Steady‐state pharmacokinetics of delavirdine in HIV‐positive patients: Effect on erythromycin breath test

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109837/1/cptclpt199754.pd

Ice structures, patterns, and processes: A view across the ice-fields

We look ahead from the frontiers of research on ice dynamics in its broadest sense; on the structures of ice, the patterns or morphologies it may assume, and the physical and chemical processes in which it is involved. We highlight open questions in the various fields of ice research in nature; ranging from terrestrial and oceanic ice on Earth, to ice in the atmosphere, to ice on other solar system bodies and in interstellar space

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

CMB-S4---the next-generation ground-based cosmic microwave background (CMB) experiment---is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semi-analytic projection tool, targeted explicitly towards optimizing constraints on the tensor-to-scalar ratio, $r$, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2--3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments given a desired scientific goal. To form a closed-loop process, we couple this semi-analytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for $r > 0.003$ at greater than $5\sigma$, or, in the absence of a detection, of reaching an upper limit of $r < 0.001$ at $95\%$ CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note: text overlap with arXiv:1907.0447

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

Abstract: CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL

Anxiogenic and stressor effects of the hypothalamic neuropeptide RFRP-3 are overcome by the NPFFR antagonist GJ14

RFamide-related peptide-3 (RFRP-3) is a recently discovered neuropeptide that has been proposed to play a role in the stress response. We aimed to elucidate the role of RFRP-3 and its receptor, NPFF1R, in modulation of stress and anxiety responses. To achieve this, we developed a new NPFF1R antagonist, since our results showed that the only commercially available putative antagonist, RF9 is in fact an agonist at both NPFF1R and the kisspeptin receptor, KISS1R. We report here the identification and pharmacological characterization of GJ14, a true NPFFR antagonist. In in vivo tests of hypothalamic-pituitary-adrenal (HPA) axis function, GJ14 completely blocked RFRP-3-induced corticosterone release and neuronal activation in corticotropin-releasing hormone (CRH) neurons. Furthermore, chronic infusion of GJ14 led to anxiolytic-like behavior while RFRP-3 infusion had anxiogenic effects. Mice receiving chronic RFRP-3 infusion also had higher basal circulating corticosterone levels. These results indicate a stimulatory action of RFRP-3 on the HPA axis, consistent with the dense expression of NPFF1R in the vicinity of CRH neurons. Importantly, co-infusion of RFRP-3 and GJ14 completely reversed the anxiogenic and HPA axis-stimulatory effects of RFRP-3. Here, we have established the role of RFRP-3 as a regulator of stress and anxiety. We also show that GJ14 can reverse the effects of RFRP-3 both in vitro and in vivo. Infusion of GJ14 causes anxiolysis, revealing a novel potential target for treating anxiety disorders

Abstracts of the 22nd International Isotope Society (UK Group) Symposium: synthesis and applications of labelled compounds 2013

Meeting Summary The 22nd annual symposium of the International Isotope Society's United Kingdom Group took place at the Møller Centre, Churchill College, Cambridge, UK, on Friday, 18 October 2013. The meeting was attended by 65 delegates from academia and industry; the life sciences; and chemical, radiochemical and scientific instrument suppliers.Delegates were welcomed by Dr Ken Lawrie (GlaxoSmithKline, UK, chair of the IIS UK group). The subsequent scientific programme consisted of oral and poster presentations on isotopic chemistry and applications of labelled compounds, or of chemistry with potential implications for isotopic synthesis. Both short‐lived and long‐lived isotopes were represented, as were stable isotopes. The symposium programme was divided into a morning session chaired by Dr Karl Cable (GlaxoSmithKline, UK) and afternoon sessions chaired by Mr Mike Chappelle (Quotient Biosciences, UK) and by Dr Nick Bushby (AstraZeneca, UK). The UK meeting concluded with remarks from Dr Ken Lawrie (GlaxoSmithKline, UK)