Relative positioning of classical benzodiazepines to the γ2-subunit of GABAA receptors.

GABAA receptors are the major inhibitory neurotransmitter receptors in the brain. Benzodiazepine exert their action via a high affinity-binding site at the α/γ subunit interface on some of these receptors. Diazepam has sedative, hypnotic, anxiolytic, muscle relaxant, and anticonvulsant effects. It acts by potentiating the current evoked by the agonist GABA. Understanding specific interaction of benzodiazepines in the binding pocket of different GABAA receptor isoforms might help to separate these divergent effects. As a first step, we characterized the interaction between diazepam and the major GABAA receptor isoform α1β2γ2. We mutated several amino acid residues on the γ2-subunit assumed to be located near or in the benzodiazepine binding pocket individually to cysteine and studied the interaction with three ligands that are modified with a cysteine-reactive isothiocyanate group (-NCS). When the reactive NCS group is in apposition to the cysteine residue this leads to a covalent reaction. In this way, three amino acid residues, γ2Tyr58, γ2Asn60, and γ2Val190 were located relative to classical benzodiazepines in their binding pocket on GABAA receptors.

The relative importance of immediate allelopathy and allelopathic legacy in invasive plant species

Abstract Some introduced invasive species may be competitively superior to natives because they release allelochemicals, which negatively affect native species. Allelochemicals can be immediately effective after being released but can also persist in soils, resulting in a legacy effect. However, to our knowledge there are no studies which distinguish between allelopathic legacy and immediate allelopathy of invasive species and also test for their relative importance and possible interdependence. We used eleven invasive species and tested whether they show immediate allelopathy and allelopathic legacy effects in a factorial pairwise competition experiment using field-collected soil (invaded/non-invaded) and activated carbon to neutralize allelochemicals. We grew two native and the invasive species in both monocultures and pairwise mixtures. In monocultures, the native species did not experience an allelopathic legacy effect of the invasives, suggesting that invaders generally lack persistent allelochemicals. However, the effects of invader allelochemicals were modulated by competitive interactions. In competition, immediate allelopathy decreased competitive ability of natives, while allelopathic legacy positively affected the natives. Moreover, immediate allelopathic and allelopathic legacy effects were strongly negatively correlated. Our results suggest that both immediately released allelochemicals and the allelochemical legacy of invasive species are important for plant performance under natural conditions, and that natives should be able to recover once the invaders are removed. To test whether immediate allelopathy is responsible for plant invasion success, further studies should compare allelopathic effects between invasive and closely related native species.

Sur une inscription hébrai͏̈que relative à la synagogue de Tàdif : extrait

M. Euting

The trouble with quality filtering based on relative Cramér-Rao lower bounds.

Cramér Rao Lower Bounds (CRLB) have become the standard for expression of uncertainties in quantitative MR spectroscopy. If properly interpreted as a lower threshold of the error associated with model fitting, and if the limits of its estimation are respected, CRLB are certainly a very valuable tool to give an idea of minimal uncertainties in magnetic resonance spectroscopy (MRS), although other sources of error may be larger. Unfortunately, it has also become standard practice to use relative CRLB expressed as a percentage of the presently estimated area or concentration value as unsupervised exclusion criterion for bad quality spectra. It is shown that such quality filtering with widely used threshold levels of 20% to 50% CRLB readily causes bias in the estimated mean concentrations of cohort data, leading to wrong or missed statistical findings-and if applied rigorously-to the failure of using MRS as a clinical instrument to diagnose disease characterized by low levels of metabolites. Instead, absolute CRLB in comparison to those of the normal group or CRLB in relation to normal metabolite levels may be more useful as quality criteria. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

Partiality, Agent-Relative Reasons, and the Individuals View

The paper offers a critical discussion of Simon Keller’s individuals view concerning the grounds of special obligations. It is argued that the view offers a misleading account of agent-relative reasons, which leads to problems with the arguments Keller offers for his view – the Kantian, consequentialist, particularistic argument. Furthermore, it argues that Keller’s argument from phenomenology suffers from not distinguishing between reasons for partiality and reasons from partiality. At best, it can be applied to reasons from partiality – reasons that agents have in virtue of standing in a relationship of partiality with some other person. Thus, the argument does not support the individuals view, as it is compatible with the other approaches Keller discusses. The paper suggests a modified relationship view to ground reasons of partiality.

Bond Strength of Resin Composite to Dentin with Different Adhesive Systems: Influence of Relative Humidity and Application Time.

PURPOSE To investigate the influence of relative humidity and application time on bond strength to dentin of different classes of adhesive systems. MATERIALS AND METHODS A total of 360 extracted human molars were ground to mid-coronal dentin. The dentin specimens were treated with one of six adhesive systems (Syntac Classic, OptiBond FL, Clearfil SE Bond, AdheSE, Xeno Select, or Scotchbond Universal), and resin composite (Filtek Z250) was applied to the treated dentin surface under four experimental conditions (45% relative humidity/application time according to manufacturers' instructions; 45% relative humidity/reduced application time; 85% relative humidity/application time according to manufacturers' instructions; 85% relative humidity/reduced application time). After storage (37°C, 100% humidity, 24 h), shear bond strength (SBS) was measured and data analyzed with nonparametric ANOVA followed by Kruskal-Wallis tests and Mann-Whitney U-tests with Bonferroni-Holm correction for multiple testing (level of significance: α = 0.05). RESULTS Increased relative humidity and reduced application time had no effect on SBS for Clearfil SE Bond and Scotchbond Universal (p = 1.00). For Syntac Classic, OptiBond FL, AdheSE, and Xeno Select there was no effect on SBS of reduced application time of the adhesive system (p ≥ 0.403). However, increased relative humidity significantly reduced SBS for Syntac Classic, OptiBond FL, and Xeno Select irrespective of application time (p ≤ 0.003), whereas for AdheSE, increased relative humidity significantly reduced SBS at recommended application time only (p = 0.002). CONCLUSION Generally, increased relative humidity had a detrimental effect on SBS to dentin, but reduced application time had no effect.

Relative estimate of accuracy in orbit determination from a short tracklet

The Astronomical Institute of the University of Bern (AIUB) is conducting several search campaigns for orbital debris. The debris objects are discovered during systematic survey observations. In general only a short observation arc, or tracklet, is available for most of these objects. From this discovery tracklet a first orbit determination is computed in order to be able to find the object again in subsequent follow-up observations. The additional observations are used in the orbit improvement process to obtain accurate orbits to be included in a catalogue. In this paper, the accuracy of the initial orbit determination is analyzed. This depends on a number of factors: tracklet length, number of observations, type of orbit, astrometric error, and observation geometry. The latter is characterized by both the position of the object along its orbit and the location of the observing station. Different positions involve different distances from the target object and a different observing angle with respect to its orbital plane and trajectory. The present analysis aims at optimizing the geometry of the discovery observation is depending on the considered orbit.