Fluorous Iminoalditols: A New Family of Glycosidase Inhibitors and Pharmacological Chaperones

A collection of new reversible glycosidase inhibitors of the iminoalditol type featuring N‐substituents containing perfluorinated regions has been prepared for evaluation of physicochemical, biochemical and diagnostic properties. The vast variety of feasible oligofluoro moieties allows for modular approaches to customised structures according to the intended applications, which are influenced by the fluorine content as well as the distance of the fluorous moiety from the ring nitrogen. The first examples, in particular in the D ‐galacto series, exhibited excellent inhibitory activities. A preliminary screen with two human cell lines showed that, at subinhibitory concentrations, they are powerful pharmacological chaperones enhancing the activities of the catalytically handicapped lysosomal D ‐galactosidase mutants associated with GM1 gangliosidosis and Morquio B disease.     

Numerical modelling of wind flow over a complex topography

Numerical modelling of wind flow over complex dune topography is an ambitious prospect. There is an increasing need to understand wind flow over complex topography for land planning purposes to enable prediction of sediment transport at a particular site. New surveying techniques permit the rapid development of digital terrain models, however a stumbling block is the ability of Computational Fluid Dynamics (CFD) to emulate the wind flow over such a landscape. To overcome these difficulties, it is important to establish the parameters within which such simulations can operate. This paper details an initial two-dimensional numerical model developed in order to test various modelling assumptions against experimental field wind data. Mason Bay, Stewart Island, New Zealand was chosen as an undisturbed but accessible experimental site with a prevalent on-shore wind perpendicular to a simple foredune and a complex down-wind parabolic dune system. A complex topographical two-dimensional model with vegetation represented as a roughness was compared against field data along a transect dissecting a dune system.This paper establishes that:

* Replicating the roughness patterns at the surface is important

* The inlet profile should be duplicated with care

* Modelling only a portion of the domain can have an effect on the flow patterns due to outflow effects

* There is a modelling decision to be made between the complexity of the topography and the sophistication of the turbulence model and degree to which vegetation and sand transportation are modelled.

The long-term aim is to instil confidence in numerical techniques so that such technology can be used for predictive purposes.     

Hydrogen storage in dinuclear Pt(II) metallacycles

Hydrogen gas physisorption in two distinct dinuclear Pt(II) metallacycles was investigated with ²H nuclear magnetic resonance (NMR) spectroscopy. Hydrogen adsorption isotherm data and ²H NMR spectroscopy indicated that hydrogen storage occurs via condensation within the cavities of one of the macrocycles and at the interstitial sites in the other. In addition, this study further supports the notion that heat of adsorption and pore size play critical roles in hydrogen storage.     

Regional brain electrical activity in posttraumatic stress disorder after motor vehicle accident.

This study examined whether patients with posttraumatic stress disorder (PTSD) related to motor vehicle accidents (MVAs) would show an abnormal pattern of electroencephalographic (EEG) alpha asymmetries, which has been proposed for particular types of anxiety. Patients with PTSD (n = 22) or subsyndromal PTSD (n = 21), traumatized controls without PTSD (non-PTSD with MVA; n = 21), and healthy controls without MVA (n = 23) underwent measurement of EEG activity during baseline and exposure to a neutral, a positive, a negative, and an accident-related picture. Differences in brain asymmetry between groups were observed only during exposure to trauma-related material. PTSD and subsyndromal PTSD patients showed a pattern of enhanced right anterior and posterior activation, whereas non-PTSD with MVA participants showed the opposite pattern. Furthermore, posterior asymmetry in nontraumatized healthy controls varied with gender, with female participants showing a pattern of higher right posterior activation. The results support the hypothesis that symptomatic MVA survivors are characterized by a pattern of right hemisphere activation that is associated with anxious arousal and symptoms of PTSD during processing of trauma-specific information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Performance in a complex task and breathing under odor exposure

We investigated the influences of odor exposure on performance and on breathing measures. The task was composed of tracking, short-term memory, and peripheral reaction parts. During rest or while performing the task, 12 participants were exposed to 4 different odors in 2 intensities. The higher intensity of the malodors induced a short-term decrement in mean inspiration flow (Vi/Ti) after stimulus onset and impaired performance in the short-term memory task, as compared with control trials; no effect was found for the positively judged odors. The study suggests that a distractor as simple as a bad smell may pull a person off task, however briefly, and may result in a detriment to performance. Actual or potential applications of this research involve designing or securing tasks in such a way that a brief withdrawal of attention does not have fatal consequences.     

Bilingual LSA-based adaptation for statistical machine translation

We propose a novel approach to cross-lingual language model and translation lexicon adaptation for statistical machine translation (SMT) based on bilingual latent semantic analysis. Bilingual LSA enables latent topic distributions to be efficiently transferred across languages by enforcing a one-to-one topic correspondence during training. Using the proposed bilingual LSA framework, model adaptation can be performed by, first, inferring the topic posterior distribution of the source text and then applying the inferred distribution to an n-gram language model of the target language and translation lexicon via marginal adaptation. The background phrase table is enhanced with the additional phrase scores computed using the adapted translation lexicon. The proposed framework also features rapid bootstrapping of LSA models for new languages based on a source LSA model of another language. Our approach is evaluated on the Chinese–English MT06 test set using the medium-scale SMT system and the GALE SMT system measured in BLEU and NIST scores. Improvement in both scores is observed on both systems when the adapted language model and the adapted translation lexicon are applied individually. When the adapted language model and the adapted translation lexicon are applied simultaneously, the gain is additive. At the 95% confidence interval of the unadapted baseline system, the gain in both scores is statistically significant using the medium-scale SMT system, while the gain in the NIST score is statistically significant using the GALE SMT system.     

Personality traits and knowledge sharing in online communities

Adopting diffusion theory and the concept of social value orientation, the effects of personality traits on knowledge sharing in a virtual open content community are investigated. In addition to the main effects of personality, it was hypothesized that intrinsic motivations would moderate the effects on knowledge sharing. A sample of N = 256 active users of Wikipedia provided measures of personality, motivation, and knowledge sharing. Latent regression analyses support the notion that authorship of Wikipedia is associated with higher levels of trendsetting and a prosocial value orientation. Moreover, moderation analyses demonstrate that the effect of the latter is moderated by individual differences in motivations to write. Differences with regard to opinion leadership could not be confirmed.     

A Donor Agency Scramble for South Africa

The international development community invests bulk of its financial aid to South Africa in establishing procedural conditions through which development actions may be realized. Accordingly, ‘democracy assistance’ is designed to target governmental structures and civil society organizations (CSOs). International donor governments and aid agencies also assign an operational role to civil society so that it may assist in the process of change. However, an overt emphasis on the procedural aspects of democracy, governance, and development ignores the context and object of planning. Consequently, development planning in South Africa is perceived in narrow procedural terms alone, and not in terms of more holistic and equitable development responses.     

Targeting Mitochondria in Diabetes

Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes.