searched with no restrictions on language. The search included articles from the start of each database until 11th February 2015. Studies were included that: (a) assessed the impact of any form of hearing instrument, including devices that re-route signals between the ears or restore aspects of hearing to a deaf ear, in adults with a sensorineural severe-to-profound loss in one ear and normal or near-normal hearing in the other ear; (b) compared different devices or compared a device to placebo or the unaided condition; (c) measured outcomes in terms of speech perception, spatial listening, or quality of life; (d) were prospective controlled or observational studies. Studies that met prospectively-defined criteria were subjected to random-effects meta-analyses. Results: Twenty-seven studies reported in thirty articles were included. The evidence was graded as low-to-moderate quality having been obtained primarily from observational before-after comparisons. The meta-analysis identified statistically-significant benefits to speech perception in noise for devices that re-routed the speech signals of interest from the worse ear to the better ear using either air or bone conduction (mean benefit 2.5 dB). However, these devices also degraded speech understanding significantly and to a similar extent (mean deficit 3.1 dB) when noise was re-routed to the better ear. Data on the effects of cochlear implantation on speech perception could not be pooled as the prospectively-defined criteria for meta-analysis were not met. Inconsistency in the assessment of outcomes relating to sound localisation also precluded the synthesis of evidence across studies. Evidence for the relative efficacy of different devices was sparse but a statistically significant advantage was observed for re-routing speech signals using abutment-mounted bone conduction devices when compared to outcomes after pre-operative trials of air-conduction devices when speech and noise were co-located (mean benefit 1.5 dB). Patients reported significant improvements in hearing-related quality of life with both re-routing devices and following cochlear implantation. Only two studies measured health-related quality of life and findings were inconclusive. Conclusions: Devices that re-route sounds from an ear with a severe-to-profound hearing loss to an ear with minimal hearing loss may improve speech perception in noise when signals of interest are located towards the impaired ear. However, the same device may also degrade speech perception as all signals are re-routed indiscriminately, including noise. While the restoration of functional hearing in both ears through cochlear implantation could be expected to provide benefits to speech perception, the inability to synthesise evidence across existing studies means that such a conclusion cannot yet be made. For the same reason, it remains unclear whether cochlear implantation can improve the ability to localise sounds despite restoring bilateral input. Prospective controlled studies that measure outcomes consistently and control for selection and observation biases are required to improve the quality of the evidence for the provision of hearing instruments to patients with unilateral deafness and to support any future recommendations for the clinical management of these patients