70 research outputs found
ΠΠ»ΠΈΡΠ½ΠΈΠ΅ N(ΡΠΎΡΡΠΎΠ½ΠΎΠΌΠ΅ΡΠΈΠ»)-Π³Π»ΠΈΡΠΈΠ½Π° Π½Π° ΡΠΎΡΡΠΎΠ»ΠΈΠΏΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΡΡ ΡΠ΅Π°ΠΊΡΠΈΡ Ρ ΡΡΠ°ΡΡΠΈΠ΅ΠΌ ΡΠΎΡΡΠΎΠ»ΠΈΠΏΠ°Π·Ρ Π2
The effect of N(phosphonomethyl)-glycine (glyphosate), the active ingredient of the Β«SquallΒ» 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.ΠΠ·ΡΡΠ΅Π½ΠΎ Π²Π»ΠΈΡΠ½ΠΈΠ΅ N(ΡΠΎΡΡΠΎΠ½ΠΎΠΌΠ΅ΡΠΈΠ»)-Π³Π»ΠΈΡΠΈΠ½Π° (Π³Π»ΠΈΡΠΎΡΠ°ΡΠ°) - Π΄Π΅ΠΉΡΡΠ²ΡΡΡΠ΅Π³ΠΎ Π²Π΅ΡΠ΅ΡΡΠ²Π° Π³Π΅ΡΠ±ΠΈΡΠΈΠ΄Π° Β«Π¨ΠΊΠ²Π°Π»Β» Π² ΡΠΈΡΠΎΠΊΠΎΠΌ Π΄ΠΈΠ°ΠΏΠ°Π·ΠΎΠ½Π΅ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΉ (1-1000 ΠΌΠΊΠ³/ΠΌΠ») Π½Π° ΡΠΎΡΡΠΎΠ»ΠΈΠΏΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΡΡ ΡΠ΅Π°ΠΊΡΠΈΡ, ΠΊΠ°ΡΠ°Π»ΠΈΠ·ΠΈΡΡΠ΅ΠΌΡΡ ΠΏΠ°Π½ΠΊΡΠ΅Π°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΎΡΡΠΎΠ»ΠΈΠΏΠ°Π·ΠΎΠΉ Π2 (Π€ΠΠ2, ΠΠ€ 3.1.1.4), Π² ΡΡΠ»ΠΎΠ²ΠΈΡΡ
, Π±Π»ΠΈΠ·ΠΊΠΈΡ
ΠΊ ΠΏΠΈΡΠ΅Π²Π°ΡΠ΅Π½ΠΈΡ Π² Π΄Π²Π΅Π½Π°Π΄ΡΠ°ΡΠΈΠΏΠ΅ΡΡΡΠ½ΠΎΠΉ ΠΊΠΈΡΠΊΠ΅ (ΡΠ 8,0, ΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠ° 37 Β°Π‘, ΠΌΠΈΡΠ΅Π»Π»ΡΡΠ½Π°Ρ ΡΠΎΡΠΌΠ° Π€Π₯). ΠΠ²ΡΠΌΡ Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΡΠΌΠΈ ΠΌΠ΅ΡΠΎΠ΄Π°ΠΌΠΈ, Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΡΡΠΈΠΌΠΈ Π½Π°ΠΊΠΎΠΏΠ»Π΅Π½ΠΈΠ΅ ΠΏΡΠΎΠ΄ΡΠΊΡΠΎΠ² ΡΠΎΡΡΠΎΠ»ΠΈΠΏΠΎΠ»ΠΈΠ·Π° - Π»ΠΈΠ·ΠΎΡΠΎΡΡΠ°ΡΠΈΠ»ΠΈΠ»Ρ
ΠΎΠ»ΠΈΠ½Π° (Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π’Π‘Π₯) ΠΈ ΠΆΠΈΡΠ½ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΡ (Ρ ΡΠ΅Π³ΠΈΡΡΡΠ°ΡΠΈΠ΅ΠΉ ΠΏΠΎΠ΄ Π΅Π΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΡΠΏΠ΅ΠΊΡΡΠ°Π»ΡΠ½ΡΡ
ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ MetHb), ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ ΡΠ°Π·Π½ΠΎΠ½Π°ΠΏΡΠ°Π²Π»Π΅Π½Π½ΠΎΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ Π³Π»ΠΈΡΠΎΡΠ°ΡΠ° Π½Π° Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π€ΠΠ2: Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΡΡ
Π΄Π»Ρ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° ΠΈ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ
Π΄ΠΎΠ· (Π΄ΠΎ 100 ΠΌΠΊΠ³/ΠΌΠ») - Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ Π² 1,4 ΡΠ°Π·Π°, Π° ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ Π·Π°ΠΏΡΠ΅Π΄Π΅Π»ΡΠ½ΡΡ
Π΄ΠΎΠ· (Π΄ΠΎ 1000 ΠΌΠΊΠ³/ΠΌΠ») - ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠ²Π°Π½ΠΈΠ΅ Π΄ΠΎ 20% ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ. ΠΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ½Π°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π³Π»ΠΈΡΠΎΡΠ°ΡΠ° Π² ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ 0,5 ΠΌΠ ΠΏΡΠΈ ΡΠ΅ΡΠΌΠ΅Π½ΡΠ°ΡΠΈΠ²Π½ΠΎΠΌ Π³ΠΈΠ΄ΡΠΎΠ»ΠΈΠ·Π΅ Π€Π₯ Π² ΠΌΠΈΡΠ΅Π»Π»ΡΡΠ½ΠΎΠΉ ΡΠ°Π·Π΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΠ΅ΡΡΡ Π²Π΅Π»ΠΈΡΠΈΠ½ΠΎΠΉ Πi ΡΠ°Π²Π½ΠΎΠΉ 24 ΠΌΠ, Π° ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π½ΠΎΡΠΈΡ ΠΊΠΎΠ½ΠΊΡΡΠ΅Π½ΡΠ½ΡΠΉ Ρ
Π°ΡΠ°ΠΊΡΠ΅Ρ. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ ΡΠΊΡΠΏΡΠ΅ΡΡ-ΠΌΠ΅ΡΠΎΠ΄ Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ in vitro ΡΠΎΡΡΠΎΠ»ΠΈΠΏΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅Π°ΠΊΡΠΈΠΈ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΏΡΠΎΡΡΠΎΠΉ ΠΌΠΎΠ΄Π΅Π»ΠΈ ΠΏΡΠΎΡΠ΅ΡΡΠ° ΡΠ°Π·ΡΡΡΠ΅Π½ΠΈΡ ΡΠΎΡΡΠΎΠ»ΠΈΠΏΠΈ-Π΄ΠΎΠ² ΠΏΠΈΡΠΈ ΠΈ ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
ΠΌΠ΅ΠΌΠ±ΡΠ°Π½ ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π΅Π½ Π² ΡΠ΅Π»ΡΡ
ΠΏΡΠ΅Π΄Π²Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠΉ ΠΎΡΠ΅Π½ΠΊΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ ΠΏΠ΅ΡΡΠΈΡΠΈΠ΄ΠΎΠ² Π΄Π»Ρ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° ΠΈ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ
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Only the best? Exploring cross-border investor preferences in US gateway cities
Despite heady growth in cross-border investment into commercial real estate over recent decades, there are few studies that examine differences in investment preferences between domestic and cross-border investors at a micro level. We address the gap by examining the characteristics of assets acquired by cross border investors in six major US metro areas, comparing them with the purchases made by US investors in those same areas. Our study uses data on more than 67 500 transactions recorded by Real Capital Analytics (RCA) over the period from Q1 2003 to Q3 2016. As well as examining cross-border investors in aggregate, we isolate and examine purchases by investors from each of the four principal source nations for cross-border real estate investment in these cities. This is important since treating cross-border investors as a single group may obscure important differences between them. We employ multilevel logit techniques and we find across a number of specifications that cross-border investors prefer larger assets, newer assets and CBD locations regardless of nationality. However, temporal and sectoral patterns of investment, as well as evidence for return chasing behavior, vary with the nationality of investor being studied
A Systems Approach for Tumor Pharmacokinetics
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
A tumor cord model for Doxorubicin delivery and dose optimization in solid tumors
<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
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 β 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
Modelling Foreign Real Estate Investment: The Spanish Case
Foreign real estate investment, Housing investment bubble, Foreign direct investment,
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