Long-term culture of primary porcine oviduct epithelial cells: Validation of a comprehensive in vitro model for reproductive science

Recently, we established a protocol for the cultivation of primary porcine oviduct epithelial cells (POEC), which promoted tissue-like morphology for a prolonged culture period. The present study focuses on developing this model into a comprehensive, standardized culture system, as a candidate tool for reproductive toxicity testing and basic research. We cultivated POEC isolated from 25 animals in our culture system for both 3 and 6 weeks and systematically analyzed effects of medium conditioning, supplementation with standardized sera, and culture duration in both freshly isolated and cryopreserved cells. The differentiation status was evaluated via histomorphometry, transepithelial electrical resistance (TEER) measurement, and expression analyses. The culture system possessed high reproducibility, more than 95% of cultures achieved a fully differentiated phenotype. Cells recapitulated in vivo–like morphology and ultrastructure from 3 to 6 weeks. Cryopreservation of the cells prior to cultivation did not affect culture quality of POEC. Employment of conditioned medium ensured optimal promotion of POEC differentiation, and different standardized sera induced fully differentiated phenotypes. Consistent TEER establishment indicated the presence and maintenance of cell type–specific intercellular junctions. The functionality of POEC was proven by consistent mucin secretion and stable expression of selected markers over the whole culture duration. We conclude that POEC are suitable for experiments from 3 weeks up to at least 6 weeks of culture. Therefore, this culture system could be used for in vitro estrous cycle simulation and long-term investigation of toxic effects on oviduct epithelium

Transepithelial electrical resistance (TEER): a functional parameter to monitor the quality of oviduct epithelial cells cultured on filter supports

Cultivation of oviduct epithelial cells on porous filters fosters in vivo-like morphology and functionality. However, due to the optical properties of the filter materials and the cells’ columnar shape, cell quality is hard to assess via light microscopy. In this study, we aim to evaluate transepithelial electrical resistance (TEER) measurement as a prognostic quality indicator for the cultivation of porcine oviduct epithelial cells (POEC). POEC were maintained in four different types of media for 3 and 6 w to achieve diverse culture qualities, and TEER was measured before processing samples for histology. Culture quality was scored using morphological criteria (presence of cilia, confluence and cell polarity). We furthermore analyzed the correlation between cellular height (as a measure of apical–basal polarization) and TEER in fully differentiated routine cultures (biological variation) and in cultures with altered cellular height due to hormonal stimulation. Fully differentiated cultures possessed a moderate TEER between 500 and 1100 Ω*cm2. Only 5 % of cultures which exhibited TEER values in this defined range had poor quality. Sub-differentiated cultures showed either very low or excessively high TEER. We unveiled a highly significant (P < 0.0001) negative linear correlation between TEER and epithelial height in well-differentiated cultures (both routine and hormone stimulated group). This may point toward the interaction between tight junction assembly and epithelial apical–basal polarization. In conclusion, TEER is a straightforward quality indicator which could be routinely used to monitor the differentiation status of oviduct epithelial cells in vitro

A dynamic pricing model for unifying programmatic guarantee and real-time bidding in display advertising

There are two major ways of selling impressions in display advertising. They are either sold in spot through auction mechanisms or in advance via guaranteed contracts. The former has achieved a significant automation via real-time bidding (RTB); however, the latter is still mainly done over the counter through direct sales. This paper proposes a mathematical model that allocates and prices the future impressions between real-time auctions and guaranteed contracts. Under conventional economic assumptions, our model shows that the two ways can be seamless combined programmatically and the publisher's revenue can be maximized via price discrimination and optimal allocation. We consider advertisers are risk-averse, and they would be willing to purchase guaranteed impressions if the total costs are less than their private values. We also consider that an advertiser's purchase behavior can be affected by both the guaranteed price and the time interval between the purchase time and the impression delivery date. Our solution suggests an optimal percentage of future impressions to sell in advance and provides an explicit formula to calculate at what prices to sell. We find that the optimal guaranteed prices are dynamic and are non-decreasing over time. We evaluate our method with RTB datasets and find that the model adopts different strategies in allocation and pricing according to the level of competition. From the experiments we find that, in a less competitive market, lower prices of the guaranteed contracts will encourage the purchase in advance and the revenue gain is mainly contributed by the increased competition in future RTB. In a highly competitive market, advertisers are more willing to purchase the guaranteed contracts and thus higher prices are expected. The revenue gain is largely contributed by the guaranteed selling.Comment: Chen, Bowei and Yuan, Shuai and Wang, Jun (2014) A dynamic pricing model for unifying programmatic guarantee and real-time bidding in display advertising. In: The Eighth International Workshop on Data Mining for Online Advertising, 24 - 27 August 2014, New York Cit

Two-hole ground state wavefunction: Non-BCS pairing in a tt-JJ two-leg ladder system

Superconductivity is usually described in the framework of the Bardeen-Cooper-Schrieffer (BCS) wavefunction, which even includes the resonating-valence-bond (RVB) wavefunction proposed for the high-temperature superconductivity in the cuprate. A natural question is \emph{if} any fundamental physics could be possibly missed by applying such a scheme to strongly correlated systems. Here we study the pairing wavefunction of two holes injected into a Mott insulator/antiferromagnet in a two-leg ladder using variational Monte Carlo (VMC) approach. By comparing with density matrix renormalization group (DMRG) calculation, we show that a conventional BCS or RVB pairing of the doped holes makes qualitatively wrong predictions and is incompatible with the fundamental pairing force in the $t$-$J$ model, which is kinetic-energy-driven by nature. By contrast, a non-BCS-like wavefunction incorporating such novel effect will result in a substantially enhanced pairing strength and improved ground state energy as compared to the DMRG results. We argue that the non-BCS form of such a new ground state wavefunction is essential to describe a doped Mott antiferromagnet at finite doping.Comment: 11 pages, 5 figure

Statistical Inference for Medical Costs and Incremental Cost-effectiveness Ratios with Censored Data

Cost-effectiveness analysis is widely conducted in the economic evaluation of new treatments, due to skyrocketing health care costs and limited resource available. Censored costs data poses a unique problem for cost estimation due to “induced informative censoring” problem. Thus, many standard approaches for survival analysis are not valid for the analysis of cost data. We first derive the confidence interval for the incremental cost-effectiveness ratio for a special case, when terminating events are different for survival time and costs. Then we study how to intuitively explain some existing estimators for costs, based on the generalized redistribute-to-the-right algorithm. Motivated by that idea, we also propose two improved survival estimators of costs, based on generalized redistribute-to-the-right algorithm and kernel method. We first consider one special situation in conducting cost-effectiveness analysis, when the terminating events for survival time and costs are different. Traditional methods for statistical inference cannot deal with such data. We propose a new method for deriving the confidence interval for the incremental cost-effectiveness ratio under this situation, based on the counting process theory and the general theory for missing data process. The simulation studies and real data example show that our method performs very well for some practical settings. In addition, we provide intuitive explanation to a mean cost estimator and a survival estimator for costs, based on generalized redistribute-to-the-right algorithm. Since those estimators are derived based on the inverse probability weighting principle and semiparametric efficiency theory, it is not always easy to understand how these methods work. Therefore, our work engenders a better understanding of those theoretically derived cost estimators. Motivated by the idea of generalized redistribute-to-the-right algorithm, we propose an estimator for the survival function of costs. The proposed estimator is naturally monotone, more efficient than some existing survival estimators, and has a quite small bias in many realistic settings. We further propose a kernel-based survival estimator for costs. The latter estimator, which is asymptotically unbiased, overcomes the deficiency of the former estimator, while preserving the nice properties. Our proposed estimators outperform existing estimators under various scenarios in simulation and real data example

Energy Consumption And Economic Growth In China: New Evidence From The Co-Integrated Panel VAR Model

This study is conducted to explore the relationship between energy consumption and economic growth in China over the period 1995-2010 using the panel time-series techniques under a multivariate framework. The results reveal that there are long-run co-integration relationship among variables real GDP, energy consumption, capital formation and labor force. Furthermore, based on the panel VEC model, there is bidirectional causality between economic growth and energy consumption, which is consistent with the growth hypothesis in terms of the energy consumption-growth nexus. The unidirectional causality from capital formation to energy consumption reveals that energy consumption cannot affect economic growth through capital formation. Additionally, real GDP, energy consumption, capital formation and labor force each respond to short-run deviations from long-run equilibrium with a slow adjustment speed. Finally, by estimating the panel VAR model, it is found that the responses of real GDP to a shock of energy consumption are negative, whereas the shock of real GDP changes is positive with most of the energy consumption response being absorbed during the six years. By variance decompositions derived from the orthogonalized impulse-response coefficient matrices, a shock in the energy consumption takes the biggest effect on real GDP in both short-run and long-run