Read-across of 90-Day Rat Oral Repeated-Dose Toxicity: A Case Study for Selected 2-Alkyl-1-alkanols

2-Alkyl-1-alkanols offer an example whereby the category approach to read-across can be used to predict repeated-dose toxicity for a variety of derivatives. Specifically, the NOAELs of 125 mg/kg bw/d for 2-ethyl-1-hexanol and 2-propyl-1-heptanol, the source substances, can be read across with confidence to untested 2-alkyl-1-alkanols in the C5 to C13 category based on a LOAEL of low systemic toxicity. These branched alcohols, while non-reactive and exhibiting unspecific, reversible simple anaesthesia or nonpolar narcosis mode of toxic action, have metabolic pathways that have significance to repeated-dose toxic potency. In this case study, the chemical category is limited to the readily bioavailable analogues. The read-across premise includes rapid absorption via the gastrointestinal tract, distribution in the circulatory system and first-pass metabolism in the liver via Phase 2 glucuronidation prior to urinary elimination. 2-Ethyl-1-hexanol and 2-propyl-1-heptanol, the source substances, have high quality 90-day oral repeated-dose toxicity studies (OECD TG 408) that exhibit qualitative and quantitative consistency. Findings include only mild changes consistent with low-grade effects including decreased body weight and slightly increased liver weight, which in some cases is accompanied by clinical chemical and haematological changes but generally without concurrent histopathological effects at the LOAEL. These findings are supported by results from the TG 408 assessment of a semi-defined mixture of isotridecanols. Chemical similarity between the analogues is readily defined and data uncertainty associated with toxicokinetic and toxicodynamics similarities are low. Uncertainty associated with mechanistic relevance and completeness of the read-across is reduced by the concordance of in vivo and in vitro results, as well as high throughput and in silico methods data. As shown in detail, the 90-day rat oral repeated-dose NOAEL values for the two source substances can be read across to fill the data gaps of the untested analogues in this category with uncertainty deemed equivalent to results from a TG 408 assessment

Coupling ultracold atoms to mechanical oscillators

In this article we discuss and compare different ways to engineer an interface between ultracold atoms and micro- and nanomechanical oscillators. We start by analyzing a direct mechanical coupling of a single atom or ion to a mechanical oscillator and show that the very different masses of the two systems place a limit on the achievable coupling constant in this scheme. We then discuss several promising strategies for enhancing the coupling: collective enhancement by using a large number of atoms in an optical lattice in free space, coupling schemes based on high-finesse optical cavities, and coupling to atomic internal states. Throughout the manuscript we discuss both theoretical proposals and first experimental implementations.Comment: 19 pages, 9 figure

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair