Maximizing Revenue in the Presence of Intermediaries

We study the mechanism design problem of selling $k$ items to unit-demand buyers with private valuations for the items. A buyer either participates directly in the auction or is represented by an intermediary, who represents a subset of buyers. Our goal is to design robust mechanisms that are independent of the demand structure (i.e. how the buyers are partitioned across intermediaries), and perform well under a wide variety of possible contracts between intermediaries and buyers. We first study the case of $k$ identical items where each buyer draws its private valuation for an item i.i.d. from a known $\lambda$-regular distribution. We construct a robust mechanism that, independent of the demand structure and under certain conditions on the contracts between intermediaries and buyers, obtains a constant factor of the revenue that the mechanism designer could obtain had she known the buyers' valuations. In other words, our mechanism's expected revenue achieves a constant factor of the optimal welfare, regardless of the demand structure. Our mechanism is a simple posted-price mechanism that sets a take-it-or-leave-it per-item price that depends on $k$ and the total number of buyers, but does not depend on the demand structure or the downstream contracts. Next we generalize our result to the case when the items are not identical. We assume that the item valuations are separable. For this case, we design a mechanism that obtains at least a constant fraction of the optimal welfare, by using a menu of posted prices. This mechanism is also independent of the demand structure, but makes a relatively stronger assumption on the contracts between intermediaries and buyers, namely that each intermediary prefers outcomes with a higher sum of utilities of the subset of buyers represented by it

Cassettes for PCR-mediated gene tagging in Candida albicans utilizing nourseothricin resistance

addresses: Biosciences, College of Life and Environmental Sciences, University of Exeter, UK.types: Journal Article; Research Support, Non-U.S. Gov't; Validation StudiesThis is the author's post-print version of an article published in Yeast, 2011, Vol. 28, Issue 12, pp. 833 – 841 Copyright © Wiley-Blackwell 2011. The definitive version is available at www3.interscience.wiley.comIn recent years a number of molecular tools have been reported for use in the human fungal pathogen Candida albicans, including PCR-mediated approaches for gene disruption, conditional expression and epitope tagging. Traditionally these methods have utilized auxotrophic markers; however, the availability of auxotrophic markers can be limiting and in some instances their use may also impact on the interpretation of results. As a result, the use of positive selection markers has now become more commonplace. Here we report the development and validation of a set of cassettes for PCR-mediated gene tagging and overexpression studies utilizing the nourseothricin resistance (CaNAT1) positive selection marker. In particular we have produced cassettes containing yeast-enhanced GFP, YFP, CFP, RFP and a combined V5-6xHis epitope tag. The cassettes are engineered for use in PCR-mediated gene tagging strategies where insertion is targeted to the 3' end of the gene of interest. In addition, to facilitate protein functional analysis and genetic suppression studies through the use of overexpression, we have also constructed a promoter replacement cassette containing the ENO1 promoter which is known to be expressed at a high level. These cassettes expand on the range of molecular tools available for working with C. albicans and may also be used in other Candida species that display sensitivity to nourseothricin

Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

Cost-Effective Strategies for Mitigating a Future Influenza Pandemic with H1N1 2009 Characteristics

Background: We performed an analysis of the cost-effectiveness of pandemic intervention strategies using a detailed, individual-based simulation model of a community in Australia together with health outcome data of infected individuals gathered during 2009–2010. The aim was to examine the cost-effectiveness of a range of interventions to determine the most cost-effective strategies suitable for a future pandemic with H1N1 2009 characteristics. Methodology/Principal Findings: Using transmissibility, age-stratified attack rates and health outcomes determined from H1N1 2009 data, we determined that the most cost-effective strategies involved treatment and household prophylaxis using antiviral drugs combined with limited duration school closure, with costs ranging from $632 to$777 per case prevented. When school closure was used as a sole intervention we found the use of limited duration school closure to be significantly more cost-effective compared to continuous school closure, a result with applicability to countries with limited access to antiviral drugs. Other social distancing strategies, such as reduced workplace attendance, were found to be costly due to productivity losses. Conclusion: The mild severity (low hospitalisation and case fatality rates) and low transmissibility of H1N1 2009 meant that health treatment costs were dominated by the higher productivity losses arising from workplace absence due to illness and childcare requirements following school closure. Further analysis for higher transmissibility but with the same, mild severit

Analysis of clinical and environmental Candida parapsilosis isolates by microsatellite genotyping – a tool for hospital infections surveillance

Candida parapsilosis emerged as an important opportunistic pathogen, causing candidaemia worldwide. Nosocomial outbreaks triggered by this species have been frequently described, particularly in cancer patients. For a better understanding of its epidemiology, several typing methods are used and microsatellite analysis has been reported as highly discriminant. The main objective of this work was to study C. parapsilosis isolates by application of microsatellite genotyping to distinguish epidemiologically related strains, compare clinical and environmental isolates and determine possible routes of dispersion of the isolates in the hospital setting. A total of 129 C. parapsilosis isolates from different origins, including hospital environment and hands of healthcare workers, were genotyped using four microsatellite markers. The isolates were recovered from different health institutions. Analysis of C. parapsilosis isolates from hospital environment showed great genotypic diversity; however, the same or very similar genotypes were also found. The same multilocus genotype was shared by isolates recovered from the hand of a healthcare worker, from the hospital environment and from patients of the same healthcare institution, suggesting that these could be possible routes of transmission and that infections due to C. parapsilosis may be mainly related with exogenous transmission to the patient. Examination of sequential isolates from the same patients showed that colonizing and bloodstream isolates had the same multilocus genotype in the majority of cases. We demonstrate that this typing method is able to distinguish clonal clusters from genetically unrelated genotypes and can be a valuable tool to support epidemiologic investigations in the hospital setting.This research was supported by FCT/MEC, Portugal through Portuguese funds (PIDDAC) - Pest-OE/BIA/UI4050/2014 (CBMA), University of Minho. Raquel Sabino was financially supported by a fellowship from FCT, Portugal (contract BD/22100/2005).info:eu-repo/semantics/publishedVersio

Acute Intermittent Porphyria: Pathophysiology and Treatment

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90337/1/j.1875-9114.1984.tb03340.x.pd

Lack of Trehalose Accelerates H2O2-Induced Candida albicans Apoptosis through Regulating Ca2+ Signaling Pathway and Caspase Activity

Trehalose is a non-reducing disaccharide and can be accumulated in response to heat or oxidative stresses in Candida albicans. Here we showed that a C. albicans tps1Δ mutant, which is deficient in trehalose synthesis, exhibited increased apoptosis rate upon H2O2 treatment together with an increase of intracellular Ca2+ level and caspase activity. When the intracellular Ca2+ level was stimulated by adding CaCl2 or A23187, both the apoptosis rate and caspase activity were increased. In contrast, the presence of two calcium chelators, EGTA and BAPTA, could attenuate these effects. Moreover, we investigated the role of Ca2+ pathway in C. albicans apoptosis and found that both calcineurin and the calcineurin-dependent transcription factor, Crz1p, mutants showed decreased apoptosis and caspase activity upon H2O2 treatment compared to the wild-type cells. Expression of CaMCA1, the only gene found encoding a C. albicans metacaspase, in calcineurin-deleted or Crz1p-deleted cells restored the cell sensitivity to H2O2. Our results suggest that Ca2+ and its downstream calcineurin/Crz1p/CaMCA1 pathway are involved in H2O2 -induced C. albicans apoptosis. Inhibition of this pathway might be the mechanism for the protective role of trehalose in C. albicans