Measurement of higher cumulants of net-charge multiplicity distributions in Au++Au collisions at sNN=7.7−200\sqrt{s_{_{NN}}}=7.7-200 GeV

We report the measurement of cumulants ($C_n, n=1\ldots4$) of the net-charge distributions measured within pseudorapidity ($|\eta|<0.35$) in Au$+$Au collisions at $\sqrt{s_{_{NN}}}=7.7-200$ GeV with the PHENIX experiment at the Relativistic Heavy Ion Collider. The ratios of cumulants (e.g. $C_1/C_2$, $C_3/C_1$) of the net-charge distributions, which can be related to volume independent susceptibility ratios, are studied as a function of centrality and energy. These quantities are important to understand the quantum-chromodynamics phase diagram and possible existence of a critical end point. The measured values are very well described by expectation from negative binomial distributions. We do not observe any nonmonotonic behavior in the ratios of the cumulants as a function of collision energy. The measured values of $C_1/C_2 = \mu/\sigma^2$ and $C_3/C_1 = S\sigma^3/\mu$ can be directly compared to lattice quantum-chromodynamics calculations and thus allow extraction of both the chemical freeze-out temperature and the baryon chemical potential at each center-of-mass energy.Comment: 512 authors, 8 pages, 4 figures, 1 table. v2 is version accepted for publication in Phys. Rev. C as a Rapid Communication. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Transverse energy production and charged-particle multiplicity at midrapidity in various systems from sNN=7.7\sqrt{s_{NN}}=7.7 to 200 GeV

Measurements of midrapidity charged particle multiplicity distributions, $dN_{\rm ch}/d\eta$, and midrapidity transverse-energy distributions, $dE_T/d\eta$, are presented for a variety of collision systems and energies. Included are distributions for Au$+$Au collisions at $\sqrt{s_{_{NN}}}=200$, 130, 62.4, 39, 27, 19.6, 14.5, and 7.7 GeV, Cu$+$Cu collisions at $\sqrt{s_{_{NN}}}=200$ and 62.4 GeV, Cu$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV, U$+$U collisions at $\sqrt{s_{_{NN}}}=193$ GeV, $d$$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV, $^{3}$He$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV, and $p$$+$$p$ collisions at $\sqrt{s_{_{NN}}}=200$ GeV. Centrality-dependent distributions at midrapidity are presented in terms of the number of nucleon participants, $N_{\rm part}$, and the number of constituent quark participants, $N_{q{\rm p}}$. For all $A$$+$$A$ collisions down to $\sqrt{s_{_{NN}}}=7.7$ GeV, it is observed that the midrapidity data are better described by scaling with $N_{q{\rm p}}$ than scaling with $N_{\rm part}$. Also presented are estimates of the Bjorken energy density, $\varepsilon_{\rm BJ}$, and the ratio of $dE_T/d\eta$ to $dN_{\rm ch}/d\eta$, the latter of which is seen to be constant as a function of centrality for all systems.Comment: 706 authors, 32 pages, 20 figures, 34 tables, 2004, 2005, 2008, 2010, 2011, and 2012 data. v2 is version accepted for publication in Phys. Rev.

Measurement of jet-medium interactions via direct photon-hadron correlations in Au++Au and dd++Au collisions at sNN=200\sqrt{s_{_{NN}}}=200 GeV

We present direct photon-hadron correlations in 200 GeV/A Au$+$Au, $d$$+$Au and $p$$+$$p$ collisions, for direct photon $p_T$ from 5--12 GeV/$c$, collected by the PHENIX Collaboration in the years from 2006 to 2011. We observe no significant modification of jet fragmentation in $d$$+$Au collisions, indicating that cold nuclear matter effects are small or absent. Hadrons carrying a large fraction of the quark's momentum are suppressed in Au$+$Au compared to $p$$+$$p$ and $d$$+$Au. As the momentum fraction decreases, the yield of hadrons in Au$+$Au increases to an excess over the yield in $p$$+$$p$ collisions. The excess is at large angles and at low hadron $p_T$ and is most pronounced for hadrons associated with lower momentum direct photons. Comparison to theoretical calculations suggests that the hadron excess arises from medium response to energy deposited by jets.Comment: 578 authors from 80 institutions, 11 pages, 7 figures, data from 2007, 2008, 2010, and 2011. v2 is version accepted for publication in Physical Review C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Technical trading and cryptocurrencies

This paper carries out a comprehensive examination of technical trading rules in cryptocurrency markets, using data from two Bitcoin markets and three other popular cryptocurrencies. We employ almost 15,000 technical trading rules from the main five classes of technical trading rules and find significant predictability and profitability for each class of technical trading rule in each cryptocurrency. We find that the breakeven transaction costs are substantially higher than those typically found in cryptocurrency markets. To safeguard against data-snooping, we implement a number of multiple hypothesis procedures which confirms our findings that technical trading rules do offer significant predictive power and profitability to investors. We also show that the technical trading rules offer substantially higher risk-adjusted returns than the simple buy-and-hold strategy, showing protection against lengthy and severe drawdowns associated with cryptocurrency markets. However there is no predictability for Bitcoin in the out-of-sample period, although predictability remains in other cryptocurrency markets

VX-659-Tezacaftor-Ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles

Background The next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector VX-659, in triple combination with tezacaftor and ivacaftor (VX-659–tezacaftor–ivacaftor), was developed to restore the function of Phe508del CFTR protein in patients with cystic fibrosis. Methods We evaluated the effects of VX-659–tezacaftor–ivacaftor on the processing, trafficking, and function of Phe508del CFTR protein using human bronchial epithelial cells. A range of oral VX-659–tezacaftor–ivacaftor doses in triple combination were then evaluated in randomized, controlled, double-blind, multicenter trials involving patients with cystic fibrosis who were heterozygous for the Phe508del CFTR mutation and a minimal-function CFTR mutation (Phe508del–MF genotypes) or homozygous for the Phe508del CFTR mutation (Phe508del–Phe508del genotype). The primary end points were safety and the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV1). Results VX-659–tezacaftor–ivacaftor significantly improved the processing and trafficking of Phe508del CFTR protein as well as chloride transport in vitro. In patients, VX-659–tezacaftor–ivacaftor had an acceptable safety and side-effect profile. Most adverse events were mild or moderate. VX-659–tezacaftor–ivacaftor resulted in significant mean increases in the percentage of predicted FEV1 through day 29 (P<0.001) of up to 13.3 points in patients with Phe508del–MF genotypes; in patients with the Phe508del–Phe508del genotype already receiving tezacaftor–ivacaftor, adding VX-659 resulted in a further 9.7-point increase in the percentage of predicted FEV1. The sweat chloride concentrations and scores on the respiratory domain of the Cystic Fibrosis Questionnaire–Revised improved in both patient populations. Conclusions Robust in vitro activity of VX-659–tezacaftor–ivacaftor targeting Phe508del CFTR protein translated into improvements for patients with Phe508del–MF or Phe508del–Phe508del genotypes. VX-659 triple-combination regimens have the potential to treat the underlying cause of disease in approximately 90% of patients with cystic fibrosis. (Funded by Vertex Pharmaceuticals; VX16-659-101 and VX16-659-001 ClinicalTrials.gov numbers, NCT03224351 and NCT03029455.

Neonatal Administration of Thimerosal Causes Persistent Changes in Mu Opioid Receptors in the Rat Brain

Thimerosal added to some pediatric vaccines is suspected in pathogenesis of several neurodevelopmental disorders. Our previous study showed that thimerosal administered to suckling rats causes persistent, endogenous opioid-mediated hypoalgesia. Here we examined, using immunohistochemical staining technique, the density of μ-opioid receptors (MORs) in the brains of rats, which in the second postnatal week received four i.m. injections of thimerosal at doses 12, 240, 1,440 or 3,000 μg Hg/kg. The periaqueductal gray, caudate putamen and hippocampus were examined. Thimerosal administration caused dose-dependent statistically significant increase in MOR densities in the periaqueductal gray and caudate putamen, but decrease in the dentate gyrus, where it was accompanied by the presence of degenerating neurons and loss of synaptic vesicle marker (synaptophysin). These data document that exposure to thimerosal during early postnatal life produces lasting alterations in the densities of brain opioid receptors along with other neuropathological changes, which may disturb brain development