Power Laws, Precursors and Predictability During Failure

We investigate the dynamics of a modified Burridge-Knopoff model by introducing a dissipative term to mimic the bursts of acoustic emission (AE) from rock samples. The model explains many features of the statistics of AE signals observed in experiments such as the crossover in the exponent value from relatively small amplitude AE signals to larger regime, and their dependence on the pulling speed. Significantly, we find that the cumulative energy dissipated identified with acoustic emission can be used to predict a major slip event. We also find a data collapse of the acoustic activity for several major slip events describable by a universal stretched exponential with corrections in terms of time-to-failure.Comment: 7 pages, 6 figures, Final version with minor change

Properties of Foreshocks and Aftershocks of the Non-Conservative SOC Olami-Feder-Christensen Model: Triggered or Critical Earthquakes?

Following Hergarten and Neugebauer [2002] who discovered aftershock and foreshock sequences in the Olami-Feder-Christensen (OFC) discrete block-spring earthquake model, we investigate to what degree the simple toppling mechanism of this model is sufficient to account for the properties of earthquake clustering in time and space. Our main finding is that synthetic catalogs generated by the OFC model share practically all properties of real seismicity at a qualitative level, with however significant quantitative differences. We find that OFC catalogs can be in large part described by the concept of triggered seismicity but the properties of foreshocks depend on the mainshock magnitude, in qualitative agreement with the critical earthquake model and in disagreement with simple models of triggered seismicity such as the Epidemic Type Aftershock Sequence (ETAS) model [Ogata, 1988]. Many other features of OFC catalogs can be reproduced with the ETAS model with a weaker clustering than real seismicity, i.e. for a very small average number of triggered earthquakes of first generation per mother-earthquake.Comment: revtex, 19 pages, 8 eps figure

Liposomes: a new non-pharmacological therapy concept for seasonal-allergic-rhinoconjunctivitis

Mucosal barrier disorders play an important role in the pathomechanism of the allergic disease. A new approach for their treatment uses liposomes, which consist of phospholipids that make up 75% of the protective nasal surfactant layer. Our aim was to investigate the efficacy of liposomal-based therapy, as a comprehensive treatment alternative to guideline cromoglycate-based therapy, in the treatment of seasonal allergic rhinoconjunctivitis (SAR). We compared nasal and conjunctival symptom reduction with LipoNasal n nasal spray used as monotherapy (LNM), or LipoNasal n nasal spray and Tears Again eye spray combination therapy (LTC), against standard cromoglycate combination therapy (CGC). This prospective, controlled, open observational study was conducted monocentrically. According to their symptoms and preferences 72 patients with SAR were distributed in three equal groups. The study comprised two visits at an interval of 7 days. The efficacy was examined by daily documenting nasal and conjunctival symptom scores. The Nasal-Spray-Sensory-Scale and the Eye-Drops/Spray-Sensory-Scale were used to investigate the tolerability. Quality of life (QoL) was evaluated, using the RHINASTHMA QoL German adapted version. LNM achieved significant improvement in nasal (p < 0.001) and conjunctival symptoms (p = 0.050). The symptom reduction using CGC was equally significant. LTC led to significant nasal symptom relief (p = 0.045). QoL did not improve significantly in all groups (p > 0.05). The tolerability of all treatments was good and no adverse reactions were observed. In all treatment groups the improvement of the nasal and conjunctival symptom scores exceeds the minimal clinically important difference (MCID). The results demonstrate good tolerability and efficacy of non-pharmaceutical liposomal-based treatment (LipoNasal n and Tears Again), given as monotherapy or combination therapy, for nasal and conjunctival symptoms caused by SAR. This study indicates that liposomal-based treatment for SAR may be a comparable alternative to cromoglycate therapy. Further studies are needed to verify these findings

On the Occurrence of Finite-Time-Singularities in Epidemic Models of Rupture, Earthquakes and Starquakes

We present a new kind of critical stochastic finite-time-singularity, relying on the interplay between long-memory and extreme fluctuations. We illustrate it on the well-established epidemic-type aftershock (ETAS) model for aftershocks, based solely on the most solidly documented stylized facts of seismicity (clustering in space and in time and power law Gutenberg-Richter distribution of earthquake energies). This theory accounts for the main observations (power law acceleration and discrete scale invariant structure) of critical rupture of heterogeneous materials, of the largest sequence of starquakes ever attributed to a neutron star as well as of earthquake sequences.Comment: Revtex document of 4 pages including 1 eps figur

Probenecid Inhibits the Human Bitter Taste Receptor TAS2R16 and Suppresses Bitter Perception of Salicin

Bitter taste stimuli are detected by a diverse family of G protein-coupled receptors (GPCRs) expressed in gustatory cells. Each bitter taste receptor (TAS2R) responds to an array of compounds, many of which are toxic and can be found in nature. For example, human TAS2R16 (hTAS2R16) responds to β-glucosides such as salicin, and hTAS2R38 responds to thiourea-containing molecules such as glucosinolates and phenylthiocarbamide (PTC). While many substances are known to activate TAS2Rs, only one inhibitor that specifically blocks bitter receptor activation has been described. Here, we describe a new inhibitor of bitter taste receptors, p-(dipropylsulfamoyl)benzoic acid (probenecid), that acts on a subset of TAS2Rs and inhibits through a novel, allosteric mechanism of action. Probenecid is an FDA-approved inhibitor of the Multidrug Resistance Protein 1 (MRP1) transporter and is clinically used to treat gout in humans. Probenecid is also commonly used to enhance cellular signals in GPCR calcium mobilization assays. We show that probenecid specifically inhibits the cellular response mediated by the bitter taste receptor hTAS2R16 and provide molecular and pharmacological evidence for direct interaction with this GPCR using a non-competitive (allosteric) mechanism. Through a comprehensive analysis of hTAS2R16 point mutants, we define amino acid residues involved in the probenecid interaction that result in decreased sensitivity to probenecid while maintaining normal responses to salicin. Probenecid inhibits hTAS2R16, hTAS2R38, and hTAS2R43, but does not inhibit the bitter receptor hTAS2R31 or non-TAS2R GPCRs. Additionally, structurally unrelated MRP1 inhibitors, such as indomethacin, fail to inhibit hTAS2R16 function. Finally, we demonstrate that the inhibitory activity of probenecid in cellular experiments translates to inhibition of bitter taste perception of salicin in humans. This work identifies probenecid as a pharmacological tool for understanding the cell biology of bitter taste and as a lead for the development of broad specificity bitter blockers to improve nutrition and medical compliance

Insights into the Binding of Phenyltiocarbamide (PTC) Agonist to Its Target Human TAS2R38 Bitter Receptor

Humans' bitter taste perception is mediated by the hTAS2R subfamily of the G protein-coupled membrane receptors (GPCRs). Structural information on these receptors is currently limited. Here we identify residues involved in the binding of phenylthiocarbamide (PTC) and in receptor activation in one of the most widely studied hTAS2Rs (hTAS2R38) by means of structural bioinformatics and molecular docking. The predictions are validated by site-directed mutagenesis experiments that involve specific residues located in the putative binding site and trans-membrane (TM) helices 6 and 7 putatively involved in receptor activation. Based on our measurements, we suggest that (i) residue N103 participates actively in PTC binding, in line with previous computational studies. (ii) W99, M100 and S259 contribute to define the size and shape of the binding cavity. (iii) W99 and M100, along with F255 and V296, play a key role for receptor activation, providing insights on bitter taste receptor activation not emerging from the previously reported computational models

Dragon-kings: mechanisms, statistical methods and empirical evidence

This introductory article presents the special Discussion and Debate volume "From black swans to dragon-kings, is there life beyond power laws?" published in Eur. Phys. J. Special Topics in May 2012. We summarize and put in perspective the contributions into three main themes: (i) mechanisms for dragon-kings, (ii) detection of dragon-kings and statistical tests and (iii) empirical evidence in a large variety of natural and social systems. Overall, we are pleased to witness significant advances both in the introduction and clarification of underlying mechanisms and in the development of novel efficient tests that demonstrate clear evidence for the presence of dragon-kings in many systems. However, this positive view should be balanced by the fact that this remains a very delicate and difficult field, if only due to the scarcity of data as well as the extraordinary important implications with respect to hazard assessment, risk control and predictability.Comment: 20 page

Subtropical grass pollen allergens are important for allergic respiratory diseases in subtropical regions

Background: Grass pollen allergens are a major cause of allergic respiratory disease but traditionally prescribing practice for grass pollen allergen-specific immunotherapy has favoured pollen extracts of temperate grasses. Here we aim to compare allergy to subtropical and temperate grass pollens in patients with allergic rhinitis from a subtropical region of Australia. Methods. Sensitization to pollen extracts of the subtropical Bahia grass (Paspalum notatum), Johnson grass (Sorghum halepense) and Bermuda grass (Cynodon dactylon) as well as the temperate Ryegrass (Lolium perenne) were measured by skin prick in 233 subjects from Brisbane. Grass pollen-specific IgE reactivity was tested by ELISA and cross-inhibition ELISA. Results: Patients with grass pollen allergy from a subtropical region showed higher skin prick diameters with subtropical Bahia grass and Bermuda grass pollens than with Johnson grass and Ryegrass pollens. IgE reactivity was higher with pollen of Bahia grass than Bermuda grass, Johnson grass and Ryegrass. Patients showed asymmetric cross-inhibition of IgE reactivity with subtropical grass pollens that was not blocked by temperate grass pollen allergens indicating the presence of species-specific IgE binding sites of subtropical grass pollen allergens that are not represented in temperate grass pollens. Conclusions: Subtropical grass pollens are more important allergen sources than temperate grass pollens for patients from a subtropical region. Targeting allergen-specific immunotherapy to subtropical grass pollen allergens in patients with allergic rhinitis in subtropical regions could improve treatment efficacy thereby reducing the burden of allergic rhinitis and asthma

Bitter Taste Receptors Influence Glucose Homeostasis

TAS1R- and TAS2R-type taste receptors are expressed in the gustatory system, where they detect sweet- and bitter-tasting stimuli, respectively. These receptors are also expressed in subsets of cells within the mammalian gastrointestinal tract, where they mediate nutrient assimilation and endocrine responses. For example, sweeteners stimulate taste receptors on the surface of gut enteroendocrine L cells to elicit an increase in intracellular Ca2+ and secretion of the incretin hormone glucagon-like peptide-1 (GLP-1), an important modulator of insulin biosynthesis and secretion. Because of the importance of taste receptors in the regulation of food intake and the alimentary responses to chemostimuli, we hypothesized that differences in taste receptor efficacy may impact glucose homeostasis. To address this issue, we initiated a candidate gene study within the Amish Family Diabetes Study and assessed the association of taste receptor variants with indicators of glucose dysregulation, including a diagnosis of type 2 diabetes mellitus and high levels of blood glucose and insulin during an oral glucose tolerance test. We report that a TAS2R haplotype is associated with altered glucose and insulin homeostasis. We also found that one SNP within this haplotype disrupts normal responses of a single receptor, TAS2R9, to its cognate ligands ofloxacin, procainamide and pirenzapine. Together, these findings suggest that a functionally compromised TAS2R receptor negatively impacts glucose homeostasis, providing an important link between alimentary chemosensation and metabolic disease

Refining associations between TAS2R38 diplotypes and the 6-n-propylthiouracil (PROP) taste test: findings from the Avon Longitudinal Study of Parents and Children

<p>Abstract</p> <p>Background</p> <p>Previous investigations have highlighted the importance of genetic variation in the determination of bitter tasting ability, however have left unaddressed questions as to within group variation in tasting ability or the possibility of genetic prescription of intermediate tasting ability. Our aim was to examine the relationships between bitter tasting ability and variation at the <it>TAS2R38 </it>locus and to assess the role of psychosocial factors in explaining residual, within group, variation in tasting ability.</p> <p>Results</p> <p>In a large sample of children from the Avon Longitudinal Study of Parents and Children, we confirmed an association between bitter compound tasting ability and <it>TAS2R38 </it>variation and found evidence of a genetic association with intermediate tasting ability. Antisocial behaviour, social class and depression showed no consistent relationship with the distribution of taste test scores.</p> <p>Conclusion</p> <p>Factors which could influence a child's chosen taste score, extra to taste receptor variation, appeared not to show relationships with test score. Observed spread in the distribution of the taste test scores <it>within </it>hypothesised taster groups, is likely to be, or at least in part, due to physiological differentiation regulated by other genetic contributors. Results confirm relationships between genetic variation and bitter compound tasting ability in a large sample, and suggest that <it>TAS2R38 </it>variation may also be associated with intermediate tasting ability.</p