Viable inflationary models ending with a first-order phase transition

We investigate the parameter space of hybrid inflation models where inflation terminates via a first-order phase transition causing nucleation of bubbles. Such models experience a tension from the need to ensure nearly scale invariant density perturbations, while avoiding a near scale-invariant bubble size distribution which would conflict observations. We perform an exact analysis of the different regimes of the models, where the energy density of the inflaton field ranges from being negligible as compared to the vacuum energy to providing most of the energy for inflation. Despite recent microwave anisotropy results favouring a spectral index less than one, we find that there are still viable models that end with bubble production and can match all available observations. As a by-product of our analysis, we also provide an up-to-date assessment of the viable parameter space of Linde's original second-order hybrid model across its full parameter range.Comment: 9 pages, 7 figures. Revised version: corrections to description of the historical development of the models. v3: Minor corrections to match version accepted by PR

Quench dynamics in the Jaynes-Cummings-Hubbard and Dicke models

Both the Jaynes-Cummings-Hubbard (JCH) and Dicke models can be thought of as idealised models of a quantum battery. In this paper we numerically investigate the charging properties of both of these models. The two models differ in how the two-level systems are contained in cavities. In the Dicke model, the $N$ two-level systems are contained in a single cavity, while in the JCH model the two-level systems each have their own cavity and are able to pass photons between them. In each of these models we consider a scenario where the two-level systems start in the ground state and the coupling parameter between the photon and the two-level systems is quenched. Each of these models display a maximum charging power that scales with the size of the battery $N$ and no super charging was found. Charging power also scales with the square root of the average number of photons per two-level system $m$ for both models. Finally, in the JCH model, the power was found to charge inversely with the square root of the photon-cavity coupling $\kappa$.Comment: 6 pages, 6 figure

Diffusive and convective transfer of cytokine-inducing bacterial products across hemodialysis membranes

Diffusive and convective transfer of cytokine-inducing bacterial products across hemodialysis membranes. The widespread use of bicarbonate dialysate, and high-flux and high-efficiency dialyzers have raised concerns regarding the transmembrane passage of bacterial products from the dialysate into the blood compartment. To study the mechanisms as well as magnitude of the transmembrane transfer of bacterial products from the dialysate, we developed a computerized in vitro dialysis model which provides continuous pressure recording from the arterial, venous, dialysate inflow and outflow ports. By virtue of a computer controlled on-line infusion pump, this model permits control of ultrafiltration/backfiltration. Heparinized (10 U/ml) whole blood (150 ml) was circulated through the blood compartment for 120 minutes at 100ml/min. Bicarbonate dialysate contaminated with Pseudomonas maltophilia filtrate was circulated through the dialysate compartment at 100ml/min. A two-point pressure of +10mm of Hg (ultrafiltration) was maintained for the first 60 minutes and -10mm of Hg (backfiltration) for the next 60 minutes. Whole blood samples (10 ml) were drawn from the blood at 0, 60 and 120 minutes. Peripheral blood mononuclear cells (PBMC) harvested from these samples were incubated for 24 hours in tissue culture medium. In addition, 0.5ml samples of dialysate were collected at 0, 60 and 120 minutes and incubated with PBMC from the same donor for 24 hours. After 24 hour incubation, total cell-associated IL-1Ra and IL-1β were measured by specific radioimmunoassay. Paired experiments were performed with eight high-flux synthetic membranes (polyamide) and eight low-flux cellulose membranes (hemophan). Cytokine production is expressed as pg/2.5 million PBMC. During the mandatory ultrafiltration phase of the experiment (first hour), the production of IL-1Ra by PBMC from the blood compartment rose from 515 ± 118 to 785 ± 209 with polyamide membranes, and from 1175 ± 365 to 3865 ± 1847 with hemophan membranes, suggesting diffusive transport of bacterial products across the membrane. In contrast, at the end of the backfiltration phase (second hour), there was no further rise in the production of IL-1Ra by PBMC from the blood compartment (702 ± 123 with polyamide, and 2284 ± 886 with hemophan). The production of IL-1Ra by PBMC harvested from the blood compartment of polyamide membranes at 0, 60 and 120 minutes was lower than that with hemophan membranes (P = 0.01). In contrast to IL-1Ra, the production of IL-1β by PBMC harvested from the blood compartment with both membranes was uniformly low. The results of this study demonstrate the diffusive transfer of bacterial products across dialysis membranes. Therefore, any condition that increases diffusive transport such as dialyzers with large surface areas and high blood and dialysate flow rates could potentially increase the reverse transfer of bacterial products from the dialysate. This risk is not greater for synthetic high-flux membranes such as polyamide. Further, IL-1β is a less sensitive indicator than IL-1Ra of the transmembrane passage of cytokine-inducing substances from the dialysate to blood compartment

Seeking the Ultraviolet Ionizing Background at z~3 with the Keck Telescope

We describe the initial results of a deep long-slit emission line search for redshifted (2.7<z<4.1) Lyman-alpha. These observations are used to constrain the fluorescent Ly-alpha emission from the population of clouds whose absorption produces the higher-column-density component of the Ly-alpha forest in quasar spectra. We use the results to set an upper limit on the ultraviolet ionizing background. Our spectroscopic data obtained with the Keck II telescope at lambda/(Delta lambda FWHM)~2000 reveals no candidate Ly-alpha emission over the wavelength range of 4500-6200 Ang along a 3 arcmin slit in a 5400 s integration. Our 3 sigma upper bound on the mean intensity of the ionizing background at the Lyman limit is J(nu 0) < 2E-21 erg/s/cm**2/Hz/sr for 2.7<z<3.1 (where we are most sensitive), assuming Lyman limit systems have typical radii of 70 kpc (q_0=0.5, H_0=50 km/s/Mpc). This constraint is more than an order of magnitude more stringent than any previously published direct limit. However, it is still a factor of three above the ultraviolet background level expected due to the integrated light of known quasars at z~3. This pilot study confirms the conclusion of Gould \& Weinberg (1996) that integrations of several hours on a 10-m class telescope should be capable of measuring J(nu 0) at high redshift.Comment: 22 pages, 2 postscipt figures. Latex requires aaspp4.sty and epsf.sty (included). Accepted for publication in the Astronomical Journal (Nov 1998

Raloxifene Enhances Material-Level Mechanical Properties of Femoral Cortical and Trabecular Bone

We have previously documented that raloxifene enhances the mechanical properties of dog vertebrae independent of changes in bone mass, suggesting a positive effect of raloxifene on material-level mechanical properties. The goal of this study was to determine the separate effects of raloxifene on the material-level mechanical properties of trabecular and cortical bone from the femur of beagle dogs. Skeletally mature female beagles (n = 12 per group) were treated daily for 1 yr with oral doses of vehicle or raloxifene (0.50 mg/kg d). Trabecular bone mechanical properties were measured at the femoral neck using reduced platen compression, a method that allows the trabecular bone to be tested without coring specimens. Cortical bone properties were assessed on prismatic beam specimens machined from the femoral diaphysis using both monotonic and dynamic (cyclic relaxation) four-point bending tests. Trabecular bone from raloxifene-treated animals had significantly higher ultimate stress (+130%), modulus (+89%), and toughness (+152%) compared with vehicle-treated animals. Cortical bone from raloxifene-treated animals had significantly greater toughness (+62%) compared with vehicle, primarily as a function of increased postyield displacement (+100%). There was no significant difference between groups in the percentage of stiffness loss during cortical bone cyclic relaxation tests. These results are consistent with previous data from the vertebrae of these same animals, showing raloxifene has positive effects on biomechanical properties independent of changes in bone volume/density. This may help explain how raloxifene reduces osteoporotic fractures despite modest changes in bone mass.This work was supported by National Institutes of Health Grants AR047838 and AR007581 and a research grant from Lilly Research Laboratories. This investigation used an animal facility constructed with support from Research Facilities Improvement Program Grant Number C06 RR10601-01 from the National Center for Research Resources, National Institutes of Health. Disclosure Summary: M.R.A. has research contracts from Eli Lilly and the Alliance for Better Bone Health. D.B.B. has research contracts from Eli Lilly, the Alliance for Better Bone Health, and Amgen; owns stock in Amgen, Eli Lilly, Pfizer, and Glaxo SmithKline; and is a speaker/consultant for Merck, Eli Lilly, the Alliance for Better Bone Health, and Amgen. A.S.K. and M.C.K. have a family member employed by Eli Lilly. H.A.H. and W.A.H. have nothing to declare

Interaction with surrounding normal epithelial cells influences signalling pathways and behaviour of Src-transformed cells

At the initial stage of carcinogenesis, transformation occurs in a single cell within an epithelial sheet. However, it remains unknown what happens at the boundary between normal and transformed cells. Using Madin-Darby canine kidney (MDCK) cells transformed with temperature-sensitive v-Src, we have examined the interface between normal and Src-transformed epithelial cells. We show that Src-transformed cells are apically extruded when surrounded by normal cells, but not when Src cells alone are cultured, suggesting that apical extrusion occurs in a cell-context-dependent manner. We also observe apical extrusion of Src-transformed cells in the enveloping layer of zebrafish gastrula embryos. When Src-transformed MDCK cells are surrounded by normal MDCK cells, myosin-II and focal adhesion kinase (FAK) are activated in Src cells, which further activate downstream mitogen-activated protein kinase (MAPK). Importantly, activation of these signalling pathways depends on the presence of surrounding normal cells and plays a crucial role in apical extrusion of Src cells. Collectively, these results indicate that interaction with surrounding normal epithelial cells influences the signalling pathways and behaviour of Src-transformed cells

miRNAome analysis of the mammalian neuronal nicotinic acetylcholine receptor gene family

Nicotine binds to and activates a family of ligand-gated ion channels, neuronal nicotinic acetylcholine receptors (nAChRs). Chronic nicotine exposure alters the expression of various nAChR subtypes, which likely contributes to nicotine dependence; however, the underlying mechanisms regulating these changes remain unclear. A growing body of evidence indicates that microRNAs (miRNAs) may be involved in nAChR regulation. Using bioinformatics, miRNA library screening, site-directed mutagenesis, and gene expression analysis, we have identified a limited number of miRNAs that functionally interact with the 3\u27-untranslated regions (3\u27 UTRs) of mammalian neuronal nAChR subunit genes. In silico analyses revealed specific, evolutionarily conserved sites within the 3\u27 UTRs through which the miRNAs regulate gene expression. Mutating these sites disrupted miRNA regulation confirming the in silico predictions. In addition, the miRNAs that target nAChR 3\u27 UTRs are expressed in mouse brain and are regulated by chronic nicotine exposure. Furthermore, we show that expression of one of these miRNAs, miR-542-3p, is modulated by nicotine within the mesocorticolimbic reward pathway. Importantly, overexpression of miR-542-3p led to a decrease in the protein levels of its target, the nAChR beta2 subunit. Bioinformatic analysis suggests that a number of the miRNAs play a general role in regulating cholinergic signaling. Our results provide evidence for a novel mode of nicotine-mediated regulation of the mammalian nAChR gene family

miRNAome analysis of the mammalian neuronal nicotinic acetylcholine receptor gene family

Nicotine binds to and activates a family of ligand-gated ion channels, neuronal nicotinic acetylcholine receptors (nAChRs). Chronic nicotine exposure alters the expression of various nAChR subtypes, which likely contributes to nicotine dependence; however, the underlying mechanisms regulating these changes remain unclear. A growing body of evidence indicates that microRNAs (miRNAs) may be involved in nAChR regulation. Using bioinformatics, miRNA library screening, site-directed mutagenesis, and gene expression analysis, we have identified a limited number of miRNAs that functionally interact with the 3\u27-untranslated regions (3\u27 UTRs) of mammalian neuronal nAChR subunit genes. In silico analyses revealed specific, evolutionarily conserved sites within the 3\u27 UTRs through which the miRNAs regulate gene expression. Mutating these sites disrupted miRNA regulation confirming the in silico predictions. In addition, the miRNAs that target nAChR 3\u27 UTRs are expressed in mouse brain and are regulated by chronic nicotine exposure. Furthermore, we show that expression of one of these miRNAs, miR-542-3p, is modulated by nicotine within the mesocorticolimbic reward pathway. Importantly, overexpression of miR-542-3p led to a decrease in the protein levels of its target, the nAChR beta2 subunit. Bioinformatic analysis suggests that a number of the miRNAs play a general role in regulating cholinergic signaling. Our results provide evidence for a novel mode of nicotine-mediated regulation of the mammalian nAChR gene family

Comparative venom-gland transcriptomics and venom proteomics of four Sidewinder Rattlesnake (\u3ci\u3eCrotalus cerastes\u3c/i\u3e) lineages reveal little differential expression despite individual variation

Changes in gene expression can rapidly influence adaptive traits in the early stages of lineage diversification. Venom is an adaptive trait comprised of numerous toxins used for prey capture and defense. Snake venoms can vary widely between conspecific populations, but the influence of lineage diversification on such compositional differences are unknown. To explore venom differentiation in the early stages of lineage diversification, we used RNA-seq and mass spectrometry to characterize Sidewinder Rattlesnake (Crotalus cerastes) venom. We generated the first venom-gland transcriptomes and complementary venom proteomes for eight individuals collected across the United States and tested for expression differences across life history traits and between subspecific, mitochondrial, and phylotranscriptomic hypotheses. Sidewinder venom was comprised primarily of hemorrhagic toxins, with few cases of differential expression attributable to life history or lineage hypotheses. However, phylotranscriptomic lineage comparisons more than doubled instances of significant expression differences compared to all other factors. Nevertheless, only 6.4% of toxins were differentially expressed overall, suggesting that shallow divergence has not led to major changes in Sidewinder venom composition. Our results demonstrate the need for consensus venom-gland transcriptomes based on multiple individuals and highlight the potential for discrepancies in differential expression between different phylogenetic hypotheses

The African Women's Protocol: Bringing Attention to Reproductive Rights and the MDGs

Andrew Gibbs and colleagues discuss the African Women's Protocol, a framework for ensuring reproductive rights are supported throughout the continent and for supporting interventions to improve women's reproductive health, including the MDGs