266 research outputs found

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

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    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.

    Physiological modeling of isoprene dynamics in exhaled breath

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    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

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

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    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

    A Systems Approach for Tumor Pharmacokinetics

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    Recent advances in genome inspired target discovery, small molecule screens, development of biological and nanotechnology have led to the introduction of a myriad of new differently sized agents into the clinic. The differences in small and large molecule delivery are becoming increasingly important in combination therapies as well as the use of drugs that modify the physiology of tumors such as anti-angiogenic treatment. The complexity of targeting has led to the development of mathematical models to facilitate understanding, but unfortunately, these studies are often only applicable to a particular molecule, making pharmacokinetic comparisons difficult. Here we develop and describe a framework for categorizing primary pharmacokinetics of drugs in tumors. For modeling purposes, we define drugs not by their mechanism of action but rather their rate-limiting step of delivery. Our simulations account for variations in perfusion, vascularization, interstitial transport, and non-linear local binding and metabolism. Based on a comparison of the fundamental rates determining uptake, drugs were classified into four categories depending on whether uptake is limited by blood flow, extravasation, interstitial diffusion, or local binding and metabolism. Simulations comparing small molecule versus macromolecular drugs show a sharp difference in distribution, which has implications for multi-drug therapies. The tissue-level distribution differs widely in tumors for small molecules versus macromolecular biologic drugs, and this should be considered in the design of agents and treatments. An example using antibodies in mouse xenografts illustrates the different in vivo behavior. This type of transport analysis can be used to aid in model development, experimental data analysis, and imaging and therapeutic agent design.National Institutes of Health (U.S.) (grant T32 CA079443

    International Frameworks Dealing with Human Risk Assessment of Combined Exposure to Multiple Chemicals

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    The development of harmonised terminology and frameworks for the human risk assessment of combined exposure to multiple chemicals (“chemical mixtures”) is an important area for EFSA and a number of activities have already been undertaken, i.e. in the fields of pesticides and contaminants. The first step prior to a risk assessment of combined exposure to multiple chemicals is problem formulation defining the relevant exposure, hazard and population to be considered. In practice, risk assessment of multiple chemicals is conducted using a tiered approach for exposure assessment, hazard assessment and risk characterisation. Higher tiers require increasing knowledge about the group of chemicals under assessment and the tiers can range from tier 0 (default values, data poor situation) to tier 3 (full probabilistic models). This scientific report reviews the terminology, methodologies and frameworks developed by national and international agencies for the human risk assessment of combined exposure to multiple chemicals and provides recommendations for future activities at EFSA in this area

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

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    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

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    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

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    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
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