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

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 $8.9B and will continue to rise at a 15landscape. Yet little, if any empirical research focuses upon search engine marketing strategy by integrating the behavior of various agents in sponsored search advertising (i.e., searchers, advertisers, and the search engine platform). The dynamic structural model we propose serves as a foundation to explore these and other sponsored search advertising phenomena. Fitting the model to a proprietary data set provided by an anonymous search engine, we conduct several policy simulations to illustrate the bene ts of our approach. First, we explore how information asymmetries between search engines and advertisers can be exploited to enhance platform revenues. This has consequences for the pricing of market intelligence. Second, we assess the effect of allowing advertisers to bid not only on key words, but also by consumers searching histories and demographics thereby creating a more targeted model of advertising. Third, we explore several different auction pricing mechanisms and assess the role of each on engine and advertiser profits and revenues. Finally, we consider the role of consumer search tools such as sorting on consumer and advertiser behavior and engine revenues. One key finding is that the estimated advertiser value for a click on its sponsored link averages about 24 cents. Given the typical$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