The effects of a background potential in star cluster evolution: a delay in the relaxation time-scale and runaway collision processes

Runaway stellar collisions in dense star clusters are invoked to explain the presence of very massive stars or blue stragglers in the center of those systems. This process has also been explored for the first star clusters in the Universe and shown to yield stars that may collapse at some points into an intermediate mass black hole. Although the early evolution of star clusters requires the explicit modeling of the gas out of which the stars form, these calculations would be extremely time-consuming and often the effects of the gas can be accurately treated by including a background potential to account for the extra gravitational force. We apply this approximation to model the early evolution of the first dense star clusters formed in the Universe by performing $N$-body simulations, our goal is to understand how the additional gravitational force affects the growth of a very massive star through stellar mergers in the central parts of the star cluster. Our results show that the background potential increases the velocities of the stars, causing an overall delay in the evolution of the clusters and in the runaway growth of a massive star at the center. The population of binary stars is lower due to the increased kinetic energy of the stars, initially reducing the number of stellar collisions, and we show that relaxation processes are also affected. Despite these effects, the external potential enhances the mass of the merger product by a factor $\sim$2 if the collisions are maintained for long times.Comment: 16 pages. Accepted for publication in Astronomy and Astrophysic

Global instability by runaway collisions in nuclear stellar clusters: Numerical tests of a route for massive black hole formation

The centers of galaxies host nuclear stellar clusters, supermassive black holes, or both, but the origin of this dichotomy is still a mystery. Nuclear stellar clusters are the densest stellar system of the Universe, so they are ideal places for runaway collisions to occur. In these dense clusters it is possible that global instability occurs, triggered by collisions and mergers forming a massive black hole. Here we test a new mechanism to form massive black holes through runaway stellar collisions in nuclear stellar clusters, performing N-body simulations using the code nbody6++gpu. Our idealized models show that there is a critical mass where collisions become very efficient making it possible to form massive black holes in nuclear stellar clusters. The most massive objects reach masses of the order of $10^4-10^5\rm~ M_\odot$. We find that our highest black hole formation efficiency is up to $50\%$ of the stellar mass at the end of the simulation. In real astrophysical systems, the critical mass scale for this transition is expected to occur in stellar clusters of $10^7-10^9\rm~M_\odot$, implying the formation of quite massive central objects.Comment: 11 pages, 6 figure

Thermosensitivity of the Saccharomyces cerevisiae gpp1gpp2 double deletion strain can be reduced by overexpression of genes involved in cell wall maintenance

A Saccharomyces cerevisiae strain in which the GPP1 and GPP2 genes, both encoding glycerol-3-phosphate phosphatase isoforms, are deleted, displays both osmo- and thermosensitive (ts) phenotypes. We isolated genes involved in cell wall maintenance as multicopy suppressors of the gpp1gpp2 ts phenotype. We found that the gpp1gpp2 strain is hypersensitive to cell wall stress such as treatment with β-1,3-glucanase containing cocktail Zymolyase and chitin-binding dye Calcofluor-white (CFW). Sensitivity to Zymolyase was rescued by overexpression of SSD1, while CFW sensitivity was rescued by SSD1, FLO8 and WSC3-genes isolated as multicopy suppressors of the gpp1gpp2 ts phenotype. Some of the isolated suppressor genes (SSD1, FLO8) also rescued the lytic phenotype of slt2 deletion strain. Additionally, the sensitivity to CFW was reduced when the cells were supplied with glycerol. Both growth on glycerol-based medium and overexpression of SSD1, FLO8 or WSC3 had additive suppressing effect on CFW sensitivity of the gpp1gpp2 mutant strain. We also confirmed that the internal glycerol level changed in cells exposed to cell wall perturbation. © 2007 Springer-Verlag

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

Marble melancholy: using crossmodal correspondences of shapes, materials, and music to predict music-induced emotions

Introduction: Music is known to elicit strong emotions in listeners, and, if primed appropriately, can give rise to specific and observable crossmodal correspondences. This study aimed to assess two primary objectives: (1) identifying crossmodal correspondences emerging from music-induced emotions, and (2) examining the predictability of music-induced emotions based on the association of music with visual shapes and materials. Methods: To achieve this, 176 participants were asked to associate visual shapes and materials with the emotion classes of the Geneva Music-Induced Affect Checklist scale (GEMIAC) elicited by a set of musical excerpts in an online experiment. Results: Our findings reveal that music-induced emotions and their underlying core affect (i.e., valence and arousal) can be accurately predicted by the joint information of musical excerpt and features of visual shapes and materials associated with these music-induced emotions. Interestingly, valence and arousal induced by music have higher predictability than discrete GEMIAC emotions. Discussion: These results demonstrate the relevance of crossmodal correspondences in studying music-induced emotions. The potential applications of these findings in the fields of sensory interactions design, multisensory experiences and art, as well as digital and sensory marketing are briefly discussed.Peer Reviewe

Nerve growth factor induces neurite outgrowth of PC12 cells by promoting Gβγ-microtubule interaction

Background: Assembly and disassembly of microtubules (MTs) is critical for neurite outgrowth and differentiation. Evidence suggests that nerve growth factor (NGF) induces neurite outgrowth from PC12 cells by activating the receptor tyrosine kinase, TrkA. G protein-coupled receptors (GPCRs) as well as heterotrimeric G proteins are also involved in regulating neurite outgrowth. However, the possible connection between these pathways and how they might ultimately converge to regulate the assembly and organization of MTs during neurite outgrowth is not well understood. Results: Here, we report that Gβγ, an important component of the GPCR pathway, is critical for NGF-induced neuronal differentiation of PC12 cells. We have found that NGF promoted the interaction of Gβγ with MTs and stimulated MT assembly. While Gβγ-sequestering peptide GRK2i inhibited neurite formation, disrupted MTs, and induced neurite damage, the Gβγ activator mSIRK stimulated neurite outgrowth, which indicates the involvement of Gβγ in this process. Because we have shown earlier that prenylation and subsequent methylation/demethylation of γ subunits are required for the Gβγ-MTs interaction in vitro, small-molecule inhibitors (L-28 and L-23) targeting prenylated methylated protein methyl esterase (PMPMEase) were tested in the current study. We found that these inhibitors disrupted Gβγ and ΜΤ organization and affected cellular morphology and neurite outgrowth. In further support of a role of Gβγ-MT interaction in neuronal differentiation, it was observed that overexpression of Gβγ in PC12 cells induced neurite outgrowth in the absence of added NGF. Moreover, overexpressed Gβγ exhibited a pattern of association with MTs similar to that observed in NGF-differentiated cells. Conclusions: Altogether, our results demonstrate that βγ subunit of heterotrimeric G proteins play a critical role in neurite outgrowth and differentiation by interacting with MTs and modulating MT rearrangement. Electronic supplementary material The online version of this article (doi:10.1186/s12868-014-0132-4) contains supplementary material, which is available to authorized users

Disease reservoirs threaten the recently rediscovered Podocarpus Stubfoot Toad (Atelopus podocarpus)

The Andes have experienced an unprecedented wave of amphibian declines and extinctions that are linked to a combination of habitat reduction and the spread of the fungal pathogen, Batrachochytrium dendrobatidis (Bd). In the present study, a range of high-altitude habitats in Southern Ecuador were surveyed for the presence of Bd. With a particular focus on Yacuri National Park, infection data are presented from across the resident amphibian community. This community contains a once putatively extinct species which was rediscovered in 2016, the Podocarpus Stubfoot Toad (Atelopus podocarpus). Across species, local Bd prevalence was 73% in tadpoles (n = 41 individuals from three species) and 14% in adults (n = 43 individuals from 14 species). Strikingly, 93% (14/15) of tested tadpoles of the recently described local endemic, Gastrotheca yacuri, were infected with a high pathogen load, suggesting that this species likely acts as a reservoir of infection in Yacuri. These findings show that the threat of disease for A. podocarpus still exists, and that this species requires urgent action to ensure its survival

Stellar collisions in flattened and rotating Pop. III star clusters

Fragmentation often occurs in disk-like structures, both in the early Universe and in the context of present-day star formation. Supermassive black holes (SMBHs) are astrophysical objects whose origin is not well understood; they weigh millions of solar masses and reside in the centers of galaxies. An important formation scenario for SMBHs is based on collisions and mergers of stars in a massive cluster, in which the most massive star moves to the center of the cluster due to dynamical friction. This increases the rate of collisions and mergers since massive stars have larger collisional cross sections. This can lead to runaway growth of a very massive star which may collapse to become an intermediate-mass black hole. Here we investigate the dynamical evolution of Miyamoto-Nagai models that allow us to describe dense stellar clusters, including flattening and different degrees of rotation. We find that the collisions in these clusters depend mostly on the number of stars and the initial stellar radii for a given radial size of the cluster. By comparison, rotation seems to affect the collision rate by at most $20\%$. For flatness, we compared spherical models with systems that have a scale height of about $10\%$ of their radial extent, in this case finding a change in the collision rate of less than $25\%$. Overall, we conclude that the parameters only have a minor effect on the number of collisions. Our results also suggest that rotation helps to retain more stars in the system, reducing the number of escapers by a factor of $2-3$ depending on the model and the specific realization. After two million years, a typical lifetime of a very massive star, we find that about $630$ collisions occur in typical models with $N=10^4$, $R=100$ $\rm~R_\odot$ and a half-mass radius of $0.1$ $\rm~pc$, leading to a mass of about $6.3\times10^3$ $\rm~M_\odot$ for the most massive object.Comment: 10 pages, 7 figure