735 research outputs found
The value of a "free" customer
We study the problem of a firm that faces asymmetric information about the productivity of its potential workers. In our framework, a worker’s productivity is either assigned by nature at birth, or determined by an unobservable initial action of the worker that has persistent effects over time. We provide a characterization of the optimal dynamic compensation scheme that attracts only high productivity workers: consumption –regardless of time period– is ranked according to likelihood ratios of output histories, and the inverse of the marginal utility of consumption satisfies the martingale property derived in Rogerson (1985). However, in the case of i.i.d. output and square root utility we show that, contrary to the features of the optimal contract for a repeated moral hazard problem, the level and the variance of consumption are negatively correlated, due to the influence of early luck into future compensation. Moreover, in this example long-term inequality is lower under persistent private informationCustomer lifetime value, CRM, Dynamic programming, GMM Estimation
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Nano-vehicles give new lease of life to existing antimicrobials.
Antibiotic resistance has become one of the greatest challenges for modern medicine, and new approaches for the treatment of bacterial infections are urgently needed to avoid widespread vulnerability again to infections that have so far been easily treatable with existing drugs. Among the many approaches investigated to overcome this challenge is the use of engineered nanostructures for the precise and targeted delivery of existing antimicrobial agents in a fashion that will potentiate their effect. This idea leans on lessons learned from pioneering research in cancer, where the targeted delivery of anti-cancer drugs to mammalian cells has been a topic for some time. In particular, new research has demonstrated that nanomaterials can be functionalised with active antimicrobials and, in some cases, with targeting molecules that potentiate the efficiency of the antimicrobials. In this mini-review, we summarise results that demonstrate the potential for nanoparticles, dendrimers and DNA nanostructures for use in antimicrobial delivery. We consider material aspects of the delivery vehicles and ways in which they can be functionalised with antibiotics and antimicrobial peptides, and we review evidence for their efficacy to kill bacteria both in vitro and in vivo. We also discuss the advantages and limitations of these materials and highlight the benefits of DNA nanostructures specifically for their versatile potential in the present context
High-throughput, multi-parametric, and correlative fluorescence lifetime imaging.
Funder: Infinitus (China), Ltd.Funder: MedImmune (AstraZeneca); doi: https://doi.org/10.13039/501100004628In this review, we discuss methods and advancements in fluorescence lifetime imaging microscopy that permit measurements to be performed at faster speed and higher resolution than previously possible. We review fast single-photon timing technologies and the use of parallelized detection schemes to enable high-throughput and high content imaging applications. We appraise different technological implementations of fluorescence lifetime imaging, primarily in the time-domain. We also review combinations of fluorescence lifetime with other imaging modalities to capture multi-dimensional and correlative information from a single sample. Throughout the review, we focus on applications in biomedical research. We conclude with a critical outlook on current challenges and future opportunities in this rapidly developing field
Genomic analysis of bacterial mycophagy
The study of bacterial-fungal interactions is essential to obtain a better understanding of terrestrial microbial ecology and may lie at the basis of novel applications in agriculture, food industry and human health. Nevertheless, the incentives, the genetic determinants and the mechanisms that underlie bacterial-fungal interactions are still poorly understood. Bacterial mycophagy is a trophic behaviour that takes place when bacteria obtain nutrients from living fungal hyphae, allowing the conversion of living fungal biomass into bacterial biomass (29). This trophic behavior was demonstrated for the first time for bacteria of the genus Collimonas, based on their ability to grow at the expenses of living fungal hyphae in a soil-like microcosm (28, 30). In this thesis I addressed the following research questions: (1) Which of the mechanisms putatively involved in Collimonas mycophagy are actually activated when Collimonas interact with a fungus (2) What is the fungal response to the presence of Collimonas bacteria? (3) What is the role played by plasmid pTer331, detected in the genome of the mycophagous bacterium C. fungivorans Ter331, in the ecology of this bacterium? Are the genes encoded on plasmid pTer331 involved in mycophagy? (4) Are the putative determinants of mycophagy uniformly distributed among Collimonas species?BSIKUBL - phd migration 201
A Dynamic Model of Sponsored Search Advertising
Sponsored search advertising is ascendant Jupiter Research reports
expenditures rose 28% in 2007 to 22 retail price of the software products advertised on the considered
search engine, this implies a conversion rate (sales per click) of about
1.1%, well within common estimates of 1-2% (gamedaily.com). Hence our
approach appears to yield valid estimates of advertiser click
valuations. Another finding is that customers appear to be segmented by
their clicking frequency, with frequent clickers placing a greater
emphasis on the position of the sponsored advertising link. Estimation
of the policy simulations is in progress
Advertiser Learning in Direct Advertising Markets
Direct buy advertisers procure advertising inventory at fixed rates from
publishers and ad networks. Such advertisers face the complex task of choosing
ads amongst myriad new publisher sites. We offer evidence that advertisers do
not excel at making these choices. Instead, they try many sites before settling
on a favored set, consistent with advertiser learning. We subsequently model
advertiser demand for publisher inventory wherein advertisers learn about
advertising efficacy across publishers' sites. Results suggest that advertisers
spend considerable resources advertising on sites they eventually abandon -- in
part because their prior beliefs about advertising efficacy on those sites are
too optimistic. The median advertiser's expected CTR at a new site is 0.23%,
five times higher than the true median CTR of 0.045%.
We consider how pooling advertiser information remediates this problem.
Specifically, we show that ads with similar visual elements garner similar
CTRs, enabling advertisers to better predict ad performance at new sites.
Counterfactual analyses indicate that gains from pooling advertiser information
are substantial: over six months, we estimate a median advertiser welfare gain
of \$2,756 (a 15.5% increase) and a median publisher revenue gain of \$9,618 (a
63.9% increase)
Analisi degli approcci scientifici per la definizione comune di rinnovazione naturale con particolare riferimento all'ambiente mediterraneo
La rinnovazione forestale è il futuro di ogni foresta ed è legata a diversi fenomeni ecologici. Molti studi hanno utilizzato vari metodi per analizzare la rinnovazione forestale; tuttavia, a livello internazionale, non esiste un metodo comune condiviso per classificare il fenomeno della rigenerazione stessa. Con l’obiettivo di trovare una possibile sintesi comune questo lavoro analizza il fenomeno della rinnovazione naturale attraverso sia l’analisi di inventari forestali sia di pubblicazioni scientifiche. La ricerca ha permesso di elaborare un elenco bibliografico multilingue attraverso l’interrogazione di database on-line, la ricerca con parole chiave e l’analisi dei riferimenti bibliografici degli articoli raccolti. L’esame di una vasta gamma di studi sulla rinnovazione forestale naturale ha permesso di selezionare i lavori scientifici che definiscono in maniera inequivocabile la rinnovazione con parametri quantitativi. I parametri presi in considerazione sono stati limitati alle misure dendrometrici più comunemente usati (altezza e diametro). Confrontando i diversi approcci quantitativi adottati nei diversi contesti ecologici è emerso che nei biomi tropicali e temperati le soglie dei parametri quantitativi tendono a valori più elevati rispetto a quelle riscontrate nei biomi Mediterraneo e della Savana. Pertanto, l’approccio comune condiviso è funzionale per standardizzare tali parametri quantitativi e per definire le soglie che caratterizzare i processi di rinnovazione in selvicoltur
Inhibition of MELK Protooncogene as an Innovative Treatment for Intrahepatic Cholangiocarcinoma
Background and Objectives: Intrahepatic cholangiocarcinoma (iCCA) is a pernicious tumor characterized by a dismal outcome and scarce therapeutic options. To substantially improve the prognosis of iCCA patients, a better understanding of the molecular mechanisms responsible for development and progression of this disease is imperative. In the present study, we aimed at elucidating the role of the maternal embryonic leucine zipper kinase (MELK) protooncogene in iCCA. Materials and Methods: We analyzed the expression of MELK and two putative targets, Forkhead Box M1 (FOXM1) and Enhancer of Zeste Homolog 2 (EZH2), in a collection of human iCCA by real-time RT-PCR and immunohistochemistry (IHC). The effects on iCCA growth of both the multi-kinase inhibitor OTSSP167 and specific small-interfering RNA (siRNA) against MELK were investigated in iCCA cell lines. Results: Expression of MELK was significantly higher in tumors than in corresponding non-neoplastic liver counterparts, with highest levels of MELK being associated with patients' shorter survival length. In vitro, OTSSP167 suppressed the growth of iCCA cell lines in a dose-dependent manner by reducing proliferation and inducing apoptosis. These effects were amplified when OTSSP167 administration was coupled to the DNA-damaging agent doxorubicin. Similar results, but less remarkable, were obtained when MELK was silenced by specific siRNA in the same cells. At the molecular level, siRNA against MELK triggered downregulation of MELK and its targets. Finally, we found that MELK is a downstream target of the E2F1 transcription factor. Conclusion: Our results indicate that MELK is ubiquitously overexpressed in iCCA, where it may represent a prognostic indicator and a therapeutic target. In particular, the combination of OTSSP167 (or other, more specific MELK inhibitors) with DNA-damaging agents might be a potentially effective therapy for human iCCA
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