244 research outputs found

    Factors Affecting Foreign Investor Choice in Types of U.S. Real Estate

    Get PDF
    Using transaction level data, we present the first analysis of the way that foreign investors choose among different types of United States real estate. Our findings based on the conditional logit model analysis for the 1980-91 period are consistent with the hypothesis that foreign investors behave in a traditional profit maximizing, risk minimizing fashion. In choosing among investments in four major categories (apartment, office, retail and industrial) foreign investor choice is most sensitive to changes in capitalization rates, market activity and current rent levels.

    Web-Based vs. Face-To-Face MBA Classes: A Comparative Assessment Study

    Get PDF
    The challenges of online learning include ensuring that the learning outcomes are at least as robust as in the face-to-face sections of the same course. At the University of Baltimore, both online sections and face-to-face sections of core MBA courses are offered. Once admitted to the MBA, students are free to enroll in any combination of web-based or face-to-face courses. This provides a unique laboratory to assess comparative learning outcomes

    Physiological modeling of isoprene dynamics in exhaled breath

    Full text link
    Human breath contains a myriad of endogenous volatile organic compounds (VOCs) which are reflective of ongoing metabolic or physiological processes. While research into the diagnostic potential and general medical relevance of these trace gases is conducted on a considerable scale, little focus has been given so far to a sound analysis of the quantitative relationships between breath levels and the underlying systemic concentrations. This paper is devoted to a thorough modeling study of the end-tidal breath dynamics associated with isoprene, which serves as a paradigmatic example for the class of low-soluble, blood-borne VOCs. Real-time measurements of exhaled breath under an ergometer challenge reveal characteristic changes of isoprene output in response to variations in ventilation and perfusion. Here, a valid compartmental description of these profiles is developed. By comparison with experimental data it is inferred that the major part of breath isoprene variability during exercise conditions can be attributed to an increased fractional perfusion of potential storage and production sites, leading to higher levels of mixed venous blood concentrations at the onset of physical activity. In this context, various lines of supportive evidence for an extrahepatic tissue source of isoprene are presented. Our model is a first step towards new guidelines for the breath gas analysis of isoprene and is expected to aid further investigations regarding the exhalation, storage, transport and biotransformation processes associated with this important compound.Comment: 14 page

    Bayesian Algorithm Implementation in a Real Time Exposure Assessment Model on Benzene with Calculation of Associated Cancer Risks

    Get PDF
    The objective of the current study was the development of a reliable modeling platform to calculate in real time the personal exposure and the associated health risk for filling station employees evaluating current environmental parameters (traffic, meteorological and amount of fuel traded) determined by the appropriate sensor network. A set of Artificial Neural Networks (ANNs) was developed to predict benzene exposure pattern for the filling station employees. Furthermore, a Physiology Based Pharmaco-Kinetic (PBPK) risk assessment model was developed in order to calculate the lifetime probability distribution of leukemia to the employees, fed by data obtained by the ANN model. Bayesian algorithm was involved in crucial points of both model sub compartments. The application was evaluated in two filling stations (one urban and one rural). Among several algorithms available for the development of the ANN exposure model, Bayesian regularization provided the best results and seemed to be a promising technique for prediction of the exposure pattern of that occupational population group. On assessing the estimated leukemia risk under the scope of providing a distribution curve based on the exposure levels and the different susceptibility of the population, the Bayesian algorithm was a prerequisite of the Monte Carlo approach, which is integrated in the PBPK-based risk model. In conclusion, the modeling system described herein is capable of exploiting the information collected by the environmental sensors in order to estimate in real time the personal exposure and the resulting health risk for employees of gasoline filling stations

    Влияние N(фосфонометил)-глицина на фосфолиполитическую реакцию с участием фосфолипазы А2

    Get PDF
    The effect of N(phosphonomethyl)-glycine (glyphosate), the active ingredient of the «Squall» herbicide in a wide range of concentrations (1-1000 |ig/ml) on phospholipolysis catalyzed by pancreatic phospholipase A2 (PLA2, 3.1.1.4), under the conditions similar to digestion in the duodenum (pH 8.0, temperature S, micellar form PC), has been studied. It has been shown that a rapid method based on the use of in vitro phospholipolytic reaction as a simple model of the process of destruction of food and phospholipids of cell membranes, is promising for preliminary evaluation of the pesticide safety to humans and animals.Изучено влияние N(фосфонометил)-глицина (глифосата) - действующего вещества гербицида «Шквал» в широком диапазоне концентраций (1-1000 мкг/мл) на фосфолиполитическую реакцию, катализируемую панкреатической фосфолипазой А2 (ФЛА2, КФ 3.1.1.4), в условиях, близких к пищеварению в двенадцатиперстной кишке (рН 8,0, температура 37 °С, мицеллярная форма ФХ). Двумя независимыми методами, характеризующими накопление продуктов фосфолиполиза - лизофосфатилилхолина (с использованием ТСХ) и жирной кислоты (с регистрацией под ее действием спектральных изменений MetHb), установлено разнонаправленное действие глифосата на активность ФЛА2: в присутствии безопасных для человека и животных доз (до 100 мкг/мл) - активация в 1,4 раза, а под действием запредельных доз (до 1000 мкг/мл) - ингибирвание до 20% остаточной активности. Ингибиторная активность глифосата в концентрации 0,5 мМ при ферментативном гидролизе ФХ в мицеллярной фазе характеризуется величиной Кi равной 24 мМ, а ингибирование носит конкурентный характер. Показано, что экспресс-метод на основе использования in vitro фосфолиполитической реакции в качестве простой модели процесса разрушения фосфолипи-дов пищи и клеточных мембран перспективен в целях предварительной оценки безопасности пестицидов для человека и животных

    PKQuest: capillary permeability limitation and plasma protein binding – application to human inulin, dicloxacillin and ceftriaxone pharmacokinetics

    Get PDF
    BACKGROUND: It is generally assumed that the tissue exchange of antibiotics is flow limited (complete equilibration between the capillary and the tissue water). This assumption may not be valid if there is a large amount of plasma protein binding because the effective capillary permeability depends on the product of the intrinsic capillary permeability (PS) and the fraction of solute that is free in the blood (fw(B)). PKQuest, a new generic physiologically based pharmacokinetic software routine (PBPK), provides a novel approach to modeling capillary permeability in which the only adjustable parameter is the PS of muscle. METHODS: All the results were obtained by applying PKQuest to previously published human pharmacokinetic data. RESULTS: The PKQuest analysis suggests that the highly protein bound antibiotics dicloxacillin and ceftriaxone have a significant capillary permeability limitation. The human muscle capillary PS of inulin, dicloxacillin and ceftriaxone was 0.6, 13 and 6 ml/min/100 gm, respectively. The ceftriaxone protein binding is non-linear, saturating at high plasma concentrations. The experimental ceftriaxone data over a wide range of intravenous inputs (0.15 to 3 gms) was well described by PKQuest. PKQuest is the first PBPK that includes both permeability limitation and non-linear binding. CONCLUSIONS: Because of their high degree of plasma protein binding, dicloxacillin and ceftriaxone appear to have a diffusion limited exchange rate between the blood and tissue and are not flow limited as had been previously assumed. PKQuest and all the examples are freely available at

    A tumor cord model for Doxorubicin delivery and dose optimization in solid tumors

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Doxorubicin is a common anticancer agent used in the treatment of a number of neoplasms, with the lifetime dose limited due to the potential for cardiotoxocity. This has motivated efforts to develop optimal dosage regimes that maximize anti-tumor activity while minimizing cardiac toxicity, which is correlated with peak plasma concentration. Doxorubicin is characterized by poor penetration from tumoral vessels into the tumor mass, due to the highly irregular tumor vasculature. I model the delivery of a soluble drug from the vasculature to a solid tumor using a tumor cord model and examine the penetration of doxorubicin under different dosage regimes and tumor microenvironments.</p> <p>Methods</p> <p>A coupled ODE-PDE model is employed where drug is transported from the vasculature into a tumor cord domain according to the principle of solute transport. Within the tumor cord, extracellular drug diffuses and saturable pharmacokinetics govern uptake and efflux by cancer cells. Cancer cell death is also determined as a function of peak intracellular drug concentration.</p> <p>Results</p> <p>The model predicts that transport to the tumor cord from the vasculature is dominated by diffusive transport of free drug during the initial plasma drug distribution phase. I characterize the effect of all parameters describing the tumor microenvironment on drug delivery, and large intercapillary distance is predicted to be a major barrier to drug delivery. Comparing continuous drug infusion with bolus injection shows that the optimum infusion time depends upon the drug dose, with bolus injection best for low-dose therapy but short infusions better for high doses. Simulations of multiple treatments suggest that additional treatments have similar efficacy in terms of cell mortality, but drug penetration is limited. Moreover, fractionating a single large dose into several smaller doses slightly improves anti-tumor efficacy.</p> <p>Conclusion</p> <p>Drug infusion time has a significant effect on the spatial profile of cell mortality within tumor cord systems. Therefore, extending infusion times (up to 2 hours) and fractionating large doses are two strategies that may preserve or increase anti-tumor activity and reduce cardiotoxicity by decreasing peak plasma concentration. However, even under optimal conditions, doxorubicin may have limited delivery into advanced solid tumors.</p

    PKQuest: a general physiologically based pharmacokinetic model. Introduction and application to propranolol

    Get PDF
    BACKGROUND: A "physiologically based pharmacokinetic" (PBPK) approach uses a realistic model of the animal to describe the pharmacokinetics. Previous PBPKs have been designed for specific solutes, required specification of a large number of parameters and have not been designed for general use. METHODS: This new PBPK program (PKQuest) includes a "Standardhuman" and "Standardrat" data set so that the user input is minimized. It has a simple user interface, graphical output and many new features: 1) An option that uses the measured plasma concentrations to solve for the time course of the gastrointestinal, intramuscular, intraperotineal or skin absorption and systemic availability of a drug – for a general non-linear system. 2) Capillary permeability limitation defined in terms of the permeability-surface area products. 4) Saturable plasma and tissue protein binding. 5) A lung model that includes perfusion-ventilation mismatch. 6) A general optimization routine using either a global (simulated annealing) or local (Powell) minimization applicable to all model parameters. RESULTS: PKQuest was applied to measurements of human propranolol pharmacokinetics and intestinal absorption. A meal has two effects: 1) increases portal blood flow by 50%; and 2) decreases liver metabolism by 20%. There is a significant delay in the oval propranolol absorption in fasting subjects that is absent in fed subjects. The oral absorption of the long acting form of propranolol continues for a period of more than 24 hours. CONCLUSIONS: PKQuest provides a new general purpose, easy to use, freely distributed and physiologically rigorous PBPK software routine
    corecore