576 research outputs found
Sequential Posted Price Mechanisms with Correlated Valuations
We study the revenue performance of sequential posted price mechanisms and
some natural extensions, for a general setting where the valuations of the
buyers are drawn from a correlated distribution. Sequential posted price
mechanisms are conceptually simple mechanisms that work by proposing a
take-it-or-leave-it offer to each buyer. We apply sequential posted price
mechanisms to single-parameter multi-unit settings in which each buyer demands
only one item and the mechanism can assign the service to at most k of the
buyers. For standard sequential posted price mechanisms, we prove that with the
valuation distribution having finite support, no sequential posted price
mechanism can extract a constant fraction of the optimal expected revenue, even
with unlimited supply. We extend this result to the the case of a continuous
valuation distribution when various standard assumptions hold simultaneously.
In fact, it turns out that the best fraction of the optimal revenue that is
extractable by a sequential posted price mechanism is proportional to ratio of
the highest and lowest possible valuation. We prove that for two simple
generalizations of these mechanisms, a better revenue performance can be
achieved: if the sequential posted price mechanism has for each buyer the
option of either proposing an offer or asking the buyer for its valuation, then
a Omega(1/max{1,d}) fraction of the optimal revenue can be extracted, where d
denotes the degree of dependence of the valuations, ranging from complete
independence (d=0) to arbitrary dependence (d=n-1). Moreover, when we
generalize the sequential posted price mechanisms further, such that the
mechanism has the ability to make a take-it-or-leave-it offer to the i-th buyer
that depends on the valuations of all buyers except i's, we prove that a
constant fraction (2-sqrt{e})/4~0.088 of the optimal revenue can be always be
extracted.Comment: 29 pages, To appear in WINE 201
The origin of [C II] 157 μm emission in a five-component interstellar medium : the case of NGC 3184 and NGC 628
With its relatively low ionization potential, C+ can be found throughout the interstellar medium (ISM) and provides one of the main cooling channels of the ISM via the [C II] 157 mu m emission. While the strength of the [C II] line correlates with the star formation rate, the contributions of the various gas phases to the [C II] emission on galactic scales are not well established. In this study we establish an empirical multi-component model of the ISM, including dense H II regions, dense photon dissociation regions (PDRs), the warm ionized medium (WIM), low density and G(0). surfaces of molecular clouds (SfMCs), and the cold neutral medium (CNM). We test our model on ten luminous regions within the two nearby galaxies NGC 3184 and NGC 628. on angular scales of 500-600 pc. Both galaxies are part of the Herschel. key program. KINGFISH,. and are complemented by a large set of ancillary ground-and space-based data. The five modeled phases together reproduce the observed [C II] emission quite well, overpredicting the total flux slightly (about 45%) averaged over all regions. We find that dense PDRs are the dominating component, contributing 68% of the [C II] flux on average, followed by the WIM and the SfMCs, with mean contributions of about half of the contribution from dense PDRs, each. CNM and dense H II regions are only minor contributors with less than 5% each. These estimates are averaged over the selected regions, but the relative contributions of the various phases to the [C II] flux vary significantly between these regions
Identification of novel macrolides with antibacterial, anti-inflammatory and type I and III IFN-augmenting activity in airway epithelium
BACKGROUND: Exacerbations of asthma and COPD are triggered by rhinoviruses. Uncontrolled inflammatory pathways, pathogenic bacterial burden and impaired antiviral immunity are thought to be important factors in disease severity and duration. Macrolides including azithromycin are often used to treat the above diseases, but exhibit variable levels of efficacy. Inhaled corticosteroids are also readily used in treatment, but may lack specificity. Ideally, new treatment alternatives should suppress unwanted inflammation, but spare beneficial antiviral immunity. METHODS: In the present study, we screened 225 novel macrolides and tested them for enhanced antiviral activity against rhinovirus, as well as anti-inflammatory activity and activity against Gram-positive and Gram-negative bacteria. Primary bronchial epithelial cells were grown from 10 asthmatic individuals and the effects of macrolides on rhinovirus replication were also examined. Another 30 structurally similar macrolides were also examined. RESULTS: The oleandomycin derivative Mac5, compared with azithromycin, showed superior induction (up to 5-fold, EC50 = 5-11 μM) of rhinovirus-induced type I IFNβ, type III IFNλ1 and type III IFNλ2/3 mRNA and the IFN-stimulated genes viperin and MxA, yet had no effect on IL-6 and IL-8 mRNA. Mac5 also suppressed rhinovirus replication at 48 h, proving antiviral activity. Mac5 showed antibacterial activity against Gram-positive Streptococcus pneumoniae; however, it did not have any antibacterial properties compared with azithromycin when used against Gram-negative Escherichia coli (as a model organism) and also the respiratory pathogens Pseudomonas aeruginosa and non-typeable Haemophilus influenzae. Further non-toxic Mac5 derivatives were identified with various anti-inflammatory, antiviral and antibacterial activities. CONCLUSIONS: The data support the idea that macrolides have antiviral properties through a mechanism that is yet to be ascertained. We also provide evidence that macrolides can be developed with anti-inflammatory, antibacterial and antiviral activity and show surprising versatility depending on the clinical need
Dapagliflozin-lowered blood glucose reduces respiratory Pseudomonas aeruginosa infection in diabetic mice.
BACKGROUND AND PURPOSE: Hyperglycaemia increases glucose concentrations in airway surface liquid and increases the risk of pulmonary Pseudomonas aeruginosa infection. We determined whether reduction of blood and airway glucose concentrations by the anti-diabetic drug dapagliflozin could reduce P. aeruginosa growth/survival in the lungs of diabetic mice. EXPERIMENTAL APPROACH: The effect of dapagliflozin on blood and airway glucose concentration, the inflammatory response and infection were investigated in C57BL/6J (wild type, WT) or leptin receptor-deficient (db/db) mice, treated orally with dapagliflozin prior to intranasal dosing with LPS or inoculation with P. aeruginosa. Pulmonary glucose transport and fluid absorption were investigated in Wistar rats using the perfused fluid-filled lung technique. KEY RESULTS: Fasting blood, airway glucose and lactate concentrations were elevated in the db/db mouse lung. LPS challenge increased inflammatory cells in bronchoalveolar lavage fluid from WT and db/db mice with and without dapagliflozin treatment. P. aeruginosa colony-forming units (CFU) were increased in db/db lungs. Pretreatment with dapagliflozin reduced blood and bronchoalveolar lavage glucose concentrations and P. aeruginosa CFU in db/db mice towards those seen in WT. Dapagliflozin had no adverse effects on the inflammatory response in the mouse or pulmonary glucose transport or fluid absorption in the rat lung. CONCLUSION AND IMPLICATIONS: Pharmacological lowering of blood glucose with dapagliflozin effectively reduced P. aeruginosa infection in the lungs of diabetic mice and had no adverse pulmonary effects in the rat. Dapagliflozin has potential to reduce the use, or augment the effect, of antimicrobials in the prevention or treatment of pulmonary infection
The emission by dust and stars of nearby galaxies in the Herschel KINGFISH survey
Using new far-infrared imaging from the Herschel Space Observatory with ancillary data from ultraviolet (UV) to submillimeter wavelengths, we estimate the total emission from dust and stars of 62 nearby galaxies in the KINGFISH survey in a way that is as empirical and model independent as possible. We collect and exploit these data in order to measure from the spectral energy distributions (SEDs) precisely how much stellar radiation is intercepted and re-radiated by dust, and how this quantity varies with galaxy properties. By including SPIRE data, we are more sensitive to emission from cold dust grains than previous analyses at shorter wavelengths, allowing for more accurate estimates of dust temperatures and masses. The dust/stellar flux ratio, which we measure by integrating the SEDs, has a range of nearly three decades (from 10(-2.2) to 10(0.5)). The inclusion of SPIRE data shows that estimates based on data not reaching these far-IR wavelengths are biased low by 17% on average. We find that the dust/stellar flux ratio varies with morphology and total infrared (IR) luminosity, with dwarf galaxies having faint luminosities, spirals having relatively high dust/stellar ratios and IR luminosities, and some early types having low dust/stellar ratios. We also find that dust/stellar flux ratios are related to gas-phase metallicity ((log(f(dust)/f(*)) over bar) = -0.66 +/- 0.08 and -0.22 +/- 0.12 for metal-poor and intermediate-metallicity galaxies, respectively), while the dust/stellar mass ratios are less so (differing by approximate to 0.2 dex); the more metal-rich galaxies span a much wider range of the flux ratios. In addition, the substantial scatter between dust/stellar flux and dust/stellar mass indicates that the former is a poor proxy of the latter. Comparing the dust/stellar flux ratios and dust temperatures, we also show that early types tend to have slightly warmer temperatures (by up to 5 K) than spiral galaxies, which may be due to more intense interstellar radiation fields, or possibly to different dust grain compositions. Finally, we show that early types and early-type spirals have a strong correlation between the dust/stellar flux ratio and specific star formation rate, which suggests that the relatively bright far-IR emission of some of these galaxies is due to ongoing (if limited) star formation as well as to the radiation field from older stars, which is heating the dust grains
Resolving the far-IR line deficit : photoelectric heating and far-IR line cooling in NGC 1097 and NGC 4559
The physical state of interstellar gas and dust is dependent on the processes which heat and cool this medium. To probe heating and cooling of the interstellar medium over a large range of infrared surface brightness, on sub-kiloparsec scales, we employ line maps of [C II] 158 mu m, [O I] 63 mu m, and [N II] 122 mu m in NGC 1097 and NGC 4559, obtained with the Photodetector Array Camera & Spectrometer on board Herschel. We matched new observations to existing Spitzer Infrared Spectrograph data that trace the total emission of polycyclic aromatic hydrocarbons (PAHs). We confirm at small scales in these galaxies that the canonical measure of photoelectric heating efficiency, ([C II] + [O I])/TIR, decreases as the far-infrared (far-IR) color, nu f(nu)(70 mu m) nu f(nu)(100 mu m), increases. In contrast, the ratio of far-IR cooling to total PAH emission, ([C II] + [O I])/PAH, is a near constant similar to 6% over a wide range of far-IR color, 0.5 , derived from models of the IR spectral energy distribution. Emission from regions that exhibit a line deficit is characterized by an intense radiation field, indicating that small grains are susceptible to ionization effects. We note that there is a shift in the 7.7/11.3 mu m PAH ratio in regions that exhibit a deficit in ([C II] + [O I])/PAH, suggesting that small grains are ionized in these environments
How to survey displaced workers in Switzerland ? Sources of bias and ways around them
Studying career outcomes after job loss is challenging because individually displaced worker form a self-selected group. Indeed, the same factors causing the workers to lose their jobs, such as lack of motivation, may also reduce their re-employment prospects. Using data from plant closures where all workers were displaced irrespective of their individual characteristics offers a way around this selection bias. There is no systematic data collection on workers displaced by plant closure in Switzerland. Accordingly, we conducted our own survey on 1200 manufacturing workers who had lost their job 2 years earlier. The analysis of observational data gives rise to a set of methodological challenges, in particular nonresponse bias. Our survey addressed this issue by mixing data collection modes and repeating contact attempts. In addition, we combined the survey data with data from the public unemployment register to examine the extent of nonresponse bias. Our analysis suggests that some of our adjustments helped to reduce bias. Repeated contact attempts increased the response rate, but did not reduce nonresponse bias. In contrast, using telephone interviews in addition to paper questionnaires helped to substantially improve the participation of typically underrepresented subgroups. However, the survey respondents still differ from nonrespondents in terms of age, education and occupation. Interestingly, these differences have no significant impact on the substantial conclusion about displaced workers' re-employment prospects
Volunteer Bias in Recruitment, Retention, and Blood Sample Donation in a Randomised Controlled Trial Involving Mothers and Their Children at Six Months and Two Years: A Longitudinal Analysis
BACKGROUND: The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not. METHODS AND RESULTS: This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i) As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13-0.67 and 0.20,0.09-0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50-0.93 and 0.55,0.28-1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57-0.92 and 0.43,0.22-0.83). ii) Mothers interested in probiotics or research or reporting infants' adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9-13.1%) to 4.6%(-1.4-+10.5%), and OR from 0.40(0.18-0.91) to 0.56(0.26-1.21). Other findings were unchanged. CONCLUSIONS: Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome. TRIAL REGISTRATION: This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children
Whole mitochondrial genomes unveil the impact of domestication on goat matrilineal variability
Background: The current extensive use of the domestic goat (Capra hircus) is the result of its medium size and high adaptability as multiple breeds. The extent to which its genetic variability was influenced by early domestication practices is largely unknown. A common standard by which to analyze maternally-inherited variability of livestock species is through complete sequencing of the entire mitogenome (mitochondrial DNA, mtDNA).
Results: We present the first extensive survey of goat mitogenomic variability based on 84 complete sequences selected from an initial collection of 758 samples that represent 60 different breeds of C. hircus, as well as its wild sister species, bezoar (Capra aegagrus) from Iran. Our phylogenetic analyses dated the most recent common ancestor of C. hircus to ~460,000 years (ka) ago and identified five distinctive domestic haplogroups (A, B1, C1a, D1 and G). More than 90 % of goats examined were in haplogroup A. These domestic lineages are predominantly nested within C. aegagrus branches, diverged concomitantly at the interface between the Epipaleolithic and early Neolithic periods, and underwent a dramatic expansion starting from ~12–10 ka ago.
Conclusions: Domestic goat mitogenomes descended from a small number of founding haplotypes that underwent domestication after surviving the last glacial maximum in the Near Eastern refuges. All modern haplotypes A probably descended from a single (or at most a few closely related) female C. aegagrus. Zooarchaelogical data indicate that domestication first occurred in Southeastern Anatolia. Goats accompanying the first Neolithic migration waves into the Mediterranean were already characterized by two ancestral A and C variants. The ancient separation of the C branch (~130 ka ago) suggests a genetically distinct population that could have been involved in a second event of domestication. The novel diagnostic mutational motifs defined here, which distinguish wild and domestic haplogroups, could be used to understand phylogenetic relationships among modern breeds and ancient remains and to evaluate whether selection differentially affected mitochondrial genome variants during the development of economically important breeds
Biodiversity in urban gardens: assessing the accuracy of citizen science data on garden hedgehogs
Urban gardens provide a rich habitat for species that are declining in rural areas. However, collecting data in gardens can be logistically-challenging, time-consuming and intrusive to residents. This study examines the potential of citizen scientists to record hedgehog sightings and collect habitat data within their own gardens using an online questionnaire. Focussing on a charismatic species meant that the number of responses was high (516 responses were obtained in 6 weeks, with a ~ 50:50% split between gardens
with and without hedgehog sightings). While many factors commonly thought to influence hedgehog
presence (e.g. compost heaps) were present in many hedgehog-frequented gardens, they were not discriminatory as they were also found in gardens where hedgehogs were not seen. Respondents were most likely to have seen hedgehogs in their garden if they had also seen hedgehogs elsewhere in their neighbourhood. However, primary fieldwork using hedgehog ‘footprint tunnels’ showed that hedgehogs were found to be just as prevalent in gardens in which hedgehogs had previously been reported as gardens where they had not been reported. Combining these results indicates that hedgehogs may be more common in urban and semi-urban gardens than previously believed, and that casual volunteer records of hedgehogs may be influenced more by the observer than by habitat preferences of the animal. When verified, volunteer records can provide useful information, but care is needed in interpreting these data
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